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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 325 records · Page 18Linked to original sources
PubMed1999

Effect of nitroglycerin and nicorandil on regional poststenotic quantitative coronary blood flow in coronary artery disease: a combined digital quantitative angiographic and intracoronary doppler study.

Little information is available concerning the effects of nitrates and potassium channel openers on local poststenotic blood flow in coronary artery disease (CAD). Combined quantitative digital angiography (QCA) and intracoronary Doppler (IVADO) velocity measurements were used to determine changes in absolute poststenotic blood flow after intracoronary injection of 0.2 mg nitroglycerin and 0.5 mg nicorandil. Quantitative blood flow (QBF) was calculated from average peak-flow velocity (APV) and angiographic cross-sectional area (CSA): QBF (ml/min) = CSA x APV x 0.5. In group I (n = 9), 0.5 mg nicorandil i.c. was identified as optimal to achieve maximal vasodilatation. In patients with CAD (group II, n = 12), i.c. injection of 0.5 mg nicorandil induced a significant increase in poststenotic CSA (+38%) and QBF (+50%). In contrast, 0.2 mg nitroglycerin (group III, n = 12) increases poststenotic CSA (+38%) without a significant change in QBF (+23%). Additional application of nicorandil in these patients induced further significant increases in CSA (+55%) and QBF (+48%) compared with baseline. There were no significant changes in stenosis area. Poststenotic blood flow can be increased by nicorandil after application of nitroglycerin. This effect is most likely mediated by the potassium channel-opening effect of nicorandil. Combined use of QCA and IVADO is a unique approach to measure local poststenotic QBF in patients with CAD.

Coronary Angiography↗
PubMed1999

Wetting of mesoscopic soft cylinders: structure and layering transitions.

The wetting of soft mesoscopic long-chain particles is studied. As a model system, a cylindrical brush with poly(vinyl)pyridine side chains on the water surface is characterized by isotherms and x-ray reflectivity. The forces from the two planar interfaces and the intra- and interparticle interactions are all of comparable magnitude. Two layering transitions occur, one from the monolayer to the double layer, the next to a homogeneous multilayer. The hard wall from which layering starts is the smooth polymer/air interface. Indeed, they particles in the top layer of both the double- and the multilayer have their cylinder axis parallel to the surface and are laterally compressed. In contrast, the polymer/water interface is diffuse due to brush swelling. Generally, the long-chain particles adjacent to the respective interfaces do not maintain their circular diameters. The thickness of the monolayer can be varied by a factor 3.5, up to 53 A. An additional phase transition occurs within the monolayer, which is attributed to a change of the side chains from a flattened to a compressed state at constant volume. Atmoic force microscope images of the monolayer transferred onto a solid indicate local cylinder alignment.

Journal Article↗
PubMed1999

Density-functional theory for soft interactions by dimensional crossover.

A density-functional theory for spherical particles interacting via an arbitrary soft pair potential is presented. The derivation is solely based on limits, where the behavior is exactly known, namely, a zero-dimensional cavity and the low-density virial expansion. The approach generalizes the fundamental-measure theory for hard bodies and yields the structure and thermodynamics of the homogeneous fluid as an output. We apply the theory to an ultrasoft logarithmic potential that mimics star polymers in a good solvent. The theory, when supplemented by a rescaling procedure, reproduces the peculiar features of the pair correlations in this system that we also find in computer simulations.

Journal Article↗
PubMed1999

GABA(A) and GABA(C) receptors have contrasting effects on excitability in superior colliculus.

We have recently found that GABA(C) receptor subunit transcripts are expressed in the superficial layers of rat superior colliculus (SC). In the present study we used immunocytochemistry to demonstrate the presence of GABA(C) receptors in rat SC at protein level. We also investigated in acute rat brain slices the effect of GABA(A) and GABA(C) receptor agonists and antagonists on stimulus-evoked extracellular field potentials in SC. Electrical stimulation of the SC optic layer induced a biphasic, early and late, potential in the adjacent superficial layer. The late component was completely inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione or CoCl(2), indicating that it was generated by postsynaptic activation. Muscimol, a potent GABA(A) and GABA(C) receptor agonist, strongly attenuated this postsynaptic potential at concentrations >10 microM. In contrast, the GABA(C) receptor agonist cis-aminocrotonic acid, as well as muscimol at lower concentrations (0.1-1 microM) increased the postsynaptic potential. This increase was blocked by (1,2,5, 6-tetrahydropyridine-4-yl)methylphosphinic acid, a novel competitive antagonist of GABA(C) receptors. Our findings demonstrate the presence of functional GABA(C) receptors in SC and suggest a disinhibitory role of these receptors in SC neuronal circuitry.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

In vitro investigations of jet-pulses for the measurement of respiratory impedance in newborns.

The aim of this in vitro study was to investigate the measuring range and accuracy of a miniaturized equipment for respiratory impedance (Zrs) measurements in newborns using jet-pulses. Brief flow pulses (peak flow=16 L x min(-1), width=10 ms) were generated by a jet-generator consisting of a solenoid valve and an injector, situated between pneumotachograph and outflow resistance. Serially arranged resistance-inertance-compliance (R-I-C) lung models (RM=1.3-6.4 kPa x L(-1) x s, CM=7.4-36.9 mL x kPa(-1), IM=1.5 Pa x L(-1) x s2) were used to measure the real and imaginary part of Zrs between 4 and 50 Hz and to determine R, C and I by means of the method of least squares. The median errors for R, C and I were -0.1 kPa x L(-1) x s (-2%), 2.4 mL x kPa(-1)(13%) and -0.2 Pa x L(-1) x s2 (-13%) for measurements without breathing signals and 0.11 kPa x L(-1) -s (3%), 3 mL x kPa(-1) (16%) and 0.28 Pa x L (-1) x s2 (19%) in mechanically ventilated models. During spontaneous breathing the influence of the breathing flow on Zrs was negligible. The equipment did not show any nonlinearity when different pulse amplitudes were used (Vmax=13-22 L x min(-1)). The investigations have shown that jet-pulses allow reliable measurements of respiratory impedance and have the potential to provide valuable information about lung mechanics in spontaneously breathing and mechanically ventilated newborns. The developed measuring head has a low apparatus dead space, is easy to disinfect, has standard connections and can be used as the T-piece in a ventilator circuit.

Airway Resistance↗
PubMed1999

Voltage-activated whole-cell K+ currents in lamina cells of the desert locust schistocerca gregaria

Voltage-dependent outward currents were studied in freshly dissociated somata of locust lamina cells. These currents were recorded in 142 somata using the whole-cell patch-clamp technique. By measuring the reversal potential at altered external [K+] and by replacing internal K+ with Cs+, we determined that the outward currents were carried by K+. The outward currents consist of a transient A-type K+ current (KA) and a delayed-rectifier-like K+ current (KD). Amongst the cells studied, we observed two distinct groups of cells. The most obvious difference between the two groups is that in group I cells the total outward current is dominated by KA (KA/KD=12.5), whereas in group II cells KA makes a smaller contribution (KA/KD=2.1). Furthermore, in cells of group I, the KA current shows a steeper voltage-dependence of activation, where VG50 is -29.9 mV and s is 11.9 (N=22), and inactivation, where VI50 is -84.5 mV and s is -6.3 (N=18), compared with the KA current in cells of group II: VG50=-7.9 mV; s=26.6 (N=36) and VI50=-68.4 mV; s=-7.5 (N=21) (VG50 is the voltage at which the whole-cell conductance G is half-maximally activated, VI50 is the voltage of half-maximal inactivation and s is the slope of the voltage-dependence). The transient KA current in group I cells decayed mono-exponentially. The decay of the KA current in group II cells was fitted with a double-exponential curve and was significantly faster than in group I cells. In contrast to the large differences in KA currents, the KD currents appeared to be quite similar in the two groups of cells.

Journal Article↗
PubMed1999

[Evaluation of guidelines in oncology].

Several activities regarding guidelines have been developed in Germany within a short time. It is desirable especially in the field of oncology that procedures are stated as proven effective, proven ineffective, and possibly effective by using procedures of evidence based medicine. However, the low impact of guidelines on the medical practice has to be taken into account. The kind of errors of known deviations should decrease the expectations. This altogether should motivate for a closer look what really happens in the daily routine. It should also reflect the hospital's and physician's outcome and might provide hints to medical standards. Improving the still insufficient documentation, which may describe quality of care, can provide important features. This has to be remembered when undertaking activities regarding guidelines.

Evaluation Studies as Topic↗
PubMed1999

[Autocrine activation of fibroblasts following irradiation].

BACKGROUND: The most important limitation of thoracic radiotherapy is radio-toxicity of the normal lung. We distinguish the pneumonitis with acute clinical onset, histologically characterised by infiltration of inflammatory cells to alveoli and interstitium, from fibrosis, which is slowly progressive and characterised by fibroblast proliferation and collagen deposition in the interstitium. Radiogenetic fibrosis can occur without evidence of alveolitis, an active role of mesenchymal lung cells in the pathogenesis of this special disorder is assumed. METHODS: Human lung fibrobasts were irradiated in vitro with single doses of 4, 7 and 10 Gy and afterwards observed or incubated together with non-irradiated cells in a co-culture system. After 3, 6, 9, and 12 days cells were counted, and TGF beta 1 and fibronectin was measured in supernatants. RESULTS: Cell growth of irradiated fibroblasts was inhibited as expected. In contrast, we observed a significant stimulation of cell growth of the non-irradiated fibroblasts, which were incubated together with the irradiated cells. This effect was obvious from day 1 until day 9 following irradiation and was dose dependent. In irradiated cells TBF beta 1 was increased in culture supernatants up to five-fold compared to sham-irradiated cells from day 6 until day 12. Fibronectin was elevated in dose dependent manner. CONCLUSION: Irradiation of fibroblasts in vitro induces synthesis of substances which stimulate cell growth. TGF beta 1 and fibronectin may be involved in this act of "self-activation".

Cell Division↗
PubMed1999

[Aspiration pneumonia caused by vertebrae of a dove in a 39 year old patient with Down syndrome].

Undetected foreign body aspiration is a well-known problem not only in children and patients with predisposing conditions like mental retardation, seizures or brain tumours, but also in healthy subjects. The clinical signs are quite different. Haemoptysis, cough, recurrent or chronic penumonia and bronchitis may occur. These symptoms are often accompanied by fever, weight loss and night sweat. Atelectasis, respiratory distress or death have been described. We demonstrate the case of a 39-year old man with Down syndrome who was transferred to our hospital because of pneumonia in the left lower lobe that had been lasting for about two months. It had been resistant to several antibiotic regimens. Computerised tomography led to the suspicion of a bronchial carcinoma with poststenotic infiltration of the lower lobe. Fibreoptic bronchoscopy and biopsy confirmed the diagnosis of a foreign body in the distal part of the left main bronchus. After two weeks of treatment with ciprofloxacin regression of the acute inflammation occurred. During a second bronchoscopy we could extract the foreign body (a 1 x 1.7 cm vertebra of a dove). It is concluded that undetected foreign body aspiration can occur in various clinical settings and fibreoptic bronchoscopy is a suitable approach providing an exact diagnosis.

Adult↗
PubMed1999

The 536C-->T transition in the human tissue factor pathway inhibitor (TFPI) gene is statistically associated with a higher risk for venous thrombosis.

Tissue factor pathway inhibitor (TFPI) is an important regulator in the extrinsic blood coagulation pathway. Although the regulatory biochemical role of TFPI is evident, the clinical significance of this proteinase inhibitor remains to be elucidated. The definition of a clinical TFPI deficiency seems to be more complex than that of other coagulation inhibitors because the activity and concentration of circulating TFPI can not be considered a true measure of in vivo levels. Its determination in plasma samples by immunological methods or functional assays has been shown to be inadequate in the detection of a clinical deficiency. Therefore, we screened genomic DNA samples of blood donors and thrombotic patients for alterations in the TFPI gene to assess the influence of a modified TFPI in venous thromboembolic diseases. We detected a single nucleotide substitution in exon 7 (536C-->T) leading to a proline to leucine exchange at amino acid position 151 of the protein ([P151L]TFPI) and found the prevalence of heterozygous carriers in German unrelated blood donors to be 0.2% (n = 5120). Four unrelated persons out of 14 probands carrying the genetic variation could be linked to venous thrombosis. For calculation of a potential risk for venous thrombosis for carriers of the mutation we investigated healthy blood donors about thrombotic events. 7 out of 308 blood donors were found to have a history of venous thrombosis, one of them carried the TFPI mutation. Statistical calculation showed a significant relative risk for venous thrombosis for individuals with the trait (odds ratio, 9.3; confidence interval, 1.8-48.6; p <0.01).

Amino Acid Sequence↗
PubMed1999

[Clinical and epidemiological data of patients with malignant melanoma from the Munich Tumor Center 1977-1997].

Since 1997, data of patients with malignant melanomas have been systematically documented in the tumor registry of the Tumor Center Munich. Analysis of data of 8071 patients revealed that tumor thickness has steadily declined over the years. While in 1977 the median tumor thickness was 1.45 mm, it is now 0.75 mm. This has been followed by a significant improvement in overall survival. Males and older patients tend to have thicker melanomas than females and younger patients. There has been a relative increase of melanomas of the trunk. At diagnosis, 95% of patients had local disease. Of these patients, 18.3% developed metastastes. At least two-thirds of these patients had progression at the primary tumor site or the regional lymph nodes, both of which can be assessed by clinical or ultrasound examinations. Overall survival of patients with thin melanomas is excellent and does not differ substantially from the overall survival of the general population comparable in sex and age.

Adult↗
PubMed1999

[Renal morphometric investigations in pre-eclampsia-like syndrome in a Wistar rat model].

OBJECTIVE: Etiology and pathogenesis of renal changes in pregnancy-induced hypertension (PIH) remain somewhat controversial. Reducing the uterine perfusion leads to the development of systemic hypertension in animal models. Aim of this study was to investigate the effect of systemic hypertension on the kidney during pregnancy. MATERIAL AND METHODS: A rat model was used and the degree of the renal changes was quantified by morphometry. Normotensive pregnant and virgin animals served as a control. RESULTS: Hypertensive animals showed a decrease of the intravascular space in comparison to the cellular component. This difference was significant not only in pregnant (p = 0.0026) but also in virgin (p = 0.001) animals. CONCLUSIONS: These findings indicate that renal changes are usually found in normotensive pregnancies, while PIH strongly aggravates these changes.

Animals↗
PubMed1999

Secretion-dependent proteolysis of heterologous protein by recombinant Escherichia coli is connected to an increased activity of the energy-generating dissimilatory pathway.

The synthesis of a proteolytically unstable protein, originally designed for periplasmic export in recombinant Escherichia coli BL21(DE3), a strain naturally deficient for the ATP-dependent protease Lon (or La) and the outer membrane protease OmpT, is associated with a severe growth inhibition. This inhibition is not observed in BL21(DE3) synthesizing a closely related but proteolytically stable protein that is sequestered into inclusion bodies. It is shown that the growth inhibition is mainly caused by a slower cell division rate and a reduced growth yield and not by a general loss of cell division competence. Cells proceed with their normal growth characteristics when exposed again to conditions that do not sustain the expression of the heterologous gene. The performance of cells synthesizing either the stable or the degraded protein was also studied in high cell density cultures by employing a new method to calculate the actual specific growth rate, the biomass yield coefficient, and the dissimilated fraction of the carbon substrate in real-time. It is shown that the growth inhibition of cells synthesizing the proteolytically degraded protein is connected to an increased dissimilation of the carbon substrate resulting in a concomitant reduction of the growth rate and the biomass yield coefficient with respect to the carbon source. It is postulated that the increased dissimilation of the carbon substrate by lon-deficient Bl21(DE3) cells synthesizing the proteolytically unstable protein may result from a higher energy demand required for the in vivo degradation of this protein by ATP-dependent proteases different from the protease Lon.

ATP-Dependent Proteases↗
PubMed1999

Neuropeptide-Y stimulation of extracellular signal-regulated kinases in human erythroleukemia cells.

We have used human erythroleukemia (HEL) cells to investigate distal signaling mechanisms of neuropeptide-Y (NPY) receptors. NPY did not activate phospholipase D, determined as a phosphatidylethanol formation, or protein kinase C (PKC) determined enzymatically as a translocation to the plasma membrane. However, NPY caused a rapid (already maximal after 30 s) and concentration-dependent (maximum at 10-100 nM) activation of extracellular signal-regulated kinase (ERK) as assessed by immunoblotting with epitope-specific, antiphosphotyrosine antibodies and in some cases enzymatically. ERK activation by 100 nM NPY was abolished by the Y(1) NPY receptor antagonist BIBP 3226 (1 microM), pertussis toxin treatment (100 ng ml(-1) overnight), the mitogen-activated protein kinase (MAPK) kinase inhibitor PD 98059 (100 microM), and the phosphatidylinositol-3-kinase inhibitor wortmannin (100 nM). Whereas the PKC inhibitor staurosporine (3 microM) inhibited ERK activation by NPY, the chemically distinct PKC inhibitors calphostin C (3 microM), Gö 6976 (3 microM), and bisindolylmaleimide I (3 microM) did not. NPY did not activate other MAPK such as jun N-terminal kinase or p38 MAPK. We conclude that NPY does not activate phospholipase D, PKC, jun N-terminal kinase, or p38 MAPK in HEL cells. However, NPY activates ERK by a pathway involving Y(1) receptors, pertussis toxin-sensitive G proteins, and phosphatidylinositol-3-kinase, whereas PKC may not be involved. Staurosporine may have PKC-independent effects on ERK activation.

Enzyme Inhibitors↗
PubMed1999

[10 years development in the treatment of opiate dependent patients in the Kaufbeuren district hospital].

Discussing drug abuse and the concept of "low-threshold" in the treatment of drug addicts, we investigated development of detoxification strategies in the Department of Psychiatry at Kaufbeuren during the last 10 years. In the following we describe 4 different phases of this development: In 1988 we admitted 34 opiate-dependent patients treated in general psychiatric units. In 1998 almost, 1,000 drug addicts were treated in specialised drug detoxification units. In the beginning we realised opiate detoxification treatment without medication. In the second phase we treated the subjects symptomatically. During the last four years we have been offering homologue opiate withdrawal with L-polamidone. Last year we extended the opiate detoxification treatment to the day hospital and outpatient setting. The comparative examination of patient moods during the so called qualified and the homologue splitted opiate withdrawal treatment shows amazing similarities regarding the oscillations, leaving out of account that the remarkable worsening after one week of drug assisted detoxification was seen one week later in the homologue splitted detoxification group.

Ambulatory Care↗
PubMed1999

Preclinical and initial clinical evaluation of 111In-labeled nonsulfated CCK8 analog: a peptide for CCK-B receptor-targeted scintigraphy and radionuclide therapy.

UNLABELLED: The presence of cholecystokinin (CCK)-B (gastrin) receptors has been shown in more than 90% of medullary thyroid cancers (MTCs) and in a high percentage of small cell lung cancers, stromal ovarium cancers and several other tumor types. METHODS: The aim of this study was to evaluate in vitro and in vivo whether 111In-labeled CCK-B receptor-specific CCK8 analog [D-Asp26,Nle28,31]CCK26-33 (D-Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2) is suitable for CCK-B receptor scintigraphy based on the finding that unlabeled nonsulfated diethylenetriamine pentaacidic acid [DTPA0]CCK8 and tetraazacyclododecanetetraacetic acid [DOTA0]CCK8 analogs show high and specific binding for CCK-B receptors in human tumors. Fifty percent inhibitory concentrations were in the low nanomolar range. RESULTS: In vitro, [111In-DOTA0]CCK8 showed specific internalization in CCK-B receptor-positive rat pancreatic tumor cells AR42J. Internalization of the analog appeared to be time and temperature dependent and receptor specific. From the data obtained with [111In-DOTA0]CCK8 and (125I)I-gastrin, the latter being a specific ligand for the CCK-B receptor, the rat pancreatic cell line CA20948 also appeared to be CCK-B receptor positive. This provides an in vitro and in vivo rat tumor model because this cell line can be grown to solid tumors in Lewis rats. In vivo biodistribution experiments in CA20948 tumor-bearing Lewis rats showed rapid clearance of [111In-DOTA0]CCK8, and specific uptake was found in the CCK-B receptor-expressing stomach and tumor. Furthermore, comparing [111In-DOTA0]CCK8 with the radioiodinated nonsulfated CCK10 analog (D-Tyr-Gly-Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2), both ligands having high affinity for the CCK-B receptor, tumor-to-blood ratios were significantly higher for [111In-DOTA0]CCK8 than for 125I-CCK10, analogous to the findings with radioiodinated and 111In-labeled octreotide. The study in humans with [111In-DTPA0]CCK8 showed receptor-specific uptake in the CCK-B receptor-positive stomach and in metastases in the neck region up to 48 h after injection. CONCLUSION: [111In-DOTA0]CCK8 is most promising for scintigraphy and, after coupling to therapeutic radionuclides, for radionuclide therapy of human CCK-B receptor-positive tumors such as MTC and small cell lung cancer.

Animals↗