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Biomedical subjects

Brian Baker

Publications and source records attributed to Brian Baker.

14 recordsLinked to original sources

The effect of alcohol and gender on ambulatory blood pressure: results from the Baseline Double Exposure study.

BACKGROUND: Research has demonstrated that psychosocial and lifestyle factors are associated with sustained increases in blood pressure (BP). METHODS: Using post-hoc analyses from the Baseline Double Exposure cohort study, alcohol consumption and gender were examined as to their association with ambulatory BP (ABP) in participants with normal or elevated and untreated BP. RESULTS: The current study included 248 subjects, 135 (54.4%) of whom were women, with a mean age (+/- SD) of 50.8 +/- 6.6 years. The main effects model, which included BMI, multiple regression analysis with 24 h systolic BP as the dependent variable found that alcohol consumption (P = .033), male gender (P = .004), and age (P = .039) were significant variables associated with higher systolic BP, whereas exercise (P = .037) was associated with lower systolic BP. From the regression analysis, the independent effect of alcohol consumption (> or = 10 drinks per week) on systolic BP was 4.4 mm Hg for all subjects during 24 h and 7.1 mm Hg during spousal contact, whereas in women with this degree of alcohol consumption the effect on systolic BP was 8.4 mm Hg during 24 h and 11.4 mm Hg during spousal contact. When the interaction term of gender by drinking status was added to the same regression model, the term was not significant for systolic BP during 24 h, but was significant during spousal contact time (P = .047). CONCLUSIONS: The current study demonstrates an association between alcohol with higher systolic BP, more pronounced in women than men, particularly during spousal contact time. This is the first time that the interaction of alcohol and gender with ABP has been demonstrated.

Adult↗

Chip-based microelectrodes for detection of single-nucleotide mismatch.

Microelectrode arrays having eight 10-microm-diameter gold microelectrodes arranged on a gold-covered Si chip were designed and characterized. The chips prove useful for the detection of single-nucleotide mismatches in unlabeled and prehybridized DNA by electrochemical impedance spectroscopy.

Base Pair Mismatch↗

Impact of job and marital strain on ambulatory blood pressure results from the double exposure study.

BACKGROUND: Psychosocial stressors such as job strain and marital stress have been associated with a sustained increase in blood pressure (BP). METHODS: We evaluated whether job strain and marital cohesion were associated with ambulatory BP in workers with normal or untreated elevated BP using baseline data from the Double Exposure study. The study population included 248 male and female volunteers who were nonmedicated, employed, and living with a significant other, all for a minimum of 6 months. Blood pressure was measured with an ambulatory BP monitor and participants completed a diary that recorded time during work, spousal contact, and sleep. Job strain and marital cohesion were calculated from the Job Content Questionnaire and the Dyadic Adjustment Scale, respectively. RESULTS: Of the subjects, 54.4% were female with a mean age of 50.8 years (6.6, SD). In all, 21.3% reported job strain. Significant assocations were found between 24-h systolic BP (SBP) and alcohol consumption (P = .033), job strain (P = .007), male gender (P = .004), and age (P = .039) and was inversely associated with exercise (P = .037). An interaction between 24-h SBP, job strain, and marital cohesion was found such that greater marital cohesion was associated with lower SBP in subjects with job strain. CONCLUSIONS: Psychosocial factors may influence the development of early hypertension. This should be clarified by the cohort phase of the Double Exposure study.

Adult↗

Paclitaxel poliglumex (XYOTAX; CT-2103): an intracellularly targeted taxane.

Paclitaxel poliglumex (CT-2103; XYOTAX) is an innovative macromolecular taxane designed to increase the therapeutic index of paclitaxel. This large macromolecule conjugate of paclitaxel and poly-L-glutamic acid accumulates in tumor tissues by taking advantage of the enhanced permeability of tumor vasculature and lack of lymphatic drainage. Paclitaxel poliglumex prolongs exposure to active drug and minimizes systemic exposure. Preclinical studies in animal tumor models demonstrate enhanced safety and efficacy relative to paclitaxel when administered as a single agent or in conjunction with radiation. Clinical pilot studies with paclitaxel poliglumex showed improved outcomes compared to standard taxanes and allowed a more convenient administration schedule. Human pharmacokinetic data are consistent with prolonged tumor exposure to active drug and a limited systemic exposure. Based on these results, three ongoing randomized phase III trials were initiated to test the efficacy of paclitaxel poliglumex in patients with advanced non-small cell lung carcinoma.

Animals↗

The influence of age, gender, and race on the prevalence of depression in heart failure patients.

OBJECTIVES: The goal of this study was to determine the prevalence of depression in an out-patient heart failure (HF) population; its relationship to quality of life (QOL); and the impact of gender, race, and age. BACKGROUND: Most studies of depression in HF have evaluated hospitalized patients (a small percentage of the population) and have ignored the influence of various patient characteristics. Although reported depression rates among hospitalized patients range from 13% to 77.5%, out-patient studies have been small, have reported rates of 13% to 42%, and have not adequately accounted for the impact of age, race, or gender. METHODS: A total of 155 patients with stable New York Heart Association functional class II, III, and IV HF and an ejection fraction <40% were given questionnaires to assess QOL and depression. These included the Medical Outcomes Study Short Form, the Minnesota Living with Heart Failure questionnaire, and the Beck Depression Inventory (BDI). Depression was defined as a score on the BDI of > or =10. RESULTS: A total of 48% of the patients scored as depressed. Depressed patients tended to be younger than non-depressed patients. Women were more likely (64%) to be depressed than men (44%). Among men, blacks (34%) tended to have less depression than whites (54%). Depressed patients scored significantly worse than non-depressed patients on all components of both the questionnaires measuring QOL. However, they did not differ in ejection fraction or treatment, except that depressed patients were significantly less likely to be receiving beta-blockers. CONCLUSIONS: Depression is common in patients with HF, with age, gender, and race influencing its prevalence in ways similar to those observed in the general population. These data suggest that pharmacologic or non-pharmacologic treatment of depression might improve the QOL of HF patients.

Adrenergic beta-Antagonists↗

Systems-based design of bi-ligand inhibitors of oxidoreductases: filling the chemical proteomic toolbox.

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases.

Animals↗

Identification of key pinch forces required to complete functional tasks.

Reconstructive hand surgeries restore key pinch to individuals with pinch force deficits caused by tetraplegia. Data that define the magnitudes of force necessary to complete functional key pinch tasks are limited. This study aims to establish target pinch forces for completing selected tasks that represent a range of useful functional activities. A robot arm instrumented with a force sensor completed the tasks and simultaneously measured the forces applied to the task objects. Lateral pinch force requirements were calculated from these measured object forces. Pinch force requirements ranged from 1.4 N to push a button on a remote to 31.4 N to insert a plug into an outlet. Of the tasks studied, 9 of 12 required less than 10.5 N. These pinch force requirements, when compared to pinch forces produced by 14 individuals with spinal cord injuries (with and without surgical reconstruction of pinch), accurately predicted success or failure in 81% of subject trials. The prediction errors indicate a need to measure other factors such as pinch opening, force location, force direction, and proximal joint control.

Adult↗

Synthesis and in vivo antitumor activity of poly(l-glutamic acid) conjugates of 20S-camptothecin.

Poly-alpha-(l-glutamic acid) (PG) conjugates of 20(S)-camptothecin (1, CPT) displayed improved aqueous solubility compared to CPT, were stable in aqueous solution at neutral pH, and were potent antitumor agents in vivo. Evaluation of PG molecular weight, CPT loading, aqueous solubility, and CPT equivalent dosing with respect to in vivo antitumor potencies of various linked conjugates led to identification of a preferred conjugate composition.

Animals↗

Marital support, spousal contact and the course of mild hypertension.

OBJECTIVE AND METHODS: To define marital support (MS) and its correlates in a sample of mild hypertensives where marital adjustment (by Dyadic Adjustment Scale, DAS) was related to 3-year left ventricular mass, a secondary analysis was performed on 103 men and women who underwent 24-h ambulatory BP (ABP) monitoring, M-mode echocardiography and completed psychosocial questionnaires at baseline and 3 years. RESULTS: MS, defined as the presence of both marital satisfaction and cohesion (upper quartiles of DAS subscales) at baseline, predicted 3-year left ventricular mass (P=.007), which decreased 8% in the MS group and increased 6.26% in the low MS group. The MS group also had lower 24-h diastolic BP over 3 years (P=.016) than the low MS group. Based on the amount of spousal contact during ABP, MS subjects spent much more time together after 3 years than at baseline (P=.008) and compared to the low MS group (P=.027). CONCLUSION: MS, a construct of both the quality and quantity of contact between spouses, was related to improved 3-year outcome in mild hypertension. Prospective clarification of the role of MS in mild hypertension is required.

Adult↗

Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect.

OBJECTIVE: To examine the correlates of therapeutic response of patients with panic disorder presenting with palpitations, we hypothesized that therapeutic response would correlate with heart rate variability (HRV) and sleep measures. METHODS: After a 1-week placebo washout, 27 patients free of structural heart disease and not on cardioactive drugs were randomized in a double-blinded fashion to 4 weeks of treatment with clonazepam (a known antipanic agent) or placebo. We performed standard sleep measures and recorded HRV from 24-hour Holter acquisitions at baseline and end of study. We defined response to therapy as a 50% improvement in the Hamilton Anxiety Rating Scale (HARS) score, confirmed by questionnaires and reaction to sodium lactate infusion. RESULTS: There were 12 responders and 15 nonresponders. Normalization of sleep pattern (including less stage 1 and rapid eye movement [REM] sleep) was observed in both drug and placebo responders (P = 0.011 and P = 0.05, respectively) and in placebo responders alone, compared with nonresponders (P = 0.006 and P = 0.013, respectively). Placebo responders were more likely to show less depression, but even after we controlled for depression, main sleep effects remained. None of the HRV measures correlated with response, but compared with placebo, clonazepam led to a decrease in all the time and frequency domain measures of HRV (all P < 0.05). CONCLUSIONS: Central mechanisms are related to the therapeutic response of patients with panic disorder presenting with palpitations, but this does not directly correlate with HRV. Larger and longer studies may allow objective explanations of placebo response in panic disorder.

Adolescent↗

Leprosy in a Mexican immigrant.

A new diagnosis of borderline lepromatous leprosy was established in a man who had immigrated to Kentucky from Mexico. He was placed on a World Health Organization treatment regimen consisting of dapsone, clofazimine, and rifampin. The biology of leprosy, its diagnosis, treatment, and worldwide impact are reviewed. Because of the potential for highly mobile populations to export endemic diseases, Kentucky physicians must expand their lists of differential diagnoses.

Adult↗

Quality of life in the Canadian Implantable Defibrillator Study (CIDS).

BACKGROUND: The primary aim of this study was to compare quality-of-life outcome between patients randomized to implantable cardioverter defibrillator (ICD) therapy and patients randomized to amiodarone treatment in the Canadian Implantable Defibrillator Study (CIDS). A secondary aim was to evaluate the effects on quality-of-life outcomes of receiving shocks from the device. METHODS: Quality of life was assessed in 317 English-speaking participants by use of the Rand Corporation's 38-item Mental Health Inventory (MHI) and the Nottingham Health Profile (NHP). Assessments were done in the hospital at baseline and with mailed questionnaires after 2, 6, and 12 months of follow-up. Sixty-two percent of patients completed the follow-up assessments at 6 and 12 months. RESULTS: Repeated measures analysis of variance revealed significant time by treatment group interaction effect on total MHI and the psychological distress and psychological well-being sub-scales, and on 5 of the 7 NHP scales (energy, physical mobility, emotional reactions, sleep disturbance, and lifestyle impairment) (P <.05). Emotional and physical health scores were shown to improve significantly in the ICD group and were either unchanged (emotional health) or deteriorated (energy and physical mobility) in the amiodarone-treated group by means of post-hoc comparisons. Quality of life did not improve in the subgroup of patients in the ICD-treated group who received > or =5 shocks from their device. CONCLUSION: Quality of life is better with ICD therapy than with amiodarone therapy. The beneficial quality-of-life effects from an ICD are not evident in patients who receive numerous shocks from their device.

Aged↗

Design and rationale for a randomized, controlled trial of interpersonal psychotherapy and citalopram for depression in coronary artery disease (CREATE).

OBJECTIVE: Recognition that depression is associated with increased morbidity and mortality in coronary artery disease (CAD) patients has augmented the need for evidence-based treatment guidelines. This article presents the design of a multisite, Canadian trial of the efficacy, safety, and tolerability of interpersonal psychotherapy (IPT), an empirically supported, depression-focused therapy, and the selective serotonin reuptake inhibitor citalopram, alone or in combination, in the treatment of major depression in CAD patients. METHODS: Two hundred eighty stable CAD patients with a current major depressive episode of at least 4 weeks' duration, based on the Structured Clinical Interview for Depression (SCID), and who have a baseline score >19 on a centralized, telephone-administered, 24-item Hamilton Depression Rating Scale (HAM-D) will be randomly assigned to receive 12 weekly IPT sessions or 12 weekly sessions of standardized clinical management (CM). Patients are also randomly assigned to receive 20 to 40 mg per day of citalopram or pill-placebo. This results in a 2-by-2 factorial design with four groups: IPT plus pill-placebo, IPT plus citalopram, CM plus pill-placebo, and CM plus citalopram. This permits the evaluation of both IPT and citalopram. Blinded, centralized, 24-item, HAM-D telephone ratings constitute the primary outcome variable. The self-report Beck Depression Inventory-II is the secondary outcome. Analyses will involve the intent-to-treat principle with last observation carried forward for incomplete assessments. RESULTS: Not applicable. CONCLUSIONS: The results of this trial will contribute to the development of evidence-based clinical guidelines for managing depression in the context of CAD.

Citalopram↗