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Biomedical subjects

A Boulton

Publications and source records attributed to A Boulton.

At least 19 recordsLinked to original sources

Chiari type I malformation and postoperative respiratory failure.

PURPOSE: To present a case of respiratory failure following suboccipital craniectomy for Chiari type I malformation. CLINICAL FEATURES: A 22-yr-old man presented with a two year history of symptoms and signs suggestive of brainstem compression at the level of the foramen magnum. This was confirmed with magnetic resonance imaging. The procedure of suboccipital craniectomy, upper cervical laminectomy and fourth ventricle exploration was performed. Three hours postoperatively the patient experienced episodes of apnea and subsequently became drowsy. Blood gas analysis revealed hypercapnic respiratory failure. Chest X-ray revealed evidence of pulmonary aspiration. The trachea was re-intubated and the lungs ventilated in intensive care for 72 hr. He was discharged home two weeks postoperatively. CONCLUSION: Chiari type I malformation is associated with a number of associated anomalies. These patients are at considerable risk of respiratory depression and bulbar dysfunction in the perioperative period. The anesthetic issues are reviewed and discussed.

Adult↗

Cortisol metabolism in human obesity: impaired cortisone-->cortisol conversion in subjects with central adiposity.

For a given body mass index (BMI), mortality is higher in patients with central compared to generalized obesity. Glucocorticoids play an important role in determining body fat distribution, but circulating cortisol concentrations are reported to be normal in obese patients. Our recent studies show enhanced conversion of inactive cortisone (E) to active cortisol (F) through the expression of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in cultured omental adipose stromal cells; the autocrine production of F may be a crucial factor in the pathogenesis of central obesity. We have now analyzed F metabolism in subjects with BMIs between 20-25 kg/m2 (group A), 25-30 kg/m2 (group B), and more than 30 kg/m2 (group C; n 12 in each group; six males and six premenopausal females; aged 23-44 yr). Glucose/insulin were measured using a 75-g oral glucose tolerance test, and each subject had total body and regional fat (scapular, waist, hip, and thigh) quantified using dual energy x-ray absorptiometry. Urinary total F metabolites (measured by gas chromatography/mass spectrometry) were increased in subjects with obesity [group A, 11,176 +/- 1,530 microg/24 h (mean +/- SE); group C, 13,661 +/- 1,444], although not significantly so (P = 0.08). There was a significant reduction in the urinary tetrahydrocortisol (THF) +/- 5alpha-THF/tetrahydrocortisone (THE) and the cortol/cortolone ratio in obesity (group A vs. C, 1.06 +/- 0.08 vs. 0.84 +/- 0.04 and 0.41 +/- 0.03 vs. 0.34 +/- 0.03, respectively; both P < 0.05). Urinary free F (UFF) excretion was similar in all three groups, as was the UFF/urinary free E (UFE) ratio. The 0900 h circulating F, E, and ACTH pre- and postovernight 1-mg dexamethasone suppression values were similar in all three groups, but a reduction in the generation of serum F from dexamethasone-suppressed values after oral cortisone acetate (25 mg) was evident in both obese groups [e.g. 546 +/- 37 nmol/L in group A vs. 412 +/- 40 in group B (P < 0.05) and 388 +/- 38 in group C (P < 0.01) 180 min post-E]. Insulin resistance was present in groups B and C, but regression analysis revealed no relationship between F metabolites or the THF +/- 5alpha-THF/THE ratio and insulin action (homeostasis model assessment analysis and insulin values in the oral glucose tolerance test). There was, however, a highly significant relationship between the THF +/- 5alpha-THF/THE ratio and BMI (t = -3.44; P < 0.01) and total body fat (t = -2.27; P < 0.05). Stepwise regression analyses indicated an inverse relationship between THF+/-5alpha-THF/THE and scapular and waist fat (t = -2.25; P = 0.03) and a direct relationship with hip and thigh fat (t = 2.42; P = 0.02) in both sexes. The fall in the THF + 5alpha-THF/THE ratio but unchanged UFF/UFE ratio together with impaired F concentrations after oral E indicates inhibition of 11betaHSD1 in subjects with obesity. This results in an increased MCR for F, explaining the increased F secretion rate in obesity in the face of normal circulating F concentrations. 11BetaHSD1 activity is highly related to body fat distribution, with android or central obesity, but not gynoid obesity, associated with reduced activity in both sexes. This reduction in 11betaHSD1 activity raises new questions as to the primary role of 11betaHSD1 in the pathogenesis of insulin resistance and central obesity.

Adipose Tissue↗

The hotspot conversion paradox and the evolution of meiotic recombination.

Studies of meiotic recombination have revealed an evolutionary paradox. Molecular and genetic analysis has shown that crossing over initiates at specific sites called hotspots, by a recombinational-repair mechanism in which the initiating hotspot is replaced by a copy of its homolog. We have used computer simulations of large populations to show that this mechanism causes active hotspot alleles to be rapidly replaced by inactive alleles, which arise by rare mutation and increase by recombination-associated conversion. Additional simulations solidified the paradox by showing that the known benefits of recombination appear inadequate to maintain its mechanism. Neither the benefits of accurate segregation nor those of recombining flanking genes were sufficient to preserve active alleles in the face of conversion. A partial resolution to this paradox was obtained by introducing into the model an additional, nonmeiotic function for the sites that initiate recombination, consistent with the observed association of hotspots with functional sites in chromatin. Provided selection for this function was sufficiently strong, active hotspots were able to persist in spite of frequent conversion to inactive alleles. However, this explanation is unsatisfactory for two reasons. First, it is unlikely to apply to obligately sexual species, because observed crossover frequencies imply maintenance of many hotspots per genome, and the viability selection needed to preserve these would drive the species to extinction. Second, it fails to explain why such a genetically costly mechanism of recombination has been maintained over evolutionary time. Thus the paradox persists and is likely to be resolved only by significant changes to the commonly accepted mechanism of crossing over.

Computer Simulation↗

A survey of contact lens wear among diabetic patients in the United Kingdom.

A survey of attitudes to the fitting of contact lenses to diabetic patients was sent to 1122 optometric, ophthalmological and dispensing members of the British Contact Lens Association; 418 completed questionnaires were analysed. Sixty-two per cent of practitioners considered rigid lenses to be the safest form of lens wear. Most preferred daily lens wear and advised frequent aftercare visits, regular soft lens replacement, special attention to hygiene and restricted wearing time. A survey of 218 diabetic patients attending three diabetic clinics revealed that 3% wore contact lenses, which is a similar percentage to the non-diabetic population. Eight patients had been advised that they could not wear contact lenses because of their diabetes. It is concluded that controlled clinical trials of contact lens wear by diabetic patients are required to supplant anecdotal opinions (such as those reported here) with sound scientific data in order to form a proper rationale for the safe fitting of contact lenses to this group of patients.

Journal Article↗