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Biomedical subjects

J J Crowley

Publications and source records attributed to J J Crowley.

At least 91 records · Page 5Linked to original sources
PubMed1992

Long-term, low-level microwave irradiation of rats.

Our goal was to investigate effects of long-term exposure to pulsed microwave radiation. The major emphasis was to expose a large sample of experimental animals throughout their lifetimes and to monitor them for effects on general health and longevity. An exposure facility was developed that enabled 200 rats to be maintained under specific-pathogen-free (SPF) conditions while housed individually in circularly-polarized waveguides. The exposure facility consisted of two rooms, each containing 50 active waveguides and 50 waveguides for sham (control) exposures. The experimental rats were exposed to 2,450-MHz pulsed microwaves at 800 pps with a 10-microseconds pulse width. The pulsed microwaves were square-wave modulated at 8-Hz. Whole body calorimetry, thermographic analysis, and power-meter analysis indicated that microwaves delivered at 0.144 W to each exposure waveguide resulted in an average specific absorption rate (SAR) that ranged from 0.4 W/kg for a 200-g rat to 0.15 W/kg for an 800-g rat. Two hundred male, Sprague-Dawley rats were assigned in equal numbers to radiation-exposure and sham-exposure conditions. Exposure began at 8 weeks of age and continued daily, 21.5 h/day, for 25 months. Animals were bled at regular intervals and blood samples were analyzed for serum chemistries, hematological values, protein electrophoretic patterns, thyroxine, and plasma corticosterone levels. In addition to daily measures of body mass, food and water consumption by all animals, O2 consumption and CO2 production were periodically measured in a sub-sample (N = 18) of each group. Activity was assessed in an open-field apparatus at regular intervals throughout the study. After 13 months, 10 rats from each group were euthanatized to test for immunological competence and to permit whole-body analysis, as well as gross and histopathological examinations. At the end of 25 months, the survivors (11 sham-exposed and 12 radiation-exposed rats) were euthanatized for similar analyses. The other 157 animals were examined histopathologically when they died spontaneously or were terminated in extremis.

Animals↗
PubMed1992

Creation of a semiannual report for a multicentre co-operative clinical trials group.

The Southwest Oncology Group (SWOG) is a multicentre co-operative group that performs prospective clinical trials in cancer. The SWOG Statistical Center is responsible for preparing a report of studies for the semiannual meetings. The report includes a summary of study design and eligibility criteria, current accrual, baseline patient characteristics, toxicity, and, for studies closed to accrual and with sufficiently mature outcome data, tumour response or patient survival. A software program, Statisticians' Report Worksheet (SRW), has been developed by the programming staff at the SWOG Statistical Center. This program enables each disease specific chapter to be created independently, but ensures that tables and graphs for all chapters are of uniform style. We describe here the coordination of the report, and the use of the SRW program. This reporting system can serve as a model for other groups.

Clinical Trials as Topic↗
PubMed1992

A graphical approach to the analysis of censored data.

The presence of censoring has hampered the graphical exploration of survival data. We present several graphical approaches to the analysis of such data here, many based on functionals of the distribution function and estimated using the Kaplan-Meier estimate of the distribution function. Topics covered include comparing two samples, comparing many samples, and regression.

Adult↗
PubMed1992

Impaired beta-adrenoceptor function, increased leukocyte respiratory burst, and bronchial hyperresponsiveness.

Inflammatory processes have potential importance in the pathogenesis of bronchial hyperresponsiveness and asthma. Because beta-adrenoceptor function may be impaired in asthma, we studied regulation of the leukocyte respiratory burst using blood samples from subjects with bronchial hyperresponsiveness to methacholine. Leukocytes from hyperresponsive subjects were less responsive to the beta-agonist isoproterenol than were leukocytes from healthy control subjects. The magnitude of the respiratory burst was increased in cells from hyperresponsive subjects and correlated with the degree of methacholine responsiveness. These results demonstrate that peripheral leukocytes reflect a functional impairment in beta-adrenergic responsiveness that parallels airway hyperresponsiveness. Because untreated subjects demonstrated a reduction in beta-adrenergic response, the impairment in beta-adrenoceptor function was not a result of drug therapy and may be associated with the pathogenesis of asthma.

Adult↗
PubMed1992

Clinical significance of crepitations in elderly patients following acute hospital admission: a prospective study.

Because of a clinical impression that lung crepitations are a common, non-specific sign in acutely ill elderly people, two investigators, blinded to each other's findings and to subject case notes, prospectively examined 207 consecutive elderly [aged 70-98 (mean 77) years] and 75 young patients [24-50 (41) years] acutely admitted to hospital. Crepitations and persistent crepitations (PCs) were commoner in the elderly patients (p less than 0.001) but agreement over their presence/absence was reduced (p less than 0.05). Both investigators agreed PCs were absent in 35% of elderly subjects suffering from conditions classically associated with their presence, and, conversely, were present in 29 elderly subjects in whom no cause for their presence was discovered (14% of the total elderly group or 42% of those with PCs). PCs without obvious cause were unrelated to smoking history and did not predict outcome, length of stay or development of cardiorespiratory complications. In view of poor sensitivity and specificity of crepitations in elderly patients undergoing acute hospital admission we caution against over-reliance on this sign in isolation in these circumstances.

Aged↗
PubMed1992

Mental health, race and ethnicity: a retrospective study of the care of ethnic minorities and whites in a psychiatric unit.

A retrospective case-note study of 152 discharged psychiatric patients (77 subjects of ethnic minority origin and 75 whites) examined for details of follow-up arrangements on discharge, compliance rate with out-patient appointments and details on length of stay, status on admission, employment status, record of illicit drug taking and diagnosis. The results show that in the areas of diagnosis, possible illicit drug involvement, status on admission and length of stay, there are significant differences between Afro-Caribbean subjects and others.

Adult↗
PubMed1992

Reduced subjective awareness of bronchoconstriction provoked by methacholine in elderly asthmatic and normal subjects as measured on a simple awareness scale.

BACKGROUND: Asthma death rates are rising, with the greatest rise and highest death rates in old age. A reduced cardiovascular response in the elderly may lead to the underestimation by physicians of the severity of acute asthma attacks. This would be compounded if elderly patients had reduced awareness of bronchoconstriction. METHODS: Methacholine provoked bronchoconstriction was compared in 34 elderly (17 asthmatic, 17 normal; age 60-83, mean 68 years) and 33 young subjects (16 asthmatic, 17 normal; 20-46, mean 30 years). None were smokers. All underwent inhaled methacholine challenge by the Newcastle dosimeter method, monitored by maximal expiratory flow-volume loops (MEFVL). The endpoints were a 35% fall in forced expiratory flow at 50% vital capacity or cumulative inhalation of 6.4 mg methacholine. The one second forced expiratory volume (FEV1) was derived from MEFVL. After challenge and before bronchodilatation subjects graded awareness of respiratory discomfort from 1 (no symptoms) to 4 (pronounced symptoms needing immediate treatment). RESULTS: Despite a greater fall in FEV1 in elderly asthmatic patients (mean (SE) 27.4% (2.2%)) than in young asthmatic patients (21.5% (1.7%)) elderly patients were less aware of bronchoconstriction (awareness score 2.00 (SE 0.15) than young patients (3.06 (0.11)). Similar differences in awareness score were seen between elderly normal subjects (1.53 (0.17)) and young normal subjects (2.76 (0.22)), despite no difference in degree of bronchoconstriction. CONCLUSIONS: Reduced awareness of moderate acute bronchoconstriction in old age may delay self referral in acute asthma and contribute to higher asthma mortality in the elderly.

Adolescent↗
PubMed1992

Relationship between nonspecific bronchial responsiveness to methacholine and peripheral mononuclear leukocyte beta-adrenergic receptor function in young drug-naive subjects.

Asthma is associated with dysfunction of the beta-adrenergic receptor adenylyl cyclase signal transduction pathway. It has been argued that this results from receptor down-regulation by beta-agonist therapy. This study examined the relationship between nonspecific bronchial responsiveness (NSBR) to methacholine (Newcastle dosimeter method) and beta-adrenergic receptor density (Bmax) and affinity (%KH) in membranes from peripheral blood mononuclear leukocytes (MNL) in 12 male (27.3 +/- 1.7 yr old) and 14 female (31.4 +/- 1.7 yr old) drug-naive subjects with and without symptoms of mild intermittent wheezing. None had ever smoked or received any antiasthma medication. "Hyperresponsive" subjects were defined as those (n = 11) whose simplified slope of FEF50 (calculated as the percent fall in FEF50 divided by the dose of methacholine) was more than one SD above the mean for asymptomatic subjects. The log of the slope was reproducible (repeatability coefficient = 0.43) on two nonconsecutive days. Multiple regression analysis (overall R2 = 0.57) revealed negative relationships between the log of the slope and both Bmax (p = 0.016) and %KH (p = 0.011). Analysis of variance confirmed a lower mean (+/- SEM) value of %KH in "hyperresponsives" (45.7 +/- 5.5%) than in "normoresponsives" (60.4 +/- 4.1%, p = 0.04) with a similar trend for Bmax (hyperresponsives = 33.5 +/- 4.1 fmol/mg, normoresponsives = 45.9 +/- 7.1 fmol/mg, p = 0.18). These relationships between bronchial responsiveness, Bmax, and %KH cannot be explained by drug therapy, and they provide further evidence that there is an intrinsic impairment in the function of beta-adrenergic receptors on peripheral MNLs from subjects with high levels of nonspecific bronchial responsiveness.

Adolescent↗
PubMed1991

Attenuation of LPS-induced neutrophil thromboxane b2 release and chemiluminescence.

Polymorphonuclear leukocytes (PMN) may play a key role in acute lung injury and ARDS. The mechanisms of PMN-mediated lung injury include the release of inflammatory mediators, such as oxygen free radicals which cause direct tissue injury, and arachidonic acid metabolites which cause pulmonary vasoconstriction and increased vascular permeability. The goals of this in vitro study were 1) to assess the effects of PMN-activating agents (lipopolysaccharide, LPS; phorbol myristate acetate, PMA; tumor necrosis factor, TNF) on PMN thromboxane B2 (TXB2) release and oxygen free radical production and 2) to determine the effects of agents purported to suppress PMN activity (pentoxifylline, PTX; adenosine; dibutyryl cyclic AMP, DBcAMP; and terbutaline, TBN) on activator-induced PMN TXB2 release and oxygen free radical production. PMN TXB2 release was determined by radioimmunoassay and oxygen free radical production was monitored by chemiluminescence. Our results show that 1) LPS and PMA significantly increase PMN TXB2 release, whereas tumor necrosis factor (TNF) has no effect; 2) LPS and PMA significantly increase PMN chemiluminescence; 3) DBcAMP and TBN significantly reduce LPS-induced PMN TXB2 release whereas PTX and adenosine do not; 4) TBN significantly reduces PMA-induced PMN TXB2 release whereas other agents do not; 5) All agents (PTX, adenosine, DBcAMP, and TBN) significantly reduce LPS-induced PMN chemiluminescence but none attenuate PMA-induced PMN chemiluminescence. We conclude that: LPS and PMA activate PMN manifested by TXB2 release and chemiluminescence. Additionally, all the PMN suppressing agents do attenuate some PMN functions. Of interest, PTX, adenosine, DBcAMP, and TBN have different effects depending upon functional assay and activating agent. It will be important to investigate the mechanisms by which PMN suppressing agents alter signal transduction resulting in differential effects on PMN function.

Adenosine↗
PubMed1991

Phase II evaluation of menogaril (NSC-269148) in non-small cell lung carcinoma. A Southwest Oncology Group study.

Forty-five patients with non-small cell lung cancer were treated in a phase II trial with menogaril 200 mg/m2 IV every twenty-eight days by a one-hour infusion. One partial response was noted while twenty-two patients had stable disease (51%). Progressive disease was noted in the remaining twenty-two patients. There was one fatal complication due to pancytopenia and pneumonia. Otherwise, the drug was reasonably well tolerated. At this dosage and schedule, menogaril has no substantial anti-tumor activity for patients with non-small cell lung cancer.

Antineoplastic Agents↗
PubMed1991

Treatment of non-small-cell lung cancer with vinblastine and very high-dose cisplatin. A Southwest Oncology Group study.

Suggestions of a dose-response effect for cisplatin in non-small-cell lung cancer have contributed to the development of very high-dose cisplatin regimens (200 mg/m2 per cycle). We treated 53 eligible patients with metastatic or recurrent non-small-cell lung cancer with a combination of 100 mg/m2 cisplatin and 4 mg/m2 vinblastine, each given on days 1 and 8 of a 28-day cycle. We observed no complete response and 4 partial responses (8%). Median survival was 6 months. Toxicities of grade III or greater included leukopenia (11 cases), nausea/vomiting (6 cases), thrombocytopenia (2 cases), anemia (2 cases), and elevation of transaminase (1 case). Neurotoxicity has been reported to be a major problem in several other very high-dose cisplatin regimens. The low level of neurotoxicity observed in this study may be attributable to the median cumulative cisplatin dose of less than 600 mg/m2. This vinblastine/very high-dose cisplatin regimen showed minor activity against non-small-cell lung cancer. The level of activity did not surpass that of standard-dose (100 mg/m2 per cycle) cisplatin-containing regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Genetic studies of four highly homologous rheumatoid factor-associated Vk genes in rheumatoid arthritis patients and normal individuals.

Rheumatoid factors (RFs) are autoantibodies directed against IgG molecules. They are present in increased quantity in most patients with rheumatoid arthritis (RA), and are implicated in tissue damage in this disease. Paradoxically, recent studies of RFs have revealed that these autoantibodies are likely a physiological component of the immune system, and may play a role in the development and function of the B cell repertoire. Previously, we found that a significant fraction of RA patients express RF bearing the 6B6.6 cross-reactive idiotype, which is a phenotypic marker of the Humkv328-like genes. In order to elucidate the possible genetic factors that may contribute to the abnormal production of RFs in RA patients, we studied restriction fragment length polymorphisms (RFLP) of four highly homologous RF-related kappa light chain variable region (Vk) genes (i.e. Humkv328, Humkv328h2, Humkv328h5 and Humkv329) in RA patients and normal controls. The results show that kv328, kv328h2 and kv329 are likely to be alleles of the kv328 locus, while kv328h5 is a highly homologous Vk gene residing in a separate locus; and that deletion in one copy of either the kv328 or the kv328h5 loci, but not both loci, occurs in several individuals. However, the frequencies of various RFLP patterns of these two Vk gene loci are similar in patients and normals.

Arthritis, Rheumatoid↗
PubMed1991

An evaluation of anesthesiologists' present checkout methods and the validity of the FDA checklist.

The United States Food and Drug Administration (FDA) published the Anesthesia Apparatus Checkout Recommendations (checklist) in order to improve the methods anesthesiologists use to check out anesthesia equipment. Whereas no published study of current checkout methods had been performed since the introduction of the FDA checklist, we compared anesthesiologists' current anesthesia equipment pre-use checkout methods with anesthesiologists' use of the FDA checklist. One hundred and eighty-eight anesthesiologists were tested to compare the number of prearranged anesthesia machine faults that could be detected with 1) their own checkout methods and 2) the FDA checklist. The average number of machine faults detected with the individual anesthesiologists' checkout methods was 1.03/4 (25.8%) and with the FDA checklist was 1.20/4 (29.9%). For only one fault, malfunction of the oxygen/nitrous oxide ratio protection system, was there a statistically significant improvement (P less than 0.01) with the use of the FDA checklist. Anesthesiologists in residency training detected more faults (average 2.46/8, 30.8%) than did anesthesiologists who primarily practiced direct patient care (1.98/8, 23.9%) (P less than 0.01). Our data indicate that the mere introduction of the FDA checklist did not improve the ability of anesthesiologists to detect anesthesia machine faults.

Anesthesiology↗
PubMed1991

Tumor necrosis factor-induced protein phosphorylation in human neutrophils.

Protein phosphorylation is central to multiple regulatory processes in cells. Tumor necrosis factor (TNF), a cytokine synthesized by macrophages, effects polymorphonuclear leukocyte (neutrophil) chemotaxis, induces superoxide anion generation, and mediates neutrophil adhesion to endothelial cells. Although protein phosphorylation is almost certainly involved in many TNF-mediated neutrophil functions, little is known about TNF's impact on neutrophil protein phosphorylation. Therefore, we studied human recombinant TNF-alpha-induced protein phosphorylation in human neutrophils. Neutrophils were preincubated with 32PO(4)2- and treated with a variety of stimulatory agents. One- and two-dimensional polyacrylamide gel electrophoresis was used to analyze phosphorylated proteins. Phosphoaminoacids were identified by two-dimensional thin layer chromatography electrophoresis. The findings were as follows: (1) TNF induces the phosphorylation of two 16-kD proteins (pI = 5.9 and 6.1) by 5- to 6-fold, and a 57-kD protein (pI = 5.8) by 3- to 4-fold compared with untreated neutrophils; (2) these proteins are phosphorylated as early as 15 min after stimulation with TNF, and phosphorylation is induced by concentrations of TNF as low as 1 ng/ml (10 U/ml); (3) TNF induces the phosphorylation of proteins at either serine or threonine residues and not at tyrosine; (4) TNF-stimulated neutrophils show a unique pattern of protein phosphorylation when compared to neutrophils treated with formylmethionylleucylphenylalanine; (5) lipopolysaccharide does not induce protein phosphorylation in neutrophils; (6) a 16-kD protein is phosphorylated in response to TNF in neutrophils but not in mononuclear cells; and (7) protein kinase inhibitors appear to have no effect on TNF-induced protein phosphorylation. Thus, the mechanism of action of TNF on neutrophils may involve protein phosphorylation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience.

We analyzed the 2,531-patient Southwest Oncology Group extensive-stage non-small-cell lung cancer (ENSCLC) data base from 1974 to 1988 to (1) assess the interactions of host- or tumor-related prognostic factors and therapy using Cox modeling and recursive partitioning and amalgamation (RPA) to determine whether each independently predicts outcome, and (2) use RPA to define prognostic subsets with different survival potentials. Good performance status (PS), female sex, and age greater than or equal to 70 years were significant independent predictors in a Cox model applied to the entire population. In a second Cox model for patients with good PS enrolled on recent studies, hemoglobin level greater than or equal to 11.0 g/dL, normal lactate dehydrogenase (LDH), normal calcium, and a single metastatic site were significant favorable factors. The use of cisplatin was an additional independent predictor of improved outcome in both Cox models after adjustments for year of accrual and all prognostic variables. The favorable effect of cisplatin was observed in each of six RPA-derived subgroups from the entire population. A second RPA of 904 patients from recent trials (nearly all received cisplatin-based therapy) resulted in three distinct prognostic subsets based on PS, age, hemoglobin, and LDH; greater than or equal to 1-year survivals were 27%, 16%, and 6% (P less than .0001). The best survival occurred for patients with a good PS who had a hemoglobin level greater than or equal to 11 g/dL and who were older than 47 years. This analysis suggests that although several factors were independent variables in the Cox models, three important prognostic subgroups were easily defined through RPA. Together with other analyses, our results suggest the need to modify the stage IV category in NSCLC.

Adult↗
PubMed1991

Long-term survival and toxicity in small cell lung cancer. Expanded Southwest Oncology Group experience.

The Southwest Oncology Group formed a database of 2,501 patients consecutively enrolled in small cell lung cancer (SCLC) trials since 1976. This report summarizes an analysis of this database to determine predictors of 2- and 5-year survival in limited stage disease (LD) and 1- and 2-year survival in extensive stage disease (ED). In addition, we analyzed the frequency of late recurrences, toxicity, and quality of life issues in the long-term survivors. For consecutive studies, greater than or equal to 2-year survival in LD were 15 percent, 21 percent, 28 percent, and 43 percent; 5-year survivals were 5 percent, 9 percent, 8 percent, and 20 percent. In ED, greater than or equal to 1-year survivals were 27 percent, 23 percent, 21 percent, and 42 percent; greater than or equal to 2-year survivals were 6 percent, 5 percent, 3 percent, and 19 percent. Using the logistic regression multivariate model, independent favorable predictors of 5-year survival for patients accrued to our older LD trials were normal lactate dehydrogenase (LDH) values and good performance status. Therapy as employed in these trials was not an independent factor. However, if patients enrolled on more recent trials were included, 2-year predictors could be assessed. Therapy with concurrent chemoradiotherapy and female gender then became additional independent favorable predictors. In ED, a single metastatic site and a normal LHH value were favorable predictors of survival beyond 1 year. The retrospective review of 63 patients with LD who survived at least 5 years found 33 asymptomatic patients with no recurrent disease; 6 with recurrent SCLC, 3 of whom died; 7 who died of non-cancer-related causes or unknown causes; 3 who died of secondary primary lung cancer; and 14 alive with persistent central nervous system symptoms and signs, possibly due to prophylactic brain radiation as given in the first 3 trials. No increased incidence of this syndrome has yet been observed in subsequent trials. For ED patients, 25 of 51 survivors greater than or equal to 2 years subsequently died of recurrent SCLC. The majority of the long-term survivors with ED (35 of 51) had either a single metastatic site or metastases limited to opposite side of the chest or regional nodes. Our multivariate models support the conclusion that aggressive combined modality, concurrent induction therapy, along with favorable prognostic variables, independently contribute to the improved long-term survival we have observed in LD. Longer follow-up is required to confirm that this improvement has occurred with less late toxicity.

Aged↗