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Biomedical subjects

W Jung

Publications and source records attributed to W Jung.

At least 217 records · Page 12Linked to original sources
PubMed1992

Increased levels of circulating cytokines in patients with untreated Hodgkin's disease.

Expression of several cytokines has been demonstrated in Hodgkin and Reed-Sternberg (H&RS) cells in vitro and in vivo. In order to determine whether interleukin-1 beta (IL-1 beta), IL-3, IL-6, GM-CSF, G-CSF, and TNF-alpha are elevated in Hodgkin's disease (HD), we tested the sera of untreated patients with HD by means of sensitive sandwich ELISAs. GM-CSF was detected in 22/56 patients (39%; range 40-140 pg/ml), IL-3 in 5/40 (13%; range 13-26 pg/ml), and IL-6 in 32/56 patients (57%; range 12-332 pg/ml). TNF-alpha and IL-1 beta were detected in only 3/43 patients (7%; range: TNF-alpha: 36-66 pg/ml; IL-1 beta: 389-1505 pg/ml) and G-CSF not at all. All patients with measurable IL-3 levels had both elevated IL-6 and GM-CSF levels, and the majority of patients with elevated IL-6 also had elevated GM-CSF levels and vice versa. In contrast, the 3/40 patients with both measurable IL-beta and TNF-alpha did not have elevated IL-3, IL-6, or GM-CSF levels. Cytokine levels were independent of stage or the presence of B-symptoms, and there was no correlation with any other clinical or laboratory parameter. Elevations of the respective cytokines might be a means to maintain normal blood cell counts in the respective patients with HD.

Adolescent↗
PubMed1991

Clinical significance of soluble CD30 antigen in the sera of patients with untreated Hodgkin's disease.

The soluble form of the CD30 antigen (sCD30), an 88-kd glycoprotein that is released by Hodgkin's-derived cell lines in vitro, can be detected in patients with Hodgkin's lymphoma, adult (HTLV-1+) T-cell leukemia, rare cases of non-Hodgkin's lymphoma, and acute infectious mononucleosis (anti-EBV-IgM+). In a prospective study of 90 consecutive untreated patients with newly diagnosed Hodgkin's disease who were treated according to the protocols of the German Hodgkin Study group, 22% had detectable levels of sCD30 in their serum. sCD30 was only detected in patients with B symptoms (20 of 44 or 45%), and maximum sCD30 levels (88 U/mL) were found in stage IVB. Of 87 patients evaluable for response, sCD30+ patients had significantly lower rates of complete remission (9 of 20 or 45% v 60 of 67 or 90%; P less than .001) and higher rates of progressive disease (9 of 20 or 45% v 6 of 67 or 9%; P less than .001) than CD30+ patients. Similarly, freedom from treatment failure curves were significantly worse for CD30+ patients (P = .0003). sCD30 disappeared after successful treatment, but increased in patients with progressive disease. It was never detected in patients in complete remission or in healthy controls. We conclude that sCD30 is a valuable marker for disease activity and has prognostic significance in Hodgkin's disease.

Adolescent↗
PubMed1991

Comparison of two antitachycardia pacing modes in supraventricular tachycardia.

The comparative efficacy of two different antitachycardia pacing techniques was evaluated in 22 consecutive patients who received the pacemaker Intertach with an atrial electrode for drug refractory, recurrent supraventricular tachycardia (SVT). The Intertach has two consecutive programmable primary and secondary termination modes. The termination programs investigated were adaptive autodecremental burst pacing and adaptive decremental scanning. Atrioventricular nodal reentrant tachycardia was present in 15 patients and atrioventricular reentrant tachycardia due to Wolff-Parkinson-White syndrome in seven patients. The prospective comparison was arranged in a randomized, cross-over study over a period of 12 months. To assess long-term efficacy, diagnostic data of the pacemakers were obtained in intervals of 3 months. In addition, noninvasive programmed stimulation was performed to compare the incidence of pacing-induced atrial fibrillation with both termination programs. During a follow-up of 12 months the overall success rate of autodecremental burst pacing and decremental scanning was 80% and 95%, respectively. Decremental scanning was more effective in 12 patients and less successful in two patients than autodecremental burst pacing. During noninvasive electrophysiological studies, pacing induced atrial fibrillation could be documented in three of ten patients (30%) using autodecremental burst pacing, compared to one of ten patients (10%) using decremental scanning. These data suggest that decremental scanning proved to be more successful in the long-term management of patients with recurrent SVT than autodecremental burst pacing. Furthermore, the occurrence of pacing-induced atrial fibrillation could be documented more frequently with autodecremental burst pacing compared to decremental scanning.

Algorithms↗
PubMed1991

Combination of antiarrhythmic drugs.

Antiarrhythmic treatment with single agents is often ineffective and can be limited by dose-dependent side effects. Therefore, combinations of antiarrhythmic drugs in smaller and well-tolerated doses are advocated in cases refractory to single antiarrhythmic drugs. Basically, substances belonging to the same electrophysiologic class should not be combined. However, drugs of different subsets of class I may be combined. Agents that have pharmacokinetic interactions, such as quinidine and amiodarone, should not be given together because this combination may be associated with a considerable proarrhythmic effect. A combination of beta-adrenoreceptor blockers with class I antiarrhythmic drugs may be effective, mainly in cases in which the arrhythmia is dependent on adrenergic stimulation. The combination of class III and IB substances can be useful in some cases, from the electrophysiological and clinical point of view. Among the successful combinations of this type are amiodarone and mexiletine, sotalol and mexiletine, or sotalol and tocainide. In 34 patients, the reduction of ventricular premature beats by sotalol alone was 28%, and by sotalol plus mexiletine or tocainide was 79%. Complex ventricular arrhythmias were suppressed by sotalol alone by less than 40% and by sotalol plus mexiletine or tocainide by more than 80%. There was no difference in the effectiveness of mexiletine and tocainide (both of them being class IB drugs) in this combination. However, mexiletine was associated with fewer adverse effects than was tocainide. In patients refractory to amiodarone alone or to a combination with mexiletine, the combined treatment with amiodarone and class IC drugs such as flecainide and encainide prolongs the cycle length of ventricular tachycardia, but does not suppress induction of ventricular tachycardia during programmed stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Which programmable functions of pacemakers are available, and what is their clinical relevance?].

Microprocessors incorporated into cardiac pacemakers enable a substantial number of programmable functions (Table 1), the clinical relevance of which is the subject of this overview. Stimulation mode: The mode of operation can be chosen as fixed-rate, triggered and inhibited stimulation. Rate: Rate-programmability enables optimal setting with respect to electrophysiologic and hemodynamic considerations. Impulse amplitude and width: With programmable impulse amplitude and width excessive stimulation energy can be avoided and the duration of the aggregate prolonged. In some pacemakers, the output current can be chosen as "unregulated or regulated" whereby with regulated current the magnitude of the output impulse remains constant until the battery is depleted. Functional impairment of the pacemaker through threshold elevation or muscle stimulation can be eliminated by reprogramming of the impulse amplitude or width. Sensitivity: Programmability of the input sensitivity enables noninvasive counteraction of detection disturbances (as undersensing especially with low-amplitude atrial signals and oversensing of interference signals with subsequent pacemaker inhibition; Figure 1). A new option, automatic sensitivity setting, regulates the registration of cardiac activity at the atrial and/or ventricular level within a safety margin of 2:1; even though somewhat problematic, undersensing is rare. Electrode polarity: Depending on the clinical situation, the unipolar or bipolar electrode may offer advantages. The programmability of the electrode polarity accordingly represents a clinically-relevant new development which provides a favourable combination of bipolar detection and unipolar stimulation. Some modern dual-chamber systems enable separate programming of the atrial and ventricular electrode configurations. Hysteresis: For single-chamber systems and, more recently, AV-sequential pacemakers, hysteresis is optionally available, that is, a programmable prolongation of the basic interval after detection of a spontaneous cardiac event. With further refinement, the so-called search hysteresis prolongs the stimulation interval after a constant number of continuous stimulation cycles to a programmed hysteresis interval to allow spontaneous cardiac activity; if this is detected during the prolonged interval, the pacemaker is inhibited, otherwise the pacemaker stimulates at the set rate. An AV-interval hysteresis - to date only available in one pacemaker system - prolongs the duration of the AV-interval in the following cycles to a programmed interval, if, within the programmed AV-interval, spontaneous AV-conduction is detected. Additionally, after a defined number of AV-cycles an AV-interval prolongation is chosen to assess the possibility of physiologic AV-conduction. AV-interval: Modern AV-sequential pacemakers incorporate integration of the differential and rate-adaptive AV-interval.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1991

[Heart-minute volume during persistent ventricular tachycardia: anti-arrhythmia intervention using ajmaline].

The hemodynamic effect of the intravenous application of ajmaline (50 mg) was studied during persistent ventricular tachycardia. With the onset of ventricular tachycardia an increase of heart rate up to 177 +/- 40 bpm and a simultaneous decrease of cardiac output from 7.1 +/- 2.7 l/min to 3.4 +/- 1.1 l/min (p less than 0.001) could be demonstrated. Ajmaline prolonged the QRS interval and slowed the ventricular tachycardia rate to 133 +/- 28 bpm. Simultaneously, an increase of cardiac output to 5.9 +/- 2.3 l/min (p less than 0.001) could be documented. A significant correlation between the increase of cardiac output and the change of ventricular tachycardia rate was found. A drug-induced termination of ventricular tachycardia by ajmaline was possible in 60% of patients. Intravenous application of ajmaline during persistent ventricular tachycardia leads to a hemodynamic improvement caused by the reduction of the tachycardia rate. This temporary stabilization of the hemodynamic status is important for emergency treatment of ventricular tachycardia.

Adult↗
PubMed1990

Detection of a soluble form of the CD30 antigen in sera of patients with lymphoma, adult T-cell leukemia and infectious mononucleosis.

Using a sandwich enzyme-linked immunosorbent assay (ELISA) we were able to detect a soluble form of the CD30 antigen (CD30s) in the supernatant of cell lines expressing membrane-bound CD30 and in T and B cells after transformation with human T-cell leukemia virus (HTLV-I) and Epstein-Barr-Virus (EBV). While CD30s was not found in 250 healthy controls, it was detected in the sera of patients with Hodgkin's disease (23/100), anaplastic large-cell (6/9), angioimmunoblastic (2/2) and one unclassified high-grade non-Hodgkin's lymphoma (NHL), as well as in 18/20 patients with acute adult T-cell leukemia (ATL, HTLV-I-positive). It was absent in a large number of patients with other high-grade NHL, all low-grade NHLs, acute or chronic leukemias and solid tumors. The only non-malignant disease with detectable levels of CD30s was infectious mononucleosis (9/10). The membrane-bound form of CD30 has a molecular weight of 120 kDa. Western blot analysis revealed that CD30s in the serum of patients has a molecular weight of 88 kDa, identical to the antigen released by cell lines in vitro. CD30s disappeared in all originally positive cases after successful treatment and reappeared in relapsing patients. Thus, CD30s may be useful as a specific marker for disease activity of certain types of lymphoma and ATL.

Adult↗
PubMed1990

Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin's disease.

Five monoclonal CD30 antibodies and two Fab' fragments were linked to deglycosylated ricin A chain (dgA), and their potential as immunotoxins for the treatment of Hodgkin's disease was evaluated. Cross-blocking experiments demonstrated that HRS-1, HRS-3, HRS-4, and Ber-H2 recognize the same epitope on the CD30 antigen and that Ki-1 binds to a different epitope. Scatchard analyses showed that HRS-3, HRS-4, and Ber-H2 bound strongly to L540 Hodgkin cells (Kd 15, 7, and 14 nM, respectively), whereas HRS-1 and Ki-1 bound more weakly (Kd 160 and 380 nM, respectively). The different affinities of the antibodies correlated closely with their cytotoxic potency as immunotoxins. HRS-3.dgA, HRS-4.dgA, and Ber-H2.dgA inhibited the protein synthesis of L540 cells by 50% at concentrations of 0.9-2.0 x 10(-10) M, whereas HRS-1.dgA and Ki-1.dgA were about 100 times less potent with 50% inhibitory concentrations of 0.8-1.0 x 10(-8) M. The most effective immunotoxins, HRS-3.dgA and HRS-4.dgA, were only 15 times less toxic than ricin itself. HRS-3 Fab'.dgA and HRS-4 Fab'.dgA were 7.8 and 3 times less potent than their IgG.dgA counterparts with 50% inhibitory concentrations of 7 x 10(-10) and 3 x 10(-10) M, respectively. Staining of human tissues revealed an unexpected cross-reactivity of HRS-4 with pancreatic cells of malignant and nonmalignant origin. HRS-1, HRS-3, Ber-H2, and Ki-1 showed very little cross-reactivity with any normal human tissues. It is concluded that HRS-3.dgA and HRS-3 Fab'.dgA are the immunotoxins of choice for in vivo therapy.

Antibodies, Monoclonal↗
PubMed1990

Role of sulfidopeptide leukotrienes in synthetic smoke inhalation injury in sheep.

Acute lung injury with smoke inhalation results in significant morbidity and mortality. Previously we have shown that synthetic smoke composed of carbon and acrolein, a common component of smoke, causes delayed-onset noncardiogenic pulmonary edema. To study the possible role of the vasoactive and edemagenic sulfidopeptide leukotrienes (SPLT) in smoke inhalation injury, we measured pulmonary hemodynamics, lung lymph flow, and SPLT and leukotriene (LT) B4 in lung lymph before and after 10 min of synthetic acrolein smoke exposure. After smoke exposure there was a significant rise in pulmonary vascular resistance caused by a rise in pulmonary arterial pressure, a fall in cardiac output, and no change in pulmonary capillary wedge pressure. This was accompanied by an increase in total systemic vascular resistance (P less than 0.05), lung lymph flow (P less than 0.05), and extravascular lung water-to-lung dry weight ratio (P less than 0.05). Both SPLT and LTB4 clearance rose significantly (P less than 0.05), but there was a 10-fold increase in SPLT over LTB4 clearance. In sheep pretreated with FPL55712, a SPLT antagonist, the early rise in pulmonary vascular resistance was attenuated, and the rise in systemic vascular resistance was blocked. This was associated with an attenuated and delayed fall in cardiac output. FPL55712 had no effect on lung lymph flow or extravascular lung water-to-dry weight ratio. SPLT, and especially LTD4, may have a role in increased pulmonary and systemic vascular resistance after smoke inhalation injury but does not appear to affect vascular permeability.

Acrolein↗
PubMed1990

New aspects of the clinical use of anti-arrhythmia agents with special reference to acute therapy of ventricular tachycardia (lidocaine vs. ajmaline).

Antiarrhythmic treatment is based on the hypothesis that ventricular premature beats (VPBs), in the presence of underlying cardiac disease and impaired ventricular function, may predispose to sudden cardiac death. The effectiveness of treatment, however, has not been proven. For acute treatment of paroxysmal ventricular tachycardia, on comparison of the effectiveness of lidocaine and ajmaline, some new aspects have been rendered. VENTRICULAR PREMATURE BEATS (VPB): Isolated VPBs can be found in 40 to 75% of healthy subjects; if their number is substantial, investigation is warranted. For VPBs with subjective symptoms, beta-receptor blockers or specific antiarrhythmic agents, if necessary in combination, may be given. In several studies it has been shown that the prognosis of patients with frequent and complex VPBs, that is couplets and salvos, without heart disease is not compromised. In one long-term study over an average of 6.5 years, sudden death was observed in only one of 70 subjects who had 566 VPBs/24 hours, 60% additionally couplets and 26% salvos in the Holter ECG. Accordingly, treatment for the sake of prognosis is not warranted. For patients with mitral valve prolapse or only mildly impaired ventricular function and asymptomatic arrhythmias, treatment is not necessary since it has not been shown to be beneficial. Coronary artery disease is the most frequent cause of ventricular arrhythmias and sudden death. In numerous studies in patients after myocardial infarction, a relationship has been recognized between frequent and complex VPBs and overall mortality as well as sudden death. Particularly at risk are patients with very frequent and complex VPBs with additional impairment of ejection fraction to less than 30 to 40% but this group only accounts for 10% of patients after infarction. Only in one interventional study, carried out with aprindine, there was a significant reduction in overall mortality from 12.5 to 7.8% with an adverse reaction rate, however, of 21%. In high-risk patients with a low ejection fraction and numerous, complex VPBs as well, in a further study with aprindine, after one year, there was no decrease in overall mortality as compared with the placebo group. The cause for the insufficient effectiveness of the antiarrhythmic agents in various interventional studies has been attributed to a limited number of patients, rigid dosing regimens, inadequate suppression of VPBs and a high incidence of adverse reactions. In the multicenter, randomized, placebo-controlled CAST study with newer substances, a total of 2309 patients with essentially asymptomatic VPBs at a rate of more than 6/hour and an ejection fraction less than 55% or 40% admitted more than 90 days after infarction, respectively, were followed from six days to two years after myocardial infarction to determine if the significant suppression of VPBs in patients with coronary artery disease with antiarrhythmic agents leads to a reduction in arrhythmia-associated deaths. Flecainide, encainide and moricizine led to a significant suppression of VPBs in 75% of the patients. After an average of ten months, the rate of arrhythmia-induced deaths of 4.5% in those treated with encainide or flecainide was significantly higher than the 1.2% observed in the placebo group. These results appear attributable to a proarrhythmic effect of the class IC drugs during long-term treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Ajmaline↗
PubMed1990

[Indications for pacemaker therapy in ophthalmoplegia plus and Kearns-Sayre syndrome].

Mitochondrial myopathies can affect the skeletal muscle, the central or peripheral nervous system, and they may be associated with chronic progressive external ophthalmoplegia (CPEO). In 7/29 patients with mitochondrial myopathies and CPEO a cardiac involvement (Kearns-Sayre syndrome) was found: incomplete right bundle branch block (n = 1), right bundle branch block (n = 1), left anterior fascicular block and right bundle branch block (n = 2), complete atrioventricular block (n = 3); congestive cardiac failure (ejection fraction 40%) (n = 2); 3/10 patients had prolonged infranodal conduction on His-bundle electrography (HV-interval 60 ms). The cardiac involvement in ophthalmoplegia plus is characterized by progressive impairment of fascicular conduction. The need for prophylactic pacemaker implantation appears to exist in patients with bifascicular block and prolonged His-ventricle conduction.

Adolescent↗
PubMed1989

Inhibition of biopterin synthesis and DOPA production in PC-12 pheochromocytoma cells induced by 6-aminonicotinamide.

Pheochromocytoma cells (clone PC-12) were treated with 6-aminonicotinamide. Tetrahydrobiopterin content and DOPA production of the cells were determined by reverse-phase HPLC and subsequent electrochemical detection. The same chromatographic system was used to determine total biopterin (tetrahydrobiopterin, dihydrobiopterin and quinoide dihydrobiopterin) by fluorescence detection. Tetrahydrobiopterin plays a decisive role as cofactor of tyrosine hydroxylase for the biosynthesis of DOPA and dopamine. Addition of 6-aminonicotinamide to the culture medium resulted in the accumulation of 6-phosphogluconate, suggesting that PC-12 cells synthesize 6-aminonicotinamide-adenine-dinucleotide-phosphate (6-ANADP) by a glycohydrolase localized in the endoplasmic reticulum. This substance is known to be a strong inhibitor of 6-phosphogluconate dehydrogenase and leads to a blockade of the pentose phosphate pathway. In our experiments, the synthesis of biopterins was depressed after application of 6-aminonicotinamide. The decrease of intracellular tetrahydrobiopterin and total biopterin by 6-aminonicotinamide at different concentrations was strongly correlated with a reduced cellular DOPA production. The decreased content of biopterin cofactor was compensated by addition of the precursor sepiapterin, indicating that the NADPH2-dependent reductases in biopterin synthesis are not inhibited by the antimetabolite. However, DOPA production remained suppressed at the same time. After application of NADH2, we observed an increased DOPA production though the decreased biopterin levels remained almost unchanged. The results imply that the first step in the synthesis of biopterin from GTP as well as the recycling pathways of the oxidized cofactor might be the site of action of the antimetabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Aminonicotinamide↗
PubMed1989

Bronchial artery ligation modifies pulmonary edema after exposure to smoke with acrolein.

Pulmonary edema can follow smoke inhalation and is believed to be due to the multiple chemical toxins in smoke, not the heat. We have developed a synthetic smoke composed of aerosolized charcoal particles to which one toxin at a time can be added to determine whether it produces pulmonary edema. Acrolein, a common component of smoke, when added to the synthetic smoke, produced a delayed-onset pulmonary edema in dogs in which the extravascular lung water (EVLW) as detected by a double-indicator technique began to rise after 42 +/- 2 (SE) min from 148 +/- 16 to 376 +/- 60 ml at 165 min after smoke exposure. The resulting pulmonary edema was widespread macroscopically but appeared focal microscopically with fibrin deposits in alveoli adjacent to small bronchi and bronchioles. Bronchial vessels were markedly dilated and congested. Monastral blue B when injected intravenously leaked into the walls of the bronchial vessels down to the region of the small bronchioles (less than or equal to 0.5 mm ID) of acrolein-smoke-exposed dogs but not into the pulmonary vessels. Furthermore, ligation of the bronchial arteries delayed the onset of pulmonary edema (87 +/- 3 min, P less than 0.05) and lessened the magnitude (232 +/- 30 ml, P less than 0.05) at 166 +/- 3 min after acrolein-smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrolein↗
PubMed1989

[Arrhythmogenic effect of flecainide--treatment with i.v. magnesium].

We report on a 46-year-old woman with ventricular tachycardia and ventricular fibrillation after starting antiarrhythmic drug therapy with flecainide. The flecainide acetate plasma levels were always in the normal range. A successful therapeutical intervention was induced with two i.v. applications of 1,000 mg magnesium glutamate. A persistent suppression of ventricular rhythm disturbance was accomplished by continuous i.v. application of 4 mg magnesium glutamate/min.

Electrocardiography↗