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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 361 records · Page 20Linked to original sources

Improving CD4+ lymphocyte counts in HIV-infected hemophilia patients. A favorable prognostic indicator?

CD4+ lymphocyte counts of 91 HIV+ hemophilia patients were monitored for a mean of 4 years (range: 15-69 months). CD4+ lymphocytes decreased in 55 but increased in 36 patients over time. The CD4+ cell increases were persistent in 5 patients, whereas they fluctuated in 31. Of the 36 patients with increasing CD4+ counts 3 developed AIDS and 1 LAS. The other 32 patients were clinically asymptomatic (CDC II), but had immunological abnormalities, such as increased serum neopterin (N = 18) and impaired in vitro T cell responses to pooled allogenic stimulator cells (N = 15) or mitogens (N = 18). In contrast, of the 55 patients whose CD4+ cells decreased, 24 developed AIDS and 5 ARC (P less than 0.0005). Only 2 of these 55 patients had normal mitogen stimulation in vitro and normal serum neopterin levels.

Acquired Immunodeficiency Syndrome↗

A 37-channel DC SQUID magnetometer system.

A 37-channel DC SQUID magnetometer system has been built for biomagnetic studies. The SQUID loop of each magnetometer serves as the active sensing element, thereby eliminating the need for flux coupling circuits. The magnetometers are located approximately 3 cm above the outer dewar bottom. The SQUIDs are directly coupled to highly simplified read-out electronics using only five wires per channel; no helium temperature impedance matching circuits are required. Each channel can be independently inserted into or removed from the dewar. Using a novel electronic noise reduction technique the system white and 1 Hz flux density noise values are typically 5 and 10 fT Hz-1/2, respectively, including the noise contribution of the in-house fabricated dewar and the magnetically shielded room. The two parts of the data-processing system allow independent handling of the acquisition and analysing task. Two example measurements demonstrate the advantage of the electronic noise reduction method.

Equipment Design↗

Contribution of cAMP-phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium.

Previous studies have shown reduced effects of cAMP-dependent positive inotropic agents in the failing human myocardium; thus other cAMP-independent mechanisms of action may be useful to increase force of contraction in this condition. The purpose of this investigation was to determine whether a positive inotropic effect of the cAMP-phosphodiesterase (PDE) inhibitor pimobendan is observed in the failing human myocardium and to study whether other factors, such as an increase in the Ca2+ sensitivity of myofilaments, play a functional role in the increase in force of contraction. Pimobendan produced a positive inotropic effect in isolated preparations from nonfailing donor hearts; however, in moderately (New York Heart Association class II-III, NYHA II-III) and severely (NYHA IV) failing myocardium, this effect was reduced. In addition, in NYHA IV specimens pimobendan inhibited the crude cAMP-PDE (crude PDE) and the isoenzymes I-III (PDE I-III) in a concentration-dependent way. As judged from the IC50 values found in this tissue for the inhibition of PDE III and of crude PDE, the potency of the compound was 18.1 times greater on PDE III. Consistent with a cAMP-PDE-dependent mechanism of action, the positive inotropic effect was potentiated by isoproterenol and inhibited by adenosine in failing myocardium. In failing myocardium, pimobendan also increased the sensitivity of skinned cardiac fibers to Ca2+ and shifted the Ca(2+)-tension relation to the left. This sensitizing effect began at 0.01 mumol/l in NYHA II-III and NYHA IV and rose to about 200% at 300 mumol/l in both groups. In contrast, the demethylated metabolite UD-CG 212 Cl failed to produce positive inotropic effects in failing myocardium alone, but in the presence of isoproterenol, it exerted an increase in force of contraction. The potency of UD-CG 212 Cl for PDE III inhibition in NYHA IV was greater than that of pimobendan. The metabolite pronouncedly decreased the sensitivity of skinned cardiac fibers to Ca2+ at 30-300 mumol/l in NYHA II-III and NYHA IV. It is concluded that in the failing human heart pimobendan inhibited PDE III and sensitized contractile proteins for Ca2+. Both effects appear to be involved in the positive inotropic effect of the compound, because its metabolite, UD-CG 212 Cl, had no effect on force of contraction and on the Ca2+ sensitivity of skinned cardiac fibers but inhibited PDE III even more potently than pimobendan.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

Calcium antagonists and myocardial microperfusion.

Recent studies have improved our understanding of the beneficial actions of calcium antagonists on myocardial microcirculation and metabolism. The effect of calcium antagonists on the microcirculation of the left ventricular rat myocardium was studied using in vivo microscopic techniques. Intravenous verapamil 0.3 mg/kg and nifedipine 75 micrograms/kg produced a 15 to 18% increase in the diameter of larger A1 and A2 coronary arterioles (range 31 to 300 microns); diameters of terminal (A4) arterioles and capillaries did not change significantly. Furthermore, verapamil significantly (p less than 0.001) increased the ratio of capillaries filled with red cells to those containing plasma alone. Verapamil pretreatment produced a similarly selective dilatation of larger coronary arterioles and protected against the ischaemia-induced fall in capillary red cell content. Spectroscopic data show that verapamil also produces an increase in myocardial phosphocreatine and preservation of adenosine triphosphate (ATP) during ischaemia in the Langendorff-perfused heart. In patients with exercise-induced angina, gallopamil decreased global myocardial 201Tl and 123I phenylpentadecanoic acid (IPPA) uptake due to a reduction in myocardial oxygen consumption. Regional 201Tl and IPPA uptake as well as IPPA clearance in post-stenotic areas tended to rise after gallopamil treatment. Thus, the beneficial effects of calcium antagonists such as verapamil or gallopamil in patients with ischaemic heart disease may result from dilatation of predominantly larger arterioles. Consequently, there is an improvement in regional perfusion and free fatty acid utilisation in reversibly ischaemic regions.

Animals↗

Effect of gallopamil on myocardial ischaemia during percutaneous transluminal coronary angioplasty.

This report summarises selected preliminary results from an ongoing study designed to investigate the effect of the calcium antagonist gallopamil on myocardial ischaemia during percutaneous transluminal coronary angioplasty (PTCA). To date, 12 adult males with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) have been randomly assigned to gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralisation of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease or renal failure were excluded from the study. PTCA was performed using at least 2 balloon inflations, each of 2 minutes' duration. Gallopamil 0.4 mg or placebo (normal saline) were administered during the 10-minute interval between the 2 inflations. Blood samples were taken simultaneously from the coronary sinus and the femoral artery before and immediately after each inflation. Lactate concentration and the relative amount of activated neutrophils were selected for trend analysis. Furthermore, ECG changes were analysed by calculating the sum of the absolute ST-segment deviations (80 msec after J point, maximal T deviation) of leads I, II, III, V2, V4 and V6. In the presence of gallopamil, the degree of ST-segment/T-wave changes induced by balloon inflation was reduced. Additionally, gallopamil attenuated myocardial lactate release and appeared to prevent the increase in activated neutrophils observed during control inflations. These preliminary results suggest a beneficial effect from intracoronary administration of gallopamil during PTCA, achieved by attenuation of the ischaemic reaction during coronary occlusion.

Adult↗

[Tangier disease--a "free radical"-associated disease. Results of HDL and anti-oxidant therapy with selenium and D-alpha tocopherol].

In a 26-year-old patient there have been benign enlargements of the lymphatic nodes and a splenomegaly since the end of the adolescence. In the 21st year of age the diagnosis of a Tangier disease was made. Allogenic HDL-rich serum fraction (COHN IV/1-fraction, prepared according to the modified method 6) infused under therapeutic aspect led to a prolonged increase of the serum total cholesterol and of the thrombocytes. The results pled for an activation of the reverse cholesterol transport. Excessively high malonic dialdehyde concentrations in the serum were relating to a "free radical"-associated metabolic defect, which was caused by the hypocholesterolaemia, the reduced transport capacity of vitamin E in the plasma and the nutrition poor in selenium and cholesterol, respectively. Under a nutritive antioxidant supplementation with sodium selenite and D-alpha-tocopherol a slight increase of the total cholesterol, of the thrombocytes as well as a normalization of the MDA values could be reached. The chronic oxidative stress appeared in the patient in a distinct lipofuscinosis of the skin and formations of naevus-cell naevi as an expression of massive denaturations of protein-lipids. In the Tangier disease we must reckon with an increased mutagenic effect of free radicals with an additional DNS repair capacity as well as an increased sensitivity to radical-generating cancerogenic xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Stem cell separation with different cell separators].

For some years, there has been an increasing success in transplanting peripheral blood stem cells (PBSC) instead of autologous bone marrow in patients suffering from different malignancies. While collecting PBSC for autologous transplantation, we compared four different separation techniques and three different cell separators (COBE Spectra, Fresenius AS 104, Haemonetics V50) routinely used for platelet production. Our results suggest that continuous flow separators seem to have some advantage over discontinuous flow machines in harvesting PBSC.

Blood Cell Count↗

[Clinical use of peripheral stem cells for autologous transplantation].

Peripheral blood derived hematopoietic stem cells (PBSC) have been transplanted successfully to eight patients suffering from different malignancies. The separations were started during chemotherapy-induced cytopenia and large volumes of peripheral blood were processed. Using this separation concept, it was possible in all cases to obtain the stem cell amount necessary for hematopoietic reconstitution.

Blood Cell Count↗

Non-invasive detection of reduced regional myocardial perfusion at rest in patients with unstable angina pectoris: increased regional 81mKr deposition following intravenous injection of 81Rb.

The present study was to investigate whether combined imaging of 81Rb and 81mKr distributions after i.v. injection of 81Rb at rest might improve the differentiation between ischemic and irreversibly damaged myocardium as compared to 201Tl scintigraphy at rest. In 21 patients who had undergone diagnostic cardiac catheterization for evaluation of chest pain, 148 MBq ultrapure 81Rb were injected i.v. at rest immediately following 201Tl scintigraphy at rest. Of 14 patients with earlier myocardial infarction, 10 patients revealed decreased regional tracer uptake of 81Rb and/or 81mKr, compared to 12 patients with regional 201Tl uptake abnormalities. In 3 patients with unstable angina pectoris, however, an evident mismatch between either the regional 201Tl or 81Rb distributions and the distribution of 81mKr was observed: in contrast to the reduced uptake of 201Tl and/or 81Rb, 81mKr activity was increased in 3 myocardial segments with normal left ventricular performance but supplied by coronary arteries with high-grade stenoses. In patients with contraindications to exercise tests (e.g. unstable angina) 81Rb/81mKr rest scintigraphy may therefore assist the differentiation between malperfused but potentially viable and irreversibly damaged myocardium.

Angina, Unstable↗

A large presecretory protein translocates both cotranslationally, using signal recognition particle and ribosome, and post-translationally, without these ribonucleoparticles, when synthesized in the presence of mammalian microsomes.

Translocation of large presecretory proteins into the mammalian endoplasmic reticulum requires the ribonucleoparticles, signal recognition particle, and ribosome and is tightly coupled to ongoing protein synthesis. We have shown previously that small presecretory proteins can translocate post-translationally in a reaction that does not require these ribonucleoparticles. We now report that one large protein, a synthetic hybrid between preprocecropin A and dihydrofolate reductase, translocates both cotranslationally (with the aid of signal recognition particle and ribosome) and post-translationally (without the involvement of these ribonucleoparticles) during its in vitro synthesis in the presence of dog pancreas microsomes. The distinction between these two modes of translocation was made possible by adding methotrexate to the translocation reaction. Methotrexate can only form a tight complex with those preprocecropin A-dihydrofolate reductase hybrid chains that have completed their synthesis and folded, but in forming this tight complex, this drug prevents translocation of the dihydrofolate reductase domain across the membrane.

Amino Acid Sequence↗

Randomized controlled study of heparin and low molecular weight heparin for prevention of deep-vein thrombosis in medical patients.

166 patients aged 40-80 years were included in a controlled, randomized, double-blind study to determine the efficacy and safety of a single daily injection of a low molecular weight (LMW) heparin for prevention of deep-vein thrombosis compared to low dose conventional heparin. Patients received 1 x 1.500 aPTT units of a LMW heparin fraction (plus 2 x placebo injection) or 3 x 5.000 IU of an unfractionated heparin. During 10 days of treatment, patients underwent repeated clinical investigation, serial impedance plethysmography, and Doppler sonography for detection of thrombosis of the lower limbs. Combined application of these methods revealed evidence of thrombosis in 4.5% of patients on unfractionated heparin and 3.6% of patients on LMW heparin. Subcutaneous hematomas were significantly smaller in diameter upon treatment with LMW heparin (p less than 0.001). Antithrombin III levels were significantly higher at the end of the observation period in the LMW heparin group (p less than 0.005). Thrombocyte count, transaminases, creatinine, and haemoglobin did not change in either group. The results indicate that LMW heparin administered by a single s.c. dose daily may be as effective as low dose heparin in prevention of deep venous thrombosis in medical inpatients.

Adult↗

[Latent antioxidant deficiency in the East German population--causes and clinical significance. II].

The hitherto yielded results of the research groups for arteriosclerosis and trace elements of the Medical Clinic of Leipzig University were summarized and valuated. The most important results were than in 800 healthy persons of three counties of the GDR who were examined depending on sex and age a serum selenium deficiency with regional differences was stated and this deficiency could be increased by an antiatherogenic mode of nutrition (n = 94, p less than 0.001). A consecutive depletion of vitamin E out of normal values was to be explained as a reference of an insufficient status of antioxidants. Analyses on nearly 1,000 foodstuffs and sorts of coffee, tea, tobacco, alcohol, etc. showed as cause a high-degree depletion of vegetable foodstuffs in selenium. The established daily minimum uptake of selenium of 12 to 15 micrograms by cooked foods was covered by above all cholesterol-rich animal foodstuffs and was further lowered by their withdrawal. In a double blind study first results of a supplementation of sodium selenite referred to a favourable influence on the immune status. After explanation of the reasons which may lead to an additional insufficiency of antioxidants was postulated that the protection from activated oxygen species is indicated both for the primary prevention of autoimmunigenic, atherogenic and cancerogenic diseases and for the curative medicine by a supplementation of selenium.

Adult↗

Evaluation of nucleolus organizer regions (NORs) by automatic image analysis: a contribution to standardization.

This study summarizes our experiences with the silver staining of nucleolus organizer regions (AgNORs) in a total of 580 tumours from ten different tissues. In contrast to other investigators, we made use of automatic image analysis for the evaluation of AgNORs. This provided good reproducibility as determined by the standard cumulative means technique and intra-observer (r1) and inter-observer (r2) agreement in 30 benign (r1 = 0.83-0.95, r2 = 0.76-0.92) and 50 malignant tissue samples (r1 = 0.72-0.85, r2 = 0.51-0.78). By using a series of staining times on sections from 30 tissue blocks taken from the ten types of tissue investigated, considerable variation in the argyrophilic staining of NORs in different tissues and in different blocks from one tumour was shown. The mean AgNOR area of resting lymphocytes or connective tissue cells within tissue blocks of the same organ system varied up to four-fold, even though identical staining times had been used. The most suitable silver reaction time which rendered a good diagnostic difference in the AgNOR content of benign and malignant tissue ranged, for example, in the breast cancer specimens, from 23 to 35 min. We therefore conclude that the staining time has to be adjusted to the individual silver-binding characteristics of each tissue block or even each section. The use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory. This, in turn, is most precisely controlled by morphometry.

Humans↗