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Biomedical subjects

U Winter

Publications and source records attributed to U Winter.

At least 19 recordsLinked to original sources

Effects of (+/-)-kavain on voltage-activated inward currents of dorsal root ganglion cells from neonatal rats.

Kava pyrones extracted from pepper Piper methysticum are pharmacologically active compounds. Since kava pyrones exhibit anticonvulsive, analgesic and centrally muscle relaxing properties, the influence of a synthetic kava pyrone, (+/-)-kavain, on voltage-dependent ion channel currents was studied. Effects of (+/-)-kavain on voltage-activated inward currents were analysed in cultured dorsal root ganglion cells derived from neonatal rats. Voltage-activated Ca2+ and Na+ currents were elicited in the whole-cell configuration of the patch clamp technique. Extracellularly applied (+/-)-kavain dissolved in hydrous salt solutions reduced voltage-activated Ca2+ and Na+ channel currents within 3-5 min. As the solubility of (+/-)-kavain in hydrous solutions is low, dimethyl sulfoxide (DMSO) was added to the saline as a solvent for the drug in most experiments. When (+/-)-kavain was dissolved in DMSO, the drug induced a fast and pronounced reduction of both Ca2+ and Na+ currents, which partly recovered within 2-5 min even in the presence of the drug. The present study indicates that (+/-)-kavain reduces currents through voltage-activated Na+ and Ca2+ channels.

Animals↗

Effects of kawain and dihydromethysticin on field potential changes in the hippocampus.

1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg2+, recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels. 3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 mumol/l and 10 to 40 mumol/l, respectively. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 mumol/l kawain and 10 mumol/l dihydromethysticin indicated additive actions of both drugs. 5. Since the serotonin-1A agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively. 6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components kawain and dihydromethysticin may enhance the effects of the anxiolytic serotonin-1A agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.

Animals↗

[Ergospirometric studies of normal probands for an unsteady-state increment test program].

One-hundred-sixteen healthy subjects (60 female and 56 male) with normal height (L) and weight (w) were selected to provide an even distribution of age (A, 20-70 years). All underwent an unsteady state cycle ergometer test with work increments of 20 watts each minute to exhaustion. A commercially available exercise testing system (EOS SPRINT, Jäger Corp., FRG) with gas analysis from a mixing chamber was used to study oxygen uptake (VO2), carbon dioxide output (VCO2), heart rate (HR), tidal volume (VT), breathing frequency (BR) and arterial oxygen tension (PO2) with special regard to the ventilatory anaerobic threshold (VAT) and maximum power output. For all parameters multiple regression equations were determined. Furthermore, heart rate reserve (HR-reserve), breathing reserve (VE-reserve), O2-pulse (VO2/HR), the dead space/tidal volume ratio (VD/VT) and the alveolar-arterial PO2-difference (AaDO2) were calculated. Day-to-day reproducibility was proven in 21 subjects. VO2max in females was 1584 +/- 300 ml/min (VO2max = -17 A + 10 L + 10 G + 58, r = 0.75, p < 0.0001), VO2AT 957 +/- 159 ml/min (VO2AT = 0.35 VO2max + 0.40 l/min, r = 0.77, p < 0.0001). The ratio VO2AT/VO2max was 50 +/- 7%. In male, VO2max was 2452 +/- 529 ml/min (VO2max = -23 A + 23 L + 9.5 G - 1395, r = 0.78, p < 0.0001), VO2AT 1209 +/- 213 ml/min (VO2AT = 0.29 VO2max + 0.51 l/min, r = 0.71, p < 0.0001), and VO2AT/VO2max 62 +/- 9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A unique scenario for coronary atherectomy.

Despite several attempts, balloon angioplasty of a slightly eccentric stenotic lesion in the proximal right coronary artery failed to result in any increase of luminal diameter. Following disruption and partial removal of a fibrous atherosclerotic cap using directional atherectomy, subsequent balloon angioplasty was highly successful.

Angioplasty, Balloon, Coronary↗

Multiple coordinate controls contribute to a balanced expression of ribulose-1,5-bisphosphate carboxylase/oxygenase subunits in rye leaves.

In the leaves of rye (Secale cereale L.), control mechanisms acting at multiple molecular levels contribute to a coordinate expression of the subunit polypeptides of ribulose-1,5-bisphosphate carboxylase. The relevance and hierarchy of the different control steps were evaluated by comparing the time courses of changes in levels of translatable mRNA, rates of in vivo amino acid incorporation, and the turnover of subunit polypeptides after selective interference with translation at either cytoplasmic 80S ribosomes, or at the 70S ribosomes of the chloroplast, by compartment-specific inhibitors, or by the use of 70S-ribosome-deficient leaves. The latter were generated by growing the plants at a non-permissive elevated temperature of 32 degrees C. The rates of synthesis of the two ribulose-1,5-bisphosphate carboxylase subunits were most rapidly adapted to each other by translational controls. Within 0.5-2.5 h after selective inhibition of the synthesis of either subunit, that of the other subunit made in the unaffected compartment also declined by more than 90% without any marked change in its mRNA. After prolonged inhibition (24 h) of either cytoplasmic or chloroplast protein synthesis, the levels of mRNAs for both subunits were greatly diminished. In rye, the mRNA levels for both subunits changed under all experimental conditions tested in a closely parallel manner and appeared to be always maintained in a balanced, fairly constant ratio by strong coordinate controls. Even 70S-ribosome-deficient leaves contained mRNAs for both the small and the large subunits, although only in small amounts. The mRNAs for both subunits were also markedly further decreased in 70S-ribosome-deficient leaves after application of an inhibitor of cytoplasmic translation. MDMP [2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamide], suggesting that the suppression of the large subunit mRNA in the plastids was not mediated through feedback effects of accumulating unassembled large subunits. Coordinate controls at both the mRNA and the translational level require a bidirectional exchange of regulatory signals between chloroplast and cytoplasm. However, these controls were not absolutely restrictive and allowed low rates of uncoupled synthesis of either large or small subunits. Large subunits made in the presence of MDMP were stable over 24 h. However, unassembled small subunits synthesized in 70S-ribosome-deficient leaves were degraded with a half-time of 10.5 h, in contrast to their behavior after integration into the holoprotein in normal leaves, where no turnover was detected. The proteolytic removal of surplus free small subunits is regarded as a final post-translational fine-tuning step to establish a balanced subunit stoichiometry in leaves.

Amino Acids↗

Immunodeficiency in old age.

Aging is a multi-facetted process, but the deterioration of the immune function seems to play a central role in this context. Paradoxically, immune reactivity against exogenous antigens declines during aging while autoimmune reactivity increases. One of the aims of our investigations on the function of the senescent immune system was to define immune parameters of 'normal' aging, i.e. those not dependent on underlying diseases. Specifically, our interest was focused on the possible role of an altered lipid metabolism of cells of the immune system during aging. The known decrease of plasma membrane fluidity of lymphoid cells and monocytes in higher age may be one of the factors responsible for the nonoptimal functioning of the immune system. This property, in turn, seems to be based on an altered lipid metabolism. Specifically, we have evidence that the finely tuned balance between the transport of cholesterol to and from lymphoid cells via the environment and the intracellular cholesterol biosynthesis seems to be disturbed with increasing age. This conclusion is drawn from experiments where low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity is assessed using fluorescently labeled lipoproteins in fluorescence-activated cell sorter (FACS) analyses. LDL receptor uptake is unexpectedly increased in the elderly, but LDL receptor regulation, and serum LDL composition itself seem to be normal. Preliminary data point out the possibility that the efflux of cholesterol via HDL may be insufficient. Attempts to modulate plasma membrane fluidity by means of the phospholipid mixture 'active lipid 721' (AL 721) showed that this drug, in contrast to literature reports, is not a 'membrane fluidizer' but rather exerts this effect as a nutrient for lymphocytes and monocytes.

Aging↗

AL 721: a potent membrane modulating agent of human T-lymphocytes?

This report deals with AL 721, a reputedly potent membrane fluidizing agent. A correlation has been sought between the effects of AL 721 on membrane fluidity and mitogen responsiveness of human peripheral blood lymphocytes. The AL 721-induced increase in membrane "fluidity", as measured by fluorescence polarisation with 1,6-diphenyl-1,3,5-hexatriene, was found to be an artefact arising from lipid uptake by monocytes. Mitogen responses were enhanced by inclusion of AL 721 in the serum-free culture medium. However, this observation is more likely explained by provision of lymphocytes with nutritional lipids required for optimal growth in vitro, than altered responsiveness of "fluidized" lymphocytes.

Adolescent↗

Lipid requirements of human T lymphocytes stimulated with mitogen in serum-free medium. Membrane "fluidity" changes are an artefact of lipid (AL721) uptake by monocytes.

A correlation has been sought between the effects of lipids on membrane fluidity and mitogen responsiveness of human peripheral blood lymphocytes (PBL). Cholesterol and the reputedly potent membrane fluidizing agent AL721 (1) were used for these studies. However, the large AL721 induced increase in membrane "fluidity", assessed by steady state polarization of the probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was found to be an artefact arising from lipid uptake by monocytes. Mitogen responses were enhanced by AL721 but unaffected by cholesterol. It is concluded that AL721 does not exert its effect through enhanced triggering of cells by altered membrane fluidity but rather that lymphocytes require an exogenous source of phospholipids/triglycerides for optimal growth in vitro, although they can synthesize sufficient cholesterol to meet their own needs.

Adult↗

Analysis of fluorescent low density lipoprotein uptake by lymphocytes. Paradoxical increase in the elderly.

Uptake of dioctadecylindocarbocyanine (DiI)-labelled low density lipoproteins (LDL) by peripheral blood lymphocytes (PBL) from young healthy donors has been characterized by flow cytometric analysis. The receptor positive cells were primarily (greater than 70%) T cells. Saturation and competition studies were performed with freshly isolated PBL as well as after a 2-3-day incubation in cholesterol-free medium. In both cases uptake was specific for LDL and not high density lipoprotein. It was also abrogated by chemical modification of apo B, and was not shown by PBL from a patient with familial hypercholesterolemia. DiI-LDL-uptake by cells from elderly donors was compared with that of PBL from young donors. There was a clear increase in uptake by freshly isolated PBL from aged donors which was shown not to stem from underlying "sickness". In contrast, uptake by pre-incubated cells was very variable, in terms of percentage receptor-positive cells and the level of uptake by those cells. However, LDL rescued mevinolin-suppressed mitogen responses from both old and young donors indicating that there is no impairment of uptake or degradation of LDL by PBL from the elderly.

Adult↗

Recovery of ventricular late potentials from body surface using the signal averaging and high resolution ECG techniques.

In 70 patients (3 females and 67 males), aged 16-72 years (mean: 51 +/- 9 years), the low noise ECG was recorded from body surface by the signal averaging and the high resolution beat-to-beat techniques. We found 61 patients were suffering from coronary heart disease, 4 had atypical coronary heart disease (syndrome X), 4 had dilatative cardiomyopathy, and one had the long QT syndrome (Romano-Ward syndrome). We found the following recovery rates for ventricular late potentials within the ST segment with the averaging technique: clearcut in 13/53 patients, doubtful in 16/53 patients, and late potentials absent in 26/53 patients. With the beat-to-beat technique the following recovery rates were found: clearcut late potentials in 27/70 patients, doubtful in 23/70 patients, none in 20/70 patients, and intermittently occurring late potentials in 18/70 patients (categorized as doubtful late potentials). When comparing the detection of late potentials with both methods in individual patients, we found concordant results in 39/53 patients studied (positive with both methods in 24/53 patients, negative with both methods in 15/53 patients), and discordant results in 14/53 patients (positive with the beat-to-beat technique and negative with the averaging technique in 12 individuals, negative with the beat-to-beat technique and positive with the averaging technique in the remaining 2 patients). The correlation between the incidence of late potentials and the presence of exercise-induced myocardial ischemia (submaximal bicycle exercise) was higher when using the high resolution beat-to-beat technique, as holds also true for the correlation to complex ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Simple method for comparing large numbers of flow cytometry histograms exemplified by analysis of the CD4 (T4) antigen and LDL receptor on human peripheral blood lymphocytes.

We have developed a simple method for comparing the relative fluorescence intensity (FI) of flow cytometry histograms. It entails assessment of the FI (equivalent to the fluorescence-activated cell sorter (FACS) channel) of the 50th or 75th percentiles of either positively stained cells or the total cell population. We illustrate the method with dilution curves of 1) monoclonal antibodies against the T4 surface antigen of human peripheral blood lymphocytes and 2) fluorescent low density lipoprotein (LDL) binding to the human peripheral blood lymphocytes LDL receptor. We demonstrate the versatility of the method by characterizing the binding properties of fluorescent LDL to their receptors. Binding was shown to be specific and of high affinity, and to reach a steady state plateau at about 2 hr; the affinity of fluorescent LDL for the receptor was found to be two to three times higher than that of the unlabeled LDL.

Antibodies, Monoclonal↗

[Treatment of fresh Achilles tendon ruptures with fibrin glue].

The surgeons of the accident hospital of the relevant professional association at Ludwigshafen have been increasingly resorting to treating fresh ruptures of the Achilles tendon with fibrin adhesive only. Initially the adhesion procedure was supplemented by and adaptational suture. The essential feature of this procedure is that no suturing material whatsoever is implanted into the tendon. The surgical procedure is quicker and simpler than by suturing the tendon rupture. Up to now 52 ruptures of the Achilles tendon have been treated with fibrin adhesive at the hospital under report. Curative results were very satisfactory with the exception of one complication where a renewed injury resulted in another rupture.

Achilles Tendon↗

[Endocardial cardioversion--a new method for treating recurrent ventricular tachycardia].

The effect of endocardial cardioversion was investigated in 17 patients (aged 26-76 years), ten of them with ventricular tachycardia, either spontaneous or initiated by programmable stimulation. During a total of 14 days of observation there were 33 episodes of spontaneous or induced ventricular tachycardia. A special cardioverter catheter had been placed into the right ventricle and endocardial microshocks were given ranging from 0.05-2.0 J. All patients could feel the shock, but in most instances it was mild to moderate, in only one painful. The tachycardia was slowed in 20% of all microshocks, moderate acceleration occurred in 6%, while in 71% the tachycardia rate remained unchanged. In 7 out of 65 microshocks sinus rhythm occurred spontaneously, after an interval in which the tachycardia slowed. Atrial fibrillation was induced in 6% of cases, but there was no instance of ventricular fibrillation. Reversion directly to sinus rhythm after endocardial cardioversion occurred in 26 of 33 episodes of ventricular tachycardia, while in 7 episodes the tachycardia rate slowed. In no case was it necessary to use external DC cardioversion to terminate a ventricular tachycardia. Threshold values for successful cardioversion of ventricular tachycardia averaged 0.77 (+/- 0.63) J. In one patient, atrial flutter with a relatively high A-V conduction rate was converted into atrial fibrillation by an intra-atrial microshock of 5.0 J. Thus endocardial cardioversion proved effective and safe in terminating ventricular tachycardia, even in patients in whom anti-tachycardic ventricular pacemaker stimulation had failed. The method is apparently not suitable for the conversion of supraventricular tachy-arrhythmias to sinus rhythm.

Adult↗

Noninvasive beat-by-beat registration of ventricular late potentials using high resolution electrocardiography.

We have developed a new high resolution ECG equipment for recording cardiac microvolt potentials from the body surface. Noise reduction has been achieved by specially designed suction electrodes, by spatial averaging of the electrocardiograms from four electrode pairs, using extremely low noise amplifiers, by performing registrations within a Faraday cage, and by teaching the patient to relax during end expiratory breath holding. Fourteen young males (controls) and 30 patients with various cardiac diseases (27 with CHD) were studied. In normals ventricular late potentials were not seen, but in 12/30 patients clearcut diastolic potentials were found. In 7/12 patients with positive findings, late potentials appeared beat-by-beat, in 5/12 patients those signals occurred intermittently, in 11/30 patients questionably, and in the remaining 5/30 patients no late potentials were recorded. One patient with the Romano-Ward syndrome revealed phases with stable beat-by-beat and intermittently occurring ventricular late potentials. These results demonstrate the feasibility of continuous non-invasive recording of ventricular late potentials, whose clinical and prognostic significance remains to be established.

Adolescent↗

[Detection of patients at risk for sudden heart death by long-term ECG. The role of life-threatening ventricular arrhythmias].

Recognition of patients at risk of sudden cardiac death and prevention of such lethal events represent important and, for the most part, unresolved problems in clinical cardiology. From pathologic-anatomical and clinical studies of instances of sudden death it is known that in more than 80% the lethal electrical events, that is ventricular fibrillation, are attributable to myocardial ischemia, usually due to coronary artery disease. Experience in experimental studies as well as in treatment of patients with myocardial infarction on coronary care units has shown that certain types of arrhythmias such as frequent, multiform, repetitive and early-occurring (R-on-T) ventricular premature beats, in particular, may be associated with sudden arrhythmic cardiac death. Accordingly, in 1971, Lown and Wolf proposed a system for grading of ventricular arrhythmias and their severity which assumed world-wide importance for clinical and prognostic studies. This system of classification contains quantitative and qualitative criteria and is ordered in part on exclusion and in part on hierarchy, in which it is implied that the hierarchy of ventricular premature beats corresponds with that of the risk of death. Since the system enables only semiquantitative delineation of ventricular arrhythmias whose absolute number, however, within a given observation period appears to be of prognostic relevance and, additionally, since the Lown system is encumbered by the fact that classification is based only on the most severe arrhythmia with subsequent loss of information regarding concurrent arrhythmias of lesser severity, Bigger and his associates, in 1978, suggested a modification to provide quantification of all ventricular premature beats. In addition to the problems inherent to grading ventricular premature beats, further problems are also incurred with respect to spontaneous variability of ventricular arrhythmias. Based on statistical considerations and clinical studies accordingly, adequate assessment of complex ventricular arrhythmias prerequisites continuous monitoring for a period of 24 to 48 hours. Furthermore, for the exact recognition and quantitative detection of ventricular arrhythmias, the reliability of the individual systems for continuous ECG monitoring plays an important role since, by no means, have they all been validated in arrhythmia-detection capabilities. Since 1971, a number of clinical studies have shown, in particular, that complex ventricular arrhythmias are of important prognostic relevance in characterization of patients at risk of sudden cardiac death. The results may be summarized as follows: Ventricular premature beats can be found frequently in

Adult↗

[Treatment of uninfected pseudarthroses of the lower extremity near the joint using the Küntscher medullary nail].

The Küntscher nail has proved successful in the treatment of non-unions of the median third of the femur and lower leg after opening of the medullary cavity; in fact, this method is described in literature as the method of choice. It is based on the assumption that a sufficiently dimensioned intramedullary Küntscher nail together with the biological stimulative action of the bone meal, will result in a rapid osseous bridging of the non-union. This method has been successfully used in 128 cases even in non-unions which were close to the joint. Healing occurred in 92% of the cases. In about 11 cases it became necessary to perform a secondary operation. The high rate of infection, amounting to 12.4%, is relatively low compared with the very high rate of infective relapses following the first operation to achieve healing of the bone fractures.

Adult↗