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Biomedical subjects

C A Morton

Publications and source records attributed to C A Morton.

34 records · Page 2Linked to original sources

Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production.

The present objective was to determine whether hydrogen peroxide (H(2)O(2)) increases transvascular albumin clearance and lung weight in an isolated rat lung and whether posttreatment with cAMP-enhancing agents can prevent these increases. Transvascular albumin clearance was assessed by (125)I-labeled albumin clearance ((125)I-albumin flux/perfusate concentration of (125)I-albumin) at a given fluid filtration. Nonlinear regression analysis of transvascular albumin clearance vs. fluid filtration yielded values for the permeability-surface area product (PS) and the reflection coefficient (sigma). H(2)O(2) decreased sigma from a control value of 0.93 to 0.38, did not change PS, and increased lung weight. Posttreatment with isoproterenol, a beta(2)-adrenergic-receptor agonist, reduced the H(2)O(2)-induced decrease in sigma to 0.65 and augmented the increase in lung weight. Posttreatment with CP-80633, a phosphodiesterase 4 inhibitor, further reduced the H(2)O(2)-induced decrease in sigma to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H(2)O(2) increased PS. Therefore, H(2)O(2) increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H(2)O(2)-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.

Adrenergic beta-Agonists↗

Guidelines for management of Bowen's disease. British Association of Dermatologists.

These guidelines for management of Bowen's disease have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

Antimetabolites↗

Clinical accuracy of the diagnosis of cutaneous malignant melanoma.

Diagnostic accuracy for melanoma was determined in a dedicated pigmented lesion clinic. We assessed the impact of duration of experience in dermatology and also the relationship between tumour thickness and accuracy of clinical diagnosis. We reviewed the histopathology request forms and reports for all biopsies generated by the Pigmented Lesion Clinic, Western Infirmary, Glasgow during 1992-94 inclusive. The clinic is staffed by two consultants, one senior registrar and one registrar. Diagnostic accuracy, index of suspicion, sensitivity, specificity and positive predictive value were calculated for the clinic overall, and for each grade of staff. One hundred and sixty-three lesions were diagnosed clinically as melanoma. A histopathological diagnosis of melanoma was made for 128 lesions during this period, 113 of which had been correctly diagnosed before surgery. The diagnostic accuracy for two dermatologists each with > 10 years experience in dermatology was 80%, with sensitivity of 91% and positive predictive value of 86%. Diagnostic accuracy rates for two senior registrars (each with 3-5 years experience) and six registrars (each with 1-2 years experience) were 62% and 56%, respectively. Thin and intermediate thickness melanomas generated the greatest inaccuracy irrespective of clinical experience, although registrars failed to recognize melanoma three times more often than the other groups. We report the diagnostic accuracy for melanoma by trained dermatologists to be higher than previously reported. In comparison with trainees, > 10 years experience in dermatology and exposure to more than 10 melanomas per year appears to be associated with greater diagnostic accuracy. Knowledge of the current clinical diagnostic accuracy at varying levels of experience is essential if the impact of training is to be evaluated. As pigmented lesions of virtually all types can be treated within dermatology departments, dermatologists are the appropriate first point of referral for suspected early melanoma.

Clinical Competence↗

Pruritus and skin hydration during dialysis.

BACKGROUND: Dry skin is frequently observed in uraemic patients and a link with the common complaint of pruritus has been suggested. Objective data on skin dryness in haemodialysed patients is sparse and equivocal. No such information exists for the many patients now receiving peritoneal dialysis. We assessed the prevalence and severity of both pruritus and skin dryness in a uraemic population receiving maintenance dialysis. METHODS: Forty-eight haemodialysis and 24 peritoneal dialysis patients were examined and skin dryness assessed by clinical grading and measurement of stratum corneum hydration using a corneometer. Forty age- and sex-matched controls were also assessed. Several biochemical parameters with possible relevance to pruritus were measured. Regular emollient therapy was prescribed to pruritic dialysis patients and efficacy assessed. RESULTS: Dialysis patients overall had clinically drier skin than controls, especially the peritoneal dialysis group. Stratum corneum hydration levels were significantly reduced in the peritoneal dialysis (P < 0.004), but not the haemodialysis, population. Twenty-seven per cent of haemodialysed and 54% of peritoneal dialysis patients complained of pruritus. Pruritic patients in each dialysis group had significantly lower hydration than non-pruritic patients (P < 0.05). Regular emollient use in pruritic patients produced a marked reduction in severity of pruritus, abolishing the symptom in nine of 21 patients treated. CONCLUSION: Reduced stratum corneum hydration correlates with pruritus in patients on maintenance haemodialysis and peritoneal dialysis, and may be alleviated by simple emollient therapy.

Adolescent↗

Thrombin increases fluid flux in isolated rat lungs by a hemodynamic and not a permeability mechanism.

Alpha-Thrombin increases endothelial protein permeability in vitro and induces weight gain in the isolated perfused lung. The objectives of this study were to determine whether thrombin increases endothelial permeability of the isolated perfused rat lung and whether a change in permeability or hemodynamics mediates the gain in lung weight. Endothelial protein permeability was assessed by regression analysis of 125I-labeled albumin clearance vs. fluid flux to determine the permeability-surface area product (PS) and the reflection coefficient (sigma). Thrombin (5 x 10(-8) or 5 x 10(-7) M) did not alter protein permeability from the control values of PS and sigma. Thrombin caused an overall increase in transvascular fluid flux, as depicted by a gain in lung weight. Pulmonary arterial and capillary pressures and arterial and venous resistances increased by 10 min after thrombin injection, and lung weight decreased due to arterial constriction. From 10 to 50 min, pressures and resistances decreased, but capillary pressure and venous resistance decreased to a lesser extent and, as a result, lung weight increased. Pretreatment with BQ-123, an endothelin-receptor antagonist, attenuated the sustained increases in pressures and resistances and the rate of lung weight gain. Indomethacin, a cyclooxygenase inhibitor, had no effect. These findings indicate that the increase in lung weight induced by thrombin results from an elevation of capillary pressure mediated, in part, by endothelin and is not due to an increase in endothelial protein permeability of the isolated perfused rat lung.

Animals↗

Acquired perforating dermatosis in a British dialysis population.

A perforating disorder of the skin developing in association with chronic renal failure and often also diabetes, acquired perforating dermatosis (APD), affects up to 10% of patients receiving maintenance haemodialysis in North America. The prevalence of this condition in British dialysis patients has not yet been ascertained. We have undertaken a skin survey of our dialysis population (n = 80) to determine the prevalence and clinical presentation of APD, with subsequent assessment of disease management and outcome. Of 72 patients who participated in the survey, eight were found to have APD, seven of whom were also diabetic. Skin lesions had developed pre-dialysis in two patients, on commencement of dialysis in one, and after 1-3 years on dialysis in the remaining five. Patients typically presented with pruritic dome-shaped papules with central crusts arising on the trunk and extensor limb surfaces. Histological examination of biopsy specimens revealed two types of lesion, typified by either narrow or broad ulcer craters, each showing perforation of both collagen and elastic fibres. Topical/intradermal steroid or topical retinoid were effective therapies in certain of our patients. Clinical clearance was achieved after 3-12 months of treatment in five patients with improvement in the remaining two patients who received treatment. Of the four patients who were alive at 2-year review, three remained clear, while one patient continued to develop new lesions. We report an 11% prevalence of APD in our dialysis population, suggesting the disorder to be as prevalent in patients with chronic renal failure in Britain as in North America. An association of the disorder with long-standing diabetes was confirmed.

Adult↗

Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease.

The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.

Aged↗

Porokeratosis and Crohn's disease.

We report the cases of three patients with Crohn's disease in whom porokeratosis developed. Disseminated superficial actinic porokeratosis developed in two patients. In one of these patients, the skin lesions arose during an exacerbation of the bowel disease. In the third patient, who had congenital linear porokeratosis, the disseminated superficial form of the disorder developed during the first severe exacerbation of Crohn's disease. A family history of porokeratosis was present in one patient, but no relatives of any of these patients were known to have Crohn's disease. In all three patients, Crohn's disease was limited to the colon.

Adult↗

Contact sensitivity to menthol and peppermint in patients with intra-oral symptoms.

We report 12 cases of contact sensitivity to the flavouring agents menthol and peppermint oil in patients presenting with intra-oral symptoms in association with burning mouth syndrome, recurrent oral ulceration or a lichenoid reaction. The patients were referred from the Glasgow Dental Hospital over a 4-year period for assessment of the possible contribution of contact sensitivity to their complaints. 5 patients with burning mouth syndrome demonstrated contact sensitivity to menthol and/or peppermint, with 1 patient sensitive to both agents, 3 positive to menthol only and 1 to peppermint only. 4 cases with recurrent intra-oral ulceration were sensitive to both menthol and peppermint. 3 patients with an oral lichenoid reaction were positive to menthol on patch testing, with 2 also sensitive to peppermint. 9 of the 12 cases demonstrated additional positive patch test results. After a mean follow-up of 32.7 months (range 9-48 months), of the 9 patients that could be contacted, 6 patients described clearance or improvement of their symptoms as a consequence of avoidance of menthol/peppermint.

Adult↗

The catalytic consequences of experimental evolution. Transition-state structure during catalysis by the evolved beta-galactosidases of Escherichia coli (ebg enzymes) changed by a single mutational event.

1. The first chemical step in the hydrolysis of galactosylpyridinium ions by the evolvant ebg enzyme is less sensitive to leaving-group acidity than in the case of the wild-type ebg enzyme, implying less glycone-aglycone-bond fission at the transition state. 2. The first chemical step in the hydrolysis of aryl galactosides by ebg enzyme is probably less sensitive to leaving-group acidity than in the case of ebg enzyme, possibly as a consequence of resulting in more effective proton donation to the leaving aglycone. 3. alpha-Deuterium kinetic isotope effects of 1.1(0) and beta-deuterium kinetic isotope effects of 1.0(0) were measured for the hydrolysis of galactosyl-enzyme intermediates derived from ebg and ebg enzymes: these effects are not compatible with reaction of the sugar ring through a 4C1-like conformation, or with an ionic glycosyl-enzyme intermediate. 4. The variation with pH of steady-state kinetic parameters for hydrolysis of p-nitrophenyl galactoside by ebg and ebg enzymes and of 3-methylphenyl beta-galactoside, 3,4-dinitrophenyl beta-galactoside and beta-galactosyl-3-bromopyridinium ion by ebg enzyme was measured. The steep, non-classical, fall in activity against p-nitrophenyl galactoside at low pH observed with ebg and ebg enzymes is not observed with ebg enzymes.

Catalysis↗