Suppression of pelvic pain during hysteroscopy with a transcutaneous electrical nerve stimulation device

OBJECTIVE: To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) as a pain control method during office hysteroscopy. DESIGN: A prospective, randomized study. SETTING: Centre for Minimally Invasive Surgery, Department of Gynecological Science and Perinatology, "La Sapienza" University, Rome, Italy. PATIENT(S): One hundred forty-two patients undergoing office hysteroscopy. INTERVENTION(S): Application of a TENS device on the patient's abdomen before and during office hysteroscopy. MAIN OUTCOME MEASURES: The level of pain experienced by the patients was assessed using a 10 cm visual analog scale; the side effects and changes in the hemodynamic parameters were evaluated. RESULT(S): The patients treated with TENS during hysteroscopy (group A, n = 71) were compared with a control group (group B, n = 71) on whom the TENS device was not used. The women in the TENS group experienced a significantly lower level of pain during hysteroscopy. No differences in side effects were observed between both group. CONCLUSION(S): TENS is a simple, efficient, and safe method of relieve pain during office hysteroscopy.     

Gene-gene and gene-environment interactions in mild hyperhomocysteinemia

Mild/moderate hyperhomocysteinemia (HHcy), a highly prevalent condition, is independently associated with an increased risk of arterial and venous thromboembolic diseases. Early reports of the association of mild/moderate HHcy with juvenile venous thromboembolism have shown familiarity for HHcy in relatives of index cases with thrombosis. Similar to inherited thrombophilia defects, inheritance of the HHcy phenotype was accordingly retained important for the definition of HHcy as an independent risk factor for thrombosis. A number of common polymorphisms in genes coding for methylenetetrahydrofolate reductase(MTHFR), methionine-synthase, methionine-synthase reductase and cysthationine beta-synthase (CBS) have been explored for their association with homocysteine levels, fasting and post-methionine load, and with thrombotic diseases. MTHFR thermolability accounts for a 10-fold increase in the risk of mild/moderate HHcy. With the possible exception of the CBS844ins68 insertion, there is no evidence for an increased risk of HHcy for any of these polymorphisms, isolated or in association with MTHFR thermolability. Environmental factors and MTHFR thermolability are main determinants of the HHcy phenotype.If mild/moderate HHcy is a pathogenetic risk factor for thrombosis, intervention aimed to improve the vitamin status appears of major importance, irrespective of common gene polymorphisms of the homocysteine metabolism.     

Candidal carriage in the oral cavity of human immunodeficiency virus-infected subjects

OBJECTIVES. We sought to assess asymptomatic oral carriage of Candida species and relative density in human immunodeficiency virus-infected (HIV+) subjects, as well as to determine whether yeast carriage is associated with CD4+ cell count, HIV-1 RNA quantity, gender, route of HIV transmission, antiretroviral therapy, or smoking. STUDY DESIGN. A cross-sectional analysis of oral rinses from HIV+ and healthy subjects was undertaken. Oral candidal carriage and relative species were investigated in 42 HIV+ and 41 healthy individuals, all of whom were seen at the Palermo University Department of Oral Sciences, Italy. Data were managed and analyzed by means of the computer software package StatView 5.0.1. RESULTS. Carriage rate was 61.9% and 29.3% (P =.003) among HIV+ and healthy subjects, respectively. Similarly, density carriage in the HIV+ group was found to be significantly higher than in the control group (P = .0002). Among HIV+ subjects, Candida carriage was significantly associated with smoking, whereas density was not. Oral candidal carriage and relative density were not significantly associated with the other 4 parameters evaluated. Candida albicans was the most frequently recovered species. CONCLUSIONS. Asymptomatic candidal carriage and relative density were found to be significantly higher in the oral cavity of HIV+ subjects-but not associated with CD4+ counts or HIV-1 RNA quantities.     

The role of levamisole in the adjuvant treatment of stage III colon cancer patients: a randomized trial of 5-fluorouracil and levamisole versus 5-fluorouracil alone

Adjuvant 5-fluorouracil (5FU) and levamisole (Lev) have been considered standard treatment for stage III colon cancer patients. However, the uncertain contribution of Lev to the efficacy of treatment has led many oncologists to prefer the 5FU/leucovorin combination. To establish the role of Lev, we conducted a randomized trial comparing the 5FU/Lev combination with 5FU alone in patients with Dukes' C colon cancer. Patients with stage III colon cancer were randomized to receive 5FU alone (450 mg/m² IV bolus daily for 5 days and then, beginning at day 28, weekly for 48 weeks) or the same plus Lev (50 mg orally three times/day for 3 days, repeated every 2 weeks for 1 year). From December 1994 to March 1998, 92 patients were assigned to receive 5FU/Lev, and 93 were assigned to receive 5FU alone. Leukopenia and hepatic toxicity were more frequent in patients receiving 5FU/Lev as compared with those receiving 5FU (respectively, p=0.003 and p=0.039), whereas other toxicities were equivalent and mild in both arms. After a median follow-up time of 48 months, 80 patients have had recurrences (40 in each arm) and no advantages in terms of disease-free survival and overall survival could be demonstrated for the combination arm. The addition of Lev to 5FU does not seem to be relevant for the clinical activity of this adjuvant regimen, whereas toxicity related to Lev should be considered when an adjuvant treatment for stage III colon cancer patients is proposed.     

Stable expression of antisense urokinase mRNA inhibits the proliferation and invasion of human hepatocellular carcinoma cells

Urokinase-type plasminogen activator (u-PA) plays a key role in malignant tumor behavior. We have previously shown that the expression of high levels of u-PA mRNA in human hepatocellular carcinoma (HCC) biopsies was inversely correlated with the survival of the patients. In order to evaluate the involvement of u-PA in the invasive and infiltrating properties of HCC cells, the SKHep1C3 cell line was stably transfected with an expression vector containing the 5' portion (257 bp) of u-PA cDNA in the antisense orientation. u-PA mRNA expression and its protein level and enzymatic activity were specifically inhibited in the antisense transfectants. A comparable inhibition of the u-PA receptor (u-PAR) mRNA and protein was also evidenced in the antisense transfected cells compared with the control ones. At the functional level, the SKHep1C3-AS cells showed a significant reduction in proliferation, Matrigel invasion, and motility assays compared to parental and vector-alone cells. These results indicate that u-PA is an essential factor in the growth and invasiveness of human hepatocarcinoma cells. Antisense u-PA strategy might be a potential approach to reduce tumor growth as well as the invasive capacity of the malignant cells in HCC.     

SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo

Acute myeloid leukemia 1 (AML1) belongs to a family of DNA-binding proteins highly conserved through evolution. AML1 regulates the expression of several hematopoietic genes and is essential for murine fetal liver hematopoiesis. We report here that the histone methyltransferase SUV39H1, a mammalian ortholog of the Drosophila melanogaster SU(VAR) 3-9, forms complex with AML1. SUV39H1 methylates lysine 9 of the histone protein H3 leading to the formation of the high-affinity binding site on chromatin for proteins of the heterochromatin protein 1 family (HP1). The interaction of AML1 with SUV39H1 requires the N-terminus of AML1 where the Runt domain is located. Binding of AML1 to SUV39H1 abrogates the transactivating and DNA-binding properties of AML1 and dissociates the net-like nuclear structure of AML1. It has been reported that AML1 is capable of interaction with histone acetyl transferases (CBP, p300, and MOZ) and with component of the histone deacetylase complex (Sin3), and that the interaction with these coregulators affects the strength of AML1 in promoter regulation. Our data suggest that other enzymes are also involved in gene regulation by AML1 activity by modulating the affinity of AML1 for DNA.     

In situ detection of telomeres by fluorescence in situ hybridization and telomerase activity in glioblastoma multiforme: correlation with p53 status, EGFR, c-myc, MIB1, and Topoisomerase IIalpha protein expression

Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.