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Biomedical subjects

C Fabian

Publications and source records attributed to C Fabian.

At least 37 records · Page 2Linked to original sources
PubMed1990

A double-blind, controlled trial in primary care patients with generalized anxiety: a comparison between buspirone and oxazepam.

Two hundred thirty patients with generalized anxiety and Hamilton Rating Scale for Anxiety (HAM-A) scores greater than or equal to 18 were subdivided at random, according to a double-blind design, into one group treated with 5-10 mg of oral buspirone t.i.d. or one group treated with 10-20 mg of oral oxazepam t.i.d. for 6 weeks. No anxiolytic treatment was allowed 3 months prior to trial entry. Analysis of demographic variables revealed no significant imbalance between the two treatment groups. Twenty patients were excluded from efficacy analysis because of treatment withdrawal before the first efficacy evaluation on Day 7. Another 4 patients were excluded because they were taking concomitant psychotropic medication. The remaining 206 patients displayed a decrease in HAM-A scores (mean +/- SD) from 23.9 +/- 4.1 to 10.6 +/- 7.7 in the buspirone group and from 23.9 +/- 4.2 to 11.5 +/- 8.0 in the oxazepam group. The two treatment groups were also found to be virtually identical in an "intent to treat" analysis of all 230 patients as well as in other ratings (Hamilton Rating Scale for Depression, Raskin Depression Scale, Covi Anxiety Scale, Physicians Questionnaire, global ratings, and Hopkins Symptom Checklist [HSCL]-56). However, oxazepam was never superior to buspirone in any of the efficacy analyses. Of the 230 patients, 127 spontaneously reported adverse events, including drowsiness, dizziness, headache, nausea, and nervousness. Adverse events were relatively similar in the two groups. In conclusion, buspirone and oxazepam appear to be equally effective in the treatment of generalized anxiety encountered by general practitioners. This outcome, in addition to a previously documented absence of any dependency liability, makes buspirone a clinically important anxiolytic drug.

Adolescent↗
PubMed1988

Effect of starch malabsorption on colonic function and metabolism in humans.

To study the impact of starch on colonic function and metabolism, 12 healthy volunteers consumed a controlled diet rich in starch for two 4-wk periods. In one of the study periods they received the glucosidase inhibitor acarbose (BAY g 5421) and placebo in the other. Stool wet weight increased by 68%, stool dry weight by 57%, fecal water content by 73%, and the mean transit time by 30% on acarbose. Breath hydrogen was significantly higher on acarbose, indicating stimulated carbohydrate fermentation in the colon. Fecal bacterial mass (+78%), total stool nitrogen (+53%), bacterial nitrogen (+200%), and stool fat (+56%) were higher in the acarbose than in the control period. The stimulation of fermentation in the human large intestine may be important in colonic and possibly other diseases.

Acarbose↗
PubMed1988

The effect of starch malabsorption on fecal short-chain fatty acid excretion in man.

To study the impact of starch malabsorption on fecal short-chain fatty acid concentrations, 11 healthy volunteers consumed a controlled diet rich in starch for 2 4-week periods. They received the glucosidase inhibitor acarbose (Bay g 5421) in one of the study periods and placebo in the other. Stool wet weight increased by 68% and stool dry weight by 57% with acarbose. The fecal concentration (mumol/g wet weight) of n-butyrate (+58%) rose significantly when acarbose was added to the diet. The fecal excretion (mmol/day) of total short-chain fatty acids (+95%) and of their constituents acetate (+97%) and n-butyrate (+182%) was significantly higher when starch malabsorption was induced by acarbose.

Adult↗
PubMed1987

Use of charcoal hemoperfusion with sequential hemodialysis to reduce serum methotrexate levels in a patient with acute renal insufficiency.

Acute renal failure induced by methotrexate can be complicated by prolonged high serum levels of methotrexate, resulting in pancytopenia and severe mucositis. The role of dialysis in these patients has not been well elucidated. Serum methotrexate levels were successfully lowered in a patient with methotrexate-induced acute renal failure by charcoal hemoperfusion and sequential hemodialysis. No rebound in serum methotrexate levels was observed after perfusion, a phenomenon previously reported as limiting the usefulness of this procedure.

Acute Kidney Injury↗
PubMed1986

Thyroid lymphoma with gastrointestinal involvement: report of three cases.

Three elderly females are reported who presented with high-grade lymphoma of the thyroid and subsequently were found to have extensive gastrointestinal (GI) lymphoma that dominated their clinical courses. One of the patients remains free of disease 30+ months after extensive resection of involved bowel and combination chemotherapy. Two died from disseminated lymphoma. Optimal delivery of therapy in both of the latter patients was impeded by massive gastrointestinal hemorrhage. A review of previously reported cases of thyroid lymphoma, plus those described here, suggests a predilection for these tumors to involve the GI tract independent of other organ metastases.

Aged↗
PubMed1983

Mitoxantrone in advanced breast cancer: a phase II trial of the Southwest Oncology Group.

124 patients with metastatic breast cancer were entered into this phase II trial of mitoxantrone (DHAD). Patients were stratified prior to treatment as good or poor risk, and whether they had received previous therapy with an anthracycline derivative. Mitoxantrone was given every 21 days at a starting dose of 12 mg/m2 for good risk patients and 10 mg/m2 for poor risk patients. Among the group who had not received anthracyclines, 12 are fully or partially evaluable for response with five classified as good risk. One complete response, ongoing at 52 weeks was seen in this group. Of the seven poor risk patients, stable disease was seen in two. 103 patients with prior anthracycline exposure are fully or partially evaluable, 31 good risk and 72 poor risk. There were three partial responses in each group. Toxicity was primarily myelosuppression, and was more severe in the poor risk group. Mitoxantrone when used on this schedule has minimal activity among heavily pretreated patients with metastatic breast cancer.

Adult↗
PubMed1983

Methyl-glyoxal bis guanyl hydrazone (methyl-GAG, MGBG) in lymphoma and Hodgkin's disease. A Phase II trial of the Southwest Oncology Group.

The Southwest Oncology Group has evaluated methyl-GAG on a weekly schedule among patients with lymphoma and Hodgkin's disease. Among 56 fully and partially evaluable patients responses were seen in 3 of 10 patients with Hodgkin's disease and 11 of 46 patients with lymphoma. Toxicity was acceptable. Methyl-GAG has significant antitumor activity among this group of heavily pretreated patients. Additional trials of methyl-GAG in combination with other agents are underway.

Adolescent↗
PubMed1982

Combination chemotherapy plus BCG in the treatment of disseminated malignant melanoma: a Southwest Oncology Group Study.

The Southwest Oncology Group performed a randomized study comparing combination chemotherapy alone versus combination chemotherapy plus BCG versus DTIC plus BCG in the treatment of disseminated malignant melanoma. A 31% response rate was noted with combination chemotherapy alone, a 27% response rate with combination chemotherapy plus BCG, and an 18% response rate with DTIC plus BCG. Survival was not influenced by type of therapy, but the responders had significantly longer survival than the nonresponders. There appeared to be some significant differences in response as related to age wherein those patients between the ages of 30 and 60 years had a higher response rate to combination chemotherapy as compared to DTIC plus BCG. Those patients older than 60 years of age had a higher response rate in the BCG groups. Furthermore, in those patients older than 60 years of age who responded, their duration of response was longer if they received BCG than those who did not receive BCG. It should be emphasized that those differences noted in various age groups could occur by chance alone. These differences should be studied in the future, by appropriate pretreatment stratifications. Patients with higher peripheral lymphocyte counts had significantly better response rates and those patients with higher numbers of positive delayed hypersensitivity skin tests had significantly greater survival. A significant improvement in survival was noted in patients whose PPD converted from negative to positive during therapy.

Adult↗
PubMed1981

Clinical pharmacology of tamoxifen in patients with breast cancer: correlation with clinical data.

Blood tamoxifen levels were determined for patients with metastatic breast cancer following initial and chronic dosing at twice daily 10 mg/m2 or a 20 mg/m2 single dose. Median time to response was six weeks. Blood tamoxifen levels at that time were ten-fold greater than those obtained after an initial single dose; however, steady-state values were not achieved until 16 weeks of chronic dosing. On a loading dose schedule of 40 mg/m2 twice daily for seven days and 20 mg/m2 daily thereafter, blood levels greater than or equal to 10 mg/m2 twice daily steady-state values were reached in one week. Levels drawn at peak and trough times suggest that tamoxifen may be given on a once-daily basis. Tamoxifen half-life was 9-12 hours after the initial dose and seven days after chronic dosing.

Breast Neoplasms↗
PubMed1981

Phase I-II trial of methyl-GAG in advanced colon cancer. a Southwest Oncology Group pilot study.

Forty-four patients with advanced colon or rectal cancer were treated with methyl-GAG on a weekly schedule. Of the 40 evaluable patients, 35 (87%) had received prior chemotherapy. Objective tumor regression was seen in six patients (one CR, five PR's). An additional nine patients had stable disease for a median of 42 weeks. The median survival (42+ weeks) for responding and stable disease patients was significantly better (p = 0.0001 Wilcoxan test) than those with progressive disease (11 weeks). Toxicity was reversible and included mild to moderate mucositis, nausea, vomiting, diarrhea, and thrombocytopenia. Responses observed in this study warrant further trials in patients with colon cancer who have no prior chemotherapy.

Adult↗
PubMed1978

Phase I evaluation of anguidine (diacetoxyscirpenol, NSC-141537).

A toxicologic evaluation of anguidine (diacetoxyscirpenol) was completed for a 5 day schedule. At 4.5 mg/M2 and 6 mg/M2 iv push CNS symptoms and hypotension were dose limiting but only mild to moderate myelosuppression was observed. At the 6 mg/M2 dose level on a 5 day schedule given by 8 hour infusion, myelosuppression was unacceptable while other toxic manifestations were minimal. An infusion of 4.5 mg/M2 over 4-8 hours appears to be an acceptable compromise between CNS, cardiovascular, and GI toxicity and myelosuppression. For patients with liver dysfunction or prior nitrosourea therapy, the starting dose should be 3.0 mg/M2.

Bone Marrow↗
PubMed1978

Clinical analysis of tamoxifen, an anti-neoplastic agent, in plasma.

Tamoxifen, a phenylstilbene derivative, is currently being used to treat metastatic breast cancer. We describe an analytical method for monitoring the parent drug and its 4-hydroxylated derivative in whole blood and plasma. After extraction from biological media, the analytes are converted to highly fluorescent products by ultraviolet irradiation, and then separated by liquid-chromatography on a muBondapak CN column, with spectrofluorometric detection of components. Detection limits for tamoxifen and its 4-hydroxy derivative are 1 and 2 microgram/liter of biological fluid, respectively. Conditions have been optimized so that the reaction proceeds fast enough for convenient sample handling without jeopardizing fluorescence yield due to the photocatalyzed degradation of the fluorescent product. Evidence suggests that the fluorophore being monitored is a phenanthrene derivative.

Breast Neoplasms↗
PubMedDate not supplied

Comparative binding affinities of tamoxifen, 4-hydroxytamoxifen, and desmethyltamoxifen for estrogen receptors isolated from human breast carcinoma: correlation with blood levels in patients with metastatic breast cancer.

The relative ability of the antiestrogen, tamoxifen, and its monohydroxy and desmethyl metabolites to displace tritiated estradiol from estrogen receptors isolated from human breast carcinoma was determined. 4-Hydroxytamoxifen binds to the estrogen receptor with affinity equal to estradiol, and with 25-50 times higher affinity than does tamoxifen. Desmethyltamoxifen binds to the estrogen receptor with less than 1 per cent of the affinity of tamoxifen. Blood level determination of tamoxifen species in breast cancer patients receiving the drug indicated that after 3 weeks of therapy, desmethyltamoxifen levels were 1.2-1.8 times greater than tamoxifen levels and 4-hydroxytamoxifen levels were 2-18 per cent of parent drug concentrations. Thus, because of its high affinity for the estrogen receptor, the 4-hydroxy metabolite may play a significant antiestrogenic role following tamoxifen therapy, despite its low relative abundance. Desmethyltamoxifen, on the other hand, may have only minor importance as an anti-estrogenic agent following tamoxifen treatment, due to its poor affinity for the estrogen receptor coupled with blood levels that are at most 75 per cent greater than tamoxifen levels at steady state.

Animals↗
PubMedDate not supplied

Phase I-II trial of methyl-GAG: a Southwest Oncology Group Pilot Study.

One hundred and nine patients with advanced malignancy, refractory to conventional therapy, were treated with a weekly schedule of methyl-GAG. Ninety-one patients (83%) were less than fully ambulatory. Sixty-five patients were fully evaluable for response. There were two complete and nine partial responses. An additional nine patients had objective tumor regressions and were classified as improved. The median duration of response was 5 months. Toxic effects were primarily mucositis (17 patients) and nausea and vomiting (14 patients). Sixty-seven patients had no manifestations of drug toxicity. Responses observed in a wide variety of solid tumors warrant further clinical trials.

Drug Evaluation↗