Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Atrial Arrhythmias in Long-QT Syndrome under Daily Life Conditions: A Nested Case Control Study

Background: The long-QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have associated defects in LQTS-causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily-life conditions.
Methods: We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case-control study. Twenty-one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher-degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results: One-third (7 of 21) of the LQTS patients developed self-terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions: LQTS patients at high risk for ventricular arrhythmias may develop short-lasting atrial arrhythmias under daily-life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.     

Anomalous Mitral Arcade: Echocardiographic and Color Flow Findings

A patient with surgically confirmed anomalous mitral valve arcade was noninvasively studied. Two-dimensional echocardiography clearly visualized the "arcade" shape and Doppler color flow mapping was useful in assessing hemodynamics. (ECHOCARDIOGRAPHY, Volume 8, November 1991)     

Thin Primary Cutaneous Melanoma in Childhood and Adolescence: Report of 12 Cases

Abstract:  Approximately, 1–4% of all new melanoma cases occur in patients younger than 20 years. The clinical presentation of melanoma in the young is often challenging. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. Study subjects were drawn from 1470 patients with histologically confirmed melanoma. From this group, melanoma developed in 12 patients younger than 19 years. For each melanoma diagnosed, histologic characteristics, treatment, and outcomes were evaluated. Of the 12 patients described in this study, four were men and eight were women. The average age was 15.6 years ranging from 11 to 18 years. Regarding invasive melanomas, Breslow thickness ranged from 0.15 to 0.66 mm with a mean thickness of 0.36 mm. Primary treatment of 12 patients included wide local excision of their primary lesions. In many cases reported in literature lesions are amelanotic, nodular, and resemble pyogenic granuloma. From our case studies it was found that the clinical characteristics detected in melanomas diagnosed in childhood and adolescence have been the same as those described in adults and that the ABCDE clinical criteria may be helpful basics of melanoma.     

Conformational preferences and self-association modes of two diastereomeric statine derivatives

The conformational preferences and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 6-methylheptanoic acid (statine) with (R, S) and (S, S) configurations at the 3-hydroxy and 4-amino carbons, respectively, have been determined in solution as well as in the solid state by infrared absorption, ¹H nuclear magnetic resonance, and X-ray diffraction. Conformational energy computations have also been performed in parallel. In the crystal state, the change in chirality of the hydroxyl group induces different intermolecular H-bonding schemes in the (R, S) isomer compared to the two structurally distinct molecules in the asymmetric unit of the (S, S) isomer. Different propensities to self-aggregate are seen in solvents of low polarity. In solvents of high polarity, however, the molecules of both isomers are largely solvated, while still keeping some local conformational restriction. Conformational energy computations indicate that in vacuo the two diastereomers exhibit different flexibility, and a preferred conformation with a different type of intramolecular H-bond.     

Unexpected Discharge from an Implanted Automatic Defibrillator

The occurrence of inappropriate discharge from an implanted cardioverter-defibrillator is reported. The device was triggered by an episode of induced nonsustained ventricular tachycardia, and the shock was delivered 10 sec after spontaneous termination of the arrhythmia.
This observation demonstrates that unexpected discharges from an implanted cardiaverter/defibrillator can occur while the patient is asymptomatic. In order to avoid such an adverse effect, improvement of the detection system of the device is advisable.     

A Population-based Study of Toenail Onychomycosis in Israeli Children

Abstract:   Onychomycosis is widespread in the adult population, but considered to be rare in children. A number of studies in recent years show a rise in the prevalence of toenail onychomycosis in children. Of these, only a few were population-based. Here, we present a comprehensive cross-sectional population-based survey of toenail onychomycosis in primary school children in Israel. The survey included 1148 children, 598 boys, and 550 girls aged 5 to 14 from primary schools in the Jerusalem vicinity. Each child underwent a physical examination and completed a personal questionnaire, which provided background information of predisposing factors. The survey shows a prevalence of 0.87% of toenail onychomycosis. Although this figure is too small for statistical analysis, some important conclusions could be drawn: prevalence increased with age: boy/girl ratio was 2.2; the dominant etiologic agent was Trichophyton rubrum followed by Trichophyton mentagrophytes and Candida albicans . Infections were probably transferred from adults via the environment to children. Infected children came from different socio-economic backgrounds. This condition should be considered in the differential diagnosis of nail diseases in children.     

Testicular function in eight patients with seminoma after unilateral orchidectomy and radiotherapy

Testicular function was monitored in eight patients with low stage seminoma who were treated with radiotherapy following unilateral orchidectomy. The absorbed gonadal radiation dose ranged from 15 to 157.5 rad. At 10-24 months after radiotherapy, serum hormone levels, sperm analysis, sperm penetration into zona-free hamster ova (HOP-test) and lymphocyte chromosome abnormalities were evaluated. Two patients were azoospermic with elevated serum levels of LH and FSH. The remaining six patients had slightly decreased (n = 3) or normal (n = 3) seminal parameters. Their HOP rates were within the normal range. A low incidence of polyspermy (i.e. only one penetrating sperm per ovum) was found in the patients, suggesting low penetrability of motile sperm. A highly significant correlation was found between sperm count or sperm penetrability and time post-irradiation. The results indicate that restitution of testicular function is time-dependent.     

Predictors of Ventricular Tachvcardia Inducibility in Programmed Electrical Stimulation and the Effectiveness of Serial Drug Testing: Polish Multicenter Study

WNUK-WOJNAR, A.M., ET AL.: Predictors of Ventricular Tachycardia Inducibility in Programmed Electrical Stimulation and Effectiveness of Serial Drug Testing: Polish Multicenter Study. In 100 patients with IHD and complex ventricular arrhythmias, programmed electrical stimulation was performed using up to three extrastimuli at sinus rhythm, and paced 100, 120, and 140 beats/min delivered from the RV apex, outflow tract or the LV with ventricular mapping to evaluate late potentials (LP) in 41 patients. Sustained monomorphic VT (SMVT) was provoked in 91% of 42 patients with a history of VT/VF, p < 0.001, all five patients had SMVT in 24-hour ECG, p < 0.005, and 91% of 21 patients with LV dyskinesis, p < 0.01. After depolarizations were found in 62% of 21 patients with a history of VT, in 58% of 31 patients with inducible VT, p < 0.01 and in five of six patients with LV dyskinesis. In patients with inducible VT, LP had a higher amplitude (105 ± 35 vs 60 ± 47 µV) and were more delayed (202 ± 96 vs 133 ± 75 msec) than in noninducible patients. In 17 patients, serial drug testing was performed after oral administration using mexilitene, disopyramide, chinidine, propafenone, sotalol, and amiodarone. If one drug was tested, the therapy efficacy was 25% if two drugs-60%, and if three drugs-75%. In eight patients, VT was inducible in all tests, but in only one of these patients chronic antiarrhythmic therapy was not effective. We conclude that the most important predictors of VT inducibility are a history of VT or 24-hour ECG, and LV dyskinesis. Serial drug testing is efficient only when many drugs are tested, but even if VT is inducible, it does not exclude the possibility of a good clinical outcome in chronic therapy.     

Baroreflex Sensitivity as a Cardiac and Arrhythmia Mortality Risk Stratifier

The last two decades have provided clear evidence for the tight and casual relation existing between arrhythmic mortality and the autonomic nervous system, particularly with imbalances characterized by decreases in vagal and/or increases in sympathetic activity. A series of compelling experimental results has represented the driving force for the clinical evaluation of the potential prognostic value of baroreflex sensitivity (BBS), a measure that can provide information on the capability to augment vagal activity. This article reviews the methodology more commonly used to quantify the clinical evaluation of this parameter, and then focuses on the key clinical studies highlighting those performed in postmyocardial infarction patients. Among them the most informative is ATRAMI, a multicenter prospective study involving almost 1300 patients. The main conclusion is that both heart rate variability and BRS are strong and independent risk factors for post-infarction mortality, thus demonstrating the clinical usefulness of autonomic markers.