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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 271 records · Page 15Linked to original sources
PubMed1999

Atheroprotection with amlodipine: cells to lesions and the PREVENT trial. Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial.

Oxidized lipid and calcium regulatory abnormalities appear to play important roles in early atherogenesis secondary to cholesterol enrichment of the cell membrane in endothelial and arterial smooth muscle cells (SMCs). However, the link between the two is poorly understood. The findings reviewed here demonstrate that amlodipine has membrane-modifying and antioxidant actions at the cell membrane level in addition to its classical calcium channel blocking properties. These multiple pharmacologic actions may explain the cellular mechanisms of the atheroprotective effects of amlodipine in spontaneous atherogenesis and in accelerated atherosclerotic syndromes. Recent animal model studies have demonstrated that amlodipine inhibits the progression of atherosclerotic lesions and protects against restenosis after angioplasty. Amlodipine inhibits the cholesterol-induced increase in calcium permeability in SMCs, and has been shown to repair abnormalities in SMC membrane structure. Recent data have also demonstrated that amlodipine has a marked antioxidant action in membrane bilayers enriched with polyunsaturated fatty acids. However, these findings have been in animal models only; the efficacy of amlodipine in atheroprotection in humans cannot be predicted. The PREVENT trial has therefore been launched to examine the atheroprotective potential of amlodipine in spontaneous lesion development in humans with ischemic heart disease and in the prevention of restenosis after angioplasty.

Amlodipine↗
PubMed1999

Translating the CAHPS 1.0 Survey Instruments into Spanish. Consumer Assessment of Health Plans Study.

OBJECTIVES: Collecting accurate health data on the growing number of ethnic minorities in the United States has increased in policy relevance in recent years. Today, most general population sample surveys conducted in the United States, including the CAHPS 1.0 Surveys, require translation into Spanish and often other languages as well. This article discusses the process used to translate the CAHPS 1.0 survey instruments into Spanish and the techniques used to evaluate these instruments. METHODS: The CAHPS team used a technique of translation-backtranslation to translate the survey instruments into Spanish and conducted cognitive testing and pretesting of preliminary versions of the 1.0 Survey Instruments in both English and Spanish. RESULTS: The translation-backtranslation method produced Spanish-language versions of the survey instruments that were adequate for more educated respondents but were inadequate for less educated respondents and respondents who seemed to be less acculturated. CONCLUSION: Adept translation of a survey instrument is an integral part of the instrument-development process, but it alone does not ensure that a culturally appropriate survey instrument will result. Producing a survey instrument that is culturally appropriate for Latinos in the United States may require modifying the English versions of instruments as well as subjecting Spanish-language instruments to more rigorous testing that includes cognitive testing, pretesting, and an evaluation of the reading level by a literacy expert.

Adult↗
PubMed1999

The impact of re-engineering and other cost reduction strategies on the staff of a large teaching hospital: a longitudinal study.

OBJECTIVES: To examine changes over time in the hospital staff's perceptions of how rapid organizational change, caused by fiscal constraints imposed by governments, affects them, their work environment, and the quality of care and services that they provide. METHODS: A random sample of hospital employees (n = 900) of a large Ontario teaching hospital participated in a longitudinal study which involved surveys at 3 measurement periods over a 2-year period. The questionnaire used in this study included scales reflecting work environment, emotional distress, personal resources, spillover from work to home and vice versa, and perceptions regarding patient care and the hospital as an employer. RESULTS: Significant increases in depression, anxiety, emotional exhaustion, and job insecurity were seen among employees, particularly during the first year of the change process. By the end of the second year, employees reported deterioration in team work, increased unclarity of role, and increased use of distraction to cope. Job demands increased throughout the period whereas little change occurred in the employee's job influence or decision latitude. Overall, the work environment was negatively affected. Although patient care was unaffected in the first year, a significant decline in perceptions of patient care, attention to quality improvement, and overall quality of care were later seen. CONCLUSIONS: This study raises questions about whether hospital re-engineering and mergers will be able to achieve the cost reductions sought without sacrificing quality of work life. Along with the rapid change, there was increase in emotional distress among staff and a deterioration in their relationship with their employer.

Adaptation, Psychological↗
PubMed1999

No evidence of linkage disequilibrium between a CAG repeat in the SCA1 gene and schizophrenia in Caucasian and Chinese schizophrenic subjects.

Several recent studies have reported evidence for a schizophrenia locus on chromosome 6p, with a variety of linked markers spanning a approximately 40 cM region between D6S470 and D6S291. However because of the wide region implicated and the difficulty of inferring phenotype from genotype in complex disorders, it is difficult to define its location precisely using linkage data. An alternative approach is to search for linkage disequilibrium. On chromosome 6p, allelic association with a (CAG)29 allele of a triplet repeat marker in the SCA1 gene has been reported, and we have attempted to replicate this finding using a Caucasian case-control sample of 211 affected subjects and 204 controls, and a Han Chinese sample of 100 affected family trios. In the case-control sample, the frequency of the (CAG)29 allele was similar in cases and controls (35%), and no other alleles provided evidence for allelic association. Likewise, there was no evidence for preferential transmission of the (CAG)29 allele to affected offspring in the Chinese sample, although a different allele, (CAG)26, was more often transmitted to the affected offspring. However this data did not reach statistical significance (P = 0.1). We conclude that our data does not support the notion that there is a locus for schizophrenia close to the SCA1 gene. However, since linkage disequilibrium will vary between distinct populations, we cannot exclude this possibility.

Asian People↗
PubMed1999

A dispensable region of the chromosome which is associated with an avirulence gene in Pseudomonas syringae pv. pisi.

Pseudomonas syringae pv. pisi comprises a number of races which fall into two phylogenetically distinct groups (designated I and II). Races are based on cultivar specificity in the host plant, pea (Pisum sativum), and are specified by the presence of avirulence genes. The avirulence gene avrPpiA1 is present on the chromosome of all strains examined in race 2, which belongs to phylogenetic group II. A race 4B strain, from phylogenetic group I, lacks this avirulence gene and a comparative study was made of the chromosome in strains representing these two races. A race 2 cosmid clone (pAV270) carrying avrPpiA1 was used as a basis for collinearity analysis of races 2 and 4B. A region of the chromosome amounting to 8.5 kb and including avrPpiA1 was absent from race 4B compared with race 2. A fragment spanning the junction of the discontinuity in race 4B was isolated, cloned and used to delimit the extent of the additional DNA present in race 2. In both races the borders of the discontinuity contained DNA sequences which showed a high degree of conservation. A 7 bp slightly imperfect direct repeat (CCAGC(T)/(A)T) flanked the additional DNA in race 2, with a single copy in race 4B. The region flanking the additional DNA was present in all races of P. syringae pv. pisi. These results confirm the phylogenetic groupings in P. syringae pv. pisi.

Base Sequence↗
PubMed1999

Effect of frusemide and hypertonic saline on electrolytes during post exercise anaesthesia.

This study evaluated the effects of pre-exercise frusemide administration and hypertonic saline (H) infusion during anaesthesia on arterial pH, blood gases and electrolytes in 6 Thoroughbred horses anaesthetised immediately post exercise. Horses received either frusemide (F) (0.5 mg/kg, i.v.) or a saline placebo (P) injection 4 h prior to treadmill exercise. Exercise consisted of a 3 min warm-up at 40% VO2max followed by exercise to fatigue. Detomidine (40 micrograms/kg, i.v.) was given within 5 min of stopping and followed 5 min later by zolazepam-tiletamine (1.25 mg/kg, i.v.) to induce anaesthesia. During maintenance of anaesthesia using isoflurane in O2, either isotonic saline solution (I) or 7.5% H (4 ml/kg, i.v.) was administered. Arterial blood was sampled at the following times: prior to (Pre-F/P) and 4 h after (Pre-ex) F or P administration, 1 min after fatigue (Fatigue), 5 min after induction of anaesthesia (Post-ind), and just prior to and 15, 30 and 60 min after beginning isoflurane (ISFL) anaesthesia. Arterial pH and blood gas tensions, pulmonary arterial blood temperature, plasma [lactate], total protein and plasma [Na+], [K+], and [Cl-] were measured. Data were analyzed using 2-way ANOVA for repeated measures (P < 0.05). There were significant differences over time for all variables except total protein. Plasma [Na+] increased at Fatigue compared to Pre-F/P or Pre-ex in all treatment groups. Plasma [Na+] and [Cl-] increased during ISFL anaesthesia compared to Pre-F/P and Pre-ex in horses given H. During ISFL anaesthesia, plasma [Cl-] decreased compared to Pre-F/P in Group F+I horses. We conclude that acid-base, blood gas, and electrolyte changes associated with F are unlikely to influence management of horses anaesthetised immediately following supramaximal exercise to fatigue. Hypertonic saline infusion may help restore plasma [Cl-] faster in hypochloraemic horses requiring anaesthesia immediately after strenuous exercise.

Acid-Base Equilibrium↗
PubMed1999

The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor.

The calcitonin receptor-like receptor (CRLR) can function as either a receptor for calcitonin gene-related peptide (CGRP) or for adrenomedullin (ADM), depending upon the coexpression of a novel family of single transmembrane proteins, which we have called receptor activity modifying proteins or RAMPs. RAMPs 1, 2, and 3 transport CRLR to the plasma membrane with similar efficiencies, however RAMP1 presents CRLR as a terminally glycosylated, mature glycoprotein and a CGRP receptor, whereas RAMPs 2 and 3 present CRLR as an immature, core glycosylated ADM receptor. Characterization of the RAMP2/CRLR and RAMP3/CRLR receptors in HEK293T cells by radioligand binding (125I-ADM as radioligand), functional assay (cAMP measurement), or biochemical analysis (SDS-polyacrylamide gel electrophoresis) revealed them to be indistinguishable, even though RAMPs 2 and 3 share only 30% identity. Chimeric proteins were created with the transmembrane and cytosolic portions of RAMP1 associated with the amino terminus of RAMP2 (RAMP2/1) and vice versa (RAMP1/2). Coexpression of RAMP2/1 with CRLR formed a core glycosylated ADM receptor, whereas the RAMP1/2 chimera generated both core glycosylated and mature forms of CRLR and enabled both ADM and CGRP receptor binding. Hence, the glycosylation state of CRLR appears to correlate with its pharmacology.

Adrenomedullin↗
PubMed1999

Clinical outcomes of newborn screening for cystic fibrosis.

AIM: To determine how early diagnosis of cystic fibrosis, using neonatal screening, affects long term clinical outcome. METHODS: Fifty seven children with cystic fibrosis born before neonatal screening was introduced (1978 to mid 1981) and a further 60 children born during the first three years of the programme (mid 1981 to 1984), were followed up to the age of 10. The cohorts were compared on measures of clinical outcome, including height, weight, lung function tests, chest x-ray picture and Shwachman score. RESULTS: Age and sex adjusted standard deviation scores (SDS) for height and weight were consistently higher in children screened for cystic fibrosis than in those born before screening. At 10 years of age, average differences in SDS between groups were 0.4 (95% CI -0.1, 0.8) for weight and 0.3 (95% CI -0.1, 0.7) for height. This translates to an average difference of about 2.7 cm in height and 1.7 kg in weight. Mean FEV1 and FVC (as percentage predicted) were significantly higher in the screened cohort at 5 and 10 years of age, with an average difference of 9.4% FEV1 (95% CI 0.8, 17.9) and 8.4% FVC (95% CI 1.8, 15.0) at 10 years. Chest x-ray scores were not different between the groups at any age, but by 10 years screened patients scored an average 5.3 (95% CI 1.2, 9.4) points higher on the Shwachman score. CONCLUSION: Although not a randomised trial, this long term observational study indicates that early treatment made possible by neonatal screening may be important in determining subsequent clinical outcomes for children with cystic fibrosis. For countries contemplating the introduction of neonatal screening for cystic fibrosis, its introduction to some areas in a cluster randomised design will permit validation of studies performed to date.

Anti-Bacterial Agents↗
PubMed1999

Molecular genetic characterisation of frontotemporal dementia on chromosome 3.

We have previously localized a locus causing familial nonspecific dementia to the centromeric region of chromosome 3 in a pedigree from the Jutland area of Denmark. This pedigree shows anticipation. Here we present further analysis of these anticipation data which are suggestive of trinucleotide repeat expansion involvement. We also outline our strategies to clone the mutant gene via its putative associated trinucleotide repeat sequence.

Adult↗
PubMed1999

Long-term influence of inhaled corticosteroids on bone metabolism and density. Are biological markers predictors of bone loss?

Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 microgram/d (high-dose group [Group HD] mean: 983 microgram/d [prescribed dose x estimated compliance]) or no or < 500 microgram/d (control group [Group C] mean: 309 microgram/d) for more than 5 yr were enrolled in this study. Each had, 3 yr ago and at this last evaluation, a clinical evaluation and measurements of expiratory flows and of bone density and bone metabolism markers. Lumbar spine bone density (last visit) was similar in the two groups with respective values of 0.94 +/- 0.03 (HD) and 0.96 +/- 0.03 g/cm2 (C) (p > 0.05). T and Z scores were -1.21 +/- 0.19 and -0.70 +/- 0.18 (HD), -0.95 +/- 0.25 and -0.47 +/- 0.21 (C) respectively (p > 0.05). A correlation was found between the decrease in bone density and the mean daily dose of corticosteroid in Group HD although these changes were quite small, mean bone density being unchanged over the 3-yr period. Serum and urinary parameters were similar in the two groups. Furthermore, neither initial bone density nor any of the biological parameters could predict changes in bone density over a period of 3 yr. In conclusion, bone density was similar in both study groups and not significantly different over a 3-yr period. Neither initial bone density nor biological markers of bone metabolism helped to predict changes in bone mass.

Administration, Inhalation↗
PubMed1999

Automated collection of quality-of-life data: a comparison of paper and computer touch-screen questionnaires.

PURPOSE: To evaluate alternative automated methods of collecting data on quality of life (QOL) in cancer patients. After initial evaluation of a range of technologies, we compared computer touch-screen questionnaires with paper questionnaires scanned by optical reading systems in terms of patients' acceptance, data quality, and reliability. PATIENTS AND METHODS: In a randomized cross-over trial, 149 cancer patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 2.0 (EORTC QLQ-C30), and the Hospital Anxiety and Depression Scale (HADS) on paper and on a touch screen. In a further test-retest study, 81 patients completed the electronic version of the questionnaires twice, with a time interval of 3 hours between questionnaires. RESULTS: Fifty-two percent of the patients preferred the touch screen to paper; 24% had no preference. The quality of the data collected with the touch-screen system was good, with no missed responses. At the group level, the differences between scores obtained with the two modes of administration of the instruments were small, suggesting equivalence for most of the QOL scales, with the possible exception of the emotional, fatigue, and nausea/vomiting scales and the appetite item, where patients tended to give more positive responses on the touch screen. At the individual patient level, the agreement was good, with a kappa coefficient from 0.57 to 0.77 and percent global agreement from 61% to 97%. The electronic questionnaire had good test-retest reliability, with correlation coefficients between the two administrations from 0.78 to 0.95, kappa coefficients of agreement from 0.55 to 0.90, and percent global agreement from 56% to 100%. CONCLUSION: Computer touch-screen QOL questionnaires were well accepted by cancer patients, with good data quality and reliability.

Adult↗
PubMed1999

Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers.

OBJECTIVE: The objective of this study was to determine the sites of zanamivir deposition in the respiratory tract and the pharmacokinetics of zanamivir after oral inhalation from the Diskhaler device and from a prototype of a novel breath-activated device. DESIGN: This was a 2-period block-randomised study in which participants inhaled zanamivir from a Diskhaler and/or the prototype device on separate days. STUDY PARTICIPANTS: 13 healthy volunteers (5 men and 8 women) aged 20 to 42 years (mean age 29 years) and weighing 54.0 to 94.0 kg (mean bodyweight 69.2 kg) entered the study. INTERVENTIONS: Participants were given dry powder zanamivir 10 mg formulated with 99mTc from the Diskhaler or the prototype device on separate days. Scintigraphic images of the chest and oropharynx were recorded. Blood samples for determination of serum zanamivir and urine for excretion studies were taken up to 8 hours after drug administration. Safety was evaluated by monitoring lung function tests, adverse events and laboratory parameters. RESULTS: Orally inhaled zanamivir was well tolerated, as demonstrated by lung function tests. A mean of 13.2% (n = 11) of the 10 mg dose from the Diskhaler was deposited in the bronchi and lungs. The deposition pattern varied between individuals, showing a preferentially central deposition pattern in some and a uniform distribution pattern in others. The major deposition site was the oropharynx (mean 77.6%), with a mean of 1.2% deposited on the trachea and a mean of 3.2% retained in the blister. Similar data were obtained with the prototype device. Inhalation of zanamivir gave a broad peak of systemic absorption with mean maximum serum concentrations of approximately 30 to 40 micrograms/L after 1.5 hours. The rate and extent of absorption were similar irrespective of inhalation device. Less than 5% of drug was excreted unchanged in urine within 8 hours of inhalation, confirming the low bioavailability of zanamivir after pulmonary delivery. A significant correlation existed between systemic exposure and peripheral lung deposition. CONCLUSIONS: The local concentrations of zanamivir that result from oral inhalation via the Diskhaler are estimated to be > 10 mumol/L throughout the respiratory tract, well in excess of the concentrations observed to inhibit influenza virus neuraminidases by 50% (0.64 to 7.9 nmol/L). Similar deposition data were obtained with the Diskhaler and the prototype device, which was consequently not developed further. Pharmacoscintigraphy was confirmed as being a reliable technique for measuring zanamivir deposition in the respiratory tract.

Administration, Inhalation↗
PubMed1999

Benefit valuation in economic evaluation of cancer therapies. A systematic review of the published literature.

Generic measures of benefit which employ individuals' preferences, such as the quality-adjusted life-year (QALY), are, in principle, the most appropriate outcome measure to use in the economic evaluation of cancer therapies. They can reflect the trade-offs between health-related quality of life (HR-QOL) and length of life, between different dimensions of HR-QOL and between the process (e.g. convenience) and outcome characteristics of treatments. This paper reviews the methods literature on preference-based measures of benefit in economic evaluation, with the aim of establishing good practice for applied studies using these methods. A systematic review of applied economic evaluations of cancer therapies which have used these types of benefit measure was performed with the aim of establishing whether studies in this area adhere to good practice. In total, 29 studies were reviewed, and the results showed that, in general, good methods are not being adopted. This may be due, in part, to authors not having the space in journals to detail their methods fully, but it is likely also to reflect the fact that good methods for the use of preference-based measures of benefit in economic evaluation have not been adequately disseminated.

Cost-Benefit Analysis↗
PubMed1999

Psychological effects of hormone replacement therapy: a comparison of tibolone and a sequential estrogen therapy.

Hormone replacement therapy (HRT) is effective in alleviating vasomotor symptoms but the effect on psychological symptoms is less clear. This study aimed to compare the psychological effects of two regimens of HRT in perimenopausal women in a randomized, initially double-blind, controlled trial. Thirty-eight women reporting climacteric symptoms were randomly allocated into either oral conjugated equine estrogen 0.625 mg daily plus progestogen (norgestrel) 150 micrograms for the last 12 days of each 28 day cycle, or tibolone 2.5 mg/day for 28 days. They were assessed using standardized psychological assessments. There were no significant differences in changes from baseline between the two types of therapy. For both groups combined there were significant improvements compared with baseline in vasomotor symptoms in the first month, plus anxiety, sleep, memory and somatic dysfunction by the second and third months, but not in scores of depression. Log linear analysis of weekly scores showed that depression scores were significantly related to improvement in vasomotor scores independent of type of therapy and time on HRT. Memory problems were related to vasomotor symptoms independent of depression. No difference between the two types of therapy was found, nor any direct effect of HRT on anxiety or depression. The results support the domino theory, suggesting that psychological improvement follows alleviation of vasomotor symptoms.

Aged↗