المؤلفون: Wei, Fen, Jia, Xiu-Jie, Yu, Su-Qin, Gu, Ye, Wang, Li, Guo, Xiao-Mei, Wang, Min, Zhu, Feng, Cheng, Xiang, Wei, Yu-Miao, Zhou, Zi-Hua, Fu, Michael, 1963, Liao, Yu-Hua

المصدر: Heart. 97(6):479-84

مصطلحات موضوعية: Dermatology and Venereal Diseases, Dermatologi och venereologi, Microbiology in the medical area, Mikrobiologi inom det medicinska området, Adult, Aged, Angiotensin II Type 1 Receptor Blockers, therapeutic use, Antihypertensive Agents, adverse effects, Autoantibodies, blood, Benzimidazoles, Blood Pressure, drug effects, Double-Blind Method, Female, Humans, Hypertension, drug therapy, immunology, physiopathology, Imidazolidines, Male, Middle Aged, Receptor, Angiotensin, Type 1, Tetrazoles, Treatment Outcome

الوصف: Anti-angiotensin II receptor subtype 1 (AT1 receptor) autoantibodies have previously been shown in sera of hypertensive patients. This study assessed whether anti-AT1-receptor autoantibody in serum is correlated with the efficacy of an AT1-receptor blocker (ARB; candesartan)-based regimen in hypertensive patients after 8 weeks of treatment.

الوصول الحر: https://gup.ub.gu.se/publication/150961Test

المؤلفون: Chaturvedi, Nish, Porta, Massimo, Klein, Ronald, Orchard, Trevor, Fuller, John, Parving, Hans Henrik, Bilous, Rudy, Sjölie, Anne Katrin, Wilhelmsen, Lars, 1932, DIRECT Programme, Study Group

المصدر: Lancet. 372(9647):1394-402

مصطلحات موضوعية: MEDICAL AND HEALTH SCIENCES, MEDICIN OCH HÄLSOVETENSKAP, Adolescent, Adult, Angiotensin II Type 1 Receptor Blockers, adverse effects, therapeutic use, Benzimidazoles, Diabetes Mellitus, Type 1, complications, drug therapy, Diabetic Retinopathy, classification, etiology, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Severity of Illness Index, Tetrazoles, Treatment Outcome

الوصف: BACKGROUND: Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of retinopathy in type 1 diabetes. METHODS: Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent 1 trial and those with existing retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or matching placebo. After 1 month, the dose was doubled to 32 mg. Investigators and participants were unaware of the treatment allocation status. The primary endpoints were incidence and progression of retinopathy and were defined as at least a two-step and at least a three-step increase on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, respectively. These trials are registered with ClinicalTrials.gov, numbers NCT00252733 for DIRECT-Prevent 1 and NCT00252720 for DIRECT-Protect 1. FINDINGS: 1421 participants (aged 18-50 years) were randomly assigned to candesartan (n=711) or to placebo (n=710) in DIRECT-Prevent 1, and 1905 (aged 18-55 years) to candesartan (n=951) or to placebo (n=954) in DIRECT-Protect 1. Incidence of retinopathy was seen in 178 (25%) participants in the candesartan group versus 217 (31%) in the placebo group. Progression of retinopathy occurred in 127 (13%) participants in the candesartan group versus 124 (13%) in the placebo group. Hazard ratio (HR for candesartan vs placebo) was 0.82 (95% CI 0.67-1.00, p=0.0508) for incidence of retinopathy and 1.02 (0.80-1.31, p=0.85) for progression of retinopathy. The post-hoc outcome of at least a three-step increase for incidence yielded an HR of 0.65 (0.48-0.87, p=0.0034), which was attenuated but still significant after adjustment for baseline characteristics (0.71, 0.53-0.95, p=0.046). Final ETDRS level was more likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds 1.16, 95% CI 1.05-1.30, p=0.0048) and DIRECT-Protect 1 (1.12, 95% CI 1.01-1.25, p=0.0264). Adverse events did not differ between the treatment groups. INTERPRETATION: Although candesartan reduces the incidence of retinopathy, we did not see a beneficial effect on retinopathy progression.

الوصول الحر: https://gup.ub.gu.se/publication/91544Test

المؤلفون: Sjölie, Anne Katrin, Klein, Ronald, Porta, Massimo, Orchard, Trevor, Fuller, John, Parving, Hans Henrik, Bilous, Rudy, Chaturvedi, Nish, Wilhelmsen, Lars, 1932, DIRECT Programme, Study Group

المصدر: Lancet. 372(9647):1385-93

مصطلحات موضوعية: MEDICAL AND HEALTH SCIENCES, MEDICIN OCH HÄLSOVETENSKAP, Adult, Aged, Angiotensin II Type 1 Receptor Blockers, adverse effects, therapeutic use, Benzimidazoles, Diabetes Mellitus, Type 2, complications, drug therapy, Diabetic Retinopathy, classification, etiology, Dose-Response Relationship, Drug, Double-Blind Method, Endpoint Determination, Female, Humans, Hypertension, Hypoglycemic Agents, Male, Middle Aged, Severity of Illness Index, Tetrazoles

الوصف: BACKGROUND: Diabetic retinopathy remains a leading cause of visual loss in people of working age. We examined whether candesartan treatment could slow the progression and, secondly, induce regression of retinopathy in people with type 2 diabetes. METHODS: We did a randomised, double-blind, parallel-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00252694. FINDINGS: 1905 participants (aged 37-75 years) were randomised to candesartan (n=951) or placebo (n=954). 161 (17%) patients in the candesartan group and 182 (19%) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale. The risk of progression of retinopathy was non-significantly reduced by 13% in patients on candesartan compared with those on placebo (hazard ratio [HR] 0.87, 95% CI 0.70-1.08, p=0.20). Regression on active treatment was increased by 34% (1.34, 1.08-1.68, p=0.009). HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30, p=0.003). Adverse events did not differ between the treatment groups. INTERPRETATION: Treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy.

الوصول الحر: https://gup.ub.gu.se/publication/91543Test

المؤلفون: Mörtsell, David, Malmqvist, K, Held, Claes, Kahan, T

المصدر: Journal of Internal Medicine. 261(5):472-479

مصطلحات موضوعية: Adult, Aged, Angiotensin II Type 1 Receptor Blockers/adverse effects/*therapeutic use, Antihypertensive Agents/adverse effects/*therapeutic use, Atenolol/adverse effects/*therapeutic use, Biphenyl Compounds/adverse effects/*therapeutic use, Blood Pressure/drug effects, Carotid Artery, Common/*drug effects/pathology, Double-Blind Method, Female, Heart Rate/drug effects, Humans, Hypertension/*drug therapy/pathology, Hypertrophy, Left Ventricular/drug therapy/pathology, Male, Middle Aged, Tetrazoles/adverse effects/*therapeutic use, Treatment Outcome, Tunica Intima/drug effects/pathology, MEDICINE, MEDICIN

الوصف: Background and purpose. Angiotensin II promotes cell growth and has been implicated in the development and maintenance of left ventricular (LV) hypertrophy and of structural vascular changes. We wished to examine whether an angiotensin receptor blocker (ARB) would influence structural vascular changes beyond the effects of blood pressure reduction.Methods. Hypertensive patients with LV hypertrophy (age 55 ± 9 years, blood pressure 162 ± 19/104 ± 8 mmHg, LV mass index 148 ± 31 g m−2; mean ± SD) were randomized double-blind to the ARB irbesartan (n = 52) or the beta1 receptor blocker atenolol (n = 56) for 48 weeks. Ultrasonography of the left and right common carotid artery (CCA) and echocardiography were performed at week 0 and 48.Results. With similar reductions in blood pressure, CCA intima-media thickness (IMT) was reduced by irbesartan (from 0.92 ± 0.14 by 0.01 ± 0.10 mm, NS), whereas it was increased by atenolol (from 0.94 ± 0.21 by 0.03 ± 0.12 mm, P = 0.018; P = 0.002 between groups). CCA lumen diameter was less reduced by irbesartan than by atenolol. Thus, CCA intima-media area was reduced by irbesartan (from 21.3 ± 5.0 by 0.90 ± 2.45 mm2, P = 0.034) but not by atenolol (from 21.3 ± 6.1 by 0.18 ± 2.71 mm2, NS; P = 0.037 between groups). Changes in CCA IMT or area did not relate to changes in LV mass.Conclusions. The favourable effects by irbesartan on CCA IMT with an outward vascular remodelling suggest that angiotensin II mediates structural vascular changes, beyond the effects of blood pressure. This may be important in the prevention of cerebrovascular events.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17365Test
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=17444886&dopt=CitationTest

المؤلفون: Svensson, Johan, 1964, Herlitz, Hans, 1946, Lundberg, Per-Arne, 1946, Johannsson, Gudmundur, 1960

المصدر: The Journal of clinical endocrinology and metabolism. 90(4):2290-6

مصطلحات موضوعية: MEDICAL AND HEALTH SCIENCES, MEDICIN OCH HÄLSOVETENSKAP, Adiponectin, Adult, Antiporters, blood, Body Composition, Cross-Over Studies, Double-Blind Method, Erythrocytes, chemistry, Female, Glucose, metabolism, Glucose Tolerance Test, Hormone Replacement Therapy, Hormones, Ectopic, Human Growth Hormone, deficiency, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor I, analysis, Intercellular Signaling Peptides and Proteins, Interleukin-6, Leptin, Male, Resistin

الوصف: In a randomized, placebo-controlled, crossover study under metabolic ward conditions, 10 GH-deficient adults received 1-wk GH replacement therapy (9.5 microg/kg.d). The effect of this treatment on the erythrocyte sodium/lithium countertransport (SLC) activity and on serum levels of adiponectin, resistin, leptin, IGF binding protein-1 (IGFBP-1) and IL-6 was determined. The 1-wk GH replacement impaired glucose homeostasis determined from an oral glucose tolerance test. The other measured variables in serum were unchanged by GH replacement. At baseline, serum adiponectin level was inversely correlated and serum leptin level was positively correlated with measures of glucose tolerance and insulin sensitivity. The changes in serum leptin level and erythrocyte SLC activity were positively correlated, and the change in serum IGFBP-1 level was negatively correlated, correlated with changes in measures of glucose metabolism. In conclusion, short-term GH treatment induced glucose intolerance but did not significantly change the erythrocyte SLC activity and the serum levels of adipokines, arguing against direct effects of GH on these measures. However, baseline values or changes in erythrocyte SLC activity, adiponectin, leptin, and IGFBP-1 correlated with glucose metabolism. This suggests that these factors are of importance for glucose homeostasis in GH-deficient adults, most likely through GH-independent mechanisms.

الوصول الحر: https://gup.ub.gu.se/publication/61272Test

المؤلفون: Yusuf, S., Ostergren, J. B., Gerstein, H. C., Pfeffer, M. A., Swedberg, Karl, 1944, Granger, C. B., Olofsson, B., Probstfield, J., McMurray, J. V.

المصدر: Circulation. 112(1):48-53

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, Adult, Angiotensin II Type 1 Receptor Blockers/pharmacology, Antihypertensive Agents/pharmacology, Benzimidazoles/*pharmacology, Body Mass Index, Diabetes Mellitus, Type 2/diagnosis/etiology/*prevention & control, Double-Blind Method, Female, Heart Failure, Congestive/*complications/*drug therapy, Humans, Incidence, Male, Middle Aged, Myocardial Infarction, Renin-Angiotensin System, Tetrazoles/*pharmacology

الوصف: BACKGROUND: Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan (an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Program). METHODS AND RESULTS: We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan (target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group (hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to 0.96; P=0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR, 0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28). CONCLUSIONS: The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.

الوصول الحر: https://gup.ub.gu.se/publication/52200Test

المؤلفون: Ciulla, M. M., Paliotti, R., Esposito, A., Diez, J., Lopez, B., Dahlöf, Björn, 1953, Nicholls, M. G., Smith, R. D., Gilles, L., Magrini, F., Zanchetti, A.

المصدر: Circulation. 110(5):552-7

مصطلحات موضوعية: MEDICAL AND HEALTH SCIENCES, MEDICIN OCH HÄLSOVETENSKAP, Adrenergic beta-Antagonists/*pharmacology/therapeutic use, Adult, Aged, 80 and over, Angiotensin II Type 1 Receptor Blockers/*pharmacology/therapeutic use, Antihypertensive Agents/*pharmacology/therapeutic use, Atenolol/*pharmacology/therapeutic use, Biological Markers, Collagen/blood, Double-Blind Method, Female, Fibrosis, Humans, Hypertension/complications/*drug therapy, Hypertrophy, Left Ventricular/blood/etiology/*prevention &, control/ultrasonography, Losartan/*pharmacology/therapeutic use, Male, Middle Aged, Myocardium/chemistry/*pathology, Peptide Fragments/blood, Treatment Outcome

الوصف: BACKGROUND: In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis. METHODS AND RESULTS: We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant. CONCLUSIONS: In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.

الوصول الحر: https://gup.ub.gu.se/publication/56061Test

المؤلفون: Burbano, X., Miguez-Burbano, M. J., McCollister, K., Zhang, G., Rodriguez, A., Ruiz, P., Lecusay, Robert, Shor-Posner, G.

المصدر: HIV Clinical Trials. 3(6):483-491

مصطلحات موضوعية: HIV hospitalization, Hospitalization costs, Selenium therapy, abacavir, antiretrovirus agent, CD4 antigen, nucleoside derivative, placebo, proteinase inhibitor, RNA directed DNA polymerase inhibitor, selenium, adjuvant chemotherapy, adult, article, cell count, chemoprophylaxis, clinical trial, controlled clinical trial, controlled study, diet supplementation, dose response, double blind procedure, drug screening, drug use, female, gender, health care cost, highly active antiretroviral therapy, hospital admission, hospital cost, hospitalization, human, human cell, Human immunodeficiency virus 1, Human immunodeficiency virus infection, major clinical study, male, pilot study, priority journal, randomized controlled trial, risk assessment, time, toxicity, treatment outcome, virus load, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Chemotherapy, Adjuvant, Dietary Supplements, Double-Blind Method, Florida, HIV Infections, Hospital Costs, Humans, Middle Aged, Viral Load

الوصف: Purpose: To evaluate the impact of selenium chemoprevention (200 μg/day) on hospitalizations in HIV-positive individuals. Method: Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. Results: At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p < .05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2-year study. A marked decrease in total admission rates (RR = 0.38; p =.002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p = .01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p = .001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p = .001). Conclusion: Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1-infected patients.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-27967Test

المؤلفون: Malmqvist, Karin, Kahan, Thomas, Edner, Magnus, Held, Claes, Hägg, Anders, Lind, Lars, Muller-Brunotte, Richard, Nyström, Fredrik, Öhman, K. Peter, Osbakken, Mary D., Östergern, Jan

المصدر: Journal of Hypertension. 19(6):1167-1176

مصطلحات موضوعية: Adrenergic beta-Antagonists/adverse effects/therapeutic use, Adult, Aged, Atenolol/adverse effects/therapeutic use, Biphenyl Compounds/adverse effects/*therapeutic use, Blood Pressure/drug effects, Double-Blind Method, Female, Heart Rate/drug effects, Humans, Hypertension/complications/*drug therapy/pathology/physiopathology, Hypertrophy, Left Ventricular/complications/*drug therapy/pathology/physiopathology, Male, Middle Aged, Receptor, Angiotensin, Type 1, Receptors, Angiotensin/*antagonists & inhibitors, Research Support, Non-U.S. Gov't, Safety, Tetrazoles/adverse effects/*therapeutic use, Vascular Resistance/drug effects, MEDICINE, MEDICIN

الوصف: BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-73124Test
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11403367&dopt=CitationTest

المؤلفون: Willis, Holly J, Thomas, William, Harkness, Laura, Eldridge, Alison L, Green, Hilary, Slavin, Joanne L

المصدر: Food and Nutrition Research. 54(5135):1