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Biomedical subjects

B A Chabner

Publications and source records attributed to B A Chabner.

At least 55 records · Page 3Linked to original sources
PubMed1977

Peritoneoscopy: a technique to evaluate therapeutic efficacy in non-Hodgkin's lymphoma patients.

Peritoneoscopy was performed in 22 patients with non-Hodgkin's lymphoma as a re-staging technique to rule out relapse or persistence of active disease after intensive chemotherapy and/or radiotherapy. Fifteen patients with previous hepatic involvement achieved a complete clinical remission; however, five patients (33%) had persistent disease proved by biopsy at peritoneoscopy. In seven patients suspected to have a clinical relapse, peritoneoscopy biopsies documented relapse in three patients (43%), including two patients with negative percutaneous liver biopsies. Because of its low morbidity rate (4%), peritoneoscopy can be utilized to re-stage hepatic involvement by non-Hodgkin's lymphoma patients more accurately than percutaneous liver biopsies and with less morbidity than laparotomy.

Humans↗
PubMed1977

Advanced lymphocytic lymphoma: randomized comparisons of chemotherapy and radiotherapy, alone or in combination.

Ninety-nine previously untreated patients with stage III and IV malignant lymphoma were randomized to receive either cyclic combination chemotherapy (50 patients) or extensive "systemic" radiotherapy (49 patients). Histologic classification included nodular poorly differentiated lymphoma (54 patients), nodular mixed lymphoma (21 patients), and diffuse poorly differentiated lymphoma (24 patients). High overall response rates were seen with either approach (90% for radiotherpy; 86% for chemotherapy) and complete remission were relatively common (60%--80%). Overall median survival of all patients in this trial will exceed 5 years regardless of the induction therapy used; however, disease-free survival is not commonly achieved with either regimen. Relapse-free survival rates at 4-year followup, regardless of induction regimen, are 13% for diffuse lymphomas and 24% for nodular lymphomas. The second prospective trial attempts to use a combined approach and compares cyclic combination chemotherapy with total-body irradiation and combination chemotherapy. Initial results on 34 patients indicate high overall response rates (100%) and similar complete remission rates (64%--67%). With 14 months' median followup no patients in either arm of the trial have died but relatively equal numbers have relapsed.

Adult↗
PubMed1977

Dose-dependent metabolism of methotrexate in man and rhesus monkeys.

Humans and rhesus monkeys receiving high-dose methotrexate (MTX) (greater than 50 mg/kg) excrete significant quantities of the metabolite, 7-hydroxy-MTX. This metabolite, though 200-fold less potent than MTX as an inhibitor of mammalian dihydrofolate reductase, is of very limited aqueous solubility, and thus may contribute to the renal toxicity of the high-dose regimen. The metabolite was not observed in previous pharmacologic studies in which conventional doses of MTX were administered (less than 10 mg/kg).

Adolescent↗
PubMed1977

The relative contribution of drug concentration and duration of exposure to mouse bone marrow toxicity during continuous methotrexate infusion.

The effects of exposure of bone marrow to specific methotrexate (MTX) concentrations were studied by constant infusion of the drug into C57BL mice. The residual marrow nucleated cell count was determined in 168 mice at specific intervals. In vitro culture of colony-forming cells (CFU-C) was also performed in 69 of these mice. Duration of exposure varied from 12 to 72 hr. Plateau plasma MTX concentrations were studied in the range from 10(-8) to 10(-5) M. The total number of nucleated cells per femur fell to a nadir of 30% of control for all drug concentrations studied. The nadir was reached earliest with the highest drug concentrations. The percentage of CFU-C per 7.5 X 10(4) nucleated cells plated increased after 48-hr infusions compared to the percentage after 24-hr infusions. This increase was seen at all plasma concentrations studied. The total number of CFU-C per femur at plasma MTX concentrations above 10(-6) M decreased in the first 24 hr to 40% of control, but then the number significantly increased to 66% of control between 24 and 48 hr. In contrast, no change was observed in CFU-C per femur between 24 and 48 hr during constant infusion at plasma concentrations below 10(-6) M. Wright's-stained smears showed no change in the differential count of marrow specimens at 24 and 48 hr that might account for the increased percentage of CFU-C at 48 hr. The increase in CFU-C per femur during high-dose infusions is probably the result of recruitment of CFU-C. The increased percentage of CFU-C suggests recruitment at the lower concentrations as well, but selective elimination of non-CFU-C cells cannot be excluded. Marrow [6-3]deoxyrudine incorporation studies in vivo during exposure to 10(-7) M MTX showed that the phenomenon of recruitment observed in vitro was initiated during the absence of DNA synthesis in vivo.

Animals↗
PubMed1977

Sequential staging in non-Hodgkin's lymphoma.

The results of staging in 170 patients with non-Hodgkin's lymphoma have been reviewed; all patients were subjected to a series of sequential procedures, including lymphangiography, bone marrow biopsy, and liver biopsy (performed percutaneously, by peritoneoscopy, or by laparotomy). A high incidence of involvement of bone marrow, liver, and abdominal nodes was found in patients with nodular types of lymphoma and in those with diffuse lymphocytic lymphoma, with less than or equal to 20% remaining in stage I or II at the completion of staging in each of these subgroups. Only in patients with histiocytic lymphoma was there an appreciable percentage (31%) remaining in the stage I-II categories after staging. In this study, 75 patients remained in stage III or less after completing the non-surgical phase of staging, and laparotomy was utilized in only 50 patients (30%). At laparotomy, involvement of the liver or the mesenteric or portal lymph nodes was found in 81% of patients with a positive lymphangiogram but in only 18% of those with a negative lymphangiogram.

Biopsy↗
PubMed1976

Abnormal pulmonary gallium accumulation in P. carinii pneumonia.

The potentially fatal interstitial pneumonia of Pneumocystis carinii is a frequent opportunistic invader of patients treated for malignancy with immunosuppressive and cytotoxic agents. Generalized Ga-67 pulmonary localization which is markedly disproportionate to the clinical and radiographic findings has led to earlier diagnoses by open lung biopsy in this setting. The potential usefulness of gallium scintigraphy in patients with suspected P. Carini pneumonia is presented.

Adult↗
PubMed1976

7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate.

Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug.

Adult↗
PubMed1976

Combination chemotherapy for advanced breast cancer: response and effect on survival.

Forty patients with metastatic breast cancer who had received no previous cytotoxic therapy were treated with a combination chemotherapy program CMF (P), which included methotrexate, 60 mg/m2, and 5-fluorouracil, 700 mg/m2 intravenously on the first and eighth days, in addition to cyclophosphamide, 100 mg/m2, and prednisone, 40 mg/m2, by mouth daily from the first to the fourteenth day of a 28-day cycle. Only 2 of 25 patients responded to hormonal therapy or endocrine ablation. Twenty-seven of the 40 patients (68%) had a complete response (8 patients) or partial response (19 patients). Lung, soft tissue, and nodal metastases were the most responsive sites. The median survival of 18 months for the responding group. The nonresponders had a median survival of 4 months. The toxicity was primarily hematologic and was especially severe in patients with functional liver impairment due to metastatic disease.

Adult↗
PubMed1976

Sequential nonsurgical and surgical staging of non-Hodgkin's lymphoma.

The yield of specific diagnostic procedures in the staging of non-Hodgkin's lymphoma was assessed in 170 consecutive patients who were evaluated with a sequence of diagnostic procedures. Stage III or Stage IV disease was established in 141 of 170 patients (80%) by nonsurgical procedures, including lymphangiography (positive in 78%), bone-marrow biopsy (positive in 39%), percutaneous liver biopsy (positive in 21%), and peritoneoscopy-directed liver biopsy (positive in 29% of those tested). Staging laparotomy showed disease outside conventional nodal irradiation fields in 21 of 26 patients with a positive lymphangiogram, but in only three of 17 patients with a negative lymphangiogram. The yield of staging procedures was highest in patients with nodular lymphomas, only 6% of whom were Stage I or Stage II after staging, but was lowest in patients with histiocytic lymphoma, 30% of whom had localized disease. This study shows that the presence of disseminated disease can be detected in the majority of patients with non-Hodgkin's lymphoma without the use of staging laparotomy.

Adult↗
PubMed1976

Bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP) combination chemotherapy in the treatment of advanced diffuse histiocytic lymphoma.

A new combination chemotherapy program for patients with diffuse histiocytic and mixed histiocytic-lymphocytic lymphoma was designed to prevent tumor recurrence during the recovery period of each treatment cycle. A myelosuppressive phase consisting of adriamycin, cyclophosphamide, and vincristine was followed by the nonmyelosuppressive agents bleomycin and prednisone to suppress regrowth of lymphoma while allowing for a return in bone marrow function. Twelve of 25 patients (48%) with advanced, previously untreated, diffuse histiocytic lymphoma achieved a complete remission as determined by restaging 1 month after discontinuation of treatment. The median duration of complete response after completion of therapy is in excess of 1 year (range, 5 to 30 months), and no patient has relapsed. Based on previous experience, it is anticipated that the majority of these patients will achieve an extended disease-free survival for what had previously been regarded as an invariably fatal disease.

Adult↗
PubMed1976

Sepsis with a new species of Corynebacterium.

Sepsis with a previously undescribed species of Corynebacterium was documented in four patients. All patients had predisposing illness at the time of infection, three patients having leukemia in relapse and one having a porencephalic cyst and a ventriculoatrial shunt. The isolates from blood cultures had a characteristic metallic sheen when grown on blood agar. They were resistant to most antibiotics tested, including the penicillins, but were uniformly sensitive to vancomycin. Common biochemical characteristics, the metallic sheen, and the unusual antibiotic sensitivity pattern suggest that these isolates comprise a new species or group of closely related species of Corynebacterium that is capable of infection in man.

Adult↗
PubMed1976

Chemotherapy of the blastic phase of chronic granulocytic leukemia: hypodiploidy and response to therapy.

Thirty-two patients in the blastic phase of Philadelphia chromosome-positive chronic granulocytic leukemia (CGL) were studied in a prospective randomized trial in which vincristine--prednisone (19 patients) was compared with cytosine arabinoside--6-thioguanine (13 patients). Seven remissions (37%), including two complete remissions, were achieved in the vincristine--prednisone group. Three of the five with predominant hypodiploid blast cell lines treated with vincristine--prednisone had complete or partial remissions. Both complete remitters presented with hypodiploidy consisting of 44 chromosomes. Four patients (30%) who were treated with cytosine arabinoside--6-thioguanine responded with one complete remission. The median survival of the responders was 8 mo, as compared to 1--2 mo for the nonresponders. Crossover to the opposite regimen as secondary therapy following refractoriness or resistance resulted in only 3 partial responses out of 21 treated. All three had previously responded to vincristine--prednisone. Of the 32 cases, 14 had an elective splenectomy during the chronic phase of the disease. Prior splenectomy did not influence the response to chemotherapy, as all three complete remitters occurred in the nonsplenectomized group. Similarly, survival in the blastic phase was not affected by prior splenectomy.

Adolescent↗