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Biomedical subjects

U Gebhardt

Publications and source records attributed to U Gebhardt.

At least 19 recordsLinked to original sources
PubMed2003

Volumetric bone mineral density in patients with childhood craniopharyngioma.

As the overall survival rate is high in patients with craniopharyngioma, the prognosis in survivors depends mainly on late effects. Late effects such as hypogonadism, growth hormone deficiency, glucocorticoid overreplacement and obesity have a strong impact on volumetric bone mineral density (vBMD). We analyzed vBMD and possible risk factors for reduced vBMD in 61 patients with childhood craniopharyngioma (29 f; 32 m) and in 14 weight, age, and sex-matched controls. VBMD was quantified by peripheral quantitative computed tomography (pQCT). Endocrine status, hormonal substitution therapy and calcium phosphate metabolism were evaluated. VBMD was in the lower normal range in 61 craniopharyngioma patients (total radial z-scores: median - 1.5; range - 3.1 to 1.4; trabecular z-scores: median - 0.4; - 2.4 to 2.3). 23 severely obese patients (body mass index [BMI] > 4 SD) had a higher total radial (p < 0.05) and trabecular (p < 0.05) vBMD when compared with 38 non-severely obese patients and 7 weight-matched controls. Although there was no gender difference in terms of obesity, endocrine substitution therapy or calcium phosphate metabolism, male patients had lower total radial (p < 0.01) and trabecular (p < 0.05) vBMD. Only in male patients' vBMD z-scores showed a positive correlation with BMI standard deviation score (SDS) (total radial z-score: Spearman r = 0.38, p = 0.03; trabecular z-score: Spearman r = 0.35, p = 0.04). We conclude that obesity has a major impact on vBMD in patients with craniopharyngioma. Lean male patients are at special risk for a lower vBMD, whereas female gender and severe obesity seem to have a protective effect regarding vBMD.

Adolescent↗
PubMed2003

Perioperative dexamethasone treatment in childhood craniopharyngioma--influence on short-term and long-term weight gain.

The substitution of dexamethasone during and after surgery of childhood craniopharyngioma is necessary in order to treat and/or prevent brain edema and adrenal insufficiency. Early post-operative weight gain is a predictor for severe obesity during long-term follow-up. In a retrospective analysis of 60 patients with childhood craniopharyngioma we inquired whether dose and duration of perioperative dexamethasone therapy (n = 68) had influence on short-term post-operative weight gain and long-term development of severe obesity. The median follow-up period was 4.2 years, ranging from 1 to 9 years. 24 patients (14 f/10 m) developed severe obesity (BMI > 3 SD). 28 patients (10 f/18 m) retained normal weight (BMI < 2 SD). Eight patients presented with a BMI between 2 and 3 SD at the final visit. Differences in terms of age at surgery or follow-up period were non-detectable between the analyzed groups of craniopharyngioma patients. Duration and cumulative dexamethasone doses (mg/m2 BSA) for perioperative dexamethasone therapy were similar for severely obese patients (duration: 8.7 d; 4.5 - 17 d, cumulative dose: 74; 42 - 177 mg/m2 BSA) and normal weight patients (duration: 10.0 d; 1 - 41 d; dose: 76; 9 - 390 mg/m2 BSA). Whereas cumulative dexamethasone doses positively (p < 0.01; rho: 0.424) correlated with weight gain during the first year following surgery, long-term development of severe obesity was not influenced by dose and duration of perioperative dexamethasone treatment. Patients who developed severe obesity during follow-up had a higher (p < 0.001) BMI already at the time of diagnosis. We conclude that dose and duration of perioperative dexamethasone treatment had short-term effects on post-operative weight gain, but not on the development of long-term severe obesity. The results of our retrospective analysis are currently tested in a prospective surveillance study Kraniopharyngeom 2000 (www.kraniopharyngeom.com).

Adolescent↗
PubMed2000

Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor.

The mechanisms underlying the hepatotropism of hepatitis A virus (HAV) and the relapsing courses of HAV infections are unknown. In this report, we show for a mouse hepatocyte model that HAV-specific immunoglobulin A (IgA) mediates infection of hepatocytes with HAV via the asialoglycoprotein receptor, which binds and internalizes IgA molecules. Proof of HAV infection was obtained by detection of HAV minus-strand RNA, which is indicative for virus replication, and quantification of infectious virions. We demonstrate that human hepatocytes also ingest HAV-anti-HAV IgA complexes by the same mechanism, resulting in infection of the cells, by using the HepG2 cell line and primary hepatocytes. The relevance of this surrogate receptor mechanism in HAV pathogenesis lies in the fact that HAV, IgA, and antigen-IgA complexes use the same pathway within the organism, leading from the gastrointestinal tract to the liver via blood and back to the gastrointestinal tract via bile fluid. Therefore, HAV-specific IgA antibodies produced by gastrointestinal mucosa-associated lymphoid tissue may serve as carrier and targeting molecules, enabling and supporting HAV infection of IgA receptor-positive hepatocytes and, in the case of relapsing courses, allowing reinfection of the liver in the presence of otherwise neutralizing antibodies, resulting in exacerbation of liver disease.

Animals↗
PubMed1997

Variability of cerebral blood flow deficits in 99mTc-HMPAO SPECT in patients with Alzheimer's disease.

The purpose of this study was to analyse the frequency of the different pathological perfusion patterns in SPECT in a clinical, unselected population of patients with Alzheimer's disease. In 91 patients and 16 control subjects regional cerebral blood flow (rCBF) was measured with Single Photon Emission Computed Tomography (SPECT) using 99mTc-hexa-methyl-propyleneamine oxime (HMPAO). 95% confidence intervals obtained from the perfusion values of the control subjects were used to define normal perfusion ranges. The frequency of perfusion deficits in the left frontal, temporal, parietal and occipital lobes were 62.2%, 60.4%. 70.3% and 23.1%, respectively. In the right hemisphere the corresponding values were 60.4%, 58.2%, 63.7% and 9.9%. With the exception of the occipital lobes these frequencies were not significantly different. The analysis of the perfusion pattern of each patient revealed 35 different combinations of lobes with perfusion deficits. The temporo-parietal perfusion deficits were not more frequent than the temporofrontal perfusion deficits. These results suggest that in the clinical routine a high variety of heterogeneous rCBF patterns have to be expected.

Aged↗
PubMed1995

The low affinity Fc gamma RIIa and Fc gamma RIIIb on polymorphonuclear neutrophils are differentially regulated by CD45 phosphatase.

Stimulation of human polymorphonuclear neutrophils through ligation and cross-linking of the low affinity Fc gamma RIIa and Fc gamma RIIIb using mAb Fab and F(ab')2 fragments led to transient intracellular calcium mobilization and activation of the respiratory burst. Fc gamma RIIIb engagement resulted in a different pattern of intracellular calcium flux, and induction of the respiratory burst was significantly more effective than in the case of Fc gamma RIIa. These data demonstrate that the capacity of Fc gamma RIIIb to transduce transmembrane signals itself contributes to full cell activation. Treatment with a mAb F(ab')2 fragment recognizing CD45 phosphatase suppressed Fc gamma R-induced calcium mobilization in a dose-dependent manner. An ongoing intracellular calcium mobilization was immediately terminated when activation was followed by co-cross-linking Fc gamma R and CD45. This suggests that the initial steps of Fc gamma R signal transduction pathways are influenced by the state of tyrosine phosphorylation. Combined cross-linking of both receptors, however, was hardly susceptible to CD45. Also, inhibition of respiratory burst by CD45 in the case of Fc gamma RIIIb was minimal compared with that for Fc gamma RIIa. Signal transduction pathways of low affinity Fc gamma RIIa and Fc gamma RIIIb are differentially regulated by CD45, underlining the essential function of Fc gamma R-mediated tyrosine phosphorylation in polymorphonuclear neutrophil activation.

Adult↗
PubMed1988

Introduction of an automatic QT interval driven rate responsive pacemaker.

QT driven rate responsive pacemakers have been implanted since 1981. The more than 6 years experience and additional knowledge gained during several clinical studies have culminated in the design of an automatic rate responsive pacemaker. The adjustment of the rate responsive function to each individual patient is carried out automatically by the pacemaker, which therefore performs several measurements both at rest and during exercise. The results of these measurements are used to adapt the rate responsive parameters in order to optimize the rate response, even under changing circumstances.

Algorithms↗
PubMed1987

DSA--control of implanted devices for arterial hepatic perfusion.

In contrast to conventional film angiography, the perfusion pattern of hepatic arterial chemotherapy was consistently visualized by DSA in 40 patients with implanted Infusaid pump or Port-A devices. Incomplete perfusion of a liver region by the cytotoxic agent was recognized by DSA as accurately as by nuclide scintigraphy. Furthermore, DSA appeared to be more sensitive in determining aberrantly perfused extrahepatic regions; this was especially true when there was a nonligated right hepatic artery. Specific details of vascular lesions and associated complicating events also could be satisfactorily analyzed by DSA only.

Adult↗
PubMed1986

Hemodynamic response to LBNP following 2 hours HDT (-6 degrees).

Central hemodynamics have been determined during stepwise decreasing LBP in head-down tilt (HDT) of -6 degrees. Measurements were performed on eight healthy volunteers using right heart catheterization. During LBNP, pressures in the right atrium, pulmonary artery, and pulmonary capillary (preload) decreased in parallel with the increase of negative pressure applied to the lower part of the body. Similarly, stroke volume and cardiac output decreased with increasing negative pressure. Heart rate moderately increased (30%) as well as total peripheral resistance. The left ventricular function curve was shifted downward and to the left during LBNP indicating hypovolemia with no evidence of decreased contractility. Cardiac dimensions determined by echocardiography changed in a similar way as those obtained by invasive measurements. There was a very close correlation between stroke volume determined by thermodilution and by echocardiography. Plasma norepinephrine and dopamine tended to increase at the end of LBNP. Echocardiography proved a useful and reliable approach to hemodynamic measurement during LBNP and is recommended for analysis of hemodynamic parameters during zero G and Gz simulation.

Adult↗
PubMed1984

Central hemodynamics during zero gravity simulated by head-down bedrest.

Central hemodynamics during head-down tilt of -6 degrees lasting for 2 h were studied using catheterization of the pulmonary artery. M-mode echocardiography was performed simultaneously. Significant increases occurred for pressures in the right atrium, pulmonary artery in pulmonary wedge position, and for pulmonary vascular resistance. Cardiac and stroke volume index, heart rate, mean arterial pressure, and total systemic resistance remained constant throughout the exposure time. Constancy was also observed for echocardiographic measures of cardiac dimensions. It is concluded that head-down tilt leads to an increase of preload without any evidence of disturbed left ventricular function. No distinct time course of hemodynamic variables could be seen. Echocardiography proved a useful method to study cardiovascular adaptations during head-down tilting.

Adaptation, Physiological↗
PubMed1981

Cardiovascular and biochemical response to simulated space flight entry.

Twelve men and 12 women were exposed to two types of short-duration (6 h) space flight entry simulation: bedrest (no head-down tilt) and water immersion (to the neck). Preceding and following the simulation, orthostatic tolerance testing using LBNP (Lower Body Negative Pressure) was performed. Male LBNP tolerance was greater than female LBNP tolerance at all four comparison points (pre- and post-bedrest, pre- and post-water immersion); whereas the short-duration bedrest reduces female LBNP tolerance about as effectively as water immersion, only water immersion leads to marked LBNP intolerance in the male subjects. If the water immersion model simulates zero G, loss of male and female orthostatic tolerance will be about equal after short-duration space flight. On the other hand, the bedrest simulation would indicate a greater loss of orthostatic tolerance for females.

Blood Pressure↗
PubMed1980

A new application of LBNP to measure orthostatic tolerance before and after 0-g simulation (water immersion).

Lower body negative pressure (LBNP) remains an important device for the generation of orthostatic stress in the space flight environment as well as a tool to measure inflight and postflight changes in orthostatic response. These applied levels of LBNP have typically not exceeded 50-60 mm Hg negative pressure. Information is incomplete as to the levels of absolute LBNP orthostatic tolerance, and the factors responsible for their variance. A better definition of the tolerance limits for males and females could be expected to aid the evaluation of lower levels of LBNP. An LBNP device was built to study absolute orthostatic tolerance; additionally, another LBNP device was constructed to permit orthostatic tolerance testing directly after a controlled water immersion period. Absolute LBNP orthostatic tolerance patterns are analyzed for a group of males and females (series I). A preliminary statement on the variations of LBNP orthostatic tolerance after limited periods of water immersion and bed rest is also provided (series II).

Adolescent↗
PubMed1979

Development of an electrocatalytic glucose sensor.

For the determination of glucose in body fluids, the electrocatalytic sensor, besides the enzyme sensor, is quite suitable, particularly for long-term intracorporeal operation. The measuring response is disturbed by the fluctuating concentrations of the interfering substances that are simultaneously present in body fluids. However, the disturbance can essentially be controlled, as is shown in the case of amino acids. Their marked influence on glucose oxidation is suppressed at a membrane-covered sensor electrode by the use of a potential step method.

Artificial Organs↗
PubMed1978

[In vitro and in vivo investigations with different nitrofurantoin formulations (author's transl)].

In vitro dissolution tests and biopharmaceutical investigations on healthy test persons were carried out with 4 different galenic tablet formulations. Three of these formulations were prepared by a special galenic process, the fourth corresponded to the usual tablet formulations. It was shown that the dissolution behaviour of the formulations in vitro, in accordance with the specifications of the American Pharmacopoeia (USP XIX), does not correlate with the parameters found in vivo. However, if the formulations in vitro are checked with the Sartorius model according to Stricker, correlations can be found with the in vivo behaviour of nitrofurantoin. A linear relationship was achieved by the special galenic formulation directly regulating the pharmacokinetic behaviour of nitrofurantoin. The known biological scatter of nitrofurantoin was strongly reduced by this process. The amount of the substance still present and circulating in the body creating the side effects could be reduced to a minimum. All facts considered, the therapeutic safety is also ensured.

Adult↗
PubMed1976

Computer assistance in multiparameter flow microphotometry of mammalian cells.

Flow system technology enables the biological and medical experimenter to investigate the distribution spectra of various cellular characteristics separately or in parameter combination on the basis of ultrarapid single cell measurements. A typical rate of recognition is about 1000 to 5000 cells per second and the precision of measurements and their statistical relevance has been previously unobtainable. According to the approach of the multiparameter analysis and high data rate, computer assistance in flow system technology is given primary consideration. In this study three different kinds of software controlled modes in data acquisition are demonstrated: normal acquisition and linear accumulation of single parameters, spectra accumulation of two correlated parameters of each single cell and documentation as linear, two- or three-dimensional distribution pattern, and linear accumulation of two correlated parameters simultaneously with their actual signal-to-signal ratio. A first attempt to analyze distribution spectra was the application of the entropy of the structure routinely used in cybernetics. This function seems to be a measure for determining the degree of synchrony in an appropriate pretreated cell population. A special mathematical strategy has been applied to the linear spectra cellular DNA content, whose advantage is the quantitative extraction of the fractions concerning the various phases of the life cycle cells. The validity of this special curve fitting procedure has been proven on various experimental cell populations.

Animals↗