Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

The αβ T Cell Receptor Clustering Upon Superantigen/MHC Recognition

Antigen recognition by T cells is the key event for the antigen specific immune responses to be triggered. This recognition is initiated by the binding of the T cell receptor (TCR) to antigen peptide/major histocompatibility complex (MHC) on the surface of the antigen presenting cells. TCR on most of the T cells is a heterodimer composed of α and β chains which are associated with CD3 γδε as well as ζ chains, the signal transmission molecules. The dynamics of this TCR complex upon antigen/MHC recognition, however, has not been well understood. In this paper the authors analyse the configuration of TCR complex on T cells from a TCR β chain gene transgenic mouse (TGM) strain. Unlike many other TGM strains reported, a considerable proportion of T cells from this TGM expresses both transgene-encoded (Vβ3) and endogenous TCR β chains on their surface. By immunoprecipitation and immunoblotting analysis of T cells stimulated with a superantigen, staphylococcal enterotoxin B (SEB), the authors found that Vβ3 was coprecipitated with Vβ8, demonstrating the clustering of TCR αβ upon superantigen/MHC recognition.     

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo

Background : We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo .
Methods : We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs.
Results : YF476 replaced the specific binding of [¹²⁵I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with K _i values of 0.068, 0.62 and 0.19 n M , respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED ₅₀ value of 0.0086 μmol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 μmol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED ₅₀ values of 0.018 and 0.020 μmol/kg, respectively, but did not affect histamine-induced acid secretion.
Conclusion : These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.     

Effects of participatory workplace improvement program on stress-related biomarkers and self-reported stress among university hospital nurses: a preliminary study

Although participatory workplace improvement programs are known to provide favorable effects on high stress occupations like nursing, no studies have confirmed its effect using biomarkers. The aim of this study was to determine whether a participatory workplace improvement program would decrease stress-related symptoms as evaluated by biomarkers and self-reported stress among hospital nurses. Three actions to alleviate job stress, which were determined through focus group interviews and voting, were undertaken for two months. A total of 31 female Japanese nurses underwent measurement of inflammatory markers, autonomic nervous activity (ANA), and perceived job stress (PJS) at three-time points; before the program (T1), within a week after the completion of the program (T2), and three months after the program (T3). A series of inflammatory markers (Interferon-γ, Interleukin (IL)-6, and IL-12/23p40) decreased significantly at T2, and IL-12/23p40 and IL-15 significantly decreased at T3 compared to T1, while ANA and PJS remained unchanged. Our participatory program exerted beneficial effects in reducing inflammatory responses, but not for ANA and PJS. Further investigations with a better study design, i.e., a randomized controlled trial, and a larger sample size are warranted to determine what exerted beneficial effects on inflammatory markers and why other outcomes remained unchanged.     

Inherited electrophoretic variants detected in a Japanese population with two-dimensional gels of erythrocyte lysates

Genetic variation has been studied in erythrocyte lysates from 100 Japanese children and their parents by means of two-dimensional polyacrylamide gel electrophoresis. Fifty-five polypeptides selected without respect to variability were considered suitable for scoring. Genetic variation was encountered in 14 of these polypeptides. Family data show that the segregation of 13 variants is consistent with an autosomal codominant mode of inheritance; the remaining variant exhibits a sex-linked mode of inheritance. Of 8 presumably identical polypeptides found variable in Japanese and/or Caucasians, differences in the occurrence or allele frequencies of polymorphisms were recognized for four. Contrary to the experience of some investigators, the amount of variation and the ethnic differences we are encountering indicate that two-dimensional polyacrylamide gel electrophoresis is a sensitive tool for the study of genetic events.     

Crohn's Disease Initially Suggested by Minute Esophageal Erosions—Report of a Case

A 19–year-old woman visited our hospital complaining of fever and epigastral-gia. Upper gastrointestinal endoscopy showed minute discrete erosions surrounded by elevated mucosa about one millimeter in diameter in the esophagus and aphthoid erosions in the stomach. Biopsy samples obtained from the esophagus showed non-caseating epitheloid granulomas, suggesting Crohn's disease. Colonoscopy showed a small erosion in the cecum adjacent to the vermiform appendix and biopsy showed non-caseating epitheloid granulomas and Crohn's disease was diagnosed. In hospital, she was treated with elemental diet and 5–aminosalicyclic acid. Clinical symptoms disappeared rapidly and laboratory data became normal. We thus report a rare case of early-stage Crohn's disease initially indicated by biopsy of minute esophageal erosions. (Dig Endosc 1999; 11: 255–258)     

Electrophysiologic Evaluation of Asymptomatic Patients with the Wolff-Parkinson-White Pattern

In the past 4 years, 34 asymptomatic patients with the Wolff-Parkinson-White (WPW) pattern underwent electrophysiologic study. The effective refractory period (ERP) of antegrade conduction over the accessory pathway was 288 +/- 29 msec. In three asymptomatic patients (9%), the antegrade ERP of the accessory pathway was shorter than 250 msec. The antegrade ERP of the accessory pathway became shorter than 250 msec in an additional 12 of 22 (55%) patients after isoproterenol administration. Nineteen (56%) of the asymptomatic patients showed the absence of retrograde conduction over the accessory pathway even after isoproterenol administration. The rate of induction of orthodromic reciprocating tachycardia in the asymptomatic WPW patients was 15% (5/34), which was significantly lower than that in the symptomatic patients. These data suggest that in the asymptomatic patients, the absence of retrograde conduction over the accessory pathway is the reason they remained asymptomatic, free of reciprocating tachycardia. However, even in the asymptomatic patients, some had the accessory pathway in which antegrade ERP was shorter than 250 msec. They may result in rapid ventricular conduction over the accessory pathway when atrial fibrillation develops.