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Biomedical subjects

M Wilkes

Publications and source records attributed to M Wilkes.

At least 19 recordsLinked to original sources
PubMed2002

Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest.

OBJECTIVES: Although retrograde cerebral perfusion has become a popular adjunctive technique and may improve cerebral ischemic tolerance during hypothermic circulatory arrest, direct cerebral metabolic benefit has yet to be demonstrated in human subjects. We investigated the post-arrest metabolic phenomena with and without retrograde cerebral perfusion in patients. METHODS: In a prospective randomized trial, 42 patients undergoing aortic surgery requiring hypothermic circulatory arrest were allocated to receive hypothermic circulatory arrest alone (n = 21) or hypothermic circulatory arrest with additional retrograde cerebral perfusion (n = 21). Circulatory arrest was commenced at 15 degrees C, and retrograde perfusion was instituted through the superior vena cava at a maximum jugular bulb pressure of 25 mm Hg. Transcranial, paired, repeated samples of the arterial and jugular bulb blood were analyzed for oxygen and glucose. Velocity in the right middle cerebral artery was also measured simultaneously. RESULTS: There were 3 (7.1%) deaths and 3 (7.1%) episodes of neurologic deficit. Mean bypass and circulatory arrest duration (in minutes) were similar between groups (P =.4 and.14). The mean retrograde perfusion duration was 23 minutes. Post-arrest nasopharyngeal temperature was similar (15.3 degrees C vs. 15.3 degrees C). Retrograde perfusion did not affect post-arrest oxygen extraction, glucose extraction, or jugular bulb Po(2). There was no immediate lactate release immediately after hypothermic circulatory arrest. CONCLUSIONS: Retrograde cerebral perfusion did not influence immediate post-arrest nasopharyngeal temperature or cerebral metabolic recovery. The low jugular bulb Po(2) suggests equivalent ischemia. These findings cast doubt on the effectiveness of retrograde cerebral perfusion as a metabolic adjunct to hypothermic circulatory arrest.

Adult↗
PubMed2001

Managed care.

Explore the source record for details and available documents.

Education, Medical↗
PubMed2001

Antineutrophil cytoplasm antibody-induced neutrophil nitric oxide production is nitric oxide synthase independent.

BACKGROUND: Antineutrophil cytoplasm antibodies (ANCAs) are implicated in the pathogenesis of systemic vasculitis. We asked whether ANCA could induce nitric oxide (NO) release from human neutrophils and, if so, whether this NO production was dependent on NO synthase (NOS) activity. METHODS: Neutrophil NO production was measured using a chemiluminescence assay, and NOS activity was determined by the conversion of [(14)C] L-arginine to [(14)C] L-citrulline and NOS mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Human neutrophils isolated from healthy donors were incubated at 37 degrees C with human ANCA, normal human IgG, murine monoclonal myeloperoxidase ANCA, murine proteinase-3 ANCA, or their respective isotypic controls for 6 to 12 hours in RPMI. Both human and monoclonal ANCA led to a dose-dependent increase of NO compared with control IgG. Neutrophils, either freshly isolated or incubated for seven hours with murine monoclonal myeloperoxidase ANCA, proteinase-3 ANCA, or a mixture of interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma plus lipopolysaccharide showed no NOS activity with low conversion rates of [(14)C] L-arginine to [(14)C] L-citrulline, which could not be inhibited by N(G)-monomethyl-L-arginine (NOS inhibitor). To detect NOS mRNA expression, RT-PCR was performed using oligonucleotide primers derived from mRNA sequences of either human constitutive endothelial NOS (eNOS), constitutive neuroneal NOS (nNOS), or human hepatocyte inducible NOS (iNOS). There was no expression of either eNOS, nNOS, or iNOS in untreated, human and murine monoclonal ANCA-treated, or cytokine-treated neutrophils. CONCLUSION: These data suggest that human neutrophils produce NO in response to ANCA but in a NOS-independent way. NO can be generated from a nonenzymatic interaction between hydrogen peroxide and arginine. We postulate that this is the predominant pathway of NO synthesis in neutrophils, since ANCAs are capable of inducing reactive oxygen species production from neutrophils.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

What students bring to medical school: attitudes toward health promotion and prevention.

INTRODUCTION: Health care providers' positive attitudes toward prevention and health promotion are important in achieving national health care goals. Limited studies of incoming medical students have been conducted that measure predictors of positive attitudes toward health promotion and prevention. METHODS: Data were obtained from a 1993 curriculum evaluation survey of first-year students at five different medical schools in California. Attitudes toward health promotion and prevention were measured using a nine-question Prevention Attitude Scale (PAS). We developed 2 multivariate linear regression models using demographics, education choices, and personal social values and beliefs to predict PAS scores. We also performed bivariate analysis. RESULTS: Five hundred ninety-nine completed surveys were analyzed, with a response rate of 95%. Mean PAS score was 36.47 +/- 3.7 on a 0 to 44 scale. Female gender, Democratic party preference, and a planned specialty choice in preventive medicine or primary care predicted the highest PAS scores on bivariate analysis (p < 0.002). Significant correlation ( p < 0. 001) was shown between PAS scores and 2 additional scales regarding beliefs in associations of social factors and illness and in the importance of caring for the poor. Linear regression model using personal social values and beliefs explained 34% of the variance, as opposed to the demographic model that explained only 9% of the variance. CONCLUSIONS: In the schools studied, participating first-year medical students had moderately positive attitudes toward health promotion and prevention, as measured by PAS scores. In designing curriculum to improve medical students' attitudes toward health promotion and prevention, medical educators may need to consider other personal and social values held by medical students and to address the "political" aspects of health promotion and prevention. Future studies are needed to longitudinally follow medical student attitudes.

Adolescent↗
PubMed2000

Possible interactions between angiotensin II and insulin: effects on glucose and lipid metabolism in vivo and in vitro.

Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin required to increase glucose uptake by 200%) were 4.5 x 10(-9) M (control) vs 3.9 x 10(-9) M and 6.2 x 10(-9) M, whereas the positive control (glucagon-like peptide-1) increased insulin sensitivity. Thus, ANGII infusion may have a modest insulin antagonist effect on glucose disposal in insulin-resistant fructose-fed rats pretreated with an AT(1)-blocker, but ANGII has no effect on TGSR or in vitro glucose uptake in L6 myoblasts. These findings are relevant to recent clinical discussions about the metabolic effects of ANGII and renin-angiotensin system blockade.

Analysis of Variance↗
PubMed1999

Learning to value ethnic diversity--what, why and how?

INTRODUCTION: Learning to value ethnic diversity is the appreciation of how variations in culture and background may affect health care. It involves acknowledging and responding to an individual's culture in its broadest sense. This requires learning the skills to negotiate effective communication, a heightened awareness of one's own attitudes, and sensitivity, to issues of stereotyping, prejudice and racism. This paper aims to contribute to debate about some of the key issues that learning to value ethnic diversity creates. CONTEXT: Although some medical training is beginning to prepare doctors to work in an ethnically diverse society, there is a long way to go. Promoting 'valuing ethnic diversity' in curricula raises challenges and the need to manage change, but there are increasing opportunities within the changing context of medical education. Appropriate training can inform attitudes and yield refinement of learners' core skills that are generic and transferable to most health encounters. CURRICULUM DEVELOPMENT: Care must be taken to avoid a narrow focus upon cultural differences alone. Learning should also promote examination of learners' own attitudes and their appreciation of structural influences upon health and health care, such as racism and socio-economic disadvantage. Appropriate training and support for teachers are required and learning must be explicitly linked to assessment and professional accreditation. CONCLUSION: Greater debate about theoretical approaches, and much further experience of developing, implementing and evaluating effective training in this area are needed. Medical educators may need to overcome discomfort in developing such approaches and learn from experience.

Culture↗
PubMed1998

Cellular localization of AT1 receptor mRNA and protein in normal placenta and its reduced expression in intrauterine growth restriction. Angiotensin II stimulates the release of vasorelaxants.

Angiotensin II (ANG II) is a potent vasoconstrictor and growth promoter. Quantitative receptor autoradiography using the nonselective radioligand [125I]ANG II and subtype-selective competing compounds demonstrated the presence of both ANG II receptor (AT)1 and AT2 receptor recognition sites. In addition, a relatively small population of apparently non-AT1/non-AT2 sites was identified that may represent a novel high affinity ANG II recognition site in human placenta. Using placental membrane preparations, the AT2 receptor antagonist PD123177 failed to compete for [3H]ANG II binding at relevant concentrations, whereas the AT1 receptor antagonist losartan competed in a monophasic manner for all the specific binding, suggesting that the non-AT1/non-AT2 recognition site identified using autoradiography may be a cytosolic binding site. AT1 receptor binding was significantly reduced (P < 0. 02) in intraeuterine growth restriction (IUGR) pregnancies. Western blot analysis confirmed this showing a reduction in AT1 receptor protein. In situ hybridization and immunocytochemistry revealed that AT1 receptor mRNA and protein were localized throughout pregnancy in the cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast, as well as in or around the blood vessels of placental villi. The intensity of the hybridization signal for AT1 receptor mRNA over the syncytium was reduced in IUGR. ANG II evoked a rapid and concentration-dependent release of NO in first trimester cytotrophoblast-like cells that was abolished by the inclusion of the competitive NOS inhibitor NG-monomethyl-L-arginine. Neither losartan nor PD123177 alone significantly inhibited ANG II-evoked NO release, and when cells were stimulated with ANG II in the presence of losartan (10 microM) and PD123177 (10 microM) in combination, NO release was significantly inhibited (P < 0.05). These observations also suggest, for the first time, the existence of a cross-talk between AT1 or AT2 receptors in trophoblast and that the reduction in placental AT1 receptors in IUGR may, in part, account for poor placental function in this disorder.

Angiotensin II↗
PubMed1998

Medical, law, and business students' perceptions of the changing health care system.

An unanswered question in previous research on attitudes to health care systems is whether the values held by medical students are unique to them or simply a cohort phenomenon. This study addresses this by measuring values and attitudes on entry to medical school, and comparing them with two other groups whose academic standing at entry and social status are likely to be comparable business and law students. In this paper four substantive areas are dealt with: managed care, cost controls such as rationing, access to care. and the role of the federal government in regulating health care. There was a high level of agreement between the three groups that society should provide health care to all citizens, and that individuals should have appropriate access. There was also a general preference for being treated in a fee-for-service setting. Some differences were that medical students held more negative views about managed care than some of the others. The students tended to disagree on cost controls, particularly on issues that might impact on their own professions. Medical students were more restrictive than others on concepts of rationing health care and with regard to high tech procedures. Thus the results reflect areas of extensive agreement, but also the fact that even at entry students may differ on issues that are likely to have an economic impact on their careers. The relationship of these attitudes to the changing health care system and to theories about professionalism and the state is discussed.

Adult↗