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Biomedical subjects

A Lipton

Publications and source records attributed to A Lipton.

At least 163 records · Page 9Linked to original sources
PubMed1979

Phase II trial of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) combination chemotherapy in advanced ovarian carcinoma.

A monthly four-drug regimen of cyclophosphamide, adriamycin, and cis-dichlorodiammineplatinum(II), each given iv of Day 1, and hexamethylmelamine, given orally on Days 1--14 (CHAP), was administered to 39 women with advanced epithelial ovarian carcinoma who had previously failed alkylating agent therapy. Of 35 evaluable patients with a measurable disease parameter, seven (20%) achieved a clinical complete response and ten (29%) achieved a clinical partial response. The median duration of complete response is greater than 9 months and the median duration of partial response is 4 months. Ninety percent of the patients required dose adjustments because of profound leukopenia, thrombocytopenia, or gastrointestinal intolerance. CHAP is an active but toxic regimen in the management of advanced ovarian cancer. The toxicity encountered reflected the intensity of the drug schedule as well as the combined influences of advanced stage of disease, poor nutritional and performance status, and prior therapy. The efficacy of this CHAP regimen warrants a controlled trial compared to other active drug programs.

Alkylating Agents↗
PubMed1978

Decreased hepatic drug demethylation in patients receiving chemo-immunotherapy.

The effect of immunotherapy and chemotherapy on hepatic N-demethylation of aminopyrine was studied by means of the aminopyrine breath test (ABT) in 32 patients with cancer. The aminopyrine breath test (ABT) was decreased in 3 of 11 patients (27.3%) receiving intradermal BCG (+/- DTIC) at a dose of 3 X 10(7) viable organisms. One of 4 (25%) patients receiving intradermal BCG (+/- DTIC) at 3 X 10(8) viable organisms per dose developed an altered ABT. Changes were not seen in patients receiving aerosol BCG (2 patients), and intravenous C. parvum (2 patients), subcutaneous C. parvum (3 patients), and intravenous Cyclophosphamide (2 patients). Six of 7 patients (85.7%) receiving both intravenous C. parvum and Cyclophosphamide had a decreased ABT. These data indicate that chemo-immunotherapy depressed hepatic aminopyrine N-demethylation and suggests that patients treated with chemoimmunotherapy should be carefully observed for possible alterations of hepatic drug metabolism.

Adult↗
PubMed1978

Medical adrenalectomy with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma.

The use of adrenalectomy and hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma is reserved for highly selected patients. As an alternate approach, a pharmacologic method of inhibiting adrenal cortical secretion was developed which consisted of the daily administration of 1000 mg of aminoglutethimide to block steroidogensis and either dexamethasone (2.0-3.0 mg/day) or hydrocortisone (40-60 mg/day) as replacement glucocorticoid. This regimen markedly suppressed plasma levels of DHA-S, androstenedione, estrone, and estradiol, and urinary levels of aldosterone. Of 50 patients treated, 19 (38%) demonstrated either a complete (8/19) or a partial (11/19) objective disease remission which lasted for 18.05 +/- 3.1 months (mean +/- SEM). In 10 (20%) patients, there was stabilization of disease (7.8 +/- 1.2 months), accompanied by symptomatic relief of bone pain in six (12%). There was disease progression in 20 (40%) patients. The acute side effects of aminoglutethimide therapy were significant and consisted of transient lethargy (41.5%) and a cutaneous rash (35.8%). Chronic toxicity was negligible. The medical adrenalectomy regimen of aminoglutethimide plus glucocorticoid offers a suitable alternative to surgical adrenalectomy or hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma.

Adrenal Cortex↗
PubMed1978

Effects of ovarian steroids and prolactin on the contractility and sodium pump site density of guinea-pig myometrium.

Ovariectomized guinea-pigs were given a single dose of oestrogen or progestogen or the two steroids combined. Controls were given 0.9% saline. Four days after the injection, myometrial contractility in response to spasmogens was measured isometrically in isolated tissue baths, both before and after incubation in Kreb's solution with or without added prolactin. Further myometrial strips were also incubated with or without prolactin and the density of Na+/K+ ATPase 'pump' sites on the surface of the myometrial cell was estimated by labelling with tritiated ouabain. Incubation with prolactin significantly reduced the contractility of myometrial tissue from guinea-pigs given saline alone, progestogen alone or progestogen plus oestrogen, but not in tissue from animals pretreated with oestrogen. When myometrial strips from animals pretreated with oestrogen or progestogen were incubated without prolactin in the medium, there was a significant increase in the density of pump sites compared with the number in saline-pretreated animals; incubation with prolactin did not further modify this effect. When both steroids were administered together there was a significant increase only when prolactin was present in the incubation medium. There was also a significant increase in the density of pump sites after incubation of myometrium from the control (saline-pretreated) animals in the presence of prolactin.

Animals↗
PubMed1978

Pancytopenia induced by aminoglutethimide in the treatment of breast cancer.

Aminoglutethimide is an investigational agent of proven benefit in the treatment of metastatic breast carcinoma. We report herein a case of aminoglutethimide-induced pancytopenia complicated by bleeding and gram-negative septicemia. Severe pancytopenia is a rare but important side effect of this new drug and is rapidly reversible when the agent is withdrawn.

Aged↗
PubMed1977

Plasma prostaglandins in hypercalcemic patients with neoplastic disease.

Peripheral plasma prostaglandin E (PGE) determinations were performed on a series of 79 patients with solid tumor neoplasms and correlated with their serum calcium levels. Fourteen patients were hypercalcemic and 11 of these had significant elevations in circulating plasma PGE. Ten of the hypercalcemic group had extensive metastases to bone. These findings support the recently developed hypothesis that prostaglandins are causally related to the genesis of hypercalcemia in malignancy.

Adult↗
PubMed1977

Plasma prostaglandins across the tumor bed of patients with gynecologic malignancy.

Prostaglandin E produced by tumors has recently been implicated as a mechanism by which tumors may subvert the immune system and grow despite their antigenicity. Arterial and venous determinations of prostaglandin E were performed in eleven patients with gynecologic malignancy. No significant difference was found when arterial and venous levels were compared and there was no difference in venous PGE levels when subjects with cancer were compared to patients with benign gynecologic disease.

Adenocarcinoma↗
PubMed1977

Immunosuppression and human cancer: role of prostaglandins.

Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have been implicated in the pathophysiology of many diseases. Prostaglandin E (PGE) levels were measured by radioimmunoassay in the plasma of 41 normocalcemic patients with various stages of malignancies. Delayed hypersensitivity was assessed by a battery of six recall skin test antigens (ST) and by Dinitrochlorobenzene (DNCB) sensitization and challenge. Twenty-five patients with one or more positive skin tests had a mean PGE level of 87+/-8 pg/ml, whereas 16 patients with negative ST had a mean PGE level of 96+/-12 pg/ml. Twenty-one DNCB negative patients had a mean PGE level of 98+/-12 pg/ml and eight totally anergic patients had a mean PGE of 96+/-12 pg/ml. All PGE values were within the normal range and there was no statistical difference between the four groups. (p less than 0.1). We concluded that circulating PGE does not correlate with the non-specific immunosuppression seen in cancer patients.

Adult↗
PubMed1977

Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer.

Approximately one-third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydrocortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily suppressed DHA-sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2-3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide-hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide-hydrocortisone regimen is simple, non-toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy.

Adrenocorticotropic Hormone↗
PubMed1977

Selective growth of transformed cell lines by rat liver perfusate.

Perfused rat liver releases growth-promoting activity for viral, spontaneous, and chemically transformed cells. After 5 days of incubation with perfusate, cell lines 3T12-NY (a spontaneous fibroblast transformant), NQ-T1 (a chemically transformed fibroblast line), W-8 (a chemically transformed epithelial rat liver cell line increase in cell growth above controls. Their respective normal counterparts: 3T3 Cl 42, A31-714, K-16, and HEF are not so stimulated. Within another set, the virally transformed mouse fibroblast cell line, SV3T3, exhibits a 27-fold increase in growth; however, 3T3 (mouse, fibroblasts), Py3T3 (polyomatransformed 3T3 cells), SV-Fl2-101 (a flat revertant line), and SV-Py-3T3 (a doubly transformed line) are nonresponsive. Perfused rat liver also release survival activity for SV-3T3 cells. The growth-stimulating activity in liver perfusate is selective for transformed cells. It is suggested that the liver may play a role in suporting neoplasia in vivo.

Animals↗
PubMed1976

Abnormal aminopyrine metabolism in patients with hepatic neoplasm. Detection by breath test.

Aminopyrine metabolism was assessed by the aminopyrine breath test (ABT) in 153 patients with malignant disease, of whom 75 had hepatic neoplasm and 78 had none. Radioactive carbon dioxide (14CO2) exhalation was measured two hours after oral administration of a trace dose of carbon-14 labeled aminopyrine. The ABT was correct in 62 of 75 (83%) patients with hepatic neoplasm and in 73 of 78 (94%) patients without. It was correct in 16 of 22 (73%) patients who had hepatic neoplasm without abnormal serum biochemistry. Aminopyrine metabolic clearance rate (AMCR) was 32.4 ml/min in patients with hepatic neoplasm and 103.4 +/- 18.8 ml/min in the patients without. There was a highly significant correlation between ABT and AMCR (r =.76, P less than .01). We conclude that aminopyrine metabolism is depressed in most patients with hepatic neoplasm and that the ABT affords a useful method for detecting malignant tumors of the liver.

Administration, Oral↗
PubMed1976

Urinary polyamine levels in patients with localized malignancy.

Polyamine levels (putrescine, spermidine, and spermine) were determined in 24-hour urine samples by a high voltage electroporesis techique. Twenty-four of 26 patients with localized malignant tumors had two or more elevated urinary polyamine levels. Seven of 12 patients with regional spread of their cancer and five of 11 patients with localized benign and/or noninvasive tumors had elevated urinary polyamine levels. Elevations were seen more frequently frequently in patients with gynecologic tumors. Our data suggest that there is no significant difference between the individual of total polyamine levels obtained in patients with localized malignant tumors, and those levels obtained in patients previously studied with widespread metastatic disease.

Adolescent↗
PubMed1976

Aminoglutethimide medical adrenalectomy for advanced prostatic carcinoma.

Complete adrenal suppression with aminoglutethimide has been accomplished in 7 patients with progressive stage D carcinoma of the prostate who had become refractory to orchiectomy and the administration of exogenous estrogens. A favorable response was noted in 3 patients. These preliminary results indicate that this agent may be as useful as surgical adrenalectomy in the treatment of progressive prostatic carcinoma. A brief discussion of the pharmacology of this agent, its mode of administration and the side effects are presented.

Adenocarcinoma↗