PubMed Health⌕ Search

Biomedical subjects

M Gillen

Publications and source records attributed to M Gillen.

16 recordsLinked to original sources
PubMed2001

Effect of age and gender on the pharmacokinetics of ebastine after single and repeated dosing in healthy subjects.

OBJECTIVES: Ebastine is a potent and selective H1-receptor antagonist indicated for allergic rhinitis which undergoes extensive first pass metabolism by CYP3A4 to form an active metabolite, carebastine. The purpose of the study was to determine age- and gender-related differences in the pharmacokinetics of ebastine and carebastine. METHODS: The upper recommended oral dose of 20 mg once daily was administered to 12 healthy young (22 to 38 years) and 12 healthy elderly (50 to 92 years; 8 m and 4 f) subjects for 5 days. Plasma concentrations of ebastine and carebastine were determined for 24 hours following the initial dose on Day 1 and for 72 hours following the dose on Day 5 using a sensitive LC/MS/MS assay. The minimum quantifiable limit (MQL) for the assay was 0.05 ng/ml and 1.0 ng/ml for ebastine and carebastine, respectively. RESULTS: Mean area under the curve and Cmax values on Day 1 and Day 5 were similar for ebastine but approximately doubled for carebastine due to its longer half-life. Mean carebastine concentrations were approximately 10 to 20 fold higher than mean ebastine concentrations. For young subjects, the mean (%CV) ebastine t(1/2) was 5.76 (28.47) h and 20.38 (46.19) h on Day 1 and Day 5, respectively. Similarily, for young subjects, the mean (%CV) for carebastine t(1/2) was 7.03 (23.21) h and 26.12 (23.39) h on Day 1 and Day 5, respectively. This apparent prolongation of t(1/2) was probably due to lack of proper estimation of terminal half-life on Day 1 as fewer samples were collected for a shorter duration on Day 1. Using a multicomparison test for Cmin values, it was determined that steady state conditions were achieved by Day 5 for both age groups for ebastine and in young subjects for carebastine. The variability in ebastine pharmacokinetic parameters was higher than carebastine. A 50% increase in ebastine AUC(0-24) and Cmax values in elderly subjects, with no changes in t(1/2), could be explained by either increased absorption of ebastine in elderly subjects or due to a decrease in first pass metabolism. As ebastine shows a high first-pass effect, even a small change in this first pass can cause large changes in plasma exposure. The ebastine pharmacokinetic parameters for elderly subjects in this study lie between the values reported in young subjects in earlier studies. Hence, the apparent age-related pharmacokinetic difference for ebastine is probably due to the inherent variability in ebastine pharmacokinetics. There were no gender-related differences in either young or elderly subjects for mean AUC, Cmax, tmax and t(1/2) ebastine and carebastine values. Ebastine was absorbed rapidly with a median tmax of 1.25 to 2.25 h for both healthy young and elderly males and females on Day 1 and Day 5. There was a delayed appearance of carebastine as expressed by median tmax of 4.0 to 5.0 h, which did not change with age, gender or repeated administration. There were no clinically relevant differences between the groups of subjects with respect to adverse events or safety parameters. CONCLUSIONS: Thus, ebastine can be safely administered to elderly subjects with no clinically important age- or gender related differences in the pharmacokinetics of ebastine/carebastine.

Administration, Oral↗
PubMed1999

A review of the cardiac systemic side-effects of antihistamines: ebastine.

The cardiac safety of ebastine, a long-acting, non-sedating antihistamine, has been thoroughly assessed in phase I-III clinical studies. Ebastine alone at the recommended doses of 10 mg and 20 mg has no clinically relevant effect on QTc interval in adults and in special patient populations (elderly, children or subjects with hepatic or renal impairment). Ebastine administered at 60 and 100 mg/day (3-5 times the maximum recommended dose) for 1 week had statistically significantly smaller effects (3.7 and 10.3 msec, respectively) on the QTc interval than terfenadine (18 msec) at three times the recommended dose (360 mg/day). The mean QTc interval prolongation observed with ebastine 100 mg/day was small and not clinically meaningful, although the results were statistically significant vs. placebo. The effect of ebastine 60 mg/day was not statistically different from placebo. Steady-state drug interaction studies demonstrated that the co-administration of ebastine 20 mg with ketoconazole or erythromycin produced significant increases in systemic exposure for ebastine, which were accompanied by small increases in QTc (approximately 10 msec above ketoconazole or erythromycin alone). Results from individual studies suggest that, when coadministered with ketoconazole, ebastine produces similar changes in QTc interval measurements compared to loratadine and cetirizine. Pooled data from clinical efficacy trials of ebastine 1-30 mg/day administered for 2-3 weeks showed no clinically relevant cardiac effects as assessed by serial electrocardiographs and Holter monitoring. The overall cardiac safety profile based on currently available information suggests that ebastine, like loratadine and cetirizine, has a lower potential for causing adverse cardiovascular effects than terfenadine.

Adult↗
PubMed1999

Injuries from construction falls. Functional limitations and return to work.

Finding a measure that distinguishes well between the severity levels of less serious injuries such as those found in occupational settings has been problematic. In this study of 255 construction workers who sustained nonfatal falls at work, two measures of injury severity were used--the Injury Severity Score (ISS) and the disability index of the Stanford Health Assessment Questionnaire (HAQ), a functional limitation measure. The HAQ scores were more normally distributed than the ISS and provided useful information about the degree to which workers were disabled from falls during their first week of recovery. The mean HAQ score was 1.46 (SD = 0.75) on a scale of 0 to 3, with higher numbers representing more limited functioning. With regard to individual tasks, participants reported having the most difficulty performing heavy chores (mean = 1.89; SD = 1.02), dressing themselves (mean = 1.54; SD = 1.05), and bending to pick up clothing from the floor (mean = 1.40; SD = 1.02). The HAQ scores were significantly and moderately correlated with days lost from work (r = .52; p < .001). Unexpectedly, 97 workers reported that they were able to return to light or modified duty following their falls.

Absenteeism↗
PubMed1997

Injury severity associated with nonfatal construction falls.

This study evaluated injury severity in a group of construction workers who sustained nonfatal falls at work. The sample consisted of 255 adults who were identified from Doctor's First Reports (DFRs) submitted to the California Department of Industrial Relations. For those that fell from heights (n = 195), the mean height of fall was 9.2 feet (SD = 7.1). The mean number of lost work days was 44.3 days (SD = 58.6) and the median was 10 days. Two measures of injury severity were used--the Injury Severity Score and the disability section of the Health Assessment Questionnaire (HAQ). Seventeen participants (7%; 95% CI, 4-10%) were deemed permanently disabled. A simultaneous multiple regression model, using five independent variables, explained approximately 21% of the variance in HAQ scores. Nonunion status and safety climate scores indicating increased risk were positively correlated with higher functional limitation as measured by HAQ scores, as were greater heights and impact on concrete surface. Higher scores on both injury severity measures were significantly and moderately associated with a greater number of days lost from work. These findings suggest that injury severity and permanent disability associated with falls in construction are notable, and identify key target areas for intervention and prevention.

Accidental Falls↗
PubMed1996

Predictors of carbon monoxide and hydrogen cyanide exposure in smoke inhalation patients.

OBJECTIVE: A prospective study of civilian (nonfirefighter) smoke inhalation patients was carried out to test the hypotheses that: 1) absorption of carbon monoxide and hydrogen cyanide from smoke can be predicted by clinical examination and historical data; and, more specifically 2) a history of exposure to burning synthetic polymers is an important predictor of systemic cyanide levels. METHODS: The study was conducted over a three-year period at six urban hospitals. Patients with or without burns who were exposed to smoke within five hours of hospital arrival were sampled for carboxyhemoglobin, whole blood cyanide, urine cotinine and urine creatinine. Controls consisted of a smaller group of smoking status-matched, nonsmoke-exposed burn patients. ANALYSIS: Historical information was obtained on SMOKING status, FIRETYPE (structural vs other), MATERIAL burned (natural vs synthetic) and LAGTIME (from exposure to sampling). A smoke inhalation SCORE (0-10) was assigned to each case, based on physical examination findings and changes on chest X ray, and carboxyhemoglobin and cyanide levels were entered into various multivariate linear regression models. RESULTS: A total of 40 cases and 9 controls were recruited, ranging in age from 15 to 92 years. Thirty-four cases were discharged alive and six expired in-hospital. Observed carboxyhemoglobin levels ranged from 1.2% to 41.6% in cases (mean 8.6%), and from 0.5 to 7.3% in controls (mean 2.9%). Observed cyanide levels ranged from nondetectable (< 0.05 micrograms/mL) to 2.79 micrograms/mL in cases (mean 0.25 micrograms/mL), and from nondetectable to 0.11 micrograms/mL in controls (mean 0.03 micrograms/mL). Among cases, linear regression models explained up to 35% of the observed variance in carboxyhemoglobin levels (p < 0.001) and up to 48% of the variance in cyanide levels (p = 0.0001). CONCLUSIONS: SCORE was the strongest predictor of both carboxyhemoglobin and cyanide levels; LAGTIME also explained significant variance for [log-transformed] carboxyhemoglobin. Historical factors, such as FIRETYPE, MATERIAL, and SMOKING status, did not explain significant variance in most of the statistical models employed.

Adolescent↗
PubMed1995

Work disability in adults with cystic fibrosis.

Greater numbers of persons with cystic fibrosis (CF) reach adulthood and, therefore, actively participate in the labor force. In this study, we estimated labor force participation rates and determined risk factors for work disability among persons with CF. We recruited 49 (73%) of 67 adults followed at one of two hospital-based CF centers. We ascertained employment history and CF-attributed work disability by structured questionnaire. Independently, we reviewed medical records for demographics and illness severity indicators. We analyzed potential risk factors for work disability by logistic regression analysis. All of those studied reported past or present labor force participation, consistent with high work motivation. Complete cessation of work attributed to CF was reported by 17 (35%; 95% CI, 21 to 49%). Although 23 (47%; 95% CI, 32 to 60%) of those surveyed stated that CF had affected career choice, only nine respondents had ever received career counselling and 16 had ever discussed job choice with their physicians. After adjusting for standard measures of disease severity by multiple logistic regression, age, adult diagnosis of CF, female gender, and single marital status, analyzed as a group, provided significant additional explanatory power to a predictive model of disability risk (model chi square [4 d.f.] = 11.5, p < 0.05). Health care professionals who design interventions targeted at work disability among persons with CF should address demographic factors as well as illness severity and should assess the vocational needs of persons with CF and the potential benefit of career counselling.

Adult↗
PubMed1994

HIV/AIDS training for health care providers working with women at risk.

Diagnosis of HIV/AIDS in women is frequently inadequate. Often women are not assessed for risk behaviors that put them at risk for HIV infection. Viral transmission is preventable through behavioral changes. Past experience has demonstrated that one effective method to educate women at risk is to train direct care providers who work with women. Highly skilled providers with expertise in prevention education strategies can facilitate and support behavioral changes in women at risk for HIV transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Occupational bladder cancer in textile dyeing and printing workers: six cases and their significance for screening programs.

Occupational bladder cancer due to aniline dye intermediates such as beta-naphthylamine and benzidine has long been known; benzidine congeners (o-tolidine and o-dianisidine) are highly suspect. Among 400 men from the Amalgamated Clothing and Textile Workers Union (ACTWU) Dyers locals in New York and New Jersey screened over a 4-year period, two cases of bladder cancer were detected. (Microscopic hematuria, not cytological evaluation, prompted further investigation.) Before a 1984 ACTWU screening program in North Carolina, three workers from the same plant self-reported bladder cancers. Another member, with inconclusive screening results, was diagnosed 2 years later. For these six cases, the mean age at detection was 56.5 years (age range, 38 to 79 years), a decade earlier than age at diagnosis of nonoccupational bladder cancer in men. The average latency from onset of exposure to diagnosis was 23.3 years. These cancers provide evidence to support the initiation of screening programs for high-risk workers. To overcome the emotional and economic disincentives faced by potential victims of occupational bladder cancer, training programs are needed. Worker involvement is required, through trade union representation where possible, to assure reliable training and the equitable distribution of screening and treatment costs.

Adult↗
PubMed1988

Inspiratory pressure generation: comparison of subjects with COPD and age-matched normals.

We continuously monitored esophageal (Pes) and gastric (Pga) pressures and used these measurements in a three-component model to estimate instantaneous diaphragmatic (DIA), inspiratory accessory muscle (IAM), and postexpiratory recoil (PER) pressures at various times during inspiration. We validated our model both by volume-pressure relationships of the respiratory system (Vrc-Pga and Vab-Pga, where Vrc and Vab are the rib cage and abdominal volumes, respectively) as well as electromyography of the respiratory muscles. Measurements were carried out at rest and during graded treadmill exercise in 11 subjects with chronic obstructive pulmonary disease (COPDs) and 8 age-matched normal subjects (AMNs). AMNs were 59 +/- 2 (SE) yr and had a forced expiratory volume at 1 s (FEV1.0) of 3.6 +/- 0.2 liters; COPDs were 66 +/- 2 yr and had a FEV1.0 of 1.0 +/- 0.1 liters. We noted the following. At rest, both AMNs and COPDs exhibited an increasing DIA pressure (PDIA) across inspiratory time (TI) at rest. As expired minute ventilation increased with exercise intensity, AMNs continued to maintain this PDIA ramp across inspiration; in contrast, COPDs exhibited higher values of PDIA during the first half of TI than during the second half. At all intensities of exercise, COPDs exhibited higher IAM and PER pressures than the AMNs.

Age Factors↗
PubMed1988

A strategy for educating health care providers about AIDS: the California Nurses Association's AIDS Train the Trainer Program.

The AIDS epidemic is increasing the demand on all levels of health care staff to provide care compassionately and safely to people with AIDS and HIV infection. Only appropriate, ongoing education of all health care workers will maintain an effective health care system as the number of cases rises. However, the fear engendered by the word AIDS can be a serious deterrent to effective care. Adult learning principles and fear reduction techniques provide the foundation for AIDS education. A train the trainer approach provides immediate AIDS expertise to health care providers within their institution or department. With adequate resources and training, health care professionals who are already in the workplace are in the best position to quell hysteria, educate health care workers about appropriate protective measures, and ensure that humane, compassionate care is provided to persons with AIDS and HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Diaphragmatic pressure waveform can predict electromyographic signs of diaphragmatic fatigue.

To evaluate the relationship between diaphragmatic pressure (Pdi) waveform and electromyographic (EMG) signs of diaphragmatic fatigue (DF), 11 chronic obstructive pulmonary disease (COPD) subjects underwent a 12-stage graded treadmill exercise test (GXT). No COPD subjects completed the GXT; all stopped exercising due to dyspnea. We then used the crural diaphragmatic EMG (EMGdi) to divide the COPD subjects into a group that exhibited EMGdi signs of fatigue during the GXT (i.e., F group) and one that did not (i.e., NF group); three COPD subjects were classified as F, and eight COPD subjects were classified as NF. At end exercise, F and NF groups did not differ with respect to peak inspiratory Pdi swing (peak Pdi); however, they did differ with respect to percent of peak Pdi manifest at 50 and 90% of inspiratory time (TI). At 50% TI, NF = 88 +/- 3%, F = 60 +/- 1%, P less than 0.01; likewise at 90% TI, NF = 58 +/- 5%, F = 12 +/- 10%, P less than 0.01. Since peak Pdi occurred in both groups during the initial 50% of TI, these data indicate that the F group maintained Pdi less well than the NF group during the latter half of TI. Based on the above results and other data in the manuscript, we suggest that this change in Pdi waveform can predict EMG signs of DF.

Diaphragm↗
PubMed1986

Description and validation of an ECG removal procedure for EMGdi power spectrum analysis.

We describe a cross-correlation procedure for removing contaminating electrocardiogram (ECG) complexes from the diaphragmatic electromyogram (EMGdi). First, the operator selects ECG templates from the EMGdi signal during expiratory intervals. Second, these templates are used to locate ECG complexes occurring during inspiratory EMGdi activity. Third, at the point of maximum correlation between the template and these ECG complexes, the template is adjusted in size and offset to "match" the ECG complex, and adjustments are determined by the linear regression coefficients. Finally, the modified template is subtracted from the EMGdi signal. To evaluate our method, we compared the power spectral density (PSD) obtained from processing EMGdi signals by our method with those obtained from the EMGdi signal in which ECG complexes had been removed by gating. Our results indicate that PSD obtained by these two different methods shows no statistically significant differences with respect to the following features: centroid frequency, median frequency, total power, standard deviation, skewness, and kurtosis.

Analysis of Variance↗