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Biomedical subjects

R Schmieder

Publications and source records attributed to R Schmieder.

At least 19 recordsLinked to original sources
PubMed2005

Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate.

BACKGROUND/AIMS: Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. METHODS: In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. RESULTS: Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. CONCLUSION: This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.

Adult↗
PubMed2005

[BENEFIT Kidney--significance of a nephrology screening at intervention outset and therapy success].

BACKGROUND AND OBJECTIVE: Early specialist care of patients with renal disease, including timely and planned onset of dialysis, determine the course of the disease, quality of life, hospitalization and life expectancy. A multi-centre enquiry by standardized questionnaire was undertaken to define and analyse medical care of newly dialysis-requiring patients. PATIENTS AND METHODS: Data on 551 patients in five different regions of Germany who for the first time required renal replacement treatment were prospectively collected between July 2002 and March 2003. Documentation of history, clinical findings and biochemical tests was done on consecutive patients with a standardized questionnaire, until the desired number of cases was reached. RESULTS: The mean age of the patients (55.4% males) was 64.8 years. 30.7% had diabetes mellitus, 22.3% arterial hypertension/nephrosclerosis and 16.9% glomerulonephritis/vasculitis. Early predominantly nephrological care had been undertaken in 38.7% of patients. 59.0% were cared for almost exclusively by their general practitioner until the time when dialysis was started. 229 patients (41.6%) were referred to specialist (nephrologists) only when dialysis had become necessary. The onset of dialysis was at the right time in only 50.5% of this group. Comparing the care given by nephrologists with that by general practitioners, elective (i.e. planned) dialysis was begun in 81.0% vs. 48.0% (p<0.05). Hospitalization in the two groups was 54.5% vs. 83.7% (p<0.05), the duration of hospital stay 11.4 vs. 17.4 days (p<0.05). CONCLUSION: Fewer than 40% of patients with chronic renal disease in preterminal renal failure (stage IV) were under the care of nephrologists. The lower the degree of nephrological care the more frequent was there a delay in the onset of dialysis treatment. The incidence and the duration of hospital stay was longer. Structured treatment pathways and incentives need to be formulated to reduce the incidence of wrong or substandard treatment of patients with impaired renal function.

Aged↗
PubMed2002

Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study rationale and design.

The PICXEL study is designed to evaluate the effects of long-term administration of very low-dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) vs enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. This multicentre, controlled, randomised, double-blind, parallel group study is carried-out to assess the variation of left ventricular mass index (LVMI) after treatment, using a centralised control of M-mode echocardiography determinations, and a dedicated software for semi-automatic measurement. Following a 4-week placebo run-in period, hypertensive outpatients aged >/=18 years, with LVH (LVMI >120 and 100 g/m(2) for men and women, respectively), are randomised to receive once daily, over 52 weeks, either Per/Ind or enalapril. According to blood pressure levels, the dose may be adjusted. In addition to clinical examinations, ECG, blood pressure, heart rate and laboratory assessments echocardiographic determinations are performed for selection, at baseline, after 24 weeks and at the end of the study. The main outcome criteria is the change from baseline in LVMI which is considered the primary efficacy criterion; changes in blood pressure and echo-Doppler parameters constitute secondary criteria. Two-sided Student's t-test for independent samples will be used to differentiate the effects of the treatment between groups with alpha = 5%, and the inter-group difference of LVMI variation will be analysed with a power of 90%. A sample size of 500 patients is required making it necessary to randomise at least 550 patients, based on a 10% proportion of potentially non-assessable patients. The results of this study, obtained after applying strict methodological procedures and requirements, are expected to provide valuable and reliable information on the effects of long-term administration of Per/Ind on LVH, and on its potential superiority over enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia.

BACKGROUND: Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. METHODS AND RESULTS: Fifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1. CONCLUSION: Patients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Adult↗
PubMed2000

[Guidelines for therapy of hypertension. One must know them--and apply them on an individual basis].

A target parameter for a cardiovascular risk in patients with hypertension is the lowering of the blood pressure. In 1999, the International Society of Hypertension (ISH) and WHO published new recommendations and redefined normal blood pressure values. When deciding the question what antihypertensive treatment for what patient, concomitant risk factors, hypertension related organ damage and contraindications must all be taken into account. The results of large prospective studies apply only in part for the majority of ambulatory patients. For the effective application of these recommendations and guidelines in the doctor's office, considerably more importance must be attached to the cooperation of all their "users"--including family doctors--when they are being established by a specialist society.

Antihypertensive Agents↗
PubMed1999

The First Cyclodiasteromeric

A mechanically linked molecule, consisting of an axle and two equivalent wheels, shows an analogous stereochemistry to the classical example tartaric acid. Though the components are not chiral themselves, a (cyclo)diastereomeric species is obtained, the enantiomers (shown schematically) and the meso form of which were completely separated and chiroptically characterized.

Journal Article↗
PubMed1997

Effect of bunazosin and atenolol on glucose metabolism in obese, nondiabetic patients with primary hypertension.

Antihypertensive drugs, recommended by the World Health Organization for use in monotherapy, exert different effects on glucose and lipid metabolism. In our study we compared the effects of the beta-blocker atenolol (AT) and the alpha1-blocker bunazosin (BU) on glucose metabolism. The doses administered were chosen to produce similar antihypertensive effects with both drugs. The study was conducted as a bicenter, parallel, controlled, and double-blind study. All patients suffered from mild to moderate primary hypertension, were obese (body mass index > 26 kg/m2), but were nondiabetic. After a drug-free period of 4 weeks, patients were treated either with 6 and 12 mg of bunazosin (n = 15) or with 50 and 100 mg of atenolol (n = 17) once daily for 12 weeks. Glucose metabolism was measured by the iv glucose tolerance test (GTT) and the euglycemic hyperinsulinemic clamp test. The results show a similar blood pressure reduction with both drugs. However, their effects on glucose metabolism were significantly (p < 0.05) different: The area under the curve (AUC) of glucose in the iv GTT increased 26.8% during atenolol treatment but decreased 30% during bunazosin treatment. The same influence on the AUC of insulin was observed [AT +478.5 +/- 441.8 (+22%) vs. BU, -588.5 +/- 411.1 (-22%)]. Similar changes were found in the glucose clamp test. The metabolic clearance rate increased 11.4% during bunazosin use and decreased 8.4% during atenolol use to the same degree that the insulin sensitivity index changed (BU +13.2% vs. AT -21.9%). The differences between the two treatment regimes were statistically significant (p < 0.05). These results in obese hypertensives confirm the well-known negative effects of beta-blockers on glucose metabolism. Additionally, they demonstrate that an alpha1-blocker such as bunazosin develops the same blood pressure-lowering effect as beta-blockers, but with a significantly better profile with regard to glucose metabolism. Therefore, the use of alpha1-blockers can be recommended for obese hypertensives without any special care for glucose metabolism.

Adrenergic alpha-Antagonists↗
PubMed1992

Pharmacological modulation of stress-induced cardiovascular hyperreactivity in essential hypertension.

The effects of the calcium antagonist isradipine and the beta-blocker metoprolol, which are based on different antihypertensive therapeutic principles, were evaluated in 52 men with mild-to-moderate hypertension in a 6-week, double-blind, randomized study. Mental stress-testing was performed before and after active treatment. With isradipine (n = 26), the stress-induced responses of cardiac output and total peripheral resistance were not significantly changed, but the blood pressure (BP) response, specifically the diastolic response, was decreased. With metoprolol (n = 26), there was a decreased response of cardiac output and an increased response of total peripheral resistance, and the BP response was even greater than it had been before treatment. Thus, these results indicate that beta-blockade is effective in reducing cardiac responsiveness but, because of vascular counterregulatory mechanisms, BP responsiveness is not decreased. In contrast, calcium antagonism preserves the physiological hemodynamic profile while reducing BP responsiveness to stress.

Calcium Channel Blockers↗
PubMed1991

[Cardiac involvement in non-Hodgkin's lymphoma].

In a 47-year-old man with non-Hodgkin's lymphoma which had been treated by polychemotherapy and radiation, cardiac involvement was suspected on computed tomography (CT) two years after diagnosis. The ECG demonstrated atrial flutter and a slow ventricular rate. After a further cycle of chemotherapy the patients declined further treatment. Two years later he was admitted urgently because of cardiac failure, atrial fibrillation with a slow ventricular rate, and clear signs of abnormal repolarization. CT of the thorax again provided signs of cardiac involvement with lymphoma. In addition there were extensive tumour infiltrates in the liver and paraaortic lymph-node. Despite intensive medical treatment he died shortly after admission from cardiac failure. At necropsy all four cardiac chambers and the coronary arteries were surrounded completely by tumour tissue. The membranous interventricular septum, the area of the Hiss bundle and the tricuspid and mitral valves had also been infiltrated. Histologically the infiltrates consisted of lymphoid cells of centrocytic type. Increasing tumour cell involvement went together with complete disintegration of myocardial fibres.

Arrhythmias, Cardiac↗
PubMed1990

[Significance of microproteinuria for early detection of hypertension-induced end organ damage].

To investigate the clinical importance of microproteinuria, we examined the prevalence of microproteinuria and its relation to cardiac structural adaptation in 80 male, middle-aged patients with essential hypertension. Patients with secondary causes of hypertension were ruled out. 14 out of 80 hypertensives (18 percent) were found to have microproteinuria defined as "negative" for urinary protein excretion in the conventional test, but "positive" (above the upper normal limit) in the 24-hour urine samples. Patients with microproteinuria had a similar age and body weight, but a higher systolic and diastolic pressure (161 +/- 14/104 +/- 12 vs 148 +/- 14/97 +/- 9 mmHg, p less than 0.02) and greater creatinine clearance (163 +/- 36 vs 136 +/- 33 ml/min, p less than 0.01) than those with normal protein excretion. Also, hypertensives with microproteinuria had a greater left ventricular mass (241 +/- 57 vs 207 +/- 45 g, p less than 0.05) and greater cross sectional area (22.2 +/- 2.8 vs 20.5 +/- 2.9 cm2, p less than 0.05) evaluated by 2-D guided M-mode echocardiography than the control group. A positive Sokolow-index was more prevalent in patients with microproteinuria than in those without (x2 = 6.2, p less than 0.02). Patients with essential hypertension and microproteinuria (prevalence 21 per cent) were characterized by a higher arterial pressure, by a higher degree of echocardiographic and electrographic evidence of left ventricular hypertrophy. Thus, microproteinuria might serve as a marker for early target organ damage in essential hypertension.

Adult↗
PubMed1990

Efficacy of long-term antihypertensive therapy with enalapril.

We examined whether long-term antihypertensive monotherapy with enalapril decreased clinical casual blood pressure (BP) as well as BP at work and during stress, and whether this angiotensin-converting enzyme (ACE) inhibitor had an adverse effect on the physiologic hemodynamic pattern during experimental mental stress. Seventeen male patients with hitherto untreated mild-to-moderate essential hypertension (mean age: 47 +/- 8 years) had 24-hour BP monitored noninvasively with the Physioport system before and during treatment with enalapril (5-10 mg/day) for 6 months. They also had a mental stress test, physical exercise test, and the cold pressor test before and after therapy. After the diagnostic observation period, average clinical casual BP was 150 +/- 12/102 +/- 7 mg Hg. Average BP at work, stress BP during all types of stimulation in the laboratory, and clinical casual BP significantly decreased during monotherapy with enalapril. Neither the circadian rhythm nor the hemodynamic pattern during mental stress was significantly altered by enalapril. BP increases during emotional stress were not significantly attenuated by the ACE inhibitor. These results demonstrated that enalapril effectively lowers BP without altering the physiologic hemodynamic pattern during emotional stress.

Adult↗
PubMed1989

Disparate hemodynamic and sympathoadrenergic responses to isometric and mental stress in essential hypertension.

The hemodynamic and sympathoadrenergic responses during isometric handgrip and mental arithmetic tests were compared in 18 patients with mild essential hypertension. Mean blood pressure increased significantly after both maneuvers (27% during isometric stress and 10.7% during mental stress), but the increase was significantly higher during isometric stress (p less than 0.001). Both stressors increased the heart rate (p less than 0.001) and cardiac output (p less than 0.001). However, the total peripheral resistance behaved differently, for it increased during isometric stress (p less than 0.05) and remained unchanged during mental stress. Both stressors increased the epinephrine levels (p less than 0.005), but only isometric stress increased the norepinephrine levels (p less than 0.001). It is concluded that both stressors increase cardiac output by way of an increase in heart rate, but isometric stress also increases total peripheral resistance and thus causes a greater increase in arterial pressure. Isometric stress activates both the adrenergic and noradrenergic systems, thereby accounting for the exaggerated response in arterial pressure, whereas mental stress stimulates the adrenergic system only.

Adolescent↗
PubMed1989

Standardized stress testing in the cardiovascular laboratory: has it any bearing on ambulatory blood pressure values?

We examined 77 males (mean age 45 years; mean casual blood pressure 139/94 mmHg; no secondary hypertension) to evaluate the relationship between cardiovascular measures from standardized stress testing (mental arithmetic, cold pressor test) in the laboratory and 24-h ambulatory recordings of blood pressure and the heart rate. The basic relationship between laboratory and ambulatory recordings was calculated by correlating the mean of our laboratory values with 24-h mean ambulatory values. Laboratory readings of baseline and stress systolic blood pressure, diastolic blood pressure and the heart rate correlated significantly (P less than 0.05) with ambulatory recordings of 24-h means and short-period means (e.g. baseline systolic blood pressure with work mean, r = 0.33; with mean, r = 0.33). However, the correlations were no closer than the basic relationship between laboratory examinations and ambulatory recordings (r = 0.41 for systolic blood pressure; r = 0.46 for diastolic blood pressure; r = 0.43 for heart rate). There was no specifically close correlation between laboratory baseline and the corresponding ambulatory rest phase (evening, sleep) or between laboratory stress values and ambulatory phases of high demand (work mean). Reactivity measures in the laboratory (stress values-baseline values) were correlated to measures of variability in ambulatory recordings (standard deviation; coefficient of variation; maximum, minimum value; range), but, again, there was no specific effect separating similar from non-similar phases. We conclude that laboratory measures have no specific bearing on ambulatory blood pressure and heart rate measures.

Blood Pressure Determination↗
PubMed1988

Hemodynamic response patterns to mental stress: diagnostic and therapeutic implications.

Stress has been identified as contributing to the development of cardiovascular disease. The pathophysiologic link between stress and disease still remains unclear. Because experimental stress testing in the laboratory permits the examination of the underlying mechanism for stress-induced blood pressure, analyses of cardiovascular reactivity during emotional stress could be of particular clinical importance. The analyses of pooled data during the past 6 years (n = 298, age from 20 to 60 years, normotensive subjects as well as patients with borderline and mild essential hypertension) reveal that stress-induced changes in stroke volume and especially in total peripheral resistance are crucial parameters to analyze the hemodynamic stress response. However, neither those simple nor complex response patterns such as "hot reactor" describe clinically distinct subgroups of persons. When physiologic testing was repeated in hypertensive patients after effective long-term antihypertensive therapy with clonidine, oxprenolol, nitrendipine, or enalapril, no attenuation of the stress-induced increase in blood pressure was found in any of these groups. However, heart rate reactivity and stress-induced changes in total peripheral resistance were altered significantly by oxprenolol and nitrendipine. The beta-adrenoceptor blocker decreased heart rate reactivity and increased reactivity of peripheral resistance; the calcium antagonist decreased stress-induced changes in peripheral resistance and increased the heart rate response. The centrally acting sympatholytic regimen and the angiotensin-converting enzyme inhibitor had no impact on the hemodynamic response pattern during emotional challenge.

Adult↗