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Biomedical subjects

Martin Vogel

Publications and source records attributed to Martin Vogel.

31 records · Page 2Linked to original sources

Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study.

A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.

Adult↗

Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection.

BACKGROUND: HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted by this allele, have been strongly associated with long-term non-progressive chronic HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not known. METHODS: Clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57 were assessed. HIV-1-specific T-cell responses were determined by peptide-specific interferon-gamma production measured using Elispot assay and flow-based intracellular cytokine quantification. RESULTS: Individuals expressing HLA-B57 presented significantly less frequently with symptomatic acute HIV-1 infection (4/116, 3.4%) than expected from the frequency of chronically infected individuals expressing this allele (43/446, 9.6%; P < 0.05). During acute infection, virus-specific CD8 T-cell responses were dominated by HLA-B57-restricted responses, with significantly broader (P < 0.02) and stronger (P < 0.03) responses restricted by HLA-B57 than restricted by all other co-expressed HLA class I alleles combined. Six out of nine individuals expressing HLA-B57 controlled HIV-1 viremia in the absence of therapy at levels < 5000 copies/ml (median, 515 copies/ml) during up to 29 months following acute infection. CONCLUSION: These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control.

Acute Disease↗

Endothelial nitric oxide synthase (NOS) is upregulated in rapid progressive pulmonary hypertension of the newborn.

OBJECTIVE: To provide evidence for the upregulation of endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) in the assumed imbalance in the pathophysiology of rapid progressive pulmonary hypertension of the newborn (RPPHN), which is characterized by abnormal hypertrophy of the pulmonary arterioles and arteries leading to increased pulmonary vascular resistance. Furthermore, to determine the cellular source and topographic distribution of eNOS and iNOS. MATERIAL AND METHODS: Lung biopsies were taken from two term neonates with clinical and echocardiographic evidence of RPPH and of three controls. Biopsies were obtained at an early stage of the disease as well as at post mortem and examined immunohistochemically for the presence of eNOS, iNOS and nitrotyrosine. RESULTS: The endothelial cells of pulmonary arterioles stained significantly for eNOS protein in RPPHN patients. This was not the case in the control infants. There were no differences for nitrotyrosine or iNOS between RPPHN patients and controls. CONCLUSION: Rapid progressive pulmonary hypertension of the newborn leads to compensatory induction of eNOS synthesis specifically in endothelial cells of the pulmonary arterioles. This mechanism of compensation can lead to delayed presentation of RPPHN during the late neonatal period. Exogenous inhaled nitric oxide therapy does not lead to suppression of the endogenous synthesis of nitric oxide.

Endothelium↗

Extracorporeal shock wave therapy for plantar fasciitis: randomised controlled multicentre trial.

OBJECTIVE: To determine the effectiveness of extracorporeal shock wave therapy compared with placebo in the treatment of chronic plantar fasciitis. DESIGN: Randomised, blinded, multicentre trial with parallel group design. SETTING: Nine hospitals and one outpatient clinic in Germany. PARTICIPANTS: 272 patients with chronic plantar fasciitis recalcitrant to conservative therapy for at least six months: 135 patients were allocated extracorporeal shock wave therapy and 137 were allocated placebo. MAIN OUTCOME MEASURES: Primary end point was the success rate 12 weeks after intervention based on the Roles and Maudsley score. Secondary end points encompassed subjective pain ratings and walking ability up to a year after the last intervention. RESULTS: The primary end point could be assessed in 94% (n=256) of patients. The success rate 12 weeks after intervention was 34% (n=43) in the extracorporeal shock wave therapy group and 30% (n=39) in the placebo group (95% confidence interval - 8.0% to 15.1%). No difference was found in the secondary end points. Few side effects were reported. CONCLUSIONS: Extracorporeal shock wave therapy is ineffective in the treatment of chronic plantar fasciitis.

Algorithms↗

Diffusive sampling of methyl isocyanate using 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ) as derivatizing agent.

A diffusive sampling method for the determination of methyl isocyanate (MIC) in air is introduced. MIC is collected using a glass fiber filter impregnated with 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ). The urea derivative formed is desorbed from the filter with acetonitrile and analyzed by means of high-performance liquid chromatography (HPLC) using fluorescence detection (FLD) with lambdaex = 471 nm and lambdaex = 540 nm. Additionally, a method was developed using tandem mass spectrometric (MS-MS) detection, which was performed as selected reaction monitoring (SRM) on the transition [MIC-NBDPZ + H]+ (m/z 307) to [NBDPZ + H]+ (m/z 250). The diffusive sampler was tested with MIC concentrations between 1 and 35 microg m(-3). The sampling periods varied from 15 min to 8 h, and the relative humidity (RH) was set from 20% up to 80%. The sampling rate for all 15 min experiments was determined to be 15.0 mL min(-1) (using HPLC-FLD) with a relative standard deviation of 9.9% for 56 experiments. At 80% RH, only 15 min sampling gave acceptable results. Further experiments revealed that humidity did not affect the MIC derivative but the reagent on the filter prior to and during sampling. The sampling rate for all experiments (including long term sampling) performed at 20% RH was found to be 15.0 mL min(-1) with a relative standard deviation of 6.3% (N = 42). The limit of quantification was 3 microg m(-3) (LC-MS-MS: 1.3 microg m(-3)) for 15 min sampling periods and 0.2 microg m(-3) (LC-MS-MS: 0.15 microg m(-3)) for 8 h sampling runs applying fluorescence detection.

Absorption↗

LC-electron capture-APCI(-)-MS determination of nitrobenzoxadiazole derivatives.

Nitrobenzoxadiazole (NBD) derivatives are determined with limits of detection ranging down to 20 nmol l(-1) using liquid chromatography-mass spectrometry (LC-MS) with electron capture (EC) ionisation. An atmospheric pressure chemical ionisation (APCI) interface operated in the negative ion mode is used as ionisation source. Amine derivatives of 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBDCl) as well as the isocyanate derivatives of 4-nitro-7-piperazino-2,1,3-nitrobenzoxadiazole (NBDPZ) have been analysed using this technique. The parameters favouring electron capture mechanisms have been investigated thoroughly under consideration of the competing mechanism of deprotonation to allow a better understanding of the electron capture process and to improve selectivity of the analysis.

Chromatography, Liquid↗

Histomorphometry of distraction osteogenesis during experimental tibial lengthening.

OBJECTIVES: The aim of the current study was to analyze distraction osteogenesis histomorphometrically to investigate the amount of enchondral ossification adjacent to intramembranous ossification. STUDY DESIGN: Species-specific, longitudinal time study. METHODS Lengthening of 25% of the right tibia was performed in 24 beagle dogs by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day with a distraction rate of 0.5 mm twice a day. Twelve dogs were killed at the end of the distraction phase of 25 days (group A) and the remaining 12 dogs after an additional consolidation period of 25 days (group B). The tibia was removed from the distracted right leg and from the left control side of each animal, and longitudinal sections were cut and stained with Pentachrome. In all tibiae, an area of 0.5 x 2.4 cm within the endosteal bone was evaluated histomorphometrically with a Merz grid, and the results were compared between distraction and control side as well as between the dogs of group A and group B. RESULTS: On the distraction side, the typical signs of an increased de novo bone formation with a significant increase of osteoblasts and osteoid in group A, as well as an additional significant increase of bone volume and trabecular thickness in group B, were found. In all distraction cases, islands of cartilage formation, which underwent enchondral ossification, were found, besides membranous ossification. The ratio between membranous and enchondral ossification was found to be five to one. CONCLUSION: Bone formation during distraction osteogenesis results from both membranous and enchondral ossification.

Animals↗

4-Nitro-7-piperazino-2,1,3-benzoxadiazole as a reagent for monitoring of airborne isocyanates by liquid chromatography.

4-Nitro-7-piperazino-2,1,3-benzoxadiazole (NBDPZ) is presented as a new reagent for the determination of mono- and diisocyanates in air samples. NBDPZ readily reacts with the airborne analytes, thus yielding the corresponding urea derivatives, which are subsequently separated by means of reversed-phase liquid chromatography. On a phenyl-modified stationary phase, excellent baseline separation for numerous mono- and diisocyanate derivatives is obtained. Both diode array and fluorescence detection are performed with limits of detection of 11-35 and 5-9 nmol/L for the individual derivatives, respectively. In contrast to established derivatizing agents for the analysis of isocyanates, NBDPZ provides for increased selectivity due to the favorable detection wavelengths in the visible range (UV/visible, absorption maximums approximately 480 nm; fluorescence, excitation maximums approximately 470 nm, emission maximums approximately 535 nm). In addition, the high molar absorptivities of the reagent and the derivatives provide excellent sensitivity that is superior to most literature-known methods. Finally, air sampling methods comprising both the use of impingers and test tubes are developed and successfully applied to the determination of isocyanates in gaseous samples. Excellent recovery reaching values of >90% is observed for each of the two techniques investigated.

Air Pollutants↗

Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels.

Interstitial proliferation of striated muscle in the lung is extremely rare. Most cases are associated with other congenital malformations, such as lung sequestration, diaphragmatic hernia, or cardiac malformations. We describe a newborn with rhabdomyomatous dysplasia of the lung associated with multiple congenital malformations of the heart and great vessels. The female neonate was born at 37 weeks of gestation as the second child to a 31-year-old woman without relevant previous medical or family history. In week 26 of gestation, a complex heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally, right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the pulmonary veins, atrial and ventricular septal defects, and double-outlet right-ventricle and multiple aortopulmonary collaterals were described. Histological examination of a biopsy of the right lung demonstrated the presence of numerous bundles of striated muscle fibers arranged randomly in the pulmonary interstitium. Unilateral resection of the right lung was not a therapeutic option, because the left lung had developed bronchopulmonary dysplasia with severe reduction in gas exchange as a consequence of long-term mechanical ventilation. Symptomatic relief and palliative cardiac surgery were offered. At age 5 months, the infant died of a pulmonary hemorrhage following cardiac surgery.

Abnormalities, Multiple↗

LC-electron capture APCI-MS for the determination of nitroaromatic compounds.

The determination of selected nitroaromatic compounds in liquid chromatography-mass spectrometry with electron capture (EC) ionisation using a commercial atmospheric pressure chemical ionisation (APCI) interface in the negative mode is described. The electron capture effect is observed for nitroaromatics which do not easily undergo deprotonation under these conditions. Depending on the structure of the analytes, either dissociative or, for the first time in LC-MS, non-dissociative electron capture is observed. Limits of detection and linear range for the determination of the analytes match those obtained for nitroaromatics which undergo deprotonation. The investigated substances comprise numerous substituted nitrobenzenes and nitrobenzooxadiazoles.

Journal Article↗

Myoid differentiation in mesoblastic nephroma: clinicopathologic and cytogenetic findings of a rare case.

The authors report the case of a benign renal mesenchymal tumor in a baby boy detected by ultrasound scanning during prenatal diagnosis. Histologically, the tumor was diagnosed as a congenital mesoblastic nephroma (CMN) with myoid differentiation. The tumor normally is characterized by a fascicular proliferation of bland, spindle-shaped cells. CMN is the most common renal tumor in the neonatal period and presumedly results from a neoplastic transformation affecting the pluripotent mesodermal nephric blastema. In embryonic life, tumorigenic influences acting on the nephric blastema might result in selective overgrowth of its mesoblastic derivates. CMN must be differentiated from other spindle-shaped tumors, like Wilms' tumor, rhabdoid tumor of the kidney, clear cell sarcoma, nephrogenic adenofibroma, fibroma and fibrosarcoma, leiomyoma, metanephric stromal tumor, and, in this case especially, from tumors with myoid differentiation like infantile myofibromatosis. Numerical molecular abnormalities are observed frequently in renal mesenchymal tumors, especially in chromosome 11. Cytogenetic findings in our tumor after comparative genomic hybridization (CGH) showed full trisomies of chromosomes 20 and 22q, partial trisomies for the distal part of 11q and 1p, and an approximately full monosomy of chromosome 4 (4qter-4p15). The chromosomal imbalances of the tumor can be described as: rev ish enh(1p31pter,11q23qter,20,22), dim(4)(p15qter).

DNA, Neoplasm↗

Second harmonic imaging of intrinsic signals in muscle fibers in situ.

We use second harmonic generation (SHG) imaging to study and quantify a strong intrinsic SHG signal in skeletal muscle fiber preparations and single isolated myofibrils. The intrinsic signal follows the striation pattern of the muscle cells and is positioned at the sarcomeric location of the myosin filaments. Interestingly, the signal is enhanced at the region where the myosin heads are located on the myosin filaments. As the intrinsic signal reflects the subcellular structure in an accurate way, SHG can be used for noninvasive high resolution structural imaging without exogenous labels in living muscle cells. This may be very important for detecting changes in myofibrillar organization occurring under pathophysiological conditions, e.g., in cardiac and skeletal myopathies. Due to the strong dependency of SHG on orientation and symmetries of the tissue, it may allow the study of dynamic interactions between the contractile proteins actin and myosin during force production and muscle shortening. Furthermore, SHG imaging can be combined with other nonlinear microscopical techniques, such as laser scanning multiphoton fluorescence microscopy, to simultaneously measure other dynamic cellular processes, representing a complementary method and extending the range of nonlinear microscopical methods.

Animals↗