Primary ovarian leiomyosarcoma. Proliferation rate and survival

OBJECTIVE: A case of Stage IIA primary ovarian leiomyosarcoma (LMS) with an unfavorable outcome 24 months after total abdominal hysterectomy with bilateral salpingo-oophorectomy, despite chemotherapy treatment, is described. Eighteen months from surgery the patient showed peritoneal spreading with ascites, liver and lung metastases. The present study was aimed to compare tumor growth fraction with cell density, lesion stage and clinical course. METHODS: The surgical specimens were evaluated by histological, histochemical, and immunocytochemical methods. Under microscopy, mitotic index (MI) was estimated, as a ratio of mitotic figures per 1000 tumor cells. Immunohistology was also carried out to reveal some intermediate-type filamentous proteins, as histogenetic markers, and the MIB1 monoclonal antibody was used to assess the percent of MIB1-positive nuclei (MIB1 labeling index). RESULTS: The histologic findings and immunohistology of the assayed intermediate filamentous proteins substantiated a diagnosis of LMS, with associated coagulation necrosis and not rare mitotic figures. A dual tumor component was observed, representing both the pleomorphic and myxoid LMS-variants. On the basis of the quantitative findings, a MI of 10.9 and a MIB1-LI of 23.1 were calculated, on average. CONCLUSIONS: The proliferation indices in the described variant of ovarian LMS, denote a fast growing malignancy. They agree with the tumor stage at operation and the subsequent fatal outcome.     

Assessing the prognostic value of coronary endothelial function in patients referred for a first coronary angiogram

At present, the value of endothelial function as a prognostic tool has been evaluated only in selected groups of patients with mild or minor coronary artery disease, not in the complete spectrum of patients presenting with angina. The objective of this study was to evaluate whether endothelium-dependent vasodilation of the coronary arteries in response to acetylcholine infusion as a marker of endothelial function would have prognostic value in patients referred for a first coronary angiogram. The data suggest that endothelial function assessment does not contribute to the prediction of outcomes in patients referred for a first coronary angiogram.     

TAS2R38 (phenylthiocarbamide) haplotypes, coronary heart disease traits, and eating behavior in the British Women's Heart and Health Study

BACKGROUND: Variation in the perception of bitter tastes has been associated with eating behavior, body composition, and cardiovascular disease. Recent observations have implicated 2 common haplotypes of TAS2R38 in the determination of bitter compound-tasting ability. OBJECTIVE: The objectives of the study were to examine, in the British Women's Heart and Health Study cohort, any association between TAS2R38 haplotypes, coronary heart disease (CHD), CHD risk factors, and eating behavior and to examine whether the associations allow for estimation of the effects of variation in diet on the etiology of common disease. DESIGN: We conducted a cross-sectional study of relations between TAS2R38 haplotypes and CHD, CHD risk factors, and eating behavior in 3383 women from 23 British towns. RESULTS: Genotyping at P49A and V262A in TAS2R38 (rs713598 and rs1726866) allowed construction of all 4 possible haplotypes. The 2 most common haplotypes corresponded with previously identified haplotypes related to bitter compound-tasting ability. No substantial evidence of association was found between these haplotypes and CHD (odds ratio for taste-defining haplotypes: 0.97; 95% CI: 0.78, 1.2), body mass index (difference between means of taste-defining haplotypes: -0.084; 95% CI: -0.45, 0.29), or a series of physiologic and dietary characteristics. A marginally lower risk of diabetes was observed among those with the nontaster haplotype than among those with the taster haplotype (odds ratio: 0.69; 95% CI: 0.48, 1.00). CONCLUSION: TAS2R38 status was not an important determinant of CHD, related risk factors, or eating behavior in the British Women's Heart and Health Study sample.     

A cross-national study of violence-related behaviors in adolescents

BACKGROUND: Violent behavior among adolescents is a significant problem worldwide, and a cross-national comparison of adolescent violent behaviors can provide information about the development and pattern of physical violence in young adolescents. OBJECTIVES: To determine and compare frequencies of adolescent violence-related behaviors in 5 countries and to examine associations between violence-related behaviors and potential explanatory characteristics.Design, Setting, and PARTICIPANTS: Cross-sectional, school-based nationally representative survey at ages 11.5, 13.5, and 15.5 years in 5 countries (Ireland, Israel, Portugal, Sweden, and the United States). MAIN OUTCOME MEASURES: Frequency of physical fighting, bullying, weapon carrying, and fighting injuries in relation to other risk behaviors and characteristics in home and school settings. RESULTS: Fighting frequency among US youth was similar to that of all 5 countries (nonfighters: US, 60.2%; mean frequency of 5 countries, 60.2%), as were the frequencies of weapon carrying (noncarriers: US, 89.6%; mean frequency of 5 countries, 89.6%) and fighting injury (noninjured: US, 84.5%; mean frequency of 5 countries, 84.6%). Bullying frequency varied widely cross-nationally (nonbullies: from 57.0% for Israel to 85.2% for Sweden). Fighting was most highly associated with smoking, drinking, feeling irritable or bad tempered, and having been bullied. CONCLUSIONS: Adolescents in 5 countries behaved similarly in their expression of violence-related behaviors. Occasional fighting and bullying were common, whereas frequent fighting, frequent bullying, any weapon carrying, or any fighting injury were infrequent behaviors. These findings were consistent across countries, with little cross-national variation except for bullying rates. Traditional risk-taking behaviors (smoking and drinking) and being bullied were highly associated with the expression of violence-related behavior.     

Use of a 22-gauge Whitacre needle to reduce the incidence of side effects after lumbar myelography: a prospective randomised study comparing Whitacre and Quincke spinal needles

In a prospective study lumbar iohexol myelography was performed in 107 consecutive patients, randomised for lumbar puncture with a Quincke or Whitacre spinal needle. All patients answered a questionnaire about possible side effects. Data from 100 patients (58 men, 42 women) were evaluated. In the Quincke group (n = 53), 23 (43 %) reported no side effects. In the 30 patients who reported various side effects, post-dural puncture headache (PDPH) occurred in 22 (42 %), of whom 9 had mild, 6 moderate and 7 (13 %) severe cephalalgia, 18 (34 %) reported increased low back pain/sciatica, 5 nausea and 7 dizziness. In the Whitacre group (n = 47), 33 (70 %) had no side effects. PDPH was reported by 9 patients (19 %), of whom 2 had mild, 6 moderate and only 1 (2 %) severe cephalalgia, 4 (9 %) reported increased low back pain/sciatica, 5 nausea and 4 dizziness. The conclusion drawn from this study is that lumbar myelography performed with the Whitacre spinal needle reduces postspinal side effects.     

Randomized controlled trial comparing argon plasma coagulation tonsillectomy with conventional techniques

Argon plasma coagulation (APC) is based on the principle of ionized argon creating a conductive plasma between an activating electrode and a tissue surface. To date, its use in tonsillectomy has not been extensively examined. The purpose of this randomized controlled trial was to assess the clinical efficacy of APC as a tool for this common surgical procedure. Forty patients were randomized into two groups--treatment A (conventional tonsillectomy, n = 20) and treatment B (APC tonsillectomy, n = 20). Trial end-points included a) operative time, b) intra-operative blood loss, and c) objective assessment of post-operative pain, by completion of a visual analogue pain score chart, over a two-week period. Thirty-one patients were available for analysis. There was a statistically significant reduction in the intra-operative blood loss with treatment B (p = 0.02). There was no statistical difference between both groups for the other outcome measures. First clinical experience with this treatment modality shows that it is an attractive alternative to conventional tonsillectomy and may offer possible benefits.     

Assessment of urinary trans, trans-muconic acid as a biomarker of exposure to benzene

OBJECTIVE: To assess the use of trans, trans-muconic acid as a biomarker of occupational exposure to benzene. METHODS: Trans, trans-muconic acid in urine samples of exposed (exposed group, n=36) and non-exposed (non-exposed group, n=116) workers to benzene. Urinary levels of trans, trans-muconic acid were quantified by high-performance liquid chromatography. The study sample consisted of subjects exposed to benzene in an oil refinery in Belo Horizonte, Brazil. Non-parametric statistical analysis was carried out using Kruskall-Wallis test, Mann-Whitney test and Spearman correlation at p<0.05. RESULTS: Workers were exposed on average to benzene levels of 0.15 +/- 0.05 mg/m3 (0.05 ppm) and they showed a urinary trans, trans-muconic acid mean value of 0.19 +/- 0.04 mg/g of creatinine. The reference value range of trans, trans-muconic acid in non-exposed subjects was 0.03 to 0.26 mg/g of creatinine (mean 0.10 +/- 0.08 mg/g of creatinine). There was seen a statistical difference between trans, trans-muconic acid levels in urine samples from exposed and non-exposed groups. There was no correlation between urinary trans, trans-muconic acid and air benzene levels. There was no correlation between urinary trans, trans-muconic acid levels in the exposed group and smoking. Alcohol consumption up to 48 hours before sampling procedure showed no effect on trans, trans-muconic acid levels in both exposed and non-exposed groups. There was however a correlation between age (range 18 to 25 years) and urinary metabolite levels in the latter group. CONCLUSIONS: The results show that it is important to evaluate the effect of age and smoking habits on urinary trans, trans-muconic acid levels.     

Determination of vessel size: a putative framework to assess clinical outcome

BACKGROUND: Unknown is the predictive value of the coronary artery diameter without the administration of vasomotor stimuli. A small reference diameter of the target vessel has been demonstrated to be an adverse prognostic factor in patients undergoing revascularisation. The present study investigated the prognostic value of the proximal non-stenotic left anterior descending coronary artery (LAD) diameter in patients referred for a first diagnostic angiogram without a previous revascularisation. METHODS: A total of 277 patients (mean age 57 year, 61% male) were eligible for analysis. The proximal non-stenotic diameter of the LAD was measured by quantitative coronary angiography without prior nitrate infusion. We defined a small LAD as a diameter < or =2.5 mm. Cardiovascular events were defined as cardiac death, myocardial infarction, and hospitalizations for unstable angina. RESULTS: During a median follow-up of 47 months, 24 major cardiac events occurred. The cumulative survival for patients with a small LAD was significantly lower, than for patients with a large LAD (hazard ratio 2.51; 95% confidence interval 1.11-5.66, p=0.03). In the multivariate analysis, a LAD diameter < or =2.5 mm remained a significant predictor of cardiovascular events after adjustment for age, gender, and the presence of significant coronary artery disease (hazard ratio 2.32; 95% confidence interval 1.01-5.34, p=0.048). CONCLUSION: In patients referred for a first diagnostic angiogram without a previous revascularisation, the diameter of the proximal non-stenotic LAD is an independent predictor of cardiovascular events.     

Implication of 5-HT<Subscript>2</Subscript> receptor subtypes in the mechanism of action of antidepressants in the four plates test

Rationale The selective serotonin reuptake inhibitors (SSRIs) and the serotonin and noradrenaline reuptake inhibitors (SNRIs) increase synaptic levels of serotonin, leading to an increased activation of a multitude of specific postsynaptic 5-HT receptors. However, it is not yet known which 5-HT receptor subtypes mediate the therapeutic effects of antidepressants.Methods The effects of the SSRI, paroxetine and the SNRI, venlafaxine were evaluated in the mouse four plates test (FPT).Results Paroxetine administered intraperitoneally (IP) (0.5, 2–8 mg/kg) potently augmented the number of punished passages accepted by mice in this paradigm. The effects of paroxetine (8 mg/kg) were not reversed by the selective 5-HT_2C receptor antagonist, RS 10-2221 (0.1 mg/kg and 1 mg/kg) or the selective 5-HT_2B/2C receptor antagonist SB 206553 (0.1 mg/kg and 1 mg/kg), at doses which lack an effect when administered alone. In contrast, the selective 5-HT_2A receptor antagonist, SR 46349B (0.1 mg/kg and 1 mg/kg) completely abolished the paroxetine-induced increase in punished passages. The acute administration of venlafaxine induced an anxiolytic-like effect in the FPT at the doses of 2–16 mg/kg. This effect was reversed by the 5-HT_2B/2C receptor antagonist as did SR 46349B, for both doses administered. Our results strongly suggest that activation of 5-HT_2A receptors is critically involved in the anxiolytic activity of paroxetine, whereas the 5-HT_2A and 5-HT_2B receptors are involved in the anti-punishment action of venlafaxine in the FPT. The co-administration of selective 5-HT_{2A, 2B, 2C} receptor agonists (DOI, 0.06 mg/kg and 0.25 mg/kg; BW 723C86, 0.5 mg/kg and 2 mg/kg and RO 60-0175, 0.06 mg/kg and 0.25 mg/kg), respectively, was subsequently investigated. The effects of sub-active doses of paroxetine (0.25 mg/kg and 1 mg/kg) were augmented by BW 723C86 and RO 60-0175 receptor agonist challenge. The anti-punishment effects of venlafaxine (0.25 mg/kg and 1 mg/kg) were potentialised only by DOI co-administration.Conclusion These results indicate that the co-administration of 5-HT₂ receptor agonists with paroxetine and venlafaxine may provide a powerful tool for enhancing the clinical efficacy of these antidepressants.