Analysis of host response modifier ORFs of ectromelia virus, the causative agent of mousepox.

From the right-hand end of the ectromelia virus (strain Moscow) genome, 32318 bps have been sequenced, and characterized to include a total of 18 open reading frames (ORFs) and six regions which apparently no longer code for functional proteins. At least six of the ORFs appear to be involved in blocking the inflammatory/immune host response to infection, and therefore probably contribute significantly to the virulence of this virus in its natural host, the mouse. One of these genes encoded an isolog of the poxvirus chemokine binding protein, and was shown to be the most abundant protein secreted from ectromelia virus infected cells. Two regions were found to have significant similarity to poxvirus genes encoding tumor necrosis factor (TNF) binding proteins. Both are distinct from cytokine response modifier (crm)B and crmC but only one is predicted to encode a functional TNF binding protein. A novel similarity between the C-terminal domain of poxvirus TNF binding proteins and several other poxvirus proteins is also presented. The results are discussed in the context of ectromelia virus pathogenesis of mice.

Subversion of cytokine networks by viruses.

Viruses and the immune system have been competitors throughout their co-evolution. It is therefore not surprising that the viruses in circulation today possess a variety of strategies to counteract those aspects of the immune system that are involved in virus clearance. Examination of these virus encoded functions provides an important view of immune function and an appreciation of the complexity of the virus-host interaction. It is clear that viruses, seeking to subvert the immune system, have become adept in blocking the communication channels of the immune system. There are numerous examples of viral proteins that target the cytokine networks, disrupting the processes by which the delicately balanced immune system is regulated. This review focuses on the gene products of poxviruses, adenoviruses and herpesviruses that function primarily as immune-modulators.

Trial of labor or repeated cesarean section. The woman's choice.

OBJECTIVE: To develop recommendations for the preferred delivery method for a pregnant woman who underwent a previous low transverse cesarean section and who has no contraindications to labor. DATA SOURCES: MEDLINE searches and the references from retrieved articles yielded 759 citations. Search terms included trial of labor (TOL), trial of scar, vaginal birth after cesarean section (VBAC), and uterine rupture. STUDY SELECTION: Articles with primary outcomes data contrasting TOL and elective repeat cesarean section (ERCS) were analyzed. Studies from developing countries or before 1980 were excluded. DATA EXTRACTION: Data from 292 articles were extracted independently by at least 2 team members using a structured form. DATA SYNTHESIS: Outcome data were combined using commercially available software and are presented as absolute differences per 10,000, with 95% Bayesian confidence intervals. Maternal outcomes showed that TOL increased the risk for uterine rupture (23.9 [0.24%]); ERCS increased the risk for infection (522 [5.22%]) and bleeding (58.6 [0.59%]). Infant outcomes differed only for 5-minute Apgar scores of less than 7, which were more likely for infants whose mothers underwent TOL (85 [0.85%]). Other outcomes (eg, disability), patient preferences, and cost data did not lend themselves to meta-analysis and were examined separately. While two thirds of women desired TOL, one third preferred ERCS. Costs were 1.7 to 2.4 times greater for ERCS. CONCLUSIONS: A woman should be given information on both delivery methods and encouraged to undergo TOL, but her preference for ERCS should be respected.

A novel poxvirus gene and its human homolog are similar to an E. coli lysophospholipase.

A novel poxvirus gene has been characterized within the genome of ectromelia virus. It has significant similarity to a family of lysophospholipases suggesting that it may function in the degradation of lysophospholipids. Since these molecules are active in the stimulation of inflammation, we hypothesize that this gene may play a role in virus virulence. This gene is expressed early in the ectromelia virus replication cycle, before DNA replication. We have also characterized a human cDNA that encodes a protein which is 49.5% identical to the ectromelia virus protein. By its presence in multiple cDNA libraries, this human gene is known to be expressed in a variety of body tissues and is likely to function in the normal regulation of lysophospholipid levels. This family of proteins have conserved blocks of amino acids that are indicative of a serine-aspartic acid-histidine catalytic triad, similar to those used by true lipases and a number of esterases.

Occupational medicine content of Oregon family physician practices.

BACKGROUND: Little has been published in the medical literature about the occupational medicine content of family practice. Little is known about the educational interventions needed for family physicians to improve the care they provide to patients suffering from occupational-related disorders. METHODS: A questionnaire based on a curriculum in occupational medicine proposed by a subcommittee of the Education Committee of the American Academy of Family Physicians for the guidance of family practice residency directors was sent to a random sample of 100 Oregon family physicians from a total of approximately 570 active practicing members of the Oregon Academy of Family Physicians. Ninety-three completed questionnaires were returned. RESULTS: Occupational medicine constituted a significant part (14 percent) of the practices of Oregon family physicians. The respondents rated management of chronic disability, disability determination, repetitive trauma disorders, and legal issues as the most important occupational medicine problems in their practices. These issues were also those about which they thought they needed additional training. CONCLUSIONS: Education in occupational medicine for family physicians must be better tailored to fit their needs and their priorities. The responses to this survey of practicing family physicians in Oregon suggest that more training in the areas of chronic disability management, disability determination, the management of repetitive trauma disorders, and legal aspects of occupational disorders is needed.

An overview of clinical policies with implications for clinical practice, medical education, and research.

Clinical policies, also known as practice parameters or practice guidelines, are gaining notoriety out of a desire to control escalating medical costs, lessen wide practice variations, and improve quality of care. The clinical policies are supposed to influence medical decision making by summarizing scientific data about a clinical problem in a format that is easily understood by patient and physician alike. Developing an evidence-based policy involves: a clearly defined clinical problem, a comprehensive literature review, a summary table of the data (known as an evidence table), a presentation of this data as outcome possibilities from alternative decisions (in the form of a balance sheet), and creation of clinical recommendations that incorporate both financial costs and patient preferences. Well-developed policies can be used by family physicians as guides in areas of clinical uncertainty and by medical educators as up-to-date literature syntheses for teaching critical appraisal and for outlining approaches to common problems. Explicit policy formulation also highlights the shortcomings of existing literature and can suggest more appropriate future research. The future of the clinical policy movement rests on its ability to reduce costs of care and improve patient outcomes. Explicit clinical policy formulation incurs significant development and implementation costs and the evidence on which many policies are based is lacking. Nevertheless, clinical policies in some form are likely to play an increasing role in medical care.

Retraining the subspecialist for a primary care career: four possible pathways.

The degree to which a reformed U.S. health care system relies on an adequate supply of primary care physicians will determine the urgency of change in the composition of the medical workforce. In many areas of the United States, the demand for primary care physicians, particularly in managed care settings, far exceeds the supply. In contrast, reports of reduced practice opportunities for medical and surgical subspecialists in the same settings are increasing. As opportunities for and incomes of primary care physicians are enhanced, some medical subspecialists may seek retraining in primary care. This article provides a context for understanding the development of physician retraining programs, examines precedents for retraining physicians, describes four possible pathways through which medical subspecialists might acquire primary care training, and emphasizes the importance of defining the scope of practice and necessary skills for providing primary care. Obstacles to retraining appear to be economic (Who will pay? Is the cost worth the benefit?) and jurisdictional (Who will define core competencies? Who will credential programs and trainees?). The current absence of demand for such retraining programs suggests either that marketplace-induced changes will not take place or that the notion of a primary care provider shortage and an oversupply of medical subspecialists is overstated. The inclusion of physician retraining programs in proposed health reform legislation suggests that policymakers are convinced that such programs offer one viable solution to the nation's medical workforce needs.

Obstetric analgesia and anesthesia.

A number of analgesic and anesthetic options are available for patients during the intrapartum period. Appropriate attention in the prenatal period to patient education regarding these options is imperative. If pharmacologic anesthesia is required, risks and benefits both to the mother and neonate must be considered. If cesarean section is necessary, consideration of regional or general anesthesia is appropriate. Women and their support people should be involved in the discussion of anesthesia and analgesic options. This discussion should begin during the prenatal period to ensure that the woman has an opportunity to make an informed choice. When the woman presents in labor, the anesthetic plan may again need to be revised. Continued patient-doctor communication throughout labor is essential with the woman's preferences, tempered by sound medical judgment, guiding optimal pain control.