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Biomedical subjects

M Vogt

Publications and source records attributed to M Vogt.

At least 19 recordsLinked to original sources
PubMed2007

Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks.

Administration, Oral↗
PubMed2006

Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein.

Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer in humans. The antiapoptotic viral E6 gene has been identified as a key factor for maintaining the viability of HPV-positive cancer cells. Although E6 has the potential to modulate many apoptosis regulators, the crucial apoptotic pathway blocked by endogenous E6 in cervical cancer cells remained unknown. Using RNA interference (RNAi), here, we show that targeted inhibition of E6 expression in cervical cancer cells leads to the transcriptional stimulation of the PUMA promoter, in a p53-dependent manner. This is linked to the activation and translocation of Bax to the mitochondrial membrane, cytochrome c release into the cytosol, and activation of caspase-3, in a PUMA-dependent manner. Moreover, inhibition of Bax expression by RNAi efficiently reverts the apoptotic phenotype, which results from inhibition of E6 expression. Thus, interference with the p53/PUMA/Bax cascade is crucial for the antiapoptotic function of the viral E6 oncogene in HPV-positive cancer cells.

Apoptosis↗
PubMed2006

Effect of acute hypoxia on maximal oxygen uptake and maximal performance during leg and upper-body exercise in Nordic combined skiers.

We examined the effect of normobaric hypoxia (3200 m) on maximal oxygen uptake (VO2max) and maximal power output (Pmax) during leg and upper-body exercise to identify functional and structural correlates of the variability in the decrement of VO2max (DeltaVO2max) and of maximal power output (DeltaPmax). Seven well trained male Nordic combined skiers performed incremental exercise tests to exhaustion on a cycle ergometer (leg exercise) and on a custom built doublepoling ergometer for cross-country skiing (upper-body exercise). Tests were carried out in normoxia (560 m) and normobaric hypoxia (3200 m); biopsies were taken from m. deltoideus. DeltaVO2max was not significantly different between leg (-9.1+/-4.9%) and upper-body exercise (-7.9+/-5.8%). By contrast, Pmax was significantly more reduced during leg exercise (-17.3+/-3.3%) than during upper-body exercise (-9.6+/-6.4%, p<0.05). Correlation analysis did not reveal any significant relationship between leg and upper-body exercise neither for DeltaVO2max nor for DeltaPmax. Furthermore, no relationship was observed between individual DeltaVO2max and DeltaPmax. Analysis of structural data of m. deltoideus revealed a significant correlation between capillary density and DeltaPmax (R=-0.80, p=0.03), as well as between volume density of mitochondria and DeltaPmax (R=-0.75, p=0.05). In conclusion, it seems that VO2max and Pmax are differently affected by hypoxia. The ability to tolerate hypoxia is a characteristic of the individual depending in part on the exercise mode. We present evidence that athletes with a high capillarity and a high muscular oxidative capacity are more sensitive to hypoxia.

Acute Disease↗
PubMed2006

Timing of repair in ventricular septal defect with aortic insufficiency.

OBJECTIVE: Trusler's valvuloplasty technique and its modifications are the standard approach for the repair of aortic insufficiency in combination with ventricular septal defect. However, recurrent aortic insufficiency may occur after repair. The timing of surgical intervention in patients with ventricular septal defect and aortic insufficiency is still controversial. METHODS: Between 1985 and 2000, 33 patients were analyzed retrospectively focusing on echocardiographic findings. For statistical analysis, the patients were divided into two groups according to the grade of preoperative aortic insufficiency: there were 5 patients with preoperative severe aortic insufficiency and 28 patients with mild to moderate aortic insufficiency. RESULTS: The mean age at operation was 6.05 +/- 3.61 years. The aortic valve was repaired by means of Trusler's valvuloplasty in the majority of the patients. All but three had patch closure of the ventricular septal defect, with a transaortic approach in 54 %. Mean follow-up was 5.1 years with a maximum of 16.9 years (168.9 patient years). Rates for freedom from reoperation at 1, 3, and 8 years were 90 %, 85 %, and 75 %, respectively. In 3 patients, a mechanical prosthesis was implanted at the time of reoperation. One sudden death occurred after 3.6 years. Patients with preoperative severe aortic insufficiency were reoperated significantly more often (P < 0.03). In patients with preoperative severe aortic insufficiency, the underlying pathology (insufficiency) was detected earlier on in life (8.4 +/- 10 months) than in patients (45.0 +/- 30 months) with mild to moderate aortic insufficiency at the time of intervention (P < 0.05). CONCLUSION: Severe aortic insufficiency at the time of operation has less favorable long-term results. Therefore, early surgical intervention, even in young patients, seems warranted to avoid potential reoperation or valve replacement.

Age Factors↗
PubMed2005

Gene expression in skeletal muscle of coronary artery disease patients after concentric and eccentric endurance training.

Low-intensity concentric (CET) and eccentric (EET) endurance-type training induce specific structural adaptations in skeletal muscle. We evaluated to which extent steady-state adaptations in transcript levels are involved in the compensatory alterations of muscle mitochondria and myofibrils with CET versus EET at a matched metabolic exercise intensity of medicated, stable coronary patients (CAD). Biopsies were obtained from vastus lateralis muscle before and after 8 weeks of CET (n=6) or EET (n=6). Transcript levels for factors involved in mitochondrial biogenesis (PGC-1alpha, Tfam), mitochondrial function (COX-1, COX-4), control of contractile phenotype (MyHC I, IIa, IIx) as well as mechanical stress marker (IGF-I) were quantified using an reverse-transcriptase polymerase chain reaction approach. After 8 weeks of EET, a reduction of the COX-4 mRNA level by 41% and a tendency for a drop in Tfam transcript concentration (-33%, P=0.06) was noted. This down-regulation corresponded to a drop in total mitochondrial volume density. MyHC-IIa transcript levels were specifically decreased after EET, and MyHC-I mRNA showed a trend towards a reduction (P=0.08). Total fiber cross-sectional area was not altered. After CET and EET, the IGF-I mRNA level was significantly increased. The PGC-1alpha significantly correlated with Tfam, and both PGC-1alpha and Tfam significantly correlated with COX-1 and COX-4 mRNAs. Post-hoc analysis identified significant interactions between the concurrent medication and muscular transcript levels as well as fiber size. Our findings support the concept that specific transcriptional adaptations mediate the divergent mitochondrial response of muscle cells to endurance training under different load condition and indicate a mismatch of processes related to muscle hypertrophy in medicated CAD patients.

Adaptation, Biological↗
PubMed2005

Right heart failure due to an unroofed coronary sinus in an adult.

An unroofed coronary sinus is a rare congenital malformation with a strong association to a persistent left vena cava superior. In most cases it occurs together with complex cardiac anomalies such as left isomerism. We report on a 72-year-old man with clinical signs of right heart failure caused by an isolated unroofed coronary sinus: The diagnosis was made by means of transesophageal echocardiography with contrast injection.

Aged↗
PubMed2005

[Comparison of chromosomal defects in primary tumor and metastases by comparative genomic hybridization (CGH)].

Molecular methods can complement the classical methods in pathology like macroscopic, histological and immunohistochemical examinations.Comparative genomic hybridization is a cytogenetic method to screen for gains and losses of chromosomal material in tumor cells. This method allows defect studies of archival paraffin-embedded and formalin-fixed tumor material. CGH can detect gains and losses of chromosomal material that are at least 10 to 20 megabases in size. This genome-wide screening method allows to study the cytogenetic relationship between differently located tumors of a patient. To answer the question if these different tumors are metastases of the primary lung tumor or independent primary tumors CGH analysis is a supplementary method that introduces new prospectives.

Chromosome Aberrations↗
PubMed2005

[Myoepithelioma of soft tissue -- case report with clinicopathologic, ultrastructural, and cytogenetic findings].

The case of a soft tissue myoepithelioma is presented including clinicopathologic, ultrastructural, and genetic findings. A 30-year-old male patient suffered from a soft tissue tumor within the deep soft tissues of the right lower leg measuring 13.2 x 8.2 x 9 cm. Histologically, the lesion was diagnosed as a myoepithelioma displaying a lobulated architecture with cords and nests of epithelioid and spindle cells without cytologic atypia lying within a fibromyxoid and partly chondroid matrix; immunohistochemistry was positive for pancytokeratin, S100-protein, calponin and partly for GFAP and EMA. Ultrastructural analysis revealed glycogen deposits and cell-membrane-associated plaque structures, whereas true myofilaments could not be identified (with immunohistochemistry being negative for actin). Using comparative genomic hybridization (CGH), a gain of chromosome Y was detected. A loss on 17p could not be detected unambiguously. However, based on the low resolution of CGH a small loss cannot be excluded. The patient was free of disease 25 months following complete tumor resection. Myoepitheliomas/mixed tumors of deep soft tissue represent rare soft tissue lesions that may reach a considerable size and may mimic other soft tissue tumors or sarcomas. Based on a local relapse rate of approximately 20% according to the literature, a complete resection with thorough follow-up should be recommended.

Adult↗
PubMed2005

Pharmacodynamics of rocuronium 0.3 mg kg(-1) in adult patients with and without renal failure.

BACKGROUND AND AIM: The neuromuscular effects of a bolus dose of rocuronium 0.6 mg kg(-1) under propofol anaesthesia in renal failure patients are prolonged compared to healthy patients. The present study aims to describe the neuromuscular effects of 0.3 mg kg(-1) rocuronium under propofol anaesthesia in patients with renal failure and to compare these effects with healthy control patients. METHODS: With institutional approval and informed consent, 18 healthy patients and 18 patients with renal failure took part in this prospective open label study. The renal failure patients were undergoing either renal transplantation or insertion of a shunt. Rocuronium 0.3 mg kg(-1) was given intravenously after induction of anaesthesia with propofol 1-2 mg kg(-1) and fentanyl 2 microg kg(-1). Propofol 6-12 mg kg(-1) h(-1) was used for maintenance of anaesthesia. Four acceleromyographic responses of the thumb after supramaximal stimulation of the ulnar nerve using surface electrodes at 2 Hz every 15 s were measured and recorded. The onset time, the time to recovery of the first twitch to 25% recovery and the time to a train-of-four ratio of 0.7 were all recorded. Wilcoxon rank sum testing was used to compare the pharmacodynamics and to see if medication, gender or electrolytes influenced the duration of the block. P < 0.05 was significant. RESULTS: No statistical differences were seen in the neuromuscular blocking effects of rocuronium between the two groups but there was a significant difference (P < 0.00001) in the variability of the total duration of the block. CONCLUSIONS: Rocuronium 0.3 mg kg(-1) is suitable for use in patients with renal failure when endotracheal intubation and neuromuscular block for a short period of time are needed. Tracheal intubation is facilitated within 4 min and the block can be antagonized within 20 min.

Adult↗
PubMed2004

Aortopulmonary window with ventricular septal defect and pulmonary atresia: prenatal diagnosis and successful early surgical correction.

We report a case in which aortopulmonary window (APW) in combination with pulmonary atresia was diagnosed correctly in a neonate by echocardiography. Prenatal echocardiography showed progression of tetralogy of Fallot to pulmonary atresia with retrograde pulmonary perfusion, concealing the concomitant APW in fetal life. Due to intractable heart failure, primary correction was successfully performed at the age of 4 weeks (weight 2280 g).

Adult↗
PubMed2004

Prevalence and risk factors of hepatitis C infection after cardiac surgery in childhood before and after blood donor screening.

BACKGROUND: Since 1974, the risk of acquiring non-A non-B hepatitis by blood transfusion is well known. In 1999, children having had polytransfusions (group 1) after cardiac surgery prior to the establishment of routine blood donor screening could be identified as a risk group for hepatitis C (HCV) infection. PATIENTS AND METHODS: In 1991, Germany began screening blood donors for hepatitis C. To describe the risk after the implementation of blood donor screening, we studied 211 children (group 2) having had open heart surgery after 1991 and compared prevalence for anti-HCV antibodies and known risk factors to group 1. RESULTS: None of the 211 patients with cardiac surgery after 1991 had detectable anti-HCV antibodies, compared to 67 of the 458 patients (14.6%) of group 1 (p < 0.001). The mean number of operations in both groups was virtually the same (mean 1.7 +/- 0.9 in group 1, mean 1.6 +/- 0.9 in group 2, p = 0.075), whereas the total number of blood products per patient differed significantly (group 1 mean 8 +/- 17.6, group 2 mean 3.5 +/- 2.8; p < 0.001). Multivariate analysis of risk factors demonstrates affiliation to group 1, transfusion of fresh blood, warm whole blood, heparinized blood (p < 0.001) and plasma (p = 0.004) as significant. CONCLUSION: After the implementation of blood donor screening, the risk for HCV infection after cardiac surgery in childhood dropped significantly from 14.6% to < 0.5%. These data show the necessity of HCV screening for patients at risk (operations before 1991) and do not favor a general screening for all patients.

Adolescent↗
PubMed2003

[Effect of hypoxia on muscular performance capacity: "living low--training high"].

Altitude training is very popular among endurance athletes. But athletes respond very different on acute altitude exposure and altitude training. There are individual differences in the decrement of maximal oxygen consumption making general advices on the effect of altitude training very difficult. During the last few years different altitude training regimes have been developed. Beside "living high--training low," the concept of "living low--training high" becomes more and more popular. By this regime, athletes train under simulated or natural hypoxic conditions, while recovery time is spent at sea-level. Several studies show that with "living low--training high" maximal oxygen consumption as well as aerobic and anaerobic endurance performance can be improved. Molecular analysis reveal that a transcription factor called Hypoxia-Inducible Factor 1 (HIF-1) acts as a master gene in the regulation of hypoxia-dependent gene expression. In human skeletal muscle "living low-training high" induces the expression of glycolytic enzymes, the angiogenic factor VEGF, myoglobin as well as the increase of capillarity and mitochondrial content in parallel to the induction of the HIF-1 system. In trained human skeletal muscle, these adaptations cause a shift of substrate selection to an increased oxidation of carbohydrates as well as to an improvement of the conditions for transport and utilization of oxygen. Depending on the kind of sports, "living low--training high" can be used to train these muscular adaptations and to increase exercise performance.

Acid-Base Equilibrium↗
PubMed2003

The response of trained athletes to six weeks of endurance training in hypoxia or normoxia.

This study was performed to investigate the effect of training under simulated hypoxic conditions. Hypoxia training was integrated into the normal training schedule of 12 endurance trained cyclists. Athletes were randomly assigned to two groups and performed three additional training bouts per week for six weeks on a bicycle ergometer. One group (HG) trained at the anaerobic threshold under hypoxic conditions (corresponding to an altitude of 3200 m) while the control group (NG) trained at the same relative intensity at 560 m. Preceding and following the six training weeks, performance tests were performed under normoxic and hypoxic conditions. Normoxic and hypoxic .VO2max, maximal power output as well as hypoxic work-capacity were not improved after the training period. Testing under hypoxic conditions revealed a significant increase in oxygen saturation (SpO 2, from 67.1 +/- 2.3 % to 70.0 +/- 1.7 %) and in maximal blood lactate concentration (from 7.0 to 9.1 mM) in HG only. Ferritin levels were decreased from 67.4 +/- 16.3 to 42.2 +/- 9.5 microg/l (p < 0.05) in the HG and from 54.3 +/- 6.9 to 31.4+/- 8.0 microg/l (p = 0.17) in the NG. Reticulocytes were significantly increased in both groups by a factor of two. In conclusion, the integration of six weeks of high intensity endurance training did not lead to improved performance in endurance trained athletes whether this training was carried out in hypoxic or normoxic conditions.

Adult↗
PubMed2003

Comparison of high frequency ultrasound and optical coherence tomography as modalities for high resolution and non invasive skin imaging.

High frequency ultrasound (HFUS) and optical coherence tomography (OCT) are techniques for high resolution imaging of tissues. The penetration depth of these modalities is limited, but it is sufficiently large enough for non invasive skin imaging. HFUS and OCT are based on the same concept. Waves (ultrasonic waves, respectively light waves) propagate along a narrow beam, are backscattered at tissue inhomogeneities and analyzed over time of flight to obtain spatially resolved morphological information. The objective of this paper is to compare HFUS and OCT in terms of resolution, dynamic range and contrast and to assess their value as tools for high resolution skin imaging. Measurements on phantoms and in vivo have been performed with a 100 MHz ultrasound system and an OCT-scanner working in the near infrared spectrum at 1300 nm wave-length. From the measurements, it can be concluded that OCT delivers an almost isotropic resolution (axial resolution about 5.8 microns, lateral resolution about 4.1 microns), whereas the resolution of the investigated HFUS system is more anisotropic (axial resolution about 9.3 microns, lateral resolution about 60 microns). HFUS and OCT show different penetration depths and a different contrast. Both techniques can, therefore, be combined advantageously in a multimodality approach to account for their individual characteristics.

Hair↗