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.     

A Permanently Implanted Endocardial Electrode Complicating Ventricular Tachycardia with A Second VT

A VVI pacemalter was permanently implanted for the purpose of suppressing recurrent ventricular tachycardia (VT). Not only did the device fail to suppress the VT, but also the permanent endocardial electrode caused a second VT which was more rapid and clinically more severe. When a new VT occurs in the presence of a permanently implanted ventricular pacing system, the implanted electrode should he considered as one of the possible etiologic causes for the VT.     

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.     

Hormonal and metabolic characteristics of geneticall obese Zucker and dietar obese Sprague-Dawle rats

Abstract. The endocrine-metabolic plasma pattern and the capacit of isolated perfused livers to produce triglcerides and ketone bodies have been studied in geneticall and diet-acquired obese rats (Zucker and Sprague-Dawle obese rats), and in control groups of the same strains.
An increased plasma insulin/glucagon molar ratio with hperinsulinaemia and hpoglucagonaemia was associated with hpertriglceridaemia, normal ketonaemia, elevated free fatt acids and normal or slight hperglcaemia in obese rats.
During oleate perfusion, the livers of Zucker and Sprague-Dawle obese rats showed an increase in triglceride output and liver triglceride content. The ketone bod output as well as the mitochondrial carnitine palmitol transferase activit were normal or slightl decreased.
In our rat population, a positive correlation between the insulin/glucagon molar ratio and triglceride output has been found.     

Swine as an In Vivo Model for Electrophysiologic Evaluation of Cardiac Pacing Parameters

Pre-clinical studies of cardiac pacemakers and new electrodes, materials, and designs are for the most part conducted in dogs. Dogs, however, have electrophysiological differences which may preclude accurate translation to clinical trials. The purpose of this study was to develop normal electrophysiological parameters for an animal whose cardiovascular system more closely resembles that of man than any nonprimate animal. The threshold (voltage and current) strength-duration curves of the pig showed the same inverse relationship between the pulse duration and threshold requirements as other species. At 0.5 ms the atrium had 3.5-5.5 times greater energy requirements, over twice the current (2.04 mA vs 0.72 mA) and twice the voltage (0.75 mV vs 0.32 mV) requirements when compared to the ventricles. The pig's S-A nodal P-wave was superior in amplitude (7.80 +/- 1.80 mV vs 4.28 +/- 2.27 mV) and the slew rate was faster (1.30 +/- 0.56 mV/ms vs 0.44 +/- 0.50 mV/ms) compared to that of the atrial appendage. The pig's left ventricular myocardial R-wave had significantly greater amplitude (19.00 +/- 6.44 mV vs 10.70 +/- 4.34 mV) and faster slew rate (1.60 +/- 0.62 mV/ms vs 0.90 +/- 0.30 mV/ms) compared to the right ventricular endocardial R-wave. The electrophysiological parameters of the pig were more similar to those of man than the dog; therefore, the pig is a useful animal model for electrophysiological studies and the testing of pacemaker equipment.     

Relationship between European Mitochondrial Haplogroups and Chronic Renal Allograft Rejection in Patients with Kidney Transplant

Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom''s MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction.     

Type II antithrombin deficiency caused by a large in‐frame insertion: structural,functional and pathological relevance

Summary. Background: The metastable native conformation of serpins is required for their protease inhibition mechanism, but also renders them vulnerable to missense mutations that promote protein misfolding with pathological consequences. Objective: To characterize the first antithrombin deficiency caused by a large in‐frame insertion. Patients/Methods: Functional, biochemical and molecular analysis of the proband and relatives was performed. Recombinant antithrombin was expressed in HEK‐EBNA cells. Plasma and recombinant antithrombins were purified and sequenced by Edman degradation. The stability was evaluated by calorimetry. Reactive centre loop (RCL) exposure was determined by thrombin cleavage. Mutant antithrombin was crystallized as a dimer with latent plasma antithrombin. Results: The patient, with a spontaneous pulmonary embolism, belongs to a family with significant thrombotic history. We identified a complex heterozygous in‐frame insertion of 24 bp in SERPINC1, affecting strand 3 of β‐sheet A, a region highly conserved in serpins. Surprisingly, the insertion resulted in a type II antithrombin deficiency with heparin binding defect. The mutant antithrombin, with a molecular weight of 59 kDa, had a proteolytic cleavage at W49 but maintained the N‐terminal disulphide bonds, and was conformationally sensitive. The variant was non‐inhibitory. Analysis of the crystal structure of the hyperstable recombinant protein showed that the inserted sequence annealed into β‐sheet A as the fourth strand, and maintained a native RCL. Conclusions: This is the first case of a large in frame‐insertion that allows correct folding, glycosylation, and secretion of a serpin, resulting in a conformationally sensitive non‐inhibitory variant, which acquires a hyperstable conformation with a native RCL.     

Home Monitoring in Patients with Implantable Cardiac Devices: Is There a Potential Reduction of Stroke Risk? Results from a Computer Model Tested Through Monte Carlo Simulations

Introduction: Patients with pacemakers and implantable defibrillators (ICD) may experience asymptomatic atrial fibrillation (AF), detected with a delay depending on the in-person follow-up schedule. Home monitoring (HM) remote control with automatic alerts for AF may drive early anticoagulation, potentially reducing stroke risk.
Methods and Results: A sample of 136 pacemaker (103) and ICD (33) patients with or without cardiac resynchronization therapy not taking anticoagulation at implant were monitored remotely with HM. Upon HM alerts for AF, patients were recalled to update therapy. Two-year data were entered in a computer Monte Carlo model, simulating 4,000 virtual subjects with the same AF and CHADS₂ stroke risk distribution of our real population. Simulations reproduced a 2-year follow-up. Two thousand subjects were supposed to be followed with HM (HM group) and 2,000 with standard in-person follow-up (SF group) at 3, 6, 9, or 12 months.
Two-year Kaplan-Meier cumulative probability of ≥24-hour AF was 15.6% (95%CI 8.5–23.3%); the AF-related symptom rate was 27% and the median CHADS₂ score was 2. As a result of simulations, stroke incidence in case of AF was 2.3 ± 1.1% in the HM group and 2.4 ± 1.1%, 2.5 ± 1.2%, 2.7 ± 1.2%, and 2.9 ± 1.3% in the SF group with 3-, 6-, 9-, and 12-month follow-up programs, with odds ratios of 0.97 (95%CI 0.93–1.01), 0.91 (0.88–0.95), 0.87 (0.84–0.90), and 0.82 (0.79–0.85) (HM better if odds ratios <1), respectively.
Conclusions: Daily HM potentially reduces the stroke risk by 9% to 18% with respect to SF with intervisit intervals of 6 to 12 months.     

Lower extremity bone mineral density in children with congenital spinal dysfunction

Aim  To assess lower extremity bone mineral density (BMD) of children with congenital spinal dysfunction and examine factors that may influence BMD in this population. Method  Forty‐four children (25 females, 19 males) aged 6 to 18 years (mean 11y 11mo, SD 3y 6mo) with congenital spinal dysfunction (35 with myelomeningocele, seven with lipomas, one with sacral agenesis, one with caudal regression) were enrolled in the study. A health survey including ambulatory status, history of bladder augmentation, and history of fracture was administered. Each participant had a physical examination including Tanner stage and neurological level. Dual‐energy X‐ray absorptiometry scans of the lateral distal femur (LDF) and, when possible, lumbar spine were obtained. We reported LDF BMD results as z‐scores for three regions of interest (metaphyseal, metadiaphyseal, and diaphyseal). Univariable and multivariable analyses examined relationships between LDF BMD and the other variables. Results  BMD was significantly related to ambulatory status (14 non‐ambulatory, 15 partly ambulatory, 15 fully ambulatory) and neurological level (13 with low‐level lesions, 15 medium‐level, 16 high‐level) in the univariable analysis (p<0.01 for both in all three regions). Neither history of fracture, nor Tanner stage, nor history of bladder augmentation showed a significant relationship to BMD. The significance of ambulatory status and neurological level in the univariable analysis failed to persist in the multivariable analysis of this study with a small sample size. Interpretation  The LDF measurement proved to be a viable technique for assessing BMD in children with congenital spinal dysfunction. LDF BMD was sensitive to differences in three categories of ambulation. The overall influence of neurological level was not deemed as important as ambulation.