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Biomedical subjects

C Huth

Publications and source records attributed to C Huth.

At least 19 recordsLinked to original sources
PubMed2007

Variants of the transcription factor 7-like 2 gene (TCF7L2) are strongly associated with type 2 diabetes but not with the metabolic syndrome in the MONICA/KORA surveys.

Recently, significant associations between common variants of the transcription factor 7-like 2 gene ( TCF7L2) and type 2 diabetes have been reported. This study was designed to replicate the reported associations of the two highly correlated (r (2)=0.86) TCF7L2 single nucleotide polymorphisms rs12255372 and rs7903146 with type 2 diabetes in a case-control study of 2369 MONICA/KORA participants (678 cases/1691 controls from Augsburg, Germany). To further investigate the pathogenic mechanism underlying these associations, we extended our analyses to the metabolic syndrome (IDF, NCEP definitions) and its components in a population-based study comprising 1404 male and female KORA participants aged 55-74 years. Results of our analyses strongly confirmed the minor T alleles as risk variants for type 2 diabetes (rs7903146: OR (TvsC) [95% CI]=1.36 [1.18;1.58], p=0.00003, and rs12255372: OR (TvsG) [95% CI]=1.31 [1.13;1.51], p=0.0003). Moreover, the T allele at rs7903146 was inversely associated with log-transformed, HOMA-%B (beta=-0.07, p=0.005) as a measure of basal insulin secretion, and log-transformed fasting insulin (beta=-0.06, p=0.02). No association was found with insulin resistance (HOMA-IR) and the metabolic syndrome. These findings support replication evidence that TCF7L2 variants increase type 2 diabetes risk. TCF7L2 may primarily affect pancreatic beta cell function.

Aged↗
PubMed2006

Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation.

Atrial tachyarrhythmia (AF) alters intracellular calcium homeostasis and induces cellular hypertrophy of atrial myocytes. The impact of the calcium-dependent calcineurin pathway on the development of AF-induced atrial hypertrophy has not yet been analyzed. In this study, atrial tissue samples from patients with sinus rhythm and chronic persistent atrial fibrillation (CAF) were used to determine changes in expression and activity of calcineurin A (CnA), and its relation to CnA-regulated transcription factors NFATc1-4, and hypertrophic markers ANP, troponin I, and beta-MHC. CnA phosphatase activity and CnAbeta protein contents were significantly upregulated in patients with CAF. Calcineurin activation led to dephosphorylation, redistribution, and subsequent accumulation of NFATc3 in nuclei during CAF, and expression of hypertrophic genes was increased. CAF-dependent changes were reproduced by ex vivo pacing (2-4 Hz) of human atrial tissue slices. FK506 abolished the hypertrophic response induced by electrical-field stimulation. Atrial tachyarrhythmia causes atrial hypertrophy by activation of the CnA signal pathway, which thereby contributes to structural remodeling of human atria.

Aged↗
PubMed2006

Successful surgical treatment of a combined abdominal and thoracic impalement injury.

Accidents do occur during the performance of different domestic chores in the garden. The resulting injuries can lead to serious morbidity and, in some cases, they can be fatal. We present a case of trauma, in a 69-year old man, caused by a fall from a tree on a vertical metal rod in his garden. The rod entered the abdominolumbal region on the right side making an exit above the left clavicle. On arrival, he was in a stable circulatory condition. A chest X-ray (Fig. ), thoracic and abdominal sonography followed by chest and abdominal CT scan (Figs. - , ) were performed and they showed no severe injury of the heart, lung, bronchi, liver and right kidney. He underwent an emergent surgical intervention by a team of cardiothoracic, vascular and abdominal surgeons. Longitudinal sternotomy and laparotomy allowed us to remove the metal rod carefully with no severe signs of injuries of abdominal and thoracic organs. There were no surgical postoperative complications.

Abdominal Injuries↗
PubMed2005

Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure.

The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Hydralazine has been shown to prevent tolerance in experimental and clinical studies, all of which may be at least in part secondary to antioxidant properties of this compound. The antioxidant effects of hydralazine were tested in cell free systems, cultured smooth muscle cells, isolated mitochondria, and isolated vessels. Inhibitory effects on the formation of superoxide and/or peroxynitrite formation were tested using lucigenin and L-012 enhanced chemiluminescence as well as DHE-fluorescence. The peroxynitrite scavenging properties were also assessed by inhibition of nitration of phenol. Prevention of impairment of NO downstream signaling and GTN bioactivation was determined by measurement of P-VASP (surrogate parameter for the activity of the cGMP-dependent kinase-I, cGK-I) and mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Hydralazine dose-dependently decreased the chemiluminescence signal induced by peroxynitrite from SIN-1 and by superoxide from HX/XO in a cell free system, by superoxide in smooth muscle cells and mitochondria acutely challenged with GTN. Moreover, hydralazine inhibited the peroxynitrite-mediated nitration of phenols as well as proteins in smooth muscle cells in a dose-dependent fashion. Finally, hydralazine normalized impaired cGK-I activity as well as impaired vascular ALDH-2 activity. Our results indicate that hydralazine is a highly potent radical scavenger. Thus, the combination with isosorbide dinitrate (ISDN) will favorably influence the nitroso-redox balance in the cardiovascular system in patients with congestive heart failure and may explain at least in part the improvement of prognosis in patients with chronic congestive heart failure.

Aldehyde Dehydrogenase↗
PubMed2005

[Open heart tricuspid valve replacement in a heroin addict Anaesthesiological management].

A 24-year-old female with a history of former heroin addiction underwent open heart surgery for a mechanical tricuspid valve replacement. Anaesthesiological management included a thoracic epidural catheter at the Th(2)/Th(3) segments and balanced general anaesthesia (remifentanil, desflurane/propofol). Additionally, clonidine (2 microg*kg(-1)*h(-1)) was continuously administered. Pain therapy was achieved using 0.375% ropivacaine via a thoracic epidural catheter (4 ml*h(-1)) and metamizole (4 x 1 g/day) intravenously. With this concept we were able to achieve an appropriate anaesthesia and analgesia and the operation was carried out without complications.

Adrenergic alpha-Agonists↗
PubMed2005

Replacement of a severe chronic post-traumatic aneurysm of the ascending aorta with aortic valve conduit--reconstruction of the anterior mitral valve ring and implantation of A-V sequential/biventricular pacemaker.

We present the case of a 23-year-old African professional footballer who was admitted on April 1, 1999 to the Cardiology Department of the University Hospital in Magdeburg, on an emergency basis, from a regional lung clinic. According to the history, he was involved in a collision with an opposing player during a football match in his country (in Africa). He lost consciousness for a short time, but continued playing to the end of the match. About two months later he was invited by a German football club for a check-up, with the view to ultimately playing for the club. The team did not find him physically fit enough to play professional football, so he decided to go to Paris by bus on March 31, 1999. During the journey he suddenly became cardio-pulmonary decompensated and had to undergo cardio-pulmonary resuscitation (CPR). He was intubated and placed on a respirator and immediately transferred to a nearby lung clinic. From the lung clinic he was transferred to the Intensive Care Unit of the Cardiology Department of the Magdeburg University Hospital, on April 1, 1999 as an emergency case. He was intensively treated with catecholamines, intravenous ACE inhibitors and diuretics. His clinical condition did not improve appreciably. His chest X-ray showed extreme dilatation of the right and left heart as well as extreme pulmonary congestion.

Adult↗
PubMed2005

[How about the uncertainty in the haplotypes in the population-based KORA studies?].

In the KORA surveys, numerous candidate genes in the context of type 2 diabetes, myocardial infarction, atherosclerosis or obesity are under investigation. Current focus is on genotyping single nucleotide polymorphism (SNPs). Haplotypes are also of increasing interest: haplotypes are combinations of alleles within a certain section of one chromosome. Analysing haplotypes in genetic association studies is often more efficient than studying the SNPs separately. A statistical problem in this context is the reconstruction of the phase: genotyping the SNPs determines the alleles of an individual at one particular locus of the DNA, but does not reveal which allele is located on which one of the two chromosomes. This information is required when talking about haplotypes. There are statistical approaches to identify the most likely two haplotypes of an individual given the genotypes. However, a certain error in prognosis is unavoidable. There are also errors in the genotypes. These errors are assumed to be small for one SNP but can accumulate over the SNPs involved in one haplotype and thus can induce further uncertainty in the haplotype. It is therefore the aim of our project to quantify the uncertainties in the haplotypes particularly for genes investigated in the KORA surveys. We conduct computer simulations based on the haplotypes and their frequencies observed in the KORA individuals and compare the results with simulations based on mathematical modelling of the evolutionary process ("coalescent models"). The uncertainties in the haplotypes have an impact on the search for association between genes and disease: an association may not be detected as the haplotype uncertainty obscures the haplotype frequency differences between cases and controls. It is a further aim of our project to elucidate the extent of this problem and to develop strategies for reducing it.

Adult↗
PubMed2005

Genetics of type 2 diabetes: impact of interleukin-6 gene variants.

The KORA studies serve as a powerful tool for the genetic analysis of complex diseases like type 2 diabetes or the metabolic syndrome. These studies include more than 2,000 prevalent and incident type 2 diabetes cases. DNA of these patients is available to be used in genetic studies. Up to now the analyses have focussed on genes coding for proteins being involved in the inflammatory response. Interleukin-6 (IL-6) as the key mediator of the acute phase reaction is of interest. Elevated protein concentrations of IL-6 in the blood have been shown to predict type 2 diabetes. We investigated the association of the IL-6 single nucleotide polymorphism (SNP) C-174G with type 2 diabetes in a case-control study of 704 elderly participants of the KORA Survey S4 (1999/2001). When BMI, HDL cholesterol, physical activity, hypertension, hormone replacement therapy and smoking were considered as covariables the SNP C-174G showed a trend for association with type 2 diabetes (- 174G: OR 1.20, 95 % CI 0.90 - 1.59, p = 0.21).

Adult↗
PubMed2003

Cardiopulmonary effects of non-invasive positive pressure ventilation (NPPV)--a controlled, prospective study.

BACKGROUND: This study was undertaken to investigate the haemodynamic effect of non-invasive positive pressure ventilation (NPPV) in patients after cardiac surgery. NPPV has recently become popular as method for treating acute respiratory failure. Its influence on cardiopulmonary haemodynamics is still unknown. METHODS: 30 extubated low-risk patients were included in four study intervals after cardiac surgery. During the first and the third interval, the patients breathed spontaneously and received oxygen via face mask for 45 min. Both intervals were followed by 45 min on NPPV. RESULTS: Cardiac index increased significantly from 2.8 to 3.1 ml/min/m2 during NPPV (p < 0.001) and from 2.7 to 3.2 ml/ min/m2 (p < 0.001). Mixed venous saturation rose significantly from 72.4 to 74.8 % (p < 0.001) and from 72.1 to 75.4 % (p < 0.001) during NPPV while the oxygen extraction ratio decreased from 25.5 and 26.1 % to 23.0 (p < 0.001) and 22.6 % (p < 0.001) during NPPV. At the same time, urine production increased significantly from 182 to 328 ml/h and from 186 to 285 ml/h (p < 0.001). Heart rate and mean arterial blood pressure rose significantly during NPPV. There were no significant changes in systemic and pulmonary haemodynamics, oxygenation or CO 2 elimination. CONCLUSIONS: NPPV improves CI significantly in stable cardiac surgery patients. Factors other than blood pressure, vascular resistance or blood gases must exert an additional influence on CI. They are still not identified. Changes in transmural pressure during NPPV may play an important role.

Cardiac Output↗
PubMed2002

Dynamic simulation of chemical industry wastewater treatment plants.

High variability, stringent effluent permits, and often extreme operating conditions define the practice of wastewater treatment in the chemical industry. This paper reviews the benefits and challenges of applying dynamic simulation to chemical-industry wastewater treatment plants by describing case studies at full-scale wastewater treatment plants (WWTP). The applications range from process troubleshooting to optimization and control. The applications have been valuable and useful in developing a deeper understanding of the plants as integrated systems. However there still remains substantial work to implement the dynamic simulations for daily real-time use by plant engineers and operators. This opportunity to improve plant operations is still largely untapped and will remain so until dynamic state estimation and data reconciliation are incorporated into simulation packages for use in developing the on-line simulations.

Bioreactors↗
PubMed2001

Expression and activity of ectopeptidases in fibrillating human atria.

Recent studies have demonstrated that atrial fibrillation (AF) occurs in the presence of degenerative changes of atrial tissue. In contrast, bradykinin (BK) appears to have cardioprotective effects diminishing myocardial hypertrophy and fibrosis. It is unknown, however, whether AF has direct effects on BK metabolism. Therefore, the purpose of this study was to determine the atrial expression of the membrane-bound peptidases, also referred to as ectopeptidases, carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPIV), and alanyl-aminopeptidase (APN) in patients with and without AF. Atrial tissue samples of 35 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or = 6 months; CAF), the remaining 18 patients (controls) had no history of AF. Peptidase expression was analyzed at the mRNA (quantitative RT-PCR) level and apparent changes were confirmed at the protein level. In case of unaltered mRNA levels, enzyme activity was determined. Reduced amounts of CPM-mRNA were found in patients with CAF (41.3+/-9.7 U nu controls: 86.1+/-17.5 U P<0.05). CPM protein was decreased to 47.5% in patients with CAF compared with controls (P<0.01). DPIV and APN mRNA amounts were similar in both groups. DPIV activity, however, was increased during CAF (219.6+/-30 pkat/mg protein v controls: 195.8+/-21.8 pkat/mg P<0.05). APN activity was unchanged. In conclusion, atrial bradykinin metabolizing activities are significantly altered during AF in humans. The observed alterations in ectopeptidase expression/activity may play a role in the structural remodeling of fibrillating atria.

Atrial Fibrillation↗
PubMed2001

[Pacing therapies for congestive heart failure considering the results of the PATH-CHF study].

Optimized uni- or biventricular pacing therapy improves left ventricular function in 80% of patients (responders) with wide QRS in surface ECG. Immediate improvement could be shown by an increase of LV dP/dt up to 28% and aortic pulse pressure up to 16%. Chronic improvement was documented by prolongation of the 6-minute-walk-test by 60 meters, an improvement of O2 uptake by 23% at exercise, and improvement of quality of life score and NYHA classification. This controlled study has shown for the first time a significant clinical improvement of congestive heart failure by pacing therapy in a selected group of patients. Conventional right ventricular stimulation is insufficient in this group of patients characterized by LBBB. These results support the hypothesis that optimized ventricular stimulation is an effective chronic therapy of congestive heart failure by improvement of left ventricular hemodynamics. Epicardial placement of the left ventricular electrodes in 50 patients was possible without operative and with low (2%) early mortality.

Aged↗
PubMed2001

Early neurobehavioral disorders after cardiac surgery: a comparative analysis of coronary artery bypass graft surgery and valve replacement.

OBJECTIVE: To analyze neurobehavioral disorders in the early postoperative period after valve replacement and coronary artery bypass graft (CABG) surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective cardiac surgery with cardiopulmonary bypass; 42 patients in the valve replacement surgery group and 42 patients in the CABG surgery group, with both groups matched post hoc for age, sex, and preoperative cognitive status. MEASUREMENTS AND MAIN RESULTS: All subjects were investigated preoperatively as well as 2 and 7 days postoperatively with a comprehensive neuropsychologic and neuropsychiatric assessment. The groups did not significantly differ with respect to the incidence of postoperative neuropsychiatric disorders. Valve replacement surgery patients exhibited more severe neuropsychologic deficits and showed a slower recovery than patients who underwent CABG surgery. In both groups, postoperative neuropsychologic alterations were most marked in fluency, arithmetic, and memory performance. CONCLUSION: These results indicate that patients after valve replacement surgery have a higher risk of postoperative neuropsychologic alterations mainly attributable to temporal lobe dysfunction. This finding corresponds to a specific vulnerability of hippocampal structures to transient hypoxia.

Adult↗
PubMed2001

Protein kinase C-dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells.

The subcellular localization of hepatobiliary transport proteins directly affects the rate of bile formation, e.g., the conjugate export pump multidrug resistance protein 2 (MRP2) is regulated on a short-term scale by retrieval from and insertion into the canalicular membrane in the liver. This study reports on the effects of protein kinase C on MRP2 localization and activity in human hepatoblastoma HepG2 cells. MRP2 was detected in HepG2 cells by immunocytochemistry and Western blot analysis. Functional activity was assessed by confocal laser scanning microscopy using fluorescent MRP2 substrates. In untreated HepG2 cells MRP2 was almost exclusively localized at the apical membrane. Treatment of HepG2 cells with phorbol-12-myristate-13-acetate (PMA) resulted in a rapid decrease of apically localized MRP2 and a loss of more than 90% of pseudocanaliculi within 4 hours. This was accompanied by a reduced pseudocanalicular secretion of the MRP2 substrate glutathione-methylfluorescein. Interestingly, PMA treatment (1-100 nmol/L) led to the appearance of immunoreactive MRP2 at the basolateral membrane within 30 minutes. This was shown by its colocalization with MRP1, human dipeptidylpeptidase IV (DPPIV), and transfected rat Ntcp. The effects of PMA on MRP2 localization were sensitive to the protein kinase C (PKC) inhibitor Gö6850 but insensitive to inhibition of MEK by PD098059. Basolateral MRP2-appearance was not inhibited by cycloheximide or by disruption of microtubules or microfilaments. In rat livers cholestasis was induced by PMA (100 nmol) and MRP2 was detected at the basolateral membrane in some areas, colocalizing with Ntcp. The data suggest that retargeting of canalicular MRP2 to the basolateral membrane due to PKC activation may represent a novel mechanism that may contribute to cholestasis.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Antioxidant and antiprotease status in peripheral blood and BAL fluid after cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) triggers systemic inflammation. Recent evidence suggests that metabolic and oxygenation management can affect the outcome of patients after cardiac surgery. We investigated the influence of oxidant/antioxidant and protease/antiprotease imbalance during the course of systemic and pulmonary inflammation. METHODS: In a study of 61 patients, we measured the intracellular thiol concentration, the intracellular activity of cathepsins and elastase, and the concentrations of secreted elastase, soluble alpha(1)-proteinase inhibitor (alpha(1)-PI), and secretory leukoprotease inhibitor (SLPI). Peripheral blood and BAL fluid (BALF) were obtained preoperatively and 2 h after CPB. RESULTS: A post-CPB depletion of thiol was found in blood granulocytes, lymphocytes, and monocytes, as well as BALF lymphocytes and macrophages. The degree of postoperative depletion correlated with PO(2) and blood glucose levels during CPB. Concomitant reduction of FEV(1) showed positive correlation with thiol depletion of blood monocytes and granulocytes. Elastase and cathepsin activities were increased in blood cells but not in lymphocytes or macrophages from BALF. The concentrations of secreted elastase were significantly increased in blood plasma but not in BALF. Enhanced antiprotease (alpha(1)-PI, SLPI) concentrations were measured in BALF but not in peripheral blood. CONCLUSIONS: The inflammatory response of the intra-alveolar compartment is clearly distinguishable from systemic inflammation. CPB causes a differentiated impairment of the antioxidant defense system as well as a protease/antiprotease imbalance in blood and BALF. Oxygenation under circumstances of CPB and concomitant pulmonary disease, as well as blood glucose metabolism, influence the antioxidative defense. Individual perioperative management of blood glucose and oxygenation could improve cellular defense systems in the peripheral blood and BALF and therefore result in a more favorable patient outcome.

Antioxidants↗
PubMed2000

Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans.

BACKGROUND: Previous studies have suggested that atrial fibrillation (AF) is associated with the activation of the atrial angiotensin system. However, it is not known whether the expression of angiotensin II receptors changes during AF. The purpose of this study was to determine the atrial expression of angiotensin II type 1 and type 2 receptors (AT(1)-R and AT(2)-R) in patients with AF. METHODS AND RESULTS: Atrial tissue samples from 30 patients undergoing open heart surgery were examined. Eleven patients had chronic persistent AF (> or =6 months; cAF), 8 patients had paroxysmal AF (pAF), and 11 patients were in sinus rhythm. AT(1)-R and AT(2)-R were localized in the atrial tissue by immunohistochemistry and quantified at the protein and mRNA level by Western blotting and quantitative polymerase chain reaction. Both types of AT-R were predominantly expressed in atrial myocytes in all groups. The amount of AT(1)-R was reduced to 34.9% during cAF (P<0.01) and to 51.7% during pAF (P<0.05) compared with patients in sinus rhythm. In contrast, AT(2)-R was increased during cAF (246%; P=NS) and pAF (505%; P<0.01). AT(1)-R/AT(2)-R mRNA content was similar in all groups. CONCLUSIONS: AF is associated with the down-regulation of atrial AT(1)-R and the up-regulation of AT(2)-R proteins. These findings may help define the pathophysiological role of the angiotensin system in the structural remodeling of the fibrillating atria.

Adult↗
PubMed2000

Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF). BACKGROUND: Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear. METHODS: Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques. RESULTS: Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis. CONCLUSIONS: An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.

Aged↗