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NIH conference. HIV vaccine development: a progress report.

The development of a safe, effective preventive vaccine for human immunodeficiency virus (HIV) infection remains an area of vigorous research. Several highly innovative vaccine candidates are being developed, and more than 13 vaccine candidates have been tested in human phase I or II trials. All have produced antibody and several have produced modest neutralizing titers, but to date no reproducible evidence has suggested prolonged, high-titer neutralization across a diversity of HIV strains. Furthermore, only the live recombinant vector approaches have produced some evidence of cytotoxic T-cell responses. The principal obstacle to progress is the lack of definitive information on what constitutes a protective immune response. There is no animal model for HIV-induced disease. Hence, the identification of the correlates of immunity and more useful animal models is among the highest priorities for HIV vaccine research. Large-scale efficacy trials raise daunting scientific, ethical, and resource issues. Nonetheless, preparation in such trials is underway in order to be in a position to evaluate the most promising vaccine candidate.

AIDS Vaccines↗

NIH Consensus Conference. Acupuncture.

OBJECTIVE: To provide clinicians, patients, and the general public with a responsible assessment of the use and effectiveness of acupuncture to treat a variety of conditions. PARTICIPANTS: A nonfederal, nonadvocate, 12-member panel representing the fields of acupuncture, pain, psychology, psychiatry, physical medicine and rehabilitation, drug abuse, family practice, internal medicine, health policy, epidemiology, statistics, physiology, biophysics, and the representatives of the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1200. Presentations and discussions were divided into 3 phases over 2 1/2 days: (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that were part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. The conference was organized and supported by the Office of Alternative Medicine and the Office of Medical Applications of Research, National Institutes of Health, Bethesda, Md. EVIDENCE: The literature, produced from January 1970 to October 1997, was searched through MEDLINE, Allied and Alternative Medicine, EMBASE, and MANTIS, as well as through a hand search of 9 journals that were not indexed by the National Library of Medicine. An extensive bibliography of 2302 references was provided to the panel and the conference audience. Expert speakers prepared abstracts of their own conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in the open forum and scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions within a few weeks of the conference. The statement is available at http://consensus.nih.gov. CONCLUSIONS: Acupuncture as a therapeutic intervention is widely practiced in the United States. Although there have been many studies of its potential usefulness, many of these studies provide equivocal results because of design, sample size, and other factors. The issue is further complicated by inherent difficulties in the use of appropriate controls, such as placebos and sham acupuncture groups. However, promising results have emerged, for example, showing efficacy of acupuncture in adult postoperative and chemotherapy nausea and vomiting and in postoperative dental pain. There are other situations, such as addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, low back pain, carpal tunnel syndrome, and asthma, in which acupuncture may be useful as an adjunct treatment or an acceptable alternative or be included in a comprehensive management program. Further research is likely to uncover additional areas where acupuncture interventions will be useful.

Acupuncture Therapy↗

Estrogen with and without progestin: benefits and risks of short-term use.

Estrogen therapy has been well established as an effective treatment for relief of vasomotor symptoms. In light of recent evidence from large randomized trials showing serious risks associated with use of estrogen treatment, current recommendations for hormone therapy emphasize using the lowest effective dose for the shortest possible time. The purpose of this review is to examine what has been learned from the Women's Health Initiative (WHI) Hormone Trials and other studies about the short-term risks and benefits of estrogen use. A second purpose is to examine whether short-term risks differ for women most likely to use hormone treatment, including individuals with vasomotor symptoms; women in their 50s; and women, with and without intact ovaries, who have had a hysterectomy. During the first 1 to 2 years of use of conjugated equine estrogens alone (E-alone) or combined with medroxyprogesterone acetate (E + P), women experience an elevated risk of coronary heart disease, stroke, and deep vein thrombosis or pulmonary embolism. The magnitude of risk is greater for E + P than for E-alone. Fracture risk is not reduced with 1 to 2 years of use, but a fracture benefit is seen within 5 years of use. Increased risk of breast cancer does not appear until after 4 to 5 years of E + P use and was not increased with E-alone use after < or =7 years of treatment. This pattern of risks and benefits is generally similar for women with vasomotor symptoms, women in their 50s, and women, with and without > or =1 intact ovary, who have had a hysterectomy.

Estrogen Replacement Therapy↗

Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report.

This consensus document provides an update for pathologists and clinicians about the interpretation of biopsy results and use of this information in the management of hematopoietic cell transplantation patients. Optimal sampling and tissue preparation are discussed. Minimal criteria for the diagnosis of graft-versus-host disease (GVHD) are proposed, together with specific requirements for the diagnosis of chronic GVHD. Four final diagnostic categories (no GVHD, possible GVHD, consistent with GVHD, and definite GVHD) reflect the integration of histopathology with clinical, laboratory, and radiographic information. Finally, the Working Group developed a set of worksheets to facilitate communication of clinical information to the interpreting pathologist and to aid in clinicopathologic correlation studies. Forms are available at . The recommendations of the Working Group represent a consensus opinion supplemented by evaluation of available peer-reviewed literature. Consensus recommendations and suggested data-capture forms should be validated in prospective clinicopathologic studies.

Biopsy↗

Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker Working Group Report.

Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials.

Biomarkers↗

Antioxidants in cystic fibrosis. Conclusions from the CF antioxidant workshop, Bethesda, Maryland, November 11-12, 2003.

Although great strides are being made in the care of individuals with cystic fibrosis (CF), this condition remains the most common fatal hereditary disease in North America. Numerous links exist between progression of CF lung disease and oxidative stress. The defect in CF is the loss of function of the transmembrane conductance regulator (CFTR) protein; recent evidence that CFTR expression and function are modulated by oxidative stress suggests that the loss may result in a poor adaptive response to oxidants. Pancreatic insufficiency in CF also increases susceptibility to deficiencies in lipophilic antioxidants. Finally the airway infection and inflammatory processes in the CF lung are potential sources of oxidants that can affect normal airway physiology and contribute to the mechanisms causing characteristic changes associated with bronchiectasis and loss of lung function. These multiple abnormalities in the oxidant/antioxidant balance raise several possibilities for therapeutic interventions that must be carefully assessed.

Animals↗