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Biomedical subjects

C A Brown

Publications and source records attributed to C A Brown.

At least 109 records · Page 6Linked to original sources
PubMed1995

Myocarditis and idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) accounts for 25% of cases of heart failure in the United States. Understanding the relationship between an inciting event or agent and the development of IDC has progressed only recently. Once IDC has developed, treatment is palliative and little can be done to alter the natural course of the disease. Active myocarditis, a suspected precursor of IDC, is myocardial inflammation and injury without ischemia. The disease ranges from a self-limited flulike illness to one of serious consequence with arrhythmias, heart failure, or death. Many agents have been associated with myocarditis, and the clinical manifestations depend on an interplay between the inciting agent and the host response. The development of a murine model and the expanded use of endomyocardial biopsy using the Dallas criteria have increased our understanding of myocarditis and its sequelae. Therapy consists of managing symptoms using conventional medical regimens for heart failure. Immunosuppressive therapy should be reserved for patients with biopsy-proven disease who have failed conventional therapy. Continued deterioration warrants ventricular assistance and consideration of cardiac transplantation.

Cardiomyopathy, Hypertrophic↗
PubMed1995

Trans fatty acids in the Scottish diet. An assessment using a semi-quantitative food-frequency questionnaire.

Trans fatty acids produced during hardening of oils have been associated with higher cholesterol levels and increased risk of heart disease. The potential risk from trans fatty acids may be greater in populations with relatively low intakes of essential fatty acids such as the Scots, who also have a high prevalence of heart disease. Means and ranges of trans fatty acid intakes are reported here for a Scottish population. A semi-quantitative food-frequency questionnaire was used to survey the diet of 10,359 Scottish men and women aged 40-59 years in 1984-6 as part of the baseline Scottish Heart Health Study. Trans fatty acid levels were calculated for each food item on the questionnaire and the total subdivided into that which is derived naturally (primarily by bacterial fermentation in ruminants) and that which is produced during industrial hydrogenation (hardening) of vegetable and fish oils. Means and ranges of intakes of each trans fatty acid variable were calculated by sex, age, smoking and social class groups. Mean total trans fatty acid intakes for men were 7.1 (SD 3.1) g/d, 2.7 (SD 2.9)% energy and for women were 6.4 (SD 2.9) g/d, 3.3 (SD 3.0)% energy. Industrially hydrogenated trans fatty acids made up nearly 58% of the total intake for men and 61% for women, with about 60% coming from cakes, biscuits and sweets, and 20% coming from the cheaper hard margarines. The main sources of the naturally derived trans fatty acids were red meat (27%), milk (20%), butter (18-19%) and cheese (13-16%). Differences between age, smoking and social class groups were apparent. However, apart from the social class differences of up to 1 g/d, these were so small that they are unlikely to be of any biological significance unless compounded by other factors such as marginal essential fatty acid adequacy. The possibility of trans fatty acid intakes up to 48 g/d and 12% total energy (compared with the Department of Health (1991) recommendations of 5 g/d or 2% energy) highlights the need for careful monitoring of the health risks at these high levels of intake.

Adult↗
PubMed1995

Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study.

STUDY OBJECTIVE: To explore the relationship between self reported environmental tobacco smoke exposure (or passive smoking), the serum cotinine concentration, and evidence of respiratory or coronary disease in men and women who have never smoked. DESIGN: Cross sectional random population survey identifying disease markers and relating them to measures of passive smoking. Disease markers were previous medical diagnoses, response to standard symptom questionnaires, and electrocardiographic signs. SETTING: Samples of men and women aged 40-59 years drawn from general practitioner lists in 22 local government districts of Scotland, between 1984 and 1986. PARTICIPANTS: A total of 786 men and 1492 women who reported never having smoked tobacco, and who had serum cotinine concentrations below 17.5 ng/ml, the cut off point for smoking "deceivers", took part. RESULTS: Fewer than one third of never smokers reported no recent exposure to environmental tobacco smoke and the same proportion had no detectable cotinine. Women had lower cotinine values than men but reported more exposure to smoke. The correlation between the measures of exposure was poor. Self-reported exposure showed strong, statistically significant, dose response relationships with respiratory symptoms and with the coronary disease markers. These relationships were weak or absent for serum cotinine, except for diagnosed coronary heart disease. Here the dose response gradient was as strong as that for self report, with an odds ratio of 2.7 (95% CI 1.3, 5.6) for the highest v the lowest exposure group, adjusted for age, housing tenure, total cholesterol, and blood pressure, and not explained by fibrinogen. CONCLUSIONS: The validity of different measures of tobacco smoke exposure needs further investigation. The gradient of diagnosed coronary heart disease with both self reported exposure and serum cotinine was, however, surprisingly strong, statistically significant, and unexplained by other factors. These findings reinforce current policies to limit passive tobacco smoke exposure.

Adult↗
PubMed1995

Single-nephron adaptations to partial renal ablation in cats.

To evaluate remnant nephron hyperfiltration, cats underwent sham surgery (group 1, n = 6) or three-fourths nephrectomy (group 2, n = 6). Four to six weeks later, micropuncture studies demonstrated increases (P < 0.01) of single-nephron glomerular filtration rate (SNGFR) in group 2 (28.1 +/- 2.8 vs. 56.0 +/- 5.9 nl/min). In group 2 the mean estimated glomerular capillary pressure of 74.0 +/- 1.7 mmHg exceeded (P < 0.01) the value for group 1 (62.6 +/- 1.4 mmHg). The mean effective filtration pressure (EFPm) for group 2 (28.7 +/- 3.1 mmHg) was greater (P < 0.05) than that in group 1 (20.8 +/- 1.9 mmHg). Similarly, the mean ultrafiltration coefficient (Kf) in group 2 of 2.03 +/- 0.24 nl.min-1.mmHg-1 exceeded (P < 0.05) the corresponding value for group 1 of 1.35 +/- 0.06 nl.min-1.mmHg-1. Morphological studies demonstrated glomerular enlargement and mesangial matrix expansion in group 2 (P < 0.05). Proteinuria, as assessed by the urine protein-to-creatinine ratio, was increased (P < 0.05) after partial renal ablation. These results demonstrate that increases in SNGFR in feline remnant nephrons occur in association with glomerular hypertension, glomerular hypertrophy, expansion of mesangial matrix, and proteinuria, and furthermore, that the observed increases in SNGFR are attributable to an augmentation of EFPm and Kf.

Adaptation, Physiological↗
PubMed1994

Inherited ventricular arrhythmias and sudden death in German shepherd dogs.

OBJECTIVES: This report describes a unique group of German shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure. BACKGROUND: There are few spontaneous animal models of sudden death that permit intensive investigation. METHODS: To determine the temporal evolution of ventricular arrhythmias and to characterize the syndrome of sudden cardiac death in these dogs, 24-h ambulatory electrocardiographic (ECG) monitoring, echocardiograms, electrophysiologic testing and breeding studies were conducted. RESULTS: The 24-h ambulatory ECGs from dogs that died showed frequent ventricular arrhythmias with rapid polymorphic ventricular tachycardia (rates > 480 beats/min). Affected dogs had a window of vulnerability for arrhythmias, with the highest incidence and severity of arrhythmias between 20 to 30 and 40 to 50 weeks of age. Affected dogs that died did not have prolongation of the QT interval over a spectrum of heart rates compared with unaffected dogs. The clinical arrhythmia was not induced in dogs during programmed electrical stimulation. Severely affected dogs monitored > 5 years did not develop any evidence of heart failure or cardiomyopathy, and no histopathologic abnormalities existed. Seventeen dogs died suddenly (age 4 to 30 months) and were either 1) found dead at first observation in the morning (n = 8), 2) observed to die during sleep (n = 4), 3) observed to die while resting after exercise (n = 3), or 4) observed to die during exercise (n = 2). All sudden deaths occurred between the end of September and April, with most (n = 11) during January and February. CONCLUSIONS: The cause of the inherited severe ventricular arrhythmias and sudden death in these young German shepherd dogs is still undetermined. A purely arrhythmic disorder is supported by the lack of cardiac pathology. Moreover, the window of vulnerability to ventricular arrhythmias and the age and circumstances of death invite speculation about the role of the autonomic nervous system.

Animals↗
PubMed1994

The imidazoline site involved in control of insulin secretion: characteristics that distinguish it from I1- and I2-sites.

1. The nature of the binding site mediating the insulin secretagogue activity of certain imidazoline compounds remains unclear and the pharmacology of the I1- and I2-imidazoline sites, described in many tissues, does not correlate with the observed responses to imidazolines in islets. In the present paper, we describe further results which support the concept that the islet imidazoline site may represent a novel subtype of imidazoline receptor. 2. Culture of rat isolated islets in the presence of imidazoline secretagogues (either efaroxan or phentolamine) resulted in loss of responsiveness on subsequent re-exposure to these agents. However, culture of islets with either idazoxan or UK14,304 (imidazoline ligands that do not stimulate insulin secretion) did not lead to any loss of response when the islets were subsequently exposed to efaroxan. By contrast, islets cultured with UK14,304 (a potent alpha 2-adrenoceptor agonist), displayed loss of sensitivity to noradrenaline, consistent with down-regulation of alpha 2-adrenoceptors. 3. In order to characterize the imidazoline site further, radioligand binding studies were performed in membranes from RINm5F insulinoma cells using [3H]-RX821002, an imidazoline insulin secretagogue that does not interact significantly with imidazoline sites in other tissues. [3H]-RX821002 labelled alpha 2-adrenoceptors with high affinity (2.01 +/- 0.7 nM) but also labelled a second, non-adrenoceptor site with much lower affinity. 4. Under conditions of alpha 2-adrenoceptor blockade (in the presence of adrenaline), efaroxan displaced [3H]-RX821002 binding to the low affinity site, in a dose-dependent manner. Competition studies employing additional imidazoline compounds of varying secretagogue activity revealed that the pharmacological profile of the low affinity site correlates well with that observed in secretion experiments.5. The results obtained from the down-regulation experiments with isolated islets and from the radioligand binding studies suggest that the low affinity [3H]-RX821002 binding site may represent the functional receptor responsible for the secretagogue activity of imidazoline compounds in the endocrine pancreas and that it has a pharmacological profile distinct from those of I,- and 12-sites.

Animals↗
PubMed1994

Failure of cigarette smoking to explain international differences in mortality from chronic obstructive pulmonary disease.

STUDY OBJECTIVE: The study aimed to explain international differences in rates and trends of chronic obstructive pulmonary disease (COPD) using two measurements of cigarette smoking, the major risk factor for this disease. DESIGN: Mortality data for COPD were obtained from the World Health Organisation for 31 countries from 1979 to 1988. Smoking data were obtained for most countries. COPD rates were compared to the percentage of current smokers and past levels of cigarette consumption. COPD trends were compared to past consumption trends. MAIN RESULTS: In men, Romania had the highest COPD mortality and Greece the lowest throughout the period. English speaking countries occupy most of the other top positions, and southern European countries and Japan the low positions. Women show a similar ranking to men (r = 0.75; p < 0.01 (1988)). Mortality rates in men are, in general, two to four times those in women. Most countries show either a decrease or no change in COPD mortality over the period. In women the opposite is true--no clear relationships are seen when comparing rates and trends of COPD with measures of smoking. CONCLUSION: This failure to explain international COPD differences suggests that national data on COPD may be unreliable or national cigarette smoking data are inadequate, or both.

Adult↗