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.

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.

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.

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.

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.

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.

Assessing obstetric risk. A review of obstetric risk-scoring systems.

The primary purpose of formal risk assessment in obstetrics is the prevention and consequent reduction of perinatal morbidity and mortality through early identification and intervention. Obstetric risk scoring quantifies identified risk factors according to their relative contribution to adverse perinatal outcomes and aggregates individual factor scores. A review of existing scoring methods reveals consistently low positive predictive values and more accurate prediction when the assessment occurs closer to the time of actual delivery. While numerous scoring systems exist in the literature, few are convenient in practice, and none appear to assess effectively the dynamic character of pregnancy.

Continuity of care and family medicine: definition, determinants, and relationship to outcome.

Continuity of care is central to the philosophy and teaching of family medicine. Studies of continuity have yielded conflicting results with regard to outcomes. Reasons for this include a failure to agree upon a theoretical definition of continuity as well as failure to account for a number of influential determinants of the continuity process. It is suggested that continuity is an attitude based upon prior knowledge of and for each participant in the medical encounter. This attitude is made operational in a process consisting of five continuity dimensions: chronological, geographical, interdisciplinary, interpersonal, and informational. A working model of analysis is proposed, and the results of various studies are critically assessed. Future research in the area of continuity of care must provide reliable measures of the different continuity dimensions followed by well-controlled trials assessing the impact of these dimensions on the satisfaction, comfort, and health status of patients.

Development of a decision aid for women choosing a method of birth control.

The choice of a contraceptive method is complex and difficult. This study identifies issues for concern for women in selecting a birth control method, examines the accuracy of a self-administered questionnaire based upon these outcomes in predicting actual use, and in a preliminary fashion evaluates the usefulness of such an instrument as a decision aid. A questionnaire was designed to assess women's perceptions of the likelihood of each issue of concern for four birth control methods--oral contraceptives, intrauterine device (IUD), diaphragm, and foam or condoms--as well as the relative value of each issue. It was then tested among a convenience sample of 106 women. A weighted score was constructed by combining likelihood and value estimates for each contraceptive method. The method with the highest score was compared with actual contraceptive use and the intention to use such methods in the future. Positive predictive values were highest for pill use (83 percent) and lowest for IUD use (40 percent). While 65 percent of the sample were satisfied with their current method, 60 percent also found the questionnaire helpful. This attitude was most prevalent among younger, unmarried women. A decision aid for contraceptive decision making appears to be reasonably predictive of actual contraceptive use and helpful in thinking about the choice of a birth control method.

Characteristics of patients seeking family-oriented care.

A self-administered questionnaire was distributed to 570 adult patients at three family practice centers to identify the demographic characteristics of those whose entire household was cared for at the same facility. Two of the three centers were free-standing community-based ambulatory care sites, and the third was situated adjacent to a community hospital. Although 95 percent of respondents considered the family practice center their usual source of care, only 54 percent sought care for every household member. Among this latter group, marital status (divorced patients) and race (white) were shown to be a significant determinants of health care utilization by families. The implications of these findings are discussed with recommendations for further research to better define the characteristics and expectations of the population served by family physicians.

Urinary tract infections among diaphragm users.

An association between diaphragm use and the subsequent development of lower urinary tract infections (urethritis, cystitis, etc) has been suggested by two recent studies in the literature. The present study uses a case-control approach to determine the relative risk of developing urinary tract infections among diaphragm users aged 15 to 45 years during a 15-month period. Patient charts at a family practice clinic were reviewed for evidence of documented urinary tract infections and method of contraception (n = 98). As a control, all women aged 15 to 45 years seen for upper respiratory tract infection during the same period were reviewed (n = 126). Depending upon how a urinary tract infection was defined (urinalysis positive, culture positive, both positive), the relative odds for the development of subsequent urinary tract infections range from 0.88 to 1.10. When all barrier methods were considered together, this odds ratio ranged from 0.88 to 1.21. Documentation of symptoms and laboratory confirmation of urinary tract infection were lacking in many charts reviewed. Despite these limitations, the study findings call into question the assumption that diaphragm use may lead to the subsequent development of urinary tract infection.

PIP: An association between diaphrragm use and the subsequent development of lower urinary tract infections (urethritis, cystitis, etc.) has been suggested by 2 recent studies in the literature. The present study uses a case control approach to determine the relative risk of developing urinary tract infections among diaphragm users ages 15-45 during a 15 month period. Patient charts at a family practice clinic were reviewed for evidence of documented urinary tract infections and method of contraception (n=98)e. As a control, all women ages 15-45 seen for upper respiratory tract infection during the same period were reviewed (n=126). Depending on how a urinary tract infection was defined (urinalysis positive, culture positive, both positive), the relative odds for the development of subsequent urinary tract infections range from 0.88-1.10. When all barrier methods were considered together, this odds ratio ranged from 0.88-1.21. Documentation of symptoms and laboratory confirmation of urinary tract infection were lacking in many of the charts reviewed. Despite these limitations, the study findings call into question the assumption that diaphragm use may lead to the subsequent development of urinary tract infection.

The relationship between assessed obstetric risk and maternal-perinatal outcome.

The relationship between antepartum risk assessment and subsequent maternal and perinatal outcome was examined in a retrospective study of 430 randomly selected deliveries at the Oregon Health Sciences University during the 1986 calendar year. Antepartum risk scores at the initial prenatal visit and at 37 weeks' gestation were positively correlated with each other. Antepartum risk scores were correlated with maternal length of stay and maternal hospital charges, but not with gestational age, birth weight, or Apgar scores. Increased intrapartum risk scores were strongly correlated with increasing length of stay for mother and baby, lower birth weight, and lower estimated gestational age at birth. The ability of the risk-scoring system to predict selected adverse outcomes was then assessed using a high-risk cutoff score of 5 or greater. Sensitivity and positive predictive value were found to be quite low while specificity and negative predictive value were reasonably high. The results suggest that the risk-scoring system used at this institution is effective in identifying low obstetrical risk and that prenatal care reduces the probability of poor neonatal outcome among infants of women at high obstetrical risk identified through antepartum multivariate assessment. Two antepartum risk assessments, each measuring different factors, may be redundant. Not yet known are which specific factors by their identification result in more effective prenatal care.