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Biomedical subjects

H Klein

Publications and source records attributed to H Klein.

At least 217 records · Page 12Linked to original sources

[Effectiveness of retard gallopamil in patients with stress-induced ST-segment depression and silent myocardial ischemias].

At a dosage of 75 mg b.i.d., gallopamil retard represents a suitable medication for the treatment of both symptomatic and asymptomatic ischemic episodes, as could be demonstrated in patients with coronary heart disease ascertained by angiography, positive exercise testing, and more than five ischemic episodes in Holter monitoring over 48 h. The results of our study furnish proof that more than 60% of ischemic episodes recorded in patients with stable angina pectoris during Holter monitoring over 48 h, have been asymptomatic, i.e., silent. It must thus be postulated that effective antianginal therapy must be able to suppress both symptomatic and asymptomatic ischemic episodes. This should be documented by Holter monitoring over 48 h. It has not been established yet which criteria: duration of ST-segment depression, frequency of ischemic episodes, or area integral of ST-segment depression, furnish the most adequate parameters for assessment of ischemia. Assessment of the three criteria, taken together, is likely to be most reliable and should thus, in particular, be adhered to in evidencing efficacy in an antianginal drug trial.

Administration, Oral↗

[Surgical therapy of life-threatening tachycardic cardiac arrhythmias in children].

Surgical techniques for tachyarrhythmias refractory to medical treatment are used with increasing frequency. Among 211 patients undergoing antiarrhythmic surgery 10 children (2 to 14 years old) were operated by electrophysiologically directed procedures. 7 patients suffered from WPW syndrome, 2 from focal atrial tachycardias and 1 from recurrent ventricular tachycardia following the repair of Fallot's tetralogy. In all cases preoperative electrophysiologic study and intraoperative mapping preceded operative ablation. Surgical treatment consisted of interruption of the bundle of Kent (3 right-sided, 2 left-sided, 3 septal), ablation of the atrial focus (1 right-sided, 1 left-sided) and right ventricular outflow tract incision. In 7 operations cryo-techniques were added. 2 children with WPW syndrome had two interventions because of tachycardia recurrences due to multiple accessory pathways. In 1 case a VVI-pacemaker was implanted postoperatively due to complete atrioventricular block. Another 2 children with prolonged postoperative bradycardia received a pacemaker prophylactically. Only the child with previous tetralogy of Fallot is still under antiarrhythmic medication while all other children are free of tachycardiac episodes. Our data confirm the efficacy of surgical treatment of tachyarrhythmias in children thereby abolishing the need for life-long antiarrhythmic medication.

Adolescent↗

Alcohol consumption and the perceived situational appropriateness of consuming different types of alcoholic beverages.

Based on a 1986 national probability sample of 2401 Americans aged 21 years and over (1069 of whom were deemed 'drinkers' on the basis of having drunk at least one alcoholic beverage in the past seven days), this study analyses the relationship between respondents' perceptions of how appropriate it is to consume either beer, wine, distilled spirits, or wine coolers in each of six social contexts (namely, at a bar, at a ballgame, 'when the party's really rolling', at a celebration, as a perfect complement to a nice dinner, and after a particularly rough, i.e. difficult, day) and subsequent alcohol consumption by these same individuals. It was hypothesized that people who considered it appropriate to drink a given beverage type would drink more of that beverage than those individuals who deemed consumption of that type of alcohol to be inappropriate. Results indicated that this is valid for certain of the social occasions in terms of the use of beer, distilled spirits and wine. Wine cooler consumption, however, was found to be unrelated to people's perceptions of how appropriate it is to drink in different social situations.

Adult↗

[Virostatic therapy of chronic hepatitis].

Interferons are glycoproteins which exert a potent inhibitory effect on the replication of hepatitis B virus (HBV). Controlled studies of interferon treatment in patients with chronic HBV infection have shown seroconversion rates, from HBeAg positive to anti-HBe positive, 2 to 3 times higher than without treatment. No enhancement of this effect was observed using combinations of interferon with other antiviral substances. The reason for poor therapeutic response to interferon in the majority of patients with chronic hepatitis B may result from its lost virostatic activity against HBV-DNA located in the cell nucleus.

Antiviral Agents↗

Subtyping of group specific component (GC) in human semen, blood and vaginal fluid by isoelectric focusing in immobilized pH gradients.

The group specific component (GC) is stable and well suited for forensic casework. Isoelectric focusing of common GC variants from semen, seminal fluid, vaginal fluid and semen stains, on Immobiline DryPlates, pH 4.5-5.4, is of practical value in criminal investigations of sexual deliquencies. GC is present in normospermia and azoospermia seminal fluids and found in about 20% of the vaginal secretions. The GC patterns observed were similar and in accordance with the bands of the individual GC type in plasma/serum.

Enzyme-Linked Immunosorbent Assay↗

Differentiation of plasma cell infiltrates in the bone marrow. A clinicopathological study on 80 patients including immunohistochemistry and morphometry.

In 80 patients immunohistochemical, morphometrical and clinical studies were performed on routinely referred trephine biopsies of the bone marrow showing an abnormal increase in plasma cells. From the approximately determined density of plasma cell infiltrates two main groups were distinguished, the first with an involvement exceeding 20% and the second with less than 10% of the total marrow area involved. The first group (n = 30; 324 +/- 130 plasma cells per square millimeter bone marrow) consisted of patients with frank malignant myeloma (MM) by clinical and histomorphological diagnosis. The second group (n = 50; 132 +/- 54 plasma cells per square millimeter bone marrow) with plasmacytic differentiation of infiltrates, had to be further divided into one component with evidence for initial or residual MM following chemotherapy (n = 27), another with obviously monoclonal gammopathy of undetermined significance--benign monoclonal gammopathy (BMG, n = 6), and a final set of cases with a reactive plasmacytosis mostly associated with an inflammatory condition (n = 17). There was an excellent agreement between the intracellular immunoglobulin staining as defined by the immunoperoxidase technique and the serum or urinary M-component detected by immunoelectrophoresis. In MM significant correlations were found between osteoclastic activity (number of osteoclasts specifically stained by acid phosphatase) per trabecular bone area, presence of lytic bone defects and the density of plasma cell infiltrates in the marrow. This latter feature corresponded well with the titer of secreted serum M-components measured by quantitative immunoelectrophoresis. Using morphological data alone, BMG cases could not be discriminated with any certainty from initial or residual plasmacytic MM. They consequently need a prolonged clinical follow up to clarify the nature of the lesions.

Bone Marrow↗

Quantitative assessment of endogenous testicular and adrenal sex steroids and of steroid metabolizing enzymes in untreated human prostatic cancerous tissue.

Total tissue content and subcellular distribution of DHEA sulfate, DHEA, androst-5-ene-3 beta,17 beta-diol, androst-4-ene-3,17-dione, testosterone, 5 alpha-DHT, and 5 alpha-androstane-3 alpha,17 beta-diol as well as the activities of steroid sulfate-sulfatase, 17 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase, 3 alpha/beta-hydroxysteroid dehydrogenase, and creatine kinase were quantified in 12 untreated primary tumors of prostatic cancer. Samples were obtained by radical prostatectomy and serial sections, and were alternately used for either biochemical or morphological evaluation. The results were compared with values determined in benign parts of the same prostates. Qualitatively, all enzymes and steroids found in the benign tissues could also be demonstrated in the cancers. Steroid patterns showed individual quantitative variation but no general differences between the carcinomas and the benign tissues. Enzymes showed a tendency to lower activities in the cancers, particularly when expressed per DNA. Substantial diminutions of creatine kinase and 5 alpha-reductase activity, the latter being often accompanied by an increased testosterone/DHT ratio, were the most striking differences seen in most of the cases between malignant and nonmalignant tissues. Some interesting individual parallels of morphological and biochemical aspects were seen, but there was no obvious general parallelism between the histological picture and endocrinological characteristics.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Inhibition of human placental aromatase in a perfusion model. Comparison with kinetic, cell-free experiments.

In vitro perfusion of human placenta was evaluated for characterization of aromatase inhibitors. The results were compared with those in kinetic experiments in cell-free system. Inhibition constants (Ki) were determined by measuring the release of tritiated water during coincubation of human placenta microsomes with varying amounts of [1 beta,2 beta 3H]androstenedione and inhibitor in the presence of NADPH-generating system. Irreversible inactivation constants (Kinact) were determined in a similar manner following preincubation of the microsomes with different amounts of inhibitor for varying times. Lineweaver-Burk plots indicated a competitive type of inhibition with Ki values of 37 nM for 4-hydroxy-androstenedione, 3,700 nM for testolactone, 15 nM for 1-methyl-androsta-1,4-diene-3,17-dione, and 7.5 nM for 19-azido-androstenedione. Additionally, irreversible enzyme inactivation by all four substances could be demonstrated with Kinact values of 3.64 x 10(-3), 0.57 x 10(-3), 0.34 x 10(-3), and 0.69 x 10(-3)sec-1, respectively. Perfusion of a single cotyledon of human term placenta was performed by infusing medium through catheters placed in a fetal artery and in the maternal intervillous space. Perfused medium was collected from a cannulated fetal vein and from the maternal basal plate. The medium was supplemented with [3H]androstenedione (4.2 nM) and inhibitor. The perfusates were analyzed for their [3H]estrone and estradiol content following phenolic partition and Sephadex-LH 20 chromatography. The main results were, (1) the recovery of labelled steroids increased rapidly after perfusion started and reached a plateau within 60 min, when 55 and 30% (mean values) of the infused radioactivity were recovered in the fetal and maternal perfusates, respectively, (2) similar amounts of estrone and estradiol were found in both effluates, whereas androgens (mainly androstenedione and lower amounts of 5 alpha-androstane-3,17-dione) were found nearly exclusively in the fetal perfusate, (3) formation of estrogens (estrone + estradiol) reached a plateau within 20 min of perfusion. (4) The percentage of estrogens formed was not changed by increasing androstenedione concentration in the perfusion medium unless this concentration exceeded 3.5 microM indicating limited capacity of aromatase. (5) The four aromatase inhibitors reduced estrogen formation by 50% at concentrations about 100-fold of their Ki determined in the cell-free system, (6) irreversible aromatase inhibition could not be demonstrated in the perfusion model. It was concluded that the human placenta perfusion model can be successfully used to evaluate aromatase inhibitors.

Androstenedione↗

Surgical alternatives in the treatment of life-threatening ventricular arrhythmias.

We present our experience in the treatment of life-threatening ventricular tachycardia using electrophysiologically guided surgery (97 patients), automatic implantable cardioverter defibrillator (AICD) (42 patients), and orthotopic heart transplantation (15 patients). Eighty-three percent of these patients had ischemic and 17%, nonischemic heart disease. Our results of electrophysiologically directed surgery show an early mortality of 10% and a recurrence of 5% in the ischemic group. In the nonischemic group, the recurrence was 45%. The AICD was implanted in 31 patients with ischemic heart disease, in 5 with ventricular dysplasia, and in 6 with dilative cardiomyopathy, the ejection fractions ranging from 12% to 65%, with a mean of 30%. Early and late mortalities were 5% and 19%, respectively. The AICD was effective in all patients. Survival rate at 1 year was 83% +/- 6.4%. Thirteen of 15 patients have survived heart transplantation for 3-20 months (mean: 11 months). Ejection fractions prior to transplantation ranged from less than 10% to 34% (mean: 16%). We conclude that electrophysiologically guided surgery is highly effective in most cases of ischemia-related ventricular tachycardia. The AICD is considered a palliative alternative in patients with either poor ventricular function, no electrophysiological substrate, or multimorphological tachycardia. Heart transplantation has to be considered especially in young patients in whom progression of the underlying disease can be anticipated. Bridging by AICD is possible when transplantation is not immediately available or recommendable.

Adolescent↗

Rate-responsive pacing as compared to fixed-rate VVI pacing in patients after ablation of the atrioventricular conduction system.

In 44 patients with supraventricular arrhythmias various pacemakers were studied after closed-chest ablation of the atrioventricular conduction system. There were 22 patients with a rate-programmable VVI pacemaker (Group I), 15 patients with an activity mode (ACTIVITRAX 8400) (Group II) and seven patients with a QT-mode pacemaker (QUINTECH 911) (Group III). To study both physical work capacity and heart-rate behaviour, exercise testing was performed using a treadmill. Sixteen patients in Group I (72.7%) complained of shortness of breath during exercise in comparison to four patients (26.7%) in Group II and three patients (42.9%) in Group III. Normal physical work capacity was observed in three of 22 patients (13.6%) in Group I and in all patients in Groups II and III. The heart rate both increased and decreased more rapidly at the onset and end of the stress test, respectively, in patients with activity-mode compared to patients with QT-mode pacing systems. These data show that, despite successful His-bundle ablation, both dyspnea and decreased work capacity are observed when VVI pacemakers are used. In contrast, the use of rate-responsive pacing systems leads to better cardiac performance.

Adult↗

Androgens, adrenal androgen precursors, and their metabolism in untreated primary tumors and lymph node metastases of human prostatic cancer.

Activities of several steroid metabolizing enzymes (steroid sulfate-sulfatase, 17 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase, and 3 alpha beta-hydroxysteroid dehydrogenase) as well as total tissue content and subcellular distribution (nuclear-extranuclear) of several androgen precursors, active androgens, and androgen deactivation products (DHEA sulfate, DHEA, 5-androstenediol, 4-androstenedione, testosterone, DHT, and 3 alpha-androstanediol) were quantified in primary tumors and lymph node metastases of human prostatic cancer obtained from patients without previous endocrine manipulation. Primary tumors were compared to benign parts of the same prostates, and the metastases were compared to their primary tumors. All enzymes and steroids found in benign prostatic tissues could also be detected in the malignant tissues. Even the capacity to accumulate active androgens in the nuclei was found to be unchanged in nearly all of the samples. Lower activities of hormone-dependent enzymes were observed in the cancers, suggesting a less efficient utilization of hormonal stimuli. Most striking changes found in the malignant tissues were a subtotal loss of 5 alpha-reductase activity and a metabolic shift to testosterone, which was more pronounced in samples from metastatic disease as compared to samples from non-metastatic disease. In conclusion, primary tumors and metastases of prostatic cancers not treated by endocrine manipulations retain their androgen receptor system and possess the same capacity to metabolize adrenal androgen precursors along the pathway to DHT as benign prostatic tissue. Consequently, they should be able to use at least androstenedione for production of active androgens directly in the target tissue.

17-Hydroxysteroid Dehydrogenases↗

Ultrastructural studies of the retina in infantile neuronal ceroid-lipofuscinosis.

A 9-year-old boy who had died of infantile neuronal ceroid-lipofuscinosis had experienced retina-derived visual failure. Ophthalmologically and morphologically, his retina was severely atrophic and scarred by a dense fibrillary gliosis while photoreceptor cells had completely disappeared, cells of the bipolar layer had decreased in number and had become atrophic beyond cytologic recognition. Retinal pigment epithelial cells had undergone either atrophy or proliferation. Disease-specific granular lipopigments had accumulated in perikarya and processes of remaining cells and were infrequently associated with melanin within huge melanolipofuscin bodies and RPE cells of sessile and migrating nature, and within cells of the atrophic retina, among them glial cells. The ubiquitous lipopigment accumulation in the retina of this patient was identical to that seen in other childhood forms of NCL and to that observed in canine NCL while the retinopathy likewise resembled that encountered in childhood NCL, and in primary human and canine retinopathia pigmentosa.

Child↗

Evaluation of global and regional left ventricular function using two-dimensional and M-mode echocardiography in patients with an automatic implantable cardioverter defibrillator.

The effects of glued epicardial patch electrodes of the automatic implantable cardioverter defibrillator on the left ventricular function was studied by two-dimensional and M-mode echocardiography in 15 patients. Pre- and postoperative end-diastolic and end-systolic left ventricular cross-sectional areas were evaluated using planimetry. Regional left ventricular wall motion at the level of the left ventricular patch electrode was analyzed by two end-diastolic and end-systolic perpendicular axes. Left ventricular end-diastolic and end-systolic diameters as well as E-point-septal-separation and fractional shortening were analyzed using M-mode echocardiography. The mean time interval between preoperative echocardiograms and implantation of the automatic defibrillator was 0.3 X 1.3 (less than 1-2) months. Postoperative echocardiograms were recorded 6.6 +/- 6.9 (0.5-24) months after implantation of the device. There were no significant differences between pre- and postoperative mean values of end-diastolic and end-systolic areas and axes as well as M-mode echocardiographic parameters. Our data show that left ventricular patch electrodes do not significantly alter global or regional left ventricular function in patients after implantation of the automatic defibrillator.

Adult↗

[Incidence of sudden cardiac death in patients with 2-vessel coronary disease in relation to anatomy and rhythm profile].

102 patients with angiographically documented double vessel coronary artery disease were followed for 1-83 months (mean: 42 months). Incidence of sudden death was studied in relation to location and severity of coronary artery lesions, left ventricular wall motion and ventricular arrhythmias found during long-term ECG monitoring. The incidence of sudden death was 30.5% (18/59 cases) in patients with lesions of the left anterior descending branch (LAD) and the right coronary artery (RCA) (Group GI), 26.1% (6/23 cases) in patients with lesions of the LAD and the left circumflex coronary artery (LCX) (Group G II) and 10.0% (2/20 cases) in patients with lesions of the RCA and the LCX (Group G III) (p less than 0.05). The incidence of isolated ventricular beats and complex arrhythmias was significantly higher in patients who died suddenly in both Group I and Group II compared to Group III (p less than 0.05). Our data show that in patients with double vessel coronary artery disease there is an increased risk of sudden death if the LAD is involved, particularly in the presence of complex arrhythmias.

Adult↗

[Torsade de pointes ventricular tachycardia in idiopathic QT syndrome: successful treatment with AAI pacing].

A 30-year-old woman with an idiopathic long QT-syndrome developed recurrent episodes of torsade de pointes ventricular tachycardia. Therapy with beta blocking agents and exhairesis of the left ganglion stellatum had failed to suppress these life-threatening tachyarrhythmias. After implantation of an AAI pacemaker system these ventricular arrhythmias disappeared. The patient remained without ventricular arrhythmias up to the time of discharge and during a 5 months' follow-up.

Adult↗

[Sudden cardiac death and arrhythmia profile in patients with single-vessel coronary disease].

214 patients with single vessel disease (high grade stenosis greater than or equal to 75% or occlusion of the LAD, RCA or LCX) were followed for 1-78 months, average 51 months. Incidence of sudden death was studied in relation to coronary artery lesions, left ventricular wall motion and ventricular arrhythmias found during ambulatory ECG monitoring at the time of angiography. Incidence of sudden death was 11.1% (16/144) in LAD, 7.3% (4/55) in RCA and 6.7% (1/15) in LCX lesions. Coronary artery occlusion was associated with a significantly higher incidence of sudden death (14.6%, 18/123) than high-grade stenosis (3.3%, 3/91) (p less than 0.05). The risk of sudden death increased markedly in patients with complex arrhythmias and an occluded LAD or RCA (21.0%, 8/38; 18.2%, 2/11) compared to patients without complex arrhythmias (14.7%, 5/34; 5.5%, 1/18) (p = ns). Only one patient (1/15, 6.7%) with an isolated LCX lesion died suddenly. Our data show that the incidence of sudden death over 51 months is relatively low in patients with single vessel disease. However, LAD occlusion or RCA lesion with akinetic left ventricular areas and complex arrhythmias are independent predictors of sudden death.

Adult↗

[Pathophysiologic principles of ventricular late potentials--mechanisms].

The majority of sustained ventricular tachycardias are caused by a reentry mechanism. Conditions prerequisite to a reentry circuit are electrophysiological changes, namely conduction delay and block which are incurred by virtue of changes in the myocardial tissue due to scarring, ischemia or fatty infiltration and result in an abnormal action potential, increased intracellular resistance and reduction in intercellular coupling (intercalated discs). Additionally, the principle of anisotropy, that is, the varying velocity of conduction parallel and perpendicular to the fiber axis (increased axial resistance) can also be responsible for circling movement. A further factor predisposing to ventricular tachyarrhythmias is the heterogeneity of repolarization. Delayed and inhomogeneous spread of conduction in morphologically altered tissue can be detected invasively as delayed and fragmented electrograms during sinus rhythm and induced ventricular tachycardia and noninvasively as high-frequency signals which begin in the terminal portion of the QRS complex and can extend far into the ST segment. In a study on our service, electrograms from post-infarct patients with sustained ventricular tachycardia were compared with those without ventricular arrhythmias. In patients with ventricular tachycardia there was markedly delayed activation (greater than 100 ms after begin of the QRS complex, mean 137 ms) over the infarct area. In patients with ventricular arrhythmias, three electrogram types could be differentiated: 1. a delayed singular deflection at the end of the QRS complex (late potential); 2. a diminished amplitude of the electrogram as well as fragmentation into many single deflections for a duration of more than 100 ms; 3. two deflections clearly distinguishable from each other. All three electrogram types represent a different extent of delayed conduction. With one singular late potential there is homogeneous conduction delay throughout the entire region of tissue under the electrode; with fragmentation there is desynchronization of the spread of conduction; with double potentials there are structures of two different velocities of conduction next to or above each other. In almost all patients with ventricular tachycardias fragmented electrograms could be registered in a circumscribed region, in more than one-half there were double potentials. The areas from which abnormal electrograms could be registered were significantly larger in patients with ventricular tachycardias than in those without tachycardia.(ABSTRACT TRUNCATED AT 400 WORDS)

Atrioventricular Node↗