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Biomedical subjects

Michael J Murray

Publications and source records attributed to Michael J Murray.

At least 19 recordsLinked to original sources

The epithelial-mesenchymal transition of the Drosophila mesoderm requires the Rho GTP exchange factor Pebble.

Drosophila pebble (pbl) encodes a Rho-family GTP exchange factor (GEF) required for cytokinesis. The accumulation of high levels of PBL protein during interphase and the developmentally regulated expression of pbl in mesodermal tissues suggested that the primary cytokinetic mutant phenotype might be masking other roles. Using various muscle differentiation markers, we found that Even skipped (EVE) expression in the dorsal mesoderm is greatly reduced in pbl mutant embryos. EVE expression in the dorsalmost mesodermal cells is induced in response to DPP secreted by the dorsal epidermal cells. Further analysis revealed that this phenotype is likely to be a consequence of an earlier defect. pbl mutant mesodermal cells fail to undergo the normal epithelial-mesenchymal transition (EMT) and dorsal migration that follows ventral furrow formation. This phenotype is not a secondary consequence of failed cytokinesis, as it is rescued by a mutant form of pbl that does not rescue the cytokinetic defect. In wild-type embryos, newly invaginated cells at the lateral edges of the mesoderm extend numerous protrusions. In pbl mutant embryos, however, cells appear more tightly adhered to their neighbours and extend very few protrusions. Consistent with the dependence of the mesoderm EMT and cytokinesis on actin organisation, the GTP exchange function of the PBL RhoGEF is required for both processes. By contrast, the N-terminal BRCT domains of PBL are required only for the cytokinetic function of PBL. These studies reveal that a novel PBL-mediated intracellular signalling pathway operates in mesodermal cells during the transition from an epithelial to migratory mesenchymal morphology during gastrulation.

Animals↗

Late-life action tremor in a southern sea otter (enhydris lutris nereis).

Although tremor is highly prevalent in human beings, there are few reports of tremor occurring in other mammals. Such tremor can further our insight into the mechanisms and anatomical basis of human tremor disorders. We report on a southern sea otter with a slowly progressive 6.5 to 8.5 Hz action tremor of late life that shared several clinical characteristics with essential tremor. The main pathological finding was in the cerebellum, where there was extensive vacuolation of Purkinje cells.

Age Factors↗

Intraoperative management of aortic aneurysm surgery.

Managing the anesthesia of patients undergoing open aortic surgical repair is a great challenge. The anesthesiologist's role in myocardial,renal, and neurologic protection is crucial to the patient's overall outcome.Each case presents different challenges, and there is no one right way to manage the patient intraoperatively.

Anesthesia↗

Vascular disease and inflammation.

The past decade has witnessed a dramatic shift in the understanding of the causes of atherosclerotic vascular disease. What was once considered to be a process of abnormal lipid deposition in the vascular wall is now understood to be a dynamic inflammatory process from inception through plaque growth, rupture and ultimately thrombosis. This article reviews the basic science research that supports this growing body of epidemiologic data and discusses the inflammatory markers that predict future clinical events,as well as the pharmacologic success in therapies that specifically target inflammation.

Animals↗

A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women.

OBJECTIVE: To refine or redefine the traditional histologic criteria used to date the secretory phase endometrium. DESIGN: Randomized, observational study. SETTING: Academic clinical research center. PATIENT(S): One hundred and thirty healthy, regularly cycling, fertile volunteers, aged 18 to 35 years. INTERVENTION(S): Patients were randomized to undergo endometrial sampling and measurement of serum estradiol and progesterone 1 to 14 days after the midcycle urinary luteinizing hormone surge. Three gynecologic histopathologists objectively scored each tissue specimen for 32 distinct histologic features and dated the endometrium using traditional histologic criteria. MAIN OUTCOME MEASURE(S): The 32 features were evaluated for [1] temporally dependent variation, [2] the amplitude of variations in score observed across the secretory phase, and [3] interobserver variability. Additionally, traditional dating criteria were analyzed. RESULT(S): The traditional endometrial histologic dating criteria are much less temporally distinct and discriminating than originally described, due to considerable intersubject, intrasubject, and interobserver variability. Neither traditional dating criteria nor any combination of the best performing histologic features identified by our objective and systematic analyses could reliably distinguish any specific cycle day or narrow interval of days. CONCLUSION(S): Histologic endometrial dating does not have the accuracy or the precision necessary to provide a valid method for the diagnosis of luteal phase deficiency or to otherwise guide the clinical management of women with reproductive failure.

Adolescent↗

Use of self-etching adhesives to seal resected apices.

The purpose of this study was to evaluate the sealing ability of four self-etching adhesives placed over blood-contaminated/uncontaminated resected root apices without root-end preparation. Extracted maxillary incisors and canines were randomly divided into four groups of 10 teeth each. After canal preparation and resection of the apex, four self-etching adhesives (Clearfil SE Bond, One-Up Bond F, Unifil Bond, and ABF) were applied over the control and contaminated surfaces. The roots were then subjected to 15 cm of water pressure to simulate periapical microleakage stress. Data were analyzed using a two-way repeated measures, ANOVA. Positive and negative controls responded as expected. Statistical analysis indicated that there were no significant differences in the sealing effectiveness among the adhesives applied to contaminated or uncontaminated groups. All contaminated groups had significantly higher leakage (p < 0.003) than their uncontaminated pairs.

Analysis of Variance↗

What is taught, what is tested: findings and competency-based recommendations of the Undergraduate Medical Education Committee of the Society of Critical Care Medicine.

INTRODUCTION: Addressing an unexpected shortfall of intensivists requires early identification and training of appropriate personnel. The purpose of this study was to determine how U.S. medical students are currently educated and tested on acute care health principles. HYPOTHESIS/METHODS: A survey of critical care education with telephone follow-up was mailed to the deans of all 126 medical schools. Web site review of medical school curricula for critical care education was performed. Upon invited request, four members of the Undergraduate Medical Education Committee (UGMEC) reviewed 1,200 pool questions of step II of the U.S. Medical Licensing Examination (USMLE) given to graduating medical students for critical care content. Descriptive statistics are employed. RESULTS: Survey response rate was 49% and 88% by the second mailing with Web site review. Forty-five percent of U.S. medical schools responding had formal undergraduate critical care didactic curricula averaging 12 +/- 3 hrs: 60% were elective, 60% taught in the 4th year. Eighty percent of clinical ICU rotations offered were elective. Sixty percent of schools taught 11 key critical care procedures in the 3rd or 4th year; 17% required them to graduate. Nineteen percent of Step II USMLE questions had critical care content; 58% dealt with pulmonary or cardiac disease. CONCLUSIONS: Graduating medical students are tested (and licensed accordingly) on critical care knowledge, despite an inconsistent exposure to the discipline in medical school. The UGMEC has drafted competency-based recommendations for acute health care delivery that encourage mandatory didactic and procedural critical care training. The UGMEC recommends that critical care rotations with didactic curricula be required for undergraduate education and that acute care procedural skills be an important component of these curricula.

Clinical Competence↗

Effect of omeprazole paste on intragastric pH in clinically normal neonatal foals.

OBJECTIVE: To evaluate the efficacy of omeprazole paste, a commonly used antiulcer drug, on intragastric pH in clinically normal neonatal foals. ANIMALS: 6 clinically normal foals between 5 and 14 days of age. PROCEDURE: Intragastric pH was recorded in each foal by use of a disposable antimony pH electrode with internal reference. Values for intragastric pH were recorded every 4 seconds by use of an ambulatory pH monitor. There were two 24-hour recordings of intragastric pH for each foal, with 24 hours between recordings. Foals were not administered any drugs during the first recording. Foals were administered omeprazole paste (4 mg/kg, PO) 1 hour after the start of the second recording. Mean pH was calculated for each hour of each 24-hour recording session. Hourly mean values were compared between the first and second 24-hour recordings. RESULTS: Complete data were obtained from 4 of 6 foals during the first 24-hour recording and 6 of 6 foals during the second 24-hour recording. Foals had significantly higher mean hourly intragastric pH for hours 2 to 22 following omeprazole administration, compared with corresponding hourly pH values in foals during the first recording. CONCLUSION AND CLINICAL RELEVANCE: Omeprazole paste can effectively increase intragastric pH in clinically normal neonatal foals within 2 hours after oral administration of the first dose and can be administered to neonatal foals at the rate of 4 mg/kg, PO, every 24 hours.

Administration, Oral↗

Assessment of the efficacy of a single dose of a recombinant vaccine against West Nile virus in response to natural challenge with West Nile virus-infected mosquitoes in horses.

OBJECTIVE: To determine the onset of immunity after IM administration of a single dose of a recombinant canarypox virus vaccine against West Nile virus (WNV) in horses in a blind challenge trial. ANIMALS: 20 mixed-breed horses. PROCEDURE: Horses with no prior exposure to WNV were randomly assigned to 1 of 2 groups (10 horses/group). In 1 group, a recombinant canarypox virus vaccine against WNV was administered to each horse once (day 0). The other 10 control horses were untreated. On day 26, 9 treated and 10 control horses were challenged via the bites of mosquitoes (Aedes albopictus) infected with WNV. Clinical responses and WNV isolation were monitored for 14 days after challenge exposure; antibody responses against WNV after administration of the vaccine and challenge were also assessed in both groups. RESULTS: Following challenge via WNV-infected mosquitoes, 1 of 9 treated horses developed viremia. In contrast, 8 of 10 control horses developed viremia after challenge exposure to WNV-infected mosquitoes. All horses seroconverted after WNV challenge; compared with control horses, antibody responses in the horses that received the vaccine were detected earlier. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, a single dose of the recombinant canarypox virus-WNV vaccine appears to provide early protection against development of viremia after challenge with WNV-infected mosquitoes, even in the absence of measurable antibody titers in some horses. This vaccine may provide veterinarians with an important tool in controlling WNV infection during a natural outbreak or under conditions in which a rapid onset of protection is required.

Aedes↗

Concentrations of gentamicin in serum and bronchial lavage fluid after once-daily aerosol administration to horses for seven days.

OBJECTIVE: To assess gentamicin concentrations in serum and bronchial lavage fluid (BLF) of horses during a 24-hour period after once-daily aerosol administration of gentamicin (GAER) for 7 days and the pattern and degree of bronchial tree inflammation associated with repeated GAER. ANIMALS: 13 healthy adult horses (9 geldings and 4 mares). PROCEDURE: The treatment group comprised 8 horses, and 5 horses were untreated control animals. Gentamicin (20 mL of gentamicin [50 mg/mL]) was administered via aerosol once daily for 7 days. Samples of serum and BLF were obtained from all horses before GAER and 0.5, 4, 8, and 24 hours after the final day of GAER. Gentamicin concentrations were determined for all samples from treated horses, and cytologic examinations were performed on all BLF samples. RESULTS: Peak median BLF gentamicin concentration detected at 0.5 hours was 2.50 microg/mL. Median serum gentamicin concentration was < 0.50 microg/mL at all time points. Significant differences were not observed in total nucleated cell counts or differential cell counts in BLF between groups at any time point. Neutrophil count in BLF for all horses was increased over baseline at 4 and 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: We did not detect evidence of gentamicin accumulation or respiratory inflammation after once-daily GAER for 7 days. This protocol appears unlikely to result in local or systemic toxicosis. Repeated daily GAER to horses appears to be a safe procedure and may have clinical use in the treatment of horses with bacterial infections of the airways.

Administration, Inhalation↗

Temporal and morphologic characteristics of pinopod expression across the secretory phase of the endometrial cycle in normally cycling women with proven fertility.

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.

Adolescent↗

The Canadian Triage and Acuity Scale: A Canadian perspective on emergency department triage.

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.

Canada↗

Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women.

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.

Antioxidants↗