Search PubMed⌕ Search

Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 109 records · Page 6Linked to original sources

Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat.

This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.

Albuminuria↗

Facilitating peer group teaching within nurse education.

Nurse teachers have an obligation to explore every teaching and learning method in order to prepare students to be able practitioners. In the wider educational field peer tutoring has been used to foster a deeper understanding of a subject area. Experiments using this method have been carried out extensively in America and are becoming more widespread in this country; however very little material is available on the use of this method in nurse education. The following article explains the use of peer tutoring as a method for developing teaching skills amongst student nurses. Two groups of learners were used in this exercise, the senior learners acting as peer tutors. Evaluation by nurse teachers and both groups of learners was favourable and the peer tutors were able to identify the benefits they received from the exercise.

Education, Nursing↗

RS 30026: a potent and effective calcium channel agonist.

1. A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2 nM. 3. Compounds were also evaluated for their effects on guinea-pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10(-9) and 10(-6) M (pEC200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10(-6) M (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10(-10) and 10(-7) M. 4. Calcium channel currents in single embryonic chick myocytes were recorded by whole-cell voltage clamp techniques. RS 30026 (100 nM-500 nM) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 nM) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 nM) were much less marked. 5. Analysis of the activation characteristics of currents showed parallel shifts in the activation curve to more negative potentials in the presence of 50 nm Bay K 8644, with a much smaller shift in the presence of 500nm Bay K 8644. RS 30026 (100 and 500nM) caused concentration-dependent shifts in the activation of the calcium channel currents with an increase of the slope of the curve. 6. RS 30026 appears to be the most potent and effective calcium channel agonist described to date.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Reversal of hepatic encephalopathy and alteration in amino acid profiles after blocking a surgical splenorenal shunt by interventional radiological techniques.

Portal-systemic shunts are effective in preventing haemorrhage from varices in portal hypertension, but at the price of hepatic encephalopathy. We describe the blockage of a splenorenal shunt using interventional radiology, in a patient with incapacitating chronic encephalopathy. The procedure successfully reversed encephalopathy, without haemodynamic disturbances or haemorrhage from recurrent varices and was associated with a return of the plasma amino acid profile towards normal, with a reduction in aromatic amino acids and an increase in branch chain amino acids. This observation supports the hypothesis that changes in plasma amino acid profiles in patients with portal-systemic shunting are due to the diversion of portal blood rather than the underlying chronic liver disease.

Amino Acids↗

The influence of diving variables on perceptual and cognitive functions in professional shallow-water (abalone) divers.

Shallow-water diving is regarded as a hazardous occupation due to such dangers as decompression sickness and carbon monoxide poisoning. Recent studies have demonstrated impairments in the neurological and neurobehavioral functioning of professional shallow-water divers, yet the reasons for these deficits are not clear. In this study 80 professional abalone divers were studied using a range of neurobehavioral tests and questioned closely on their diving experience. Multiple linear regression analysis was then performed to determine the extent to which characteristics of the diver's occupation influenced neurobehavioral impairment. The results demonstrated that divers who were at greatest risk of decompression sickness due to their diving technique showed the clearest functional impairments. In particular problems of visual function, psychomotor abilities, and short-term memory were most evident. It appears that professional shallow-water diving is not necessarily a hazardous occupation provided that safe diving practices are observed. However, divers who fail to observe these practices and put themselves at risk of decompression sickness are likely to have impairments in neurobehavioral function which affect their everyday life, and more importantly their responses in emergency situations.

Adult↗

Effect of infused adenosine on cardiac output and systemic resistance in normal subjects.

1. The purine nucleoside adenosine relaxes smooth muscle in vitro and is a vasodilator in animals, but its effects on cardiac output and systemic vascular resistance have not been measured in normal conscious human subjects. 2. We have studied the effects of infused adenosine in doses of 0.005, 0.03 and 0.07 mg kg-1 min-1 on pulmonary blood flow and systemic vascular resistance in eight healthy volunteers, using a non-invasive, inert gas method and mass spectrometry. 3. At a dose of 0.07 mg kg-1 min-1, there was a rise in effective pulmonary blood flow (which is approximately equivalent to cardiac output) of 0.52 +/- 0.08 l min-1 m-2 (mean +/- s.e. mean) and a fall in estimated systemic vascular resistance of 357 +/- 44 dyn s cm-5. Despite this marked systemic vasodilation, there was no significant change in mean heart rate. 4. The effects of this dose of adenosine were maximal 2 min after starting the infusion, and had disappeared within 5 min of stopping it. 5. Adenosine may be therapeutically useful in the reduction of left ventricular afterload, where the absence of reflex tachycardia may be advantageous. We suggest that adenosine in doses of 0.03 mg kg-1 min-1 should be evaluated as a selective pulmonary vasodilator.

Adenosine↗

In vitro susceptibility studies of vancomycin-resistant Enterococcus faecalis.

Vancomycin resistance exhibited by Enterococcus faecalis isolates V583, V586, and V587 is described. The vancomycin MICs ranged from 32 to 64 micrograms/ml. Although resistant to vancomycin, the isolates were susceptible to teicoplanin (MIC, less than or equal to 0.5 micrograms/ml). Such a glycopeptide susceptibility profile has not been previously described for E. faecalis. Time kill studies showed that vancomycin resistance adversely affected the synergistic activity that vancomycin and aminoglycoside combinations usually demonstrate against enterococci. However, the ability to detect vancomycin resistance varied with the susceptibility testing method used. Whereas broth microdilution, broth macrodilution, and agar dilution methods detected resistance, disk-agar diffusion and the AutoMicrobic system Gram-Positive GPS-A susceptibility card (Vitek Systems Inc., Hazelwood, Mo.) did not. To detect vancomycin resistance reliably and establish the incidence of such E. faecalis isolates, adjustments in some susceptibility testing methods may be necessary.

Anti-Bacterial Agents↗

A high-molecular-weight fraction of smooth lipopolysaccharide in Klebsiella serotype O1:K20 contains a unique O-antigen epitope and determines resistance to nonspecific serum killing.

The lipopolysaccharide (LPS) O-antigen side chains of Klebsiella serotype O1 have been studied by using mutants selected by resistance to a Klebsiella bacteriophage designated O1-A. Two classes of LPS mutants were identified. The major group (90%) synthesized rough LPS. The remaining 10% of the mutants produced a novel LPS profile that lacked the highest-molecular-weight O-substituted molecules (HMW-LPS) but still produced lower-molecular-weight O-substituted species (LMW-LPS). By using antisera raised against mutant Klebsiella strains and antiserum specific for Pasteurella haemolytica serotype 4, it was demonstrated that HMW-LPS and LMW-LPS contain shared epitopes. HMW-LPS also contained an epitope absent in LMW-LPS. This unique epitope was recognized by a monoclonal antibody (O1-52.6) and appears to be responsible for the serological cross-reaction between the O antigens of Klebsiella O1 and Escherichia coli O19. This HMW-LPS epitope was present in eight other Klebsiella O1 isolates which were examined. Electron microscopy demonstrated that HMW-LPS excluded overlying capsular polysaccharide for a distance of 25 to 40 nm. The distance was reduced to 10 to 18 nm in strains which synthesized only LMW-LPS and to zero in rough LPS strains. The HMW-LPS of Klebsiella O1 was shown to be an important virulence determinant, since this molecule was responsible for the resistance of the bacterium to nonspecific, complement-mediated serum killing.

Animals↗

Efficacy and safety of adenosine in the treatment of supraventricular tachycardia in infants and children.

One hundred and seventeen episodes of supraventricular tachycardia in 50 children, including 28 infants, were treated with intravenous adenosine. Adenosine was prepared in a sterile solution of 0.9% saline (1 mg/ml) and given in incremental doses of 0.05 mg/kg every two minutes to a maximum of 0.25 mg/kg. Ninety of the 117 episodes were terminated. This included 88 of the 102 episodes of junctional tachycardia (79 of the 92 episodes of atrioventricular reentry tachycardia, seven of the eight episodes of atrioventricular nodal reentry tachycardia, and both of the episodes of long R-P' tachycardia). Only one of four episodes of His bundle tachycardia and one of the eight episodes of ectopic atrial tachycardia were terminated. None of the three episodes of atrial flutter were terminated. Side effects were frequent but mild and included transient complete atrioventricular block (less than 6 s), sinus bradycardia (less than 40 s), ventricular extrasystoles, flushing, nausea, headache, and respiratory disturbance. Reinitiation (within 5 s) of supraventricular tachycardia occurred in 13 of the terminated episodes. Although reinitiation limited its clinical efficacy in some patients, intravenous adenosine offered a safe and efficient method of rapid termination of most episodes of supraventricular tachycardia and in some cases facilitated diagnosis of the mechanism.

Adenosine↗

Characterization of adenosine receptors in human pulmonary arteries.

We have characterized the effects of adenosine, the A1-receptor agonist N6-(L-2-phenylisopropyl)-adenosine (PIA) and the A2-receptor agonist 5'-(N-ethyl)-carboxamido-adenosine (NECA), in isolated human pulmonary vessels. Fresh human lung tissue was obtained from nine patients, and small pulmonary arteries (200-400 micron ID) were dissected and mounted in an organ bath. The effects of the adenosine antagonist 8-phenyltheophylline (8-PT) and endothelial denudation were also studied. Adenosine, NECA, and PIA (1-300 microM) all caused a dose-dependent vasodilation with log EC30 values of -4.31, -4.31, and -3.53, respectively. 8-PT (10 microM) caused a rightward shift of the adenosine dose-response curve, significantly decreasing the effect of adenosine (pKB = 6.3). Mechanical removal of endothelial cells had no significant effect on adenosine-mediated vasodilation. We also compared the effects of adenosine on eight large (7-10 mm ID) and eight small (200-400 micron ID) arteries and found no significant difference in the sensitivity to adenosine between these vessels. Our findings suggest that the pulmonary vasodilator effects of adenosine in humans are mediated through A2 receptors that are localized to vascular smooth muscle. Adenosine may function as a regulator of pulmonary vascular tone in humans and may have therapeutic potential.

Adenosine↗

Therapy for symptoms in the carcinoid syndrome.

The clinical course and results of drug treatment for manifestations of the carcinoid syndrome are reviewed in 63 patients. The five-year actuarial survival in this group of patients was 48 per cent. The only markers of a poor prognosis that could be identified at diagnosis were marked weight loss and a high (over 1000 mumol/day) 5-hydroxyindole acetic acid excretion. The relative effectiveness of well-established drugs that either block 5-hydroxytryptamine synthesis or block 5-hydroxytryptamine receptors is reported, with respect to the different manifestations of the syndrome, and compared with a small group of patients treated with long-acting somatostatin analogue. In over one-third of patients, primary tumours were not detected on initial investigation, and in none of these did symptoms referrable to the primary site become apparent later.

Adult↗