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Biomedical subjects

M Middeke

Publications and source records attributed to M Middeke.

89 records · Page 5Linked to original sources
PubMed1988

Review of major intervention studies in hypertension and hyperlipidemia: focus on coronary heart disease.

The ultimate aim in treating hypertension and hyperlipidemia is to reduce cardiovascular mortality and morbidity, especially strokes and coronary events, for example, fatal and nonfatal myocardial infarction and sudden death. Extensive intervention studies in moderate-to-severe hypertension have revealed the significance of antihypertensive therapy in reducing total cardiovascular mortality and morbidity, particularly from cerebrovascular causes. However, the reduction of coronary events has not been equally successful. The situation in mild-to-moderate hypertension is even more disappointing: recent studies, such as the Medical Research Council hypertension trial, the international Prospective Primary Prevention Study in Hypertension, and the Heart Attack Primary Prevention in Hypertensives trial could not demonstrate any benefit from antihypertensive treatment with beta-blockers or diuretics in the prevention of coronary heart disease. The reasons for these negative results are not obvious. However, metabolic side effects associated with certain antihypertensive drugs, which counteract the beneficial effects of blood pressure reduction, are one topic of discussion. For the genesis of atherosclerosis of the coronary vasculature, hyperlipoproteinemia appears to be of greater importance than hypertension and has to be treated simultaneously. Two extensive intervention studies, the Lipid Research Clinics coronary primary prevention trial and the Helsinki Heart Study, showed a significant reduction of coronary events with lipid-lowering treatments with cholestyramine and gemfibrozil, respectively. These findings are in agreement with the results of a recent secondary prevention study, which showed a regression of atherosclerosis in coronary arteries and aortocoronary bypass grafts. Moreover, antihypertensive treatment aimed at a reduction in coronary heart disease has to focus on serum lipids, especially in mild hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Unexplained edema in females--diuretic-induced or idiopathic?].

Both women with diuretic induced edema and with idiopathic edema present a typical history leading to the diagnosis in most cases. These women are almost exclusively in the reproductive age and they tend to have some other characteristics in common additionally. There is controversy whether idiopathic edema exists as a syndrome with multifactorial pathogenesis or if fluid retention in these women is due to diuretic abuse. In either case the use of diuretics is not indicated as they can increase and perpetuate the edema and moreover may bring about impairment of renal function. Abstinence of diuretic intake is the only way out of the vicious circle of fluid retention induced by intermittent diuretic intake resulting in intermittent edema and prostrained use of diuretics. Therapy of idiopathic edema is difficult; it includes physical therapy, psychotherapy and pharmacotherapy with aldosterone antagonists or ACE-inhibitors in some severe cases.

Diuretics↗
PubMed1987

Serum lipoproteins during antihypertensive therapy with beta blockers and diuretics: a controlled long-term comparative trial.

The influence of hydrochlorothiazide and atenolol on serum lipoproteins was investigated in a randomized, prospective study on 68 men with essential hypertension. Cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDH) cholesterol, triglycerides, and the apolipoproteins AI and B were followed up to 42 months after starting therapy. Following atenolol serum (HDL) cholesterol decreased and serum triglycerides increased significantly (p less than 0.01) from 6 to 42 months. After hydrochlorothiazide serum triglycerides, LDL cholesterol and total cholesterol all increased significantly (p less than 0.01) from 12 to 42 months. The changes were more pronounced under higher doses with beta blockade, but not with diuretics. Thus, both atenolol and hydrochlorothiazide have adverse but different effects on serum lipoproteins after long-term administration. Continuing investigation is necessary to determine whether these side effects decrease the benefit of blood pressure reduction in patients with hypertension.

Adult↗
PubMed1985

[Digitalis therapy: prescription frequency, serum concentrations and withdrawal trials].

The frequency of therapy with digitalis glycosides was determined in 4.143 patients on their first visit at a medical outpatient clinic. 508 (12.3%) patients said to take digitalis. Of 480 (94.5%) patients, a digoxin serum concentration was obtained. It was in 229 (47.7%) patients below, in 31 (6.5%) above, and in 220 (45.8%) within the therapeutic range (0.8-2.0 ng/ml). From the 251 patients with a serum digoxin concentration greater than or equal to 0.8 ng/ml, 220 (87.7%) were not included in a withdrawal trial on the basis of predetermined criteria, mainly because of cardiac diseases (52%). Digitalis therapy was withdrawn in 31 patients. 5 patients started to take the drug again on their own; they were considered drop-outs. In the remaining 26 patients, no symptoms of heart failure appeared during a 3-month observation period; in 2 patients, however, atrial fibrillation requiring intervention occurred. Our results confirm the frequent use of digitalis therapy in Germany, but also the frequent presence of subtherapeutic serum digoxin concentrations. Withdrawal should be considered in patients with a questionable indication for this therapy; the occasional occurrence of supraventricular arrhythmias, and not so much of heart failure, should be anticipated.

Aged↗
PubMed1985

Adrenergic hyposensitivity during long-term diuretic therapy--a possible explanation for the antihypertensive effect of diuretics?

The long-term effect of hydrochlorothiazide on beta 2-adrenoceptor density on mononuclear cells was investigated in 10 male patients with essential hypertension. There was a 40% reduction in beta 2-adrenoceptor density but no change in receptor affinity. This down-regulation of beta 2-adrenoceptors may explain the observed adrenergic hyposensitivity after long-term diuretic therapy. If lymphocytic beta 2-adrenoceptors represent presynaptic beta-adrenoceptors, a down-regulation of presynaptic beta 2-receptors may occur too, and result in a decrease of adrenergic transmitter release. Under this assumption long-term diuretic treatment causes its antihypertensive effect by modulating adrenergic sensitivity at the receptor level on the presynaptic side leading to an attenuated response to pressor hormones on the postsynaptic vascular side.

Adult↗
PubMed1985

Partial nephrectomy and furosemide in toxic and ischemic nonoliguric acute renal failure in rats.

Reduction of the renal mass causes similar tubulo-dynamic changes as furosemide, e.g., hyperperfusion of the single nephron. Therefore, the effect of 5/6 nephrectomy (NX) and furosemide (F) either alone or in combination was evaluated in nonoliguric acute renal failure, using two toxic (glycerol and HgCl2) and one ischemic model. In the HgCl2 model, NX and F alone had a protective effect on whole kidney function, e.g., the increase in serum creatinine was smaller as compared to control rats. NX plus F was followed by the lowest mortality and the smallest increase in serum creatinine. A significant increase in mercury excretion was observed following NX plus F. In the ischemic model, NX and F had no protective effect-when combined, they even enhanced renal insufficiency. The outcome of animals treated with glycerol is neither modified by F nor by NX, although both interventions induced a significant increase of glycerol excretion. It seems that the beneficial effect of 5/6 NX and F depends on the type of acute renal failure (ARF) and the models used, and that the elimination of a toxic agent is not the common pathway of protection in the HgCl2-and the glycerol-induced ARF.

Acute Kidney Injury↗
PubMed1984

The influence of sex, age, blood pressure and physical stress on beta 2-adrenoceptor density of mononuclear cells.

The influence of sex, age, blood pressure and physical stress on beta 2-adrenoceptor density on intact mononuclear cells was investigated in normotensives and in patients with essential hypertension using (+/-) 125-iodocyanopindolol as radio-ligand. The intra-individual receptor status under basal conditions at rest was fairly constant. The mean individual deviation of beta 2-adrenoceptor density was 11% after a time period of 3 +/- 1.9 months. The receptor number increased with age: there was a positive correlation (r = 0.59) between age and beta 2-adrenoceptor density. No significant difference existed between men and women matched for age and mean arterial blood pressure (548 +/- 179 versus 481 +/- 246 maximal binding sites per cell). A highly significant positive correlation (r = 0.73) existed between the mean arterial blood pressure and the beta 2-adrenoceptor density over a wide range of normal and increased blood pressure. A factorial analysis revealed a significant correlation between mean arterial pressure and beta 2-adrenoceptor density, but not between age or sex and beta 2-adrenoceptor density. Physical stress led within 15 min to a significant increase in beta 2-adrenoceptors followed by a fall to or even below the starting values after 15 to 30 min rest. It is concluded that beta 2-adrenoceptor density on intact mononuclear cells correlates significantly with mean arterial blood pressure and with age. However, factorial analysis revealed a significant positive correlation only between mean arterial blood pressure and the receptor number but not between age and the receptor number. Sex has no significant influence on the receptor density.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Blood pressure during isometric and dynamic exercise under long-term antihypertensive treatment with beta receptor blockaders and diuretics].

In 34 men with essential hypertension the increase in blood pressure during static and dynamic exercise, after long-term antihypertensive medication, was investigated in a randomized prospective study. The patients were randomized to either hydrochlorothiazide or to atenolol. The exercise tests were performed after a mean treatment duration of 14 months. At this time, the entering blood pressure was significantly and equally lowered from 163/108 to 148/96 mm Hg with a mean dose of 71 mg hydrochlorothiazide and from 164/108 to 147/91 mm Hg with a mean dose of 144 mg atenolol. The heart rate was significantly lower under beta-blocker therapy (62 min-1) than with diuretics (78 min-1). There were no significant differences in the systolic and diastolic blood pressure rise between the two therapy groups during static exercise with the hand grip (33% of the earlier determined individual maximum for 2 min duration) and with the squatting technique (for 2 min). During dynamic exercise on the bicycle ergometer (50-100 W) the increase in the systolic blood pressure was significantly lower between 70 and 100 W, with a range from 12 to 28 mm Hg, in the beta-blocker group than in the diuretic group. There were no differences in diastolic blood pressure between the two therapy groups. Rate-pressure product as a parameter for the myocardial oxygen consumption and heart rate were significant lower in the beta-blocker group as compared with the diuretic group, at rest and during both kinds of exercise and at all exercise steps.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1983

Beta 2-adrenoceptor density on membranes and on intact mononuclear cells in essential hypertension.

Alterations in the status or in the regulation of adrenoceptors may contribute to essential hypertension. This could be studied using the recently introduced radio-ligand binding techniques to characterize the adrenoceptors on human peripheral blood cells. The present study shows that patients with essential hypertension have a twofold increase of beta 2-adrenoceptor density on intact mononuclear cells as compared to normotensive controls: 859 +/- 260 (n = 10) vs. 420 +/- 119 (n = 10) maximal binding sites for (+/-) 125-Iodocyanopindolol expressed as molecules per cell (P less than 0.001). Furthermore, there is a highly significant correlation (r = 0.86) between the calculated mean arterial blood pressure and the beta 2-adrenoceptor density over a wide range of normal and increased blood pressure. These findings could only be demonstrated with intact mononuclear cells but not with membrane fractions. No difference was found in receptor affinity between patients with essential hypertension and normotensive controls. Thus, essential hypertension is combined with a higher beta 2-adrenoceptor density on intact mononuclear cells which might represent, for example, an increased density of prejunctional beta 2-adrenoceptors. Mean arterial blood pressure is positively correlated with beta 2-adrenoceptor density over a wide range of blood pressure in normotensives and hypertensives. The expression of beta 2-binding sites on the cell surface is possibly altered in essential hypertension resulting in a disparity between intracellular and extracellular binding sites as compared with normotensives.

Adult↗
PubMed1981

[Potassium metabolism during antihypertensive treatment with beta-receptor blocker and diuretic treatment].

In a controlled, prospective, cross-over study 15 patients with essential hypertension received for four weeks either a combination of beta-receptor blocker and diuretic (twice 10 mg pindolol and 5 mg clopamide daily) or of three drugs: beta-receptor blocker, diuretic and sodium-preserving diuretic (twice daily 10 mg timolol, 25 mg hydrochlorothiazide and 2.5 mg amiloride). Both drug combinations produced quantitatively comparable and definite blood pressure lowering from 162/102 mmHg to 128/82 and 130/82, or 130/84 and 127/82, respectively, after two and four weeks. A significant fall in serum potassium from 4.24 to 3.77 and 3.92 mmol/l occurred with the combined two drugs but not the combination of three. With the two-drug combination renal potassium excretion was significantly raised at one of two control points in time. Heart rate remained constant with the two-drug treatment but fell significantly on three-drug administration. There were more side effects with the two-drug preparation. Combinations of beta-receptor blockers and diuretics are thus by no means potassium neutral but can cause renal potassium loss, fall in serum potassium and hypokalaemia. For this reason combining potassium-sparing diuretic with beta-receptor blocker and diuretics is reasonable and justified.

Adrenergic beta-Antagonists↗
PubMed1980

[New developments in diagnosis and treatment of renovascular hypertension (author's transl)].

Catheter-dilatation (percutaneous Transluminal Angioplasty=PTA) of renal artery stenoses can be applied successfully and without major risk even in patients with high operative risks. Therefore, the indication for the diagnostic evaluation of renal artery stenosis should be expanded to all patients suspected to have renovascular hypertension. Excretory urography combined with angiotomography offers the possibility to visualize the renal arteries and to either detect or exclude arterial stenosis. In the first part results of this procedure are presented. The bolus injection have been carried out on 415 patients without any serious side-effects. Using angiotomography 49 renal artery stenoses, 1 aneurysm and 1 AV fistula could be detected. Catheter-angiograms, angiotomograms and conventional rapid sequence urograms were compared in 91 patients. For angiotomography a sensitivity for the presence of renal artery stenosis of 93% and a specifity for the absence of arterial stenosis of 99% can be attained. In the second part, the results of PTA of renal artery stenoses in 35 patients are described. PTA was technically successful in 29 patients (83%). Three clinically silent complications are reported. In a mean follow-up period of 8,2-months, hypertension was normalized in 13 (45%) and improved in 10 (34%) patients. Renal insufficiency could be normalized in 7 out of 11 patients. These results make PTA the method of choice in treating renovascular hypertension. Only if this method is not applicable or technically not feasible, is the alternative for treatment surgical revascularization or conservative antihypertensive therapy.

Adult↗
PubMed1978

Nephroblastoma and neuroblastoma--histology and prognosis.

Statistically evaluating the influence of a histological grading, respectively of morphological differences on prognosis of nephroblastomas and neuroblastomas, better chances for survival become evident not only for earlier clinical stages, but also for nephroblastomas with high differentiation, or neuroblastomas with signs for differentiation. Only for neuroblastomas a relevant predeliction of tumors with signs of differentiation for the early clinical stage I is present. Combined subclassification according to clinical stages and histological grades results in 3 risk groups with different chances for survival. These 3 groups may play a role for specific therapeutic considerations.

Child, Preschool↗
PubMedDate not supplied

Comparison of the efficacy and safety of losartan (50-100 mg) with the T-type calcium channel blocker mibefradil (50-100 mg) in mild to moderate hypertension.

The objective of this study was to compare the antihypertensive efficacy and safety of losartan and mibefradil. 324 outpatients (57 +/- 9.2 years) with mild to moderate hypertension were randomly allocated in a double-blind fashion to receive 50 mg of losartan or mibefradil once daily p.o. for 6 weeks after 2 weeks of placebo run-in. Titration was then forced to 100 mg of losartan or mibefradil for an additional 6 weeks. Patients were assessed at baseline, 6 and 12 weeks. The primary efficacy variable was change in predose sitting diastolic (SDBP) and systolic (SSBP) blood pressure at 12 weeks. Secondary variables included change in mean 24-hour ambulatory blood pressure and comparison of safety and tolerability. Both treatments lowered SSBP and SDBP at 6 and 12 weeks (week 6: mibefradil -14/-9 mm Hg; losartan -12/-7 mm Hg) (P <0.001). The primary objective, a difference between treatments in reduction of SSBP and SDBP at week 12 could be demonstrated (mibefradil -22/-16 mm Hg; losartan -16/-10 mm Hg) (P=0.003 and P=0.001, respectively). Twenty-four-hour SBP and 24-hour DBP were reduced (P<0.001) within each treatment group at weeks 6 and 12. The secondary objective, a difference between treatments in reduction of 24-hour blood pressure at week 12 could be demonstrated (P<0.001). Twenty-four-hour heart rate was lowered in the mibefradil group at weeks 6 and 12 (P < 0.001). Responder rates at 6 and 12 weeks were 56.2% and 78.5% for mibefradil versus 56.1% and 55.3% for losartan (P = 0.001). Both treatments were equally well tolerated. This study demonstrates that 50 mg losartan is comparably effective to 50 mg mibefradil in the treatment of mild to moderate hypertension with 100 mg mibefradil being more potent than losartan.

Adolescent↗
PubMedDate not supplied

Normalization of lipid metabolism after withdrawal from antihypertensive long-term therapy with beta blockers and diuretics.

Blood pressure and serum lipoprotein concentrations were assessed in 40 men with essential hypertension at the end of a long-term, controlled intervention study (HAPPHY) after 5.2 +/- 1.4 years of treatment with hydrochlorothiazide (n = 23) or atenolol (n = 17) and after a wash-out period. After withdrawal from antihypertensive medication, the blood pressures of patients treated with diuretics or beta blockers rose from 142/93 and 145/91 to 159/106 and 165/104 mm Hg, respectively. At the same time, low density lipoprotein cholesterol decreased by 17 and 12 mg/dl, respectively, in the diuretic and beta blocker groups (p less than 0.05). In addition, total cholesterol decreased by 16 mg/dl (p less than 0.05) in the diuretic group, whereas high density lipoprotein cholesterol increased by 8 mg/dl (p less than 0.01) and triglycerides decreased by 27 mg/dl (p less than 0.05) in the beta blocker group at the end of the wash-out period as compared to the final phase of the HAPPHY study. The data indicate the persistence of lipid changes during long-term treatment with hydrochlorothiazide and atenolol. For the first time, it was clearly demonstrated that the well-known unfavorable effects of diuretics and beta blockers on lipid metabolism are reversible after cessation of long-term therapy of several years' duration.

Antihypertensive Agents↗