Subject: Imuthiol; German Enzymes; Dextran Update; New Studies Date: Mar 28 1988 (706 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Volume 2 Number 2 Mar 28, 1988 In this issue: Imuthiol, DTC, and Antabuse German Enzyme Therapy Dextran Sulfate Update In Brief New Studies Imuthiol/DTC and the Antabuse Connection Last year Dr. Robert Gorter at San Francisco General Hospi- tal treated at the AIDS outpatient clinic a patient with lym- phadenopathy syndrome (LAS) who showed a T-cell count of 1100. Hearing of another LAS patient with a similarly phenomenal T-cell count, Dr. Gorter did some checking and discovered that both men were recovering alcoholics taking disulfiram, commonly known as Antabuse, a substance that has been used to help alcoholics stop drinking since 1952. Could Antabuse have a stimulatory effect on T-cells? Upon further investigation, it was learned that in the bloodstream disulfiram is rapidly converted to DTC, a drug -- trademarked as Imuthiol -- that French researchers had been examining for several years because of its apparently successful immuno- enhancing effect on people with AIDS and ARC. What is DTC? How does it work? And in the absence of avai- lability, pending FDA approval of Imuthiol for treatment of AIDS, how good a substitute is the available-by-prescription Antabuse? Background DTC stands for diethyldithiocarbamate, a chelating (metal- removing) agent used for chemical and agricultural purposes which had primarily been used in humans to treat nickel, mercury, cad- mium, and copper poisoning (1,2,3). In laboratory animals, it has been shown to provide protection against the immunosuppres- sive effects of radiation and chemotherapy (4,5). In the mid- '70s, French doctors treating stomach cancers with platinum, added DTC to remove the platinum and discovered an increase in T-cells. In 1985, French researchers searching for immuno- modulators that would replace the depleted T-cells in AIDS patients treated a number of ARC patients with DTC. They found unanimous clinical improvement, improvement in many laboratory measures, and no evidence that increased T-cell counts encouraged replication of the HIV virus (6,7). Subsequent studies in rheu- matoid arthritis, tuberculosis and chronic infections in the eld- erly have led French researchers to state that "Imuthiol is an effective agent for treatment of syndromes and disease states where the underlying defect is a T-cell deficiency or dysfunc- tion." (8) Lupus is an "auto-immune" disease that has been suc- cessfully treated with DTC (9). AIDS is thought to be, in part, an autoimmune disease as well. In addition, one study showed direct antiviral properties of DTC against HIV in the laboratory (10), but this has not been tested in humans. Based on these studies, there seems to be a good rationale for studying the use of DTC in AIDS. Mechanism of action It's not entirely clear how DTC works, whether it stimulates the liver to produce a thymic hormone-like substance called hepa- tosin or whether its immune-modulating action starts in the brain and then affects the liver and subsequently the T-cells. In any case, claims have been made that DTC speeds the maturation of T4 cells (thus increasing their total number), enhances overall T- cell functions, improves T4/T8 ratios, and slows reproduction of the AIDS virus. It is said not to cause stimulation of T cells but only to help existing cells reach maturity and become effec- tive, thus avoiding concerns about providing additional fuel for viral replication. Clinical research In the first French study of 6 people in 1985, all showed clinical improvement, all but one showed an increase in T4 cells, and three showed increased sensitivity in skin tests. After discontinuing the drug, these improvements disappeared (6). In 1987, a study of 26 patients at the University of Arizona showed that DTC slowed the progression of ARC and recommended combining DTC with AZT, but nothing has been published of this study. A double-blind placebo-controlled French trial of 90 ARC patients at five medical centers in France, sponsored by the manufacturer, showed impressive clinical and laboratory improvements -- fewer opportunistic infections, an average increase of 169 in T-cell counts -- with no significant side effects aside from some stomach pains, nausea, and a metallic taste in the mouth (11). The French researchers claim that these improvements were sus- tained in four patients over 2 years or more, but that they were lost if the patient stopped therapy. We must be cautious in interpreting the French study, espe- cially the T-cell data. Large, random fluctuations can occur in the individual patient without any therapy whatsoever. Many researchers feel that as much as 30% increase or decrease in T- cells may be attributable to such fluctuations. In the French study, the increase in T-cells falls well within that 30% and thus may not be attributable to the drug. The reported improve- ment in clinical status, however, seems unlikely to be a random event. Treatment Issues has obtained data on 14 American patients who have traveled to France to get Imuthiol. They are a diverse group ranging from asymptomatic seropositives to people with full-blown AIDS. Most are also taking other substances such as AL721, AZT or Naltrexone. Therefore, their data is highly anec- dotal and by no means authoritative. 11 of the 14 have only been on the therapy for 2 months (the French study showed benefit after 4 months). Of the 3 patients (2 with AIDS and one healthy seropositive) who have been on Imuthiol for 4 months or more, no increases in T-cells have been noted. Of the other 11 who have been on therapy for at least 2 months (mostly people with full- blown AIDS), 3 have had a greater than 30% increase in T-cells, 8 have not. Moreover, 2 months is too short a time to label anyone as "clinically stable." Thus, the available data on Imuthiol is scanty and no conclusions can really be drawn. A large, 9-month, placebo-controlled clinical trial is now taking place at six med- ical centers in California, Texas, Arizona and North Carolina. A New York center has recently been added (see Treatment Issues Volume 1 number 1, p. 8). No data has yet been released from this study; however, inside sources claim that less than 5% of the patients in the San Francisco arm of the study experienced significant rises in T-cells. If true, this is quite discourag- ing. Conversations with Dr. Livrozet, affiliated with l'Hopital Eduard Herriot in Lyons, France have confirmed a continued enthusiasm with the drug. He reported that his hospital has fin- ished a placebo-controlled study of Imuthiol. Patients with ARC exhibited a mean T-cell increase from 390 to 560 (greater than 30% increase). The results for patients with full-blown AIDS are not yet available. Many trials of DTC continue in France, including the combination of Imuthiol with AZT and trials of Imu- thiol in healthy seropositives. We will report on these trials as information is released. The Antabuse connection Disulfiram (Antabuse) has a history separate from DTC. It was originally used in the rubber industry. Workers exposed to disulfiram developed a reaction to alcohol. Two Danish physi- cians, who had taken disulfiram in the course of investigating its usefulness as a treatment for intestinal worms, became ill at a cocktail party and realized that the disulfiram had altered their response to alcohol. They initiated the studies that led to the use of disulfiram as a treatment for chronic alcoholism. The idea is that disulfiram, given to alcoholics, will prevent them from drinking by making them acutely sick if they do. In the 1950s, doses of 2500-3000 mg/day were used, but because of several deaths in people with heart disease who drink while on these doses, the standard dosage was gradually reduced to 500 mg/day, which is enough to produce very unpleasant reactions if the patient drinks. When taken orally, according to the manufacturer, roughly 64% of Antabuse is converted to DTC in the bloodstream (12). Oth- ers put the figure at 90%. These figures should be regarded as guesses and have not been verified. Moreover, nothing is known about the precise way in which Antabuse is metabolized as com- pared to DTC (Imuthiol). Some (especially the French research- ers) claim that Antabuse is not as effective as pharmaceutical DTC. When DTC (Imuthiol) gets absorbed it goes directly to the liver, giving the patient a high dose. Antabuse is absorbed and is then metabolized to DTC, which may result in lower blood lev- els. There are, at this time, no formal studies of Antabuse planned for AIDS. However, a number of physicians are now prescribing Antabuse for patient with AIDS and ARC. The Community Research Initiative in New York has developed a suggested proto- col for the standard dosing of Antabuse -- one 500 mg tablet twice a week -- and the collection of data from physicians treat- ing patients with Antabuse. Patients taking Antabuse should have their physician call the CRI at (212) 463-8981 to get enrolled in the monitoring project. All data is reported anonymously, with no patient names. Results to date with Antabuse There is considerably more data available on Antabuse, which is readily available by prescription. A substantial number of patients are taking Antabuse in the New York area, and informal conversations with several community physicians present us with some interesting information. It must be emphasized, however, that such surveys can be misleading because patients are always on a number of agents, including AL721, AZT or Naltrexone. How- ever, since patients need to make decisions today on therapies, it is hoped that this data may be useful in making decisions about Antabuse therapy. T-cell counts were obtained on 29 patients taking Antabuse. All patients were taking the drug for 3 months or more; the majority (83%) for 4 months or more. Doses ranged from 750 mg once weekly to 1250 mg weekly (500 mg and 750 mg on 2 different days). Most patients were taking 500 mg twice weekly. Of these patients, most have full-blown AIDS. Some had ARC and one was healthy and seropositive. Overall, 11 (38%) had a significant (greater than 30%) increase in T-cells. Healthier patients seemed to do better on Antabuse. Of the 10 people who started with fewer than 100 T-cells, only 2 (20%) showed a rise. Of the 9 people who started with between 100 and 200 T-cells, 5 (56%) showed a rise. Of the 10 people who started with over 200 T-cells, 4 (40%) showed a significant rise. All patients were clinically stable during the observation period with no new opportunistic infections occurring. All were being treated aggressively, including PCP prophylaxis and prompt treat- ment of other chronic infections. The most commonly-used medica- tions in addition to Antabuse were AZT, AL721, Acyclovir (Zovirax), and Naltrexone, but there were no obvious patterns with different drug combinations as to whether an individual responded to Antabuse. Side effects and warnings Most physicians indicated a significant frequency of toxic reactions to Antabuse. The most common reaction was diarrhea and intestinal cramping, followed by nausea, vomiting and a general ill feeling. One physician reported that up to 30% of AIDS patients started on Antabuse had to be taken off the drug because of these reactions. Some doctors say Antabuse may cause problems with the liver, which in turn can make other drugs more toxic. Therefore, anyone on Antabuse should be carefully monitored by a physician. Finally, there is one report of an AIDS patient who was quite ill, on a number of potent medications including chemotherapy, who rapidly deteriorated and died 2 weeks after starting Antabuse. Although this is the first and only such report, it underscores the necessity of close physician monitor- ing of anyone taking Antabuse. Antabuse may interfere with the metabolism of several drugs including Dilantin (Phenytoin), Isonizide (a TB medication), Fla- gyl (Metronidazole) and certain barbiturates and anti-anxiety and sleeping medications. Antabuse should be taken with caution by patients who are sensitive to rubber or rubber derivatives, since they may be sensitive to Antabuse also. Anyone taking DTC or Antabuse should avoid all forms of alcohol, including foods cooked with alcohol and liquid medica- tions containing alcohol (usually called elixirs or tinctures). Since small amounts of alcohol can be absorbed into the body through the skin, topical products containing alcohol -- such as rubbing alcohol, after-shave and astringents -- should be avoided, along with foods made with alcohol which is not cooked off by heating, fermented vinegars, candy containing alcohol, etc. Availability Developed by Institut Merieux, a French pharmaceutical com- pany, Imuthiol is not approved for use outside of the current clinical trials (some of which are still open for participants), which are being financed by the manufacturer rather than the U.S. government. There is some feeling that FDA approval might come quicker if the government were involved. In the meantime, clini- cal trials continue in Paris and Lyons, France. Contact Dr. Rosenbaum, Hopitalier Petie SeltPeltier, 47-83 Blvd. Del-hopital 75013 Paris, France. Phone: 45-70-2861. Dr. Livrozet can be reached at l'Hopital Eduard Herriot, Pavillon P, 69437 Lyon Cedex 03, France. Phone: 72-34-4689. The New York study is being coordinated by Dr. Adrian Marcel at Downstate Medical Center in Brooklyn. Contact him at (212) 270-1849. The raw chemical diethyldithiocarbamate (DTC) can be pur- chased or even made in a laboratory, but there are problems with administering DTC in this form. It must be taken rectally or in enteric coated capsules, to prevent DTC from being destroyed by the acidity of the stomach, possibly producing toxic byproducts. The dose of DTC being used in clinical trials in France is 10 milligrams per kilogram of body weight per week (to calculate this dose in milligrams, multiply body weight in pounds by 4.5). Some people take it rectally, dissolving it in about 10 cc of warm water. It is said that DTC has a strange smell, like gar- bage, that lasts from 30 minutes to 90 minutes after taking it. This is not a problem but a sign that the drug is being properly absorbed. Whether taken orally or rectally, though, the raw chemical is risky and/or clumsy to use. Antabuse is, of course, a prescription drug, and can be prescribed by any doctor. Summary Imuthiol (DTC) is an interesting immunomodulating drug that may boost the immune system of AIDS patients by stimulating the production of more T-cells. The French have reported some impressive findings, but they have not been corroborated by research in this country. Antabuse is a prescription drug that seems to be a precursor of Imuthiol and is metabolized into Imu- thiol in the body. A cursory look at 39 patients taking Antabuse in the New York area is encouraging and has shown that T-cells have risen significantly in 11. Considering its availability, cost, and manageable side-effects, it is worth considering as an adjunctive therapy. For more information about DTC, you can call Project Inform, (800) 334-7422 from within California, (800) 822-7422 from other states, or (415) 928-0293 from anywhere. They have an excellent fact sheet on DTC. You can also call the San Diego AIDS Project, (619) 543-0300, or Steve Gavin at (201) 677-2795. [Ed. note: A special thanks to Don Shewey for his help with this article.] WoBe Mugos and Wobenzym: German Enzyme Therapy Two drugs have been in widespread use in Germany for the treatment of a variety of illnesses including AIDS. The drugs, called WoBe-Mugos and Wobezyme, have been said to produce signi- ficant results in AIDS. There have been numerous inquiries about them, particularly because there are, in this country, prepara- tions which are said to be generic equivalents and which are readily available over-the-counter as nutritional supplements. The drugs WoBe-Mugos and Wobenzym are both tablets contain- ing a collection of proteolytic enzymes (enzymes that digest pro- teins). German researchers have claimed that these enzyme preparations have resulted in improvement in a number of diseases in which circulating immune complexes (CICs) have been thought to play an important role, including lupus and rheumatoid arthritis. Largely ignored by researchers in this country, they are said to work by digesting the abnormally high levels of CICs seen in these diseases. CICs are essentially large tangles of antibodies that circu- late in the blood and can attach themselves to normal cells. Nor- mally, antibodies are formed in response to a foreign protein and stick to that protein and only that protein. This "flags" the invading protein for engulfment by certain cells in the immune system. The antibodies in CICs, however, do not function prop- erly and clump together. These clumps can circulate in the bloodstream and can clog the filtration system of the kidneys or lodge in the joints to produce inflammation and arthritis. They can also attach to normal cells of the immune system (including the T4 cell), impede their function, and mark them for destruc- tion, a situation where, in effect, the body's own immune system destroys itself. CICs also impair the functions of other key cells of the immune system, including lymphocytes, natural killer (NK) cells and macrophages. Indeed, the presence of such high levels of CICs in AIDS offers an attractive hypothesis of why, when only a tiny fraction of T-cells are infected by HIV, there is such widespread damage to the immune system. The presence of high levels of CICs was noted early on in AIDS (13,14,15). In fact, they have been noted by some researchers in healthy homosexual males who are not infected by HIV. The level of CICs seems to correlate with the state of disease, with full-blown AIDS patients having the highest levels of all. This has led some researchers to feel that CICs play an important role in the progression to AIDS. Others feel that they are the inevitable result of the profound uncoordination of the immune system seen in AIDS and may not be a cause of the immunosuppression per se. In any case, several attempts were made in the past to "cleanse" the blood of AIDS patients from CICs by techniques including plasmaphoresis or protein A treatment (16). Results of these studies have not been impressive, although there was some reduc- tion of KS in many patients. German researchers have confirmed the high levels of CICs in patients with ARC and AIDS (17). Since they have showed reduc- tion of CICs in other diseases, they felt that the drugs may have a use in AIDS. Theoretical arguments aside, however, they have not yet demonstrated the ability of WoBe-Mugos and Wobenzym to reduce the levels of CICs in AIDS as they have with rheumatoid arthritis (18). Thus, while there is a reasonable theoretical rationale for looking at therapies that may reduce CICs in AIDS, there is no convincing data to support the use of these enzymes at this time. Many of the enzymes in WoBe-Mugos and Wobenzym are already present in the body. Moreover, it seems possible that the enzymes would be digested and never reach the bloodstream in their intended form. Nevertheless, proponents of the therapy claim that these supplemental enzymes are absorbed by the intes- tines at a rate of 20-40% and, once absorbed, can reduce the level of CICs in the blood. The lack of research on enzyme therapy in this country makes corroboration of this claim impos- sible. A large, controlled study of WoBe-Mugos and Wobenzym for the treatment of AIDS and ARC is underway in Europe. Hopefully, the findings will be reported at the 4th International Conference on AIDS in Stockholm this summer. The Community Research Initiative (CRI) has recently been approached by the American company that manufactures a generic "equivalent" of the German enzymes. The first product, Polyzym 021, is the substitute for Wobenzym. It is an enteric-coated tablet containing pancreatin, trypsin, bromelin, lipase, amylase and other enzymes. The product Polyzym 022 substitutes for WoBe-Mugos and contains pancreatin, papain, chymotrypsin and other enzymes. A third product, Polyzym 023, is a similar to Polyzym 022 but also contains a thymus extract. It is being used by AIDS patients in lieu of Polyzym 022 (WoBe-Mugos). The German study involves the daily administration of 30 tablets of Wobenzym plus 15 tablets of WoBe-Mugos. Some patients receive WoBe-Mugos by injection for the first 4 weeks but doctors claim to have achieved results with only the tablet form. They also state that results have been seen with Wobenzym alone, although patients take several weeks longer to respond. Since we don't know exactly what these enzymes are doing (if anything) or precisely what their mechanism of action is, one can only take the Germans' word as to type of preparation and dosage. Anecdotal reports from several patients in the New York area indicate that many so- called "constitutional" symptoms (such as fever, muscle and joint pains, fatigue and weakness) as well as chronic sinusitis have been improved on enzyme therapy. This type of benefit might be expected if circulating immune complexes, which cause inflamma- tory reactions, were reduced. Availability As mentioned, the generic "equivalents" of Wobenzym (Polyzym 021) and WoBe-Mugos (Polyzym 022 and Polyzym 023) are available in this country as health supplements. Patients are taking 10 tablets of Polyzym 021 3 times a day (30 tablets total). Polyzym 023 tablets are being dissolved in water and taken as an enema once daily (the absorption is supposedly better), but this can result in an unpleasant burning sensation around the anus. As mentioned, German researchers are also achieving good results with Wobenzym alone, so many patients in this country are taking the generic equivalent, Polyzym 021, exclusively (30 tablets daily). The manufacture of the generic products, General Research Laboratories, Inc, can be contacted at 8900 Winnetka Ave, Northridge CA 91324 to obtain the names of local distribu- tors. Of course, no health claims are being made by the company. The New York distributor is Vince LaRocca; he can be contacted at (201) 842-3322. The General Research Laboratories products, Polyzym 021 and Polyzym 023 are available at Willner Chemists, 330 Lexington Ave (phone: (212) 685-0448) but the price is higher (about $190 for a month's supply of Polyzym 012 plus Polyzym 023) as compared to obtaining it through Mr. LaRocca (about $124 per month). Summary Many claims have been made about these enzymes helping patients with AIDS and ARC. They are, at present, largely unsub- stantiated. Even the most fundamental purported effect of these enzymes, the reduction of circulating immune complexes, has not yet been convincingly demonstrated in the setting of AIDS. How- ever, there are anecdotal reports of patients on enzyme therapy that are somewhat encouraging. The rationale for their use remains largely theoretical at this time; therefore, they cannot be enthusiastically endorsed in this article. Although non- toxic, WoBe-Mugos and Wobenzym and their generic counterparts are expensive. We will be reporting information is it becomes avail- able from the forthcoming CRI trials and elsewhere. Dextran Sulfate Update [Ed. note: See original article on Dextran sulfate in Treatment Issues, Volume 1 number 2, December 31, 1987.] There is a burgeoning interest in the antiviral drug Dextran sulfate in the AIDS community. Encouraged by preliminary reports and hearsay, many patients are procuring and ingesting Dextran sulfate. Unfortunately, little authoritative data has accumulated since our last report. Researchers at the NIH have confirmed that Dextran sulfate is a potent antiviral drug in the test tube. Because of these encouraging results, it is very likely that a formal study of the drug will begin in New York in the very near future. Very little new data has been released from the ongoing San Francisco study. Rumor had it that the drug was causing reduc- tion of white cell counts; this was denied by researchers. More- over, physicians monitoring patients taking Dextran sulfate have not made this observation. The only serious side effect seen to date is an abnormality in liver function at high doses (4,500 mg daily). This is over twice the dose commonly being used for AIDS (1,800-2,700 mg daily). Thus, there is not yet a sound basis for recommending any particular dosage of Dextran sulfate. Hopefully, this will emerge in the coming months. Dextran is widely available in the "underground" market. Project Inform (1-800-822-7422) stays abreast of sources. The PWA Health Group in New York City (212-242-9102) is researching a domestic source of Dextran. Unfortunately, the first shipment did not meet specifications, and alternatives are being sought. Meanwhile, they are taking names of people interested in obtain- ing Dextran. In Brief Northern Lights Alternatives ("NLA") is an organization that was created to help PWAs channel their energy in positive, heal- ing directions. The cornerstone of NLA is a program of weekend retreats called AIDS Mastery Workshops. The main goal of these workshops is to teach NLA's central philosophy: PWAs can improve the quality of their lives through self-empowerment. NLA dissem- inates material through the telecommunications network of GayCom. NLA Online has launched, as of September 1987, an AIDS Biblio- graphic and Abstract Service (ABAS). This database gathers together over 2000 medical articles from a variety of sources. For each entry, users may access the journal title, volume, issue number and date, the title and author of each article and a brief abstract about the contents. For more information on NLA Online and ABAS, contact Bob Morse at 718-565-0087. For more information about NLA in general and the AIDS Mastery Workshops, contact Chuck Baier or Victor Phillips at 212-877-4846. New Studies Memorial Sloane-Kettering, a participant of the NIH network of AIDS Clinical Trials Groups, is recruiting patients for two studies. The first is a randomized, double-blind study comparing 1500 mg daily of AZT versus 500 mg of AZT daily versus placebo in asymptomatic seropositives. The study will continue for three years. Candidates must have T4-Cell counts of fewer than 500. There had been rumors that patients had to front over $500 for evaluation expenses. This is not true. Interested parties may call Cynthia Vassallo, RN or Delia Brown, RN at (212) 794-7164. The hospital is also monitoring an open-label (no placebo) Phase 1 study examining AL721 (see Treatment Issues, Volume 2 number 1). Participants must have T4-Cell counts of no more than 200 as well as Persistent Generalized Lymphadenopathy (PGL) or other ARC symptoms. This is essentially a dose finding study and it will run for eight weeks with a four week follow-up period. This is an important study of a substance that is already in wide use but for which little dependable data exists, and it is a way to get AL721 for free. Contact the individuals above for more informa- tion. For both studies, women participants must be willing to practice adequate birth control and have a negative pregnancy test within 30 days of entry for the AZT study and within 15 days for the AL721 study. The same study of AL721 will be conducted by Dr. Donna Mild- van at Beth Israel Medical Center. She is in need of more patients with lymphadenopathy or ARC to enroll in the study. We all need reliable information on AL721 and, hopefully, this study will begin to provide it. Call Dr. Mildvan at (212) 420-4005. The Community Research Initiative (CRI) continues to recruit patients for its Aerosolized Pentamidine study for prophylaxis of PCP in persons with AIDS. The study is not yet fully enrolled and is a way to get pentamidine for free. Anyone with CDC- defined AIDS who has not received aerosolized pentamidine for more than 3 months is eligible. Call the CRI at (212) 463-8981. For more information on aerosolized pentamidine, see Treatment Issues, Vol. 1 no. 1. The CRI is finalizing a protocol of Ampligen for persons with AIDS (the other trials underway in the new York area are for people with ARC). Hopefully, patient recruitment will begin in April. Stay tuned. Correction In the last issue of Treatment Issues, we ran a story on the reorganization of the NIH AIDS research groups. We incorrectly identified the new name of the AIDS clinical research groups. They are now called AIDS Clinical Trials Groups (ACTGs), not AIDS Clinical Cooperative Groups (ACCGs) as the article stated. Other Resources American Foundation for AIDS Research (AmFAR) has compiled a catalog of trials involving experimental drugs. The "AmFAR Directory of Experimental Treatments for AIDS & ARC" also includes some background information, updated regularly, about AIDS. Write to AMFAR at 40 West 57th St., New York, N.Y. 10019, or call (212) 333-3118 "AIDS Treatment News" is a short, biweekly report which chroni- cles current developments in experimental and alternative treat- ments and deals with public policy issues. Contact John S. James at P.O. Box 411256, San Francisco, CA 94141 or call (415) 282-0110. "PWA Coalition Newsline", published "by and for people with AIDS and AIDS Related Conditions," is a grass-roots news magazine that appears monthly. The publication reports news developments deal- ing with the health crisis as well as alternative treatments. Editorials and literary contributions add another interesting dimension to this excellent source of information. Write PWA Coalition Inc., 263A West 19th St., Room 125, New York, N.Y. 10011, or call (212) 627-1810. Ask about their other publica- tion, "Surviving and Thriving with AIDS". The Universal Fellowship of Metropolitan Community Churches publishes a monthly newsletter called "Alert", covering AIDS related legislation, education, research and treatment. Write to Rev. Steve Pieters, UFMCC, 5300 Santa Monica Blvd., Suite 304, Los Angeles, CA 90029. "ATIN" (AIDS Targeted Information Newsletter) performs a monthly search of hundreds of medical journals worldwide. Definitely aimed at doctors and researchers, it is the best ongoing litera- ture search available. It has an impressive cast of editors who comment on the significance of the studies cited. Published by Williams & Wilkins, P.O. Box 23291, Baltimore, MD 21203 or phone 1-800-638-6423. Project Inform publishes an excellent newsletter called "PI Per- spective" which deals with experimental treatments and focuses special attention on drug regulatory issues and public policy. Another valuable resource is their up-to-date drug hotline. Call them at 1-800-822-7422. Body Positive is a new organization established by and for HIV- antibody-positive people to exchange information, advocate research, fight discrimination, and provide mutual emotional sup- port. They publish a monthly newsletter called "The Body Posi- tive." Write to: 263A West 19th Street, New York, NY 10011 or call 212-633-1782. Treatment Issues is GMHC's newsletter devoted to experimental AIDS therapies. Describing an experimental therapy should not be construed as recommending it. All new treatments should be done under a physician's care. Treatment Issues is published ten times yearly. Copyright 1988 Gay Men's Health Crisis, Inc. All rights reserved. Non-commercial reproduction is encouraged. Subscription lists are kept confidential. Editor: Barry Gingell, M.D. Associate Editor: Kevin Armington GMHC, Department of Medical Information, 132 West 24th Street, Box 274, New York, NY 10011 Footnotes: 1 Sunderman FW et al. The effects of the protracted administra- tion of the chelating agent, sodium diethyldithiocarbamate (Dithiocarb). Amer J Med Sci 254:46, 1967. 2 Sunderman FW. Chelation therapy of nickel poisoning. Swansea Conference on Nickel Toxicology, Sept. 3-6, 1980, Swansea, Wales. 3 Sunderman FW et al. Sodium Diethyldithiocarbamate administra- tion in nickel-induced malignant tumors. Ann Clin Lab Sci 14(1):1, 1984. 4 Evans RG et al. An in vivo study of protective effect of diethyldithiocarbamate (DTC) 31st Annual Meeting of the Radiation Research Society, 1983, San Antonio, Texas. Radiation Research Society, 145 pp., 1983. 5 Evans RG et al. An in vivo study of the radioprotective effect of diethyldithiocarbamate (DTC). Int J Radiat Oncol Biol Phys 9(11):1635, 1983. 6 Lang G et al. Immunomodulation with diethyldithiocarbamate in patients with AIDS-related complex. The Lancet, November 9, 1985, p. 1066. 7 Pompidou A et al. Isoprinosine and Imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms. Cancer Research 45 (9 suppl):4671s, 1985. 8 Lemarie E et al. Clinical characterization of imuthiol. Methods Find Exp Clin Pharmacol 8(1):51, 1986. 9 Delepine N et al. Sodium diethyldithiocarbamate inducing long-lasting remission in a case of juvenile systemic lupus erythematosus. The Lancet, November 30, 1985, p. 1246. 10 Pompidou A et al. In vitro inhibition of LAV/HTLV-III infected lymphocytes by dithiocarb and inosine pranobex. The Lancet, December 21/28, 1985, p. 1423. 11 Lang et al. Treatment of ARC patients with DTC - A multicen- tric, randomized, double-blind placebo controlled trial. III International Conference on AIDS, Washington DC, 1987, MP.227. 12 Project Inform fact sheet on DTC-Imuthiol. 13 Gupta S et al. Circulating immune complexes in AIDS. NEJM 310:1530, 1984. 14 Euller HH et al. Precipitable immune complexes in healthy homosexual men, AIDS and LAS. Clin exp immunol 59:267, 1985. 15 Lightfoote MM et al. Circulating IgA immune complexes in AIDS. Immun Invest 14(4):341, 1985. 16 Kiprov DD et al. J Clin Apheresis (3):133, 1986. 17 Stauder G et al. The use of hydrolytic enzymes as adjuvant therapy in AIDS/ARC patients. Unpublished. 18 Steffen C et al. Enzymetherapie im Vergleich mit Immunokom- plex Bestimmunger bei chronischer polyarthritis. Z. Rheumatol 44:51, 1985. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display