A Canine Model of Torsades de Pointes

Although quinidine has been reported to induce QT interval prolongation and torsades de pointes clinically, the only experimental model currently available for quinidine-induced torsades de pointes requires the concurrent use of ischemia, reperfusion and cardiac pacing of the isolated, perfused heart. Our purpose in this study was to determine the circumstances under which quinidine might elicit torsades de pointes consistently in the intact dog. We found that maintenance of therapeutic plasma quinidine concentrations, alone, did not induce the arrhythmia. Rather, arrhythmia induction required the additional application of aconitine, which induces early afterdepolarizations and triggered activity. When aconitine was applied to two epicardial sites in dogs having quinidine-induced QT interval prolongation greater than 10%, torsades de pointes occurred in 80% of instances. When QT prolongation was less than 10%, aconitine-induced torsades de pointes was seen in only 21% of animals. Our results suggest that in a previously healthy heart quinidine-induced QT prolongation is, itself, insufficient to induce torsades de pointes consistently, and two independent sites of ectopic activity are needed as well. The ectopic foci appear to modulate one another's impulse initiation or activation sequence, thereby giving rise to the classical "twisting of the points" associated with the arrhythmia.     

β-defensins and the epididymis: contrasting influences of prenatal,postnatal, and adult scenarios

β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility.     

Bacterial penetration through temporary restorative materials in root-canal-treated teeth in vitro

Seventy extracted single-rooted mandibular premolars were used in this study to determine the length of time needed for bacteria present in natural human saliva to penetrate through three commonly used temporary restorative materials and through the entire root canal system obturated with the lateral condensation technique. Five intact teeth with no decay were used in the negative control group and five teeth with extensive decay in communication with the canal, in the positive control group. The 60 teeth used in the experimental group were divided into three groups. In Group 1, the access cavities of 20 teeth were temporarily restored with gutta percha, in Group 2 with IRM and in Group 3 with Cavit-G. All 70 teeth were mounted individually where the crown was placed in contact with human saliva. All five teeth in the positive control group caused broth turbidity within 24 h. In contrast, broth in the negative control group remained clear throughout the entire experimental period. In the experimental group, the average time for broth contamination of access cavities closed with gutta percha, IRM and Cavit-G was 7.85, 12.95 and 9.80 days, respectively. The Kruskal-Wallis nonparametric test showed significant differences among the groups, while the multiple comparison test showed that the IRM group was statistically better than the gutta percha group when the average lengths of time for contamination were compared ( P < 0.05).     

Serum eosinophilic cationic protein may predict clinical course of wheezing in young children

Thirty eight children aged between 2 and 4 years with three or more episodes of wheezing were studied to evaluate the role of eosinophil inflammation and its relation to persistence of wheezing two years later. Serum eosinophilic cationic protein, total eosinophil count, total IgE, skin prick test, and clinical features were evaluated at visit 1. Two years later at a second clinical evaluation the children were separated into two groups: group 1, those with persistent wheezing (n = 20); group 2, those who had been asymptomatic over the past six months (transient wheezing) (n = 18). Mean (SEM) eosinophilic cationic protein at visit 1 was higher in group 1 than in group 2 (29.63 (5.16) v 14.42 (2.77) micrograms/l), and the probability of continuing wheezing at age 5 years was greater in children with values > or = 20 micrograms/l at visit 1 than in those with lower values (relative risk = 2.88, 95% confidence interval 1.42 to 5.87, p < 0.001). Eosinophil inflammation is present from the beginning of the disease in the children who are going to continue with wheezing at age 5 years. The measurement of serum eosinophilic cationic protein may help in evaluating which wheezing infants are going to continue with asthma in the future.     

Adenocarcinoma of prostate: Role of 17β-estradiol and 5α-dihydroterosterone binding proteins

Presence of a specific 17β-estradiol-binding protein in prostates of patients with adenocarcinoma without hormonal manipulation prior to surgical resection has been reported by us earlier.' The present study involves 40 patients with carcinoma of prostate analyzed during the period December, 1974, through June, 1978. Thirty-four patients had metastatic disease, 26 of these were manipulated hormonally after and 8 prior to receptor protein assay. The other 6 were in clinical Stage C and were subjected to transurethral resection alone. The study confirms our earlier report and outlines the role of 17β-estradiol (E₂) and possibly 5_α-dihydrotestosterone (DHT) receptor protein in hormonally responsive and refractory patients. Based on the preliminary findings it seems possible to classify the prostatic carcinoma similar to human mammary cancer for the purpose of selecting patients for endocrine manipulation or treatment with other available modalities.