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Biomedical subjects

J Bevan

Publications and source records attributed to J Bevan.

At least 19 recordsLinked to original sources

Exploration of the impact of messages about genes and race on lay attitudes.

The effect of messages about genetics on lay audiences was assessed through an experimental study that exposed participants (n = 96) to a Public Service Announcement about race, genes, and heart disease. Participants who received a message that specified either 'Whites' or 'Blacks' as the subject of the message demonstrated elevated levels of racism, genetic basis for racism, and one dimension of genetic discrimination as compared to those receiving a version of the message with no race specification or in a no-message control condition. The presentation of such messages to the public is not recommended until additional research clarifies this finding and perhaps describes mitigating vocabularies or approaches.

Attitude to Health↗

AccuStat whole blood fingerstick test for Helicobacter pylori infection: a reliable screening method.

Helicobacter pylori antibody testing is accurate for diagnosing untreated patients. Rapid serum testing is as accurate as formal enzyme-linked immunosorbent assay (ELISA) testing. As whole blood fingerstick tests may become the diagnostic method of choice if they are of similar accuracy, 51 patients were studied who had not taken antibiotics, bismuth, sucralfate, or proton pump inhibitors. Concordance between C-14 Urea Breath Testing and HM-CAP ELISA testing served as the study standard for H. pylori diagnosis. Rapid antibody testing was performed with the AccuStat whole blood (Boehringer Mannheim, Mannheim, Germany) and FlexSure HP (Smith Kline Diagnostics, San Jose, CA) serum tests. Antral biopsy for CLO testing and histological evaluation with thiazine staining were available for 18 (35.3%) and 20 patients (39.2%), respectively. Nineteen of 50 patients (38%) were infected. (One patient had discordant tests and was excluded.) FlexSure HP and AccuStat were each positive in 18 (36%) and 19 patients (38%) with sensitivity, specificity, and positive and negative predictive values of 89.5% and 89.5%, 96.8% and 93.5%, 94.4% and 89.5%, and 93.8% and 93.5%, respectively. There were two false-negative FlexSure HP and AccuStat tests and three false-positive tests--1 FlexSure and 2 AccuStat results. CLO test and histology concurred in every case tested. We conclude that both rapid antibody tests are accurate and suitable for screening patients not previously treated for H. pylori infection. Since the AccuStat has preserved diagnostic strength, is less costly, takes less time, and is less labor intensive, whole blood testing is the screening test of choice.

Adult↗

Crystallization and preliminary X-ray studies on Candida cylindracea lipase.

As part of the programme to understand the mechanism and specificity of lipase enzymes used in biotransformation reactions, the lipase from Candida cylindracea has been purified and crystallized. This lipase has been widely used by organic chemists for hydrolysis and esterification reactions. Crystals were obtained using polyethylene glycol 6000 as a precipitant and grew to 0.6 mm in the maximum dimension. The enzyme crystallized in the space group P2(1) with unit-cell dimensions a = 94.3, b = 117.0, and c = 114.2 A with beta = 109.2 degrees. Calculations indicate that there are four molecules in the asymmetric unit. The crystals diffract to at least 2.5 A resolution and the structure has been solved by molecular replacement using the lipase from Geotrichum candidum as a search model.

Journal Article↗

Urease-based tests for Helicobacter pylori gastritis. Accurate for diagnosis but poor correlation with disease severity.

To determine whether the urease-based CLOtest or low-dose 14C urea breath test can predict severity of gastritis or the presence of peptic ulcers, we studied 84 patients presenting for upper endoscopy. Antral biopsies were obtained for histologic analysis and CLOtesting, and urea breath testing was performed. The time to a positive CLOtest and the breath test peak values were correlated with endoscopic findings, severity of gastritis, and bacterial burden. Twenty-four patients had positive urea breath test results (22 with positive CLOtests). Patients with positive breath test results were more likely to have duodenal ulcers, higher grades of gastritis, and increased bacterial burden (p < 0.01 for all comparisons). Correlation between the time to a positive CLOtest or peak breath test values and gastritis severity or bacterial burden was poor (p > 0.05 for all comparisons). In patients with positive tests, no difference was observed between the time to a positive CLOtest or peak breath test value in patients with or without peptic ulcers (p < 0.2 for all comparisons). The low-dose 14C urea breath test and the CLOtest are both accurate for Helicobacter pylori diagnosis. However, neither test predicts the severity of the gastritis, the degree of bacterial burden, or the presence of peptic ulcers.

Adult↗

Protecting the interests of participants in research into illicit drug use: two case studies.

This paper addresses the conflict between the ethical and legal responsibilities of researchers engaged in illicit drug use research. Fundamentally, the primary ethical responsibility is to protect research subjects from any harm which may come to them as a consequence of having taken part in the research. Legal responsibilities, however, might lie in assisting police with their enquiries into the conduct of an individual who is a research subject, and allowing research data to be searched and possibly used in evidence against the individual. There is no Western Australian legislation which protects research, nor Australian legislation which can be applied to most studies. Using two case studies, we give examples of the conflict and suggest that legislation may be the most effective way to overcome it. However, we also raise a number of issues which would need to be considered before solutions are enacted.

Australia↗

Regulation of vascular tone.

The intimal surface of the blood vessel in vivo is subject to shear stress resulting from blood flow, which in most of the circulation, at least at rest, is laminar. Turbulence can occur at bifurcations, especially those of the large arteries, and where vessels curve significantly. Shear stress is a frictional tangential force exerted at the fluid-intimal interface in the long axis of the vessel. It is now known that hemodynamic shear stress can influence a large variety of biological processes in endothelial cells, which vary from those with a short response time, just a few milliseconds, such as the opening of ion channels, to those that change over a period of minutes to several hours, for example, endocytosis and cytoskeleton rearrangement, and those features that alter much more slowly, such as cell shape and stiffness. In addition to these types of changes, there are suggestions that flow acting through shear stress may be responsible for several basic attributes of the vasculature, including the relative size and diameter of the components of a branching vascular system. In this symposium on the flow regulation of the blood vessel, the first presentation dealt with optimality principles that appear to govern the dimensions of the vasculature, in particular the geometry of the arterial branching and the role of shear stress. An optimally designed system is one that requires the least metabolic work to perform its function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clentiazem reduces infarct size in rabbit middle cerebral artery occlusion.

We assessed the value of pretreatment with clentiazem (8-chlorodiltiazem), a diltiazem derivative with cerebroselective properties, on the consequences of surgical occlusion of the middle cerebral artery via a transorbital approach in 38 rabbits. Nineteen rabbits received 1.7 (n = 5), 5 (n = 8), or 15 (n = 6) mg/kg clentiazem orally four times a day for 24 hours before and 48 hours after occlusion. Upon sacrifice, a segment of the right middle cerebral artery distal to the occlusion and a corresponding segment from the nonoccluded left middle cerebral artery were mounted on myographs for in vitro study of their reactivity to histamine, acetylcholine, serotonin, norepinephrine, and electrical stimulation of intramural sympathetic nerves. Morphometric measurements of 2,3,5-triphenyltetrazolium chloride-stained brain slices permitted us to estimate infarct volume. Pretreatment with 1.7, 5, and 15 mg/kg clentiazem significantly reduced infarct volume (p less than 0.05, p less than 0.01, and p less than 0.01, respectively). Mean infarct volume of the 15 mg/kg-treated group was only 4% that of the untreated group. There were no postoperative deaths in any treated group compared with a death rate of 36% in the untreated group. Mean values for vascular smooth muscle contractility to histamine and relaxation to acetylcholine were significantly enhanced in vessels from treated rabbits. These studies indicate that pretreatment with clentiazem offers cerebral protection and significantly reduces infarct volume as well as arterial wall damage beyond the occlusion.

Acetylcholine↗

Verapamil is a potent inhibitor of 5-HT-induced platelet aggregation.

We have studied the effects of verapamil, diltiazem and amlodipine on 5-HT-induced platelet aggregation and compared the results with those obtained for other platelet aggregating agents. Experiments were carried out using both human whole blood and platelet-rich plasma (PRP). Verapamil (but not diltiazem or amlodipine) inhibited 5-HT-induced platelet aggregation at much lower concentrations (IC50 = about 1 microM) than were required for inhibition of aggregation induced by other aggregating agents. Like some other selective inhibitors of 5-HT-induced platelet aggregation, it was not possible to completely overcome the inhibition by increasing the concentration of 5-HT. The antiaggregatory effects of verapamil were similar, but not identical, in whole blood and PRP. These results show that the Ca2+ channel blocker verapamil has some selectivity as an inhibitor of 5-HT-induced platelet aggregation and that this behaviour as a 5-HT antagonist should be taken into account when interpreting any therapeutic benefit ascribed to this drug.

Adenosine Diphosphate↗

Effect of etidronate disodium on bone turnover following surgical menopause.

A longitudinal study was performed to document the effect of surgical menopause and postmenopausal etidronate disodium therapy on several nonhistomorphometric indices of bone turnover. Twenty healthy, premenopausal women undergoing oophorectomy for nonmalignant conditions were studied preoperatively and at 3 monthly intervals postoperatively. Sequential measurements of serum calcium (Ca), alkaline phosphatase (AP), bone Gla protein (BGP), and urinary calcium and hydroxyproline excretion, expressed as a ratio of urinary creatinine (UCa/Cr and UOHp/Cr, respectively) were obtained. Twenty-four-hour whole body retention of diphosphonate (WBR) and radial bone density were also measured. When a postoperative increase in bone turnover was observed, patients were randomized to receive either 400 mg etidronate disodium daily or placebo for 3 months. Oophorectomy was associated with a significant increase in WBR, Ca, AP, and BGP and an insignificant rise in UCa/Cr. A variable pattern of UOHp/Cr was seen. Patients on placebo maintained these elevated levels of Ca, BGP, and UCa/Cr. WBR and AP continued to rise. Etidronate disodium therapy resulted in a fall towards premenopausal levels in WBR, Ca, and UCa/Cr. AP and BGP were unchanged. Three months after stopping etidronate, BGP fell significantly and the decrease in Ca was maintained; however, WBR and UCa/Cr had returned towards pretreatment values. Bone density measurements did not change significantly. An increase in several of the indices of bone turnover was seen following oophorectomy. Etidronate disodium suppressed this increase, affecting indices of both resorption and formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Cryopreservation of innervation, endothelial and vascular smooth muscle function of a rabbit muscular and resistance artery.

The extent of preservation of endothelial, neurogenic and vascular function following frozen storage was studied using the rabbit central ear artery and a resistance artery branch. Fresh and frozen-stored artery segments were placed in tissue baths containing a physiological buffer solution and attached to a wire myograph apparatus for measurement of isometric force. Responses to cumulative additions of norepinephrine, histamine, acetylcholine and sodium nitroprusside were compared between fresh arteries and adjacent segments that had been stored frozen for 2-8 days at -70 degrees C. Responses to transmural nerve stimulation were measured in central ear artery segments that were fresh or stored frozen for 13-26 days. Large and small artery segments were frozen in ampules containing newborn calf serum and 1.8 M dimethylsulfoxide used as a cryoprotective agent. Following frozen storage, the vascular sensitivity of large and resistance arteries to norepinephrine and histamine were unaltered although maximal contractile responses were significantly reduced. Agonist affinity (KA values) to norepinephrine was also unchanged following frozen storage of large artery segments. Constrictor responses to varied frequencies of transmural nerve stimulation were similar between fresh and frozen-stored large arteries, suggesting that adrenergic nerve function is well preserved. In resistance arteries, vascular sensitivity and maximal relaxation to acetylcholine and sodium nitroprusside were unchanged. Similarly, relaxation of large arteries to sodium nitroprusside was well preserved. Although vascular sensitivity to acetylcholine was reduced in large arteries following frozen storage, much of the endothelial function was still preserved as indicated by only a 10% decrease in maximal relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

How can we inhibit 5-HT-induced platelet aggregation and why should we bother?

Different 5-HT receptor antagonists inhibit 5-HT-induced platelet aggregation with different potencies. The inhibitory effects of seven relatively potent antagonists could not be surmounted by increasing the concentration of 5-HT, but the inhibitory effects of seven less potent antagonists could be surmounted by 5-HT. Verapamil has in insurmountable inhibitory effect on 5-HT-induced aggregation at relatively low concentrations. Amlodipine is a very weak inhibitory of 5-HT-induced aggregation. Verapamil is more effective as an inhibitory of 5-HT-induced aggregation than it is of aggregation induced by PAF, adrenaline or ADP. The platelet aggregation obtained in whole blood in response to 5-HT, PAF, U46619 or ADP is not different in patients with peripheral vascular disease and age-sex matched controls.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Effects of combinations of 5-hydroxytryptamine receptor antagonists on 5-HT-induced human platelet aggregation.

We have examined the effects of fourteen 5-HT-receptor antagonists on 5-HT-induced platelet aggregation in whole blood. Two different types of inhibitory profile were obtained. The inhibitory effects of seven of the antagonists (designated type 1) could be surmounted by increasing the concentration of 5-HT; the inhibitory effects of the other antagonists (type 2) were insurmountable by 5-HT. The effects of combinations of pairs of different antagonists were investigated. The inhibitory effects of pairs of type 1 antagonists and of pairs of type 2 antagonists were additive. However, a type 1 antagonist interfered with the inhibitory effects of a type 2 antagonist. The two types of antagonist differed in the rate at which they inhibited 5-HT-induced aggregation, a type 2 antagonist exerting its effect more slowly than a type 1 antagonist. Two possible explanations of these results are considered. It is possible that there are two different types of receptors on the surface of platelets, one causing stimulation and the other causing allosteric inhibition of platelet aggregation. Alternatively, the results may stem from different rates of association and dissociation of the agents at a single 5-HT receptor.

Drug Interactions↗

Human parathyroid hormone (1-34) and salmon calcitonin do not reverse impaired mineralization produced by high doses of 1,25 dihydroxyvitamin D3.

We have reported recently that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) stimulated bone matrix formation but impaired mineralization. The objective of this study was to determine if parathyroid hormone (hPTH 1-34) or calcitonin (sCT) would mineralize the osteoid induced by 1,25(OH)2D3 in rat long bones. In one experiment, male Sprague-Dawley rats were given daily subcutaneous injections of vehicle: 8 micrograms hPTH(1-34); 125 ng 1,25(OH)2D3; or both 8 micrograms hPTH and 125 ng 1,25(OH)2D3 per 100 g body weight for 12 days. In a second experiment, rats received daily injections of vehicle: 2 U sCT; 125 ng 1,25(OH)2D3; or both 2 U sCT and 125 ng 1,25(OH)2D3 per 100 g body weight for 18 days. Calcium (Ca), hydroxyproline (Hyp), and dry weight (DW) of the distal femur and serum calcium, phosphate, and serum bone Gla protein (BGP) were measured. In rats given both 1,25(OH)2D3 and hPTH, total bone DW and Hyp increased (P less than .01) without a corresponding increase in bone Ca so that Ca/Hyp decreased 47% (P less than .01) from control and remained comparable to values for rats treated with 1,25(OH)2D3 alone. In rats treated with both 1,25(OH)2D3 and sCT, total bone DW and Hyp increased while Ca decreased so that Ca/Hyp decreased 38% from control (P less than .05), and remained comparable to values for rats treated with 1,25(OH)2D3 alone. These results indicate that hPTH or sCT, given by intermittent injection to rats for 12 or 18 days respectively, failed to mineralize the osteoid induced by high doses of 1,25(OH)2D3.

Animals↗