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Biomedical subjects

I Brown

Publications and source records attributed to I Brown.

At least 91 records · Page 5Linked to original sources

Mechanism of the apparent parasympathetic inhibition of adenosine induced heart rate slowing in the dog.

The inhibitory action of intravenously administered adenosine on the sinoatrial (SA) node is not expressed in the conscious dog in the presence of normal vagal tone. After pharmacological or surgical parasympathetic blockade, however, adenosine exerts a powerful negative chronotropic effect. In order to determine the reason why this action of adenosine is blocked by the intact parasympathetic nervous system, we measured the chronotropic effects of adenosine while applying a constant cholinergic stimulus to the SA node. In conscious dogs during a systemic infusion of acetylcholine at a rate sufficient by itself to inhibit the SA node, intravenous adenosine injections caused further dose dependent reductions in heart rate. In anaesthetised, vagotomised dogs, intravenous adenosine caused similar negative chronotropic effects with or without concomitant electrical stimulation of the vagus nerve. As an example, 5 mumol.kg-1 adenosine reduced heart rate by 22 (SEM 4)% from a baseline heart rate of 172(10) beats.min-1; when heart rate was lowered to 66(1) beats.min-1 by electrical vagal stimulation, this dose of adenosine reduced heart rate by 36(8)%. Propranolol had no effect on these responses. We conclude that there is no direct cholinergic inhibition of the negative chronotropic action of adenosine on the canine SA node but rather that the inhibitory action of systemically administered adenosine on the SA node is simply masked by the withdrawal of vagal tone in response to the arterial hypotension resulting from this mode of adenosine administration.

Acetylcholine↗

The question of clustering of Creutzfeldt-Jakob disease.

Clustering of Creutzfeldt-Jakob disease has been reported in several countries. The authors review these reports, and they describe their statistical analysis of clustering among 329 cases that died in France during 1968-1982. Paris was found to have a much higher case rate than the rest of France, while some large areas in the north and west had remarkably few cases relative to their populations. No rural clusters were identified. A number of explanations for regional variations in case rates are possible, including population characteristics and case finding artifacts. Based on their results and those of other studies, the authors conclude that the strongest evidence for clustering of Creutzfeldt-Jakob disease is familial and ethnic, rather than geographic.

Africa, Northern↗

Pathogenicity of experimental infection with 'pneumotropic' porcine coronavirus.

Virus localisation and lesions were studied in 14-one-week-old piglets following combined intranasal-oral inoculation with a British isolate of 'pneumotropic' porcine coronavirus (PCV) and were compared with the effects of transmissible gastroenteritis virus (TGEV) infection in five piglets. Unlike TGEV-infected piglets, all PCV-inoculated piglets remained clinically healthy. Seroconversion was detected at seven days after inoculation. Mild bronchointerstitial pneumonia involving terminal airways was consistently present at two days after infection and thereafter. Both PCV and TGEV infected bronchiolar epithelium and alveolar macrophages but, unlike TGEV, replication by PCV in villous enterocytes was limited and did not cause villous atrophy.

Animals↗

Infertility due to congenital communication between vas deferens and refluxing triplicated ureter: successful insemination with sperm retrieved from urine. A case report.

A rare congenital malformation consisting of ectopic opening of the vas deferens into the fused segment of a refluxing triplicated ureter (trifid ureter) in an azoospermic man is described. Sperm were found in urine voided after ejaculation. Artificial insemination with sperm recovered from alkalinized urine resulted in pregnancy.

Adult↗

Identification of human herpesvirus 6-specific DNA sequences in two patients with non-Hodgkin's lymphoma.

Human herpesvirus 6 (HHV-6) is a recently discovered virus which has not been causally linked to any particular disease. In order to investigate the possible role of this virus in the pathogenesis of lymphoid malignancies, we examined tissue samples from 117 patients for the presence of HHV-6-specific DNA sequences. Two cases of non-Hodgkin's lymphoma were found to be positive. One patient had a T cell lymphoma and a preceding history of angioimmunoblastic lymphadenopathy; the other had a B cell lymphoma occurring in the context of Sjögren's syndrome. HHV-6 has been isolated previously from a patient with angioimmunoblastic lymphadenopathy, and viral sequences have been identified in another patient with Sjögren's syndrome and B cell lymphoma. The relationship between HHV-6 and these conditions therefore warrants further investigation.

Aged↗

Reduction in S100 protein beta subunit mRNA in C6 rat glioma cells following treatment with anti-microtubular drugs.

S100 protein is a calcium-binding protein found in vertebrate nervous tissue. Synthesis of S100 protein in the rat glioma cell line, C6, is inhibited by the addition of anti-microtubular drugs. We have cloned a cDNA for the beta subunit of S100 protein from rat brain in a lambda gt 11 expression vector and used this cDNA to measure the amounts of S100 beta subunit mRNA in C6 cells after treatment with anti-microtubular drugs. Levels of alpha-tubulin and beta-actin mRNAs were also measured. All measurements were performed using RNA-RNA hybridization techniques at high stringency with rat mRNA-specific probes. After 24 h of treatment, the S100 beta subunit mRNA was reduced to levels of 25% by colchicine and 32% by vinblastine when compared to untreated controls. In contrast, the levels of tubulin and actin mRNAs were only slightly changed by these treatments. These studies demonstrate that disruption of the microtubular cytoskeleton causes a specific reduction in the level of S100 protein mRNA in C6 cells.

Amino Acid Sequence↗

Interference in the measurement of red cell glycogen by glycogen from white cells.

An enzymatic method for determining red cell glycogen was developed and its recovery and precision ascertained. Initial red cell glycogen values in 24 healthy volunteers ranged from 11-60 micrograms/g haemoglobin which compares with 20-105 micrograms/g haemoglobin previously reported. More thorough removal of leucocytes suggested however that variations in the determined red cell glycogen were due to glycogen derived from leucocytes. In 34 red cell preparations with varying leucocyte numbers, the glycogen concentration correlated positively with leucocyte count (r = +0.81, p less than 0.001), whereas glycogen concentration showed poor correlation with red cell count (r = -0.30, 0.1 greater than p greater than 0.05). The results question the reported presence of glycogen in normal red cells and suggest that contamination by leucocytes has been responsible for the previously reported normal range.

Erythrocytes↗

Secondary hypertension in a blood pressure clinic.

The prevalence, reversibility, and mortality of secondary hypertension among 3783 patients with moderately severe nonmalignant hypertension attending the Glasgow (Scotland) Blood Pressure Clinic were assessed. Underlying causes of hypertension were found in 297 patients (7.9%). Eighty-seven patients (2.3%) were considered to have a potentially reversible cause for their hypertension, including the oral contraceptive pill (38 patients), renovascular disease (27 patients), and primary hyperaldosteronism (ten patients), but of these only 33 patients (0.9% of total clinic population) were cured by specific intervention. Two hundred ten patients (5.6%) had irreversible renal parenchymal disease and significantly higher mortality than men and women with other causes of hypertension. Excess deaths in the renal group were attributed to renal failure (International Classification of Diseases [ICD] 580 to 589) and vascular causes (ICD 390 to 458) but not to cancer (ICD 140 to 208; 235 to 239) or other nonvascular disease. These results suggest that investigation of hypertension for an underlying cause will reveal a small number of patients with treatable disorders, of whom only a few will be cured by specific intervention, and a moderate number with irreversible disease who are at high risk of myocardial infarction and stroke.

Adult↗

Astatine-211: its possible applications in cancer therapy.

The cyclotron-produced radiohalogen, 211At, is eminently suitable as a possible therapeutic radionuclide. It decays by the emission of 6.8 MeV mean energy alpha-particles, which from a radiobiological viewpoint are of near optimal therapeutic LET. This paper reviews developments in the possible application of [211At]astato-labelled molecules as potential anti-tumour agents. Additionally, radio-dosimetric evidence is presented, and its implications for human cancer therapy are discussed.

Animals↗

Mortality in patients of the Glasgow Blood Pressure Clinic.

The mortality of 3783 non-malignant hypertensive patients attending the Glasgow Blood Pressure Clinic between 1968 and 1983 and followed for an average of 6.5 years was compared with that in three control groups: the general population of Strathclyde a group of 15 422 subjects aged 45-64 years and screened in Renfrew and Paisley between 1972 and 1976, and a group of hypertensives seen in a blood pressure clinic based on general practice in Renfrew. Average blood pressure for men at entry to the Glasgow Clinic was 181/111 mmHg falling to 158/96 mmHg during treatment. Corresponding values for women were 185/109 mmHg and 161/96 mmHg. Seven hundred and fifty clinic patients (451 males) died during follow-up, the commonest causes of death in both sexes being myocardial infarction and stroke. All-cause age-adjusted mortality (deaths per 1000 patient-years) was 41.4 for men and 22.1 for women. At all ages in both sexes and for all levels of initial blood pressure mortality was less in patients whose blood pressure was reduced most. Without a randomized control group it is not certain that lower mortality in those with well controlled blood pressure was due to treatment, although this is the most likely explanation. Cigarette smoking, a history of myocardial infarction, angina or stroke, retinal arterio-venous nipping, raised blood urea, an abnormal electrocardiogram (ECG) and secondary hypertension were associated with increased risk, but heavy alcohol intake, obesity, haematocrit greater than 45%, hypokalaemia and social class were not. Life table analysis showed that, despite some reduction of mortality by treatment, the relative risk to men and women in the clinic remained two- to five-times that of the general population. The benefits of treatment were not such as to restore normal expectation of life even when blood pressure was well controlled. Excess mortality in the clinic could not be explained by difference of smoking habit or social class. This suggests that there is in the hypertensive patients of the Glasgow Clinic an element of irreducible risk, that treatment may be beneficial in some respects but harmful in others, or that patients at particularly high risk are selectively referred to the clinic.

Actuarial Analysis↗

Mild hypokalaemia is not a risk factor in treated hypertensives.

The possibility that hypokalaemia might increase the mortality of treated hypertensives in the Glasgow Blood Pressure Clinic has been examined by comparison of serum potassium in decedents and survivors and by calculation of age-adjusted mortality rates for patients grouped in quartiles of serum potassium measured at the last clinic visit. In this study, 3783 patients with non-malignant hypertension were followed for an average of 6.5 years and of these 1907 had one or more measurements of serum potassium during their last year of attendance. Serum potassium fell in 414 patients given diuretics with or without other drugs except beta-blockers. This fall was similar in those who died of ischaemic heart disease (3.71 mmol/l) and in those who survived (3.72 mmol/l). Serum potassium rose in 167 patients who received beta-blockers with or without other drugs except diuretics and fell slightly among 1326 patients taking other combinations of drugs. There were no significant differences in serum potassium between decedents and survivors in either of these treatment groups. Age-adjusted mortality in deaths per 1000 patient-years in the lowest quartile of serum potassium (less than 3.7 mmol/l) was 28.1 for men and 15.0 for women. Higher serum potassium was associated with slightly, but not significantly, higher mortality in both sexes. There was no relation between serum potassium and mortality in patients with left ventricular hypertrophy, nor was there a relation when death due to ischaemic heart disease was considered separately. Failure of hypokalaemia to predict outcome was confirmed by univariate and multivariate analyses which included, in addition to potassium, assessment of cigarette smoking, initial blood urea and electrocardiographic findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Maximum flow ratios at mid-vital capacity in young healthy adults.

Upper airway obstruction is usually diagnosed by visual examination of maximum expiratory and inspiratory flow-volume curves and by calculating a ratio of expiratory to inspiratory flow at 50 percent of vital capacity (mid-vital capacity flow ratio); however, reference values of this ratio have not been well established, and considerable variability exists. The purpose of this study was to examine the range of mid-vital capacity flow ratios in a group of healthy subjects and to determine if some of the variability is accounted for by different maximum inspiratory pressures. We measured maximum expiratory and inspiratory flows at 50 percent of vital capacity from the flow-volume curves, and maximum inspiratory pressures in a group of 60 healthy nonsmokers (30 men and 30 women) whose ages ranged from 21 to 40 years. We found that mid-vital capacity flow ratio (mean +/- SD) was 0.72 +/- 0.19 in men and 0.77 +/- 0.18 in women. The coefficient of variation of the mid-vital capacity flow ratio was 28 percent for men and 23 percent for women. The 95 percent confidence limits for the mid-vital capacity flow ratio were 0.65 to 0.79 for men and 0.70 to 0.84 for women. Maximum inspiratory pressures (mean +/- SD) were 129 +/- 30 cm H2O in men and 91 +/- 16 cm H2O in women, not significantly different from previous studies. Normalizing maximum inspiratory flow for maximum inspiratory pressure did not reduce the coefficient of variation, which became 29 percent in men and 30 percent in women. We conclude that the range of mid-vital capacity flow ratios is wide, and it cannot be reduced by standardizing it for maximum inspiratory pressures.

Adult↗

Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chloride sensor.

A new sweat test (CF Indicator; Medtronic, Inc.) for cystic fibrosis (CF) features a compact, portable configuration of electrodes that dispense pilocarpine for iontophoresis. A disposable chloride sensor patch absorbs a specified volume of sweat, in which the chloride concentration is immediately determined as less than 40, 40-60, or greater than 60 mmol/L. We assessed the performance of the system in a five-center study, in relation to the clinical diagnosis and to the Gibson-Cooke sweat test (GCST) as a control test. With sweat chloride concentrations of less than or equal to 40 mmol/L defined as normal and greater than 40 mmol/L as indicating persons at risk for CF, the new system showed 91% specificity and 100% sensitivity for CF, as compared with 92.8% and 100%, respectively, for the GCST. When we used sweat chloride concentrations of less than or equal to 60 mmol/L as probably normal and greater than 60 mmol/L as probably indicative of CF, the new system showed a 99.1% specificity and 98.6% sensitivity, vs 97.8% specificity and 97.9% sensitivity for the GCST test. In both procedures, occasionally insufficient sweat was collected, and this appeared related to the age of the subject. We conclude that the new sweat test system is potentially useful in physicians' offices, in clinics, and similar settings.

Adolescent↗

The effect of vitamin A supplementation on serum retinol and retinol binding protein levels.

A randomised double blind controlled trial was conducted to see whether vitamin A supplementation in the form of retinyl palmitate would increase the concentrations of serum retinol and retinol binding protein. A total of 376 people were studied and were allocated to one of 7 regimens covering doses of vitamin A from O (placebo) to 36,000 IU daily. Supplementation continued for 6 months and blood samples were collected immediately before the start of supplementation, after 3 months and after 6 months. There was a small but statistically significant increase in serum retinol levels associated with supplementation, but no significant increase in serum retinol binding protein. The extent of the increase in serum retinol was related to the extent of the supplementation. On average, for every 10,000 IU of retinyl palmitate per day, the serum retinol concentration increased by 13 micrograms/l after 3 months (an increase of 2%) and 12 micrograms/l after 6 months of supplementation (2% increase). All the regimens used showed no evidence of toxicity other than minor symptomatic and physical changes affecting the skin and mucous membranes.

Adult↗