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Biomedical subjects

E Hoffmann

Publications and source records attributed to E Hoffmann.

At least 19 recordsLinked to original sources

A comparison of electrophysiologically guided antiarrhythmic drug therapy with beta-blocker therapy in patients with symptomatic, sustained ventricular tachyarrhythmias.

BACKGROUND: Antiarrhythmic drug therapy guided by invasive electrophysiologic testing is now widely used in patients with symptomatic, sustained ventricular tachyarrhythmias. METHODS: We conducted a prospective, randomized trial in 170 patients to investigate whether this approach would improve long-term outcome. Patients whose arrhythmia was inducible by programmed electrical stimulation were assigned to treatment with electrophysiologically guided drug therapy based on serial testing (61 patients) or with metoprolol (54 patients). Electrophysiologically guided therapy consisted of serial testing of antiarrhythmic agents to identify the first one that rendered the arrhythmia noninducible. The 55 patients whose arrhythmia was noninducible during the initial electrophysiologic test were also treated with metoprolol. RESULTS: During a mean (+/- SD) follow-up period of 23 +/- 17 months, recurrent, nonfatal arrhythmia occurred in 44 patients and sudden death due to cardiac factors in 27. The incidence of symptomatic arrhythmia and sudden death combined was virtually the same in the two groups with inducible arrhythmia after two years of observation (electrophysiologically guided therapy vs. metoprolol therapy, 46 percent vs. 48 percent). The outcome was more favorable in the patients with noninducible arrhythmia at base line (75 percent had neither adverse event) than in those with inducible arrhythmia who were assigned to metoprolol therapy (P = 0.009 by log-rank test). Only 6 of the 29 patients (21 percent) with inducible arrhythmia that became noninducible during drug therapy had recurrent arrhythmia or sudden death, as compared with 21 of the 32 patients (66 percent) with arrhythmia that continued to be inducible (P less than 0.001). A multivariate regression analysis identified continued inducibility of the arrhythmia as an independent predictor of recurrent arrhythmia or sudden death (relative risk, 7.3; 95 percent confidence interval, 2.3 to 23.2; P less than 0.001). CONCLUSIONS: As compared with metoprolol therapy, electrophysiologically guided antiarrhythmic drug therapy did not improve the overall outcome of patients with sustained ventricular tachyarrhythmias. However, effective suppression of inducible arrhythmia by antiarrhythmic drugs was associated with a better outcome than was lack of suppression.

Adrenergic beta-Antagonists

A novel cyclic analog of neuropeptide Y specific for the Y2 receptor.

The low-molecular-mass, cyclic analog of neuropeptide Y, [Ahx5-24, gamma-Glu2-epsilon-Lys30] NPY (YESK-Ahx-RHYINKITRQRY; Ahx, 6-aminohexanoic acid; NPY, neuropeptide Y), was synthesized and investigated for receptor binding, inhibition of forskolin-stimulated cAMP accumulation, inhibition of electrically stimulated rat vas deferens contractions and ability to increase blood pressure. Like the linear peptide [Ahx5-24] NPY (YPSK-Ahx-RHYINLITRQRY), the more rigid, cyclic analog showed good correlation between receptor binding to rabbit kidney membranes and biological activity in the vas deferens assay. Binding of this peptide to a new Y2-receptor-expressing cell line was slightly reduced, compared to the linear peptide [Ahx5-24] NPY, however inhibition of cAMP accumulation was even more efficient. Unlike the linear peptide [Ahx5-24] NPY, the cyclic analog did not induce a blood pressure increase in rats. Reduced binding to Y1 receptor-expressing SK-N-MC cells, as well as the loss of capability of signal transduction, suggest that only Y2-mediated activity is preserved after cyclization. The selectivity of the cyclic compound for Y2 subtypes of NPY receptors with respect to inhibition of cAMP accumulation is more than fortyfold increased, as compared to the linear NPY-(13-36) peptide, which has been used to determine Y2 selectivity so far.

Amino Acid Sequence

[Massive gastrointestinal hemorrhage from a hepaticojejunostomy in pancreatogenic mesenteric vein thrombosis. Diagnosis and therapy].

Gastrointestinal hemorrhage in a patient with a biliodigestive anastomosis necessitates exclusion of a bleeding source in the region of the choledocho- or hepaticojejunal anastomosis. This cannot be achieved by endoscopic methods. The source of bleeding can sometimes, though rarely, be localised by performance of selective angiography during hemorrhage. Laparotomy with exploration of the anastomosis during such an episode is at the same time a diagnostic and a therapeutic intervention. The surgical procedure of choice is de-anastomosis, resection of the bypassed jejunal loop and formation of a hepatico-duodenostomy.

Anastomosis, Roux-en-Y

Biophysical parameters of radiofrequency catheter ablation.

Radiofrequency catheter ablation has been shown to be an effective treatment for patients with accessory pathways in Wolff-Parkinson-White syndrome and other supraventricular tachycardias. However, the biophysical parameters used so far in vivo did not correlate to the size of myocardial lesions and provided no information about the myocardial wall contact of the electrode. In this study 104 radiofrequency applications were performed on excised pig myocardium in circulating heparinized pig blood as well as in blood alone, and root mean square (rms) voltage, root mean square current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% when measured at the point of maximum current during coagulation. A drop of current following a rise in impedance led to a phase displacement of more than 80 degrees and thereby to a drop of effective power to 17% of the output power. Hence, apparent output power consists mainly of ineffective power. The time dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the media blood and myocardium. These results show that physical parameters measured during radiofrequency catheter ablation may help to control electrode position in the clinical situation and reduce the number and duration of ineffective energy applications.

Animals

[The magnesium and calcium content of pre- and postmenopausal myometrium].

Magnesium and calcium, as well as sodium and potassium, have an important influence on the physiology of contraction of the uterus. The ionic concentrations in the pre- and postmenopausal myometrium were examined. We assumed, that there are differences in the electrolytic contents because of the different functions of the corpus, isthmic part and cervix uteri during pregnancy and throughout labour. Small tissue samples from 37 premenopausal and 20 postmenopausal patients, who underwent an operation with different indications, were dissected after hysterectomy. Magnesium and calcium levels were determined by atomic absorption spectrophotometry and potassium and sodium by emission spectrometry in the wet tissue. In both groups, we found significant differences of the electrolytic contents of the myometrium. In the premenopausal uteri, the magnesium levels decrease significantly (p < 0.001) from the corpus (mean = 4.14 mmol/kg) to the cervix (mean = 2.14 mmol/kg). The same scenario can be observed for the potassium levels (Corpus mean = 56.2 mmol/kg and cervix mean = 25.4 mmol/kg). In contrary, the calcium levels (Corpus mean = 1.60 mmol/kg and cervix mean = 2.26 mmol/kg) and sodium levels (Corpus mean = 69.3 mmol/kg and cervix mean = 93.0 mmol/kg) increase significantly (p < 0.001). In the postmenopausal group, we found slightly elevated concentrations of magnesium, sodium and potassium. Only the calcium content of the corpus uteri rises up to three times about 20 years after the menopause (from mean = 1.60 mmol/kg) (p < 0.001). The electrolytic contents in the myometrium were shown to be different in the corpus, isthmus and cervix uteri.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Diagnosis of mycobacterial infections by PCR and restriction enzyme digestion.

A method for the diagnosis of mycobacterial infections by PCR amplification followed by selective restriction enzyme digestion of the PCR product was developed. The amplified DNA sequence used in this study occurs within the gene encoding for the mycobacterial 65 kDa heat shock protein (Hance et al. 1989), which is found in all mycobacteria. However, there are minute differences in the amplified sequence from the Mycobacterium tuberculosis complex compared with the corresponding sequence from the Mycobacterium avium complex. These differences made it possible to rapidly identify to which mycobacterial complex a particular sample belonged by restriction enzyme digestion of the PCR product. A total of 66 samples were tested and all of them were correctly identified. This and similar methods should provide a sensitive, specific and rapid (within 12 h) way of diagnosing mycobacterial infections to the species level.

Animals

Efficacy of automatic multimodal device therapy for ventricular tachyarrhythmias as delivered by a new implantable pacing cardioverter-defibrillator. Results of a European multicenter study of 102 implants.

BACKGROUND: Third-generation implantable cardioverter-defibrillators are devices designed to treat ventricular tachycardia (VT) and ventricular fibrillation (VF) by means of overdrive pacing, cardioversion, or defibrillation. So far, the efficacy of tiered therapy has been documented only in small series. Therefore, a European multicenter clinical evaluation study of a new tachyarrhythmia control device, the Medtronic PCD pacer-cardioverter-defibrillator with epicardial patch-lead configuration, was undertaken. METHODS AND RESULTS: We report on 102 patients (mean age, 55 +/- 13 years) from 11 European centers. PCD devices implanted between May 1989 and February 1991 were included. The patients suffered from hemodynamically significant ventricular tachyarrhythmias not suppressed by antiarrhythmic drug therapy and unrelated to acute myocardial infarction; one patient had nonsustained VT and severely depressed left ventricular function. Seventy patients had coronary artery disease with old myocardial infarctions, 23 had cardiomyopathies of various etiologies, and nine patients had no detectable heart disease. Mean ejection fraction was 36 +/- 14% (range, 10-76%). Mean intraoperative defibrillation threshold (51 patients) was 10.6 +/- 5.1 J (range, 2-18 J). The documented follow-up ranged from 1 to 21 months (mean, 9.4 +/- 5.8 months), or 79.9 cumulative patient-years. Perioperative mortality was 3.9%. The actuarial survival rate at 12 months was 91%. One sudden arrhythmic death occurred. Sixty patients (58%) received device therapy. Seventeen patients had therapies only for "VF" episodes, 16 patients only for VT, and 28 patients for VT and "VF" episodes. Based on device memory data, 1,235 spontaneous VT episodes were detected and treated in 43 patients. Twelve hundred four of these VT episodes received painless initial antitachycardia pacing therapy, restoring sinus rhythm in 91%. The 108 ongoing episodes received 209 multiple therapeutic attempts. Eighty-five additional overdrive pacing therapies restored sinus rhythm in 30%. Initial ineffective antitachycardia pacing therapies received 51 cardioversion pulses. The success rate was 61%. Seventy-three additional cardioversion pulses were delivered to backup ineffective pacing therapy as well as ineffective secondary cardioversion pulses. Their success rate was only 40%. Two hundred eighty-six spontaneous episodes were detected in 44 patients as "VF." Overall defibrillation efficacy was 97.6%. CONCLUSIONS: The implanted device nearly eliminates sudden arrhythmic death in patients with documented, potentially fatal ventricular tachyarrhythmias. Automatic tiered therapy is highly effective to restore sinus rhythm, provided that an integrated two-zone tachycardia detection algorithm is used, assigning lower tachycardia rates to overdrive pacing and/or cardioversion and higher tachycardia rates to defibrillation. In general, spontaneous VTs can be terminated by automatic overdrive pacing, and painful or disturbing countershock therapies are not required to terminate the majority of spontaneous VT episodes.

Death, Sudden, Cardiac

[Importance of physical parameters for the effectiveness of radiofrequency catheter ablation].

Radiofrequency catheter ablation has been shown to be an effective form of treatment of accessory pathways in patients with WPW-syndrome and other supraventricular tachycardias. However, the biophysical parameters so far used in vivo neither correlated with the size of the myocardial lesion nor did they provide any information about contact of the electrode with the myocardial wall. In this study, 104 radiofrequency energy applications were performed on excised pig myocardium in circulating heparinized pig blood, and in blood alone, and root mean square (rms) voltage, current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% measured at the point of maximum current during coagulation. A progressive drop in current following a rise in impedance led to a phase shift of more than 80 degrees with a decrease in effective power to 17% of the output power. Hence, apparent output power was mainly ineffective power. The time-dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the coagulated media. These results show that physical parameters measured during radio-frequency catheter ablation may help to monitor electrode position in the clinical situation and reduce the number of ineffective energy applications.

Animals

[Anti-arrhythmia and pro-arrhythmia effects of oral cibenzoline therapy in sustained ventricular tachycardia].

The efficacy and safety of the new class-I antiarrhythmic drug cibenzoline was assessed in 12 patients with spontaneous and inducible ventricular tachycardia. Programmed ventricular stimulation, 24-h ambulatory electrocardiogram (ECG), and continuous ECG monitoring were performed without antiarrhythmic drugs and after oral administration of 254 +/- 80 mg of the substance. Oral cibenzoline suppressed the induction of tachycardia in only one patient. Induction of tachycardia was more difficult in two patients, unchanged in four patients, and easier in two patients. Cycle length of induced tachycardia and QT-interval corrected for frequency were not changed significantly; effective refractory period of the right ventricle was prolonged. Twenty-four hours of ambulatory monitoring during cibenzoline treatment (n = 9) showed no significant increase in the frequency of ventricular premature complexes. However, spontaneous sustained ventricular tachycardia developed in three patients after initiation of cibenzoline treatment. In two patients, termination of induced ventricular tachycardia was significantly more difficult under cibenzoline; several DC-shocks were required to terminate the tachycardia. Thus, the use of oral cibenzoline in patients with sustained spontaneous and inducible ventricular tachycardias showed a low antiarrhythmic efficacy at programmed stimulation and a high incidence of spontaneous ventricular tachycardia.

Adult

[Left ventricular catheter ablation of the AV conduction system with radiofrequency electric current].

We report on a 32-year-old female patient with a history of recurrent atrial fibrillation and rapid ventricular response (up to 240 beats/min) resistant to multiple drug therapy. In this patient, we successfully performed a radiofrequency catheter ablation of the atrioventricular (AV) junction from the left ventricle, after radiofrequency energy application in His-position above the tricuspid valve was unsuccessful. This technique offers an-alternative treatment in patients in whom the conventional right-sided catheter ablation of the AV junction proves ineffective.

Adult

Kinetic parameters of enzymatic reactions in states of maximal activity; an evolutionary approach.

A theoretical investigation is presented which allows the calculation of states of maximal reaction rates for single enzymes and for unbranched enzymatic chains. As an extension to previous papers (Heinrich & Holzhütter, 1985, Biomed. biochim. Acta 44, 959-969; Heinrich et al., 1987, Bull. math. Biol. 49, 539-595) a detailed enzymatic mechanism was taken into consideration. Conclusions are drawn for the optimal values of the microscopic rate constants as well as of the maximal activities and Michaelis constants. Ten solutions are found which depend on the equilibrium constant as well as on the concentrations of substrates and products. It is shown that for high equilibrium constants one of the solutions applies to a very large range of the concentrations of the outer reactants. This solution is characterized by maximal values of the rate constants of all forward reactions and by non-maximal values of the rate constants of all backward reactions. In contrast to previous assumptions (Albery & Knowles, 1976b, Biochemistry 15, 5631-5640; Burbaum et al., 1989, Biochemistry 28, 9293-9305) states of maximal reaction rate are not always characterized by the highest possible values of the second-order rate constants which are related to the diffusion of the substrate and the product to the active site of the enzyme. Predictions are made concerning the ratios of maximal activities in optimal states as well as for the adaptation of the Michaelis constants to the concentrations of the outer reactants. Using metabolic control analysis it is shown that the solutions obtained for single enzymes may also be applied in multi-enzyme systems.

Animals

[Diabetic ketoacidosis (169 episodes in 131 patients in the course of 10 years)].

Diabetic patient material--presenting hyperglycaemic ketoacidotic episode--observed in Gyula and Szekszárd County Hospitals in period 1980-89, was reviewed by authors. 131 patients were admitted with 169 ketoacidotic episodes (among them 23 patients had 62 recurrences). The mean age of patients were 49.4 years (14-84 years), duration of diabetes 9.5 years (from one month to 45 years). The common cause of diabetic ketoacidosis was respiratory (26 per cent) and enteral (35.5 per cent) infection. The consciousness of patients had shown close correlation with the increase of blood sugar and urea nitrogen level as well as with the decreasing of the pH value of capillary blood. The first step of the therapy was the parenteral fluid intake with isotonic solution (in the first hour the average 1351 ml). In 18 patients fast-acting insulin (Novo Actrapid MC) was given by constant infusion, in the remaining cases intravenous or intramuscular low doses of the same insulin were administered. The importance of early potassium replacement, and the dangers of forced and rapid correction of acidosis is emphasized. Lethality related to episodes was 10 per cent, related to the patients 12.9 per cent. The number of ketoacidotic cases did not decrease parallel with the improvement of therapeutic possibilities, as it was experienced by their earlier evaluations. The importance of the prevention of acute metabolic disorders is outlined might be resulted from increasing the efficacy of patients education and better knowledge of GP's, as well.

Adolescent

[Possibilities of early diagnosis of autonomic neuropathy in diabetics].

The possibilities of the diagnosis of autonomous neuropathy were investigated by the authors in 71 insulin-treated diabetes mellitus patients with the use of dynamic esophageal scintigraphy and determination of cardiac reflex tests. It has been found that the extent and severity of the lesion can be earlier and more exactly recognized with the help of these two methods. Important information can be obtained by the determination of esophageal transit time about the functional condition of vagal nerves supplying gastrointestinal organs. In patients suffering from autonomous neuropathy the esophageal transit time proved to be significantly prolonged (p less than 0.01). The injury of parasympathetic heart innervation is earlier indicated by the pulmo-cardiac reflexes, while the troubles of symphathic functions are shown more responsively by the sustained handgrip test. Cases with considerable degree of orthostatic hypotension were not observed, its incidence may be probably higher only in advanced forms of autonomous neuropathy. The injury of vegetative nerve fibers develops mostly parallel in diabetes mellitus, but partial functional disorders can be also observed. Detailed neurological examinations were performed in 30 patients, and it has been found, that the lesion of peripheral nerves can be only later observed. Specific complications involving the nervous system are more frequent in cases with longer duration of the disease. In the authors opinion, for investigation and follow-up of larger number of diabetic patients, the dynamic esophageal scintigraphy and determination of pulmo-cardiac reflex and sustained handgrip tests seem to be suitable.

Adult

A new phloroglucinol derivative from Hypericum calycinum with antifungal and in vitro antimalarial activity.

The new phloroglucinol derivative 1 has been isolated from the light petroleum ether extract of the aerial parts of Hypericum calycinum. Its structure has been established by means of 1H- and 13C-NMR spectroscopy and by nOe, MHQC, and HMBC experiments on its monomethyl ether derivative 3. Compound 1 was fungicidal against Cladosporium cucumerinum in a TLC bioassay. In addition, this new phloroglucinol derivative was also found to exert an interesting antimalarial activity in an in vitro test system.

Animals

Clinical nursing research priorities: a Delphi study.

Using the delphi technique, a group of clinical nurse specialists was surveyed regarding delineation of clinical nursing research priorities. Upon completion of the four-round survey, the results suggested that the top priorities for nursing research are: (1) factors which influence longevity in clinical nursing practice, (2) patient care delivery systems as related to nurse satisfaction, and (3) indicators of quality nursing care.

Attitude of Health Personnel