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Biomedical subjects

C Bell

Publications and source records attributed to C Bell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans.

The sympathetic nervous system (SNS) plays an important role in the regulation of energy expenditure. However, whether tonic SNS activity contributes to resting metabolic rate (RMR) in healthy adult humans is controversial, with the majority of studies showing no effect. We hypothesized that an intravenous propranolol infusion designed to achieve complete beta-adrenergic blockade would result in a significant acute decrease in RMR in healthy adults. RMR (ventilated hood, indirect calorimetry) was measured in 29 healthy adults (15 males, 14 females) before and during complete beta-adrenergic blockade documented by plasma propranolol concentrations > or =100 ng/ml, lack of heart rate response to isoproterenol, and a plateau in RMR with increased doses of propranolol. Propranolol infusion evoked an acute decrease in RMR (-71 +/- 11 kcal/day; -5 +/- 0.7%, P < 0.0001), whereas RMR was unchanged from baseline levels during a saline control infusion (P > 0.05). The response to propranolol differed from the response to saline control (P < 0.01). The absolute and percent decreases in RMR with propranolol were modestly related to baseline plasma concentration of norepinephrine (r = 0.38, P = 0.05; r = 0.44, P = 0.02, respectively). These findings provide direct evidence for the concept of tonic sympathetic beta-adrenergic support of RMR in healthy nonobese adults.

Adrenergic beta-Antagonists↗
PubMed2001

Crossover trial of pagoclone and placebo in patients with DSM-IV panic disorder.

Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the gamma-aminobutyric acid (GABA)-A/benzodiazepine (BDZ) receptor. In theory, such partial agonists should be anxiolytic but lack the adverse side-effects of sedation, tolerance and withdrawal associated with full GABA-A/BDZ agonists. The objective of the randomized double-blind crossover study was to assess whether pagoclone was an effective anti-panic agent and also to assess its side-effect profile. Patients recruited had a diagnosis of Panic Disorder (DSM-IV) with at least one panic attack per week. Following a 2-week screening period, patients entered a 6-week trial consisting of two 2-week treatment periods, each followed by a 1-week washout. Patients were randomly assigned to receive either pagoclone 0.1 mg t.d.s. or placebo on their first treatment period and the converse on their second. The primary measure was daily panic attack dairy. Fourteen patients completed the study, the mean number of panic attacks during screening was 5.8+/-0.8 (SEM), this fell to 3.6+/-0.5 during treatment with pagoclone (p = 0.05) and 4.3+/-0.8 with placebo (p = 0.14). There was no significant difference on direct comparison of pagoclone with placebo or in any of the secondary measures (including Rickels withdrawal scale) or the adverse event profiles. The study provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects. This is consistent with its theoretical mode of action as a partial agonist at the GABA(A)/BDZ receptor.

Adult↗
PubMed2001

Polyclonal sandwich ELISAs to detect F18 fimbriated Escherichia coli in pigs in Northern Ireland.

F18 fimbriated Escherichia coli are a newly described cause of postweaning diarrhea in pigs. Polyclonal rabbit antisera were raised to the antigenic variants, F18ab and F18ac, of these fimbriae and were used to develop monospecific sandwich enzyme-linked immunosorbent assays (ELISAs). The ELISAs were standardized with type cultures characterized by polymerase chain reaction techniques (PCR) and then used to conduct a study of the prevalence of F18 fimbriated E. coli in pigs in Northern Ireland. A total of 176 isolates were tested by ELISA and PCR. Eight isolates were positive for F18 by ELISA, of which 2 were shown to be false positives by PCR and one was PCR positive but ELISA negative. Of the 6 confirmed ELISA positives, all produced VT2 toxin and 3 produced ST toxin. Four positives were from serogroups O138 and O139, previously associated with porcine diarrhea.

Animals↗
PubMed2001

Tryptophan depletion and its implications for psychiatry.

BACKGROUND: Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems. AIMS: To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders. METHOD: Systematic review of preclinical and clinical studies. RESULTS: Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar. CONCLUSIONS: The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.

Anxiety Disorders↗
PubMed2001

Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle, and female sex in healthy adults.

We recently demonstrated in young adult humans that the sympathetic nervous system contributes to the control of resting metabolic rate via tonic beta-adrenergic receptor stimulation. In the present follow-up study we determined the respective effects of age, habitual exercise status, and sex on this regulatory mechanism. Resting metabolic rate (ventilated hood, indirect calorimetry) was determined in 55 healthy sedentary or endurance exercise-trained adults, aged 18-35 or 60-75 yr (29 men and 26 women), before (baseline) and during the infusion of either a nonselective beta-adrenergic receptor antagonist (propranolol) or saline (control). Relative to baseline values, during beta-adrenergic receptor antagonism resting metabolic rate adjusted for fat-free mass was reduced to a lesser extent in older (mean +/- SE, -130 +/- 46 kJ/d) compared with young (-297 +/- 46) adults, sedentary (-151 +/- 50) compared with endurance exercise-trained (-268 +/- 46) adults, and women (-105 +/- 33) compared with men (-318 +/- 50; all P < 0.01). Reductions in resting metabolic rate during beta-adrenergic receptor antagonism were positively related to higher baseline resting metabolic rate and plasma catecholamine concentrations and negatively related to adiposity (all P < 0.05). Resting metabolic rate was unchanged in response to saline control in all groups. These results provide experimental support for the hypothesis that aging, sedentary living, and female sex are associated with attenuated sympathetic nervous system support of resting metabolic rate in healthy adult humans.

Adolescent↗
PubMed2001

Aptamers as reagents for high-throughput screening.

The identification of new drug candidates from chemical libraries is a major component of discovery research in many pharmaceutical companies. Given the large size of many conventional and combinatorial libraries and the rapid increase in the number of possible therapeutic targets, the speed with which efficient high-throughput screening (HTS) assays can be developed can be a rate-limiting step in the discovery process. We show here that aptamers, nucleic acids that bind other molecules with high affinity, can be used as versatile reagents in competition binding HTS assays to identify and optimize small-molecule ligands to protein targets. To illustrate this application, we have used labeled aptamers to platelet-derived growth factor B-chain and wheat germ agglutinin to screen two sets of potential small-molecule ligands. In both cases, binding affinities of all ligands tested (small molecules and aptamers) were strongly correlated with their inhibitory potencies in functional assays. The major advantages of using aptamers in HTS assays are speed of aptamer identification, high affinity of aptamers for protein targets, relatively large aptamer-protein interaction surfaces, and compatibility with various labeling/detection strategies. Aptamers may be particularly useful in HTS assays with protein targets that have no known binding partners such as orphan receptors. Since aptamers that bind to proteins are often specific and potent antagonists of protein function, the use of aptamers for target validation can be coupled with their subsequent use in HTS.

Animals↗
PubMed2000

Clinical and laboratory findings in cases of toxic mastitis in cows in Northern Ireland.

This paper describes the clinical and laboratory findings from 264 cases of toxic mastitis in cows in Northern Ireland between October 1995 and May 1997. Nearly all the cases occurred during the winter housing period, with 84 per cent occurring between November and March inclusive, and 30 per cent in March. Sixty per cent of the cases occurred within one month of calving, and 29 per cent within four days of calving. The most common clinical signs were lethargy (92 per cent), discoloured milk (90 per cent), anorexia (72 per cent), tachypnoea (23 per cent), diarrhoea (23 per cent), recumbency (18 per cent) and staggering (15 per cent). Severe pyrexia (18 per cent) and clinical dehydration (44 per cent) were relatively common findings. Pure growths of Escherichia coli were isolated from 50 per cent of the milk samples, but 11 per cent yielded no bacterial growth. In vitro sensitivity tests indicated that enrofloxacin was effective against 98 per cent of the bacteria isolated, and framycetin and amoxycillin/clavulanic acid against 91 per cent. Abnormally high blood urea levels were observed in 31 per cent of cases, high blood creatinine levels in 42 per cent, and severe leucopenia in 56 per cent. Of the cases which were followed up, 14 per cent died, 21 per cent were culled early and a further 22 per cent lost milk production from the affected quarter.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2000

Reduced inflammation in genetically hypertensive rat airways is associated with reduced tachykinin NK(1) receptor numbers.

The airways of the genetically hypertensive rat (GH) are hyperinnervated by substance P-containing sensory nerves and exhibit reduced inflammatory responsiveness to substance P and to capsaicin. The present study measured tracheal inflammation to resiniferatoxin (1.0 microgram/kg i.v.), a capsaicin analogue, which lacks the hypotensive action of capsaicin itself, alone or after the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole (TRIM) (50 mg/kg i.p.). The inflammatory response to resiniferatoxin alone was 50% lower in untreated GH than in control rats, a similar strain difference to that seen previously with capsaicin. Pre-treatment with TRIM had no effect on inflammation in either strain. Binding kinetics of the tachykinin NK(1) receptor antagonist [3H](S)-1-(2-[3-(3, 4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl)-4- phenyl-l-azoniabicyclo[2,2,2,]octane chloride ([3H]SR140333)(0.125-16.0 nM) showed 50% reduction of B(max) in GH versus control tracheae (74+/-13 cf.165+/-26 fmol/mg protein). Our results indicate that the reduced neurogenic inflammatory responsiveness in GH rats can be attributed entirely to reduced tachykinin NK(1) receptor numbers.

Animals↗
PubMed2000

The effects of exercise and training on human cardiovascular reflex control.

During physical activity, there is a graded withdrawal of vagal cardiac tone and a graded increase in sympathetic cardiac and vasomotor tone, initiated through both central command from the somatic motor cortex and muscle chemoreceptive and mechanoreceptive inputs. In parallel, there is an upward resetting of the operating point of the arterial baroreflex, with preserved reflex sensitivity. In contrast to the traditional interpretation that blood flow through exercising muscle is independent of vasomotor neural influences because of the dominance of local dilator metabolites, recent evidence suggests that both constrictor and dilator sympathetic neural influences may be involved in determining absolute levels of perfusion. Post-exercise, there is a period of relative hypotension that is associated with decreased peripheral resistance. Some, but not all, evidence indicates a causal role for reduced sympathetic drive. Chronic exercise training appears to reduce resting sympathetic activity, with parallel changes in the gain of a variety of cardiovascular autonomic reflexes initiated from cardiovascular sites. These changes may be attributable at least partly to masking of arterial baroreflexes by the impact of elevated blood volume on low-pressure baroreceptors. The reductions in sympathetic drive that follow training are more pronounced in patients with essential hypertension than in normotensive individuals and are likely to underlie the anti-hypertensive effect of exercise.

Blood Pressure↗
PubMed2000

Genomewide search for type 2 diabetes susceptibility genes in four American populations.

Type 2 diabetes is a serious, genetically influenced disease for which no fully effective treatments are available. Identification of biochemical or regulatory pathways involved in the disease syndrome could lead to innovative therapeutic interventions. One way to identify such pathways is the genetic analysis of families with multiple affected members where disease predisposing genes are likely to be segregating. We undertook a genomewide screen (389-395 microsatellite markers) in samples of 835 white, 591 Mexican American, 229 black, and 128 Japanese American individuals collected as part of the American Diabetes Association's GENNID study. Multipoint nonparametric linkage analyses were performed with diabetes, and diabetes or impaired glucose homeostasis (IH). Linkage to diabetes or IH was detected near markers D5S1404 (map position 77 cM, LOD = 2.80), D12S853 (map position 82 cM, LOD = 2.81) and GATA172D05 (X-chromosome map position 130 cM, LOD = 2.99) in whites, near marker D3S2432 (map position 51 cM, LOD = 3.91) in Mexican Americans, and near marker D10S1412 (map position 14 cM, LOD = 2.39) in African Americans mainly collected in phase 1 of the study. Further analyses showed evidence for interactions between the chromosome 5 locus and region on chromosome 12 containing the MODY 3 gene (map position 132 cM) and between the X-chromosome locus and region near D12S853 (map position 82 cM) in whites. Although these results were not replicated in samples collected in phase 2 of the GENNID study, the region on chromosome 12 was replicated in samples from whites described by Bektas et al. (1999).

Age of Onset↗
PubMed2000

Flumazenil challenge in social phobia.

The benzodiazepine antagonist, flumazenil, can provoke panic attacks in some panic disorder patients. It has been predicted that panic responses to flumazenil may be associated with situational fear. Patients with social phobia frequently experience situational anxiety and panic attacks. The current study tested whether flumazenil induces panic in patients with social phobia. Fourteen patients with social phobia (DSM-III-R) and 14 age- and sex-matched controls were tested in a single session, double blind crossover challenge design, using intravenous flumazenil 2 mg/20 ml or matched placebo infusions 1 hour apart. Panic attacks occurred during flumazenil challenge in 2/14 subjects with social phobia. The rate of panic attacks and the severity of panic symptoms following flumazenil were not significantly greater in patients than in controls. Situational fears that are provoked by social cues therefore do not predict panic responses to flumazenil.

Adult↗
PubMed2000

Sleep changes during long-term treatment of depression with fluvoxamine--a home-based study.

RATIONALE: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. OBJECTIVES: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. METHODS: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients' own homes, using the Oxford Medilog system. RESULTS: At 12 weeks, 7/12 patients had responded (HAM-D decreased by > 50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non-significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders. CONCLUSIONS: The effects of the SSRI fluvoxamine on objective sleep measures are in the direction predicted by its pharmacological actions and some persist for at least 12 weeks. In addition subjective appraisal of sleep is strongly affected by mood state. All patients found the home recording procedure acceptable and only minimally disruptive.

Adult↗
PubMed2000

The influence of patient geometry on the selection of chest wall irradiation techniques in post-mastectomy breast cancer patients.

BACKGROUND AND PURPOSE: To evaluate three chest wall (CW) irradiation techniques: wide tangential photon beams, direct appositional electron field and electron arc therapy with regards to target coverage and normal tissue tolerance. MATERIALS AND METHODS: Thirty-two post-mastectomy breast cancer patients were planned using three CW irradiation techniques. Computed tomography (CT) simulation was done on all patients and clinical target, heart and lung volumes were contoured. For each technique, dose distributions and dose-volume histograms (DVH) were calculated. Pass/fail criteria were applied based on volumetric target and critical structure dose coverage. Passing criteria for target was 95% of target receiving 95% of dose using a standard dose of 50 Gy/25 fractions, for heart </=10% volume receiving 50% dose (i.e. 25 Gy) and for lung </=25% volume ipsilateral lung receiving 50% dose (i.e. 25 Gy). RESULTS: The number of patients optimally treated by each technique were as follows: wide tangential photon beams 23/32 (72%), direct appositional electron field 1/32 (3%), electron arc 4/32 (12.5%) and in 4/32 (12.5%) no technique was optimal. Geometric predictors for technique suitability include CW thickness, medial to lateral CW curvature, uniformity of superior to inferior CW curvature and length of mastectomy scar. CONCLUSIONS: This study confirms the utility of CT planning and DVH analysis for treatment planning of breast cancer. Patient factors that predict for treatment technique suitability and aid in technique selection can be identified. In a small subset of patients, none of the currently studied techniques were optimal and more novel methods of chest wall irradiation are required.

Adult↗
PubMed2000

Cost-utility analyses of clinical preventive services: published ratios, 1976-1997.

BACKGROUND: Cost-effectiveness analyses of clinical preventive services are a potential means to aid public health resource allocation. Cost-utility analysis (CUA) is a specific form of cost-effectiveness analysis where results are expressed in terms of cost per quality-adjusted life year (QALY) gained. To increase the transparency and comparability of CUAs, standardization of methods has been recommended. OBJECTIVES: The purposes of this study were as follows: (1) identify published articles with original CUAs of primary and secondary clinical preventive services, (2) summarize the ratios found in these analyses, (3) identify articles employing comparable methods, and (4) explore analytic methods employed over time. METHODS: As part of a larger study we conducted a comprehensive search of published CUAs in the area of clinical preventive services and systematically collected data on the results of the analyses and analytic methods employed. Cost-effectiveness ratios were standardized and organized into a table. RESULTS: We found 50 CUAs pertaining to clinical preventive services (primary, n=22, 44%; and secondary, n=28, 56%) and 174 cost-effectiveness ratios. These ratios ranged from cost-savings up to $27,000,000/QALY, with a median of $14,000/QALY. Only three (6%) of the CUAs met minimum reference case requirements. There was no apparent improvement of methods over time. CONCLUSIONS: Immunizations and chemoprophylaxis have the most favorable cost-effectiveness ratios, and preventive services are more cost-effective when targeted at high-risk populations. However, there is wide variation in the methods used in these analyses. This study allows us to define where improvements in methodologic rigor need to occur, provides a base-line for future audits, and highlights disease areas in clinical preventive services that have been omitted or underevaluated.

Cost-Benefit Analysis↗
PubMed2000

Cumulative effect of family environment on psychiatric symptomatology among multiethnic adolescents.

PURPOSE: To examine the influence of family adversity and support on levels of psychiatric symptomatology in Hawaiian and non-Hawaiian adolescents. METHOD: More than 4000 students from five high schools in Hawaii completed a survey during the 1992-1993 school year about their family environment and mental health. The response rate was approximately 60%. Logistic regression analyses were performed and responses for Hawaiians and non-Hawaiians were compared. RESULTS: Hawaiian adolescents experienced significantly more adversity than their non-Hawaiian counterparts. The cumulative effect of family adversity had a greater effect on psychiatric symptomatology than any single indicator. Family support reduced the risk for internalizing symptoms, particularly for Hawaiian adolescents. The influence of family support was less clear for externalizing symptoms, increasing the risk for some adolescents and decreasing the risk for others. CONCLUSION: We identified strong associations between family adversity and levels of psychiatric symptomatology. We found that Hawaiian adolescents are at increased risk for psychiatric symptomatology, given the presence of family adversity and the effect of reduced family support. However, risk was also substantial for non-Hawaiians. Clinicians need to assess the family environment routinely and implement family-oriented interventions.

Adolescent↗
PubMed2000

Use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in patients with stroke. Canadian Task Force on Preventive Health Care.

BACKGROUND: Patients with stroke commonly undergo investigations to determine the underlying cause of stroke. These investigations often include ambulatory electrocardiography to detect paroxysmal atrial fibrillation. There is conflicting evidence in the literature regarding whether routine ambulatory electrocardiography should be performed in all or selected stroke patients. This paper reviews the available evidence on (1) the yield of ambulatory electrocardiography in detecting paroxysmal atrial fibrillation in patients with stroke or transient ischemic attack and (2) the effectiveness of anticoagulation in preventing recurrent stroke in patients with paroxysmal atrial fibrillation. METHODS: A MEDLINE search for primary articles was performed, and the references were reviewed manually. In addition, citations were obtained from experts. The evidence was systematically reviewed using the evidence-based methodology of the Canadian Task Force on Preventive Health Care. RESULTS: Ambulatory electrocardiography can detect atrial fibrillation not found on initial electrocardiogram in between 1% and 5% of people with stroke. Ambulatory electrocardiography is generally safe. The risk of recurrent stroke in the setting of paroxysmal atrial fibrillation is uncertain, but appears to be similar to that seen with chronic atrial fibrillation (about 12% per year). Therapy with warfarin may reduce this risk by about two-thirds as compared to placebo. The annual risk of major bleeding with warfarin therapy is between 1% and 3% but rates for individual patients depend on various specific risk factors. INTERPRETATION: There is insufficient evidence to recommend for or against the use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in either selected or unselected patients with stroke (C Recommendation). There is fair evidence to recommend therapy with warfarin for patients with stroke and paroxysmal atrial fibrillation (B Recommendation).

Anticoagulants↗