Date: Sun, 10 Sep 95 21:18:41 -0400 From: Bob Broedel To: als@huey.met.fsu.edu Subject: ALSD215 ALS-ON-LINE =============================================================== == == == ----------- ALS Interest Group ----------- == == ALS Digest (#215, 10 September 1995) == == == == ------ Amyotrophic Lateral Sclerosis (ALS) == == ------ Motor Neurone Disease (MND) == == ------ Lou Gehrig's disease == == ------ maladie de Charcot == == == == This e-mail list has been set up to serve the world-wide == == ALS community. That is, ALS patients, ALS researchers, == == ALS support/discussion groups, ALS clinics, etc. Others == == are welcome (and invited) to join. The ALS Digest is == == published (approximately) weekly. Currently there are == == 970+ subscribers. == == == == To subscribe, to unsubscribe, to contribute notes, == == etc. to ALS Digest, please send e-mail to: == == bro@huey.met.fsu.edu (Bob Broedel) == == Sorry, but this is *not* a LISTSERV setup. == == == == Bob Broedel; P.O. Box 20049; Tallahassee, FL 32316 USA == =============================================================== == Back issues of the ALS Digest are available on-line at: == == http://http1.brunel.ac.uk:8080/~hssrsdn/alsig/alsig.htm == =============================================================== CONTENTS OF THIS ISSUE: 1 .. dental materials 2 .. some questions 3 .. ALS and Arthrogryposis Multiplex Congenita 4 .. re: feeding tube 5 .. re: Should my wife have a tracheostomy? 6 .. International Symposium on Oxidative Stress, Apoptosis and Brain Damage 7 .. MDA Research Report #59 (1) ===== dental materials ========== Date : Mon, 4 Sep 1995 20:56:33 -0400 >From : Don2737@aol.com Subject: dental materials I am sure you can consult experts both with ALS and Dental organizations that will tell you that dental materials, including amalgam, are safe. All SCIENTIFIC studies, (not anecdotes of "I took out this persons fillings and their ALS or arthritis or ms or allergies or bad luck at the race track improved"). I could get the similar anectdotal "proof" of any cure you can conjure up. I particularly liked the part about the order of fillings being removed being key to the "electrical" success. What effect did the moon phase have on this well controlled, double blind, statistically meaningful group? The most recent study I've seen regarding amalgam was on women over many years and the women with fillings were overall healthier and had fewer ill children. There are many, many studies on amalgam. Anyway, if there was one shred of evidence that amalgams were causing my dear mother's ALS, I'd have them out by noon tomorrow. So, to use the statements the Multiple Sclerosis scientists have used in the past regarding amalgam, "It is a cruel hoax to link amalgam to this disease." I look to the ALS Digest for information, not "cruel hoaxes". I just spent the entire day today helping with the MDA Telethon, in support of real cures, so I guess I'm just a bit tired and annoyed at this point. Donald W. Davison, DDS, son of an ALS patient ps You may run this if you want in the ALS Digest. (2) ===== some questions ========== Date : Mon, 4 Sep 1995 16:49:19 -0400 >From : LPask@aol.com Subject: Re: ALSD213 ALS-ON-LINE I have two questions, I hope this is the right forum. I was diagnosed in June of 1993 with ALS. I have severe pain in my toes, feet, ankles, knees, thighs and shoulder, the pain is constant, I can only sleep om my sides for about 30 minutes at a time, then wake up in severe agony and my wife rolls me to the other side. This goes on all night. Any suggestions, advice or admonishments. A good freind of mine has been told he has "STURG-STRAUESS SYNDROME". Is it a motor neuron disorder? Is it curable? My address is LPask@AOL.com (3) ===== ALS and Arthrogryposis Multiplex Congenita ========== Date : Tue, 29 Aug 1995 11:23:10 -0400 >From : GabyH@aol.com Subject: ALS My grandfather died in 1988 of ALS and I have just found out that it may have a connection with my disability (Arthrogryposis Multiplex Congenita), which I have had since birth. I am trying to find a connection and would appreciate it if anyone can send me any information. Sincerely, Gaby (4) ===== re: feeding tube ========== Date : Thu, 31 Aug 1995 09:46:51 -0700 (PDT) >From : Leigh Redding To : Wayne Phillips <70303.173@compuserve.com> Cc : Bro Broedel Subject: Your input in ALSD#211 Wayne and Mike, Good post guys, I'm glad to see Mike's comments, VERY GOOD. Wayne let me offer a point or two on feeding tubes. First mine is not a stomach peg, I have an alignment problem. Something about being to high behind my diaphragm. I have a neck tube that goes down the esophagus. My wife Shawn is my principal care giver. She has found that a stone, maybe it's marble, mortar and pestle works wonders on pills. You can find these at a good cooking equipment store. We have two, one for my medications only and another for spices and such. Shawn puts the ground pills in a cup and with about 20 cc's of water pulls the medications into the syringe. She then "pushes-and-pulls" the medications in and out of the syringe till they dissolve, or at least till they are in suspension. She also makes sure that there is at least 10 cc's of air in the syringe. With the syringe, plunger end up, she can "see" when all of the liquid has entered the feeding tube by watching the air cushion. If this is with meals - she first gives me the medications and chases the medications with the bolus mixture. If this is between meals - she "chases" the syringe of medications with a syringe refill of plain water from a little 50 ml plastic medication cup. Mike's point about the extra water is so very important for keeping the lung secretions thin. Shawn's trick here is that every feeding is followed up with the water but as important, it guarantees that the feeding tube is always flushed with clear water. So I get the water and we know the tube has been flushed, always. Thanks again guys for your inputs. Regards, Leigh and Shawn (5) ===== re: Should my wife have a tracheostomy? ========== Date : Sun, 3 Sep 1995 18:06:45 -0700 (PDT) >From : Leigh Redding To : Marj & Dick Tauber Cc : Bro Broedel Subject: Your Questions >Date : Thur., 31 Aug 1995 >From : dick.tauber@turner.com >Subject : Should my wife have a tracheostomy? Dear Marjorie and Dick, First, we just saw Dr. Oppenheimer's well thought out response to you. He covered most everything except from a PALS or caregiver's perspective. I am a PALS with a tracheostomy. Mine was prompted by a collapsed lung just shy of my first year's diagnoses. My onset was bulbar. I was nearly without a voice when I had the operation. Now the trach is a way of life. I also have a feeding tube. My geometry didn't allow for a PEG, my stomach is to high or some such. Anyway mine goes down through the neck to the esophagus. >1. Is there anyone familiar with supporting a patient with a trach who That is tough. My perspective keeps changing. I know at first I couldn't chew well and my speech was going fast and I couldn't imagine a trach. The collapsed lung changed that fast. Our doctors also kept at us to not forget the feeding tube. >2. I've heard that there is much discomfort with a trach. Is this so? Or The first couple of days were the worse. Since you are thinking vent means that the trach will be a low pressure cuffed model. The reason I bring that up is that you will have to have it changed every 4 to 6 weeks. Home care can be trained to do that, if not you will need to plan on an ENT visit for changes. Does it better the life of the patient? It sure does! I can relax and daydream about who knows what all and not be thinking about taking another breath. When it starts to gurgle I either try and cough it up with the help of the vent's cycle or Shawn, (friend, wife and caregiver) suctions me out. >3. I've heard that a feeding tube can only be in for a limited period of The Doctor covered that. I will say it sure has its advantages. If I fall asleep and it's time for medication or a feeding Shawn just uses the tube and I sleep through it. >4. While some patients can effect talking by controlling the venting of There is what are called fenestrated trachs. These allow you to block the trach with you finger which will let air vent out of the top, through the fenestration, into your upper windpipe to work your vocal cords. With my bulbar onset that became a moot issue. There is also a little jobber that goes on the outside of the inner canula called a "passey muir" valve. This jobber is a one way valve for breathing in only. When you breath out the air is forced out the fenestration so you exhale out you mouth. This alows you to use your vocal cords until you poop out and then all you do is pop off the one way valve jobber and plug back into the vent and relax and let the vent take over. >5. Since ALS effects the voluntary muscles, are there any muscles or I'm not a medico so I'll only say that my bulbar onset has weakened my neck muscles but that is not an issue reclining in bed or my powered chair. I think with what is available today I will be able to wiggle my nose or look at a screen and blink to activate a menu and - yes - be able to communicate for a long time. >6. How have patients with advanced ALS done while on a trach? I can't answer that. Like the good Doctor said, "look at Stephen Hawking." I will say that I'm not looking forward to it but I will when it happens. And for as long as possible. We might not see our kids and grandkids as much as we want but every time we do they are cherished and make us that much more eager for the next time. I plan to keep on keeping on as long as possible. >7. If all muscles fail, how can an advanced patient let you know they The Doctor brought up logical steps to follow. Shawn and I have done some of them but I guess I have acted a bit like an ostrich on others. That was a good wake up call. We need to finish what we started. I mentioned the feeding tube installation early rather than late. That is very important! I came home from the colapsed lung and the trach at about 150 pounds. But still had my stregth. The Dietician wanted me at 175 minimum. Rich shakes and creamed soups helped some Then the feeding tube went in and Shawn has me at a healthy 186 ever since. If I had been weakened and wore out the surgery would have taken longer to heal and who knows if I would have gotten all my weight back? I will echo what the Doctor said about "should I" that is your choice. No one can make it for you. But I can say that I am sure glad that I did. As we speak my brother from the "other" coast is here for a week with our uncle and we are having a ball. I talk with a syntasizer and I have to butt in with my stuff maybe 2 or 3 subjects out of sequence, I am a slow one finger typer, but I am involved - I sure am! Good luck and keep in touch, we can help each other through this. Shawn says that we will live with ALS, not the other way around. Regards, Leigh and Shawn (6) ===== International Symposium on Oxidative Stress, Apoptosis and Brain Damage ========== >From : manev@ASRI.EDU (Hari Manev) Subject: PITTSBURGH: SYMPOSIUM REGISTRATION Date : 30 Aug 1995 12:25:04 -0700 INTERNATIONAL SYMPOSIUM ON OXIDATIVE STRESS, APOPTOSIS AND BRAIN DAMAGE, September 21 - 24, 1995 Pittsburgh, PA 15212, USA For information: tel. +412-359-4952; fax +412-359-8218 (7) ===== MDA Research Report #59 ========== Date : 07 Sep 95 22:14:30 EDT >From : Barry Goldberg <71154.330@compuserve.com> Subject: MDA Research Report #59 Here is the newest report to MDA Clinic Directors regarding ongoing research findings. I hope you find this interesting and informative. Research Update from the Muscular Dystrophy Association (MDA) MDA STAFF RESEARCH UPDATE -- SRU #59 -- 08/29/95 ************************************************ MYASTHENIA GRAVIS (MG) is an autoimmune neuromuscular disease. For unknown reasons the immune system begins to mistakenly attack a component at the neuromuscular junction, where signals pass from nerve to muscle, which interferes with the transmission of those signals. Immunosuppressive drugs that can block the unwanted immune response have been beneficial in treating MG, however, researchers are trying to find other medications that may have fewer side effects and possibly improved effectiveness as a treatment. In an animal model that is affected by a form of MG, MDA-supported scientists recently tested a substance that can apparently inhibit the type of immune response that causes problems in people with MG. The substance, IFN- a, is a naturally occurring factor that functions to modulate various activities of the immune system. The results of the experiments indicate that IFN-a, if given early in the development of MG, might be beneficial and it should be explored further. (Shenoy, M. et al. Journal of Immunology 1995; 154:6203-6208). In a family affected by a type of congenital myasthenic syndrome -- SCCMS -- MDA-supported researchers found that a defect exists in an acetylcholine receptor (AChR) gene. Congenital myasthenic syndromes are inherited disorders affecting the transmission of signals from nerve to muscle and the AChR is a key component in the signal transmission process. The AChR defect just found has an effect similar to the effects of two other previously identified defects found associated with other forms of congenital myasthenic syndromes. The researchers have been studying how AChR function is altered and the findings have also given the researchers insight into the functions involved in signaling at the neuromuscular junction. (Sine, S. M. et al. Neuron 1995; 15:229-239). Researchers from Japan analyzed muscle tissue from individuals affected by POLYMYOSITIS (PM) to determine the possible effects of a virus called HTLV-1. Samples from individuals with PM who tested positive or negative for the virus were compared. In either case the scientists could not detect HTLV-1 in muscle fibers, however, the virus was detected in certain circulating cells from the immune system only in the examined muscle tissue of HTLV-1-positive PM cases. The researchers conclude that a direct infection of muscle fibers by the virus does not result in HTLV-1-associated PM. What may actually happen is that an inflammatory response is triggered in HTLV-1- positive PM that involves immune system cells found in the muscle tissue. HTLV-1-negative cases may involve the same immune system cells triggering PM without infection by the virus. (Higuchi I. et al. Muscle and Nerve 1995; 18:854-858). MYOBLAST transplantation (MT) as a treatment for Duchenne muscular dystrophy (DMD) has not yet proven to be successful, either in human studies or animal studies designed to mimic the MT procedure that would be safe to use in humans. Researchers continue to explore the possibilities for improving the technology for MT as it is hard to predict at this time whether MT, gene transfer, some other procedure or a combination of procedures will be beneficial in treating DMD in the future. Recent MT experiments demonstrated that the growth factor, bFGF, could increase the number of donor myoblasts to be delivered to dystrophic muscle, improve the long-term health of the donor muscle cells and improve the ability of the donor cells to fuse with the muscle tissue when injected. Each of these aspects appeared to need improvement in the earlier MT studies in order for the muscle cell transplantation technique to be successful. Unfortunately, the level of improvement in the recent experiments using bFGF cannot be considered therapeutic at this time. (Kinoshita, I. et al. Muscle and Nerve 1995; 18:834-841). Additional myoblast transfer experiments in mice showed that an immunosuppressive agent called FK-506 appears to have potential to block the immune system rejection of introduced donor myoblasts. The researchers observe that use of FK-506 in MT may ensure that dystrophin expression can be restored to a level seen in carriers of DMD. (Asselin, I. et al. Muscle and Nerve 1995; 18:980- 986). Several MDA-supported researchers are exploring GENE TRANSFER as a possible method for treating Duchenne muscular dystrophy (DMD). One of the many challenges of developing such a procedure is the design of a vector -- carrier -- for the dystrophin gene. Since this gene is one of the largest known and it will not fit into most currently available viral vectors, researchers are working to develop a vector capable of carrying the entire gene, although another solution may be the use of shortened versions of the dystrophin gene. A quick and useful way to test the function of these mini-genes is to give them to mdx mice using transgenic technology, which will show if the mini-gene can express a dystrophin protein that will function, overcoming the existing defective dystrophin in the mouse. Recent reports demonstrate that certain shorter versions of the dystrophin gene are capable of directing the production of a dystrophin protein that can reduce or eliminate the dystrophy in mdx mice. In addition, the amount of dystrophin that is necessary to restore normal muscle function is lower than expected, however, it appears that a low, uniform level of expression throughout muscle is more important than a high, overall expression of dystrophin with variability in the amount of protein expressed in different muscle groups. (Wells, D. et al. Human Molecular Genetics 1995; 4:1245-1250 and Phelps, S. F. et al. Human Molecular Genetics 1995; 4:1251-1258). Modified viruses appear to be the most promising vehicles as GENE TRANSFER vectors. A number of them may be useful for the delivery of therapeutic genes to muscle and MDA-supported researchers are exploring the promising possibilities. One is a modified version of the herpes simplex virus 1 (HSV-1). Recent tests of the potential of an HSV-1-based vector indicate that it is efficient in delivering genes to muscle. The HSV-1 vector may also be beneficial in that it would be capable of carrying large genes, including the full-length dystrophin gene. However, more research on this vector is necessary and future studies will need to determine: how long the introduced gene can survive, whether the viral vector can be toxic, and whether the viral vector will trigger an immune response as does the original unmodified virus. (Huard, J. et al. Gene Therapy 1995; 2:385-392). MDA researchers are working to determine the effect of the unstable, expanded region in the defective gene associated with MYOTONIC DYSTROPHY (DM). Recent evidence indicates that the gene defect may interfere with the production of the message that is used to direct the assembly of the protein, called DMPK. To produce a protein a message is first made from the gene. That message must then be adjusted slightly before it can be used as directions for making the protein. It appears that in individuals affected by myotonic dystrophy, the initial form of the message is produced, however, the final form of the message from the DMPK gene is not made. Apparently, the unstable, expanded area is impairing the production of the final form of the message that is used to direct the assembly of DMPK protein, although further study is necessary to determine the exact details of the effects involved. (Krahe, R. et al. Genomics 1995; 28:1-14). FRIEDREICH'S ATAXIA (FA) is the most common of the inherited ataxias and is a progressive disorder affecting the nervous system. Genetic researchers have determined that the defective gene causing the disease is located on chromosome 9. In fact, the scientists have limited the region on chromosome 9 to a small enough area that they are now examining genes in this region to determine if any of these genes could be associated with FA. The data obtained so far points to one gene that the molecular geneticists are now characterizing. No defect in this gene has been identified as yet, although the location of the gene indicates that, if defective, it is a candidate for being associated with FA. (Carvajal, J. J. et al. Human Molecular Genetics 1995; 4:1411-1419). The MITOCHONDRIAL MYOPATHY, Kearns-Sayre Syndrome (KSS) can develop in individuals originally diagnosed with Pearson marrow-pancreas syndrome (MIM). Both disorders are associated with defects in the DNA -- genes -- located within mitochondria. Mitochondria are found in every type of cell and are responsible for energy production, which involves use of their own specific genes. A French research group has looked at the type of mitochondrial DNA defects associated with MIM and the defects associated with the cases of MIM that eventually develop into KSS. The group was looking at the possibility that certain types of mitochondrial DNA defects might be specifically associated with certain clinical features of either MIM or KSS. In the individuals examined, the scientists could not find a connection between the type, size or location of the mitochondrial DNA defects and the clinical expression of the diseases. However, the researchers propose that a better understanding of how the mitochondrial defects are passed on to each cell during development could help explain how MIM and KSS arise. (Rvtig, A. et al. Human Molecular Genetics 1995; 4:1327-1330). The region on chromosome 5 that contains the defective gene(s) associated with SPINAL MUSCULAR ATROPHY (SMA) contains areas that exist in multiple copies which has made genetic analysis of the area difficult. Two genes, NAIP and SMN, were recently shown to be disrupted in individuals with SMA, however, it is still unclear how defects in either gene may cause the disease. Recent molecular genetic data revealed that there is a possibility that certain chromosomal arrangements or structures in the SMA region could make the area more susceptible to deletion defects. The researchers believe, for example, that a certain chromosome structure could have a higher risk of giving rise to a severe defect associated with SMA. (Wirth, B. et al. Human Molecular Genetics 1995; 4:1273-1284). A possible cause of the motor neuron disease, AMYOTROPHIC LATERAL SCLEROSIS (ALS), has been proposed to result from an abnormal immune response to a certain cellular component called the calcium channel, which the cell uses to control the flow of calcium. Another research group examined certain immune system substances that typically exist in serum and spinal cord fluid looking for evidence that an immune response is triggered in motoneurons of individuals with ALS. The conclusion was that the immune system substances found in motoneurons in ALS are not a result of a specific process and motoneurons apparently take up the substances nonselectively. The researchers believe that the presence of immune components in motoneurons from individuals with ALS does not result from a response guided by the immune system. (Fishman, P. et al. Neurology 1995; 45:1551-1554). Type 4 CHARCOT-MARIE-TOOTH disease (CMT4) is known to be associated with a defective gene on chromosome 8. MDA-supported scientists recently reported that they have considerably narrowed the region in which they expect to find the disease gene. In fact, the researchers have already eliminated a likely candidate gene that is located in the area. The gene is PMP-2, which codes for a peripheral myelin protein. Certain peripheral nerve disorders have been found to be associated with defects in other PMP proteins. Different forms of CMT as well as Dejerine-Sottas disease result from certain defects affecting either PMP-22 or P0. (Ben Othmane, K. et al. Genomics 1995; 28:286-290). --- MDA -- Working to find the cure for neuromuscular disease --- === end of als 215 ===