Acute phase toxoplasma abortions in sheep

Within 13 days of the experimental infection of 15 oestrus-synchronised ewes with 2000 sporulated oocysts of Toxoplasma gondii at 80 to 90 days of gestation 11 had aborted. The infection induced pyrexia and specific antibody in all the ewes. One ewe resorbed its fetus, 11 ewes aborted and three delivered, at full term, live congenitally infected lambs whose pre-colostral serum was antibody-positive. Tissues from the aborted fetuses and placentae from the live lambs were examined for toxoplasma infection by polymerase chain reaction (PCR) amplification of the B1 gene and by mouse inoculation. The live lambs were all shown to be infected by both methods, but there was no evidence of infection in any of the tissues from the acute phase abortions, suggesting that these fatalities occurred before the placenta or the fetus had been invaded by T gondii. Such toxoplasma-induced, acute-phase abortions are likely to be impossible to diagnose from fetal tissues. These results have implications not only for the diagnosis of naturally occurring ovine abortions but also for the understanding of the pathogenesis of toxoplasma-induced abortion.     

A bibliography of mental patients' autobiographies: an update and classification system

OBJECTIVE: This article brings to the present earlier bibliographies of books written by former mental patients. These books provide an inside view of mental disorder that can be useful in teaching, public education, theory, and research, and they have played a catalyzing role in mental health reform and in theory development. METHOD: The authors list seven anthologies and 48 autobiographies of former patients published since 1980 and introduce a classification system intended to increase the research value of this important archive. RESULTS: Recent books of this genre show more individuals with a mood disorder and more therapists and more women as authors. CONCLUSIONS: The research potential of these books suggests the value of an electronic database for classifying and retrieving the information they contain.     

Pretransplant renal dysfunction predicts poorer outcome in liver transplantation

BACKGROUND: Numerous clinicians and researchers have expressed concern about the necessity and potential adverse consequences of many cesarean births in the United States. The purpose of this study was to explore college students' attitudes and beliefs about cesarean section. METHODS: One hundred two college students (66% women) completed a 20-item questionnaire that asked if they viewed cesarean delivery as a potentially negative experience, as a normal or acceptable method of childbirth, and as medically necessary, and asked about their beliefs concerning risk and prevention of cesarean birth. RESULTS: The number of "undecided" responses in the study was striking (7.8% to 69.6% across the 20 items). In general, women and men responded similarly, although women were significantly more likely than men to say they would be profoundly disappointed if their babies had to be delivered by cesarean section. Despite expressing cynicism about the cesarean birth rate (40% agreed that many unnecessary cesarean births occurred) and not viewing the procedure as a normal way of giving birth (47%), most respondents (over 70%) disagreed that giving birth by cesarean would be a negative experience or would make a woman feel like a failure. CONCLUSION: A high level of uncertainty exists about certain aspects of cesarean birth among young women and men, highlighting the need for information for prospective parents. Most college students did not view the cesarean birth experience as either potentially negative or normal. Future research should explore coverage of cesarean birth in childbirth education classes and the roles physicians, nurses, and midwives play in preparing expectant parents for the possibility of cesarean delivery.     

The role of managed care: the national and Tennessee experiences

The United States is the only developed country with no national health care policy. What exists is a national health insurance system. The problem with this system arises when paying for health care for the poor, who often require the most expensive type of care for acute or episodic ailments. Managed care, though not a panacea, has the potential of providing the organization to effectively control costs and change the existing health care paradigm from one of fee-for-service inpatient care to one of ambulatory care, home-based care, and physician office-based procedures. An example of a state-based initiative that has cut medical costs is Tennessee's TennCare. Under TennCare, approximately 1.2 million Tennesseans are covered, nearly 400,000 of whom were previously uninsured. Such programs, both state and national, must now look to including prevention and wellness care to effectively change the underlying epidemiology of illness among the poor.     

Fas-induced apoptosis of T cells occurs independently of ceramide generation

The Fas receptor is one of a number of important physiological inducers of programmed cell death (apoptosis). Current models for regulation of this process involve rapid conversion of sphingomyelin to ceramide by cellular sphingomyelinases. Induced changes in cellular levels of such sphingosine-based ceramides are normally extrapolated from measurements of sphingomyelinase activity or following their conversion to ceramide phosphate by treatment of cellular lipid extracts with bacterial diacylglycerol kinase (DAGK). To allow direct study of cellular sphingosine- and sphinganine-based ceramide levels, we developed a mass spectrometric technique capable of determining inducible changes in both overall ceramide levels and species distribution in cellular lipid preparations. Contrary to current models, we detected no changes in cellular ceramide levels up to 2 hr poststimulation of Jurkat T cells with an anti-Fas IgM, although this treatment did induce apoptosis. We also determined in the same system that, when utilizing the DAGK assay, increased phosphorylation of substrates that comigrated with ceramide standards was apparent but that this effect was due to an enhancement of DAGK activity rather than increases in levels of cellular ceramides as substrates per se. Thus, the first direct measurement of ceramides present in cells undergoing apoptosis indicates that, insofar as it can be measured, the induction of apoptosis does not involve the generation of sphingosine-based ceramides, contrary to many published accounts.     

Analysis of factors affecting U.S. emergency physician workforce projections. SAEM Workforce Task Force

OBJECTIVES: To use existing data sources to refine prior estimates of the U.S. emergency medicine (EM) workforce and to estimate effects of proposed changes in the U.S. health care system on the EM workforce. METHODS: Relevant data were extracted from the American College of Emergency Physicians (ACEP) 1995 Membership Activity Report, the American Medical Association (AMA) publication "1995/96 Physician Characteristics and Distribution in the U.S.," the American Hospital Association (AHA) 1994 hospital directory, a written survey of each state's medical licensing board and state medical society, and the American Board of Emergency Medicine (ABEM) annual activity report for 1995. These data were used to project workforce supply and demand estimates applicable to workforce models. RESULTS: None of the available information sources had complete data on the number and distribution of emergency physicians (EPs) currently practicing in the United States. Extrapolating the limited reliable statewide EP numbers to make nationwide projections reveals a shortage of EPs needed to fully staff the nation's existing EDs. At least 22 states had an average ratio of < 5 EPs per existing ED. Additional national projections incorporating a decreasing number of U.S. EDs indicate that the current annual number of EM residency graduates will not eliminate the deficit of EPs for at least several decades, given that projected numbers of retiring EPs annually will soon equal the total annual EM residency graduate production. CONCLUSIONS: Although the current data on EPs in practice in the United States are incomplete, the authors project a relative shortage of EPs. More accurate and complete information on the numbers and distribution of EPs in America is needed to improve workforce projections.     

SSU rDNA characterization of lymnaeid snails transmitting human fascioliasis in South and Central America

OBJECTIVE: To develop an acceptable model system to study calcium activation of human oocytes. DESIGN: Study of oocyte development and intracellular calcium [Ca]i dynamics of activated oocytes. SETTING: Research center affiliated with infertility service. MAIN OUTCOME MEASURE: Morphologic evidence of meiotic maturation and cell division under high-power Hoffman optics with an inverted microscope. Meiotic maturation was determined by the number of polar bodies or the presence of a pronucleus, and cell division was determined by evidence of a cleavage furrow or presence of blastomeres. To monitor the effect of calcium ionophore on [Ca]i levels, oocytes were incubated with fura-2 (2 microM) for 30 minutes and [Ca]i was determined by rationing the emission fluorescence (510-nm long-pass filter) during simultaneous excitation at 340 and 380 nm with a microspectrofluorimeter. RESULT(S): All oocytes loaded with fura-2 and then exposed to ionophore exhibited an isolated elevation of [Ca]i, followed by prompt return to baseline levels. None of the oocytes showed signs of cleavage or of meiotic maturation after treatment with calcium ionophore. CONCLUSION(S): Human oocytes activated with calcium ionophore A23187 or ionomycin exhibited elevated [Ca]i but remained resistant to subsequent meiotic maturation and cleavage. Our results differ from some reports of parthenogenetic activation of human oocytes. These differences may result from different activation protocols or culture conditions. Because none of the 126 oocytes cleaved after the activation protocols used in these experiments, this approach should provide an ethically acceptable model system to study calcium dynamics in human oocytes.     

Assessment of clinical skills in midwifery: some ethical and practical problems

Previous studies have shown that sensitivity to high extracellular levels of Zn2+ is a general feature of cells in vitro and that a prerequisite of the toxic action of zinc is entry into cells via channels that are shared with iron or calcium. As the biochemical and toxicological behaviour of zinc chelate complexes could be different from that of free Zn2+, the effect of chelating agents on zinc transport into human melanoma cell lines was tested. EDTAcal and tetracycline reduced the toxic action of zinc ions in vitro, whereas phenytoin and diethyldithiocarbamate potentiated its effects. D-penicillamine, an effective chelator of zinc in vivo, also exerted a protective action in vitro. Comparison of sensitivity to Zn2+ in vitro between human melanoma lines and several lines of pigment cells from skin of various origins demonstrated that melanoma cells are killed by zinc ions at concentrations which are only partially toxic for normal pigment cells. This is consistent with the repeatedly observed high uptake of 65Zn by melanoma cells.     

Cellular uptake properties of a 2''-amino/2''-O-methyl-modified chimeric hammerhead ribozyme targeted to the epidermal growth factor receptor mRNA

PURPOSE: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. METHODS: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. RESULTS: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. CONCLUSIONS: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.