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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 271 records · Page 15Linked to original sources

Ureteral stenting using a combined antegrade/retrograde procedure. A technique for difficult cases.

Ureteral stenting is a procedure of daily routine. There are however cases in which cystoscopic placement of a stent fails despite various technical aids. Percutaneous nephrostomy is usually performed in those patients. In some cases however it is no reasonable alternative. For these special cases we used a combined antegrade/retrograde technique consisting in antegrade guide wire insertion followed by retrograde ureteral stenting. In 8 of 12 cases it was finally possible to insert a ureteral stent with this method. To our mind this technique should be applied when other attempts of stenting have failed and percutaneous nephrostomy is no reasonable alternative.

Cystoscopes↗

Angiotensin I converting enzyme gene polymorphism and diabetic nephropathy in type II diabetes.

BACKGROUND: The factors leading to diabetic nephropathy (DN) are not completely understood. Besides glycaemic control, genetic predisposition seems to play an important role for the development of DN. Genes of the renin-angiotensin system are potential candidate genes. An insertion/deletion polymorphism in the gene coding for the angiotensin I converting enzyme (ACE) has been extensively examined, but results were conflicting. METHODS: We studied 658 patients with type II diabetes (n = 347 without DN, n = 311 with DN). RESULTS: No difference was found in genotype distribution or allele frequencies between diabetic patients with and without nephropathy as defined by albumin excretion > or = 30 mg/day, but patients on dialysis had more frequently the DD-genotype. CONCLUSION: Although we acknowledge certain problems in the design of the study the results in this large cohort suggest that the I/D polymorphism of the ACE gene does not play a major role in the development of DN. They are compatible, however, with a role of the gene in progression.

Adult↗

[Attitude of established physicians to medical rehabilitation: an empirical study of the access to rehabilitation problem].

Office-practice physicians' attitudes towards and knowledge of available medical rehabilitation benefits are crucial influences concerning the manner and extent to which they pursue their patients' access to rehabilitation. Covering some 1200 office-practice physicians in the catchment area of a workers pension insurance agency, LVA Oldenburg-Bremen, the present questionnaire study is directed at a closer analysis of these influences. The findings, for one, indicate great diversity of overall approval of rehabilitation measures, for the other they however also reveal varying judgements of the relevancy of rehabilitation benefits for the various disease groups. Suggestions are set out on the basis of our findings on how access to rehabilitation could be upgraded.

Adult↗

Leuko-reduction using an integral Sepacell filter early (4 h, 24 h) or late (48 h, 120 h) after plateletpheresis does not affect platelet function.

Leuco-reduction of aliquots of single-donor platelet concentrates with an integral Sepacell PLS-5A filter was performed 4, 24, and 48 h after apheresis including a control after 120 h (not recommended by the manufacturer) to evaluate the effect of both early and late filtration on the concentrates in a paired study. Highly efficient (> 2 log10) leuko-reduction was consistently observed for filtration any time after apheresis. Various proaggregatory stimuli were tested to determine the stimulus concentration (EC50 values) required for half-maximal aggregation of platelet samples (200 platelets/nl). Neither glycoprotein IIb/IIIa-dependent (thrombin-, collagen-, and APD-induced) nor glycoprotein Ib-mediated (ristocetin-induced) platelet function were affected by filtration 4, 24, 48, or 120 h after plateletpheresis. For single-donor plateletpheresis using a closed system with an integral Sepacell filter, our in vitro results suggest that the timing of leuko-reduction does not affect the platelet-dependent hemostatic qualities of the product.

Equipment Design↗

Platelet aggregation in response to collagen and thrombin reliably detects the ingestion of low-dose aspirin.

The exposure of blood donors to aspirin is not reliably excluded by pharmacokinetic measurements due to the irreversible effects of aspirin which persist even after elimination of aspirin and its metabolites from plasma. Tests of platelet functions do overcome this deficit, but are usually limited by substantial inter-individual variability of parameters of platelet function. We have evaluated platelet aggregation ex vivo in 20 aspirin-treated (100 mg single oral dose/day) patients in comparison with a control group of 20 aspirin-free donors. The results demonstrate a significant reduction in the collagen(2.5 micrograms/ml)-induced platelet aggregation by aspirin treatment, whereas thrombin(50 mumol/l TRAP-6)-induced platelet aggregation was not affected at all. Assessment of collagen-induced platelet aggregation relative to platelet responses of the same subject elicited either by thrombin or by a combination of collagen and thrombin does substantially improve the reliability of functional assays of aspirin.

Administration, Oral↗

Genetic determinants of diabetic renal disease and their impact on therapeutic interventions.

Approximately 30% of patients with type 1 and type 2 diabetes develop diabetic nephropathy. Apart from metabolic control, genetic predisposition plays an important role in its genesis. Analysis of intermediate phenotypic markers showed that the activity of Na/Li- and Na+/H(+)-countertransport is increased in patients with diabetic nephropathy. The renin-angiotensin system is of crucial importance as a system for therapeutic intervention and as genetic marker for susceptibility to renal disease. Consequently, the analysis of molecular genetic markers has focused on a polymorphism in the gene for the angiotensin II converting enzyme (ACE). However, the analysis of the I/D-polymorphism with respect to development of diabetic nephropathy in type 1 and type 2 diabetes has yielded conflicting results, at least in type 1 diabetes. These discrepant results may be due to differences in definition, sample size and ethnic background of the patients. In IgA glomerulonephritis it has been shown that the DD genotype (which is correlated with higher serum and tissue ACE activity compared to II genotype) is associated with a more rapid deterioration of renal function. The same adverse effect of the DD genotype could also be demonstrated in patients with diabetic nephropathy. Two studies examined the response to treatment according to the different genotypes, with contradictory results. A Japanese study showed a more pronounced reduction in proteinuria under ACE inhibitor treatment in patients with DD genotype, whereas a Danish study showed that patients with the DD genotype exhibited a steeper decline in renal function despite ACE inhibitor treatment. The data available for other candidate genes are fragmentary and negative throughout.

Diabetic Nephropathies↗

[Criteria for successful outcome of external fetal version from breech presentation to cephalic presentation].

The technique of external version of breech presentations has been proposed as a tool to reduce morbidity of fetus and mother. 79 cases of a 3 year period were evaluated aiming at identification of risk factors improving the success rate of the intervention. A total of 48% of attempts was successful. The most frustrating single factor was identified to be the oligohydramnion. Posterior implantation of the placenta improved the rate to 61%. The umbilical cord being localized by coloured Doppler had little influence even if positioned around the neck as neither success nor complications were predictable in this case. Maternal adipositas had a negative influence on the success rate. Perinatal morbidity war not increased in the group of external versions.

Breech Presentation↗

[Modification of transplacental digoxin transfer in the isolated placental lobule].

Digoxin is widely used in the transplacental therapy of fetal tachyarrhythmia. Unfortunately, in cases with severe cardiac insufficiency and hydrops fetalis, transplacental passage of digoxin is often hampered and therapy therefore ineffective. The present study was designed to establish the isolated placental lobule to quantify transplacental digoxin passage under different experimental conditions. Ten human placentas were obtained immediately after delivery, and a lobule was dually perfused after cannulating a small artery and vein of the chorionic plate and piercing four catheters through the corresponding basal plate. Flow rates were 12 ml/min in the maternal circuit and 6 (I) respectively 3 ml/min (II) in the fetal circuit. The maternal circuit was spiked with digoxin to 6.18 +/- 0.40 ng/ml, and transplacental passage was calculated from repeated fetal and maternal perfusate samples (Fluorescence-Polarization-Immunoassay; TDx, Abbott Laboratories). Within three hours of recirculating perfusion with a fetal flow rate of 6 ml/min (I), digoxin concentrations in the maternal circuit (400 ml) declined to 3.56 +/- 0.09 ng/ml, whereas digoxin levels in the fetal compartment (200 ml) increased to 2.58 +/- 0.37 ng/ml. With a fetal perfusion rate of 3 ml/min (II), the efflux of digoxin out of the maternal circuit was lower (p < 0.05) and the influx in the total compartment was reduced (fetal digoxin concentrations reached only 26.9 +/- 10.6% vs. 39.1 +/- 5.5% of the initial maternal digoxin concentrations). These data suggest that severe fetal cardiac insufficiency with reduced placental perfusion may be in part responsible for the decrease of transplacental digoxin passage in fetuses with hydrops.

Anti-Arrhythmia Agents↗

Temporal integration in the echolocating bat, Megaderma lyra.

Temporal integration is a crucial feature of auditory temporal processing. We measured the psychophysical temporal integration of acoustic intensity in the echolocating bat Megaderma lyra using a two-alternative forced-choice procedure. A measuring paradigm was chosen in which the absolute threshold for pairs of short tone pips was determined as a function of the temporal separation between the pips. The time constants determined with this paradigm are a crucial characteristic of the sonar system of M. lyra, a species orientating in its environment by very short broadband sonar calls emitted at high rates. Two different carrier frequencies for the tone pips were used to obtain data from the lower and the higher half of the hearing area of M. lyra. Both in the lower and in the higher frequency range, M. lyra showed very short time constants of about 220 microseconds. Our results are comparable to data from the echolocating dolphin, Tursiops truncatus, showing click integration times of about 260 microseconds and to estimates of auditory temporal integration in the context of echo clutter interference in the big brown bat.

Acoustic Stimulation↗

Electron transfer dynamics of Rhodopseudomonas viridis reaction centers with a modified binding site for the accessory bacteriochlorophyll.

Femtosecond spectroscopy in combination with site-directed mutagenesis was used to study the influence of histidine L153 in primary electron transfer in the reaction center of Rhodopseudomonas viridis. Histidine was replaced by cysteine, glutamate, or leucine. The exchange to cysteine did not lead to significant changes in the primary reaction dynamics. In the case of the glutamate mutation, the decay of the excited electronic level of the special pair P* is slowed by a factor of 3. The exchange to leucine caused the incorporation of a bacteriopheophytin b instead of a bacteriochlorophyll b molecule at the BA site. As a consequence of this chromophore exchange, the energy level of the electron transfer state P+BA- is lowered to such an extent that repopulation from the next electron transfer intermediate state P+HA- takes place, resulting in a long-lasting P+BA- population. The observed differences in time constants are discussed in the scope of nonadiabatic electron transfer theory considering the influence of the amino acids at position L153 and the chromophore exchange on the energy level of the intermediate state P+BA-. The results show that the high efficiency of primary electron transfer is reduced substantially, if the energy level of P+BA- is lowered or raised by several hundred wave numbers.

Bacteriochlorophylls↗

Base and sugar requirements for RNA cleavage of essential nucleoside residues in internal loop B of the hairpin ribozyme: implications for secondary structure.

The hairpin ribozyme is a small self-cleaving RNA that can be engineered for RNA cleavage in trans and has potential as a therapeutic agent. We have used a chemical synthesis approach to study the requirements of hairpin RNA cleavage for sugar and base moieties in residues of internal loop B, an essential region in one of the two ribozyme domains. Individual nucleosides were substituted by either a 2'-deoxy-nucleoside, an abasic residue, or a C3-spacer (propyl linker) and the abilities of the modified ribozymes to cleave an RNA substrate were studied in comparison with the wild-type ribozyme. From these results, together with previous studies, we propose a new model for the potential secondary structure of internal loop B of the hairpin ribozyme.

Base Composition↗

Identification of interleukin 1-induced apoptosis in rat islets using in situ specific labelling of fragmented DNA.

To study the ability of interleukin 1-beta (IL-1) to induce apoptosis in the endocrine pancreas, rat islets of Langerhans obtained from 14-day-old BB.1A rats were exposed to 25 U/ml IL-1 for 40 h. In order to prove the role of nitric oxide (NO) in this process islets were exposed either to 1 mmol/l N-nitro-L-arginine methylester (NAME) or to 25 mmol/l nicotinamide (NA) or to a combination of NA or NAME with IL-1. In dispersed cells oligonucleosomes, resulting from cleavage of nuclear DNA due to apoptosis, were identified by enzymatic labelling the free 3'-OH-DNA ends with fluorescein-dUTP and quantified by means of flow cytometry. After exposure to IL-1, the islets were characterized by elevated basal (in response to 2 mmol/l glucose) insulin release while glucose-stimulated (20 mmol/l glucose) insulin secretion was nearly completely abolished. In contrast, glucose-stimulated insulin secretion was well preserved in NAME-exposed islets, but was markedly inhibited after NA treatment. Accordingly, only the IL-1-induced inhibition of glucose-stimulated insulin secretion was significantly restored in the presence of NAME but was reinforced by NA. IL-1 exposure resulted in a significant increase in the percentage of apoptotic cells (untreated controls 3.8 +/- 0.5% IL-1 18.8 +/- 1.8%, P < 0.01). This effect was significantly reduced in the presence of NA and NAME. Nitrite production which was assayed as an equivalent of NO generation of islets was highest under the influence of IL-1 (16.48 +/- 1.40 versus 2.89 +/- 0.37 pmol/islet for control islets) which was correlated with the percentage of apoptotic cells. IL-1-stimulated nitrite production was reduced to 9.25 +/- 0.48 and 3.41 +/- 0.36 pmol/islet in the presence of NA or NAME, respectively. The results demonstrate the potency of IL-1 to induce apoptosis in rat islets. Since inhibition of NO production was always paralleled by a reduced ability of IL-1 to induce programmed cell death, this radical appears to be involved in this process. Remarkably, the near-complete prevention of NO generation as demonstrated under the influence of NAME was able to prevent the IL-1-induced deterioration of glucose-stimulated insulin secretion in parallel to the prevention of apoptosis-related appearance of DNA double-strand breaks. It is concluded that the elimination of damaged beta cells due to IL-1 exposure is partly achieved by induction of apoptosis.

Animals↗

Studies on the immunoglobulin-E system of the common marmoset in comparison with human data.

In the common marmoset (Callithrix jacchus jacchus) immunoglobulin E (IgE) serum levels and IgE synthesis of peripheral blood mononuclear cells (PBMC) in vitro were investigated in order to look for homologies to the human system. While IgE was not found in marmoset blood plasma with three commercial antihuman IgE-kits with monoclonal antibodies (mAbs), two other kits using polyclonal antibodies against human IgE revealed detectable IgE concentrations of up to 10 kU/liter in plasma samples of 19 out of 21 marmosets. In accord with human data, rhIL-4 showed biological functions under in vitro conditions in PBMC of the New World monkey. Proliferation, measured by 3H-thymidine incorporation, of isolated PBMC of marmosets could be induced by rhIL-4. FACScan analysis showed an enhanced expression of the low affinity IgE receptor CD23 (Fc epsilon RII) on CD20+ B lymphocytes after incubation with rhIL-4. Furthermore, PBMC from marmosets could be stimulated by IL-4 alone or in combination with dexamethasone as well as with lipopolysaccharide (E. coli) to produce IgE in culture. The results indicate that Callithrix jacchus is using an IgE system that is rather similar to that of humans, although not completely identical. Antihuman mAbs and rhIL-4 can be used to investigate IgE regulation in vitro of marmoset PBMC. These data encourage the development of a primate animal model for studying possible modifications of the IgE system under pathological conditions to find new therapeutic strategies in atopic diseases.

Animals↗

Auditory enhancement at the absolute threshold of hearing and its relationship to the Zwicker tone.

Auditory enhancement describes an improvement in the detection of a tonal signal in a broad-band masker with a spectral gap at the signal frequency if the signal is delayed in its onset relative to the masker. This auditory enhancement may be based on an increase of the effective signal level instead of a decline in the effective masker level. In order to evaluate whether this signal enhancement also exists at the threshold of hearing, we measured the absolute threshold for pure-tone pulses of different frequencies with and without preceding band-rejected noise. Such noise also causes the sensation of the Zwicker tone-a faint pure tone lasting for a few seconds immediately after the noise presentation. The pitch of this sensation is a complex function of the noise parameters but always lies at a frequency within the rejected band. During the Zwicker tone sensation, auditory sensitivity for tone pulses at frequencies adjacent to the Zwicker tone was improved by up to 13 dB instead of being reduced which might be expected due to the presence of the simultaneously audible Zwicker tone. The failure to influence this threshold shift with low-frequency tones and measurements of the ear's acoustical response indicate that this threshold improvement may be produced through neuronal disinhibition rather than through a release from mechanical suppression in the cochlea.

Acoustic Stimulation↗

The role of angiotensin I-converting enzyme gene polymorphism in renal disease.

Some renal diseases (e.g. diabetic nephropathy and IgA glomerulonephritis) cluster within families, consistent with a strong genetic component for the development or progression of these diseases, or both. In this context it is attractive to examine the insertion/deletion polymorphism of the angiotensin I-converting enzyme. This polymorphism determines the concentration of angiotensin I-converting enzyme not only in serum, but also in tissues and thereby presumably the locally available concentration of angiotensin II. Several studies have examined whether this polymorphism is associated with the development of diabetic nephropathy, but most of these failed to show such an association. Studies in patients suffering from IgA glomerulonephritis or other renal diseases, including diabetic nephropathy, demonstrated that the insertion/ deletion polymorphism plays a role in the progression of renal diseases and in the response to treatment with angiotensin I-converting enzyme inhibitor.

Angiotensin-Converting Enzyme Inhibitors↗

Cerebral tissue oxygenation during hypoxia and hyperoxia using artificial placentation in lamb.

Aiming at a better understanding of the pathophysiologic basis of perinatal encephalopathy, we evaluated patterns of tissue oxygenation during hypoxia and hyperoxia. We utilized both laserspectroscopy and invasive tissue-Po2 microneed measurements synchronously in five newborn lambs (141-143 days of gestation). The model of artificial placentation provided defined changes of the blood gases, using a extracorporeal circuit with interposition of membrane lung. During hyperoxia, the Po2 at the blood outlet port of the lung was raised to > 300 mmHg for five minutes. During hypoxia, Po2 was diminished as oxygen at the gas phasis was replaced by nitrogen. After the induction of hyperoxia, a rise of tissue-Po2 was observed. The synchronously recorded data of the laserspectroscopy showed adequately rising HbO2 values in concordance (r = 0.97, p < 0.001). As a constant finding we did not observe Cyt-aa3 changes during induced hyperoxia with tissue-Po2 values of < 40 mmHg. Furthermore, no changes in blood volume occurred in this case. A different pattern of the laserspectroscopic parameters was found when the tissue-Po2 rose above a value of > 40 mmHg and Cyt-aa3 rose after a lag-time occurred. During induced hypoxia an immediate fall of tissue-Po2 corresponding with a fall of HbO2 in the spectroscopic tracing occurred (r = 0.87, p < 0.001). A fall of the Cyt-aa3 level was seen with a lag-time when the tissue-Po2 had reached values of below 10 mmHg. In addition, a rise of blood volume was recorded in all cases of induced hypoxia. In conclusion, the results indicated that cellular redoxe state remains stable over a large range of oxygen partial pressure changes.

Animals↗