From alt.support.mult-sclerosis Fri Aug 27 12:37:05 1993 Path: klaava!news.funet.fi!sunic!uunet!cs.utexas.edu!uwm.edu!psuvax1!psuvm!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TAUNIVM.TAU.AC.IL:owner-mslist-l@TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 6188122 X-Genie-From: R.KOREJWO Message-ID: <9308252300.AA14652@relay2.geis.com> Date: Wed, 25 Aug 1993 23:50:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: r-MBP Lines: 72 Status: RO -Alex The primary reason that you didn't see the results of the VAMC Portland/OSU was that they didn't exactly make a lot of noise about it. This kind of came as an "also ran" in the Apr '92 report. (see below) 92368443 Vandenbark AA Chou YK Bourdette DN Whitham R Hashim GA Offner H T cell receptor peptide therapy for autoimmune disease. J Autoimmun 1992 Apr;5 Suppl A:83-92 Synthetic peptides corresponding to germline T cell receptor (TCR) V beta sequences shared by encephalitogenic T cells can prevent and treat experimental autoimmune encephalomyelitis in rats. The operative mechanism apparently involves boosting of anti-TCR immunity that develops during the course of experimental autoimmune encephalomyelitis (EAE), leading to the induction of autoregulatory T cells and antibodies. Striking parallels are present between patients with multiple sclerosis and animals with EAE in the T cell frequency and TCR V gene bias of BP reactive T cells, suggesting the involvement of an encephalitogenic process in multiple sclerosis. Preliminary trials with the appropriate human TCR peptides indicate that anti-TCR immunity can be boosted efficiently and safely, with concomitant loss of BP response, thus providing an effective strategy for selective regulation of autoimmunity in man. Institutional address: Neuroimmunology Research Veterans Affairs Medical Center Portland OR 97201. Clearly this was not a resounding success story but it ran its' course and we are now on to other things. BTW, I have been told that Dr. Larry Steinman at Stanford is going for a monoclonal (read - patentable) form from the peptide study to keep money in the company down there. (I'm can't remember that name) Re:"Also, what do you mean by "The fact that the paper's authors were Oettinger...." If you have the letterhead, you will notice who the heavy hitters are. Weiner, Hafler, Dawson etc. (please don't take it personal if you are an etc...) are their biggest guns. They tend to grab the most important work and attract the most grant money. By no means am I saying that it is not well deserved. Re:"What is a "non-professional" presenter?" and "...Could you point me to an accessible book or article " I suggest the Antonio Lanzavecchia paper because it is very accessible. Try "Science" 14 May 1993 260;937-44. While he did not even mention MS in the paper his theoretical presentation is a perfect fit for some of the data that has been accumulating around MS. Re:"What does all of this have to do with heterogeneity?" Part of the problem that was determined was that the TCR sequence that was thought to be common to MS patients was not. There is a hunt on to find a subset of markers on the TCR which is common or has enough affinity to work as a match. A few papers have surfaced already. Here again, the Lanzavecchia paper suggest that we must also consider exclusion of the ligation of CD28. In the "Vaccination" paper by Weiner & Hafler the patient specific factors were unaccounted for because they used T cells from the patients themselves.(N=4) Getting past this patient specific parameter may be the next true challenge. Re:"Don't forget that p.b.m. has MBP plus a lot of other stuff, some of which could be the antigen in MS." That's exactly why the synthetic is probably safer. If you would like to speculate on the MS antigen, you have to throw out most of the research in the last 5 years and certainly the peptide and antigen feeding trial. If you believe that whole brain antigen feeding really works, then there are food products that would certainly meet your needs. Regards, Rick From alt.support.mult-sclerosis Fri Aug 27 12:37:52 1993 Path: klaava!news.funet.fi!sunic!mcsun!uknet!pipex!uunet!europa.eng.gtefsd.com!howland.reston.ans.net!agate!ames!koriel!west.West.Sun.COM!male.EBay.Sun.COM!jethro.Corp.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: Re: r-MBP Date: 26 Aug 1993 17:47:22 GMT Organization: Sun Lines: 23 Message-ID: References: <9308252300.AA14652@relay2.geis.com> NNTP-Posting-Host: chrysos Status: O In article <9308252300.AA14652@relay2.geis.com> Richard Korejwo writes: ... > BTW, I have been told that Dr. Larry > Steinman at Stanford is going for a monoclonal (read - patentable) form from > the peptide study to keep money in the company down there. (I'm can't > remember that name) ... i have been participating in steinman's study of monoclonal antibodies designed to suppress cd4 tcells at stanford. the phase 1 study of toxicity has completed and the phase 2 study of efficacy including the double blind tests is happening in england. a patent seems far off, but i wish it was sooner, including fda approval. the treatments i received definitely helped, i think i would be much worse without them. and since the study has completed at stanford, no more treatments will be available (unfortunately). what steinman plans is to treat patients with beta interferon as soon as it becomes available. and to keep track of cd4 tcell counts (as mine is *way* below normal as a result of the monoclonal antibody treatments). i believe the company he is involved with is neurocrine biosciences inc. in la jolla, ca. gale snow From alt.support.mult-sclerosis Mon Sep 13 10:49:54 1993 Path: klaava!news.funet.fi!sunic!pipex!uunet!cs.utexas.edu!uwm.edu!psuvax1!psuvm!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 2569889 X-Genie-From: R.KOREJWO Message-ID: <9309111041.AA26340@relay2.geis.com> Date: Sat, 11 Sep 1993 11:21:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: The Swank Diet Lines: 80 Status: O -=Brian Gee=- >> ...with the diet outlined in the MS Diet book by Dr.Shwank. I know of >> one who began the diet very shortly after diagnosis and recovered). > Do you think that this person may have gone into remission? Almost certainly. No diet has ever been demonstrated to have a definitive influence on the course of MS. The one thing that is good about the Swank diet was that it received a very large and very long (17 year) study. The study ultimately proved that the diet had no effect on the course of MS. I had some of the original work on this in the files but it ultimately got pitched out. (The Swank diet originated in 1950!) A list of the diets that have been evaluated and found to have no value that I can recall are: Swank diet Allergen free diet (this could be even older than Swank) Gluton free diet Raw food diet - sometimes called the Evers diet MacDougal diet - combined low-fat and gluton free Roger MacDougal, BTW, was a playwright and actor I believe. Pectin and Fructose Restricted diet - I think this was based on a hypothesis that methanol generated by metabolism of complex sugars would attack myelin. Cambridge diet - the low calorie liquid diet Sucrose and tobacco-free diet - Some of this is lost, but I think besides restrictions in these areas, there was a restriction on certain shampoos. (I am not making this up.) Vitamin and Megavitamin therapies - this included a test of megavitamin C Cerebrosides - this was a dietary supplement with fatty acids from bovine spinal cord. Aloe Vera diet Enzyme diet - this was an Evers diet with bacterial and plant enzymes If you're really into old there was a mineral supplement diet that dates back to the late 1800's, about the time of Charcot. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -=Gerald Gold=- > Is this relapsing-remitting MS and would I possibly be a candidate for beta-interferon? *Is* there a sharp distinction between relapsing-=remitting and chronic-progressive MS?< I assume that you had a positive diagnosis of MS. Based on your description you are definitely not currently chronic progressive. Without further neurological evidence you seem to have a very mild form of the disease. I'm definitely not a person to advise you about Betaseron. I have read the study and it's companion MRI paper and did not see any clear evidence of benefit from the data presented at that time. The most common definition that I am aware of for CP included the parameter that the patient never showed any sign of improvement and worsened by one EDSS point/year. Can ER(RR) become CP. Yes. Even more amazing, CP can become ER. > Is my 'stable' condition partially a product of the fact that I have been taking 4-6 capsules daily, of evening primrose oil, 4 capsules of lecithin (which has inositol, as an ingredient.< I doubt it. As regards the subsequent four points. 1) No. 2) I have known people who followed the Swank diet with great devotion. They did not appear to benefit from it. 3) I don't know of anyone who still follows the gluton free diet. 4) I am not confused by it but I have spoken with some people who seem to be. My experience with neurologist is varied. Since I maintain a database of current MS research on an endowment, I come in relatively frequent contact with neurologist and I find they tend to fall into two dominate groups. Those who think they understand MS and those who know they don't but want to learn. I prefer the latter. At least they are humble enough to admit their lack of knowledge and have honest questions. Regards "Is there *anyone* who has considered these issue?" Comment:Of course. -Rick From alt.support.mult-sclerosis Sun Oct 3 19:28:56 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!math.ohio-state.edu!uwm.edu!psuvax1!psuvm!auvm!VM1.YORKU.CA!GERRY Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:GERRY@VM1.YORKU.CA> Message-ID: Date: Sat, 2 Oct 1993 21:15:35 EDT Sender: Multiple Sclerosis Discussion/Support From: Gerald Gold Subject: MS Autoimmune Vaccination Lines: 35 Status: O MHC-RESTRICTED DEPLETION OF HUMAN MYRLIN BASIC PROTEIN REACTIVE T-CELLS BY T-CELL VACCINATION This article, from Science 261:1451-1454 (Sept. 10, 1993) raises a number of is sues about MS and immuno-therapy. Specifically, mylein basic protein reactive c ells are being taken from MS patients, both relapsing-remmitting and chronic-pr ogressive MS, irradiated and then re-injected into these persons. As I understa nd it, their immune systems reacted to these irradiated cells and eliminated th e mylein-reactive cells in thir systems. The frequencies of these T-cells fell fell below the detectable limit .... (*) Jingwu Zhang, Robert Medaer, Piet Stinissen, David Hafler, Jef Raus ABSTRACT Activated autoreactive T cells are potentially pathogenic and regulated by clonotypic networks. Experimental autoimmune diseases can be treated by inoculation with autoreactive T cells (T cell vaccination). In the present study, patients with multiple sclerosis were inoculated with irradiated myelin basic protein (MBP)-reactive T cells. T cell responses to the inoculates were induced to deplete circulating MBP-reactive T cells in the recipients. Regulatory T cell lines isolated trom the recipients inhibited T cells used for vaccination. The cytotoxicity of the CDS+ Tcell lines was restricted by major histocompatibility antigens. Thus, clonotypic interactions regulating autoreactive T cells in humans can bi-, induced by T cell vaccination. (*) J. Zhang, P, Stinissen. J. Raus Multiple Sclerosis Research Unit and Dep R. Medaer, Multiple Sclerosis Research Unit and Department of Immunology, Dr. L. D. Hafler, Center for Neurologic Diseases, Division of Neurology, Department of (*) To whom correspondence should be addressed. From alt.support.mult-sclerosis Sun Oct 3 19:32:17 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!vixen.cso.uiuc.edu!uwm.edu!psuvax1!psuvm!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 8478410 X-Genie-From: R.KOREJWO Message-ID: <9310030433.AA25226@relay2.geis.com> Date: Sun, 3 Oct 1993 04:50:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: MS Autoimmune Vaccination Lines: 45 Status: O Gerald Gold I think you'll find that the paper you referred to is a close approximation of the prior work by Hafler, Weiner et al 18 months ago in: 92174421 Hafler DA Cohen I Benjamin DS Weiner HL T cell vaccination in multiple sclerosis: a preliminary report. Clin Immunol Immunopathol 1992 Mar;62(3):307-13 Multiple sclerosis (MS) is a presumed autoimmune disease of the central nervous system. Inoculation of attenuated T cell clones recognizing immunodominant regions of myelin autoantigens can protect animals from the induction of experimental autoimmune diseases. In this phase one trial, we investigated whether inoculations with attenuated T cell clones are feasible in humans for eventual trials with autoreactive clones and whether there are any associated immunologic effects. A total of seven inoculations with attenuated, autologous T cell clones isolated from the cerebrospinal fluid in four subjects with progressive MS was performed. No untoward side effects were observed. Immunologic studies suggested that the inoculation of autologous activated T cell clones followed by partial, short-term, immunosuppression as evidenced by a decrease of subsequent responses to stimulation via the CD2 pathway and increases in the autologous mixed lymphocyte response. We conclude that the use of attenuated autoreactive T cell clones appears feasible for further clinical trials in humans with autoimmune diseases. Institutional address: Department of Medicine Brigham and Women's Hospital Boston Massachusetts. ------ There is an interesting thesis presented by Antonio Lanzavecchia in Science 14 May 1993;260:937-44. While there are alternative concepts presented for the mechanism, the effect is real. The problem that was not addressed in either of the two Hafler papers is the issue of homogeneity. If T-cell deletion or anergy can be achieved by either mechanism, it is still patient specific. There is a body of evidence that corroborates that cell to cell contact is necessary for either mechanism. Now we need a break on heterogeneity. -Rick From alt.support.mult-sclerosis Tue Oct 12 12:30:51 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!TECHNION.TECHNION.AC.IL!CCANACW Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:CCANACW@TECHNION.TECHNION.AC.IL> Message-ID: Date: Tue, 12 Oct 1993 11:13:39 IST Sender: Multiple Sclerosis Discussion/Support From: Chanoch Weil Organization: Technion - Israel Institute of Technology, Computer Centre Subject: Re: Thankyou for the neurologist recommendation at Standford In-Reply-To: Message of Mon, 11 Oct 1993 23:48:11 GMT from Lines: 28 Status: O Sejal, On Mon, 11 Oct 1993 23:48:11 GMT you said: >I have just finished my denial stage and am trying to accept MS as >a posative thing in my life. It is extremly difficult but I keeping in >there.... > -Sejal Thanks for your posting. Such sharing strengthen all of us. >P.S. I would like to subscribe to this group. Please can someone send >details. Thanks..... The procedure is simple. Send an e-mail message to LISTSERV@TECHNION.TECHNION.AC.IL with a one-line text: SUB MSLIST-L yourname where 'yourname' is your name in real life, or the name by which you wish to be known. Best regards, |--------------------------|--------------------------------------------| | Chanoch Weil | Fax : 972-4-236212 | | User Support Group | Bitnet : ccanacw@TECHNION | | The Computer Centre | TCP/IP : ccanacw@TECHNION.TECHNION.AC.IL| | Technion, Haifa 32000 | | | Israel | | |--------------------------|--------------------------------------------| From alt.support.mult-sclerosis Wed Oct 13 11:34:57 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 6689674 X-Genie-From: R.KOREJWO Message-ID: <9310122307.AA02244@relay2.geis.com> Date: Tue, 12 Oct 1993 23:11:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Kurtzke Lines: 301 Status: RO Chanoch Weil - "Would you care to explain to the uninformed what Kurtze numbers/scale are?" My apologies. I usually try to avoid "technobabble" and it was rude to take off on that. I really am sorry. Here is an extracted paper that I wrote on the Kurtzke DSS and EDSS. If anyone catches me ever "short- handing" something and you don't know what I'm talking about, it's my fault, not yours. Ask! What follows is probably more than anyone wanted to know about a Kurtzke or EDSS ratings but I figure it's best to get it out rather than try to clarify it with 6 messages. WARNING! Long post follows: What's a Kurtzke? by Rick Korejwo There seems to be a rash of questions about Kurtzke numbers and I have to admit that I can't just say "read such-and-such." What is a Kurtke number and what does it mean? This would have been a lot easier to explain prior to 1983 but it's too late for that now. Let me begin with Dr. John F. Kurtzke. Back in 1955 Dr. Kurtzke set out to establish a quantified scale which rated the disabilities of MS patients. The scale, known as the Disability Status Scale (DSS) was relatively straight forward and, in simplified terms was as follows: Kurtzke rating general observed status 0 a normal neurological exam 1 No disability, minimal abnormal signs 2 Minimal disability in only one of the functional systems: strength, coordination, sensation,bladder, vision, mental 3 Independently walking but moderate disability in one of the functional systems. 4 Walking independently for up to 12 hours/day, but sever disability in one functional system 5 Walking without aid for 200 meters but with disability sever enough to prevent working a full day. 6 A cane, crutch or brace is required to walk 100 meters 7 Walking limited to 5 meters with an aid; the patient is mostly confined to a wheelchair 8 Confined to bed or chair; maintained effective use of arms. 9 Helpless bed bound patient 10 Death from MS OK, that seems pretty clear so far and it would be if things hadn't changed. They did. The old Kurtzke scale had some shortcomings. It was a little mobility dependant and was not sufficiently precise if it was to be used by everyone at any location to describe MS patients. A universal rating system is required for a number of reasons. It allows an ability for the total description of a patients status in a shorthand which would be reasonably understood by any number of people separated in time and place. It would also provide a criteria upon which, by objective clinical evaluation, a patients progress or regression might be measured. Objectivity in evaluation is important because subjective comments like "better" and "fine" which might be given by a patient are more likely to be distorted by such non-MS factors as, whether they got three green lights in a row on the way to the office or by simple denial of disability. To refine the process of ratings, a clearer consideration of all of the areas which MS effects had to have a place in the rating system. It was reasonably clear that other areas of disability had to receive higher priority in evaluation. To this end there was a restatement of the Kurtzke scale by Kurtzke in 1957. Most noteworthy in the changes was the emergence of functional groups, later to be called functional systems(FS). These were identified as Pyramidal (motor function)(P), Cerebellar (Cll), Brain Stem (BS), Sensory (S), Bowel & Bladder (BB), Visual (V), Cerebral or Mental (Cb), and, the always necessary, Other(O). Rather than these individual areas running from 1-10 as the full scale these FS generally ran on scales of 0 to 5 or 6. The "Other" FS was simply given a "problems=yes" or "problems=no" rating. If you are interested in understanding how these various FS scale values are derived I have included a supplement which was provided as an appendix to the 1983 EDSS paper by Kurtzke. Since there were 8 FS areas of up to 6 degrees of variability and our original 10 degree criteria of ambulation we ended up with a scale with well over 20000 possible values. To say that rater variability could create different impressions would be a gross understatement. Clearly some structure had to be imposed that would allow two people communicating about a level of disability to have some common scale of measurement. What emerged from this was a revised scale with a fair number of ambiguities and informed subjective decisions. To an extent it has remained unchanged since it was revised in 1983. It is a widely accepted measure of clinical evaluation of MS based on clinically observed, not patient described, problems associated with MS. The revised measurement tool is most commonly referred to as the Expanded Disability Status Scale (EDSS) What follows is a generalized overview of the EDSS. EDSS step 0 This is roughly the same as the old DSS step 0 which described an uneventful clinical neurological examination. All the FS areas except the Cll FS were unremarkable. The exception for the Cll was to allow mood aberrations such as Euphoria or depression. EDSS step 1.0 This includes one FS grade of 1 excluding Cll but no FS grades above 0. EDSS step 1.5 This includes two or more FS grades of 1, again except the Cll FS but no FS grade above 1 EDSS step 2.0 One FS grade of 2 but all other FS equal or less than 1. EDSS step 2.5 This includes 2 FS grades of 2 or less and all other FS grades equal or less than 1. EDSS grades of 3.0 but less than 4.0 are generally areas where normal day to day activities can be followed but with mild disorders present and observed. Persons in steps 3 and 4 are generally able to be active for the normal course of a day can engage in normal activities provided that they are not attempting activities which require special physical skills. EDSS step 3.0 One FS grade of 3, OR three or four FS grades of 2. Other FS grades are 1 or 0. EDSS step 3.5 One FS grade of 3 PLUS one or two grade 2, two FS grade 3,or five FS grade 2, other FS grades are 1 or 0. EDSS grades between 4.0 but less than 5.0 are areas where ambulation/work/daily activities start to take precedence over the precise FS grades. EDSS step 4.0 Combinations of two FS grades just exceeding 3. or one grade 3 plus grade 2; or one FS grade 4 alone. With FS grades exceeding 3.5 there must be full ambulation (including the ability to walk without aid for 500 meters. There must also be the ability to carry out full daily activities to include work of average physical difficulty. EDSS step 4.5 The same minimum grade requirement as step 4.0 plus the ability to walk without aid or rest for approximately 300 meters and to work a full day in a position of average physical difficulty. EDSS steps five and 6 involve a greater latitude of subjective evaluation by the doctor. In general this area involve a broader range of possible problems in the various FS. In these steps the patient may not be house bound but is seldom able to perform a full day of work. The primary discriminator in the four steps from 5.0 to 6.9 rest with walking. To demonstrate the subjective nature of the area, these criteria are further weighed by "usual best function" rather than by supramaximal effort or insufficient performance. EDSS step 5 requires ambulation of about 200 meters without aid or rest. Disability is sufficient to impair full daily activities. Usual FS criteria is one FS 5 or a combination of grades which exceed step 4.0. EDSS step 5.5 requires ambulation of about 100 meters without aid or rest. Other criteria are inability to work part time without special provisions. Two or more FS grades of 5 are ample criteria also. EDSS step 6 requires assistance to walk about 100 meters. This may include rest or the assistance of aids. More than two FS grades of 3 plus are an alternate criteria. EDSS step 6.5 requires assistance to walk about 20 meters without resting but aids (canes, crutches, braces, or people) are required. FS equivalents are as they were in 6.0 with two or more FS of 3+. EDSS steps 7-9 are for the severely involved who are typically restricted to bed or wheelchairs. Although the FS scores are still computed, they become less relevant and the scale starts to take on an appearance similar to the original DSS. EDSS step 7.0 The patient is essentially restricted to a wheelchair with the ability to walk limited to about 5 meters with aid. Usual FS equivalents are multiple FS grades greater than 4 or a pyramidal grade of 5. EDSS step 7.5 describes a patient essentially restricted to a wheelchair with the ability to take only a few steps. A transfer capability is still present. In general they are capable of movement in a wheelchair by themselves but are incapable of continuing a course of daily activities. EDSS step 8.0 describes a patient in a bed or, passively, in a wheelchair. In general they maintain many selfcare abilities and, typically, maintain the use of their arms. EDSS step 8.5 describes patients who are primarily restricted to bed with only limited periods when they are able to use a wheelchair. They may still have effective use of one or both arms and can provide some selfcare functions. EDSS step 9.0 are helpless *bedbound patients who can communicate and eat with assistance. FS grades are usually multiple groups of 4+. EDSS step 9.5 describes the totally helpless bed bound patient who is incapable of communicating, eat or swallow. Again, FS scores are multiples of 4+. EDSS step 10 is equated as death due to MS. Although relatively rare, it includes death caused by *brainstem involvement or death as a consequence of chronic bedridden state typical of terminal pneumonia, uremia, or cadiorespiratory failure. Now you have a full range knowledge of what the EDSS or "Kurtzke" numbers are and what they mean. It is simply a rating system developed, over time, to describe the general state of a patient. If over the course of a test period 90% of the patients have an decrease in their Kurtzke score of one step, this is a good thing. Conversely, if they have an increase in their "Kurtzke" score of 1 or more steps you have an idea that you didn't accomplish much. Let me just emphasize that these are all to be based on the objective results of a neurological exam and not on the reported conditions by the patient. While the patient can assist the neurologist in identifying the areas of potential problem, it is the neurologist who must objectively document the state of the patients condition. More recent studies (circa 1992) have indicated inter and intra ratings scores have shown remarkable similarities indicating that the scale, although not perfect, has provided a fairly accurate means of defining neurological conditions. ---------------- FS scores Pyramidal Functions 0. Normal 1. Abnormal signs without disability 2. Minimal disability 3. Mild or moderate paraparesis or hemiparesis; sever monoparesis 4. Marked paraparesis or hemiparesis; moderate quadriparesis; or monoplegia. 5. Quadraplegia V. Unknown Cerebellar Functions 0. Normal 1. Abnormal signs without disability 2. Mild ataxia 3. Moderate truncal or limb ataxia 4. Severe ataxia, all limbs 5. Unable to perform coordinated movements due to ataxia. V. Unknown X. is used throughout after each number when weakness (grade 3 or more on pyramidal) interferes with testing. Brain Stem Functions 0. Normal 1. Signs only 2. Moderate nystagmus, or other mild disability 3. Severe nystagmus, marked extraocular weakness, or moderate disability of other cranial nerves. 4. Marked dysarthria or other marked disability 5. Inability to swallow or speak. V. Unknown Sensory Functions 0. Normal 1. Vibration or figure-writing decrease only, in one or two limbs. 2. Mild decrease in touch or pain or position sense, and/or moderate decrease in vibration in one or two limbs; or vibratory (c/s figure writing) decrease alone in three or four limbs. 3. Moderate decrease in touch or pain or position sense, and/or essentially lost vibration in one or two limbs; or mild decrease in all proprioceptive tests in three or four limbs. 4. Marked decrease in touch or pain or loss of proprioception, alone or combined, in one or two limbs; or moderate decrease in touch or pain and/or severe proprioceptive decrease in more than two limbs. 5. Loss (essentially) of sensation in one or two limbs; or moderate decrease in touch or pain and/or loss of proprioception for most of the body below the head. 6. Sensation essentially lost below the head. V. Unknown Bowel & Bladder Functions 0. Normal 1. Mild urinary hesitancy, urgency, or retention. 2. Moderate hesitancy, urgency, retention of bowels or bladder, or rare urinary incontinence. 3. Frequent urinary incontinence. 4. In need of almost constant Catherization. 5. Loss of bladder function. V. Unknown Visual Functions 0. Normal 1. Scotoma with visual acuity (corrected) of 20/30 to 20/59. 3. Worse eye with large scotoma, or moderate decrease in fields, but with maximal visual acuity (corrected) of 20/60 to 20/99. 4. Worse eye with marked decrease in fields and maximal visual acuity (corrected) of 20/100 to20/200; grade 3 plus maximal acuity of better eye of 20/60 or less. 5. Worse eye with maximal visual acuity (corrected) less than 20/200; grade 4 plus maximal acuity of better eye of 20/60 or less. 6. Grade 5 plus maximal visual acuity of better eye of 20/60 or less. V. Unknown X. is added to grade 0 to 6 for presence of temporal pallor. Cerebral Functions 0. Normal. 1. Mood alteration only (Does not affect DSS score) 2. Mild decrease in mentation. 3. Moderate decrease in mentation. 4. Marked decrease in mentation (chronic brain syndrome -moderate) 5. Dementia or chronic brain syndrome - sever or incompetent. V. Unknown Other Functions. 0. None. 1. Any neurologic findings attributed to MS (specify). V. Unknown. ----------------------- One supplemental comment. As a scientist and an MSer I can tell you that I am acutely aware of the fact that there are a number of things which "fall through the cracks" in even this new and improved system. If you are an MSer, you are already aware of this. To you, I recommend that you might keep track of you own condition. This is a standard way that a neurologist might look at you so you at least know what he's not looking at. BTW as a follow up to Tzip's comment, can a file server be designated for this kind of stuff? I really feel quilty about clogging up the List with these things. -Rick From alt.support.mult-sclerosis Thu Oct 14 17:49:46 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!news.moneng.mei.com!howland.reston.ans.net!paladin.american.edu!auvm!TECHNION.TECHNION.AC.IL!CCANACW Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:CCANACW@TECHNION.TECHNION.AC.IL> Message-ID: Date: Thu, 14 Oct 1993 11:16:05 IST Sender: Multiple Sclerosis Discussion/Support From: Chanoch Weil Organization: Technion - Israel Institute of Technology, Computer Centre Subject: Retrieving files from LISTSERV archives, Gerald Gold's inquiry In-Reply-To: Message of Wed, 13 Oct 1993 15:17:43 EDT from Lines: 154 Status: O Hi, Gerald Gold inquired about retrieving files from MSLIST-L archives. Files are archived with LISTSEV@TECHNION.TECHNION.AC.IL I append instructions on how to retrieve files. --------------------------------------------------------- How to Use the ListServ Database Function by Jean Veronis (originally published as Humanist 4.844, Thursday, 20 Dec 1990) Edited by Willard McCarty for distribution on Arachnet Messages processed by ListServ are archived in notebooks. You can retrieve them by sending a GET command to ListServ at the node of the discussion group, e.g. to ListServ@BrownVM for Humanist. These notebooks are, however, often very large files and so require considerable time to get. Keeping at least a year's worth of them on your hard disk, for each group to which you belong, is a good idea, but few of us have the storage space. ListServ provides database facilities that enable you to access archived information in a less demanding way. Instead of getting the whole archive, you retrieve only the subject lines. If, for example, you want to know all the topics discussed on Humanist during December 1990, send to ListServ@BrownVM a message with the following lines: //SEARCH JOB ECHO=NO DATABASE SEARCH DD=RULES //RULES DD * SEARCH * IN humanist SINCE 01-DEC-90 INDEX (You can, of course, replace "01-DEC-90" by any other date in the same format, and you can replace "humanist" with the name of any active ListServ group.) From the above request, you will receive a file that looks like this: > SEARCH * IN humanist SINCE 01-DEC-90 --> Database HUMANIST, 55 hits. > INDEX Item # Date Time Recs Subject ------ ---- ---- ---- ------- 002600 90/12/02 22:14 68 4.0782 Renaissance Meeting in Toronto (1/56) 002601 90/12/02 22:18 91 4.0783 Grad Prog in Humanities Computing (1/25) 002602 90/12/02 22:20 103 4.0784 Classics Review (e-)Journal (1/91) 002603 90/12/02 22:25 120 4.0785 Conf: Machine Translation (1/108) 002604 90/12/02 22:38 192 4.0786 Confs: NL & Ontology; Sentence Proc 002605 90/12/02 22:58 46 4.0787 Jobs: Computational Linguistics (1/35) 002606 90/12/02 23:19 136 4.0788 Qs: French SW; French & Spanish CAI 002607 90/12/02 23:21 24 4.0789 Etext Q: Oral History, World War II ....... Searches can also be restricted to messages containing specified words. Suppose, for example, you want to retrieve all messages on Humanist that refer to SGML or the TEI (if you don't know what these acronyms refer to, never mind). To get these messages from Humanist, send the following file to ListServ@BrownVM: //SEARCH JOB ECHO=NO DATABASE SEARCH DD=RULES //RULES DD * SEARCH (SGML or TEI) IN humanist SINCE 01-JAN-90 INDEX (You can of course replace "SGML" and "TEI" with other keywords; you can use AND" instead of OR, or more complex AND/OR combinations.) From the above request, you will get a file that looks like this: > SEARCH (SGML or TEI) IN humanist SINCE 01-JAN-90 --> Database HUMANIST, 117 hits. > INDEX Item # Date Time Recs Subject ------ ---- ---- ---- ------- 001343 90/01/01 18:54 140 3.885 Poetics Today (141) 001370 90/01/08 20:28 179 3.912 WP/NB; NotaBene's Ibid (180) 001386 90/01/14 22:31 206 3.928 discussion groups (207) 001427 90/01/29 19:47 73 3.969 German poetry? samhell? SGML? (74) 001431 90/01/29 19:53 192 3.973 call for software reviewers (192) 001433 90/01/30 20:34 88 3.975 Sam Hill (89) 001460 90/02/05 20:43 104 3.1002 SGML; hanzi; pingpong; bib managers 001492 90/02/12 21:34 94 3.1034 audio input; Mac troubles (95) ....... You may want to restrict the search for keywords to the subject line (in the previous example, ListServ was searching for "SGML" or "TEI" in the whole message). In that case, send the following: //SEARCH JOB ECHO=NO DATABASE SEARCH DD=RULES //RULES DD * SEARCH * IN humanist - WHERE SUBJECT CONTAINS (SGML or TEI) - SINCE 01-DEC-90 INDEX Here is the file you'll get: > SEARCH * IN humanist - > WHERE SUBJECT CONTAINS (SGML or TEI) - > SINCE 01-JAN-90 --> Database HUMANIST, 26 hits. > INDEX Item # Date Time Recs Subject ------ ---- ---- ---- ------- 001427 90/01/29 19:47 73 3.969 German poetry? samhell? SGML? (74) 001460 90/02/05 20:43 104 3.1002 SGML; hanzi; pingpong; bib managers 001499 90/02/13 20:35 84 3.1041 decline of noisy reading? SGML 001508 90/02/14 20:50 153 3.1050 SGML and hypertext (154) 001514 90/02/15 19:56 195 3.1056 e-crit edns; bib of SGML/hypertext 001518 90/02/15 20:15 161 3.1060 book; resource person; talk on SGML 001526 90/02/16 22:48 125 3.1068 SGML and hypertext, cont. (126) 001543 90/02/22 21:10 90 3.1086 Chi's no Mega; SGML and hypertext (90) ....... If you want some of the documents sent to you, specify PRINT instead of INDEX, along with the item numbers. Suppose, for example, that you want the two documents on SGML and hypertext listed above; send the following to ListServ@BrownVM: //SEARCH JOB ECHO=NO DATABASE SEARCH DD=RULES //RULES DD * SEARCH * IN humanist - WHERE SUBJECT CONTAINS SGML or TEI - SINCE 01-DEC-90 PRINT 1508 1526 From this request you will receive a file containing the documents. The database function is capable of much more. If you want to know the full range of its capabilities, send to ListServ the following message: INFO DATABASE A reminder: these commands should always be sent to ListServ at the node where the group resides (except for the INFO DATABASE command, which may be submitted to any node where ListServ resides), not to the userid of the group itself. *****END***** From alt.support.mult-sclerosis Sun Oct 17 12:42:56 1993 Path: klaava!hydra.Helsinki.FI!news.funet.fi!sunic!pipex!howland.reston.ans.net!newsserver.jvnc.net!netnews.upenn.edu!achun From: achun@netnews.upenn.edu (Alex Chun) Newsgroups: alt.support.mult-sclerosis Subject: Re: ref. for betaseron articles, please Message-ID: <155237@netnews.upenn.edu> Date: 17 Oct 93 01:03:33 GMT References: <199310150830.AA03983@caneva> Sender: news@netnews.upenn.edu Lines: 17 Nntp-Posting-Host: mail.sas.upenn.edu X-Newsreader: TIN [version 1.2 PL2] Status: O Susan E. Struthers (susan@IRST.IT) wrote: : I am new to the net (end Sept.) and would like to read the betaseron : research articles... : Having the reference will help greatly.... "Interferon beta-1b is effective in relapsing-remitting multiple sclerosis." NEUROLOGY 1993;43 (Apr.):655-661 See also pages 641 and 662 Good luck, Susan. -Alex -- Alex T. Chun achun@mail.sas.upenn.edu From alt.support.mult-sclerosis Mon Oct 18 17:39:49 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 0462523 X-Genie-From: R.KOREJWO Message-ID: <9310180430.AA06643@relay2.geis.com> Date: Mon, 18 Oct 1993 05:24:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: MS Therapies Lines: 66 Status: RO There seems to be a level of confusion, both amongst MSers and their doctors, about the treatment of choice for an exacerbation. To be fair one has to realize that therapies frequently are dictated by where the doctor went to school or did his residency. Although there are relatively frequent seminars on MS, they are not universally attended and their impact is frequently limited to the those who attended. The medical Journals are a good source but I frequently encounter doctors who do not have the time to plow through all these and keep a clear running image of efficacy for each disease he treats. Customary practice for MS tends to take on a local flavor much like it does in other diseases. I think this is one of the primary reasons that MSers need to become knowledgeable about MS therapies. The members of the Therapeutic Claims Committee, an international committee of nine well known neurologist, was recently asked what they would prescribe for a major acute exacerbation of MS in a exacerbating/remitting MSer. The choices were: High dose IV methyleprednisolone ACTH Oral prednisone Dexamethisone or betamethasone Other There was near unanimity for pulse methyleprednisolone (Solumedrol ) with durations of 3-5 days. Only one member of the Committee gave an alternate which was High dose IV methyleprednisolone or decadron. Note that none referred to ACTH which was the treatment of choice as recently as 10 years ago. In the case of a CP patient the treatment choices where: High dose IV methyleprednisolone Oral prednisone Azathioprine Cyclosporine Cyclophosphamide Cyclophosphamide and *steroids and plasma exchange Methotrexate Copolymer I Levamisole No drug treatment Refer to a drug trial Other Three members opted for high dose IV methyleprednisolone and would use azathioprine on a continuing basis after that. Two members would give Cyclophosphamide, two members would use no drug treatment but prescribe rehabilitation. The final two members would refer the patient to a drug trial. This is the medical equivalent of "throw up your hands." What was very interesting was that no members opted for copolymer I, cyclosporine, plasma exchange, Methotrexate or levamisole. Clearly there is not a single treatment of choice in this case. Just like MS itself, treatments are often based on the patients response to prior medications and a lot of factors that the doctor has experienced. What would you expect? Since many MSers find themselves far from medical centers, it is possible that their doctor may not have the time to stay current on what is happening in just MS. An informed MSer is probably their own best source of information. The variations you see are products of the variability of MS and the variability of knowledge. With ER, where therapies are generally reliable, the consensus is clear. With CP there is no apparent consensus. -Rick From alt.support.mult-sclerosis Fri Oct 22 12:57:14 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 7421376 X-Genie-From: R.KOREJWO Message-ID: <9310220135.AA28204@relay2.geis.com> Date: Fri, 22 Oct 1993 01:22:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: MS/Hormones Lines: 112 Status: O As regards the discussion of women, hormones and MS- There is, of course, a direct communications between the neuro and the hormonal systems via the neuroendocrine communications path. Typically this could be represented by some of the axons of the hypothalumus which extend into the posterior pituitary. in the opposite direction we have an example like the pituitary hormone ACTH having a direct effect in the adrenal cortex to produce steroids. A few studies seem relevant: 93059046 Smith R Studd JW A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. J R Soc Med 1992 Oct;85(10):612-3 A questionnaire enquiring about changes in severity of symptoms of multiple sclerosis with the menstrual cycle, menopause and use of hormone replacement therapy was answered retrospectively by 11 premenopausal and 19 postmenopausal women. Eighty-two per cent of menopausal women reported an increase in severity premenstrually. Of the postmenopausal women 54% reported a worsening of symptoms with the menopause, and 75% of those who had tried hormone replacement therapy reported an improvement. The results of this pilot study indicate the need for further research to clarify the effects of the menopause and hormone replacement therapy upon multiple sclerosis. Institutional address: King's College Hospital Denmark Hill London. 90039097 Grinsted L Heltberg A Hagen C Djursing H Serum sex hormone and gonadotropin concentrations in premenopausal women with multiple sclerosis. J Intern Med 1989 Oct;226(4):241-4 Dysfunctions within the hypothalamic-pituitary-gonadal axis occur frequently among women with multiple sclerosis (MS) and may induce menstrual disturba8ces and subsequent infertility. We have measured serum concentrations of prolactin. gonadotropins and sex hormone binding globulin (SHBG) as well as free and bound oestrogen and androgen levels in 14 women of fertile age with MS. These women all displayed regular cycles without having experienced fertility problems. As controls 14 normal women with regular periods and ideal body weight of 91% (range 80-101) were included. Serum from both groups was sampled during the early follicular phase. The MS-patients had significantly (P less than 0.05) higher concentrations of prolactin, LH, FSH, total and free testosterone (P less than 0.01) and a significantly lower serum concentration of oestrone sulphate (P less than 0.01). The abnormal hormone concentrations were not related to clinical status of the disease. We propose that the increased androgen levels are of ovarian origin as adrenal androgens were normal. The reason for the slight increase of prolactin and the marked increase of gonadotropins in women with MS is speculative. As oestradiol levels, however, were within normal range, we assume that a peripheral resistance to gonadotropins combined with an abnormal central regulation causes the increased pituitary secretion. Institutional address: Department of Obstetrics and Gynaecology University Hospital of Copenhagen Denmark. 90252511 Akimov GA Golovkin VI Khavinson VKh [Homeostatic effect of thymalin in multiple sclerosis] Zh Nevropatol Psikhiatr 1990;90(2):16-9 (Published in Russian) The paper is concerned with interaction of the immune, endocrine and nervous systems in patients with multiple sclerosis. Dexamethasone and vasopressine tests were made. Lymphocyte sensitivity to hydrocortisone and thymalin, the main protein of myelin, was detected. It is advisable that arginine-vasopressine combined with thymalin be used for correction of homeostatic abnormalities and secondary disease prophylaxis. Not directly a gender-specific paper: 93293432 Sandyk R Awerbuch GI Nocturnal plasma melatonin and alpha-melanocyte stimulating hormone levels during exacerbation of multiple sclerosis. Int J Neurosci 1992 Nov-Dec;67(1-4):173-86 The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS). To investigate this hypothesis further, we studied nocturnal plasma melatonin levels and the presence or absence of pineal calcification (PC) on CT scan in a cohort of 25 patients (5 men, 20 women; mean age: 41.1 years; SD = 11.1; range: 27-72) who were admitted to a hospital Neurology service for exacerbation of symptoms. Plasma alpha- melanocyte stimulating hormone (alpha-MSH) estimations were included in the study since there is evidence for a feedback inhibition between alpha-MSH and melatonin secretion. Abnormal melatonin levels were found in 13 patients (52.0%), 11 of whom had nocturnal levels which were below the daytime values (i.e.,< 25 pg/ml). Although melatonin levels were unrelated to the patient's age and sex, there was a positive correlation with age of onset of symptoms (p < .0001) and an inverse correlation with the duration of illness (p < .05). PC was noted in 24 of 25 patients (96%) underscoring the pathogenetic relationship between MS and the pineal gland. Alpha-MSH levels were undetectable in 15 patients (60.0%), low in two patients (8.0%), normal in seven patients (28.0%), and elevated in one patient (4.0%). Collectively, abnormal alpha-MSH levels were found in over 70% of patients. These findings support the hypothesis that MS may be associated with pineal failure and suggest, furthermore, that alterations in the secretion of alpha- MSH also occur during exacerbation of symptoms. The relevance of these findings to the pathogenesis of MS are discussed. Institutional address: NeuroCommunication Research Laboratory Danburg CT 06811. From alt.support.mult-sclerosis Thu Oct 28 14:49:59 1993 Path: klaava!news.funet.fi!sunic!pipex!uunet!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 5898719 X-Genie-From: R.KOREJWO Message-ID: <9310272323.AA06821@relay2.geis.com> Date: Tue, 26 Oct 1993 22:58:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Affective disorders/MS Lines: 172 Status: O -=Terry Gritton=- Thank you for the information. The incidence of mis-diagnosis of MS has declined substantially and, while it still occurs, it is far less than it was just a few years ago. One recent reference implies the Cbl deficiency is an effect of high dose methylprednisolone-succinate (MP) and not a causal factor and at least two other recent papers leave this to speculation. There is, additionally, some evidence to suggest that low Cbl levels are an effect of MS. Regardless of it's origin, I can see were the aetiology of low Cbl levels is a candidate for further research. No evidence was presented, to my knowledge, which linked Cbl levels to EDSS ratings. This would be a factor which would suggest a stonger correlation. It is also noteworthy that this does not play any role in the currently proposed aetiologies of MS nor do I find evidence to support this. It is even unclear to me how this would, in fact, prove to be a causal factor under these constraints. Perhaps the prevailing MS aetiological thesis is in error? Do you suggest a causal effect on MS from these papers? If not, it is more likely anecdotal - much like the fact that a certain number of MS patients have brown hair. I have included abstracts from some other recent papers and the EH Reynolds paper you did reference to save some readers the library time. 93316108 Frequin ST Wevers RA Braam M Barkhof F Hommes OR Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone. J Neurol 1993 May;240(5):305-8 Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59, P = 0.0084) between serum vitamin B12 and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of vitamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B12 and folate were below the reference medians. We hypothesize that low or reduced vitamin B12/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low vitamin B12/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B12 and folate metabolism in patients with MS. Institutional address: Department of Neurology University Hospital Nijmegen The Netherlands. 92281466 Reynolds EH Bottiglieri T Laundy M Crellin RF Kirker SG Vitamin B12 metabolism in multiple sclerosis. Arch Neurol 1992 Jun;49(6):649-52 We have previously described 10 patients with multiple sclerosis (MS) and unusual vitamin B12 deficiency. We have therefore studied vitamin B12 metabolism in 29 consecutive cases of MS, 17 neurological controls, and 31 normal subjects. Patients with MS had significantly lower serum vitamin B12 levels and significantly higher unsaturated R- binder capacities than neurological and normal controls, and they were significantly macrocytic compared with normal controls. Nine patients with MS had serum vitamin B12 levels less than 147 pmol/L and, in the absence of anemia, this subgroup was significantly macrocytic and had significantly lower red blood cell folate levels than neurological and normal controls. Nine patients with MS had raised plasma unsaturated R-binder capacities, including three patients with very high values. There is a significant association between MS and disturbed vitamin B12 metabolism. Vitamin B12 deficiency should always be looked for in patients with MS. The cause of the vitamin B12 disorder and the nature of the overlap with MS deserve further investigation. Coexisting vitamin B12 deficiency might aggravate MS or impair recovery from MS. Institutional address: Department of Neurology King's College Hospital London England. 91378790 Reynolds EH Linnell JC Faludy JE Multiple sclerosis associated with vitamin B12 deficiency. Arch Neurol 1991 Aug;48(8):808-11 We describe 10 patients with a previously unreported, to our knowledge, association of multiple sclerosis and unusual vitamin B12 deficiency. The clinical features and the age at presentation were typical of multiple sclerosis, with eight cases occurring before age 40 years, which is a rare age for vitamin B12 deficiency. Nine patients had hematologic abnormalities, but only two were anemic. All six patients examined had low erythrocyte cobalamin levels. Only two patients had pernicious anemia; in the remaining patients the vitamin B12 deficiency was unexplained. A vitamin B12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder. Institutional address: Department of Neurology King's College Hospital London England. 90327993 Crellin RF Bottiglieri T Reynolds EH Multiple sclerosis and macrocytosis [see comments] Acta Neurol Scand 1990 May;81(5):388-91 Twenty-seven patients with multiple sclerosis had mild but significant macrocytosis when compared with an individually matched neurological control group and the normal laboratory reference range. The cause of the macrocytosis is unknown, but our recent clinical observations implicate a possible disturbance in vitamin B12 metabolism, binding or transport. Institutional address: Department of Neurology King's College Hospital London England. 91132228 Nijst TQ Wevers RA Schoonderwaldt HC Hommes OR de Haan AF Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia. J Neurol Neurosurg Psychiatry 1990 Nov;53(11):951-4 Vitamin B12 and folate concentrations were measured in serum and cerebrospinal fluid (CSF) in 293 neurological patients. Serum and CSF vitamin B12 concentrations showed a positive correlation. In individual patients CSF B12 concentrations varied considerably for a given serum concentration. The median serum vitamin B12 concentration of the Alzheimer's type dementia group was significantly lower compared with that of a control group. Lower median CSF vitamin B12 concentrations were found in groups of patients with multiple sclerosis and Alzheimer's type dementia. Five patients with heterogeneous clinical pictures had unexplained low serum and CSF B12 concentrations without macrocytosis. Two patients had very high serum B12 and low-normal CSF concentrations which could be explained by a blood-brain barrier transport defect. Serum and CSF folate concentrations did not show significant differences between the various groups. Institutional address: Institute of Neurology University Hospital Nijmegen The Netherlands. ------------------------------------------------ 93055348 Reynolds EH Multiple sclerosis and vitamin B12 metabolism. J Neuroimmunol 1992 Oct;40(2-3):225-30 Multiple sclerosis (MS) is occasionally associated with vitamin B12 deficiency. Recent studies have shown an increased risk of macrocytosis, low serum and/or CSF vitamin B12 levels, raised plasma homocysteine and raised unsaturated R-binder capacity in MS. The aetiology of the vitamin B12 deficiency in MS is often uncertain and a disorder of vitamin B12 binding or transport is suspected. The nature of the association of vitamin B12 deficiency and MS is unclear but is likely to be more than coincidental. There is a remarkable similarity in the epidemiology of MS and pernicious anaemia. Vitamin B12 deficiency should always be looked for in MS. The deficiency may aggravate MS or impair recovery. There is evidence that vitamin B12 is important for myelin synthesis and integrity but further basic studies are required. Institutional address: Maudsley Hospital London UK. ------------------------------------------------------------ From alt.support.mult-sclerosis Thu Oct 28 15:00:05 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!cs.utexas.edu!math.ohio-state.edu!magnus.acs.ohio-state.edu!usenet.ins.cwru.edu!agate!darkstar.UCSC.EDU!usenet From: Terry Gritton Newsgroups: alt.support.mult-sclerosis Subject: Re: Affective disorders/MS/B12 - tests/classification problems Date: 27 Oct 1993 19:42:52 GMT Organization: The great outdoors Lines: 187 Distribution: world Message-ID: <2amivs$k2r@darkstar.UCSC.EDU> References: <9310252137.AA21035@eco.twg.com> NNTP-Posting-Host: snow.cse.ucsc.edu X-UserAgent: Nuntius v1.1.2 X-XXDate: Wed, 27 Oct 93 12:45:05 GMT Status: RO >From: Sejal Ruparelia >I was diagnosed 2 years ago, My ancestory is Indian. My uncle who >is a MD refuses to >believe that I have MS. He said that I could >have the same results if I had a defiency >of Vitamin B12. Myy neurologist at the time said that he feels unlikely that I am >deficient of Vitamin B12. >.... >I would be very interested in finding out further about the Vitamin B12 issue. I was >wondering if people who were diagnosed were actually tested for the defiency? Vitamin B12 (cobalamin, Cbl) A. Detection of defects in Cbl/Cbl-binders/Cbl-metabolic mechanisms. Given the present understanding of Cbl/Cbl-binders/Cbl-metabolism !deficiencies! are detected (tested) by 1) measuring Cbl absorption, 2) Cbl affects on blood cell cytology, 3) measuring Cbl concentration directly 4) Cbl affects on biochemical pathways. The classic Schilling test uses very small doses of ingested radioactive tracer Cbl (Co57) to determine uptake. One of the early tests for pernicious anemia. Blood cells are accessible and their cytological parameters are routinely measured in automated systems. Increased mean corpuscular volume (MCV) may be attributable to a Cbl deficiency. However this method sometimes fails even to detect a megaloblastic anemia [1,2] and may fail to indicate deficiencies in other cell lines. More detailed examination of nuclear morphology (neutrophil nuclear segmentation) by specialist hematologists may disclose subtle deficiencies but this involves a certain amount of subjective judgement. Cobalamin concentrations (serum, intracellular cytosolic, cerebrospinal fluid ) may be determined. Microbiological assays were used early on and are still used but they are labor intensive. Techniques that lend themselves to automation (RIA, etc.) are available from routine labs and are the tests most used today. These techniques have had technical problems [3,4] but they have been improved. Non-anemic patients with neurological manifestations are most at risk for misdiagnosis with these tests [5] and they miss errors of metabolism [6]. The preceding tests are primarily used to detect defects in the !distal! Cbl mechanisms - acquisition of Cbl from the environment to the blood. Tests of !proximal! dysfunctions - delivery to cells and intracellular mechanism - rely on measuring disturbances to known Cbl metabolic pathways or the concentration or function of Cbl-binders. Two commonly used tests at the biochemical pathway level are the methylmalonic acid test (MMA) [7] and the deoxy-uridine suppression test [8] (dU suppression). The dU test using bone marrow is invasive (but a newer method is less invasive [9], also lymphocytes may be used [10]) and the MMA test requires special instruments which makes them non-routine measures. However, some believe that the MMA test [11] or dU test [12] may be more inclusive, detecting subtle defects. B. The essential problem - the MS classification If one suspects that the existing classifications of MS and Cbl disorders are not optimal then one may hypothesize that multiple sclerosis may be either 1) a heterogeneous classification, some autoimmune, some subtle Cbl deficient with fundamentally different mechanisms. or 2) a homogeneous classification, common mechanism spanning autoimmunity and Cbl disfunction ( e.g. Cbl binder receptors effected), with a wide clinical spectrum. In the former instance more effort is needed to better utilize existing tests to differentiate a perhaps small but significant segment that would benefits from special Cbl therapies ( methyl-Cbl or OH-Cbl i.m. weekly). Many neurologic multiple sclerosis tests are not specific [13-24]. Tests sensitive to specific cell line deficiencies, as mentioned by Herbert [25] in the context of megaloblastic anemias, might better segment the MS population. If MS is a homogeneous classification with a wide clinical spectrum there still may be those at one end of the spectrum who would benefit from special Cbl therapy until a full understanding of a molecular etiology is achieved. Conclusion Some small subset of those patients diagnosed as MS may benefit from Cbl oriented approaches. Cbl is part of the folklore of MS, but have all those who might benefit been identified and treated. References Diagnostic tests 1. Dawson, DW(1979). Megaloblastic anemia with normal mean cell volume. Lancet 1:675. 2. Foster, DW(1980). Thirty-three year old Caucasian female with easy fatigueability. South Dakota J. Med. 33(9):5-12. 3. Cohen, KL(1980). Unreliability of RDI technique in B12 deficiency. J.A.M.A. 244(17):1942-5. 4. Norman, EJ(1986). Falsely high serum B12 levels [letter]. Am J. Clin. Pathol. 86(5):692. 5. Cooper, BA(1978). Evidence that some patients with pernicious anemia are not recognized by radio-dilution assay for cobalamin in man. N. Engl. J. Med. 299:816 6. Linnell, JC(1981). The value of radioisotopic assays for !serum B12! in the diagnosis of cobalamin deficiency disorders. Clin. Lab. Haematol. 3(2):99-106. 7. Norman, EJ(1982). Cobalamin (Vitamin B12) deficiency detection by urinary MMA quantitation. Blood 59:1128-31. 8. Wickramasinghe, SN(1974). Assessment of deoxyuridine suppression test in diagnosis of vitamin B12 or folate deficiency. Br. Med. J. 3:148. 9. Petty, AC(1986). New micro method for deoxyuridine suppression test. J. Clin. Pathol. 39(10):1155-6. 10. Das, KC(1978). The lymphocyte as a marker of past nutritional status: persistence of abnormal lymphocyte deoxyuridine suppression test and chromosomes in patients with past deficiency of folate and B12. Br. J. Haematol. 38:219-33. 11. Norman EJ(1983). High incidence of neurologic disease in covert B12 (cobalamin) deficiency: early detection of cobalamin deficiency through urinary methymalonic acid screening. Clin. Res. 31:686A abstract. 12. Carmel, R(1985). The deoxyuridine suppression test identifies subtle cobalamin deficiency in patients without typical megaloblastic anemia. J.A.M.A. 253(9):1284-7. MS neuro nonspecific 13. Butler, WM(1981). Lhermitte!s sign in B12 deficiency. J.A.M.A. 245(10):1059 14. Carmel, R(1988). Hereditary defect of cobalamin metabolism (cblG mutation) presentling as a neurologic disorder in adulthood. N.Engl. J. Med. 318(26):1738-41. 15. Crellin, RF(1990). Multiple sclerosis and macrocytosis. Acta Neurol. Scand. 81:388-91. 16. Gamstorp, I(1961). Denervation extraocular and skeletal muscles in pernicious anemia. Neurol. Minneap. 11:182-4. 17. Gautier-Smith, PC(1973). Lhermitte!s sign in subacute combined degeneration of the cord. J. Neurol. Neurosurg. Psychiat. 36:861-3 18. Jones, SJ(1987). Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels. J. Neurol. Sci. 82(1-3):55-65. 19. Lauer, K(1986). An evaluation of laboratory investigations in patients with multiple sclerosis. J. Chron. Dis. 39(10):767-74. 20. Karnaze, DS(1990). Neurological and evoked potential abnormalities in subtle cobalamin deficiency states, including deficiency without anemia and normal absorption of free cobalamin. Arch. Neurol. 47(9):1008-12. 21. Krumholz, A(1981). Evoked responses in vitamin B12 defiency. 22. Ransohoff, RM(1990). Vitamin B12 deficiency and multiple sclerosis. [letter] Lancet 335:1285-6. 23. Reynolds, EH(1987). Vitamin B12 deficiency, demyelination, and multiple sclerosis [letter]. Lancet 2(8564):920. 24. Troncoso, J(1979). Visual evoked responses in pernicious anemia. Arch. Neurol. 36:168-9. 25. Herbert, V(1985). Biology of disease: Megaloblastic anemia. Laboratory Investigation 52(1):3-19. ------------------------------------------------------------------ Terry N. Gritton "I think that it is much more interesting to live not knowing, than to have answers which might be wrong.I can live with doubt, and uncertainty, and not knowing.I have Research interests: approximate answers, and possible beliefs signal glycoproteins and different degrees of certainty about logic programming different things, but I'm not absolutely sure of anything." Richard Feynman ------------------------------------------------------------------ From alt.support.mult-sclerosis Fri Oct 29 11:28:19 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!olivea!koriel!newscast.West.Sun.COM!seven-up.East.Sun.COM!news2me.EBay.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: Re: Betaseron Date: 28 Oct 1993 17:29:26 GMT Organization: Sun Lines: 58 Message-ID: References: <9310261543.AA09209@leo.austin.nam.slb.com> NNTP-Posting-Host: chrysos Status: O In article <9310261543.AA09209@leo.austin.nam.slb.com> "Carol Prochnow, 512-331-3438" writes: ... >Hi. I just received my packet from Berlex about Betaseron. I am trying >to get as much information as I can on the drug to help in making >a decision about whether or not to take it. I have the April Neurology >article on the study, but it's really not enough!!! Does anyone >out there have any more information about it? I am interested in >more anecdotal information, such as about the side effects. ... this is from a booklet i received from berlex, contained in a packet of info, including a video tape on how to reconstitute and inject beta seron (interferon beta-1b). Common side effects. Betaseron therapy is considered to be generally well tolerated. As with any prescription medication, side effects related to therapy can occur. If you have specific questions about side effects, ask your healthcare professional. Betaseron should not be used during pregnancy or if you are trying to become pregnant. If you wish to become pregnant while taking Betaseron, discuss the matter with your doctor. Women of childbearing potential should take appropriate birth control measures. If you do become pregnant, you should discontinue treatment and contact your doctor immediately. Injection site reactions are common. They include redness, pain and swelling, and discoloration. To minimize the chances for a reaction, ask your doctor to suggest a series of injection sites so that you will not have to use the same one repeatedly. Do not make an injection into skin that is tender, red or hard. Flu-like symptoms are also common. They include fever, chills, sweating, fatigue, and muscle aches. Taking Betaseron at night may help lessen the impact of flu-like symptoms. Laboratory abnormalities, including SGPT (a diagnostic test to determine enzyme activiy in the liver) and SGOT (also a diagnostic test of enzyme activity), neutropenia (a decrease in the number of white blood cells) and leukopenia (another form of white blood cell reduction), have been observed. Other side effects associated with Betaseron treatment are palpitations, myalgia (muscle pain), dyspnea (difficulty in breathing), and menstrual disorders. Depression, including suicide attempts, has been reported by patients. Common symptoms of depression are anxiety, irritability, low self-esteem, guilt, poor concentration, indecisiveness, confusion, and eating and sleep disturbances. If you experience any of these symptoms, contact your doctor promptly. Consult with your physician if you have any problems, whether or not you think they may be related to Betaseron therapy. Gale Snow From alt.support.mult-sclerosis Fri Oct 29 11:34:54 1993 Path: klaava!news.funet.fi!sunic!mcsun!uknet!pipex!howland.reston.ans.net!agate!darkstar.UCSC.EDU!usenet From: Terry Gritton Newsgroups: alt.support.mult-sclerosis Subject: Re: MS/Classification/B12 binders Date: 28 Oct 1993 21:22:20 GMT Organization: The great outdoors Lines: 113 Distribution: world Message-ID: <2apd6c$6um@darkstar.UCSC.EDU> References: <9310272323.AA06821@relay2.geis.com> NNTP-Posting-Host: snow.cse.ucsc.edu X-UserAgent: Nuntius v1.1.2 X-XXDate: Thu, 28 Oct 93 14:24:28 GMT Status: O >Affective disorders/MS >From: Richard Korejwo >Date: Tue, 26 Oct 1993 22:58:00 BST >Subject: Affective disorders/MS >The incidence of mis-diagnosis of MS has declined substantially and, >while it still occurs, it is far less than it was just a few years ago. >One recent reference implies the Cbl deficiency is an effect of high >dose methylprednisolone-succinate (MP) and not a causal factor and at >least two other recent papers leave this to speculation. There is, >additionally, some evidence to suggest that low Cbl levels are an >effect of MS. Regardless of it's origin, I can see were the aetiology >of low Cbl levels is a candidate for further research. No evidence was >presented, to my knowledge, which linked Cbl levels to EDSS ratings. >This would be a factor which would suggest a stonger correlation. It >is also noteworthy that this does not play any role in the currently >proposed aetiologies of MS nor do I find evidence to support this. It >is even unclear to me how this would, in fact, prove to be a causal >factor under these constraints. Perhaps the prevailing MS aetiological >thesis is in error? Do you suggest a causal effect on MS from these >papers? If not, it is more likely anecdotal - much like the fact that >a certain number of MS patients have brown hair. -= Richard Korejwo =- Thank you for your reply My response Testing/classification In another posting I touched on testing and classification. To reiterate and simplify. 1. Tests are not yet available which will detect and classify dysfunctions of the extracellular glycoproteins that bind cobalamins (B12) and folates. 2. Until there is a better model of the function of these so called !binders! it will be difficult to built tests to classify disorders related to the folate/cobalamin binders. 3. Even within the narrow classification of megaloblastic anemias, rigid interpretation of what a test means has slowed discovery of new patients with novel dysfunctions. 4. The neuropsychiatric aspects of cobalamin and folate disfunction are interesting when compared to multiple sclerosis. 5. Some patients with neuropsychiatric complaints ( not classified, pernicious anemia classified, MS classified ) have substantial response to i. m. methyl or hydroxyl cobalamin and others are benefited in less dramatic ways. I suppose one could view the former as !mis-diagnosed! and the latter as due to placebo effect. Alternatively, perhaps the classification/testing paradigm does not contribute to the discovery of new dysfunctions or the reinterpretation of old classifications. Adrenocortical steroids Since steroid have been used by so many with MS I have collected references to their effects in cobalamin classified diseases [1-11].One might assume that their effects in these cases was due to mediation of autoimmunity but one of the reports indicates otherwise [1]. Abstracts Reading abstracts is a helpful first screen but my experience is that there is useful information buried in the papers themselves. I will be referencing the paper regarding prednisolone and cobalamin/folate levels in the near future. References 1. Ardeman (1965). Steroids and pernicious anemia. N. Engl. J. Med. 273:1352-8. 2. Arrowsmith, WR(1953). Production of megaloblastic marrow by administration of cortisone in aplastic anemia, with subsequent response to B12. A relationship not previously described. J.Lab. Clin. Med. 42:778. 3. Doe, RP(1982). B12 deficiency: a heretofore undescribed control mechanism for plasma corticosteroid-binding globulin concentration in man. J. Clin. Endocrinol. Metab. 54(2):381-5. 4. Doig, A(1957). Response of megaloblastic anemia to prednisolone. Lancet 2:966. 5. Frost, JW(1958). Observations on B12 absorption in primary pernicious anemia during administration of adrenocortico steroids. N.Engl. J. Med. 258:1096. 6. Granat, M(1983). Effect of dexamethasone on serum transcobalamin II concentration in women undergoing pelvic surgery. Eur. J. Clin. Pharmacol. 25(5):621-4. 7. Kristensen, HPO(1960). The mechanism of prednisone effect upon B12 absorption in pernicious anemia. Acta Med. Scand. 168:457-9. 8. Krintensen, HPO(1960). Effect of prednisone on B12 absorption in pernicious anemia. Acta Med. Scand. 166:249-54. 9. Jeffries, GH(1966). Effect of prednisolone in pernicious anemia. J. Clin. Invest. 45:803-12. 10. Strickland, RG(1973). Response to prednisone in atrophic gastritis: effect on B12 absorption. Gut 14:13-9. 11. Taylor KB(1976). Immune aspects of pernicious anemia. Clinic in Haematology 5:502. ------------------------------------------------------------------ Terry N. Gritton "I think that it is much more interesting to live not knowing, than to have answers which might be wrong.I can live with doubt, and uncertainty, and not knowing.I have Research interests: approximate answers, and possible beliefs signal glycoproteins and different degrees of certainty about logic programming different things, but I'm not absolutely sure of anything." Richard Feynman ------------------------------------------------------------------ From alt.support.mult-sclerosis Fri Oct 29 11:36:31 1993 Path: klaava!news.funet.fi!sunic!pipex!uunet!cs.utexas.edu!swrinde!emory!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 1176192 X-Genie-From: R.KOREJWO Message-ID: <9310290010.AA15035@relay2.geis.com> Date: Thu, 28 Oct 1993 22:38:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Multiple TCRs Lines: 20 Status: O Anyone interested- Just so we don't get the idea that we know what we're doing, we get a surprise now and then. Over the last two years then has been more than a little interest in the discussion of T-cell receptors.(TCRs) There have been some trials and some mixed results. It's a little hard to figure out why things didn't come out the way they were supposed to. To add a little confusion and present a new twist to the saga, a recent paper by Elisabetta Padovan et al, working out of the Basel Institute for Immunology, has presented strong evidence that there is a substantial probability that as many as 30% of T-cells may not express for just one antigen. The "one cell/one receptor concept" has been a dominate part of our thinking for some time. Thankfully the multiplicity seems to be restricted to the alpha arm. It is a little early to speculate how such a difference will benefit or hamper us in the effort to control autoimmune diseases. Once some of the rules which govern this are sorted out, it may account for the rather mixed performance of antigen feeding and peptide injection studies. Somebody a lot smarter than us, did the design work. -Rick From alt.support.mult-sclerosis Sat Oct 30 13:32:09 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 5088428 X-Genie-From: R.KOREJWO Message-ID: <9310300217.AA22553@relay2.geis.com> Date: Sat, 30 Oct 1993 01:04:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Cop-1/RLS Lines: 182 Status: O I'm still trying to figure out why there is this sudden flair in COP interest. It certainly is not new. Arnon did her work on this years ago and Bornstein has been working on it from the early '80's. I had the pleasure of being briefed by Dr. Arnon when she was in the states. She addressed a local meeting of neurologist. Since I hold no one as God, I openly challenged her stats. The first year figures were mildly in favor of COP but the second year were clearly in favor of the placebo. The placebo was cheaper too. I saw some COP references but I don't think the following were posted. I apologize if these are dupes. 91187214 Bornstein MB Miller A Slagle S Weitzman M Drexler E Keilson M Spada V Weiss W Appel S Rolak L et al A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology 1991 Apr;41(4):533-9 We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant. Institutional address: Saul R. Korey Department of Neurology Albert Einstein College of Medicine Bronx NY 10461. 91190785 Grgacic E Bernard CC Cell-mediated immune response to copolymer I in multiple sclerosis measured by the macrophage procoagulant activity assay. Int Immunol 1990;2(8):713-8 The macrophage/monocyte procoagulant activity (MPCA) assay, a sensitive and specific in vitro test for cell-mediated immunity, has been used to ascertain the reactivity of MS peripheral blood mononuclear cells (PBM) to copolymer I (Copl), a synthetic peptide analogue of myelin basic protein (MBP) currently being tested as a possible therapeutic agent in multiple sclerosis (MS). Because the suppressive effect of Copl is believed to lie in its possible cross- reactivity with MBP, the reactivity of PBM of MS patients to MBP was also tested. MS patients either at the stable phase of the relapsing/remitting form or with chronic progressive disease were investigated and compared with patients with other diseases and with healthy subjects. The reactivity to Copl was significantly increased in patients with chronic progressive disease but not in stable MS patients or in control subjects. No difference in reactivity to MBP between MS patients and healthy subjects was found regardless of disease status. However, in the control group comprising patients with other diseases, MBP reactivity was significantly elevated. In chronic progressive MS patients, a relationship was found between the response to Copl and that to MBP, supporting the possibility of an immunological cross- reactivity between these two antigens. There was no significant difference in reactivity to the non-specific stimulant, lipopolysaccharide, between the MS and control groups. Institutional address: Department of Psychology La Trobe University Bundoora Victoria Australia. 90129708 Arnon R Teitelbaum D Sela M Suppression of experimental allergic encephalomyelitis by COP1--relevance to multiple sclerosis. Isr J Med Sci 1989 Dec;25(12):686-9 The evidence in this presentation clearly indicates that in the case of the model disease EAE, desensitization procedures are effective in suppressing the symptoms of the disease and in providing protection against it. The antigens used in our studies are all synthetic materials immunologically relevant to the myelin encephalitogenic protein, but not encephalitogenic themselves. The most effective of these materials is a random basic copolymer of alanine, glutamic acid, lysine and tyrosine, denoted COP 1. The finding that the suppressive polymers show immunological cross- reactivity with the encephalitogenic protein provides a logical basis for the explanation of their suppressive activity in terms of an immunological desensitization mechanism. Our studies suggest that the effectiveness of COP 1 in preventing EAE results from the production of antigen- suppressor T cells, and/or from blocking MBP-specific effector T cells. The results of the clinical trial presented here show demonstrable improvement in the COP 1-treated patients as compared with the placebo subjects, particularly for those patients with less severe MS at the start of the treatment. Thus, although the evidence supporting the antigenic role of MBP in MS is not strong, COP 1, a synthetic polypeptide simulating some of the properties of MBP, appears to be effective in altering the course of MS and is of potential value as a modality for the treatment of this disease. Institutional address: Department of Chemical Immunology Weizmann Institute of Science Rehovot Israel. 90034439 Teitelbaum D Arnon R Sela M Abramsky O [Clinical trial of copolymer 1 in multiple sclerosis] Harefuah 1989 May 1;116(9):453-6 (Published in Hebrew) A synthetic copolymer of amino acids, copolymer 1 (Cop 1), proved to be very effective in suppressing experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). It is 1 of a series of synthetic amino acid copolymers which simulate the basic protein constituent of the myelin sheath and the autoantigen responsible for induction of EAE. It cannot induce EAE but it does suppress it in a variety of animals. The immunological cross-reaction between Cop 1 and the basic protein is the basis for this suppressive activity. In view of the resemblance between EAE and MS, clinical trials with Cop 1 in MS were started. The first preliminary clinical trial was at this hospital and involved 4 patients with severe MS. A double-blind, randomized placebo- controlled pilot trial was carried on for 2 years in 50 patients with the exacerbating-remitting form of MS but with a Kurtzke Disability Status Scale rating of no more than 6. There were statistically significant differences in the number of patients with exacerbations in the placebo group, 23, as compared to only 16 in the Cop 1-treated group. As to exacerbations per patient, the 2- year averages were 2.7 and 0.6, respectively. Side-effects of Cop 1 were minimal. These results suggest that Cop 1 may be beneficial when given early in the exacerbating-remitting form of MS. Further trials, necessary to establish its efficacy in MS, are being run at the Albert Einstein College of Medicine in NY. -------------------- A lot of this kind of information is weakened by a few unstated factors. First, we have probably cured EAE about 9 times but have yet to get close to MS. While this makes some rodents very happy, this is not a perfect model for MS. Lewis rats are a little better but the results are still mixed. Second, when evaluating exacerbating remitting MSers, you best have a lot of people in the trial and run, at least, for two years. I can take any small random group of ER patients and find "improvement" at some time during a a 2 year period by just playing with the times or population. You can claim statistical significance on the basis of a small group (<200-300) or a limited time (<2-3 years) but it is pretty unimpressive to people who work the numbers and know what to look for. (p=.03 on a P=103 is better but still, if that's the best evidence we have, we're in trouble.) Words like "...may, ...suggest,...no significant difference,...appears to be " do not lead me to a belief that the results are clear or strong even in the eyes of the investigators. Lemmon Co.(US) has resurrected COP-I under the orphan drug application. They claim to have a supply capability and will run 200 patients in a Phase III 20/mg IM daily protocol. I believe they have enough data to apply for a treatment IND. If anybody has anything on this, I would appreciate more information. What is the status? Trial centers? Who's principle? Sorry, I just don't have the time to get much further. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- Chanoch Weil "When the cast was taken off, I experienced severe "spasms", i.e night-time muscle pains ..." It's a little hard to guess from that. If the leg was immobilized in a bent position you had a lot of lengthening to get back to normal. Since you specified the "muscle" I assume you did not suffer from any joint pain. I'm not too sure how you broke a leg and didn't use a "cast" unless it was a minor break. If you never stopped to use a muscle group you would never have experienced pain in recovery. Re "nocturnal leg motions" - Lioresal (trade name Baclofen) is certainly a common muscle relaxant and not infrequently used for restless leg. The question is whether the symptom was generated by the muscle or the nervous system. I would suggest the latter. In this case, Lioresal would be successful in weakening muscles but provide little regulation of the cause. Some patients have found relief from serotonin modulators. You didn't indicate the dose rate of Baclofen. I assume that you were aware that it must be taken daily and blood levels might take a week to establish. -Rick From alt.support.mult-sclerosis Mon Nov 1 13:33:00 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 0491926 X-Genie-From: R.KOREJWO Message-ID: <9311010121.AA15489@relay2.geis.com> Date: Sun, 31 Oct 1993 23:56:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: none Lines: 104 Status: O The size of the wire as a factor in determining the validity of the coefficient of transmission extends this beyond the laws of physics and anatomy. The distribution of a current in a wire is a factor of the frequency of the applied EMF. (Wave guides don't even have a conductor in their center.) Wire size is important as frequency decreases and becomes unitary at DC only. As regards a neuron this is even more invalid. "Transmission" is predominantly conducted by the differential in Na and K ions and occurs between the nodes of Ranvier along the _exterior_ of the axon. It is that extended distance between nodes, induced by demyelination, which contributes to both the attenuation and delay in the nominal 70mv signal generated by ionic migration. MS has nothing what-so-ever to do with the diameter of the axon. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- another fact: "One important characteristic of myelin, however, is that it can repair itself..." incorrect- myelin is generated by a cell called an oligodendroglia in the CNS and a Swann cell in the peripheral nervous system. Nerves or myelin do not repair themselves. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- Regards the question of intrathecal baclofen, the following might prove of benefit: Savoy SM Gianino JM Intrathecal baclofen infusion: an innovative approach for controlling spinal spasticity. Rehabil Nurs 1993 Mar-Apr;18(2):105-13 Severe and disabling spasticity frequently occurs in people with multiple sclerosis and spinal cord injury. Approximately 30% of these people are treated with oral antispasmodic medications that do not provide adequate relief from spasticity (Hattab, 1980). Clinical trials with spinal stimulation and ablative neurosurgical procedures have not been as uniformly successful for controlling spasticity as has intrathecal baclofen injection (Kasdon, 1986). Delivered by an implantable programmable drug pump, intrathecal baclofen injection has proven to be successful in treating individuals with intractable spasticity. Significant reduction in muscle tone and frequency of spasms have contributed to improved function with activities of daily living, bladder management, overall comfort, and quality of sleep (Penn et al., 1989; Parke, Penn, Savoy, & Corcos, 1989). This article introduces an innovative therapy for controlling spasticity and discusses the nurse's role in patient selection and management. 93132564 CoffeY JR Cahill D Steers W Park TS Ordia J Meythaler J Herman R Shetter AG Levy R Gill B et al Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 1993 Feb;78(2):226-32 A total of 93 patients with intractable spasticity due to either spinal cord injury (59 cases), multiple sclerosis (31 cases), or other spinal pathology (three cases) were entered into a randomized double-blind placebo-controlled screening protocol of intrathecal baclofen test injections. Of the 88 patients who responded to an intrathecal bolus of 50, 75, or 100 micrograms of baclofen, 75 underwent implantation of a programmable pump system for chronic therapy. Patients were followed for 5 to 41 months after surgery (mean 19 months). No deaths or new permanent neurological deficits occurred as a result of surgery or chronic intrathecal baclofen administration. Rigidity was reduced from a mean preoperative Ashworth scale score of 3.9 to a mean postoperative score of 1.7. Muscle spasms were reduced from a mean preoperative score of 3.1 (on a four-point scale) to a mean postoperative score of 1.0. Although the dose of intrathecal baclofen required to control spasticity increased with time, drug tolerance was not a limiting factor in this study. Only one patient withdrew from the study because of a late surgical complication (pump pocket infection). Another patient received an intrathecal baclofen overdose because of a human error in programming the pump. The results of this study indicate that intrathecal baclofen infusion can be safe and effective for the long- term treatment of intractable spasticity in patients with spinal cord injury or multiple sclerosis. Institutional address: Department of Neurologic Surgery Mayo Clinic Rochester Minnesota. 93071266 Saltuari L Kronenberg M Marosi MJ Kofler M Russegger L Rifici C Bramanti P Gerstenbrand F Indication, efficiency and complications of intrathecal pump supported baclofen treatment in spinal spasticity. Acta Neurol (Napoli) 1992 Jun;14(3):187-94 In 19 patients, who suffered from severe spinal spasticity of different etiologies and did not respond sufficiently to oral antispastic therapy, intrathecal Baclofen test boli were administered. In 11 patients a DAD (Drug Administration Device) [SynchroMedR Model 8611 H, Medtronic Inc. Minneapolis, USA] was implanted. Catheter dislocation or torsion was the most common complication to be observed in these 11 patients. Long term intrathecal Baclofen application was effective in all patients, as reducing spasticity, flexor spasms and spasm induced pain. In some cases the motor performance ameliorated. Institutional address: Department of Neurology University Hospital Innsbruck Austria. --------- From alt.support.mult-sclerosis Wed Nov 3 12:09:58 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!europa.eng.gtefsd.com!library.ucla.edu!agate!ames!koriel!newscast.West.Sun.COM!news2me.EBay.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: Re: : Betaseron Date: 2 Nov 1993 17:53:25 GMT Organization: Sun Lines: 10 Message-ID: References: <9311011918.AA20710@nic.ddn.mil> NNTP-Posting-Host: chrysos Status: O In article <9311011918.AA20710@nic.ddn.mil> Dana Small writes: >Gale or whoever >Did they tell you physically where the injection is supposed to be >given??? the injections are sub-cutaneous. there are 4 areas for injections: 1: thighs (front), 2: stomach, 3: buttocks, 4: upper arms (rear). gale snow From alt.support.mult-sclerosis Thu Nov 4 15:24:15 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 8356588 X-Genie-From: R.KOREJWO Message-ID: <9311040421.AA20100@relay2.geis.com> Date: Thu, 4 Nov 1993 00:57:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Abstract Lines: 44 Status: O The abstract for the reference follows: 93023370 Tienari PJ Wikstrom J Sajantila A Palo J Peltonen L Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene. Lancet 1992 Oct 24;340(8826):987-91 Genetic factors have been implicated in the aetiology of multiple sclerosis (MS), but the genes conferring susceptibility to MS have not been identified. We carried out genetic linkage and association analyses by studying polymorphism of the myelin basic protein (MBP) gene on chromosome 18, a candidate gene for MS, in 21 MS families, 51 additional unrelated patients with definite MS, and 85 controls. All subjects were Finnish, and 14 of the families were from an area with an exceptional familial clustering of MS. Magnetic resonance imaging (MRI) was used to examine subclinical disease in symptom-free family members. In the association analysis, the allele frequencies between MS patients and controls differed significantly, p = 0.000049), the difference being attributable mainly to a higher frequency of a 1.27 kb allele among patients. In the linkage analysis, based on an autosomal dominant model and penetrance 0.05, a maximum LOD score of 3.42 (theta = 0.00) was obtained when patients with optic neuritis and their symptom-free siblings with abnormal MRI findings were classified as "affected". When these subjects were classified as "unknown" the maximum LOD scores ranged from 2.99 to 3.25 (theta = 0.00). The results suggest that in this population genetic predisposition to MS is closely linked to the MBP gene and that polymorphism at the MBP locus or an adjacent locus has a role in the aetiology of MS. Institutional address: Department of Human Molecular Genetics National Public Health Institute Helsinki Finland. ----------------------- If there is a desire to document the existence of "silent" lesions, there are a number of references which have spoken to this. I do not believe that there is anyone working in the MS area who challenges the existence of "silent" lesions. Even MSers can have some "silent" lesions. Some lesions produce disabilities which break through the consciousness of the patient or the observer and some do not. It is even possible for the patient and observer to differ on what is "silent." -Rick From alt.support.mult-sclerosis Fri Nov 5 16:48:08 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!news.moneng.mei.com!howland.reston.ans.net!news.cac.psu.edu!psuvm!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 9866295 X-Genie-From: R.KOREJWO Message-ID: <9311050014.AA15850@relay2.geis.com> Date: Thu, 4 Nov 1993 23:13:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Books Lines: 89 Status: O Joel Haugen & J. Craighead Joel probably said it a lot better than I did. Now you know why I was so angry when I learned what information was being provided to MSers. I have, at the request of a number of people, reviewed various books concerning MS which they have found and mailed to me. Most of these books are marginally better than bad. I get ask "What can I read to get some of the factual information about MS? I honestly don't know. To often books fall into a class of books which I refer to as "warm and fuzzy". These are biographical and pseudo-biographical stories about people who have "triumphed" over MS. On occasion they have a factually accurate statement in them but they are often full of psycho-babble. (I did my masters in clinical psychology so believe me when I say I know psycho-babble when I see it.) For the most part, these offer very little in the way of scientific knowledge. Some of the literature sent out by organizations like the NMSS is fair. Most of it is seriously outdated because by the time they get something staffed through the various departments that have to sign off on it, get it to the printers and then get it distributed, it is a year or two behind the state of knowledge. Fortunately, anatomy does not change much so that part is usually accurate. Ten years ago, being a year or two late was not too important. At the rate things have been moving lately, you can be out of touch in a few months. Back as recently as 1989, it was relatively common to find 12-20 medical papers published which related to MS in a month. In recent months I've seen as many as 52 in a month and finding a month with less than 25 is a rare exception. I'm not to familiar with current start up literature. For a while, "Research in Multiple Sclerosis" Waksman, Reingold and Reynolds was a starter. The last edition of that was back in 1987 (third edition) but that's no longer stocked by the publisher. Published in 1987 would make it pretty marginal anyway. Maybe some of you know of a good book that can help people with the medical fundamentals for MSers. If someone can suggest a book that, at least, is based in reality I'm interested. In my opinion, "Therapeutic claims in MS", Third edition from Demos (800) 532-8663 is fair but not very informative and filled with weak ambiguities which look like they were written by the legal department. The two previously mentioned books by Shapiro are about fair also. Demos also. Remember I said they were "fair". I didn't say "great". From there things get grim and gritty. If you are a stranger to medical terminology you might arm yourself with a good medical dictionary. Two, kind of "off-beat" books, called "The Physiology Coloring Book" (Harper & Row) and it counter part "The Human Brain Coloring Book" (HarperPerennial) both can be helpful. Don't get fooled by the titles. These are definitely not children's books. They aren't what your neurologist trained on (thank God!) but they have a lot of basic information in them. From there you can start reading everything in the medical journals about MS. That last part is a tough order. First, this is a pretty expensive thing to do and second, most hospital medical libraries will not let you in the door unless you have privileges. There are some summaries published and these help. What I post here are abstracts of papers that were published. An abstract is a 500 word, or less, summary of the paper. In a given month there might be 40 papers published. I usually read all the abstracts. From them I select a subset of papers which I think would be helpful to me and "pull" them. It's pretty hard to say how many I read in a month. It's probably about 20-30. I have to admit that I don't read all of them completely because, sometimes, it becomes obvious that the authors used poor data analysis, failed to meet some minimum criteria for objectivity or generally "fudged". If you spent two years of your life planning and executing a study and then found out that you were wrong to start with, you might try to put a brave face on too. It happens. Also keep in mind that no single paper "proves" anything. A journal paper is a glimpse into the collective mind of medicine as it is thinking about something. 3 or 4 papers which independently give you the same conclusion should be a good flag. Something probably makes "proof" with me when it has been demonstrated by about 5 or more independent observers. I sometimes bend that rule when it is someone who is very well respected in the community. Sorry to be so windy but this is what I do and I'm more than mildly upset with the kind of information I find being made available to MSers and those that care for them. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- Tzip- Due to my chronic hypertension, my doctor no longer permits me to read "Inside MS" or listen to the tapes. For what it's worth, I have a collection of books-on-tape and find one problem quite common. Many books are recorded by one person and I often find that I fall asleep when I try to listen to them. The same tones just capture me. I can appreciate your frustration however. -Rick From alt.support.mult-sclerosis Sat Nov 13 14:12:22 1993 Path: klaava!news.funet.fi!sunic!mcsun!uunet!pitt.edu!stern From: stern+@pitt.edu (Eric G Stern) Newsgroups: alt.support.mult-sclerosis Subject: Ankle braces to help walking Message-ID: <6701@blue.cis.pitt.edu> Date: 11 Nov 93 23:00:11 GMT Sender: news+@pitt.edu Organization: University of Pittsburgh Lines: 34 Status: O Hi everyone, When I was in the hospital last week for treatment of optic neuritis, I had a visit from the physical therapist. She got me to try out some anke braces to help my walking. I walk fine for short distances but for longer distances I had been using a forearm crutch as a cane. These ankle braces fit inside my shoes and keep my feet from bending downwards. I had thought that they were for treating foot-drop which I don't have so I hadn't considered using them before. Also, I had seen people use them walk very slowly and stiffly which turned me off. I was pleasantly surprised at how much easier I was able to walk with the braces. With them, I can walk further without becoming tired and I don't trip as much. The way the physical therapist explained it was that I when my foot bends downwards, my ankle goes into spasms (clonus). In walking, I have to spend a lot of energy fighting this which is fatiguing. Also, I can't walk fast because my foot is still spasming when I need to bring it forwards so I trip. By keeping my foot from bending past ninety degrees, the braces prevent these problems. In short, with the braces I can walk further, faster and with less fatigue than I could without them, and they aren't that evident for normal walking. Going up and down stairs is a little difficult, but then it was difficult without the braces. Driving with the braces takes some adjustments, but it is still possible. Anyway, my point is that if your problems sound like this, you might try these braces. I think the technical term for them is ankle orthoses. A physical therapist will certainly know what they are. Eric Stern From alt.support.mult-sclerosis Tue Nov 23 10:10:56 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!cs.utexas.edu!koriel!male.EBay.Sun.COM!jethro.Corp.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: re-intro Date: 22 Nov 1993 18:49:15 GMT Organization: Sun Microsystems Inc., Mountain View, CA, USA Lines: 46 Message-ID: NNTP-Posting-Host: chrysos Status: RO hi, i've been reading and posting to this newsgroup for some time, but with all the new people who have recently joined, i feel a need to reintroduce myself and talk about my experiences with ms. i was diagnosed just over 5 years ago, by a neurologist at the palo alto medical clinic (in california). the diagnosis was made after tests were completed, an mri and a visual evoked potential test. my symptoms included optic neuritis, loss of balance, fatigue, to name a few. dr. j.r. lacy, the diagnosing neurologist, has connections with the stanford university medical center and referred me for inclusion in a study for a new treatment for ms going on there. this study was lead by dr. lawrence steinman (see 9/93 article in the scientific american). in the study i was infused with an anti cd4-tcell monoclonal antibody. this was to supress the cd4 tcells which includes the tcell which is mistakenly armed to destroy the myelin in the nervous system. and let me tell you this treatment helped me greatly! not that i'm cured, but i believe i would be much worse without this treatment. in recent mris, dr. steinman found many of the lesions in my brain were "resolved" and no new lesions. but the study (phase 1, toxicity) was completed in the fall of this year, so i haven't had access to this treatment for the last several months and i miss it! recently i'm getting pretty shakey. so now i'm "looking forward" to the betaseron treatments. "looking forward" in quotes since i do have some reservations. it's expensive and will take some effort to do the shots every other day. but also it seems that the way betaseron works is not really understood (even by steinman) while the treatment with monoclonal antibodies and how it works is known. so watch for a continuation of the monoclonal antibody treatment study (phase 2, efficacy, dbl blind) in england and australia (and perhaps other locations as well). i have no idea of the process for fda approval in the united states, but i wish it would happen soon! anyway, i'm waiting for my card from berlex for access to betaseron. don't make the mistake i did - i neglected to fill out and return the credit application, otherwise i would probably have already started with the betaseron treatment by now. my insurance should cover it, but now that they've had time to think about it, they have questions, too. so there is a delay ... there is hope in these times for a real cure! steinman has recently identified the tcell which is armed to destroy myelin. he is currently working on something which will wipe these tcells out, a treatment sure to be better than immune system suppression. once the demyelination, or disease process is halted, then we can focus on remyelination to reverse the symptoms of ms! regards to all (and happy thanksgiving!), gale snow From alt.support.mult-sclerosis Wed Dec 1 18:22:42 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!IRST.IT!susan Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:susan@IRST.IT> X-Envelope-to: MSLIST-L@TECHNION.bitnet Content-transfer-encoding: 7BIT X-Sender: susan@192.70.136.1 Message-ID: <199312011043.AA01893@caneva> Date: Wed, 1 Dec 1993 10:42:50 +0000 Sender: Multiple Sclerosis Discussion/Support From: "Susan E. Struthers" Subject: Re: betaseron Lines: 43 Status: O It doesn't exactly make me happy, but I see I'm not the only one who has been desperate for info on this betaseron stuff. To Pamela Ryba and everyone else: The only real info on betaseron is the April 93 Neurology article. Worth reading. Things that I got from it: The treatment is *very* long term. It takes two months to get started and the best results came after *three years* of use. This treatment takes commitment and it takes time. Since it does not reverse handicaps but does delay their onset, it is probably best suited to those starting down the MS road rather than those who already have severe handicaps. My impression was that since the MRI scans in the study showed definite reductions in lesions in brain, the doctor writing article was surprised not to have found more reduction in handicap in patients. He wants to see what happens after 5 years of use. The study continues. The poor types getting placebo were given option to have real thing and continue study. Negatives: injection site irritation (like junkies or diabetics), flu-like symptoms [not for everyone, not all the time], individual adverse reactions [totally unpredictable]. Note also that MRI scan result does not necessarily coordinate with clinical manifestation of symptom. This, also, is a second shot in the dark. The first, gamma interferon, worsened MS symptoms and was abandoned. Although much is known about beta interferon, some things are still not known. My overall impression: [i am 38 soon to be 39] Worth trying because in five to ten years time there could be something to stop the progress of MS altogether -- best to slow it down first if possible. The chances of reversing handicaps once they are settled in hovers between slim and none and is quite individual in any case. After 10 years of MS I can see where I'm headed, it is not so pleasant, so even just slowing arrival sounds ok. For chronically undecided: Keep your lottery number, take your time. This treatment requires commitment. It is an individual thing. Perhaps some have not arrived at MS acceptance yet but have a lottery number. Whatever. I am still miffed that on my summer visit to U.S. I could not see a neuro and all info given me about betaseron was "It's not available". This and lottery create frustration and anxiety. Bad, bad, bad. For women under 30 there is a major decision to make regarding childbirth. Must one give birth? Or is it better to take care of oneself first and be a good aunt? Now, I would opt for latter. But hindsight is always 20/20. New drugs and child bearing don't mix. This has been shown many times by medical science. I am not a doctor. If any doctors out there see mistakes, please correct. Susan Struthers ECCAI Secretariat email: susan@irst.it fax: +39 461 314591 From alt.support.mult-sclerosis Thu Dec 2 10:35:49 1993 Path: klaava!news.funet.fi!sunic!pipex!uunet!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 2260662 X-Genie-From: R.KOREJWO Message-ID: <9312020304.AA22549@relay2.geis.com> Date: Thu, 2 Dec 1993 02:02:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: cell origin/bias Lines: 95 Status: O -=Gordon Banks=- Re:"...The debate is not about boosting or suppressing the immune system but about which immune cells are at fault...." Comment: That was not what I said however, I think I disagree with the statement. Immune system suppression has been, and continues to be, the cornerstone of clinical MS therapy especially at higher Kurtzke numbers.(6+) The research is not really in debate at all. I think most people are happy with the conclusion that T-cells for myelin and B-cells for oligodendroglia are the agents of assault together with the astrocytes, machrophages etc. associated with the destruction. While the initial focus was on v-Beta regions of the TCR as the differentiating agent, subsequent study suggest that antigen presentation may prove to be an important mechanism. The dramatic control of protein specific T-cell response achieved (but not appreciated) in the early Hafler et al studies and now replicated in the Belgium work are remarkable although patient specific. The discovery of multiple TCR expressions on a discreet T-cell has made things a bit more uncertain but not without resolution. I really do not see a body of evidence building which suggest the etiology to be other than cell mediated immunology driven primarily by the T-cells activated by antigen presentation and the associated B-cells prompted by the cytokines. If there is a contrary thesis I don't think I've seen it. The mechanism seems clear but the method of intervention seems illusive. The only major alternative to manipulation of the T-cell response has been the work of Steinman et al which focuses on the same cells at the point of intrusion through the bloodbrainbarrier.(BBB) The target cell to block is still the T-cell. Same cell, different point in etiology. It is very possible that I simply misunderstood what you were saying but if I'm wrong, I sure would like to know. Refs: Hafler DA Cohen I Benjamin DS Weiner HL T cell vaccination in multiple sclerosis: a preliminary report. Clin Immunol Immunopathol 1992 Mar;62(3):307-13 Wucherpfennig KW Newcombe J Li H Keddy C Cuzner ML Hafler DA T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. J Exp Med 1992 Apr 1;175(4):993-1002 Wucherpfennig KW Newcombe J Li H Keddy C Cuzner ML Hafler DA Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci U S A 1992 May 15;89(10):4588-92 Maimone D Reder AT Gregory S T cell lymphokine-induced secretion of cytokines by monocytes from patients with multiple sclerosis. Cell Immunol 1993 Jan;146(1):96-106 Shimonkevitz R Colburn C Burnham JA Murray RS Kotzin BL Clonal expansions of activated gamma/delta T cells in recent-onset multiple sclerosis. Proc Natl Acad Sci U S A 1993 Feb 1;90(3):923-7 Valli A Sette A Kappos L Oseroff C Sidney J Miescher G Hochberger M Albert ED Adorini L Binding of myelin basic protein peptides to human histocompatibility leukocyte antigen class II molecules and their recognition by T cells from multiple sclerosis patients. J Clin Invest 1993 Feb;91(2):616-28 Perrella O Carrieri PB De Mercato R Buscaino GA Markers of activated T lymphocytes and T cell receptor gamma/delta+ in patients with multiple sclerosis. Eur Neurol 1993;33(2):152-5 Satyanarayana K Chou YK Bourdette D Whitham R Hashim GA Offner H Vandenbark AA Epitope specificity and V gene expression of cerebrospinal fluid T cells specific for intact versus cryptic epitopes of myelin basic protein. J Neuroimmunol 1993 Apr;44(1):57-67 Salvetti M Ristori G D'Amato M Buttinelli C Falcone M Fieschi C Wekerle H Pozzilli C Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis. Eur J Immunol 1993 Jun;23(6):1232-9 Noronha A Toscas A Jensen MA Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol 1993 Jul;46(1-2):145-53 -=Brian Gee=- Re:"...I was wondering if...industrialized countries have higher incidences of MS because...(they)...have more health-care professionals who could make a diagnosis..." Comment: Absolutely. You forgot diagnostic facilities etc. The incidence tables have become less clear as the significance of variations in diagnostic ability and gene specificity have become better understood. The leading proponents of incidence models are the statisticians. -Rick From alt.support.mult-sclerosis Tue Dec 7 10:45:30 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!BTDACR.MED.NAVY.MIL!acr Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:acr@BTDACR.MED.NAVY.MIL> Message-ID: <9312051300.AA06398@btdacr.med.navy.mil> Date: Sun, 5 Dec 1993 08:00:40 -0500 Sender: Multiple Sclerosis Discussion/Support From: Charlie Richardson Subject: Recent list comments Lines: 46 Status: O To all: In fairness, and for what it's worth, I would like to add some comments about the recent messages concerning the message traffic on this list. I have been reading (and archiving) the messages on this list for about a year. In this time, I have found the list to be largely informative, stimulating, and valuable to me as both a MS'er and scientist. (Thanks, Chanoch, for your efforts!!) In the last week or so, the tone of messages has changed, to include complaints about perceived attitudes and innuendo. This only serves to drive folks away (although maybe that is what the accuser intends). Maybe there have been private messages that upset people, but I have seen nothing in the public part of the list that deserves the current tirades. The result? You will no doubt see a decrease in informed scientific discussion (which -requires- a level of scholarly skepticism), and an increase in unsubstantiated rumor (psssst - my aunt Faye says that her neighbor's cousin's brother cured his MS with castor oil - pass it on....). I love to read discussions of new and novel treatments, and includes the wonderful messages from Europe about research there. But in every case, all sides of an issue can and should be heard. Please do not stop those reports!! Believe me, if you think that there have been nasty messages on this list, then you have not seen the rest of the Internet, where often truly groundless flame-wars erupt with regularity. This MS list is very refined in comparison (which it certainly should be). I think several recent complaints have been oversensitive. And the result will be a homogenized list of hand-holding messages without controversy. MS is a difficult disease that requires perspective and informed opinion to manage successfully. Some answers you read on the list may appear to be "condescending" or "abrupt", but not everyone has the time or desire to couch their answers in flowery euphemisms. Hey! We are all adults here, and you need to be able to separate the wheat from the chaff yourself. This list is a great place to beat around ideas - don't kill it by suppressing well-meaning comments. Now..... I will shut-up and go back to monitor mode. Thanks for being here...... ALL of you. - Charlie From alt.support.mult-sclerosis Tue Dec 7 10:47:33 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!SKIVS.SKI.ORG!sarah Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:sarah@SKIVS.SKI.ORG> Message-ID: <9312060457.AA29279@skivs.ski.org> Date: Sun, 5 Dec 1993 20:57:38 PST Sender: Multiple Sclerosis Discussion/Support From: Sarah Clarke Subject: another clue to MS Lines: 76 Status: O I read a real interesting article that seems to be very significant in giving a clue to the nature of MS and other autoimmune diseases. The article is about rheumatoid arthritis, an autoimmune disease where the lining of the joints is attacked. Just like in MS, women with RA tend to enjoy remissions during pregnancy. This article describes research that seems to explain why this happens. As I understand it, the immune system, in certain circumstances, needs to regulate itself in order that the fetus not be attacked. Under these circumstances, a remission occurs: the fetus is not attacked, nor is the lining of the joints (or the myelin, in the case of MS). This article describes those circumstances. I'll just quote from the article. It's a long article that I will edit down, so it might be a little disjointed. Researcher J. Lee Nelson was intrigued by the number of remissions of RA in preganant women, and her team "recently published findings suggesting that the remarkable improvement in some arthritis cases appears to result from the genetic differences between a mother and her fetus". "Researchers gathered information on 57 pregnancies in 41 women with RA. In 18 cases, the researchers followed the woman through a pregnancy. In 39 others, the team asked the woman to recall details of a previous pregnancy... "Their analysis revealed significant improvement or remission of joint disease in 34 cases. In 12 others the arthritis remained active throughout pregnancy, and in 11 cases there were not enough data to assess the status of the disease. "Next, the researchers used molecular techniques to study genetic material from each mother and her offspring... they analyzed the DNA in each sample and homed in on genes that are part of the human leukocyte antigen (HLA) system. From her search of the literature on pregnancy and the immune system, Nelson concluded that HLA genes might shed some light on the remission of arthritis during pregnancy. These genes carry the blueprint for manufacturing so-called HLA proteins, which sit on the surface of certain immune cells, including white blood cells called lymphocytes. These proteins enable the immune system to differentiate between the body's own cells and foreign cells, such as those of the fetus. "...Some fetal cells carry HLA proteins coded for by genes inherited from the father. Researchers have long wondered why the mother's immune system doesn't mount an attack against those paternally derived HLA proteins. "...the team first looked at the 34 pregnancies in which the women had reported improvement in their symptoms. They found marked differences in mother-child HLA in 26 of those pregnancies (76%). Of the remaining 12 pregnancies -- those with no remission -- only 3 (25%) exhibited marked HLA differences. In the other 9 cases, the fetus had inherited HLA types similar to the mother's. "They could find no other factor to explain the difference between mothers who got better and those who remained the same during pregnancy" "How do genetic differences between maternal and fetal HLA genes lead to temporary remission of symptoms? One possiblity is that when a mother's HLA genes are very different from those of the fetus, some sort of protective mechanism kicks in to shield the developing child from its mother's immune cells... An alternative explanation for the remission is that the mother's immune system, noting the potential danger for the genetically different fetus, actually manufactures a substance that quiets the immune system... "[another team] plans to take Nelson's theory one step further. They will give people with RA white cells bearing HLA proteins that are different from the patient's own. That therapy may coax the patients to secrete a chemical that blocks the attack on joints" The article I read is in Science News, Vol 144, October 23, 1993. It refers to research reported in New England Journal of Medicine, August 12. I haven't read the NEJM article. Sarah Clarke sarah@skivs.ski.org From alt.support.mult-sclerosis Tue Dec 7 10:52:49 1993 Newsgroups: alt.support.mult-sclerosis Path: klaava!news.funet.fi!sunic!pipex!uunet!portal!patrik From: patrik@shell.portal.com (Patrick M Crumhorn) Subject: Re: vaccinations ^# Message-ID: Sender: news@unix.portal.com Nntp-Posting-Host: jobe.shell.portal.com Organization: Portal Communications Company X-Newsreader: TIN [version 1.2 PL2] References: <931129195030.e614@APSICC.APS.EDU> Date: Sun, 5 Dec 1993 23:19:57 GMT Lines: 13 Status: O Thanks to everyone who posted regarding my flu shot question. The consensus was that getting the flu shot carried less risk of an exacerbation than not getting the shot, and getting the flu instead. I have tended to agree for the past couple of years, and indeed have had no ill effects that I can directly relate to the flu shot (although as we all know, the timing of exacerbations is hard to analyze sometimes). Indeed, my only doubts about the wisdom of the flu shots came from reading the immune system discussions on this newsgroup, so I'm glad to get some feedback from people who've been dealing with this issue longer, and to a greater degree, than I have. Thanks again. Patrick Crumhorn patrik@cup.portal.com From alt.support.mult-sclerosis Tue Dec 7 10:56:34 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!spool.mu.edu!olivea!news.bu.edu!noc.near.net!news.delphi.com!tomhogarth From: tomhogarth@delphi.com (Tom Hogarth) Newsgroups: alt.support.mult-sclerosis Subject: Patent for CD8 Date: 7 Dec 1993 01:40:12 GMT Organization: General Videotex Corporation Lines: 65 Message-ID: <9312062034591.tomhogarth.DLITE@delphi.com> NNTP-Posting-Host: delphi.com Status: O This item appeared in the weekly PATENTS column in today's (12/6/93) NEW YORK TIMES. The columnist is Sabra Chartrand. It is a good example of presenting a complex medical discussion in terms that are understandable. That is why Sabra has a job at THE NEW YORK TIMES. Washington: Two doctors find a cell-coating process that keeps the body's immune system from going off track. The immune system is usually one of the body's most efficient and essential mechanisms. It seeks out and destroys foreign substances like bacteria. But sometimes T-cells, the soldiers of the immune system go haywire and turn on healthy cells, causing diseases like multiple sclerosis and diabetes. Or they attack a transplanted organ, prompting the body to reject it. Under those circumstances, the immune system must be suppressed. Selective suppression may be possible with a patent won by two doctors at Case Western Reserve University in Cleveland. Their invention neutralizes T-cells with a genetically engineered molecule, and they said they hoped it would be used to treat auto-immune diseases and organ transplant patients. Dr. Mark L. Tykocinski and Dr. David R. Kaplan said their technology could be tailored to target specific T-cells alone. That is possible because T-cells have receptors that react to different foreign substances. Cells called antigen-presenting cells bring foreign substances to the attention of specific T-cells and activate them. T-CELLS ARE CONVERTED Dr. Tykocinski and Dr. Kaplan have patented a process for coating the antigen-presenting cells with a genetically engineered form of a molecule called CD8. They said this converted those cells from triggers into suppressors of harmful T-cells. "The T-cells have been tricked," Dr Tykocinskd. "They meet up with the antigen-presenting cells they were made to see, and suddenly the T-cell is tricked. It was ready to be activated, and pow! Instead it gets inhibited." Though the doctors said they were not sure how CD8 accomplished the feat, they said they believed it worked through a molecule on the T-cell's surface. "The antigen-presenting cell will only confront T-cells which have a receptor for the antigen they are presenting," Dr. Tykocinski said. Multiple sclerosis, for example, occurs when defective T-cells attack nerve sheaths. So antigen-presenting cells from a multiple sclerosis patient would be coated with CD8 and infused with body cells that would help build nerve sheath. When te combination is reinjected into the patient, the defective T-cells will be attracted to the nerve sheath cells and then neutralized by the CD8. "It won't go around inhibiting every T-cell," Dr. Tykocinski added. "It inhibits the bad ones while leaving healthy T-cells intact." In the case of an organ transplant, he said, "we would simply use cells from the orga donor." A patient would be injected with donors' cells coated with CD8 before the transplant surgery to deactivate T-cells that would otherwise attack the organ. Dr. Tykocinski and Dr. Kaplan said they hoped to begin Food and Drug Administration trials next year. They received patient 5,242,687. ----------------------------------------------------------------------- whew! i hope i got it all hogarth ---------------------------------------------------------------------- Tom Hogarth VOICE: 201-656-8043 903 Park Ave. FAX: 201-656-6644 Hoboken, NJ 07030 INTERNET: tomhogarth@delphi.com ------------------------------------------------------------------- From alt.support.mult-sclerosis Tue Dec 7 21:17:28 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!COMPUSERVE.COM!71054.322 Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:71054.322@COMPUSERVE.COM> Message-ID: <931206223605_71054.322_CHJ30-1@CompuServe.COM> Date: Mon, 6 Dec 1993 17:36:06 EST Sender: Multiple Sclerosis Discussion/Support From: Merle Spector <71054.322@COMPUSERVE.COM> Subject: DSG Lines: 520 Status: O This is a partial file from the Multiple Sclerosis Library on CompuServe. I hope it is useful. Merle Spector Multiple Sclerosis Section Leader CompuServe 15+/-Deoxyspergualin 27-Nov-92 On Wednesday, 25th, again Dr. Franke referred here in Osnabrueck about 15 +/- Deoxyspergualin (DSG). This time there were not only a lot of MSers but also many doctors, neurologists. Three of them joined him sitting on the podium to signalize, that they will support him in his efforts to make DSG available, at least in an open study. Again Franke agreed Dr. Haller, that a double-blind-study should be done, but could be done also later. Those 3 neurologists (one of them is treating me, a good neuro- radiologist) are working at Paracelsus-Clinic in Osnabrueck, which belongs to a chain of Paracelsus-Clinics in Germany and abroad. So I think, it will be likely, that DSG will be available soon here. Parallelly I got the news from the Wuerzburg-Clinic, where the official Behring-DSG-multi-center-double-blind-study is running, that they will give a meanwhile-report about April, 93. If that will be positive, the study could be opened. Franke has built up a society named "Verein fuer MS-Therapieforschung" (society for ms-therapy-research). His address is: Prof. Dr. med. Niels Franke, Bothmerstr. 2, D-8000 Muenchen 19, Tel. 089/13 37 34 (+49 89 ...) Fax: 089/16 85 59. ---------- 16-Feb-93 The name of Dr.med. U. Fratzer also now can be read in german journals as "inventor" of a new ms-therapy. It is difficult for me, to describe his theory in english. Fratzer is no neurologist but internist. He tries to stop inflammation process before it goes through the blood-brain- barrier. Curious and main sign of his theory is to forbid those high essential fats, that are judged to be good by many ms-scientists and -therapists. Also some enzymes and minerals are essentials of his therapy. They are available by a company Dr. Fratzer is near to (Kirchheimbolanden, Germany). I heard him, when he talked here in Osnabrueck with our local ms-group. Yesterday I read about him in our pharmaceutical journal (DAZ). He was cited with his trial (about 1000 patients!). But there was no judgement from neurologist or other scientists. So, still I share in the doubts of the DMSG-medical board. Of corse, as with every unconventional therapy there are many ms-patients, who say, they would have profit from this therapy. One of them is a ms-friend here. But I think, he has not developed to the better end, since he took part in that method, even worse, as I see. ---------- A number of immunosuppressants are in use or I think, YES, and I thought, that would have become clear by my hints: (and it is described in that article, just as I heard it from Franke) If it works - as it can be hoped with resaons -, 15-DOS provides a immunotolerance against those destroying compartiments of the autoimmunological 'happening" with ms. So You take it once (14 days, perhaps once retried) by infusions - and that's it (much less burdening than other immunosuppessants. And as the animal-trials (I KNOW the differences!) show, the side effects are much lower than in comparable stuffs. Of course, all these hypothesises must be proved by that randomised study. But there are reasons to believe, that it can be proved. As I understand that developing doctor (in my vtx-program), it is till now Schorlemmer (also in Behring-internal scripts) who describes the differences. I had not yet the opportunity to get that literature. But, that doctor too says: we must wait for the 'confirmative judgement' at the end of the study. It should be possible for those in CIS engaged MSers to get a translation of that german literature, shouldn't it? You have more power and options there, than me alone here. ___________________________________________________________ English translation Nachricht Nr. 0003 aus Area SYMBIOSE.INF ------------------------------------------------ Datum: 16 Feb 93 15:40:40 Betr.: 03 MS: DSG-Studie I (2) ----------------------------------------------- February 1993 15+/-Deoxyspergauline- Hope for MS patients? In the past months, several reports appeared in various media, especially the popular press, of a new immune-modulating drug from Japan which N. Franke, a Professor of Anesthesia and MS patient in Munich, administered to himself. He observed a clear and sustained improvement in his symptoms. This drug is called 15+/-Deoxyspergauline. The purpose of this publication is to summarize the literature on the effects and side effects of this substance and to report on the recently initiated early phase-II trials. Recent efforts to develop a therapy against Multiple Sclerosis were based on the assumption of immunological and animal studies which can not be elaborated upon here. The immune-suppressive drugs that are currently in use or being tested in controlled studies all cause a more or less global suppression of the immune symptom, effecting primarily the T-lymphocytes. A series of detailed studies indicate that globally acting immune-suppressive drugs cause small but significant reduction in the frequency of episodes and slowing of disease progression. For azathiprin, this has been demonstrated convincingly by 25 years of treatment, whereas a recent Canadian study casts doubt on the efficacy of cyclophosphamid. Controlled studies are not available for mitoxantron, a cytostatic drug with potentially less severe side effects tested in the past three years. In a German study, cyclosporin A, the first immune-suppressive substance tested with MS, was found to be moderately effective for patients with chronically progressing disease. However, because of serious side effects, this drug can not be generally recommended. An immune-suppressive therapy can result in a global attenuation of the immune system, or it can act selectively on individual compartments. Ideally, it should suppress the activation of autoaggressive T-cells in an antigen specific manner, thus slowing the progress of the disease in an early phase. An alternative possibility is the inhibition of inflammatory agents and myelin-toxic substances. This seems to be the basis for the substantial, yet non-specific effect of steroids. Because of its effects on T-cell and macrophage function, 15+/-Deoxyspergauline appears to be an especially interesting immune modulator. What is 15+/-Deoxyspergauline? 15+/-Deoxyspergauline is produced by dehydroxilation of spergualine, a natural product from _bacillus laterosporous_. Chemically, it is a guanidine-analog of spermadine. It is highly water soluble and has a molecular weight of 496.91. It is a recemic mixture (+/_ ) of enantiomers in position 11, but it is presently not known which form is active. This cytostatic properties of spregualine and its derivatives were found more than ten years ago in a series of pharmacological tests. They prove to be effective chemotherapeutic drugs in the treatment of some lympho-and hematopoetic neoplasias. However, recent interest focused on its immune-suppressing properties, due to their more general importance. Together with FK506, rapomycin and mycophenolic acid derivatives deoxyspergualine is among the most promising immune-suppressing drugs in organ transplant medicine. The exact molecular mechanics of deoxyspergauline function is still unknown. One still unsubstantiated hypothesis assumes that the polyamine Deoxyspergauline inhibits the formation of ornithin decarboxylise, resulting in an elevated intracellular concentration of ornithin. Elevated ornithin levels specifically inhibit the differentiation of cytotoxic T-lymphocytes, which might explain the inhibition of B-and T-cell maturation caused by deoxyspergauline. The main effect appears to be the inhibition of the maturation of T-lymphocytes to functional cytotoxic cells and of B-cells to antibody- secreting cells. On the other hand, mature cytotoxic effector T-cells are hardly effected by the drug. Further more, only a weak inhibition of the secretion of cytokines such as interlukin-1 and interlukin-2 has been observed. There are both experimental and clinical indications that deoxyspergauline enhances the long-term antigen-specific immune tolerance in certain cases. In addition to its effects on B-andT-lymphcytes, deoxyspergauline also suppresses the functions of macrphages and monocytes. Thus, it prevents the formation of toxicoxygen radicals and lysosomal enzymes. Prevention of these antigen-specific reactions would be of substantial therapeutic importance, since they contribute significantly to lesion formation and myelin damage. Function in transplantation medicine 15+/-Deoxyspergauline has so far been used mainly in Japan for the prevention of tissue rejection reactions. Success rates of 78% have been reported in the case of kidney rejection that can not be controlled by conventional means. Effects on animal models of autoimmune reactions 15+/-Deoxyspergauline suppresses and retards the manifestation of lupus nephritis in mice, experimental uveoretinitis in rats, collagen- induced arthritis in mice and experimental autoimmune neuritis. In the case of experimental autoimmune encephalomyelitis as a model of multiple sclerosis, profilactic use of deoxyspergauline prevents the formation of EAE in guinea pigs. In the Lewis rat, deoxyspergauline suppressed the formation of EAE caused both by active immunization as well as passive transfer of basic myelin-specific T-cell lines. In a model for chronically relapsing EAE in older Lewis rats, it was also possible to demonstrate a therapeutic effect of deoxyspergauline. Side effects of the substance: Until now, in phase one investigations, only slight, seldom serious undesirable effects (WHO-definition) have been observed. It is to be noticed that for an immunomodular treatment doses were put into effect were significantly below those which were in the early phase of the development used in the treatment of malignoma. Side effects: nausea, sometimes vomiting, hyperparathesia of various skin parts, heightened blood pressure values as well as passing headaches and feelings of heat of short duration. Considering the changes of the laboratory parameters, it was noticed that there was a small decrease of leukocytes, or seldom also of erythrocytes or thrombocytes. Planning of the study Beginning in 1989, a planning of a clinical test for Multiple Sclerosis in conjunction with Firma Behringmerke was begun. This test arose from the interesting and somewhat different in comparison to other immunosuppresive and immunomodulating substances of the effect profile of 15+/-Deoxyspergauline in conjunction with animal experimental data. As is known, individual observations and uncontrolled pilot investigations of Multiple Sclerosis are not very indicative since their spontaneous and unpredictable progression of the disease, makes it impossible to make a differentiation between accidental changes in the progression and the effects of therapy. Therefore, only the tedious and difficult way remains via controlled and randomized therapy studies with sufficiently large groups of patients and sufficiently long observation times with strict recording criteria and selection of the success criteria, retardation of the disease progression which is being captured in quantified clinical scales. This means that sufficient is approximately 80-100 patients per therapy branch and that a minimum observation time is 24-36 months. Significantly higher, however, must be the number of cases if other even more variable clinical criteria is to be investigated for example-the extent of the reformation of a **push** with the introduction of MRT and increasing experiences in its use with longitudinal examinations. It became clear that this method was comparable with clinical parameters according to the frequency of investigations a multiple of disease activities to have recognized. The given of paramagnetic contrasting devices permitted it to identify newly appearing sources or spots of disease within the time window of 2 to a maximum 12 weeks. Because the required number of cases and the observation time for a therapy study decreases with the frequency of the appearance of a change which is to be measured as a result there is as a result of using MRT the possibility to get a first reliable estimation of the therapy effects of a new substance in relatively a short time and with noticeably fewer patients. In this process one may, however, not forget that with MRT there is a surrogate variable which is significant with the actually interesting disease determined impedance but is only weakly correlated. Most authors maintain that in the course of time, this correlation becomes tighter. The final proof for such a convergence is still not present lacking sufficiently large and prospective studies to this question. For this reason one can not avoid to introduce clinical parameters as primary goal variables with a primary study which is oriented on MRT changes. The currently running study of the effects of 15+/-Deoxyspergaulin tries to draw consequences with MS therapy from these considerations. Study design It is planned to have a prospective controlled study with the treatment and subsequent observation time per patient of 2 years. These participating patients will be randomized into three therapy group 15+/-Deoxyspergaulin in medium dose, 15+/-Deoxyspergaulin in high doses and placebo. The most important recording criteria are: secured clinical diagnosis of MS, an existing neurological deficit (however still remaining capabilities at least with help), age between 18 and 50, the progression should be a secondarily chronic or noticeable increase. There should be with MS in common areas of the disease in the cranial MRI which should be provable and of those at least one with a contrast in the two weeks in the beginning of the treatment. The effectiveness will be evaluated according to two main criteria: a) average number of gadolinium (contrast-substance, that is used to show veins and arteries in MRI) receiving lesions in the 4th to 24th study week conducted cranial MRI. This will be evaluated through a central MR evaluation center b) clinically the changes of the EDSS, in comparison between the beginning and the end of the study. The case number estimation is oriented on the MRI criteria and result in consideration of possible therapy stoppages. A required number of 36 patients per therapy branch in order to have to have a sufficient chance to shot therapy relevant differences, it is required to have planned the firming clinical final evaluation with a second study or with significantly more seldom carried out MRI controls. The second study there would be group strengths of taken together 60-80 patients per therapy branch of the time span. It is seen to have a conclusion of the concluding phase of the first study still in the year 1992. The MRT analysis after completion after of the first 6 months will probably take place in the fall if 1993. The authors thank their coworkers in the Firma Behringmerke particularly Drs. J. Racenberg and J. Mueller-Cohrs for their support and planning of the conduct of the study, M. A. Weber for the careful production of the manuscript and support of the Swiss Multiple Sclerosis Society. The clinical research group for MS and the Neurological University of Wuerzburg which is being supported with means from the state government and also the research and technology of the federal republic. Appendix Beteiligte Zentren: Neurologische Universitaetsklinik, Kantonsspital Basel (L.Kappos, Studienleitung), Neurologische Universitaetsklinik Knappschaftskrankenhaus Bochum-Langendreher (W. Gehlen), Neurologische Universitaetsklinik Bonn (H.L. Lagreze), Neurologische Universitaetsklinik Eppendorf, Hamburg (Ch. Harthard), Neurologische Klinik der Medizinischen Hochschule Hannover (J. Haas), Neurologische Universitaetsklinik Homburg/Saar (H. Ruettinger), Neurologische Universitaetsklinik Wuerzburg (H.-P. Hartung), Service de Neurologie, Hopital St. Antoine Paris, (E. Roullet). Zentrale MRT-Evaluation: Neuroradiologie Kantonsspital Basel (E.W. Radue). Finanzierung und Organisation: Behringwerke AG (J. Racenberg, K. Theobald). publiziert in: Der Nervenarzt (1992) 63:768-771 ----- "reflections of a 15-DOS/DSG-expert in the developping team." What should I answer to the message you forwarded to me? The problem is that we still have no data up to now proving any efficacy of the compound in humans. The difference of 15-DSG to other immunosuppressants is obvous: In the animal experimental auto immune models the compound was effective even when applied after the onset of the illness in the animals. This is quite different to Cyclosporine A which has to be applied from the time of induction of the illness to show any efficacy. The problem is that we do not know whether these models are relevant. But they are the best we have for the time being. In the transplantation models the application of the compound was effective even if the acute rejection crisis already started (which is in contrast to Cyclosporine A and Azathioprine) and caused in different animal models transplant suvival enen if all immunosppressive was stopped. (Remarkable was an experiment in South Africa were 8 baboons were kidney transplanted. They were treated with the normal triple drug immunosppressive treatment and in addittion with 15-DSG. In all animals the immunosuppressive treatment was stopped after one month. 4 of the 8 animals survived, with functioning graft and without any immunosuppression for at least one year. The biologists say, that the compound does not effect macrophages but I believe that T-cell effects are mainly responsible for what we see. We have as well good data proving that the compound dies effect B-Cells (which makes it quite unique). But most interesting for me is the fact that we see both, immunosuppression and cell proliferation in the experiments. It seems that the compound distinguishes between different T-Cell-sub populations and under circumstances it is able to proliferate certain clones. If I am right, these clones are specific cytotoxic clones. But of Course, I am not an expert, so understand this as a speculation. We have to wait until the end of this year. Then the results of the ongoing study will be available. Then we will know whether this compound has an influence on MS. -------- 23-Feb-93 Today I got further informations from a faxed copy of the german medical journal 'Der Allgemeinarzt 11/1992' (4 pages). In it Prof. Franke and his Book, Multiple Sklerose, is presented and criticized by Monika Wruck, MS-patient herself. For the first time I read here, that 15-DOS is developped by the japanese company 'Nippon Kayaku', which gave the license for Europe to 'Behringwerke AG, Marburg, Germany'. They write about a therapeutical dose of 5 mg/kg body weight, given in an 3 - 4 hours infusion. They too write about a rather specific ("clonal") effect of 15-DOS. Wonder that, even when in germany every general practitioner could read about DOS, here nothing is known or leads to actions and reactions. Study References Fortsetzung zum Text ueber 15+/-Deoxyspergualin (02, 03) Literature 1. Beck RW, Cleary PA, Anderson MM Jr et al (1992) A randomized, controlled trial of corticoides in the treatment of acute optic neuritis. N Engl J Med 326:581-588 2. Dickneite G, Schorlemmer HU, Weinmann E, Sedlacek HH (1988) 15-Deoxyspergualin: from cytostasis to immunosuppression. Behring Inst Mitt 82:231-239 3. Gannedahl G, Ohlman S, Persson R et al (1992) Rejection associated with early appearance of donor-reactive antibodies after kidney transplantation treated with plasmapheresis and administration of 15-deoxyspergualin. Transplant Int 5:1992 4. Gonsette RE, Demonty L (1989) Mitoxantrone, a new immunosuppressive agent in multiple sclerosis. In: Gonsette RE, Delmonte P (eds) Recent advances in MS therapy. Elsevier, Amsterdam, pp 161-164 5. Goodin DS (1991) The use of immunosuppressive agents in the treatment of multiple sclerosis: a critical review. Neurology 41:980-985 6. Hartung H-P, Hughes RAC, Taylor WA, Heininger K, Reiners K, Toyka KV (1990) T cell activation in Guillain-Barre syndrome and in MS. Neurology 40:215-218 7. Hartung H-P, Heininger K (1989) Non-specific mechanisms of inflammation and tissue damage in MS. Res Immunol 140:226-233 8. Hartung H-P, Jung S, Stoll G et al (1992) Inflammatory mediators in demyelinating disorders of the CNS and PNS. J Neuroimmunol 40:197-210 9. Hintzen RO, Polman CH, Lucas CJ et al (1992) Multiple sclerosis: immunological findings and possible implications for therapy. J Neuroimmunol 39:1-10 10. Hohlfeld R (1990) Neurological autoimmune disease and the trimolecular complex of T-lymphocytes. Ann Neurol 25:531-538 11. Iwasawa H, Kondo S, Ikeda D et al (1982) Synthesis of (-)-15-deoxyspergualin and (-)-spergualin-15-phosphate. J Antibiotics 35:1665-1669 12. Kappos L (1990) Immunsuppressive Therapie der Multiplen Sklerose mit Azathioprin und Cyclosporin A. Langzeiteffekte, risiken, kernspintographische und immunologische Befunde. Springer, Berlin Heidelberg New York 13. Kappos L, Gold R, Kuenstler E et al (1990) Mitoxantrone in the treatment of rapidly progressive MS. A pilot study with serial Gadolinium enhanced MRI. 42. annual Meeting, American Academy of Neurology, miami, April 30th-May 6th, 1990. Neurology 40 [Suppl 1]:261 14. Kappos L, Mertens HG (1989) Immunsuppression und -modulation bei neurologischen Erkrankungen. Nervenarzt 60:135-140 15. Kappos L, Patzold U, Dommasch D et al (1988) Cyclosporine vs azathioprine in the long-terme treatment of MS - results of the German multicenter study. Ann Neurol 23:56-63 16. Kappos L, Radue EW (1991) Magnetische Resonanztomographie bei Multipler Sklerose: Eine Bestandsaufnahme. Klin Neuroradiol 2:83-140 17. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444-1452 18. Mauch E, Kornhuber HH, Fetzer U, Krapf H, Laufen H, Schoog R (1991) Die erfolgreiche Therapie der multiplen Sklerose mit dem Zytostatikum Mitoxantron: Ergebnisse einer Pilot-Studie nach 1 Jahr. Verh Dtsch Ges Neurol 6:204-205 19. Miller DH, Barkhof F, Berry I, Kappos L, Scotti G, Thompson AJ (1991) Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action (CEC) guidelines. J Neurol Neurosurg Psychiatry 54:530-533 20. Morris RE (1991) +/-15-deoxyspergualin: a mystery wrapped in an enigma. Clin Transplant 5:530-533 21. Nemoto K, Abe F, Takita T (1987) Suppression of experimental allergic encephalomyelitis in guinea pigs by spergualin and 15-deoxyspergualin. J Antibiotics 40:1193-1194 22. Nishimura K, Tokunaga T (1989) Mechanism of action of 15-deoxyspergualin I. Suppressive effect on the induction of alloreactive secondary cytotxic T-lymphocytes in vivo and in vitro. Immunology 68:66-71 23. Paty DW, Willoughby E, Whitaker J (1992) Assessing the outcome of experimental therapies in multiple sclerosis patients. In: Rudick RA, Goodkin DE (eds) Treatment of multiple sclerosis Springer, Berlin Heidelberg New York, pp 47-90 24. Rudick RA, Goodkin DE (1992) (eds) Treatment of multiple sclerosis. Springer, Berlin Heidelberg New York, 99 47-90 25. Schorlemmer HU, Seiler FR (1991) 15-Deoxyspergualin (15-DOS) for therapy in an animal model of multiple sclerosis (MS): Disease modifying activity on acute and chronic relapsing experimental allergic encephalomyelitis (EAE). Agents Actions 34:156-160 26. Simmons RL, Wang SC (1991) New horizons in immunosuppression. Transplant Proc 23:2152-2156 27. Seinman L (1991) The development of rational strategies for selective immunotherapy against autoimmune demylinating disease. Adv Immunol49:357-379 28: Takeuchi T, Iinuma H, Kunimoto S et al (1981) A new antitumor antibiotic, spergualin: Isolation and antitumor activity. J Antibiotics 34:1619-1621 29. The Canadian Cooperative Multiple Sclerosis Study Group (1991) The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet 337:441-446 30. The Multiple Sclerosis Study Group (1990) Efficacy and toxicity of cyclosporin in chronic progressive multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial. Ann Neurol 27:591-605 31. Waaga AM, Ulrichs K, Krzymanski M et al (1990) The immunosuppressive agent 15-deoxyspergualin induces tolerance and modulates MHC-antigen expression and interleukin-1 production in the early phase of rat allograft response. Transplant Proc 22:1613-1614 32. Weinshenker BG, Sibley WA (1992) Natural history and treatment of multiple sclerosis. Curr Opinion Neurol Neurosurg 5:203-211 33. Wekerle H (1984) Immunospecific therapy of central nervozs system autoaggression with an antigen specific T-Cell line. In: Alvord EC, Kies MW, Suckling AJ (eds) Experimental allergic encephalomyelitis. Liss, New York, pp 435-441 34. Yamamura T, Da-Lin Y, Stoh J, Tabira T (1987) Suppression of experimental allergic encephalomyelitis by 15-deoxyspergualin. J Neurol Sci 82:101-110 35. Yudkin PL, Ellison GW, Ghezzi A, Goodkin DE, Hughes RAC, McPherson K, Mertin J, Milanese C (1991) Overview of azathioprine treatment in multiple sclerosis. Lancet 338:1051-1055 Priv.-Doz. Dr. L. Kappos Neurologische Universitaetsklinik Kantonsspital Basel Petersgraben 4 CH-4031 Basel Quelle: Der Nervenarzt (1992) 63:768-771 From alt.support.mult-sclerosis Wed Dec 8 13:51:07 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!BTDACR.MED.NAVY.MIL!acr Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:acr@BTDACR.MED.NAVY.MIL> Message-ID: <9312071558.AA08339@btdacr.med.navy.mil> Date: Tue, 7 Dec 1993 10:58:34 -0500 Sender: Multiple Sclerosis Discussion/Support From: Charlie Richardson Subject: Flu Vaccine Lines: 38 Status: O To add another comment to the Flu Vaccine discussion, I personally always get the flu vaccine shot, because I will do ANYTHING to avoid a fever from a flu attack. Fever makes me a blind vegetable, so for my form of MS, whatever it is, I'll take anything that helps to avoid a flu fever. Here's a citation from the neurology literature that may be of interest: AU - Michielsens B AU - Wilms G AU - Marchal G AU - Carton H TI - Serial magnetic resonance imaging studies with paramagnetic contrast medium: assessment of disease activity in patients with multiple sclerosis before and after influenza vaccination. LA - Eng AB - Eleven patients with a relapsing-remitting form of multiple sclerosis (MS) were examined clinically and with magnetic resonance imaging scans 3 weeks before, at the day of vaccination with killed influenza virus and 3 weeks afterwards. No exacerbations were noted in the pre- or postvaccination period. Eight contrast-enhanced or active lesions were present at the onset of the study. Three new active lesions appeared at the end of the prevaccination period while only 1 new active lesion was found at the end of the postvaccination period. We conclude that vaccination with killed influenza virus has no clinical or subclinical short-term effect on the activity of MS. SO - Eur Neurol 1990;30(5):258-9 Note: Only you and your neurologist can decide what is the best course of action for YOUR particular form of MS. Just some more to consider. The above is obviously a smalll number of studied patients; but nonetheless interesting. It would be nice to see this study repeated for a greater number of subjects - but like most things, probably too expensive. - Charlie P.S. "Life is like a Ferrari. It goes too fast, and it costs too much." From alt.support.mult-sclerosis Wed Dec 8 13:52:40 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!cs.utexas.edu!koriel!newscast.West.Sun.COM!news2me.EBay.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: betaseron Date: 7 Dec 1993 18:56:31 GMT Organization: Sun Lines: 25 Message-ID: NNTP-Posting-Host: chrysos Status: O i've started with the betaseron injections. i thought maybe there would be some interest, i certainly hope others will share their experience with it. there are several who have started in the group signed up from stanford, so i had a couple of tips. one tip is to take tylenol a half hour before the injection to help reduce the flu-like symptoms (documented side effect). another is to be sure to let the alcohol prep air dry before injecting (otherwise the injection may sting or burn as the alcohol goes in with the needle). and berlex recommends doing the injections in the evening. i decided to do the first injection friday night so i would have saturday (and the weekend) to see how it effects me. i'm glad i did wait - i felt like shit saturday morning. very achy and a pretty severe headache too. so i lazed around the house most of saturday, recovering. by sunday i was feeling ok, and had another injection sunday evening. on monday morning i was doing much better than saturday morning (a good thing - i needed to work on monday). my husband is helping and actually does the injection for me. the hardest part is preparing the drug, reconstituting the betaseron cake using the diluent. anyway it's too soon to tell if it's helping my ms symptoms, we'll see. i'm optimistic though. this morning i met the horseshoer (is was time for my mare, c'est jolie, to have her hooves trimmed and shoes reset), and she (the shoer) thought i was definitely looking better! gale snow From alt.support.mult-sclerosis Thu Dec 9 17:57:21 1993 Path: klaava!news.funet.fi!sunic!EU.net!uunet!cs.utexas.edu!math.ohio-state.edu!magnus.acs.ohio-state.edu!usenet.ins.cwru.edu!news.ysu.edu!psuvm!auvm!ALEXANDRIA-EMH2.ARMY.MIL!MACPHERSON Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:MACPHERSON@ALEXANDRIA-EMH2.ARMY.MIL> Message-ID: Date: Mon, 6 Dec 1993 08:49:00 EST Sender: Multiple Sclerosis Discussion/Support From: "MACPHERSON, DOUGLAS" Subject: Re: Deoxyspergualin (DOS) ^# ^# Lines: 49 Status: O To Margret and others who want to do their own literature searches: It's very easy. UnCover has a menu system that allows you to seacch on names or words. All you have to do is cycle through the menus for new searches. TELNET database.carl.org The computer asks you your terminal type: apple ... unknown (or TTY?) It asks you to identify yourself -- you don't have to this is to bill you for faxes you may order You choose a database: 1 for UnCover (it's free) It asks you to choose a search type: N for name, W for word It prints some explanation/instructions. At the bottom of the page you get a prompt and you enter any two words, maybe: > SCLEROSIS MULTIPLE It the looks through its documents for these words, anywhere, in any order. It tells you how many it found. >914 (I think). It gives you a choice: D display the titles, ... enter a new search word. >Betaseron for instance And it looks through the 900+ documents for Betaseron. Problems: It is very "string" literal -- you must spell exactly right and choose exactly the words the authors used. Treatment and therapy got different articles. It only waits 30 seconds for you to enter words, before it prompts you to enter something. The authors and title listings are truncated, the journal reference is cryptic. There's really not enough info to be certain you want the article. The articles are >= $8.50 and are faxed, and I'm not sure they'll mail them. GOOD THINGS: Searches are free, articles are faxed (some in 2 hours), new stuff is entered within the week (2 days I think). Faxing is good or bad, depending on your fax access. Doug M. aka macpherson@26.1.0.50 From alt.support.mult-sclerosis Thu Dec 16 12:38:53 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 4895706 X-Genie-From: R.KOREJWO Message-ID: <9312160502.AA22722@relay2.geis.com> Date: Thu, 16 Dec 1993 03:11:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: incidence/Beck et al Lines: 30 Status: O Just a short note, first, to thank the many people who sent me E-mail. I heard you and agree. WARNING TECHNICAL STUFF FOLLOWS. I'm running about a little behind because I've been buried in Journals and phone calls. I seem to recall a comment about incidence and diagnosis and the old story regards temperate climate and MS. There are some anomalies associated with diagnostic capability but it is pretty uncertain how much. The most peculiar story that I can recall was a West African country which had an astronomical rise in incidence when they got a new neurologist. The climatic variance has been largely discounted with a better understanding of MS. CM Poser's recent review of pathogenesis attributes the old climatic node concept to be a long standing misunderstanding of genetic factors which are more distinctly understood.(i.e. DR2) I have not seen the climatic distribution used in any authoritative reference since the better understanding about the genetic susceptibility. A recent reference worth noting is the Beck et al paper in the 9 December issue of NEJM. The paper suggest that not only are the duration and recovery of early ON favorably influenced by IV methylprednisolone (see prior reference from the Optic Neuritis Study Group), but further that the progression from ON to MS is favorably affected. There was a marked difference in the incidence rate for MS exhibited through the 3.5 year mark. It is suggested that this benefit might extend into therapy for MS. Based on the data I've seen over the last 12 years, this projection to "outcome" was expected. With the dramatic and in my view, undeserved, focus on other therapies, it is a worthy realization that a therapy widely used for MS may show benefits greater than previously claimed. -RJK From alt.support.mult-sclerosis Fri Dec 17 14:53:22 1993 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!noc.near.net!news.delphi.com!tomhogarth From: tomhogarth@delphi.com (Tom Hogarth) Newsgroups: alt.support.mult-sclerosis Subject: Re: Bladder and bowel control Date: 17 Dec 1993 03:41:49 GMT Organization: General Videotex Corporation Lines: 49 Message-ID: <9312162236591.tomhogarth.DLITE@delphi.com> References: NNTP-Posting-Host: delphi.com Status: O >Much-much worse, bowel control. This can be TERRIBLY unpleasant and >humiliating. If there are others who face similar probs, and dare come >out of the cupboard, welcome. >3. Listenlisten, listen to the signals. Enough of the technical talk - beta this cop that ..... Now we are getting down to the real essence of life ka-ka, do-do, po-po and pe-pe. This is an ALT news group. BLADDER, see my earlier stuff on this, Bottom line - be prepared BOWEL - Besides the awful experience that I documented in the post about the rectal exam preparation . Yes folks, I have shit my pants, a couple of times. But not in the last couple of years. I have developed a few rules of thumb (maybe the wrong part of the anatomy). - Lots of fiber, Kellog's Bran Buds contains psyllium - start slowly. - Lots of fruit - Exercise - I NEVER leave the house until my morning DUMP. When I was still working the management knew that I could not commit to early meetings, etc. But because of the diet, I was never late for work because of bowel stuff. My morning routine may help also. Get up early and read the paper with a cup of coffee and light breakfast (fuit, cerial or muffins). Within ahour or two nature calls and I'm safe for the rest of the day. I'm a one dump a day man. The morning coffee is the only one. Hot drinks affect my vision and fatigue when taken later in the day. Margret. On doing it in the car and other un-lady like places. I have seen advertised in hiking/outdoor supply catalogs a devise called "JANE". It looks like a funnel with the wide part molded to fit a female's part. (Can't be sure about this, it's been too long, know what i mean.) It is supposed to allow you to take a leak without dropping your drawers. So Margret, you can do it like a man. hogarth -8 yrs CP ---------------------------------------------------------------------- Tom Hogarth VOICE: 201-656-8043 903 Park Ave. FAX: 201-656-6644 Hoboken, NJ 07030 INTERNET: tomhogarth@delphi.com ----------------------------------------------------------------------- From alt.support.mult-sclerosis Mon Dec 20 12:13:50 1993 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!uunet!pitt.edu!toads.pgh.pa.us!geb From: geb@cs.pitt.edu (Gordon Banks) Newsgroups: alt.support.mult-sclerosis Subject: Re: B12 Message-ID: <2f2sbo$edl@toads.pgh.pa.us> Date: 20 Dec 93 00:41:28 GMT References: <9312172133591.tomhogarth.DLITE@delphi.com> Reply-To: geb@cs.pitt.edu (Gordon Banks) Organization: Univ. of Pittsburgh Computer Science Lines: 19 NNTP-Posting-Host: speedy.cs.pitt.edu Status: O Except in a very few vegetarians, and people with short bowel syndrome, B12 deficiency is caused by disease of the stomach wall. The most common form is autoimmune, as is MS. Patients with pernicious anemia can display neurologic symptoms and signs quite similar to progressive spinal MS. The disorder is known as subacute combined degeneration. They become spastic, weak, and have loss of sensation in the extremities, very similar to MS patients. The neurologic damage is partially reversible. The B12 must be administered in the form of injections since oral B12 is not absorbed in these patients. I have seen cases that were misdiagnosed as MS. Once suspected, the disease is easily diagnosed by Schilling test, in which labelled B12 is given orally and checked for in the urine. If the labelled B12 is not absorbed, you have the problem and need the shots. Of course, many MS patients are given the shots for insufficient reasons also. -- ------------------------------------------------------------------------------ Gordon Banks N3JXP |"I can eat more fat meat than you can cook in a week geb@cadre.dsl.pitt.edu | I can tell more of them doggone lies." T. Jarrell ------------------------------------------------------------------------------ From alt.support.mult-sclerosis Tue Dec 21 18:30:09 1993 Path: klaava!news.funet.fi!sunic!EU.net!uunet!spool.mu.edu!agate!darkstar.UCSC.EDU!128!grbr From: grbr@arapaho.ucsc.edu (Terry Gritton) Newsgroups: sci.med,alt.support.mult-sclerosis Subject: Re: Parathesia (?) and MS Followup-To: sci.med,alt.support.mult-sclerosis Date: Tue, 21 Dec 93 00:02:06 GMT Organization: University of California, Santa Cruz Lines: 123 Message-ID: References: <1993Dec10.084820.23689@leland.Stanford.EDU> <1993Dec14.075526.4164@inland.com> NNTP-Posting-Host: snow.cse.ucsc.edu X-Newsreader: VersaTerm Link v1.1 Xref: klaava sci.med:47327 alt.support.mult-sclerosis:913 Status: O In Article , rabinoff@csn.org (Robert Rabinoff) wrote: >... >... incidences of MS ... >Does anyone have any solid facts other than the latitude/climate connection? There are other interpretations of the "medical geography" of MS. Here are a few quotes and some citations. "According to one interpretation [A9], the geographical distribution of MS resembles a parabolic gradient (Figure 3.2) which increases sharply with latitude. An alternative interpretation [A10] of these same data is that zones of varying frequency exist in different parts of the world. The latitude of the zones may overlap considerably (Figure 3.3). According to the gradient interpretation, MS should have the highest frequency at the extremes of latitude. However, available data from communities in northern areas, for example, northern Norway [A11] and Canada [A12,A13], suggest that MS may actually be lower in frequency at extreme latitudes than regions farther south [A14-A16]. In Europe, MS appears to be highest in frequency in the central part [A6] and frequency decreases toward the north as well as south (Figure 3.4). An east-west gradient may also exist in Europe [A17]. When the prevalence of MS is plotted against geographical latitude in different parts of the world, remarkably similar gradients result (Figure 3.5)." [1] and later in the same paper when discussing the enteric pathogens - age of exposure hypothesis "Alter and Olivares [A20] argued that the important aspect of the environment in so far as the rate of MS was concerned was the quality of water sanitation. It was postulated that in 'sanitary' environments contact with enteric pathogens was delayed until later childhood or even adulthood. As in poliomyelitis later infections was postulated to be associated with a high incidence of central nervous system involvement and a higher rate of MS. The attractiveness of the sanitation hypothesis was enhanced by the demonstration that industrialized areas with poor overall levels of sanitation like Japan and Mexico City had _low_ rates of MS. Thus, although these communities were like 'developed regions' as regards levels of industrialization, they were like primitive areas in level of sanitation and in frequency of MS." [1] Although dated, this is a nice source with graphics and many references (148 refs) allowing one to reflect on the many possible interpretations. It includes a section on immigrate MS rate studies done in England, the USA and especially Israel. In these studies the action of a protective/deleterious factor was detected whose effect occurred before the age of five. A quote from another source summarized this information. "Childhood exposure to some unknown factor is important: adults who migrate have the risk of their place of origin, whereas small children take on the risk of their destination. The new generation of native Israelis, surprisingly, has high MS rates despite low latitude, implying that some environmental condition associated with industrialization and developed economics is important [Lowis, 1986). In the United States, however, California, though more industrial, has lower MS rates than Washington state. Migrants from the low-rate South and high-rate North to California and Washington state have been studied. Children assume the high or low rates of their destination, as in the Israeli study. Adult migrants from the South to Washington have higher MS rates than their birthplace but lower than for native Washingtonians. This implies that some protective factor continues to shield the migrants in the presence of greater environmental hazard. In the absence of a United States registration system, however, it is very difficult and expensive to get a large enough stream of migrants to be able to analyze rare diseases" [2] The last sentence brings me to my question for some knowledgeable soul on the net. Has anybody developed sources of raw MS prevalence rates by _county_ for the entire USA in electronic form available by FTP (file transfer protocol) or lacking the above, any compilation of MS data covering the USA. Refs 1. Alter, M (1977). Clues to the cause based upon the epidemiology of M.S. In - Multiple Sclerosis: A Critical Conspectus pg. 35-83. EJ Field (editor) University Park Press, Baltimore. (RC 377 M84 Univ. Cal. S. F. lib) 2 Meade, M (1988). In Medical Geography pg. 219. (RA 792 M42 UCSF lib.) 3. A9 Alter,M. (1973). The geographic distribution of multiple sclerosis: an examination of mathematical models. J. Chronic Dis. 26:755. A10 Kurtzke,JF (1974). An epidemiologic approach to multiple sclerosis. Arch. Neurol. 14:213. A11 Kurtzke,JF (1966). Further features of the Fennoscandian focus of multiple sclerosis. Acta Neurol. Scand. 50:478. A12 White, DN (1959). Disseminated sclerosis: a survey of patients in the Kingston, Ontario, area. Neurology 9:256. A13 Alter, M (1960). The geographic distribution of multiple sclerosis. II. Prevalence in Halifax County, Nova Scotia. N.S. Med. Bull. 39:203. A14 Siedler, HD (1958). The prevalence and incidence of multiple sclerosis in Missoula County, Montana. J. Lancet 78:358. A15 Percy, AK (1971). Multiple sclerosis in Rochester, Minnesota. A 60-year appraisal. Arch. Neurol. 25:105. A16 Detels, R (1974). Multiple sclerosis in Japanese-Americans. A preliminary report. Int. J. Epidemiol. 3:341. A17 Morariu, M (1974). Multiple sclerosis in Transylvania: a zone of transition frequency. Neurology 24:673. Lowis, GW (1986). Sociocultural and demographic factors in the epidemiology of multiple sclerosis: An annotated selected bibliography. International Journal of Environmental Studies 26:295-320. ------------------------------------------------------------------ Terry Gritton "I think that it is much more interesting to live not knowing, than to have answers which might be wrong.I can live with doubt, and uncertainty, and not knowing.I have Research interests: approximate answers, and possible beliefs signal glycoproteins and different degrees of certainty about logic programming different things, but I'm not absolutely sure of anything." Richard Feynman From alt.support.mult-sclerosis Sat Jan 1 21:52:33 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!agate!darkstar.UCSC.EDU!128!grbr From: grbr@arapaho.ucsc.edu (Terry Gritton) Newsgroups: alt.support.mult-sclerosis Subject: Re: Cobalamin (B12) (long) Followup-To: alt.support.mult-sclerosis Date: Sat, 1 Jan 94 02:52:15 GMT Organization: University of California, Santa Cruz Lines: 366 Message-ID: NNTP-Posting-Host: snow.cse.ucsc.edu X-Newsreader: VersaTerm Link v1.1 Status: O >From: geb@cs.pitt.edu (Gordon Banks) >Subject: Re: B12 >Date: 20 Dec 93 00:41:28 GMT >Except in a very few vegetarians, and people with short bowel >syndrome, B12 deficiency is caused by disease of the stomach >wall. The most common form is autoimmune, as is MS. Patients >with pernicious anemia can display neurologic symptoms and signs >quite similar to progressive spinal MS. The disorder is known as >subacute combined degeneration. They become spastic, weak, and >have loss of sensation in the extremities, very similar to MS >patients. The neurologic damage is partially reversible. The >B12 must be administered in the form of injections since oral B12 >is not absorbed in these patients. I have seen cases that were >misdiagnosed as MS. Once suspected, the disease is easily >diagnosed by Schilling test, in which labelled B12 is given >orally and checked for in the urine. If the labelled B12 is not >absorbed, you have the problem and need the shots. Of course, >many MS patients are given the shots for insufficient reasons >also. _A more complex view_ >Except in a very few vegetarians, and people with short bowel >syndrome, B12 deficiency is caused by disease of the stomach >wall. The most common form is autoimmune, as is MS. Diseases of the stomach, pancreas, and ileum affect cobalamin absorption into the blood [Herbert 1985, Parmentier 1979]. But not to be overlooked are deficiencies even when absorption into the blood is fully functional. Cell uptake and/or internal use by the cell may be defective (errors of so called transport [Hall 1981] and errors of metabolism [Rosenberg 1980]). >Patients with pernicious anemia can display neurologic >symptoms and signs quite similar to progressive spinal MS. >The disorder is known as subacute combined degeneration They >become spastic, weak, and have loss of sensation in the >extremities, very similar to MS patients. The neurologic damage >is partially reversible. Among other neurological presentations are optic neuritis [Foulds 1969] and postural hypotension [White 1981]. The extent to which cobalamin deficiency and MS can or should be differentiated is questioned by some researchers. The overlap viewpoint "The present data support the view that an investigation of B12 metabolism should be performed in each MS patient since a B12 deficiency might, in every case, be an additional factor." [Lauer 1986] "The nature of the association of vitamin B12 deficiency and MS is unclear but is likely to be more than coincidental. There is a remarkable similarity in the epidemiology of MS and pernicious anaemia. Vitamin B12 deficiency should always be looked for in MS. The deficiency may aggravate MS or impair recovery. There is evidence that vitamin B12 is important in myelin synthesis and integrity but further basic studies are required" [Reynolds 1992a] Another view is that MS and cbl deficiency are entirely separate entities and cobalamin responsive patients have been misdiagnosed and further that this seldom happens [Murray 1984]. But others have had different experience [Hunter 1984] >The B12 must be administered in the form of injections since >oral B12 is not absorbed in these patients. Some forms of cobalamin may be more advantageous than others. Although cyanocobalamin is the traditional form available hydroxocobalamin maintains higher serum levels [Hall 1984] and intracellular levels [Chu 1993][Note 1]. In Japan methylcobalamin is being used for neurological and neuropsychiatric conditions. "A vogue for the oral and parental administration of methylcobalamin (Methylcobal) to patients with neurologic and psychologic disorders has arisen in Japan in recent years. The practice is without rigorous scientific justification; however, anecdotal reports persist of unusual benefits in individual cases." [Beck 19??] [Note 2]. "It is of interest that methylcobalamin is widely prescribed in Japan for various peripheral-nerve disorders. The Japanese literature has demonstrated the value of methylcobalamin in many cases but has not shown whether it is superior to cyanocobalamin or hydroxocobalamin." [Beck 1988] A recent in vitro study showed no MeCbl advantage. [Chu 1993] >I have seen cases that were misdiagnosed as MS. Once suspected, >the disease is easily diagnosed by Schilling test, in which >labelled B12 is given orally and checked for in the urine. If >the labelled B12 is not absorbed, you have the problem and need >the shots. The Schilling test is not always certain [Dawson 1984] and "... neurologic deficits occur not only in classic cobalamin deficiency but also in subtle or atypical cobalamin deficiency states in which anemia is absent and Schilling test results are normal." [Karnaze 1990] or "Even a normal serum cobalamin level or a normal result on the Schilling test may occasionally be associated with such a neurologic disorder." [Lindenbaum 1988] and other standard tests exhibit variable precision "Currently, the standard test used to diagnose vitamin B12 deficiency is the 'serum B12 level' ... . The standard test used to diagnose that a given vitamin B12-deficient patient has pernicious anemia ... is the Schilling test ... . All ... of these tests fail in a substantial number of cases, hence the need for newer tests. Millions of people develop these deficiencies, with standard tests artifactually normal ... ." [Herbert 1985] Deficient blood cells display aberrant morphology and this was the most notable sign before modern tests. The ruling concept for many years was that this change in blood cell morphology was sufficient to signal cobalamin status of all cell types. When this was found to be mistaken a cyclic process ensued, definitive test - exceptions - the next definitive test. The aphorism "It's not what you don't know that hurts you, it's what you think you know but don't." may apply here. Much is unknown about cobalamin system function in diverse cell types. "Research in the next few years will also aim to assess the frequency of hidden deficiency of vitamin B12 and/or folate, particularly of selective such hidden deficiency in one cell line or tissue but not another, ... ." [Herbert 1985] >Of course, many MS patients are given the shots for insufficient >reasons also. Apparently many patients are given parenteral cobalamin for insufficient reasons [Fraser 1983]. But perhaps this reflects the inadequacy of existing tests and concepts and the summary dismissal of partial response. A number of researchers note, in passing, this possibility "... patients with unexplained neuropsychiatric disorders ... a course of cobalamin therapy should be strongly considered, even in doubtful cases." [Lindenbaum 1988] "Could it be that the many cobalamin injections given over the years for vague symptoms were in fact justified?" [Beck 1988] "Although some of the patients studied have seemed to do well on vitamin B12 therapy (Reynolds, unpublished data), such uncontrolled observations are notoriously unreliable in MS." [Reynolds 1992a] "The fact is that for some 30 years there has been a vogue for treating MS with injections of vitamin B12. Although this is done for placebo purposes, this was not the original intention, and furthermore, some patients are impressed with their neurological benefit." [Reynolds 1992b] and patients have of their own accord discovered cbl "...five more patients with R binder abnormalities have been identified. Two of them have normal neurologic function. A third, who is stated to have multiple sclerosis, has refused further medical workup. However, her symptoms have remained relatively stable over more than 20 years, during which she has received vitamin B12 therapy" [Sigal 1987] _Missing - understanding clinical heterogeneity_ Given the complexity of the molecular mechanism involved in the cobalamin system a clinical heterogeneous picture is inevitable. Rigid etiological concepts may be premature and confound an optimally helpful diagnosis. For instance conditions with a primary hereditary component may not be clinically apparent at birth or even in the first decade but may appear much later. "We describe a patient in whom neurologic symptoms developed when she was 21 years old and were misdiagnosed as symptoms of multiple sclerosis because the low serum cobalamin level and malabsorption expected in acquired cobalamin deficiency were absent. This case report shows that hereditary disorders of cobalamin metabolism that are mild or delayed in expression can be responsible for neurologic symptoms appearing in adults, and should be suspected in all patients with neurologic syndromes of obscure origin, regardless of the patient's age." [Carmel 1988] "In this report, we describe an adolescent girl with progressive dementia and myelopathy secondary to a familial intracellular defect of B12 (cobalamin C mutation), whose symptoms and biochemical abnormalities improved markedly after she received large doses of hydroxocobalamin. The patient was a 14-year-old girl who had been a straight-A student and in excellent health until one year before admission. ...The frequency of these inherited cobalamin disorders is not known. ... They raise the intriguing possibility of the existence of other, heretofore undiagnosed and treatable cases of cobalamin defects." [Shinnar 1984] _Unknown mechanisms_ I will only note in passing that in my opinion there are some interesting anomalies regarding the basic functionality of glycoproteins (particularly the R binders ) that bind cobalamins both in mammalian systems [Hall 1981,1975] and unicellular marine eukaryotes [Droop 1968, Pintner 1979, Davies 1985]. Perhaps unicellular eukaryotic systems will prove useful to compare and contrast the functionality of glycoproteins that bind cbl. _Cost Benefit Risk_ The cost and risk would appear to be relatively low but the benefits may also be low benefit = number helped x improvement Of course this is the social view, if you are one of the lucky ones helped the equation looks different. Cost Material - $30.00/30 injections ( Note 1 ) Labor - $15/injection physician? $0 prescription for home use Benefit Patients - Not easily quantified with existing data, most probably some small subset of MS patients. Studies in the literature are conducted on a population attending academic medical centers. To what extent does the medical center population resemble the general population? What percentage of MS diagnosed patients have been diagnosed at academic medical centers? Research - If a subpopulation of cobalamin responsive MS patients is discovered by empirical trials of cobalamin then further formal studies of this group may shed light on basic mechanisms. Risks Anaphylactic reaction [Ugwu 1981] Mask folate deficiency Mask or exacerbate other conditions ?? Psychological - majority realize no benefit for effort _Summary_ It may be that fixed ideas are keeping a small but significant number of people suffering neurological/psychiatric problems from beneficial treatments with cobalamins. Some elements of the research community are showing a renewed interest in the relationship between cobalamin disorders and neurological disorders such as MS. Very high levels of serum cobalamins created by 1 mg./week injections of hydroxyl[note1] or methyl[note2] cobalamin may ameliorate symptoms of neurologic/psychiatric conditions resulting from yet unknown dysfunctions in the complex molecular mechanism related to cobalamins and the glycoproteins/proteins that bind cobalamins. _References and notes_ Beck,WS (19??). Cobalamin Patterns in Man. pg.21 In: ??? (notes incomplete) Beck,WS (1988). Cobalamin and the nervous system. N. Engl. J. Med. 318(26):1752-4. Carmel,R (1988). Hereditary defect of cobalamin metabolism (cblG mutation) presenting as a neurologic disorder in adulthood. N. Engl. J. Med. 318(26):1738-41. Chu,RC (1993). The methylcobalamin metabolism of cultured human fibroblasts. Metabolism: Clinical and Experimental 42(3):315-9. Dawson,DW (1984). Malabsorption of protein bound vitamin B12. Br. Med. J. (Clin. Res.) 288(6418):675-8. Davies,AG (1985). Vitamin B12 binding by microalgal ectocrines - dissociation - constant of the vitamin - binder complex determined using an ultrafiltration technique. Marine Ecology Progress Series 21:267-73. Droop, MR (1968). Vitamin B12 and Marine Ecology: IV The Kinetics of uptake, growth and inhibition in monochrysis lutheri. J. Mar. Biol. Assoc. U.K. 48:689-733. Fraser,RC (1983). Audit of the use of vitamin B12 in general practice. Br. Med. J. (Res.Ed.) 287(6394):729-31. Foulds,WC (1969). The optic neuropathy of pernicious anemia. Arch. Ophthalmol. 82:427-32. Hall,CA (1975). Transcobalamin I and II as natural transport proteins of vitamin B12. J. Clin. Invest. 56:1125-31. Hall,CA (1981). Congenital disorders of vitamin B12 transport and their contribution to concepts II. Yale J. Biol. Med. 54:485-95. Hall,CA (1984). The availability of therapeutic hydroxocobalamin to cells. Blood 63(2):335-41. Herbert,V (1985). Biology of Disease: Megaloblastic Anemia. Laboratory Investigation 52(1):3-19. Hunter,GN (1984). Characteristics of patients found not to have multiple sclerosis.[letter] Can. Med. Assoc. J. 131(9):1014. Karnaze,DS (1990). Neurologic and Evoked Potential Abnormalities in Subtle Cobalamin Deficiency States, Including Deficiency Without Anemia and With Normal Absorption of Free Cobalamin. Arch. Neurol. 47:1008-12. Lauer,K (1986). An evaluation of laboraroty investigations in patients with multiple sclerosis. J. Chron. Dis. 39(10):767-74. Lindenbaum,J (1988). Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. New Engl. J. Med. 318(26):1720-28. Murray,TJ (1984). Characteristics of patients found not to have multiple sclerosis. Can. Med. Assoc. J. 131(4):336-7. Parmentier,Y (1979). The intraluminal transport of vitamin B12 and the exocrine pancreatic insufficiency. Proc. Soc. Exp. Biol. Med. 160(4):396-400. Pintner,IJ (1979). Vitamin B12 binder and other algal inhibitors. J. Phycol. 15:391-98. Reynolds,EH (1992a). Multiple sclerosis and vitamin B12 metabolism. J. Neuroimmunology 40:225-30. Reynolds,EH (1992b). Vitamin B12 metabolism in multiple sclerosis. Arch. Neurol. 49:649-52. Rosenberg,LE (1980). The inherited MMA's: A model system for the study of vitamin metabolism and apoenzyme-coenzyme interactions. In: Transport and Inherited Disease, Belton, NR and Toothill, C editors. Schneider,Z (1987). Comprehensive B12 : chemistry, biochemistry, nutrition, ecology, medicine. De Gruyter (probably the most comprehensive reference on cobalamins) Sigal,SH (1987). Plasma R binder deficiency and neurologic disease. N. Engl. J. Med. 317(21):1330-32. Shinnar, S (1984). Cobalamin C mutation (methylmalonic aciduria and homocystinuria) in adolescence. N. Engl. J. Med. 311(7):451-4. Sigal,SH (1987). Plasma R binder deficiency and neurological disease. N. Engl. J. Med. 317(21):1330-32. Ugwu, CN (1981). Anaphylactic reaction to B12 appearing after several years therapy. Age and Aging 10(3):196-7. White,WB (1981). Pernicious Anemia Seen Initially as Orthostatic Hypotension. Arch. Intern. Med.141:1543-44. Note 1: Hydroxycobalamin - While cyanocobalamin is most readily available in the USA, pharmacies can order hydroxycobalamin (e.g. Rugby Hydroxocobalamin Injection, USP 1000 mcg/ml. 30ml vial. approx. $15.00). Tuberculin syringes 1 cc 25g 5/8 > $.50 apiece Note 2: Methylcobalamin ( MeCbl, MethylB12) - For use in the USA a physician must have an IND from the Food and Drug Administration. MeCbl is photolabile so use most likely requires special procedures (I presume darkroom redlight conditions for handling, drawing up injection and administration). Some pharmaceutical preparations of methylcobalamin [Schneider 1987] Methylcobal(Eisai,Japan): vial 5 mg. Methylcobalamin(Sefton AG, Switzerland) vial 1g, 5g,10g, 25g Methylcobaz(Labaz, France): caps. 3 mg. ... ------------------------------------------------------------------ Terry Gritton "I think that it is much more interesting to live not knowing, than to have answers which might be wrong.I can live with doubt, and uncertainty, and not knowing.I have Interests: approximate answers, and possible beliefs signal glycoproteins and different degrees of certainty about logic programming different things, but I'm not absolutely sure of anything." Richard Feynman From alt.support.mult-sclerosis Sat Jan 1 21:56:31 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!usenet.ins.cwru.edu!usenet.mcs.kent.edu!Nimitz.mcs.kent.edu!jhusvar From: jhusvar@Nimitz.mcs.kent.edu (John Husvar) Newsgroups: alt.support.mult-sclerosis Subject: Re: Swank Diet (my 2 cents worth) Date: 1 Jan 1994 17:49:56 GMT Organization: Kent State University Lines: 107 Message-ID: <2g4d45$3tv@usenet.mcs.kent.edu> References: <1994Jan1.112511.15162@inca.comlab.ox.ac.uk> NNTP-Posting-Host: nimitz.mcs.kent.edu Status: O In article <1994Jan1.112511.15162@inca.comlab.ox.ac.uk> boris@kimura.jr2.ox.ac.uk (Boris The Cat) writes: >P.S. A quick note about that job I applied for. They would have (Deleted conversation about Fatty Acids, etc.) >offered it to me if I hadn't mentioned the MS. Of course I was >legally obliged to - and I did. Now no-one knows what to do. >Unfortunately there are no anti-discrimination laws protecting people >with disabilities in this neck of the woods. The powers that be want >me to do a few "motor function" and "memory" tests, but it's all up in >the air at the moment because everyone is on holiday. Oh, it can be a >cruel world at times :-). Yes, it surely can be so. I realize now that my "advice" about the Americans with Disabilities Act was inappropriate for Boris' situation. It seems that USA laws just don't apply in the UK. Wonder why that is? :-) I've just been lurking about here for the past several weeks waiting for the results of my examinations at the Mellen Center for MS Research and Treatment at the Cleveland Clinic. Well, they are in; it _is_ MS. After more than 2 years wondering, being diagnosed, undiagnosed, poked, prodded, sent to psychologists, Physical Therapists, Occupational Therapists, feeling my legs deteriorate in strength, losing my balance, being nearly blind for 6+ weeks, and so on and on and on, I'm almost euphoric to _finally_ have (at least) a label to stick on it. Everyone is cordially invited to take a breath now. :) (I _do_ tend to run on at times) Anyway, Boris, here in Ohio, USA, the cruelty (?) is that one can be financially destroyed while awaiting diagnosis and _for_ (it seems) trying to get oneself back into the workforce. For example: (I'll try not to be too polemical here) When my physical condition deteriorated to the point I felt it unsafe to continue climbing up onto buildings, machinery, etc. and I began reacting to the extreme heat in many of the places I had to work, I approached my employer with a request for changes to my job duties. I was told, in effect, that, if I could not do the whole job, I should not try to hold on to it and keep someone who could from having it. Well, I tried my best to keep up until I was injured by a defective piece of test equipment, possibly avoidable if my reactions to heat had not reduced my attention, possibly not. Who knows? After several months off work from that,(lost sensation and developed spasticity in my left arm and hand) my employer "released" me from their employ. I appraoched the Ohio Bureau of Vocational Rehabilitation which eventually agreed to help me finish my college education. (Good news) I also approached Social Security for Social Security Disability so I could pay living expenses while finishing my education. Well, I'm still in the appeals process for that. ( >2 years now) They denied my claim because," A person who is eligible for rehabilitation can obviously do some gainful work." (bad news) While I'm not unalterably opposed to working and attending school, getting a job would result in my being ineligible for rehabilitation. (Not certain but sufficiently probable that I'm reluctant to take the risk) As well, the several employers I've approached have been "excited by my resume'" but have seemed just a bit put off when I wheel into their personnel offices. No one says anything directly, but it's fairly clear that I'mabout as likely to hear from them again as a snowstorm is in Midwestern Gehenna. :) None the less, I try to appear competent, confident, polite, and professional. So far I haven't received any offers. Disability concerns and rehabilitation over here are a "Catch-22" of in- coordination and governmental inefficiency. the Americans with Disabilities Act is a Good Thing (tm) in my opinion, but many US businesses are past masters of the art of the "work-around." Socially, disabled people are not subjected to much active discrimination but, economically, passive discrimination is at least as harmful. Right now, my wife (also disabled) and I are living on approximately US$200 per month, food stamps, and marginal medical benefits. (The Cleveland Clinic bills are "under consideration.") That amount doesn't even meet basic housing and utilities costs so we have been borrowing from our church to bring the ends somewhere near to each other. (We live in a mortgaged home that is cheaper than any rental housing in the region. It's a bit of a dump, but it's a clean dump and we fix up as much as we can as we can. Also, someday, it will be _our_ dump. :) Well, I ramble on, don't I? The final diagnosis is in. I _do_ have either Chronic-Progressive MS.(Or... I'm having the longest exacerbation on record.:) The Visual Evoked Potential, Spinal Fluid Studies, and Urodynamics (OUCH!) tests together add up to MS that shows very few brain lesions. My neurologist says that puts me in the "rare" category. I'm going back to the Mellen Center for a Neuro-Psychological Evaluation next month to test for (or confirm) some cognitive and perceptual problems. Also, the Dr. there says I should consider counselling as all the frustration,anxiety, and depression that accompanies MS and diagnosis problems may have some effect on my symptoms or vice versa, the symptoms oftem produce frustration, anxiety, and depression. Chicken or Egg situation, anyone? This newsgroup has been most helpful for me in many ways and, Boris, believe me; there is at least one person around here who knows exactly what you're going through with employment, etc, probably many. My best regards to all, John -- John Husvar, Art History, Kent State University (Yes, THAT Kent State :) jhusvar@mcs.kent.edu - john.husvar@akron-info.com - bf910@cleveland.freenet.edu Pres. ICBAGWA (Int'l Confraternity of Bad-Ass Gimps With Attitudes) From alt.support.mult-sclerosis Sun Jan 2 20:07:14 1994 Path: klaava!news.funet.fi!sunic!pipex!uunet!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 9050483 X-Genie-From: R.KOREJWO Message-ID: <9401021522.AA06868@relay2.geis.com> Date: Sun, 2 Jan 1994 14:49:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Neiper/4-AP Lines: 153 Status: O -=Manohar Singham=- Re: Dr. Hans Nieper I think you're speaking specifically about the use of Calcium aminoethyl phosphate (calcium EAP) and calcium orotate(CO). CO and Calcium EAP are calcium salts of synthetic organic compounds. I haven't heard about Dr. Hans Neiper for a long time. I thought that the FRG had closed that clinic down. The treatment goes back about 15 years so I don't have any current data on it. To the best of my recollection, it was considered as a therapy for any inflammatory or autoimmune disease. I know of no data, beyond that provided by Dr. Neiper, which purported to prove that the treatment would have any effect on MS. It is a very expensive therapy because you have to deal not only with the cost of therapy, but with the cost of travel for the patient and the travelling companion. When I was given information on this many years ago, there was a gasthaus, conveniently run by a relative, which was recommended at additional cost, of course. Dr. Nieper has been advocating these two substances, sometimes used in conjunction with phosetamin, for many years as a treatment for any number of autoimmune diseases. Some years ago the German Multiple Sclerosis Society correctly advised MS patients against becoming involved with this therapy because it was worthless. The Neiper's clinic was also sited for false (re-read that FALSE) claims that it was the only treatment for MS that was accepted in the Federal Republic of Germany(FRG). I think the FRG got that part stopped at least. The treatment for MS, as I recall, involved 5 or 6 injections over a period of a week followed by injections every other day. There probably was a "two week plan" for overseas patients. Follow-on therapy required daily oral doses for the rest of the patient's life. Fortunately, Dr. Nieper's clinic had a mail order service. I believe that a "revitalization" injection sequence was required annually or bi-annually depending on the patients ability to pay. There was one study back in 1966. It was done in Aachen, Germany. It clearly failed to prove that the course of the disease was changed by the therapy. If you're interested in cost, when I last heard about it, the cost were something like 3500 DM (approx $2100 which included 2 weeks for one person at the Gasthaus (inn) which was affiliated with the clinic. That, of course, does not include round trip air fare from wherever you are and Gasthaus accommodations for a spouse or companion. It's a long way to go for something worthless when you can get something worthless for a lot less money. I would definitely try to get some real evidence that the therapy has value before spending the kind of money you're talking about here. Such data did not exist before and I doubt that it does now. This is very old stuff so I'm not sure that I can even find anything on it in the medical libraries. Sorry, I've long ago given up on E-mail for questions like this because I end up sending the same message 20 times. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -=Tom Hogarth=- Re: "...Maybe it would be good for someone to give a description of 4AP for those who are new to this group or forgetful (like me." I just had to post an update on 4AP on another net so I'll provide that for your info. 4AP- 4-aminopyridine was used first, as I recall, in the treatment of myasthenia gravis. It's from a family of relatively simple chemicals that bind to potassium ions. The net result of this is that 4-AP will improve nerve conduction. In simple terms it reduces the transmission resistance to nerve "pulses". (They are really potassium/sodium waves.) Since transmission deterioration is a common problem in MS it was only natural that this found it's way into the prospective therapies for MS. The first attempts were somewhat interesting in that they precipitated serious seizures. Drugs are generally equal opportunity employers. The effect is global -i.e in areas where greater conduction is desired and in areas where greater conduction is not desired. This was circa 1988, I believe. With such adverse results, there was a new sense of caution. Subsequent work attempted to find a threshold were the positive results could be achieved without the negative effect. Two facts emerged. First, 4- aminopyridine seemed to work best on patients who were temperature sensitive. Second, 4-aminopyridine had effects with a very limited time period of favorable result. At doses which avoided seizures, periods of 1- 5 hours were common. During the last 4 years there have been a number of studies which attempted to find some useful way to extend the period of beneficial effect. In "Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis", Ann Neurol 1990 Feb;27(2):186-92, Davis FA Stefoski D Rush J demonstrated that measurable improvement could be made at doses as low as 10 mg. Drug effect was detected within 60 minutes but duration lasted only 4-7 hours. This was followed with a study by Bever CT Jr Leslie J Camenga DL Panitch HS Johnson KP entitled "Preliminary trial of 3,4-diaminopyridine in patients with multiple sclerosis." Ann Neurol 1990 Apr;27(4):421-7. This was a conservative trial of just 10 patients with equally conservative results. There was a substantial amount of interest when D Stefoski, F Davis et al. published "4-Aminopyridine in multiple sclerosis: prolonged administration." in Neurology 1991 Sep;41(9):1344-8. At last we had broken the back of the relatively short-lived effect. Unfortunately, the definition of the word "prolonged" became clear. 4-Aminopyridine was administered in one to three daily doses at 3 to 4 hour intervals over 1 to 5 days. I don't know about you, but when I saw "prolonged" I had something a little longer in mind. The study to prove that smaller multiple doses could be used with relative safety. Thirteen of the 17 patients (76%) given 4-AP showed clinically important motor and visual improvements compared with three of nine in the placebo group. Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo. By this time people were getting more bold. "The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study" was published in Ann Neurol 1992 Aug;32(2):123-30 While the trial was not as definitive as some had hoped, it involved 70 patients in multiple doses over a period of as long as 12 weeks. Unfortunately, more than 16% of the patients being given 4-AP suffered an unexplained decline of greater than 1 EDSS point. This is not an insignificant fact. A more recent reference "Increased visual impairment after exercise (Uhthoff's phenomenon) in multiple sclerosis: therapeutic possibilities." (Eur Neurol 1992;32(4):231-4) This study concentrated on the heat factor of increased exercise and consideration of whether 4-AP could compensated for it. It was a very small study (2 patients) and it was not conclusive. The most recent reference that I have is "4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety." published in Clin Neuropharmacol 1993 Jun;16(3):195-204. This was a bilateral study involving both oral and IV administration. This was a well done double blind placebo-controlled trial. The papers results are summarized in the following extract: "The use of 4-AP in oral doses three times a day showed a large variation and fluctuation in serum levels. After 12 weeks of oral treatment (maximum daily dosage 0.5 mg/kg body weight), a statistically significant improvement was found for the smooth pursuit gain of the eye movements .... The amount of improvement was significantly related to 4-AP serum levels (p = 0.0013). Side effects after intravenous 4-AP occurred frequently and were very troublesome (pain in infusion arm, dizziness). Side effects during oral treatment (dizziness, paresthesias) were very mild and occurred 30-45 min after intake of the medication and could be related to high serum levels." The work was performed Van Diemen HA Polman et al and reported to the Department of Neurology, Free University Hospital, Amsterdam, The Netherlands. There is a new found tendency to press forward with the use of 4-AP in clinical setting. To some extent this is based on the old axiom that "half a loaf is better than none." Although, in the case of 4-AP, I would think that the axiom would be better stated as "one-tenth of a loaf is better than none." -Rick From alt.support.mult-sclerosis Wed Jan 5 16:25:24 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!usenet.ins.cwru.edu!po.CWRU.Edu!mxs24 From: mxs24@po.CWRU.Edu (Manohar Singham) Newsgroups: alt.support.mult-sclerosis Subject: Interferon Beta (Betaseron) trials outside the USA Date: 5 Jan 1994 02:17:51 GMT Organization: Case Western Reserve University, Cleveland, OH (USA) Lines: 15 Message-ID: <2gd80f$lk8@usenet.INS.CWRU.Edu> Reply-To: mxs24@po.CWRU.Edu (Manohar Singham) NNTP-Posting-Host: slc5.ins.cwru.edu Status: O Has the drug Interferon Beta (also known as betaseron) been tried outside the USA and how has it performed with respect to MS? p.s. I would like to thank all those who took the time to respond to my earlier question regarding Hans Nieper. I have forwarded the responses to my friend. This board is very invaluable. I am trying to absorb all the information. I am not very well informed on the subject of MS (as yet). Is there some sort of FAQ for MS so that newcomers to this board can get up to speed on the topics being discussed? -- Mano Singham Physics Department, Case Western Reserve University Cleveland, OH 44106-7079. (Office: Rockefeller 330C, Telephone: (216)368-8844) From alt.support.mult-sclerosis Sat Jan 8 11:43:29 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 0616146 X-Genie-From: R.KOREJWO Message-ID: <9401080050.AA26562@relay2.geis.com> Date: Sat, 8 Jan 1994 00:30:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: anti T cell/temps Lines: 36 Status: O -=Gale Snow=- Re:"...what i am waiting for is anti-cd4 tcell monoclonal antibodies. i was in a study at stanford..." Comment: Maybe I missed something or you've combined two therapies. The anti-T cell/T cell work was a product of two approaches. The first was the peptide injection study performed by Halina et al. at VAMC/Portland and the U of Oregon. The second was the recent Belgium work by Zwang et al. which was a replication, in extended form, of the work by Weiner and Hafler in 1991. The results of this study have been striking. To my knowledge Steinman was working predominantly on a monoclonal antibody for "jacketing" T-4 cells to make blood brain barrier passage more difficult. I was not aware that any anti-T cell/T cell work was being done by Steinman. Was this reported? I think it would be a little premature to approve this prior to a phase II trial. It is possible that I've just confused what you said. If so, sorry. -Rick -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -=Gerald Gold=- Re:"...I have problems when the temperature drops below about 8 degrees (Celsius). that point, my legs shiver and become spastic..." Comment: I and a number of other MSers have experienced a rather disturbing problem which occurs for some at temperatures as high as 5 degrees C. You indicated "spasticity" and I would like to confirm that you meant rigidity when you say "spastic"(ity). A number of us experience a convulsive response as an alternative to the customary shiver. This is clearly not spasticity but the meaning of the word has taken more than a little abuse and I want to be sure that you are referring to rigidity. Thanks -Rick From alt.support.mult-sclerosis Sun Jan 9 18:08:41 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 2531991 X-Genie-From: R.KOREJWO Message-ID: <9401090116.AA05723@relay2.geis.com> Date: Sun, 9 Jan 1994 01:07:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Belgium study Lines: 5 Status: O Carolyn I'm sorry, but I didn't know you were looking for the Belgium paper: Science, 10 September 1993;261:1451-54 -Rick From alt.support.mult-sclerosis Tue Jan 11 11:43:42 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!darwin.sura.net!sgiblab!sgigate.sgi.com!olivea!koriel!news2me.EBay.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: Re: anti T cell/temps Date: 10 Jan 1994 21:55:40 GMT Organization: Sun Lines: 30 Message-ID: References: <9401080050.AA26562@relay2.geis.com> NNTP-Posting-Host: chrysos Status: O In article <9401080050.AA26562@relay2.geis.com> Richard Korejwo writes: >Re:"...what i am waiting for is anti-cd4 tcell monoclonal antibodies. i > was in a study at stanford..." > Comment: Maybe I missed something or you've combined two therapies. The > anti-T cell/T cell work was a product of two approaches. The first was the > peptide injection study performed by Halina et al. at VAMC/Portland and the > U of Oregon. The second was the recent Belgium work by Zwang et al. which > was a replication, in extended form, of the work by Weiner and Hafler in > 1991. The results of this study have been striking. To my knowledge > Steinman was working predominantly on a monoclonal antibody for "jacketing" > T-4 cells to make blood brain barrier passage more difficult. I was not > aware that any anti-T cell/T cell work was being done by Steinman. Was > this reported? the study i was in at stanford was with dr steinman where i and others were infused with anti-cd4 tcell monoclonal antibodies. my last infusion was around 5/93, i think, and i had received several such infusions over a 2-3 year period. i believe there was a report in nature? but i don't have the details with me here at work. yes, it is premature to approve. (but i wish they'd hurry) i was in a phase I trial, the phase II part is taking place in england (or already took place). it is apparently also continuing in the netherlands and in austrailia. the monoclonal antibodies were manufactured by a company called centocor (in pennsylvania). i don't believe it was related to the peptide work. whatever, my cd4 tcell count was reduced at times to less than 200. (isn't it normally close to 1000?) so this is a good thing, maybe better than betaseron from a patient perspective at least. gale snow From alt.support.mult-sclerosis Thu Jan 13 10:59:07 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!agate!ames!koriel!news2me.EBay.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: Re: T cell/hiccups/steroids Date: 12 Jan 1994 19:48:03 GMT Organization: Sun Lines: 61 Message-ID: References: <9401120313.AA20505@relay2.geis.com> NNTP-Posting-Host: chrysos Status: O In article <9401120313.AA20505@relay2.geis.com> Richard Korejwo writes: >-=Gale Snow=- > >I'm still lost here. I didn't find a Nature reference for Steinman but I > might have missed it. The most recent thing that I saw from Steinman was a > provocative paper which cast doubt on the V region hypothesis. > >Wilson DB Steinman L Gold DP > The V-region disease hypothesis: new evidence suggests it is probably > wrong. > Immunol Today 1993 Aug;14(8):376-80; discussion 380-2 > >The time frame you suggest is consistant with the Steinman's work on > monoclonal antibody jacketing of T4 cells. You could be in a fortunate > location if the anti-T cell/T cell work gets a phase II study. > >Regards Centacor - the only monoclonal antibody work in MS that they are > persuing, according to my contact, was "CENTARA" which is an IgG monoclonal > antibody. She could be wrong. Who knows? At any rate, I agree that anti- > T cell work is getting a lot of exposure. I don't know of any Phase II > work which you suggest. Do you have any other details? > ... rick, (i'm trying!) it's hard because my info comes from direct consultation with steinman, and papers (informed consent given to participate in the study at stanford) i've signed, but not from any research i've been doing. i'm just living with ms. i found the nature article - actually in the letters section from vol. 362 dated 4 march 1993. "Selection for T-cell receptor Vb-Db-Jb gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis." (but don't claim to understand this article!) note that his study of monoclonal antibodies (anti-cd4 tcell) was completed summer of last year. that was the completion of phase I (toxicity) of the trial that i participated in. phase II is (or was) taking place in england, and i've heard that they are in the process of writing up their findings while the study continues elsewhere (netherlands, australia). i've actually exchanged email with someone in the netherlands who is aware of an anti-cd4 tcell study occurring near his location (and follows the alt.support.mult-sclerosis group). this could be part of the phase II double blind testing that is being done. hmm, maybe it was just the jacketing, but this is the first i've heard of that terminology. would jacketing reduce the cd4-tcell count as well? and centocor, i had been infused with a product of theirs (the anti-cd4 monoclonal antibody) at the time they were trying to get approval for a drug that people were dying from (2,3 years ago) this was unrelated to ms but i can't remember the exact story. i do remember being concerned about it at the time. they were having major financial difficulties because of that (no wonder!). that may be when steinman started dealing with immulogic (?), another company, for help in his work. anyway this is all in the past tense. i guess it just came up when i compared betaseron treatments (which i am now doing) with the treatments i had received at stanford. i do feel very fortunate to be living near stanford. steinman has apparently identified the tcell that damages myelin and is doing animal studies to knock out just that one tcell. this seems much better than knocking out the entire immune system like steroids (prednisone) do. so i'm just waiting to hear from him to sign me up for his next study! gale snow From alt.support.mult-sclerosis Fri Jan 14 14:17:14 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 8104513 X-Genie-From: R.KOREJWO Message-ID: <9401140152.AA21103@relay2.geis.com> Date: Thu, 13 Jan 1994 23:23:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Patent EP0463101 Lines: 10 Status: O The European Patent Office has just granted a Patent No.EP0463101. The patent is entitled Vaccination and Methods Against Diseases Resulting from Pathogenic Responses by Specific T-Cell Populations. The patent names Drs. Mark D. Howell, Steven W. Brostoff and Dennis J. Carlo, as the inventors. All are employed in the European labs of Autoimmune Disease Technology of Carlsbad, Calif. I am unable to get specific information on the process but my informal enquiries suggest that this is a process similar to the previously documented antiT cell/T cell work. Does anyone have any details on this? -Rick From alt.support.mult-sclerosis Sat Jan 15 13:57:20 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 1483271 X-Genie-From: R.KOREJWO Message-ID: <9401150244.AA19189@relay2.geis.com> Date: Fri, 14 Jan 1994 23:19:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: anti-T/cold/multiple Lines: 56 Status: O -=Gale Snow=- Re:"...(i'm trying!).." Comment: And doing a fine job at it. Don't get the idea that I'm saying anything else. Thanks for the Nature reference. It narrows the field a little. There are a number of theories to explain the "anti T cell" effect. The concept that one creates a true anti T4 T cell is one. There is an interesting theoretical presentation by Antonio Lanzavecchia (Science, 14 May 1993 260;937-44) which postulated that the presenting cell was the key to triggering a specific response. This could explain some of the results. The original work by Weiner and Hafler noted the effect of induced "anergy" from "attenuated" (irradiated) T cells presenting with MBP. They did not follow this up at the time because they were headed in another direction. The VAMC Portland/UofO peptide study used a subset of peptides in IM injection and was a little vague on what their anti-T cell T cell really was. It appears that something is happening but I'm not certain that there is one mechanism. In some cases (B&W,Belgium) we can trace to the existence of a true antiT cell/T cell. In some cases the evidence points more to an effect that could be attributed to a antiT cell/T cell rather than evidence that same existed. The next few months could be interesting. Re:"...phase II..." Comment: I have not seen a comprehensive phase II proposed but, then again, I might be missing something. The only work that I've seen was an extension of the original Belgium study. Re:"...i had been infused with a product of theirs (the anti-cd4 monoclonal antibody) at the time they were trying to get approval for a drug that people were dying from (2,3 years ago)..." Comment: Dead right and no pun intended. If you take examples like that and the recent Hep B debauchee, it is pretty clear why the FDA better be there. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- Susan, Bruce Re:"...layers for warmth..." Comment: This sounds OK if you don't have fatigue as a major factor in MS. During the one year I spent up North AD (after diagnosis) my wife would help me don the boots, sweater, overcoat, gloves etc. and when we got me finally ready to go outside I was so tired I couldn't do anything except take all the outer wear off and lay on the floor to recover. We tried it about 6 times and ended up laughing *everytime. I never did make it out that Winter except for a few rides in the car. If you don't have a sense of humor, don't get MS. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- Bruce, Sejal Re:"...Maybe if we are susceptible to one autoimmune disease we are susceptible to others..." Comment: I have seen this go much further. CM Poser suggested that you never have just one autoimmune disease. -Rick From alt.support.mult-sclerosis Sat Jan 15 14:02:04 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 5540057 X-Genie-From: R.KOREJWO Message-ID: <9401150420.AA28564@relay2.geis.com> Date: Sat, 15 Jan 1994 00:19:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: SA/colchicine Lines: 28 Status: O -=Gale Snow=- Re:"...Scientific American magazine, September 1993..." Comment: It's a good reference and since you mentioned it, examine the diagram on page 110. The right portion of that diagram describes the "jacketing" process and I believe you will also find Stanford has performed well there. If you examine the last para on page 113 you will see where Steinman indicates his involvement with the monoclonal antibody with VLA-4. This is the primary work in BBB passage. At least I have always considered it so. The VAMC Portland/UofO work is mentioned on page 109. This is a very good article and should be a primary read for anyone want to understand some of what is going on. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- Re:"colchicine" Comment:This is a very old drug. I think they put roman numerals on the bottles originally. Colchicine was originally known as Colchicum and, if I'm not mistaken, has a history in ancient Greece. Actually, it's an extract of crocus flowers and, in contemporary times, I think it is primarily used for the treatment of gout. I could get technical about the long list of things it can't do or the very limited list of things it can do. Like a number of other things, it is effective in suppressing EAE and it therefore could be of use to rats. It does reduce the number of T "helper" cells and T "suppressor" cells. It also enhances prostagladin production as well as limits macrophage functions. I know of no use for MS which has ever been demonstrated to be effective. -Rick From alt.support.mult-sclerosis Mon Jan 17 13:54:29 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!cs.utexas.edu!rutgers!concert!news.duke.edu!soc13.acpub.duke.edu!nelson From: nelson@soc13.acpub.duke.edu (Robert E. Nelson) Newsgroups: alt.support.mult-sclerosis Subject: Research on support for MS Message-ID: <2hbm2k$sfo@news.duke.edu> Date: 16 Jan 94 15:21:56 GMT Reply-To: nelson@soc13.acpub.duke.edu (Robert E. Nelson) Organization: Duke University; Durham, N.C., USA Lines: 13 NNTP-Posting-Host: soc13.acpub.duke.edu Status: O I am a Med Student at Duke University doing research on support systems for people with MS. I am interested in hearing about what people do as their primary means of coping with the stresses of this disease, be it this newsgroup, other support groups, or the like. Please send e-mail to nelson@duke.acpub.edu Thanks so much for your time. Robin Nelson From alt.support.mult-sclerosis Wed Jan 26 14:14:19 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 9450852 X-Genie-From: R.KOREJWO Message-ID: <9401250734.AA09496@relay2.geis.com> Date: Tue, 25 Jan 1994 03:35:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Biogen/Gamma/Beta Lines: 52 Status: O -=MACPHERSON, DOUGLAS=- Re: Biogen product Comment: Biogen is in Phase III testing of their Beta interferon product. I believe there are 300 patients in the study and lead investigator is Lawrence Jacobs MD from the University of Buffalo. It's a double blind, placebo controlled trial with once/week injections IM of 600 MIU. It's a recombinant product. I didn't think they were that close to market but they could be. There was a preliminary marketing agreement with Astra Medico for the European market. Hope this helped. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -=Margret Schuman=- I think I already commented on COP-1 but can add a little on Gamma Globulin. I don't keep historical files but there was a 6 month trial of Gamma run on MS patients some years ago and it netted a general impression that gamma was of little or no benefit for MS. This, in no way detracts from it's effectiveness for other diseases. There was a very small, 10 patient, study done at Beilinson Medical Center, Petah-Tiqva Isreal in 1992. Primary was Anat Achiron MD. It reported a minor exacerbation frequency reduction but was not very definitive. see ARCH Neurology 49;1233-36. I'm sorry I can't give you precise details but the original study was a little while ago and that is all I can recall. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -=Paul Sweeney=- Re:"...The studies seemed to indicate that statistically 1 subject out of 3 receiving the drug realized some diminution in the number of exacerbations they might otherwise have had over time...." Comment: Not my copy - and exacerbation rate does not necessarily indicate relative disability which appeared unaffected. Re:"... will there ever be a point where my physician and I can review my progress, and say "yes, the Betaseron is having a salutary effect..." Comment: To quote directly from the study.(page 659) "...there was no significant change in the EDSS score by treatment arm..." If trained observers could not consistently detect a change in disability after three years of treatment, why would you expect that it would be different for you and your neurologist? The concern over "what if" and "maybe" could well extend to virtually anything. Make a decision and don't second guess it. Good luck on what ever. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -Rick From alt.support.mult-sclerosis Wed Jan 26 14:47:03 1994 Newsgroups: alt.support.mult-sclerosis Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!uunet!world!lazzaro From: lazzaro@world.std.com (joe j lazzaro) Subject: Adaptive Technology Book Message-ID: Organization: The World Public Access UNIX, Brookline, MA Date: Wed, 26 Jan 1994 00:14:17 GMT Lines: 62 Status: O NEW GUIDE DESCRIBES HOW TO ADAPT PC'S FOR THE DISABLED "Adaptive Technologies for Learning and Work Environments" by Joseph J. Lazzaro is a 250 page illustrated guide on how to adapt personal computers for individuals with disabilities. The book concentrates on using computers to access information, which is critical to job and scholastic performance. The book is intended for individuals with visual, hearing, motor, and speech impairments. The text is aimed at end users, office administrators, rehabilitation professionals, librarians, managers, teachers, human resource specialists, computer consultants, network administrators, anyone who must provide reasonable accommodation or adaptive equipment to comply with the Americans with Disabilities Act. The book discusses speech synthesizers and screen readers, magnification systems, braille displays and printers, braille translation software, optical character recognition systems, text telephones, baudot/ascii modems, assistive listening devices, signaling systems, alternative keyboards and input devices, voice recognition systems, keyboard enhancement software, alternative communications systems, environmental controls, and much more. The text also discusses how to convert an adapted personal computer into a library of information by linking with local area networks, accessing online databanks, or using compact disk reference systems. Included are lists of bulletin boards, online services, CDROM providers, as well as public access Internet sites. The book also describes how to select appropriate adaptive hardware and software for any situation, as well as how to furnish training and technical support. Sources of financial aid are also presented. Throughout the book, more than 120 specific adaptive products are described as examples of the innumerable devices available. Practical, how-to- do-it sections explain installation procedures and provide examples of how to interface mainstream and adaptive systems. Extensive appendixes provide names and addresses of useful resources. These include equipment manufacturers, conferences, journals and newsletters. A subject and product index is also included. The book is currently being produced on computer disk for print impaired users by Recording For The Blind. ORDERING INSTRUCTIONS "ADAPTIVE TECHNOLOGIES FOR LEARNING AND WORK ENVIRONMENTS" JOSEPH J. LAZZARO THE AMERICAN LIBRARY ASSOCIATION 50 EAST HURON STREET CHICAGO, IL 60611 PHONE: 312-280-5108 ISBN: 0-8389-0615-X PAGES: 251 PRICE: $35.00 US TOLL FREE ORDER LINE: 800-545-2433 PRESS #7 FROM THE VOICE MENU FOR THE ORDERING DEPT. INTERNATIONAL ORDERING INSTRUCTIONS Eurospan 3 Henrietta Street Covent Garden London England WC2E8LU Phone: 011-44-71-240-0856 From alt.support.mult-sclerosis Wed Jan 26 15:11:05 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 1767278 X-Genie-From: R.KOREJWO Message-ID: <9401260331.AA27531@relay2.geis.com> Date: Wed, 26 Jan 1994 01:29:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: databases etc. Lines: 25 Status: O Just a note on health databases. There are many and my experiences vary. It should be noted that items appear in databases most often when they become a matter of public record. That is frequently months after events take place. Besides the standard medical sources like USNLM, NEJM, Indice Medicine - Elsevier Science Publishers (Amsterdam) maintains an excellent database which was formerly the Excerpta Medical. It is now referred to as EMBASE. I still find Martindale a good general reference on pharmaceuticals. The big problem with most databases is that they do not provide comprehensive data on just one subject like MS and thus need a substantial filter. Searches are often fruitless unless you know other information. Many people are aware, for example, of the recent oral tolerance trials sponsored in part, by Autoimmune Inc. If you did not know that the designation for the antigen was Al-100, searches could be futile. Where is it written that EL-470 is, for example, really our old friend 4-aminopyridine? And on and on..... I find out a lot through personal contacts but that's a pretty imperfect system. -=Phyllis Lugger=- I've tried two responses to you at: LUGGER@PEGASUS2.ASTRO.INDIANA.EDU and lugger@pegasus2.astro.indiana.edu This worked fine two days ago but suddenly it is not acceptable. Suggestions? -Rick From alt.support.mult-sclerosis Sat Jan 29 23:26:50 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!cs.utexas.edu!koriel!news2me.EBay.Sun.COM!seven-up.East.Sun.COM!dr-pepper.East.Sun.COM!missmarple!foliver From: foliver@missmarple.East.Sun.COM (Fred Oliver - SMCC) Newsgroups: alt.support.mult-sclerosis Subject: Biogen's Beta Interferon Date: 28 Jan 1994 18:49:23 GMT Organization: Sun Microsystems Inc. - BDC Lines: 63 Distribution: world Message-ID: <2ibmnj$blk@dr-pepper.East.Sun.COM> NNTP-Posting-Host: missmarple.east.sun.com Status: O ----------------------------------- From the Boston Globe, January 12, 1994 Front Page, BUSINESS section (not Health/Science!) [Transcription errors are mine, of course.] ----------------------------------- Report rockets Biogen stock Firm to seek FDA approval for a drug a year early; shares up 12% By Ronald Rosenberg, Globe Staff ----------------------------------- Stock in Biogen Inc. yesterday soared $5 a share in heavy trading after the company said it would seek federal approval for its beta interferon one year ahead of schedule. The Cambridge-based biotechnology company called an end to clinical tests of the drug, which combats multiple sclerosis, because there was a low dropout rate among patients, indicating there were few or no side effects from the treatments. The announcement sent Biogen's stock to 46 1/4 a share, up 12% for the day on the NASDAQ market. Speaking at a Hambrecht & Quist Life Science conference in San Francisco, Jim Vincent, Biogen's chairman said the critical and final patient trials would be completed next month. Biogen's beta interferon is designed to slow down the progression of multiple sclerosis, a debilitating muscular disease that affects 250,000 Americans. If the US Food and Drug Administration approves the theraputic drug, it could be on the market by late 1995. Vincent's comments prompted Vector Securities to upgrade its rating of Biogen stock. Vincent also said the company's 1993 earnings would be slightly in excess of 90 cents a share and that Biogen would achieve fiscal 1993 revenues of $150 million. Last year the company earned $38.1 million or $1.12 a share on revenues of $135 million. If recombinant interferon is approved, Biogen will face a competitive drug called Betaseron, which was approved for multiple sclerosis treatment by the FDA last spring. It was developed by Chiron Corp, of Emeryville, Calif., and is considered the first effect treatment of the disease. Demand for the drug is so great that a patient lottery for Betaseron prescriptions is oversubscribed. Yesterday's announcement by Biogen prompted Chiron's shares to drop 3 3/4 to close at 83. Betaseron, which is expected to generate $200 million in revenues next year is designed to reduce the disease's debilitating flareups that can cause problems with vision and hand coordination. About 125,000 patients - half the multiple sclerosis population - would be eligible for either the Chiron or Biogen treatments according to David A. Ebersman, a biotech research analyst at Oppenheimer & Co. who estimated the total market at over $1 billion annually. ------------------------------------------------ [At closing on Wed 1/26, Biogen is at 47 1/8, Chiron is at 91 3/4.] Fred Oliver From alt.support.mult-sclerosis Sun Jan 30 11:29:45 1994 Newsgroups: alt.support.mult-sclerosis Path: klaava!news.funet.fi!sunic!EU.net!uunet!well!casey From: casey@well.sf.ca.us (Kathleen Creighton) Subject: Methotrexate Message-ID: Sender: news@well.sf.ca.us Nntp-Posting-Host: well.sf.ca.us Organization: The Whole Earth 'Lectronic Link, Sausalito, CA Date: Sat, 29 Jan 1994 16:29:21 GMT Lines: 71 Status: O CHEMOTHERAPY Copyright 1993 National Multiple Sclerosis Society The literal meaning of the term 'chemotherapy' is 'to treat with a chemical agent'; however, it generally refers to the potent cytotoxic (cell killing) agents that are prescribed for some forms of cancer. These drugs not only kill tumor cells, but can destroy the body's own normal cells as well. The cells that are most vulnerable to cytotoxic agents are those which grow and divide rapidly. Among those affected are cancer cells, hair and intestinal cells, blood cells, and also the white cells comprising the immune system. The rationale for the use of chemotherapy to treat MS stems from the fact that MS is considered to be an autoimmune disease, whereby an abnormal, heightened immune action of certain white blood cells mounts an attack on myelinated nerves of the central nervous system. Administration of chemotherapeutic agents diminishes the numbers of white blood cells, and therefore would (theoretically) slow down or halt this autoimmune destruction. Among the chemotherapeutic agents that have been used to treat MS are azathioprine ('Imuran'), cyclophosphamide ('Cytoxan'), cyclosporine ('Sandimmune') and methotrexate ('Felex'; 'Mexate'). The results of many trials with these agents have not conclusively shown them to be of definite value, and their use in treating MS remains highly controversial. The side effects of these agents include nausea, vomiting, hair loss, danger of infection and an increased long-term risk of developing certain malignancies. Because of these problems, the use of chemotherapy in MS at this time is generally reserved for those patients with progressive disease. As more information is acquired about the mechanisms of the autoimmune response in MS, more specific immunologic therapies may be developed, that will be more effective and have a lower incidence of side effects. SEE ALSO: AUTOIMMUNE DISEASE, AZATHIOPRINE, CLINICAL TRIAL PARTICIPATION, CLINICAL TRIALS, CYCLOPHOSPHAMIDE, CYCLOSPORINE-A, RESEARCH PUB DATE: JUNE 1992 DISCLAIMER: The National Multiple Sclerosis Society is proud to be a source of information about multiple sclerosis. Our comments are based on professional advice, published experience and expert opinion, but do not represent therapeutic recommendation or prescription. For specific information and advice, consult your personal physician. To contact the Information Resource Center and Library of the NMSS call 1-800/LEARN MS (1-800/532-7667). SOURCE: NMSS Information Resource Center and Library. Compendium of Multiple Sclerosis Information (CMSI), Rev. ed., New York: National Multiple Sclerosis Society, c. 1992. Transmitted: 93-08-26 12:15:08 EDT From alt.support.mult-sclerosis Sun Jan 30 19:31:16 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!newsserver.jvnc.net!news.cac.psu.edu!psuvm!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 9414370 X-Genie-From: R.KOREJWO Message-ID: <9401270557.AA13318@relay2.geis.com> Date: Thu, 27 Jan 1994 01:01:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: methotrexate/MBP/COP Lines: 83 Status: O -=CYNTHIA LOBUE=- Regards: Methotrexate There is one recent reference: Currier RD Haerer AF Meydrech EF Low dose oral methotrexate treatment of multiple sclerosis: a pilot study. J Neurol Neurosurg Psychiatry 1993 Nov;56(11):1217-8 An 18-month double-blind treatment of multiple sclerosis with low dose oral methotrexate showed it to be well tolerated and suggested effectiveness in exacerbating-remitting MS but not in the exacerbating progressive and chronic progressive stages. Institutional address: Department of Neurology University of Mississippi Medical Center Jackson 39216. As was suggested by Eric Stern, it's the immunosuppressant aspect which would be of interest for an MS therapy. This is an already crowded field and I didn't see anything in the study which suggested any unique quality. Re:Zanaflex Comment: Tulane is one of the data centers mentioned in the package. I was glad to hear your favorable report. To your knowledge, does Zanaflex tend to create tolerance like lioresal? Re:'...Are you a doctor?.." Comment: I'm a Ph.D., not an MD. I maintain a database on MS under the terms of an endowment. This started when I was diagnosed 14 years ago and found out that even the "experts" didn't have a collective knowledge base. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -=Gerald Gold=- Re: myelin basic protein in Canada Comment: MBP or analogs of it is already available. The issue is whether it does any good and how to use it, if at all. Your message suggest oral ingestion. There was a large study done at B&W which did not produce remarkable results. They excluded the results from about 300 patients which did not produce data that strengthened their thesis and reported on 30. see: Weiner HL Mackin GA Matsui M Orav EJ Khoury SJ Dawson DM Hafler DA Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis [see comments] Science 1993 Feb 26;259(5099):1321-4 Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing- remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases. Institutional address: Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA 02115. Despite their effort to place a good face on this, it was a Phase II which became a re-Phase I. The statement is clearly made that this in no way demonstrates efficacy. There are other approaches which have also met with the same result. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- For the record, again - COP-1 is nothing except a 4 amino acid analog of MBP. It is certainly not new. NOT NEW! I attended a lecture by Dr. Arnon back in 1985 on this after she had completed two years of data. I was unimpressed then and am still unimpressed. Maybe we will see some new data. It sure would help. -Rick From alt.support.mult-sclerosis Sun Jan 30 19:35:49 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!newsserver.jvnc.net!news.cac.psu.edu!psuvm!auvm!UMIACS.UMD.EDU!jbub Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:jbub@UMIACS.UMD.EDU> X-Mailer: ELM [version 2.3 PL11] Message-ID: <199401270048.TAA00406@skippy.umiacs.UMD.EDU> Date: Wed, 26 Jan 1994 19:48:08 EST Sender: Multiple Sclerosis Discussion/Support From: Jeffrey Bub Subject: Hello Lines: 43 Status: O Hello, Chanach asked me to introduce myself. I am a new subscriber. My name is Robin Shuster and I am a 40 year old woman who was diagnosed with ms 4 years ago. I am a publishing executive and I live in Washington, DC , USA. I am new on the internet so forgive any lapses of netiquette. I haven't really picked up the nuances yet. I am a physically active woman who has found having ms very distressing as I am sure we all do. I apparently have the remitting-relapsing variety and I seem to suffer my exacerbations in the Spring and Summer, starting in May-August. Generally I am well all Fall and Winter. MOst of the time I am very optimistic about my life, but every time I experience a new type of exacerbation-- optic neuritis in my right eye that left my vision damaged, bladder problems that have never totally recovered, loss of muscle strength, spasticity-- I feel a great deal of fear and despair. I cry for a few hours, wonder what what kind of life I will be able to lead in 10 years and recover. It seems each time as though I had made a silent "pact with god," ie I will accept this exacerbation if you promise me that there will be no more new ones. And I am shocked each time the pact is broken. At the same time I am always amazed at how I am able to adjust to each problem and eventually laugh at them. Three days before our annual hiking trip in France, I went blind in my right eye. Scared the hell out of me. But we went anyway and I hiked in the Auvergne with a patch, a very sturdy walking stick, two knee supports, and two wrist supports/. I looked like a low tech robotcop with all my patches and "prosthetics. The children of each tiny village would point at me and laugh when we hiked into these tiny towns, but I felt wonderful because I COULD hike anyway. But there are still times when I am afraid. Lately I have been very aware of memory losses in the middle of conversations and that is troubling because I am a very verbal and verbal agile person. I look forward to "meeting" you all and sharing knowledge, information, insights, support. Robin Shuster email address: jbub@skippy.umiacs.umd.edu 1318 Wallach Place NW Washington, DC 20009 USA From alt.support.mult-sclerosis Wed Feb 9 15:20:32 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!cs.utexas.edu!koriel!news2me.EBay.Sun.COM!exodus.Eng.Sun.COM!appserv.Eng.Sun.COM!chrysos!gale From: gale@chrysos.Eng.Sun.COM (Gale Snow) Newsgroups: alt.support.mult-sclerosis Subject: Re: How to get Betaseron Date: 8 Feb 1994 19:22:22 GMT Organization: Sun Lines: 20 Distribution: world Message-ID: References: <2itp4u$s9n@bigboote.WPI.EDU> <1994Feb7.153816.4443@inland.com> NNTP-Posting-Host: chrysos Status: O In article <1994Feb7.153816.4443@inland.com> gee@inland.com writes: >In article <2itp4u$s9n@bigboote.WPI.EDU>, bert@bigwpi.WPI.EDU (Bertram V Dunskus) writes: ... >> now that I know more about it, I would like to know if it is possible to purchase BS in >> the US, as I am thinking of bringing it to my friend in Germany. ... > >Betaseron is available to people with E-R form of MS and are ambulatory. Since >the amount of Betaseron has been limited, there was a lottery to ensure that >people had somewhat the same chance of getting the drug. ... i have exchanged email with an alt.support.mult-sclerosis reader in finland. there is apparently a company in switzerland, serono, which is making interferon beta 1-b for ms patients in europe. but it is also a limited supply. it is available if your doctor recommends that you take it, not by lottery. just fyi. gale snow From alt.support.mult-sclerosis Wed Feb 9 15:21:46 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!WORLDBANK.ORG!MSCHUMAN Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:MSCHUMAN@WORLDBANK.ORG> MR-Received: by mta EDSEL; Relayed; Wed, 09 Feb 1994 08:05:06 -0500 MR-Received: by mta EARTH; Relayed; Wed, 09 Feb 1994 08:07:45 -0500 Alternate-recipient: prohibited Disclose-recipients: prohibited MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT Posting-date: Wed, 09 Feb 1994 08:03:00 -0500 (EST) Importance: normal Priority: normal X400-MTS-identifier: [;60508090204991/229245@EDSEL] A1-type: MAIL Hop-count: 1 Message-ID: <01H8O0BQS6QUA0WDT1@mr.worldbank.org> Date: Wed, 9 Feb 1994 07:49:00 -0500 Sender: Multiple Sclerosis Discussion/Support From: Margret Schuman EDS02 80107 Subject: Re: How to get Betaseron ^# Lines: 32 Status: O Gail: I am not so sure if the stuff they make in Switzerland is the "real" thing. I checked with a German Neurologist last year and he gave me an article from Schering Werke about the Betaseron situation in Germany. This article, and he confirmed it, did not mention anything about Betaseron being available anywhere in Europe anytime soon. I would be very careful about the Swiss stuff. The article from Schering was written shortly before Betainterferon was approved by the FDA and said roughly the following: It described how Berlex was handling the manufacturing of Betaseron and mentioned that a lottery would be established (has been in the meantime). Schering had bought Berlex and they are apparently expanding the manufacturing facilities (my neuro told me today that they are apparently progressing faster than originally expected and that the lottery numbers are coming up quicker and quicker). The article also mentioned that all the stages of tests on Betaseron were finished only in the US and that, therefore, the medication is sofar only produced and legalized here. They explained that the medication is presently tested in Germany and should be approved there sometime in 1995. Europeans, especially Germans might want to contact Schering to find out about the progress and status of the Betainterferon (this may also give them an "incentive" that they should perhaps speed up the process, so it will be available in Europe too, very soon. I am also sure that German Neurologists are informed and kept updated by Schering (a German Pharmaceutical Company). Margret From alt.support.mult-sclerosis Thu Feb 10 15:22:07 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!WORLDBANK.ORG!MSCHUMAN Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:MSCHUMAN@WORLDBANK.ORG> MR-Received: by mta EDSEL; Relayed; Thu, 10 Feb 1994 04:20:05 -0500 MR-Received: by mta EARTH; Relayed; Thu, 10 Feb 1994 04:22:29 -0500 Alternate-recipient: prohibited Disclose-recipients: prohibited MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT Posting-date: Thu, 10 Feb 1994 04:18:00 -0500 (EST) Importance: normal Priority: normal X400-MTS-identifier: [;50024001204991/229786@EDSEL] A1-type: MAIL Hop-count: 1 Message-ID: <01H8P6QRIL3AA0WY3Y@mr.worldbank.org> Date: Thu, 10 Feb 1994 02:47:00 -0500 Sender: Multiple Sclerosis Discussion/Support From: Margret Schuman EDS02 80107 Subject: Re: How to get Betaseron ^# Lines: 60 Status: O Info on Betaseron in Europe: Last year, I got the following information from a neurologist I visited in Germany. Schering AG distributed this info to neurologists there. Since it is already "outdated", I am sure that a neurologist in Germany (or for that matter Schering) will be able to provide more recent information. The letter I am referring to is dated March 19, 1993. Following are relevant excerpts in a "very rough translation": "Berlex is a subsidiary of Schering AG, Germany. The substance (Beta Interferon) was originally developed by a small biotechnical company in the U.S. Due to the difficult and limited biotechnical manufacturing procedure, the clinical development of the product was at first limited to North America. In 1990, Schering AG acquired this biotechnical enterprise and announced to make the development of Betainterferon for worldwide availability a crucial priority. As soon as we have prepared and submitted the necessary paperwork for approval of the product by the European authorities, we will start taking all necessary steps to initiate that the production and supply of Betainterferon will satisfy its worldwide demand. However, until then it will not be possible to supply the product (Betaseron) for clinical studies or the treatment of various patients. We want to reiterate that based on available clinical trial results, Schering AG rates the therapeutical potential of Betainterferon very highly............ We are aware of the fact that the approval of Betainterferon in the USA, before its availability in Europe, may cause critical questions from you (neurologists) and patients. However, we want to again assure you that we will try our utmost to keep the time-difference in availability of the product as short as possible and hope to be able to make the product available to patients in Europe by 1995. We hope that this letter provides important first information......... If you have further questions, please write to us or call Dr. Stuerzenbecher, tel.: 0 30/3 00 03-3 67. Sincerely, Schering Aktiengesellschaft P.O. Box 65 03 11 1000 Berlin 65 Berlin-Charlottenburg Heerstrasse 18-20" I hope this will answer some of your questions. Please forgive me for the terrible translation, but its very late and I'm so tired that I could not do better. Good luck, Margret From alt.support.mult-sclerosis Mon Feb 14 12:32:01 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!ALEXANDRIA-EMH2.ARMY.MIL!MACPHERSON Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:MACPHERSON@ALEXANDRIA-EMH2.ARMY.MIL> Message-ID: Date: Fri, 11 Feb 1994 20:42:00 EST Sender: Multiple Sclerosis Discussion/Support From: "MACPHERSON, DOUGLAS" Subject: FAQ: Research supporting Dr. Roy Swank's MS diet Lines: 359 Status: O WARNING: THIS IS A VERY LONG POST. BEST TO PRINT IT. Sandi Truslow asked me to send her some info on Dr. Roy Swank's diet. As luck would have it our computers don't speak to each other even though we're both on ARMY.MILnet, the same part of internet. This should not be, but it is. My WHOIS command can't find a path to her computer and her EMAIL to me doesn't get through. Anyway, I've strung together everything in my email with Swank in it. I have also added more Swanky citations, Swank's microcirculation theory, and my additions to/justifications of it. I'm posting it all as a FAQ so that others can find it later with the LISTSERV search commands. Roy Swank's last known address was Dept. of Neurology, Oregon Health Science University, Portland Oregon. The university is known as ohsu.edu on internet. Below are some of the IP numbers which should guarentee that your message gets through. Not mine, but maybe yours. I've tried EMAILING directly to Dr Swank, neurology, and POSTMASTER@OHSU, with equal success. Maybe you can succeed where I've failed. swank@137.53.0.0 199.48.32.0 ... 199.48.37.0 137.53.1.40 137.53.1.30 Subj: For Gordon: Opinion on Roy Swank's cookbook requested [Cookbook -- give me a break] Actually he calls it: The multiple sclerosis diet book. New York: Doubleday, 1987. It's the only diet book I've seen with 130 references from such medical journals as Neurology (and only a dozen by Roy himself). The only diet book by someone who's followed the same 156 MSers for 35 years, and who was hired by Wilder Penfield. The only anything that demonstrates almost arresting the progress of MS for decades. Is he a quack or what? Anyway, I found his Chapter 8 on the "First Twenty Years" on the diet encouraging. In his follow up study at 34 years he found 80% of those who ate more than 20 grams of fat didn't make it vrs 31% who kept their dietary fat below 20 g/day. If anybody else is interested Dr Swank's diet it's simple to state: Swear off red meat and solid/tropical fat forever. Substitute vegetable/unsaturated oils -- corn, sunflower, olive, etc. -- for the butter, cheese, pork, dark chicken/turkey meat. If anybody is interested in the book, which includes a lot of stuff on what MSers experience and what to expect, well, you've got the reference up there. I haven't read Swank's research reports yet, and I haven't even started to search the medical literature for criticisms of his work. I do have doubts about his theory, but it's his results that count. ==================================================================== Subj: Re: exhaustion From Claire Smith Here's a direct quote re: Swank's MS diet from the Rosner and Ross MS book (my favorite MS reference book): The first modern claim for an "MS diet" was made in 1950, when Dr. Roy Swank of Oregon suggested that in geographical locations around the world with higher MS populations, the intake of fat in the diet is greater. Supporting this theory was the belief that fat particles in the blood, or possibly blockage in blood vessels, could cause myelin damage. None of this, however, could explain why white South Africans had a high-fat diet and low MS incidence. Ultimately, a study of a large group of MS patients followed for seventeen years proved the low-fat diet had no effect on the course of the disease. A lower death rate, along with reduction in frequency of attacks, was reported, however. The low-fat diet, of course, is a healthy diet in general and will improve general health by keeping weight down, lowering blood pressure, and preventing arteriosclerosis. These factors are more likely to have influenced the good test results. The low-fat diet is actually a favorite diet of the American Heart Association, and one I recommend, but now necessarily as a treatment for MS. As you will see below the poor dieters died of MS related problems (Doug M.) =============================================================================== FROM: [oops, I lost the author on this one. My apologies] Subj: replies .. Tom, Doug and Gale Just when I thought that I could "lurk," I find that there is much that needs a response. Doug M.: I followed the Swank diet dutifully from 1986-1988, but I found that it was creating familial tensions. Not everyone cares for fresh fish and dollops of oil, So, alas, I have settled for a compromise: - *Lean* pork and beef IS a low-fat diet and, as no one around cared for the scrumprious fresh fish that I bought, I settled for white chicken, tofu and the largely meat-less diet that has become an everyday regimen. But, increasingly, I cheat, and go for that fresh pie and ================================================================================ ============= ... ~From: Gordon Banks Organization: Univ. of Pittsburgh Computer Science ~Subject: Re: For Gordon: Opinion on Roy Swank's cookbook requested I am not familiar with the book, but it would appear to be good nutritional advice, although not specific to MS. As far as I know, there is no scientific evidence that MS patients differ from other people in what is a healthy diet for them. The typical USA diet is not particularly healthy for anyone. The heart and circulatory system, however, rather than the nervous system and the immune system appear to bear the brunt of the damage. The only evidence I've seen linking MS and food is some suggestive evidence that the inclusion of myelin in the food can influence the immune cells in the gut to recognize it as a food and not attack it. There is research going on to see if this might lead to a treatment for MS. At the present time, the jury is not in. There are many people who feel very strongly that certain foods, for example milk, or glutens, should be avoided like the plague by MS patients. They have not, to date, presented scientific evidence ------------------------------------------------------------------------------ Gordon Banks N3JXP |"I can eat more fat meat than you can cook in a week geb@cadre.dsl.pitt.edu | I can tell more of them doggone lies." T. Jarrell ------------------------------------------------------------------------------ ============================================================================== Gordon, if you didn't know, is our resident neurologist. He's wrong about the lack of info on effects of nutrition on MS, but that's about all (Doug M.). ====================================================================== ~From: STARS::MACPHERSON 15-DEC-1993 09:29:34.82 I beg to differ with Gordon Banks on the association of MS with latitude. Norway is the disconfirming example. Norway runs a remarkable distance latitudinally and shows a very distinct geographical pattern of MS. But the pattern is not with latitude but with distance from the sea. The frequency of MS is much less among the fish eating fishermen than the fat consuming people of the inland areas. R. Swank published this in N Eng J Med, 1952, 246, 721-28. (Alter, Yamoor, and Harshe, (1974), Multiple Sclerosis and Nutrition, Arch Neurol, 31, 267-272 investigated the latitudinal and diet hypotheses. Latitude gave a good fit, but two partial estimates of dietary fat provided better fits, with correlations of .7. More skillful statistical analysis would, I think, have provided even higher correlations. Doug M.) This is the finding that started Dr Swank on his dietary approach to MS. You can read his latest paper, "Effect of low saturated fat diet in early and late cases of multiple sclerosis," The Lancet., V 336 (July 7, 1990), pp. 37-39. His earlier clinical papers were in American Journal of Clinical Nutr., 1988, 48, 1387-93; Arch. Neurol., 1970, 23, 460-74; J Nerv Ment Dis, 1960, 131, 468-88; AMA Arch Neurol Psych, 1953, 69 91-103; N Eng J Med, 1952, 246, 721-28; Am J Med Sci, 1950, 220, 421-30. His papers and his clinical experience are distilled into English in "The multiple sclerosis diet book," Garden City: Doubleday, 1987. I've now read all of these papers, I think, and they represent good clinical research. Clinical research -- reports of treatment carried out to reasonable scientific standards, but NOT blinded. Go to the end for his work developing animal models of the effects fo diet on the circulation and brain systems. ====================================================================== FROM: Macpherson Subj: Stats on 34 years of dieting to control MS (not for squeamish) We've been having a discussion on the possible benefits of a very low fat diet on MS. Let me show you why I'm interested in it by abstracting from Swank's Lancet paper. (The Lancet = most respected Brit med journal.) He started with 156 MSers, all but 9 diagnosed by others and confirmed by him. He was able to follow 144 of them 34 years or until death. He broke the sample into 2 groups -- good (<20 grams/day) and poor (>20 grams/day) fat consumers. For him fat is anything hydrogenated, not just the solid stuff. He further broke the group into subgroups based on their original disability using a 7 point scale like the standard Kurtzke scale. The least disabled group (disability level 1) had normal performance signs, frequent fatigue and periodic exhaustion or less disability. The intermediate group, scale value 2, were ambulant but mildly impaired, able to work at least part time, but always fatigued and periodically exhausted and occasionally showing memory impairment. The third group included everybody else -- from the ambulant but severely impaired who usually held part time jobs, usually had widespread neurological impairment and variable memory impairment (level 3) to those confined to bed and chair (5). 34 YEARS LATER Nineteen of those starting in the best shape had dieted for an average of 30 years, one died of MS, and the rest had an average disability score of 1.9. There were 6 poor dieters who had been in the study an average of 24 years. Four died of MS related problems and one of something else. Their average score 2 years before death was 5.2 (very severely impaired). Intermediate group (initial score 2): Of the 25 good dieters 8 died of MS related problems and 2 of other problems, thus about 25% of this group died of MS. They had dieted for an average of 27 years and ended up with an average score of 3.3. Of the 33 poor dieters 25 died, and 16 (50%) of those died of MS. They had (not) dieted for an average of 20 years. Those who died of MS had an average disability of 5.2 two years before death. Severe disability (avg. scale 3.2): Of the 24 good dieters 5 (21%) died of MS complications and 3 of other causes, all after dieting an average of 29 years. Their average disability was 3.6. Of the 33 poor dieters 25 (83%) died of MS and three of other causes. After dieting an average of 20 years their average disability was 5.6 two years before death. (Death is rated 6 on Swank's disability scale.) Bottom line: No matter how disabled you are you may be able to slow the MS progression and stay alive on this diet. If you really hate fish you can point out that the interviewers may have unintentionally fudged the dietary habit records because they knew the person's disability score or fudged that score because they knew the dietary habits. It's harder to fudge those death statistics. Swank also talks about this in his diet book. He even has a fat lethality curve there showing the dose relationship between fat consumption and death. The line rises very rapidly above 20 grams, peaking out around 30 grams. But I don't have the book now and am doing this from memory. Swank, R. L. & Dugan, B. B. Effect of low saturated fat diet in early and late cases of MS, The Lancet, 336, 1990, 37 ===================================================================== CC: MACPHERSON Joe Daus asked about Dr ? MS Diet Book. It's Dr Roy Swank. All the diet book has to recommend it are these three things: 1. In round numbers 80% of the MSers who stayed on his diet for the duration lived. 80% of those who didn't, didn't. The duration was 34 years. This was reported in The Lancet in '90. 2. Those who stuck with his diet for the duration also pretty much arrested the progress of the disability and those who didn't, didn't. They progressed a step or two on a seven point scale from unnoticable problem to the discontinuous endpoint. 3. In the diet book Swank reports that those who stuck with the diet experienced exacerbations about a decade apart. Those who didn't got these experiences on about an annual basis. Perhaps a psychologist trained in introspection would find these experiences interesting. Most of us would rather not, thank you very much. I can summarize the diet for you. NO FAT! No more than 4 teaspoons a day, anyway. Substitute poly-unsaturated oils. This translates to fish and chicken/turkey breast meat cooked with the skin off. Actually fairly close to the Pritikin (sp) diet. Swank says that the diet takes a year to begin showing effects. Apparently your energy level begins to improve in the second year. Others on this net disagree with me, and I suspect that you will see postings from them, or can search out the old ones. ================================================================== New stuff from Doug M. Swank and his associates spent some time and effort developing animal models demonstrating his fat hypothesis. Here are their publications. Swank & Cullen (1953) Circulatory changes in the hampster's cheek pouch associated with alimentary lipemia. Proc Soc Exp Biol Med, 82,381-384 Cullen & Swank (1954) Intravascular aggregation and adhesiveness of the blood elements ... : Effect on the blood-brain barrier. Circulation, 9, 335-346 Swank, (1959) Changes in the blood of dogs and rabbits by high fat intake. Amer J. Physiol, 196,473-477 -- & Nakamura (1960) Oxygen availability in brain tissues after lipid meals. Amer J Physiol, 198,217-220 Nakamura & Swank (1960) Electrocardiogram in hamsters after large fat meals. Proc Soc Expl Biol Med, 105,195-197 Swank, & Nakamura (1960) Convulsions in hamsters after cream meals. Arch Neurol, 3, 594-600. (Killing em with kindness?! Doug M.) He apparently summarized and systematized his findings in his "A biochemical basis of multiple sclerosis," Springfield, Ill: Charles C. Thomas, 1961. I haven't read any of these reports, but I have them on order. I'll report on them, primarily to show Gordon Banks that good research has been done, and that neurologists should attend to the microcirculatory theory of MS. ========================================================================== Swank's microcirculation theory with my additions: Swank claims that MSers have unusually tangled capillaries, and that this can be observed through the fingernails. He also claims that the red blood cells of MSers are unusually sticky, as shown by an electrophoresis test. As a result the red blood cells jam up in the tangled capillaries, cause oxygen starvation with capillary/venule damage downstream of the jam. The weakened walls allow the white blood cells through this blood-brain barrier where they go to work on the mylin. Treat either one of these problems and MS symptoms will be avoided. My addition is from Clark, E. R. & Clark, E. L. (1940) Microscopic observations of the extraendthelial cells of living mamalian blood vessels, as reprinted in M. P. Wiedeman (Ed.) (1974) Benchmark papers in human physiology: Microcirculation. Stroudsburg, PA: Dowden, Hutchinson, & Ross. Capillaries do not grow from arteriole to venule. They develop from extra endothelial tissue in the area lacking a blood supply. Then they blindly and randomly connect to each other and to existing arterioles and venules. They may even differentiate into arterioles and venules themselves. This produces a tangled mess. In the last phase they simplify and cut out the excess. I propose that this phase does not occur (to the extent that it should) in MS prone individuals, that it is inherited and, going way out on a limb, that the same "pruning" gene also works during development to dispose of the excess of neurons that appear during early development. These observations and hypotheses provide an empirical and theoretical underpinning for the microvascular hypothesis that was missing from Swank's publications, or at least the ones I've read. They offer the oppertunity to perform genetic studies by simply observing the capillary structure of MS relatives. If there is a variation then the other half of my modification of Swank's theory should be examined -- that MS red blood cells are sticky, and that that tendency is also inherited. I posit the pruning gene because Swank complains that MSers are too intelligent and active for good treatment. They won't stay horizontal, they won't take naps when tired, they are always intellectually involved in their treatment and searching the literature on their own. Totally unlike the average patient. (It's as if they had a whole lot of extra neurons popping off, ones that would normally have been pruned before birth.) If you have useful observation or criticisms of this post please insert them, indented, or append them, and repost. I would like to keep all this together so that we can see where (or if) it's going more easily. Disclaimer: One quarter of what I know Ain't so. Doug M. aka Macpherson@198.97.199.1 From alt.support.mult-sclerosis Mon Feb 14 12:49:22 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 6112441 X-Genie-From: R.KOREJWO Message-ID: <9402131438.AA26526@relay2.geis.com> Date: Sun, 13 Feb 1994 13:32:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Betaseron Lines: 92 Status: O The following information was forwarded to me by an reliable source and you will have to accept the brevity and format because I do not want to corrupt any of the details. -------------------------- The following comments have been attributed to Dr. Barry L. Levin, M.D., a Neurologist, who writes a column called "Ask the Professional" for the Rhode Island NMSS Chapter quarterly newsletter.(USA) He is also on the RI Chapter board of directors. When Beta was first being hyped, Dr. Levin was a strong supporter of it. He spoke at a RI NMSS quarterly Chapter meeting on 9 February 1994. He was scheduled to give a lecture on Beta. He did. In it he stated that he wanted to apologize to everyone who took his advice about Beta. He told anyone who was on it, or contemplating going on it, that he thought they should get off it immediately. He said he should not have been so ready to presume that Berlex had done their homework. He told everyone that Beta was a very dangerous drug. He also stated that his own investigations were showing that the suicide attempts are increasing, and that they are now directly attributed to the use of Beta. On his list of "bad things" was that Berlex may have to offer an extended list of side effects since many more are now showing up. None of them nice. He stated that a dozen people or more have experienced severe exacerbations on Beta, and symptoms were diminished once they stopped. In closing he stated that he had contacted the NMSS (US) and presented his feelings, and was calling for a medical investigation into the release of it prematurely. When asked, why the US FDA approved it, he stated "that was because people like me told people like you, to write a letter to the FDA telling them to release it, and they did" Some of the important aspects of speech were as follows: He stated that, although he was a strong initial supporter of Beta, the reports he is currently seeing are, in his opinion, very much against it's use. He apologized for changing his feelings towards it, but he felt in the interest of all his patients and readers of the Newsletter, it was best that at this time, he present the facts as he now interprets them. He stated that the Berlex study was not done on a large enough group and the results were not satisfactory enough to warrant release to the public at large. He stated that the FDA passed it only after tremendous pressure from the public, and neurologists who thought it was the best thing for their patients even though a large enough study wasn't done. He confessed he was one that pressured the US FDA also. He stated that the US FDA passed it by a very slim margin. He stated that since it's release the following has occurred: 4 suicide attempts attributed to Beta, 2 successful. Very wide mood swings. Existing stomach problems had been greatly enhanced. One side effect reported by Berlex was small redness at the injection site. Now, large red welts had been reported. He stated since the numbers are now at 20,000, the side effects are increasing He stated that a reported "flu-like symptoms" are now in the neighborhood of a "Severe flu-like symptoms" for six months now being attributed as the cause of SEVERE stimulation of the immune system and severe exacerbations had been reported. He stated that because of the numbers of people now involved in this, that some are now worse off He reported menstrual cycles were reported as disturbed. Current symptoms people now have are enhanced in many cases but subside after stopping beta. They do not always return to the level "Before Beta". He stated that if you are already on Beta, and have any doubts, then stop taking it. He stated he is advising his patients NOT to take it, or to stop. He stated his advice would be to wait a time, until something more substantive than Beta comes out. He felt that most people, at this time, would not benefit from Beta's use, and may lose what they already had. He apologized for initially supporting it. ------------------------------- While most of you know I opposed the approval of Beta and have never recommended it. I, however, take no joy in this report. While this is one person's opinion it is worthy of note based in his credentials. I suggest that caution be observed until there is more concrete evidence available. I'm sorry that I cannot provide you more specific detail and corroboration. Perhaps someone on the network was also there and can provide explanation or further information. Although my source is impeccable, the statements attributed have been paraphrased by both me and my source. No tape recordings were made, to my knowledge. -Rick From alt.support.mult-sclerosis Mon Feb 21 12:40:33 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 5710107 X-Genie-From: R.KOREJWO Message-ID: <9402192056.AA15038@relay2.geis.com> Date: Sat, 19 Feb 1994 20:24:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: pregnancy Lines: 180 Status: O -=Linda Bennett=- The body of evidence surrounding the impact of pregnancy and MS is not clearly conclusive. In general, one can say that while there is a reduced risk associated during, at least the two trimesters prior to birth there is a slightly increased risk in the 6 months post partum. It's pretty much a conjecture to explain whether the post partum increase is due to the stress of delivery, the sleepless nights which frequently plague the parents of a new born, the hormonal changes associated with delivery or yet another undetermined factor. The net result is that accumulated risk, protection plus higher risk period, combine to produce little in the way of a clear change in exacerbation rate. Some references which you can check are: 93244498 Duquette P Girard M Hormonal factors in susceptibility to multiple sclerosis. Curr Opin Neurol Neurosurg 1993 Apr;6(2):195-201 Evidence implies that hormonal factors are involved in susceptibility to multiple sclerosis. Diseases associated with a class II allele occur more frequently in women than in men. Multiple sclerosis is more frequent in women, particularly in the early- and late-onset groups. Pregnancy has a favorable effect on the course of multiple sclerosis on both a short- and a long-term basis. Experimental allergic encephalomyelitis, an animal model with similarities to multiple sclerosis, is also influenced by hormonal factors in both occurrence and severity. The multiple levels of interaction between immune, endocrine, neurologic, and genetic systems probably explain the action of sex steroids in multiple sclerosis susceptibility. Institutional address: Hopital Notre-Dame Quebec Canada. 93193447 Villard-Mackintosh L Vessey MP Oral contraceptives and reproductive factors in multiple sclerosis incidence. Contraception 1993 Feb;47(2):161-8 Data from the Oxford.FPA prospective study show that oral contraceptive use and pregnancy have no discernible effect on the risk of developing multiple sclerosis (MS). Women of parity 0-2 developed MS twice as often as women of parity 3 or more but the difference did not reach statistical significance. Smoking may be a risk factor for developing MS. A nested case-control analysis did not identify any associations between MS onset and preceding illnesses. Institutional address: Department of Public Health and Primary Care Radcliffe Infirmary Oxford England. 92133204 Bernardi S Grasso MG Bertollini R Orzi F Fieschi C The influence of pregnancy on relapses in multiple sclerosis: a cohort study [see comments] Acta Neurol Scand 1991 Nov;84(5):403-6 The influence of pregnancy on the relapse rate (number of relapses per person per year) in MS was analysed for 52 women who had a pregnancy during the disease. The relapse rate was lower during the pregnancy-year (9 months of pregnancy and 6 months immediately post partum) than the non-pregnancy time. There was a heterogeneous pattern during the pregnancy-year with a sharp decrease in the relapse rate observed during pregnancy and a slight non-significant increase in the puerperium: both these relapse rates were compared with figures observed in the same group of women during the non- pregnancy time. Pregnancy does not appear to be a period at greater risk for exacerbations but, on the contrary it seems to act, on the whole, as a protective event. These data allow physicians to provide reassuring counselling to women. Institutional address: Department of Neurological Sciences University of Rome Italy. 92223624 Levy M Pastuszak A Koren G Fetal outcome following intrauterine amantadine exposure. Reprod Toxicol 1991;5(1):79-81 Amantadine hydrochloride is a well-known antiviral agent that has been used for the prevention of influenza A2, the treatment of Parkinson disease, and, more recently, multiple sclerosis. However, very few data exist about its use in pregnant women. We report a 34- year-old woman who had used amantadine to prevent relapse of her multiple sclerosis throughout two of her pregnancies who subsequently delivered two normal infants. We review the available animal data and two other human pregnancy exposure reports. Institutional address: Department of Pediatrics Hospital for Sick Children Toronto Ontario Canada. 91172596 Stenager E Stenager EN Jensen K [Disseminated sclerosis: sexual and obstetrical aspects] Dissemineret sclerose: sexologiske og obstetriske aspekter. Nord Med 1991;106(2):45-7 (Published in Danish) The onset of Multiple Sclerosis (MS) usually occurs at an early age and consequently often causes sexual problems. In the case of women, it also gives rise to doubts concerning whether or not it is justifiable to undertake pregnancy and childbirth under these circumstances. Such difficulties and doubts are described and guidelines submitted for appropriate forms of help, support and therapy which could be offered. Institutional address: Neurologisk afd Odense Sygehus. 90290372 Birk K Ford C Smeltzer S Ryan D Miller R Rudick RA The clinical course of multiple sclerosis during pregnancy and the puerperium. Arch Neurol 1990 Jul;47(7):738-42 Eight women with multiple sclerosis were followed up through pregnancy. Clinical conditions, T-cell subsets, and levels of immunoactive pregnancy- associated proteins were measured twice during the pregnancy and twice during the first postpartum year. None of the women's conditions worsened during pregnancy, although one woman reported a slight increase of symptoms. Six of the eight women experienced relapses within the first 7 weeks after delivery. The number and percent of CD8 suppressor T cells were lower, and the CD4 helper-CD8 suppressor T-cell ratio was higher in the pregnant patients with multiple sclerosis compared with pregnant control women throughout pregnancy and the first 6 months post partum. There was no evident relationship between these parameters and clinical disease activity. Levels of alpha-fetoprotein, alpha 2-pregnancy-associated glycoprotein, and pregnancy-associated plasma protein A, all immunosuppressive proteins associated with pregnancy, were not significantly different in pregnant patients wytT multiple sclerosis and pregnant controls without multiple sclerosis. The study suggested that the risk of clinical relapse after delivery may be higher than has been reported previously. Furthermore, although there were differences in suppressor T cells, they were not predictably linked to changes in clinical disease activity. Institutional address: Department of Obstetrics and Gynecology Genesee Hospital Rochester NY. 90180501 Bader AM Hunt CO Datta S Naulty JS Ostheimer GW Anesthesia for the obstetric patient with multiple sclerosis. J Clin Anesth 1988;1(1):21-4 Data on all obstetric patients delivering at the Brigham and Women's Hospital during the years 1982 through 1987 were collected. The anesthetic techniques used, the type and amount of anesthetic agents administered, and the postpartum relapse rate of multiple sclerosis patients were compared. Women who received epidural anesthesia for vaginal delivery did not have a significantly higher incidence of relapse than those who received local infiltration. However, all of the women who experienced postpartum relapses had received concentrations of bupivacaine greater than 0.25%. This finding may suggest that a higher concentration of drug over a longer period of time may adversely influence the relapse rate. Institutional address: Department of Anesthesia Brigham and Women's Hospital Harvard Medical School Boston MA 02115. ------------------------------------- If the sum total of this sounds like uncertainty, welcome to MS. -Rick From alt.support.mult-sclerosis Mon Feb 21 12:47:58 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!SKIVS.SKI.ORG!sarah Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:sarah@SKIVS.SKI.ORG> Message-ID: <9402202143.AA20624@skivs.ski.org> Date: Sun, 20 Feb 1994 13:43:09 PST Sender: Multiple Sclerosis Discussion/Support From: Sarah Clarke Subject: betaseron Lines: 220 Status: O I would like to comment on Rick's bizarre series of postings regarding Barry Levin's alleged remarks about betaseron. When I first skimmed the posting, my jaw just dropped. I found it hard to believe that an MD, presumably somewhat intelligent as well as knowledgable about way a new drug's usefulness is evaluated, would make such an illogical series of statements. So it didn't come as a surprise that Rick's "impeccable source" turned out to be a figment of someone's imagination. Regarding the reports of new or increased incidence of side effects: >He stated that since it's [sic] release the following has occurred: > 4 suicide attempts attributed to Beta, 2 successful. > Very wide mood swings. People with MS commit suicide. Depression rates are high, and the nature of the disease itself can make some people decide that life is no longer worth living. A suicide rate of 4 per 20,000 doesn't seem unreasonably high to me. > He stated that a reported "flu-like symptoms" are now in the > neighborhood of a "Severe flu-like symptoms" for six months > now being attributed as the cause of SEVERE stimulation of > the immune system and severe exacerbations had been > reported. 1) As we can tell just from the experience of people reporting their experiences to this list, this side effect is quite variable among patients, and varies from injection to injection. An adjustment of dosage will undoubtedly be required for some people. (I intend to start off at half-doses for awhile until I see how bad this side effect is for me) 2) Severe exacerbations happen to people with MS. Nobody ever claimed that beta would "cure" MS. The study's results showed a *reduction* in exacerbation frequency and duration, but not total elimination. To blame severe exacerbations on beta based on anecdotal evidence (as opposed to a controlled study) is just as illogical as it would be to credit beta when a particular individual has a remission. 3) "Severe stimulation of the immune system" Don't you think this was considered as a possibility? Especially after the gamma-interferon trials (where nearly everyone had an immediate relapse). I'm sure that the first question to be answered was "will this stimulate the immmune system into a relapse the way gamma did?" Obviously not, or beta trials would have died as quickly as the gamma trials. I have this vision of a bunch of researchers sitting around scratching their heads and saying "damn! stimulation of the immune system! Why didn't we think of that!" > Existing stomach problems had been greatly enhanced. This is a new one for me. But lots of drugs bother the stomach. Again, if this is true, then dosage adjustment, or some people being taken off beta, is the logical response. > One side effect reported by Berlex was small redness at the injection > site. Now, large red welts had been reported. Golly. Ugly welts. Maybe I'll reconsider my decision to take beta, since it will make me look funny in a bathing suit :) Seriously, though, speaking as one who gets ugly welts from the least provacation (I have constant hives), skin reactions may be a serious problem for some people. Again, this is absolutely no reason to say the drug should be withdrawn. (Aspirin gives me ugly skin welts; it gives some people ulcers; should we ban it?) > He stated since the numbers are now at 20,000, the side effects are > increasing Obviously. y% of 20,000 is a larger number than is y% of a smaller number. > He stated that because of the numbers of people now involved in this, > that some are now worse off Again, nobody ever claimed beta to be a cure. To say that it is a worthless drug because it is not a cure is incredibly naive. > He reported menstrual cycles were reported as disturbed. Menstrual cycles become disturbed often, and often for no reason at all. In women with MS, apparently the disease itself can cause disturbance in the cycle. I didn't know this until I posted a question about hormones' effects on MS, which Rick misunderstood as a question about MS' effect on hormones and posted some abstracts on the subject. To call this a beta side effect is a bit premature. > Current symptoms people now have are enhanced in many cases but > subside after stopping beta. They do not always return to > the level "Before Beta". People with MS have erratic courses of relapses/remissions. This is another purely illogical attribution to beta for something that is unpredictable. To summarize the side effects: 1) A bunch of anecdotal "evidence" that beta does nasty stuff, completely ignoring the fact that lots of these "side effects" can happen spontaneously to anyone with MS, and some of them to people without MS (eg menstrual irregularies, injection site reactions). 2) Reports of increased numbers of side effects; no surprise to people who understand that this will happen as increased numbers of people are taking the drug. 3) Reports that some of the reported side effects are severe in some people. Anybody who expected otherwise is foolish. *Any* drug has wide ranges of effects in individuals. 4) A lack of consistency in the people whose response to reported benefits of beta is: "people with MS have spontaneous remissions and you can't credit beta" (disbelieving the statistical analysis), and then when a relapse or some other bad thing happens, blaming it on beta (ignoring the lack of statistical evidence). You can't have it both ways. Regarding FDA's approval of beta, Rick's mysterious source says: > When asked, why the FDA approved it, he stated "that was > because people like me told people like you, to write a letter to the FDA > telling them to release it, and they did"... He stated that the FDA > passed it only after tremendous pressure from the public... He confessed > he was one that pressured the FDA also. I have worked with the FDA. I was involved in getting a new drug approved, from the Investigation New Drug stage through the various phases of trials through the New Drug Application through approval. My job ranged from statistical analysis of the clinical trials to quality control (sterility tests, etc) to regulatory affairs to quality assurance (making sure that all FDA regulations were followed). I have been through FDA inspections, and FDA analysis of my own statistical analyses. I have a very high respect for the FDA. Not only are they *very* sharp, (at least in the Biologics division, which is also the one involved with beta), but they are quite immune to lobbying efforts. They are scientists, and understand the scientific method of evaluating a new drug's safety and effectiveness. The drug I was involved in was very heavily lobbied, but FDA would not approve it until we showed it was safe. This took awile -- our fault; we were awfully understaffed, as you can tell by all the hats I wore -- and FDA never budged under the lobbying efforts. > He stated that the Berlex study was not done on a large enough group and > the results were not satisfactory enough to warrant release to the public > at large... and neurologists who thought it was the best thing for > their patients even though a large enough study wasn't done. Statistical significance is statistical significance. With a smaller number of subjects in a study, you just have to have a larger proportion of results that fit the hypothosis. It's true that extremely rare side effects might not show up in a study of this size; you just have to realize that these will be very rare side effects. However, in the study I worked on, the size of it was a source of amazement to the folks at FDA -- about 5,000 subjects. It was unprecedented -- the usual study ran to 200-300 subjects, according to them. So the size of the beta study is not at all unusual. (The reason our study was so big is that it became uncontrolled near the end; it was obviously safe and effective so FDA gave us permission to give it out on a "compassionate use" basis) > He stated that the FDA passed it by a very slim margin. Given the source of these statements, I don't know whether or not to give this any credence at all. If it's true, which it probably is not, it was still passed by a majority. In closing, Rick says: > While most of you know I opposed the approval of Beta and have never > recommended it. I, however, take no joy in this report. Coulda fooled me. My impression is you were absolutely delighted. You have now stated that since this whole posting was false, your opinion of Dr. Levin has changed. How so? You no longer respect him because he didn't say these things? > While this is one person's opinion Yes, but whose? > it is worthy of note based in his credentials. It most certainly is. Credentials being: a figment of somebody's imagination. Worthy of note because it is a beautiful example of the irresponsible steps some will take to further an opinion. > Although my source is impeccable (no comment here... I just couldn't resist including it :) And finally, the only thing in this whole posting that made any sense: > I suggest that caution be observed until there is more concrete > evidence available. Caution being the keyword here. Caution that any sensible person would use when taking any drug, and caution when interpreting anything that is said about such a controversial subject. Apologies for the flaming nature of this, but I am pretty angry. Not just at the irresponsiblity of the post, but at the complete lack of rational thought contained within the post itself. Betaseron is a drug that deservedly has opposition, and I am eager to hear arguments against its use, since I have decided to take it. But this amazing bit of propaganda (intentional or not on Rick's part) has absolutely no place in the discussion. The immune system is so closely tied with other systems in the body that is should not be a big surprise, or reason to panic, if unexpected side effects show up, or unexpectedly severe side effects. They benefit to risk ratio should be continually evaluated, as it is with any drug. But this is not the way to evaluate it. Sarah Clarke sarah@skivs.ski.org From alt.support.mult-sclerosis Mon Feb 21 12:50:40 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 4348897 X-Genie-From: R.KOREJWO Message-ID: <9402210414.AA00425@relay2.geis.com> Date: Mon, 21 Feb 1994 03:29:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Betaseron Lines: 162 Status: O -=Sarah Clarke=- I can't spend as much time on this as you did but I think I wouldn't have to. First, you really should read the papers and the Berlex data. You are not even close to following what the thread was. What I suggested and, it turns out, what Dr. Levin was saying was "follow the literature." Regards Levin's comments, the following message is cross posted here from GEnie. It was based on Dr. Levin attempt to restate what he said. You'll just have to fill in the blanks because I'm not running errands on this. ------------------------- #: 73351 S11/Multiple Sclerosis 20-Feb-94 08:22:22 Sb: #72911-Message from Barry Levin Fm: Merle Spector 71054,322 To: Barry Levin, MD 74032,1474 Item 7390126 94/02/19 20:42 ~From: A.MANGARELLI Albert Mangarelli To: M.SPECTOR1 Merle Spector cc: A.MANGARELLI Albert Mangarelli Dear Merle, ... Since I believe that Rick Korejwo has repeated a story regarding Beta and a Dr. Levin with pretty good accuracy, and since I have no access to CIS anymore I was wondering if you would think it in good taste to post my position regarding this statement from Levin. I was in attendance at that meeting. Dr. Levin's statements are absolutely untrue and severely lacking in accuracy regarding the intent of his communications. Since I have no way of knowing if anyone else has responded with the same opinion of that evening, I offer my view below, in the interest of correcting the "bad taste" that Levin has put in my mouth, and possible the mouth of others. Thank you. Please let me know if you think this would precipitate further flames. MY intent now is only to let people know that R.Korejwo did what others and myself know to be correct that evening. Al Mangarelli The comment follows. ------------- -= To All =- After reading Dr. Barry Levin's scathing post to Dr. Korejwo. I've decided to step forward and present my interpretation of what Dr.Levin implies here. Shame on you Dr. Levin. I was at that meeting. For the most part, what Dr. Korejwo describes as taking place, did in fact take place. However, I must make it clear at the onset, that after consulting with several others who were there, the OPERATIVE word here is INTENT. If it was your intent to give the impression to the audience that you were very familiar with Betaseron and it's adverse effects, you certainly did do that. If the audience knew in advance, that the extent of your knowledge was based on the "fact sheet" enclosed in the Beta package, as you stated, as the source of your information search, then most of the audience would have left. You presented yourself as having great knowledge in that area. You stated here that you spoke on a "wide range of topics". Other than pointing to your "Perot type charts", you spoke only on Beta. When people in the audience presented their questions to you, you stated that you were among the physicians that wrote letters to the FDA requesting an early release of Beta. That statement is correct. Unfortunately, the phrases, context, and general sprinkling of dangling participles, left many in the audience feeling that you were definitely trying to say the drug was "dangerous". Especially when YOU stated there were four attempted suicides two successful. It was "implied" that this was "new" knowledge, not taken from the Berlex fact sheet. I believe that is where the "dangerous" originated. From YOU. IMPLIED. You added at that time or thereabouts, that "Beta is not what it was cracked up to be". Those are YOUR words, not mine. Not R.Korejwo's You stated that some people are experiencing increased exacerbations once on Beta. As a matter of fact, the young woman sitting near me stated to you she was on Beta and had increased symptoms on Beta, but that they has subsided quite a bit, later, after the Q & A, you walked past her and said she was very lucky that they has subsided. You said she was on of the lucky ones. I wonder why it is that if you are such a strong supporter of Beta, why is it that none of your patients are on it? Is it that you do believe there may be a problem? It's true, Dr. Levin, you may not have said "I apologize for backing Beta". Unfortunately, your dialogue gave that impression to more than just myself. I am a professional person, and am not used to misinterpreting the hidden meaning of lectures. What was posted earlier, referring to you and particular Beta statements,is EXACTLY the impression you gave to myself and others, if that was NOT your intent, a different method of communication skills may be in order. I cannot find a statement regarding effects of Beta, that read like the words were not your own. I attended because I thought you had performed your own research regarding the facts of Beta. You gave the impression that as a neurologist, you were staying in the forefront on this Beta thing. Had I known you were only going to present a dialogue from a fact sheet put out by Berlex, I might have reconsidered attending. I apologize to the members of this forum for such a long discourse, but I think it is unfair to have the reputation of Dr. Richard J. Korejwo impuned by the callous remarks of Dr. Levin, without re-assessing the situation and saying.. "Well...maybe I did err... and give a wrong impression of what I was trying to accomplish." I'm sure Dr. Levin, that you meant to help people in your audience. I know that as I left, people thought you were "the white knight" fighting the bad guys. They were very impressed, as I was, that you would take a stand on your patients behalf. How would they get that impression, if not by what was "implied" at that meeting? I certainly thought you were "revealing new facts and feelings". A. Mangarelli ------------------------------------ My goodness, someone other than I got that information also. Re:"..A suicide rate of 4 per 20,000 doesn't seem unreasonably high to me..." Comment: I've already mentioned this. It would not be so to me either but it was 1 suicide and 3 attempted suicides in a population of 249 over 3 years. There were no attempted suicides in the placebo group during the same period. I appreciate your rage but you really need to read the papers before you run on. You attacked me and not the facts. I did not appreciate it nor do I believe I deserved it. I stated clearly that the information I was posting was attributed and called attention to the potential as soon as I was aware of any possibility that it was not accurate. I could have delayed further and added A.MANGARRELLI's post. Then I could be very safe and waited a few more years to announce the discovery of penicillin. Getting information out to people is what I do. I try to make it accurate and if I error, I'm quick to correct it. Are you? What you have done is attack me. Now, I suppose A.MANGARELLI is your next target. Before you do I recommend that you read the literature. Baseline blood work is recommended by Berlex prior to the start of use and at three month intervals thereafter. If you're watching the counts and liver function you can detect problems when they develop and can discontinue therapy per the recommendations of Berlex. Don't forget your ire for them too. If you would like me to stop posting here so that you can be the sole fountain of information I will do so. You really don't have to insult me to do it. Just ask. I don't need the INTERNET in my life and certainly have seen more than my share of "experts" who don't read. -Rick From alt.support.mult-sclerosis Mon Feb 21 14:59:41 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!U.WASHINGTON.EDU!livesey Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:livesey@U.WASHINGTON.EDU> Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Message-ID: Date: Sun, 20 Feb 1994 23:32:21 -0800 Sender: Multiple Sclerosis Discussion/Support From: "John C. Livesey" Subject: BetaSeron In-Reply-To: <9402202202.AA26952@tolstoy.u.washington.edu> Lines: 104 Status: O The following message was posted Wednesday, Feb 16 to the Disabilities Forum, Section 11 (Multiple Sclerosis) on CompuServe. Since the message to which he refers was posted here as well as on CompuServe, I felt that Dr. Levin would appreciate having his comments relayed as widely as was the original. John - - - - - Dr. John Livesey, Radiation Oncology, U. Washington, Seattle, WA 98195 livesey@u.washington.edu // livesey@max.bitnet // 75540,3454 (CIS) 206-548-4090 (voice) 206-548-6473 (fax) - - - - - Message: #72911, S/11 Multiple Sclerosis ~Date: Wed, Feb 16, 1994 6:58:15 ~Subject: Message from Barry Levin ~From: Barry Levin, MD 74032,1474 To: All On Saturday, February l2, l994, a message was sent over CompuServe by Mr. Richard Korejwo about a lecture that I gave on February 3, l994 at the annual meeting of the Rhode Island Chapter of the National MS Society. I have reviewed that letter from Mr. Korejwo and am quite upset over his misquotes and misrepresentations of the information that I actually presented in my lecture. I do not know specifically how Mr. Korejwo obtained information with regard to my lecture which covered a wide range of MS topics, including Betaseron. Unfortunately, the quotes attributed to me are for the most part incorrect and highly misleading. I believe, and in my talk I stressed, that Betaseron can be an effective medication for some people with MS, but that the decision with regard to taking this medication had to be reached after careful individual consideration. I did NOT state that Betaseron was a dangerous drug and I do not believe that it is a dangerous drug. Korejwo alleges that I stated my "own investigations were showing that the suicide attempts are increasing and that they are now directly attributed to the use of Beta" I have done NO personal investigations and have NO personal information that suicide attempts are increasing. Rather, what I quoted at the meeting was information right out of the Betaseron package insert. To the best of my knowledge, there is no reported increased incidence of suicide attempts and there has been no direct attribution tying such attempts to Betaseron. Korejwo states that I "wanted to apologize to everyone who took my advice about Beta.." This is NOT true. I neither apologized to anyone nor advised anyone who is taking the medication to stop it. What I emphasized was that it is important when taking any drug to consider the prospective benefits versus potential adverse effects and to become as informed as possible by, among other things, discussing the use of BetaseronR with your neurologist to help you determine whether or not this is a good medication for you. Betaseron was carefully investigated prior to its release, and I believe it was approved appropriately as a treatment for MS. I think the study was well done and that the information released to the public was correct. Korejwo quotes that I have "contacted the National Multiple Sclerosis Society ..calling for a medical investigation into the release of it prematurely." This is NOT true. I have neither contacted the Society nor believe that a medical investigation of Betaseron is at all warranted. Korejwo states that I was "one that pressured the FDA." This is NOT correct. Prior to Betaseron being released, as a professional, I did express my support with a positive letter requesting an FDA evaluation of the drug as soon as possible. I have supported the release of Betaseron and continue to support its usage. As a practicing neurologist, I am concerned over the potential benefits and side-effect of any medication that I prescribe. IT IS TOTALLY FALSE and outrageous that Korejwo claims I advised people to stop taking Betaseron, that most people would not benefit from the use of the drug, or worse, and that I "apologized for initially supporting it." At the present time, I have no patients on Betaseron. I have several patients with whom I did discuss the pros and cons of Betaseron use who decided not to go on the drug at this time. I do emphasize to my patients and in my talks that individuals who may want to take the drug now or in the future register for it with Berlex. I stress that there are continuing treatment trials and ongoing assessments of Betaseron. Over the next several years, we should know a great deal more about this medication. As a responsible physician I do have concerns over the side effects of all medications, Betaseron included. The operative word is "medication." Multiple sclerosis is a serious disease. The drugs that treat it are serious as well and require monitoring. I believe the major problem with Betaseron is over- expectation on the part of physicians and patients alike. Despite knowing that Betaseron is not a cure for MS, we have all been hopeful that indeed such a cure has been found. This leads to disappointment. I believe, and I emphasized in my lecture, that we are all on a learning curve with Betaseron and that treatment with the drug has only just begun. We need more time before assessing what the true impact of this medication will be in people with MS. I have been and continue to be a supporter of Betaseron. The information tha Mr. Korejwo presented is a slanted and biased view of the drug, with the bias being Mr. Korjwo's rather than my own. My view is that Betaseron is not a perfect medication, nor is it a cure, but it is the best medication for the treatment of MS that we have to date, and that, with careful clinical supervision and careful decision making on the part of each person with MS, Betaseron can be a helpful medication in the treatment of MS. It is disturbing to me as an individual who cares for and about such a large number of individuals with MS to see how one unverified letter can create a such a fire storm of misguided responses. As I seldom get into CompuServe because of the demands of my practice, if you wish to respond to me, please write to: 333 School Street, Pawtucket, RI 02860. **End of Relayed Message** From alt.support.mult-sclerosis Wed Feb 23 17:26:21 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 1717645 X-Genie-From: R.KOREJWO Message-ID: <9402221435.AA08517@relay2.geis.com> Date: Tue, 22 Feb 1994 13:50:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: The rest of twins Lines: 144 Status: O -=Dawn=- "Zygosity" is a reference to egg. If twins are born from a single egg fertilization and division they are identical or monozygotic. If twins are born from two separate eggs fertilized individually they are non-identical or dizygotic. While I was giving you the short answer on twins and I forgot to include a list of some of the current references. That follows: 94033025 Briant L Avoustin P Clayton J McDermott M Clanet M Cambon-Thomsen A Multiple sclerosis susceptibility: population and twin study of polymorphisms in the T-cell receptor beta and gamma genes region. French Group on Multiple Sclerosis. Autoimmunity 1993;15(1):67-73 Multiple sclerosis (MS) is a demyelinating auto-immune disease of the central nervous system with a suspected genetic component. Previous publications have demonstrated that MS susceptibility is influenced by Major Histocompatibility Complex (MHC) genes and recent studies have focused on additional susceptibility genes. The accumulation of activated T-cells in demyelinating MS lesions, the possible auto-immune mechanism of this disease and the functional relationship between MHC and T cell receptor (TCR) molecules support the hypothesis that TCR genes are good candidates to influence MS development. Published results in this domain are conflicting and still a matter of controversy. In the present study we analysed the influence of V beta, C beta, P lambda G3 and V gamma gene polymorphisms defined by Restriction Fragments Length Polymorphism (RFLP) on 48 pairs of monozygotic and dizygotic twins with at least one of each pair affected, and also in 63 unrelated MS patients for V gamma gene polymorphism. These results have been compared with those in the non affected twins and with data from a control group (Beall et al., 1989) regarding C beta and V beta polymorphisms and with a local control population for V gamma. No significant correlation between C beta, V gamma or P lambda G3 polymorphisms and MS was found, only a non significant tendency to reduced P lambda G3 allele sharing among dizygotic non concordant twin pairs was observed. However one V beta 11, 25 kb allele and a haplotype defined by V beta 11 and C beta alleles showed a correlation with MS susceptibility of borderline significance.(ABSTRACT TRUNCATED AT 250 WORDS) Institutional address: Centre de Recherches sur le Polymorphisme Genetique des Populations Humaines CRPG/CNRS UPR 8291 CHU Purpan Toulouse France. 93309587 Utz U Biddison WE McFarland HF McFarlin DE Flerlage M Martin R Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis [see comments] Nature 1993 Jul 15;364(6434):243-7 Although the cause of multiple sclerosis (MS) is unknown, it is thought to involve a T cell-mediated autoimmune mechanism. Susceptibility to the disease is influenced by genetic factors such as genes of the HLA and T- cell receptor (TCR) complex. Other evidence for a genetic influence includes the low incidence in certain ethnic groups, the increased risk if there are affected family members and the increased concordance rate for disease in monozygotic twin pairs (26%), compared to dizygotic twins. Epidemiological studies indicate that there may be an additional role for environmental factors. Although the target antigen(s) are not yet identified, several myelin or myelin-associated proteins have been suspected, among them myelin basic protein. A lack of genetically comparable controls has impaired the analysis of the T-cell response in MS patients and caused disagreement on TCR usage in the disease. Here we analyse the role of TCR genes in MS by comparing TCR usage in discordant versus concordant monozygotic twins in response to self and foreign antigens. We find that after stimulation with myelin basic protein or tetanus toxoid, control twin sets as well as concordant twin sets select similar V alpha chains. Only the discordant twin sets select different TCRs after stimulation with antigens. Thus exogenous factors or the disease shape the TCR repertoire in MS patients, as seen by comparison with unaffected genetically identical individuals. This skewing of the TCR repertoire could contribute to the pathogenesis of MS and other T-cell- mediated diseases. Institutional address: Neuroimmunology Branch National Institute of Neurological Disorders and Stroke NIH Bethesda Maryland 20892. 93244497 Sadovnick AD Familial recurrence risks and inheritance of multiple sclerosis. Curr Opin Neurol Neurosurg 1993 Apr;6(2):189-94 The cause of multiple sclerosis is unknown. There is considerable circumstantial evidence that multiple sclerosis is a complex trait, probably autoimmune in nature, and is determined by both genetic and environmental factors. It is recognized that relatives of multiple sclerosis patients are at greater risk for developing the disease than the general population, although this risk is still relatively low in absolute terms. Monozygotic co-twins of multiple sclerosis patients appear to have the highest risk of any group of relatives, although the absolute risk is well under 100%, as would be predicted if multiple sclerosis is purely a genetic disorder. Institutional address: Department of Medical Genetics University of British Columbia Vancouver Canada. 93270426 Sadovnick AD Armstrong H Rice GP Bulman D Hashimoto L Paty DW Hashimoto SA Warren S Hader W Murray TJ et al A population-based study of multiple sclerosis in twins: update. Ann Neurol 1993 Mar;33(3):281-5 This study is a 7.5-year follow-up of a population-based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Canadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8% and the dizygotic-like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population-based studies and to our own modified replication twin data reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These data also have important implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unambiguously demonstrates the powerful effect of nonheritable factors. Institutional address: University of British Columbia Vancouver Canada. There is also another French study but the numbers were so small that it is more confusing than helpful. It is: 93111695 French Research Group on Multiple Sclerosis Multiple sclerosis in 54 twinships: concordance rate is independent of zygosity. French Research Group on Multiple Sclerosis [see comments] Ann Neurol 1992 Dec;32(6):724-7 -Rick From alt.support.mult-sclerosis Sun Feb 27 15:25:53 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!GENIE.GEIS.COM!r.korejwo Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 7392227 X-Genie-From: R.KOREJWO Message-ID: <9402260113.AA24053@relay2.geis.com> Date: Thu, 24 Feb 1994 00:22:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: Betaseron Lines: 562 Status: RO The following file was provided by Merle Spector. EXCERPT from Patient Journal pages 21-27 BETASERON (Interferon beta-1b) Full prescribing information DESCRIPTION Betaseron (Interferon bet-alb) is a purified, sterile, Lyophilized protein product produced by recombinant DNA techniques and formulated for use by injection. Interferon beta-lb is manufactured by bacterial fermentation of a strain of Escherichia coli that bears a genetically engineered plasmid containing the gene for human interferon beta[ser l7]. The native gene was obtained from human fibroblasts and altered in a way that substitutes serine for the cysteine residue found at position 17. Interferon beta-1b is a highly purified protein that has 165 amino acids and an approximate molecular weight of 18,500 daltons. It does not include the carbohydrate side chains found in the natural material. The specific activity of Betaseron is approximately 32 million international units (IU)/mg Interferon beta-lb. Each vial contains 0.3 mg (9.6 million IU) of Interferon beta-lb. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Dextrose and Albumin Human, USP (15 mg each/vial) are added as stabilizers. Prior to 1993, a different analytical standard was used to determine potency It assigned 54 million IU to 0.3 mg Interferon beta-lb. Lyophilized Betaseron is a sterile, white to off-white powder intended for subcutaneous injection after reconstitution with the diluent supplied (Sodium Chloride, 0.54% Solution). CLINICAL PHARMACOLOGY General: Interferons are a family of naturally occurring proteins, which have molecular weights ranging from 15,000 to 21,000 daltons. Three major classes of interferons have been identified: alfa, beta, and gamma. Interferon beta - I b, interferon alfa, and interferon gamma have overlapping yet distinct biologic activities. The activities of Interferon beta-lb are species-restricted and, therefore, the most pertinent pharmacologic information on Betaseron is derived from studies of human cells in culture and in humans. Biologic Activities: Interferon beta-lb has been shown to possess both antiviral and immunoregulatory activities. The mechanisms by which Betaseron exerts its actions in multiple sclerosis (MS) are not clearly understood. However, it is known that the biologic response-modifying properties of Interferon beta-lb are mediated through its interactions with specific cell receptors found on the surface of human cells. The binding of Interferon beta-lb to these receptors induces the expression of a number of interferon- induced gene products (e.g., 2',5'-oligoadenylate synthetase, protein kinase, and indoleamine 2,3-diox,vgenase) that are believed to be the mediators of the biological actions of Interferon beta-lb.' A number of these interferon-induced products have been readily measured in the serum and cellular fractions of blood collected from patients treated with Interferon beta-lb." Pharmacokinetics: Because serum concentrations of Interferon beta-lb are low or not detectable following subcutaneous administration of 0.25 mg (8 million IU,) or less of Betaseron, pharmacokinetic information in patients with MS receiving the recommended dose of Betaseron is not available. Following single and multiple daily subcutaneous administrations of 0.5 mg (16 million IU) Betaseron to healthy volunteers (N =12), serum Interferon beta-lb concentrations were generally below 100 IU/ml. Peak serum Interferon beta-1b concentrations occurred between 1 to 8 hours, with a mean peak serum interferon concentration of 40 IU/ml. Bioavailability, based on a total dose of 0.5 mg (16 million IU) Betaseron (Interferon beta-lb) given as two subcutaneous injections at different sites, was approximately 50%. After intravenous administration of Betaseron (0.006 mg l0.2 million IU] to 2.0 mg [64 million IU]), similar pharmacokinetic profiles were obtained from healthy volunteers (N=12) and from patients with diseases other than MS (N=142). In patients receiving single intravenous doses up to 2.0 mg (64 million IU), increases in serum concentrations were dose proportional. Mean selum clearance values ranged from 9.4 mL/min-kg to 28.9 mL/min-kg and were independent of dose. Mean terminal elimination half-life values ranged from 8.0 minutes to 4.3 hours and mean steady-state volume of distribution values ranged from 0.25 L/kg to 2.88 l/kg. Three-times-a-week intravenous dosing for 2 weeks resulted in no accumulation of Interferon beta-1b in the serum of patients. Pharmacokinetic parameters after single and multiple intravenous doses of Betaseron were comparable. Clinical Trials: The effectiveness of Betaseron in relapsing-remitting MS was evaluated in a double-blind multiclinic (11 sites: 4 Canadian and 7 United States), randomized, parallel, placebo-controlled clinical investigation of 2 years duration. The study enrolled MS patients, aged 18 to 50, who were ambulatory (Kurtzke expanded disability status scale [EDSS] of less than 5.5), exhibited a relapsing-remitting clinical course, met Poser's criteria for clinically definite and/or laboratory supported definite MS and had experienced at least two exacerbations over 2 years preceding the trial without exacerbation in the preceding month. Patients who had received prior immunosuppressant therapy were excluded. An exacerbation was defined, per protocol, as the appearance of a new clinical sign/symptom or the clinical worsening of a previous sign/symptom (one that had been stable for at least 30 days that persisted for a minimum of 24 hours. Patients selected for study were randomized to treatment with either placebo (N=123), 0,.05 mg (1.6 million IU) of Betaseron (N=125), or 0.25 mg (8 million IU) of Betaseron (N=124) self-administered subcutaneously every other day. Outcome based on the 372 randomized patients was evaluated after two years. Patients who required more than three 28-day courses of corticosteroids were removed from the study. Minor analgesics (acetaminophen, codeine), antidepressants, and oral baclofen were allowed ad libitum but chronic nonsteroidal anti-inflammatory drug (NSAID) use was not allowed. The primary, protocol defined, outcome assessment measures were 1) frequency of exacerbations per patient and 2) proportion of exacerbation free patients. A number of secondary outcome measures were also employed as described in Table 1. [TABLE 1: 2 Year Study Results; Primary and Secondary Clinical Endpoints] could not be reproduced within this medium. In addition to clinical measures, annual magnetic resonance imaging (MRI) was performed and quantitated for extent of disease as determined by changes in total area of lesions. In a substudy of patients (N=52) at one site, MRls were performed every 6 weeks and quantitated for disease activity as determined by changes in size and number of lesions. Results at the protocol designated endpoint of 2 years (see Table 1): In the 2-year analysis, there was a 31% reduction in annual exacerbation rate, from 1.31 in the placebo group to 0.9 in the 0.25 mg (8 million IU) group. The p-value for this difference was 0.0001. The proportion of patients free of exacerbations was 16% in the placebo group, compared with 25% in the Betaseron (Interferon beta-1b) 0.25 mg (8 million IU) group. The p-value this difference was 0.0001. The proportion of patients free of exacerbations was 16% in the placebo group, compared with 25% in the Betaseron (Interferon beta-lb) 0.25 mg (8 million IU) group. Of the 372 patients randomized, 72 (19%) failed to complete 2 full years on their assigned treatments. The reasons given for withdrawal varied with treatment assignment. Excessive use of steroids accounted for 11 of the 26 placebo withdrawals, but only 2 of the 21 withdrawals from the 0.05 mg (1.6 million IU) assigned group and 1 of the 25 withdrawals from the 0 25 mg (8 million IU) assigned group. Withdrawals for adverse events attributed to study article, however, were more common among Betaseron-treated patients: 1, 5, and 10 withdrew from the placebo, 0.05 mg (1.6 million IU), and 0.25 mg (8 million IU) groups, respectively. Over the 2-year period there were 25 MS-related hospitalizations in the 0.25 mg (8 million IU) Betaseron~ (Interferon beta-lb)-treated group compared to 48 hospitalizations in the placebo group. In comparison, non-MS hospitalizations were evenly distributed among the groups, with 16 in the 0.25 mg (8 million IU) Betaseron group and 15 in the placebo group. The average number of days of MS-related steroid use was 41 days in the 0.25 mg (8 million IU) Betaseron group and 55 days in the placebo group (p=0.004). MRI data were also analyzed for patients in this study. A frequency distribution of the observed percent changes in MRI area at the end of 2 years was obtained by grouping the percentages of successive intervals of equal width . Figure 1 displays a histogram of the proportions of patients who fell into each of these intervals. The median percent change in MRI area for the 0.25 mg (8 million IU) group was -1.1% which was significantly smaller than the 16.5% observed for the placebo group (p = 0.0001). [FIGURE 1: Distribution of change in MRI area] could not be reproduced within this medium. In an evaluation of frequent MRI scans (every 6 weeks) on 52 patients at one site, the percent of scans with new or expanding lesions was 29% in the placebo group and 6% in the 0.25 mg (8 million IU) treatment group (p=0.006). MRI scanning is viewed as a useful means to visualize changes in white matter that are believed to be a reflection of the pathologic changes that, approximately located within the central nervous system (CNS), account for some of the signs and symptoms that typify relapsing-remitting MS. The exact relationship between MRI findings and the clinical status of patients is unknown. Changes in lesion area often do not correlate with clinical exacerbations probably because many of the lesions affect so-called "silent" regions of the CNS. Moreover, it is not clear what fraction of the lesions seen on MRI become foci of irreversible demyelinization (i.e., classic white matter plaques). The prognostic significance of the MRI findings in this study has not been evaluated. At the end of 2 years on assigned treatment, patients in the study had the option of continuing on treatment under blinded conditions Approximately 80% of patients under each treatment accepted. Although there was a trend toward patient benefit in the Betaseron (Interferon beta-lb) groups during the third year, particularly in the 0.25 mg (8 million IU) group, there was no statistically significant difference between the Betaseron-treated vs. placebo-treated patients in exacerbation rate, or in any of the secondary endpoints described in Table 1. As noted above, in the 2-year analysis, there was a 31% reduction in exacerbation rate in the 0.25 mg (8 million IU) group, compared with placebo. The p-value for this difference was 0.0001. In the analysis of the third year alone, the difference between treatment groups was 28%. The p-value was 0.065. The lower number of patients may account for the loss of statistical significance, and lack of direct comparability among the patient groups in this extension study make the interpretation of these results difficult. The third year MRI data did not show a trend toward additional benefit in the Betaseron arm compared with the placebo arm. Throughout the clinical trial, serum samples from patients were monitored for the development of antibodies to Interferon beta-lb. In patients receiving 0.25 mg (8 million IU) of Betaseron (N=124) every other day in the clinical trial, 45% were found to have serum neutralizing activity at one or more of the time points tested. The relationship between antibody formation and clinical efficacy is not known. INDICATIONS AND USAGE Betaseron is indicated for use in ambulatory patients with relapsing-remitting multiple sclerosis to reduce the frequency of clinical exacerbations. (See CLINICAL PHARMACOLOGY, Clinical Trial section.) Relapsing-remitting MS is characterized by recurrent attacks of neurologic dysfunction followed by complete or incomplete recovery. The safety and efficacy of Betaseron (Interferon beta-lb) in chronic- progressive MS has not been evaluated. CONTRAINDICATlONS Betaseron is ccntraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, Albumin Human USP, or any other component of the formulation. WARNINGS One suicide and 4 attempted suicides were observed among 372 study patients during a 3-year period All five patients received Betaseron (three in the 0.05 mg [1.6 million IU] group and two in the 0.25 mg [8 million IU] group). There were no attempted suicides in patients on study who did not receive Betaseron. Depression and suicide have been reported to occur in patients receiving interferon alfa, a related compound. Patients to be treated with Betaseron should be informed that depression and suicidal ideation may be a side effect of the treatment and should report these symptoms immediately to the prescribing physician. Patients exhibiting depression should be monitored closely and cessation of therapy should be considered. PRECAUTIONS General: Patients should be instructed in injection techniques to assure the safe self-administration of Betaseron. (See PRECAUTIONS: Information to patients, and Betaseron (Interferon beta-lb) Patient Information sheet.) Information to patients: Instruction on self-injection technique and procedures. Patients should be instructed in the use of aseptic technique when administering Betaseron. Appropriate instruction for reconstitution of Betaseron and self-injection should be given including careful review of the Betaseron (Interferon beta-lb) Patient information sheet. If possible, the first injection should be performed under the supervision of an appropriately qualified health care professional. Patients should be cautioned against the re-use of needles or syringes and instructed in safe disposal procedures. A puncture resistant container for disposal of used needles and syringes should be supplied to the patient along with instructions for safe disposal of full containers. Eighty-five percent of patients in the controlled MS trial reported injection site reactions at one or more times during therapy. In general, these were transient and did not require discontinuation of therapy, but the nature and severity of all reported reactions should be carefully assessed. Patient understanding and use of aseptic self-injection technique and procedures should be periodically reevaluated. Flu-like symptoms are not uncommon following initiation of therapy with Betaseron. In the controlled MS clinical trial, acetaminophen was permitted for relief of fever or myalgia. Patients should be cautioned not to change the dosage or the schedule of administration without medical consultation. Awareness of adverse reactions. Patients should be advised about the common adverse events associated with the use of Betaseron (Interferon beta-lb, particularly, injection site reactions and the flu-like symptom complex (see ADVERSE REACTlONS section). Patients should be cautioned to report depression or suicidal ideation (see WARNINGS). Patients should be advised about the abortifacient potential of Betaseron (see PRECAUTlONS, Pregnancy - Teratogenic effects). Laboratory tests: The following laboratory tests are recommended prior to initiating Betaseron therapy and at periodic intervals thereafter: hemoglobin, complete and differential white blood cell counts, platelet counts and blood chemistries including liver function tests. In the controlled MS trial, patients were monitored every 3 months. The study protocol stipulated that Betaseron therapy be discontinued in the event the absolute neutrophil count fell below 750/mm. When the absolute neutrophil count had returned to a value greater than 750/mm therapy could be restarted at a 50% reduced dose. No patients were withdrawn or dose reduced for neutropenia or lymphopenia. Similarly, if hepatic transaminase (SGOT/SGPT) levels exceeded 10 times the upper limit of normal, or if the serum bilirubin exceeded 5 times the upper limit of normal, therapy was discontinued. In each instance during the controlled MS trial, hepatic enzyme abnormalities returned to normal following discontinuation of therapy. When measurements had decreased to below these levels, therapy could be restarted at a 50% dose reduction, if clinically appropriate. Two patients were dose reduced for increased liver enzymes; one continued on treatment and one was ultimately withdrawn. Drug interactions: Interactions between Betaseron and other drugs have not been fully evaluated. Although studies designed to examine drug interactions have not been done, it was noted that corticosteroid or ACTH treatment of relapses for periods of up to 28 days has been administered to patients (N=180) receiving Betaseron. Betaseron administration to three cancer patients over a dose range of 0.025 mg (0,8 million IU) to 2.2 mg (71 million IU) led to a dose-dependent inhibition of antipyrine elimination. The effect of alternate-day administration of 0.25 mg (8 million IU) of Betaseron on drug metabolism in MS patients is unknown. Carcinogenesis: The carcinogenic potential of Betaseron was evaluated by studying its effect on the morphological transformation of the mammalian cell line BALBc-3T3. NO significant increases in transformation frequency were noted. No carcinogenicity data are available in animals or humans. Betaseron was not mutagenic when assayed for genotoxicity in the Ames bacterial test in the presence or absence of metabolic activation. Impairment of fertility: Studies in rhesus monkeys at doses up to 0.33 mg (10.7 million lU)/kg/day which were designed to measure effects on menstrual cycle and hormone profiles have not been completed. It is not known whether Betaseron can affect human reproductive capacity. Pregnancy- Teratogenic effects: Pregnancy Category C: Betaseron was not teratogenic at doses up to 0.42 mg (13.3 million lU)/kg/day in rhesus monkeys, but demonstrated a dose-related abortifacient activity when administered at doses ranging from 0.028 mg (0.89 million IU)/kg/day (2.8 times the recommended human dose based on body surface area comparison) to 0.42 mg (13.3 million lU)/kg/day (40 times the recommended human dose based on body surface area comparison). The extrapolability of animal doses to human doses is not known. Lower doses were not studied in monkeys. Spontaneous abortions while on treatment were reported in patients (N=4) who participated in the Betaseron (Interferon beta-lb) MS clinical trial Betaseron given to rhesus monkeys on gestation days 20 to 70 did not cause teratogenic effects, however, it is not known if teratogenic effects exist in humans. There are no adequate and well-controlled studies in pregnant women. If the patient becomes pregnant or plans to become pregnant while taking Betaseron, the patient should be apprised of the potential hazard to the fetus and it should be recommended that the patient discontinue therapy. Nursing mothers: It is not known whether Betaseron is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Betaseron, a decision should be made as to whether either to discontinue nursing or discontinue the drug, taking into account the importance of drug to the mother. Pediatric use: Safety and efficacy in children under 18 years of age have not been established. ADVERSE REACTIONS Experience with Betaseron in patients with MS is limited to a total of 147 patients at the recommended dose of 0.25 mg (8 million IU) every other day or more. Consequently, adverse events that are associated with the use of Betaseron in MS patients at a low incidence may not have been observed in premarketing studies. Clinical experience with Betaseron in other populations (patients with cancer, HIV positive patients, etc.) provides additional data regarding adverse reactions; however, experience in non-MS populations may not be fully applicable to the MS population. Injection site reactions (85%) and injection site necrosis (5%) occurred after administration of Betaseron. Inflammation, pain, hypersensitivity, necrosis, and non-specific reactions were significantly associated (p<0.05) unth the 0.25 mg (8 million IU) Betaseron-treated group. Only inflammation, pain, and necrosis were reported as severe events. The incidence rate for injection site reactions was calculated over the course of 3 years. This incidence rate decreased over time, with 79% of patients expenencing the event during the first 3 months of treatment compared to 47% during the last 6 months. The median time to the first occurrence of an injection site reaction was 7 days. Patients with injection site reactions reported these events 183.7 days per year. Three patients withdrew from the 0.25 mg (8 million IU) Betaseron-treated group for injection site pain. Flu-like symptom complex was reported in 76% of the patients treated with 0.25 mg (8 million IU) Betaseron. A patient was defined as having a flu-like symptom complex if flu-like symptoms or at least two of the following symptoms were concurrently reported: fever, chills, myalgia, malaise, or sweating. Only myalgia, fever, and chills were reported as severe in more than 5% of the patients. The incidence rate for flu-like symptom complex was also calculated over the course of 3 years. The incidence rate of these events decreased over time, with 51% of patients experiencing the event dunng the first 3 months of treatment compared to 4% during the last 6 months. The median time to the first occurrence of flu-like symptom complex was 3 days and the median duration per patient was 10.4 days per year. Laboratory abnormalities included absolute neutrophil count less than 1500/mm (18%) (no patients had absolute neutrophil counts less than 500/mm), WBC less than 3000/mm (16%), SGPT greater than 5 times base- line value (19%), and total bilirubin greater than 2.5 omes baseline value (6%). Tbree patients were withdrawn from treatment with 0 25 mg (8 million IU) Betaseron ~Interferon beta-lb) for abnormal liver enzymes including one following dose reduction (see PRECAUTIONS, Laboratory Tests). Twenty one (28%) of the 76 premenopausal females treated at 0.25 mg (8 million IU) Betaseron and 10 (13%) of the 76 premenopausal females treated with placebo reported menstrual disorders. All of these reports were of mild to moderate severity and included: intermenstrual bleeding and spotting, early or delayed menses, decreased days of menstrual flow, and clotting and spotting during menstruation. Mental disorders have been observed in patients in this study. Symptoms included depression, anxiety, emotional liability, depersonalization, suicide attempts, confusion, etc. In the treatment group, two patients withdrew for confusion. One suicide and four attempted suicides were also reported. It is not known whether these symptoms may be related to the underlying neurological basis of MS, to Betaseron treatment, or to a combination of both. Some similar symptoms have been noted in patients receiving interferon alfa and both interferons are thought to act through the same receptor. Patients who experience these symptoms should be closely monitored and cessation of therapy considered. Additional common adverse clinical and laboratory events asociated with the use of Betaseron are listed in the following paragraphs. These events occurred at an incidence of 5% or more in the 124 MS patients treated with 0.25 mg (8 million IU) of Betaseron every other day for periods of up to 3 years in the controlled trial, and at an incidence that was at least twice that observed in the 123 placebo patients. Common adverse clinical and laboratory events associatcd with the use of Betaseron were: injection site reaction (85%), irgection DEe necrosis (5%), flu-like symptoms (53%), palpitation (8%), hypcrtension (7%), tachycardia (6%), peripheral vascular disorders (5%), gastrointestinal disorders (6%), absolute neutrophil count <1500/mm (18%), WBC <3000/mm (16%), SGPT >5 times baseline value (19%), total bilirubin >2.5 times baseline value (6%), somnolence (696), dyspnea (8%), laryngitis (6%), menstrual disorder (17%), cystitis (896), breast pain (7%), pelvic pain (6%), and menorrhagia (6%). A total of 277 MS patients have been treated with Betaseron in doses ranging from 0.025 mg (0.8 million IU) to 0.5 mg (16 million IU). During the first 3 years of treatment, withdrawals due to clinical adverse events or laboratory abnormalities not mentioned above included: fatigue (276, 6 patients), cardiac arrhythmia ( Return-Path: <@TECHNION.TECHNION.AC.IL, @TAUNIVM.TAU.AC.IL:r.korejwo@GENIE.GEIS.COM> X-Genie-Id: 1650966 X-Genie-From: R.KOREJWO Message-ID: <9403010144.AA19617@relay2.geis.com> Date: Tue, 1 Mar 1994 00:46:00 BST Sender: Multiple Sclerosis Discussion/Support From: Richard Korejwo Subject: "PULSE" Lines: 263 Status: O -=Ruth (Ruti) Lewin=- Re:"...Does anyone with chronic progressive MS have experience with steroid pulse therapy?..." Comment: I'll include a more detailed discussion regarding steroids but there is a short answer. In general, "pulse" is a perfectly effective therapy for chronic progressive MS but not in the method you seem to suggest. If you are CP and greater than a Kurtzke 6, you should be considering a monthly pulse of methyl (1000mg) to counter the collateral effects of secondary inflammation with a possible once a month immunosuppressant like azathioprine (Imuran) to attempt to deal with the primary demyelination. Keep in mind that the steroid is only meant to deal with the secondary effect of MS. Re:"...I am trying various alternative methods like homopathy and Reiki (self-healing), without significant physical benefits ..." Comment: I don't think you should be spending valuable time trying therapies which have no basis in good empirical evidence. If you are CP, you are wasting time. That is something you don't have. Re:"...I had 2 short courses of Prednisone orally, 1 and 2 years ago..." Comment: Of little value for MS. This was an old therapy for optic neuritis. It's considered of little value and potentially dangerous. While methyl is not without side effects, at least you can take some faith that the therapy might have a reasonably good outcome. Oral prednisone is of little value for MS. Certainly not worth much if you are CP. I apologize to everyone for the length of this post but I don't have time to crop this accurately. Based on your comments, I doubt that you meet the Kurtzke 6+ criteria. In this case, a monthly infusion of methyl would seem more appropriate. The group at Massachusets General Hospital Boston USA is the largest center that I'm aware of using this approach for management of CP. (Drs. Weiner, Hafler et al.) ------- Steroids - More than they appear? What follows is the compilation of a discussion about steroids which occurred over a period of a few weeks and was participated in by Barbara McMillen, Susie Perutelli, Doreen Samelson, and myself. Since there are a number of questions which arouse, it seemed fruitful to bring these ideas and facts together in one comprehensive paper. This was not written as a full and complete discussion of the technical issues but as a practical means to reach an appreciation for the rationale behind steroid therapy for MS and it's potential impact on "outcome." Steroids and, in particular, methylprednisolone have been a mainstay of MS therapy for some time and it's important to understand why. It is not uncommon for MSers to feel that high dose steroid therapy provide a control mechanism for acute exacerbations. This is not correct in the direct sense and that response needs some explanation. To understand the role and function of steroids, it is wise to first understand what is happening in an MS attack. For the purposes of this discussion we will accept the traditional view that MS is an autoimmune disease and is manifest by way off an assault by our immune system upon our own myelin in the central nervous system.(CNS) Since that is a fairly safe premise, I don't think it will meet with much objection. It would appear that some of our T-cells make their way through the blood-brain-barrier and, due to inappropriate coding of their T-cell receptors(TCR), start to attack the myelin. A number of things take place at this point. The T-cell which makes it to the scene of the crime first, sends out a number of messages which mobilize more T-cells designed to kill this "foreign" object, mobilize some specific B-cells which target the oligodendroglia cells which grow myelin, call in inflammatory T-cells, and finally call a wide range of other members of the damage control team like astrocytes, macrophages, etc.. One important result of all this congestion is that an inflammation develops at the primary site not unlike the inflammation that develops when you get a splinter in you hand. This inflammation adds some additional damage of it's own and generally enlarges the destruction. If this were a splinter in your finger you might say "Go for it!" The more damage done to this splinter the better. Unfortunately, this is not a splinter but a part of you that you would just as soon keep. While we are only marginally effective, at best, in controlling these T-cells, the next best thing is to try to limit the damage. Since part of the damage is occurring as a result of the general inflammation therfore control of inflammation seems like a reasonable thing to do. Under normal circumstances your body naturally generates steroids and these are adequate for day to day anti-inflammatory needs. Since this assault on the CNS is certainly not a desirable objective, it may be worth intervening to try to limit the damage. In general, two tools are available to medicine. We could, in severe cases, try to shut down the immune system to keep it from attacking the CNS. Medically this takes the form of some rather indiscriminate and potentially harmful immunosuppressants. We won't get into those here. The second approach is to try and control the inflammation which, although secondary to the original attack, has started to do damage on its' own. The bodies primary anti-inflammatory agents are those steroids. It is clear that the steroids that the body produces might, in time, reduce the inflammation and thus limit the amount of damage. It is also true that this is a very undesirable inflammation and deserves more than casual concern. It is contributing to your loss of function. Note that it didn't start the attack but it has become a contributing factor. At this point a doctor is confronted with some limited choices. First, he can sit back and let the body try to regulate the problem. Second, he can attempt to intervene on the side of the "good guys" and supplement your normal steroids with some additional ones. Which decision is best? Beats me! There is no way to say for sure that some additional steroids will really be enough to control the inflammation so that damage is limited and myelin is spontaneously regenerated sufficient to restore function, at least partially. There is also no clear proof that your body does not have enough natural capacity to overcome this inflammation. A doctor must weight the appropriate time to intervene. Originally, a common hormone, the anti-inflammatory agent adrenocorticotropic hormone (ATCH), was used to treat MS. This is a cortisone-type drug, administered over a short period of time by infusion. While it appeared that treatment with ACTH did not affect the long-term course of multiple sclerosis, studies have established that acute exacerbations were shortened and less intense in many persons receiving ACTH. In general this was most often effective of earlier disease than for relapses which occur later in the course of the disease. Following the clinical trials in the early 1970's, the F.D.A. approved ACTH in 1978 as a short term treatment for acute exacerbations of multiple sclerosis. The primary function of ACTH is really to stimulate the brain to produce prednisone, one of those common anti-inflammatory agents. For many years, and still continuing today, the administration of ACTH was a mainstay of MS therapy. Using a rule that "if some of something is good, more is better" it became clear that certain conditions might lend themselves to higher quantities of prednisone. Higher quantities than the brain can produce normally. While oral prednisone can sometimes be useful for short periods, it has a number of problems. It is not likely that it can be given in the quantities that have proven effective for intervention in MS. Dose levels of 200mg/day are generally considered to be the upper limit. Another factor to consider is the fact that it is difficult on the digestive tract. It should also be noted that extended use of any steroid can produce some serious problems and there is a tendency to maintain patients on oral prednisone for longer periods because of the patients general feeling of well being. While it may be desired by the patient, the results of long-term use of corticosteroids can produce cataracts, glaucoma and osteoporosis. As I said, the brain normally generates prednisone in response to ACTH and the amount of ACTH generated is linked to the amount of prednisone seen in the blood. There is one problem that needs to be mentioned here. If we artificially instill prednisone directly into the blood, it is possible that this will completely override the necessity for ACTH and production will stop completely. This is medically referred to as drug induced secondary adrenocortical insufficiency. The solution is obvious. You can only allow the patient to be maintained on this artificial level for a limited length of time and then you must insure that the normal production of prednisone is resumed. This was the birth of what we refer to as "pulse" methylprednisolone. In this therapy, the MS patient is given a very high dose of methylprednisolone (upwards of 1000mg/day) for a period of between 3-7 days. The number of days is often dictated by the doctors and/or patients past experience with the therapy. Since there is a clear possibility that ACTH production can still be affected permanently, the patient is often given decreasing doses of oral prednisone in the days following the "pulse". It's important to understand that none of the procedures is without side effects and ACTH, oral prednisone and methylprednisolone are no exception. Does this really do any good? A few years ago the Optic Neuritis Study Group took a look at the use of steroids for treatment of optic neuritis.(ON) As most of you know, ON is frequently a precursor for MS. In that trial, patients were given either a placebo, oral prednisone only or pulse methylprednisolone followed by a taper of oral prednisone. The conclusion of that study was: "Intravenous methylprednisolone followed by oral prednisone speeds the recovery of visual loss due to optic neuritis and results in slightly better vision at six months. Oral prednisone alone, as prescribed in this study, is an ineffective treatment and increases the risk of new episodes of optic neuritis." If, in the long run, you have less time in the destructive phase of MS, one might argue that the net result is a better "outcome." That's an unproven assertion. The Beck et al. ON paper was rather interesting in this area. (NEJM 27 Feb 1992 326;9:583-8) Clearly, the methylprednisolone treated patients improved more rapidly. (see charts on page 584) While this appears to be an effective change to the disease, it is really not. It really is a shortening of the inflammatory period. Beck et al suggested that at the end of 6 months the outcome was approximately the same, although he did concede a statistically better outcome for the methylprednisolone patients. In his case, he tended to dismiss the difference as small. I would disagree. Even a less-than-dramatic difference is very significant when measured over the rest of your life. Ask anyone who has taken integral calculus. In reality, that minor but "statistically significant" difference could be extremely important to the patient. If we now multiply this effect over 20 or more exacerbations, the net effect could arguably be said to even contribute to the outcome. While one can debate the results to exhaustion, I'd like to focus, for now, on one aspect only. The fact that the "pulse" patients were "slightly better" than the placebo patients. While the paper tended to dismiss the difference between the placebo and the "pulse" patients as small, it did acknowledge that there was a statistically better outcome at the end of 6 months. Under the assumption that we can project this small differential benefit forward into the situation of an MS exacerbation, one might say that there is a net accumulated benefit of receiving pulse for repeated attacks of MS. The paper did not deal with that. In 1993 that same group re-examined the patients in the study group to attempt to determine whether there might be any long term impact of the trials. (Science 9 Dec 1993 329;24:1764-69) While I don't tend to completely endorse the findings of the group, it is probably worth noting the result. Based on there analysis, a statistically significant difference was suggested in the outcome after a period of between two and four years. The one criteria they used was the definitive measurement of the percentage of patients who had developed multiple sclerosis. Under normal conditions, a rather significant percentage (20%) of ON patients develop MS within two years of the initial ON attack. After 15 years the figures can increase to as much as 80%. In their second study the ON Study Group determined that the incidence rate for MS in the methylprednisolone arm of the study was indeed less. While the total number of patients in each arm was small (approx 130) and the actual incidence (21-24) was equally small the results raise an interesting question. Are the effects of repeated use of pulse methylprednisolone really cumulative and therefore do they really impact the "outcome" of the disease? The question is most noteworthy in the wake of the substantial hype generated by Betaseron and the lottery. The primary claim to fame for Betaseron was that it was the first treatment that actually affected the course of the disease or, in other words, the "outcome." Anyone who has read the paper and the accompanying MRI study, quickly realizes that, from the patients perspective, the net benefit was relatively small after three years of therapy. It is not an issue as to whether there might have been a reduced total lesion area in the MRIs of the 8MIU Betaseron group. There was. But this effect was largely noticed by the radiologist and not the patients or the "blinded" neurologist who examined them. Although only suggested by the more recent study of the ON Study Group, it seemed that there was also a potential net effect from the administration of "pulse". While getting MS is certainly a definitive event, the data does suggest that, if we add together the accumulated benefits of prompt methylprednisolone therapy, the net result to the patient is a better outcome. I was not overwhelmingly impressed by the Betaseron data because it was largely exhibited in radiological measurements and only marginally in physical outcome. I do think that the radiological data is valuable but question whether we have lost sight of the patient. The only thing that really matters is the extent of disability that the patient realizes. I'm not sure whether the radiological evidence would be as promising for "pulse" as it was for Betaseron because it was never gathered. I'm not sure that it matters. If the Betaseron radiological data was, in fact, better, it certainly was not clearly exhibited in the net extent of disability as measured by the Expanded Disability Status Scale.(EDSS) The immediate response from the Betaseron study group was to disparage the accuracy of the EDSS. While that might be justified, it remains that the net effect on disability was not significantly changed. I think it's important to keep a good grasp on what "outcome" really means. We have all laughed at the comment "the operation was a complete success but the patient died." What that statement points out is the difference in the meaning of the result. "Outcome" is just such a word. The "outcome" as seen from the prospective of the radiologist in the Betaseron study was clear and beneficial. As seen by the evaluating physicians "outcome" was, at best, marginal. In the end, the accumulated effect of Betaseron and the end of 5 or 10 years (at approximately $10,000/year) has yet to be documented. Likewise, the most recent paper on methylprednisolone suggest the potential of a favorable "outcome" that might be realized from that treatment. In the end the only "outcome" that really matters is whether the patient is better off. -RJK From alt.support.mult-sclerosis Thu Mar 10 21:31:19 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!news.ans.net!mrtnt.ntrs.com!tntvax!mml Newsgroups: alt.support.mult-sclerosis Subject: Re: Animal Fat Message-ID: <1994Mar9.115910.1@tntvax> From: mml@tntvax.ntrs.com Date: 9 Mar 94 11:59:10 -0600 References: Lines: 58 Status: O In article , "STARS::MACPHERSON" writes: > Yes Michelle, > > I'm ranting on the Swank diet. Do it every chance I get. I've read > about half of his 30 scientific publications. He's follwed his dieters > for 34 years now, and 80% are still around, having suffered about one > Kurtzke scale loss in the interim. Only 20% of his non-dieters > survived. > > I've just finished his "A biochemical basis of multiple sclerosis" > Springfield, IL: Charles C. Thomas, 1961, which I got on interlibrary > loan from the Erie Public Libary, Eris, PA. Chapter 3 provides the > historical scientific basis for his research. Even the original > researcher, Dawson, found the plaques most frequently around veins. > He and others also observed loss of mylin before they spotted any > microglia, and so concluded that the immune response was a response to > the original problem which caused the damage to the mylin. > > Swank did a series of animal studies which demonstrated that animal > fat caused red blood cells to change shape, stick together, and jam in > the capillaries. His research showed that blocking > capillaries increased the permiability (sp) of the downstream veins. So > his animal research supported the histological examinations, and his > treatment was demonstrated to alter the course of the disease. Other > than this and a 35 year record of success he has nothing going for > him. > > Something I usually neglect to mention is that the effects are not > immediate, but can take a year to become apparent. You have to stick > to it to get the good effects. > > Doug M. Doug: Thanks for the data. I had optical nueritis last year with no other symptoms before or after. However, the nuerologist I saw seemed to think it was quite possible I would develop symptoms of MS in the future. He went on to say there was absolutly nothing I could do to prevent or minimize or in any way affect the development of MS. If it is to be, it is to be in his opinion. I don't like hopeless situations and I don't like the feeling I can do nothing so I did some research on my own and found many references to the Swank diet. I've been following it religiously since last October. The good news is that I have had no other symptoms develop so far and some of the other things which had been troubling me, joint pain and insomnia, have all bu gone away. I'm also loosing weight at the rate of about 1/2 pound a week. This is great because I have a weight problem any how but I hate to diet. For any others who are following the Swank diet, you might also want to review the offerings in alt.fat_free. The folks on that board have all kinds of neet ideas about how to minimize fat of all kinds in your diet. -- Michele M. LaMar MML@ntrs.com | Statements and opinions expressed are my Northern Trust Co. MB05 | own and are measured by weight not volume. 50 S. LaSalle | Some settling of contents may occur. Chicago, IL 60675 USA | From alt.support.mult-sclerosis Sat Mar 12 17:02:55 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!!"STARS::MACPHERSON" Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:MACPHERSON%STARS.decnet @ALEXANDRIA-EMH2.ARMY.MIL> Message-ID: Date: Fri, 11 Mar 1994 00:03:00 EST Sender: Multiple Sclerosis Discussion/Support From: "STARS::MACPHERSON" Subject: Re: MS - Diet Lines: 36 Status: O Gabriel posted a letter presenting the problems of evaluating any MS treatment with a self selection component. An approach to the problem is to consider an ABA combination of treatments, as described in Campbell and Cook's (or visa versa) "Quasi-Experimental Design." So in your study you pay particular attention to erratic dieters -- those who go off diet and then back on. Swank observed that patients who went off diet did report exacerbations and that the exacerbations ceased when they resumed dieting. But Swank hadn't read the book, because it hadn't been written yet so he didn't present numbers. His A M A Archives of Neurology and Psychiatry paper "Treatment of multiple sclerosis with a low fat diet" does present exacerbation graphs for 47 patients, for three years prior to the diet and up to four years afterwards. The two non-exacerbating progressives didn't have any exacerbations before or after, they just got steadily worse. Two of the 11 "exacerbating-remitting type-late progressive had no exacerbation either before or after the starting the diet. The other nine had one to six major exacerbations each before starting the diet, and only one had a major exacerbation in the two plus years after starting the diet. Of the 34 "early" patients, all had had two to seven major exacerbations before starting the diet and no major exacerbations after starting the diet. On the average these patients had fewer minor exacerbations after starting the diet than they had major exacerbations before starting the diet. This is called a subject as his own control design. It would be better if he put patients on a placibo diet for some period, but he has ethical qualms about such a procedure. I find his graphs pass the "inter-ocular impact test" -- the results hit you between the eyes. Disclaimer: He said it, I just paraphrased him. Doug M. Sorry, I don't have the date for the paper on my xerox copy, but it's early '50ies. From alt.support.mult-sclerosis Sun Mar 13 12:18:50 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!usenet.ins.cwru.edu!news.ysu.edu!psuvm!auvm!!"STARS::MACPHERSON" Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:MACPHERSON%STARS.decnet @ALEXANDRIA-EMH2.ARMY.MIL> Message-ID: Date: Sun, 13 Mar 1994 00:09:00 EST Sender: Multiple Sclerosis Discussion/Support From: "STARS::MACPHERSON" Subject: Re: BOOKS Lines: 97 Status: O Might as well reply to your request, Jeff And make use of your subject line. I could repost my description of Swank, R. L., and Dugan B. B. The multiple sclerosis diet book. New York: Doubleday, 1987 but instead I'll start again. I'm reviewing this as scientific psychologist. I see a lot of BS and I run checks on the "face" validity and "construct" validity of the book. First some comparisons. Swank is the book we and our daughter use to deal with her MS. We had another book, a collection of papers on different aspects of MS, published in the late 80ies. We've forgotten the title to that one, nuf said. We paid the Health Resource, 290 Katherine Drive, Conway AR 72032 or (501)329-5272 for a literature search on MS. 150 pages for $175 and free updates upon request. That produced a variety of articles, including Swank's 34 year followup in the Lancet and a large number of abstracts from Medline for the last 3 years. The quality of the articles was variable, including even bee sting therapy. The Health Resource (HR) was useful because it gave us the confidence that we were being exposed to everything currently going on in MS, in English anyway. I don't recommend that others get it. This forum is as informative. However HR reproduced pp 303-307 from Nutritional Influences on Ilness: A sourcebook of clinical research by Werbach. The first citation was "low fat diet" and reviewed Swank's "20 year" report as an experimental study. So we know from that and other mentions in other parts of the HR compilation that Swank is worth considering. The book itself: About 230 pages of receipes preceeded by 100 pages of living with MS and his research then followed by 130 references, including a half dozen by Swank himself. The man is a serious scientist. I don't vouch for the receipes, although they look good. In the introduction Swank says he has examined about 3500 MSers, and "maintained contact with approximately 2000 of them for 10 to 36 years." He seems to have enough clinical experience to write on MS. But you're interested in Ch 4, where he gives general information on MSer characteristics like active, intelligent, highly productive, vital, usually attractive, tense and perceptive. Anxiety and nervious tension of any cause produce fatigue and a reduced ability to perform. MSers are heat intolerent, but can get a temporary improvement by dropping their body temp .6 to 1.2 degrees. He also covers weather changes, seizures, headaches, hypertension, sex problems, genetics, race, latitude, sex differences, alcohol, cigarettes, caffeine, marijuana, mental functions and age, but only 1-3 paragraphs each. Chapter 5, the clinical picture: Neither primary physicians nor neurologists diagnose MS correctly in the very early stages -- they misdiagnose and send you to a psychiatrist who agrees with them that you're nuts (not his words). He then characterizes early and late symptoms. Ch 6, diagnosis. If you are American you've experienced the tests, except for the red cell mobility test which Swank favors but is only used in Europe. Ch 7 Introduction to treatment. (Or how to live with MS). Diet and daytime horizontal rest. What to do about fatigue, the flu, irritability, depression, divorce, pregnancy, surgery, exercise, heat, vision, pain, facial pain, accidents, elimination, sex, wakeup symptoms,steroids, diagnostic procedures to be avoided, and plasma therapy. Ch 8 has the results of the first 34 years of his diet research. Ch 9 has the technical information about the circulatory characteristics of MS patients. Ch 10 is general information about nutrition and a balanced diet. Ch 11 gives the low fat diet instructions. Ch 12 deals with milk substitutes. The remaining chapters are the receipes for breakfast, lunch, the cocktail hour, soups, seafood, beef, oriental cruisine, meatless cooking, veggies, bread, and several chapters on desserts and sweets right down to the icing on the cake. Swank does not cover Betaseron or the other treatments that are being developed so you don't look to him for that, just for how to live with your current condition and stop or slow the progress. Obviously, since I sent the time to do all this I think Swank has written a very good book on living with MS. I would say the best book but I haven't read the others. For Gordon I would recommend Swank's "Biochemical basis of multiple Sclerosis" which describes how he came to focus on microcirculation as the cause of MS. But it's out of print and he'll have to get it the way I did, on interlibrary loan from the Erie Public Library. Enough, I hope this helps you to decide if you want to get the book. Doug M. From alt.support.mult-sclerosis Wed Mar 16 10:04:42 1994 Newsgroups: alt.support.mult-sclerosis Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!hookup!nic.hookup.net!xenitec!golem!davidf From: davidf@golem.waterloo.on.ca (David J. Fiander) Subject: BOOKS: Some reading material Date: Tue, 15 Mar 1994 00:07:38 GMT Message-ID: <1994Mar15.000738.2263@golem.waterloo.on.ca> References: Lines: 71 Status: O According to "STARS::MACPHERSON" : >David suggests a MS bibliography FAQ. He also has some books that were >recommended by his neuro or the MS society. Hmmm, if he would list >them, maybe with comments, and include "good books" in the title then >we would have a start on an annotated bibliography. Great ;-) This is a perfect example of "you touched it, you own it", which is why many programmers refuse to learn new software. Once she's fixed a bug, she's responsible for mantaining the whole program until somebody else slips up and fixes something. It's been just over five years since my wife was diagnosed, so our (smaller than I thought) library is that old. I have three books that I'm going to describe, but only one of them is about MS directly. While flipping through our stuff, I found that the MSS of Canada provides a free annotated bibliography. I'll get one of these and find out about redistribution. Scheinberg, Labe C. and Holland, Nancy J. eds. _Multiple Sclerosis: A guide for patients and their families_. 2nd ed. New York: Raven Press, 1987. This is a collection of essays (sample chapters: "Epidemiology and genetics of MS", "Sexuality"), written by various health professionals involved with the treatment of MS. The most difficult article in the book is simpler than your average Scientific American article, so most people on this list should be able to manage with little difficulty. An added bonus is that the book's royalties are being contributed to support the New York City chapter of the NMSS. Hanson, Peter G. _The Joy of Stress_. 2nd ed. Islington, Ontario: Hanson Stress Management Organization, 1986. This may look like a vanity publication, but it was recommended by a neurologist at Princess Margaret Hospital in Toronto (Dr. Gray, we think), which has a very prominent MS research program. We found it in a large chain bookstore, so it should be generally available. The book starts with a discussion of what stress is, and why a certain amount of stress is actually good for you. It then gives the "Hanson Stress Test", which is based on the "Homes-Rahe" test. The important thing about this test is that, rather than asking questions and giving an answer, it asks questions and explains _why_ your answer can affect your health. Weekes, Claire. _Hope and help for your nerves_. New York: Bantam, 1969. Our neurologist recommended this book (we think). Rather than talking about "stress" or "fatigue," it uses the phrase "nervous illness." This is partly due to the book's age and partly due to the fact the the author is British. It's been a while since I read this, and it must have some good things to say, but I just flipped through it and found the following sentence: The sound of the very words [shock treatment] is frightening and yet, despite its name, it may bring quick relief. Caveat lector. - David From alt.support.mult-sclerosis Wed Mar 16 10:08:59 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!vixen.cso.uiuc.edu!prairienet.org!jnovak From: jnovak@prairienet.org (Jean L. Novak) Newsgroups: alt.support.mult-sclerosis Subject: Re: Megadose of Steroids ~# Date: 16 Mar 1994 04:49:30 GMT Organization: University of Illinois at Urbana Lines: 46 Message-ID: <2m634q$cu1@vixen.cso.uiuc.edu> NNTP-Posting-Host: firefly.prairienet.org Originator: jnovak@firefly.prairienet.org Status: O Here's what I know about Imuran (aka azathioprine). It's most common use is to prevent rejection after a kidney transplant.... it's a pretty strong immunosuppressant. It's also used in rheumatoid arthritis sometimes....RA is thought to be an autoimmune disease. Imuran supresses immunity and changes antibody formation...meaning that your body will have trouble fighting off infection (ASK before you receive immunizations, avoid people with active infections, etc.) It's hard on your liver, and your liver governs blood clotting factors, among other things, so bleeding COULD be a side effect. The ever- present "flu-like" symptoms of nausea, vomiting, fever, chills, of course, apply here too. The onset of action for orally administered Imuran is 6-8 weeks, with a peak at 12 weeks (this could be one reason you haven't had effects yet). Part of the teaching with Imuran used for RA is that "joint damage will not be reversed, the goal is to slow or stop the disease process" (directly from my reference source, Davis' Drug Guide for Nurses, 2nd Edition). It would make sense to me that the same would be expected for MS. Just for comparison, Solu-Medrol (aka Methylprednisolone) supresses inflammation, and it also affects the immune response, but not as markedly as Imuran. Over the long haul, it also supresses your adrenal gland (which is why you need to taper if you've been on it long term...you need to let your adrenal gland "remember" to do it's job when the Solu-Medrol stops doing it). Side effects (besides those above): depression, euphoria, high blood pressure, nausea, anorexia, delayed wound healing, acne, excess hair growth, and increased chance of infection (but not as increased as with Imuran). From what I've read about Methylprednisolone related to MS, orally administered MP _without_ a three day course of IV MP to start is not very effective. Of course, I've only started reading about MS after my January 25 diagnosis, and my views are biased by my neurologist who believes the above. As I said, my main reference is my drug guide...a nursing guide may be a good investment for interested folks. You can usually buy last year's issue at discount bookstores for a couple bucks (the current one is usually <$25US, depending on the publisher). Nursing drug books are usually good for the general public because most include patient teaching information, which is what you need to know, and they don't go into the boring detail that the Physician's Desk Reference (DRUG BIBLE) or pharmacology books do. Hope some of this helps! Jean From alt.support.mult-sclerosis Thu Mar 17 22:31:25 1994 Path: klaava!news.funet.fi!sunic!EU.net!uknet!pipex!bnr.co.uk!corpgate!news.utdallas.edu!chpc.utexas.edu!cs.utexas.edu!swrinde!emory!europa.eng.gtefsd.com!paladin.american.edu!auvm!VMA.CC.ND.EDU!LMESSERS Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL,@VMA.CC.ND.EDU:LMESSERS@VMA.CC.ND.EDU> Message-ID: Date: Tue, 15 Mar 1994 06:37:08 EST Sender: Multiple Sclerosis Discussion/Support From: "Linda L. Messersmith" Organization: University Libraries of Notre Dame Subject: MS Bibliography 1992-1993 Lines: 39 Status: O Here are some recent titles. I will start to look at some of these this summer but there is no evaluation for any right now. Sorry about that. Multiple sclerosis: new hope and practical advice for people with MS and their families / by Louis J. Rosner. N.Y.: Simon & Schuster, 1992. This says 1st Fireside ed. which might indicate it was published before. Inspirational persuasion: experiencing multiple sclerosis / by W. Randy Taylor. Alexander, N.C.: WorldComm Press, 1993. Multiple sclerosis: its impact from childhood to old age / by H. J. Bauer. London: W.B. Saunders, 1993. This is from the series: Major problems in neurology ; v. 26. Multiple sclerosis: a neuropsychiatric disorder / (no author) Washington, DC: American Psychiatric Press, 1993. This is from the series: Progress in psychiatry series ; no. 37 - it's probably a bunch of separate papers. Coping when a parent has multiple sclerosis / by Barbara Cristall. N.Y.: Rosen Pub. Group, 1992. In spite of everything / by Janis M. Hogan. Tucson, Ariz.: J.M. Hogan, 1992. Multiple sclerosis and the family / (no author). N.Y.: Demos, 1992. One particular harbor / by Janet Lee James. Chicago: Noble Press, 1993. That's enough for now. There should be enough info here to go to your library and request it through interlibrary loan. It's usually free (ask) and find out how long you can have it. It might be just a few (2) weeks but that varies. Linda M. From alt.support.mult-sclerosis Sat Mar 19 11:29:47 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!WORLDBANK.ORG!MSCHUMAN Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:MSCHUMAN@WORLDBANK.ORG> MR-Received: by mta EDSEL; Relayed; Thu, 17 Mar 1994 23:04:57 -0500 MR-Received: by mta EARTH; Relayed; Thu, 17 Mar 1994 23:07:48 -0500 Alternate-recipient: prohibited Disclose-recipients: prohibited MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT Posting-date: Thu, 17 Mar 1994 23:04:00 -0500 (EST) Importance: normal Priority: normal X400-MTS-identifier: [;75403271304991/244603@EDSEL] A1-type: MAIL Hop-count: 1 Message-ID: <01HA369HB6P28ZEQ47@mr.worldbank.org> Date: Thu, 17 Mar 1994 21:15:00 -0500 Sender: Multiple Sclerosis Discussion/Support From: Margret Schuman EDS02 80107 Subject: THE MYELIN PROJECT- RESEARCH - Glial Cells - Gamma Globulin ~# Lines: 216 Status: O VERY LONG TEXT FOLLOWING- but, please read on, this might interest you. Many of you heave heard about or even seen the movie Lorenzo's Oil. If you haven't, I suggest you get the Video from the store. It is worth seeing (starring Susan Sarandon, Nick Nolte). Lorenzo is the son of an ex-colleague of mine, Augusto Odone. I didn't know him when he was at the World Band, but met him about 2 years ago at the premiere of the movie. (Susan Sarandon was there, unfortunately Nick wasn't!!) The movie and Lorenzo's oil were unduly criticised by some critics and members of the medical and scientific field, but please don't let this influence you. Fact is, that Lorenzo's oil does bring adrenoleukodystrophy (ALD) to a stillstand in about 50-60% or more of all children treated. My humble guess is that much like MS, the disease might have multiple causes and is different in almost every case. Serious Neurologists and Scientists familiar with the case do fully recognize Lorenzo's Oil, however. Just in case, LORENZO'S OIL IS ONLY PRESCRIBED FOR CLEAR CASES OF ALD-IT IS NOT AVAILABLE FOR ANY OTHER DE-MYELLINATING DISEASES. I said, I know Augusto, have collected contribution for the Project at times and am planning to work voluntarily in his offices as soon as my condition allows me to. Augusto Odone is a walking medical dictionary. I have never met anybody who knows more than him about de-myelating diseases, MS included. (He also was one of the first people, if not the first, to tell me about Betaseron- he suggested at the time to invest in Berlex Stock. I'm sure he did, unfortunately I didn't!) He founded and oversees/manages the Myelin Project, which is indeed is non-profit. Every penny donated goes to research. Only a very limited amount goes to overhead. Augusto did not found this Project to gain fame and glory, but for the sole purpose of finding a cure for his son. The Project is run on the tightest budget possible. The Odone family lives from the profits Augusto makes from his own consulting firm. Currently, the Project is contributing to and organizing independent research on Re-Myelation, which also is obviously extremely important to MS-sufferers. The Oil, by the way is not effective on MS. The re-myelating research however, if successful, will be essentially extremely helpful and open new doors to MS sufferers. I am copying the latest information on the projects funded and research currently supported and/or financed by the Myelin Project. Please note the research done on Gammaglobulin by the Mayo Clinic, which also answers some of my earlier questions. Mr. Odone is currently working on an updated report of the last meeting of the scientific members of the Project and an update on their research. I will copy it to you as soon as I get it. Here is the Summary Report on the Fifth Meeting of The Myelin Project Work Group (Rome, Sept. 17-19, 1993), and the cover letter for the Project's Christmas donation drive, which gives a short update (by the way, if you do want to donate something to the Project, I'll give the details at the end of this report.) "The Meeting focused on three major topics: glial cells, transplantation experiments, and immunoglobulin G (IgG). Glial Cells Studies conducted over the last decade have shown how the central nervous system (CNS) of dysmyelinated or demyelinated animals can be remyelinated by transplanting glial cells extracted from fetal, neonatal and adult CNS of healthy animals. It would appear, however that the best cells for remyelination purposes are those of fetal origin. As these cells mature, they give rise to oligodendrocytes, the cells specialized in remyelinating CNS nerve fibers, or axons. [Fetal glial cells are thus also referred to as oligodendrocytes progenitors (OP)]. Participants agreed that an important step towards myelin repair in humans would be to establish appropriate lineages of OP which could provide a source of myelin-producing cells without continuously resorting to fresh fetal material. Setting up such a cell resorting to fresh fetal material. Setting up such a cell "factory" would call for isolating stem cells or oligodendrocyte progenitors (OP) from human fetal CNS tissue, growing them with appropriate growth factors and obtaining expanded cell populations that could be induced to differentiate into oligodendrocytes. To test the cells' ability to migrate and remyelinate naked axons, they would be transplanted into dysmylinated/demylinated rodents, previously immunosuppressed to minimize the rejection risk associated with cross-species transplants. To accelerate this work, participants in the meeting decided to establish a task force which would focus on developing human cell cultures for use in clinical trials. Six members of the Work Group agreed to constitute the task force. 1) They will meet a first time in Washington, DC on November 7, 1993. -------------------------------- 1) These researchers are: Dr. Francisco Aloisi, Instituto Superiore di Sanita, Rome; Dr. Annick Baron-Van Evercoren, Laboratoire de Neurobiologie Cellulaire, Moleculaire et Clinque, Hopital de la Salpetriere, Paris; Dr. Patrick Brunden, Restorative Neurology Unit, University of Lund, Sweden; Dr. Charles ffrench-Constant, Wellcome/CRC Institute of Cancer and Developmental Biology, Cambridge; Dr. Monique Dubois-Dalcq, National Institudes of Health, Bethesda, Maryland; Dr. Ian Duncan, Department of Veterinary Medicine, University of Wisconsin --------------------------------- Transplantation Work Group members were optimistic about the feasibility of human transplant trials in the near future. This upbeat mood is underscored in an excerpt from Dr. Duncan's letter following the Rome meeting: "I enjoyed the recent meeting in Rome and think that real progress was made. I think this year will definitely see the first human glial cell grafts into animals and then the next year, I really believe the first human transplants will be carried out. The task force on the derivation and characterization of human glial for transplant purposes will really help accelerate the work". In the course of the meeting Dr. Duncan illustrated the transplantation experiments he is currently conducting, and those he is about to initiate with funding from The Myelin Project's fourth year grant to his laboratory. As already mentioned in the last progress report (July 19, 1993), these experiments will be conducted not only on the shaking pups but also on various dysmyelinated/demyelinated rat mutants. Dr. Duncan also described an experiment conducted jointly with Dr. Dubois Dalcq on myelin deficient rats. This experiment called for implanting in the rat spinal cord cells belonging to a cell line (Central Glial 4, or CG 4) developed in vitro by a Californian laboratory. (Dr. Duncan has just reported that this experiment was highly successful; the newly implanted CG 4 had migrated far from the site of implant and had remyelinated vast areas of the animals' spinal cords.) IgG Drs. Rodriguez and Noseworthy of the Mayo Clinic illustrated the putative role of IgG, not only as an autoimmune system regulator but also as a remyelinating factor. They also described an experiment they propose to conduct on the use of IgG in multiple sclerosis. Although these researchers have already obtained grants from the National Institutes of Health and from the American Multiple Sclerosis Society, they have asked the Myelin Project for a $143,000 grant. This additional financing would allow monitoring 30 patients with serial MRIs to detect any possible remyelination, following IgG administration. I have asked the other members of the Work Group to give me their advice on the above proposal and I intend to seek similar advice from an outside reviewer specializing in MRI studies. Dr. Annnick Baron-Van Evercooren of the Salpetriere informed that after some initial problems the monkey experiment is proceeding well. By reducing lysolecithin dosages and lengthening the injection time she is obtaining more and more "viable" lesions in the animal cerebral myeling. If this progress continues, her team will soon shift attention from establishing myelin lesions to repairing them by glial cell tran,splant. Dr. Baron mentioned that in one variant of the prospective transplants she intends to try Schwann cells, as an alternative to monkey glial OPs, in order to verify whether or not these cells cans produce "good" myelin and repair central myelin lesions. ------------------------------------- Excerpt from Christmas Fund Drive cover letter, dtd. 12/1993: "Our research is advancing rapidly on three crucial fronts. Experiments being conducted at the Salpetriere in Paris and at the University of Wisconsin at Madison are expected soon to provide conclusive evidence that transplanting myelin-producing cells (glial cells) leads not only to the remyelination of animal central nervous systems but also to the restoration of functions. A task force recently created from among Work Group members is focusing on developing human glial cell lines to provide an adequate supply of cells for prospective clinical trials. We have pledged our support for a Mayo Clinic trial on the use of IgG in MS and have specifically targeted our funds at serial MRI studies which will determine whether or not IgG has remyelinating properties." --------------------------------- Ok, this is it. Please overlook any typos. Also, please keep in mind that Augusto Odone is writing his reports in as simple a language as possible so people with non-scientific/medical background can understand what is going on. If you are interested and would like to donate something to the Myeling Project, following is their address. Please, PLEASE DO NOT however, call them about questions on MS, and Lorenzo's Oil. This just would waste their precious time and money (donated for the research. LORENZO'S OIL HAS NO EFFECT ON MS. The Myelin Project 1747 Pennsylvania Ave., N.W., Suite 950 Washington, DC 20006 Fax: 202-785-9578 Tel.: 202-452-8994 1-800-8-MYELIN (The Myelin Project does accept VISA and MASTERCARD - just in case you're interested in making a donation. Of course, they also accept checks and cash!!!) I'll copy Mr. Odone's latest report to you as soon as I get it. Onwards, Margret From alt.support.mult-sclerosis Sat Mar 19 20:39:51 1994 Path: klaava!news.funet.fi!sunic!trane.uninett.no!eunet.no!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!MARY.IIA.ORG!blackb Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL,@CUNYVM.CUNY.EDU:blackb@MARY.IIA.ORG> Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Message-ID: Date: Thu, 17 Mar 1994 16:07:05 -0500 Sender: Multiple Sclerosis Discussion/Support From: Barbara Black Subject: Re: MS Bibliography 1992-1993 In-Reply-To: <199403170547.AA12996@mary.iia.org> Lines: 11 Status: O A book that I think should be on anyone's list is McAlpine's Multiple Sclerosis by Matthews, Compston, Allen, and Martyn. Published by Churchill Livingston in Edinburgh. The second edition was published in 1991. It is not cheap ($90 or thereabouts) and used to be hard to find; but I think now that a new edition is out, libraries will get it. It is a classic and has sections on epidemiology; clinical aspects; genetics & immunology; pathology. If you're interested in the medical aspects of this disease, this is a good resource. Barbara Webster Black BLACKB@IIA.ORG 3319 Holly Court Falls Church, Virginia 22042 From alt.support.mult-sclerosis Wed Mar 23 18:04:05 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!paladin.american.edu!auvm!SFSUVAX1.SFSU.EDU!pflavel Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:pflavel@SFSUVAX1.SFSU.EDU> Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Message-ID: Date: Tue, 22 Mar 1994 22:34:00 -0800 Sender: Multiple Sclerosis Discussion/Support From: Paul Flavell Subject: Beta/MS Test/R/R Lines: 42 Status: O I'm more or less a lurker, not a writer in this group although I occasionally respond to an individual. I've learned from sad experience that I don't understand the protocol or whatever of this particular type of communication and often get flamed. But I logged on tonight after just three days and there were 68 messages for me to read. It's taken over an hour and I feel compelled to make comments on 2-3 subjects that were being discussed. #1 - Betaseron... I live in San Francisco, just a few miles from the headquarters of Chiron, the beta manufacturers... Berlex is the distributor for Chiron. Last summer before its liscensure was even won, folks (investors mainly) asked if Chiron could keep up with demand IF beta were licensed. No problem, they said then. WE've got barrels of the stuff already! A couple of days later they retracted that statement. My understanding is that it's not the manufacture per se that's the problem but the BOTTLING. On NPR's Science Friday program in October '93, Thomas Murray, Professor and Director of the Center for Biomedical Ethics, Case Western University, Cleveland, OH said, "Suppose we discovered tomorrow an even more dramatic drug (than Betaseron), one that cold literally cure AIDS. And it was made by a very small company that simply didn't have the capacity to scale up production rapidly enough. What would happen? Would we insist that company not keep it to themselves but at least license it to other, large, producers so that we could get it out to everyone who needs it right away?" How is Chiron/Berlex going to gain additional information from current beta users? None that I know are being monitored in any formal, controlled, quantitative fashion - although I imagine that the few hundreds who got their supplies via a few selected medical centers (extra lottery, by the way) ARE being studied without specific consent being requested. Many are also paying and happily so. And as for capacity being low because it's a bacterial side product, ever hear of beer, or wine, or know how many other things we owe to bacteria? #2 - Relapsing/remitting, when will the symptoms go away? The disorder is called multiple sclerosis (many scars) for a reason. Inter-episodic symptoms may not subside at all, it's the active degeneration that disappears between episodes. No one is sorrier about this than me. And I read with glee that numbness in someone hand, disappeared after 2 years! #3 fusing... how many of us have heard how many really horrible diagnostic tales and for how long are we going to continue to listen to these tales without taking some action? The NMSS recently turned back a request for research funds from a doctor (whose daughter and niece have MS) who's earlier work found a blood test that was correct 66% of the time in detecting MS. The NMSS said finding a test "is not a priority at this time." As General Dugan said, "There are MRI's and spinal taps and hundreds of good neurologists all over the country." We ought to demand a test, IMHO. From alt.support.mult-sclerosis Fri Mar 25 21:10:03 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!U.WASHINGTON.EDU!britell Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:britell@U.WASHINGTON.EDU> X-Sender: britell@stein3.u.washington.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Message-ID: Date: Thu, 24 Mar 1994 07:32:14 -0800 Sender: Multiple Sclerosis Discussion/Support From: Catherine Britell Subject: Bladder Function in MS In-Reply-To: <9403240954.AA26507@mx2.u.washington.edu> Lines: 236 Status: O Because there have been a number of questions about bladder problems in MS here, I thought I'd upload an edited version of a short discussion of bladder function in MS that I originally wrote for people on the MS BB on the Prodigy Service. Here it is: The demyelination caused by MS often affects the motor and sensory pathways of the bladder. When a person has this he/she is said to have a "neurogenic bladder". Bladder symptoms can vary in MS, depending which nerves are affected. Also, they can change with time, just as other aspects of the disease change. It has been estimated that 50-80% of people with MS experience some kind of bladder difficulty. There are three main types of neurogenic bladder symptoms seen in MS, related to the area of the lesion.: (1) The urine seems to want to come out too frequently and too easily. When a person first gets the urge, he/she doesn't have very long to get to the bathroom, and has to go quite often... more than 6-8 times per day and more than once at night. And, sometimes if a person doesn't make it to the bathroom, they do lose control. (2) The urine just doesn't seem to want to come out. The stream is weak or intermittent, and it's difficult to get it started. And sometimes when the bladder gets full, the urine overflows and starts dribbling out. The person may have frequent infections. (3) A combination of the above. These symptoms can be caused by a variety of functional bladder problems. The bladder wall muscle (detrusor) might contract too hard...or it might not contract hard enough. The sphincter may contract at the same time the detrusor contracts, thus keeping the urine in and causing high pressure in the system. (That's called "detrusor-sphincter dyssynergy") Or, the sphincter may not contract when it needs to in order to hold the urine in. Or, some of those can happen together. As you can well imagine, it's pretty difficult for the doctor to tell exactly which of these things is happening from the symptoms you're having. Therefore, some diagnostic tests are usually done, in order to determine the best way to deal with this. A "cystometrogram" or "CMG-EMG" is often done in order to tell what's happening to the detrusor and sphincter muscles as the bladder fills and empties. Other tests that are sometimes performed to further diagnose the problem may include Ultrasound of the abdomen, kidney X-rays with dye injected into your vein or into the bladder via a catheter, measurement of how much urine is left after you've finished voiding, or cystoscopy (looking up through the urethra) if a prostate problem is also suspected to be part of the problem. The goals of treatment include: (1) maintaining continence (2) Preventing infection (3) keeping the kidneys healthy (4) achieving socially acceptable, dignified, convenient and comfortable bladder management. Treatment will vary depending on what the particular problem is. If there are significant involuntary bladder wall muscle (detrusor) contractions at low urine volumes, anticholinergic medicationa, such as oxybutinin and propantheline are often the first line of treatment. These meds can cause dry mouth, blurring of vision, and severe constipation, however, so must be used with some caution and a knowledge of the side effects. If the sphincter also contracts strongly when the bladder wall contracts ("detrusor-sphincter dyssynergy",) intermittent catheterization may have to be added in order to get the bladder to empty completely and keep dry. If the bladder wall doesn't contract well (the bladder is "flaccid") timed voiding by straining or pushing on the bladder (also called crede) is often tried first. If that's not successful, then intermittent catheterization is the treatment of choice. In general, the bladder should be emptied about every 4-6 hours, or every time it has 250-400 cc of urine in it....more often if the bladder capacity is low. One will generally will make about 1,000 cc less urine than the fluid you drink (you lose the rest from sweating and respiration). So, if you drink eight glasses (2400 cc) of fluid per day, you'll make about 1400-1500 cc of urine, and will have to void about 5 times per day if your bladder capacity is 300 cc. The reason for understanding and keeping track of bladder capacity and fluid intake is that if you empty your bladder on a timed basis, rather than waiting until you have to go, you'll often be able to avoid accidents very consistently. Where this gets difficult is when you collect fluid during the day in the form of edema or swelling of your legs and feet, and then put it out at night. That can make for a difficult problem of having to urinate a great deal at night. Some doctors prescribe a small dose of a diuretic (water pill) in the afternoon so that the fluid will not accumulate so significantly. So, to recapitulate: When there are bladder problems, the first step is to see a doctor (neurologist, urologist, physiatrist) who specialises in MS treatment, and have this evaluated. Next, controlled fluid intake and timed voiding are the simplest and most effective first-line treatment. Often the doctor will prescribe medications to relax the bladder wall at this time. If this doesn't work, a regimen of regular clean intermittent self-catheterizations (with or without bladder relaxants) is most often prescribed. This is not as difficult as it might seem, and often works quite well on a long-term basis. But what if a person doesn't have good enough hand function to do this, or what if this is just not effective in keeping the person dry? If the bladder can't be made to drain adequately, some kind of mechanical emptying is needed. Sometimes, if a person does not have adequate hand function to perform self-catheterization, or just can't maintain continence between catheterizations, an indwelling catheter (one that stays in the bladder) seems to be the best way to manage bladder dysfunction, though most doctors generally prescribe this only after having tried other measures. It used to be that catheters were always pretty awful and led to a great many infections, but with modern materials and management, complications are not frequent, and things can be managed quite easily. Catheters can be inserted through the urethra (tube where the urine normally comes out of the body) or through an opening made below the belly button called a "suprapubic cystostomy". Often for women, the latter is recommended because of greater ease of management and not having to sit on a catheter or stretch out the urethra. It also has an advantage in men and women of interfering less with sexual practice. The catheter is a rubber tube with two passages in it...one going to the end to drain the urine and the other going to a balloon near the end that holds the catheter in place when filled with sterile water. The catheter is connected to a drainage tube which then goes under the clothing to a latex or polyethylene bag that is strapped to the lower leg under the pants and has a valve on the bottom to open and drain the bag as necessary under the pants cuff. When one has an indwelling catheter, the doctor usually encourages high fluid intake...3 to four liters of fluid per day...to keep bacteria and crystals washed out. Usually the catheter is changed about every two weeks, and the tubing and leg bag are washed out daily with diluted chlorine bleach and hung to dry. If the bladder drains adequately but uncontrollably, an indwelling catheter may not be needed. For some men who just have overactive bladder muscles that don't respond well to anticholinergics but whose sphincter muscles don't contract to hold the urine in, an external collecting device may be sufficient. This is like a condom (with an adhesive on the inside) with a tube on the end to connect to tubing and the leg bag. It really is a lifesaver if one has this kind of bladder picture...definitely worth talking to your doc/nurse about. Women are not as lucky in this regard, in that they don't have anything to "hang" an external device on. If there's just a little dribbling an incontinence pad may suffice; however if urine gushes out in huge amounts, either emptying regularly by intermittent catheterization or using an indwelling catheter may be necessary. Preventing Infections...Science, Lore, Common Sense. There is much information around about how to prevent infections if you have a tendency to get them with MS...and everybody, even in the medical profession, believes something a little different in this regard. First, it's really important not to get dehydrated. When the urine becomes concentrated and flow slows down, the bacteria grow and infections often occur. Of course, that's difficult, particularly when traveling or attending a family reunion, etc. Who wants to drink fluids and risk an accident? The wisest thing is, if possible, to maintain a fluid intake of about 2000 cc per day (more if you have an indwelling catheter) and try to make provisions to empty your bladder frequently, no matter where you are or what you need to do. Sexual activity is another thing that sometimes predisposes to infections. In both women and men (more in women) coitus tends to introduce some normal skin bacteria into the urethra. Bathing with an antibacterial soap prior to making love ("Honey, please excuse me while I do a surgical prep") decreases the bacteria in this area, but may not be very feasible or romantic. One thing that does help, however, is making sure to urinate after sex, to wash out the urethra and empty the bladder. Cranberry juice and/or Vitamin C...are they any good? Well, if you look at the scientific literature, there have been studies on this with spinal cord injury, and the conclusions are that it does nothing to prevent symptomatic infections. However, I have patients who swear by it, and indeed, since they've started using either cranberry juice in large amounts, or vitamin C tablets, they seem to have fewer or no infections. The only drawback to cranberry juice is the sugar (bad for diabetics or those with weight problems) and if aspartame (Nutra-sweet) is added instead, it seems to cause an inordinate amount of gas. There is some evidence that a substance called Mandelamine (available by prescription), when added to a urinary acidifying agent (such as Vitamin C or Cranberry juice) will prevent bacteria from growing in standing urine. I've had some good luck with this with some of my patients, though, again, the medical literature says it doesn't work. Sometimes patients respond well to a very low-dose mild antibiotic (such as Macrodantin or Septra) given on a routine basis, though the medical literature also questions the effectiveness of this. These drugs are not as harmless, however, as they may seem. People with hypersensitivity to Sulfa, for instance, have had fatal reactions to Septra, so it's something that one's physician needs to prescribe with care. As with most health issues, it's vital to have a physician who understands MS and can follow you carefully, performing urine cultures if you get symptoms and treating infections appropriately. Your doc is needs to be aware of this problem and how you are managing it so that he/she can help you be as healthy and infection-free as possible. In conclusion, then, bladder problems in people with MS are frequent, occur for a number of reasons, and may differ among individuals. There are a number of ways to approach bladder issues, and it's vitally important to form an alliance with a health care professional who understands the pathophysiology of these problems, knows how to treat them, and maintains sensitivity to your emotional needs and lifestyle. Catherine W. Britell, M.D. From alt.support.mult-sclerosis Sat Mar 26 16:58:33 1994 Path: klaava!news.funet.fi!sunic!trane.uninett.no!eunet.no!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!!"STARS::MACPHERSON" Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:MACPHERSON%STARS.decnet @ALEXANDRIA-EMH2.ARMY.MIL> Message-ID: Date: Fri, 25 Mar 1994 08:32:00 EST Sender: Multiple Sclerosis Discussion/Support From: "STARS::MACPHERSON" Subject: Betaseron production and pricing Lines: 48 Status: O Doak asked for my source on Chiron slowing production of Betaseron so I called Jay Silverman, Biotech stock analysis for Wertheim Schroder, and asked him. He said that, during Chiron's report of their annual earnings in early March, they announced that they were stopping production of Betaseron to switch to a more efficient method of production. (And I don't remember that they said that the new method would increase their production rate for the year or made an estimate of the total number of doses they expected to be available by the end of the year.) My own rather jaundiced eye saw the announcement as confirmation of an oversupply caused by lack of demand due to price resistance. First, if you're very small and looking at competitors starting up soon then you don't stop production for anything. Second, they forcast that lottery number 25000 might not come up till Dec, and I believe that they based their estimate on an assumption that everybody who registered would get the serum. Thus the only ways # 25000 could come up in Feb would be if 80% of the people in the lottery were not buying or stopped buying, perhaps because of adverse reactions. We know about the latter, and they don't seem to have caused 80% of the people who started to stop, so the available information support the idea that MSers aren't buying as much as expected. On the pricing: Chiron, the manufacturer, gets only 30% of the Betaseron sales to cover their research and production expenses. Berlex and the retailer split 70% for packaging, promotion, and distribution. That suggests that there is plenty of room to cut the price so keep your options open. On making the decision: From what I've read here Betaseron works best when you don't feel you need it and by the time you're really ready for it it is less effective. That is it seems to work best early in the course of the disease and while it is still relapsing/remitting, and works less well as the damage gets worse. Dr. Swank reports the same problem with his diet. The two together suggest that you have to take action before before the five years is up and you know what you're doing -- while you're still in denial. And when you do take action you'll never know if it was necessary till you stop. Hmmm, I'd better add Disclaimer: One quarter of what I know Ain't so. Doug M. aka Macpherson@198.97.199.1 From alt.support.mult-sclerosis Fri Apr 1 15:12:18 1994 Newsgroups: alt.support.mult-sclerosis Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!agate!ihnp4.ucsd.edu!pacbell.com!att-out!cbnewsl!dkk From: dkk@cbnewsl.cb.att.com (david.k.kallman) Subject: AutoImmune begins Phase III trials Organization: AT&T Bell Laboratories Date: Fri, 1 Apr 1994 05:37:48 GMT Message-ID: Lines: 25 Status: O Folks, Seen on the Dow Jones newswire: AutoImmune has begun the Phase III trial for its bovine myelin product (now called Myloral). The trial will last 2 years and involve 500 patients in 13 medical centers in the U.S. and Canada. The purpose of the trial is to determine safety and efficacy. The press release announcing the Phase III trial said that the earlier Phase II trial (with 30 patients) produced a 50% reduction in attacks with no toxicity. [This seems better that my recollection.] Anyone involved in the trial? Thanks. Dave Kallman -- ---- Dave Kallman, AT&T, 480 Red Hill Rd., Middletown, NJ 07748 d_k_kallman@att.com, (908)615-2989, fax: (908)615-2507 From alt.support.mult-sclerosis Sat Apr 2 16:05:52 1994 Path: klaava!news.funet.fi!sunic!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!U.WASHINGTON.EDU!britell Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:britell@U.WASHINGTON.EDU> X-Sender: britell@stein3.u.washington.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Message-ID: Date: Tue, 29 Mar 1994 12:37:30 -0800 Sender: Multiple Sclerosis Discussion/Support From: Catherine Britell Subject: Re: Cognitive/Mental issues In-Reply-To: <9403290614.AA26586@mx1.u.washington.edu> Lines: 603 Status: O Larry, I can't help responding to your note...what you said about cognitive dysfunction is something so common among people with MS, and often so difficult to talk about...both for the people who have MS and health care providers and families... Warning...here comes one of Chatty Cathy's Big Missives! Cognitive and Perceptual Problems in MS. Catherine Britell, M.D. Problems with memory, thinking, perception, and language associated with MS are becoming recognized more and more -- twenty years ago it was though that cognitive impairments were present in only about 3% of people with MS. More recent studies show that 43% - 65% of people with MS have some kind of cognitive impairment. Because of a general misunderstanding of the nature and management of cognitive impairment, it's probably one of the biggest threats to "personhood" for the individual with MS. Many people fear that having a cognitive problem will make them completely unable to hold down their jobs, unable to be the head of a family, and even incompetent to manage their own legal and financial affairs. This is scary, to say the least, even if not true. In addition, there's often a stigma associated with cognitive dysfunction. It's morally and socially OK to walk with a cane or drive a scooter -- but if you can't THINK normally, you're somehow in a different category of disability. There's almost a medieval way of thinking here -- as though the brain is somehow the "seat of the soul" and that the person with cognitive dysfunction is spiritually damaged, or lessened in some basic essence of humanity -- silly and dangerous, but all too common. Enough philosophizing -- I think I hear "Twilight Zone" music in the background. Probably the most important thing one can do, from an attitudinal point of view, is to look at the brain as just another part of the nervous system -- a nervous system that can be affected in a myriad of ways by MS. And it's important to remember that, just as people compensate for or accommodate a weak or uncoordinated or numb limb and continue living their lives effectively, so too do people in various ways compensate or accommodate for cognitive dysfunction and continue being competent, effective, powerful individuals. There are a number of ways in which cognition is affected in MS. Here are some of them: I. Attention/Concentration and Short-term memory. This is probably the most common thing one sees in MS. It's often characterized by easy interruption in your train of thought. You're sitting in your cubicle at work, sorting out a tough statistical problem in your research and somebody looks in the door and tells you that it's raining outside....just what you needed to know, right? Normally, you'd just ignore it and go on with your work. But often with MS, that interruption will interrupt your entire train of thought, making it necessary to go back and start over, losing 30 or 40 minutes' worth of productive work. Another thing that frequently happens with this type of problem is that you can't concentrate on two things at once. You're trying to sit and read a journal while keeping track of the kids playing noisily in the room. You simply can't make sense out of the article. Or spouse comes in while you're fixing a broken light switch and asks you to pick up Geordie at his soccer practice at 3:00 while she's taking Samantha to her flute lesson. They come in at 4:00 and she asks you where Geordie is...you "spaced" the information and you feel terrible as you rush out the door to look for your son. There are some specific ways to deal with this type of problem. One simple job accommodation is to give a person a private office and phone that can be transferred to phone-mail when one is working on a project. This is not at all unreasonable and is perfectly justifiable when this specific cognitive disorder is identified. Another useful accommodation is the sacred Post-it Note. Setting a timer or alarm clock that will have to be turned off and attaching one of those little sticky pieces of paper to it with a reminder of the task that needs to be completed at that time is something I do a great deal in my household (where nobody has MS). It's a particularly useful trick if you do tend to lose track of time and have some memory/concentration problems. In the computer age, it's wonderful to have these devices that "ding" you and tell you what you need to do at what time. Obviously, there are a number of other manifestations of this problem, and at least twice as many ways of effectively dealing with it. II. Information Processing. There's some evidence that some folks with MS require a longer time to digest new material...they may not be able to take in information as quickly. Also, it may take longer to process information and formulate the proper response. This may put one at a disadvantage at business meetings or deciding whether to let the 16-year-old have the car on Friday night. (Having a 16-year-old right now, I can assure you that the complexity of this decision and all the data that goes into making it is not to be underestimated.) Any situation where one has to think quickly "on one's feet" will often be uncomfortable for a person who exhibits information processing problems. The most usual accommodation here is to allow more preparation time and to avoid situations where quick processing is imperative. Just because you can't think quickly, it doesn't mean you can't think effectively or profoundly or cleverly. It's important to realize this and not discount a person's effectiveness overall because of inability to function at lightning speeds. III. Executive Functions. We all have many, many thoughts and emotions rattling around in our heads all the time, and one of our important automatic cognitive functions is choosing which of those we're going to concentrate on and express at the moment, and which we're going to push to the background of our consciousness. A few individuals with MS have some trouble organizing and prioritizing thoughts, controlling expression of emotions, and changing topics of thought. This can make it difficult to deal with others sometimes, and not to seem "strange" or "weird". When this happens, a person can often compensate quite effectively by understanding what's happening and developing a voluntary executive ability where the automatic one has been lost. Of course, all this takes some energy and training. IV. Perception. Of course, people with MS often have visual problems. Another problem that sometimes happens is an additional problem in making sense of what one sees. This might be characterized by being unable to find the blue socks or the egg beater in a drawer (hopefully different drawers) when it's in with a great many items and staring right at you. V. Speech. Although many people who have MS experience some speech difficulties, it's usually more on the basis of not being able to form words quickly in a coordinated fashion than not being able to think of the right word to say. Occasionally, however, this does happen, and a person will know exactly what he wants to say, yet not be able to think of the right word. This is called aphasia, and is rare in MS. VI. Intellectual function. This seems to be often the least affected cognitive function in MS. That is, the abilities to reason, learn and make appropriate conclusions and judgments are the least affected. People with MS seldom lose their ability to perform on intelligence tests, except where speed in performing math problems is required. So, while performing long division by hand may be a problem, understanding of numbers concepts and mathematical problem-solving is unimpaired. VII. Things that add to the confusion.... Fatigue, depression, and stress can often cause the same kinds of cognitive difficulties described above. And what could be more stressful at times than dealing with MS and trying to manage work, parenting, community activities, financial security, and remembering to take out the garbage? So...how do you deal with these issues? First, it's probably a good idea to get them defined specifically. A psychologist with a good understanding of the physical, psychological, and social consequences of MS can be immensely helpful, both in defining the problems and helping come up with ways of coping with them. Often professional help in the workplace can be vital in keeping a person on the job. Frequently, families need some support and education around how to help their family member with MS. They need to understand that the things that they are seeing are often part of the disease rather than a volitional issue of not caring or not listening. And lastly, the individual with the cognitive impairment often can benefit from education and supportive counseling around issues of stress, depression, self-worth, and coping. One of the most disabling things about cognitive issues in MS is not having a good understanding of what's happening. YOU AND THE PEOPLE AROUND YOU NEED TO KNOW: 1. If the quantity of your work output is going down, it's not because you're goofing off. 2. If you forget what your spouse just told you, it's not because you don't care. 3. If you wore your brown socks with your black pants because you couldn't find the black ones, it's not because you didn't look. 4. If you can't keep up with the thread of conversation at a big meeting, it's not because you're not interested or can't understand. 5. If you can't make a decision quickly, it's not because you're indecisive. 6. If you can't beat everybody else out with the answer at "Jeopardy", it's not because you're stupid. 7. If you can't always express your ideas and feelings, it's not because you don't have them. The following is a selection of recent articles that have been published in the medical literature on the issue of cognitive dysfunction in MS. These journals are available at most large hospital and all medical school libraries. Author: Pugnetti-L. Mendozzi-L. Motta-A. Cattaneo-A. Biserni-P. Caputo-D. Cazzullo-C-L. Valsecchi-F. Author Affil.: IRCCS S. Maria Nascente, Multiple Sclerosis University Center, Milan, Italy. ~Title: MRI and cognitive patterns in relapsing-remitting multiple sclerosis. Source: J-Neurol-Sci. 1993 Apr. 115 Suppl. P S59-65. Language: eng. Pub. Type: journal-article. Author: Pozzilli-C. Gasperini-C. Anzini-A. Grasso-M-G. Ristori-G. Fieschi-C. Author Affil.: Department of Neurological Science, University of Rome La Sapienza, Italy. ~Title: Anatomical and functional correlates of cognitive deficit in multiple sclerosis. ~References: REVIEW ARTICLE: 37 REFS. Source: J-Neurol-Sci. 1993 Apr. 115 Suppl. P S55-8. Language: eng. Pub. Type: journal-article. review. review-tutorial. Author: Wallace-G-L. Holmes-S. Author Affil.: Department of Audiology and Speech Pathology, University of Tennessee, Knoxville. ~Title: Cognitive-linguistic assessment of individuals with multiple sclerosis. Source: Arch-Phys-Med-Rehabil. 1993 Jun. 74(6). P 637-43. Language: eng. Pub. Type: journal-article. Author: DeLuca-J. Johnson-S-K. Natelson-B-H. Author Affil.: Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark. ~Title: Information processing efficiency in chronic fatigue syndrome and multiple sclerosis. Source: Arch-Neurol. 1993 Mar. 50(3). P 301-4. Language: eng. Pub. Type: journal-article. Author: Beatty-W-W. Author Affil.: Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City. ~Title: Cognitive and emotional disturbances in multiple sclerosis. ~References: REVIEW ARTICLE: 76 REFS. Source: Neurol-Clin. 1993 Feb. 11(1). P 189-204. Language: eng. Pub. Type: journal-article. review. review-tutorial. Author: Mahler-M-E. Author Affil.: Neurobehavior Program, Brentwood Division, West Los Angeles Department of Veterans Affairs Medical Center, California. ~Title: Behavioral manifestations associated with multiple sclerosis. ~References: REVIEW ARTICLE: 56 REFS. Source: Psychiatr-Clin-North-Am. 1992 Jun. 15(2). P 427-38. Language: eng. Pub. Type: journal-article. review. review-tutorial. Author: Huber-S-J. Bornstein-R-A. Rammohan-K-W. Christy-J-A. Chakeres-D-W. McGhee-R-B. Author Affil.: Department of Neurology, University of Kansas Medical Center, Kansas City 66103. ~Title: Magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. Source: J-Neuropsychiatry-Clin-Neurosci. 1992 Spring. 4(2). P 152-8. Language: eng. Pub. Type: journal-article. Author: Triantafyllou-N-I. Voumvourakis-K. Zalonis-I. Sfagos-K. Mantouvalos-V. Malliara-S. Papageorgiou-C. Author Affil.: Neurological Clinic, Athens University Medical School, Eginition Hospital, Greece. ~Title: Cognition in relapsing-remitting multiple sclerosis: a multichannel event-related potential (P300) study. Source: Acta-Neurol-Scand. 1992 Jan. 85(1). P 10-3. Language: eng. Pub. Type: journal-article. Author: Rao-S-M. Leo-G-J. Ellington-L. Nauertz-T. Bernardin-L. Unverzagt-F. Author Affil.: Department of Neurology, Medical College of Wisconsin, Milwaukee 53226. ~Title: Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning [see comments] Comment: Comment in: Neurology. 1991 Dec. 41(12). P 2014-5. Source: Neurology. 1991 May. 41(5). P 692-6. Language: eng. Pub. Type: journal-article. Author: Stenager-E. Knudsen-L. Jensen-K. Author Affil.: Clinical Neuropsychiatric Research Unit, Odense University Hospital, DK. ~Title: Multiple sclerosis: the impact of physical impairment and cognitive dysfunction on social and sparetime activities. Source: Psychother-Psychosom. 1991. 56(3). P 123-8. Language: eng. Pub. Type: journal-article. Author: Mariani-C. Farina-E. Cappa-S-F. Anzola-G-P. Faglia-L. Bevilacqua-L. Capra-R. Mattioli-F. Vignolo-L-A. Author Affil.: Istituto di Clinica Neurologica, University of Milan, Italy. ~Title: Neuropsychological assessment in multiple sclerosis: a follow-up study with magnetic resonance imaging. Source: J-Neurol. 1991 Oct. 238(7). P 395-400. Language: eng. Pub. Type: journal-article. Author: Grafman-J. Rao-S. Bernardin-L. Leo-G-J. Author Affil.: Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. ~Title: Automatic memory processes in patients with multiple sclerosis. Source: Arch-Neurol. 1991 Oct. 48(10). P 1072-5. Language: eng. Pub. Type: journal-article. Author: Ron-M-A. Callanan-M-M. Warrington-E-K. Author Affil.: National Hospital for Neurology and Neurosurgery, London. ~Title: Cognitive abnormalities in multiple sclerosis: a psychometric and MRI study. Source: Psychol-Med. 1991 Feb. 21(1). P 59-68. Language: eng. Pub. Type: journal-article. Author: Rao-S-M. Leo-G-J. Bernardin-L. Unverzagt-F. Author Affil.: Department of Neurology, Medical College of Wisconsin, Milwaukee 53226. ~Title: Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction [see comments] Comment: Comment in: Neurology. 1991 Dec. 41(12). P 2014-5. Source: Neurology. 1991 May. 41(5). P 685-91. Language: eng. Pub. Type: journal-article. Author: Jennekens-Schinkel-A. Laboyrie-P-M. Lanser-J-B. van-der-Velde-E-A. Author Affil.: Neuropsychology Section, University Leiden, The Netherlands. ~Title: Cognition in patients with multiple sclerosis After four years. Source: J-Neurol-Sci. 1990 Nov. 99(2-3). P 229-47. Language: eng. Pub. Type: journal-article. Author: Minden-S-L. Moes-E-J. Orav-J. Kaplan-E. Reich-P. Author Affil.: Division of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115. ~Title: Memory impairment in multiple sclerosis. Source: J-Clin-Exp-Neuropsychol. 1990 Aug. 12(4). P 566-86. Language: eng. Pub. Type: journal-article. Author: Jennekens-Schinkel-A. van-der-Velde-E-A. Sanders-E-A. Lanser-J-B. Author Affil.: Neuropsychology Section, State University Leiden, The Netherlands. ~Title: Memory and learning in outpatients with quiescent multiple sclerosis. Source: J-Neurol-Sci. 1990 Mar. 95(3). P 311-25. Language: eng. Pub. Type: journal-article. Author: Jennekens-Schinkel-A. Lanser-J-B. van-der-Velde-E-A. Sanders-E-A. Author Affil.: Neuropsychology Section, State University Leiden, The Netherlands. ~Title: Performances of multiple sclerosis patients in tasks requiring language and visuoconstruction. Assessment of outpatients in quiescent disease stages. Source: J-Neurol-Sci. 1990 Jan. 95(1). P 89-103. Language: eng. Pub. Type: journal-article. Author: Beatty-W-W. Goodkin-D-E. Author Affil.: Clinical Neuroscience Research Program, Neuropsychiatric Research Institute, Fargo, ND. ~Title: Screening for cognitive impairment in multiple sclerosis. An evaluation of the Mini-Mental State Examination. Source: Arch-Neurol. 1990 Mar. 47(3). P 297-301. Language: eng. Pub. Type: journal-article. Author: Petersen-R-C. Kokmen-E. Author Affil.: Department of Neurology, Mayo Clinic, Rochester, MD 55905. ~Title: Cognitive and psychiatric abnormalities in multiple sclerosis. ~References: REVIEW ARTICLE: 50 REFS. Source: Mayo-Clin-Proc. 1989 Jun. 64(6). P 657-63. Language: eng. Pub. Type: journal-article. review. review-tutorial. disorder. Author: Franklin-G-M. Nelson-L-M. Filley-C-M. Heaton-R-K. Author Affil.: Rocky Mountain Multiple Sclerosis Center, University of Colorado School of Medicine, Denver. ~Title: Cognitive loss in multiple sclerosis. Case reports and review of the literature. ~References: REVIEW ARTICLE: 40 REFS. Source: Arch-Neurol. 1989 Feb. 46(2). P 162-7. Language: eng. Pub. Type: journal-article. review. review-of-reported-cases. Author: Iwasaki-Y. Kinoshita-M. Ikeda-K. Takamiya-K. Author Affil.: Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan. ~Title: Cognitive function in multiple sclerosis and its relation to functional abilities. Source: Int-J-Neurosci. 1989 Oct. 48(3-4). P 219-23. Language: eng. Pub. Type: journal-article. Author: Beatty-W-W. Goodkin-D-E. Monson-N. Beatty-P-A. Author Affil.: Clinical Neuroscience Research Program, Neuropsychiatric Research Institute, Fargo, ND. ~Title: Cognitive disturbances in patients with relapsing remitting multiple sclerosis. Source: Arch-Neurol. 1989 Oct. 46(10). P 1113-9. Language: eng. Pub. Type: journal-article. Author: Beatty-W-W. Goodkin-D-E. Beatty-P-A. Monson-N. Author Affil.: Cognitive Neuroscience Research Program, Neuropsychiatric Institute, Fargo, North Dakota. ~Title: Frontal lobe dysfunction and memory impairment in patients with chronic progressive multiple sclerosis. Source: Brain-Cogn. 1989 Sep. 11(1). P 73-86. Language: eng. Pub. Type: journal-article. Author: Jennekens-Schinkel-A. Sanders-E-A. Lanser-J-B. Van-der-Velde-E-A. Author Affil.: Neuropsychology Division, State University Leiden, The Netherlands. ~Title: Reaction time in ambulant multiple sclerosis patients. Part I. Influence of prolonged cognitive effort. Source: J-Neurol-Sci. 1988 Jun. 85(2). P 173-86. Language: eng. Pub. Type: journal-article. ************************************************** From alt.support.mult-sclerosis Sun Apr 3 20:50:46 1994 Newsgroups: alt.support.mult-sclerosis Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!cs.utexas.edu!swrinde!sgiblab!pacbell.com!att-out!nntpa!bigtop!elvis!jhs From: jhs@elvis.dr.att.com (131A30000-ShoreJ(DR7239)250) Subject: Re: drop-foot Message-ID: Originator: jhs@elvis Sender: news@bigtop.dr.att.com (Netnews Administration Login) Reply-To: jhs@elvis.dr.att.com Organization: AT&T References: Date: Sat, 2 Apr 1994 13:22:40 GMT Lines: 36 Status: O > Dale: > Last year, when I was walking, I has s terrible problem with 'drop-foot' > on my left side. The Rehab Centre recommended a custom brace ($900!). > I ignored the advice and bought an off-the-shelf brace which, while > I used it, solved some of the problem of drop-foot. They also > taught me how to walk *from my hip* which is what I do now .. when I > walk (works well on 1 foot, like Chester in the old westerns. A variation: At my HMO, Kaiser, the physical therapist did an evaluation (prompted by my request to my then-neurologist) and decided that a custom brace running down the back of my calf and under my foot to the toes would be best. He explained that the full length brace would give me better control of my lower leg and foot (howeever, a friend of mine just got a ready-made "short" ankle brace which works best for him). The PT described the differences between a custom brace and a ready-made model. When doing a lot of walking, a standard brace may not give proper support for the foot and the upper portion could cause severe chaffing. He had my neurologist prescribe the custom brace (fortunately my HMO covers certain "durable" aids). The custom version, made from a full cast impression (knee to toes) cost $300 and has been wonderfully helpful and very comfortable. A comparable ready-made model was about $100. Scott Orthotics (Denver) made my custom one and also offers ready-made. It is made from a mildly flexible nylon-like material and uses two velcro straps to fix it in place. I guess which one you select depends on how much you walk, what the exact problem is, and if one can afford the custom version. BTW, I never wear the brace in the house (partially because it must be worn with a lace-up shoe) and the old "Chester walk" does work well! Of course, for me, using my walking stick, whether I am using the brace or not, makes all the difference. With the brace and without the stick I still must do a Chester routine! :-) Jeff From alt.support.mult-sclerosis Mon Apr 4 21:51:48 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!paladin.american.edu!auvm!WORLDBANK.ORG!MSCHUMAN Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:MSCHUMAN@WORLDBANK.ORG> MR-Received: by mta EDSEL; Relayed; Mon, 04 Apr 1994 16:49:55 -0400 MR-Received: by mta EARTH; Relayed; Mon, 04 Apr 1994 16:53:40 -0400 Alternate-recipient: prohibited Disclose-recipients: prohibited MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT Posting-date: Mon, 04 Apr 1994 16:49:00 -0400 (EDT) Importance: normal Priority: normal X400-MTS-identifier: [;55946140404991/251323@EDSEL] A1-type: MAIL Hop-count: 1 Message-ID: <01HARYFIQE068ZFX6G@mr.worldbank.org> Date: Mon, 4 Apr 1994 15:34:00 -0400 Sender: Multiple Sclerosis Discussion/Support From: Margret Schuman EDS02 80107 Subject: Allergies/MS-time of day/Hormones ~# Lines: 83 Status: O Aapo from Helsinki writes (Hi Aapo) that his symptoms are much better at night. I seem to recall that we have discussed this here a while ago and that many of the MSers share this experience. I too feel MUCH better at night. As a matter of fact I already did before I was diagnosed and often remark(ed) that a "night-job" (not that one) would be ideal for me. Aapo also brings up the production of a hormone called melatonin which is produced at night. Here we go again, hormones. Thanks for posting the papers that mention research done on hormones and MS. I am just now trying to find all the facts about this issue. One on the release of histamine which is not exatly a hormone (?) but, in the dictonary I consulted under (anti)histamin it says: ".......Histamine causes large blood vells to constrict and smaller blood vessels, including capillaries, to dilate, or open; it increases the permeability of capillaries, permitting the fluid part, or plasma, of the blood to escape and cause swelling; and it constricts small air passages, or bronchioles, in the lungs. Symptoms of histamine activity may include flushing, hives, headache, wheezing, facial puffiness, and lowered blood pressure (didn't we find in earlier discussions that a high number of MSers have low blood pressure?). .....Antihistamies act by blocking or displacing histamine at the H(1) receptor sites found in most tissues and organs, but particularly in the blood vessels, skin, uterus, and bronchioles. By means of this action, the drugs prevent, reverse, or minimize the naturally occurring histamine. The effectiveness of antihistamines is rarely complete because of the existence of other chemicals, such as SEROTONIN, that have the same action as histamine. These chemicals have their own specific receptor sites, bot blocked by antihistamines. Another effect of histamines is the increased production of acid by specialized cells in the stomachs of mammals (us!)...histamine action is on a different group of receptors, called H2, and is not affected by standard antihistamines. Some newer drugs, called H2 receptor antagonists, can modify histamine at these sites." Now I looked at SEROTONIN (be patient, I will get to Aapo's "melatonin": "SEROTONIN, also known as 5-hydroxytryptamine (5HT), is a hormone and neurotransmitter involved chiefly in the excitation of organs and the constriction of blood vessels. .......in mammals, serotonin is manufactured by specialized cells, called enterochromaffin cells, which are located throughout the gastrointestinal tract. Serotonin is also found in blood platelets and located in the hypothalamus and midbrain. Several possible functions of serotonin include a regulatory role during light sleep and a role as a neurotransmitter in the organs; these organs are stimulated in their characteristic functions when serotonin molecules occupy the receptors. Excessive serotonin production ....results in flushing of the skin, varying blood pressure, colic and diarrhea. NOW I GET TO THE POINT (IF THERE IS ONE) PINEAL GLAND "..lying above the cerebellum, it is richly supplied with blood vesses and nerve fibers. ......in all species the pineal is affected by light. The gand produces a HORMONE called melatonin, from the neurotransmitter SEROTONIN. This hormone is associated in varying and not yet well-understood ways with a number of biorythms, including such long-term ones as the onset of puberty (around which time the susceptability of getting MS is established?)..." I don't know exactly what all this means in connection to MS. But.... seems to me that hormones play a significant role! Is anybody out there who can make more sense of all this? Cathy? Eric? Hope you had HAPPY Holidays. Margret From alt.support.mult-sclerosis Wed Apr 6 12:31:31 1994 Path: klaava!hydra.Helsinki.FI!news.funet.fi!sunic!trane.uninett.no!eunet.no!EU.net!howland.reston.ans.net!paladin.american.edu!auvm!U.WASHINGTON.EDU!britell Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU Newsgroups: alt.support.mult-sclerosis Return-Path: <@AUVM.AMERICAN.EDU, @TECHNION.TECHNION.AC.IL:owner-mslist-l@TECHNION.TECHNION.AC.IL> Return-Path: <@TECHNION.TECHNION.AC.IL:britell@U.WASHINGTON.EDU> X-Sender: britell@stein3.u.washington.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Message-ID: Date: Tue, 5 Apr 1994 08:13:58 -0700 Sender: Multiple Sclerosis Discussion/Support From: Catherine Britell Subject: Re: Alternative Treatments? In-Reply-To: <9404051415.AA01525@mx2.u.washington.edu> Lines: 51 Status: O On Tue, 5 Apr 1994, Dr. Daniel R. Lewin wrote: > you too...Do you have information that you could share with us about > alternative means of help (i.e. acupuncture, homeopathy etc.) Another > question - what is your recommended conventional treatmant for CP > patients? specifically me... I am one of those, diagnosed 4 years ago, Ruti: First, your language skills are fine. (You should see me in Hebrew...) Next, about alternative treatments. This is a question about which I could, I suppose "pontificate" for hours on end...there are so many ways to look at these things. First, many established medical treatments started out as "alternative treatments", were scoffed by the medical profession as useless and then were proven to be of benefit and finally accepted. On the opposite end of the spectrum, there are so MANY people out there hawking something for every known (and imagined) human ailment, and hoping to make money from someone else's misfortune. (And sadly, that can include some "established" medical professionals). So how do you decide whether something is useful or not? Unfortunately, we come back to the old problem of MS itself. It's such a variable and unpredictable disease and so basically tenacious ("treatments" so far have produced often only subtle changes) that one is often hard-pressed to tell whether a specific treatment is useful or not. That's why we do research with very large groups of people and pool the information we get in order to make some kind of valid determination on the basis of statistical evidence. But that doesn't really address your question, does it? I like to think of all therapeutic modalities as falling into one of these groups: (1) cures the ailment or arrests the disease process (2) doesn't cure the ailment but makes the person feel and function better (3) doesn't help; doesn't hurt (4) might help; might hurt as well...need to balance risks and benefits (5) hurts people through (a)biological action or (b) deceit and fraud Now, for MS, we don't yet have any (1) treatments, which would be optimal. Most of our medical treatments fall into (4). What I do as a rehab doctor often falls into (2). Somebody here was talking about massage a bit ago. I think that's also a Category (2) treatment. Not bad, in the large scheme of things. I think what you have to watch out for is being hurt physically and emotionally and financially by those Category (5) things by learning to recognize them, and not to waste your precious time on Category (3). And now I shall "punt" to the rest of the group, because they have had a great deal more collective experience than I have in the area of figuring out what helps them...and also unfortunately in dealing with the disappointment of useless therapeutic endeavors. Cathy From alt.support.mult-sclerosis Tue Apr 12 17:44:55 1994 Path: klaava!news.funet.fi!sunic!pipex!howland.reston.ans.net!europa.eng.gtefsd.com!news.umbc.edu!eff!news.kei.com!news.byu.edu!news.mtholyoke.edu!nic.umass.edu!twain.ucs.umass.edu!verdant From: verdant@twain.ucs.umass.edu (Sol Lightman) Newsgroups: alt.support.mult-sclerosis Subject: MS AND MARIJUANA Date: 7 Apr 1994 20:53:42 GMT Organization: University_of_Massachusetts_at_Amherst_Cannabis_Reform_Coalition Lines: 137 Message-ID: <2o1rsm$fra@nic.umass.edu> Reply-To: verdant@twain.ucs.umass.edu NNTP-Posting-Host: twain.ucs.umass.edu X-Newsreader: TIN [version 1.2 PL2] Status: O Copyright (c) 1993 Yale University ___________________________________________________ | | | MARIHUANA THE FORBIDDEN MEDICINE | | | | by | | Lester Grinspoon, M.D. | | James B. Bakalar | | | | Available from Yale University Press, | | | | New Haven | | << ISBN 0-300-05435-1 >> and | | London | | | --------------------------------------------------- Multiple sclerosis (MS) is a disorder in which patches of myelin (the protective covering of nerve fibers) in the brain and spinal cord are destroyed and the normal functioning of the nerve fibers themselves is interrupted. It seems to be an autoimmune response in which the body's defense system treats the myelin as a foreign invader. The symptoms usually appear in early adulthood, then come and go unpredictably for years. Attacks last from weeks to months, and remission is often incomplete, with gradual deterioration and eventual severe disability. Injury, infection, or stress may cause a relapse. The average survival time is thirty years, but some patients deteriorate much faster, and the others stabilize after a few attacks. The symptoms depend on which part of the central nervous system is affected by demyelination. Because the brain and spinal cord control the entire body, the effects may appear almost anywhere. Some common symptoms are tingling, numbness, impaired vision, difficulty in speaking, painful muscle spasms, loss of coordination and balance (ataxia), fatigue, weakness or paralysis, tremors, loss of bladder control, urinary tract infections, constipation, skin ulcerations, and severe depression. No effective treatment is known. Corticosteriods, especially adrenocorticotropic hormone (ACTH) and prednisone, provide some relief for the acute symptoms, but they also produce weight gain and sometimes cause mental disturbances. The drugs most commonly used to treat muscle spasms are diazepam (Valium(R)), baclofen (Liorensal(R)), and dantrolene (Dantrium(R)). Diazepam and other drugs in the benzodiazepine class, which must be given in large doses, cause drowsiness and can be addictive. Both dantrolene and baclofen are of marginal medical utility. Baclofen is a sedative and sometimes causes dizziness, weakness or confusion. Dantrolene is a last resort because of potentially lethal liver damage; it also has a variety of other side effects, including drowsiness, dizziness, weakness, general malaise, abdominal cramps, diarrhea, speech, and visual disturbances, seizures, headaches, impotence, tachycardia, erratic blood pressure, clinical depression, myalgia, feelings of suffocation, and confusion. Understandably, many patients cannot tolerate the immediate side effects of the standard drugs or become concerned about the long-term effects. Most MS patients in the United States now learn about marihuana through support groups or the grapevine. Many anecdotes testify to its capacity to relieve tremors and loss of muscle coordination. Neurologists often hear about it from their patients. Yet the medical literature includes only a few cases. A recent report was published by neurologists at the University of Gottingen in Germany, who noticed that one of their patients, a thirty-year-old man with multiple sclerosis, used smoked marihuana to treat his motor and sexual handicaps. They tested him with clinical ratings, electromyographic study of his leg reflexes, and electromagnetic recording of his hand tremors. Their conclusion was that cannabis warranted further evaluation as a treatment for both muscle spasms and ataxia (loss of coordination)[1]. There are hints ... that cannabis not only relieves symptoms of multiple sclerosis -- muscle spasms, tremor, loss of muscle coordination and bladder control, insomnia -- but also retards progression of the disease. Multiple sclerosis is a disorder caused by an immune system gone haywire; current treatments include the use of steroids that suppress immune functioning. Although smoked marihuana apparently does not increase susceptibility to infectious disease, there is evidence that THC has immunosuppressive effects. With this in mind, a group of investigators tested its ability to suppress experimental autoimmune encephalitis (EAE), a disease that has been used as a laboratory model of multiple sclerosis in guinea pigs. When animals were exposed to the disease and then treated with a placebo, all developed severe EAE and more than 98 percent died. Animals treated with THC had either no or only mild symptoms, and more than 95 percent survived. On inspection the brain tissue of the animals treated with THC proved to be much less inflamed[2]. [1] H. M. Meinck, P. W. Schonle, and B. Conrad, ``Effect of Cannabinoids on Spasticity and Ataxia in Multiple Sclerosis,'' Journal of Neurology 236 (1989): 120-122. [2] W. D. Lyman, J. R. Sonett, C. F. Brosnan, R. Elkin, and M. B. Bornstein, ``Delta-9-tetrahydrocannabinol: A Novel Treatment for Experimental Autoimmune Encephalitis,'' Journal of Neuroimmunology 23 (1989): 73-81. -- The University of Massachusetts at Amherst | _________,^-. Cannabis Reform Coalition ( | ) ,> S.A.O. Box #2 \|/ { 415 Student Union Building `-^-' ? ) UMASS, Amherst MA 01003 verdant@twain.ucs.umass.edu |____________ `--~ ; \_,-__/ * To find out about our on-line library, mail a message with the * pattern "{{{readme}}}" contained IN THE SUBJECT LINE. * You will be mailed instructions; your message will be otherwise ignored