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Biomedical subjects

H Scholz

Publications and source records attributed to H Scholz.

At least 37 records · Page 2Linked to original sources

[Five days ceftibuten versus 10 days penicillin in the treatment of 2099 patients with A-streptococcal tonsillopharyngitis].

UNLABELLED: Group A Streptococci have remained sensitive to penicillins and other betalactam antibiotics, e. g. cephalosporins. Since the beginning of the 1950s oral penicillin V given three times daily in a dose of 50,000 IU daily has been the drug of choice against Group A streptococcal infection. The German Society for Pediatric Infectious Diseases (DGPI) undertook a large scale multicenter randomized study of culture-proven A-streptococcal tonsillopharyngitis to compare the efficacy and safety of a five day regimen of ceftibuten (9 mg/kg KG, once daily) with 10 days of penicillin V (50,000 I.E./kg KG, divided in three doses), testing for equivalence of clinical and bacteriological efficacy. A one year follow-up served to assess poststreptococcal sequelae like rheumatic fever or glomerulonephritis. RESULTS: The clinical efficacy at the clinical end-point 7-9 days after end of treatment was 86.9% (419/482) for ceftibuten and 88.6% (1,198/1,352) for penicillin V. This result is statistically equivalent (P = 0.0152). Resolution of clinical symptoms was significantly faster in the ceftibuten group (P = 0.043/Fisher-Test) and compliance was significantly superior as well (P (0.001). Eradication of group A streptococci at an early control 2-4 days after end of treatment was not equivalent, 78.49% for ceftibuten and 84.42% for penicillin V (P = 0.5713). Both eradication rates were comparable 7-8 weeks after end of treatment (84.65%, 375/443 ceftibuten vs. 86.82%, 1,067/1,229 penicillin V), the difference not being significant. No cases of poststreptococcal sequelae, e.g. rheumatic fever or glomerulonephritis, attributable to either ceftibuten or penicillin were observed in the course of the study.

Adolescent↗

Nitric oxide activates the beta 2 subunit of soluble guanylyl cyclase in the absence of a second subunit.

Previously characterized mammalian soluble guanylyl cyclases form alpha/beta heterodimers that can be activated by the gaseous messenger, nitric oxide, and the novel guanylyl cyclase modulator YC-1. Four mammalian subunits have been cloned named alpha(1), beta(1), alpha(2), and beta(2). The alpha(1)/beta(1) and alpha(2)/beta(1) heterodimeric enzyme isoforms have been rigorously characterized. The role of the beta(2) subunit has remained elusive. Here we isolate a novel variant of this subunit and show that the beta(2) subunit does not need to form heterodimers for catalytic activity because enzyme activity can be measured when it is expressed alone in Sf9 cells. In analogy to the beta(3) subunit recently isolated from the insect Manduca sexta, activity was dependent on the presence of 4 mm free Mn(2+). The EC(50) values for the NO-donor diethylamine/NO were shifted to the left by 1 order of magnitude as compared with the alpha(1)/beta(1) heterodimeric form. In the presence of the detergent Tween, NO sensitivity of beta(2) was abolished, but the enzyme could be activated by protoporphyrin IX, indicating removal of a prosthetic heme group and exchange for the heme precursor. We suggest that the beta(2) subunit is the first mammalian NO-sensitive guanylyl cyclase lacking a heterodimeric structure.

Amino Acid Motifs↗

Developmental changes of nitric oxide-sensitive guanylyl cyclase expression in pulmonary arteries.

Inhaled nitric oxide (NO) is known to influence the contractile state of pulmonary arteries most likely by activation of soluble guanylyl cyclase (sGC) in smooth muscle cells. However, the cellular distribution of sGC has not been determined empirically, due to a lack of specific antibodies. Here, we describe a novel antibody directed against the beta1 subunit of sGC to study the cellular distribution of sGC in lung during development. Using the novel antibody, the enzyme was demonstrated in fetal, neonatal, and adult lungs by Western blot, showing maximum expression in neonatal lung. These data were confirmed by measurements of sGC activity. In pulmonary arteries of fetal lung sGC-beta1 immunoreactivity was present in smooth muscle cells and absent in endothelial cells. With postnatal development an increase in immunoreactivity in endothelial cells and a reciprocal decrease in smooth muscle cells was apparent. The reported changes in sGC expression likely contribute to the known age-dependent differences in response to inhaled NO.

Aging↗

Small blood volumes from children for quantitative sotalol determination using high-performance liquid chromatography.

A sensitive high-performance liquid chromatographic method using fluorescence detection has been developed for sotalol determination in small plasma samples of children and newborns with limited blood volume. In sample sizes of 100 microl of plasma, sotalol was extracted using an internal standard and solid-phase extraction columns. Chromatographic separation was performed on a Spherisorb C6 column of 150x4.6 mm I.D. and 5 microm particle size at ambient temperature. The mobile phase consisted of acetonitrile-15 mM potassium phosphate buffer (pH 3.0) (70:30, v/v). The excitation wavelength was set at 235 nm, emission at 300 nm. The flow-rate was 1 ml/min. Sotalol and the internal standard atenolol showed recoveries of 107+/-8.9 and 97+/-8.1%, respectively. The linearity range for sotalol was between 0.07 and 5.75 microg/ml, the limit of quantitation 0.09 microg/ml. Precision values expressed as percent relative standard deviation of intra-assay varied between 0.6 and 13.6%, that of inter-assay between 2.4 and 14.4%. Accuracy varied between 86.1 and 109.8% (intra-assay) and 95.4 and 103.3% (inter-assay). Other clinically used antiarrhythmic drugs did not interfere. As an application of the assay, sotalol plasma concentrations in a 6-year-old child with supraventricular tachycardia treated with oral sotalol (3.2 mg/kg per day) are reported.

Anti-Arrhythmia Agents↗

The beta 2 subunit of nitric oxide-sensitive guanylyl cyclase is developmentally regulated in rat kidney.

We have recently shown that nitric oxide activates the beta2 subunit of soluble guanylyl cyclase. In the present study, we show developmental regulation of this subunit. Analysis of mRNA expression by RT-PCR and RNase protection analysis in kidneys revealed no expression of the beta2 subunit in neonatal and strong expression in adult rats. A reciprocal regulation with much lower expression levels was observed in rat lung. Further examination of kidneys from 3, 6, 16, 22, 25, 31 and 36-day-old rats showed that significant expression appears between postnatal day 16 and 22. Isolation of the rat beta2 promoter by genome walking and cloning into a reporter gene vector showed promoter activity for the sense but not the antisense construct providing an in vitro assay for further analysis of the developmental beta2 subunit regulation.

Animals↗

Mechanically induced potentials in rat atrial fibroblasts depend on actin and tubulin polymerisation.

When atrial tissue contracts, mechanically induced potentials (MIPs) are generated in fibroblasts, presumably by activation of a non-selective cation conductance Gns. Non-stimulated atrial fibroblasts had a mean (+/-SD) membrane potential (Em) of -22 +/- 2 mV and an input resistance of 510 +/- 10 MS. MIP amplitude (AMIP) was 38+/-4 mV when current injection had polarised Em to Vm = -50 mV. The slope of the function relating AMIP to Vm can be regarded as a mechanosensitive factor (Xms) that describes the relative increase in Gns during a MIP. Putative involvement of cytoskeletal fibres in activation of Gns was studied by delivering drugs from the intracellular recording microelectrode. Destabilisation of F-actin by 0.2 mM cytochalasin D reduced AMIP from 38 to 16 mV and Xms from 5 to 1.8. Destabilisation of tubulin with 0.2 mM colchicine reduced AMIP to 21 mV and Xms to 2.1. The combination colchicine plus cytochalasin D reduced AMIP to 9 mV and Xms to 1.4. Promoting F-actin stability with exogenous adenosine 5'-triphosphate (ATP) increased AMIP and Xms and attenuated the effects of cytochalasin D. Similarly, facilitation of tubulin stability with guanosine 5'-triphosphate (GTP) or taxol increased AMIP and Xms and attenuated the effects of colchicine. The results suggest that transfer of mechanical energy from the deformed fibroblast surface to the Gns channel protein depends on intact F-actin and tubulin fibres.

Actins↗

Prevalence of genotypes 1 and 2 of bovine viral diarrhea virus in Lower Saxony, Germany.

The aim of this study was to find whether an antigenic drift had occurred in Lower Saxony in the past 40 years. For this, the genetic diversity of bovine viral diarrhea virus (BVDV) isolates mainly from Lower Saxony was estimated by RT-PCR and sequencing of a 420 bp fragment of the E2 glycoprotein gene. Sixty-one field virus isolates collected during routine diagnostics between 1960 and 2000 in Lower Saxony, Northern Germany, were analyzed. Phylogenetic analysis allowed discrimination of genotypes BVDV 1 and 2. Excepting two isolates, which were of BVDV type 2, most of the isolates were classified as BVDV type 1. This group could be further subdivided into four subgroups and one disparate isolate. Independent of the year of isolation and geographical localization, 54 isolates clustered in two subtypes (BVDV subtypes 1b and 1d). Only one isolate was classified as BVDV type 1a, thus being similar to the North American NADL strain, and to the vaccine strain Oregon C24V, which was extensively used for vaccination in Germany. The remaining isolates belonged to new clusters tentatively designated as BVDV subtypes 1g and 1f. To compare the cluster designation with that of other studies, phylogenetic analysis of representatives of each of the subgroups based on the 5' untranslated region (5'UTR) was performed. It grouped the viruses similarly. The results indicate that the BVDV population seems to be relatively stable over 40 years in Lower Saxony.

5' Untranslated Regions↗

Contractile function of rat myocardium is less susceptible to hypoxia/reoxygenation after acute infarction.

In this study we tested the hypothesis that induction of heat shock proteins (HSPs) and antioxidant enzymes is a compensatory mechanism, which preserves the contractility of the surviving myocardium after acute myocardial infarction. For this purpose, mechanical function of isolated rat papillary muscles was tested 15 h after experimental myocardial infarction and sham operation, respectively. Contractility of the preparations was compared to the expression of HSP25, HSP72, and glutathione peroxidase activity (GSH-Px) at normoxia and during hypoxia/reoxygenation. At normoxic conditions, rates of isometric contraction and, in particular, of relaxation were significantly higher after acute myocardial infarction than after sham operation. Improved relaxation rates were reflected in 2- to 3-fold higher heat shock protein levels in papillary muscles from rats with myocardial infarction compared to sham operated animals. During hypoxia/reoxygenation, the rates of contraction and relaxation were better preserved after myocardial infarction than after sham surgery. Recovery of relaxation rates during reoxygenation was associated with increased HSP25 levels and enhanced GSH-Px activity after myocardial infarction. In conclusion, heat shock proteins exert a beneficial effect on cardiac muscle relaxation after acute myocardial infarction. Enhanced heat shock protein expression and GSH-Px activity may protect the contractile function of the surviving myocardium against the damaging influence of hypoxia/reoxygenation during the early post-infarct period.

Animals↗

The influence of intraarterial prostaglandin E(1) on vascular hydraulic impedance and infrainguinal graft patency.

OBJECTIVES: To evaluate the influence of intraoperative arterial prostaglandin E(1)(alprostadil) infusion on hydraulic impedance in relation to graft patency. METHODS: Hydraulic impedance was measured in 115 infrainguinal bypasses by means of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and 57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 microg of alprostadil were administered into a temporary bypass and the haemodynamic changes were recorded. The reactions of input (Z(x)) and characteristic (Z(0)) impedances as well as phase relations were derived and related to graft outcome after three years. RESULTS: Significant changes after administration of prostaglandin were observed for overall pressure (74 vs. 84 mmHg, p<0.01), flow rate (194 vs 160 ml/min, p<0.01), input impedance (0.55 vs. 0.75 PRU, p<0.01) and the phase angle of the first harmonic (-18 degrees vs -26 degrees, p<0.01). An increase of at least one degree of the first harmonic phase angle following alprostadil injection in the crural bypass group was associated with a significant better graft prognosis of crural (p<0.01) but not popliteal grafts. Primary and secondary patency rates after three years for crural grafts with an increase of at least one degree were 62% and 63% (n=45) and for non-responders 18% and 0% (n=12, p(prim)<0.01, p(sec)<0.001). All crural bypasses with poor prostaglandin reaction occluded within 9 months (n=12) after the operation. CONCLUSIONS: The EBF method allows a combined assessment of peripheral resistance and impedance parameters. The response of the first harmonic phase angle provides important predictive information regarding femoro-crural grafts.

Adult↗

Tissue differentiation and cytokine synthesis during strain-related bone formation in distraction osteogenesis.

To investigate the contributions of various cytokines that are involved in mechanically related bone formation, we applied defined uniaxial strains in a rabbit model of mandibular elongation and examined the regenerating bone during early stages of dist raction osteogenesis by histomorphometry. We also measured serum concentrations of various cytokines during the distraction. Cell proliferation and differentiation indices correlated significantly (P<0.001) with the extent of load application. Serum concentrations of insulin-like growth factor-1 (IGF-1) decreased after osteotomy whereas transforming growth factor beta1 (TGFbeta1) showed a postoperative increase. Prostaglandin E2 (PGE2) concentrations were constant throughout the experimental period. Collagen degradation decreased slightly postoperatively and increased in samples exposed to higher magnitudes of strain. Our data show that it is the magnitude of mechanical strain that decides tissue response by a characteristic cell proliferation and differentiation. The operative trauma leads to inverse changes in serum concentrations of TGFbeta1 and IGF-1, thereby promoting the recruitment of osteoblastic precursor cells as well as collagen matrix synthesis.

Animals↗

[Femoro-distal ePTFE bypass grafting using femoro-crural patch prosthesis (FCPP). Results of a prospective clinical study].

Femorodistal bypass using exclusively PTFE is known to have a poor prognosis, mostly because of the development of myointimal hyperplasia (MIH). Several vein patch techniques are established but the role of hemodynamics within the anastomotic site has only been explained insufficiently and is hardly considered clinically. In a prospective study, between 6/1992 and 7/1998 129 patients (89 m/40 f, mean age 65.2 +/- 10.0 years) with critical limb ischemia and no usable saphenous vein were included to undergo femorodistal ePTFE bypass grafting with a new, hemodynamically optimized distal end-to-side anastomosis. Patients were followed at 6-month intervals with clinical investigation and color-coded Doppler sonography. Primary and secondary graft patency (PPR, SPR), limb salvage, and patient survival were calculated according to Kaplan-Meier. With a median follow-up of 45 (range 6 to 72) months, PPR and SPR at 1, 3 and 5 years were 63.0, 35.7 and 27.6% and 74.5, 44.8%, and 37.6%, respectively. Limb salvage at 1, 3 and 5 years was 86.4%, 78.7% und 73.2%. There was no perioperative mortality. Graft infection occurred in 7 patients (5.2%). ePTFE bypass grafting represents a valuable option for infragenicular and crural reconstruction in the absence of autologous vein. The new anastomotic design was feasible and represents another adjunct to possibly improve patency of femorodistal bypass allografts.

Aged↗

Determination of carvedilol in human cardiac tissue by high-performance liquid chromatography.

A new high-performance liquid chromatographic method has been developed for the determination of the beta-receptor blocker carvedilol in human cardiac tissue. After homogenizing tissue samples in a microdismembrator, carvedilol and the internal standard naftopidil are extracted with acetone. The extract is evaporated to dryness and reconstituted in a potassium acetate buffer of pH 3.5. Samples are cleaned up with solid-phase extraction columns. Carvedilol and the internal standard show recoveries of 69.8 +/- 12.2% and 63.9 +/- 9.34%, respectively. The linearity range for carvedilol is 0.01-0.35 ng/mg (parts per billion) tissue (wet weight), and the limit of quantitation is 0.01 ng/mg. The percentage coefficient of variation of the intra-assay varies between 1.45 and 5.38% and the interassay between 4.25 and 6.96%. To use as an application of the assay, the cardiac carvedilol tissue level in a patient on oral carvedilol therapy for congestive heart failure is reported.

Adrenergic beta-Antagonists↗

Immunodiagnostic identification of dairy cows infected with Prototheca zopfii at various clinical stages and discrimination between infected and uninfected cows.

Protothecosis is a severe form of mastitis in cattle that is caused by colorless algae of the genus Prototheca. So far, no suitable serological test for the identification of infected animals is available for routine diagnosis. In this study an indirect enzyme-linked immunosorbent assay (ELISA) for the identification of infected cows and for discriminating among infected cows at various clinical stages was developed. Immunoglobulin G (IgG) in serum and IgA and IgG1 in whey were used as antibody isotypes. The ELISA was evaluated using serum and whey from animals at different clinical stages of infection. A total of 12 cows with acute clinical manifestation of protothecal mastitis, 22 cows with clinical signs of chronic mastitis, 40 Prototheca zopfii-negative cows, and 18 cows with chronic clinical signs and earlier cultures positive for P. zopfii but with presently negative culturing results were investigated. A sensitivity of 96% and a specificity of 94% were calculated for the ELISA based on IgA levels. Intra-assay and interassay variations were calculated to be 6.08 and 6.32%, respectively. Based on these data, this ELISA was found to be suitable for discrimination between infected and uninfected animals and might therefore be useful for screening affected herds.

Animals↗

Expression and tissue localization of soluble guanylyl cyclase in the human placenta using novel antibodies directed against the alpha(2) subunit.

The cytoplasmic or soluble forms of guanylyl cyclase (sGC) are heme-containing heterodimeric enzymes that are regulated by nitric oxide (NO) and carbon monoxide (CO). These gaseous messenger molecules are produced in the human placenta and are potential regulators of vasodilation and trophoblast invasion. The alpha(2)-subunit of sGC has only recently been shown to naturally occur in placental extracts. In the present study, two novel antibodies directed against different epitopes of the alpha(2) subunit, were generated. Western Blot analysis confirmed the presence of a 82 kDa protein, identical with alpha(2) protein overexpressed in Sf9 cells. According to RNase protection analysis the alternatively spliced alpha(2i) variant was absent from human placenta. Immunohistochemical analysis showed the presence of alpha(2) protein in syncytiotrophoblast and villous and umbilical blood vessels, which are known sites of NO production. Strong expression was observed in the extravillous (intermediate) trophoblast, where the expression of CO-generating hemeoxygenases has recently been documented. Localization of alpha(2) subunit expression suggests a role for sGC in mediating the actions of both NO and CO. The novel antibodies characterized in the present study will be powerful tools to further elucidate the role of the NO/CO/cGMP signaling pathways in pathologic states such as preeclampsia and intrauterine growth retardation.

Amino Acid Sequence↗

[Influences on the occurrence of abomasal displacements in German Holstein cows].

The objectives of this study were to analyse risk factors for the prevalence of abomasal displacement in German Holstein cows. In the period from 02/01/1999 to 01/31/2000 five veterinary surgeons in Northern Lower Saxony registered all cases of abomasal displacement in German Holstein cows being under the official milk recording scheme. In total, the investigation included 160 farms and 9315 cows. An abomasal displacement was registered in 151 German Holstein cows, corresponding to a frequency of 1.6%. More than 75% of the abomasal displacements appeared during the first 30 days after calving. The left abomasal displacement (74.8%) was recorded more often than the right abomasal displacement (25.2%). Milk recording and pedigree data were supplied by the VIT (Vereinigte Informationssystem Tierhaltung), Verden, and merged with the own recordings. The influences of the calving month, the lactation number, the age at calving, the inbreeding coefficient, calving performance, duration of pregnancy, breed of calf sire, calf sire and the breeding values for the milk performance did not explain a significant part of the variation of the frequency of the abomasal displacement. Significant effects of the sire, birth of twins or even more calves and the herd were obtained for the leftsided abomasal displacement. For the rightsided abomasal displacement and for all abomasal displacements the herd effect was not significant. Heritability estimates using bivariate linear REML models were h2 = 0.043 +/- 0.012 for the leftsided abomasal displacement, and h2 = 0.007 +/- 0.004 for the rightsided abomasal displacement, respectively. Using the threshold model the heritabilities yielded estimates of h2 = 0.51 for the left abomasal displacement, and for the right abomasal displacement of h2 = 0.19, respectively.

Abomasum↗

Myocardial contractility after infarction and carnitine palmitoyltransferase I inhibition in rats.

Inhibition of carnitine palmitoyltransferase I with etomoxir increases sarcoplasmic reticulum Ca(2+)-transport and V(1) isomyosin expression. To test whether etomoxir attenuates contractile dysfunction after myocardial infarction, we compared the contractility of papillary muscles from etomoxir- and placebo-treated rats 6 weeks after infarction. Etomoxir induced cardiac hypertrophy in animals with small infarctions, and enhanced compensatory heart growth at large infarct size. Contractile function of papillary muscles from etomoxir-treated rats was improved particularly in animals with small infarctions. Thus, induction of mild cardiac hypertrophy by etomoxir in rats with small infarctions may be beneficial for myocardial performance.

Animals↗

Short-course antibiotic treatment of 4782 culture-proven cases of group A streptococcal tonsillopharyngitis and incidence of poststreptococcal sequelae.

A large-scale study with a 1-year follow-up was performed to compare 10 days of penicillin V with a short-course treatment (5 days) of other oral antibiotics in the treatment of group A beta-hemolytic streptococcus (GABHS) tonsillopharyngitis, to evaluate the efficacy and the incidence of poststreptococcal sequelae. The clinical response rates after completion of therapy were 94.5% in the 5-day group and 93.4% in the penicillin group (P<.001, equivalence test). The GABHS eradication rates were 83.3% in the 5-day group and 84.4% in the penicillin group (P=.022, equivalence test). Poststreptococcal sequelae were rare (5 patients) and did not occur in the context of this study. The efficacy of 5-day antibiotic regimens was equivalent to 10 days of penicillin V, but resolution of clinical symptoms was faster in the 5-day group (P<.001, Fisher's exact test). Recurrent tonsillopharyngitis occurs more frequently after treatment with penicillin (P=.03, Fisher's exact test).

Adolescent↗