Dietary genistein stimulates anion secretion across female murine intestine

Genistein, a naturally occurring isoflavone, augments in vitro epithelial anion transport via activation of the cystic fibrosis transmembrane conductance regulator chloride channel. In this study, we examined whether chronic dietary exposure to 600 mg/kg genistein (600 G) for 1 mo would stimulate anion secretion across wild-type (Wt, normal) murine intestine. Anion secretion was assessed in freshly excised segments of murine jejuna by measuring short circuit current (I(sc)) and comparing with jejunal segments from mice fed 0 mg/kg genistein (0 G). Basal and forskolin-stimulated anion secretions were augmented (P < 0.05) in female but not in male mice fed 600 G, compared with their counterparts fed 0 G. Serum genistein concentrations were greater in both female and male mice fed 600 G (approximately 3.5-6.9 micromol/L) than those fed 0 G (approximately 100 nmol/L). Anion substitution experiments and bumetanide-sensitivity demonstrated that chloride was the major anion mediating the increased secretion. A smaller bicarbonate component was not augmented by consumption of the genistein diet. These data indicate that chronic exposure to dietary genistein stimulates a sex-dependent increase in basal and forskolin-stimulated chloride secretion across murine intestine.     

Immunological identification of lactoferrin as a shared antigen on radioiodinated human sperm surface and in radioiodinated human seminal plasma

After lactoperoxidase-catalyzed iodination of either human sperm surface or human seminal plasma, a 72–76 kdalton component was resolved on SDS-7.5% polyacrylamide gels. The approximate molecular weight of this component was consistent with that of human lactoferrin, a major sperm-coating antigen. Immunoprecipitation of labeled sperm surface and of labeled seminal plasma with specific anti-human lactoferrin antibody identified lactoferrin as a constituent of this 72–76 kdalton component both on human sperm surface and in human seminal plasma. These data show that components which have been inferred to be shared because of similarities in biochemical characteristics also contain immunologically identical components.     

The development and preliminary validation of a brief measure of chronic pain impact for use in the general population

From a biopsychosocial perspective, assessing chronic pain's psychological impact should involve at minimum the measurement of pain severity, functional interference, and pain-related emotional burden. This article details the development of a brief instrument, the 15-item Profile of Chronic Pain: Screen (PCP:S), designed to address these three key elements in a national (US) sample of over 2400 individuals recruited via random digit dialing. Retest reliability, internal consistency, and preliminary validity were excellent. The scales also demonstrated minimal social desirability response bias. A series of confirmatory factor analyses on several distinct samples revealed a stable, 3-factor solution reflecting pain severity, interference, and emotional burden. Finally, national norms were developed by gender and three age groups. In view of its strong psychometric properties, the PCP:S has the potential to serve as a brief, cost-effective assessment tool for identifying individuals whose chronic pain merits more detailed psychosocial evaluation.     

Surgical dilemma: liver resection or liver transplantation for hepatocellular carcinoma and cirrhosis. Intention-to-treat analysis in patients within and outwith Milan criteria

Background:

The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution.

Objective:

The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis.

Methods:

During 1997–2007, 179 patients with cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child–Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT).

Results:

The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups (P= 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P= 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis.

Conclusions:

Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.