From <@VMS.DC.LSOFT.COM:owner-mednews@ASUVM.INRE.ASU.EDU> Tue Sep 5 01:56:18 1995 (LSMTP for OpenVMS v0.1a) with SMTP id 3B2A60B4 ; Tue, 5 Sep 1995 1:48:58 -1300 release 1.8b) with NJE id 2760 for MEDNEWS@ASUVM.INRE.ASU.EDU; Mon, 4 Sep 1995 22:47:11 -0700 (LMail V1.2a/1.8a) with BSMTP id 3779; Mon, 4 Sep 1995 22:47:10 -0700 V2R3) with TCP; Mon, 04 Sep 95 22:47:05 MST (8.6.12/8.6.9) with UUCP id WAA28521 for mednews@asuvm.inre.asu.edu; Mon, 4 Sep 1995 22:31:35 -0700 mednews@asuvm.inre.asu.edu Comments: To: asumednews@stat.com HICNet Medical News Digest Mon, 04 Sep 1995 Volume 08 : Issue 31 Today's Topics: AIDS Summary File 1 AIDS Summary File 2 Heart Attack, Allergy Connection Nothing to Sneeze At Insulin Resistance/Potential for CVD in Mexican-American Common "K" May Offer Easy Way to Prevent High Blood Pressure Smoking Accelerates Arterial Thickening Beta-Blockers: Not Just for Blood Pressure Anymore +------------------------------------------------+ ! ! ! Health Info-Com Network ! ! Medical Newsletter ! +------------------------------------------------+ Editor: David Dodell, D.M.D. 10250 North 92nd Street, Suite 210, Scottsdale, Arizona 85258-4599 USA Telephone +1 (602) 860-1121 FAX +1 (602) 451-1165 Internet: mednews@stat.com Bitnet: ATW1H@ASUACAD Mosaic WWW *Asia/Pacific: http://biomed.nus.sg/MEDNEWS/welcome.html *Americas: http://outland.cardinal.com/hicn *Europe: http://www.dmu.ac.uk/ln/MEDNEWS/ Compilation Copyright 1995 by David Dodell, D.M.D. All rights Reserved. License is hereby granted to republish on electronic media for which no fees are charged, so long as the text of this copyright notice and license are attached intact to any and all republished portion or portions. The Health Info-Com Network Newsletter is distributed biweekly. Articles on a medical nature are welcomed. If you have an article, please contact the editor for information on how to submit it. 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Cross, B.S Health Care Admin, 882 Medical Trng Grp, USAF Albert Shar, Ph.D. CIO, Associate Prof, Univ of Penn School of Medicine Stephen Cristol, M.D. MPH, Dept of Ophthalmology, Emory Univ, Atlanta, GA Subscription Requests = mednews@stat.com anonymous ftp = vm1.nodak.edu; directory HICNEWS FAX Delivery = Contact Editor for information ---------------------------------------------------------------------- To: hicnews cc: Dr David Dodell AIDS Daily Summary The Centers for Disease Control and Prevention (CDC) National AIDS Clearinghouse makes available the following information as a public service only. Providing this information does not constitute endorsement by the CDC, the CDC Clearinghouse, or any other organization. Reproduction of this text is encouraged; however, copies may not be sold, and the CDC Clearinghouse should be cited as the source of this information. Copyright 1995, Information, Inc., Bethesda, MD In this issue **************************************************************** "Tuberculosis Knowledge Among New York City Injection Drug Users" "Treatment of HIV-Associated Kaposi's Sarcoma with Paclitaxel" "Energy Expenditure and Wasting in HIV Infection" "The Cost-Effectiveness of Voluntary Counseling and Testing of Hospital Patients for HIV" "Risk Factors for Tuberculosis in HIV-Infected Persons" "Failure of T-Cell Homeostasis Preceding AIDS in HIV-1 Infection" "Therapies Outside the Mainstream" "Interleukin-2 as Therapy for HIV Disease" "Reducing the Impact of Opportunistic Infections in Patients with HIV Infection" "Preventing AIDS: Have We Lost Our Way?" "Oral Manifestations of HIV Infection" "The Effects of Vitamin A Supplementation on the Morbidity of Children Born to HIV-Infected Women" "Seizure Associated with Zidovudine" **************************************************************** "Tuberculosis Knowledge Among New York City Injection Drug Users" American Journal of Public Health (07/95) Vol. 85, No. 7, P. 985; Wolfe, Hannah; Marmor, Michael; Maslansky, Robert et al. Between November 1992 and February 1993, as part of a cohort study of HIV infection among injection drug users, Wolfe et al. recruited nearly 500 members of New York City methadone maintenance treatment programs to assess their knowledge of tuberculosis (TB). More than 30 percent of this group reported having tested positive to a tuberculin skin test in the past. Almost all subjects identified TB as an airborne infection, and more than 50 percent also identified possible indirect methods of transmission. Seventy-five percent did not understand the difference between infection and active disease, but those who reported a history of skin test reactivity were two times more likely to comprehend the distinction. A total of 40 percent of those surveyed did not understand the necessity of medication adherence. The majority, however, did understand that TB is potentially fatal, and realized that HIV-infected persons are more susceptible to it. The study's authors concluded that these misunderstandings--which could be the result of faulty TB education and overgeneralization of knowledge about HIV--may contribute to the fear and confusion that hamper TB control efforts "Treatment of HIV-Associated Kaposi's Sarcoma with Paclitaxel" Lancet (07/01/95) Vol. 346, No. 8966, P. 26 Saville, M. Wayne; Lietzau, Jill; Pluda, James M. Saville et al. conducted a phase II trial to determine whether the drug paclitaxel (Taxol), which is active against various carcinomas, is effective against AIDS-related Kaposi's sarcoma (KS). The drug's cellular target is similar to that of vinca alkaloids, which are active against KS. Although none of the 20 patients achieved a complete response, 13 had a partial response. All six of the patients who had received prior systemic treatment responded, as did the five with pulmonary Kaposi's sarcoma. The other six remained stable, while just one progressed. The most common dose-limiting toxic effect was neutropenia. Novel toxic effects included late fevers, rash, and eosinophilia. The authors say their findings suggest that paclitaxel is active against HIV-associated KS, including in those patients with aggressive disease, advanced AIDS, and previous receipt of systemic therapy. "Energy Expenditure and Wasting in HIV Infection" NEJM (07/12/95) Vol. 333, No. 2, P.83 Macallan, Derek C.; Noble, Carole; Baldwin, Christine et. al. To determine the contribution of total energy expenditure to weight changes in patients with HIV-related wasting, Macallan et al. performed more than 50 tests of energy metabolism in HIV-infected men at various stages of the disease. The results of the tests were compared with the rate of weight gain or loss. The average total energy expended was 2750 kilocalories (kcal) per day, give or take 650 kcal, which is no more than that expended by healthy men. The researchers observed a significant positive relation between total energy expenditure and the rate of weight change. During rapid weight loss, therefore, total energy expenditure fell to 2180 kcal per day, which is primarily the result of reduced exercise. In addition, they observed that in periods of rapid weight loss, people infected with HIV used less energy. The key determinant of weight loss in HIV-related wasting, the authors concluded, was reduced energy intake--not increased energy expenditure, as some have suggested. "The Cost-Effectiveness of Voluntary Counseling and Testing of Hospital Patients for HIV" JAMA (07/12/95) Vol. 333, No. 2, P. 129 Lurie, Peter; Avins, Andrew L.; Phillips, Kathryn A. et al. In response to letters to the editor published in the Journal of the American Medical Association written by members of the Johns Hopkins University School of Medicine and the Centers for Disease Control and Prevention (CDC), Lurie et al. state that--contrary to the letters' assertion--they are aware of the existence of universal safety precautions. Their research concluded that inpatient HIV screening for the purpose of preventing health care worker infection was not cost-effective, but that it could be cost-effective in areas of 1 percent seroprevalence or more. The analyses were based in three diverse hospitals, and reflect the reality of adherence to universal safety measures, rather than an idealized version of compliance, Lurie et al. assert. It seems unlikely, they conclude, that the study will be interpreted as implying that the CDC endorses inpatient HIV testing for preventing the infection of health care professionals--particularly when it was stated that "the CDC has explicitly rejected this position." "Risk Factors for Tuberculosis in HIV-Infected Persons" JAMA (07/12/95) Vol. 274, P. 143 Antonucci, Giorgio; Girardi, Enrico; Raviglione, Mario C. et al. Antonucci et al. conducted a multicenter cohort study in Italy to evaluate factors predictive of active tuberculosis (TB). In this article, they analyze how demographic, clinical, and laboratory characteristics influence the risk of TB in HIV-infected persons. They found that being tuberculin-positive, anergic, or having a CD4 lymphocyte count either less than 20 or between 20 and 35 were indicators significantly associated with the risk of TB. In the three groups of patients with different levels of skin responsiveness, the incidence of TB increased as the level of CD lymphocytes decreased. Such factors as age, sex, place of residence, HIV transmission category, and antiretroviral therapy were not associated with an increased risk of the disease. By considering both skin test reactivity and CD4 lymphocyte count, HIV-infected patients' risk of TB can be more precisely measured. The researchers propose that regular skin tests in tuberculin-negative nonanergic individuals can be useful in identifying those who are at high risk for active disease. "Failure of T-Cell Homeostasis Preceding AIDS in HIV-1 Infection" Nature Medicine (07/95) Vol. 1, No. 7, P. 674 Margolick, Joseph B.; Munoz, Alvaro; Donnenberg, Albert D. Many have theorized about "blind" T-cell homeostasis--that a constant level of T lymphocyte cells is maintained independent of CD4 or CD8 phenotype. In a recent study, Margolick et al. confirm the relatively constant T-cell counts of HIV-1-infected gay men who have not developed AIDS for as many as eight years after seroconversion. It was observed, however, that seroconverters who did develop AIDS had rapidly decreasing T-cell levels for approximately two years before full-blown AIDS developed. These findings indicate that homeostasis failure may be a key factor in HIV disease progression. The researchers conclude that, in light of the high rate of T-cell turnover in HIV-1 disease, blind T-cell homeostasis may augment HIV pathogenesis through a CD8 lymphocytosis that interferes with the regeneration of lost CD4 T cells. "Therapies Outside the Mainstream" Washington Post (Health) (08/01/95) P. 10 Herman, Robin Increasingly, Americans frustrated with their standard medicine are discovering "alternative" or "unconventional" treatments that have been shunned by the higher-tech medical world. As methods that involve massage therapists, homeopaths, herbalists spread, so has the concern that some treatments may not have been sufficiently tested, and thus may be ineffective or even harmful. But most people who use alternative therapies are adding them to their usual health care. According to James Gordon of the Georgetown University School of Medicine, the two major groups of people who seek such treatments are those who just do not feel good and those "people who have come to the limits of traditional Western medicine for chronic illness or life-threatening conditions." Studies, for example, have found that as many as 50 percent of HIV-infected people are using unconventional treatments. Some of the more problematic therapies involve the ingestion of pills and potions that supposedly prevent disease or boost the immune system. These remedies are largely unregulated and are outside the control of the Food and Drug Administration because they are described as supplements and do not claim to cure disease. "Interleukin-2 as Therapy for HIV Disease" NEJM (07/20/95) Vol. 333, No. 3, P. 192 Lane, H. Clifford; Kovacs, Joseph A. There is a complex association between activation of the immune system and levels of viral replication, write Lane and Kovacs in response to letters to the editor published in the New England Journal of Medicine. For example, activation of CD4 T lymphocytes by interleukin-2 (IL-2) can bring about cell division and an increased number of cells. Activation of CD8 cells by IL-2 can lead to increased immunity against viral infections. The overall effect of IL-2 in a given patient, therefore, is a function of many variables. The authors, however, state that the main point of their March 2 article was that it is possible to induce and maintain a polyclonal expansion of CD4 T lymphocytes in some HIV-infected individuals using intermittent courses of IL-2. "Reducing the Impact of Opportunistic Infections in Patients with HIV Infection" JAMA (07/26/95) Vol. 274, No. 4, P. 347 Kaplan, Jonathan E.; Masur, Henry; Jaffe, Harold W. et al. With new knowledge of the environmental sources of opportunistic pathogens, ways to reduce exposure, and the role of chemoprophylaxis, a practical strategy for preventing opportunistic infections in HIV-infected people has become particularly important. The U.S. Public Health Service, with the Infectious Diseases Society of America, is now publishing comprehensive guidelines to prevent such infections. Previous efforts dealt with Pneumocystis carinii, Mycobacterium tuberculosis, and Mycobacterium avium-intracellulare complex, and focused on chemoprophylaxis. The new patient- and pathogen-oriented guidelines provide background information and recommendations for clinicians and patients on the behavioral shifts, drug therapies, and immunizations that are most likely to be effective, safe, and cost-effective. The guidelines also discuss the relative importance of several prevention measures and attempts to integrate them. "Preventing AIDS: Have We Lost Our Way?" Lancet (07/29/95) Vol. 346, No. 8970, P. 262 Lifson, Alan R. Although the best way to curb AIDS is by preventing the transmission of HIV, millions of people already test positive for the virus, notes Alan R. Lifson in the British medical journal The Lancet. Prospective studies have demonstrated that years can pass between HIV infection and the emergence of related infections and disorders. Two findings, however, now challenge the theory that HIV resides for years in a quiescent phase. The first is that active viral replication occurs in the lymphoid system well before significant replication is evident in the peripheral circulation. The second finding is that HIV replication occurs continuously in vivo at high rates, which results in the rapid turnover of CD4 cells. These findings, along with others, suggest that AIDS should not be considered a separate entity from HIV infection, that current reliance on reverse transcriptase inhibitors needs to be re-evaluated, and that HIV-related opportunistic infections need to be prevented. As more becomes known about HIV, Lifson concludes, it is important to refrain from concentrating on one strategy to the exclusion of others, and that whatever preventative strategies are developed are useful to the millions of infected persons as well. "Oral Manifestations of HIV Infection" NEJM (08/03/95) Vol. 333, No. 5, P. 328 Seldin, Edward B. "Oral Manifestations of HIV Infection," edited by John S. Greenspan and Deborah Greenspan, is a service to both the medical and dental fields, in part because it marks an interdisciplinary effort to identify often-ignored medical and dental aspects of HIV and AIDS. The chapters--which were contributed by participants in the Second International Workshop on the Oral Manifestations of HIV Infection--include descriptions of specialized dental facilities that have been built for the treatment of AIDS patients, as well as formal reports from research laboratories. The majority of the chapters are grouped according to the clinical manifestations of HIV or AIDS in the oral cavity, such as candidiasis, salivary-gland disease, and Epstein-Barr virus. One particularly interesting section contains six chapters on periodontal disease in the context of HIV or AIDS. Overall, the book clearly conveys a sense of urgency in regards to HIV and its path of destruction. "The Effects of Vitamin A Supplementation on the Morbidity of Children Born to HIV-Infected Women" AJPH (08/95) Vol. 85, No. 8, P.1076 Coutsoudis, Anna; Bobat, Raziya A.; Coovadia, Hoosen M. et al. To determine the effects of vitamin A supplementation on the morbidity of children born to HIV-infected women, Coutsoudis et ·_ al. conducted a randomized, placebo-controlled study of 118 infants in Durban, South Africa. Among all the children, the vitamin A supplemented group had a reduced average morbidity. The rates of morbidity for those receiving supplementation were lower for almost every condition when assessed individually. Also in the supplemented group, all diarrhea was reduced by 29 percent, diarrhea lasting more than 7 days was reduced by 38 percent, and hospital admissions for diarrhea declined by 77 percent. Among the 85 children whose HIV status was known, diarrhea-related morbidity was almost reduced by half in the supplemented HIV-infected group. Vitamin A, however, had no effect on diarrheal morbidity in the uninfected children. The researchers concluded that, in a population where vitamin A deficiency is not endemic, vitamin A supplementation for the children of HIV-infected women appeared to be beneficial and to reduce morbidity. This benefit was particularly diarrheal morbidity among HIV-infected children. "Seizure Associated with Zidovudine" Lancet (08/12/95) Vol. 346, No. 8972, P. 452 D'Silva, Marisa; Leibowitz, David; Flaherty, John P. In a letter to the editor published in the Lancet, D'Silva et al. report the incidence of a generalized seizure related to the prophylactic use of zidovudine. After receiving a large-caliber contaminated needlestick injury from an HIV- and hepatitis C-infected individual, a man was given intramuscular immunoglobulin and tetanus toxoid, and oral zidovudine. The zidovudine therapy was continued three to four times daily. During the next few days, the patient complained of nausea, anorexia, and emesis--which were treated with ondansetron--as well as exercise intolerance, dull occipital headaches, and insomnia. Six days after the needlestick, he experienced a generalized seizure. The patient had never suffered seizures or adverse drug reactions before, but he had had several concussions from childhood accidents. The zidovudine was abandoned, and no other seizures took place. More than one year later, the patient remains negative for both HIV and hepatitis C. Although it is still not clear whether zidovudine caused the seizure, the potential for severe toxicity should be considered when recommending unproven treatment, the authors note. ------------------------------ To: hicnews cc: Dr David Dodell AIDS Daily Summary The Centers for Disease Control and Prevention (CDC) National AIDS Clearinghouse makes available the following information as a public service only. Providing this information does not constitute endorsement by the CDC, the CDC Clearinghouse, or any other organization. Reproduction of this text is encouraged; however, copies may not be sold, and the CDC Clearinghouse should be cited as the source of this information. Copyright 1995, Information, Inc., Bethesda, MD In this issue **************************************************************** "Benefits of HIV Screening of Blood Transfusions in Zambia" "New Roles for AZT?" "A Comparison of Immediate with Deferred Zidovudine Therapy..." "Mixed Results with Octreotide for AIDS-Related Diarrhea" "No Cheers for Baboon to AIDS Patient Xenotransplant" "Cancer Drug May Join the AIDS Arsenal" "Natural History of HIV-1 Cell-Free Viremia" "HIV-Associated Diarrhea and Wasting" "Resisting AIDS: Another Vaccine Approach" "Wasting Syndrome--Affordable Treatments" "Guidelines for Management of HIV Infection with Computer-Based Patient's Record" "New Antiviral Drug Could Slow AIDS-Related Blindness" **************************************************************** "Benefits of HIV Screening of Blood Transfusions in Zambia" Lancet (07/22/95) Vol. 346, No. 8969, P. 225 Foster, Susan; Buve, Anne Although blood transfusion continues to be a major path of HIV transmission in developing countries, testing for the virus is often expensive, and dependable donor support is hard to secure. Foster and Buve examined the cost and benefits of screening blood for HIV. They used data obtained at a district hospital in Zambia, where HIV seroprevalence among blood donors was nearly 16 percent. At the Monze District Hospital in 1991, more than 1,000 transfusions were given and approximately 150 cases of transfusion-related HIV infection were averted. Overall, the HIV screening cost U.S. $4745, while the cost per case of HIV prevented was $31.62. This protection for the community served by the hospital cost $0.03 per person. The researchers estimate that 3,625 undiscounted healthy years of life were saved, of which nearly 70 percent were in children under six. The cost was $1.32 per year of life preserved. In sum, the savings from blood screenings exceed the costs of screening by a factor of between 2.7 and 3.5. Therefore, the authors feel that it is critical to maintain both financial and political support for the HIV screening of blood for transfusions. "New Roles for AZT?" Science (07/14/95) Vol. 269, No. 5221, P. 163 Recent scientific reports have hinted at additional uses of the AIDS drug AZT--including for two diseases that involve an abnormal proliferation of cells, leukemia and psoriasis. In an article in the New England Journal of Medicine, researchers from the University of Southern California reported that they tested a combination of AZT and interferon-alpha in 19 patients who had an extremely lethal form of adult T cell leukemia-lymphoma. Four were also HIV-positive. According to the researchers, 11 patients had "major responses" to the treatment, including five total remissions. The scientists suggested that the fast-growing cancer cells are targeted because they absorb the most AZT. Another study, published in the June issue of the Journal of the American Academy of Dermatology, reported that AZT cleared up most of the psoriasis in four of 12 patients. One researcher from the University of Texas at Houston theorized that AZT, which disables a key enzyme that HIV needs to copy itself, may slow skin cell reproduction. Both teams hope to further test these treatments in larger, controlled trials. "A Comparison of Immediate with Deferred Zidovudine Therapy for Asymptomatic HIV-Infected Adults with CD4 Cell Counts of 500 or More per Cubic Millimeter" NEJM (08/17/95) Vol. 333, No. 7, P. 401 Volberding, Paul A.; Lagakos, Stephen W.; Grimes, Janet M. et al. To assess the clinical benefits of zidovudine in asymptomatic HIV patients who have CD4 counts greater than 500, Volberding et al. compared immediate zidovudine therapy to deferred therapy in such patients. The participants were randomly assigned either zidovudine or a placebo, though the study was modified with open-label treatment two years later for those people whose CD4 levels fell below 500. After 6.5 years, there was no significant difference in AIDS-free survival or overall survival in the deferred-therapy group, compared to the low-dose or high-dose group of zidovudine. However, the two immediate therapy groups did experience a slower decrease of CD4 cells than the deferred group. Although side effects were rare, the high-dose zidovudine group experienced more severe anemia and granulocytopenia than the deferred group. The researchers concluded that zidovudine slows the decline of CD4 cells in symptom-free, HIV-infected adults with more than 500 CD4 cells, but does not extend either AIDS-free or overall survival. The results, therefore, do not necessarily justify the standard use of zidovudine monotherapy in this group. "Mixed Results with Octreotide for AIDS-Related Diarrhea" AIDS Clinical Care (08/95) Vol. 7, No. 8, P. 68 A multicenter study of the somatostatin analogue octreotide for the treatment of diarrhea produced mixed results. Nearly 130 AIDS patients were given octreotide or a placebo subcutaneously three times a day. After 21 days, 46 percent of the octreotide group had achieved the goal of a 30 percent decrease in stool weight, compared to 36 percent of the placebo group. The two groups had similar reductions in bowel-movement frequency. Although patients with idiopathic diarrhea--diarrhea lasting more than 13 weeks, body weight under 60 kg, or CD4 levels below 50--showed a better response to the treatment, the differences between the two groups remained nonsignificant. During the open-label phase, the octreotide dose was increased, and after eight weeks, both stool weight and bowel-movement frequency decreased significantly. Even though the results of the controlled study were disappointing, the open-label results indicate that longer-term treatment at higher doses could be effective. "No Cheers for Baboon to AIDS Patient Xenotransplant" Lancet (08/05/95) Vol. 346, No. 8971, P. 369 Thompson, Clare The xenotransplant of baboon bone marrow into an AIDS patient has several transplant scientists worried. The operation, they argue, is severely flawed and has little experimental justification. "The likelihood that this will work is extremely small," claims surgeon Hugh Auchincloss of Massachusetts General Hospital. "The difficult procedure will probably hasten [the patient's] death and not prevent it." The transplant is based on the assumptions that the baboon marrow is HIV-resistant, and that "facilitator cells" will allow engraftment without the development of graft-versus-host disease (GVHD). Suzanne Ildstad--one of the two scientists involved in the procedure--plans to isolate the facilitator, stem, and T cells from the baboon bone marrow; filter out the T cells, which are thought to be the cause of GVHD; repackage the stem and facilitator cells; and transplant them into the patient. The problem with the concept, however, is that Ildstad is the only one who has been able to identify the facilitator T cells. These and other technical questions should have been answered by animal experimentation, some opponents say. "Cancer Drug May Join the AIDS Arsenal" JAMA (08/16/95) Vol. 274, No. 7, P. 523 Voelker, Rebecca The cancer drug hydroxyurea may not be a success in itself, but researchers claim it is particularly effective in fighting HIV when used in combination with the nucleoside analogue didanosine (ddI). Dr. Franco Lori, director of the new Research Institute for Genetic and Human Therapy (RIGHT) in Italy, is trying to determine why HIV-1 does not replicate in quiescent cells. According to Lori, his hypothesis that focused on the lack of deoxynucleoside triphosphates (dNTPs) was correct. "When HIV enters a quiescent cell, there is not enough food to survive," he explains. Research published in the journal Science later showed that in vitro anti-HIV activity is increased without additional toxicity when hydroxyurea is used with ddI. Lori thinks that hydroxyurea may reduce problems related to drug resistance. When used with ddI, he says, hydroxyurea lessens viral replication so significantly that there is less virus able to mutate, which could potentially delay the onset of ddI-resistance. In addition to Lori's trial, which has a U.S. counterpart that began testing last month, hydroxyurea research is also being conducted in France and other U.S. locations. "Natural History of HIV-1 Cell-Free Viremia" JAMA (08/16/95) Vol. 274, No. 7, P. 554 Henrard, Denis R.; Phillips, Jack F.; Muenz, Larry R. et al. In an attempt to characterize the natural history of viremia with HIV and its relationship with disease progression, Henrard et al. studied 42 homosexual men who seroconverted to HIV-1 in the early- to mid-1980s. The subjects were tested each year for quantitative virion-associated HIV-1 RNA, p24 antigen, and CD4 cells. During the course of the study, the HIV-1 RNA levels remained stable; only 14 percent of the subjects had at least 10-fold increases in the three to 11 years of follow-up. Both univariate and multivariate analyses revealed that initial and subsequent HIV-1 RNA levels, p24 antigenemia, and a percentage of CD4 cells were independently predictive of disease progression to AIDS. The findings indicate that there is a balance between HIV-1 replication and efficacy of immunologic response that is created soon after infection and continues through the asymptomatic phase of the disease. The faulty immunologic control of HIV-1 infection, therefore, could be as important as the rate of viral replication in assessing survival free from AIDS. HIV-1 RNA levels may be effective markers for predicting clinical outcome, the authors conclude, because the individual stable levels of viremia were established soon after infection. "HIV-Associated Diarrhea and Wasting" Lancet (08/05/95) Vol. 346, No. 8971, P. 352 DuPont, H.L.; Marshall, G.D. DuPont and Marshall present the case of a 34-year-old Hispanic bisexual male who, nearly four years after his HIV diagnosis, began to experience bothersome diarrhea without fever. The diarrhea persisted for more than a year, despite treatment with a number of drugs. The two primary explanations for this HIV/AIDS-related problem are opportunistic enteric infection and HIV enteropathy. Approximately half of the patients with AIDS-related diarrhea are diagnosed with an infectious agent. DuPont and Marshall's patient was infected with a member of the order Microsporidia. He was treated with metronidazole without effect, though it has occasionally been useful in relieving illness related to microsporidiosis. This patient illustrates several of the clinical problems associated with HIV, diarrhea, and wasting. The illness is generally prolonged. In addition, the cause may not always be obvious, and may often involve a complex interaction between infection by enteric pathogens and intestinal immune defects. Because the cause can vary, the authors conclude that it may be necessary to conduct numerous evaluations and to use combinations of both specific and non-specific drugs to improve quality of life and provide relief. "Resisting AIDS: Another Vaccine Approach" Technology Review (07/95) Vol. 98, No. 5, P. 23 Shearer, Gene M.; Clerici, Mario Seeking evidence of cellular response to HIV, Shearer and Clerici's team at the National Cancer Institute (NCI) studied a group of high-risk people who showed no traditional signs of infection with the virus. They found that between 35 and 65 percent of the various subsets of the group showed evidence in their white cells of "cellular immune activity." The team then tried to determine whether an AIDS vaccine should depend on the body's cellular immune response, instead of the antibody response. Several labs--including the one at NCI--have noted changes in the types of cytokines produced before an HIV-infected person progresses to full-blown AIDS. Cytokines are the proteins that regulate the immune system. The NCI lab found that production of the type of cytokines that primarily promote a cellular immune response falls before a person develops AIDS, while the output of cytokines that enhance an antibody response increases. It was also found that most of the HIV-infected people who progress to AIDS quickly produce more of the second type of cytokines, whereas long-term nonprogressors produce far more of the first type. The concept of a type 1-to-type 2 shift in most HIV-infected individuals has prompted researchers to consider treating them with type 1 cytokines, with other molecules that cause the body to increase type 1 cytokine production, or with antibodies to type 2 cytokines. "Wasting Syndrome--Affordable Treatments" AIDS Treatment News (07/07/95) No. 226, P. 6 James, John S. There are inexpensive treatments for AIDS wasting syndrome, which is defined as the extreme loss of lean body mass not due to obvious causes such as nutritional deficiency or intestinal infection. Early data indicates that most patients can be successfully treated using these approaches. One affordable treatment for non-severe, AIDS-related weight loss is testosterone enanthate, when used in combination with an exercise program. The drug has not been proven in clinical trials, but according to Dr. Marcus Conant in San Francisco, it has offered good results. Conant's team has found that people with true wasting respond very well to human growth hormone. Fourteen of 16 severely wasting patients gained weight with the hormone, after finding no success with the approved treatments Megace and Marinol. Ketotifen is another possibility for treatment, though not much research has been done yet on using it for AIDS-related wasting. It is believed to be very safe, and is used widely in Europe for asthma and allergies. A third possibility is thalidomide, which is now available though an "underground compassionate access" program through the PWA Health Group in New York or Healing Alternatives in San Francisco. The two FDA-approved drugs for AIDS-related wasting are expensive, and their effectiveness for increasing lean body mass is controversial. "Guidelines for Management of HIV Infection with Computer-Based Patient's Record" Lancet (08/05/95) Vol. 346, No. 8971, P. 341 Safran, Charles; Rind, David M.; Davis, Roger B. et al. Safran et al. studied more than 100 physicians and nurse practitioners to determine the efficacy of electronic medical records when used for HIV patients. The scientists examined the clinicians' response times to the situations that caused alerts and reminders, the number of ambulatory visits, and hospitalization. They found that the average response time to the 388 alerts in the control group was 52 days, while the intervention group's median response time to 303 alerts was 11 days. The average response times to 432 reminders in the intervention group and 360 reminders in the control group were 114 days and more than 500 days, respectively. Although the system had no effect or difference on visits to the primary care practice; admission rates; admissions for pneumocystosis; visits to the emergency room; or survival, there was a dramatic increase in the number of visits outside of the primary care practice--which is due to an increased rate of opthalmology visits. Overall, the researchers concluded that computer medical records helped clinicians treating HIV patients adopt new practice guidelines more rapidly and more thoroughly. "New Antiviral Drug Could Slow AIDS-Related Blindness" American Medical News (07/17/95) Vol. 38, No. 26, P. 23 Cidofovir--the first of a new class of antiviral drugs--appears to help AIDS patients ward off the blinding cytomegalovirus infection, according to manufacturer Gilead Sciences. The drug's potential is beginning to draw attention to nucleotide analogs to fight AIDS-related infections, as well as HIV, experts say. "We believe this class of drugs does confer some real advantages to patients," says Gilead's Dr. Howard Jaffe. Nucleotide analogs, cousins to nucleoside analogs such as AZT, have a chemical structure that allows them to enter any cell and begin working without having to be "turned on," explains Dr. Arnold Friedland of St. Jude's Children's Hospital. Tests show that cidofovir fought blindness progression for 120 days, compared to just 50 days for the current treatment, says Jaffe. As a result of this success, Gilead has begun early human testing of an oral HIV therapy that would work similarly, although results are years in the future. ------------------------------ ·_ To: hicnews HEART ATTACK, ALLERGY CONNECTION NOTHING TO SNEEZE AT The type of cell responsible for the symptoms of allergies and allergic asthma also may play a key role in triggering heart attacks. Mast cells are the source of allergy and asthma symptoms because of the chemicals they contain, such as histamine. What happens in the case of an allergic reaction is that a foreign protein, such as a pollen molecule, locks onto an antibody that sits on the surface of the mast cell. This causes a series of reactions that result in the breakdown of the cell membrane, releasing the chemical contents allergists refer to as the mediators of allergy and asthma symptoms. But researchers at the Wihuri Research Institute in Helsinki, Finland, have discovered that activated mast cells also are concentrated at the edge of fatty deposits that clog the arteries feeding the heart muscle with blood. These fatty deposits are known as atherosclerotic plaques. Petri T. Kovanen, M.D., Ph.D., and his associates theorize that mast cells "actively participate in the destabilization and ensuing rupture: if these atherosclerotic plaques, contributing to the development of heart attack. Their research report was published in the October 1994 issue of the AHA journal Circulation. Activated mat cells secrete enzymes that can break down the protein components of the "Fibrous cap" that covers plaque. Rupture of the cap increases the chances that a blood clot will form there. The scientists compared normal an diseased sections of coronary arteries from 32 autopsy patients who ranged in age from 13 to 67 years. They tested the arteries for the presence of two enzymes that degrade the cap proteins. They found that the density of activated mast cells at the edges of the plaques was 50 times higher than in non-diseased arteries. These finding, Kovanen and his colleagues report, strongly suggest the mast cell is directly involved in the often fatal final event of coronary atherosclerosis. Other studies have implicated other immune system components--white blood cells called macrophages--in the development of heart attacks. What is activating mast cells and macrophages? Kovanen suggests that chemicals in cigarette smoke might be part of the problem. Cigarette smoke, he says, increase blood levels of the mast-cell activating antibody, which is called immunoglobulin E, or IgE. "Smoking might make mast cells more prone to release their chemicals." The term mast cell comes from the German "mastung," which means well-fed. Association Vol. 5, No. 2 Spring 1995 --- Internet : david@dental.stat.com Telephone: +1-602-860-1121 FAX : +1-602-451-1165 ------------------------------ To: hicnews INSULIN RESISTANCE AND THE POTENTIAL FOR CVD SEEN IN MEXICAN- AMERICAN CHILDREN Mexican-American children may have a greater chance of developing a blood chemistry syndrome associated with increased risk of heart disease in adults. "Having insulin resistance may precede the development of diabetes. And there is evidence that high insulin levels promote atherosclerosis, the depositing of fatty materials that narrow blood vessels and increase the likelihood of heart attack," says David C. Goff, M.D., Ph.D., assistant professor of epidemiology an medicine at the University of Texas at Houston School of Public Health and School of Medicine. Insulin resistance is a condition in which the body makes insulin but cannot use it efficiently to metabolize, or break down, dietary sugar. The result is high insulin levels and often high blood sugar levels. High blood levels of insulin also can contribute to high blood pressure, a risk factor for heart disease and a major risk factor for stroke. Goff and his associates studied 191 Mexican-American children and 179 non-Hispanic white children who were eight to nine years old. They measured the children's height, weight and blood pressure and analyzed fasting blood samples. The researchers also sent questionnaires to the children's homes to get a family medical history. They looked at five factors associated with insulin resistance: blood insulin levels, triglycerides (a form of blood fat), systolic blood pressure (the pressure in the arteries created by the heartbeat), body mass index (a measure of obesity) and levels of high-density lipoprotein cholesterol (HDL-C, the so-called "good" cholesterol that helps clear other cholesterol from the blood). Blood insulin levels were 34 percent higher in the Mexican- American children. "We also saw lower HDL-C but higher triglycerides, higher systolic blood pressure and greater body mass index in the Mexican-American children," says Goff. "The pattern was exactly the pattern one would expect to see in the insulin resistance syndrome in adults." The scientists also found that 34 percent of the Mexican- American children had four to five adverse risk factors, while only 16.8 percent of the non-Hispanic white children had multiple risk factors. "We still don't know from this study if these differences are related to genetic or environmental influences, especially diet and physical activity," Goff explains, "But this may be a way to identify children who may be at particularly high risk for cardiovascular disease as adults." Goff presented this information at the AHA's Scientific Sessions in Dallas in November 1994. Association Vol. 5, No. 2 Spring 1995 --- Internet : david@dental.stat.com Telephone: +1-602-860-1121 FAX : +1-602-451-1165 ------------------------------ To: hicnews "COMMON K" MAY OFFER EASY, CHEAP WAY TO PREVENT HIGH BLOOD PRESSURE Taking in extra potassium may offer a safe, simple and inexpensive way to prevent high blood pressure in some African-Americans. A three-week course of oral potassium supplements reduced blood pressure in 43 African-Americans with acceptable or "normal," blood pressure. In contrast, average blood pressure in the 44 health African-Americans who received a placebo, or medically inactive substance, did not change, Frederick L. Brancati, M.D., reported at the AHA's 67th Scientific Sessions in Dallas. "The results of this study also suggest that a prudent diet should include foods that are high in potassium," says Brancati, assistant professor of medicine and epidemiology at the Johns Hopkins Medical Institutions in Baltimore. "Increased dietary potassium intake could help prevent high blood pressure in high-risk individuals." Examples of foods high in potassium are bananas, dried fruits, potatoes and orange juice. At the beginning of the study, dietary potassium from food in both groups was similar to the national average of 50-60 milliequivalents (mEq) daily and somewhat higher than the norm for African-Americans (who generally consume less dietary potassium than do whites). During the study, all 87 participants followed a low-potassium diet that contained no more than 40 mEq of potassium daily. After three weeks, systolic blood pressure decreased by 6.9 points in people who received the potassium supplements, and diastolic pressure fell by 2.5 points. IN the placebo group, neither measurement changed. Systolic blood pressure is a measure of the force generated by the heartbeat and is the first number in a blood pressure reading. Diastolic blood pressure refers to the pressure when the heart rests between beats, and it is the second number. According to the AHA there is no "ideal" blood pressure. For most adults a reading no higher than 140/90 millimeters of mercury indicates a mild blood pressure. But risk of heart attack, stroke and kidney disease rises steadily with increasing blood pressure. The mechanism by which potassium supplementation affects blood pressure remains unclear, notes Brancati. One prominent theory suggests that potassium affects the tone or tension in small blood vessels. Another theory traces the element's effects to kidney function and the elimination of water and salt. Compared to whites, African-Americans have a much higher risk of developing high blood pressure. Overall, more than 28 percent of all African-Americans have high blood pressure, and the condition affects nearly 70 percent of African Americans aged 65 and older. Association --- Internet : david@dental.stat.com Telephone: +1-602-860-1121 FAX : +1-602-451-1165 ------------------------------ To: hicnews SMOKING ACCELERATES ARTERIAL THICKENING, INCREASES RISK OF HEART ATTACK AND STROKE Smoking cigarettes is like putting your blood vessels into a time machine headed into the future. As people age, the walls of their arteries gradually thicken. Research published in the December 1994 issue of the AHA journal Circulation shows that cigarette smoking accelerates this process by more than a decade. By adding the equivalent of 10 years of aging to their arteries, smokers are increasing their risk of stroke and heart attack. Grethe S. Tell, Ph.D.,M.P.H., professor of epidemiology at Bowman Gray School of Medicine in Winton-Salem, N.C., and her colleagues, analyzed data from ultrasound exams of the carotid arteries of 5,116 people older than 64. They found "clinically significant" (50 percent or more of the artery's width) narrowing of these major blood vessels in 4.4 percent of people who had never smoked, 7.3 percent of former smokers and 9.5 percent of current smokers. Ultrasound imaging is a non-invasive technique that uses high frequency sound waves to help produce images of the body's interior. Located in the neck, the carotid arteries carry blood to the brain. If narrowed by atherosclerosis--a condition of arteries characterized by deposits of fat, cholesterol and other substances--a stroke may result. The carotids are important and very easy to examine with ultrasound, Tell says. "We know that what we find in the carotids is a reflection of what's happening elsewhere in the body." "The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never- smoking participants," the scientists wrote in their report. Until now there have been some doubts as to whether smoking is harmful in older people, Tell says. "But we found smoking has bad effects even among the elderly. People who continue to smoke in old age have more clogged arteries than people who don't." The men and women who participated in this study were selected from Medicare eligibility lists from Allegheny County (Pittsburgh), Pa; Forsyth County, N.C.; Sacramento County, Calif.; and Washington County, Md. The scientists say there is "abundant evidence" that cigarette smoking causes atherosclerosis. Cigarette smoking is firmly established as a risk factor for coronary heart disease, peripheral vascular disease and stroke, Tell and her associates note. Their study, which is part of the Cardiovascular Health Study, is designed to determine if asymptomatic disease detected with ultrasound progresses less in people who quit smoking. Association Vol. 5, No. 2 Spring 1995 --- Internet : david@dental.stat.com Telephone: +1-602-860-1121 FAX : +1-602-451-1165 ------------------------------ To: hicnews BETA-BLOCKERS: NOT JUST FOR BLOOD PRESSURE AND HEART RATE ANYMORE In the October 1994 issue of the AHA journal Circulation, and analysis of about two dozen studies that involved more than 2,300 patients showed a promising treatment for congestive heart failure, which hospitalized more than 800,000 Americans in 1992. The new therapy? Beta-blocker drugs, which have been around since the 1960s. Beta-blockers block a portion of the adrenergic nervous system, slowing the heart rate and reducing blood pressure. The class of drugs gets its name from the beta receptors, proteins on the surface of heart cells that control the uptake of nervous system chemicals that, in turn, control the force and rate of the heartbeat. Eric Eichhorn, M.D., of the University of Texas Southwestern Medical Center at Dallas and the Dallas VA Medical Center, says, "We've found that beta-blockers are not just slowing down the rate of progression of heart failure, but actually reversing some of the damage." Congestive heart failure is a disease process in which the heart muscle becomes damaged or overworked, and is unable to pump out all the blood that returns to it. Hundreds of thousands of new cases occur each year and it is the most frequent cause of hospitalization in people age 65 and older. In related research, Ake Hjalmarason, M.D., of the University of Goteborg, Sweden, and his colleagues found that chronic treatment with the beta-blocker metroprolol could reduce the need for heart transplantation in patients with severe heart failure from a condition called idiopathic dilated cardiomyopathy. And a trial called CIBIS (Cardiac Insufficiency Bisoprolol Study) shows that beta-blockers appear to have a favorable impact on the survival of patients with heart failure. In CIBIC 320 patients in nine countries received the beta- blocker bisoprolol while 321 patients received a placebo, a medically inactive substance. But Eichorn says the CIBIS trial did not include enough patient to tell if treatment with beta-blockers really had an impact on survival. He is the principal investigator of BEST (Beta-blocker Evaluation of Survival Trial), which began in January 1995 and hopes to gain enough statistical power from at least 2,800 patients over five years to answer the question about survival. Many people who develop heart failure have had coronary heart disease and have undergone coronary angioplasty or bypass surgery earlier in life. But their disease has progressed and their hearts have begun to fail. Other causes of heart failure include the cardiomyopathies (structural problems of heart muscle) and viral infections. Association Vol. 5, No. 2 Spring 1995 --- Internet : david@dental.stat.com Telephone: +1-602-860-1121 FAX : +1-602-451-1165 ------------------------------ End of HICNet Medical News Digest V08 Issue #31 *********************************************** --- Editor, HICNet Medical Newsletter Internet: david@stat.com FAX: +1 (602) 451-6135