Outcomes of Prostatectomy versus Radiation Therapy in the Management of Clinically Localized Prostate Cancer Patients Within the PLCO Trial

Background

The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.

Subchronic vaginal toxicity studies of Alcide Allay gel and liquid in guinea pigs

Alcide Allay, an antimicrobial preparation produced in gel and liquid forms, was evaluated for vaginal toxicity in guinea pigs. 1.0 g/kg Allay gel or placebo was administered intravaginally once per day over a 30 day period while 2.5 g/kg Allay liquid (containing either of two concentrations of sodium chlorite and lactic acid as active ingredients) or placebo was applied vaginally three times per day for 10 days. At the conclusion of the studies, hematology, blood and urine clinical chemistry tests and necropsies were performed. RBC, HGB, HCT, MCHC and direct bilirubin increased while CO2, SGPT and CPK decreased in blood after Allay liquid treatment. Creatinine, urea nitrogen and uric acid in urine were statistically reduced in the liquid groups. Hematology and clinical chemistry parameters were within the normal range of values reported in the literature for guinea pigs, indicating no clinical significance due to drug treatment. Significant differences in organ body/weight ratios were observed between controls and Allay gel and liquid groups. However, only the livers in the gel study and the vaginas in both studies were changed histologically.     

Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

BACKGROUND： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. AIMS： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. METH ODS： Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. RESULTS： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. CONCLUSIONS： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

The urodynamic characteristics of different ileal reservoirs: an experimental study in dogs.

Using adult mongrel dogs, the urodynamic characteristics of three types of ileal reservoirs were studied and compared. Segments of ileum of the same length were utilized to construct simple loop pouches (five dogs), DeKlerk pouches (five dogs) and Kock pouches (five dogs). Six to eight weeks after surgery, urodynamic evaluation was carried out. This included determination of the volume/pressure relationship and measurement of the contractions of the circular and longitudinal muscle fibers. Results indicate that the Kock pouch offers the best features in terms of the volume capacity, the volume/pressure relationship and contractile activity. Detubularization abrogated the muscle tone but it did not affect the phasic contractile activity of the circular muscle layer.     

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.     

Hoechst staining and exposure to UV laser during flow cytometric sorting does not affect the frequency of detected endogenous DNA nicks in abnormal and normal human spermatozoa

Controlling the sex of offspring by the separation of X and Y chromosome-bearing spermatozoa using flow cytometry has been reported as a clinical technique aiding prevention of X-linked diseases. Although this technique has resulted in several hundred normal births in animals and at least one human birth, there is still concern over its genetic safety due to the involvement of two potentially mutagenic agents: UV light and the fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly those considered abnormal, may be more likely to suffer DNA damage following exposure to mutagenic agents, compared with other mammalian species. The stability of normal fresh and decondensed human spermatozoa were examined after exposure to a range of levels of UV and H33342 staining, using an assay that detects endogenous nicks in the DNA of spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed human spermatozoa was examined following UV laser, H33342 staining and flow cytometry treatments utilizing the same assay. There was an increase in the presence of endogenous nicks when spermatozoa were decondensed compared with fresh spermatozoa. There was no increase in the incidence of nicks in any group of spermatozoa after UV and fluorochrome exposure compared with controls without exposure.      

Examining Trichophyton tonsurans genotype and biochemical phenotype as determinants of disease severity in tinea capitis.

Trichophyton tonsurans infections occur in various host populations, on various body sites and with varying degrees of inflammation. This investigation was undertaken to determine whether fungal factors could explain the degree of severity in clinical symptomatology among infected children. Otherwise healthy children (n=54) presenting with tinea capitis were enrolled in this study. A thorough history was performed, the extent and severity of infection graded and a fungal specimen collected from each child. Strain type was determined by genotyping for 11 sequence variations in the rDNA and ALP1 loci. Secreted protease activity was quantitated after 5 days of growth in aqueous medium. Forty participants were evaluable. Infection duration ranged from 1 day to 3 years and clinical severity score (CSS) from 4-19. Seventeen unique fungal genotypes were present. Keratinase, collagenase and elastase activity varied 32.7-fold, 64.9-fold and 303.3-fold, respectively. A significant association was observed between genotype and disease severity with the rDNA sequence variations accounting for over 50% of the variation observed in CSS (r2=0.539; P<0.001). Phylogenetic analyses appear to suggest that the ancestral strain types of T. tonsurans cause more severe disease. These observations are consistent with reports that recently diverge anthropophilies are associated with diminished inflammatory involvement.     

Role of the sympathetic control of vascular resistance in ethanol-clonidine hemodynamic interaction in SHRs.

Our previous studies showed that ethanol selectively counteracts centrally mediated hypotensive responses. In this study, we investigated the role of sympathetic nerve activity, cardiac output (CO), and total peripheral resistance (TPR) in this antagonistic hemodynamic interaction between ethanol and clonidine. Changes in blood pressure (BP), heart rate (HR), CO, stroke volume (SV), and TPR elicited by intracisternal (i.c.) clonidine and subsequent ethanol or saline were evaluated in conscious freely moving spontaneously hypertensive rats (SHRs). Clonidine (0.5 microg, i.c.) evoked hypotension was due to a significant reduction in TPR (from 3.6+/-0.21 to 2.8+/-0.17 mm Hg/ml/min/100 g), which was associated with a significant (p < 0.05) reduction in plasma norepinephrine (NE, from 660+/-115 to 310+/-50 pg/ml), measured as index of sympathetic activity. Ethanol (1 g/kg, i.v.) counteracted the hypotensive effect of clonidine and produced significant (p < 0.05) increases in plasma NE and TPR. Further support for the hypothesis that ethanol selectively counteracts centrally mediated hypotension was sought by investigating the effect of ethanol on peripherally mediated hemodynamic responses to hydralazine. Hydralazine (0.4 mg/kg, i.v.) produced a hypotension similar in magnitude to that produced by clonidine, which was also due to a significant reduction in TPR. However, unlike the case with clonidine, reflex increases in HR, SV, and hence CO were evident. Ethanol given after hydralazine produced a short-lived pressor effect (<10 min vs. 60 min in case of clonidine) in spite of a sustained increase in TPR. The latter was offset by the simultaneous decreases in CO, SV, and HR. A 30% increase in plasma NE caused by hydralazine returned to baseline level after ethanol or saline. Blood ethanol concentrations were similar in all treatment groups. These findings suggest that ethanol selectively counteracts centrally evoked hypotensive responses by counteracting the sympathoinhibition-mediated decreases in TPR elicited by centrally administered clonidine in conscious SHRs.