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Biomedical subjects

S Cowan

Publications and source records attributed to S Cowan.

16 recordsLinked to original sources

Bioelectrical impedance analysis in the measurement of the body composition of surgical patients.

The evaluation of nutritional status in surgical patients remains a difficult problem. Bioelectrical impedance analysis (BIA) is a new method of body composition analysis which is easily performed at the bedside. This study determined the accuracy of BIA in the measurement of total body water (TBW) and potassium (TBK) in a heterogeneous group of surgical patients. The resistance and reactance components of impedance were measured with a whole body impedance analyser. Tritiated water dilution and whole body monitoring were the reference methods for TBW and TBK analysis. With the BIA technique the coefficient of variation for the estimation of TBW was 8.1 per cent and for TBK was 6.4 per cent. Allowing for the errors of the reference methods these results show that BIA is of limited value in the estimation of TBW but may provide a useful index of TBK.

Adult

The effects of renzapride, a novel prokinetic agent, in diabetic gastroparesis.

Gastric emptying was measured in 9 diabetic patients with autonomic neuropathy (Group 1) and 8 normal controls (Group 2) on 4 occasions after swallowing placebo, 0.5, 1.0 or 2.0 mg of the newly developed prokinetic drug renzapride given double-blind and in random order. The liquid component of the test meal was labelled with In113m and the solid with Tc99m. Liquid emptying was uni-exponential. Solid emptying comprised an initial lag phase, followed by a linear component. Following placebo, the mean lag phase of solid emptying was 40 +/- 7 (S.E.M.) min in Group 1 and 16 +/- 2 min in Group 2 (P less than 0.01). In Group 1 subjects renzapride reduced the mean lag phase by 20-26 min at all doses (P less than 0.01). No effect was seen in Group 2. The linear rate of solid emptying was similar in both groups (0.9 +/- 0.1 and 1.0 +/- 0.2%/min) and was not altered by renzapride. Mean liquid t1/2 was similar in Groups 1 and 2 after placebo (30 +/- 6 and 29 +/- 4 min, respectively) and was decreased with increasing doses of renzapride in both groups. No adverse effects were encountered in any subjects. Renzapride may be useful in the treatment of diabetic gastroparesis.

Adult

PREOP: development of an evidence-based expert system to assist with preoperative assessments.

PREOP is a prototype expert system that is designed to provide physicians with evidence-based recommendations concerning the assessment and care of patients with comorbid medical problems who are about to undergo surgery. The knowledgebase for this system is currently undergoing transition from the conventional advice of medical experts, which is variably related to evidence published in the medical literature, to a more formal approach in which the best available evidence is used for each recommendation and the quality of the evidence made apparent to the user. This work seeks to address important questions concerning improvement of the information contained in expert knowledgebases, namely, how to find and recognize new evidence when it is published, how to assess the quality of evidence in a uniform and efficient fashion, how to replace evidence in the knowledgebase efficiently when it has been superseded by higher quality evidence, and how to represent evidence in a manner that is most valuable for the user.

Decision Making, Computer-Assisted

Estrogen and progesterone receptors in ovarian cancer.

To determine whether steroid hormone receptor expression is clinically relevant in ovarian cancer, cytoplasmic and nuclear estrogen (ER) and progesterone (PR) receptor levels have been measured and their concentration calculated by Scatchard analysis. Of 89 samples from patients with non-pretreated epithelial ovarian cancer, 33% were ER-positive, PR-positive (ER+PR+) and 40% ER-negative, PR-negative (ER-PR-); 20% were ER+PR-, and 7% ER-PR+. There was no correlation between receptor status and patient age, menopausal status, or tumor grade, although serous tumors were more likely to be ER+. The incidence of PR+ tumors was highest in early disease and decreased with increasing International Federation of Gynecology and Obstetrics (FIGO) stage. Survival of patients with advanced disease (FIGO Stages IIC, III, or IV) was significantly prolonged by optimal initial cytoreductive surgery (P = 0.002), platinum therapy (P = 0.003), and tumor expression of PR (P = 0.009). On multivariate analysis, PR positivity was still associated with improved survival, although this did not retain statistical significance (P = 0.09).

Adult

Androgen receptors in transitional cell carcinoma.

Androgen receptors were measured in transitional cell carcinoma tissues obtained from 13 patients with bladder tumours and 3 patients with ureteric tumours. Scatchard analysis of binding of mibolerone, a synthetic androgen, was used for receptor measurement. None of the patients were receptor positive. This study suggests that human male hormones do not play any direct role in the malignant transformation of human transitional cell epithelium.

Aged

Androgen receptors--a method to measure functional behaviour in human prostatic cancer.

Androgen receptors were measured in soluble and nuclear fractions of tissues obtained from 25 patients. A method using mibolerone, a synthetic androgen, as a ligand is described. This method, which includes the presence of excess ORG 2058 to eliminate interaction with progesterone receptors, gives a reliable determination of androgen receptor content and has been used to predict response to hormonal treatment. However, the results suggest that the presence of functional receptor is not, in itself, a sufficient index of hormonal dependence of the tumour.

Aged

The cytostatic effects of alpha-interferon may be mediated by transforming growth factor-beta.

There is some evidence to suggest that transforming growth factor-beta (TGF-beta) mediates the cytostatic effects of the anti-oestrogen tamoxifen. In this study we have demonstrated that alpha-interferon has a significant anti-proliferative effect on the oestrogen receptor-positive human breast cancer cell line ZR-75. There is decreased phenotypic expression of the oestrogen receptors (to about 30% of control values) and increased TGF-beta mRNA. Under the growth conditions used here, ZR-75 cells had approximately 5800 TGF-beta binding sites per cell, with an apparent dissociation constant of 70 pm, and we have shown that the anti-proliferative effects of alpha-interferon can be reduced by 60% by co-treating the cells with a TGF-beta polyclonal antibody. The cytostatic effects of alpha-interferon may therefore be mediated by TGF-beta in this human breast cancer cell line.

Antibodies

Stability of oestrogen receptor status in sequential biopsies from patients with breast cancer.

Sequential biopsies of breast cancer tissue were obtained from a total of 210 women in order to assess any change in oestrogen receptor (ER) status arising spontaneously or as a result of intervening therapy. A combined assay measuring both cytosol and nuclear oestrogen receptors was used for all samples. One hundred and fifty-five patients had biopsies of their primary tumour and of a later loco-regional recurrence; 26 had biopsies of their primary tumour and a recurrence or new primary in the opposite breast; and 29 had sequential biopsies of recurrent disease only. Overall only 61.2% of the primary tumours retained their original status with respect to both cytosol and nuclear oestrogen receptors on recurrence. These results were influenced by intervening therapy, however, and if only untreated patients are considered, over 70% of their recurrences contain the same combination of cytosol and nuclear receptors as found in the primary tumours. For tumours 'recurring' in the opposite breast, the pattern was similar with 69.2% retaining the same status as the first primary. The agent found most likely to alter I:R status was tamoxifen and in the samples taken from patients undergoing treatment with this drug, no tumour was found to contain measurable receptor.

Biopsy

Primate population structure: evaluation of models.

Genetic markers among macaques on Cayo Santiago island were analyzed in an attempt to infer aspects of mating structure. Several models that included high levels of gene flow among groups could not be distinguished, but the data are clearly incompatible with group endogamy and with high variance in male fitness. Drift effective size is approximately one half census size in this population.

Animals

Oestrogen receptor status of breast cancers from related patients.

Breast tumours from nine pairs of related women have been studied with respect to their oestrogen receptor (ER) concentrations and histological appearance and grade. 72% of these tumours were oestrogen receptor positive in both soluble and nuclear fractions. in eight of the nine pairs, the tumours were of the same ER status. Apart from a suggestion of a similar host response to the tumours in two related pairs, the histological appearance of the tumours showed no striking similarities. This small study suggests that familial breast cancers are more likely to be hormone dependent.

Breast Neoplasms

Pre-operative determination of oestrogen receptor status in breast cancer by immunocytochemical staining of fine needle aspirates.

The results of pre-operative staining of fine needle aspirate (FNA) samples from 48 breast cancers, with a polyclonal antibody raised against highly purified oestrogen receptor (ER) protein, have been compared with our standard biochemical method for measurement of cytosol and nuclear ER. FNA antibody staining correctly predicted the presence of ER in 20 of 21 ERC +/N+ tumours. There were 2 false positive results in 24 ER C-/N-tumours though both these tumours showed marked heterogeneity of staining. Three ER C+/N- tumours were negative by antibody staining, in keeping with the tendency for such tumours to be hormone independent in behaviour. This pre-operative method for ER determination appears to be a reliable alternative to other micro-assays for oestrogen receptors.

Biopsy, Needle

A study of endometrial RNA polymerase activity in infertile women.

Endometrial RNA polymerase activity, which is sensitive to oestrogens and progesterone, has been measured in normal and infertile patients. One-third of the infertile patients studied had abnormal values. An analysis of the relationship of abnormal RNA polymerase activity to clinical abnormalities and to pregnancies occurring without treatment suggests that this assay may detect a biochemical fault in the endometrium which is related to the failure to conceive.

DNA-Directed RNA Polymerases