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Biomedical subjects

M Lesser

Publications and source records attributed to M Lesser.

At least 73 records · Page 4Linked to original sources
PubMed1983

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.

Adult↗
PubMed1983

Phase II trial of sequentially administered cisplatin, cyclophosphamide and doxorubicin for urothelial tract tumors.

A total of 32 patients with urothelial tract tumors, 31 of whom had bidimensionally measurable disease parameters, underwent sequential intravenous administration of 70 mg./m.2 cisplatin, 250 mg./m.2 cyclophosphamide and 45 mg./m.2 doxorubicin on days 1 to 3 every 3 to 4 weeks. Of these patients 28 (88 per cent) were treated adequately, including 13 (46 per cent, 95 per cent confidence limits of 28 to 64 per cent) who achieved a complete (2) or partial (11) remission. Almost all remissions occurred within 1 to 3 weeks and persisted for a median duration of 8 months (range 4 to 16 months), with 5 patients responding for 1 or more years. Responders lived significantly longer than nonresponders, with a median of 91 versus 38 weeks, respectively (p less than 0.001). The over-all response rate with this 3-drug combination was not statistically different from that which has been observed in previously untreated, selected patients given cisplatin only. When the results of the 3-drug combination (92 responses in 202 patients) are compared to those of cisplatin alone (85 responses in 255 patients) the 3-drug regimen is statistically superior (p less than 0.002).

Aged↗
PubMed1983

Bronchioalveolar carcinoma arising in areas previously irradiated for Hodgkin's disease.

A man who received therapeutic irradiation to limited areas of each lung for intrapulmonary Hodgkin's disease developed bronchioalveolar carcinoma in the same areas more than 20 years later. This is the first report of a malignant process developing in areas of the lung that had been previously irradiated for treatment of a primary lung condition.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1983

Effect of phase I and II chemotherapeutic agents against human lymphomas heterotransplanted in nude mice.

Ten chemotherapeutic agents, mostly phase I and II drugs, were tested for activity against two human lymphomas heterotransplanted in nude mice. Three of these agents have been tested in phase II trials in patients with lymphoma and found to lack activity; a corresponding lack of activity was found in lymphoma-bearing nude mice. Apart from cyclophosphamide, which is known to have activity against lymphoma and was used as a positive control, only dianhydrogalactitol (DAG) had antitumor activity in the lymphoma-bearing nude mice. Tumor regressions induced by DAG in a heterotransplanted diffuse histiocytic lymphoma were determined to be significant using a statistical method designed for such studies. These data suggest there should be further study of DAG in patients with lymphoma.

Adult↗
PubMed1983

Dexamethasone suppression tests in patients with panic disorder.

Dexamethasone suppression tests were given to 10 patients with panic disorder and 22 depressed patients. All patients with panic disorder were normal suppressors, and nine depressed patients were nonsuppressors. The mean cortisol levels of the two groups differed significantly.

Adult↗
PubMed1983

Cathepsin B and prolyl endopeptidase activity in rat peritoneal and alveolar macrophages. Stimulation of peritoneal macrophages by saline lavage.

Cathepsin B and prolyl endopeptidase activity was determined in purified rat pulmonary and peritoneal macrophages and cathepsin B was determined in blood monocytes. The activity of cathepsin B in pulmonary macrophages was more than two times higher than in resident peritoneal macrophages and about eight times higher than in circulating monocytes. The simple process of peritoneal lavage with PBS induced an increase in cathepsin B activity in peritoneal macrophages that by 96 and 144 hr reached those levels observed in pulmonary macrophages. Both pulmonary and peritoneal macrophages contain prolyl endopeptidase activity. Repeated peritoneal lavage induced a significant increase in the activity of the enzyme, but not of the magnitude observed for cathepsin B. The data suggest that the transformation of monocytes into macrophages is associated with a significant increase in cathepsin B activity and that this increase is much greater in pulmonary than in peritoneal macrophages.

Animals↗
PubMed1982

Perinatal death and respiratory apparatus dysgenesis due to a bis (dichloroacetyl) diamine.

N, N1-bis (dichloroacetyl) diamine 1, 8-octomethylenediamine (WIN 18,446) is an experimental drug which was first investigated as a male contraceptive. It is soluble in lipid solvents but not in water. The administration of 1,200 to 1,600 mg/kg to pregnant rats on the tenth day of gestation produced multiorgan fetal malformations. Smaller doses, 400 to 800 mg/kg, especially if divided over 2 or 3 days, caused perinatal death. Thus, 60 to 100% of offspring of rats given WIN 18,446 on the tenth and 11th days of gestation died at birth or within 4 days (Taleporos et al., 78). The present study investigated such deaths. At doses of 200 mg/kg on day 10 or 50 mg/kg on days 10 and 11, 67% of offspring had defective or absent diaphragms, 48% had tracheobronchiomegaly with cystic lungs, and 67% had pleural hemorrhage. At doses of 100 mg/kg given on 1 day or 25 mg/kg each day for 2 days, 50% had tracheobronchiomegaly with cystic lungs and rudimentary acini. At lower doses (18.8 mg/kg X 2 or 12.4 mg/kg X 3), a majority of fetal lungs had rudimentary acini, thick septa, few capillaries, and wide cuffs of perivascular connective tissue. Thus, a chemical given during organogenesis produced dysgenesis of the respiratory apparatus. Varying the dose produced malformed lungs with persistently deficient acini which model such human lung faults as tracheobronchiomegaly (Mournier-Kuhn Syndrome; Mounier-Kuhn, '32), bronchiolar dysplasia (Wilson-Mikity Syndrome), and perinatal death with acinar failure resembling neonatal hyaline membrane disease.

Abnormalities, Drug-Induced↗
PubMed1981

Adjuvant chemotherapy of soft-part sarcomas with ALOMAD (S4).

Sixty-four adult patients with soft-tissue sarcomas received adjuvant chemotherapy with a six-drug combination regimen after surgery. Seventy percent remain free of disease with a median follow-up of 50 months. Only seven patients have died of their disease, all within the first 24 months after surgery. Most patients experienced severe nausea and vomiting secondary to the actinomycin D and dacarbazine parts of the protocol, and three patients experienced frank Adriamycin cardiomyopathy. Toxicity from this combination was otherwise mild. The 58% recurrence rate of 12 patients who discontinued therapy early because of nausea was significantly greater than the 23% rate for those who completed or relapsed on therapy (P = 0.01). Adjuvant chemotherapy should be considered after surgery for patients with soft-part sarcomas, especially those with high-grade tumors that have a considerable risk of recurrence.

Adolescent↗
PubMed1981

Proteolytic enzymes in bronchopulmonary lavage fluids: cathepsin B-like activity and prolyl endopeptidase.

Two proteolytic enzymes, a cathepsin B-like activity and prolyl endopeptidase activity, were demonstrated in cellular elements and fluids obtained from human bronchopulmonary washings and in fragments of human lung tissue. Model synthetic substrates were used for the determination of enzyme activities. Cathepsin B-like activity was determined with N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-arginyl-2-naphthylamide. The rate of reaction with this substrate was 300 times greater than the rate with alpha-N-benzoyl-DL-arginyl-2-naphthylamide, a substrate commonly used for the determination of cathepsin B activity. Prolyl endopeptidase was determined with N-benzyloxycarbonyl-glycyl-L-prolyl-sulfamethoxazole as the substrate. The two model substrates make possible the determination of enzyme activities in as little as 10 to 50 microliters of lavage fluid. High cathepsin B-like activity and prolyl endopeptidase were generally associated with high macrophage counts in lavage fluids. This observation and the findings that cathepsin B activity is more than 4.5 times higher in normal monocytes than in neutrophils and that prolyl endopeptidase activity could not be detected in normal neutrophils suggest that the enzymes in lavage fluids are mainly derived from macrophages. Large differences in cathepsin B-like activity in certain lavage fluids containing similar macrophage counts suggest the possibility of enzyme induction in these cells. High cathepsin B-like activity and prolyl endopeptidase were also found in lavage fluids after removal of cells by centrifugation. The possibility that these enzymes affect collagen turnover and lung remodeling needs to be explored.

Adult↗
PubMed1980

Evaluation of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA, NSC 249992) on human tumors in nude mice.

The nude mouse human tumor-bearing system is a useful model for studying the efficacy of new drugs against human tumors. A panel of six selected human tumor heterotransplants was used to assess the activity of m-AMSA. No effect was seen against malignant schwannoma, malignant lymphoma, liposarcoma, neuroblastoma, or malignant melanoma. A testicular carcinoma appeared to respond to m-AMSA: however, statistical evaluation demonstrated that this was not significant. No evidence was found to support the use of m-AMSA as a sensitizing agent for radiation.

Aminoacridines↗
PubMed1980

A radioisotopic leukocyte adherence test.

A modification of the leukocyte adherence inhibition method is described which utilizes 51Cr-labeled blood mononuclear cells placed in microwells. The test is reproducible, objective, employs approximately 2,000 cells per well, and allows multiple replicates of several antigens. With the two antigens tested, SK-SD and PPD, both increases and decreases of leukocyte adherence are observed. Serum proteins are important in the medium and inactivated AB serum gave the best results. A good correlation was observed between this leukocyte adherence test and positivity of skin testing,

Chromium Radioisotopes↗
PubMed1978

Silicosis in kaolin workers and firebrick makers.

Nine patients with disabling pneumoconiosis were selected over a three-year period for study because of a work history of kaolin exposure. All had worked in the Missouri firebrick industry. Chest roentgenograms from all nine and lung tissue from two were consistent with silicosis. Worksite analysis of airborne dust at several Missouri firebrick factories revealed that some current workers are exposed to both free silica (up to 4.5%) and cristobalite (up to 8.9%) at levels exceeding the threshold limit value (TLV). Analysis of airborne dust from several kaolin processing plants in South Carolina and Georgia revealed that a few workers are exposed to about 1% free silica at levels occasionally exceeding the TVL. We conclude that silicosis is a serious risk for Missouri kaolin workers and a potential risk for workers in South Carolina and Georgia. A prevalence survey is needed in Missouri to assess the problem.

Aged↗
PubMedDate not supplied

Hypertension in cats with chronic renal failure or hyperthyroidism.

The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in 28 cats with naturally occurring renal failure, 39 cats with hyperthyroidism, and 33 clinically normal cats. The mean systolic and diastolic blood pressures in the normal cats were 118.4 +/- 10.6 mm Hg and 83.8 +/- 12.2 mm Hg, respectively. In the cats with chronic renal failure, both the systolic (146.6 +/- 25.4 mm Hg) and diastolic (96.6 +/- 15.2 mm Hg) blood pressures were significantly higher (P less than 0.0001 and P less than 0.01, respectively) than in the normal cats. Elevations in systolic and/or diastolic blood pressure were recorded in 17 (61%) of the 28 cats with chronic renal failure. In the 39 untreated hyperthyroid cats, both the mean systolic (167.9 +/- 28.9 mm Hg) and diastolic (111.6 +/- 21.5 mm Hg) pressures also were significantly higher (P less than 0.0001) than normal. Increased systolic and/or diastolic blood pressure was recorded in 34 (87%) of the 39 hyperthyroid cats. In seven cats with hyperthyroidism that were reevaluated two to four months after successful treatment of the hyperthyroid state, there was a significant fall in mean systolic pressure (P less than 0.05) from a pretreatment value of 159.5 +/- 15.4 mm Hg to a posttreatment value of 132.0 +/- 1.62 mm Hg. Overall, the results of this study indicate that mild to moderate hypertension is common in cats with chronic renal failure and in cats with untreated hyperthyroidism. In addition, the hypertension appears to be reversible following successful treatment of the hyperthyroid state.

Animals↗