Date: Thu, 27 Jun 1996 21:18:53 -0700 (PDT) From: "John S. James" Subject: AIDS Treatment News #250 AIDS TREATMENT NEWS Issue #250, July 5, 1996 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Cryptosporidiosis: NTZ at Buyers' Club; Customs Holds Second Shipment NAC: First Controlled Trial, Positive Results Nevirapine Approved Vancouver Conference: Each Day Summarized Nightly on World Wide Web SCIENCE Publishes Major AIDS Issue June 28; Full Text on Web CMV Retinitis and Treatment: CME Course on World Wide Web Delavirdine Expanded Access Program Information on World Wide Web West Hollywood: AIDS and Chinese Medicine Conference, July 25-28 Neuropathy: Nutrient Therapies World Wide Web: AIDS TREATMENT NEWS Lists Over 100 Sites ***** Cryptosporidiosis: NTZ Available at Buyers' Club; Customs Holds 2nd Shipment NTZ (nitazoxanide), an experimental drug which may be the first effective treatment against cryptosporidiosis (which causes severe diarrhea in persons with AIDS) was recently approved in Mexico, and for the first time is now available at a U.S. AIDS buyers' club, the PWA Health Group in New York. An officially approved compassionate access program recently was expanded from 100 to 150 slots. But for weeks many people who desperately needed this drug found it impossible to obtain, no matter how well connected they were. The PWA Health Group recently called people on its long list to buy NTZ, and found that half of them had died. NTZ is inexpensive to manufacture, and is being studied for treating many parasites in developing countries. In the U.S., it is in phase I trials for cryptosporidiosis. On June 21 a U.S. Customs office seized half of the PWA Health Group shipment of NTZ. Because such cases happen frequently and are usually resolved fairly rapidly, the PWA Health Group suggests that people contact them concerning how they might help if necessary. The shipment may have already been released by the time you receive this newsletter. Meanwhile the PWA Health Group has enough NTZ to treat about 50 people. They require a doctor's prescription for this drug. To obtain a fact sheet on NTZ, to order the drug, or to offer to help politically if necessary, contact the PWA Health Group at 212/255-0520. ***** NAC: First Controlled Trial, Positive Results by John S. James NAC (N-acetylcysteine), a low-cost potential treatment approved for certain non-HIV medical uses, has for years been one of the most popular "alternative" treatments sold by the AIDS buyers' clubs in the U.S. For many years researchers have had well-designed research protocols ready to go to scientifically test whether NAC can be helpful in HIV infection, but finding the funds for this work has been extraordinarily difficult. The first controlled trial started in late 1993 at Stanford University; now its results have been publicly reported at the May 21-24, 1996 meeting OXIDATIVE STRESS AND REDOX REGULATION: CELLULAR SIGNALING, AIDS, CANCER, AND OTHER DISEASES, at the Institut Pasteur in Paris.(1) Although the design of this study was too limited to tell definitively if NAC improves patient survival, it did show that the condition NAC is intended to correct (low glutathione levels in blood cells) strongly predicts poor survival. NAC was found to increase glutathione levels, and possibly to improve survival. (Glutathione is an antioxidant found in all cells, and is the primary intracellular defense against oxidative stress. It is critical for energy metabolism, cell division, and other functions, and is essential for the life of the cell. Glutathione is a small peptide, consisting of three amino acids; NAC supplies cysteine, which is the limiting amino acid for the production of glutathione. In addition to the need to maintain glutathione levels to prevent oxidative damage, it is possible that low glutathione levels may accelerate HIV replication.) History NAC has been controversial in the U.S. medical community, because several years ago a small study conducted at the U.S. National Institutes of Health reported that NAC was not found in the blood when taken orally. Other scientists replied that the NAC was well known to be absorbed but was quickly changed by the liver into other chemicals which did not show up in the tests which were used in that study. But the case against NAC being absorbed in useful amounts is the only one that got widespread attention. (Several years ago, this writer asked the lead researcher on the NIH NAC study how he would answer the argument that the test he used could not usefully determine bioavailability, as the NAC would be changed into related chemicals which that test would not measure. He told us that his trial was the kind required by the FDA for a pharmacokinetic study -- and that in addition his results were consistent with other reports in the literature. We did not think that this defense addressed the issue. At about that time, we were in a room with hundreds of AIDS physicians and research assistants where the NIH trial results were presented. Those doctors walked out of that room convinced that NAC was not absorbed and therefore useless. We would have thought the same thing too, if we had not talked to the parties involved. This is why most of the U.S. AIDS medical community today is convinced that NAC is not absorbed and therefore ineffective.) The Stanford Trial Now there is new data. The recent NAC trial was done at Stanford's Herzenberg Laboratory, one of the world's leading research groups on flow cytometry, the technology which is widely used to measure CD4 and CD8 counts, and which can also count many other kinds of cells. Flow cytometry works by treating cells so that different kinds will glow differently when exposed to a particular wavelength of light (which is usually provided by a laser). The cells move individually past the laser beam, and the fluorescence (glowing) of each is measured by a sensor and counted by computer. This technology allows cells to be divided into different populations based on many different characteristics. And by chemically reacting glutathione so that it will fluoresce, this method is also able to measure the glutathione level within each cell while simultaneously detecting if it is a CD4 cell, a CD8 cell, or some other cell type. As explained above, glutathione is a vital antioxidant in the cell -- and low intracellular glutathione is the condition which NAC is proposed to correct. The Stanford study collected baseline data on over 200 HIV- positive volunteers; 83 of them were enrolled in a double- blind placebo-controlled trial designed primarily to test whether HIV-infected people can absorb NAC (since the earlier NIH study had raised doubts). Since all but two deaths occurred in those who entered the study with a CD4 count under 200, further survival analysis was limited to this group. Two to three years later (depending on how soon people enrolled in the trial), the researchers surveyed all subjects who contributed baseline data, to see who had survived. Some of the details of the study are complex, but basically the findings were: (1) Low glutathione levels in CD4 T-cells mean increased risk of death. This analysis was done in those volunteers who for any reason did NOT take NAC in the study (so the researchers could see the natural-history association of mortality with glutathione levels, in the absence of treatment to restore those levels). Statistical analysis showed that those with glutathione levels equal to the group mean (0.98) had a two- to three-year survival rate of 65%. But of those with glutathione levels of 0.6, only 25% survived. The group mean itself was below normal, as glutathione levels are lower than normal in people with AIDS, as with many other serious illnesses. (2) Oral use of NAC increases glutathione levels in blood cells. A comparison of the 27 subjects who received NAC and for whom data was available, vs. the 26 who received placebo for the 8 weeks of the formal trial, showed that those on placebo had essentially no change; but in those who took NAC, glutathione levels went up about two thirds of the way to normal. (While the amount of change was only 10-12%, it could be meaningful since glutathione levels are fairly tightly regulated by the body, and normally cannot change very much.) (3) This study found that NAC was safe; there were no adverse effects attributed to the drug. (There have been other reports of gastrointestinal distress at high doses.) (4) Taking NAC was associated with increased survival -- although causality could not be proved by this study. In this trial, a direct survival comparison between those assigned to take NAC vs. those assigned to placebo was not meaningful, for two reasons. First, volunteers in both groups were offered open-label NAC for six months after the 8-week formal study was completed -- and most accepted the offer. This means that most of those assigned to "placebo" really took almost as much NAC as those assigned to the NAC group. Since this trial was not designed to test survival, there was no one who received placebo for the whole time. So the researchers looked at other comparisons -- which made the interpretation of the data more difficult and more uncertain. They found that on the average, the group that took NAC (for six to eight months) survived about six to eight months longer than the group that didn't take NAC. However, this was not a comparison between randomized groups, because this trial was not designed to allow such a comparison; those who took NAC were self-selected, and it is possible that these patients were healthier, or took better care of themselves in other ways, or had a better prognosis for some other unknown reason. This means that from this trial there is no way to be sure that using NAC contributed to survival. Therefore the investigators could only state that they see the results as consistent with the idea that NAC may improve survival. They hope to find funding as soon as possible for a proper prospective clinical trial to test this possibility. [Note on acetaminophen (Tylenol, etc.): NAC in very large doses has long been approved by the FDA for treating poisoning caused by acetaminophen overdose. NAC is an antidote because overdoses of acetaminophen drastically deplete the glutathione in the liver, resulting in severe liver damage, and NAC provides the cysteine necessary to replenish the glutathione. The FDA has warned heavy drinkers that alcohol use can reduce levels of glutathione, and acetaminophen can depress these levels further, causing risk of liver toxicity. Since HIV infection also causes reduced glutathione levels, Leonard Herzenberg, Ph.D., and Lenore Herzenberg, Ph.D., both of Stanford University Genetics Department and principle investigators in the NAC study described above, have long been concerned that acetaminophen or other medications which reduce glutathione levels might be harmful for persons with AIDS or HIV, and that patients and physicians could be cautious about using these drugs. References 1. Herzenberg LA, De Rosa S, and Herzenberg LA. Low glutathione (GSH) Levels in CD4 T Cells Predict Poor Survival in AIDS; N-Acetylcysteine (NAC) May Improve Survival. OXIDATIVE STRESS AND REDOX REGULATION: CELLULAR SIGNALING, AIDS, CANCER, AND OTHER DISEASES, Institut Pasteur, Paris, May 21-24, 1996. ***** Nevirapine Approved Nevirapine (Viramune(R)) received accelerated approval by the FDA on June 24, for use in adults in combination with other antiretrovirals. It is expected to be available in August. It is the first drug approved in a new class, the non-nucleoside reverse transcriptase inhibitors. For more information about nevirapine, see our previous issue, AIDS TREATMENT NEWS #249, which reported on the recent FDA Antiviral Drugs Advisory Committee meeting which recommended approval. The actual approval came after our issue was published. ***** Vancouver Conference: Each Day Summarized Nightly on World Wide Web Persons not attending the XI International Conference on AIDS (Vancouver, July 7-12) can follow the highlights in detail by taking a daily one-hour CME (continuing medical education) course, written nightly by a team of 22 practicing physicians and medical writers, and presented each day on the World Wide Web. The material is being produced by Clinical Care Options for HIV(SM), and will be presented on two different sites on the Web. Anyone throughout the world can get an immediate in- depth report on the conference through these modules -- which will remain available after the Conference. The two sites are http://www.immunet.org/meded and http://www.cmegateway.com; the material will be identical but the presentation on the Web will be different. See the article about the CMV RETINITIS AND TREATMENT CME course on the World Wide Web (below) for more information about the different sites. ***** SCIENCE Publishes Major AIDS Issue June 28; Full Text on Web by John S. James The journal SCIENCE will publish a major AIDS issue on June 28, and will release the full text that day on its Web site, http://www.sciencemag.org. This issue includes six journalistic articles, two research reports, three scientists' viewpoints (on vaccines, drug treatments, and chemokines and receptors), and an editorial. Two thousand copies will be distributed at the Vancouver conference. Of particular note is a new picture of HIV, drawn by a leading medical illustrator based on the best current information from top scientists throughout the world. The reporting includes a view of AIDS research based on information used by the investment community, and a table looking at the most-cited scientists among those who have published frequently. Note to Readers: This issue of AIDS TREATMENT NEWS went to press a week early, on June 26, so that we can print copies to take to the Vancouver AIDS conference. We did not review the SCIENCE coverage, but talked to their AIDS reporter Jon Cohen. ***** CMV RETINITIS AND TREATMENT CME Course on World Wide Web by John S. James The first AIDS/HIV CME course on the World Wide Web -- and one of the first CME courses by computer in any medical field -- begins operation on June 24. CMV RETINITIS AND TREATMENT offers one hour credit for physicians, nurses, and pharmacists; patients, advocates, and others interested can also take the course without credit. This module covers not only the approved treatments (ganciclovir and foscarnet), but also some experimental treatments and delivery systems available through clinical trials and other special programs to some patients. While the course is available throughout the world, it focuses on U.S. treatment approaches. To prevent the material from becoming dated, this CMV module will be available for six months and then discontinued. Other AIDS-related CME modules will be online by that time. This CMV course was written by Charles van der Horst, M.D., in a project sponsored jointly by Healthcare Communications Group and Medical Education Collaborative, and funded by an unrestricted educational grant from Roche Laboratories, Inc. The material was peer reviewed by the Clinical Care Options for HIV National Advisory Board, a panel of internationally recognized experts in HIV treatment. Presentation on the Internet The same material has been formatted differently and placed on two different Internet World Wide Web sites. Although the medical information is identical, there are substantial differences in the Web presentation which can affect how the end user receives the information. Because AIDS TREATMENT NEWS has a business relationship with Immunet, one of the organizations which has presented the material on the Web (see AIDS TREATMENT NEWS #247), we are uncomfortable judging or comparing two sites. But readers should know that the Immunet site was designed to work well with many different Web browsers and different Internet connections -- and "to address the needs and values of three unique communities: the medical, AIDS, and Web communities," according to Lisa Nelson, the site's graphic designer. The other site, by the Medical Education Collaborative, can also be reached through a link on the home page of the American Medical Association (http://www.ama-assn.org). (Note: the period at the end of the sentence is NOT part of this or other World Wide Web addresses.) The Immunet site is at http://www.immunet.org/meded. The Medical Education Collaborative site can be reached through http://www.cmegateway.com. Note: During the Vancouver conference, July 7-12, both Immunet and Medical Education Collaborative will present the same one-hour summary of each day of the conference; see separate announcement in this issue of AIDS TREATMENT NEWS. ***** Delavirdine Expanded Access Program Information on World Wide Web On June 25 Pharmacia & Upjohn, Inc. opened an Internet site on the World Wide Web for information about the expanded access program for its antiretroviral delavirdine (brand name Rescriptor(R)); this program started on April 1. The company will soon apply to the FDA for marketing approval. Delavirdine is in the same class of antiretrovirals as nevirapine, which was recently approved. The address of the delavirdine site is http://www.pnuaids.com. Physicians in the U.S. and Canada who would like to register patients for the expanded access program, or others who want written information, can call 800/779-0070. ***** West Hollywood: AIDS and Chinese Medicine Conference, July 25-28 The 4th HIV/AIDS & Chinese Medicine Conference will be held July 25-28 at the Wyndham Bel Age Hotel, West Hollywood, California. This is a conference for directors of Chinese medicine clinics and professional practitioners of Chinese medicine: licensed acupuncturists, medical doctors, nurses, and others who provide health care to people with HIV/AIDS. For more information, call Howard Moffet, L.Ac., AIDS & Chinese Medicine Institute, 415/282-4028, fax 415/282-2935. ***** Neuropathy: Nutrient Therapies by Lark Lands [Editors note: Lark Lands, Ph.D., a well-known health educator and consultant, is the author of POSITIVELY WELL: LIVING WITH HIV AS A CHRONIC, MANAGEABLE SURVIVAL DISEASE, an 800-page book which will be published in late summer 1996. Before her current work in HIV treatment, she was employed for six years as a scientist for the MITRE Corporation, a large think tank near Washington D.C., "conducting research, designing experiments, and compiling, assessing, and integrating information to provide problem resolutions and answers to government questions." When AIDS began, she was working in clinical nutrition, and has since educated people living with HIV on the importance of nutrition with this disease. She uses her professional skills to collect and organize HIV treatment information -- including not only drug therapies but also nutritional and other approaches often overlooked by the medical establishment because they do not involve proprietary drugs. She has worked with thousands of people with HIV infection to help them develop integrated treatment programs. Dr. Lands also has had lifelong diabetes, and is an expert on diabetic neuropathy, which has been much better researched than neuropathy caused by HIV. She believes that some (not all) kinds of HIV-related neuropathy may be similar to the diabetic condition, and may respond to some of the same treatments. AIDS TREATMENT NEWS asked Dr. Lands if we could interview her on what has been learned about treating diabetic neuropathy, and how that might apply to HIV. It turned out to be more practical to publish a section of Dr. Lands' new book than to conduct a separate interview. Readers should know that Dr. Lands emphasizes an integrated program of HIV disease management -- including antivirals and other mainstream medical treatments, nutritional approaches, and other kinds of therapy -- rather than using nutrition to treat only a specific symptom. Also, her book includes a detailed section on different kinds of HIV neuropathies. Other sections focus in detail on specific nutrients and other therapies, providing much information not included here. Unfortunately the book is not yet available. But readers should know about potential therapies which, although not conclusively proven and not officially approved, are supported by research, and have appeared to be helpful for many people. Patients should talk with their physician before using any therapy, including nutritional treatments. Even if the physician is not familiar with or does not approve of the treatment, he or she may know about specific cautions or contraindications, due to a patient's medical condition. The following is a small example of the useful information Dr. Lands has compiled. Her book will be an important advance in providing practical treatment information for persons with HIV disease. [Note: POSITIVELY WELL can be ordered by calling 800/542-8102 within the U.S. and Canada (from elsewhere, call 905/672- 7470), 9:00 a.m. to 5:00 p.m. Eastern time. The price is $24.95 plus shipping and handling. People can leave their name, address, phone number, and VISA or MasterCard number, which will not be charged until the book is ready to be shipped. (Remember that POSITIVELY WELL is not yet available, with estimated publication date of late summer. JSJ] From POSITIVELY WELL: LIVING WITH HIV AS A CHRONIC, MANAGEABLE SURVIVAL DISEASE: Although there has been virtually no research on the use of nutrient therapies for HIV-related neuropathies, there has been a fair amount of research (mostly in other countries) on their use for diabetic neuropathies. Since it appears likely that at least some of the mechanisms for the nerve damage may be similar in the two diseases (inflammation and oxidative damage to the nerves combined with B vitamin deficiencies), there is reason to believe that therapies which have proven useful for diabetics may also work for at least some people living with HIV who develop neuropathy. Many people living with HIV have reported to me that they have successfully eliminated neuropathy with some combination of the nutrient therapies discussed here. Thus, in addition to the other treatments mentioned, I would stress the importance of therapy with the B vitamins and other nutrients, especially acetyl-L-carnitine, gamma-linolenic acid, alpha-lipoic acid, magnesium, and chromium. I would definitely consider including the nutrients that have been shown to help rebuild the myelin sheath around nerves and/or improve nerve functioning such as choline, inositol, gamma linolenic acid, B6, B12, niacin, thiamine, biotin, folic acid, and magnesium. Biotin, choline, inositol, and thiamine are B vitamins that have all been found useful in treating the peripheral and autonomic neuropathies found in diabetes and may also help with HIV-related neuropathies. In a study at the University of Athens, it was shown that regular, long-term use of biotin in diabetics was very effective both for improvement in nerve conduction and relief of pain.(1) Improvement in nerve conduction occurred after only 4-8 weeks of therapy. In this study, biotin was given via daily intramuscular injection (10 mg/day) for 6 weeks; then 3 times per week (10 mg), intramuscularly, for 6 weeks; then 5 mg/day taken orally for up to two years. The researchers hypothesize that deficiency, inactivity, or unavailability of biotin in diabetics may result in disordered activity of the biotin-dependent enzyme, pyruvate carboxylase, leading to an accumulation of pyruvate and/or a depletion of aspartate, either of which could adversely affect nervous system metabolism. There are a number of reasons why HIV-positive persons may be deficient in biotin and, thus, potentially at risk for a similar problem. It has been suggested that those with neuropathy symptoms might try 10-15 mg/day orally, taken in conjunction with the other B vitamins found useful for improving nerve function. B12 deficiency is a known cause of neuropathy so this vitamin, along with its coworker folic acid, should certainly be included in any program aimed at eliminating this symptom. Typical symptoms of peripheral neuropathy related to B12 deficiency include the type of leg and foot pains experienced by many. B6 deficiencies are also known to cause both carpal tunnel syndrome (with symptoms of numbness, tingling, and pain in the hands and wrists) and degeneration of peripheral nerves and may be responsible for some peripheral neuropathy problems. Choline and inositol also seem to be very important parts of the combination of vitamins needed for neuropathy resolution. Diabetic neuropathy is known to be associated with a reduction in myo-inositol levels in nerves and tissues. The decreased level of myo-inositol is believed to cause a decrease in the activity of the sodium-potassium pump and, thus, to change the sodium permeability of nerves. Both diets high in inositol and inositol supplementation have been shown to improve diabetic neuropathy. Researchers at the University of Alabama found a statistically significant improvement in nerve function in diabetics placed on a diet high in inositol. Included in the diet were high-inositol foods such as cantaloupe, peanuts, grapefruit, and whole grains. Other researchers have reported that supplementation with inositol in doses of 2-6 grams per day has resulted in improvements in neuropathy. Robert Atkins, M.D., has reported his successful use of 2-6 grams per day for reversing diabetic neuropathy, and notes that physicians at St. James Hospital in Leeds, England, have reported good results with even smaller dosages.(2) In addition to the use of inositol itself, treatment with acetyl-L-carnitine can help raise nerve myo-inositol content. Florida researchers have found that peripheral nerve function in diabetes is linked to nerve myo-inositol content and that acetyl-l-carnitine can raise the levels of myo-inositol in the nerves of animals with experimentally induced diabetes.(3) It also apparently protects the nerve membranes from free-radical damage, as evidenced by reduced malondialdehyde levels in the animals treated with acetyl-l- carnitine. Thiamine has also been seen to be useful in treating diabetic neuropathy. Stanley Mirski, M.D., has reported that a large percentage of his diabetic patients who suffer from neuropathy have achieved improvements with daily thiamine supplementation in doses of 50-100 mg. Using a fat-soluble form of thiamine such as thiamine tetrahydro-furfuryl disulfide may be preferable because of the relatively poor absorption of water-soluble forms of this vitamin. This type is contained in Cardiovascular Research's Allithiamine. A large number of HIV-positive people have reported to me their successful elimination of neuropathy with the combined use of the B vitamins discussed here. The information on acetyl-l- carnitine is too recent for much in the way of anecdotal reports to have surfaced, but it might be an important addition to improve the chances for successful elimination of neuropathy. Research has made it clear that people living with HIV are often deficient in carnitine. Alpha-lipoic acid has long been used in Europe for the treatment of peripheral neuropathy in diabetics. A number of controlled clinical trials have shown its usefulness for reducing both the pain and numbness suffered by those with diabetic neuropathy, and its use for this condition is approved in Germany.(4) Its antioxidant properties may help protect the nerves from the inflammation and oxidative damage that HIV induces, as has been shown to be true with diabetic neuropathy.(5) Because of its liver protective and antioxidant benefits, it has been included as a component of the programs of many of my clients for several years now. It may have contributed to the success of the neuropathy elimination programs some of them have used. Gamma linolenic acid is an essential fatty acid found in borage oil, grape seed oil, black currant oil, and evening primrose oil that has been shown to be successful in reversing nerve damage in diabetics suffering from peripheral neuropathy. In a double-blind, placebo-controlled study using 480 mg of GLA daily, all the diabetics given the fatty acid experienced gradual reversal of nerve damage and improvement in the symptoms related to the peripheral neuropathy, while those on placebo gradually worsened.(6) It is thought that GLA may help to rebuild the myelin sheath around the nerves, thus restoring proper nerve conduction. Magnesium is also known to be necessary for nerve conduction; deficiency is known to cause peripheral neuropathy symptoms. Thus, including optimal amounts of magnesium might contribute to elimination of neuropathy. There have also been reports of chromium deficiency causing peripheral neuropathy. I learned this too recently for chromium to have been included in most of the neuropathy therapy programs used by my clients in the past and, thus, I'm not sure what it might contribute. However, chronic infection is known to deplete body stores of chromium, so adding a dose of perhaps 200-400 mcg/day to a complete nutrient protocol might be reasonable. In addition to all the nutrient supplements, an analysis of data coming out of the Immune Enhancement Program in Portland, Oregon, appears to show that their program, which includes Chinese herbs along with acupuncture and various other therapeutic approaches, results in improvement in neuropathy for some. For additional information on the nutrients which might be helpful for eliminating neuropathy, including appropriate dosage ranges, see the individual nutrient entries in Chapter Six of POSITIVELY WELL, "Therapeutic Basics." If you are considering supplementation with any of the B vitamins discussed above, never forget that although B vitamins are by and large non-toxic, any individual B vitamin should always be taken along with the full B complex to prevent imbalance in the body. Long-term use of very high doses of individual B vitamins taken alone, without the rest of the B complex, can induce imbalances or deficiencies in other B vitamins. References 1. Koutsikos D, Agroyannis B, and Tzanatos-Exarchou H. Biotin for diabetic peripheral neuropathy. BIOMED. PHARMACOTHER. Volume 44, number 10, pages 511-514. 2. Atkins R. DR. ATKIN'S NUTRITION BREAKTHROUGH New York: William Morrow, 1981, page 194. 3. Lowitt S, Malone JI, Salem AF, and others. METABOLISM. 1995; volume 44, pages 677-680. 4. Packer L, Wiott EH, and Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. FREE RADICAL BIOLOGY & MEDICINE 1995; volume 19, number 2, pages 227-250. 5. Kehler W, Kuklinski B, Ruhlman C, and Plotz C. Diabetes mellitus -- a free radical-associated disease: Effects of adjuvant supplementation of antioxidants. In: Gries FA and Wessel K (editors), THE ROLE OF ANTIOXIDANTS IN DIABETES MELLITUS: OXYGEN RADICALS AND ANTI-OXIDANTS IN DIABETES Frankfurt am Main: pmi Verl-Gruppe, 1993:33-53. 6. The Gamma Linolenic Acid Multicentre Trial Group. Treatment of diabetic neuropathy with gamma-linolenic acid. DIABETES CARE 1993; volume 16, number 1, page 8. ***** World Wide Web: AIDS TREATMENT NEWS Lists Over 100 Sites by Tadd Tobias and John S. James As this issue goes to press, AIDS TREATMENT NEWS is opening its second Web site, the AIDS TREATMENT NEWS Internet Directory (http://www.aidsnews.org). This site will help people find AIDS treatment and related information on the Internet. Also, it will report news about AIDS-relevant World Wide Web sites, and the information they have available. The list below shows the titles of the sites we are including initially, organized by categories. We published it here to show readers the variety of information currently available on the Internet. We did not include the URLs (Internet addresses), because of limited space, and because anybody with access to the World Wide Web can visit our site (http://www.aidsnews.org) and use the most current version of the list to link to any of the sites. Please let us know about sites we overlooked, and about any other ideas for improving this directory. Treatment Advocates and Information Providers * ACT UP / Golden Gate * ACT UP/Paris * ACT UP/Philadelphia * ACT UP/New York * AIDS Info BBS Database * AIDS Research Information Center * AIDS Treatment Data Network * Californians for Compassionate Use/ Cannabis Buyers Club * CATTY * Critical Path AIDS Project * Hemophilia Home Page * HIVNET/GENA Information Server * Joint Project on Legal and Ethical Issues of AIDS/HIV * Mothers' Voices Home Page * NATAP (National AIDS Treatment Advocacy Project) * Outline * Project Inform * PWA Health Group * The Body * Treatment Action Group * VACTUP Service Organizations * ACSN - AIDS Caregivers Support * AIDS Project Los Angeles * Gay Mens' Health Crisis * KAIROS Support for Caregivers * NAMES Project * Project Open Hand Newsletters * AIDS TREATMENT NEWS Online * Antiviral Agents Bulletin Home * CDC AIDS Daily Summary * Critical Path Project, AIDS Treatment Publications * HIV/AIDS Treatment Information * Keep Hope Alive Home Page * NAM AIDS Treatment Update Alternative/Complementary Treatment Information * Acupuncture Home Page * ALTMED WEB Home Page * Bastyr University AIDS Research * Critical Path AIDS Project * Homeopathy Home Page * Immune Enhancement Project * Power - Program For Wellness Restoration * The Alternative Medicine Homepage * World Health Network * Yoga for HIV/AIDS Clinical Trials Information * AIDS Clinical Trials Information * AIDS Clinical Trials Unit at Washington University * Canadian Trials Network * CenterWatch Clinical Trials List * Clinical Trials offered in Hawaii * Critical Path AIDS Project * NAM AIDS Treatment Update * Trials Search: California HIV Clinical Trials * UCLA Care Center Experts Online to Answer Your Questions * AIDS on line! * AMA Expert Advice * Profnet * Vanderbilt Univ. Med. Center HIV/AIDS Online Help CME (Continuing Medical Education) Online * CMV Retinitis & Treatment (an online CME course) * Online HIV CME Conferences and Abstracts, Medical Literature * Cambridge Healthtech Institute * Establish_Online_Account (MEDLARS) * Infectious Diseases Society of America * Internet Grateful Med * National Library of Medicine - MEDLARS * Pharmaceutical Information Network * SCIENCE On-Line * XI International Conference on AIDS Medical Sites, Miscellaneous * British Columbia Centre for Excellence in HIV and AIDS * Glossary of Terms * International Association of Physicians in AIDS Care * JAMA - HIV Site * Medscape * OncoLink, The University of Pennsylvania * Resources by Disease & Condition * Roxane Pain Institute * Spinnaker * The World-Wide Web Virtual Library Corporate Sites * Immune Network Research Ltd. * Pharmacia and Upjohn: Expanded Access ... delavirdine * Stadtlanders' HIV & AIDS Focus * VSB Corp. (Viatication) * Welcome to Isis Pharmaceuticals Children and AIDS * Children with AIDS Project * Mothers' Voices Home Page * MSSM: Adolescent AIDS Prevention * Pediatric AIDS Canada * The CANDII Program Spiritual * AIDS National Interfaith Network * Belly of the Buddha * The HIV/AIDS Ministries Network Government * CDC National AIDS Clearinghouse * Food and Drug Administration * HyperDOC: U.S. National Library of Medicine * National Institute of Allergy and Infectious Diseases * National Institutes of Health * Social Security Administration * Thomas: Legislative Information on the Internet Unconventional Theories * AIDSAuthority (including Duesberg theory) AIDS Directories on the Web * AIDS TREATMENT NEWS Internet Directory * Emory University MedWeb: AIDS and HIV * Galaxy/EINet AIDS and HIV Resources * HIVNET AIDS Resources on the Internet * HIV: Electronic Media Information Review * JRI Health InfoWeb * Links to Other Resources * Marty Howard's HIV/AIDS Home Page * Medical Matrix-AIDS Information * New York Academy of Medicine * NOAH: AIDS and HIV Resources * Queer Resources Directory (QRD) * The World-Wide Web Virtual Library * Vanderbilt AIDS Resources * Yahoo! - Health:Diseases and Conditions Web Search Engines * Alta Vista * Architext Querying * Critical Path AIDS Project * Deja News Research Service * Internet Searching Center * Search.com International Focus * AIDS Surveillance in the Americas * AVERT HOME PAGE * Crusaid HIV Information Exchange * Educational Information on HIV for Singapore * European Information Center for HIV and AIDS * FQD: AIDS/HIV Resources for Filipinos * Harvard AIDS Institute * HIV/AIDS Statistics in Thailand * HIV: Electronic Media Info. Review from Australia * Hong Kong AIDS Foundation * IRCAM AIDS and HIV - informations and resources * World Health Organization [Note: http://www.aidsnews.org also includes listings of sites for technical/specialized research topics, Internet free speech, and AIDS sites in French, German, Italian Spanish, and other languages. Our resource list for women and AIDS was not complete when this issue went to press, but will be in the Web site.] ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number fax: 415/255-4659 Internet: aidsnews@aidsnews.org Editor and Publisher: John S. James Reader Services and Business: Richard Copeland Tom Fontaine Denny Smith Tadd Tobias Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1996 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.