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Biomedical subjects

W Ehrlich

Publications and source records attributed to W Ehrlich.

At least 19 recordsLinked to original sources
PubMed2001

Dual-coil vs single-coil active pectoral implantable defibrillator lead systems: defibrillation energy requirements and probability of defibrillation success at multiples of the defibrillation energy requirements.

AIMS: The aim of the study was to compare the defibrillation energy requirements and the probability of successful defibrillation at multiples of the minimum defibrillation energy requirements in active pectoral implantable defibrillators with single- and dual-coil lead systems. METHODS AND RESULTS: Eighty-three consecutive patients undergoing implantation of an active pectoral cardioverter-defibrillator were randomized to receive a dual- or single-coil lead system. Defibrillators of two manufacturers with a fixed tilt biphasic defibrillation waveform were used. Defibrillation energy requirements were determined using a step-down defibrillation testing protocol. According to the randomization protocol, the patients were assigned to three additional consecutive defibrillation attempts during device implantation and during pre-discharge testing of either 1.0, 1.5 or 2.0 times the determined defibrillation energy requirement. Patients presenting defibrillation energy requirements > 15 J were excluded from analysis. Eighty of 83 patients (96%) completed the study protocol. Three patients were excluded due to elevated defibrillation energy requirements. The defibrillation energy requirements in the dual- and single-coil patient groups were 8.0 +/- 3.6 J and 8.4 +/- 3.7 J (ns), respectively. A comparable percentage of study patients showed defibrillation energy requirements <10 J (dual-coil: 88% vs single-coil: 83%). Defibrillation impedance was significantly different (dual-coil: 50 +/- 5.8 Ohm; single-coil: 39.8 +/- 4.2 Ohm). Regarding the probabilities of successful defibrillation, there were no significant differences between the two patient groups. The probabilities of defibrillation at the three multiples of the defibrillation energy requirement using a dual- and single-coil lead system were 82, 89.7 and 93.6 and 77.8, 94.1 and 95.8%, respectively (P=0.88, P=0.42, P=0.62, respectively). CONCLUSIONS: Dual- and single-coil active pectoral defibrillator systems show no difference in defibrillation energy requirements and no difference in the probability of successful defibrillation at multiples of the minimum defibrillation energy requirement. The use of more simplified defibrillator lead systems may contribute to a future lead design focusing on improvement in lead durability.

Aged↗
PubMed2000

[Recurrent syncope of unknown origin. Diagnosis with implantable "loop" recorders].

BACKGROUND: In about a third of cases of recurrent syncope a diagnosis cannot be established despite extensive cardiovascular and neurologic testing. In patients without underlying heart disease the sensitivity of conventional diagnostic testing is low. CASE REPORT: A 33-year-old male patient underwent implantation of a loop recorder (Reveal) after negative neurological and cardiovascular testing. One month after implantation sinus node arrest could be documented during a presyncope. The patient underwent pacemaker implantation and remains asymptomatic since then. CONCLUSION: In patients with syncope and a negative conventional diagnostic workup the implantable loop recorder is a helpful and cost-effective diagnostic tool.

Adult↗
PubMed2000

Do patients want minimally invasive aortic valve replacement?

OBJECTIVE: Access to aortic valve can be performed through small incisions. However, a considerable advantage of this approach has not been proven by randomized studies so far. We wanted to elucidate the opinion of patients when they are informed objectively about advantages and disadvantages of minimally invasive approach prior to operation. METHODS: This prospective study was performed with 27 patients undergoing isolated aortic valve replacement. These patients were informed prior to operation by the same resident concerning objective data. A photograph was shown illustrating a patient with postoperative wound after a standard- and a mini-incision, respectively. After the interview the patient could decide between full and partial sternotomy. RESULTS: After the interview 21/27 (78%) patients preferred to have a full sternotomy (group F) and 6/27 (22%) patients (group P) decided to have a partial sternotomy. Comments of group F: surgeon should have best exposure (n=15); cosmetics aspects unimportant (n=14); operation time as short as possible (n=7). Group P: cosmetic aspects important (n=6). Significant differences between groups (group F vs. group P): age (years), 69.1+/-1.5 vs. 49.2+/-7.3 (P=0.024); operation time (min), 142+/-7 vs. 189+/-15 (P=0.002); CK (IU/l), 111+/-11 vs. 374+/-114 (P=0.0007); CKMB (IU/l), 17+/-2 vs. 45+/-17 (P=0.006); ICU-stay (days), 2.6+/-0.2 vs. 3.2+/-0.2 (P=0.044). Pericardial effusion requiring drainage was observed in two patients of group P. One patient of group P suffered myocardial infarction. CONCLUSION: When patients are informed objectively about advantages and disadvantages of minimal invasive aortic valve surgery only a smaller number decides to have a mini incision. The patients preferring short incisions are significantly younger since cosmetic aspects are more important. Longer duration of operation may be due to longer hemostasis based on limited exposure. Air bubbles due to inadequate de-airing might be responsible for higher CK and CK-MB levels in group P.

Adult↗
PubMed1999

The effect of tryptophan plus methionine, 5-azacytidine, and methotrexate on adjuvant arthritis of rat.

Within the wider framework of our studies on the genesis of rheumatoid arthritis we have investigated the two signal processes in arthritis: adenoribosylation of proteins and DNA methylation. Arthritis can be induced when Freund's complete adjuvant is applied to rats. This form of arthritis can then be reduced or even totally suppressed through the application of several different substances. In the present article we have investigated if the effect of two of these substances, 5-azacytidine and methotrexate can be influenced by the application of tryptophan plus methionine. When applied singly, these latter two substances are known to reduce the formation of arthritis. This effect is intensified by a combination of tryptophan plus methionine. Application of tryptophan plus methionine without methotrexate or 5-azacytidine causes an enhanced development of an adjuvant induced arthritis.

Animals↗
PubMed1999

Bipolar atrial sensing thresholds in sinus rhythm and atrial tachyarrhythmias. A comparative analysis in patients with DDDR pacemakers.

UNLABELLED: Automatic mode switching (AMS) function in dual chamber pacemakers depends on adequate detection of atrial tachyarrhythmias. There are few data on showing how intra-operative atrial signal amplititude during sinus rhythm can predict atrial tachyarrhythmias after pacemaker implantation. In 43 patients undergoing DDDR pacemaker implantation and atrioventricular nodal ablation for the treatment of drug-refractory paroxysmal atrial fibrillation, atrial sensing thresholds during sinus rhythm and during induced atrial tachyarrhythmias (24-48 h after device implantation) were analysed. Five different DDDR pacemaker systems were implanted (Chorus 7034, Ela Medical n = 13; Meta DDDR 1254, Telectronics Pacing Systems n = 12; Vigor DR 1230, Guidant n = 6; Trilogy DR 2364, Pacesetter, n = 2; Kappa DR 401, Medtronic USA n = 10). Every patient received a steroid-eluting, screwing, bipolar atrial lead (Medtronic, Capsure-Fix 4068). The mean P wave amplitude during implantation was 3.91 +/- 1.14 mV. The mean atrial sensing threshold during sinus rhythm and during all modes of induced atrial tachyarrhythmias was 3.35 +/- 1.0 mV, and 1.52 +/- 0.92 mV, respectively (P < 0.001). Atrial fibrillation was induced in 36 patients. The mean sensing threshold during sinus rhythm in this patient group was 3.39 +/- 1.01 mV, the mean sensing threshold during atrial fibrillation was 1.27 +/- 0.56 mV, reflecting a 63% reduction of sensing threshold compared with sinus rhythm (P < 0.001). Atrial flutter was induced in seven patients. The mean sensing threshold during sinus rhythm was 2.92 +/- 1.19 mV, the mean sensing threshold during atrial flutter was 2.79 +/- 1.26 mV, reflecting a reduction of 5% (ns) compared with sinus rhythm. Atrial sensing thresholds during sinus rhythm were significantly correlated with sensing thresholds during atrial tachyarrhythmias (r = 0.44; P < 0.002), but there were significant variations in intra-individual results. The reduction of atrial sensing thresholds between sinus rhythm and induced atrial tachyarrhythmias ranged from 30% to 82%. CONCLUSION: Bipolar atrial sensing thresholds during sinus rhythm are correlated with sensing thresholds during atrial tachyarrhythmias, but there is a large degree of variance in individual patients. A 4:1 to 5:1 atrial sensing safety margin based on sensing threshold during sinus rhythm is a predictor for adequate postoperative detection of atrial tachyarrhythmias and the function of AMS devices.

Arrhythmia, Sinus↗
PubMed1998

Enhancement of the effect of methotrexate on collagen II induced arthritis in mice by nicotinamide.

Treatment with a combination of 10 mg/kg i.p. methotrexate and 100 mg/kg i.p. nicotinamide inhibits the development of collagen II induced arthritis in male DBA/1 X B.10(4R) mice, as assessed by the arthritic index and whole blood chemiluminescence. The effect is much more pronounced than with either methotrexate or nicotinamide alone at the same concentrations. Determination of GOT and GPT levels in the blood revealed that the treatment causes no toxic side effects on the liver.

Alanine Transaminase↗
PubMed1997

Protection from acetaminophen-induced liver damage by the synergistic action of low doses of the poly(ADP-ribose) polymerase-inhibitor nicotinamide and the antioxidant N-acetylcysteine or the amino acid L-methionine.

1. An array of therapeutically used analgetic and antirheumatic drugs cause severe liver damage. The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions and of antioxidants in analgesic-induced hepatic injury. 2. Male NMRI mice were treated PO with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. 3. The acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited in a dose-dependent manner, when mice were injected additionally either with increasing amounts (from (25 mg/kg to 100 mg/kg i.p.) of the PARP-inhibitor nicotinamide, with increasing amounts (from 25 mg/kg to 100 mg/kg i.p.) of the antioxidant N-acetylcysteine, or with increasing amounts (from 50 mg/kg to 300 mg/kg i.p.) of the amino acid L-methionine. 4. A combination of both nicotinamide and N-acetylcysteine (at the low dose of 12.5 mg/kg i.p. each) results in a complete protection from acetaminophen-induced release of GOT and GPT from injured liver cells. 5. A combination of both L-methionine and N-acetylcysteine or nicotinamide (at the low dose of 12.5 mg/kg IP each) resulted also in complete protection from acetaminophen-induced release of GOT and GPT.

Acetaminophen↗
PubMed1997

Intracellular metabolism of 4-hydroxynonenal in primary cultures of rabbit synovial fibroblasts.

The intracellular metabolism of 4-hydroxynonenal (HNE), a secondary product of lipid peroxidation and mediator of inflammation, which was found in the joints of patients with rheumatoid arthritis, was investigated in primary cultures of rabbit synovial fibroblasts. A consumption rate of 27.3 nmol/min x 10(6) cells was measured for the cultivated fibroblasts. It could be shown, that 4-hydroxynonenal enters the synovial fibroblasts and is metabolized mainly oxidatively to 4-hydroxynonenoic acid, intermediates of the tricarboxylic acid cycle and water and by formation of the glutathione-HNE adduct. The share of protein-bound HNE was about up to 8% of the total added HNE after 10 min of incubation. All metabolites accumulates intracellularly within the incubation time except of 4-hydroxynonenal itself. An increase of 4-hydroxynonenoic acid could be detected also extracellularly during the intracellular metabolism of 4-hydroxynonenal. Therefore, an involvement of synovial fibroblasts in the secondary antioxidant defense system of the joints during conditions of higher HNE concentrations like rheumatoid arthritis is suggested.

Aldehydes↗
PubMed1996

Inhibition of poly(ADP-ribose) formation by 4-hydroxynonenal in primary cultures of rabbit synovial fibroblasts.

The formation of poly(ADP-ribose) in primary cultures of rabbit synovial fibroblasts after treatment with active oxygen released by xanthine/xanthine oxidase is inhibited by addition of 1 and 10 microM 4-hydroxy-2,3-trans-nonenal (HNE). The endogenous formation of HNE by the xanthine/xanthine oxidase system is not responsible for the inhibitory effect of the aldehyde, owing to the low accumulation rate of the lipid peroxidation product in the system used. HNE is able to inhibit the isolated nuclear enzyme ADP-ribosyltransferase, as shown by an in vitro assay with an Ki of 4 mumol/litre. Therefore the molecular basis of HNE-mediated effects on cell proliferation, differentiation and transformation might be due to the inhibitory effect of poly(ADP-ribos)ylation.

Aldehydes↗
PubMed1996

The influence of antagonists of poly(ADP-ribose) metabolism on acetaminophen hepatotoxicity.

An array of therapeutically used analgetic and antirheumatic drugs causes severe liver damage. The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions in analgesics-induced hepatic injury. Male NMRI mice were treated perorally with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. In addition, the activity of poly(ADP-ribose)polymerase (PARP) was quantified in liver cell nuclei. While the PARP-activity remained essentially unchanged, the acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited by 90-99%, when mice were injected additionally with the selective PARP-inhibitors nicotinic acid amide, benzamide, caffeine, theophyline, and thymidine, respectively. We see the main application of inhibitors of adenoribosylation reactions as for the combinational use in pharmaceutical preparations of analgesics and antirheumatic drugs in order to avoid hepatic damage.

Acetaminophen↗
PubMed1996

Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice.

Recently, we demonstrated the hepatoprotective effects of nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) on mice suffering from acetaminophen (AAP)-hepatitis, suggesting that the AAP-induced liver injury involves a step which depends on adenoribosylation. The present study investigates the effects of a diet free of precursors of NAD, the substrate on which PARP acts, in female NMRI mice with AAP hepatitis and evaluates the influence of simultaneous ethanol consumption in these animals. Liver injuries were quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). While AAP caused a 117-fold elevation of serum transaminase activities in mice kept on a standard laboratory diet, which was significantly exacerbated by ethanol and inhibited by nicotinic acid amide (NAA), adverse effects were noted in animals fed a diet free of precursors of NAD. In these animals, only minor increases of serum transaminase activities were measured in the presence of AAP, and unlike the exacerbation caused by ethanol in mice on a standard diet, the liver damage was inhibited by 50% by ethanol. A further 64% reduction of hepatitis was observed, when NAA was given to ethanol/AAP-mice. Our results provide evidence that the AAP-induced hepatitis and its exacerbation by ethanol can either be reduced by end-product inhibition of PARP by NAA or by dietary depletion of the enzyme's substrate NAD. We see the main application of NAA as for the combinational use in pharmaceutical preparations of acetaminophen in order to avoid hepatic damage in patients treated with this widely used analgesic.

Acetaminophen↗
PubMed1996

The therapeutic effect of a combination of cofpropamine, a caffeine derivative, and cyclophosphamide on the development of adjuvant arthritis of rats and collagen arthritis of mice.

1. Cofpropamine (Cofa), a caffeine derivative that inhibits polyadenoribosylation, enhances the therapeutic effect of cyclophosphamide (CPA) in two animal models of arthritis. 2. The development of adjuvant arthritis of rats is reduced by treatment with 2 x 50 mg/kg IP CPA and 2 x 50 mg/kg IP Cofa. 3. The development of collagen arthritis in mice is prevented by treatment with 12.5 mg/kg IP CPA and 150 mg/kg IP Cofa three times per week.

Alkylating Agents↗
PubMed1995

Induction and activation of procollagenase in rabbit synovial fibroblasts after treatment with active oxygen released by xanthine/xanthine oxidase.

Treatment of rabbit synovial fibroblasts with active oxygen (AO) released by xanthine/xanthine oxidase resulted in an induction of procollagenase in these cells in concentrations ranging from 12.5 micrograms/ml xanthine plus 0.0025 U/ml xanthine oxidase to 50 micrograms/ml xanthine plus 0.01 U/ml xanthine oxidase. Preceding this there was an accumulation of poly(ADP-ribose) for the same concentration range of xanthine/xanthine oxidase. Furthermore, it was found that AO caused activation of the latent procollagenase to the active enzyme in concentrations ranging from 0.1 micrograms/ml xanthine plus 0.00002 U/ml xanthine oxidase to 1 microgram/ml xanthine plus 0.0002 U/ml xanthine oxidase. It is suggested that poly(ADP-ribosyl)ation participates in the induction of procollagenase by relaxing chromatin. Furthermore, it is proposed that AO activates latent procollagenase under physiological conditions.

Animals↗
PubMed1995

Inhibition of the induction of collagenase by interleukin-1 beta in cultured rabbit synovial fibroblasts after treatment with the poly(ADP-ribose)-polymerase inhibitor 3-aminobenzamide.

3-Aminobenzamide is an inhibitor of poly-(ADP-ribosyl)ation. In concentrations from 3 to 10 mM it reduced the collagenase activity in culture supernatants of interleukin-1 beta-stimulated rabbit synovial fibroblasts. 3-Aminobenzoate, not an inhibiter of poly(ADP-ribosyl)ation, had no effect on collagenase activity at a concentration of 10 mM. We concluded that poly(ADP-ribosyl)ation plays a role in the induction of the expression of collagenase and that 3-aminobenzamide can inhibit this process.

Animals↗
PubMed1995

[Discovery of the pacemaker and heart conduction system in mammals. Fantasy and truth].

The first report about experimental investigations on the origin of the rhythms in the mammalian heart were published in 1888 by McWilliam. Similar experiments were described by Hering in several publications starting from 1900. The results led to the hypothesis of the myogenic genesis of the rhythms. However, in 1907, Hering stated that the origin of the stimulus in the mammal heart was probably a nervous function. In 1898, 1903, and 1906 Wenckebach described the function and the functional localization of the pacemaker in the heart of the intact man, and in 1906, he described the morphology of the pacemaker and its blood supply in the post mortem human heart. In the same year, Adam analyzed the localization of the "natural" pacemaker and the regions of the secondary pacemakers in the mammal heart. In 1907, Keith and Flack introduced the term "sino-auricular node". They quoted the findings of Wenckebach and Hering, and they mentioned McWilliam. A muscular connection between the right atrium and both ventricles of the mammal heart was found by Kent and by His in 1893. In 1907, Tawara called the structure of the origin of the a-v connection "atrio-ventricular node". It was, however, the scientific discovery of Tawara that the a-v pathway was connected with the muscles of the ventricles by the Purkinje fibers. He discovered that the pathway consists of muscles which are histologically divided and functionally different from the other heart muscles. It is a system of specialized muscles which conduct the stimulus for the contraction without contracting themselves.

Animals↗