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Biomedical subjects

W Jung

Publications and source records attributed to W Jung.

At least 181 records · Page 10Linked to original sources
PubMed1994

[Non-pharmacologic therapy of atrial fibrillation].

Since patients with recurrent atrial fibrillation are prone to recurrences, even under treatment with antiarrhythmic agents, alternative treatment modalities are being sought. Today, the non-pharmacological treatment modalities such as modification or ablation of the AV node or the operative procedures ("maze" or "corridor" operation) do not cure these patients. The non-pharmacological therapies are indicated if severe symptoms are due to high ventricular rate with hemodynamic compromise. In such cases, His bundle ablation followed by rate adaptive pacing can achieve control of symptoms in the majority of patients. In the future, more refined techniques for ablation or the introduction of automatic atrial cardioverters will extend therapeutic options.

Anti-Arrhythmia Agents↗
PubMed1994

Effects of the renin inhibitor N-[N-(3-(4-amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histid inyl] -(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2-amide acetate in anesthetized rhesus monkeys.

The renin inhibitory effect of the non-peptide renin inhibitor S 2864 (N-[N-(3-(4-Amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histidinyl]-(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2- amide acetate, CAS 135683-92-0) was characterized in vitro and in vivo in primates. In vitro, S 2864 inhibited the activity of purified human plasma renin with an IC50 of 3.8 x 10(-10) mol/l and did not affect related human aspartyl proteases like human cathepsin E, cathepsin D or pepsin. In vivo, in anesthetized sodium depleted rhesus monkeys S 2864 decreased mean arterial blood pressure after intraduodenal (i.d.) administration of 2 mg/kg significantly by 27% from 94 +/- 8 to 62 +/- 6 mmHg for 90 min. Heart rate was not changed. Cumulative intravenous (i.v.) administration of S 2864 or remikiren in doses of 1, 10 and 30 micrograms/kg significantly decreased systemic blood pressure, dP/dtmax and cardiac output while heart rate was not changed. Plasma angiotensin II (ANG II) levels as well as renin activity were dose dependently reduced after 10, 30 and 60 min. It is concluded that S 2864 is an effective specific inhibitor of human renin eliciting marked blood pressure lowering activities in primates.

Anesthesia↗
PubMed1994

[The effect of the impulse form of the defibrillation shock on its effectiveness and device technology of the implantable cardiac defibrillator].

Efforts have been focussed on the development of implantable cardioverter-defibrillator systems that reduce the size of the devices, simplify the methods of electrode implantation, and increase device longevity. The size of implantable units is predominantly determined by the capacitors and batteries, and this is dependent on the output energy requirements. The energy required for defibrillation and therefore the size of the devices can be reduced by utilizing optimal lead systems and waveforms. This report describes our experience with various shock waveforms in 86 consecutive patients undergoing implantation of a cardioverter-defibrillator with a nonthoracotomy approach. Table 1 provides information on the demographic characteristics of the study population, the various shock waveforms and lead configurations tested. In 20 patients, a bidirectional lead configuration was tested using simultaneous and sequential monophasic waveforms. In 18 patients, simultaneous monophasic and biphasic waveforms with a fixed pulse duration of 6.3 ms were employed utilizing a bidirectional lead system. In 31 patients, a undirectional lead configuration was used, and simultaneous monophasic and biphasic shocks with a constant tilt were delivered. In 17 patients, the defibrillation efficacy of biphasic and triphasic shock waveforms with a fixed pulse duration of 10 ms was evaluated. The study design was an open, randomized and prospective evaluation in all patients. Defibrillation threshold was determined in a randomized sequence using a step down protocol. The defibrillation threshold was defined as the lowest energy required for effective defibrillation on two occasions. In the 20 patients using a bidirectional lead configuration, there was no significant difference in defibrillation energy requirements between simultaneous and sequential monophasic shock waveforms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Adenosine in prediction of the success of radiofrequency ablation in Wolff-Parkinson-White syndrome].

Rapid bolus injection of adenosine has been shown to produce transient atrioventricular (AV) nodal block while having almost no direct effect on accessory pathway conduction. The aim of this study was to determine the efficacy of adenosine for prediction of success of catheter ablation in WPW syndrome in 31 patients (23 with preexcitation; 8 with concealed conduction) before and 30 min, 5-7 days, and 3-6 months after attempted radiofrequency catheter ablation. Before ablation 6 mg adenosine produced maximal preexcitation (QRS duration increased from 100 +/- 15 ms to 123 +/- 18 ms) in patients with manifest preexcitation, while AV block occurred in all patients (100%) with concealed conduction for 1.5 +/- 0.5 s. No patient had accessory pathway conduction unmasked by adenosine. In 30/31 (96%) of patients retrograde conduction was unchanged prior to ablation. Immediately after ablation adenosine induced AV and VA block in 29 (93%) patients. These results were also present 5-7 days and 3 months later and were confirmed by electrophysiologic study. The positive and negative predictive values are 96% and 100%, respectively. Adenosine is reliable and useful to predict short- and long-term success following radiofrequency catheter ablation.

Adenosine↗
PubMed1993

Monoselenophosphate: synthesis, characterization, and identity with the prokaryotic biological selenium donor, compound SePX.

A labile, selenium donor compound required for synthesis of selenium-dependent enzymes and seleno-tRNAs is formed from ATP and selenide by the SELD enzyme. This compound, tentatively identified as a selenophosphate [Veres, Z., Tsai, L., Scholz, T. D., Politino, M., Balaban, R. S., & Stadtman, T. C. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 2975-2979], is indistinguishable from chemically prepared monoselenophosphate by 31P NMR spectroscopy and ion pairing HPLC. Furthermore, addition of chemically prepared monoselenophosphate caused a dose-dependent decrease in the amount of 75Se incorporated into tRNAs from 75SePX generated in situ by SELD enzyme. A procedure is described for the chemical synthesis of monoselenophosphate in which the readily prepared (MeO)3PSe is converted in quantitative yield to (TMSO)3PSe followed by complete cleavage of the latter to monoselenophosphate in oxygen-free aqueous buffer. The chemical properties of chemically synthesized monoselenophosphate are described.

Adenosine Triphosphate↗
PubMed1993

A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo.

In order to target NK cells against the Hodgkin's-derived cell line L540, we developed bispecific monoclonal antibodies (Bi-MAbs) by somatic hybridization of the 2 mouse hybridoma cell line HRS-3 and A9 which produce monoclonal antibodies (MAbs) with reactivity against the Hodgkin and Reed-Sternberg cell-associated CD30 antigen and the CD16 antigen (Fc gamma III receptor), respectively. The CD16 MAb-producing cell line A9 was selected as a partner for HRS-3 because of its efficiency in inducing lysis of the A9 hybridoma cells by resting NK cells. The hybrid hybridoma cell line HRS-3/A9 produced the supernatant with the strongest bispecific reactivity and was repeatedly subcloned and used for ascites production. Crude supernatant and purified HRS-3/A9 Bi-MAb triggered specific lysis of the CD30+ Hodgkin's-derived cell line L540, but not of the CD30- cell line HPB-ALL by unstimulated peripheral-blood lymphocytes and NK-cell-enriched populations. Moreover, treatment of SCID mice bearing heterotransplanted human Hodgkin's tumors with HRS-3/A9 and human peripheral blood lymphocytes induced specific complete tumor regression in 10/10 animals. We thus report successful tumor treatment in an in vivo model using NK-cell-associated Bi-MAbs and show that the Bi-MAb HRS-3/A9 is an efficient promoter of the anti-tumor effects of NK cells in vitro and in vivo.

Animals↗
PubMed1993

CD30-antigen-specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: potential use for the treatment of Hodgkin's lymphoma.

Cross-linking of specific tumor antigens with the T-cell-associated CD3 and CD28 antigens can increase IL-2 secretion, proliferation and antigen-specific cytotoxicity in resting T cells. This cross-linking can be achieved effectively by bispecific monoclonal antibodies (BiMAb) with specificity for both the tumor antigen and CD3 or CD28 antigen, respectively. To take advantage of the enhanced activation of CD3 pre-activated T cells by additional activation via the CD28 antigen, BiMAb OKT3/HRS-3 with reactivity to both CD3 and the Hodgkin's-lymphoma-associated CD30 antigen and the BiMAb 15E8/HRS-3 with reactivity to both CD28 and CD30 antigen were generated by hybridoma fusion. Resting T cells, represented by Jurkat cells (CD3+/CD28+) were specifically activated to produce IL-2 by co-cultivation with an EBV-transformed B-cell line (LAZ509, CD30+/CD19+) only in the presence of the CD30/CD28 cross-linking BiMAb and an additional cross-linking anti-CD3/CD19 BiMAb (OKT3/6A4). Neither the cross-linking BiMAbs alone nor any combination of the monospecific parental MAbs induced a comparable IL-2 production by Jurkat cells in the presence of LAZ509. In addition, using a combination of these BiMAbs, an antigen-dependent cytotoxicity was induced by targeting APC-depleted peripheral blood lymphocytes to CD30+ L540 cells. T cells, previously specifically activated by CD3/CD30 in the presence of CD30 antigen, were cytotoxic to CD30+ cell lines only after incubation with BiMAb anti-CD28/CD30. Neither of the BiMAbs nor any of the parental antibodies induced a comparable effect. Our results indicate that such BiMAbs may offer a new approach for specific immunotherapy of Hodgkin's lymphoma, which takes advantage of cytokine secretion and cytotoxicity of activated T cells.

Antibodies, Monoclonal↗
PubMed1993

CD30-specific AB1-AB2-AB3 internal image antibody network: potential use as anti-idiotype vaccine against Hodgkin's lymphoma.

The tumor-associated CD30 antigen is presently under study as a target for active specific immunotherapy of Hodgkin's lymphoma with anti-idiotypic antibodies. Internal image antibodies (Ab2 beta) 9G10 and 14G9 against the CD30-specific antibody HRS-4 (Ab1) have been described, which induce a CD30-specific T- and B-cell response in BALB/c mice and New Zealand white rabbits. In extension of this work, murine monoclonal anti-idiotypic Ab2 beta 9G10, mimicking structures of the nominal CD30 antigen, was used to generate monoclonal Ab3 in mice and polyclonal Ab3 in rabbits with specificity for CD30. The Ab2 beta 9G10-specific murine monoclonal Ab3 4A4 bound specifically to the 120-kDa band of CD30 present on Hodgkin cell lines and Hodgkin tumor tissue, and effectively inhibited binding of Ab1 HRS-4 to Ab2 9G10 as well as to CD30+ cells. Monoclonal Ab3 4A4 was cytotoxic for CD30+ cell lines in vitro and effectively prevented the s.c. growth of L540 cell tumors after passive i.v. administration in a SCID mouse tumor model. While this cytotoxic effect of the IgM subclass monoclonal Ab3 4A4 was due to complement activation, the murine monoclonal Ab1 HRS-4 and a polyclonal Ab3 preparation of IgG-subclass from New Zealand white rabbits were cytotoxic by an antibody-dependent cell-mediated mechanism in vitro. In conclusion, Ab2 beta 9G10 is able to induce a CD30-specific cytotoxic IgG and IgM response. Cytotoxicity was shown to be mediated by complement activation and antibody-dependent cell-mediated cytotoxicity in vitro and in vivo and across species barriers. Thus, the CD30-like Ab2 beta 9G10 may hold promise for effective active specific immunotherapy of human Hodgkin's lymphoma.

Animals↗
PubMed1993

[Radiofrequency ablation of accessory pathways in pre-excitation syndrome].

Various parameters relating to the radio-frequency ablation of accessory pathways were studied in 53 patients (27 males, 26 females: mean age 38.5 [14-64] years) with a history of paroxysmal tachycardia (over 1 month to 50 years), shown to be caused by an accessory pathway (Wolff-Parkinson-White syndrome). In all patients the following values were obtained: (1) number of procedures necessary to achieve permanent blockage of the accessory pathway (1-4); (2) duration of each procedure (45-420 min); (3) duration of fluoroscopy (5-102 min); (4) number of necessary radio-frequency applications (1-48); and (5) cumulative energy per procedure. To ablate left-lateral pathways (n = 10) required fewer procedures, shorter duration per procedure, shorter fluoroscopy time, fewer current applications and less total energy than coagulation of right-sided pathways (n = 10). Those various parameters were greatest for ablation of septal and para-septal pathways (n = 9). Pathways which conducted only retrogradely (n = 15) were more difficult to ablate than those with anterograde conduction (n = 38). There were two complications. In one case a tension pneumothorax occurred after faulty puncture of the subclavian vein; in the other, the left ventricle was perforated causing an acute tamponade which required pericardiocentesis with subsequent suture closure of the perforation. It is concluded that, in principle, all accessory pathways, regardless of their conduction potential and site, can be ablated by a radio-frequency current.

Adolescent↗
PubMed1993

[The quality of life after the implantation of a cardioverter/defibrillator in malignant arrhythmias].

Quality of life after implantation of an automatic implantable cardioverter/defibrillator (ICD) was assessed by questionnaire in 43 patients (38 males, 5 females; mean age 57 +/- 16 years) with treatment-resistant symptomatic ventricular arrhythmias. 37 of the 43 patients felt better after ICD implantation. 23 were always conscious of having an ICD, but 18 had got used to it in less than 2 months. 15 patients reported being afraid of an ICD shock, while eight noted physical discomfort caused by the ICD. Limitations concerning their professional, recreational and social activities were reported by six patients. 41 of the 43 patients confirmed that the ICD had been helpful, enabling 23 to return to an active life. 42 would recommend implantation to others if indicated. These data demonstrate that there is a remarkably high degree of acceptance of the ICD. Survival rate after implantation is thus not the only criterion of success. All aspects of the quality of life should be taken into consideration before implantation is decided upon.

Adult↗
PubMed1993

Effects of antiarrhythmic drugs on epicardial defibrillation energy requirements and the rate of defibrillator discharges.

Antiarrhythmic drugs are commonly used with the implantable cardioverter/defibrillator to treat recurrent ventricular tachyarrhythmias. Since various antiarrhythmic drugs have been reported to alter defibrillation threshold, an important question is whether the device will provide adequate energy for defibrillation during long-term follow-up and to what extent antiarrhythmic drug treatment will affect defibrillation energy requirements. To answer these questions, the defibrillation thresholds were determined in 20 patients using an epicardial patch-patch lead configuration at the time of implantation and at the time of pulse generator replacement. During a mean follow-up period of 24 +/- 6 months, the defibrillation threshold increased significantly from 14.2 +/- 3.7 joules to 18.3 +/- 5.5 joules in the entire group (P < 0.05). This increase in defibrillation threshold was due to a marked elevation of defibrillation energy requirements in the subgroup of patients taking amiodarone compared with patients receiving mexiletine. Based on these results it is mandatory to retest defibrillation threshold at any time of pulse generator replacement to guarantee continued effectiveness. In particular, if amiodarone treatment is initiated after implantation of a defibrillator, it is recommended to reevaluate defibrillation threshold to ensure an adequate margin of safety.

Amiodarone↗
PubMed1993

Efficacy and safety of combination therapy with amiodarone and type I agents for treatment of inducible ventricular tachycardia.

In a prospective study the efficacy of amiodarone in combination with the three Class I drugs mexiletine, flecainide, or encainide was evaluated consecutively in 12 patients with recurrent ventricular tachycardias (VT) by programmed stimulation. None of the tested drug combinations suppressed induction of sustained VT. The combination of amiodarone with Class IC drugs flecainide and encainide prolonged the cycle length of VT significantly, whereas the combination with mexiletine did not have the same degree of slowing on the VT cycle length. Several proarrhythmic effects occurred during the combination therapy with encainide: (1) frequent, spontaneous recurrences of hemodynamically well tolerated VT in four patients; (2) enhanced inducibility of VT in three patients; (3) impaired termination of VT in three patients. Though a marked increase in QRS and QTc intervals was observed by combined treatment with encainide, no significant correlation could be established between aggravation of arrhythmia and plasma levels of encainide, degree of QRS widening, JT or QTc prolongation. The only predictor for the occurrence of proarrhythmic events was found in left ventricular ejection fraction. These findings suggest that in patients refractory to amiodarone alone or a combination with mexiletine, the combined treatment of amiodarone with other Class IC drugs prolongs the VT cycle length but does not suppress induction of VT during programmed stimulation. Combination therapy of amiodarone with encainide was associated with a high incidence of proarrhythmic effects.

Adult↗
PubMed1993

Patient acceptance of the implantable cardioverter defibrillator in ventricular tachyarrhythmias.

Besides surgical problems, recipients of implantable cardioverter defibrillators (ICDs) are faced with psychological and social adjustments. Successful ICD therapy is influenced by the patients' perceived concerns regarding device, discharge, changes in life style, and complications. In order to assess patients' acceptance of the ICD, the psychological profile of 57 consecutive patients was evaluated using a specifically designed questionnaire and the State Trait Anxiety Inventory (STAI). The results showed that 20 patients stated fear of ICD discharge, 12 patients revealed physical discomfort due to the device, and limited quality-of-life occurred in 8 patients. Fifty-five of 57 patients answered that it was worth having an ICD device implanted, 30 (53%) patients returned to active life, and 56 (98%) would advise another patient to undergo implantation if necessary. Overall, there was only a slight, but insignificant, decrease in the level of anxiety within the total patient population after ICD implantation. However, a comparison of two subgroups indicated that the state of anxiety was significantly higher in patients < 50 years of age as well as in patients having received > 5 shocks versus those > 50 years of age and having experienced < 5 shocks. In general, the acceptance of the ICD as a tool in managing life-threatening ventricular tachyarrhythmias is high. Besides the increased survival rate, quality-of-life and patient acceptance are important criteria for successful ICD therapy.

Activities of Daily Living↗
PubMed1993

[Non-pharmacologic treatment of pre-excitation syndromes].

Paroxysmal tachyarrhythmias due to accessory atrioventricular pathways are usually not completely suppressible with antiarrhythmic drug therapy. These patients can be treated by implantable antitachycardia pacemakers or surgical or catheter ablation of accessory pathways. The antitachycardia pacemaker offers a symptomatic treatment, which is indicated in patients with less often arrhythmias, without atrial fibrillation and with haemodynamically stable tachycardias. The surgical interruption of accessory pathways depends on thoracotomy and often the cardiopulmonary bypass. This therapy is a curative treatment, which is indicated in patients with further cardiac disease needing surgical intervention. Catheter ablation of accessory pathways with radiofrequency energy is the modern treatment. Our own experience with 12 patients with preexcitation syndrome and antitachycardia pacemakers, 50 patients with surgical interruption of accessory conduction and 63 patients with catheter ablation is referred and the results are discussed.

Adolescent↗