Halting the growth in diagnostic testing.
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Biomedical subjects
Publications and source records attributed to Michael J Murray.
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OBJECTIVE: To assess the temporal and morphologic characteristics of pinopod expression on the surface of endometrium across the secretory phase, in LH-timed endometrial samples in normal, healthy women. DESIGN: Prospective, randomized study. SETTING: Academic teaching hospital. PATIENT(S): Sixty-eight healthy volunteers with proven fertility. INTERVENTION(S): Urinary LH-timed endometrial and blood sampling was performed on each subject on a randomly selected day of the secretory phase. MAIN OUTCOME MEASURE(S): Histologic dating, assessment of pinopods using scanning electron microscopy, and comparison with serum P levels. RESULT(S): Eighty-six endometrial tissue samples obtained from 68 subjects were evaluated under scanning electron microscopy. Pinopods were first observed on luteal day 5, corresponding with the onset of the midluteal phase increase in serum P levels. Pinopods persisted for the entire duration of the secretory phase, but their morphology changed as the cycle advanced. CONCLUSION(S): The present findings demonstrate that pinopods are a characteristic feature of the mid to late secretory phase endometrial epithelium, exhibit cycle-dependent changes in morphology, and are most prominent during the putative implantation interval.
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The Canadian Triage and Acuity Scale has received widespread acceptance in Canada as a reliable and valid tool for emergency department triage. The importance of accurate triage becomes more apparent as emergency department volumes increase, and resources shrink. The need to ensure that those patients requiring more urgent care receive care first is the basis for all triage scales. Through the Canadian Triage and Acuity Scale National Working Group, the scale became the recommended triage tool for Canadian emergency departments. Work has been done on the interrater reliability of Canadian Triage and Acuity Scale among health care providers. There is a need to further assess the validity of the scale. This scale has now been applied in the out of hospital setting by paramedics and is being used in measurements of emergency physician workload. The future may see an electronic triage tool develop for emergency department use to reduce variability in its application. The Canadian Triage and Acuity Scale has become an integral component of Canadian emergency departments.
BACKGROUND: Controversy exists about the ability of soy protein and isoflavones to modulate vascular reactivity and biochemical cardiovascular disease risk markers in healthy, normolipidemic postmenopausal women. OBJECTIVE: The objective was to investigate whether the consumption of soy protein with isoflavones would result in improved vascular reactivity and decreased biochemical markers of endothelial dysfunction and inflammation, independent of enhanced lipid and antioxidant effects. DESIGN: Healthy postmenopausal women (n = 28) were enrolled in a randomized, double-blind, crossover study, and they consumed 25 g of 3 protein products/d for 6 wk each, with intervening washout periods. The products were isolated soy protein with isoflavones, ethanol-washed isolated soy protein with trace isoflavones, and total milk protein, which supplied 107, 2, and 0 mg total isoflavone (aglycone) units/d, respectively. We studied vascular function by using brachial artery reactivity values, plasma concentrations of vasoactive factors, endothelial inflammatory markers, and plasma isoflavone concentrations. The resistance of whole plasma and isolated LDL to copper-mediated oxidation was measured by conjugated diene formation. RESULTS: Postocclusion peak flow velocity of the brachial artery was significantly (P = 0.03) lower after treatment with isolated soy protein with isoflavones, which is consistent with a vasodilatory response, than after treatment with total milk protein. Plasma isoflavones and metabolites were significantly (P < 0.01) higher after treatment with isolated soy protein with isoflavones. There were no significant changes in biochemical cardiovascular disease risk markers or conjugated diene formation between the 3 dietary groups. CONCLUSION: Daily consumption of soy protein with isoflavones can result in positive vascular effects that are independent of lipid and antioxidant effects in healthy postmenopausal women.
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OBJECTIVE: To assess the effect of diisopropyl phenol (propofol), with and without Intralipid, on the cardiopulmonary system and on thromboxane production in endotoxic pigs. DESIGN: Prospective, randomized animal study. SETTING: Animal research laboratory at a major teaching hospital. SUBJECTS: Twenty-four pigs, divided into three groups (n = 8). INTERVENTIONS: Pulmonary arterial catheters and arterial cannulas were inserted into all pigs. Each pig received a 30 ng/kg bolus of endotoxin at 1 hr, followed by a continuous infusion of endotoxin at 24 ng x kg-1 x hr-1. Diisopropyl phenol at 25, 75, and 200 microg x kg-1 x min-1 was administered to all pigs, beginning at 1, 2, and 3 hrs, respectively. The pigs were divided into three groups to receive 0.25 g x kg-1 x hr-1, 0.08 g x kg-1 x hr-1, or no Intralipid, starting at time t = 0. Heart rate and mean arterial, central venous, and pulmonary arterial pressures were recorded continuously. Core temperature, arterial blood gases, mixed venous oxygen saturation, pulmonary arterial occlusion pressure, and cardiac output were measured intermittently. Thromboxane B(2) concentrations were measured at baseline and at 60, 75, 120, 135, 180, 195, and 240 mins. Data are expressed as mean +/- sd. Groups were compared by using repeated analysis of variance, with p <.05 used for statistical significance. MEASUREMENTS AND MAIN RESULTS: All pigs completed the 4-hr study. Marked variabilities were noted for individual pigs. Following the infusion of endotoxin, compared with baseline, there was a significant increase in pulmonary vascular resistance and a decrease in Pao(2) (p <.001 and p <.008, respectively). This response was not affected by the increasing dose of diisopropyl phenol, nor were there differences between the Intralipid and control groups. Pao(2) remained significantly lower in all groups, compared with the baseline measurements (p <.001) over the 4 hrs of the experiment. Thromboxane B(2) concentrations remained elevated compared with baseline and were significantly higher (p <.05) in the high-dose Intralipid group, compared with the low-dose and the control groups, during the last hour of the experiment. CONCLUSIONS: Small doses of endotoxin, when given to pigs, induce major perturbations of cardiopulmonary function. Neither Intralipid, high vs. low dose, nor diisopropyl phenol, at sedating vs. anesthetizing doses, worsened the physiologic derangement associated with the stress of low-dose endotoxemia.
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The southern sea otter (Enhydra lutris nereis) population in California (USA) and the Alaskan sea otter (E. lutris kenyoni) population in the Aleutian Islands (USA) chain have recently declined. In order to evaluate disease as a contributing factor to the declines, health assessments of these two sea otter populations were conducted by evaluating hematologic and/or serum biochemical values and exposure to six marine and terrestrial pathogens using blood collected during ongoing studies from 1995 through 2000. Samples from 72 free-ranging Alaskan, 78 free-ranging southern, and (for pathogen exposure only) 41 debilitated southern sea otters in rehabilitation facilities were evaluated and compared to investigate regional differences. Serum chemistry and hematology values did not indicate a specific disease process as a cause for the declines. Statistically significant differences were found between free-ranging adult southern and Alaskan population mean serum levels of creatinine kinase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, cholesterol, creatinine, glucose, phosphorous, total bilirubin, blood urea nitrogen, and sodium. These were likely due to varying parasite loads, contaminant exposures, and physiologic or nutrition statuses. No free-ranging sea otters had signs of disease at capture, and prevalences of exposure to calicivirus, Brucella spp., and Leptospira spp. were low. The high prevalence (35%) of antibodies to Toxoplasma gondii in free-ranging southern sea otters, lack of antibodies to this parasite in Alaskan sea otters, and the pathogen's propensity to cause mortality in southern sea otters suggests that this parasite may be important to sea otter population dynamics in California but not in Alaska. The evidence for exposure to pathogens of public health importance (e.g., Leptospira spp., T. gondii) in the southern sea otter population, and the naïveté of both populations to other pathogens (e.g., morbillivirus and Coccidiodes immitis) may have important implications for their management and recovery.
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Human endometrium expresses the critical complement component C3 in a cyclic fashion, with the highest expression in the secretory phase. As activated complement can kill cells, self or foreign, the secretory endometrial epithelium protects itself by concomitant expression of complement-protective proteins. The objectives of our present study were to describe the spatial and temporal regulation of the complement-protective protein decay-accelerating factor (DAF) in human endometrium and to identify local regulators of its expression. To describe the cyclic regulation of DAF, immunohistochemistry was performed using the IH4 monoclonal antibody on secretory phase endometrial biopsies taken from normal fertile volunteers in LH-timed cycles (n = 114). DAF expression in human endometrium was predominantly localized to the apical membrane of glandular and luminal epithelium. DAF expression, as assessed by histological scoring analysis, was minimal in the proliferative and early secretory phases and increased markedly on approximately day LH +7 (lumen) and LH +8 (glands). Maximal expression was seen in both glands and lumen by LH +8, and this persisted into menses. Using the RL95-2 endometrial epithelial cancer cell line as a model system, we next examined the cellular regulation of DAF. Treatment with E2 and progesterone, alone or in combination, had little effect on DAF expression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) treatment increased cell surface and total DAF protein, increasing the signal by 260% on flow cytometry and by 200% on Western blot analysis. Stimulation of DAF protein expression was dose dependent, with maximal expression seen at 1 ng/ml. The stimulatory effects of HB-EGF were also observed at the mRNA level. EGF had effects similar to those of HB-EGF on DAF mRNA and protein expression, suggesting that the HB-EGF effect was mediated at least in part by the Her1 EGF receptor subunit. These studies suggest that DAF expression in the midsecretory phase is stimulated by HB-EGF or other members of the EGF family and may function to protect the epithelial integrity of human endometrium in the face of increased complement expression.
OBJECTIVE: To test the hypothesis that soy protein isolate (SPI) with isoflavones opposes the proliferative effects of exogenous estradiol (E2) on the endometrium after menopause. DESIGN: Thirty-nine postmenopausal women were randomized to receive daily for 6 months either 0.5 mg E2 + placebo, 1.0 mg E2 + placebo, 0.5 mg E2 + 25 g SPI with 120 mg isoflavones, or 1.0 mg E2 + 25 g SPI with 120 mg isoflavones. Primary outcome measures were endometrial histology, ultrasound endometrial thickness, and Ki67 staining quantification, a marker of cellular proliferation. Secondary outcome measures were serum lipids and markers of bone resorption. RESULTS: Endometrial hyperplasia, endometrial stromal and epithelial cellular proliferation, and sonographically measured endometrial thickness were similarly affected in all groups. SPI did not lessen the beneficial effects of E2 on lipids and markers of bone resorption. CONCLUSION: In this pilot study, SPI with isoflavones did not protect the endometrium from E2-induced hyperplasia in postmenopausal women. If higher, long-term doses of isoflavone supplementation are found to be safe for postmenopausal women, then future studies combining E2 with isoflavones may be feasible as an alternative to traditional hormone replacement therapy.