Incidence and clinical significance of false-negative sextant prostate biopsies

PURPOSE: Since most patients do not undergo repeat sextant prostate biopsies after a biopsy is positive for prostate cancer, the true incidence of false-negative biopsies is not well defined. We assess the incidence and clinical significance of false-negative sextant prostate biopsies in patients undergoing radical prostatectomy. MATERIALS AND METHODS: A total of 118 patients with biopsy proved prostate cancer underwent repeat sextant prostate biopsy before enrollment in a prospective randomized trial of radical prostatectomy with or without neoadjuvant hormonal therapy. Clinical parameters were assessed to determine potential sources of bias. Pathological parameters and prostate specific antigen relapse-free survival rates were compared to determine the clinical significance of false-negative biopsies. RESULTS: Of the 118 patients 27 (23%) had a negative repeat sextant biopsy. Except for initial clinical stage, no differences were noted in the clinical or pathological parameters, or prostate specific antigen relapse rates in patients with negative versus positive repeat biopsies. CONCLUSIONS: Our findings suggest that this 23% incidence of false-negative biopsies represents significant cancer. This relatively high incidence is important to consider in treatment modalities in which prostate biopsy may be performed to determine response to therapy.     

Effect of a high-beef diet on the fecal bacterial flora of humans

Ten human volunteers completed a 4-month diet series consisting of 1 month each of a control diet, a meatless diet, a high-beef diet, and the same control diet. Fat and fiber contents were essentially the same in all four diets, but protein content was doubled during the high-beef diet. During the 4th week on each diet, three stool specimens collected from each volunteer were analyzed for chemical composition and content of facultative, aerobic, and anaerobic bacteria. The bacteriological data are presented in this paper. High beef protein consumption had little effect on the composition of the intestinal flora. There were no significant differences in total counts of facultative and aerobic or anaerobic organisms in the feces when volunteers were on meatless or high-beef diets. At the species level, when counts during the two control diets were comparable, in only three instances did the change from the meatless to a high-beef diet significantly influence the bacterial numbers. The ratio of mean counts of anaerobic to facultative and aerobic organisms was approximately 15:1 during the meatless diet and 34:1 during the high-meat diet. The data indicate that animal protein consumption has little effect on the fecal bacterial profile in humans.     

Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism

Raf-1, A-Raf and B-Raf comprise a small family of highly conserved serine/threonine protein kinases, whose activities play a fundamental role in the control of proliferation and differentiation. The best studied family member, Raf-1, is expressed ubiquitously and constitutively, and its activity is regulated by post-translational mechanisms. Raf-1 can be activated by many signals that include growth factors, tumor promoters, inflammatory cytokines, calcium mobilization, DNA damaging agents, and oxygen radicals. Ras-mediated translocation of Raf-1 to the plasma membrane is a crucial step in its activation process, and is thought to facilitate phosphorylation by membrane-bound kinases. Raf-1 has also been reported to undergo intracellular redistribution following its activation: to the perinuclear space in murine NIH3T3 cells and rat hepatic Ito cells, and into the nucleus in gerbil hippocampal pyramidal cells and human MO7 leukemia cells. In contrast to the translocation to the plasma membrane, the perinuclear and/or nuclear translocation of Raf-1 has not been investigated in detail. In this paper, we report an examination of the subcellular localization of endogenous Raf-1 in a fibroblastic cell line (Rat-1) commonly used in transformation assays. Using the methods of cellular fractionation as well as in situ immunofluorescence, we show that no detectable movement of Raf-1 to the perinuclear or nuclear space can be observed. Tethering of activated Raf to the plasma membrane does not interfere with its transforming activity.     

Effects of triphenyltin and other organotins on hepatic monooxygenase system in fish

The interaction of the organotin fungicide triphenyltin chloride (TPT) with fish microsomal monooxygenase systems has been studied in vitro and in vivo in the marine fish scup (Stenotomus chrysops). In vitro incubation of fish liver microsomes with TPT resulted in the conversion of about 40% of the native total spectral P450 to P420. In addition, a strong concentration-related inhibition of ethoxyresorufin O-deethylase (EROD) activity was observed, with a complete loss at 1.0 mM TPT. Pentoxyresorufin-O-dealkylase (PROD) activity was inhibited only at the highest concentration tested. This suggests either some specificity for the EROD catalyst CYP1A1, or a loss of reductant NADPH cytochrome c reductase as the cause. Further in vitro incubations showed that NADPH, but not NADH, cytochrome c reductase was strongly inhibited at 100 microM TPT and higher. To further investigate this effect, fish were injected with single doses of 5, 25 and 50 microM TPT (1.9, 9.6 and 19.3 mg kg-1 TPT), and 24 and 48 h later, hepatic microsomes were analyzed for total P450 content, EROD activity, NAD(P)H cytochrome c reductase, and the content of three CYP forms. EROD activity tended to be decreased in TPT-treated scup, with the response being stronger after 48 than 24 h. No significant conversion of spectrally determined P450 to cytochrome P420 was found, and cytochrome b5 was not affected. However, both NAD(P)H cytochrome c reductases were significantly inhibited at all concentrations. Immunoblot analysis showed reduction of CYP1A1 content at all doses, being significant at 25 mM after 48 h, but no decrease in CYP3A-like protein, the dominant catalyst of testosterone 6 beta-hydroxylation, nor CYP2B-like protein, the major contributor to indicates significant effects of TPT at high concentrations on fish hepatic CYP1A1 protein, EROD activity and the reductases. TPT seems to act more specifically on CYP1A1 than on other CYP forms. These findings combined with those of our previous studies (Brüschweiler BJ, Würgler FE, Fent K. Environ Toxicol Chem 1996;15:827-735; Fent K, Bucheli TD. Aquat Toxicol 1994;28:107-126; Fent K, Stegeman JJ. Aquat Toxicol 1991;20:159-168; Fent K, Stegeman JJ. Aquat Toxicol 1993;24:219-240) indicate a general degenerative effect of organotins on the fish microsomal monooxygenase system, although some differences are seen between the organotins, and between species. We conclude that these effects of organotins have consequences for use of CYP1A as a biomarker and endocrine disruption.     

Baseball implant. A method of secondary insertion of an intraorbital implant

A surgical technique for secondary emplacement of an orbital implant is described in which a spherical implant encased in a scleral homograft is placed in the orbit through a transconjuctival incision and sutured to the superior part of the periosteum.