Biomedical subjects

A S Brown

Publications and source records attributed to A S Brown.

At least 19 recordsLinked to original sources

PubMed2006

Value of transoesophageal echocardiography for diagnosis of intraoperative tumour embolization.

Malignant neoplasms such as renal cell carcinoma may invade the inferior vena cava leading to a risk of pulmonary tumour embolization during surgical excision. Although massive pulmonary tumour embolism occurs relatively rarely, it can have catastrophic consequences. We report the case of an acute intraoperative pulmonary tumour embolism during resection of a renal cell carcinoma. The use of transoesophageal echocardiography allowed the immediate diagnosis and appropriate management of the underlying cause of acute haemodynamic instability. The role of transoesophageal echocardiography in the diagnosis of pulmonary embolism is discussed.

Carcinoma, Renal Cell↗

PubMed2004

Role of lung macrophages on susceptibility to respiratory infection following short-term moderate exercise training.

Moderate exercise training is associated with a decreased risk for upper respiratory tract infection in human and animal studies, but the mechanisms have not been elucidated. Lung macrophages play an important role in resistance to respiratory infection, and moderate exercise can enhance macrophage antiviral resistance, but no studies have directly tested the role of lung macrophages in this response. This study tested the effect of lung macrophage depletion on susceptibility to infection following short-term moderate exercise training. Mice were assigned to one of four groups: exercise (Ex) and resting controls (Con) with and without clodronate encapsulated liposomes (CL(2)MDP-lip). Ex mice ran for 1 h on a treadmill for 6 days at 36 m/min, 8% grade. Fifteen minutes following exercise or rest on the last day of training, mice were intranasally inoculated with a standardized dose of herpes simplex virus type 1. Clodronate (Ex-CL(2)MDP-lip and Con-CL(2)MDP-lip) or PBS liposomes (Ex-PBS-lip and Con-PBS-lip) (100 microl) were intranasally administered following exercise or rest on the 4th day of training and again on the 4th day postinfection. Morbidity, mortality, and symptom severity were monitored for 21 days. Exercise decreased morbidity by 36%, mortality by 61%, and symptom severity score on days 5-7 (P < 0.05). Depletion of lung macrophages negated the beneficial effects of moderate exercise. This was indicated by no differences between Ex-CL(2)MDP-lip and Con-PBS-lip in morbidity (89 vs. 95%), mortality (79 vs. 95%), or symptom severity. Results indicate that lung macrophages play an important role in mediating the beneficial effects of moderate exercise on susceptibility to respiratory infection.

Animals↗

PubMed2004

Effects of moderate exercise and oat beta-glucan on lung tumor metastases and macrophage antitumor cytotoxicity.

Both moderate exercise and the soluble fiber beta-glucan can have beneficial effects on the initiation and growth of tumors, but the data are limited, and there is no information on their combined effects. This study tested the independent and combined effects of short-term moderate-exercise training and the soluble oat fiber beta-glucan (ObetaG) on the metatastic spread of injected tumor cells and macrophage antitumor cytotoxicity. Male C57BL/6 mice were assigned to one of four groups: exercise (Ex)-H2O, Ex-ObetaG, control (Con)-H2O, or Con-ObetaG. ObetaG was fed in the drinking water for 10 days before tumor administration and death. Exercise consisted of treadmill running (1 h/day) for 6 days. After rest or exercise on the last day of training, syngeneic B16 melanoma cells (2 x 10(5)) were administered via intravenous injection (n = 8-11 per group). Lungs were removed 14 days later, and tumor foci were counted. Additional mice (n = 8 per group) were killed, and peritoneal macrophages were assayed for cytotoxicity against the same mouse tumor cell line at various effector-to-target ratios. Both moderate exercise and ObetaG decreased lung tumor foci and increased macrophage cytotoxicity. However, there were no differences in lung tumor foci and macrophage cytotoxicity between Ex-ObetaG and either Ex-H2O or Con-ObetaG. These data suggest that, although not additive in their effects, both short-term moderate-exercise training and consumption of the soluble ObetaG can decrease the metatastic spread of injected B16 melanoma cells, and these effects may be mediated in part by an increase in macrophage cytotoxicity to B16 melanoma.

Administration, Oral↗

PubMed2003

Effects of moderate exercise and oat beta-glucan on innate immune function and susceptibility to respiratory infection.

Both moderate exercise and the soluble oat fiber beta-glucan can increase immune function and decrease risk of infection, but no information exists on their possible combined effects. This study tested the effects of moderate exercise and oat beta-glucan on respiratory infection, macrophage antiviral resistance, and natural killer (NK) cell cytotoxicity. Mice were assigned to four groups: exercise and water, exercise and oat beta-glucan, control water, or control oat beta-glucan. Oat beta-glucan was fed in the drinking water for 10 days before intranasal inoculation of herpes simplex virus type 1 (HSV-1) or euthanasia. Exercise consisted of treadmill running (1 h/day) for 6 days. Macrophage resistance to HSV-1 was increased with both exercise and oat beta-glucan, whereas NK cell cytotoxicity was only increased with exercise. Exercise was also associated with a 45 and 38% decrease in morbidity and mortality, respectively. Mortality was also decreased with oat beta-glucan, but this effect did not reach statistical significance. No additive effects of exercise and oat beta-glucan were found. These data confirm a positive effect of both moderate exercise and oat beta-glucan on immune function, but only moderate exercise was associated with a significant reduction in the risk of upper respiratory tract infection in this model.

Animal Nutritional Physiological Phenomena↗

PubMed2002

Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery.

AIMS: Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and vasoprotective molecule whose expression is modulated by hypoxia and inflammatory mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are influenced by pre-existing coronary artery disease and by changes in circulating interleukin-6 (IL-6). METHODS AND RESULTS: Plasma VEGF-A and IL-6 were measured prior to and at various time intervals following surgery in individuals with angiographically normal coronary arteries requiring cardiac valve replacement (N group) and in patients with coronary artery disease and stable angina undergoing coronary artery bypass grafting (CAD group). Baseline VEGF-A levels were not significantly different in CAD (22.3+/-2.6 pg x ml(-1)) compared to the N group (14.9+/-2.9 pg x ml(-1)). Following cardiac surgery there was a significant rise of VEGF-A in CAD (P<0.0005 vs baseline), but not in the N group, reaching a maximum (approximately 2 fold increase) after 24 h. Surgery caused a rapid increase of plasma IL-6 in both groups, but the rise was significantly larger in CAD patients (P<0.0005 vs N) where it preceded the increase in VEGF-A. Furthermore, in patients with CAD there was a significant correlation between the change in VEGF-A and the change in IL-6 (P<0.04). CONCLUSION: These findings demonstrate that in patients with coronary artery disease cardiothoracic surgery leads to an acute rise in VEGF-A. We suggest that this rise may result from an interaction between the pre-existing atheromatous process and a systemic increase of inflammatory mediators.

Aged↗

PubMed2001

Effectiveness of the electronic medical record in cholesterol management in patients with coronary artery disease (Virtual Lipid Clinic).

This study demonstrates that the Virtual Lipid Clinic, an electronic medical record with computer-assisted cholesterol management, is associated with improved lipid management in patients with coronary artery disease. In comparison to traditional documentation methods with "pen and paper" charts, outpatient visits utilizing the electronic medical record were associated with a twofold increase in low-density lipoprotein (LDL) documentation, a threefold increase in achieving LDL goal, and a 30% increase in the use of lipid-lowering drugs.

Aged↗

PubMed2001

A.E. Bennett Research Award. Prenatal rubella, premorbid abnormalities, and adult schizophrenia.

BACKGROUND: Premorbid neurocognitive, neuromotor, and behavioral function tends to be disturbed in schizophrenia. We previously demonstrated that a birth cohort clinically and serologically documented with prenatal rubella evidenced a marked increase in risk of nonaffective psychosis. In our study, we examined whether rubella-exposed subjects destined to develop schizophrenia and other schizophrenia spectrum disorders (SSD), compared with exposed control subjects, had greater impairment in several premorbid functions. METHODS: Subjects were interviewed using a direct, comprehensive research assessment and diagnosed by consensus. We compared the degree of IQ decline, as well as premorbid neuromotor and behavioral dysfunction, between rubella-exposed subjects who developed schizophrenia spectrum psychosis (SSP) and exposed control subjects from the cohort. We also compared the gestational timing of rubella infection between the cases and control subjects. RESULTS: This rubella-exposed birth cohort evidenced a markedly increased risk of SSD (20.4% or 11/53). Rubella-exposed SSP cases, compared with rubella-exposed control subjects, demonstrated a decline in IQ from childhood to adolescence, and increased premorbid neuromotor and behavioral abnormalities. Moreover, it appears that early gestational rubella exposure may represent a period of increased vulnerability for SSD. CONCLUSIONS: These findings link a known prenatal exposure, a deviant neurodevelopmental trajectory in childhood and adolescence, and SSP in adulthood within the same individuals.

Adolescent↗

PubMed2001

Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia.

Although acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown to reduce lipid levels in several animal models, the safety and lipid modifying activity of any single agent in this class has not been demonstrated in humans. The safety and efficacy of avasimibe (CI-1011), a new, unique, wholly synthetic ACAT inhibitor, was evaluated in the treatment of 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia (low levels of high-density lipoprotein cholesterol [HDL-C]). Following an 8-week placebo and dietary-controlled baseline period, patients were randomly assigned to double-blind treatment with placebo, 50, 125, 250, or 500 mg avasimibe administered as capsules once daily for 8 weeks. At all evaluated doses, avasimibe treatment resulted in prompt and significant reductions (P<0.05) in plasma levels of total triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) with mean reductions of up to 23% and 30% respectively, apparently independent of dose. No statistically significant changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C or apolipoprotein (apo) B were detected. ApoAI levels were also unchanged on all doses of avasimibe apart from the 500 mg dosage, which was associated with a significant decrease in plasma apoAI. The relevance of this latter finding in only one dosage group is not known. All doses of avasimibe were well tolerated with no resulting significant abnormalities of biochemical, hematological, or clinical parameters.

Acetamides↗

PubMed2001

Evaluation of scatter contribution from shielding materials used in scatter measurements for calibration range characterization.

The contribution of scatter from the shielding material used in scatter measurements at the Ohio Emergency Management Agency was evaluated. This was accomplished by comparing physical measurements with results generated by detectors modeled in the Monte Carlo shielding code, MCNP4B. The high purity germanium (HPGe) detector model was improved by using radiographs to more accurately represent the detector geometry, including a model of the lithium-contact transition region, and considering the effects of the non-uniform electric field in the germanium crystal. Photons scattered from the shielding material were found to contribute 4.25% of the total scatter recorded by the HPGe detector (thus contributing only 0.26% of the total dose) at a point 5 m from a 1.35 GBq (36.4 mCi) 137Cs source.

Calibration↗

PubMed2001

Prevalence of physical activity among South Carolina adults.

Participating in regular PA is associated with many health benefits. Overall, the prevalence of inactivity in South Carolina (33 percent) is among the highest in the Southeast and in the US as a nation. While few gender differences exist between the proportion of adults who report participation in sufficient PA (females 21 percent and males 23 percent), racial and age differences are apparent with ethnic minorities and older adults as the least active. The most popular PA among all adults is walking. Physicians can play a key role, through counseling, to help increase the prevalence of regular PA among those who are currently obtaining insufficient amounts of activity to derive optimal health benefits.

Adult↗

PubMed2000

Genome-wide variation in recombination in female meiosis: a risk factor for non-disjunction of chromosome 21.

Altered recombination patterns along non-disjoined chromosomes is the first molecular correlate identified for non-disjunction in humans. To understand better the factors related to this correlate, we have asked to what extent is recombination altered in an egg with a disomic chromosome: are patterns limited to the non-disjoined chromosome or do they extend to the entire cell? More specifically, we asked whether there is reduced recombination in the total genome of an egg with a non-disjoined chromosome 21 and no detectable recombination. We chose this subclass of non-disjoined chromosomes to enrich potentially for extremes in recombination. We found a statistically significant cell-wide reduction in the mean recombination rate in these eggs with non-disjoined chromosomes 21; no specific chromosomes were driving this effect. Most importantly, we found that this reduction was consistent with normal variation in recombination observed among eggs. Thus, given that recombination is a multifactorial trait, these data suggest that when the number of genome-wide recombination events is less than some threshold, specific chromosomes may be at an increased risk for non-disjunction. Further studies are required to confirm these results, to determine the importance of genetic and environmental factors that regulate recombination and to determine their impact on non-disjunction.

Adult↗

PubMed2000

Lipid management in a private cardiology practice (the Midwest Heart experience).

Emerging evidence that lowering cholesterol levels reduces the incidence of coronary heart disease led Midwest Heart Specialists to establish a lipid clinic in 1985. The physician-directed, nurse-managed program was developed to improve patient adherence to National Cholesterol Education Program (NCEP) guidelines and provide high-quality preventive services while preserving productivity for the busy interventional cardiologist who was the medical director of the program. From 1996 to 1997, Midwest Heart Specialists was one of 140 medical practices to participate in a national Quality Assurance Program (QAP). The purpose of the project was to evaluate the degree of treatment of hyperlipidemia in patients with coronary heart disease. Although the overall physician practice results were significantly better than the national averages, the lipid-clinic results were dramatically more impressive: 100% of the lipid-clinic patients were on lipid-lowering therapy and 97% of the patients had a low-density lipoprotein (LDL)-cholesterol level documented on the chart. Of these, 71% met their LDL goal, as compared with only 11% nationally. The results of the QAP within the physician practice stimulated the development of a new practice-wide lipid-management system. This new systematic approach to lipid management has improved overall lipid outcomes dramatically. The success of the Cholesterol Management Program has enhanced the reputation of the practice in the community, tied high-risk patients and their families to the practice, and improved the marketability of a full complement of cardiovascular services via Midwest Heart Specialists.

Anticholesteremic Agents↗

PubMed2000

Social class of origin and cardinal symptoms of schizophrenic disorders over the early illness course.

BACKGROUND: This study describes the relationship of social class of origin to cardinal symptoms of schizophrenic disorders over the early illness course. METHOD: The sample of subjects was drawn from the Suffolk County Mental Health Project, a longitudinal epidemiologic study of first-hospitalized subjects with psychotic disorders; the present study focused on patients with schizophrenic disorders. At baseline, subjects were dichotomized into upper/middle and lower social class of origin groups, based on occupation of the head of the household of origin. The patients in both groups were assessed for the major symptoms of schizophrenic disorders using standard structured instruments at both baseline and 6-month follow-up. The 6-month symptom severity levels were compared between the groups, controlling for baseline symptom status and potential confounders. RESULTS: At 6-month follow-up, the upper/middle social class of origin group, as compared to the lower social class of origin group, had lower symptom levels for hallucinations (adjusted OR = 4.88, chi2 = 8.49, P = 0.004) and delusions (adjusted OR = 2.46, chi2 = 4.16, P = 0.04). There were no notable group differences for any of the negative or thought disorganization symptoms. CONCLUSIONS: Social class of origin is associated with positive symptoms of schizophrenia over the early illness course.

Adult↗

PubMed2000

Primary prevention of coronary heart disease: implications of the Air Force/Texas coronary atherosclerosis prevention study (AFCAPS/TexCAPS).

Over the past 15 years several studies have examined the benefits of treating patients with dyslipidemia in order to prevent a first cardiac event and to prevent the onset of clinical symptoms of coronary atherosclerosis. Some of the pitfalls of these studies have been that they have been performed predominantly in men, and also in patients with extremely high cholesterol levels. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) provides substantial additional information regarding the benefits of primary prevention in the general population. The study included large numbers of women as well as subjects with a wide variety of ethnic backgrounds, and showed substantial benefit across this population. Patients with average cholesterol levels, but below-average high-density lipoproteins, had substantial reduction in risk of a first cardiac event with aggressive treatment of their dyslipidemia, using lovastatin. The majority of the patients in the AFCAPS/TexCAPS study would not warrant therapy, based on the current National Cholesterol Education Program Adult Treatment Panel guidelines. The data suggest that new strategies are warranted to better identify those patients who are at high risk and those who will receive benefit from aggressive lipid-lowering therapy.

Adult↗

PubMed2000

Multipoint estimation of genetic maps for human trisomies with one parent or other partial data.

Centromeric-mapping methods have been used to investigate the association between altered recombination and meiotic nondisjunction in humans. For trisomies, current methods are based on the genotypes from a trisomic offspring and both parents. Because it is sometimes difficult to obtain samples from both parents and because the ability to use sources of DNA previously not available (e.g., stored paraffin-embedded pathological samples) has increased, we have been interested in creating similar maps for trisomic populations in which one of the parents of the trisomic individual is unavailable for genotyping. In this paper, we derive multipoint likelihoods for both missing-parent data and conventional two-parent data. We find that likelihoods for two-parent data and for data generated without a sample from the correctly disjoining parent can be maximized in exactly the same way but also that missing-parent data has a high frequency of partial data of the same sort produced by intercross matings. Previously published centromeric-mapping methods use incorrect likelihoods for intercross matings and thus can perform poorly on missing-parent data. We wrote a FORTRAN program to maximize our multipoint likelihoods and used it in simulation studies to demonstrate the biases in the previous methods.

Algorithms↗

PubMed2000

The design of the prenatal determinants of schizophrenia study.

This paper describes the Prenatal Determinants of Schizophrenia (PDS) Study; three companion papers report the first results. The PDS Study was designed to study early antecedents of schizophrenia in a birth cohort of 1959-1967 for whom a wealth of archived prenatal data--including maternal sera--was available. Making use of the registries of a health plan into which the cohort was born, we ascertained and then diagnosed 71 cases of schizophrenia and spectrum disorders in the cohort. We describe herein the available prenatal data, the process of case diagnosis, and the strategies used to analyze prenatal determinants of schizophrenia in this cohort. Data are presented that bear on the main sources of potential bias and are important to understanding the strengths and limitations of this unique data set.

Adult↗

PubMed2000

Maternal prepregnant body mass and risk of schizophrenia in adult offspring.

This study examined the relation between maternal prepregnant body mass index (BMI) and development of schizophrenia and schizophrenia spectrum disorders in adult offspring from the Prenatal Determinants of Schizophrenia Study. The study drew on a previously studied cohort of births occurring between 1959 and 1967 to women enrolled in a prepaid health plan. Computerized treatment registries were used to identify possible cases of schizophrenia and spectrum disorders in adult offspring belonging to the health plan from 1981 to 1997. Diagnostic interviews and medical record reviews resulted in diagnosis of 63 cases of schizophrenia and spectrum disorders; these cases and 6,570 unrelated and unaffected cohort members whose mothers also had prepregnancy measures of BMI comprised the sample for analyses. High (> or = 30.0), compared with average (20.0-26.9), maternal prepregnant BMI (kg/m2) was significantly associated with schizophrenia and spectrum disorders in the adult offspring (relative risk [RR] = 2.9; 95% confidence interval [CI] 1.3-6.6), independently of maternal age, parity, race, education, or cigarette smoking during pregnancy. Low (< or = 19.9) maternal BMI was not associated with schizophrenia and spectrum disorders (RR = 1.2; 95% CI 0.64-2.2). Future studies of this cohort will examine factors that may help explain the relationship of high maternal prepregnant BMI with schizophrenia, including nutritional and metabolic factors, toxic exposures, and obstetrical complications.

Adolescent↗

PubMed2000

Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: a prospective birth cohort study.

We sought to examine the relationship between maternal exposure to adult respiratory infections and schizophrenia spectrum disorder (SSD) in the Prenatal Determinants of Schizophrenia (PDS) Study, a large birth cohort investigation. Previous work suggests that second trimester exposure to respiratory infection may be a risk factor for SSD. We therefore examined whether this class of infection was associated with adult SSD. For this purpose, we capitalized on several design advantages of the PDS Study, including a comprehensive, prospective data base on physician-diagnosed infections and a continuous followup in which diagnoses of SSD were made, in the majority, by face-to-face interview. Second trimester exposure to respiratory infections was associated with a significantly increased risk of SSD, adjusting for maternal smoking, education, and race (rate ratio [RR] = 2.13 [1.05-4.35], chi2 = 4.36, df= 1,p = 0.04); no associations were shown for first trimester and third trimester exposure to these respiratory infections. These findings support-and extend-previous studies suggesting that second trimester respiratory infections are risk factors for SSD. This study therefore has implications toward uncovering the etiology of schizophrenia and developing preventive strategies.

Adult↗