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Biomedical subjects

H Kuhn

Publications and source records attributed to H Kuhn.

At least 19 recordsLinked to original sources
PubMed2006

Effect of transcoronary ablation of septal hypertrophy on clinical outcome in hypertrophic obstructive cardiomyopathy associated with atrial fibrillation.

BACKGROUND: Relatively few reports on the clinical impact of atrial fibrillation (AF) in hypertrophic obstructive cardiomyopathy (HOCM) are available. The aims of our study are to report the effect of transcoronary ablation of septal hypertrophy (TASH) on clinical outcome in HOCM associated with AF and to evaluate the influence of AF on symptoms and quality of life in HOCM. PATIENT AND METHODS: In 80 consecutive patients (38 f, mean age 56 +/- 17 years) with severely symptomatic HOCM referred for interventional treatment, we analyzed the prevalence of AF based on 240 Holter ECG recordings and patients' history, retrospectively. Symptoms, quality of life, number of hospital admissions and hemodynamic performance were obtained in all patients before and after TASH. Mortality was additionally investigated by letter and telephone contact. RESULTS: The overall prevalence of AF was 29%. Paroxysmal AF was detected in 17 pts (21.3%), persistent AF in 5 pts (6.3%). Only 1 pt (1.3%) suffered from permanent AF. Symptoms due to AF were present in 52.6% of the AF patients. Quality of life score was markedly improved after TASH (15.9 +/- 3.8 vs. 20.7 +/- 3.8, p < 0.001) with no difference between sinus rhythm and atrial fibrillation. However, hospital admissions were more frequent in the AF group (0.85 +/- 1.84 vs. 0.28 +/- 0.81, p = 0.03) in 32 +/- 13 months. AF patients suffered more often from syncope before TASH (30 +/- 70% vs. 10 +/- 30%, p = 0.008). Two patients with sinus rhythm at baseline died after 32 +/- 13 months from cardiovascular cause. CONCLUSIONS: Atrial fibrillation is the major cardiac arrhythmia in severe HOCM. The majority of AF patients demonstrate AF specific symptoms. The paroxysmal type of atrial fibrillation dominates by far. Both patients with and without atrial fibrillation showed similar quality of life with marked improvement after TASH.

Atrial Fibrillation↗
PubMed2005

Catheter-based septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: follow-up results of the TASH-registry of the German Cardiac Society.

INTRODUCTION: In late 1997, the German Cardiac Society set up a multicenter registry to evaluate the acute and mid-term course of all patients (pts.) treated with septal ablation for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). An analysis of the acute results has already been published. We now report on the mid-term course (3-6 months) of 242 pts. registered through September 1999. RESULTS: Follow-up was 92% complete (n=222). During follow-up (mean: 4.9+/-2.3 months), an additional 3 pts. died (in-hospital mortality: 3 pts.). A satisfactory clinical effect was reported by 195 pts. (88%); 27 pts. (12%) remained in NYHA classes III and IV. Overall symptomatic improvement (NYHA class: from 2.8+/-0.7 to 1.7+/-0.7) paralleled the outflow gradient (LVOTG) reduction which was further accentuated as compared with the acute result (Doppler measurement at rest: from 57+/-31 to 25+/-25 mmHg to 20+/-21 mmHg; with provocation: from 107+/-53 to 49+/-40, to 44+/-40 mmHg, p<0.001, resp.). Left atrial (LA) diameter (from 46+/-8 to 44+/-7 mm) and septal thickness (from 20+/-5 to 15+/-5 mm; p<0.001, resp.) were also reduced. Comparing the methods for target vessel selection (i.e., with contrast echo monitoring vs pressurefluoroscopy guidance), at followup clinical improvement and hemodynamic measurements were comparable. CONCLUSION: Clinical success can be achieved by septal ablation, both with the echocontrast guided and gradient-fluoroscopy guided method, in 88% of highly symptomatic HOCM pts. At mid-term follow-up, symptoms, left atrial size and septal thickness are reduced, and outflow gradients are further improved as compared to the acute result.

Adolescent↗
PubMed2004

Enzymatically modified low-density lipoprotein upregulates CD36 in low-differentiated monocytic cells in a peroxisome proliferator-activated receptor-gamma-dependent way.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been suggested to upregulate CD36. Since free oxidized polyunsaturated fatty acids are PPARgamma ligands, we studied the effects of LDL modified by the simultaneous action of sPLA2 and 15-lipoxygenase (15LO) on CD36 expression and PPARgamma activation in monocytic cells. Exposure of MM6 cells, which do not express CD36 or other scavenger receptors, to such enzymatically modified LDL (enzLDL) resulted in upregulation of CD36 surface protein and mRNA expression. Similar effects were observed with free 13-hydroperoxyoctadecadienoic acid but not its esterified counterpart. Less pronounced effects were observed with LDL modified by 15LO alone. Upregulation of CD36 was inversely correlated to the state of cell differentiation, as showed by lower response to enzLDL of the scavenger receptor-expressing MM6-sr and THP1 cells. Importantly, LDL modified by sPLA2 and 15LO did not efficiently induce upregulation CD36 in PPARgamma-deficient macrophage-differentiated embryonic stem cells confirming a role of PPARgamma in CD36 expression in cells stimulated with enzLDL. Our data show that LDL modified with physiologically relevant enzymes stimulates CD36 expression in non-differentiated monocytes and that this process involves PPARgamma activation. These effects of enzLDL can be considered pro-atherogenic in the context of early atherosclerosis.

Arachidonate 15-Lipoxygenase↗
PubMed2004

Endocardial radiofrequency ablation of septal hypertrophy. A new catheter-based modality of gradient reduction in hypertrophic obstructive cardiomyopathy.

Transcoronary alcohol ablation of septal hypertrophy (TASH) is a therapeutic catheter based option and an alternative to surgery in the treatment of patients with hypertrophic obstructive cardiomyopathy. However, the anatomic variability of the vascularisation of the obstructing septal bulge may limit the therapeutic efficacy. Thus, we examined an endocardial approach as an alternative. Based on the effects of radiofrequency energy in the treatment of cardiac arrhythmias this is the first report about the use of this modality. It refers to a 45-year-old patient with severe HOCM. The energy was applied by using a cooled-tip ablation catheter at the right side of the ventricular septum. The site corresponded to the obstructing area of the left ventricle. The following changes could be observed: a reduction of the intraventricular pressure gradient during the therapeutic session, a gradient reduction at cycle exercise as assessed by Doppler echocardiography 7 days after intervention, a subaortic septal hypokinesia, an enlargement of the left ventricular outflow tract, a reduction of the septal thickness and an increase in the exercise capacity using the 6-minute walk test. These changes are in accordance with the results after TASH and surgical treatment. The new modality might extend the possibilities in the catheter-based treatment of patients with severe HOCM.

Cardiomyopathy, Hypertrophic↗
PubMed2004

Catheter-based therapy for hypertrophic obstructive cardiomyopathy. First in-hospital outcome analysis of the German TASH Registry.

BACKGROUND: Registry results of the new catheter-based method in the treatment for HOCM are missing so far. In 1997, the Transcoronary Ablation of Septal Hypertrophy Registry (TASH Registry) was established by the German Cardiac Society (GCS) as a multicenter, national registry of patients with HOCM undergoing the new catheter interventional therapy. This is the report of the in-hospital outcome of patients who underwent the procedure during the first two years of data collection in the registry. METHODS AND RESULTS: Information was based on three standard forms for each patient, with a total of 86 variables. Information was collected on an "intention to treat" basis. The TASH Registry includes the establishment of a data base in the data collecting center. Ten centers participated. Enrollment forms were received for 264 patients out of 279 patients registered up to January 2000. There was a history of medical treatment of 3.6+/-3.9 years. The vast majority of patients (91%) were treated in three centers. The Vasalva maneuver and the exercise Doppler echocardiography were used for noninvasive stress testing. Exercise Doppler echocardiography induced a significantly higher augmentation of the baseline gradient (70.1% vs 133.4%; p<0.01). The echo-contrast guided technique was used for the intervention in 50.8% and the pressure angiography guided technique in 49.2%. On the average 2.8+/-1.3 ml of alcohol were injected. Before the procedure, the gradient measured by catheterization was 60.4+/-38.6 mmHg at baseline and 142.7+/-46.2 mmHg following the extrasystolic beat. At the end of the session it was reduced significantly by 75% and 67%. The peak phosphocreatine kinase activity was 482.5+/-246.4 U/L. Major complications occurred in 15.6% including a mortality rate of 1.2% and a permanent pacemaker implantation rate because of total heart block in 9.6%. There was an early in-hospital improvement of dyspnoe corresponding to a significant decrease of NYHA functional class from 2.8+/-0.7 to 1.8+/-0.6 (p<0.001). Similar hemodynamic and clinical benefit was found in patients with and without resting gradient at baseline. CONCLUSION: This analysis for the first time gives a comprehensive overview of clinical characteristics, technique, procedural data, in-hospital outcome and complications in a large number of patients with HOCM who were treated by the new catheter-based method and prospectively enrolled in a registry. The results contribute considerably to critical evaluation and validation of the new technique. This analysis supports the catheter-based method to constitute a new therapeutic option for very symptomatic patients, to be effective both in patients with and without intraventricular pressure gradient at rest and to be an alternative to surgical treatment, as has been stated recently.

Adolescent↗
PubMed2004

[Apoptosis and necrosis induced by cyclic mechanical stretching in alveolar type-II-cells--influence of captopril and L-Arginine].

BACKGROUND: Alveolar type-II(ATII)-cells are exposed to mechanical stretch during breathing and mechanical ventilation. Increased stretch may contribute to lung injury. METHODS: The influence of three stretching patterns (characterized by frequency [min (-1)] - increase in surface area [%]: S40 - 13, S60 - 13, S40 - 30) on parameters of apoptosis, necrosis and membrane integrity in rat ATII cells was compared with that in static cultures. The S40 - 13 stretching pattern simulated normal breathing. The other patterns were chosen to study increased amplitude and frequency. RESULTS: There were no significant differences between the S40 - 13 group and static cultures. LDH release and early apoptotic cells were significantly increased in S60 - 13 and S40 - 30 in comparison with static cultures (LDH: 0.089 +/- 0.014 microg/ml and 0.177 +/- 0.050 microg/ml versus 0.050 +/- 0.011 microg/ml; early apoptosis: 17 +/- 3.5 % and 23 +/- 3.1 % versus 9.7 +/- 1.4 %) at 24 h. Necrosis was significantly increased only in the S40-30 group (13 +/- 2.4 % versus 6.1 +/- 0.9 % in static culture at 24 h). Captopril as well as L-Arginine prevented apoptosis and reduced apoptotic cells to static culture levels in the S40 - 30 group but did not influence necrosis and LDH release. CONCLUSION: Increased mechanical stretch may contribute to lung injury by induction of apoptosis and necrosis in ATII cells. Apoptosis induced by high amplitude mechanical stretch is prevented by captopril and L-Arginine.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

[Expired diagnosis?--the potential of exhaled breath analysis].

Analysis of breath condensate is an innovative approach to biochemical information from the lung. It provides a new tool to estimate and characterize the burden of oxidative and inflammatory processes in the airways/lung. Clinical applications in asthma, COPD and CF can be envisioned as well as determining organ-specific inflammation in mechanically ventilated patients or monitoring patients with transplanted lungs. However, besides inflammation other important areas have begun to be evaluated, such as the demonstration of p53 mutations in NSCLC patients or an increased ratio of EBC nitrite to tidal volume in mechanically stressed lungs. Of course a careful validation of each and every parameter is paramount to the use in clinical applications. The comparison to BAL is oftentimes called for but at the same time is not the comparison to a gold standard because of the well-known problems of BAL. The scope of this review is a summary of facts and theories concerning exhaled breath condensate generation, collection and analysis but at the same time the representation of the many aspects that remain to be resolved.

Breath Tests↗
PubMed2004

Transcoronary ablation of septal hypertrophy for hypertrophic obstructive cardiomyopathy: feasibility, clinical benefit, and short term results in elderly patients.

OBJECTIVE: To evaluate symptomatic and haemodynamic results of transcoronary ablation of septal hypertrophy for hypertrophic obstructive cardiomyopathy in elderly patients. SETTING: Tertiary referral centre for patients with hypertrophic obstructive cardiomyopathy. DESIGN: Retrospective study of two groups of consecutive patients divided at a median age (59 years). PATIENTS: Transcoronary ablation of septal hypertrophy was compared for 80 patients (group 1) < 60 years of age and 77 patients (group 2) > or = 60 years of age. At baseline both groups were similar concerning the proportion of familial hypertrophic cardiomyopathy, concomitant moderate hypertension, prior syncope, left ventricular outflow obstruction, left ventricular end diastolic pressure, and left ventricular ejection fraction. Patients in group 2 had a lower interventricular septal thickness and more severe disease as measured by New York Heart Association (NYHA) functional class, exercise capacity, pulmonary artery mean pressure at workload, and cardiac index at peak exercise. RESULTS: Median follow up was seven months after transcoronary ablation of septal hypertrophy. Both groups had a significant and similar improvement in basal and provokable obstruction, septal thickness, NYHA functional class, exercise tolerance, peak oxygen consumption, and pulmonary artery mean pressure at workload. Significant differences, compared with the younger group, were a higher proportion of persistent total atrioventricular block (5% v 17%, p = 0.015) and a slight decrease in left ventricular ejection fraction (3 (12) v -6 (11)%, p = 0.001) in the elderly, despite a trend to a lower induced peak creatine kinase activity (596 (339) v 491 (331) U/l, p = 0.051). CONCLUSIONS: Short term results with transcoronary ablation of septal hypertrophy suggest that independent of a patient's age similar treatment strategies are justified in hypertrophic obstructive cardiomyopathy.

Adult↗
PubMed2004

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer.

The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients. Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1. Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months). This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.

Aged↗
PubMed2003

Mid-systolic septal deceleration. A new sign of left ventricular outflow tract obstruction obtained by color-coded tissue Doppler echocardiography.

Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by the presence of a dynamic left ventricular outflow tract gradient. We studied septal longitudinal motion by color coded tissue Doppler echocardiography in a 69-year old HOCM patient during and after catheter based treatment by trans coronary alcohol ablation of septal hypertrophy. The presence of dynamic left ventricular outflow tract obstruction was associated with a characteristic abrupt mid-systolic septal deceleration pattern in the tissue Doppler velocity trace. Five weeks after treatment, this pattern was no longer visible at rest.

Aged↗
PubMed2002

[Simultaneous hypertrophic obstructive cardiomyopathy and long QT syndrome: a potentially malignant association].

Hypertrophic obstructive cardiomyopathy (HOCM) and long-QT syndrome (LQTS) are cardiac diseases with known genetic disorders. They are inherited in an autosomal-dominant way. From a clinical point of view, both diseases share a disturbed repolarization and the risk of sudden cardiac death. In 1998, during the annual meeting of the German Cardiac Society, we presented the case report of two patients (mother and daughter) with the combination of both diseases, being the first scientific communication on this subject. Both patients experienced sudden cardiac death due to ventricular fibrillation more than 10 years after the first diagnosis of the diseases. Resuscitation resulted in an apallic syndrome in both. The mother died from complications during the course of the apallic syndrome. In contrast to actual therapeutic strategies and data on prophylactic ICD-implantation available today, the daughter received no defibrillator. Sudden death in the presented cases may be due to either disease or their possible malignant association. Thus, the combination of both diseases forms the argument for early prophylactic ICD-implantation in these rare cases. Moleculargenetic studies are needed in large families to elucidate the potential of a common etiology.

Adult↗
PubMed2002

Fabry disease in patients with hypertrophic cardiomyopathy (HCM).

Fabry disease is an X-linked recessive lysosomal storage disorder with variable phenotype characterized by the accumulation of glycosphingolipid in various tissues. Unlike patients with the classical systemic Fabry disease entity, who present with multiple organ involvement, patients with a cardiac variant of Fabry disease are characterized mainly by myocardial hypertrophy. Therefore, the cardiac variant of Fabry disease may be defined as a cardiomyocytic storage disorder, thus, mimicking the clinical features of hypertrophic obstructive and especially non-obstructive cardiomyopathy. In patients with unexplained left ventricular hypertrophy the diagnosis of a cardiac variant of Fabry disease is performed by light- and electron microscopic evaluation of endomyocardial catheter biopsy specimens and/or serologic investigations (decreased activity of alpha-galactosidase A in plasma or leucocytes). Several studies show that between 4% and 8% of unselected patients with the clinical features of hypertrophic non-obstructive cardiomyopathy have a cardiac variant of Fabry disease. In each patient with unexplained myocardial hypertrophy concealed myocardial storage disease, especially cardiac Fabry disease has to be considered and should be ruled out or confirmed by endomyocardial catheter biopsy. This is important because of the recently reported alpha-galactosidase A enzyme replacement therapy in Fabry disease. Randomized, multicenter studies are mandatory to test the hypothesis that enzyme replacement therapy leads to a beneficial clinical effect in the cardiac variant form of Fabry disease and may prevent the progression of the disease in asymptomatic patients.

Aged↗
PubMed2002

BAX and p16INK4A are independent positive prognostic markers for advanced tumour stage of nonsmall cell lung cancer.

Clinical studies suggest prognostic relevance of p16INK4A in nonsmall cell lung cancer (NSCLC) while conflicting results for p53 have been published. However, the importance of the apoptosis regulating gene BAX, a downstream regulator of p53, on the prognosis of NSCLC is unknown. The present study investigated the prognostic relevance of BAX with respect to the status of p53 and P16INK4A in 61 patients with advanced NSCLC. Protein expression of BAX, p53 and p16INK4A was investigated retrospectively by immunohistochemistry. Tumour deoxyribonucleic acid (DNA) was screened for p53 mutations by single strand-conformation polymorphism polymerase chain reaction (PCR) and BAX frameshift mutations by fragment length analysis. Patients with positive BAX protein expression had a significantly longer median survival (14 months) than those patients without BAX expression (6 months, p=0.0004). In contrast, p53 status did not influence prognosis. Patients with p161NK4A negative tumours had a significantly shorter survival (4 months) than those with p16INK41 protein expression (15 months, p=0.0001). Furthermore, the loss of p16INK4A protein expression correlated strongly with the pressure of distant and advanced lymph-node metastases. The best survival was seen in a subgroup of 20 patients with positive p16INK4A expression and intact BAX (p=0.0002). The results of the present study suggest that the loss of BAX and p16INK4A expression are independent markers for poor prognosis in nonsmall cell lung cancer. The study suggests that multimarker analysis of genes involved in apoptosis may be useful for determining individual therapy and for identifying targets for gene-replacement therapy. This should be assessed in a prospective study with a larger cohort of patients.

Aged↗
PubMed2002

Adenovirus-mediated E2F-1 gene transfer in nonsmall-cell lung cancer induces cell growth arrest and apoptosis.

Since overexpression of E2F-1 has been shown to induce apoptosis, the ability of adenovirus-mediated transfer of E2F-1 to inhibit tumour growth in nonsmall-cell lung cancer cell lines was investigated. Three cell lines with various genomic status were infected with AdE2F. Cell proliferation and viability were determined by trypan blue exclusion. Apoptosis induction was assessed by flow cytometry and poly-adenosine diphosphate-ribose-polymerase cleavage assay. In vivo, the effect of E2F-1 on tumour growth was determined in severe combined immunodeficiency (SCID) mice. The current experiments showed that overexpression of E2F-1 suppressed tumour cell growth. The population of apoptotic cells was dramatically increased 96 h after infection with AdE2F. Inhibition of cell growth and induction of apoptosis was not dependent on genomic status. Moreover, treatment of implanted tumours in SCID mice with AdE2F inhibited tumour growth. These data suggest that adenovirus-mediated E2F-1 gene therapy may be effective in the treatment of nonsmall-cell lung cancer.

Adenoviridae↗