Evaluation of intensive postremission chemotherapy for adults with acute nonlymphocytic leukemia using high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide.

In order to test the toxicity and efficacy of intensive postremission therapy with high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide in adults with acute nonlymphocytic leukemia (ANL), 100 adults (ages 19 to 75) with previously untreated ANL were entered into a study using six sequential cycles of chemotherapy. Cycles 1 (induction), 3, and 5 included conventional doses of daunomycin, cytosine arabinoside, 6-thioguanine, vincristine (VCR), and prednisone. Cycle 2 was cytosine arabinoside 3 g/m2 intravenously (IV) every 12 hours for four doses, followed by L-asparaginase 10,000 U intramuscularly (IM) at hour 42; this combination was repeated 1 week later. Cycle 4 included amsacrine 120 mg/m2/d and etoposide 100 mg/m2/d, both IV for five days, and cycle 6 was three monthly courses of VCR on day 1, and prednisone, mercaptopurine, and methotrexate each for five days. Seventy-four patients (74%) achieved complete remission (CR) (51 with cycle 1 and 23 after cycle 2). The overall disease-free survival (DFS) for patients achieving CR is 27% at 3 years by Kaplan-Meier analysis, while for patients achieving CR with cycle 1 it is 34%. The actuarial probability of being free from relapse at 3 years for patients achieving CR is 34%. Sixteen of the 74 CR patients (22%) died in CR while continuing to receive intensive chemotherapy, including 12 (18%) who succumbed to infection (nine bacterial, three fungal). After a median follow-up of 20 months, 36 patients have relapsed and 21 remain alive in CR. Intensive consolidation with high-dose cytosine arabinoside, amsacrine, and etoposide can modestly prolong DFS compared with historical controls. However, relapse continued to be a major problem and, in addition, with more aggressive consolidation therapy, infection during marrow aplasia resulted in a significant number of deaths.

Combined treatment with chemotherapy and neutron irradiation for limited non-small-cell lung cancer: a Southwest Oncology Group Study.

Seventy-three patients with regional, inoperable non-small-cell lung cancer received treatment with initial chemotherapy for two cycles (vinblastine-mitomycin followed in 3 weeks by vinblastine-cisplatin), with planned subsequent neutron irradiation to the primary site and concurrent, elective whole-brain irradiation using photons, followed by two more cycles of identical chemotherapy. Histology was reported as adenocarcinoma or large cell in 75%, and 60% had Radiation Therapy Oncology Group (RTOG) stage 3 disease; the remainder had stage 4. The response rate to chemotherapy induction was 51%. There were 58 patients in a second phase of the study who were potentially eligible for treatment with a medically dedicated cyclotron having more favorable characteristics with regard to treatment planning and dose delivery (neutrons "B"). The overall response rate in this group was 79%. Chemotherapy toxicity included four fatalities (5%), with three related to mitomycin C induced bilateral pneumonitis, and an additional five patients (7%) with life-threatening events that required hospitalization. Two fatalities were attributed to combined effects of chemotherapy and radiation, and six more to chest radiation therapy, for an overall treatment-related death incidence of 12 of 73 (16%). Four of the six deaths related to chest irradiation occurred after treatment with a "physics-based" neutron generator (neutrons "A"). Among the 45 who received neutrons in the B group, two (4%) had radiation-related deaths, and another four (10%) had clinically evident radiation pneumonitis. Pretreatment performance status (PS) and response to chemotherapy, but not RTOG stage or weight loss, were significantly associated with survival. Among patients who actually received chest irradiation, only initial response to chemotherapy remained as a significant predictor of survival in univariate analysis, with a median survival of 20 months in responders v 9 months in chemotherapy nonresponders. The patterns of first relapse observed in B group patients revealed that 28% were distant, while 64% were locoregional. This represents a reversal of the usual pattern in studies of chest irradiation alone. It probably reflects elimination of brain relapse by the use of elective whole-brain irradiation, impact of systemic chemotherapy on micrometastases elsewhere, and conservative treatment volumes employed for the chest irradiation in an attempt to minimize its toxicity. Further exploration of combined modality therapy is indicated for regional non-small-cell disease, with a real potential for survival impact if the therapeutic index can be improved.

Psychiatrists' attitudes toward prescribing medication for patients treated by nonmedical psychotherapists.

Although many psychiatrists prescribe medications for patients whose primary therapist is a nonmedical professional, few guidelines exist for this practice. Two-thirds of a sample of Connecticut psychiatrists surveyed by mail provided medication backup services, but only one-third considered the practice generally ethical. Seventy-five percent of respondents who provided this service reported that the arrangement was initiated by the nonmedical therapist. Many of the respondents were concerned about the prescribing psychiatrist's legal responsibility for the therapist's activities, but responses suggested that few psychiatrists use a consistent method to evaluate the therapist's qualifications. The authors propose areas that need further study before professional guidelines can be developed.

The aggressive surgical management of hypercalcemia due to ectopic parathormone production.

A patient with slowly progressive metastatic renal cell carcinoma had life-threatening hypercalcemia secondary to ectopic parathormone production. Aggressive surgical debulking resulted in prolonged control of the hypercalcemia. This case illustrates the value of this surgery in the control of paraneoplastic endocrine syndromes refractory to medical management in patients with slow-growing metastatic disease.

Clinical toxicologic and pharmacologic studies of gallium nitrate.

Gallium nitrate, administered intravenously to patients with advanced cancer, produced renal functional abnormalities consistently at a dose of 750 mg/m2. The toxicity at that dose could be modified by fluid loading and osmotic diuresis. Pharmacokinetic studies revealed a biphasic half-life, (T 1/2 alpha = 87 minutes and T 1/2 beta = 24.5 hours). Osmotic diuresis reduced the urinary concentration of gallium but did not affect serum levels or clearance.

Medication backup in psychiatry residency programs.

All directors of U.S. adult psychiatry residency training programs (N = 202) were surveyed in 1988 about the practice of medication backup by trainees in their programs. Medication backup was defined as "the provision of medications by psychiatrists to patients receiving psychotherapy from nonphysicians." Of 110 respondents, 94 of the programs (85%) had residents providing medication backup, the majority in the PGY-3 and -4 years. The university hospital inpatient service and the community mental health center outpatient clinic were the most common sites. Supervision was the most prevalent training method (84 programs), followed by lectures and seminars (45). Sixty-four program directors mewed medication backup as a useful and important function for the psychiatrist; 48 raised ethical concerns. Results point to the need for further investigation into the practice of medication backup in residency training.

Combination chemotherapy of colorectal cancer with 5-fluorouracil, methyl-1,3-cis(2-chloroethyl)-1-nitrosourea, and vincristine.

The combination of 5-fluorouracil (5-FU), methyl-1,3-cis(2-chlorethyl)-1-nitrosourea (methylCCNU), and vincristine (VCR) has been reported to produce a 43.5% response rate in metastatic colorectal cancer, although subsequent studies did not produce such good response rates. The clinical trial reported here was undertaken to assess the reported results. In 52 evaluable patients the overall response rate was 11%. No complete remissions were observed. Six patients with colon carcinoma had a partial remission lasting for a median of ten months, with a median survival of 15 months. No responses were observed in rectosigmoid cancer. The median survival for nonresponders was 7.5 months. Thirty-three percent of the patients had significant hematological toxicity (while count) less than or equal to 1,000/mm3, platelets less than or equal to 50,000/mm3); 58% of the patients experienced nausea and vomiting; and 32% experienced some degree of neurotoxicity. In our hands the combination of 5-FU, methylCCNU, and VCR produced a response rate of 11% in metastatic colorectal cancer with a considerable amount of toxicity.

Studies on diabetes mellitus after ventromedial hypothalamic lesions in adult and aged rats.

The signs of obesity and diabetes in 49 adult and 56 aged female Wistar rats were studied following complete and histologically confirms bilateral lesions of ventromedial hypothalamic nuclei. Persistent diabetes was found in 14 out of a total of 56 aged animals, while in a group of 49 adult females only one animal showed definite signs of this disease. In addition, several changes of lipid and glucose metabolism together with increased level of immunoreactive insulin and severe changes in the histological picture of pancreatic islets and beta-cells were observed.

Combination radiotherapy and chemotherapy for small cell carcinoma of the lung.

Twenty previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide, 400 mg/m2 and Adriamycin, 40 mg/m2 IV on day 1, followed by cytosine arabinoside, 20 mg/m2, every 12 hours subcutaneously on days 5--9; this regimen was repeated every 28 days. On days 14--28 of the first cycle, each patient received 3,000 rads to the primary tumor and whole brain. Following eleven courses, Adriamycin was discontinued and patients received cyclophosphamide, 800 mg/m2 IV on day 1 and methotrexate, 15 mg/m2 IV on days 5--7. This regimen was repeated every 28 days. Toxicity included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and esophagitis. Overall response rate was 65%. Media survival in limited disease was 14.5 months, and in extended disease it was 4.5 months. This combination is active in localized small cell carcinoma but provides no superiority over other regimens.

Phase I study of pentamethylmelamine.

Pentamethylmelamine is a soluble monodemethylated derivative of hexamethylmelamine. Its activity in animal tumors is similar to that of hexamethylmelamine. When given iv at a dose of 1200 mg/m2 to patients with advanced cancer, it produced severe nausea and vomiting, severe psychotropic effects, and EEG changes. When this dose was given for 10 consecutive days, there was marked but reversible myelosuppression. The severe CNS effects which occurred at doses sufficient to produce myelosuppression cast doubt on the potential utility of pentamethylmelamine.

Lung abscesses following corticosteroid therapy for central nervous system metastases.

Although the occurrence of lung abscesses has decreased among the general population since the advent of antibiotics, a specific subgroup of cancer patients has demonstrated a propensity for this complication. Four patients with lung cancer, receiving corticosteroid therapy for brain metastases, developed large lung abscesses. These patients represent 12% of the 33 patients with central nervous system metastases seen in this institution over the period of one year. Physicians should be alert to this possible complication of corticosteroid therapy in patients with lung cancer.

Biochemical testing in patients with alcoholic liver disease.

We evaluated physicians' laboratory utilization patterns for hospitalized patients with alcoholic liver disease and examined the relationship between the frequency of test ordering and certain variables in clinical outcome. During the study, 185 patients with alcoholic liver disease were hospitalized 378 times at the VA Medical Center, Long Beach, California. Physicians ordered liver panels (including serum albumin, alkaline phosphatase, total bilirubin, lactic dehydrogenase, glutamic pyruvate transaminase, and glutamic oxaloacetic transaminase) an average of 7.4 times per hospitalization. Increased biochemical testing did not decrease length of stay or improve clinical outcomes such as development of complications or survival of hospitalization. Since the treatment of alcoholic liver disease is largely supportive and not dependent upon frequent biochemical testing, we recommend that these tests be ordered only when patients are admitted to or discharged from the hospital, and when there has been a clinical change.

Combination chemotherapy and high-dose cyclophosphamide intensification for poor prognosis breast cancer. A Southwest Oncology Group Study.

Thirty-seven patients with poor prognosis, metastatic breast cancer were treated with 5-fluorouracil, vinblastine, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (FUVA) induction chemotherapy. All 26 patients (74%) with responsive or stable disease after induction chemotherapy received intensification with high-dose cyclophosphamide (120 mg/kg). Continued responders received additional FUVA as consolidation. The response rate to induction therapy was 54% (with complete response [CR] in 11%). With intensification, three patients (11%) showed improved response (partial response [PR] in one, PR to complete response [CR] in two); however, six patients (23%) progressed within 2 months of cyclophosphamide intensification, three within 1 month. The overall response rate to all three phases of the study was 69%, with CR in 23%. The median survival of all patients entered in this study was 15 months. For cyclophosphamide intensification, major toxicity consisted of leukopenia with fever requiring broad-spectrum antibiotics in 27%. The authors conclude that a single cycle of high-dose cyclophosphamide intensification in metastatic breast cancer does not result in significantly improved responses or prolonged survival.

Combination chemotherapy and systemic irradiation consolidation for poor prognosis breast cancer.

Seventy patients with poor prognosis, metastatic breast cancer were treated with FUVAC induction chemotherapy (5-fluorouracil, vinblastine, Adriamycin [doxorubicin] and cyclophosphamide). Consolidation therapy was given to 30 of 48 responders (63%), of whom 23 received sequential hemibody irradiation (HBI) at 8 cGy, corrected in the upper half for lung transmission. Seven received high dose cyclophosphamide and total body irradiation (TBI) with subsequent infusion of stored, cryopreserved autologous bone marrow. The response rate to induction therapy was 71% (complete [CR] in 21%). The median survival for all patients entered in this study is 12 months. With consolidation, one CR patient who received cyclophosphamide and TBI is disease free at 20+ months, off all treatment, while HBI did not produce longterm remissions. Of 17 partial response (PR) patients, two of 12 improved to CR with HBI, and one of five improved with cyclophosphamide plus TBI, but all ultimately relapsed. The main toxicity of sequential HBI was myelosuppression, with prolonged thrombocytopenia in 13%; only one case of radiation pneumonitis occurred (3%). Cyclophosphamide and TBI produced temporary, reversible marrow aplasia without other major toxicity. We recommend further investigation of Cytoxan (Bristol Myers Oncology Division, Evansville, IN) and TBI for breast cancer patients in remission after chemotherapy.

Ciclo reprodutivo de Parauchenipterus striatulus (Pisces-Auchenipteridae) na represa de Riberäi das Lajes - RJ / Reproductive cycle of Parauchenipterus striatulus (Pesces-Auchenipteridae) in the Ribeiräo das Lajes reservoir - Brazil

Este trabalho teve como objetivo avaliar o ciclo reprodutivo do bagre de água doce Parauchenipterus striatulus, na represa de Ribeiräo das Lajes, Rio de Janeiro. Foram descritos aspectos morfológicos dos estádios de maturaçäo gonadal bem como variaçöes no índice gonadossomático, relaçäo peso: comprimento, fator de condiçäo gonadal. A amostragem dos peixes foi feita bimestralmente entre abril de 1996 e maio de 1997 com o uso de redes de espera de 100m de comprimento, 4m de altura e com malha entre 25 e 65mm de distância entrenós. Os 339 indivíduos capturados ao longo do período de amostragem corresponderam a 40 por cento do total de peixes. Cinco estádios de maturaçäo gonadal foram determinados por meio de análise macroscópica para ambos os sexos: imaturo, maturaçäo I, maturaçäo II, maduro, desovado (fêmeas) e esvaziado (machos). O índice gonadossomático foi mais elevado entre outubro e março para ambos os sexos, sugerindo amplo período de desova enquanto o fator de condiçäo atingiu seu máximo entre fevereiro a junho, mostrando uma relaçäo inversa entre essas duas características. A relaçäo peso-comprimento para machos foi de W=0,0095L3,0862 sobrescrito e fêmeas de W=0,0116L3,0126 sobrescrito, näo tendo sido encontradas diferenças significativas entre os coeficientes de alometria para ambos os sexos