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Biomedical subjects

M Lehmann

Publications and source records attributed to M Lehmann.

At least 235 records · Page 13Linked to original sources

Catecholamine metabolism in patients with congestive heart failure under acute and chronic oral levodopa therapy.

Catecholamine metabolism was assessed in 14 patients with chronic congestive heart failure (NYHA class IV; cardiac index 2.4 +/- 0.2 l min-1, ejection fraction 20 +/- 11%) on levodopa (L-Dopa-ratiopharm) treatment: 1. prior to the start of levodopa treatment; 2. following acute administration of levodopa in the 14 patients and in 4 healthy control subjects; 3. after 30 days +/- 1 day with 2-4 g levodopa p.o. daily in the group of patients. Only a minority of the patients showed sustained clinical and/or hemodynamic improvement. Free and conjugated plasma dopamine and urinary/excretion of dopamine increased 20- to 40-fold in the group of patients and in the healthy control subjects subsequent to levodopa administration. An increase in noradrenaline and adrenaline levels (conjugated plasma fractions and urinary excretion of free noradrenaline and adrenaline) was only observed in the healthy control subjects, but not in the group of patients. Free noradrenaline and adrenaline plasma fractions did not show any significant change on levodopa treatment, either in the group of patients or in healthy control subjects. Clinical and hemodynamic changes seen on levodopa treatment are related to elevated dopamine concentrations. The lack of increase in noradrenaline and adrenaline in the group of patients may be related to reduced activity of dopamine-beta-hydroxylase in patients with congestive heart failure NYHA class IV.

Administration, Oral↗

[Possibilities of computerized arthrotomography in the diagnosis of shoulder instabilities].

Shoulder instability can usually be diagnosed by examination of the history and a careful physical examination. Additional diagnostic studies include radiographic investigations and arthroscopy as a functional and very comprehensive diagnostic procedure for shoulder lesions. Conventional radiographic investigations with special projections have proven to be reliable in revealing bony changes of the glenoid and of the humeral head, whereas CT arthrography is very helpful in evaluating capsulolabral lesions associated with shoulder instability. This kind of investigation is a highly sensitive and less invasive technique. Combined with intraarticular application of contrast medium the extent of pathologic changes associated with instability can be imaged and differentiated from other intraarticular causes of dysfunction. During a 1-year period, 42 patients were studied by double contrast arthrography followed by CT examination, and 33 were found to have a shoulder instability. The intention of this report is to describe a few CT arthrographic findings in the presence of pathologic anatomy of unstable shoulders.

Adolescent↗

Ecdysteroid receptors of the blowfly Calliphora vicina. Characterization of binding to nonspecific DNA.

Ecdysteroids, the molting hormones of arthropods, act like vertebrate steroid hormones by binding to an intracellular receptor protein. We have recently isolated a protein from nuclei of blowfly larvae which has satisfied the requirements of an ecdysteroid receptor. The receptor was partially purified and its ecdysteroid-binding properties were characterized. The availability of receptor preparations which have been stabilized by partial purification now enables us to study the general DNA-binding properties of ecdysteroid receptors. DNA-binding characteristics of ecdysteroid receptors were studied with calf thymus DNA. Affinity for DNA was observed both in the presence and in the absence of steroid ligand but the ligand clearly enhanced binding of receptors to DNA. Receptor preparations contained a heterogeneous mixture of receptors; up to 25% of DNA-binding receptors, and nonbinding forms of ecdysteroid receptors. The ability to bind to DNA was subject to inactivation which was not affected by partial purification, but which could be decelerated by dilution of the receptor preparation. Thus, dilution resulted in a spurious activation of DNA binding. A genuine activation, which would have led to an increase in the percentage of the DNA-binding form of the ecdysteroid receptor complex, was not observed.

Animals↗

Copy number and distribution of P and I mobile elements in Drosophila melanogaster populations.

The distribution of the number of copies of P and I transposable elements per genome was investigated by in situ hybridization for a large set of Drosophila melanogaster strains. These included the P, Q and M' types of the P-M system of hybrid dysgenesis. P element copy number varied widely (range 5-59). P and Q strains had around 40 copies whereas M' strains generally had lower numbers (between 5 and 35) with one extreme value (52). The copy number of I elements appeared to be precisely regulated, as no strains were found outside the 15 +/- 5 range. The number of copies of the two families were independent. An excess of P copies on the X chromosome compared with the autosomes was found for the P and Q strains, but not for M' strains. Among X-inserted P sites, a very high frequency of occupation was found at the tip of the X chromosome (cytological site 1A), especially for P and Q strains. The possible regulatory role in the P-M system of X-inserted P sites is discussed.

Animals↗

Comparison of the regulation of P elements in M and M' strains of Drosophila melanogaster.

M and M' strains of Drosophila melanogaster in the P-M system of hybrid dysgenesis were compared in two series of tests, with the following results. (1) The singed-weak hypermutability regulation test showed that M' strains had lower P excision rates than M strains, suggesting that P-elements repression must occur in M' strains although it is not detectable by gonadal dysgenesis assays. (2) The evolution of mixed P+M and mixed P+M' populations was compared, using a strong P strain. The P+M cultures invariably evolved in a few generations into strong P cultures, while the P+M' cultures evolved into P-type cultures with reduced P-factor potentials. However, after 30 generations of culture, both these types of mixed cultures had similar P copy numbers, suggesting that regulation of copy number had occurred in them.

Animals↗

Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. A double-blind, placebo-controlled trial.

To discover the underlying mechanisms involved in the beneficial long-term effects of angiotensin converting enzyme (ACE) inhibitors, we investigated the systemic and peripheral effects of short- and long-term ACE inhibition in patients with chronic heart failure. After assessing the short-term effects and dose titration with cilazapril, a new long-acting ACE inhibitor, 21 patients were randomized to receive either placebo or the ACE inhibitor. Seventeen patients completed the 3-month treatment. Central hemodynamic output, femoral blood flow (measured by thermodilution), oxygen saturation, and lactate and norepinephrine levels were determined simultaneously in the femoral vein and radial artery during treatment and after a 3-month rest and during symptom-limited bicycle exercise. Short-term ACE inhibition improved rest and exercise hemodynamic output, but it did not alter peak femoral blood flow, calculated leg oxygen consumption, or systemic oxygen uptake during exercise, despite significant reduction in femoral norepinephrine extraction and arterial angiotensin levels during exercise. In contrast, long-term ACE inhibition further improved exercise cardiac output and increased leg blood flow (from 2.3 to 2.9 l/min, p less than 0.05), leg oxygen consumption (from 277 to 403 ml/min, p less than 0.05), and systemic oxygen uptake (from 1,133 to 1,453 ml/min, p less than 0.05), whereas these variables remained unchanged with placebo treatment (p less than 0.02 between groups). Moreover, a moderate but significant increase in femoral oxygen extraction occurred after long-term therapy (ACE inhibitor: from 76% to 83%, p less than 0.05; placebo: from 75% to 74%, NS; p less than 0.01 between groups). We conclude that long-term ACE inhibition is clinically beneficial in that it improves blood flow to skeletal muscle during exercise over time. The long-term effects of ACE inhibition are, in part, probably related to peripheral (vascular) mechanisms, for example, by reversing the inability of peripheral vessels to dilate and by improving oxygen utilization.

Angiotensin-Converting Enzyme Inhibitors↗

Myocardial energetics in patients with dilated cardiomyopathy. Influence of nitroprusside and enoximone.

Cardiotonic agents influence myocardial energy consumption by vasodilation, which may reduce energy demand, and by inotropism, which may increase it. To distinguish between the two effects, myocardial oxygen consumption must be analyzed in relation to its hemodynamic determinants. The coupling of myocardial oxygen consumption with its determinants was investigated in 22 patients with idiopathic dilated cardiomyopathy (NYHA Class II and III). Predicted myocardial oxygen consumption by the pressure-work index, the Bretschneider index, and the pressure-volume area correlated moderately with measured myocardial oxygen consumption (r = 0.57, p less than 0.001; r = 0.52, p less than 0.005; and r = 0.63, p less than 0.001). Multiple regression analysis, including left ventricular peak systolic wall stress, systolic stress-time integral, pressure-volume work, maximum rate of left ventricular pressure rise, and mean velocity of circumferential fiber shortening indicated that systolic stress-time integral is the major determinant of myocardial oxygen consumption (r = 0.75, p less than 0.001) in these patients. Enoximone, a phosphodiesterase inhibitor, has an inotropic and a vasodilating effect. To investigate the inotropic portion of the energy cost of this phosphodiesterase inhibitor, the influence of enoximone on myocardial oxygen consumption and systolic stress-time integral was compared with the effects of nitroprusside, which is a vasodilator only. Nitroprusside (10 patients) and enoximone (12 patients) reduced left ventricular systolic stress-time integral from 109 +/- 22 to 71 +/- 21 (p less than 0.005) and from 104 +/- 23 to 42 +/- 10 (p less than 0.001) 10(3) dynes.sec/cm2, respectively. Myocardial oxygen consumption decreased from 159 +/- 44 to 112 +/- 23 (p less than 0.005) and from 134 +/- 28 to 109 +/- 21 (p less than 0.001) microliters/beat/100 g, respectively. In both groups, there was a significant correlation between the decrease in myocardial oxygen consumption and the decrease in systolic stress-time integral. The slopes of the respective linear regression lines were significantly different (1.27 for nitroprusside and 0.51 nl.cm2/100 g.dynes.sec for enoximone, p less than 0.05), indicating a smaller decrease of myocardial oxygen consumption for a given decrease of stress-time integral with enoximone. Applying the pressure-work index or the pressure-volume area instead of systolic stress-time integral yielded comparable results. Thus, vasodilation reduces myocardial oxygen consumption in proportion to the reduction of stress-time integral. With enoximone, the energy-saving effect of vasodilation is counteracted in part by the increased energy d

Adult↗

[Regression of hypertension-induced left heart enlargement in an endurance athlete treated with verapamil RR].

In October 1987, Stage II arterial hypertension, probably of primary genesis, was diagnosed in a 52-year-old male patient. There was marked left-ventricular hypertrophy (left-ventricular muscle mass 224g, corresponding to 2.99 g/kg: mass-volume ratio of the left ventricle 1.9 g/ml; end-diastolic septum thickness 15 mm, posterior wall thickness 13 mm). The patient is engaged in endurance sports for 5-12h each week and participates regularly in competitions. He was not advised to terminate athletic activities. The patient's submaximum performance (supine ergometry) is 3.3 watts per kg body weight. Under therapy with 2 x 240 g Verapamil per day, blood pressure decreased in the course of a year by 30/30 mm Hg at rest and 30/20 mm Hg at a specified exercise level. The left ventricular muscle mass decreased by about 70g, the mass-volume ratio normalized to 1.3 g/ml.

Blood Pressure↗

Plasma catecholamine and cardiovascular responses to nifedipine in hypertensives WHO-stage II.

77 patients with arterial hypertension were consecutively examined. An evaluable echocardiogram could be recorded for 75 patients. 54 (72%) had non-pathological cardiac findings, 15 (20%) showed concentric left ventricular hypertrophy of the heart (mean left ventricular muscle mass (LVM) 2.5 g/kg or 113 g/m2; mean LVM/EDV 1.6 g/ml). 6 patients had an excentric hypertrophy of the left ventricle (8%). The influence of 10 mg nifedipine (Adalat) sublingual on the heart, blood pressure and sympathetic activity was examined in 15 patients with left ventricular hypertrophy of the heart. 5-10 min after administration, a significant decrease in systolic and diastolic pressures (p less than 0.05) and an increase in plasma noradrenaline (p less than 0.05) and heart rate (p less than 0.01) could be registered. The thickness of the posterior wall and septum decreased in 8 to 10 of the 15 patients, EDV, shortening fraction and ejection fraction increased in 8 of the 15 patients. A reduction in peripheral resistance, sympathetic counterregulation accompanied by an increase in heart rate, shortening and ejection fractions with increased enddiastolic volume and decrease in wall thickness can be observed as the gross effect in the majority of the 15 patients with left ventricular concentric hypertrophy. The decrease in wall thickness as a relaxation effect should not be confused with a regression of hypertrophy, whereby the mass-volume ratio shifts toward the normal range under nifedipine.

Administration, Sublingual↗

[Hypertension, the heart and physical activity (sports)].

Cross-sectional analyses show a lower incidence of hypertension among endurance athletes compared to the general population, but not among strength athletes or high-performance swimmers. The favorable influence of increased physical activity of the endurance type on cardiovascular regulation is based on peripheral adaptation processes with a reduction in sympathetic tone and elevation of parasympathetic tone. The results are a reduction in catecholamine release, in heart rate, and in mean arterial pressure at the same exercise level. Following chronic strength training there is also a slight reduction in catecholamine levels at the same time the vagal activity decreases, so that no reduction in heart rate and pressure, and thus no economization of cardiac work results. Thus, endurance training is suited for prevention and also for the reduction of blood pressure in primary hypertension and for cardiac relief, while strength training is not. In the case of hypertension, physical activity may only be engaged in when the cardiac functional status and other organ impairments are known. The stages of cardiac adaptation and damage, particularly the differentiation between concentric and eccentric hypertrophy, are particularly important. Exercise ECG and echocardiography are therefore obligatory measures prior to initiating physical activity and for continuous monitoring of hypertension. In primary hypertension Stage I (70-80% according to WHO), in which no cardiac hypertrophy is present, endurance training may be started without drug therapy if diastolic pressure is not greater than 104 mmHg and systolic pressure up to 170 mmHg (mild hypertension). Additional drug therapy does not show any convincing advantages. Higher pressures require adjuvant drug therapy. In concentric cardiac hypertrophy (Stage II), there is clear indication for the use of hypotensive drugs. An endurance sport is to be recommended additionally after normalization of blood pressure; the regression of cardiac hypertrophy should be examined within one year. In eccentric hypertrophy (damage stage), "training" is not indicated in addition to drug therapy, but rather physical therapy according to defined exercise capacity. The selection of medications for reducing blood pressure in sportsmen must take into consideration that they have varying performance limiting effects, which may be an essential factor in compliance.

Blood Pressure↗

Serum phosphate concentration. Effect on serum ionized calcium concentration in vitro.

We examined the effects of variations of serum phosphate levels on serum ionized calcium concentrations in vitro. A single donor serum sample was divided into 25 aliquots stored in tubes sealed with carbon dioxide and divided into 5 subsets of tubes. The pH was altered in 4 of the 5 subsets by adding various concentrations of hydrochloric acid or sodium hydroxide. The pH levels studied ranged from 7.09 to 7.63. The phosphate concentration was altered in each subset by adding various concentrations of a phosphate buffer. The phosphate concentrations studied ranged between 0.81 and 3.58 mmol/L. There was an inverse relationship between ionized calcium and phosphate at all pH levels studied. The ionized calcium concentration correlated inversely with pH. We suggest that in addition to factors well known to influence serum ionized calcium concentration (such as protein, bicarbonate, and pH values), serum phosphate concentration also plays an important role.

Calcium↗

Monoclonal glucose-oxidase-anti-glucose-oxidase (GAG) immunosandwich assay for the detection of monoclonal antibodies on routine hematological smears.

A murine monoclonal antibody specific for aspergillus niger glucose oxidase has been prepared and used in an unlabeled antibody bridge technique for the detection of monoclonal antibodies. This procedure--the monoclonal glucose oxidase anti-glucose oxidase (GAG) immunosandwich assay--provides excellent immunocytochemical labeling of routine hematological films in combination with optimal preservation of cellular details. In contrast to conventional immunofluorescence procedures, routine hematological films can be used, and these can be stored before and after the immunolabeling. Compared with other immunoenzyme techniques such as those using alkaline phosphatase or peroxidase, the GAG assay is as sensitive and has the advantage that no problems with endogenous enzyme activity are encountered. The availability of alcohol-resistant disclosing reagents allows for routine hematological counterstaining which provides a very clear visualization of both the immunoreaction and the individual morphology of the blood cells.

Antibodies, Monoclonal↗