Mental health care reform: implications for social work.
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Cost Control↗
Biomedical subjects
M Raber
Publications and source records attributed to M Raber.
Phase I trial of a 72-h continuous-infusion schedule of fazarabine.
Fazarabine (Ara-AC), a structural analog derived from the antitumor nucleoside cytosine arabanoside (Ara-C) and 5-azacytidine (5-AC), was studied in a phase I clinical trial. Doses ranging from 0.2 to 2.0 mg m-2 h-1 were given intravenously over 72 h every 28 days. The maximum tolerated dose (MDT) was 2.00 mg m-2 h-1. The dose-limiting toxicity was myelosuppression, with granulocytopenia being quantitatively more important than thrombocytopenia or anemia. Nonhematologic toxicity was minimal. Associated with the solvent dimethylsulfoxide (DMSO) was a bitter taste and a garlic-like odor.
Adult↗
Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting.
Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.
Adult↗
A phase II trial of taxol in metastatic melanoma.
Taxol is an investigational new drug which is currently undergoing Phase II evaluation in various tumors. It is a plant alkaloid extracted from the western Yew, Taxus brevifolia. In this study, patients with metastatic melanoma who were previously untreated, received Taxol at a starting dose of 250 mg/m2 delivered as a continuous intravenous (IV) infusion over 24 hours, at 3-week intervals. All patients were premedicated with oral dexamethasone and IV diphenhydramine hydrochloride as prophylaxis against allergic reactions. Three of 25 patients had a partial response (PR) for a response rate of 12% (CI, 3%-31%). In addition four patients had objective regression of tumor that failed to qualify for a PR but these responses were as durable, lasting 6 to 17 months. No patient experienced acute allergic reactions. The major toxicity of Taxol was neutropenia requiring dose reduction to 200 mg/m2 in a majority of the patients. Our data confirm that Taxol has definite although limited activity against metastatic melanoma.
Adult↗
Intrapleural etoposide for malignant effusion.
The pharmacology, toxicity, and therapeutic effectiveness of etoposide (VP-16) given by the intrapleural route were examined in a phase I trial. Ten patients with malignant pleural effusion received 100, 150, or 225 mg/m2 VP-16 infused over 2 h into the pleural space after drainage of pleural fluid. The administration of VP-16 was tolerated well, with no local pain, increase in cough, dyspnea, or infection. Myelosuppression was mild at doses of 150 mg/m2 or less but severe at 225 mg/m2. Drug levels were followed in both plasma and pleural fluid for up to 12 h. Clearance of VP-16 from the pleural cavity was low at 2 ml/min m2. Peak pleural-fluid drug levels in patients receiving 225 mg/m2 exceeded 300 micrograms/ml, whereas peak drug concentrations in corresponding plasma samples obtained at the same time amounted to less than 10 micrograms/ml. Serial chest X-rays showed no disappearance of pleural effusion in nine evaluable patients. However, follow-up investigation of pleural fluid characteristics [carcinoembryonic antigen (CEA), lactic dehydrogenase (LDH), and cytologic examination] suggested some evidence of local therapeutic benefit.
Adult↗
The use of sodium sulfide to separate mercury from tissues preserved in Cialit and Merthiolate solutions.
The purpose of the present experiment was to look at the dissolution time in physiological sodium chloride (0.9% NaCl) and sodium sulfide (Na2S) of any mercury (Hg) contained in human auditory ossicles and cartilage after preservation in Cialit and Merthiolate. Both homograft tissues produced almost identical graph complexes. Under static conditions 10 micrograms Hg could be found in NaCl after 15 min, whereas there was complete demercurization after 3 min in Na2S. The dissolution time in NaCl subjected to constant stirring was about 10 min and was less than 1 min in Na2S. For the rapid elimination of Hg from auditory ossicles stored in preservatives containing Hg, our studies show that the use of a flowing solvent is advisable. Further, the extraction of Hg is quicker in sodium sulfide than in an isotonic solution of sodium chloride.
Cartilage↗
Phase I clinical investigation of benzisoquinolinedione.
A phase I study of benzisoquinolinedione (amonafide) was conducted in 30 patients with advanced solid tumors refractory to conventional therapy. The starting dose was 10 mg/m2/day X 5 days and the highest tolerated dose was 625 mg/m2/day X 5. The daily dose was mixed in 100 ml of normal saline and infused over 30-60 minutes. The dose-limiting toxicity was myelosuppression with nadirs of blood counts reached on Day 15 and recovery by Day 21-28. Other side effects included mild nausea and vomiting, mild phlebitis, skin rashes, and alopecia in some patients. A majority of the patients experienced dizziness, tinnitus, and hot flushes occurring predominantly at the higher dose levels. These were related to the rate of drug infusion and resolved on prolonging the infusion to 60 minutes. Pharmacokinetic studies of amonafide revealed a monoexponential plasma disappearance curve with a mean half-life of 3.5 +/- 1.9 hours. The recommended dose of amonafide for phase II studies in solid tumors is 400 mg/m2/day X 5 for good-risk and 300-320 mg/m2/day X 5 days for poor-risk patients with courses repeated at 21-28-day intervals.
Adenine↗
Estrogen receptor analysis by flow cytometry.
A fluorescently labeled estradiol, N'-fluoresceino-N'-(17 beta-estradiol hemisuccinamide) thiourea (FE) was used for measuring estrogen receptor content per cell in tumor cells. The cellular content of FE was measured quantitatively by flow cytometry. Binding of FE occurs in the nanomolar concentration range, an indication of the high affinity of the labeled estradiol. Competition of FE for binding sites is observed with estrogens, but not with progestins, androgens, or glucocorticosteroids, indicating the specificity of FE binding. In contrast to other estrogen receptor assays, this new technique requires a small sample size (about 5000 cells) and permits the assessment of heterogeneity in estrogen receptor expression among tumor cells.
Binding, Competitive↗
Analysis of pleural effusions using automated flow cytometry.
Flow cytometry allows rapid and accurate analysis of the deoxyribonucleic acid (DNA) content of a large number of cells. In solid tumors, the presence of aneuploidy has been shown to correlate wall with the presence of neoplastic cells. Both cytologic examination and DNA analysis by flow cytometry were performed on pleural effusions from 33 patients. Results of the two examinations were in agreement in 10 of 12 malignant pleural effusion (two false-negatives) and in 20 of 21 benign effusions. One patient with cirrhosis, ascites and Nocardia pneumonia had hypodiploid cells (false-positive) in the pleural fluid. All patients who had a malignancy, but whose pleural effusion proved to be due to a benign cause, had cells with normal DNA content in their pleural effusion. DNA analysis using flow cytometry can be rapidly performed and is highly specific and sensitive. The finding of hyperdiploid cells is highly suggestive of malignancy.
Adult↗
Anaplastic myeloma with massive extramedullary involvement. Report of two cases.
Two patients developed anaplastic myeloma associated with prominent extramedullary disease one and four years after the initial diagnosis of multiple myeloma. Most tumor cells in the extramedullary sites were primitive-appearing and anaplastic, although plasmacytoid differentiation was evident. One patient had concurrent bone marrow involvement by cytologically similar cells, while the other patient was in bone marrow remission when he developed clinically evident soft tissue infiltration. Immunoperoxidase staining showed similar cytoplasmic immunoglobulin in both the mature-appearing and anaplastic cells in both patients. Electron microscopy in both cases showed a morphologic spectrum between the mature-appearing and anaplastic cells. DNA flow cytometric studies following the onset of extramedullary disease revealed a tumor cell population with a high degree hyperdiploid abnormality and unusually high proliferative activity in both cases, consistent with the morphologic anaplasia. Anaplastic myeloma appears to represent a distinct, aggressive variant of multiple myeloma which may result from a transformation of well differentiated myeloma cells to poorly differentiated immunoblast-like cells.
Abdominal Neoplasms↗
Flow cytometry and cytomorphology in primary resectable breast cancer.
Using flow cytometry for DNA analysis, ploidy and proliferative activity were measured in 43 cases of primary resectable breast cancer, 24 of which were also assayed for estrogen receptors. Tumors were studied histopathologically by multiple samples and cytopathologically by means of imprint smears and pepsinized cell suspensions. Cytologic preservation was far superior in imprint smears than in cell suspensions or histologic sections. As determined by the DNA index (tumor G1/G0:normal G1/G0), 72% of the tumors were aneuploid, with the majority falling between diploid and tetraploid. There was no correlation of ploidy with tumor cell proliferation expressed as percentages in the S-phase. A high percentage of S-phase cells was associated with estrogen receptor negativity and tended to correlate with cytologic atypia but showed no correlation with UICC stage, menopausal status, tumor size, lymph node involvement or histologic degree of malignancy. In contrast, ploidy showed no correlation with any of the above parameters but served as a reliable marker for individual tumors since it did not change with time in multiple biopsies of the primary site.
Adult↗
In vivo cellular kinetic and pharmacological studies of 1-beta-D-arabinofuranosylcytosine and 3-deazauridine chemotherapy for relapsing acute leukemia.
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3-Deazauridine↗
Short schedule intravesical mitomycin preceding transurethral resection for recurrent Ta-T1, G1-G2 bladder cancer.
AIMS AND BACKGROUND: Intravesical instillations commonly follow resection, when all visible lesions have been removed, making impossible any direct assessment of efficacy. The study was conceived to evaluate the ablative effect on the tumor and the efficacy in reducing the risk of recurrence of short schedule intravesical chemotherapy administered before endoscopic resection. STUDY DESIGN: Four weekly intravesical instillations of mitomycin C followed by transurethral resection (TUR) were administered to 31 patients with recurrent small volume superficial bladder cancer. RESULTS: At TUR no evidence of disease was found in 22 patients (70.9%) and residual disease in the remaining 9 (29.1%). At a median follow-up of 15 months (range, 3-33) 16 of 31 patients (51.6%) had recurrence of disease. The treatment was well tolerated. CONCLUSIONS: Short-schedule intravesical chemotherapy can completely ablate small volume recurrent superficial bladder cancer in a relevant number of patients but is probably not sufficient to obtain long-term prophylaxis.
Administration, Intravesical↗
Clinical pharmacology of 1-beta-D-arabinofuranosyl-5-azacytosine (fazarabine) following 72-hour infusion.
The clinical pharmacology of fazarabine (1-beta-D-arabinofuranosyl-5-azacytosine), a structural analogue of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine, was assessed in 14 patients with various malignancies during a phase I trial. Since the starting dose for the protocol was low (0.2 mg/m2/hr over a 72-hr continuous iv infusion), a radioimmunoassay (RIA) using commercially available ara-C antibody and [3H]ara-C was developed to measure the anticipated low plasma drug levels. The assay could be used to measure fazarabine accurately in plasma and urine with a sensitivity of 0.08 ng/ml. The RIA does not require extraction of samples. Using both RIA and HPLC, similar results were obtained in plasma samples from a patient receiving a high dose (180 mg/m2/hr) of fazarabine. The assay is simple, sensitive, reproducible, and specific. Following the infusion, plasma levels declined triphasically with a terminal half-life of 5.7 +/- 2.0 hr. The AUC was linearly related to dose. When the various doses were normalized to 1.75 mg/m2/hr (the maximum tolerated dose as determined from the phase I trial) the mean AUC value was 4232 +/- 987 (ng/ml)hr. Plasma steady-state drug levels (CPss) were achieved in 2-4 hr and were linearly dependent to dose. Also, when normalized, the mean CPss was 58 +/- 13 ng/ml, which is within the reported concentration range necessary for inhibiting malignant cell growth. Total clearance was rapid, 528 +/- 138 ml/(m2.min), and not dose-related.
Adult↗