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Biomedical subjects

H Klein

Publications and source records attributed to H Klein.

At least 19 recordsLinked to original sources

[Results and experiences of transvenous endocardial defibrillator therapy].

We studied the follow-up of 72 patients who underwent implantation of a transvenous defibrillation lead system (ELS) (Endotak, CPI). All patients had ventricular tachycardia (VT) or fibrillation (VF) refractory to antiarrhythmic drug therapy. There were 51 patients with coronary disease and 21 patients had non-ischemic VT/VF. ELS was combined with a subcutaneous patch in 52 patients and implanted alone ("single lead only") in 20 patients. 40 patients received the ELS combined with antitachycardia pacing devices (Ventak PRx, CPI; Cadence, Ventritex) and 32 patients with the Ventak P 1600 or P2, CPI. Implantation of the ELS was attempted in 80 patients and performed in 72 patients (90%): Intraoperatively, the mean defibrillation threshold (DTF) was > 25 Joule (J) in five patients and no reliable ELS position was possible to achieve in three patients. These eight patients underwent thoracotomy with epicardial patch implantation. The mean DFT was < or = 20 J in all 72 patients with a mean DFT of 14 +/- 8 J in VT patients and 17 +/- 10 J in VF patients. Two of 80 patients (3%) died: one patient died intraoperatively and one during the mean follow-up of 6 +/- 2 (< 1 to 18) months. Complications occurred in three patients (4%): Dislocation of the Endotak electrode was observed in two patients (3%) and one patient developed pneumothorax postoperatively. Our data show that the ELS is most suitable in the majority of patients with VT/VF and is the approach of first choice for cardioverter defibrillator implantation at the present time. However, despite a relatively low intra- and perioperative complication rate, this approach should not be performed in institutions without cardiac surgery.

Adolescent

Eicosanoid-mediated contractility of hepatic stellate cells.

To approach experimentally the problem of contractility, stellate cells from rats were isolated and grown on a flexible silicone rubber substrate. Increases or decreases in the number of wrinkles of the silicone membrane beneath the cells that were easily observable by microscopy was employed as semi-quantitative measure of stellate cell motility. Contraction of stellate cells accompanied by diminution of cell body size was induced by U46619 (a thromboxane A2 analogue) and prostaglandin (PG) F2 alpha. Wrinkle formation became detectable 1.5 min after addition of 2 microM-U46619 and reached its maximum 10-15 min later. The effect of PGF2 alpha was not so striking, but lasted for a longer period of time. On the other hand, dibutyryl cyclic AMP, Iloprost (a PGI2 analogue) and PGE2 led to the disappearance or decrease in the number of wrinkles, indicating relaxation of contracted stellate cells. For instance, after addition of 2 microM-Iloprost, 47, 75 and 82% of contracted stellate cells had relaxed within 5, 10 and 20 min respectively. Moreover, dibutyryl cyclic AMP induced disappearance of alpha-smooth muscle actin stress fibres. This response became recognizable 10 min after addition of dibutyryl cyclic AMP; 40 min later, 97% of stellate cells were devoid of stress fibres. Thus stellate cells are able to undergo reversible contraction in primary culture, and the contraction of these cells may be mediated by eicosanoids that can be produced within the liver.

Animals

The bisphosphonate, alendronate, prevents bone loss in ovariectomized baboons.

We examined the effect of the amino bisphosphonate alendronate, administered IV every 2 weeks at 0.05 and 0.25 mg/kg for 1 year, on bone loss and parameters related to bone metabolism in ovariectomized baboons. Relative to non-OVX animals, the OVX baboons experienced increased bone turnover, reflected in biochemical and histomorphometric measurements, and bone loss assessed by dual-beam absorptiometry in the lumbar spine, which was similar to changes observed in ovariectomized women. Alendronate treatment maintained all parameters of bone turnover at control (nonovariectomized) levels and prevented the bone loss in a dose-dependent manner. We concluded that ovariectomized baboons offer a suitable model for the bone changes observed in ovariectomized women and that these changes can be prevented by sustained administration of an appropriate dose of this aminobisphosphonate.

Acid Phosphatase

Role of mapping-guided surgery in patients with recurrent ventricular tachycardia.

To assess the value of ventricular tachycardia (VT) surgery 108 patients with recurrent episodes of VT were studied. There were 97 patients with coronary artery disease (group I) and 11 patients without coronary artery disease (group II). All patients in group I underwent subendocardial resection; 12 patients also underwent cryoablation. Cryoablation alone was performed in all patients in group II. During a mean follow-up period of 40 +/- 27 months, 29 patients (30%) in group I and two patients (18%) in group II died (p = 0.33). There were nine patients (9%) in group I and six patients (55%) in group II who had nonfatal recurrences of VT after surgery (p less than 0.01). In group I, there was a higher mortality rate among patients who had VT of posterolateral origin (14 of 31 patients; 45%) compared with 3 of 11 patients (28%) who had VT of anterolateral origin, 1 of 8 patients (12%) who had VT of inferoseptal, and 11 of 39 (29%) patients who had VT of anteroseptal origin. None of the eight patients with two distinct origins of VT died.

Adult

Surgical therapy for drug-refractory ventricular tachycardia: role of additional aneurysmectomy or bypass grafting.

To assess whether additional aneurysmectomy and/or bypass grafting influence prognosis we studied 97 patients with recurrent sustained monomorphic ventricular tachycardia after an old myocardial infarction. All patients underwent subendocardial resection due to drug-refractory ventricular tachycardia. There were 41 patients who had resection alone, 27 patients had resection and aneurysmectomy, 13 patients had resection and bypass grafting and the remaining 16 patients had resection with both, aneurysmectomy and bypass grafting. During the mean follow-up of 40 +/- 27 months 29 patients died (30%) (total mortality), 7 patients suddenly (7%) and 20 patients from cardiac causes (20%). There were no significant differences in total mortality between patients with resection alone (32%), patients with resection and aneurysmectomy (22%), patients with resection and bypass grafting (31%) and patients who had resection, aneurysmectomy and bypass grafting (38%). In addition, no significant differences were observed in the incidence of sudden death and nonfatal recurrences between patients with resection alone: sudden death 12%, recurrences 7%; patients with resection and aneurysmectomy: sudden death 0%, recurrences 19%; patients with resection and bypass grafting: sudden death 0%, recurrences 8%; and patients with resection, aneurysmectomy and bypass grafting: sudden death 13%, recurrences 0%. Postoperatively, left ventricular function improved in 56% of patients who had resection and aneurysmectomy compared to 17% of patients with resection alone, 31% of patients with resection and bypass grafting and 19% of patients who had resection, aneurysmectomy and bypass grafting. There is a low risk of sudden death and nonfatal recurrences after subendocardial resection. An influence of additional surgical approaches (aneurysmectomy or bypass grafting) on prognosis is not visible.

Adult

Rectal prolapse after oral cathartics.

Complete rectal prolapse or procidentia is an uncommon condition long recognized but of uncertain pathogenesis. We report two patients, seen a decade apart, both of whom developed complete rectal prolapse after ingestion of oral cathartics in preparation for diagnostic studies. To our knowledge, cathartic-induced complete rectal prolapse has not been reported previously in the current medical literature, despite the thousands of bowel preparations performed annually. These two cases address the implications of such an occurrence, and we discuss the pertinent management issues.

Aged

Catheter ablation of ventricular tachycardia: role of the underlying etiology and the site of energy delivery.

The role of DC catheter ablation (CA) to treat patients with sustained monomorphic ventricular tachycardia (VT) is still debated. To assess the efficacy of VT CA, we studied the follow-up of 49 patients with VT who underwent CA. There were 33 patients with an old myocardial infarction (MI) (group G I) and 16 patients had noncoronary VT (group G II): CA was performed at the earliest endocardial activation (EEA) (20 patients in G I, 14 patients in G II) or at the area of slow conduction (ASC) (13 patients in G I, 2 patients in G II). During the mean follow-up of 35 +/- 25 (1-79) months, there were 17 patients in G I (52%) and 12 patients in G II (75%) with VT recurrences (P less than 0.05). Recurrences of VT was observed in 4 of 15 patients (27%) when CA was performed at the ASC, compared to 25 of 34 patients (74%) with CA at the EEA (P less than 0.01). These data show that DC CA is more successful in patients with coronary artery disease, particularly when CA is performed at the ASC.

Adult

Effect on ventricular performance of direct current electrical shock for catheter ablation of the atrioventricular junction.

In ten patients undergoing catheter ablation of the atrioventricular junction (CAVJ) because of therapy refractoriness of supraventricular arrhythmias, the effect of repeated high energy direct current (DC) shock on left ventricular function has been investigated. End-systolic pressure-volume relation (ESPVR) and the positive first derivative of ventricular pressure (dP/dt) have been used as indices of left ventricular systolic function, while the time constant of isovolumic pressure decay, the diastolic stiffness, and the negative dP/dt represented the diastolic function parameters, respectively. Each patient received at least two and no more than three DC shocks for successful CAVJ, with an energy of 360 joules. Significant acute reduction of both systolic and diastolic function was noted after each DC shock, with a slow partial recovery of both phases. The recovery process involved the systolic phase earlier and more completely than the diastolic one. The alterations observed could not be predicted from preablation values, but were significantly related to cumulative energy dose index for body weight. In conclusion, repeated high energy DC shocks acutely, but reversibly, impair left ventricular function; in addition, the ventricular function reduction is primarily related to the total ablation energy indexed for body weight.

Adult

Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition.

Urodilatin is a new member of the family of natriuretic peptides. It is of renal origin. Previous reports indicate that urodilatin is natriuretic in lower doses than atrial natriuretic factor (ANF)-(99-126) and that it might be more effective than ANF in the treatment of cardiovascular edema. The present study was designed to compare the pharmacokinetics of the hydrolysis and clearance of 125I-labeled urodilatin and 125I-ANF. In control rats, the volume of distribution (Vss), metabolic clearance rate (MCR), and distribution half-life (distribution t1/2) of urodilatin in plasma were not significantly different from those of ANF. Infusion of clearance (c)ANF-(4-23), a specific ligand for receptors that clear ANF in excess amounts (i.e., a bolus injection of 100 micrograms/kg followed by a continuous infusion of 10 micrograms.kg-1 x min-1), increased the amount of intact peptide in the plasma to the same extent for both urodilatin and ANF. In addition, cANF-(4-23) decreased the Vss and the MCR and increased the distribution t1/2 of both peptides to about the same degree. Prior treatment of rats with SQ-28,603, a specific neutral endopeptidase (NEP; EN 3.4.24.11) inhibitor, was without significant effect on the metabolic clearance of urodilatin, whereas it decreased the clearance of ANF by 65%. Furthermore, an infusion of SQ-28,603 suppressed the appearance of the hydrolytic products of ANF in blood but not of urodilatin. Moreover, the inhibitor increased the total amount of ANF recovered in the kidneys to five times the control values, whereas it did not alter the renal uptake of urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine

Splenic megakaryocytopoiesis in primary (idiopathic) osteomyelofibrosis. An immunohistological and morphometric study with comparison of corresponding bone marrow features.

An immunohistochemical and morphometric study has been performed on splenic tissue of 10 patients with primary (idiopathic) osteomyelofibrosis (OMF) to determine characteristic features of megakaryocytopoiesis in myeloid metaplasia. Using the periodic acid-Schiff reaction (PAS) and particularly the monoclonal antibody CD61 (Y2/51), all elements of this cell lineage including precursors could be identified. In comparison with bone marrow specimens from our file material (40 patients with OMF, 15 control cases) which were processed in a similar way, megakaryocytes in the spleen revealed significant differences. These differences included smaller cell sizes, a disturbed nuclear-cytoplasmic ratio, and a conspicuous increase in the relative frequency of promegakaryoblasts. In conclusion, extramedullary megakaryocytopoiesis in OMF did not only show more pronounced abnormalities of differentiation, but also a higher degree of immaturity. Our finding of a significant accumulation of megakaryocytic precursors in the spleen as opposed to the bone marrow, corroborates the so-called filtration theory which has been introduced to explain the evolution of splenic myeloid metaplasia in OMF.

Aged

Regulation by prostaglandin E2 of cytokine-elicited nitric oxide synthesis in rat liver macrophages.

Nitric oxide (NO), apart from its properties as a vasodilator, is a cytotoxic agent released from macrophages upon stimulation with immunomodulating agents such as interferon-gamma and endotoxin. In rat Kupffer cells endotoxin causes the release of NO as well as of tumor necrosis factor-alpha and prostaglandin E2 (PGE2). This eicosanoid and its second messenger, cyclic AMP, have been shown to increase nitric oxide formation in Kupffer cells treated with endotoxin (Gaillard et al. (1991) Pathobiology 59, 280-283). But not only added PGE2 but also the prostaglandin produced endogenously upon stimulation with endotoxin increases NO synthesis. Neither tumor necrosis factor-alpha nor interleukin-1 beta stimulate NO synthesis by themselves, but together with PGE2 they are as effective as lipopolysaccharide plus PGE2. To replace PGE2 in the combination with the cytokines, however, dibutyryl cAMP has to be present in higher concentrations than with LPS. Interleukin-6 alone or in combination with PGE2 or dibutyryl cAMP is without any effect. Anti-TNF-alpha as well as anti-PGE2 antibodies reduce the release of NO upon stimulation with LPS. Consequently, the effect of LPS on NO production seems to be in part due to the self-stimulating effect of PGE2 and some cytokines, both produced by Kupffer cells upon LPS stimulation.

Animals

The fatty acid synthase (FAS) gene and its promoter in Rattus norvegicus.

Screening of rat liver genomic libraries yielded 5 overlapping clones for rat fatty acid synthase (FAS). From these clones we determined the 18,170 bp sequence of the rat FAS together with 5,028 bp of the 5'-flanking region and 515 bp of the 3'-adjacent genomic sequence. The two FAS transcripts which differ only in the positions of their polyadenylation/termination sites consist of one untranslated and 42 translated exons. Surprisingly, the substrate binding site for enoyl reductase, one of the FAS component functions, is interrupted by an intron. The sizes and the boundaries of the individual domains could be mapped in relation to the exon/intron structure of the gene. These eight partial functions coincide with discrete units of exons. The acyl carrier protein with its prosthetic 4'-phosphopantetheine group is located within a single exon supporting the idea that rat FAS has evolved by gene fusion. Using primer extension the main transcription start site of the FAS mRNA in both hepatic and mammary gland tissues was located at 5,028 bp in the sequence determined. As expected of a gene which is pretranslationally regulated the 5'-flanking region contains, in addition to TATA and CAAT boxes, consensus sequences for several DNA binding proteins.

Amino Acid Sequence

[Implantable defibrillators].

Automatic implantable defibrillator therapy has changed the approach to life-threatening ventricular tachycardia completely and essentially improved survival after aborted sudden cardiac death. Since the first implantation of a defibrillator in 1980, 20,000 patients have received such a device. Nonetheless, in Germany still too many patients die of sudden cardiac death because defibrillator therapy fails to be known enough and keeps not being made use of (no more than 1,000 implants to date). In this group of patients characterized by poor ventricular function, antiarrhythmic drug therapy proved to be unreliable or even dangerous in many cases, while electrophysiologically-guided surgical interventions use to be impossible. The introduction of the implantable defibrillator enabled the incidence of sudden cardiac death to be reduced to about 2% during the first year after implant, and to 5% in the third year, respectively. In most centers with more extensive experience in defibrillator implantations, operative mortality is about 2-3%. Long-term results with defibrillator patients are controlled by the course of the underlying disease, which is coronary artery disease with large scars due to infarction in some 75% of cases. In a large group of about 10,000 patients, total mortality has been calculated to be 15% after three years. Defibrillator systems of the latest generation offer multiple programmability of tachycardia identification parameters and permit differentiated modification of therapeutic intervention. Defibrillator therapy has now been improved essentially by the introduction of endocardial lead systems and, in addition, by the defibrillator being combined with an antitachycardia pacing system.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial