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D R Millar

Publications and source records attributed to D R Millar.

15 recordsLinked to original sources

Results of low-dose methotrexate treatment of persistent gestational trophoblastic disease in Sheffield 1980-1987.

Between January 1980 and October 1987, 115 evaluable patients were treated in Sheffield for persistent gestational trophoblastic disease (GTD) with a low dose methotrexate regimen (LD-MTX). Each course comprised MTX 50 mg given by i.m. injection for 4 doses on alternate days. Courses were repeated every 2 weeks and serum beta-hCG was used to monitor response. Overall, 80/115 (70%) of patients attained durable complete remissions (CR). Twenty-nine patients received the 'AVC' salvage combination of actinomycin-D 0.5 mg i.v. for 5 days, sequenced with cyclophosphamide 500 mg i.v. and vincristine 1 mg i.v., both given for 3 doses on alternate days. Sixteen (55%) patients attained a durable CR but 11 (38%) required further measures, 7 ultimately requiring hysterectomy. Two (7%) died during treatment. With 4 deaths overall (3 from metastatic GTD and 1 from infarction of the bowel), actuarial survival is 94% at over 7.5 years. A new Charing Cross prognostic scale weighted especially for hCG levels, number and sites of metastases, interval between pregnancy and start of treatment (score 0-6 each factor), was applied retrospectively to obtain a total score for each patient. Thus, 21/26 (81%) patients who scored greater than 8, required additional treatment after LD-MTX, compared with 18/89 (20%) of lower scoring patients (p less than 0.001). Because of the frequent morbidity associated with prolonged chemotherapy as well as the development of drug-resistant GTD, it is concluded that the 'high-risk' patients should receive more intensive combination chemotherapy at the outset.

Adult

Pregnancy diagnosis.

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An assessment of urodynamic examination in incontinent women.

Urodynamic investigation was performed in 100 consecutive incontinent women. The clinical diagnosis was confirmed in only 65 women and management was significantly altered in 31 women. Pressure-flow studies should precede, whenever possible, the treatment of incontinent patients.

Female

Enzymes of glucose metabolism in carcinoma of the cervix and endometrium of the human uterus.

Twelve enzymes related to the direct oxidative and glycolytic pathways of glucose metabolism were assayed in 88 cancers of the cervix and 48 cancers of the endometrium of the human uterus, and the activities compared with those obtained from a group of control tissues. Significant increases for all but one of the enzymes studied (alpha-glycerolphosphate dehydrogenase) were found in cancer of the cervix, when compared with normal cervix epithelium. Hexokinase, phoshofructokinase, and aldolase appear to be rate-limiting in normal cervix epithelium; however, since the increase in activity of the first two in cancers was least of all the glycolytic enzymes, redundant enzyme synthesis probably occurs in the malignant cell for the enzymes catalysing reversible reactions. There was virtually no correlation between the activity of any enzyme measured in the cancer sample and histological assessments of the degree of malignancy of the tumour, or the clinical stage of the disease. All enzymes except pyruvate kinase had significantly higher activity in normal endometrium than in normal cervix epithelium, presumably reflecting the greater metabolic requirements of the former tissue. Only phosphoglucose isomerase and pyruvate kinase were significantly higher in endometrial cancer than in normal endometrium, and there were few significant differences between cancers of the cervix and of the endometrium, despite the marked differences in their tissues of origin. These results suggest the changes occur during malignant transformation to the activities of both regulatory enzymes and those catalysing reversible reactions, in a manner justifying the conclusion that the general metabolism of tumours is convergent.

Adult

Properties of glycolytic and related enzymes of normal and malignant human uterine tissues studied to optimise assay conditions.

The properties of 12 enzymes related to the glycolytic and oxidative metabolism of glucose were examined in normal and malignant epithelium of human uterine tissues to develop optimised assays suitable for both types of tissue and to delineate important kinetic differences that may exist between them. All assays gave acceptable long-term precision, although instability of phosphofructokinase and 6-phosphogluconate dehydrogenase prevented proper assessment; and all were linear with concentration to an absorbance change of 0.04/min, or more in the case of several enzymes. Notable differences between pyruvate kinase of normal and malignant uterine epithelium were found with D-fructose-1,6-diphosphate (FDP) which caused significantly greater activation of the latter as well as a dramatic reduction in Km for phosphoenol pyruvate; inhibition by DL-alanine was greater for pyruvate kinase of malignant than normal cervix epithelium, whereas endometrium did not show this difference. The ratio of aldolase activity with FDP to that with D-fructose-1-phosphate was greater in malignant than in normal cervix epithelium, no significant difference being apparent in endometrium.

Female

The use of laparoscopy in gynaecology.

Diagnostic laparoscopy is of most value in the evaluation of infertility and for completing the gynaecological investigation of obscure cases of chronic pelvic pain. Its use to exclude ectopic pregnancy, salpingitis and pelvic cancer is more controversial. The management of some cases of primary amenorrhoea is aided by laparoscopic gonadal biopsy. The excessive demand for female sterilization will ensure that the laparoscope continues to be used for this purpose and is leading to a compromise. The surgical techniques which have been proved to be most effective are being replaced by methods favoured for their potential reversibility and rapid patient turn-over. If all our laparoscopes were abandoned, gynaecological surgery would perhaps not suffer a major setback, but, for the present, those who neglect laparoscopy are losing an important dimension of modern practice.

Acute Disease