Biomedical subjects
J Crowley
Publications and source records attributed to J Crowley.
Phase II study of fludarabine phosphate for the treatment of advanced non-small cell carcinoma of the lung: a Southwest Oncology Group Study.
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Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study.
This pilot study in limited-stage small-cell carcinoma of the lung using concurrent cisplatin (Platinol) and etoposide (VePesid) chemotherapy with radiotherapy has yielded a high complete response rate in 23 of 40 patients evaluable for response. Five of these responders have survived greater than 2 years off all therapy with a stable, high performance status. Median survival of all patients is 18 months. Toxicity has been acceptable, the most common being neutropenia. Radiation toxicities include 17 of 40 patients experiencing mild to moderate esophagitis, with one severe toxicity; and three of 40 patients developing mild to moderate radiation pneumonitis. The high complete remission observed with this program and the long tumor-free interval seen off maintenance therapy deserve further exploration. Toxicities appear only moderately greater than with other programs currently utilized.
Abortion and medical discipline.
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Arachidonic acid metabolic pathway of the rabbit placenta.
Placenta microsomes prepared from animals late in gestation (29 days) efficiently metabolize arachidonic acid into PGE2, PGF2 alpha, PGD2, TxA2 and little or no prostacyclin. In contrast to the late gestation placenta, the early (17 day) placental microsomes synthesize primarily PGE2. The cytosolic (100,000 X g supernatant) fraction from early or late gestation placentae converted arachidonic acid, with a calcium dependent enzyme, into non-polar metabolites whose synthesis was inhibited by ETYA but not indomethacin. These metabolites were purified by HPLC and GC-MS analysis indicated the presence of 12-hydroxy-, 15-hydroxy-, and 11-hydroxy-eicosatetraenoic acid. The mitochondrial (8,000 X g pellet) produced PGE2; PGF2 alpha; 12-, 11-, 15-HETE; the C-17 fragment HHT; and the unusual cyclooxygenase metabolite 15-keto-PGE2. These biologically active metabolites may play a vital role in the reproductive function of the placenta.
Post-delivery bleeding due to group B beta-haemolytic streptococcal infection.
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Statistical analysis of survival data.
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Bone marrow transplantation or chemotherapy after remission induction for adults with acute nonlymphoblastic leukemia. A prospective comparison.
We compared the outcome of marrow transplantation with that of continued chemotherapy for adults with acute nonlymphoblastic leukemia who achieve a first remission. From May 1977 to July 1982, 111 consecutive adults (ages 17 to 50) with newly diagnosed acute nonlymphoblastic leukemia were treated with induction chemotherapy. Ninety patients (81%) had a complete remission. Forty-four remission patients had available donors: 33 received a transplant and 11 did not. Forty-six patients in remission without matched donors were treated with continued chemotherapy. Kaplan-Meier estimates of 5-year, disease-free survival from complete remission are 49% +/- 18% for the transplant group and 20% +/- 13% for the chemotherapy group. When compared to the chemotherapy group, patients undergoing transplantation had a higher risk of dying during the first 6 months after remission induction but a lower risk of dying thereafter. Within the transplant group, only age influenced survival. Within the chemotherapy group, a leukocyte count of greater than 10 000 mm3 at diagnosis, a French-American-British (FAB) Cooperative Group morphologic status of M-4, M-5, or M-6, and the presence of infection at diagnosis were all associated with shorter survival.
Communication in medicine.
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Selective antimicrobial modulation as prophylaxis against infection during granulocytopenia: trimethoprim-sulfamethoxazole vs. nalidixic acid.
Sixty-two profoundly granulocytopenic patients with acute leukemia undergoing induction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or nalidixic acid plus nystatin for prevention of infection. Patients given trimethoprim-sulfamethoxazole plus nystatin during initial remission induction experienced an increased duration (22.6 vs. 13.6 days) of profound granulocytopenia (less than 100 granulocytes/mm3; P = 0.007). Acquisition of gram-negative bacilli was more frequent among patients treated with nalidixic acid plus nystatin while filamentous fungi were acquired more frequently by patients receiving trimethoprim-sulfamethoxazole plus nystatin (P = 0.05). The median duration of on-study time prior to documentation of first infection was longer for patients receiving trimethoprim-sulfamethoxazole plus nystatin (17 days) than for those receiving nalidixic acid plus nystatin (eight days) (P = 0.0002). Three infection-related deaths occurred among patients receiving nalidixic acid; seven occurred among patients receiving trimethoprim-sulfamethoxazole, five of which were secondary to pneumonia due to Aspergillus flavus. Both of these methods of selective antimicrobial modulation have apparent advantages, but each has disadvantages serious enough to limit their routine use.
Room service at the hospital.
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Dibromodulcitol and adriamycin +/- tamoxifen in advanced breast cancer.
The therapeutic effectiveness of combining tamoxifen with a combination chemotherapy regimen was tested in 135 patients with advanced breast cancer previously treated with chemotherapy. Patients were randomly allocated to received dibromodulcitol + Adriamycin (DA, 55 patients) or DA + tamoxifen (DAT, 67 patients). An additional 13 patients less than 50 years of age were assigned to DAT (DATN). Pretreatment characteristics were similar across both regimens. DAT and DATN yielded similar results in the less than 50-year-old cohort. DAT tended to be superior to DA with respect to response rate (55% versus 36%, p = 0.004), time to treatment failure (medians: 170 days versus 110 days, log rank p = 0.001), responders' time to treatment failure (360 days versus 220 days, p = 0.035), and survival (340 days versus 270 days, p = 0.18). Toxicity was similar in both regimens. Thus, addition of tamoxifen to a second-line DA regimen appears to increase the therapeutic effectiveness. It is suggested that the addition of this antiestrogen to other chemotherapy regimens would also be beneficial.
A pilot study of mitomycin-C and tamoxifen (MT) versus dibromodulcitol, adriamycin, and tamoxifen (DAT).
The aim of this study was to compare the treatment efficacy of mitomycin-C plus tamoxifen (MT) to adriamycin, dibromodulcitol and tamoxifen (DAT) in previously treated patients with metastatic breast cancer. Thirty-two patients with measurable or evaluable disease were entered on the study. Twenty-three were prospectively randomized to receive DAT (Group 1) or MT (Group 2). Nine patients with prior exposure to adriamycin were directly assigned to receive MT (Group 3). Thirty-one patients were evaluable for response and toxicity. The hematological toxicities were comparable among the three treatment groups. DAT gave more nausea and vomiting than MT. One patient developed irreversible fatal congestive heart failure while receiving DAT. The response for Group 1 was 5/11, Group 2, 3/12, and Group 3, 3/8. The duration of response for patients in Group 1 was 455+, 315, 251, 239, 231 days, in Group 2 it was 328+, 144+, 119, and in Group 3 it was 35+, 84, and 112 days. The median time to treatment failure did not differ significantly between Group 1 (114 days), 2 (83 days) and 3 (61 days) (p = 0.24). The median survival time was similar among the three groups (p = 0.41). This pilot study suggests that MT and DAT are both effective treatment programs in patients with metastatic breast cancer who have failed prior chemotherapy regimens.
Phase I--II evaluation of combination cyclophosphamide, 5-fluorouracil, hexamethylmelamine, and prednisone in advanced breast cancer.
A four-drug combination of intermittent high-dose cyclophosphamide with 5-fluorouracil, hexamethylmelamine, and prednisone was given to 19 patients with advanced breast cancer. Objective response was documented in 7 of 18 evaluable patients. The median duration of response was 99 days. Response was observed in 6/7 patients without visceral disease and 1/11 patients with visceral disease. Toxicity was acceptable and no life-threatening toxicity was observed. Three patients have received the four-drug combination for more than 1 year without serious side effects. This regimen may serve as an alternative treatment for patients without visceral metastasis who have failed to respond to other combination chemotherapy regimens.
Transplantation system for determining the clonogenic survival of parenchymal hepatocytes exposed to ionizing radiation.
An in vivo transplantation technique has been developed which can be utilized to determine the reproductive survival of parenchymal hepatocytes exposed either in vitro or in vivo to both physical and chemical genotoxic agents. We have used this assay system to determine the survival of liver cells exposed to sparsely ionizing radiation. The D0 value of the survival curve was 249 rads and the extrapolation number was 1.2. These results indicate that hepatocytes irradiated while in the G0 phase are unable to accumulate sublethal damage to an appreciable extent if they are stimulated to undergo replication within 24 hr after the infliction of the damage.
Using patients' christian names.
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Hyperaldosteronism associated with liver metastases.
Plasma aldosterone levels were measured in 50 patients with confirmed liver metastases from various histologically proved primary tumors. None of these patients had electrolyte abnormalities or history of benign liver disease, congestive heart failure, hypertension, or renal disease. Patients with edema, ascites, or both had significantly greater elevation of plasma aldosterone levels compared to nonedematous patients; these patients also demonstrated a substantial degree of hepatic dysfunction as evidenced by lower serum albumin levels and higher bilirubin and alkaline phosphatase levels. This study provides a rational basis for the use of the specific aldosterone inhibitor spironolactone in the treatment of patients with advanced metastatic liver disease and edematous states.