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Biomedical subjects

J A West

Publications and source records attributed to J A West.

At least 19 recordsLinked to original sources
PubMed2001

Inhaled naphthalene causes dose dependent Clara cell cytotoxicity in mice but not in rats.

Current OSHA standards for naphthalene exposure are set at 10 ppm (time-weighted average) with a standard threshold exposure concentration of 15 ppm. While several studies have thoroughly delineated the time course and dose response of injury by naphthalene administered ip, the pattern and severity of injury by inhalation exposure are unknown. These studies compare the regiospecific and dose-dependent cytotoxicity of naphthalene after inhalation exposure. Mice and rats were exposed for 4 h to naphthalene vapor at concentrations of 0-110 ppm. In rats, no injury was observed in the lung epithelium at exposure concentrations up to 100 ppm. Exposures as low as 2 ppm produced proximal airway injury in mice, with increased severity in a concentration-dependent fashion up to 75 ppm. Terminal airways of exposed mice exhibited little or no injury at low concentrations (1-3 ppm). Exposures of 8.5 ppm or higher were required to produce injury to Clara cells in the terminal airways. In contrast, administration of naphthalene (</=200 mg/kg ip) caused Clara cell cytotoxicity, which was limited to distal airways in mice. Higher doses (>300 mg/kg) extended the injury pattern toward the lobar bronchus. We conclude (1) the pattern of injury to naphthalene is highly dependent on the route of exposure, (2) lung injury to inhaled naphthalene is species dependent, and (3) Clara cells of mouse airways are exquisitely sensitive to inhaled naphthalene at concentrations well below the current OSHA standard for human exposure.

Administration, Inhalation↗
PubMed2001

Weight loss in overweight subjects following low-sucrose or sucrose-containing diets.

OBJECTIVES: To compare the response by overweight individuals, counselled in a work environment, to energy-reduced diets in which the amount of sucrose-containing foods is varied. DESIGN: Two energy-reduced diets were designed as a weight-reducing programme. A low-sugar diet (LSD) providing 5% of its energy from sucrose and a sugar-containing diet (SCD) providing 10% of its energy from sucrose incorporated as sweet foods were devised. Both diets were constructed to contain about 33% of the energy from fat. The diets, designed to provide a deficit of 2.51 MJ/day (600 kcal/day) per individual, were randomly allocated to subjects in an 8 week parallel design study. SUBJECTS: Ninety-five subjects were recruited from a large service industry if they were more than 7 kg (1 stone) in weight above body mass index (BMI) 25 kg/m(2). Sixty-eight subjects completed the programme. MEASUREMENTS: Fortnightly body weight measurements were taken using calibrated scales; BMI at baseline and week 8; and nutrient intake using 2 day food record diaries at baseline and weeks 2, 4 and 8. RESULTS: Weight loss over the 8 weeks was 2.2 kg (LSD) and 3.0 kg (SCD). BMI changed from 29.2 on the LSD and 30.1 kg/m(2) SCD at baseline to 28.2 and 28.8 kg/m(2) at week 8 respectively. The actual prescribed commercially added sucrose intakes were 5% energy (LSD) or 10% energy (SCD). Reported percentage energy from fat was significantly lower on the SCD (and would seem to support the theory of an inverse relationship between fat and sugar) than on the LSD, where there was seen to be no significant reduction. There was no evidence of micronutrient dilution that could be directly attributed to the sucrose content of the diets. CONCLUSION: These results provide no justification for the exclusion of added sucrose in weight-reducing diets.

Body Mass Index↗
PubMed2000

Veterans Affairs Quality Enhancement Research Initiative in chronic heart failure.

Chronic heart failure (CHF) is a highly prevalent condition associated with serious morbidity, intense levels of health services use, and shortened survival. It is also a condition for which ameliorative therapies exist. The evidence indicates that there is substantial need to change clinical practice and health care delivery for people with CHF and thereby improve their outcomes. The goal of the Veterans Affairs (VA) Quality Enhancement Research Initiative in CHF (CHF QUERI) is to create measurable, rapid, and sustainable improvements in quality of care and health outcomes of veterans with heart failure. This article describes the current state of knowledge and practice in care for people with CHF. Using the framework of the 5 steps of the QUERI process, we point out the gaps in research and practice that must be filled if the CHF QUERI is to achieve its goal. We relate our recommendations for how the VA can put its research and administrative infrastructure to work to fill the gaps. Lessons learned about CHF in the course of the CHF QUERI will be applicable to all people with heart failure and to all health care systems--VA as well as non-VA--that care for them.

Benchmarking↗
PubMed2000

Heterogeneity of clara cell glutathione. A possible basis for differences in cellular responses to pulmonary cytotoxicants.

Clara-cell populations show a high degree of variation in susceptibility to injury by bioactivated cytotoxicants. Because glutathione (GSH) is critical for detoxification of electrophilic metabolites, heterogeneity in Clara cell GSH levels may lead to a wide range of cytotoxic responses. This study was designed to define the distinct GSH pools within Clara cells, characterize heterogeneity within the population, and examine whether heterogeneity contributes to susceptibility. Using fluorescent imaging combined with high-performance liquid chromatography analysis, semiquantitative measurements were obtained by evaluation of GSH using monochlorobimane and monobromobimane. In steady-state conditions, the GSH measured in isolated cells was in the femtomole range, but varied 4-fold between individual cells. Clara cells analyzed in situ and in vitro confirmed this heterogeneity. The response of these cells to compounds that modulate GSH was also variable. Diethylmaleate depleted GSH, whereas GSH monoethylester augmented it. However, both acted nonuniformly in isolated Clara cells. The depletion of intracellular GSH caused a striking decrease in cell viability upon incubation with naphthalene (NA). The sulfhydryl-binding fluorochrome BODIPY, which colocalized with tetramethylrosamine, a mitochondrial dye, demonstrated by confocal microscopy that cellular sulfhydryls are highest in the mitochondria, next-highest in cytoplasm, and lowest in the nucleus. These pools responded differently to modulators of GSH. We concluded that the steady-state intracellular GSH of Clara cells exists in distinct pools and is highly heterogeneous within the population, and that the heterogeneity of GSH levels corresponds closely to the response of Clara cells to injury by NA.

Acetylcysteine↗
PubMed2000

Elevated airway GSH resynthesis confers protection to Clara cells from naphthalene injury in mice made tolerant by repeated exposures.

Repeated exposures to Clara cell cytotoxicants, such as naphthalene (NA), render target cell populations resistant to further acute injury. Previous studies suggest that alterations in bioactivation enzymes in target sites (bronchioles) of tolerant mice are insufficient to account for the marked reduction in susceptibility. Mice were made tolerant by seven daily injections of NA. GSH in the terminal airways was 2.7-fold greater in tolerant mice than in vehicle controls and a NA (300 mg/kg) challenge dose did not produce injury. Tolerant mice, allowed to recuperate for 96 h after the seventh NA injection, were again susceptible to NA injury, and terminal airway GSH levels had declined to control levels. To determine whether alterations in GSH resynthesis account for tolerance, the activity of gamma-glutamylcysteine synthetase (gamma-GCS) was measured or mice were treated with a combination of buthionine sulfoximine (BSO), a gamma-GCS inhibitor, and NA. gamma-GCS activity was elevated in resistant airways of tolerant mice. Tolerant mice treated with both BSO and NA appeared as susceptible to injury as NA-challenged controls. We conclude that GSH is critical for Clara cell resistance to NA injury in tolerant mice because: 1) GSH levels in target airways from NA-tolerant animals are elevated; 2) after a 96-h recuperation period, tolerant mice had lower GSH levels and are again susceptible to NA injury; 3) alterations in the activity of gamma-GCS correspond with changes in susceptibility to NA injury; and 4) inhibition of gamma-GCS with BSO increases susceptibility to NA injury in tolerant mice.

Animals↗
PubMed1999

Panretinal photocoagulation during cataract extraction in eyes with active proliferative diabetic eye disease.

PURPOSE: Cataract surgery in the presence of active proliferative diabetic eye disease carries a high risk of progression of retinopathy and neovascular glaucoma. Lens opacities may prevent panretinal photocoagulation (PRP) before surgery, and applying PRP in the immediate post-operative period can be difficult. The purpose of this study is to report results of cataract extraction combined with per-operative indirect laser PRP in a group of these patients. METHODS: Nine eyes of 9 diabetic patients with active retinal or iris neovascularisation in which lens opacities prevented adequate pre-operative PRP underwent cataract surgery combined with indirect laser PRP after cortex aspiration and before intraocular lens implantation. RESULTS: Regression of neovascularisation with this combined procedure alone was achieved in 5 eyes, 3 responded to further PRP, and 1 developed neovascular glaucoma. Visual acuity improved in all eyes, 4 achieving > or = 6/12. Four patients developed increased post-operative uveitis. One developed clinically significant macular oedema. CONCLUSIONS: The method described has definite practical advantages over PRP attempted in the immediate post-operative period, when many factors can prevent its application or reduce its effectiveness, and when neovascularisation may be progressing rapidly. In addition, adjunctive per-operative indirect laser PRP appears to improve the outcome of cataract surgery in eyes with active proliferative diabetic eye disease.

Adult↗
PubMed1999

A mitochondrial marker for red algal intraspecific relationships.

Intraspecific studies of red algae have relied on nuclear or plastid markers rather than mitochondrial data to address questions of systematics, biogeography or population genetics. In this study, primers were developed that spanned the noncoding intergenic region between the mitochondrial cytochrome oxidase subunit 2 and cytochrome oxidase subunit 3 genes. These primers were demonstrated to be successful on a variety of red algae in different orders: Gracilariales, Bonnemaisoniales and Ceramiales (families: Delesseriaceae, Ceramiaceae and Rhodomelaceae). Amplification products were between 450 and 320 bp in length, with variation in length shown among geographically distant isolates within a species. The region was variable within a single species, as shown for Bostrychia moritziana and B. radicans, and within populations of Caloglossa leprieurii. In the latter species, four mitochondrial haplotypes were observed in isolates from a single locality in Woolooware Bay, New South Wales, Australia. Analysis of hybrids between different mitochondrial haplotypes of B. moritziana revealed that the mitochondria are maternally inherited in this species. This is the first report of a mitochondrial marker that is variable within red algal populations and may lead to a better understanding of the population ecology of these important marine organisms.

Base Sequence↗
PubMed1999

Community study using a polymerase chain reaction panel to determine the prevalence of common respiratory viruses in asthmatic and nonasthmatic children.

We developed a sensitive polymerase chain reaction (PCR) panel, suitable for the detection of seven common respiratory viruses, to study the prevalence of viruses in nasal swabs obtained from clinically stable asthmatic children (n = 21), non-physician diagnosed asthmatic children with exercise-induced bronchoconstriction (EIB) (n = 16), and nonasthmatic, non-EIB controls (n = 33). The PCR panel detected viruses in 43/70 (61.4%) specimens but there were no significant differences in prevalence of these viruses between the three groups of children. These results indicate that clinically stable asthmatic and nonasthmatic children frequently harbor viruses in the upper respiratory tract.

Adenoviruses, Human↗
PubMed1999

Familial context of genetic testing for cancer susceptibility: moderating effect of siblings' test results on psychological distress one to two weeks after BRCA1 mutation testing.

OBJECTIVES: To determine whether psychological distress differs among individuals tested for a BRCA1 mutation and is moderated by the pattern of their siblings' test results. MATERIALS AND METHODS: Participants in this study are members of a large kindred identified with a BRCA1 mutation. Subjects included 87 males and 125 females who completed a baseline interview, were tested for a BRCA1 gene mutation, received their results in person from a genetic counselor, completed a follow-up interview 1-2 weeks after the receipt of their test results, and had complete data on all variables used in the analysis. The main outcome of the study was psychological distress as measured by the Impact of Event Scale during the 1-2 week follow-up interview. Data were analyzed based on multiple regression. RESULTS: Male carriers, relative to noncarriers, experienced significantly more distress if they were the first tested than when all of their tested siblings were already known to be negative. Noncarrier males whose siblings all tested positive also encountered significant test-related distress. The largest adverse psychological consequences for female carriers, relative to noncarriers, were for those who were tested first and those whose tested siblings were noncarriers. CONCLUSIONS: The familial context in which genetic testing is conducted may be important for understanding how individuals react to their own test results.

Adult↗
PubMed1998

Genetic analysis using genomic representations.

Analysis of the genetic changes in human tumors is often problematical because of the presence of normal stroma and the limited availability of pure tumor DNA. However, large amounts of highly reproducible "representations" of tumor and normal genomes can be made by PCR from nanogram amounts of restriction endonuclease cleaved DNA that has been ligated to oligonucleotide adaptors. We show here that representations are useful for many types of genetic analyses, including measuring relative gene copy number, loss of heterozygosity, and comparative genomic hybridization. Representations may be prepared even from sorted nuclei from fixed and archived tumor biopsies.

Blotting, Southern↗
PubMed1997

A comprehensive management system for heart failure improves clinical outcomes and reduces medical resource utilization.

The effectiveness of heart failure management in clinical practice is limited by physicians' suboptimal utilization of effective medications, patients' poor adherence to dietary sodium limitation and optimal drug therapy, and the lack of systematic monitoring of patients after hospitalization. The present study evaluated the feasibility and safety of MULTIFIT, a physician-supervised, nurse-mediated, home-based system for heart failure management that implements consensus guidelines for pharmacologic and dietary therapy using a nurse manager to enhance dietary and pharmacologic adherence and to monitor clinical status by frequent telephone contact. Fifty-one patients with the clinical diagnosis of heart failure were followed for 138 +/- 44 days. Daily dietary sodium intake fell by 38%, from 3,393 to 2,088 mg (p = 0.0001); average daily medication doses increased significantly (lisinopril: 17 to 23 mg, p <0.001; hydralazine: 140 to 252 mg, p = 0.01). Functional status and exercise capacity improved significantly (p = 0.01). Compared with the 6 months before enrollment and normalized for variable follow-up, the frequency of general medical and cardiology visits declined by 23% and 31%, respectively (both p <0.03); emergency room visits for heart failure and for all causes declined 67% and 53%, respectively (both p <0.001). Hospitalization rates for heart failure and for all causes declined 87% and 74%, respectively (p = 0.001), compared with the year before enrollment. The MULTIFIT system enhanced the effectiveness of pharmacologic and dietary therapy for heart failure in clinical practice, improving clinical outcomes and reducing medical resource utilization.

Aged↗
PubMed1997

An agreement approach to predict severe angiographic coronary artery disease with clinical and exercise test data.

OBJECTIVE: To demonstrate that an agreement approach to applying equations on the basis of clinical and exercise test variables is an accurate, self-calibrating, and cost-efficient method for predicting severe coronary artery disease in clinical populations. DESIGN: Retrospective analysis of consecutive patients with complete data from exercise testing and coronary angiography referred for evaluation of possible coronary artery disease. After developing an equation in a training set, this equation and two other equations developed by other investigators were validated in a test set. The study was performed at two university-affiliated Veteran's Affairs medical centers. PATIENTS: 1080 consecutive men studied between 1985 and 1995 who had coronary angiography within 3 months of the treadmill test. The population was randomly divided into a training set of 701 patients and a test set of 379 patients. Patients with previous coronary artery bypass surgery, valvular heart disease, marked degrees of resting ST depression, and left bundle branch block were excluded. MEASUREMENTS: Recording of clinical and exercise test data along with visual interpretation of the electrocardiogram recordings on standardized forms and abstraction of visually interpreted angiographic data from clinical catheterization reports. RESULTS: Simple clinical and exercise test variables improved the standard application of exercise-induced ST criteria for predicting severe coronary artery disease. By setting probability thresholds for severe disease of <20% and >40% for the three prediction equations, the agreement approach divided the test set into three groups: low risk (patients with all three equations predicting <21% probability of severe coronary disease), no agreement, and high risk (all three equations with >39% probability) for severe coronary artery disease. Because the patients in the no agreement group would be sent for further testing and would eventually be correctly classified, the sensitivity of the agreement approach was 89% and the specificity was 96%. The agreement approach appeared to be unaffected by disease prevalence, missing data, variable definitions, or even angiographic criteria. CONCLUSIONS: Requiring diagnosis of severe coronary disease to be dependent on agreement between these three equations has made them likely to function in all clinical populations. The agreement approach should be an efficient method for the evaluation of populations with varying prevalence of coronary artery disease, limiting the use of more expensive noninvasive and invasive testing to patients with a higher probability of left main or triple-vessel coronary artery disease. This approach provides a strategy that can be applied by inputting the results of basic clinical assessment into a programmable calculator or a computer to assist the practitioner in deciding when further evaluation is appropriate, thus assuring patients access to subspecialty care.

Confounding Factors, Epidemiologic↗
PubMed1997

Atypical choristomatous cysts of the orbit.

BACKGROUND: The commonset choristomatous cysts of the orbit are dermoid and epidermoid cysts, which are lined by kerantinizing squamous epithelium. They typically occur in the superior orbit, most commonly superotemporally. Other types, lined by different epithelia, and other orbital sites are much less common. METHODS: Five cases of atypical orbita cystic choristomas that presented over the past 6 years are reported. The clinical and radiological features, surgical approach and findings, and histology, are described. Similar cases from the literature are reviewed and possible aetiology discussed. RESULTS: Four of the cysts were lined by a non-keratinizing epithelium resembling conjunctiva; two had adnexal structures in their walls. Compared with typical dermoid and epidermoid cysts, these 'conjunctival dermoids' and 'conjunctival cysts' of the orbit tended to present later in life, none were associated with bony defects, and three of the four occurred in the superomedial quadrant. One case occurred inferiorly, a rare site for orbital conjunctival dermoids and cysts, or typical dermoids and epidermoids. The fifth case, also inferior, is an example of a cyst within choristomatous lacrimal tissue. CONCLUSION: Choristomatous cysts of the orbit may occur with non-keratinizing epithelial linings, and such cysts tend to differ clinically from the commoner dermoids and epidermoids. They may also occur in atypical sites such as the inferior orbit.

Adult↗
PubMed1997

Cost-effective strategies for the management of vascular disease.

Cardiovascular disease accounts for over 950,000 deaths and an estimated $151 billion in direct and indirect costs. Because of this escalating clinical and financial burden, economic analysis has become essential for the evaluation of preventative therapies for vascular disease. Economic analysis compares competing interventions or management strategies for costs and benefits; more specifically, cost-effectiveness analysis compares cost in financial terms like dollars to measures of effectiveness like years of life saved. Important concepts in the creation of a valid cost-effectiveness analysis include perspective, time horizon, measurement of costs and effectiveness and sensitivity analysis. In patients with peripheral arterial occlusive disease, most morbidity and mortality arises from complications of coronary artery disease. Because coronary artery disease and peripheral arterial occlusive disease commonly occur together and share risk factors, pathophysiology and response to preventative therapy, economic evaluations of preventative therapies for coronary artery disease have relevance for patients with vascular disease. Cost-effectiveness analysis reveals that modification of vascular risk factors like tobacco use, hypertension and hypercholesterolemia improve clinical outcomes at acceptable cost-effectiveness ratios, usually less than $20,000 per year of life saved. More importantly, interventions like smoking cessation or lipid modification in high-risk groups may be cost saving, with treatment costs outweighed by financial benefits. From the patient, clinician and societal perspective, cost-effectiveness analysis supports the aggressive modification of cardiovascular risk factors in patients with peripheral arterial occlusive disease.

Cost-Benefit Analysis↗
PubMed1997

A consensus approach to diagnosing coronary artery disease based on clinical and exercise test data.

OBJECTIVE: To demonstrate that a consensus approach for combining prediction equations based on clinical and exercise test variables derived from different populations can stratify patients referred for possible coronary artery disease (CAD) into low-, intermediate-, and high-risk groups. DESIGN: Retrospective analysis of consecutive patients with complete data from exercise testing and coronary angiography referred for evaluation of possible CAD. After derivation of a logistic equation in our own training set of patients, this equation, along with two other equations developed independently by other investigators, was validated in a test set. The validation strategy for the consensus approach included the following: (1) calculation of probability scores for each patient using each logistic equation independently; (2) determination of probability thresholds in the training set to divide the patients into three groups-low risk (prevalence CAD <5%), intermediate risk (5 to 70%), and high risk (>70% prevalence of CAD); (3) using agreement among at least two of three of the prediction equations to generate "consensus" for each patient; and (4) application of the consensus approach thresholds to the test set of patients. SETTINGS: Two university-affiliated Veteran's Affairs medical centers. PATIENTS: We studied 718 consecutive men between 1985 and 1995 who had coronary angiography within 3 months of an exercise treadmill test for suspected CAD. The population was randomly divided into a training set of 429 patients and a test set of 289 patients. Patients with previous myocardial infarction or coronary artery bypass surgery, valvular heart disease, left bundle branch block, or any Q waves present on their resting ECG were excluded from the study. MEASUREMENTS: Recording of clinical and exercise test data along with visual interpretation of the ECG recordings on standardized forms and abstraction of visually interpreted angiographic data from clinical catheterization reports. RESULTS: We demonstrated that by using simple clinical and exercise test variables, we could improve on the standard use of ECG criteria during exercise testing for diagnosing CAD. Using the consensus approach divided the test set into populations with low, intermediate, and high risk for CAD. Since the patients in the intermediate group would be sent for further testing and would eventually be correctly classified, the sensitivity of the consensus approach is 94% and the specificity is 92%. The consensus approach controls for varying disease prevalence, missing data, inconsistency in variable definition, and varying angiographic criterion for stenosis severity. The percent of correct diagnoses increased from the 67% for standard exercise ECG analysis and from the 80% for multivariable predictive equations alone to >90% correct diagnoses for the consensus approach. CONCLUSIONS: The consensus approach has made population-specific logistic regression equations portable to other populations. Excellent diagnostic characteristics can be obtained using simple data and measurements. The consensus approach is best applied utilizing a programmable calculator or a computer program to simplify the process of calculating the probability of CAD using the three equations.

Coronary Angiography↗
PubMed1996

Psychologic profiles as predictors of success in a cardiovascular risk factors life-style intervention program.

The risk for cardiovascular events can be reduced by modifications in life-style. However, only a small percentage of subjects are able to adopt such changes. We determined whether psychologic profiles measured on entry into a life-style intervention program correlated with objective measurements of success after 1 year of enrollment. When compared with patients who had dropped out, patients still enrolled in the program after 1 year differed statistically on scales 1 and 6 of the Minnesota Multiphasic Personality Inventory, showing a lower level of paranoia and more concern about health issues. Among patients remaining in the program, psychologic profiles differed between those who met an objective measure of success (responders) and those who did not. In addition, profiles differed among responders as a function of the aspect of life-style that they successfully changed. These findings suggest that psychologic profiles can be used to identify which life-style changes an individual can easily adopt.

Adaptation, Psychological↗