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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed2001

A paradox: urgent BRCA genetic testing.

Diagnostic or predictive testing for germline mutations in cancer predisposition genes is inherently slow as result of both genetic counselling and mutation analysis. The overall time taken for mutation testing is not generally perceived as harmful to the individual and may be positively beneficial in order to permit full reflection on the implication of the genetic test results. However, we present three cases where we considered urgent genetic testing for the presence of mutations in th BRCA 1 and 2 genes to be necessary as the test result would have altered the subsequent clinical management of these individuals or their families.

Breast Neoplasms↗
PubMed2001

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women.

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women Fifteen healthy premenopausal female volunteers underwent weekly nipple aspiration of ductal fluid from both breasts during two menstrual cycles to investigate the variability of the cellular profile of the ductal fluid. Ductal fluid was successfully obtained using breast massage and nipple-areolar suction from 247/280 (89%) breasts. 83% of samples available for cytological analysis were cellular and 30% of cellular aspirates contained ductal epithelial cells identified using standard morphological criteria. No significant variation in cell number or cell type was identified during the menstrual cycle. All samples tested had an 'H' score of zero for oestrogen receptor. Seven out of 14 women expressed the proliferation marker Mcm-2 in the cells of at least one of the specimens, with no evidence of a menstrual cycle influence on expression. In conclusion, the cellular profile of breast ductal fluid did not vary consistently during the menstrual cycle, permitting future breast cancer screening studies incorporating serial nipple aspirations to be performed independent of the phase of the cycle.

Adult↗
PubMed2001

Rectal temperature measurement results in artifactual evidence of selective brain cooling.

Selective brain cooling (SBC) is defined as a brain temperature cooler than the temperature of arterial blood from the trunk. Surrogate measures of arterial blood temperature have been used in many published studies on SBC. The use of a surrogate for arterial blood temperature has the potential to confound proper identification of SBC. We have measured brain, carotid blood, and rectal temperatures in conscious sheep exposed to 40, 22, and 5 degrees C. Rectal temperature was consistently higher than arterial blood temperature. Brain temperature was consistently cooler than rectal temperature during all exposures. Brain temperature only fell below carotid blood temperature during the final few hours of 40 degrees C exposure and not at all during the 5 degrees C exposure. Consequently, using rectal temperature as a surrogate for arterial blood temperature does not provide a reliable indication of the status of the SBC effector. We also show that rapid suppression of SBC can result if the animals are disturbed.

Animals↗
PubMed2001

Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I).

Increased stiffness of the conduit arteries has been associated with increased risk of death and cardiovascular death in a number of populations. None of these populations, however, are fully representative of the US population. The cohort examined in the First National Health and Nutrition Examination Survey (NHANES I) that was free of overt cardiovascular disease was selected to be representative of the US population. We assessed and quantified the increased risk of death associated with elevated pulse pressure in this population. A cohort of 5771 subjects from NHANES I was used to determine the value of adding pulse pressure to standard cardiovascular disease risk factors for assessment of the risk of death during a mean follow-up period of 16.5 years. Analyses were performed by use of the SUDAAN statistical package for performing Cox proportional regression, logistic regression, and other standard methods in complex, weighted samples. Pulse pressure increased with increasing age, body mass index, cholesterol level, and mean arterial pressure. With increasing pulse pressure, the percentage of cigarette smokers decreased and the percentage of diabetics increased. Despite these associations with known risk factors, pulse pressure was independently predictive of an increased risk of death from cardiovascular disease, coronary heart disease, and all-cause mortality. It provides independent prognostic information beyond that provided by known risk factors that were evaluated in this study, including the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension classification. A 10 mm Hg increase in pulse pressure in persons 25 to 45 of age was associated with a 26% increase in risk of cardiovascular death (95% confidence interval [CI], 5 to 50) and with an 10% increase (95% CI, 2 to 19) in persons 46 to 77 years of age. In a cohort designed to be representative of the US population, elevated pulse pressure has been shown to provide independent prognostic information. This variable may be a marker for the extent of vascular disease and may contribute to the occurrence of clinical events.

Adult↗
PubMed2001

Infertility and testicular defects in hormone-sensitive lipase-deficient mice.

The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, where a specific 120-kDa testis-specific isoform is expressed, is unknown. To study this, we examined the fertility and testicular histology of gene-targeted hormone-sensitive lipase-deficient mice. Homozygous hormone-sensitive lipase-deficient male mice are infertile and have decreased testis weights; female homozygotes are fertile. Testicular abnormalities, detected at the light and electron microscopic levels, included the presence of multinucleated round and elongating spermatids, vacuolization of the seminiferous epithelium, asynchronization of the spermatogenic cycle, sloughing of postmeiotic germ cells from the seminiferous epithelium into the lumen, and a marked reduction in the numbers of late spermatids. Extensive nuclear head deformation was noted in late spermatids as well as the sharing of a common acrosome in multinucleated cells. In some multinucleated cells, nuclei were separated from their acrosomes, with the acrosomes remaining attached to areas of ectoplasmic specializations, suggesting defects in intercellular cytoplasmic bridge integrity. Although the lumen of the epididymis was essentially devoid of spermatozoa and filled instead with spherical degenerating cells, the epididymal epithelial cells appeared normal. The few late spermatids present in the epididymis were abnormal. There was no morphological evidence, as judged by the absence of lipid droplets of triacylglycerol or cholesteryl ester accumulation in the testis. Together, the data suggest that hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility. We speculate that a metabolite downstream from the hormone-sensitive lipase reaction may be essential for membrane stabilization and integrity in the seminiferous epithelium and, in particular, may play an important role in the maintenance of intercellular cytoplasmic bridges between postmeiotic germ cells.

Animals↗
PubMed2001

Coping, burnout, and emotion in staff working in community services for people with challenging behaviors.

Staff in mental retardation services identify challenging behavior as a significant source of work-related stress. However, there has been little examination of the psychological processes that may explain an association between challenging behavior and staff stress. In the present study, direct-care staff (N = 83) from five community services completed a questionnaire on their emotional reactions to aggressive behavior, the coping strategies that they employ, and their experience of burnout. Staff more frequently reported using adaptive strategies than maladaptive ones to cope with aggressive behavior. Regression analyses showed that staff disengagement and adaptive coping strategies and their emotional reactions to aggressive behavior predicted burnout scores. Implications of these results for future research and for staff mental health are discussed.

Adaptation, Psychological↗
PubMed2001

Developing palliative care services in regional areas. The Ipswich Palliative Care Network model.

BACKGROUND: Although there are over 350 palliative care services present in Australia and New Zealand, the distribution of these is patchy. Patients in some regional and rural areas have little or no access to specialist services, and manage with the enthusiasm and general expertise of local practitioners. OBJECTIVE: This paper discusses the problems encountered in maintaining skills in palliative care in the face of small patient numbers and poor resources, and describes a solution that was developed in Ipswich, Queensland. DISCUSSION: The twin problem of GP skills maintenance and adequate community service provision in palliative care can be overcome by developing a general practice based service in conjunction with local health authorities and the community. Highlighting the benefits to the health authority and the community of maximal general practitioner involvement is the most important lever in securing cooperation.

Australia↗
PubMed2001

General practice research. Problems and solutions in participant recruitment and retention.

BACKGROUND: Increasing interest in general practice research, especially postal surveys, has been met with decreasing response rates. Prospective, longitudinal surveys pose additional concerns for general practice researchers, one of the major problems being sample attrition after project commencement. OBJECTIVE: This article draws on the authors' experiences from seven studies conducted by them to identify useful strategies for researchers who need to recruit general practitioners and/or their patients, with particular reference to retaining participants across time. A list of issues, lessons learned and possible strategies was developed which, although not exhaustive, probably reflects those commonly encountered in many general practice studies. DISCUSSION: The issues identified here are not necessarily new, but it is useful to revisit such issues and to review and reiterate methods and processes, as even experienced researchers encounter problems from time to time. Studies involving prolonged participation especially, require diligent consideration of likely recruitment/retention problems.

Australia↗
PubMed2001

Skin flaps.

Explore the source record for details and available documents.

Dermatologic Surgical Procedures↗
PubMed2000

A new disease-burden method for estimating the impact of outdoor air quality on human health.

Urban air quality is a serious problem, with an estimated 40 million people in Europe exposed to exceedences of existing WHO air-quality guidelines, with prospects of further declines in air quality due to projected growth in motor vehicle traffic. Air-quality management strategies, underpinned by legislation are attempting to combat this problem. To support such strategies, assessment of the costs and benefits of remedial measures is required, including an assessment of the impact of urban air quality on human health. This paper describes a disease burden estimation approach, developed to assess 'health gain' from recreational water quality improvement, and its application to urban air quality and incidence of respiratory disease. The method represents an improvement over existing disease-burden estimation techniques applied to air quality, in that by considering the probability density function of pollutant concentrations, improved estimates of exposure and hence disease burden, and also 'health gain' from air-quality improvement, are possible. Estimations of mortality advanced by fine particulate matter (PM10) are presented for five UK cities. Implications of the method for disease burden and air-quality standards are discussed. The utility of integrating the disease-burden assessment model with linked dynamic models of land-use, vehicle movement and pollutant dispersion, as a means to identify remedial strategic planning initiatives, is highlighted.

Air Pollutants↗
PubMed2000

Identification of a novel mechanism for endotoxin-mediated down-modulation of CC chemokine receptor expression.

In the present study, we explored the molecular mechanisms by which bacterial endotoxin (LPS) mediates the down-regulation of CCR2 receptors on human monocytes. We found that LPS induced a marked reduction in CCR2 cell surface protein levels which was blocked by pretreatment with the tyrosine kinase inhibitors genistein and herbimycin A. The effector mechanism underlying LPS-induced CCR2 down-modulation appears to involve the enzymatic activity of proteinases since Western blot analysis of LPS-stimulated monocytes revealed the degradation of a 38-kDa species corresponding to the CCR2B monomer. In RBL cells expressing the CCR2B-green fluorescent protein (GFP) fusion chemokine receptor, LPS stimulated the internalization and degradation of CCR2. The serine proteinase inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone blocked LPS-induced down-modulation of CCR2 in monocytes and CCR2B-GFP in RBL cells. This work describes a previously uncharacterized mechanism for CC chemokine receptor down-modulation that is dependent upon tyrosine kinase activation and serine proteinase-mediated receptor degradation and may provide further insight into the mechanisms of leukocyte regulation during immunological and inflammatory responses.

Chemokine CCL2↗
PubMed2000

Determination of succinylcholine in plasma by high-pressure liquid chromatography with electrochemical detection.

The plasma concentration of the neuromuscular blocking drug, succinylcholine, is difficult to measure. We have measured concentrations of the breakdown product of succinylcholine, choline, to assess whether choline concentration gives an accurate measure of succinylcholine concentration. Choline concentration was measured by HPLC and electrochemical detection in two blood or plasma samples, one in which succinylcholine hydrolysis was inhibited by 10(-5) M physostigmine and another in which succinylcholine was completely hydrolysed in 20 min by 200 mU butyrylcholinesterase at 37 degrees C. The difference in choline content between the two samples gives the succinylcholine concentration. Ninety-five per cent recovery of choline was achieved. Choline standard curves were linear from 156 pmol ml-1 to 200 nmol ml-1. Within-day and between-day mean coefficients of variation for succinylcholine hydrolysis were small (mean (SD) 3.7% (1.2%) and 3.8% (1.6%), respectively). We conclude that this method of measuring succinylcholine concentration in blood is accurate, repeatable and relatively easy.

Calibration↗
PubMed2000

Medical and veterinary students' structural knowledge of pulmonary physiology concepts.

PURPOSE: The goal of this study was to assess quantitatively medical and veterinary students' knowledge structures of 12 pulmonary physiology concepts before and after receiving a focused instructional block. The "goodness of fit" and internal consistency reliability of the students' knowledge structures were evaluated. Indexes of the students' structural knowledge were correlated with customary measures of student learning of the same concepts. METHOD: Knowledge structures were assessed using a questionnaire that requested similarity judgments about all possible pairs of the concepts: n(n - 1)/2 = 66 pairs. The similarity judgment data were analyzed using the individual differences (INDSCAL) model of multidimensional scaling (MDS). Dimension weights for individual students were then correlated with their final examination scores. RESULTS: A four-dimensional MDS solution provided the best structural fit to the pairwise concept-similarity data. Dimension 1 ranges from control of breathing to lung gas exchange. Dimension 2 ranges from control of breathing to respiratory mechanics. Dimension 3 separates perfusion from diffusion. Dimension 4 addresses ventilatory control. Hierarchical concept clusters are located within this framework. However, indexes of structural learning did not correlate with other measures of knowledge about the same concepts. CONCLUSION: The study outcomes, in contrast to research in other fields, suggest that structural knowledge in this domain differs from knowledge assessed by standard examinations. Further research involving other basic science or clinical concept sets is needed to verify or refute this finding.

Education, Medical↗
PubMed2000

North American Indian cirrhosis in children: a review of 30 cases.

BACKGROUND: North American Indian childhood cirrhosis (NAIC) is a distinct, rapidly evolving form of familial cholestasis found in aboriginal children from northwestern Quebec. This is a retrospective review of the 30 patients treated in Quebec since the discovery of NAIC in 1970. METHODS: The clinical records and histologic samples from 30 patients were reviewed. Extensive metabolic, biochemical, viral, genetic, and radiologic studies were performed in most patients. RESULTS: Genetic analysis suggests autosomal recessive inheritance and a carrier frequency of 10% in this population. Gene mapping studies showed that the NAIC gene is located on chromosome 16q22. Typically, patients have neonatal cholestatic jaundice (70%) or hepatosplenomegaly (20%) with resolution of clinical jaundice by age 1 year but persistent direct hyperbilirubinemia. Portal hypertension was documented in 29 patients (91%). Variceal bleeding (15 patients, 50%) occurred as early as age 10 months. Surgical portosystemic shunting was performed in 13 of these 15 patients (87%); 4 (31%) rebled after 1 to 5 years. Fourteen patients died (47%). In 10 (71%), liver disease was the cause. Four children died of liver failure before liver transplantation became available. In transplanted livers, no recurrence of NAIC was observed after 1 to 10 years. Recognized infectious, metabolic, toxic, autoimmune, and obstructive causes of cirrhosis have been eliminated. The histologic features of NAIC show early bile duct proliferation and rapid development of portal fibrosis and biliary cirrhosis, suggesting a cholangiopathic phenomenon. CONCLUSION: Together with gene mapping studies showing that the NAIC gene is different from those of other familial cholestases, these observations suggest that NAIC is a distinct entity that could be classified as "progressive familial cholangiopathy."

Adolescent↗
PubMed2000

Quantitative concept mapping in pulmonary physiology: comparison of student and faculty knowledge structures.

Quantitative concept mapping, in contrast with qualitative approaches, is rigorous scientifically and permits statistical analyses of data about concept learning. This study extends past quantitative research on the structure of student concept learning in pulmonary physiology. Pathfinder scaling is used to derive concept maps for medical and veterinary students and their physiology instructors at Northwestern University and the University of Wisconsin, respectively. The concept maps are evaluated for coherence (internal consistency), student-instructor similarity, and correlation of similarity with final examination scores. Results show that student and instructor concept maps are coherent and that student concept maps become increasingly similar to instructors' concept maps from pre- to postinstruction, but that student-instructor concept map similarity does not correlate with examination performance. Research outcomes are discussed concerning possible sources of variation in student and faculty knowledge structures.

Data Collection↗
PubMed2000

False positive 131I whole body scans in thyroid cancer.

Well differentiated thyroid cancer is a rare disease in the UK. It is the only cancer which, having metastasized, remains curable by radioisotope therapy with 131I. The main indication for administering repeat doses of 131I is the appearance of abnormal uptake in a whole body scan following diagnostic or therapeutic 131I administration. False positive scans, showing the presence of 131I uptake in the absence of residual thyroid tissue or metastases can occur, although they are uncommon. Unless recognized as a false positive, 131I uptake may result in diagnostic error and lead to administration of an unnecessary therapy dose. We describe a series of nine patients in whom the scans showed false positive uptake of 131I, including cases where the cause of the uptake is still uncertain. We demonstrate the common sites of false positive uptake, discuss the underlying mechanisms and suggest a systematic approach to the interpretation of whole body scans in order to prevent unnecessary treatment with 131I.

Adolescent↗
PubMed2000

Absence of selective brain cooling in free-ranging zebras in their natural habitat.

We used implanted miniature data loggers to measure brain and arterial blood temperatures in three free-ranging zebras (Equus burchelli) in their natural habitat, every 5 min for 9 days. The animals experienced globe temperatures exceeding 40 C, and radiant heat load of about 1000 W m-2. Arterial blood exhibited a moderate amplitude (1.7 C) nychthemeral rhythm, with an acrophase at 19.00 h and a nadir late in the morning, at 10.00 h. Brain temperature consistently exceeded blood temperature, on average by 0.2-0.4 C, and changes in brain temperature closely tracked changes in blood temperature. There was no evidence of selective brain cooling, even during the hyperthermia which followed surgery or that associated with intense, short-duration exercise. The relationship between brain and arterial blood temperatures in free-ranging zebras was unlike that reported for horses in the laboratory. Our results do not support the view that mammals lacking a carotid rete can achieve selective brain cooling.

Animals↗