We review the clinical phenotype, pathological changes, and results of cytogenetic and molecular genetic studies in 90 probands with lissencephaly (smooth brain) with emphasis on patients with the classical form (type I). We also describe the recent discovery of the lissencephaly gene (LIS1), deletions of which have been implicated as the cause of this disorder in many patients.

To test the hypothesis that female prevalence is greater than expected among reported cases of torsades de pointes associated with cardiovascular drugs that prolong cardiac repolarization.

This document summarizes recommendations from a state-of-the-art conference convened to evaluate the role of nucleoside analogue reverse transcriptase inhibitors in the treatment of human immunodeficiency virus (HIV) infection. Data from controlled clinical trials of zidovudine, didanosine, and zalcitabine were reviewed by an expert panel, which then formulated guidelines to assist clinicians and HIV-infected patients in the use of these agents. Recommendations were framed in the context of clinical scenarios for patients with asymptomatic HIV infection who have not had prior antiretroviral therapy; those with signs and symptoms of HIV-related disease who have not received prior therapy; clinically stable patients who are tolerating initial zidovudine therapy; patients experiencing clinical progression while on zidovudine therapy; and those who are intolerant of antiretroviral therapy. The panel concluded that physicians need to integrate up-to-date scientific knowledge with other relevant needs to improve the care of HIV-infected patients.

To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease.

To review the rationale for and progress toward the goal of isolating and analyzing fetal cells circulating in maternal blood, and to explore the feasibility of this method in providing noninvasive prenatal cytogenetic diagnosis.

In privacy terms, genetic information is like medical information. But the information contained in the DNA molecule itself is more sensitive because it contains an individual's probabilistic "future diary," is written in a code that has only partially been broken, and contains information about an individual's parents, siblings, and children. Current rules for protecting the privacy of medical information cannot protect either genetic information or identifiable DNA samples stored in DNA databanks. A review of the legal and public policy rationales for protecting genetic privacy suggests that specific enforceable privacy rules for DNA databanks are needed. Four preliminary rules are proposed to govern the creation of DNA databanks, the collection of DNA samples for storage, limits on the use of information derived from the samples, and continuing obligations to those whose DNA samples are in the databanks.

The purpose of this investigation was to provide an empirical summary of the evidence regarding the association between beta-agonist use and death from asthma. This effort integrated the results of case-control studies that examined the use of beta-agonists among asthmatic patients who died and the use of beta-agonists among asthmatic patients who did not die. The possible moderating effects of patient sample age and mode of delivery (oral, metered-dose inhaler, and nebulizer) were also examined.

This review discusses the latest developments in selected clinical features and catheter-based therapy of mitral stenosis.

While it is statistically true that clinical cancer occasionally occurs following development of immune incompetency, the fact remains that the most common forms of cancer (ie, breast, lung, and colon) are not experienced by immunosuppressed individuals. Since there is strong scientific evidence that the unprovoked, normal immune system does not recognize and destroy cancer cells that arise spontaneously, the concept of an immune surveillance system that continuously protects clinically normal humans from cancer remains an appealing but unproven hypothesis. Burton's theory of immune surveillance against cancer appears to be nothing more than a rehash of the hypotheses of many other investigators, embellished with his postulate that four specific anticancer protein factors exist and function in the normal human immune system. The IAT he invented as a treatment for cancer is based on his presumption that he has proven the existence of these factors. But neither his declarations nor those of his proponents offer any objective evidence to support such a conclusion. They have not proven that the IAT components exist or can be extracted from blood without the loss of biologic activity. The tests that are described cannot quantitatively measure the specific IAT proteins and there is no evidence that the IAT fractions possess any immunologic activity. Thus, Burton's tumor antibody has never been shown to be a tumor specific immunoglobulin that can interact with tumor antigens and activate complement. His tumor complement fraction has no complement activity (written communication, G.J. Gray, PhD, June 21, 1984), his blocking protein has not been shown to block anything, his deblocking protein has not been shown to deblock anything, and his human tumor cells have never been shown to lyse following the interaction of tumor antibody and tumor complement. Finally, since there is no information on the quality control procedures being used in the manufacture of the IAT materials, there is the possibility that they may be unsterile and, therefore, hazardous for use in humans. Patients who are considering IAT as treatment for cancer should be made aware of these facts when attempting to reach an informed decision regarding its safety and potential efficacy. While this paper was being reviewed for publication, an IAT proponent newsletter called The Cancer Chronicles published the news that Lawrence Burton died of a heart attack in March 1993. The editor of this newsletter, Ralph Moss, PhD, stated that Burton's clinic would remain open under the direction of its medical director, R. John Clement, MD, and would continue to offer IAT to cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

To investigate the effects of prophylactic therapy with antiarrhythmic agents on mortality in patients with myocardial infarction.

Health care reform proposals that seek to increase access for almost 40 million uninsured Americans will require an expansion of primary care. Simply expanding available primary care services is likely to be prohibitively expensive. Developing a rational and efficient strategy for the provision of primary care to all Americans will require understanding of the relationships among primary care and access, costs, and quality--relationships that are often obscured by the complexity of the US health care system. Those relationships are examined to identify some key areas of research needed to inform policy development and improve primary care services. Despite significant gaps in our knowledge, the evidence strongly suggests that restructuring and strengthening the role of primary care practitioners in the health care system will facilitate access to affordable, high-quality health care for all Americans.

To determine the efficacy of antibiotics for prophylaxis of recurrent otitis media and treatment of otitis media with effusion (OME) in children.

To review new insights in the pathogenetic mechanisms involved in the development of disseminated intravascular coagulation (DIC) in septic patients, in order to develop new directions for therapeutic intervention.

To provide an overview of the published scientific information on the safety and efficacy of very low-calorie diets (VLCDs) and to provide rational recommendations for their use.