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Biomedical subjects

M Cooper

Publications and source records attributed to M Cooper.

At least 163 records · Page 9Linked to original sources
PubMed1994

Surprising activity of flutamide withdrawal, when combined with aminoglutethimide, in treatment of "hormone-refractory" prostate cancer.

BACKGROUND: The best treatment for patients with "hormone-refractory" metastatic prostate cancer is unclear, particularly in patients for whom suramin and hydrocortisone have failed. PURPOSE: We investigated a combination of flutamide withdrawal and aminoglutethimide in suramin- and hydrocortisone-pretreated patients with "hormone-refractory" prostate cancer. METHODS: Twenty-nine patients with metastatic prostate cancer were treated with simultaneous flutamide withdrawal and aminoglutethimide (250 mg given orally four times daily). All patients were taking flutamide at the time of entry, and previous treatments with medical or surgical castration, flutamide, suramin, and hydrocortisone had failed in all of these patients. Because of suramin-induced adrenal insufficiency, all patients had previously received, and continued to receive, physiological doses of hydrocortisone. Treatment of all non-surgically castrated patients had previously failed; however, these patients continued to receive depot leuprolide. RESULTS: In 14 (48%) of 29 patients, the prostate-specific antigen (PSA) decreased by more than 80% for 4 or more weeks. Improvements in anemia, thrombocytopenia, soft-tissue masses, bone scans, and symptoms were also noted. Factors associated with response included prolonged flutamide pretreatment, a markedly elevated pretreatment PSA, and the absence of soft-tissue disease. CONCLUSIONS: Flutamide withdrawal, when combined with the simultaneous administration of aminoglutethimide, is a therapeutically active approach in patients with "hormone-refractory" prostate cancer. IMPLICATIONS: On the basis of these and additional data, we hypothesize that prolonged exposure to flutamide results in the selective proliferation of cancer cells containing a mutant androgen receptor that aberrantly recognizes flutamide metabolites and nonandrogenic steroids as androgenic stimuli.

Aged↗
PubMed1994

Critical pathway methodology: effectiveness in congenital heart surgery.

Critical pathway methodology has been demonstrated to provide producible reduction in average length of stay (ALOS) in adults in certain diagnostic-related groups and operations such as coronary artery bypass grafting. The efficacy of this approach in congenital heart surgery was explored. Two hundred eighty-six consecutive patients from a health maintenance organization treated by a single surgeon since the institution of diagnostic-related group coding at that health maintenance organization constituted the study group. One hundred fourteen patients were treated at a university hospital without critical pathway methodology (group 1) and 172, subsequently at the health maintenance organization institution using the methodology (group 2). Operation/lesion, age, and diagnostic-related group matching was possible in 61 pairs. Examination of the ALOS Hospital (operative and postoperative days) for the entire cohort revealed a 43.8% reduction in ALOS Hospital (p < 0.0001) and a 39.0% reduction in ALOS Intensive Care Unit (p < 0.0001). There was also significant reduction in ALOS Hospital and ALOS Intensive Care Unit in the operation/lesion-matched subsets. Outcome measures including operative and late mortality, readmission, unscheduled emergency room and clinic visits, and health maintenance organization family assessment survey demonstrated no improvement in outcome with increased hospital stay. Thus, critical pathway methodology when used in patients undergoing a congenital heart operation produces a significant reduction in hospital stay and intensive care unit stay as well as quality patient care with uniformity of outcome.

Adolescent↗
PubMed1994

Stored skin--stored trouble?

Quantitative bacteriology is presented on 102 consecutive split-skin grafts. A sample of graft was cultured whenever skin was taken and whenever stored skin was used. Stored skin unused at 21 days was also cultured. The percentage take of grafts was inversely proportional to number of organisms/g of skin (r = -0.24, p < 0.05). Commonly used storage conditions facilitated bacterial multiplication. There was no significant difference in organisms/g contaminating grafts for different surgeons, skin preparations, types of grafts, cutting tools or mode of anaesthesia. Male patients had a significantly greater count for initial grafts (p = 0.02), but after 3 weeks storage there was no sex difference.

Adolescent↗
PubMed1994

Simultaneous 60-electrode mapping of ventricular tachycardia using percutaneous catheters.

OBJECTIVES: We developed a new approach for mapping ventricular tachycardia at electrophysiologic study using simultaneous recordings from up to 60 catheter electrodes. BACKGROUND: Good results for surgical or catheter ablation of ventricular tachycardia are limited by the ability to detect and completely map all of the underlying arrhythmogenic areas. Currently, catheter mapping of all configurations of ventricular tachycardia is impossible or unsatisfactory in at least 60% of patients because of poorly tolerated rapid rates, nonsustained ventricular tachycardia or multiple configurations. METHODS: Twenty-four patients with recurrent ventricular tachycardia refractory to antiarrhythmic drugs were studied using up to six percutaneous decapolar catheters introduced into the ventricles. Left ventricular maps of ventricular tachycardia were achieved by two to three transseptal catheters, two to three transaortic catheters, a coronary sinus catheter and right ventricular catheters. Simultaneous endocardial maps of either right or left ventricles were possible with a resolution of approximately 1 to 2 cm. Up to 60 electrograms were digitized and recorded simultaneously using a custom-computerized mapping system. RESULTS: Successful maps of 73 ventricular tachycardia configurations were obtained in 22 patients. The mapping procedure failed in two patients because of inability to catheterize the left ventricle in one and inability to induce monomorphic ventricular tachycardia in the other. The mean (+/- SD) ventricular tachycardia cycle length was 285 +/- 53 ms (range 215 to 470). A total of 39 separate arrhythmogenic areas (median 1, interquartile [25% to 75%] range 1 to 3/patient) were detected, of which 21 (54%) were in the left ventricular free wall, 17 (44%) were in the ventricular septum, and 1 (2%) was in the right ventricular outflow tract. Ten patients (45%) had at least two arrhythmogenic areas. Thirteen patients subsequently underwent operation. All but one of the arrhythmogenic areas found at surgical mapping had been identified at preoperative catheter mapping. Complications of the preoperative mapping procedure occurred in four patients, with complete resolution in three and minor long-term sequelae in the other. CONCLUSIONS: This technique permits detailed catheter mapping of all types of monomorphic ventricular tachycardias, including those leading to hemodynamic collapse, and should enable better choice and direction of surgical or catheter ablation.

Adult↗
PubMed1994

Suramin inhibits proliferation and DNA synthesis in transitional carcinoma cell lines.

Suramin is polysulfonated naphthylurea which has a broad range of antitumor activity. The mechanism of action of suramin is not completely understood, although it is known to inhibit enzymes in all cellular compartments, inhibit steroidogenesis and interfere with ligand-receptor binding. Suramin's large molecular size and negative charge should make it poorly absorbed through the bladder mucosa, a desired characteristic for an intravesical chemotherapeutic agent. We examined the ability of suramin to inhibit thymidine uptake and decrease cellular proliferation in 4 transitional cell carcinoma cell lines grown in vitro to determine if suramin might be a new candidate drug of treatment for patients with superficial bladder cancer. Suramin inhibited cellular proliferation of all cell lines tested (MBT2, T24, RT4 and TCCSUP) in a dose-dependent fashion. Fifty per cent inhibition of cellular proliferation compared with controls was seen with suramin concentrations of 250 to 400 micrograms/ml. by, at most, 5 to 9 days of exposure. The cell line RT4 was the cell line most sensitive to the growth inhibitory effect of suramin, with 50% growth inhibition compared with controls achieved after 3 days' exposure to a suramin concentration of 100 micrograms/ml. Suramin inhibited DNA synthesis in a dose-dependent fashion, as measured by thymidine uptake, in 3 of the 4 cell lines tested (MBT2, T24, and RT4). Suramin inhibited thymidine uptake by TCCSUP in a dose-dependent fashion, but did not achieve statistical significance.

Animals↗
PubMed1994

Vasopressin V1 and V2 receptors in diabetes mellitus.

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

Animals↗
PubMed1993

Development of a device for measuring adherence of skin grafts to the wound surface.

Adherence of a biological graft to the wound surface is the most important factor influencing the ultimate success of graft viability. A machine has been developed to test the adherence of biological graft materials to a substrate such as a wound surface. The peeling mode, which yields reproducible quantitative measurements of adherence, is a standard method for testing adhesives. The device is designed to continuously measure the force required to peel the graft from the substrate at a constant rate. This force is a function of the energy of adhesion per unit area of adhered surface. This device has been used to measure the peeling force of (2 x 2 cm) skin grafts which are applied to full-thickness wounds on mice. Results of tests on adherence of autografts on mice show that the peeling force increases significantly with time over the first 9 days of healing. Thus, this device is useful in quantitative comparison of various skin grafting techniques and artificial grafts.

Adhesiveness↗
PubMed1993

Ophthalmic herpes zoster.

A current review of ophthalmic zoster is presented including its virology, immunology, epidemiology and pathogenesis. We give our findings in 1356 patients referred to the Zoster Clinic at Moorfields Eye Hospital, London. The treatment of the disease and its ocular complications is discussed.

Fluorescein Angiography↗