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Biomedical subjects

D B Barnett

Publications and source records attributed to D B Barnett.

At least 37 records · Page 2Linked to original sources
PubMed1998

Results of Helicobacter pylori screening and eradication in a multi-ethnic community in central England.

OBJECTIVES: To determine the prevalence of Helicobacter pylori and risks for infection in a multi-ethnic inner city population, and to assess the effectiveness with which the infection can be eradicated in a relatively asymptomatic population of this type. DESIGN: Analysis of results from a small research-based community programme of screening and eradication. Tests were offered to matched groups of Asians and non-Asians from the general population. METHODS: Those who attended for screening had a serological screening test for infection with H. pylori. Data concerning possible risk factors for infection were collected by means of questionnaires. Subjects testing positive were offered a prescription for eradication therapy (ranitidine bismuth citrate and clarithromycin) through their general practitioner, and success of eradication therapy was assessed by urea breath test. RESULTS: The overall prevalence of infection in 155 subjects was found to be 51%. The difference between positive test rates in Asians (53%) and non-Asians (47%) was not significant (P=0.611). In Asians, age and social class were risk factors for infection, but not gender or birth outside the UK. Results were similar in those born in India and East Africa. Of the 79 people who tested positive, 64 (81%) elected to take eradication therapy. Compliance with medication was estimated to be 95% and successful eradication was achieved in 92% of cases. CONCLUSION: Social class is more important than Asian ethnic origin as a predictor of H. pylori status. Good rates of H. pylori eradication can be achieved in subjects from the general population living in inner city communities.

Breath Tests↗
PubMed1998

General population screening for infection with Helicobacter pylori: a realistic option?

OBJECTIVES: To consider the effectiveness of a community programme of Helicobacter pylori (H pylori) screening and eradication run in collaboration with general practitioners. Specifically, to assess numbers successfully eradicating H pylori and consequently reducing the prevalence of infection, and to identify and consider areas of poor compliance. SETTING: A large general practice in Market Harborough, Leicestershire, UK. METHODS: A general population sample of 4015 subjects aged 21-55 was offered a serological screening test for H pylori through their general practitioners. Those testing positive were offered a prescription for eradication treatment and an information pack designed to encourage good compliance. Successful eradication was assessed by a urea breath test. RESULTS: The screening test was accepted by 1566 (39%) of those invited, with men and younger people least likely to attend. Of the 235 (15%) subjects who tested positive, 186 (79%) were treated and eradication was confirmed in 170 (95%) of the 179 subjects who had a urea breath test. Overall, eradication was confirmed in 4% (170/4015) of those offered screening. Assuming a 15% overall prevalence of H pylori infection, it is estimated that H pylori was eradicated in 29% of those infected in the target group. CONCLUSIONS: When an intervention was used to encourage good compliance, the eradication rate was high. Effectiveness was limited most strongly by the acceptance rate for the screening test, but also by the rate of uptake of eradication treatment. If benefits of population screening can be shown, appropriate interventions to improve compliance in these areas would need consideration.

Adult↗
PubMed1995

Cardiac chamber-specific beta-adrenoceptor regulation and sympathetic innervation.

We assessed by radioligand binding techniques the effect of cardiac failure on beta-adrenoceptor density in 5 hearts from patients undergoing repeat transplantation and 5 normal (unused donor) hearts. Right ventricular total and subtype beta-adrenoceptors in the denervated repeat-transplant hearts were down-regulated compared with the normally innervated controls. Within the denervated hearts, beta 1-adrenoceptors were selectively down-regulated in the right ventricle compared with the left ventricle. Tissue noradrenaline content confirmed sympathetic denervation in the transplanted hearts. Thus, regional sympathetic innervation is not necessary for chamber-specific beta-adrenoceptor down-regulation; other mechanisms for this process should be sought.

Adolescent↗
PubMed1995

Beta adrenoceptor density in the donor heart: a guide to prognosis?

BACKGROUND: Failure of the donor (graft) heart is the main cause of mortality in the first month after orthotopic cardiac transplantation. In a preliminary study marked downregulation of cardiac beta adrenoceptor density was found in apparently normal donor hearts of recipients who developed severe cardiac failure soon after implantation. Cardiac beta adrenoceptors are an important factor in the development of cardiac failure in the human heart. The aim of this study therefore was to determine whether fatal graft failure in the first month after transplantation is associated with downregulation of beta adrenoceptor density in the donor heart. PATIENTS AND METHODS: Right ventricular endomyocardial biopsy specimens were taken from consecutive adult donor patients immediately before implantation. A previously described radioligand binding method was used to determine beta adrenoceptor density in consecutive patients who developed fatal graft failure and died within 1 month of transplantation and in a group of control donors transplanted during the same period. RESULTS: Perioperative fatal graft failure developed in 13 patients. Forty one specimens from donor hearts that were transplanted into recipients who did not develop fatal graft heart failure formed the control group. There were no systematic differences in donor or recipient characteristics between the graft heart failure and control groups. In particular donor catecholamine requirement and recipient pulmonary vascular resistance did not differ between groups. Total beta adrenoceptor density was reduced in the fatal graft heart failure group compared with that in the controls (13.4 (7) fmol/mg v 21 (7) fmol/mg; P < 0.01). There was a positive correlation between beta adrenoceptor density in the donor heart and time to death in the graft heart failure group (r2 = 0.3, P < 0.05). The beta adrenoceptor binding affinity (Kd) did not differ between the graft failure group and the controls (47 (6) pM v 44 (7) pM). CONCLUSION: The development of perioperative fatal cardiac failure after orthotopic cardiac transplantation is associated with downregulation of beta adrenoceptors in the donor heart before implantation.

Adult↗
PubMed1994

Long-term evaluation of treatment for chronic heart failure: a 1 year comparative trial of flosequinan and captopril.

Two hundred and nine patients with moderate to severe chronic heart failure, all of whom remained symptomatic despite at least 80 mg of frusemide daily, were randomized to 12 months treatment with flosequinan or captopril. The patients were stratified into two groups, a treadmill group and a corridor walk test group, depending upon their exercise capability. Sixty-five out of 102 patients randomized to flosequinan and 43 out of 107 randomized to captopril (p < 0.001) did not complete the study. There was no difference between the groups in mortality: 19 patients died while taking flosequinan and 15 while taking captopril. Both drugs had similar effects on treadmill exercise tolerance; the mean increase at week 52 was 117 seconds in the flosequinan group and 156 seconds (p = 0.57) for the captopril group. For those patients stratified to the corridor walk test only, there was also very little difference in the improvement at 52 weeks; the mean increase for patients randomized to flosequinan was 61 meters and captopril was 75 meters (p = 0.65). However, when the walk tests from all patients are examined, captopril produced a significant improvement compared with flosequinan at week 52 (p = 0.015). Flosequinan has similar long-term efficacy to captopril but is associated with a higher incidence of adverse events.

Blood Pressure↗
PubMed1993

Subtype selective regulation of coupling of rat cardiac beta adrenoceptors to adenylate cyclase.

There is now evidence from human studies to suggest that cardiac beta-adrenoceptor density and coupling to adenylate cyclase may be regulated in a subtype selective fashion. An animal model was used to investigate this further. Rats were infused for 6 days with the non-selective full agonist isoprenaline (n = 6) or the beta 1-selective partial agonist xamoterol (n = 6) with sham operated rats (n = 6) for control. beta-Adrenoceptor subtype density and coupling to adenylate cyclase were determined in left ventricular membranes. Isoprenaline infusion downregulated both beta 1- (30%) and beta 2- (63%) adrenoceptor subtypes with associated reduction in adenylate cyclase stimulation through both subtypes. Xamoterol did not downregulate either subtype, but selectively uncoupled beta 1-adrenoceptors. beta 1- and total beta-adrenoceptor-mediated stimulation of adenylate cyclase was reduced less by xamoterol than isoprenaline. We conclude that coupling of rat cardiac beta-adrenoceptors can be regulated in a subtype selective fashion and that the partial agonist xamoterol does not desensitise beta-adrenoceptor mediated stimulation of adenylate cyclase to the same extent as the full agonist isoprenaline.

Adenylyl Cyclases↗
PubMed1993

Flosequinan.

Explore the source record for details and available documents.

Heart Failure↗
PubMed1993

Beta adrenergic and muscarinic receptors in compensatory cardiac hypertrophy of the adult rat.

The beta adrenergic (beta AR) and muscarinic (MR) receptors have been quantitated in parallel, using 125I-pindolol and 3H-quinuclidinylbenzilate, in a model of compensatory left ventricular (LV) hypertrophy (LVH), which developed in rats 4-6 weeks after an abdominal aortic stenosis. Since aortic banding resulted in a pronounced LVH of 62%, the results were expressed both in terms of density (fmol/mg protein) and quantity (fmol per LV). In addition, competition curves using either a specific beta 1-antagonist or isoproterenol or carbachol allowed the determination of the two beta AR subtypes and of the low and high affinity sites (defined by the inhibitory constant Ki) for both beta 1AR and MR. In LVH, receptor density decreased for each of total beta AR, beta 1AR subtype, high affinity (Ki 6-8 nM) beta 1AR sites (from 26 +/- 2 to 19 +/- 3 fmol/mg protein, P < 0.05), total MR and high affinity (Ki 12 nM) MR sites (from 63 +/- 6 to 40 +/- 4 fmol/mg protein, P < 0.001). The beta AR and MR densities dropped in parallel so that the MR/beta AR ratio remained unchanged. In sharp contrast (because the LVs were bigger) the quantities of total beta AR, beta 1AR subtype, beta 1AR high affinity sites, total MR and MR high affinity sites per LV were unmodified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1993

In vivo regulation of human cardiac beta-adrenoceptors by a partial agonist as compared with a full antagonist: selective differences in coupling to adenylate cyclase.

Chronic therapy with the beta 1-selective adrenoceptor partial agonist xamoterol is not associated with the tolerance observed with other beta-adrenoceptor agonists. A possible explanation is that xamoterol therapy does not desensitise human cardiac beta-adrenoceptors in vivo. beta-Adrenoceptor density and adenylate cyclase activities were determined in right atrial appendages obtained from 40 patients randomised in a double-blind fashion to receive either xamoterol or atenolol for at least 5 weeks before coronary artery bypass surgery. There was no significant difference in total or subtype beta-adrenoceptor densities, but basal and isoproterenol stimulated adenylate cyclase activity were significantly greater in the atenolol-treated group, as was the intrinsic activity of the beta 2-adrenoceptor partial agonist procaterol, suggesting that chronic therapy with xamoterol does not downregulate human cardiac beta-adrenoceptors in vivo. Coupling of beta-adrenoceptors to adenylate cyclase, predominantly mediated by the beta 2 subtype, is enhanced, however, after therapy with atenolol relative to therapy with xamoterol.

Adenylyl Cyclases↗
PubMed1992

Effects of age, sex and the oral contraceptive on the platelet membrane fibrinogen binding site (glycoprotein IIb/IIIa).

1. We have studied the effects of age, sex and the oral contraceptive pill on platelet fibrinogen 'receptor' density (Bmax) and affinity (Kd). 2. [125I]-fibrinogen binding to gel-filtered platelets was assessed after stimulation with adenosine 5-diphosphate (ADP) and thrombin in 60 normal subjects; 37 females and 23 males. 3. For both agonists there was no significant difference in Bmax or Kd between the sexes. A trend towards increasing affinity (reduced Kd) with age was noted in the female group following ADP stimulation. This was not considered to be physiologically relevant. In the group as a whole no significant relationship of Bmax and Kd with age was demonstrated. 4. A further group of eight women taking low dose oestrogen combined oral contraceptive pill were studied on days 7, 14, 21 and 28 of the treatment cycle and compared with eight women with regular ovulatory cycles. No significant variations in Bmax or Kd were detected within or between cycles in these two groups.

Adenosine Diphosphate↗
PubMed1991

125I-fibrinogen binding to platelets in myeloproliferative disease.

Recent reports have suggested a variation in the density and affinity of fibrinogen binding sites in platelets from patients with myeloproliferative disorders (MPD) which may reflect platelet functional abnormalities in these subjects. We have investigated the binding of 125I-fibrinogen (125I-Fb) to gel-filtered platelets from a large relatively homogeneous group of patients with MPD compared to normal age matched controls. Twenty-two of the patients investigated had polycythaemia vera and four essential thrombocythaemia. The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel-filtered platelets (GFP) stimulated with either 10 microM ADP or 150 mU thrombin. In addition the functional significance of the binding sites was studied by evaluating the response of GFP from the two experimental groups by assessing the effects of increasing concentrations of added fibrinogen on the response to 10 microM ADP using standard light transmission aggregometry. In both groups the density of fibrinogen binding sites expressed in response to thrombin stimulation was significantly higher (approximately 2-3 fold) than that found in response to ADP. However, fewer binding sites were detected in the MPD group as compared with the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower than that found in the MPD subjects. Although the 125I-Fb binding study results indicate a significant reduction in both the number and affinity of fibrinogen binding sites in patients with myeloproliferative disorders, the clinical and functional significance of these findings remain uncertain.

Blood Platelets↗
PubMed1991

Cardiac beta-adrenoceptor regulation and the effects of partial agonism.

The in vivo effects of xamoterol on the regulation of rat cardiac beta adrenoceptors were investigated. Rats were implanted subcutaneously with osmotic minipumps and exposed to the following treatment regimens: (1) subcutaneous infusion of saline (control), isoprenaline or xamoterol for 6 days, (2) subcutaneous infusion of isoprenaline with co-administration of xamoterol for various periods up to 96 hours, and (3) subcutaneous infusion of xamoterol for up to 96 hours after previous treatment with isoprenaline for 72 hours. Xamoterol did not induce beta-adrenoceptor down-regulation after short-term (72-hour) or long-term (6-day) infusions. When coadministered with isoprenaline xamoterol did not affect the rate or extent of down-regulation induced by isoprenaline alone. In addition, recovery of beta adrenoceptors down-regulated by isoprenaline treatment was not influenced by xamoterol treatment. In all studies, doses of xamoterol were equivalent to those producing full functional responses to the drug in vivo.

Adrenergic beta-Agonists↗