bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safe at School: A Virginia Experience
Authors: Hellems Martha A. , Clarke William L. 
Published: May 2007

OBJECTIVE—The Commonwealth of Virginia passed legislation in 1999 requiring nonmedical school personnel to assist students with the management of type 1 diabetes when school nurses were unavailable. This study was designed to determine which school personnel in Virginia currently assist type 1 diabetic students with insulin administration and management of hypoglycemia and to determine if these students are being cared for in a safe manner.
RESEARCH DESIGN AND METHODS—Parents of children with type 1 diabetes who attended public school in Virginia during the previous year and who were receiving their diabetes care at the University of Virginia diabetes clinics were asked to participate in an anonymous survey. The survey asked parents which school personnel were responsible for their child's diabetes care while at school and which persons helped with specific care tasks including blood glucose monitoring, insulin administration, and assistance with treatment of hypoglycemia. Questions were asked regarding the occurrence and treatment of hypoglycemia and any adverse effects of such treatment.
RESULTS—A total of 185 parents whose children attended 153 different schools responded, 69% of whom reported that a full-time school nurse was assigned to their child's school. In other schools, teachers, administrators, coaches, and cafeteria workers supplemented part-time nurses in assisting students with diabetes management tasks. Although hypoglycemia was not a rare event (75% of students experienced a median of five episodes per year), only one severe event requiring the use of glucagon was reported. In that case, glucagon was administered appropriately by a part-time school nurse, and the student experienced no adverse effects related to the treatment.
CONCLUSIONS—Students with type 1 diabetes can be cared for safely during the school day by a variety of trained medical and nonmedical personnel. The occurrence of one severe hypoglycemic event among 185 students suggests that as many as 3% of students could experience severe hypoglycemia in a given school year. Legislation that permits nonmedical school personnel to assist students with their diabetes management could make the diabetic children's school day safer and improve their overall glucose control.
Insulin-like growth factor induces up-regulation of AT1-receptor gene expression in vascular smooth muscle cells
Authors: Müller Cornelius , Reddert Anja , Wassmann Sven , Strehlow Kerstin , Böhm Michael , Nickenig Georg 
Published: May 2007

Background Insulin-like growth factor-1 (IGF-1), as well as AT1-receptor activation, plays a central role in growth processes of cardiac and vascular cells. In order to assess relevant interactions of both systems, the effect of IGF-1 on AT1-receptor expression was evaluated in vascular smooth muscle cells. Methods and results Incubation of cultured vascular smooth muscle cells (VSMC) with IGF-1 led to a dose- and time-dependent up-regulation of AT1-receptor mRNA, as measured by Northern hybridisations. The maximal AT1-receptor overexpression of 201±70% of control levels was reached after a 24-hour incubation with 100 ng/ml IGF-1. Consequently, AT1-receptor protein expression was increased to 231±35% of control levels. Experiments under transcriptional blockade showed that AT1-receptor mRNA stability was not altered by IGF-1, suggesting that transcriptional mechanisms may be involved in IGF-1-induced AT1-receptor regulation. Preincubation with various pharmacological inhibitors revealed that IGF-1 up-regulated AT1-receptor expression via activation of p42/44 MAP kinase, whereas tyrosine phosphorylation and PI-3 kinase seemed not to participate in this regulative pathway. Conclusions IGF-1-induced up-regulation of the AT1-receptor may be an important interaction by which cellular growth is modulated in the heart as well as in the vasculature. This may have implications for the treatment regimen of patients suffering from hypertension, cardiac hypertrophy, and coronary heart disease.
The effects of the addition of losartan on uric acid metabolism in patients receiving indapamide
Authors: Nikas Spyros , Rizos Evangellos , Milionis Haralampos , Bairaktari Eleni , Kalaitzidis Rigas , Siamopoulos Kostas , Elisaf Moses 
Published: May 2007

Objective A number of adverse metabolic effects are associated with indapamide administration, including an increase in serum uric acid levels. It has been reported that losartan can significantly decrease serum uric acid levels. However, there are no data on the effects of combination therapy of losartan with indapamide on uric acid metabolism. Methods We studied 20 hypertensive patients in whom serum metabolic parameters, including uric acid levels in serum and urine, were studied before and after eight weeks of indapamide administration (2.5 mg once daily) as well as eight weeks after combination treatment with indapamide (2.5 mg once daily) and losartan (50 mg/day). Results Indapamide evoked a significant decrease in systolic and diastolic blood pressure from a mean value of 157±12 mmHg/96±10 mmHg to a mean value of 139±14 mmHg/92±5 mmHg (p<0.01 for both comparisons). However, a significant increase in serum uric acid levels was noticed after indapamide administration (from a mean value of 4.9±1.6 mg/dl to a mean value of 5.9±1.2 mg/dl, p<0.01), associated with a decrease in the fractional excretion of uric acid (from a mean value of 9±5% to a mean value of 7±5.5%, p<0.05). The addition of losartan caused a further decrease in blood pressure from a mean value of 139±14 mmHg/92±5 mmHg to a mean value of 120±15 mmHg/84±4 mmHg (p<0.01 for both comparisons). This was followed by a significant decrease in serum uric acid levels to 5±1.1 mg/dl (p<0.01) due to a substantial increase in fractional urate excretion (from 7±5.5 to 8.7±6%, p<0.05). Conclusion The addition of losartan could offset the hyperuricaemic effect of indapamide administration.
Improving the prognosis of diabetic patients: Evaluating the role of intensive versus moderate blood pressure control with selective angiotensin II receptor blocker (ARB) therapy
Authors: Bedigian Martin P 
Published: May 2007

Summary The ABCD (Appropriate Blood Pressure Control in Diabetes) and ABCD-2V (Part 2 with Valsartan) are prospective, randomised clinical trials which will provide important data on the impact of intensive vs. moderate blood pressure (BP) control on microvascular and macrovascular complications in normotensive and hypertensive patients with type 2 diabetes mellitus (DM). The ABCD trial was a five-year study that compared the effects of intensive vs. moderate BP control on the endpoints of nephropathy, retinopathy, neuropathy, and cardiovascular disease events using a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor as the primary antihypertensive agents. The recently published results of the hypertensive cohort of ABCD are reviewed herein. The follow-up study, ABCD-2V, is ongoing and was designed to compare intensive vs. moderate BP control on the same endpoints as the ABCD study, using the highly selective angiotensin II receptor blocker (ARB) valsartan as the primary antihypertensive agent. First results of ABCD-2V are expected in 2004. The baseline characteristics for the patients enrolled thus far in the hypertensive cohort of ABCD-2V are reviewed. These studies will provide insight into the role of intensive vs. moderate BP control in the management of normotensive and hypertensive patients with type 2 DM.
Acute effects of ACE inhibition on coronary endothelial dysfunction
Authors: Nickenig Georg , Stäblein Alexander , Wassmann Sven , Wyen Christoph , Müller Cornelius , Böhm Michael 
Published: May 2007

The prerequisite of atherosclerosis, endothelial dysfunction, is characterised by impaired endothelium-dependent vasodilation caused by the reduced bioavailibility of nitric oxide (NO). In order to assess the role of acute ACE inhibition in this setting, coronary arterial endothelial function was quantified following acute intracoronary administration of the angiotensin-converting enzyme (ACE) inhibitor quinapril. Twenty-one patients with non-limiting coronary artery disease were studied before and after acute intracoronary administration of 10 mg quinapril. Nine patients received pre-treatment with the angiotensin AT1-receptor antagonist losartan (2x50 mg, p.o.). Coronary cross-sectional diameter was measured via quantitative angiography and microvascular reaction was investigated by intracoronary Doppler flow measurement during intracoronary infusion of 0.1 to 10 µmol/l acetylcholine. Quinapril acutely improved endothelial dysfunction on the macro- as well as the microvascular level. Losartan did not alter macrovascular function but facilitated microvascular endothelial function. Acute quinapril application led to no further improvement of endothelial dysfunction in patients pre-treated with losartan. Acute quinapril infusion improved endothelial function in patients with coronary heart disease. Treatment with the AT1-receptor antagonist losartan led to a slight improvement in microvascular endothelial function, but pre-treatment with losartan blunted the vascular effect of quinapril, suggesting that the combination of ACE inhibition and AT1-receptor antagonism may not exert a synergistic benefical impact on the coronary vasculature.
Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats
Authors: Wienen Wolfgang , Richard Serge , Champeroux Pascal , Audeval-Gerard Chantal 
Published: May 2007

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day) and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus. It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9—10 weeks. Animals were treated with telmisartan (3 or 10 mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n=18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/ day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.
The effects of candesartan on vascular responses to angiotensin II and norepinephrine in normal volunteers
Authors: Tran Diane , Phoon Stephen , Howes Laurence 
Published: May 2007

The effects of chronic administration of candesartan, 16 mg once-daily, to normal volunteers on cardiovascular responses to angiotensin II (Ang II) and norepinephrine (NE) were examined. Fifteen healthy, non-smoking volunteers participated in a randomised, double-blind crossover study of two weeks of candesartan therapy, compared with two weeks of placebo. Blood pressure (BP) responses were measured to increasing infusion rates of intravenous Ang II and NE, along with forearm blood flow (FBF) responses into intra-brachial arterial Ang II, 2 and 24 hours after the last dose of candesartan or placebo. FBF responses to intra-brachial arterial NE were recorded approximately 2 hours following the final dose. Systolic and diastolic BP responses to intravenous infusions of Ang II during candesartan treatment were completely suppressed and significantly lower than during placebo treatment, 2 hours (candesartan 96±10/55±8 mmHg; placebo 105±5/64±8 mmHg) and 24 hours (candesartan 94±8/54±8 mmHg; placebo 103±7/64±7 mmHg) following the last dose. In contrast, FBF responses to intra-brachial arterial Ang II were significantly suppressed by candesartan compared with placebo in a subgroup of subjects 2 hours following the last dose (n=9), but not 24 hours after the last dose (n=8). FBF responses to NE were also suppressed by candesartan treatment 2 hours following the last dose, while BP responses to intravenous NE were unaltered. Chronic candesartan therapy, 16 mg once-daily effectively suppresses pressor responses to Ang II over the duration of the dosing interval.
High serum enalaprilat in chronic renal failure
Authors: Elung-Jensen Thomas , Heisterberg Jens , Kamper Anne-Lise , Sonne Jesper , Strandgaard Svend , Larsen Niels Erik 
Published: May 2007

Background Most angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally and doses should hence be reduced in renal insufficiency. We studied whether the dosage of enalapril in daily clinical practice is associated with drug accumulation of enalaprilat in chronic renal failure. Methods Fifty nine out-patients with plasma creatinine >150 µmol/L and chronic antihypertensive treatment with enalapril were investigated, in a cross-sectional design. Results Median glomerular filtration rate (GFR) was 23 (range 6—60) ml/minute/1.73 m2. The daily dose of enalapril was 10 (2.5—20) mg and the trough serum concentration of enalaprilat was 31.8 (<2.5—584.7) ng/ml. Ninety percent of the patients had higher serum concentrations of enalaprilat than has been reported in subjects with normal kidney function, and a marked elevation of serum enalaprilat was observed in patients with GFR <30 ml/minute. All but three patients had serum ACE activity below the reference range. The ACE genotype did not influence the results. Additional pharmacokinetic studies were done in nine patients in whom GFR was 23 (10—42) ml/minute/1.73 m 2. The median clearance of enalaprilat was 28 (16—68) ml/minute and correlated linearly with GFR (r=0.86, p=0.003). Intra-subject day-to-day variation in trough concentrations was 19.7%. Conclusion Patients with chronic renal failure given small or moderately high doses of enalapril may thus have markedly elevated levels of serum enalaprilat. Whether this affords extra renoprotection, or on the contrary may inappropriately impair renal function, is not known, and should be investigated in prospective, controlled studies.
Role of endothelin in cardiovascular disease
Authors: Agapitov Alexei V , Haynes William G 
Published: May 2007

Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system. The overall action of endothelin is to increase blood pressure and vascular tone. Therefore, endothelin antagonists may play an important role in the treatment of cardiac, vascular and renal diseases associated with regional or systemic vasoconstriction and cell proliferation, such as essential hypertension, pulmonary hypertension, chronic heart failure and chronic renal failure. Long-term anti-endothelin therapy may improve symptoms and favourably alter the progression of heart failure. Endothelin appears to participate in induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease. Anti-endothelin therapy might offer additional benefits in the prevention of progression of chronic renal failure in addition to the known benefits of RAAS inhibition. Clinical trials have demonstrated potentially important benefits of endothelin antagonists for patients with essential hypertension, pulmonary hypertension and heart failure. Further studies are necessary to determine the role of anti-endothelin therapy in the treatment of cardiovascular diseases and determine the different roles of selective receptor antagonism vs. mixed ETA/B-receptor antagonism in human diseases.
Comparative effects of cilazapril, carvedilol and their combination in preventing from left ventricular remodelling after acute myocardial infarction in rats
Authors: Yuejin Yang  , Yida Tang  , Yingmao Ruan  , Yongli Li  , Yanwen Zhou  , Runlin Gao  , Jilin Chen  , Zaijia Chen  
Published: May 2007

Objectives To compare the effects of cilazapril, carvedilol and their combination in preventing left ventricular remodelling (LVRM) after acute myocardial infarction (AMI) in rats. Methods Twenty-four hours after left coronary artery ligation, 100 surviving AMI female Sprague-Dawley rats were randomly assigned to: (1) AMI control (n=25); (2) cilazapril (Cila, 1 mg/kg/day) (n=25); (3) carvedilol (Car, 1 mg/kg/day) (n=25), and (4) cilazapril (1 mg/kg/day)+ carvedilol (1 mg/kg/day) (combination) (n=25) groups. A sham-operated group (n=17) was selected randomly as a non-infarction control. After four weeks of therapy with the drugs given by gastric gavage, haemodynamic studies were performed, following which the rat hearts were fixed and pathologically analysed. Rats with MI size <35% or >55% were excluded. Complete data were obtained in 64 rats, comprising AMI control (n=13), Cila (n=12), Car (n=12), Combination (n=14), and sham-operated (n=13) groups. Results There were no significant differences in MI size between the four AMI groups (45.2—46.7%, p>0.05). Compared with the sham-operated group, left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), weight (LVW), septal thickness (STh) and right ventricular weight (RVW) were all significantly increased (all p<0.001) in the AMI group, while the LV pressure maximal rate of rise and fall (±dp/dt) was significantly decreased (all p<0.001). In comparison with the AMI group, LVEDP, LVV, LVW, STh and RVW were all significantly decreased, while ±dp/dt was significantly increased in the Cila, Car, and combination groups, with LVEDP and STh decreasing more in the combination group than in the two monotherapy groups (p<0.05—0.01). There were no significant differences in other variables between the three therapy groups. Conclusions Cilazapril, carvedilol and their combination are all effective in preventing LVRM after AMI in rats, and in improving haemodynamics and LV function, with the combination therapy being superior to monotherapy in all respects.
ACE-I and ARBs in early diabetic nephropathy
Authors: Mauer Michael , Zinman Bernard , Gardiner Robert , Drummond Keith N , Suissa Samy , Donnelly Sandra M , Strand Trudy D , Kramer Michael S , Klein Ronald , Sinaiko Alan R 
Published: May 2007

Introduction Antihypertensive treatment of patients with clinical manifestations of diabetic nephropathy, and especially, renin-angiotensin system (RAS) inhibition, slows, but may not fully arrest progression towards end-stage renal disease. Studies using `hard' endpoints such as doubling of serum creatinine, dialysis, or death that are initiated before emergence of any renal functional abnormalities in diabetes, would be of impractical length and size. We therefore undertook a primary prevention study (The Renin-Angiotensin System Study or RASS) to determine if inhibition of the RAS could slow the development of a key diabetic glomerulopathy structural endpoint, increase in mesangial fractional volume (Vv[Mes/glom]). Methods This is a parallel group, double-blind, placebo-controlled trial with 285 patients with Type 1 diabetes mellitus (95 per group) randomised to receive the angiotensin-converting enzyme inhibitor, enalapril, the angiotensin II receptor blocker, losartan, or placebo. All patients are normotensive, normoalbuminuric and have normal or increased glomerular filtration rates at study entry. The study is based on primary endpoint of change in Vv(Mes/glom) from baseline to the five-year renal biopsy, with baseline and interval measures of albumin excretion rate, glomerular filtration rate, blood pressure, and glycaemia. Baseline, mid-point, and five-year retinal fundus photography are also performed. Results One thousand and sixty-five patients were interviewed, 707 refused participation and 73 were excluded. The target of 285 subjects were randomised and their clinical and demographic characteristics are described. Biopsy complications occurred in 17 (6%), only one of which required hospitalisation. There were no permanent biopsy-related sequelae. Conclusions Renal structural variables are reasonable surrogate endpoints for studies of progression of early diabetic nephropathy. Although requiring substantial recruitment effort, diabetic nephropathy primary prevention trials based on change in renal structure are feasible.
Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease
Authors:   Pacific Study Group, Neal Bruce 
Published: May 2007

Introduction Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BPlowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system. Methods Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo. Results After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/—0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p<0.05 for all). Premature discontinuations were more frequent with omapatrilat than with placebo (p<0.001 for 20 mg and 40 mg). Conclusions Omapatrilat produced changes in BP, neurohormone and biochemical parameters that were similar for the two doses. The long-term clinical implications of the observed effects are uncertain and a large-scale randomised trial would be required to reliably establish the effects of omapatrilat on the risks of major vascular disease events among patients with coronary heart disease.