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Biomedical subjects

J Costello

Publications and source records attributed to J Costello.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cardiotoxic mechanisms and interrelationships of cocaine: including a single case depicting several of these mechanisms.

The underlying mechanisms of myocardial infarction as a result of cocaine abuse appear to be multifactorial. The various cardiotoxic mechanisms and interrelationships of cocaine are fully reviewed, and a chart has been reconstructed to give the reader a clearer understanding of them. Moreover, an unusual case of a 29-year-old male cocaine abuser is presented because it illustrates many of the reported cardiotoxic effects, all of which are present in the same individual.

Journal Article↗
PubMed1998

Inhibition of serum and transforming growth factor beta (TGF-beta1)-induced DNA synthesis in confluent airway smooth muscle by heparin.

1. Airway remodelling occurs in asthma and involves an increase in airway smooth muscle mass through cell proliferation and hypertrophy. Increased eosinophil density in the airways is a feature of asthma. Eosinophils exhibiting activation in the airways of asthmatics also exhibit increased expression of transforming growth factor beta (TGF-beta1). We have examined the capacity of TGF-beta1 and epidermal growth factor (EGF) to influence airway smooth muscle division and the effect of heparin on TGF-beta1. EGF and serum-induced smooth muscle DNA synthesis in confluent airway smooth muscle cells (ASMC) as an indication of entry into S phase preceding mitogenesis. 2. ASMC were obtained from cell populations growing out from explanted bovine trachealis muscle sections. Cell division was monitored in sparse plated cells by direct cell counting following nuclear staining. Cell DNA synthesis in confluent cells was monitored by uptake of [3H]-thymidine. 3. TGF-beta1 (100 microM) inhibited FBS (10%)-induced smooth muscle division in sparsely plated cells (40%). TGF-beta1 (100 pM) increased cell DNA synthesis (200%) in confluent cells in the presence of bovine serum albumin (BSA, 0.25%). EGF (0.7 nM) also increased airway smooth muscle DNA synthesis (69%) in the presence of BSA (0.25%). The facilitatory effect of TGF-beta1 was observed between 1-100 pM, while that of EGF was observed between 20 200 pM. 4. Heparin inhibited serum and TGF-beta1-induced DNA synthesis in confluent ASMC (55%), consistent with our previous observation of inhibition of division in sparsely populated ASMC (Kilfeather et al., 1995a). This action of heparin was observed between concentrations of 1-100 microg ml(-1). Heparin did not inhibit DNA synthesis in response to EGF. An anti-mitogenic effect of heparin was also observed against responses to combined exposure to TGF-beta1 and EGF. 5. There was a clear inhibitory effect of heparin in absolute terms against serum-induced division in cells plated at 10, 20 and 45 x 10(3) cells cm(-2). The inhibitory effect of heparin was also observed at a plating density of 45,000 cells cm(-2) when responses to serum were expressed as fold-stimulation of basal DNA synthesis. 6. These findings demonstrate a potential role of TGF-beta1, EGF and heparin-related molecules in regulation of airway smooth muscle division.

Animals↗
PubMed1998

Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies.

We do not have an estimate of how much tissue is needed for a reliable measure of bronchial epithelial reticular basement membrane (RBM) thickness or for counts of inflammatory cells. An assessment of the frequency distribution and variance of data from repeat measurements of RBM thickness and biopsy section inflammatory cell counts in cases with asthma (n=6), chronic obstructive pulmonary disease (COPD; n=5), and normal healthy subjects (n=7) was made. Tissue sections were stained with haematoxylin and eosin or by immunohistochemistry for EG2, mast cell tryptase and CD3-positive cells. Measurements of RBM thickness in individuals followed a log-normal distribution. For a precision of approximately +/-15%, 31-45 measurements were required. In contrast, inflammatory cell counts for each individual did not follow a normal distribution. There was high variance such that the cumulative weighted mean did not become stable until at least 5-10 mm of tissue underlying the RBM had been included. In conclusion multiple measurements of reticular basement membrane thickness or tissue section cell counts should be made for each individual in studies of bronchial biopsies. It is recommended that reticular basement membrane thickness should be measured at 20 mm intervals over a 1 mm reticular basement membrane length and that a zone beneath it of at least 5-10 mm of reticular basement membrane should be included for counts of inflammatory cells.

Adult↗
PubMed1997

Complete remission of extensive metastatic renal cancer following immunotherapy.

The authors describe the case history of a 54-year-old female patient, who presented with breathlessness, deteriorating general health and a 12 kg weight loss due to extensive metastatic renal cancer. Pulmonary emboli complicated the presentation. The patient entered a remarkable complete radiological remission by 18 weeks following the introduction of interleukin-2/alpha-interferon immunotherapy. The possibility of immediate nephrectomy or warfarin contributing to the augmentation of the effects of the immunotherapy is discussed.

Anticoagulants↗
PubMed1997

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects.

Recent studies have suggested that theophylline, a nonspecific phospho-diesterase inhibitor, has useful anti-inflammatory actions in asthma. Phosphodiesterase 4 (PDE4) represents the predominant PDE isoenzyme present in inflammatory cells. PDE4 inhibitors might, therefore, have beneficial effects in asthma. Side-effects, specifically nausea, have limited the use of existing agents. CDP840 is an orally active, potent and selective PDE4 inhibitor. We have examined the effect of CDP840 on the allergen-induced asthmatic response, its possible modes of action, and its tolerability at therapeutic doses. A total of 54 patients were recruited to three double-blind, placebo-controlled studies. The first study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on the allergen-induced asthmatic response in patients with known dual response to allergen. A second study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on airway responsiveness to histamine. A third study examined whether single dose CDP840 (15 and 30 mg) had significant bronchodilatory effects. In all studies, CDP840 was well-tolerated, with no patients reporting nausea. CDP840 did not lead to changes in baseline forced expiratory volume in one second (FEV1) as compared to placebo. The late asthmatic response (LAR) to allergen, expressed as area under the curve at 3-8 h (AUC3-8h), was inhibited by 30% (p=0.016), an effect which persisted to the end of the observation period. The early asthmatic response (EAR) was unaffected, and there was no bronchodilatory effect at the doses used. Treatment with CDP840 did not affect bronchial hyperresponsiveness to histamine. In conclusion, CDP840 significantly attenuated the late asthmatic response to allergen challenge in the absence of any bronchodilatory or histamine antagonist effect. This suggests that CDP840 may exert its effects via an anti-inflammatory mechanism.

Adolescent↗
PubMed1997

Family partnership in care: integrating families into the coronary intensive care unit.

Since the introduction of Family Partnership in Care in the CICU and other pilot units, many changes have been made. Education sessions are now unit specific rather than in groups with multiple units. This facilitates the discussion of unit-specific educational and implementation needs. In addition, unit-specific sessions allow for some case scenario/role playing activities to facilitate learning and application of the FPCP elements to the unique culture of the unit. Finally, less emphasis is placed on the documentation, while greater emphasis is placed on the philosophy behind the program and the nurses values and attitudes towards families. Overall, the implementation of the FPCP in CICU has had a positive impact on staff and patients. Staff awareness regarding the importance of involving family in the patient's care and the benefits of this has been heightened. Staff who were initially very skeptical have become strong advocates for the program. The successful shift with families in "doing for" to "working with" has enhanced the professional practice of many nursing staff and contributed to the overall unit functioning. Finally, the feedback from patients and their care partners and the independence and informed decision-making fostered by designing a plan of care with staff validates the importance of this program in a critical care area.

Coronary Care Units↗
PubMed1996

Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics.

Theophylline has been shown by several investigators to attenuate the late asthmatic response (LAR) to inhaled allergen, suggesting that it has anti-inflammatory or immunomodulatory properties. We have, therefore, undertaken a double-blind, placebo-controlled study to examine the effects of low-dose theophylline on bronchoalveolar lavage (BAL) and blood T-lymphocyte profile and activation in asthmatics following antigen challenge and the development of a LAR. Peripheral blood and BAL samples were obtained from 17 subjects with mild atopic asthma before and after 6 weeks of treatment with either oral theophylline or placebo. The mean serum theophylline concentration achieved was 6.6 micrograms.mL-1, which is below the currently accepted therapeutic range. Following theophylline therapy, there was a significant decrease in the number of BAL lymphocytes compared to placebo. On flow cytometric analysis of BAL cells, a significant loss of CD3+ T-lymphocytes, comprising both CD4+ and CD8+ subsets, was demonstrated. Moreover, there was a decrease in the number of BAL CD4+ T-cells expressing the activation marker very late activation antigen-1 (VLA-1), and an apparent reduction in human leucocyte antigen-DR (HLA-DR). Correspondingly, this was accompanied in the blood by an elevation in the proportion of activated CD4+ T-lymphocytes, in particular those expressing HLA-DR. These findings provide further evidence that theophylline has an anti-inflammatory action in asthma.

Adult↗
PubMed1996

Identification of a killer by a definitive sneaker pattern and his beating instruments by their distinctive patterns.

A 39-year-old male service station attendant was found murdered on the floor of a gasoline service area by a passing motorist who had stopped for gas. The victim had been brutally beaten all over his entire body. After carefully examining the body and scene and taking selective photographs, special procedures were implemented in an attempt to preserve and transport the body without disturbing any items of evidence. In addition, specific evidentiary items were noted and collected for processing. The victim was meticulously examined externally at autopsy using a special protocol to locate clues that might assist in identifying a suspect or instrument of injury or death. Patterned impressions and subsequent DNA analysis proved successful in identifying the perpetrator of the crime and the instruments used in inflicting the beating. It is the purpose of this paper to show how a meticulous examination of the body for the presence of patterned injuries and critical studies of these patterns and impressions led to the identification of a killer and the instruments he used in a brutal beating.

Adult↗
PubMed1995

Mortality of a cohort of U.S. workers employed in the crushed stone industry, 1940-1980.

The mortality of 3,246 males who had been employed 1 or more years during 1940-1980 at 20 crushed stone operations was evaluated for possible association between employment and death from lung cancer, pneumoconiosis, and other respiratory diseases. Four deaths were attributed to pneumoconiosis. Based on available work histories, at least two of these deaths were probably due to dust exposures in the crushed stone industry. Mortality attributed to pneumoconiosis and other nonmalignant respiratory diseases, including chronic obstructive lung disease, was significantly increased overall (SMR: 1.98; 95% CI: 1.21-3.05), and especially so for a subcohort of crushed stone workers that processed granite (SMR: 7.26; 95% CI: 1.97-18.59). With regard to lung cancer, overall SMRs were elevated (although not statistically significant). Analyzed by rock type, there was a significantly elevated lung cancer SMR among granite workers with at least 20 years latency (SMR: 3.35; 95% CI: 1.34-6.90). Although not definitive, results of this study are consistent with the hypothesis that exposure to respirable silica dust is a risk factor for lung cancer.

Cohort Studies↗
PubMed1995

Occupational exposures to fibers and quartz at 19 crushed stone mining and milling operations.

From 1979 to 1982, the National Institute for Occupational Safety and Health (NIOSH) conducted a cross-sectional exposure assessment and mortality study of selected crushed stone facilities in the United States. This study was undertaken in part to address concerns that asbestos exposures could be occurring in some crushed stone operations due to the presence of amphibole and serpentine minerals. The investigation was also designed to characterize exposures to crystalline silica and other mineral compounds. Nineteen crushed stone operations, mining limestone, granite, or traprock were surveyed to assess exposures to respirable and total dusts, mineral compounds including crystalline silica, asbestos, and mineral fibers. At the initiation of the study, crushed stone operations were selected from a Mine Safety and Health Administration (MSHA) listing of the active industry in 1978. With the exception of requiring inclusion of the traprock operation in Maryland where asbestos fibers were initially discovered, a stratified sample of operations was randomly selected by rock type (granite, limestone, traprock, or sandstone). However, because of reluctance or refusal of some companies to participate and because of the closures of some of the selected operations, replacements were randomly selected. Some replacement selections were likewise replaced due to lack of cooperation from the companies. The studied sample included only 10 of the 27 randomly selected operations in the original sample. Asbestos fibers were detected at one traprock facility, the Maryland operation where asbestos was originally found. Measured personal exposures to fibers exceeded the NIOSH Recommended Exposure Limit (REL) for two out of 10 samples. All of the samples were below the MSHA Permissible Exposure Limit (PEL), which was in effect at the time of the survey. However, due to the presence of nonasbestos mineral fibers in the environment, it could not be stated with certainty that all of the fibers counted by phase contrast microscopy were asbestos. A variety of silicate mineral fibers (other than those classified by NIOSH as asbestos) were detected in the traprock operations and at one granite operation. Crystalline silica was detected at 17 of the 19 surveyed crushed stone operations. Overexposures to crystalline silica were measured at 16 of the crushed stone operations; approximately one in seven personal-respirable dust samples (14%) exceeded the MSHA PEL for crystalline silica. Approximately 25% of the respirable dust samples exceeded the NIOSH REL for crystalline silica. Mill operators and mill laborers consistently had the highest and most frequent overexposures to crystalline silica.

Asbestos↗