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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

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

Normal personality traits and comorbidity among phobic, panic and major depressive disorders.

High comorbidity among anxiety and depressive conditions is a consistent but not well-understood finding. The current study examines how normal personality traits relate to this comorbidity. In the Baltimore Epidemiologic Catchment Area Follow-up Study, psychiatrists administered the full Schedules for Clinical Assessment in Neuropsychiatry to 320 subjects, all of whom completed the Revised NEO Personality Inventory. The disorders of interest were simple phobia, social phobia, agoraphobia, panic disorder, and major depression. Analyses were carried out with second-order generalized estimating equations. The unadjusted summary odds ratio (SOR - or weighted mean odds ratio) for all five disorders was 1.72 (95% confidence interval=1.21-2.46). Neuroticism, introversion, younger age, and female gender were all significant predictors of prevalence of disorders. After adjustment for the relationships between these personality and demographic predictors and prevalence, the association among disorders was much weaker (SOR=1.11, 95% CI=0.79-1.56). However, subjects with high extraversion had a SOR 213% as high (95% CI=102-444%) as those with low extraversion (1.60 vs. 0.75). Therefore, neuroticism and introversion are associated with increased comorbidity due to relationships in common with the prevalence of the different disorders. In contrast, extraversion is associated with increased comorbidity per se.

Major Depressive Disorder↗
PubMed2001

Management of acute exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence.

PURPOSE: To review critically the available data on diagnostic evaluation, risk stratification, and therapeutic management of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). DATA SOURCES: English-language articles were identified by searching MEDLINE (1966 to 2000, week 5), EMBASE (1974 to 2000, week 18), HealthStar (1975 to June 2000), and the Cochrane Controlled Trials Register (2000, Issue 1). STUDY SELECTION: The best available evidence on each subtopic was selected for analysis. Randomized trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic interventions. Cohort studies were used to evaluate diagnostic tests and risk stratification. DATA EXTRACTION: Study design and results were summarized in evidence tables. Individual studies were rated by internal validity, external validity, and quality of design. Statistical analyses of combined data were not performed. DATA SYNTHESIS: Data on the utility of most diagnostic tests are limited. However, chest radiography and arterial blood gas sampling seem useful while acute spirometry does not. Identifiable clinical variables are associated with risk for relapse and risk for death after hospitalization for an acute exacerbation. Evidence of efficacy was found for bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation. There is also support for the use of antibiotics in patients with more severe exacerbations. On the basis of limited data, mucolytics and chest physiotherapy do not seem to be of benefit, and oxygen supplementation seems to increase the risk for respiratory failure only in an identifiable subgroup of patients. CONCLUSIONS: Although suggestions for appropriate management can be made on the basis of available evidence, the supporting literature is scarce and further high-quality research is necessary. Such research will require an improved, generally acceptable, and transportable definition of acute exacerbation of COPD, as well as improved methods for observing and measuring outcomes.

Acute Disease↗
PubMed2001

Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice.

Erythroid Kruppel-like factor (EKLF) is a transcription factor of the C2H2 zinc-finger class that is essential for definitive erythropoiesis. We generated immortal erythroid cell lines from EKLF(-/-) fetal liver progenitor cells that harbor a single copy of the entire human beta-globin locus and then reintroduced EKLF as a tamoxifen-inducible, EKLF-mutant estrogen receptor (EKLF-ER) fusion protein. Addition of tamoxifen resulted in enhanced differentiation and hemoglobinization, coupled with reduced proliferation. Human beta-globin gene expression increased significantly, whereas gamma-globin transcripts remained elevated at levels close to endogenous mouse alpha-globin transcript levels. We conclude that EKLF plays a role in regulation of the cell cycle and hemoglobinization in addition to its role in beta-globin gene expression. The cell lines we used will facilitate structural and functional analyses of EKLF in these processes and provide useful tools for the elucidation of nonglobin EKLF target genes.

Active Transport, Cell Nucleus↗
PubMed2001

Emergence of Salmonella enteritidis phage type 4 in the Caribbean: case-control study in Trinidad and Tobago, West Indies.

A prospective case-control study involving 46 case patients and 92 age- and neighborhood-matched control subjects was conducted in Trinidad and Tobago (T&T) between March 1998 and May 1999 to determine the etiology, sources, and risk factors for Salmonella enteritidis (SE) infection. SE infection in T&T was found to be associated with the consumption of shell eggs, and in particular raw or undercooked eggs. SE isolates from 30 (88%) of 34 patients and from 9 implicated egg or egg-containing food samples were phage type 4. Homemade eggnog and ice cream, cake batter, and egg-containing beverages were the main raw egg-containing foods, reflecting the cultural practices of the people of T&T. Public health education on the risks of eating raw or undercooked eggs, thorough cooking of all egg dishes, and refrigeration of shell eggs and egg dishes; studies tracing infected eggs to their sources; and testing of flocks of layer chickens for SE are needed to reduce the incidence of this infection.

Adolescent↗
PubMed2001

Membrane-perturbing domains of HIV type 1 glycoprotein 41.

Structural and functional studies were performed to assess the membrane actions of peptides based on HIV-1 glycoprotein 41,000 (gp41). Previous site-directed mutagenesis of gp41 has shown that amino acid changes in either the N-terminal fusion or N-leucine zipper region depressed viral infection and syncytium formation, while modifications in the C-leucine zipper domain both increased and decreased HIV fusion. Here, synthetic peptides were prepared corresponding to the N-terminal fusion region (FP-I; gp41 residues 519-541), the nearby N-leucine zipper domain (DP-107; gp41 residues 560-597), and the C-leucine zipper domain (DP-178; gp41 residues 645-680). With erythrocytes, FP-I or DP-107 induced dose-dependent hemolysis and promoted cell aggregation; FP-I was more hemolytic than DP-107, but each was equally effective in aggregating cells. DP-178 produced neither hemolysis nor aggregation, but blocked either FP-I- or DP-107-induced hemolysis and aggregation. Combined with previous nuclear magnetic resonance and Fourier transform infrared spectroscopic results, circular dichroism (CD) spectroscopy showed that the alpha-helicity for these peptides in solution decreased in the order: DP-107 >> DP-178 > FP-I. CD analysis also indicated binding of DP-178 to either DP-107 or FP-I. Consequently, DP-178 may inhibit the membrane actions mediated by either FP-I or DP-107 through direct peptide interactions in solution. These peptide results suggest that the corresponding N-terminal fusion and N-leucine zipper regions participate in HIV infection, by promoting membrane perturbations underlying the merging of the viral envelope with the cell surface. Further, the C-leucine zipper domain in "prefusion" HIV may inhibit these membrane activities by interacting with the N-terminal fusion and N-leucine zipper domains in unactivated gp41. Last, exogenous DP-178 may bind to the N-terminal and N-leucine zipper domains of gp41 that become exposed on HIV stimulation, thereby preventing the fusogenic actions of these gp41 regions leading to infection.

Amino Acid Sequence↗
PubMed2001

Fast ignition by intense laser-accelerated proton beams.

The concept of fast ignition with inertial confinement fusion (ICF) is a way to reduce the energy required for ignition and burn and to maximize the gain produced by a single implosion. Based on recent experimental findings at the PETAWATT laser at Lawrence Livermore National Laboratory, an intense proton beam to achieve fast ignition is proposed. It is produced by direct laser acceleration and focused onto the pellet from the rear side of an irradiated target and can be integrated into a hohlraum for indirect drive ICF.

Journal Article↗
PubMed2001

Early prediction of 30-day mortality after Q-wave myocardial infarction by echocardiographic assessment of left ventricular function--a pilot investigation.

BACKGROUND: The GUSTO angiographic substudy demonstrated that left ventricular function measured 90 min after thrombolytic therapy was given had important prognostic implications at 30 days in patients with an acute myocardial infarction (MI). HYPOTHESIS: Thirty-day prognosis after Q-wave MI can be determined by early echocardiographic assessment of left ventricular function. METHODS: Using transthoracic echocardiography, semiquantitative ejection fraction and wall motion score index was assessed prospectively in 201 consecutive patients within 24 h following Q-wave MI. Independent experts blinded to the patient's status performed the echocardiographic assessment. All patients received standard medical care as dictated by the attending cardiologist. RESULTS: Of the 201 patients, 24 (11.9%) died within 30 days, with 70% of the deaths occurring within 10 days after the infarction. Three deaths occurred in the 120 patients with an ejection fraction > or = 45% (2.5% mortality rate). In contrast, 21 deaths occurred among the 81 patients with an ejection fraction <45% (25.9% mortality rate) p = 0.0003. Two of the three patients who died in the high ejection fraction group died as a result of intracerebral hemorrhage from thrombolytic therapy. Ejection fraction was lower in nonsurvivors (32.3+/-10.3 vs. 46.3+/-13%) than in survivors, p < 0.0002. Wall motion score index (WMSI) of < 1.4 was associated with a 2.9% 30-day mortality (two deaths in 76 patients); WMSI of > or = 1.4 was associated with a 17.6% 30-day mortality (22 deaths in 125 patients), p = 0.0007. Average WMSI was higher in the nonsurvivors (1.95+/-0.5) than in survivors (1.52+/-0.45), p = 0.00001. CONCLUSIONS: Echocardiographic assessment of left ventricular function during the first 24 h after an acute Q-wave MI can be performed in all patients regardless of stability. High-risk patients are identified early in the hospital course, with relative ease, at no risk and at an acceptable cost. An ejection fraction < 45% or WMSI > or = 1.4 identifies patients who are at a high risk of dying within 30 days. These are the patients who may benefit most from aggressive medical therapy and early angiography to assess coronary pathology.

Humans↗
PubMed2001

Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis.

The rapid progress in the isolation of genes associated with human disease has resulted in an increasing demand for mutation screening methods. The molecular diagnosis of the long QT syndrome (LQTS), a cardiac disorder characterized by prolongation of the QT(c) interval in the ECG, syncopes, and sudden death, requires mutation screening of all exons in at least five genes, encoding cardiac Na(+) and K(+) channel subunits. A method for automated dideoxy fingerprinting (ddF) using capillary array electrophoresis (CAE) was developed and the efficiency of the method was tested by analyzing 24 DNA samples with mutations in one of the genes KCNQ1 and KCNH2, which are involved in 50% of LQTS cases. One of these mutations, 362insQK in KCNQ1, is novel. The sensitivity was 100% using a single electrophoresis temperature of 18 degrees C or 25 degrees C. However, analysis of the samples in both the sense and anti-sense direction were required for high sensitivity. Analysis in a single direction resulted in a decrease of the sensitivity to 74% and 70%, respectively. The throughput of the ddF method, if performed with a 16 capillary CAE instrument, is 288 samples per seven hr if each sample is analyzed on both strands.

Automation↗
PubMed2001

HLA-B typing by reference strand mediated conformation analysis using a capillary-based semiautomated genetic analyzer.

The application of reference strand conformation analysis (RSCA) to HLA-A typing using the ABI PRISM 310 capillary based genetic analyzer has recently been described. This study outlines the development and validation of capillary RSCA for HLA-B typing. Mobility values for 93 HLA-B alleles were defined following electrophoresis of known controls through the system. Three fluorescently labelled references, labelled with three different dyes can be electrophoresed simultaneously. The technique was validated by comparing results from 296 cord blood donors with those obtained using reverse SSO. Following capillary RSCA 14.5% of samples required confirmatory typing, compared with a repeat rate of 5.1% following reverse SSO. In samples where no other typing was necessary there was 100% correlation between the two methods. Capillary RSCA for HLA-B typing is quick, easy to implement, and with the introduction of new FLRs and gel matrices has the potential to evolve into a high resolution typing method.

Alleles↗
PubMed2001

Absence of germline and somatic p53 alterations in children with sporadic brain tumors.

Cancers of the central nervous system are the most common solid tumors of childhood. Although somatic alterations of the p53 tumor suppressor gene have been implicated in brain tumorigenesis, the role of germline p53 mutations in the development of childhood brain tumors has not been well defined. As a component of an ongoing extensive study of the epidemiology of childhood brain tumors, we prospectively examined the germline and tumor p53 gene status in 85 children without a family history of cancer who were diagnosed with a sporadic malignant central nervous system tumor. Using PCR/single-strand conformational polymorphism analysis and direct DNA sequencing, 85 children were screened for the presence of constitutional p53 sequence alterations in exons 2 and 4 through 11. No mutations were identified. Commonly reported sequence polymorphisms were observed at codon 72, as well as in 2 other previously described nucleotide residues. Forty-four brain tumor samples were available for analysis and of these 40 were paired with peripheral blood. Once again, no p53 mutations were found. Of the 5 germline samples with the 2 common polymorphisms, only one had a paired tumor sample for comparison and the tumor contained the same alteration as the germline. Of note, one tumor, a PNET of the cerebellum (medulloblastoma), showed loss of heterozygosity at codon 72. We can conclude that the frequency of germline and somatic p53 mutations in sporadic childhood brain tumors is very low, probably less than 1%, and there is no need to screen these patients routinely for their germline p53 status. However, the potential significance of LOH at codon 72 remains to be elucidated.

Brain Neoplasms↗
PubMed2001

A novel HLA allele, B*4104, identified in a cord blood donor.

Results from a number of HLA typing methods prompted the DNA sequencing (SBT) of a cord blood sample at the HLA-B locus. A novel HLA-B allele, B*4104, was identified. This was confirmed by sequencing the mother of the cord blood unit for HLA-B.

Alleles↗
PubMed2001

How important is intrinsic spirituality in depression care? A comparison of white and African-American primary care patients.

We used a cross-sectional survey to compare the views of African-American and white adult primary care patients (N = 76) regarding the importance of various aspects of depression care. Patients were asked to rate the importance of 126 aspects of depression care (derived from attitudinal domains identified in focus groups) on a 5-point Likert scale. The 30 most important items came from 9 domains: 1) health professionals' interpersonal skills, 2) primary care provider recognition of depression, 3) treatment effectiveness, 4) treatment problems, 5) patient understanding about treatment, 6) intrinsic spirituality, 7) financial access, 8) life experiences, and 9) social support. African-American and white patients rated most aspects of depression care as similarly important, except that the odds of rating spirituality as extremely important for depression care were 3 times higher for African Americans than the odds for whites.

Adolescent↗
PubMed2001

Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic.

BACKGROUND/PURPOSE: In 1990, the authors began a multidisciplinary follow-up clinic for congenital diaphragmatic hernia (CDH) patients. Although the nonpulmonary complications associated with CDH have been reported previously from this clinic, the purpose of this report is to detail the pulmonary outcome in survivors of CDH with severe pulmonary hypoplasia. METHODS: Between 1990 and 1999, one hundred patients were seen in the clinic. Before hospital discharge, all patients had baseline tests performed, which were repeated per protocol at clinic during follow-up. The data were analyzed by regression analysis to identify and determine the impact of factors on outcomes associated with the long-term pulmonary morbidity. RESULTS: The average birth weight was 3.16 kg (+/-0.7) with a mean Apgar score of 7 (+/- 2) at 5 minutes. Forty-one patients had an antenatal diagnosis performed. Extracorporeal membrane oxygenation (ECMO) was utilized in 29 patients, and a patch repair was required in 32, whereas 16 patients received both. Average time to extubation was 20.7 (+/- 20) days and mean time to discharge was 59.7 (+/- 61) days. Regression analysis showed that both the need for ECMO and a patch repair were independent predictors of delay in extubation (P <. 001, R(2) = 36%), and delay in discharge from the hospital (P =.001, R(2) = 29%). ECMO also was significantly correlated with the need for diuretics at discharge (P <.001, R(2) = 18%), and with the presence of left-right mismatch (P =.009, R(2) = 9%) and V/Q mismatch (P =.005, R(2) = 11%) on subsequent pulmonary ventilation-perfusion examinations. Sixteen patients required O(2) at discharge, and diuretics were necessary in 43 patients. Seventeen patients at discharge required bronchodilators, and during the first year an additional 36 required at least transient therapy. Similarly, 6 patients at discharge required steroids, and an additional 35 patients required at least transient therapy during the first year. Chest x-rays, although frequently abnormal, had little correlation with clinical outcome, but did influence medical therapy. V/Q scans had limited utility in patient management, and the presence of V/Q mismatch was not highly specific for future obstructive airway disease. Nevertheless, V/Q mismatch was sensitive for obstructive airway disease assessed by spirometry. Twenty-five patients over 5 years of age performed pulmonary function tests (PFTs), which showed 72% normal PFT results and 28% with evidence of obstructive airway disease. Before January 1997, 2 of 8 patients who required urgent treatment in the emergency department (ED) were admitted to the intensive care unit (ICU) secondary to acute respiratory distress. After the implementation of respiratory syncytial viral prophylaxis in January 1997, 8 patients were treated in the ED for acute respiratory distress, but none required admission to the ICU. CONCLUSIONS: Pulmonary problems continue to be a source of morbidity for survivors of CDH long after discharge. The need for ECMO and the presence of a patch repair are both predictive of more significant morbidity, but the data clearly show that non-ECMO CDH survivors also require frequent attention to pulmonary issues beyond the neonatal period. These data show the need for long-term follow-up of CDH patients preferably with a multidisciplinary team approach.

Extracorporeal Membrane Oxygenation↗
PubMed2001

Providing information on complementary and alternative therapies and practitioners by producing a directory of practitioners.

This article describes the experience of the authors in producing a booklet to provide information on complementary and alternative therapies (CAM) in their local area. The practical steps needed to produce a booklet are described, including ways of involving local general practitioners, meeting with local therapists, recruiting contact persons for each therapy, designing and producing a booklet and launching the final version. The feedback from general practitioners and CAM practitioners is reported.

Complementary Therapies↗
PubMed2001

Primary care physicians' attitudes, knowledge, and practices related to cancer clinical trials.

BACKGROUND: Participation of patients in cancer clinical trials is disappointingly low and several physician-based factors are thought to be responsible. METHODS: In 1998-1999, the National Cancer Institute (NCI) conducted a probability survey of three primary care physician groups to gain a better understanding of the barriers to clinical-trial patient accrual from their perspective. RESULTS: Findings from this survey of 706 primary care physicians indicate that the vast majority (98%) refer their patients with cancer to a specialist for cancer treatment and rarely bring up the topic of cancer clinical trials. Frequently cited reasons for not mentioning clinical trials are preferring to leave that discussion to the oncologist (41%) and being unaware of any clinical trials that may be available for the patient (37%). CONCLUSION: Primary care physicians may represent an important untapped resource for introducing the concept of clinical trials as an option to newly diagnosed cancer patients.

Clinical Trials as Topic↗
PubMed2001

Primary care patients' personal illness models for depression: a preliminary investigation.

BACKGROUND: Despite the fact that more than half of depressed persons are treated for this disorder by primary care physicians, depression is often under-recognized or treated inadequately. There is continued emphasis on effective treatment of depression in primary care patients, but little attention has been paid to the role of the depressed person's illness cognitions in coping with this disorder. Given the often recurring and chronic nature of depression, the individual's self-management strategies may be critical to effective treatment, recovery and remaining well. OBJECTIVES: The purpose of this pilot study was to determine whether primary care patients' personal illness cognitions for depression are associated with depression coping strategies and treatment-related behaviour. METHODS: Forty-one primary care patients with depressive symptoms or disorder completed interviews and questionnaires assessing illness cognitions for depression, depression coping strategies and other treatment-related behaviour. Descriptive statistics are used to present patients' illness cognitions for depression. t-tests and correlational analyses were completed to assess the relationship between illness cognitions, depression coping strategies and treatment-related behaviour. RESULTS: Preliminary data describing illness cognitions for depression are presented. Participants' illness cognitions for depression were significantly associated with current and past treatment-seeking behaviour, medication adherence and coping strategies. CONCLUSIONS: Although preliminary, these findings indicate that patients' understanding of depression and its consequences are associated with how they manage this illness. Future research is needed to examine the mediating and moderating effects of illness cognitions for depression on medication adherence and other self-management behaviours of depressed primary care patients. Knowledge about primary care patients' personal illness models will aid in the development of adherence interventions, self-management training and support services appropriate to patients' needs in the primary care setting.

Adaptation, Psychological↗
PubMed2001

Antiviral efficacy and pharmacokinetics of oral adefovir dipivoxil in chronically woodchuck hepatitis virus-infected woodchucks.

The antiviral efficacy of orally administered adefovir dipivoxil was evaluated in an 18-week study (12 weeks of treatment and 6 weeks of recovery) conducted with woodchucks chronically infected with woodchuck hepatitis virus (WHV). Adefovir dipivoxil is a prodrug of adefovir designed to enhance its oral bioavailability. Following administration of 15 mg of adefovir dipivoxil per kg of body weight in four WHV-infected animals, the mean maximum concentration of adefovir in serum was 0.462 microg/ml, with an elimination half-life of 10.2 h, and the oral bioavailability of adefovir was estimated to be 22.9% (+/-11.2%). To study antiviral efficacy, the animals were divided into three groups. There were six animals each in a high-dose group (15 mg/kg/day) and a low-dose group (5 mg/kg/day). A vehicle control group consisted of five animals because WHV DNA was detectable only by PCR at the time of the study in one of the original six animals. Efficacy was evaluated by determining the levels of WHV DNA in serum. The geometric mean WHV DNA level for the high-dose group diminished by >40-fold (>1.6 log(10)) after 2 weeks of treatment and >300-fold (>2.5 log(10)) at 12 weeks. There was a >10-fold reduction in five of six low-dose animals by 2 weeks, but levels were unchanged in one animal. By 12 weeks of treatment there was a >45-fold (>1.6 log(10)) reduction of WHV DNA levels, and serum WHV DNA levels were below the limit of quantification in three of six animals. Viral DNA levels returned to pretreatment levels during the 6-week recovery period. There were no clinically significant changes in body weight, hematology, or serum chemistry values, including bicarbonate or lactate, in any of the treated animals. No histologic evidence of liver injury was apparent in the biopsies. Under the conditions of this study, adefovir dipivoxil was an effective antihepadnaviral agent.

Adenine↗