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Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 19 recordsLinked to original sources

Effects of gender and gonadectomy on responses to chronic benzodiazepine receptor agonist exposure in rats.

Gonadal steroid hormones or their derivatives have been shown to modulate the GABA receptor complex and GABA-mediated responses in a manner similar to the benzodiazepines. The present study examines if hormonal status modulates the development of tolerance and/or the neural adaptations in GABAA receptors associated with chronic benzodiazepine exposure. Anticonvulsant effects of diazepam were compared in groups of male, female, orchidectomized, and ovariectomized rats following acute (3 day) and chronic (3 week) exposure to diazepam-filled silastic implants. Results indicated that hormonal status did not significantly modify either the neural levels of drug resulting from the diazepam implants or the diazepam-induced increases in bicuculline seizure thresholds following acute (3 day) exposure. Unlike males and gonad-intact females, ovariectomized rats continued to display elevated seizure threshold values due to the diazepam released from the implants even after chronic diazepam exposure. This suggests that the tolerance to benzodiazepine actions observed in male and intact female rats was prevented by ovariectomy. Analysis of the anticonvulsant effects of additional challenge doses of diazepam in chronic diazepam-treated rats paradoxically suggested that benzodiazepine tolerance developed in all hormone groups. The discrepancies between these two tests of anticonvulsant tolerance may be related to the divergent neural GABAA receptor adaptations seen between hormone groups. Ovariectomized rats displayed a reduction in GABA IC50 values for [3H]bicuculline-thiocyanate binding in cortex following chronic diazepam exposure that was not observed in males or intact females. These results suggest that the diminution of ovarian steroid hormones may modulate the neural GABAergic changes associated with the development of tolerance to benzodiazepine actions during chronic agonist exposure.

Animals

Determination of bone mineral density by dual x-ray absorptiometry in patients with uncemented total hip arthroplasty.

Bone remodeling is an expected sequela with total hip arthroplasty (THA). Although there are several methods of estimating bone response in THA patients from radiographs, there are no accurate and generally accepted methods for quantitative determinations in vivo. In this study, we describe an application of dual x-ray absorptiometry (DXA) for measuring bone mineral content and bone mineral density in the proximal femur following THA. DXA is a noninvasive technique with minimal radiation exposure (< 5 mrem). Various aspects of measurement error (accuracy and reliability) of this application of DXA were determined in a series of studies reported here. Accuracy error (how similar are the measured and actual values) was < 1% determined in bone phantoms of four densities. Precision error (how reproducible are the measurements) was also < 1% at all four densities in the phantoms and was only slightly elevated (0.9-1.5%) in repeated measurements of implanted cadaver femora. Precision error in vivo, determined both from multiple replicates on five patients and from duplicate scans on 30 patients, was further elevated but remained < 5%. Contributions to precision error, rotation of the leg, and interoperator variability were assessed; none was found to elevate precision error appreciably. We suggest that DXA is a feasible method for quantifying bone response following THA, and will allow discrimination of small changes (> 5%) not previously measurable.

Absorptiometry, Photon

Regeneration in the Xenopus tadpole optic nerve is preceded by a massive macrophage/microglial response.

Changes in the optic nerve following a crush lesion and during axonal regeneration have been studied in Xenopus tadpoles, using ultrastructural and immunohistological methods. Degeneration of both unmyelinated and myelinated axons is very rapid and leads to the formation, within 5 days, of a nerve which consists largely of degeneration debris and cells. Immunohistological analysis with monoclonal antibody 5F4 shows that there is a rapid and extensive microglial/macrophage response to crush of the nerve. Regenerating axons have begun to enter the distal stump by 5 days and grow along the outer part of the nerve in close approximation to the astrocytic glia limitans. Between 5 and 10 days after nerve crush, regenerating axons reach and pass the chiasma. Macrophages are seen in the nerve at the site of the lesion within 1 h, and the response peaks between 3-5 days, just before axonal regeneration gets under way.

Animals

Influences of gender, gonadectomy, and estrous cycle on GABA/BZ receptors and benzodiazepine responses in rats.

Benzodiazepines (BZ) and steroid hormone derivatives can potentiate the inhibitory actions of GABA through interactions with the GABAA/BZ/chloride ionophore complex. The present study examines whether the in vivo hormone milieu of rats modulates GABA/BZ receptors and/or benzodiazepine responses. The influences of gender, estrous cycle, and the diminution of steroid levels on GABA/BZ receptors and BZ anticonvulsant responses were tested by comparing these parameters in groups of intact male, intact female, orchidectomized, and ovariectomized rats. The hormonal milieu appears to modulate the GABA recognition site and possibly GABA-related responses in rats. This is evidenced by the decrease in cortical GABAA receptor affinity seen in females compared with other hormone groups and the gender-related difference observed in susceptibility to seizures induced by the GABA antagonist bicuculline. In cycling females, high circulating levels of progesterone were correlated with heightened seizure thresholds, suggesting that progestins serve a protective role in the control of seizure activity. Although a gender-related difference in cortical BZ binding affinity was observed, BZ receptor parameters in several other brain areas and BZ anticonvulsant responses were unaffected by physiological fluctuations in gonadal hormones.

Animals

Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans.

Encapsulated and nonencapsulated cryptococci differ in their activation of the complement system. Incubation of nonencapsulated cryptococci in normal human serum (NHS) initiates both the classical and alternative pathways. This activation is characterized by an immediate, synchronous activation and binding of C3 to the yeast cells. Encapsulated cryptococci activate only the alternative pathway. This activation is characterized by a delayed (4 to 5 min), asynchronous activation and binding of C3. We examined the properties of antibodies in NHS that mediate immediate, synchronous binding of C3 to nonencapsulated cryptococci and zymosan. Adsorption of NHS with nonencapsulated cryptococci or zymosan produced a 4- to 6-min delay in the kinetics for activation and binding of C3 from the adsorbed serum to each respective yeast cell. This delay was similar to the delay observed when nonencapsulated cryptococci or zymosan was incubated in NHS in which the classical pathway was blocked by chelation of Ca2+. Proteins bound to serum-treated nonencapsulated cryptococci or zymosan were eluted and found to be predominantly immunoglobulin G (IgG), with lesser amounts of IgM. The eluted IgG could restore to adsorbed serum the rapid early kinetics for activation and binding of C3 characteristic of classical pathway initiation. Cross-adsorption showed that there was considerable cross-reactivity between the antibodies which restored rapid, early activation kinetics to NHS adsorbed with zymosan or nonencapsulated cryptococci. Encapsulated cryptococci were unable to adsorb the antibodies from NHS that mediated the rapid, early activation and binding of C3 to zymosan and nonencapsulated cryptococci. The latter results show that occlusion of antigenic sites at the cryptococcal cell wall is a newly recognized property that can be added to the repertoire of biological activities of the cryptococcal capsule.

Adsorption

Comparison of DNA fingerprints and somatic serotypes of serogroup B and E Pasteurella multocida isolates.

The DNA fingerprint profiles and somatic serotypes of 71 Pasteurella multocida capsule serogroup B isolates, 13 capsule serogroup E isolates, and 16 somatic reference serotype strains were compared. Each of the 16 reference somatic serotypes had a unique DNA fingerprint profile with the HhaI restriction endonuclease. Fifty-four serogroup B isolates (isolated from classical cases of hemorrhagic septicemia) reacted with somatic serotype 2 or 5 antiserum and had DNA fingerprint profiles which resembled that of the serotype 2 reference strain. Seven DNA fingerprint profiles were found among 16 serogroup B strains representing other somatic serotypes. The DNA fingerprints of these isolates were different from the fingerprints of the 16 somatic reference serotype strains. All 13 serogroup E isolates had identical somatic serotypes and identical DNA fingerprint profiles when the HhaI endonuclease was used. The HhaI fingerprint profile of the serogroup E isolates did not match any fingerprint profile of the reference somatic serotype strains. Following DNA profiling with the HhaI endonuclease, the 13 serogroup E isolates were differentiated sequentially with HpaII restriction endonuclease. A descriptive identification epithet for P. multocida isolates was constructed. The descriptive epithet consists of serologic identification and sequential DNA profiles with restriction endonucleases HhaI and HpaII, respectively. DNA fingerprinting of P. multocida is a precise characterization method. In conjunction with serologic typing, it can further classify P. multocida isolates for epidemiologic studies.

Animals

Prevalence and serovars of leptospira involved in equine abortions in central Kentucky during the 1990 foaling season.

A study to determine the prevalence of leptospira-induced abortions in the central Kentucky equine population during the 1990 foaling season and to determine the leptospira serovars responsible was conducted. From July 1, 1989 through June 30, 1990, 32 (4.4%) of 726 submissions (fetuses, stillborn foals, and/or placentas) were diagnosed as leptospirosis by the fluorescent antibody test and/or microscopic agglutination test. Attempts were made to isolate leptospires from the fetal tissues and/or the dam's urine in 31 of these cases. Leptospira interrogans serovar kennewicki was isolated from 11 (35.5%) and serovar grippotyphosa from 2 (6.5%) of the 31 cases. Of 12 cases that were culture negative with serologically positive fetal fluids, 8 had titers against serovar pomona, 1 against bratislava, 1 against grippotyphosa, 1 against hardjo, and 1 against both bratislava and pomona.

Abortion, Veterinary

Home from hospital: a survey of hospital discharge arrangements in Northamptonshire.

The timeliness and adequacy of inpatient discharge communication between hospitals and general practitioners (GPs) in Northamptonshire was examined by a postal questionnaire survey of GPs of patients recently discharged from hospital, with the aim of improving the co-ordination of discharge procedures, and hence improving continuity of care. The questionnaire measured when and how the GP was informed of the discharge, and examined the adequacy of medical, therapeutic and social details in the discharge documents sent out by the hospital. It was found that 67 per cent of discharges had been notified to the GP by the hospital within five days of discharge. With notable exceptions the discharge documents were considered timely. General practitioners were less satisfied with the adequacy of discharge communication in terms of 'social' topics such as transport needs, social services back-up, and whether a patient with a malignancy knew about his or her diagnosis. The GPs of patients under geriatricians were more satisfied with the quality of discharge documents. Comparison with an earlier study suggested that the speed of communication and involvement of GPs in discharge in Northamptonshire is not as satisfactory as that found in Oxford in 1986. It was concluded that within the county there appear to be models of good practice in terms of discharge communication with GPs. These standards should be adopted by other specialties to match or improve on existing good practice.

Aftercare

Pentoxifylline preserves small-intestine microvascular blood flow during bacteremia.

BACKGROUND: Intestinal mucosal ischemia with subsequent mucosal dysfunction has been implicated in the pathogenesis of ongoing sepsis and multiple systems organ failure. We have previously reported vasoconstriction and hypoperfusion in the intestinal microcirculation during sepsis. Efforts to improve microcirculatory blood flow during sepsis may lead to more effective treatment or prevention of multiple systems organ failure. Pentoxifylline improves survival and visceral organ perfusion in experimental sepsis and hemorrhage. The purpose of this study was to determine whether pentoxifylline would improve microvascular blood flow in the small intestine during bacteremia. METHODS: In vivo videomicroscopy was used to quantitate alterations of the small-intestine microcirculation during Escherichia coli bacteremia in rats pretreated with either intravenous pentoxifylline or saline solution. Systemic hemodynamic and microvascular variables were measured every 15 minutes for 2 hours. RESULTS: Tachycardia and increased cardiac output developed in bacteremic rats while they remained normotensive. Intestinal vasoconstriction and hypoperfusion occurred in bacteremic rats treated with saline solution. Microvessel diameters and blood flow remained within 5% to 10% of baseline in bacteremic rats pretreated with pentoxifylline. Pentoxifylline in nonbacteremic rats resulted in intestinal vasodilation and increased blood flow. CONCLUSIONS: Pentoxifylline prevented small-intestine vasoconstriction and preserved microvascular blood flow during hyperdynamic sepsis. Pentoxifylline in nonbacteremic rats increased microvascular blood flow.

Animals

Acute and chronic hypoxia in rats. I. Effect on organismic respiration, mitochondrial protein mass in liver and succinic dehydrogenase activity in liver, kidney and heart.

The objective of this investigation was to characterize organismic, organ and mitochondrial alterations in rats over the course of 27 days at 0.4 atm. In the adjustment phase (day 1 through 5) a significant decrease in systemic oxygen uptake and body weight (23% of pre-altitude values) occurred. In the acclimating state (day 7 to 27) body weight was regained but oxygen consumption remained depressed. Hematocrit increased hyperbolically from 45% in 0-day rats to 79% in 27-day rats. Liver, kidney and heart weights and total organ protein paralleled the changes observed in body weight. Total organ succinic dehydrogenase activity showed a wave-like oscillation for liver and kidney; activity was decreased in both organs by day 5, showed a transient but significant increase on days 16 through 18 and a return to diminished activity on day 27. Succinic dehydrogenase activity for heart became depressed in the adjustment phase but showed a stable level comparable to pre-altitude values in the accliminating phase, days 7 through 27. Liver mitochondrial protein mass was unchanged from pre-altitude values on days 5 and 27 even though succinic dehydrogenase activity was significantly depressed. Therefore, the changes in succinic dehydrogenase activity are not representative of altered mitochondrial mass but suggest that mitochondrial function was altered.

Adaptation, Physiological

Starvation and refeeding in rats: effect on organismic respiration, cytoplasmic constituents of liver, and succinic dehydrogenase activity in liver, kidney, and heart.

An analysis of starvation and starvation followed by refeeding was undertaken to characterize some organismic, organ, and mitochondrial responses to these two circumstances. Body weight, organismic respiration as well as weight protein and succinic dehydrogenase activity for liver, kidney, and heart were determined over the course of 6 days of starvation and 5 days refeeding for adult male rats. Assays of marker enzyme activities for mitochondria (cytochrome oxidase), lysosomes (acid phosphatase), endoplasmic reticulum (glucose-6-phosphatase), and plasma membranes (5'-nucleotidase) were conducted for liver in addition to quantitations of mitochondrial protein. All enzyme determinations were done on whole tissue homogenates and reported as total organ activity. Liver mitochondria were harvested quantitatively directly from whole liver homogenates by zonal centrifugation for determination of mitochondrial protein. Starvation resulted in a major loss of body weight, organ weight, and organ protein; liver greater than kidney greater than heart. These changes were accompanied by a major reduction in organ succinic dehydrogenase activity; liver greater than kidney. In heart, succinic dehydrogenase was doubled in activity at day 2 of starvation and subsequently diminished to values not significantly lower than controls. In liver, mitochondrial mass (protein) was severely diminished. From analysis of marker enzyme activities, it appeared that lysosomes, endoplasmic reticulum, and plasma membrane were also decreased. Refeeding restored the greatest part of these losses within 5 days.

Animals

Blind man living in normal society has circadian rhythms of 24.9 hours.

A psychologically normal blind man, living and working in normal society, suffered from a severe cyclic sleep-wake disorder. Investigations showed that he had circadian rhythms of body temperature, alertness, performance, cortisol secretion, and urinary electrolyte excretion which were desynchronized from the 24-hour societal schedule. These rhythms all had periods which were longer than 24 hours and indistinguishable from the period of the lunar day.

Adult

Quantitation of mitochondrial DNA, RNA, and protein in starved and starved-refed rat liver.

The purpose of this study was to investigate the problem of mitochondrial biogenesis in rat liver. The approach consisted of isolating mitochondria from control, 6 day starved and 6 day starved-5 day refed rats and comparing their DNA, RNA and protein content. This was performed by isolating the mitochondria by reorienting rate zonal centrifugation in sucrose gradients. It was found that six days of starvation resulted in a loss of 30% of the body weight, 55% of the liver weight, 40% of the mitochondrial protein, 60% of the mitochondrial RNA, but only 20% of the mitrochondrial DNA. It was also shown that refeeding of the rats for five days resulted in a restoration to normal or near normal levels in all the parameters measured. Further experiments employing the incorporation of 3H-TTP into into isolated mitochondria indicated that the maintenance of mitochondrial DNA was not the result of continuous DNA sythesis.

Animals

An introduction to the proficiency examination.

The public's right to quality health care requires that health practitioners be competent to carry successfully the responsibilities of the positions they seek to fill, and that individuals seeking to practice must be evaluated as possessing the required expertise. The proficiency examination is used to judge the possession of such expertise. This article describes the proficiency examination, its characteristics, the basis upon which it is developed, and how it contributes to the assurance that practitioners are competent. Common misconceptions that practitioners may have about the proficiency examination are also discussed. The proficiency examination is defined as a criterion-referenced appraisal of the individual's possession of the performance knowledge and skill competencies required to execute the role responsibilities of the given practitioner generic position.

Clinical Competence