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Biomedical subjects

A T Evans

Publications and source records attributed to A T Evans.

At least 19 recordsLinked to original sources

Cutaneous malignant melanoma, Scotland, 1979-89. The Scottish Melanoma Group.

The Scottish Melanoma Group (SMG) was established in 1979 to assess mortality from and incidence, features, pathological data, and management of cutaneous malignant melanoma in Scotland. Incidence during the first five years and five-year survival have already been reported. We now have data about incidence and mortality over eleven years in relation to anatomical site and pathological types. From 1979 to 1989, 1354 male and 2459 female patients with primary cutaneous malignant melanomas were first diagnosed in Scottish residents. The incidence rate per 100,000 population per year has increased from 3.4 in 1979 to 7.1 in 1989 for men, and from 6.6 to 10.4 for women. The overall increase over eleven years is 82% (7.4% per year). The greatest rates of increase are seen in lesions of the superficial spreading histogenetic type, arising on the female leg and the male trunk. Following public education programmes started in 1985, the proportion of all melanomas less than 1.5 mm thick has shown a sustained and significant increase. Mortality data for 1661 patients for whom a minimum of five-year follow-up is available shows five-year survival of 71.6% overall (77.6% for women, 58.7% for men). The survival advantage for women persists when appropriate statistical adjustment is made for thickness, ulceration, and histogenetic type. These data are useful in designing public education programmes aimed at both primary and secondary prevention of melanoma and in auditing changes in trends that might result from such education.

Adolescent

Mitotic indices, anti-PCNA immunostaining, and AgNORs in thick cutaneous melanomas displaying paradoxical behaviour.

Those melanomas which fail to behave as expected from their Breslow thickness provide interesting material for study. In an attempt to explain differences in behaviour, we have evaluated three distinct proliferative markers in 23 thick melanomas which failed to metastasize and in 20 well-matched control tumours with documented metastasis. The test group demonstrated significantly greater numbers of mitoses when expressed as an index (mitoses per 1000 cells), whilst no difference was found when the results were expressed in terms of mitoses per unit area. Tumours showing epidermal ulceration possessed higher mitotic indices than those of non-ulcerated lesions. High fractions of PCNA immunolabelling combined with low mitotic indices were observed frequently in the non-metastasizing group. This result and its possible relation to survival advantage are discussed in detail. Both AgNOR numbers and patterns failed to act as prognostic variables--indeed, AgNORs failed to correlate with the other proliferative indices, suggesting that their value as a marker of tumour growth is severely limited.

Cell Division

The case for maintenance of general anesthesia with an inhalational agent.

Control of anesthetic depth is the primary advantage of general anesthesia with inhalational anesthetics as opposed to injectable agents. In addition, inhalational anesthetics provide good intraoperative stress reduction, adequate muscle relaxation, and an elimination pathway (lungs) independent of liver and kidney function. There is little postoperative respiratory depression and no rebound effect, which is sometimes seen with injectable anesthetics. The incidence of anesthetic-related toxicity is rare and is not considered a problem.

Anesthesia, Inhalation

Precautions when using opioid agonist analgesics.

Opioid agonist analgesics are effective drugs for treating postoperative pain. Contraindications for their use are primarily respiratory depression and increased intracranial pressure. Their use may mask potentially serious postoperative complications.

Analgesics

Anesthesia for severe mitral and tricuspid regurgitation.

Anesthesia for mitral or tricuspid regurgitation should be designed to maintain cardiac output by decreasing systemic and pulmonary vascular resistance to aortic and pulmonary outflow, respectively, and by carefully preserving venous return. A moderate increase in heart rate may be helpful with mitral regurgitation; bradycardia should be avoided. Isoflurane, halothane, or opioid anesthesia is preferred.

Anesthesia

The potent irritancy of the daphnane orthoester, resiniferatoxin, exhibits features of a mixed aetiology.

Resiniferatoxin-induced erythema of mouse ear was shown to possess characteristics of both a phorbol ester-mediated response and that induced by the neurogenic irritant, capsaicin. Whereas the response to the phorbol ester, sapintoxin D, was delayed and prolonged, and was augmented by capsaicin pretreatment, the response to resiniferatoxin was biphasic, with the early phase being antagonized by capsaicin desensitization. However, resiniferatoxin was most potent in inducing a delayed erythema which, unlike the capsaicin response, was sensitive to inhibition by low dose hydrocortisone treatment, but not to chronic capsaicin desensitization. It is concluded that the erythema response to resiniferatoxin has a mixed aetiology, which may explain the unique potency of this toxin.

Animals

Perinatal toxicology screening.

Accurate identification of substance abusing mothers and their infants is critical for appropriate medical management as well as the collection of accurate information on the effects of illicit drug use on perinatal morbidity, mortality, and long-term neurobehavioral outcome in the infants. This study examines the differences found using two methods for urine toxicology screening at the time of obstetrical admission to the hospital. The institution of universal screening identified significantly more women than were previously identified through the use of a risk-directed protocol (P less than .0001). Women identified using either protocol were significantly more likely than toxicology-negative women to have had poor prenatal care and to have smoked and used alcohol during pregnancy (P less than .001). In the population studied, the multiple criteria needed to accurately identify mothers with positive-toxicology screens would also include screening over one half of the toxicology-negative mothers.

Female

Creatine kinase and its MB isoenzyme in the third trimester and the peripartum period.

Forty-nine normal pregnant women were recruited late in the third trimester for serial determinations of creatine kinase (CK) and its MB isoenzyme fraction (CK-MB) at four different times: (1) on recruitment between 36 and 40 weeks' gestation, (2) on admission in active labor, (3) immediately after delivery, and (4) on the first postpartum day. In the patients with vaginal delivery (n = 43) total CK was significantly elevated at time 4 compared with times 1, 2 and 3 (P value < .0001). CK-MB fraction was also significantly elevated at time 4 compared with times 1, 2 and 3 (P value < .0001). In 35.7% of the patients at time 4, CK-MB was sufficiently elevated to give the laboratory interpretation of "borderline" or "consistent with a myocardial infarction," even though none of the patients had cardiac symptoms or complications. A review of the literature shows that CK-MB is found not only in myocardium but also in uterus and placenta. The implication of this study is that elevations in total CK and CK-MB should be used with caution during the peripartum period to diagnose myocardial ischemia or infarction.

Adult

Activation of the PKC-isotypes alpha, beta 1, gamma, delta and epsilon by phorbol esters of different biological activities.

Phorbol esters, tetradecanoylphorbolacetate, sapintoxin-A, 12-deoxyphorbol-phenylacetate, 12-deoxyphorbol-phenylacetate-20-acetate, thymeleatoxin and resiniferatoxin were investigated for their abilities to activate the PKC-isotypes alpha, beta 1, gamma, delta and epsilon. PKC-isotypes were grouped into two classes on the basis of Ca2+ requirements for activation by phorbol esters; alpha, beta 1, and gamma being Ca(2+)-dependent forms and delta and epsilon being Ca(2+)-independent. PKC-isotype selective activation by phorbol esters was observed in that SAPA failed to activate PKC-delta up to a concentration of 1000 ng.ml-1 and DOPPA only activated PKC-beta 1 over the same range of concentrations.

Animals

NADPH-oxidase activation by protein kinase C-isotypes.

The cell free activation of NADPH-Oxidase in membranes of mouse peritoneal macrophages by purified PKC-isotypes was investigated. Unstimulated intrinsic activity of PKC-isotypes showed little dependence on Ca2+ for activation of the oxidase. In the presence of TPA, the activation of the oxidase was greatly enhanced, and alpha-, and gamma-subtypes were strongly Ca2+ dependent in this system. Beta-, delta- and epsilon-subtypes were active both in the presence and absence of free Ca2+ ions. The results suggest that at resting Ca2+ levels certain PKC-isotypes can activate NADPH-oxidase.

Animals

A critical evaluation of AgNOR counting in benign naevi and malignant melanoma.

There is considerable variation in the quoted mean numbers of AgNORS per nucleus for benign melanonaevi and malignant melanomas. This is partly attributable to different approaches to AgNOR counting. This study summarizes our experience in devising an optimal technique for counting AgNORs. We show that it is essential to count intra-nucleolar AgNORs in addition to those lying outside the nucleolus to obtain clear separation of naevi from melanoma. Although this seems an onerous task, we further demonstrate that a maximum of only 30 nuclei need to be counted to obtain a mean AgNOR count per nucleus which is representative of the whole lesion. This compares with the arbitrary figure of 100 nuclei chosen by most workers. Only by optimizing and standardizing all aspects of the AgNOR technique including fixation, staining, and counting will mean AgNOR counts per nucleus become a useful quick, reproducible method which can be applied to lesions which pose diagnostic problems such as borderline melanocytic lesions.

Cell Nucleolus

Re-evaluating silver-stained nucleolar organizer regions (AgNORs) in problematic cutaneous melanocytic lesions: a study with quantitation and pattern analysis.

Previous studies enumerating AgNORs in cutaneous melanocytic lesions have produced inconsistent results. It is probable that such inconsistencies arise from differences in fixation, staining technique, and counting strategies. Our group, having demonstrated an improved method of silver staining and having optimized counting, is now able to reconsider the role of AgNORs in evaluating borderline melanocytic lesions. Diagnostic problems similar to those encountered in routine practice have been examined. It is shown that only by counting intra- and extranucleolar AgNORs in combination with assessing the pattern of AgNOR dispersal is it possible to (1) discriminate dysplastic naevi from melanoma and (2) distinguish Spitz naevi and pigmented spindle cell naevi from melanoma. An analysis of AgNOR numbers alone results in considerable overlap between the groups studied. The value of assessing patterns of AgNOR dispersal within and outside clustered nucleolar structures is emphasized. Lesions labelled as minimal deviation melanoma (by experts in dermatopathology) were also investigated. The majority of these specimens form a distinct group lying apart from control naevi and melanomas. This finding, whilst of interest, is difficult to evaluate because of poorly defined diagnostic criteria.

Cytological Techniques

Confidence intervals for post-test probability.

Confidence intervals are a natural way to describe the uncertainty of post-test probability in diagnostic tests. We consider confidence intervals for two different scenarios. At a site, for example, hospital emergency room or student health centre, with measured values of disease prevalence, sensitivity and specificity available, the confidence interval is similar to results in the literature, but at a site where measured values of these indices are unavailable, we develop a method, using the values of disease prevalence, sensitivity and specificity from other sites, to obtain a confidence interval for post-test probability. We use the diagnosis of strep throat to illustrate the results. We also obtain confidence intervals from simulations to compare with the results of both scenarios.

Adult