HIV: the more things change, the more they stay the same.

PIP: The syndrome known as AIDS is eventually brought on after initial infection with HIV. Infection with either HIV-1 or HIV-2 will lead to AIDS. However, different strains of HIV-1 have been found to exist, varying between continents. The strains, or clades, vary quite significantly in their surface antigens and genetic sequences. HIV-1 subtype B, the initial causative virus of AIDS in Western industrialized countries, is reproducibly different from subtypes C and E, respectively found in sub-Saharan Africa and northwestern Thailand. Each subtype provokes divergent host immune responses substantial enough to affect the course of vaccine development. There are currently two HIV/AIDS epidemics in Thailand, one spawned from the initial outbreak of HIV-1 subtype B in 1988 among IV drug users in Bangkok, and the other involving subtype E in and around Chiang Mai. Max Essex and his group have reported recent data which suggest that HIV-1 subtype E may be capable of more efficient spread than subtype B during vaginal intercourse. Both subtypes were found to replicate in almost the same manner in cells of lymphoid origin. Subtype E, however, thrives in vitro among Langerhans cells from either vaginal mucosa or penile foreskin, while subtype B replicates only sluggishly at best. Infection of the Langerhans cells could not be blocked by soluble CD4, reflecting a differential preference of subtype E for another, as yet unidentified, receptor. Clade E could be considered the heterosexual AIDS virus. Essex's hypothesis is worthy of pursuit. The same experiments need to be conducted with other clades in the laboratory along with ongoing epidemiologic monitoring of the pandemic to potentially spot newly introduced clades capable of altering transmission patterns. It has also been suggested that mixed infection occurs and that HIV-1 recombinations are possible. Regardless of whether or not Essex's findings eventually prove true, however, the author stresses that HIV-1 of all clades can spread through all sexual routes; it is just a question of variable efficiency. Appropriate efforts and precautions to prevent the spread of HIV must continue.^ieng

Mapping a non-carious cervical lesion using stereoimagery and dental casts incorporating optical texture.

OBJECTIVES: Recent advances in digital photogrammetry have enabled a new approach to high resolution mapping of tooth surfaces. The aim of this study was to assess the accuracy and the precision of a new system using automatic digital stereo-photogrammetry combined with an experimental casting material and to measure tooth surface loss in a non-carious cervical lesion. METHODS: A test object and tooth replicas incorporating optical texture obtained at baseline, one and 2 years were imaged with a pre-calibrated stereocamera. The stereoimagery was then processed with digital photogrammetric software to automatically generate digital surface models. Test object models were analysed for accuracy and precision and tooth surface models were aligned with point cloud analysis software and tooth surface loss determined. RESULTS: Replicas were mapped to an accuracy of (6+/-13)microm. The sensitivity of change detection on tooth replicas was 40 microm with change ranging from 40 to 70 microm per annum in a discrete part of the lesion. CONCLUSIONS: In the case examined, the change detection data were of sufficient accuracy and resolution to draw meaningful conclusions about the spatial distribution and quantum of tooth hard tissue loss. The results of this investigation suggest that annual change detection studies will provide a clearer picture of the pattern of tooth surface loss and, in combination with other analytical techniques, a more detailed explanation of the natural history of these lesions.

AIDS prevention: issues and strategies.

Prospects for vaccines to prevent HIV infection and disease have dimmed appreciably in the past year, and drugs for chemoprophylaxis and/or chemical cure are both unlikely and grossly unrealistic as a means of global HIV control. However, the paucity of transmission routes and their susceptibility to strategies of blood screening and of education for behavior modification point in a clear direction for concerted effort. Where they have been applied, blood screening programs have resulted in a dramatic reduction in transfusion-associated infections, and efforts at enhancing donor- and unit-deferral strategies offer promise of further decrease in risk. There is much encouragement in recent reports of education for prevention. While there has been some unevenness in the extent to which successful risk reeducation has occurred, it is nonetheless dramatic compared with prior health educational efforts, and especially so given the exceptional sensitivity of the sexual and illicit drug using behaviors at issue. Finally, clearly articulated public education and particularly correction of misinformation, can contribute significantly to overall prevention efforts by easing fear and enhancing the climate in which persons at behavioral risk of HIV infection can receive and respond to targeted messages.

PIP: Modes of preventing the spread of AIDS that have been successful are reviewed. Marked reduction in rates of seroconversion have been recorded among homosexuals in San Francisco and Stockholm, despite high seroprevalence of HIV, due to cohesiveness of the community and intense, direct educational campaigns. Although condoms used with nonoxynol-9 spermicide reduce markedly the likelihood of HIV transmission, heterosexual spread of HIV has not been curtailed. Particularly difficult to reach groups are bisexual men, prostitutes using oral contraceptives, heterosexuals already infected with sexually transmitted diseases, especially chancroid, herpes and syphilis, and young people. In Sweden, needle exchange programs have contained AIDS spread abruptly. Paradoxical effects of fear of AIDS in the drug community have worsened the situation in the U.S. For example, fear that heroin causes AIDS has increased the use of cocaine, with its more demanding addiction, that ultimately spreads HIV more rapidly by sexual routes. Spread of HIV by blood products and to health care workers has become a very rare event recently in the U.S. There is hope that the health message is being articulated more effectively, easing fear and enhancing the response by individuals at risk.

Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

BACKGROUND: Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. OBJECTIVE: Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. METHOD: The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). RESULTS: Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of vaccine safety, immunogenicity, and efficacy; postlicensure measurements of the public health impact of the vaccine and a track record of the vaccine's safety and acceptance with large-scale use; and the critical need for international collaborations to evaluate vaccines against diseases of global importance that are rare in the United States (eg, typhoid fever). It was clear that the critical step-up from bench scale to pilot lots and then to large-scale production, which depends on a small group of highly trained individuals, is often a particularly vulnerable point in the development process. CONCLUSIONS: One fundamental lesson learned is that within the varied and comprehensive US vaccine development infrastructure, multiple and rather distinct paths can be followed to reach vaccine licensure. The National Vaccine Advisory Committee review process should be conducted periodically in the future to ascertain that the US vaccine development network, which has been enormously productive heretofore and has played a leadership role globally, is adapting appropriately to ensure that new, safe, and efficacious vaccines become available in a timely manner.

The clinical use of verapamil.

Verapamil was the first of a class of agents known as calcium entry blockers to be released for clinical use in the United States. Although only recently approved by the Food and Drug Administration (August 1981), verapamil has been used clinically in countries other than the United States for more than 15 years and has been extensively studied experimentally. Because it is now available, it is necessary for physicians to have a working understanding of its pharmacologic effects and clinical applications. Accordingly, we are reviewing reported experience with verapamil and results of its use at the Mayo Clinic.

The nature of public health after reform.

Many of the pressures now building to reform the American health care system can be traced to an unfortunate fragmentation of the health professions, notably between medicine and public health. Medicine has advanced strikingly in its curative potential in recent decades, but for that very reason has fallen prey to hubris, as technology has outpaced overall strategies of care. Public health offers counterbalance to this effect in that it stresses a population-based perspective on medical care and underscores the importance of prevention in any rational, comprehensive system devoted to the health of the public. Critical elements that must be factored into any major restructuring of the present costly health care arrangements include provision for universal access, enhancement of preventive and primary care capabilities, and education of the public about their health status and its maintenance in such ways that they can become informed collaborators in their overall care. Enhanced appreciation of behavioral cofactors in the etiology of many diseases will play an important role in that education of the public, but it must be achieved in ways that are nonjudgmental lest it be counterproductive to the overall goals of prevention and compassionate care.

Communication and the health of the public.

In a lecture delivered in July 1999 at an international meeting on Communication in Medicine, the author underscored the increasing importance of educating to ensure effective communication between health care providers and their patients. Among the factors cited were the decreasing amount of time available, the escalating complexity of medical information and treatment regimens, and diversity of populations. Key elements in meeting these challenges include an awareness of the importance of patient dignity in health care encounters and an improved ability to listen to patients and their concerns.

Viral vaccines under development: a third generation.

In summary then, my purpose has been two-fold: on the one hand, I have tried to highlight the kinds of basic science advances in both cellular and virologic research that can (and should) be focussed both on vaccines under development and, retrospectively, on those whose origins were strictly empiric. On the other hand, I have attempted a partial survey of some of the prominent members of a potential new generation of vaccines to point out areas where these advances can and should contribute either to progress or to a sense of caution about the further reliance on pure empiricism. It is clear that we are not finished with new viral vaccines. It is equally clear that narrowing the persistent gap between basic science and its application to public health needs will require much energy and attention as vaccine development progresses.

AIDS: challenges to our health care systems.

The presentation excerpted here was given at the Cleveland Clinic's Second Annual Update on the Acquired Immunodeficiency Syndrome in May 1989. At that time, the numbers herein were current. Since then, the number of reported cases of AIDS in the United States has surpassed 120,000, and includes more than 2,000 children; the number of American deaths from AIDS has exceeded those occurring as a result of the Vietnam war; and AZT has been recommended for use in both mildly asymptomatic and asymptomatic HIV-infected persons.

Schooling affects the feeding success of Australian salmon (Arripis trutta) when preying on mysid swarms (Paramesopodopsis rufa).

When feeding on mysid swarms (Paramesopodopsis rufa), juvenile Australian salmon (Arripis trutta) had higher rates of successful attacks when foraging in a group of six fish (55% total advances) than when foraging alone (39% total advances). Six schooling fish had lower approach rates than solitary fish (25% and 37% of total advances, respectively). This result indicated that schooling fish were better at reducing the confusion effect of swarming prey, resulting in more efficient feeding. In larger areas, schools achieved higher rates of successful attacks (19 prey/fish in the large tank, compared with 11 prey/fish in the smaller tank). There was no influence on the feeding success of individual fish when changes were made to the number of prey presented to each fish. Nearest neighbour distances were smallest in the absence of prey, and increased with the introduction of prey and again in an attack sequence. Six fish schooled more cohesively than three fish, indicating increased benefits of schooling in larger groups that contribute to advanced vigilance and foraging techniques.

The 1986 Armstrong lecture. AIDS and the world of the 1990s: here to stay.

The 1986 Armstrong Lecture--21st in a series of annual lectures named for the late Col. Harry Armstrong, USAF, MC--was delivered April 24 during the Aerospace Medical Association's Annual Scientific Meeting in Nashville, TN, April 20-24. The history of the onset of the AIDS epidemic was reviewed along with pertinent aspects of the underlying biomedical science which have enabled precise recommendations concerning its control. The prospects of drug treatment or vaccine interventions are remote and, therefore, health education and prevention are the chief weapons available to combat the epidemic for years to come. Numerous impediments to those effective strategies were discussed.

Whatever happened to AIDS?

The HIV/AIDS epidemic has caught millions of people in its path worldwide during the first 13 years since it surfaced; half a million Americans have been diagnosed with AIDS, and hundreds of thousands more are in earlier stages of HIV disease. Yet the sense of urgency one would expect should attend such awful numbers is strangely absent, prompting the bitter query "Whatever happened to AIDS?" This paper discusses the present status of progress with respect to the epidemic and explores some of the reasons that might partially explain both the inherent difficulties of research and the inappropriate public sense of quiescence. It then puts forward some suggested areas of research endeavor and/or public policy that could re-energize the flagging public response to this massive health disaster.

The changing definition of AIDS. What's in a name?

Earlier this year, the U.S. Centers for Disease Control proposed altering its definition of acquired immune deficiency syndrome (AIDS) to include those with 200 or fewer CD4 cells. That proposal, scheduled to take effect April 1, 1992, would dramatically increase the number of Americans officially considered as having AIDS. The previous definition relied on a list of specific opportunistic infections, tumors, or itemized manifestations of HIV disease. While eventually the definition of AIDS should be replaced with a definition of HIV disease--which would include all those who are infected with the human immunodeficiency virus--the CDC proposal would be a useful stopgap measure. It would provide access to needed treatments such as AZT to thousands of men and women who now are excluded from reimbursement systems including private health insurance and Medicaid.

The AIDS epidemic: multidisciplinary trouble.

PIP: The author presents an overview of the diversity of issues involved in the acquired immunodeficiency syndrome (AIDS) epidemic. The 1st round of AIDS cases has severely strained both human and societal resources in the US. To appreciate the economics of the problem, its is useful to think of evey case of AIDS as costing the same as a heart transplant. The anticipated doubling in numbers of patients diagnosed in the next year will have far more than twice the impact of the 1st wave on the health care industry, especially in the cities where the majority of cases are concentrated. Progress in the area of biomedical science has been spectacular in terms of the speed with which the virus was isolated and blodd screening techniques were developed. Problematic, however, has been the antigenic variation of the AIDS virus. It is possible that monoclonal technology will help to identify on parts of antigenic molecules that pervade the immune response to many variants and might be effective in neutralization. On the scientific level, there is cause of concern regarding a vaccin for AIDS, since the cellular receptor that the virus requires to initiate infection is the receptor for the T-cell antigen. On the practical level, the logistics of testing such a vaccine are complex. The largest hope for intervention may rest in understanding the role of various co-factors in determining whether a person remains asymptomatic or develops the disease. At present, however, preventive medicine appears to be the solution.^ieng

AIDS and the politics of compassion.

The AIDS epidemic presents the health care community with an exceptionally complex set of challenges, says June E. Osborn, M.D., the chairwoman of the National Commission on AIDS. Care-giver burnout, clinical and cost issues, and above all the challenge the disease poses to health care provider--and societal--compassion, make this epidemic unusually difficult to tackle, she writes.