Is ultrasound of the retroperitoneum a valuable staging method in selecting testicular cancer patients for primary retroperitoneal lymph node dissection?

OBJECTIVE: In nonseminomatous testicular cancer patients with normal serum tumor markers and no distant metastasis, postorchiectomy surgery is a valid treatment option if the disease extension into the retroperitoneum is not advanced. We assessed the ability of ultrasound (US) to exclude the presence of bulky retroperitoneal disease. MATERIALS AND METHODS: One hundred and forty testicular cancer patients underwent US and computed tomography (CT) of the retroperitoneum. US results were analyzed using three cutoffs: 5 cm (conventional staging), 3 cm (based on the minimal sonographical dimension of actual bulky disease) and 0 cm ('clean retroperitoneum' or any detectable nodes), and were compared with CT data using the 5-cm cutoff ('gold standard'). RESULTS: The sensitivity, specificity, overall accuracy, positive and negative predictive values of US in detecting of bulky retroperitoneum for the 5-cm cutoff were 83, 96, 93, 88 and 94%, for the 3-cm cutoff 100, 91, 94, 80 and 100%, and for the 0-cm cutoff 100, 66, 74, 49 and 100%, respectively. CONCLUSIONS: In stage I and IIA/B marker-negative nonseminomas if the treatment strategy is surgery, US may facilitate the selection process; the report of a clean retroperitoneum safely excludes the presence of bulky disease and may be an indication for lymphadenectomy, although in case of positive findings a CT should be performed.     

Estrogen receptors alpha and beta mediate different aspects of the facilitatory effects of female cues on male risk taking

Male risk taking and decision making are affected by sex-related cues, with men making poorer and riskier decisions in the presence of females and, or their cues. In non-human species, female cues can also increase male risk taking, reducing their responses to predator threat. As estrogen receptors alpha and beta (ERalpha and ERbeta) are involved in the mediation of social and sexual responses, we investigated their roles in determining the effects of female-associated cues on male risk taking. We examined the effects of brief pre-exposure to the odors of either a novel or familiar estrous female on the avoidance of, and aversive responses to, predator threat (cat odor) in ERalpha and ERbeta wild type (alphaERWT, betaERWT) and gene-deleted (knockout, alphaERKO, betaERKO) male mice. Exposure of alphaERWT and betaERWT males to the odors of a novel, but not a familiar, estrous female mouse resulted in enhanced risk taking with the males displaying reduced avoidance of, and analgesic responses to, cat odor. In contrast, alphaERKO male mice failed to show any changes in risk taking, while betaERKO males, although displaying greater risk taking, did not distinguish between novel and familiar females, displaying similarly reduced avoidance responses to cat odor after exposure to either a novel or familiar female odor. These findings indicate that the gene for ERalpha is associated with the sexual mechanisms (response to estrous female) and the genes for ERbeta and ERalpha with the social (recognition of novel female) mechanisms underlying the effects of female cues on male risk taking.     

Antimalarial activity of alkaloids isolated from Stephania rotunda

Stephania rotunda (Menispermaceae) is used in traditional medicine for the treatment of fever. Four major alkaloids: dehydroroemerine, tetrahydropalmatine, xylopinine, cepharanthine as well as aqueous extract (SA), dichloromethane extracts (SD1 and SD2) from this plant were tested against Plasmodium falciparum W2 in vitro. Dehydroroemerine, cepharanthine and SD1 were the most active against W2 with IC(50) of 0.36, 0.61microM and 0.7microg/mL, respectively. Their IC(50) on human monocytic THP1 cells were 10.8, 10.3microM and >250microg/mL, respectively. Cepharanthine, SD1 and SA were selected for in vivo antimalarial test against Plasmodium berghei in mice. The results of SD1 and SA at dose of 150mg/kg showed a decrease of 89 and 74% of parasitaemia by intra-peritoneal injection and 62.5 and 46.5% of parasitaemia by oral administration, respectively. The result of cepharanthine at dose of 10mg/kg showed a decrease of 47% of parasitaemia by intra-peritoneal injection and 50% of parasitaemia by oral administration. Drug interaction of chloroquine and major alkaloids indicates that cepharanthine-chloroquine and tetrahydropalmatine-xylopinine associations are synergistic. These results are in agreement with the use of this plant in the treatment of malaria. This is the first report on in vivo antimalarial investigation for Stephania rotunda.     

Urban background particulate matter and allergic sensitization in adults of ECRHS II

BACKGROUND: Epidemiological studies have shown weak or inconsistent associations between ambient air pollutants and allergic sensitization. The aim of this study was to evaluate whether regional urban air pollution may partly explain the large variation in the prevalence of allergic sensitization across cities of the European Community Respiratory Health Survey (ECRHS) II. METHODS: ECRHS is a cross-sectional survey initiated in 29 countries across Europe in the 1990s (ECRHS I) with a follow-up conducted 10 years later (ECRHS II). Subject characteristics were measured by questionnaires and blood tests conducted for the measurement of specific immunoglobulin E. Fine particle mass (PM(2.5), <2.5 microm) and sulphur on PM(2.5) were measured in 21 centres and annual averages of urban regional background air pollution were calculated. Results were scaled by an interquartile range increase in ambient PM(2.5) (6.03 microg/m(3)) and sulphur (1336 ng/m(3)). Generalized estimating equations were applied to compute population average effect estimates with adjustment for age, gender, smoking habit, education and number of siblings. RESULTS: A notable variation in pollution level and prevalence of allergic sensitization was observed. Moreover, exposure to urban regional background air pollution was not associated with allergic sensitization; adjusted odds ratios and 95% confidence interval were 1.02 (0.95-1.09) for PM(2.5) and 1.08 (0.86-1.31) for sulphur. These statistically non-significant associations were sensitive to model specification. CONCLUSIONS: The study suggests that regional air pollution measured at fixed sites is not associated with allergic sensitization among adults in ECRHS II.     

Influence of hyperthermal regimes on experimental teratoma development in vitro

We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air‐liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ? .0001) and enhanced differentiation of both myotubes (P ? .01) and cylindrical epithelium (P ? .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ? .01) and diminished cell proliferation (P ? .0001). Long‐term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ? .005). Long‐term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ? .0001), overall growth (P ? .01) and cartilage differentiation (P ? .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum‐free medium (CEM43°C 630 minutes) or treatment with an anti‐HSP70 antibody before long‐term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.     

Albiglutide efficacy and safety in the Latino/Hispanic subpopulation for the integrated phase III program

Objective: to evaluate the efficacy and safety of albiglutide compared with placebo and active comparators from an integrated trial subpopulation of Latino/Hispanic patients whose type 2 diabetes mellitus (T2DM) was inadequately controlled on their current regimen of diet and exercise, with or without oral antidiabetic drugs (OADs) and/or insulin.

Methods: Latino/Hispanic patient subpopulations (N = 1204) across 7 phase III albiglutide studies (N = 4400) were evaluated post-hoc for efficacy and safety. Comparators were placebo, sulfonylureas, insulin, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors. Glycatedhemoglobin (HbA_1c) change from baseline to the time of the primary endpoint assessment (from 26 to 104 weeks) was evaluated in patients on diet and exercise and/or OADs, with or without insulin. Patients were allowed to continue in the study if hyperglycemic rescue was required, according to a prespecified algorithm and at the discretion of the investigator.

Results: At baseline in the Latino/Hispanic subpopulation, the mean HbA_1c was 8.3%, mean age was 53 years, mean body mass index was 32 kg/m², and mean duration of T2DM was 8.0 years. The primary endpoint of mean HbA_1c difference (albiglutide – placebo) was ?0.94% for the Latino/Hispanic subpopulation and ?0.86% (p < 0.001) for the overall phase III population. Changes in fasting plasma glucose mirrored those of HbA_1c. Weight loss with albiglutide was numerically greater than with OADs and insulin in both populations, but it was smaller than with liraglutide. Within the Latino/Hispanic subpopulation, more injection-site reactions were reported with albiglutide vs all comparators, while gastrointestinal and hypoglycemic adverse events were comparable between the two groups, and the latter was uncommon when used without insulin and/or a sulfonylurea.

Conclusions: In the Latino/Hispanic population, albiglutide resulted in effective lowering of glucose and modest weight loss, and it was generally well tolerated.     

Lung function decline, chronic bronchitis, and occupational exposures in young adults

RATIONALE: Occupational exposures to vapors, gas, dust, or fumes have been shown to be a risk factor of airway obstruction in cross-sectional studies in the general population. OBJECTIVES: Our aim was to study the relationships between specific occupations and occupational exposures during a 9-yr follow-up period and changes in lung function and symptoms of chronic bronchitis. METHODS: Subjects from the general population aged 20 to 45 yr were randomly selected in 1991-1993 within the European Community Respiratory Health Survey. Follow-up took place from 1998 to 2002 among 4,079 males and 4,461 females in 27 study centers. A total of 3,202 men and 3,279 women twice completed lung function measurements. Job history during follow-up was linked to a job exposure matrix and consequently translated into cumulative exposure estimates. MAIN RESULTS: Individuals exposed to dusts, gases, and fumes during the period of follow-up did not have a steeper decline of FEV1 than did individuals with consistently white-collar occupations without occupational exposures (relative change among men and women, + 1.4 and -3.1 ml/yr, respectively; p > 0.2), nor an increase of prevalence or incidence of airway obstruction defined as an FEV1/FVC ratio of less than 0.7. The incidence of chronic phlegm increased in men exposed to mineral dust (relative risk, 1.94 [1.29-2.91]) and gases and fumes (relative risk, 1.53 [0.99-2.36]), which was not modified by smoking. CONCLUSION: Occupational exposures to dusts, gases, and fumes occurring during the 1990s are associated with incidence of chronic bronchitis, although these did not impair lung function in a population of relatively young age.