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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 631 records · Page 35Linked to original sources

Prostatic carcinoma cell DNA content measured by flow cytometry and its relation to clinical outcome.

DNA content of prostate tumour cells has been measured by flow cytometry of cell suspensions prepared from fixed tissue by an enzyme disaggregation technique. Two classes of tumours have been identified: diploid tumours, with a DNA content similar to benign cells and aneuploid tumours with grossly abnormal DNA values. The prognosis for the aneuploid tumours was significantly worse than diploid tumours (P less than 0.001). When ploidy is combined with histological grading, here using the Gleason numerical system, it is possible to predict which patients, whatever their age at diagnosis, will die from their tumour and which patients will probably die before their tumour kills them. With these facts it is possible to select patients for active or expectant treatment.

Aged↗

Length polymorphism in the pro alpha 2(I) collagen gene: an alternative explanation in a case of Marfan syndrome.

A 38 base pair (bp) insertion in the pro alpha 2(I) collagen gene (COL1A2) of a patient with Marfan syndrome has been proposed to be the possible cause of the disease (Henke et al. 1985). However, analysis of this insertion in DNA from the patient in question and from random normal individuals reveals it to be a common polymorphism. We suggest that the 38 bp insertion is not related to the primary defect in this case of Marfan syndrome.

Base Sequence↗

Total body calcium measurements using neutron-activation analysis in Cushing's syndrome.

Total body calcium content (TBCa) was estimated by in vivo neutron activation analysis in 16 patients (14 female, 2 male) with active Cushing's syndrome, pituitary driven in all but two cases. Apart from being nonreproductive, patients were unselected. TBCa was below the predicted young normal value in all patients (mean +/- SD, 85.2 +/- 5.8% of predicted, P less than 0.01 vs. predicted) and in 13 of the 16 patients, was also below the predicted value when allowance was made for expected postmenopausal skeletal losses (mean +/- SD, 92.7 +/- 12.5% of predicted, P less than 0.02). However, individual values of TBCa were significantly lower (P less than or equal to 0.05) than the predicted normal range, corrected for postmenopausal losses, in only 3 patients (19% of the group). Initial TBCa apparently was not related to duration of the disease or to current urinary-free cortisol levels. At presentation, radiographic signs of significant osteoporosis (multiple vertebral and/or rib fractures) were present in four patients, three of whom had subnormal or borderline TBCa compared with the young normal predicted range. TBCa measurements were repeated in 9 patients 1-10 years after successful treatment, and were generally unchanged. During this period, only one vertebral fracture (consistent with simple postmenopausal osteoporosis) appeared in these patients. We conclude that bone mass tends to be low in newly diagnosed Cushing's syndrome, but that significant reduction beyond expected postmenopausal losses is relatively uncommon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Seminal plasma composition in budgerigars (Melopsittacus undulatus).

Seminal plasma composition was studied in budgerigars. Semen was obtained from adult male budgerigars by applying gentle pressure to both sides of the cloaca. Pooled samples were centrifuged at 15,000 g for 2 min, and the seminal plasma separated for biochemical analysis. Osmolality, Na+, K+, Cl-, pH, glucose and fructose values were determined. The biochemical composition of budgerigar seminal plasma obtained in this study was: Osmolality 329.9 +/- 14.5 mOs/kg; Na+ 158.6 +/- 8.4 mEq/l; K+ 16.39 +/- 6.24 mEq/l; Cl- 109.2 +/- 7.4 mEq/l; pH 8.20 +/- 0.18 glucose 4.25 +/- 0.96 mmol/l; fructose 0.59 +/- 0.29 mmol/l. The results are discussed in relation to the values reported for the domestic fowl. This forms part of a reproductive biology study of non-domesticated avian species.

Animals↗

Increase in skin mast cells following chronic house dust mite exposure.

Application of inhalant allergens in high concentration to the mildly abraded skin of sensitive patients with atopic dermatitis gave rise to eczematous skin responses at 48 h. These lesions, infiltrated by basophils, eosinophils and mononuclear cells, are examples of cutaneous basophil hypersensitivity. Repeated application of allergen induced an increase in skin mast cells by 6 days, the mast cell hyperplasia replacing the earlier basophil infiltration. No electron microscopic evidence of mast cell heterogeneity among the recruited cells was found.

Administration, Topical↗

Objective responses to ketoconazole therapy in patients with relapsed progressive prostatic cancer.

The contribution of adrenal androgens to the maintenance and progression of so-called hormone-unresponsive prostatic carcinoma was studied in 20 patients with advanced relapsed disease. The role played by testicular androgens had been negated by prior orchiectomy or concurrent LHRH analogue therapy. Ketoconazole, an antifungal agent which inhibits adrenal and testicular androgenesis, administered in a dose of 400 mg 8-hourly, resulted in optimal suppression of adrenal androgens. The mean serum androstenedione concentration fell from 8.01 +/- 0.84 nMol/l to 1.55 +/- 0.25 nMol/l, P less than 0.001, and serum testosterone from 1.25 +/- 0.14 nMol/l to 0.36 +/- 0.06 nMol/l, P less than 0.01, after 6 months treatment. There was, however, no significant difference between patients receiving 400 and those receiving 200 mg. Androgen suppression resulted in six objective and ten subjective clinical responses. Ablation of both testicular and adrenal androgens can now be achieved using ketoconazole in combination with orchiectomy or LHRH analogues, but the high incidence of side effects may preclude its use in all patients with prostatic cancer. The results of this study support the concept of "total androgen ablation" as primary therapy in advanced prostatic cancer as a possible means of improving survival in this common malignancy.

Acid Phosphatase↗

Bayesian analysis versus discriminant function analysis: their relative utility in the diagnosis of coronary disease.

Both Bayesian analysis assuming independence and discriminant function analysis have been used to estimate probabilities of coronary disease. To compare their relative accuracy, we submitted 303 subjects referred for coronary angiography to stress electrocardiography, thallium scintigraphy, and cine fluoroscopy. Severe angiographic disease was defined as at least one greater than 50% occlusion of a major vessel. Four calculations were done: (1) Bayesian analysis using literature estimates of pretest probabilities, sensitivities, and specificities was applied to the clinical and test data of a randomly selected subgroup (group I, 151 patients) to calculate posttest probabilities. (2) Bayesian analysis using literature estimates of pretest probabilities (but with sensitivities and specificities derived from the remaining 152 subjects [group II]) was applied to group I data to estimate posttest probabilities. (3) A discriminant function with logistic regression coefficients derived from the clinical and test variables of group II was used to calculate posttest probabilities of group I. (4) A discriminant function derived with the use of test results from group II and pretest probabilities from the literature was used to calculate posttest probabilities of group I. Receiver operating characteristic curve analysis showed that all four calculations could equivalently rank the disease probabilities for our patients. A goodness-of-fit analysis suggested the following relationship between the accuracies of the four calculations: (1) less than (2) approximately equal to (4) less than (3). Our results suggest that data-based discriminant functions are more accurate than literature-based Bayesian analysis assuming independence in predicting severe coronary disease based on clinical and noninvasive test results.

Bayes Theorem↗

The effect of single and repeated doses of thiopentone and fentanyl on liver function in the rat.

Single doses (0.3 MAC) of thiopentone or fentanyl did not affect the serum liver enzyme concentrations (SGPT, SGOT) in the rat. 0.3 MAC of fentanyl but not of thiopentone given for six consecutive days led to significantly higher SGPT levels (P less than 0.01) versus the control group. Rats that received repeated injections of thiopentone or fentanyl had significantly higher SGPT levels versus the groups that received one injection (P less than 0.05 and P less than 0.01 respectively). Rats that had repeated injections of thiopentone showed a significantly higher SGOT versus the groups that had one injection of thiopentone, fentanyl or normal saline (P less than 0.01, P less than 0.05 and P less than 0.05 respectively.

Alanine Transaminase↗

Postprandial effects of SMS 201-995 on gut hormones and glucose tolerance.

SMS 201-995 (5-100 micrograms) injected subcutaneously in normal and type-2 diabetic subjects 30 min before a test meal caused dose-related suppression of plasma concentrations of insulin, glucagon, and several regulatory gut peptide hormones (gastrin, gastric inhibitory peptide, pancreatic polypeptide, secretin, neurotensin, and motilin). Effective hormone suppression was achieved even at the lowest dose of 5 micrograms. In the normal subjects SMS caused postprandial hyperglycaemia, but there was no overall deterioration in glucose tolerance in the type-2 diabetic patients. This suggests that counterregulatory hormones play an important part in the metabolic disturbance of type-2 diabetes.

Aged↗

Hyperthyroidism due to non-tumoural inappropriate TSH secretion. Effect of a long-acting somatostatin analogue (SMS 201-995).

Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 micrograms/day). The serum alpha-subunit: TSH molar ratio was less than 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 micrograms injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.

Adult↗