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Biomedical subjects

J Crowley

Publications and source records attributed to J Crowley.

At least 19 recordsLinked to original sources
PubMed1992

Low-risk intensive therapy for multiple myeloma with combined autologous bone marrow and blood stem cell support.

To improve the safety of autotransplantation for myeloma, peripheral blood stem cell (PBSC) collection was attempted in 75 previously treated patients after the administration of high-dose cyclophosphamide (HD-CTX; 6 g/m2) with or without granulocyte-macrophage colony-stimulating factor (GM-CSF). Sixty patients subsequently received melphalan 200 mg/m2 (57 patients) or melphalan 140 mg/m2 and total body irradiation (850 cGy) (3 patients) supported by both autologous bone marrow and PBSC; 38 patients received GM-CSF posttransplantation. Among 72 patients undergoing PBSC apheresis, "good" mobilization (greater than 50 colony-forming units granulocyte-macrophage [CFU-GM] per 10(5) mononuclear cells) was achieved when prior chemotherapy did not exceed 1 year and when GM-CSF was used post-HD-CTX; similarly, rapid platelet recovery to 50,000/microL within 2 weeks was associated with "good" PBSC mobilization. These same variables also predicted for rapid engraftment after autotransplantation, so that hematologic recovery (granulocytes greater than 500/microL and platelets greater than 50,000/microL) proceeded within 2 weeks among the 37 patients with "good" PBSC collection. As a result of rapid neutrophil recovery (greater than 500/microL) within a median of 2 weeks, infectious complications both post-HD-CTX and posttransplant were readily manageable, resulting in only one treatment-related death post-HD-CTX. The cumulative response rate (greater than or equal to 75% cytoreduction) for all 75 patients was 68%, with 12-month event-free and overall survival projections of about 85%. Using both bone marrow and PBSC together with GM-CSF, autotransplants are safe and appear effective in myeloma, especially when prior therapy had been limited to less than 1 year. More than 80% of transplanted patients achieved complete hematologic recovery within a median of 1 month posttransplant (granulocytes greater than 1,500/microL; platelets greater than 100,000/microL; hemoglobin greater than 10 g%), thus providing sufficient hematopoietic reserve for further chemotherapy in the event of posttransplant relapse.

Bone Marrow Transplantation↗
PubMed1992

A phase II randomized study comparing sequential and combined intraarterial cisplatin and radiation therapy in primary brain tumors. A Southwest Oncology Group study.

The Southwest Oncology Group conducted a trial of intra-arterial cisplatin (150 mg intravenously every 21 days for 2 doses) administered concomitant with or before radiation therapy. Because of technical difficulties cannulating the artery, 27 of 33 eligible patients were able to receive the cisplatin by arterial injection. Five patients died before completion of the study, and 11 patients in each treatment arm were evaluable for response. Three patients (27%) had an objective tumor regression in each treatment arm. Thromboembolic problems complicated 8 of 57 (14%) chemotherapeutic courses. The median survival for the 33 eligible patients was comparable for both groups: 10.8 months in the concomitant treatment arm and 9.6 months with sequential therapy. Problems related to drug administration and toxicity made it impossible to determine the role of intraarterial cisplatin in the initial management of primary high-grade gliomas.

Adolescent↗
PubMed1992

Exploitation of gene(s) involved in 2,4-diacetylphloroglucinol biosynthesis to confer a new biocontrol capability to a Pseudomonas strain.

Tn5 mutagenesis and complementation analysis were used to clone a 6-kb genomic fragment required for biosynthesis of 2,4-diacetylphloroglucinol (Phl) from fluorescent Pseudomonas sp. strain F113. A recombinant plasmid, pCU203, containing this region partially complemented a Phl production-negative mutant (F113G22) derived from strain F113. When sugar beet seeds were sown into an unsterilized soil, in which sugar beet was subject to damping-off by Pythium ultimum, the emergence of sugar beet seeds inoculated with strain F113 was significantly greater than that of seeds inoculated with F113G22. Transfer of pCU203 into eight other Pseudomonas strains conferred the ability to synthesize Phl in only one of these strains, Pseudomonas sp. strain M114. Strain M114(pCU203) showed enhanced antagonism towards P. ultimum in vitro and significantly increased the emergence of sugar beet seeds in the same soil compared with emergence induced by the parent strain M114.

Anti-Bacterial Agents↗
PubMed1992

Relative risk trees for censored survival data.

A method is developed for obtaining tree-structured relative risk estimates for censored survival data. The first step of a full likelihood estimation procedure is used in a recursive partitioning algorithm that adopts most aspects of the widely used Classification and Regression Tree (CART) algorithm of Breiman et al. (1984, Classification and Regression Trees, Belmont, California: Wadsworth). The performance of the technique is investigated through stimulation and compared to the tree-structured survival methods proposed by Davis and Anderson (1989, Statistics in Medicine 8, 947-961) and Therneau, Grambsch, and Fleming (1990, Biometrika 77, 147-160).

Age Factors↗
PubMed1991

Prognostic correlation of plasma cell acid phosphatase and beta-glucuronidase in multiple myeloma: a Southwest Oncology Group study.

In 1982 a randomized trial of either alternating or syncopated VMCP/VBAP regimens for the treatment of active multiple myeloma was begun (Southwest Oncology Group Study 8229/30). A concurrent investigation was undertaken to evaluate the clinical importance and significance of cytochemically stainable plasma cell acid phosphatase (AP) and beta-glucuronidase enzymes (BG). Pretreatment bone marrow aspirates were available for analysis from 399 patients for AP and 398 patients for BG. The AP scores ranged between 42 and 395, and the BG scores ranged between 1 and 346. There was a significant increase of AP (P = .001) and BG (P = .002) in multiple myeloma as compared with a set of patients with benign plasmacytosis. The enzyme scores did not significantly relate to Ig idiotype of myeloma or other prognostic variables except that the BG scores varied significantly with the level of albumin (P = .03) and hemoglobin (P = .01). Analysis of patient groups with different levels of enzyme scores showed that 61 of 398 patients with an AP score of less than 130 had a poorer median survival of 1.7 versus 2.8 years for patients with higher scores (P = .001). In the multivariate analysis of survival, low AP score was an important prognostic factor (P = .006), but BG did not contribute significantly. It is suggested that the subset of patients presenting with low AP should be considered for specialized or more aggressive therapy.

Acid Phosphatase↗
PubMed1991

Cisplatin and novobiocin in the treatment of non-small cell lung cancer. A Southwest Oncology Group study.

Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin. Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four cycles) after steady-state dosing with novobiocin (1000 mg or four 250-mg capsules every 12 hours for six doses, four of which were administered before each dose of cisplatin). One patient remains on study and cannot be evaluated for response. No complete responses were seen. Three patients (8%) had partial responses and an additional patient had an unconfirmed partial response. The median survival time of all patients was just less than 7 months. These results are comparable with those of other concurrent Southwest Oncology Group (SWOG) Phase II and III trials of high-dose cisplatin in non-small cell lung cancer (NSCLC). Novobiocin plasma levels were obtained for three patients and were approximately 50% of the optimal concentration as reported in cell culture for potentiation of cytotoxicity. It was concluded that an optimum test of novobiocin as a modulator of cytotoxicity may require the availability of an intravenous preparation.

Administration, Oral↗
PubMed1991

A weekly cisplatin-based induction regimen for extensive non-small cell lung cancer. A Southwest Oncology Group study.

The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach.

Adult↗
PubMed1991

Early post-treatment with pentoxifylline or dibutyryl cAMP attenuates Escherichia coli-induced acute lung injury in guinea pigs.

We examined effects of early post-treatment with the methylxanthine pentoxifylline (PTXF), or the cell-permeable adenosine 3', 5'-cyclic monophosphate (cAMP) analog dibutyryl cAMP (db-cAMP) on Escherichia-coli-induced acute lung injury in guinea pigs. Acute lung injury was assessed by measurements of lung water (lung wet/dry weight ratio; W/D ratio), the concentration ratio of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (albumin index; BAL-AI or tissue-AI), and total differential leukocyte count in BAL fluid. Mean arterial pressure (Pa) and peripheral WBC counts were monitored continuously over the 8-h experiment. Septicemia was induced by a bolus injection of 2 x 10(9)/kg live E. coli. Thirty minutes later the animals received a bolus injection followed by continuous infusion of PTXF (20 mg/kg + 20 mg/kg/h; n = 8) or db-cAMP (2 mg/kg + 2 mg/kg/h; n = 8) or saline (septic control; n = 8). Nonseptic control groups were also studied. The lung W/D ratio, BAL-AI, lung tissue-AI, and BAL leukocyte count increased significantly in the septic control group. The PTXF-septic and db-cAMP-septic groups showed no significant increase in lung W/D ratio, BAL-AI, and lung tissue-AI. However, there was no difference in BAL total and differential leukocyte count as compared with the septic control group. PTXF and db-cAMP had no effect on E. coli-induced changes in peripheral WBC count and Pa. Comparison in vitro experiments demonstrated that PTXF and db-cAMP inhibited the endotoxin-induced (E. coli) chemiluminescent response of isolated guinea-pig polymorphonuclear leukocytes (PMN).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Treatment of limited small-cell lung cancer with concurrent etoposide/cisplatin and radiotherapy followed by intensification with high-dose cyclophosphamide: a Southwest Oncology Group study.

Between March 1986 and May 1988, the Southwest Oncology Group enrolled 58 previously untreated patients with limited small-cell lung cancer on a treatment program that administered high-dose cyclophosphamide (150 mg/kg) as late intensification. Treatment consisted of induction chemo-radiotherapy, (weeks 1 to 11), consolidation chemotherapy (weeks 11 to 18), and intensification (week 18). Median age was 61.5 years. Eighty-nine percent of patients had a Southwest Oncology Group (SWOG) performance status of 0-1. Twenty-one patients completed all prescribed treatments. There were seven treatment-related deaths, four as a result of intensification. Fifty-six patients are available for response analysis. Thirty-two patients achieved a complete remission (CR) (57%) and fifteen achieved a partial remission (PR) (26%). Median survival for all patients is 11.1 months. Among the 21 patients who received intensification, nine remain alive in a CR with a median survival of 27 months. This sequence of treatments was not associated with a survival advantage for the group as a whole, possibly because of the toxicity of induction and consolidation treatment and the delayed administration of high-dose cyclophosphamide.

Adult↗