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Biomedical subjects

K Kelly

Publications and source records attributed to K Kelly.

At least 19 recordsLinked to original sources
PubMed2006

Prediction of urinary symptoms after 125iodine prostate brachytherapy.

AIMS: To evaluate the post-treatment urinary morbidity experienced by a cohort of men undergoing ultrasound-based transperineal prostate brachytherapy, as monotherapy for early stage carcinoma of the prostate. MATERIALS AND METHODS: One hundred and thirty-four consecutive patients received prostate brachytherapy between March 2000 and July 2002, and were asked to complete the International Prostate Symptom Score (IPSS) and Hospital Anxiety and Depression (HAD) questionnaires before treatment and at 1, 3, 6, 9, 12 and 18 months after implant. Data on catheterisation and surgical interventions were also recorded. Pre-treatment IPSS, dosimetry and other variables were analysed in relation to catheterisation rates and post-treatment IPSS scores at each time window. RESULTS: One hundred and eleven patients returned sufficient data for meaningful analysis. Of the patients who completed IPSS at 1 month, 85 (97%) reported deterioration in IPSS scores. This peak of symptoms, identified by a rise in median IPSS, started to improve by 3 months, and was approaching baseline by 18 months. The only significant determinants of early urinary toxicity were pre-treatment IPSS, pre-treatment prostate volume and the difficulty of implant. However, prostate volume was not significant beyond 1 month. Twenty-six patients required catheterisation at a median of 10 days after implant. Significant predictors of urinary retention were pre-treatment prostate volume and pre-treatment IPSS. Patients requiring catheterisation continued to have significantly higher IPSS at 18 months than patients who had never required a catheter. CONCLUSION: Brachytherapy was generally well tolerated, with urinary toxicity in most patients persisting for at least 3-6 months after prostate brachytherapy. Those whose pre-treatment prostate volume and IPSS were high experienced more severe urinary symptoms in the first few months.

Aged↗
PubMed2005

Evaluation of 1047-nm photoacoustic instruments and photoelectric aerosol sensors in source-sampling of black carbon aerosol and particle-bound PAHs from gasoline and diesel powered vehicles.

A series of measurements have been performed at Hill Air Force Base to evaluate real-time instruments for measurements of black carbon aerosol and particle-bound PAHs emitted from spark and ignition compression vehicles. Vehicles were operated at idle or fast idle in one set of measurements and were placed under load on a dynamometer during the second series. Photoacoustic instruments were developed that operated at a wavelength of 1047 nm where gaseous interference is negligible, although sensitivity to black carbon is good. Compact, efficient, solid-state lasers with direct electronic modulation capabilities are used in these instruments. Black carbon measurements are compared with samples collected on quartz fiber filters that were evaluated using the thermal optical reflectance method. A measure of total particle-bound PAH was provided by photoelectric aerosol sensors (PAS) and is evaluated against a sum of PAH mass concentrations obtained with a filter-denuder combination. The PAS had to be operated with a dilution system held at approximately 150 degrees C for most of the source sampling to prevent spurious behavior, thus perhaps compromising detection of lighter PAHs. PA and PAS measurements were found to have a high degree of correlation, perhaps suggesting that the PAS can respond to the polycyclic nature of the black carbon aerosol. The PAS to PA ratio for ambient air in Fresno, CA is 3.7 times as large in winter than in summer months, suggesting that the PAS clearly does respond to compounds other than BC when the instrument is used without the heated inlet.

Acoustics↗
PubMed2004

Phosphorylation of critical serine residues in Gem separates cytoskeletal reorganization from down-regulation of calcium channel activity.

Gem is a small GTP-binding protein that has a ras-like core and extended chains at each terminus. The primary structure of Gem and other RGK family members (Rad, Rem, and Rem2) predicts a GTPase deficiency, leading to the question of how Gem functional activity is regulated. Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel beta subunit and Rho kinase beta, respectively. We show here that these functions are separable and regulated by distinct structural modifications to Gem. Phosphorylation of serines 261 and 289, located in the C-terminal extension, is required for Gem-mediated cytoskeletal reorganization, while GTP and possibly calmodulin binding are required for calcium channel inhibition. In addition to regulating cytoskeletal reorganization, phosphorylation of serine 289 in conjunction with serine 23 results in bidentate 14-3-3 binding, leading to increased Gem protein half-life. Evidence presented shows that phosphorylation of serine 261 is mediated via a cdc42/protein kinase Czeta-dependent pathway. These data demonstrate that phosphorylation of serines 261 and 289, outside the GTP-binding region of Gem, controls its inhibition of Rho kinase beta and associated changes in the cytoskeleton.

14-3-3 Proteins↗
PubMed2003

Peripheral retinal dysfunction in patients taking vigabatrin.

OBJECTIVE: To assess the wide-field multifocal electroretinogram (WF-mfERG) for assessment of retinal function in vigabatrin-treated patients. METHODS: Thirty-two adults who had taken vigabatrin for at least 3 years for localization-related epilepsy underwent WF-mfERG, ERG, logMar visual acuity and color vision evaluation, Humphrey visual field analysis (static perimetry), and funduscopy. The group was matched with a cohort of patients who had never received vigabatrin. Results were compared with a normative data set (120 drug-free controls) with respect to potential bilateral abnormalities in response timing. RESULTS: There were no significant differences between groups in visual acuity or color vision testing. Of the vigabatrin patients, 19 (59%) had bilateral visual field defects compared to none of the controls. Using WF-mfERG, all patients on vigabatrin with visual field defects showed abnormalities (100% sensitivity) and only 2 of the 13 patients without a field defect showed retinal abnormalities (86% specificity). CONCLUSIONS: WF-mfERG may be useful for detecting retinal pathology in patients taking vigabatrin. The majority of previous reports based on subjective testing may have underestimated the prevalence of peripheral retinal toxicity related to the drug.

Adult↗
PubMed2002

Immobilisation and functional treatment for acute lateral ankle ligament injuries in adults.

BACKGROUND: Acute lateral ankle ligament injuries (ankle sprains) are common problems in acute medical care. The treatment variation observed for the acutely injured lateral ankle ligament complex suggests a lack of evidence-based management strategies for this problem. OBJECTIVES: The objective of this review was to assess the effectiveness of methods of immobilisation for acute lateral ankle ligament injuries and to compare immobilisation with functional treatment methods. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (December 2001); the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966-May 2000), EMBASE (1988-May 2000), reference lists of articles, and contacted organisations and researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing either different types of immobilisation or immobilisation versus functional treatments for injuries to the lateral ligament complex of the ankle in adults were included. Trials which investigated the treatment of chronic instability or post-surgical treatment were excluded. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors. Where appropriate, results of comparable studies were pooled using fixed effects models. Individual and pooled statistics were reported as relative risks with 95% confidence intervals for dichotomous outcomes and weighted (WMD) or standardised (SMD) mean differences and 95% confidence intervals for continuous outcome measures. Heterogeneity between trials was tested using a standard chi-squared test. MAIN RESULTS: Twenty-one trials involving 2184 participants were included. The mean validity score of the included trials increased from 9.1 (SD 3.0) to 10 (SD 2.9) after retrieving further information (maximum 18 points). Statistically significant differences in favour of functional treatment when compared with immobilisation were found for seven outcome measures: more patients returned to sport in the long term (relative risk (RR) 1.86, 95% confidence interval (CI) 1.22 to 2.86); the time taken to return to sport was shorter (WMD 4.88 (days), 95% CI 1.50 to 8.25); more patients had returned to work at short term follow-up (RR 5.75, 95% CI 1.01 to 32.71); the time taken to return to work was shorter (WMD 8.23 days, 95% CI 6.31 to 10.16); fewer patients suffered from persistent swelling at short term follow-up (RR 1.74, 95% CI 1.17 to 2.59); fewer patients suffered from objective instability as tested by stress X-ray (WMD 2.60, 95% CI 1.24 to 3.96); and patients treated functionally were more satisfied with their treatment (RR 1.83, 95% CI 1.09 to 3.07). A separate analysis of trials that scored 50 per cent or more in quality assessment found a similar result for time to return to work only (WMD (days) 12.89, 95% CI 7.10 to 18.67). No significant differences between varying types of immobilisation, immobilisation and physiotherapy or no treatment were found, apart from one trial where patients returned to work sooner after treatment with a soft cast. In all analyses performed, no results were significantly in favour of immobilisation. REVIEWER'S CONCLUSIONS: Functional treatment appears to be the favourable strategy for treating acute ankle sprains when compared with immobilisation. However, these results should be interpreted with caution, as most of the differences are not significant after exclusion of the low quality trials. Many trials were poorly reported and there was variety amongst the functional treatments evaluated.

Humans↗
PubMed2002

Natural rubber latex allergy in the occupational setting.

Over the last decade, the prevalence of natural rubber latex (NRL) allergy has reached epidemic proportions among workers who use or who are exposed to powdered latex products. NRL-associated occupational asthma is confined largely to those exposed to powdered latex glove use or other latex aerosols. The most frequent presenting symptom of NRL allergy is contact urticaria; inhalation may cause symptoms of allergic rhinitis and asthma. Skin prick testing is the most accurate tool for diagnosis of NRL allergy. The cornerstone of management is cessation of exposure; substitution with non-NRL or nonpowdered NRL gloves results in predictable rapid disappearance of latex aeroallergen.

Asthma↗
PubMed2002

Quality of life in advanced non-small-cell lung cancer: results of a Southwest Oncology Group randomized trial.

PURPOSE: The main purpose of this paper is to present the results of a randomized trial comparing the effects of two chemotherapy regimens on the Quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). Trials in advanced stage disease represent an important treatment context for QOL assessment. A second purpose of this paper is to examine methods for handling the level of missing data commonly observed in the advanced stage disease context. METHODS: Patients were randomized to receive cisplatin plus vinorelbine or carboplatin plus paclitaxel. The QOL of 222 patients was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) prior to randomization; follow-up assessments occurred at 13 and 25 weeks. Three methods were used to analyze the QOL data: (1) cross-sectional analysis of four patient categories (improved, stable, missing, and declined) based on changes in the FACT-L score, (2) a mixed linear model, and (3) a pattern mixture model. The longitudinal analyses addressed two potential data biases. RESULTS: Questionnaire submission rates were 91% at baseline, 68% at 13 weeks, and 47% at 25 weeks. The cross-sectional and mixed linear model analyses did not show significant differences by treatment arm in patient-reported QOL. The pattern mixture model analysis, more appropriate given non-ignorable missing data, also found no statistically significant effect of treatment on patient QOL. CONCLUSION: We present a sensitivity analysis approach with multiple methods for analyzing treatment effects on patient QOL in the presence of substantial, non-ignorable missing data in an advanced stage disease clinical trial. We conclude that the two treatment arms did not differ statistically in their effects on patient QOL over a 25-week treatment period.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Financial loss and suicidal ideation in a rural community sample.

OBJECTIVE: To examine the prevalence and correlates of suicidal ideation in a community-based rural sample. METHOD: The sample was a random sample of people living in a single county in Iowa. Participants aged 18 or older (n=1617) were asked about suicidal ideation in the past year as well as mood, alcohol use, social support, and stressful life events. RESULTS: About 8.2% of the sample reported suicidal ideation. Depressive symptoms, problems resulting from alcohol use, infrequent social contact and financial loss characterized the suicidal group. CONCLUSION: Depressive symptoms were the strongest correlate of suicidal ideation in this rural sample. In the multivariate analysis, financial loss rather than low income remained a significant correlate of suicidal ideation after controlling for depression. This suggests that change in financial status rather than chronic poverty poses a risk for suicidal ideation.

Adolescent↗
PubMed2002

The population health perspective as a framework for studying child maltreatment outcomes.

The population health perspective (PHP) is commonly used in addressing a wide range of health issues. This article examines the strengths and limitations of the perspective. The determinants of health that are an integral part of the PHP are used as a framework in considering the range of outcomes associated with exposure to child maltreatment. Directions for further research are outlined.

Child↗
PubMed2001

Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial.

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

Adult↗
PubMed2001

The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma.

Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol.

Animals↗
PubMed2001

Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists.

Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.

Animals↗