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Biomedical subjects

U Nellessen

Publications and source records attributed to U Nellessen.

At least 19 recordsLinked to original sources

Association between polymorphisms in candidate genes and morbid obesity.

Polymorphisms in a number of candidate genes have been reported to be associated with obesity. We have determined the incidence of the following polymorphisms in the following candidate genes in a group of 388 morbid obese patients (mean body mass index (BMI) 52+/-8.01) who underwent gastric banding surgery: lipoprotein lipase (LpL) t-93 g and N291S; peroxisome proliferator receptor gamma (PPARgamma), P12A, P115Q and c1431t; peroxisome proliferator receptor alpha (PPARalpha) L162V; beta-adrenergic receptor 2 (beta-AR 2), Q27E; beta-adrenergic receptor 3 (beta-AR 3) W64R; uncoupling protein 1 (ucp-1), a-3826g, ucp-2, 45 bp insertion. Only for the ucp2 polymorphism did we find a statistically significant association with obesity. The beta-AR 3 W64R and ucp-1 a-3826g polymorphisms influenced the rate of the development of obesity and may act synergistically.

Adult↗

Rest and exercise hemodynamics before and after valve replacement--a combined Doppler/catheter study.

BACKGROUND: Hemodynamic improvement is a common finding following valve replacement. However, despite a normally functioning prosthesis and normal left ventricular ejection fraction, some patients may show an abnormal hemodynamic response to exercise. METHODS: In a combined catheter/Doppler study, rest and exercise hemodynamics were evaluated in 23 patients following aortic (n = 12) (Group 1) or mitral valve (n = 11) (Group 2) replacement and compared with preoperative findings. Patient selection was based on absence of coronary artery disease and left ventricular failure as shown by preoperative angiography. Cardiac output, pulmonary artery pressure, pulmonary capillary pressure, and pulmonary resistance were measured by right heart catheterization, whereas the gradient across the valve prosthesis was determined by Doppler echocardiography. Postoperative evaluation was done at rest and during exercise. The mean follow-up was 8.2 +/- 2.2 years in Group 1 and 4.2 +/- 1 years in Group 2. RESULTS: With exercise, there was a significant rise in cardiac output in both groups. In Group 1, mean pulmonary pressure/capillary pressure decreased from 24 +/- 9/18 +/- 9 mmHg preoperatively to 18 +/- 2/12 +/- 4 mmHg postoperatively (p < 0.05), and increased to 43 +/- 12/30 +/- 8 mmHg with exercise (p < 0.05). The corresponding values for Group 2 were 36 +/- 12/24 +/- 6 mmHg preoperatively, 24 +/- 7/17 +/- 6 mmHg postoperatively (p < 0.05), and 51 +/- 2/38 +/- 4 mmHg with exercise (p < 0.05). Pulmonary vascular resistance was 109 +/- 56 dyne.s.cm-5 preoperatively, 70 +/- 39 dyne.s.cm-5 postoperatively (p < 0.05), and 70 +/- 36 dyne.s.cm-5 with exercise in Group 1. The corresponding values for Group 2 were 241 +/- 155 dyne.s.cm-5, 116 +/- 39 dyne.s.cm-5 (p < 0.05), and 104 +/- 47 dyne.s.cm-5. There was a significant increase in the gradients across the valve prosthesis in both groups, showing a significant correlation between the gradient at rest and exercise. No correlation was found between valve prosthesis gradient and pulmonary pressures. CONCLUSION: Exercise-induced pulmonary hypertension and abnormal left ventricular filling pressures seem to be a frequent finding following aortic or mitral valve replacement. Both hemodynamic abnormalities seem not to be determined by obstruction to flow across the valve prosthesis and may be concealed, showing nearly normal values at rest but a pathologic response to physical stress.

Adult↗

Ultrastructural changes of human cardiac atrial nerve endings in diabetes mellitus.

BACKGROUND: Autonomic neuropathy resulting from long-term diabetes mellitus may affect heart innervation. However, so far diabetes induced morphological changes of cardiac nerves are not well-known. In this study human cardiac atrial tissue from diabetic patients was analysed by electron microscopy for structural alterations as a result of diabetic neuropathy. METHODS: In coronary bypass surgery, an edge of the right auricle was routinely resected for reason of extracorporal circulation. Thin cardiac tissue sections of 100 nm were studied by electron microscopy. Atrial tissue samples were collected from 5 patients with long-standing diabetes (for at least 8 years) and compared to atrial tissue samples from 5 patients without diabetes, equally undergoing coronary bypass surgery. RESULTS: In all atria-free nerve endings with unmyelinized, axons were observed. Cross sections of 479 axons from diabetic patients were compared to 419 axons of nondiabetic patients. The number of altered axons was significantly higher in cardiac tissue of diabetic patients (32%) in comparison to normal subjects (17%). In diabetic patients, 20% of the intra-axonal mitochondria were condensed or hydropic, whereas in nondiabetic patients only 4% of the mitochondria were altered. Membrane fragments were present in 21% of the axons in atria of diabetic patients compared to 10% in nondiabetic subjects. Only in cardiac axons from diabetic patients there were lamellar bodies, dissolved axoplasma and junctions between neighbouring axons in a minor number. Few vacuoles were present in axons of both groups. CONCLUSION: In myocardial atrial-free nerve fibre bundles of diabetic patients, the amount of degenerative changes was higher in comparison to atrial cardiac tissue from nondiabetic subjects. These morphological alterations may indicate manifestation of diabetic neuropathy and might contribute to the impairment of autonomic neural control affecting the heart in long-standing diabetes mellitus.

Aged↗

Permanent pacemaker therapy before and after the reunification of Germany: 16 years of experience at an East German regional pacing center.

The reunification of Germany had a significant influence on the management of patients with bradyarrhythmias. The current study was performed in a regional pacing center located in the former German Democratic Republic. It compares the situation of patients with critical bradyarrhythmias before and after the reunification of Germany in 1990 focusing on (1) indication for pacemaker implantation, (2) pacemaker modalities and function, (3) type of leads, (4) frequency of reintervention, and (5) early and late complications. The study covers 9 years before and 7 years after the reunification. A total of 1,125 patients were included, and the database was formed by the patients' files and the protocols of implantation. The situation before reunification was characterized by a nonavailability of modern physiological pacing devices and insufficient diagnostic equipment. Between 1981 and 1990, 384 patients underwent pacemaker implantation solely receiving single chamber devices with no or only minimal feasibility of programming. Between 1990 and 1996, 741 patients were treated, and they all received modern pacemakers having the capability of multiprogramming and telemetry. Regarding complications of pacemaker therapy, lead related problems significantly decreased after the reunification (dislocation, 5.3% vs 1.7%, P < 0.05; exit block, 6.7% vs 1.4%, P < 0.05) opposite to pacemaker infections, which significantly increasing after dual chamber pacemakers were implanted (2.2% vs 6.0%, P < 0.05). The reunification of Germany dramatically improved the situation of patients with critical bradyarrhythmias leading to free access to high-tech pacing equipment within a few months. However, the abrupt change from antiquated to modern pacemaker therapy created some new problems, especially regarding application and handling of modern physiological pacing devices.

Equipment Design↗

Natural history of a ventriculoatrial fistula after a gunshot injury in 1945.

We describe an exceptional case of a patient who suffered a penetrating heart injury from a gunshot wound in 1945 leading to a left ventricular-right atrial fistula. Despite the resulting left-to-right shunt the patient remained relatively asymptomatic for 50 years before the onset of congestive heart failure necessitated an operation.

Aged↗

Lipid peroxidation and cardiac troponin T release during routine cardiac surgery.

Myocardial injury after cardiac surgery with cardiopulmonary bypass may be related to free oxygen radical-induced lipid peroxidation. The purpose of this study was to monitor perioperative changes of cardiac troponin t and malondialdehyde as an indicator of lipid peroxidation in patients who underwent routine cardiac operation and had no signs of perioperative myocardial infarction. Patients with thoracic surgery alone served as controls. We studied 20 patients with cardiopulmonary bypass (CPB) and 9 patients with other thoracic operations. Serum troponin t, malondialdehyde, myoglobin, creatine kinase (CK) including CK-MB isoenzyme levels were monitored before CPB, immediately after cessation of CPB, 20 and 44 h after CPB. Patients with signs of myocardial infarction before or up to 44 h after surgery were excluded. Of 20 patients with CBP, 18 patients showed a significant increase of troponin t and 16 patients had elevated malondialdehyde serum levels following CPB. Troponin t serum values were raised immediately after CPB to 0.60 +/- 0.12 microg/l and increased further to 0.90 +/- 0.17 microg/l after 44 h (p < 0.005, in comparison to preoperative: 0.08 +/- 0.02 microg/l). Patients undergoing the other thoracic operations showed neither any detectable troponin t serum values nor significant changes of serum malondialdehyde during the observed period. In the CPB group serum malondialdehyde peaked immediately after CPB to 98 +/- 9 nmol/g albumin (p < 0.005) and returned to preoperative levels (63 +/- 3 nmol/g albumin) within 20 h (60 +/- 3 nmol/g albumin). Individual maximal troponin t serum levels did not correlate with individual maximal serum malondialdehyde levels. The observed increase of troponin t levels had no influence on patients' outcome followed up for 18 months. The results demonstrate that troponin t and lipid peroxidation increase during uncomplicated cardiac surgery in patients without signs of myocardial infarction. Following uncomplicated cardiac surgery, a moderate increase of cardiac troponin t may not reflect severe cardiac injury.

Cardiac Surgical Procedures↗

Modification of cisplatin-induced renal p-aminohippurate uptake alteration and lipid peroxidation by thiols, Ginkgo biloba extract, deferoxamine and torbafylline.

To determine whether inhibition of lipid peroxidation modifies cisplatin-induced changes of renal p-aminohippurate (PAH) uptake, we examined the effects of various radical scavengers and torbafylline on cisplatin-induced lipid peroxidation and PAH accumulation changes in rat renal cortical slices. Renal cortical slices were incubated with different cisplatin concentrations (0.3, 0.6, 1.0 mg/ml) in the presence of either glutathione, N-acetylcysteine, the iron chelator deferoxamine, Ginkgo biloba extract or the xanthine derivate torbafylline. Lipid peroxidation monitored as the production of malondialdehyde (MDA) was stimulated by increasing cisplatin concentrations in a dose-related manner. At a cisplatin concentration of 1.0 mg/ml, MDA production was twofold compared to controls (0.69 +/- 0.06 vs. 1.36 +/- 0.07 nmol/mg; p < 0.05). In turn, cisplatin decreased PAH uptake of kidney slices dose-dependently from 13.3 +/- 1.3 to 2.6 +/- 0.2 (p < 0.01). All agents tested inhibited cisplatin-induced lipid peroxidation; however, at a cisplatin concentration of 1.0 mg/ml, none of them prevented the decline of cisplatin-induced PAH uptake. Of the agents tested, deferoxamine proved to be the most effective antioxidant, completely inhibiting cisplatin-induced lipid peroxidation but in contrast preventing the decrease in PAH uptake only at a cisplatin concentration of 0.3 mg/ml. No strict association between lipid peroxidation and decline of PAH uptake was found, suggesting that lipid peroxidation may only in part participate in cisplatin-induced alterations of PAH uptake.

Acetylcysteine↗

[Acquired heart valve defects. Diagnostic and therapeutic strategies].

BACKGROUND: Diagnostic and therapeutic strategies in patients with acquired valvular heart disease, are determined by clinical symptoms, hemodynamics and empirical information. DIAGNOSIS: A quantitative assessment of cardiac disease can made largely on the basis of echocardiography or Doppler echocardiography with consideration also being given to the results of clinical findings. As a rule, cardiac catheterization should be done only once, immediately prior to operation. OUTLINE OF THERAPY: In chronic mitral and aortic valve insufficiency, the surgical indication is based primarily on the clinical symptoms, while in aortic and mitral valve stenosis, it is based primarily on the hemodynamic findings. Promising interventional procedures such as balloon valvuloplasty, represent useful alternatives to valve replacement in the case of mitral valve stenosis alone. In the event of significant aortic valve stenosis alone. In the event of significant aortic valve stenosis, balloon valvuloplasty is not a promising procedure. In patients with aortic or mitral valve insufficiency, but normal left ventricular function, medical treatment should first be attempted.

Catheterization↗

[Noninvasive quantification of aortic and mitral insufficiency. Comparison of dynamic magnetic resonance imaging and Doppler color echocardiography].

The degree of valvular regurgitation was measured by dynamic magnetic resonance imaging (MRI) and colour-Doppler echocardiography (CDE) in 23 patients (14 men, 9 women; mean age 53 [19-75] years) with aortic (n = 13) or mitral (n = 10) regurgitation. Quantification by MRI was from a section corresponding to the four-chamber view. In aortic regurgitation, maximal regurgitant jet area (JA), ratio of JA to left-ventricular area (JA/LVA) were measured, while in mitral regurgitation, the ratio of JA to left atrial area (JA/LAA) was measured, as well as jet volume (JV) and the ratio of JV to the corresponding volume of the receiving chamber (JV/LVV or JV/LVA). The results were compared with corresponding measurement obtained by CDE in the four-chamber view. The degree of regurgitation was graded as small if JA/LVA or JA/LAA, respectively, was less than 0.2, moderate if 0.2-0.4, and marked if more than 0.4. In the patients with aortic regurgitation the correlation between the two methods was r = 0.91 regarding the jet area, 0.93 regarding JA/LVA and 0.92 regarding JV/LVV and JA/LVA. For mitral regurgitation the r values were 0.93 for JA, 0.89 for JA/LAA, and 0.85 for JV/LAV to JA/LAA. The grading of aortic regurgitation by MRI and CDE agreed in 12 of 13 patients (92%), and in nine of ten (90%) with mitral regurgitation (deviation by one degree of severity in each). These data indicate that quantification of aortic and mitral regurgitation gives similar results with MRI and CDE: thus, MRI is an equal substitute to CDE in patients with inadequate conditions for sonography.

Adult↗

Evidence for partial sympathetic cardiac reinnervation following cardiac transplantation.

Heart transplantation causes total cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenal metabolite, dihydroxyphenylglycol (DOPEG, exclusively neuronal in origin), were used to examine the possibility of sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 15 heart transplant recipients (28-68 years of age at the time of transplantation with the transplant ageing from 0.5 to 4 years at the time of investigation) and in nine control patients (45-75 years of age). In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arteriovenous increment: 60 +/- 10%; P < 0.001). In the heart transplant recipients nine patients showed an arteriovenous increment in plasma DOPEG. For the mean group results it was found that the ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (r = 0.92; n = 5; P < 0.05). Thus, our data provide neurochemical evidence for partial sympathetic reinnervation in some of the heart transplants. Moreover, it is suggested that the time after transplantation is unlikely to be the only determinant for the occurrence and extent of sympathetic reinnervation.

Adult↗

Enhancement of cyclosporin A induced hepato- and nephrotoxicity by glutathione depletion.

The role of glutathione in cyclosporin A (cyclosporin) hepato- and nephrotoxicity has not been clarified yet. The hypothesis that a glutathione deficit enhances the hepato- and nephrotoxicity of cyclosporin was tested in an animal model. Glutathione depletion was achieved by administration of diethyl maleate (DEM). Adult Sprague Dawley rats were divided into four groups (A-D; n > or = 8) and treated for 8 d as follows: group A, glucose 5% (0.4 ml kg-1, i.p.) +3 h later olive oil (0.5 ml kg-1, oral); group B, DEM (0.4 ml kg-1, i.p.) +3 h later olive oil (0.5 ml kg-1, oral); group C, glucose 5% (0.4 ml kg-1, i.p.) +3 h later cyclosporin (50 mg kg-1, oral); group D, DEM (0.4 ml kg-1, i.p.) +3 h later cyclosporin (50 mg kg-1, oral). Cyclosporin alone increased bilirubin concentration from 1.0 +/- 0.6 mumol l-1 to 8.4 +/- 1.9 mumol l-1 (P < 0.05) without changing transaminases. In glutathione depleted rats cyclosporin caused a further elevation of serum bilirubin up to 23.4 +/- 5.5 mumol l-1. This was accompanied by a 50% increase of serum glutamic oxaloacetic transaminase (GOT). Cyclosporin alone significantly decreased creatinine clearance to 50% of controls (P < 0.05). Cyclosporin treatment following glutathione depletion resulted in a further decline of creatinine clearance to 22% of controls. DEM had no effect on kidney or liver function. In conclusion glutathione depletion increases the susceptibility to cyclosporin-induced liver and kidney injury. The results support the hypothesis that sufficient cellular glutathione concentrations may be important to prevent cyclosporin-induced hepato- and nephrotoxicity.

Animals↗

[Analysis of the pressure-surface relation of the left ventricle with automatic echocardiographic contour detection].

UNLABELLED: Echocardiographic automatic border detection is a new on-line technique determinating the interface between blood and myocardial tissue thus having the potential to calculate cyclic changes in left ventricular cavity area in real time. It was the main purpose of the current study to evaluate left ventricular pressure-area relationship after administration of nitrates. In 12 patients with normal left ventricular function pressure-area relation was studied after a Swan-Ganz thermodilution catheter was placed in the wedge position and a high fidelity pig tail catheter was placed in the left ventricle. Left ventricular pressure and cyclic changes of cavity area were simultaneously analysed and displayed together as waveforms on the echo screen using a computer interfaced with the echo machine. All measurements were done before and five minutes after administration of 0.8 mg nitroglycerin. Mean systolic and diastolic blood pressure decreased significantly from 145/12 mmHg to 127/8 mmHg (p < 0.05). Mean systolic area decreased slightly from 10 cm2 to 9 cm2 (n.s.) whereas mean enddiastolic area decreased significantly from 18 cm2 to 15 cm2 (p < 0.05). Accordingly there was a downward and leftward shift of the diastolic pressure-area relationship following administration of nitroglycerin. CONCLUSION: Echocardiographic automated border recognition seems to be a promising new on-line method in the detection of left ventricular cavity area changes underlining its potential usefulness in the evaluation of left ventricular performance.

Adult↗

[Neurochemical studies of adrenergic reinnervation after heart transplantation].

Heart transplantation causes sympathetic cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenaline metabolite, dihydroxyphenylglycol (DOPEG, the plasma pool of which is exclusively neuronal in origin), were used to examine sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 27 heart transplant recipients (transplant age ranging from 0.5 to 5 years) and in 9 control patients. In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arterio-venous increment: 57.3 +/- 8.7%; p < 0.001). However, in heart transplant recipients, 18 out of 27 patients showed an arteriovenous increment in plasma DOPEG (mean increment in all patients 12.6 +/- 2.0%; p < 0.05). The ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (p = 0.02 for individual results and p < 0.01 for mean group results). Thus, our data provide evidence for a time-dependent partial sympathetic reinnervation of the transplanted heart.

Adrenergic Fibers↗

[Pericardial lipoma as the cause of extensive mediastinal space-occupying lesion].

Lipomas of the heart are benign neoplasias and have rarely been described. Due to the fact that they normally cause no symptoms, diagnosis is often purely accidental. In the current report, the case of a 55-year-old patient is described in whom serial chest x-rays showed massive, progressive cardiac enlargement. Echocardiography and NMR showed a large pericardial mass confirmed by subsequent surgery which revealed a giant pericardial lipoma.

Diagnosis, Differential↗

Lack of inotropic effect of cyclosporin A in isolated guinea pig left atria.

OBJECTIVE: Cyclosporin A is being widely used to prevent graft rejection in organ transplantation and to treat autoimmune diseases. Since various toxic side effects have been observed, the aim of this study was to look for even a subtle deleterious effect of cyclosporin A on cardiac inotropy in electrically stimulated guinea pig left atria. METHODS: The left atrial muscles of guinea pigs, in Tyrode's solution containing 2.7 or 5.4 mM potassium, were electrically stimulated by one of two methods: (1) continuously at 3 Hz, during which cyclosporin A was applied cumulatively (from 10(-9) to 10(-5) M); or (2) stimulated intermittently at 2.5 Hz in 5 mM cyclosporin A, with rest periods of 4 s duration interposed every 4 min. The effects of cyclosporin A on contractile force were observed for 150 min in the first stimulation method, and the effects on the steady state contractile force and amplitude of post-rest contraction were observed for 240 min in the second method. RESULTS: The steady state contractile force of the atria declined within the 4 h period at 2.7 mM potassium in Tyrode's solution both in the cyclosporin A group (n = 10) and in the control group (n = 5) to 68(SD 11)% and to 63(4)%, respectively. After 4 h the amplitudes of the post-rest contraction were 101(16)% and 101(4)% in cyclosporin A and control groups, respectively. At 5.4 mM potassium, the following values were obtained (cyclosporin A v control): steady state force 70(8)% (n = 11) v 69(8)% (n = 5); post-rest force 105(9)% v 102(7)%. CONCLUSIONS: Cyclosporin A does not influence the steady state contractile force or the amplitude of the post-rest contraction, suggesting the absence of inotropic effects on isolated guinea pig left atria.

Animals↗

[Correlation between Doppler echocardiography and invasive determination of left ventricular hemodynamic valve parameters. A comparative study under routine conditions in a cardiology center].

UNLABELLED: Simultaneously performed combined Doppler/catheter studies have shown excellent correlations regarding the comparison of invasively and non-invasively obtained valve gradients. To reflect daily clinical life the current study compared the valve parameters obtained by Doppler echocardiography to those obtained later by catheterization in all consecutive patients who underwent invasive procedure between October 1988 and December 1990. A total of 113 patients was included in the study, 76 with aortic and 37 with mitral stenosis. Regarding the mean aortic valve gradient the following correlations were obtained: all patients: r = .79, patients with an ejection fraction > 50% (n = 59): r = .81, patients with an ejection fraction < 50% (n = 17): r = .67, patients with additional aortic insufficiency (n = 21): r = .77. When the mean mitral valve gradient was compared the correlation was r = .71 for all patients and r = .44 when additional mitral regurgitation was present (n = 10). The comparison of the mitral valve orifice area (n = 30) showed a correlation of r = .58. CONCLUSION: Non-simultaneously performed combined Doppler/catheter studies in unselected patients do reflect daily clinical life, however, correlations are not as good as in corresponding simultaneously performed investigations, thus emphasizing the impact of the study conditions on the final results.

Adult↗