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Biomedical subjects

J J Crowley

Publications and source records attributed to J J Crowley.

At least 19 recordsLinked to original sources
PubMed2005

Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour infusion (SWOG 9714): a Southwest Oncology Group study.

BACKGROUND: There are no published prospective trials of chemotherapy for advanced bronchioloalveolar carcinoma (BAC), a subtype of non-small-cell lung cancer for which there is no current standard therapy. This phase II study assesses the efficacy and toxicity of 96-h paclitaxel in chemotherapy-naive patients with advanced BAC. PATIENTS AND METHODS: Patients with histologically confirmed stage IIIB (with pleural effusion) or stage IV BAC were eligible. Treatment consisted of paclitaxel 35 mg/m2/24 h continuously infused over 96 h (days 1-4) every 21 days for up to six courses. RESULTS: A total of 58 eligible patients were enrolled. The objective response rate was 14% (all partial responses, 9% confirmed); 40% of patients demonstrated stable disease. The median progression-free and overall survivals were 5 and 12 months, respectively. Grade 3 or greater toxicities included neutropenia/granulocytopenia (43%), febrile neutropenia (12%), infection (22%), and stomatitis/pharyngitis (10%); there were five treatment-related deaths. CONCLUSIONS: S9714 represents the first prospective multi-institutional cooperative group trial focusing on treatment outcomes in BAC. Studies targeting this population are feasible, and while first-line paclitaxel administered as a prolonged infusion is active in this setting, toxicities limits the utility of this regimen. S9714 serves as a historical control for BAC patients against which future therapeutic approaches can be compared.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003).

Current information on Waldenström macroglobulinemia (WM) is based on retrospective or single-institution studies of patients requiring therapy. Between 1992 and 1998, 231 patients with WM were enrolled in a prospective observational multicenter clinical trial. Of these, 182 patients with symptomatic or progressive disease were treated with 4 to 8 cycles of therapy with a purine nucleoside analogue, fludarabine (FAMP; 30 mg/m(2) of body-surface area daily for 5 days every 28 days). A serum beta2-microglobulin (beta2M) level below 3 mg/L and a hemoglobin level of at least 120 g/L (12 g/dL) at presentation predicted a lower likelihood of requiring therapy. The overall rate of response to FAMP therapy was 36% (95% confidence interval, 29%-44%), with 2% complete remissions. Patients who were 70 years old or older had a substantially lower likelihood of response (odds ratio, 0.34; P =.004) than younger patients. On multivariate analysis, a serum beta2M level of 3 mg/L or higher, hemoglobin level below 120 g/L, and serum IgM level below 40 g/L [4 g/dL] were significant adverse prognostic factors for survival. We developed a simple staging system for WM by using these variables and identified 4 distinct subsets of patients with estimated 5-year overall survival rates of 87%, 64%, 53%, and 22%, and 5-year progression-free survival rates of 83%, 55%, 33%, and 12%. Prognosis in WM is highly variable and serum beta2M was the dominant predictor of a need for therapy and of survival. FAMP has activity against WM. Our staging system may provide guidance for a risk-based approach to the treatment of WM.

Age Factors↗
PubMed2001

Intra-arterial thrombolysis (reteplase) and ReoPro for subacute thrombosis of the distal aorta accomplished by radial arterial access: the radial-kissing-thrombolytic technique.

A 33-year-old woman with subacute thrombosis of the distal aorta after aorto-bi-iliac stenting had local thrombolysis with reteplase in conjunction with systemic abciximab. The infusion was given as a bolus and then continuously for 14 hr by radial artery access with two selective kissing catheters. Patency of the stented segments was achieved with this technique in conjunction with resolution of her clinical symptoms.

Abciximab↗
PubMed2001

Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

OBJECTIVE: To conduct timely epidemiologic investigations of molecular/genetic markers that may contribute to the development of prostate, lung, colorectal, or other cancers within the Selenium and Vitamin E Cancer Prevention Trial (SELECT), and to evaluate interactions between these markers and the study interventions. METHODS: The epidemiologic studies within SELECT will be based on 32,400 men aged 55 years or older (age 50 or older for the African-American men) enrolled into an intergroup, randomized, placebo-controlled, double-blind, phase III prevention trial of supplemental selenium and vitamin E developed and funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500-2000 cases of prostate cancer, 800 lung cancers, and 500 colon cancers are estimated to be diagnosed, based on data from the ongoing Prostate Cancer Prevention Trial of finasteride. A modified fasting blood sample will be processed to collect plasma for analysis of micronutrients, hormones, cytokines, and other proteins. Buffy-coat derived white blood cells collected at baseline will be used for isolation of DNA and establishment of immortalized cell lines. Red blood cells will be stored for analysis of hemoglobin adducts and other components. RESULTS: Specific results anticipated from these molecular studies will provide information on factors hypothesized to contribute to prostate cancer risk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins affecting androgenic stimulation of the prostate, including the androgen receptor, steroid 5alpha-reductase type II, CYP17, and beta-hydroxysteroid dehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism genes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive intermediates (e.g., glutathione S-transferase M1); DNA and protein adducts; and insulin-like growth factors and leptin. CONCLUSION: SELECT offers an excellent opportunity to conduct molecular epidemiologic investigations to assess gene-environment interactions and their role in prostate, lung, and colon carcinogenesis.

Colorectal Neoplasms↗
PubMed2001

Primary renal artery stenting: characteristics and outcomes after 363 procedures.

BACKGROUND: Stenting improves the acute results of percutaneous balloon angioplasty for atherosclerotic renal artery stenosis. Predictors of benefit and angiographic restenosis are not well understood. We describe the technical and clinical success of renal artery stenting in a large consecutive series of patients with hypertension or renal insufficiency. We identify clinical, procedural, and anatomic factors that might influence outcome, restenosis, and survival. METHODS: Primary renal artery stenting was performed in 300 consecutive patients who underwent 363 stent procedures in 358 arteries. Angiograms were analyzed quantitatively. Clinical and angiographic follow-up data are available after a median of 16.0 months. RESULTS: At baseline, 87% of patients had hypertension, and 37% had chronic renal insufficiency. The mean age was 70 years (interquartile range 63.1-74.6) years. The stenosis was unilateral in 49% and bilateral in 48% and involved a solitary functioning kidney in 3.6%. The stenting procedure was successful in all attempts. There were no procedural deaths or emergency renal surgical procedures. Postprocedure azotemia was seen in 45 of 363 (12%) procedures but persisted in only 6 patients (2%), all of whom had baseline renal insufficiency. Systolic and diastolic blood pressures were significantly reduced (systolic blood pressure from 164.0 +/- 28.7 to 142.4 +/- 19.1 mm Hg, P <.001). At follow-up, 70% of patients had improved blood pressure control regardless of renal function. In patients with baseline renal insufficiency, 19% had improvement in serum creatinine levels at follow-up, 54% had stabilization, and 27% had deterioration. Follow-up mortality was 10% and was predicted by baseline creatinine levels (odds ratio 1.72 for each 1 mg/dL creatinine increment, 95% confidence interval 1.13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased coronary artery, 95% confidence interval 1.03-2.67). Angiographic restenosis was found in 21% of 102 patients overall and was less common (12%) in arteries with a reference caliber >4.5 mm (P <.01 vs caliber <4.5 mm). Neither poststenotic dilation nor severity of angiographic stenosis predicted clinical outcome. CONCLUSIONS: Primary renal artery stenting can be performed safely with nearly uniform technical success. The majority of patients with hypertension or renal insufficiency derive benefit. Follow-up mortality is 5-fold higher in patients with baseline renal insufficiency. Clinical and angiographic features did not predict blood pressure or renal functional outcome. Restenosis is more common in renal arteries with a reference caliber less than 4.5 mm.

Aged↗
PubMed2001

Cisplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in untreated patients with extensive-stage small cell lung cancer: a phase II trial of the Southwest Oncology Group.

PURPOSE: This study was designed to determine the efficacy and toxicity of cisplatin, etoposide, and paclitaxel (PET) in patients with extensive-stage small cell lung cancer (ES-SCLC). EXPERIMENTAL DESIGN: Chemo-naive adult patients with a performance status (PS) of 0-2 and adequate organ function were eligible. Patients received cisplatin 80 mg/m(2) i.v., etoposide 80 mg/m-2 i.v., and paclitaxel 175 mg/m(2) i.v. over a 3-h period on day 1 followed by etoposide 160 mg/m(2) p.o. on days 2 and 3 every 21 days for six cycles. G-CSF 5 microg/kg was injected s.c. on days 4-14. RESULTS: Eighty-eight patients were assessable. The median age was 60 years; 50% were male, 78% had PS of 0-1, 28% had PS of 2, 53% had multiple sites, and 13% had brain involvement. The overall response rate was 57% with 10 (12%) of 84 patients achieving a complete response. Median progression-free survival was 6 months [95% confidence interval (CI), 5-7 months] with a median survival of 11 months (95% CI, 8-13 months) and a 1-year survival rate of 43% (95% CI, 33-54%). Six patients (7%) died from toxicity. Grade 5 toxicity occurred in 3 (14%) of 22 patients (with a PS of 2) versus 3 (5%) of 61 patients (with a PS of 0-1; P, not significant). Grade 4 neutropenia developed in 40% of patients. Grade 3 nonhematological toxicities were primarily nausea (20%), vomiting (16%), and fatigue (14%). CONCLUSION: The survival result achieved was superior to prior SWOG experiences; however, the toxic death rate was unacceptably high in PS-2 patients. These results provide the largest database for the ongoing randomized Intergroup trial comparing PET to cisplatin+etoposide in PS-0-1 patients with ES-SCLC.

Adult↗
PubMed2000

Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team.

OBJECTIVE: This phase II trial assessed the feasibility, as measured by response rate, toxicity, resectability rate, and surgical morbidity and mortality rates, of perioperative paclitaxel and carboplatin chemotherapy in patients with early-stage non-small cell lung carcinoma. METHODS: All patients required negative mediastinoscopy results and adequate medical parameters to undergo induction chemotherapy and an operation. Superior sulcus patients were excluded. Chemotherapy consisted of paclitaxel 225 mg/m(2) over 3 hours and carboplatin (area under the curve = 6) every 21 days for 2 cycles preoperatively. Three postoperative cycles of chemotherapy were planned for patients undergoing complete resection. RESULTS: Between June 1996 and July 1998, 94 patients were entered into the study. Sixty-five (69%) were men, and the median age was 64 years (range, 34-79 years). After induction chemotherapy, 53 of 94 (56%; 95% confidence interval, 46%-67%) had a major objective response, 88 (94%) underwent surgical exploration, and 81 (86%; 95% confidence interval, 78%-92%) underwent complete resection. Reasons for not undergoing an operation included disease progression (n = 3), clinically unresectable status (n = 1), death (n = 1), and patient lost to follow-up (n = 1). Two postoperative deaths occurred. Six (6%; 95% confidence interval, 0%-13%) pathologic complete responses were observed. Ninety (96%) patients received the planned preoperative chemotherapy versus 45% receiving postoperative chemotherapy. No unexpected chemotherapy or surgical morbidity occurred. The 1-year survival is currently estimated at 85%, and the median survival has not yet been reached. CONCLUSIONS: Induction chemotherapy with paclitaxel and carboplatin is feasible and produces a high response rate with acceptable morbidity and mortality rates in early-stage non-small cell lung carcinoma. A prospective randomized trial comparing 3 cycles of induction chemotherapy and surgery with surgery alone in early-stage non-small cell lung carcinoma is planned.

Adult↗
PubMed2000

Phase II clinical trial design for noncytotoxic anticancer agents for which time to disease progression is the primary endpoint.

Phase II evaluation is a critical screening step in the development of new cancer treatments. Historically, anticancer agents have been cytotoxic; they kill existing cells. As such, the primary endpoint for phase II evaluation has been tumor response rate, the percentage of patients whose tumors shrink > 50%. Biotechnology has led to promising new anticancer agents that are cytostatic. In contrast to cytotoxics, these agents modulate tumor environments and/or cellular targets and are expected to delay tumor growth. Phase II evaluation of such agents may instead focus on failure-time endpoints, such as time to disease progression. We examine a phase II trial design that evaluates clinical benefit by comparing sequentially measured paired failure times within each treated patient. Clinical efficacy is defined by a hazard ratio. Assuming patients eligible for a phase II study of a new cytostatic agent have failed previous cancer treatment, their most recent prior time to progression interval, TTP(1), is uncensored. Time to progression after the cytostatic agent, TTP(2), may or may not be censored at analysis. The design is motivated by a "growth modulation index" (TTP(2)/TTP(1)) and the proposition that a cytostatic agent be considered effective if the index is greater than 1.33. A chi(2) test statistic is employed to evaluate the paired failure-time data (TTP(1), TTP(2)). The degree of correlation between the paired failure times is a key feature of this design. Power of the test was evaluated through simulation of trials. Assuming a null hazard ratio equal to 1.0, a trial designed to detect an alternative hazard ratio equal to 1.3, based on accrual of 25 patients/year for 2 years (50 patients total) and with an additional 2 years of follow-up, has 25%, 46%, and 83% power based on correlations of 0.3, 0.5 and 0.7, respectively. These results demonstrate efficiency of the trial design, given moderate to strong correlations between paired failure times.

Antineoplastic Agents↗
PubMed2000

A clash of cultures: A&E and mental health.

Accident and emergency (A&E) departments have attracted little attention from psychiatric services, with the exception of emergencies and the management of self harm. Emergency staff gravitate towards those attenders with concrete physical needs, typifying mental health attenders as low status. The aim of this project, which took place over a 12 month period, was to improve the quality of care provided to persons attending an A&E department with mental health needs, through a staff development programme. It was initiated for the generic A&E nurse with no formal training in mental health care. The programme was based on knowledge generated through a collaborative approach using an action research process. This article particularly focuses on the mindsets, values and strategies which evolved through the study. The project indicated that facets of the A&E culture such as staff values, technology, communication patterns and the environment give mental health a low status. Conflict is generated between the individual and the macro culture, dominated by the excitement of trauma care and the short-term, immediate nature of the work.

Attitude of Health Personnel↗
PubMed1999

Underrepresentation of patients 65 years of age or older in cancer-treatment trials.

BACKGROUND: Studies have documented the underrepresentation of women and blacks in clinical trials, and their recruitment is now federally mandated. However, little is known about the level of participation of elderly patients. We determined the rates of enrollment of patients 65 years of age or older in trials of treatment for cancer. METHODS: We analyzed data on 16,396 patients consecutively enrolled in 164 Southwest Oncology Group treatment trials between 1993 and 1996 according to sex, race (black or white), and age under 65 years or 65 or older. These rates were compared with the corresponding rates in the general population of patients with cancer, derived from the 1990 U.S. Census and from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program for the period from 1992 through 1994. Fifteen types of cancer were included in the analysis. RESULTS: The overall proportions of women and blacks enrolled in Southwest Oncology Group trials were similar to or the same as the estimated proportions in the U.S. population of patients with cancer (women, 41 percent and 43 percent; blacks, 10 percent and 10 percent, respectively). In contrast, patients 65 years of age or older were underrepresented overall (25 percent vs. 63 percent, P<0.001) and in trials involving all 15 types of cancer except lymphoma. The underrepresentation was particularly notable in trials of treatment for breast cancer (9 percent vs. 49 percent, P<0.001). The findings were similar when data on patients who were 70 years of age or older were analyzed, when 15 trials that excluded older patients were eliminated from the analysis, and when community-based enrollment was analyzed separately from enrollment at academic centers. CONCLUSIONS: There is substantial underrepresentation of patients 65 years of age or older in studies of treatment for cancer. The reasons should be clarified, and policies adopted to correct this underrepresentation.

Age Factors↗
PubMed1999

Balloon mitral valvuloplasty: comparison of haemodynamic and echocardiographic assessment of mitral stenosis at different heart rates in the catheterisation laboratory.

AIMS: To compare echo-Doppler, Gorlin equation and haemodynamic methods of measuring mitral valve stenosis during right ventricular pacing-induced tachycardia before and after Inoue balloon mitral valvuloplasty to determine which method gave the most consistent results. METHODS AND RESULTS: Measurements were made before and after valvuloplasty at: baseline heart rates, paced at 115 and then 145 beats/min. Mitral valve area by echo-Doppler was 1.1(+/-0.1) cm2 (mean +/- S.E.) before and 1.8(+/-0.2) cm2 after valvuloplasty; and by Gorlin equation: 0.9(+/-0.1) cm2 before and 1.5(+/-0.1) cm2 after. Echo-Doppler measurements were heart rate dependent but those by Gorlin measurements were not. At baseline, cardiac index was 2.08(+/-0.2) l min(-1), left atrial pressure 23.3(+/-7.9) mm Hg and mean mitral diastolic gradient 16.9(+/-9.9) mm Hg. After valvuloplasty, cardiac index was 2.31(+/-0.1) l min(-1), left atrial pressure fell to 19.2(+/-5.6) mm Hg and mean diastolic gradient was reduced to 8.5(+/-1.8) mm Hg. CONCLUSIONS: The Gorlin mitral valve area appeared to be the most heart rate independent indicator of success following valvuloplasty.

Aged↗
PubMed1999

Local drug delivery of argatroban from a polymeric-metallic composite stent reduces platelet deposition in a swine coronary model.

Thrombus formation after intracoronary stent implantation provides a stimulus for neointimal hyperplasia and if excessive can result in stent thrombosis. We tested the hypothesis that local delivery of an antithrombin drug from a polymeric-metallic stent inhibits platelet thrombus formation. An uncoated metal slotted tube, a jellyroll slotted metal stent with an Argatroban-loaded polymeric sleeve, and a jellyroll slotted metal stent with a drug-leached polymeric sleeve were randomly deployed into the coronary arteries of eight juvenile farm swine. Platelet deposition in the stented segments was determined at 2 hr using autologous 111Indium oxime-labeled platelets. Platelet deposition was significantly less in the Argatroban-loaded stents compared to the Argatroban-leached stents (1.40 x 10(8) platelets/cm2 vs. 26.8 x 10(8) platelets/cm2; P=0.005). When corrected for differences in the metal surface area exposed to blood, platelet deposition was significantly lower in the Argatroban-loaded stent (1.74+/-1.95 x 10(8)/cm2) compared to the Argatroban-leached stent (33.5+/-39.1 x 10(8)/cm2; P=0.005) and the uncoated metal stent (36.2+/-73.3 x 10(8)/cm2; P=0.006). In this coronary stent thrombosis model Argatroban has local antithrombotic properties when delivered with a polymer-metallic stent. Improved polymeric designs may reduce risk of thrombus deposition at the site of stent implantation.

Animals↗
PubMed1999

Imaging of sickle cell disease.

Sickle cell disease is an important health care issue in the United States and in certain areas in Africa, the Middle East and India. Although a great deal of progress has been made in understanding the disease at the molecular and pathophysiologic level, specific treatment which is safe and accessible for most patients is still elusive. Going into the next millennium, the management of this disease is still largely dependent on early diagnosis and the treatment of complications with supportive care. Thus, diagnosis and evaluation of the complications of the disease are crucial in directing clinical care at the bedside. Modern imaging modalities have greatly improved, and their application in the patient with the sickling disorders has enhanced the decision - making process. The purpose of this article is to review the clinical aspects of common complications of the disease and to discuss imaging approaches which are useful in their evaluation.

Anemia, Sickle Cell↗
PubMed1999

PGG-glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)-glucan receptor.

PGG-Glucan, a soluble beta-(1,6)-branched beta-(1,3)-linked glucose homopolymer derived from the cell wall of the yeast Saccharomyces cerevisiae, is an immunomodulator which enhances leukocyte anti-infective activity and enhances myeloid and megakaryocyte progenitor proliferation. Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of subsequently isolated blood leukocytes to both soluble and particulate activators in a dose-dependent manner, and increased leukocyte microbicidal activity. No evidence for inflammatory cytokine production was obtained under these conditions. Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an NF-kappaB-like nuclear transcription factor in purified human neutrophils. The binding of 3H-PGG-Glucan to human leukocyte membranes was specific, concentration-dependent, saturable, and high affinity (Kd approximately 6 nM). A monoclonal antibody specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the NF-kappaB-like factor by PGG-Glucan, and ligand binding data, including polysaccharide specificity, suggested that the PGG-Glucan binding moiety was lactosylceramide. These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and human neutrophils is mediated by the glycosphingolipid lactosylceramide present at the cell surface.

Adjuvants, Immunologic↗
PubMed1999

High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial.

PURPOSE: To evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma. PATIENTS AND METHODS: Multiple myeloma patients with alkylating agent or vincristine/doxorubicin/dexamethasone-refractory disease were eligible for the phase II multi-institutional Southwest Oncology Group trial S8993. Patients up to age 70 years were enrolled between April 15, 1991, and May 1, 1996. Patients without prior stem-cell collection were primed with high-dose cyclophosphamide (HD-CTX; 6 g/m(2)) and granulocyte-macrophage colony-stimulating factor. After stem-cell procurement, patients received melphalan 200 mg/m(2) with autologous transplantation. Upon recovery from melphalan, patients were to receive interferon alfa-2b until relapse. RESULTS: Seventy-two patients were enrolled onto S8993; five were ineligible and one received no therapy. Of the 66 assessable patients, 56 patients underwent the transplant procedure; 54 were assessable for response and 56 for toxicity. The response to HD-CTX (n = 37) included three complete remissions (CRs; 8%) and five partial remissions (PR; 14%); response to melphalan (n = 54) included 16 CRs (30%) and 19 PRs (35%), for an overall CR and >/= PR (n = 66; intent-to-treat) of 27% and 58%, respectively. Toxicities included six treatment-related deaths: two during HD-CTX and four during transplantation. The median progression-free survival (PFS) and overall survival (OS) durations on an intent-to-treat basis from transplant registration was 11 months and 19 months (95% confidence interval, 14 to 29 months), respectively. The 3-year actuarial PFS and OS rates were 25% and 31%, respectively. CONCLUSION: High-dose therapy with melphalan 200 mg/m(2) is feasible with high response rates (58% overall) and an OS of 19 months in patients with refractory multiple myeloma.

Adult↗