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Biomedical subjects

B Maisch

Publications and source records attributed to B Maisch.

At least 145 records · Page 8Linked to original sources

Antibodies against stress proteins in sera of patients with dilated cardiomyopathy.

The pathogenesis of dilated cardiomyopathy (DCM) is as yet unknown. However, it is widely believed that autoimmune mechanisms contribute to the manifestations of the disease. In sera of patients with dilated cardiomyopathy, antibodies against different antigens, including heat shock protein (hsp) 60, were found. Antibodies against other stress proteins have not yet been reported. The aim of this study, therefore, was to screen sera of patients with DCM for the presence of antibodies against the major stress proteins. Lysate of stressed human endothelial cells was used as antigenic substrate in 1- and 2-dimensional immunoblot, since this cell type has recently been shown to express the major stress proteins. Antibodies against hsp60, hsp70, and heat shock cognate protein (hsc) 70 were detected in sera of patients with dilated cardiomyopathy as compared to healthy controls. Interestingly, antibodies against hsp70 and hsc70 were found in sera of patients younger than 30 years significantly more often than in older individuals. A correlation between the presence of antibodies against stress proteins and disease activity, clinical status, or histological findings was not detected. These findings support the view that DCM might be a consequence of an infectious disease, because stress proteins are immunodominant antigens in microbial agents and antibodies against stress proteins were detected in sera of patients with infectious diseases. Whether these antibodies are of pathogenetic significance or may be used as a disease marker will have to be elucidated in future experiments.

Adolescent↗

Point mutations in mitochondrial DNA of patients with dilated cardiomyopathy.

Mitochondrial (mt) DNA mutations are hypothesized to be involved in the pathogenesis of dilated cardiomyopathy, because the mtDNA encodes 13 polypeptides that are essential for oxidative phosphorylation, upon which the heart relies for energy. To test this hypothesis, we amplified the mitochondrial genome by long PCR and then used restriction analysis and direct sequencing to examine 58 unrelated patients with dilated cardiomyopathy and 49 controls for the detection of point mutations. The results demonstrated that point mutations were significantly more frequent in the mtDNA of patients than in that of controls (173 in 58 patients v 54 in 49 controls, 2=16.51, P<0.001). In addition to normal variants and mutations common to both patients and controls, 43 mutations were identified only in patients. All but four of these mutations were homoplasmic. Mutations involving the evolutionarily conserved residues of cytochrome c oxidase subunit I, NADH dehydrogenase 5, tRNAAla and tRNAArg were identified. As many as 13 point mutations were found in an 8-month-old patient. In conclusion, there exist significantly more point mutations in mtDNA of patients than in controls, suggesting that multiple mutations may exert a cumulative effect on heart function. Thus, by altering the function of respiratory enzyme subunits or tRNAs, mtDNA point mutations could be relevant for the pathogenesis of dilated cardiomyopathy.

Adult↗

Patients' profiles in end stage coronary artery disease. Indications for treatment with transmyocardial laser revascularisation.

There is a subgroup of patients with coronary artery disease who are refractory to the therapeutical methods so far applied. We report on 128 patients who fulfill this definition and have therefore undergone pure transmyocardial laser revascularisation (TMLR) or transmyocardial laser revascularisation in combination with coronary bypass surgery at our institution. The patients can be characterized by a long history of coronary artery disease with multiple revascularizing procedures, e.g. bypass surgery or percutaneous transluminal coronary angioplasty (PTCA), pronounced symptoms of coronary artery disease and chronic heart failure in the presence of markedly reduced left ventricular ejection fractions and intense antiischemic medical therapy. The patients were 62.2 +/- 9.8 (SD) years of age, in 89.9% of them at least one bypass operation and in 44.5% up to more than three percutaneous transluminal coronary angioplasties (PTCAs) had been performed prior to TMLR. There was a history of myocardial infarction in 90.7% of patients and 89.8% were in the Canadian Cardiovascular Society (CCS) classes III or IV and 94.5% of them were in the NYHA classes III or IV. The left ventricular ejection fraction was 49.5 +/- 16.4% and all of the patients were under intense antiischemic medical treatment which included nitrates or molsidomine in 96.9%, beta blockers in 53.1%, angiotensin converting enzyme inhibitors (ACE inhibitors) in 44.5%, digitalis in 22.7% and diuretics in 52.3% of patients. The preoperative data on myocardial viability, inducible ischemia and coronary morphology provided important clinical information for the decision, which revascularizing method would be the most appropriate for each vessel or myocardial region. This had to be weighed against the patient's operative risk, which is predominantly determined by the left ventricular ejection fraction, the arteriosclerotic involvement of the remaining vascular system and concomitant diseases, particularly of pulmonary origin.

Aged↗

[Transmyocardial laser revascularization in stable and unstable angina pectoris].

Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum medical therapy. This fact has directed the interest again towards surgical techniques of indirect revascularization, which had been introduced by Beck and other surgeons more than 60 years ago. Among these attempts we can also find transmyocardial needle punctures, firstly performed by Sen in Bombay. In the early eighties it was Mirhoseini, who used a laser for creating these transmural channels, primarily in combination with coronary bypass surgery at the arrested heart and later on together with Crew as a sole therapy at the beating heart. The idea behind this transmyocardial laser revascularization (TMLR) was a "reptilization" of the human heart, which meant a direct blood supply from the ventricle into the ischemic myocardium. Whereas this theory has not proven to be true, as the surface area of these channels is not sufficient for the nutrition of the surrounding myocardial tissue by diffusion or convection, different models have been developed by anatomical, experimental and clinical studies, such as the connection between the laser channels and intramyocardial vessels or capillaries, analogous to ventriculo-coronary connections in human anatomy or pathology as for example those connections described in children with pulmonary atresia and intact ventricular septum or the Thebesian veins. Moreover the laser trauma may also simply contribute to the induction of neoangiogenesis. While the function of TMLR is still not clearly defined, clinical studies in the United States and also in other countries have proven the clinical efficacy in a cohort of severely diseased patients undergoing this procedure. Accordingly more than 2/3 of all patients after TMLR showed a significant improvement of more than 2 angina classes (CCS) as well as a decrease in medication and hospitalization. Moreover there was also a reduction of ischemic areas demonstrated by szintigraphy and, in one study from Houston, also by positron emission tomography. While the overall mortality in all those studies is still considerably high, a reduction could be achieved by a stricter selection of patients excluding especially those with a severely impaired left ventricular function. As demonstrated by preliminary data from the last phase III FDA-study, TMLR may even reduce long-term mortality compared to maximum medical therapy in a randomized group of patients. Our own experiences in 134 patients also confirmed a significant reduction of angina after TMLR alone (n = 67) or in combination with bypass surgery (n = 67) with the majority of patients being in angina class 1 and 2 (CCS) 6 months after surgery. All of these patients were in angina class 3 and 4 before surgery. Nuclear scans could demonstrate an improved perfusion in more than 40%. Further studies as well as other clinical and also experimental investigations have still to be awaited, before the definitive role of TMLR within the armamentarium against coronary artery disease can be determined. However, it is already a therapeutic option for those highly symptomatic patients, who cannot be offered a different treatment modality.

Adult↗

[Transmyocardial laser revascularization and rehabilitation].

Transmyocardial laser revascularization (TMLR) is a new technique for patients with CAD or heart attack to revascularize ischemic areas of the myocardium in which the localisation or the condition of the vessels does not allow bypass grafting. This study shows the results in observation of patients before and during the first 3 months after TMLR. Of 110 patients operated on from 1994 to 1996, 86 were evaluated for well being (quality of life), using NYHA- and CCS-classification, stress test and nitril-scintigraphy at rest and under stress conditions. 51 patients, of whom 11 were females, underwent TMLR combined with coronary artery bypass graft (CABG). 35 male patients were treated singularly with TMLR. The average age in both groups was 59 years (+/- 23). All patients were subject to phase I rehabilitation in specialised institutions after being mobilised in the operating hospital. The evaluations took place on the day of admission to the hospital prior to surgery, within 10 days after surgery and 3 months following. The average stay in the rehabilitation-institution was between 4 and 6 weeks. Our findings demonstrate that both groups profited from the procedures, while the TMLR/CABG group showed a faster recovery and a better outcome. In comparison to 57% of the TMLR group, 85% of the patients in the TMLR/CABG group reported an improvement ranging from good to significant in quality of life assessments. The TMLR/CABG rated from an average of initially 3.4 (+/- 0.6) to 2.1 (+/- 0.8) after 3 months at NYHA- and 3.3 (+/- 0.7) to 1.7 (+/- 0.8) at CCS-classification. The TMLR group rated from 3.6 (+/- 0.5) to 2.4 (+/- 0.8) in NHYA- and from 3.4 (+/- 0.5) to 1.9 (+/- 0.7) on the CSS-scales. A remarkable improvement was noted in the stress test with an increase in power and endurance from 21 to 89 watts for the combined group and 8 to 81 watts for the TMLR treated patients, who generally recovered more slowly. The perfusion scan showed the same tendencies as previously reported but in some cases the results were not congruent with other findings. Overall, our findings indicate that there is a benefit for terminally symptomatic CAD patients after TMLR, but an observation period of 3 months does not allow for final conclusions on this matter. Rehabilitation seems to be of value for TMLR-patients since they have shown a markedly better performance following 3-month treatment, but further data from clinical randomised trials are needed to determine the influence of TMLR with short- and long-term rehabilitation on the prognosis of the disease.

Adult↗

[Endomyocardial biopsy--helpful in differential diagnosis between myocarditis and dilated cardiomyopathy. A case report].

Endomyocardial biopsy is an established technique to distinguish between myocarditis and dilated cardiomyopathy. Even when clinical symptoms for myocarditis are lacking, immunohistologic findings may establish a clear diagnosis. For treatment, however, an early diagnosis is mandatory. We report on a 44 year old patient who was admitted with the echocardiographic diagnosis of dilated cardiomyopathy. He underwent diagnostic angiocardiography and endomyocardial biopsy. The latter demonstrated an active myocarditis. At the time of read-mission, 2 weeks later, the patient had deteriorated. Now, additional to a symptomatic therapy, prednisolone, azathioprine and human immunoglobulin G were given and patient conditions improved dramatically. The use of endomyocardial biopsy seems recommendable in order to define patients diagnosis and their results may be necessary to decide patients therapy.

Adult↗

Syncope recurrence can better be predicted by history than by head-up tilt testing in untreated patients with suspected neurally mediated syncope.

BACKGROUND: Head-up tilt testing is widely used in the evaluation of patients with suspected neurally mediated syncope. Although it remains unclear which patients require medical therapy to prevent recurrent syncope, most centres initiate empiric medical therapy in all patients in whom neurally mediated syncope has been diagnosed. To determine the natural history of this condition, we followed 80 untreated patients. METHODS: All 80 study patients fulfilled the following inclusion criteria: (1) > or = 1 syncope in the upright position, (2) absence of structural heart disease, (3) unremarkable work-up for other known causes of syncope. Thirty-nine patients had a history of one episode of syncope (group A) and 41 > or = 2 episodes of syncope (group B). Head-up tilting was performed in all patients at 60 degrees for a maximum of 45 min without medical provocation ('Westminster Protocol'). RESULTS: Suspected neurally mediated syncope could be reproduced by tilt testing in four of 39 patients from group A vs 10 of 41 patients from group B (10% vs 24%, P = 0.1). Independent of the result of head-up tilt testing, all patients were prospectively followed without medical therapy. During 23 +/- 8 months follow-up, syncope recurred in four of 39 group A patients vs 22 of 41 group B patients (10% vs 54%, P < 0.05). The incidence of syncope during follow-up was not significantly different between patients with and without positive baseline tilt test (43% vs 30%, P = ns). CONCLUSIONS: (1) 90% of patients with a single episode of syncope remain free of recurrent syncope without medical therapy irrespective of the result of tilt testing. (2) About half of patients with a history of > or = 2 syncopal episodes have recurrent syncope and, thus, may be appropriate candidates for prophylactic medical therapy. (3) Although head-up tilt testing at 60 degrees for up to 45 min does not appear to be useful to predict recurrent syncope in untreated patients, it is still a useful test in its evaluation.

Adolescent↗

Papillary muscle injury after blunt chest trauma.

In many cases blunt chest trauma involves cardiac lesions, such as pericardial effusion, aneurysma dissecans, or valvular rupture. Early diagnosis with routine transthoracic and/or transesophageal echocardiography is essential to prevent a fatal outcome. In the case reported, a previously healthy 68-year-old woman fell 7 meters from the roof of a barn and sustained blunt injury to the chest as well as fractures of the face. Physical examination revealed a systolic murmur at the cardiac apex, and chest x-ray film showed a severe pulmonary edema. Transesophageal echocardiography demonstrated a ruptured anterolateral papillary muscle with fourth degree mitral insufficiency. An immediate mitral valve replacement was necessary.

Accidental Falls↗

Magnetic resonance imaging and signal-averaged electrocardiography in patients with repetitive monomorphic ventricular tachycardia and otherwise normal electrocardiogram.

Early or localized forms of arrhythmogenic right ventricular dysplasia (ARVD) have been proposed as the arrhythmogenic substrate of repetitive monomorphic ventricular tachycardia (RMVT) originating in the right ventricular outflow tract in patients without any underlying cardiac abnormality on clinical examination and echocardiography. To further examine this hypothesis, magnetic resonance imaging (MRI) and signal-averaged electrocardiography (SAECG) were performed on 23 patients with RMVT and normal 12-lead standard ECG of conducted sinus beats. MRI was performed using ECG-gated turbo spin-echo images of the heart in order to detect signs of early or localized forms of ARVD, such as localized wall thickness reductions, signal intensity increase indicating adipose tissue infiltrates, and regional bulgings or aneurysms. MRI was normal in 22 (96%) of 23 study patients. In the remaining patient (4%), MRI demonstrated signal intensity increase in the intraventricular septum but not in the right ventricular outflow tract. Time-domain analysis of the SAECG was normal in 21 (91%) of 23 patients and revealed ventricular late potentials in 2 study patients (9%). Frequency-domain analysis of the SAECG was normal in 22 (96%) of 23 patients and revealed ventricular late potentials in one study patient (4%). We conclude that normal MRI findings of the heart and absence of ventricular late potentials in the SAECG in most patients with RMVT and otherwise normal ECG do not support the hypothesis that early or localized forms of ARVD create the arrhythmogenic substrate in the majority of these patients.

Action Potentials↗

Schedule-induced psychological stress and molecular structures of cardiomyocytes.

To establish a psychological stress model, we characterized in rats the effects of chronic (5-6 wk) scheduled food pellet feeding (35 mg/80 s for 8 h/day). Because the scheduled intake of pellets required that rats have access to 80% of ad libitum intake, the effect of food restriction was also examined by withholding food intermittently for 24 or 48 h each, followed by 24 h free access to food. Cardiac norepinephrine concentration was significantly increased (1,076 +/- 169 vs. 693 +/- 107 ng/g, P < 0.05) in rats subjected to pellet feeding compared with pair-fed rats (same amount of pellets in one portion) or 24- or 48-h intermittently fasted rats; similarly, the epinephrine content of adrenal glands was increased (P < 0.05). Left ventricular rate of sarcoplasmic reticulum Ca2+ uptake was decreased (P < 0.05) compared with pair-fed rats, reaching values observed for 24-h fasted rats, whereas the proportion of alpha-myosin heavy chains was only slightly reduced. Thus the schedule-induced stress arising from pellet feeding exhibits features of stress models involving physical pain and appears to stimulate the adrenergic system with subsequent impairment of Ca2+ cycling that is typical of various heart diseases.

Animals↗

[Effects of lipid lowering measures on coronary perfusion].

Secondary intervention trials in coronary heart disease have unequivocally proven the effectiveness of lipid-lowering medication in addition to dietary means. Orderly application of available drugs leads to reductions in LDL cholesterol and triglycerides accompanied by increases in HDL cholesterol. Specifically, LDL cholesterol lowering is associated with clinical benefits in coronary heart disease, it reduces the necessity of hospitalization and interventions, and leads to significant reductions in coronary as well as in overall mortality. Besides morphological changes of coronary vessels like regression or retarded progression of plaques, lipid-lowering was shown to normalize endothelial dysfunction associated with hyperlipidemia. Restoring endothelial function and improving coronary perfusion may be one of the factors responsible for the huge clinical benefits in secondary intervention trials as compared to the modest morphological changes. As the fact of lipid-lowering rather than the means by which it is achieved is of specific importance, dietary means have to precede and then accompany an eventual additional drug treatment.

Combined Modality Therapy↗

Dietary linolenic acid-mediated increase in vascular prostacyclin formation.

To define vascular effects of an enhanced dietary alpha-linolenic acid intake, 28 spontaneously hypertensive rats were fed a 3% sunflowerseed oil (44% linoleic acid) diet; in 3 groups (7 rats each), the diet was supplemented with 1, 2.5 or 5% linseed oil containing 62% alpha-linolenic acid. alpha-Linolenic acid was incorporated up to 12% in the aorta of the 5% linseed oil group. The eicosapentaenoic acid content was not significantly increased. The content of arachidonic acid and docosatetraenoic acid was moderately reduced in rats fed 5% linseed oil. The generation of 6-keto-PGF1 alpha (degradation product of prostacyclin) assessed by HPLC/electrochemical detection was, however, markedly increased (p < 0.05) in rats fed 2.5 and 5% linseed oil. The minor prostanoids TXB2, PGE2 and PGF2 alpha were not significantly altered. The high systolic and diastolic blood pressure of SHR monitored by radio telemetry was more effectively reduced (p < 0.05) in the light, i.e. sleep, cycle. An increased prostacyclin formation and lowered vascular arachidonic acid content associated with enhanced dietary alpha-linolenic acid intake would thus be expected to prove beneficial in the prevention of vascular disorders.

6-Ketoprostaglandin F1 alpha↗

QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy.

QT dispersion was measured in the 12-lead standard electrocardiogram in 107 patients with idiopathic dilated cardiomyopathy (IDC) and 100 age- and sex- matched controls without structural heart disease. All 107 study patients with IDC were prospectively followed in order to determine possible associations between QT dispersion and arrhythmic events, i.e., sustained ventricular tachycardia, ventricular fibrillation, or sudden death. QT dispersion, rate-corrected QT dispersion, and adjusted QTc dispersion, which takes account of the number of leads measured, were significantly greater in patients with IDC than in controls. During 13 +/- 7 months follow-up, arrhythmic events occurred in 12 of 107 study patients with IDC (11%). QT dispersion was increased in patients with versus without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms; p=0.03). QTc dispersion and adjusted QTc dispersion were not significantly different between patients with and without arrhythmic events (80 +/- 21 vs 75 +/- 35 ms, and 27 +/- 6 vs 24 +/- 10 ms, respectively). Thus, although QT dispersion was increased in patients with IDC and arrhythmic events during follow-up, its usefulness for arrhythmia risk prediction was limited by the large overlap of QT dispersion between patients with and without arrhythmic events.

Anti-Arrhythmia Agents↗

Electrophysiologic evaluation of sinus node function and atrioventricular conduction in patients with prolonged ventricular asystole during obstructive sleep apnea.

In 15 patients with ventricular asystole of 8.5 +/- 3.5 seconds (range 5.0 to 16.8) occurring exclusively during obstructive sleep apnea, electrophysiologic study of sinus node function and atrioventricular conduction before and after administration of intravenous atropine (0.02 mg/kg) was performed. Electrophysiologic parameters of sinus node function were normal in 12 of 15 patients (80%) and atrioventricular (AV) nodal function was normal in 7 patients (47%). Almost all abnormal findings of sinus node function and AV nodal function were reversible by administration of atropine. The HisPurkinje system function was normal in 6 patients (40%). Prolonged HV intervals (57 to 73 ms) were found in 9 patients (60%). Intra- or infra-His block was not observed in any patient. In summary, electrophysiologic parameters of sinus node function and AV conduction were normal or only slightly abnormal in all 15 study patients, which suggests that prolonged ventricular asystole during obstructive sleep apnea is not due to fixed or anatomic disease of the sinus node or the AV conduction system.

Atrioventricular Node↗

Identification of stress proteins in endothelial cells.

Endothelial cells have been shown to play a major role in the pathophysiology of various diseases including ischemic heart disease and viral infection leading to myocarditis or dilated cardiomyopathy, conditions in which stress proteins (heat shock protein-hsp; glucose-related protein - grp) are likely to be involved. For further characterization of stress proteins and their possible role in these diseases, the major stress proteins in human endothelial cells were separated by two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in the first dimension and identified by immunoblotting and either N-terminal or internal amino acid sequencing, respectively. Ubiquitin, hsp27, hsp60, hsp70, heat shock cognate protein 70, grp78 and grp75 were found to be constitutively expressed; hsp72 was found in stressed cells, exclusively, in line with results obtained in other human cell lines. Three additional proteins with molecular masses between 34 and 40 were regularly detected in stressed cells that were found to have identical amino acid sequences with those of members of the hsp70 family.

Amino Acid Sequence↗