Vaginal delivery vs. a 'nice clean cut': giving more attention to mothers' postpartum health.
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Biomedical subjects
Publications and source records attributed to S Alexander.
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The occurrence of a pleiomorphic population of cytoplasmic fragments is a common characteristic of early human embryos fertilized in vitro. Here, temporal, spatial, fine structural, and biochemical aspects of fragmentation were examined in fragmented monospermic and dispermic pronuclear to early cleavage stages human embryos classified as stage-appropriate during the first 3.5 days of culture. The morphodynamics of certain common patterns of fragmentation and the movement and composition of fragments were analysed by time-lapse video, mitochondrial fluorescent probes, and transmission electron microscopy. Plasma membrane and nuclear DNA integrity were assessed by annexin V staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and single-cell alkaline gel electrophoresis ('comet') assays respectively. Developmental competence for affected embryos was related to outcome after embryo transfer. The results demonstrate that certain common forms of spontaneous fragmentation affecting early human embryos are not lethal, and that clusters of apparent fragments are often transient structures, which disappear by resorption or lysis. The findings suggest that the occurrence and fate of fragments characteristic of these phenotypes may be related to oncosis-like processes associated with transient and focal ATP deficiencies in blastomeres and mitochondrial deficiencies or absence in extracellular fragments.
There is a growing volume of research on trauma brain injury (TBI) as evidenced by a recent Medline search that reported over 6000 articles published on TBI in the past 5 years.
OBJECTIVE: To determine what factors related to health services in France might explain substandard care of severe morbidity due to obstetric haemorrhage. DESIGN: Retrospective questionnaire survey. SETTING: Three administrative regions of France. POPULATION: All women who were pregnant or had recently given birth during the year before the survey. METHODS: A European survey (MOMS-B) defined severe haemorrhages as blood loss > or = 1500mL. A specific questionnaire was added in France to analyse the quality of care of these haemorrhages. The survey was carried out in three different administrative regions: Champagne-Ardenne, the Centre and Lorraine. An expert committee was appointed and began by establishing a framework for qualitative assessment. One hundred and sixty-five cases of severe haemorrhage were reviewed and classified into one of three levels of care: appropriate, inadequate or mixed. Inadequate care and 'mixed' care were both considered substandard. The 165 cases were coded and then studied with uni- and multivariate analysis (logistic regression with SAS and SPSS software). RESULTS: Of the 165 cases identified, 51% (85/165) were vaginal, 19% (31/165) operative vaginal, and 30% (49/165) caesarean. The leading cause of haemorrhage was uterine atony. Overall, 62% of the cases received appropriate care, 24% received totally inadequate care and 14% mixed care. After adjustment for sociodemographic factors, antenatal care and organisational aspects, the lack of a 24-hour on-site anaesthetist at the hospital and a low volume of deliveries (<500 births per year) were the factors associated with substandard care. CONCLUSION: Organisational features are so important that application of good clinical practices for safer motherhood reinforce the need for new organisation of obstetric services. For the first time, the presence of an anaesthetist is shown to have a measurable effect on the quality of care for women giving birth. These results need to be confirmed by others.
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Little is known about the underlying mechanisms that result in a sexually dimorphic response to Vibrio vulnificus endotoxic shock. V. vulnificus is a gram-negative bacterium, considered one of the most invasive and rapidly fatal human pathogens known. However, 85% of individuals that develop endotoxic shock from V. vulnificus are males. Using the rat, we have developed a model for V. vulnificus endotoxic shock that mimics the sexually dimorphic response in humans. Gonadectomy in females results in increased mortality, and estrogen replacement results in decreased mortality in both gonadectomized males and females. These results demonstrate that estrogen is providing protection against V. vulnificus lipopolysaccharide-induced endotoxic shock.
Sphingosine-1-phosphate, a product of sphingomyelin degradation, is an important element of signal transduction pathways that regulate cell proliferation and cell death. We have demonstrated additional roles for sphingosine-1-phosphate in growth and multicellular development. The specific disruption in Dictyostelium discoideum of the sphingosine-1-phosphate lyase gene, which encodes the enzyme that catalyzes sphingosine-1-phosphate degradation, results in a mutant strain with aberrant morphogenesis, as well as an increase in viability during stationary phase. The absence of sphingosine-1-phosphate lyase affects multiple stages throughout development, including the cytoskeletal architecture of aggregating cells, the ability to form migrating slugs, and the control of cell type-specific gene expression and terminal spore differentiation. This pleiotropic effect, which is due to the loss of sphingosine-1-phosphate lyase, establishes sphingolipids as pivotal regulatory molecules in a wide range of processes in multicellular development.
Learning and teaching of health and medical Informatics is currently supported by web based material, which in the main has been derived from traditional texts. Aided by contributions from the expert community, the web site of the handbook of Medical Informatics has been developed to incorporate increased interactivity (with question and answers related to each section). This approach has proved beneficial to both student and teacher. To further increase the interactivity of the WWW we investigate the suitability of authoring tools for developing complex simulations and interactive tutorials, using an example from the area of quantitative decision support (Bayes Theorem). We propose that these tools provide a suitable platform for the preparation and delivery of collaboratively produced HMI courses, which address open and distance learning and pedagogic issues.
Cells of Dictyostelium discoideum are highly resistant to DNA damaging agents such as UV-light, gamma-radiation and chemicals. The genes encoding nucleotide excision repair (NER) and base excision repair (BER) enzymes are rapidly upregulated in response to UV-irradiation and DNA-damaging chemicals, suggesting that this is at least partially responsible for the resistance of this organism to these agents. Although Dictyostelium is also unusually resistant to high concentrations of H(2)O(2), little is known about the response of this organism to oxidative stress. To determine if transcriptional upregulation is a common mechanism for responding to DNA-damaging agents, we have studied the Dictyostelium catalase and Cu/Zn superoxide dismutase antioxidant enzymes. We show that there are two catalase genes and that each is differentially regulated both temporally and spatially during multicellular development. The catA gene is expressed throughout growth and development and its corresponding enzyme is maintained at a steady level. In contrast, the catB gene encodes a larger protein and is only expressed during the final stages of morphogenesis. Cell type fractionation showed that the CatB enzyme is exclusively localized to the prespore cells and the CatA enzyme is found exclusively in the prestalk cells. Each enzyme has a different subcellular localization. The unique developmental timing and cell type distribution suggest that the role for catB in cell differentiation is to protect the dormant spores from oxidative damage. We found that exposure to H(2)O(2) does not result in the induction of the catalase, superoxide dismutase, NER or BER mRNAs. A mutant with greatly reduced levels of catA mRNA and enzyme has greatly increased sensitivity to H(2)O(2) but normal sensitivity to UV. These results indicate that the natural resistance to oxidative stress is not due to an ability to rapidly raise the level of antioxidant or DNA repair enzymes and that the response to UV-light is independent from the response to reactive oxygen compounds.
The pathogenic differences between CXCR4 (X4)- and CCR5 (R5)-utilizing strains of HIV-1 may be predominantly due to differences in viral tropism, which in turn may be due to differential coreceptor utilization. We tested this hypothesis in the human thymus organ of the SCID-hu Thy/Liv mouse, using recombinants of NL4-3 that were isogenic except for Env coreceptor-binding determinants of the V1-V3 loops. Conversion of NL4-3 from an X4 to an R5 isolate was associated with altered tropism for cell subpopulations within the Thy/Liv organ (with a higher frequency of infection of thymic stromal cells, including macrophages), a slower rate of replication, and a lower level of cytopathicity. These observations underscore the causal relationships between tropism, coreceptor use, and cytopathicity in the human thymus in vivo.
BACKGROUND: Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection. HYPOTHESIS: Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status. DESIGN: Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team. RESULTS: Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation. CONCLUSION: One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.
The genesis of the spore coat of Dictyostelium represents an exquisite example of developmentally regulated protein secretion. The proteins that are destined to be assembled into the extracellular matrix of the spore coat are stored in unique prespore vesicles that are triggered to secrete their contents at terminal differentiation. The regulation of this process is being revealed by the identification of the individual proteins in these vesicles.
RATIONALE AND OBJECTIVES: The authors attempted to define the value of good medical student teaching to the profession of radiology by examining the effect of radiology course improvements on the number of 4th-year students applying to radiology residencies. MATERIALS AND METHODS: Course evaluation and residency application data were obtained from six consecutive classes of 4th-year medical students at the study institution, and these data were compared with national data. RESULTS: Between 1995 and 2000, the number of 4th-year U.S. medical students applying to radiology increased 1.6 times. At the study institution, that number increased 4.5 times, a statistically significant difference (P = .020, chi2 test). Student survey data indicate that this increase reflects a general increase in the quality of radiology teaching in the study institution and specific changes in a required 2nd-year medical school course. CONCLUSION: These results strongly suggest that good medical student teaching pays important dividends, not only to the departments that provide it but also to the profession of radiology as a whole. Exposing students to good radiology teaching early in their medical school careers is especially important. Radiology departments that provide outstanding medical student education should be studied to help develop a model of educational best practices.
To determine the relationship between maternal anemia [hemoglobin (Hgb) < 10-11 g/dL] and various birth outcomes, a meta-analysis was conducted based on published literature identified by MEDLINE and manual search from 1966 through 1999. Odds ratios (OR) from selected studies were pooled according to the gestational age at anemia diagnosis. The meta-analysis shows that maternal anemia during early pregnancy was associated with slightly increased preterm birth [pooled adjusted OR (aOR): 1.32, 95% confidence interval (CI): 1.01-1.74], and nonstatistically significant increased low birth weight [pooled aOR: 1.39 (0.70-2.74)], and was not associated with fetal growth restriction [pooled aOR: 1.01 (0.73-1.38)]. However, there was a nonstatistically significant inverse relationship between anemia during late pregnancy and preterm birth [pooled aOR: 0.92 (0.54-1.84)] and low birth weight [pooled aOR: 0.80 (0.64-1.00)]. Anemia was not statistically significantly associated with hypertensive disorders of pregnancy regardless of stage of pregnancy [pooled OR: 0.80 (0.53-1.20)]. The relationship between anemia and perinatal mortality was inconclusive. A few studies indicated that severe maternal anemia (Hgb < 8-8.5 g/dL) was associated with increased risk of poor outcomes. We conclude that early pregnancy anemia is associated with slightly increased risk of preterm birth. The trend toward an inverse association of anemia determined during late pregnancy with preterm birth and low birth weight may reflect the benefit of plasma volume expansion.
It has been suggested that mitochondrial DNA defects that effect metabolic capacity may be a proximal cause of failures in oocyte maturation, fertilization, or early embryonic development. Here, the distribution of mitochondria was examined by scanning laser confocal microscopy in living human pronuclear oocytes and cleavage stage embryos, followed either by measurements of the net ATP content of individual blastomeres or anti-tubulin immunofluorescence to determine the relationship between mitochondrial distribution and microtubular organization. The results indicate that specific patterns of perinuclear mitochondrial aggregation and microtubular organization are related, and that asymmetrical mitochondrial distributions at the pronuclear stage can result in some proportion of blastomeres with reduced mitochondrial inheritance and diminished ATP generating capacity. While the inability to divide appears to be a development consequence for an affected blastomere, for the embryo, reduced competence may occur during cleavage if several blastomeres inherit a mitochondrial complement inadequate to support normal cellular functions. The findings provide a possible epigenetic explanation for the variable developmental ability expressed within cohorts of morphologically normal early cleavage stage human embryos obtained by in-vitro fertilization.
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The coordinate fusion of the prespore vesicles (PSVs) with the plasma membrane at the terminal stage of spore differentiation in Dictyostelium discoideum is an important example of developmentally regulated protein secretion. However, little is known about the composition of the vesicles, the molecular signals regulating secretion, or the mechanics of the membrane fusion. Taking a biochemical approach, we purified PSVs from different developmental stages. These preparations are highly enriched for their specific cargo of spore coat proteins while devoid of markers for other cellular compartments. Electron microscopic observations show that the PSV preparations are homogenous, with the soluble spore coat protein PsB/SP85 distributed throughout the lumen and the acid mucopolysaccharide localized in the central core. During development the PSVs increase in size and density concomitant with an increase in their protein cargo. The PSVs contain approximately 80 proteins, and we have identified a PSV-specific GTP-binding protein that may be involved in regulating vesicle fusion. The PSVs are not clathrin-coated and do not contain the SpiA spore coat protein. The PSV preparations are ideal for a global proteome analysis to identify proteins involved in signal reception, vesicle movement, docking, and fusion in this developmentally regulated organelle.
OBJECTIVES: To estimate the incidences of caesarean sections in Latin American countries and correlate these with socioeconomic, demographic, and healthcare variables. DESIGN: Descriptive and ecological study. SETTING: 19 Latin American countries. MAIN OUTCOME MEASURES: National estimates of caesarean section rates in each country. RESULTS: Seven countries had caesarean section rates below 15%. The remaining 12 countries had rates above 15% (range 16.8% to 40.0%). These 12 countries account for 81% of the deliveries in the region. A positive and significant correlation was observed between the gross national product per capita and rate of caesarean section (r(s)=0.746), and higher rates were observed in private hospitals than in public ones. Taking 15% as a medically justified accepted rate, over 850 000 unnecessary caesarean sections are performed each year in the region. CONCLUSIONS: The reported figures represent an unnecessary increased risk for young women and their babies. From the economic perspective, this is a burden to health systems that work with limited budgets.