Intracerebral haemorrhage in a population-based stroke registry (LuSSt): incidence, aetiology, functional outcome and mortality.

Data on incidence of intracerebral haemorrhage (ICH) vary widely. Population-based data on predictors of ICH survival and functional outcome are rare. The Ludwigshafen Stroke Study is a prospective, population-based stroke registry which started in January 2006. All residents of the city of Ludwigshafen, Germany, who suffer from acute stroke or transient ischaemic attack are registered. Patients with first-ever primary intracerebral haemorrhage (FE-pICH) between 2006 and 2010 were included in the present analysis. Between January 1st, 2006 and December 31st, 2010, 152 patients suffered a FE-pICH. Crude and age-adjusted incidence rates per 100,000 for FE-pICH were 18.7 (95 % CI 15.9-21.9) and 11.9 (95 % CI 10.2-14.0), respectively, and remained stable over time. Case-fatality rates for FE-pICH were 27.0, 34.9 and 44.1 % at days 28, 90 and 365, respectively. In 21 patients, an (21.3 %) early do-not resuscitate-order was documented. Excluding these patients from multivariate analyses, National Institute of Health Stroke Scale (NIHSS) (OR 1.22, 95 % CI 1.08-1.36), hypercholesterolemia (OR 0.16, 95 % CI 0.05-0.55) and modified Rankin Scale (mRS) prior to stroke (OR 1.56, 95 % CI 1.06-2.3) were independently associated with risk of 1-year mortality, whereas NIHSS (OR 1.41, 95 % CI 1.20-1.66) and leukocyte count on admission (OR 1.48, 95 % CI 1.16-1.89) were independently associated with good or moderate functional outcome (mRS ≤ 3) after 1 year. Incidence of FE-ICH is in the lower range of those reported from other registries and remained stable over the observation period. Higher treatment rates for hypertension might partly account for this. Stroke severity as indicated by NIHSS was independently associated with mortality and functional outcome after 1 year. We found no association between aetiology and outcome in ICH patients.

Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen Stroke Study, a population-based stroke registry.

BACKGROUND: Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates. METHODS: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke. RESULTS: Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 ± 12.6 years) than men (n = 299; 69.7 ± 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20-1.56) than in women (1.12; 95% CI 0.97-1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), small-artery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and 'probable atherothrombotic stroke' (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p < 0.001), coronary artery disease (p = 0.0015) and peripheral artery disease (p = 0.024) was significantly more common in men than in women. Overall, 1-year survival was not different between both sexes; however, a significant age-sex interaction with higher mortality in elderly women (>85 years) was detected. CONCLUSIONS: Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men.

Amphotericin B and liver function.

Amphotericin B is well established as a highly efficacious agent against systemic fungal infections in humans. The therapeutic potential of amphotericin B is limited due to its side effects. Although in clinical use for more than 35 years, impairment of liver function is not considered to be a typical adverse effect of amphotericin B. Experimental data suggest that the drug may interfere with the hepatic cytochrome P450 and may thus influence the metabolic capacity of the liver. A confirmation of such a finding in patients treated with amphotericin B would be of value. The incidence of severe acute or subacute hepatotoxicity in response to amphotericin B is very low. Frequently, in critically ill patients, it is not always clear whether liver abnormalities are caused by an antifungal agent or whether they are due to the critical condition of these patients. Nevertheless, there are experimental data suggesting that amphotericin B may influence the metabolic capacity of the liver. Accordingly, drug interactions during prolonged amphotericin B treatment seem possible. Careful monitoring of liver function in those patients receiving amphotericin B in combination with other drugs, which undergo hepatic metabolism or are potentially hepatotoxic, is recommended. In this review, the current understanding and knowledge of the clinical significance, detection, and possible pathogenesis of amphotericin-B-induced liver damage are presented. With respect to the current experimental data, the influence of the drug on the hepatic microsomal cytochrome P450 are also presented and discussed, as is the impact of several clinical studies using different amphotericin B formulas in humans.

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.

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.

Comparison of the effects of liposomal amphotericin B and conventional amphotericin B on propafenone metabolism and hepatic cytochrome P-450 in rats.

The effects of conventional amphotericin B (AmB) dissolved in sodium deoxycholate on microsomal cytochrome P-450 concentrations and propafenone metabolism to 5-hydroxy-propafenone and N-desalkyl-propafenone were compared with those of liposomal AMB (Li-AMB) in rats. AmB (3 mg/kg/day, intravenously [i.v.]) given for 4 days caused a significant decrease in the concentration of hepatic microsomal cytochrome P-450 (0.43 +/- 0.06 nmol/mg versus 0.62 +/- 0. 05 nmol/mg for the control [P < 0.05]). Following the application of Li-AMB (15 mg/kg/day, i.v.), hepatic microsomal cytochrome P-450 concentrations were unchanged at 0.64 +/- 0.08 nmol/mg. AmB decreased ex vivo propafenone metabolism to 5-hydroxy-propafenone and N-desalkyl-propafenone significantly. Sodium deoxycholate (the vehicle of AmB) by itself induced a significant decline of 5-hydroxy-propafenone and N-desalkyl-propafenone production, while microsomal cytochrome P-450 concentrations remained unchanged. In contrast, Li-AMB did not change the levels of production of 5-hydroxy-propafenone or of N-desalkyl-propafenone at either substrate concentration tested (50 micromol and 200 micromol). Microsomal AmB concentrations were significantly higher following Li-AMB application (21.1 +/- 6.2 microg/g versus 3.7 +/- 1.4 microg/g for AmB [P < 0.05]). We conclude that Li-AMB, in contrast to AmB, decreases neither hepatic microsomal cytochrome P-450 nor hepatic propafenone metabolism in rats ex vivo. Sodium deoxycholate alone decreases propafenone metabolism in a similar way to AmB, suggesting that it participates in AmB-induced disturbance of hepatic metabolic function.

Liposomal amphotericin B (AmBisome) application and hepatic microsomal enzyme function in the rat.

In the present study we investigated the influence of AmBisome, a lyophilized liposomal amphotericin B formulation on various hepatic cytochrome P450-dependent mixed function oxidases, antipyrine clearance and hepatic glucose-6-phosphatase activity in rats. Animals were treated intravenously for 6 days with AmBisome (15 mg kg-1 body weight). Subsequently, the enzyme activities and cytochrome P450 concentrations were measured ex vivo in hepatic microsomes. Following AmBisome the activity of the microsomal ethoxycoumarin-O-deethylase increased significantly from 333 +/- 77 pmol mg-1 to 459 +/- 125 pmol mg-1, whereas benzpyrenhydroxylase and glucose-6-phosphatase did not change compared with the controls. Accordingly, antipyrine clearance was not affected by AmBisome treatment. Microsomal cytochrome P450 concentrations as well as total microsomal protein concentrations were not changed following treatment with AmBisome and it did not affect either serum levels of liver transaminases or bilirubin. The results show that the application of a high AmBisome dose had no adverse effects on a variety of microsomal hepatic enzymes and the antipyrine clearance in rats. Thus, it seems likely that AmBisome does not seriously impair metabolic liver function.

Activating beta-1-adrenoceptor antibodies are not associated with cardiomyopathies secondary to valvular or hypertensive heart disease.

OBJECTIVES: We investigated whether autoantibodies against the human beta-adrenergic receptor (beta-AR) might be involved in cardiomyopathies secondary to valvular heart disease (VHD) or hypertensive heart disease (HHD). BACKGROUND: Autoimmunity to beta-AR has been proposed as a pathogenic principle in human cardiomyopathy. Recently, by the use of intact recombinant human beta-AR, we were able to confirm the existence of functionally active anti-beta-1-AR autoantibodies in patients with dilated cardiomyopathy (26% prevalence) or ischemic cardiomyopathy (10% prevalence); however, their prevalence in other (secondary) cardiomyopathies remained to be determined. METHODS: Immunoglobulin G (IgG) was prepared from the sera of 28 VHD and 19 HHD patients and first screened by a peptide-based enzyme-linked immunosorbent assay (antigens: aminoterminus, second extracellular loop [ECII] and carboxyterminus of human beta-1- and beta-2-AR). IgG from 108 gender- and age-matched healthy subjects served to define the threshold for positive immunoreactions. Positive sera were further screened for their ability to recognize and activate native human beta-AR situated in a cell membrane. RESULTS: Twenty-five percent (VHD) or 11% (HHD) of the patients and 4% of the healthy controls had IgG antibodies randomly directed against all the three domains tested and both beta-AR subtypes. Only one patient with aortic valve and concomitant coronary heart disease and one healthy subject had functionally active anti-b1-AR (targeting beta-1-ECII). Moreover, one HHD patient with concomitant collagenosis had IgG that was cross-reacting with recombinant beta-AR in immunological assays but was unable to affect receptor function. CONCLUSIONS: Autoimmune reactions against the human beta-AR do not appear to be associated with cardiomyopathies secondary to VHD or HHD.

Heat stress produces an early phase of protection against oxidative damage in human muscle.

BACKGROUND: It has been rarely reported that heat stress induces an early phase of protection against oxidative damage, whereas a delayed phase of protection is shown in heat stress. To explore the early effect of heat stress against oxidative damage, we evaluated the changes in contractility, lipid peroxidation, and ultrastructure induced by hydrogen peroxide (H2O2) with or without heat stress (HS) in human skeleton muscle. METHODS: Thirty-two muscle samples were obtained from the vastus lateralis muscle of 7 subjects. These specimens were divided into three groups based on form of treatment: HS (n = 13), non HS (n = 14), and control group (n = 5). The control group was performed under identical conditions without H2O2. Specimens in the HS group were incubated at 42 degrees C for 20 min, while those in the non-HS and control groups were maintained at 37 degrees C. RESULTS: The control group showed no significant change in contractile force. Although contractile force significantly decreased 30 min after H2O2 administration in both the HS and non-HS groups, only the HS group showed apparent recovery of contractile force 60 min after H2O2 administration. Lipid peroxidation was lower in the HS group than in the non-HS group. Ultrastructural examination revealed less mitochondrial damage in the HS group compared with the non-HS group. CONCLUSION: We found that human skeleton muscle escaped cellular damage induced by H2O2 in the early phase after heat stress. These data suggest evidence for an early effect of heat stress against ischemia/reperfusion injury in human muscle.

Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure.

BACKGROUND: Autoantibodies against synthetic peptides of beta-adrenergic receptors have been observed in human cardiomyopathy. However, it has never been shown that such antibodies really interact with native human beta-adrenergic receptors, nor has the clinical impact of such an interaction been investigated in larger groups of patients. METHODS AND RESULTS: We screened 104 patients with dilated or ischemic cardiomyopathy (NYHA functional classes II to IV) and 108 healthy subjects for IgG antibodies reacting with beta-receptor peptides. Such IgGs were further analyzed for binding and functional interactions with native recombinant human beta-adrenergic receptors. Antibodies reacting with synthetic receptor peptides were present in 51% of the patients. However, only a subgroup directed against the second extracellular receptor domain also recognized native human beta-adrenergic receptors situated in a cell membrane. All antibodies of this subgroup impaired receptor ligand binding and enhanced receptor-mediated signaling, which could be blocked by 5 micromol/L bisoprolol in vitro. Their prevalence was 1% in healthy subjects and 10% in ischemic cardiomyopathy, whereas it amounted to 26% in dilated cardiomyopathy and was associated with a significantly poorer left ventricular function. CONCLUSIONS: Our data show that activating autoantibodies against human beta-adrenergic receptors exist in approximately 25% of patients with dilated cardiomyopathy. Counteraction of such autoantibodies might contribute to the beneficial effects of beta-adrenergic receptor blockade in chronic heart failure.

Atrial ejection force in systemic autoimmune diseases.

Systemic autoimmune disorders may affect several organs, including the heart. We analyzed two-dimensional and pulsed Doppler echocardiograms of patients (n = 37) with systemic lupus erythematosus (SLE, n = 24) or rheumatoid arthritis (RA, n = 13) to determine whether atrial ejection force (AEF) could represent a suitable parameter for detecting left ventricular filling abnormalities in SLE and RA. In both patient subgroups, AEF was significantly higher than in healthy controls (n = 40) matched for gender and age (14.0 +/- 5.4 vs. 11.0 +/- 3.5 kdyn, p < 0.01). Because conventional echocardiographic parameters of left ventricular function failed to detect such a difference, AEF might serve as an additional sensitive parameter for detecting left ventricular diastolic filling abnormalities early in the course of a systemic autoimmune disease.

A primary osteosarcoma of the heart as a cause of recurrent peripheral arterial emboli.

The case of a 66-year-old woman with a primary cardiac osteosarcoma is described. These distinctly rare malignant tumors arise preferentially in the left atrium. Clinically, they often present symptoms of both, intramural and intracavitary neoplasm in addition to general weakness, recurrent breast pain, and dyspnea. As shown in the present case, with growing intracavitary tumor masses the risk for peripheral arterial including cerebral embolism increases. Consequently, in most patients with symptoms of systemic arterial embolism of unknown origin performance of transesophageal echocardiography seems advisible, which is presently the most convenient noninvasive imaging method to exclude or to identify intracardiac sources of emboli, irrespective of their type.

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.

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.

Influence of amphotericin B treatment duration of hepatic microsomal enzyme function in rats.

The influence of amphotericin B on various cytochrome P450-dependent mixed-function oxidases, antipyrine clearance and glucose-6-phosphatase was investigated in rats treated daily with deoxycholate amphotericin B (3 mg/kg body weight, intravenously) either for 1 or 4 days. Enzyme activity was measured ex vivo in hepatic microsomes. Following amphotericin B plus deoxycholate application for day 1, ethoxycoumarin-O-deethylase activity decrease significantly whereas microsomal cytochrome P450 concentration, cytochrome c reductase activity, antipyrine clearance and glucose-6-phosphatase activity did not change significantly. In contrast, following application of amphotericin B plus deoxycholate for 4 days the cytochrome P450 concentration was reduced by 50% (p < 0.05) as well as ethoxycoumarin-O-deethylase activity, antipyrine clearance and glucose-6-phosphatase activity: ethoxycoumarin-O-deethylase 232 +/- 68 pmol/mg/min, control 442 +/- 99 pmol/mg/min (p < 0.01); antipyrine clearance 0.56 +/- 0.21 ml/min, control 0.96 +/- 0.18 ml/min (p < 0.01), and glucose-6-phosphatase 193 +/- 28 mU/mg, control 351 +/- 95 mU/mg (p < 0.05). Cytochrome c reductase activity did not decrease significantly. Besides an increase in cytochrome c reductase activity, sodium deoxycholate (a vehicle of amphotericin B) alone induced no significant changes. Microsomal protein related to liver wet weight was significantly reduced by 50% (p < 0.01) only in animals treated for 4 days with amphotericin B plus deoxycholate. The results show that a 1-day treatment of rats with amphotericin B decreases ethoxycoumarin-O-deethylase activity, whereas the hepatic microsomal cytochrome P450 content, cytochrome c reductase and glucose-6-phosphatase activity did not change. Amphotericin B given for 4 days significantly decreases hepatic microsomal enzyme function. The inhibitory effect of amphotericin B on hepatic cytochrome P450 may be due to inhibition of hepatic protein synthesis.

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.

[Analysis of the pressure-surface relation of the left ventricle with automatic echocardiographic contour detection]. / Analyse der Druck-Flächen-Beziehung des linken Ventrikels mittels automatischer echokardiographischer Konturerkennung.

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.

[Acquired heart valve defects. Diagnostic and therapeutic strategies]. / Erworbene Herzklappenfehler. Diagnostische und therapeutische Strategien.

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.

[Pericardial lipoma as the cause of extensive mediastinal space-occupying lesion]. / Perikardlipom als Ursache einer ausgedehnten mediastinalen Raumforderung.

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.

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.