Correlation between oncological family history and clinical outcome in a large monocentric cohort of pediatric patients with rhabdomyosarcoma

International Journal of Clinical Oncology - Rhabdomyosarcoma (RMS), an aggressive soft tissue sarcoma of the skeletal muscle generally affecting children and adolescents, shows extensive...     

Tobacco use and smoking cessation among third‐year dental students in southern Brazil

The aim of the present cross‐sectional study was to assess tobacco use and smoking cessation among third‐year dental students in southern Brazil. The Global Health Professions Student Survey questionnaire was used in eight dental schools in Rio Grande do Sul state, Brazil. Of the 663 eligible students, 576 (87%) participated. The prevalence of current smoking was 19.1% [95% confidence interval (CI): 12.9–25.3%], and 61.6% (95% CI: 54.9–68.3%) of students reported having smoked at least once in their lifetime. The prevalence of dental students who had smoked ≥100 cigarettes in their lifetime was 17.1% (95% CI: 12.5–21.7%). Being frequently exposed to other smokers at home or in other places (second‐hand smoke) increased the likelihood of current smoking by two‐ to threefold. Approximately 6.1% (95% CI: 3.5–8.7%) of the students reported that they currently wanted to stop smoking and 7.5% (95% CI: 5.3–9.6%) had tried to stop smoking in the last year. Friends and family were the most frequent sources of help or counselling, and only a limited proportion of students received help from health professionals. Tobacco use and exposure to second‐hand smoking is widespread among dental students in southern Brazil. Smoking‐cessation initiatives targeting health care students are urgently needed.     

Choice of azathioprine or 6-mercaptopurine dose based on thiopurine methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study

BACKGROUND/AIMS: To prospectively evaluate whether, in patients with inflammatory bowel disease, the choice of azathioprine (AZA) or 6-mercaptopurine (6-MP) dose based on thiopurine methyltransferase (TPMT) activity prevents myelotoxicity. METHODOLOGY: TPMT activity in red blood cells was measured in 99 patients with Crohn's disease and 32 with ulcerative colitis prior to initiating AZA/6-MP treatment. AZA/6-MP dose was chosen based on TPMT activity, which was again determined one month after starting therapy. Incidence of adverse effects was evaluated for at least 6 months of follow-up. RESULTS: Mean basal TPMT value was 21.6 +/- 5 U/mL. No patient had low levels (< 5 U/mL), 6.9% had intermediate levels (5-13.7 U/mL), and 93.1% had high levels (> 13.8 U/mL). In patients with Crohn's disease, mean TPMT activity significantly decreased after AZA/6-MP therapy, while in patients with ulcerative colitis this activity did not change. Among the 4 patients having myelotoxicity, one had intermediate basal TPMT levels, and 3 even had high levels, but no patient had low levels. CONCLUSIONS: In this prospective study we could not confirm that the choice of AZA/6-MP dose based on TPMT activity prevents myelotoxicity in patients with inflammatory bowel disease. Routine analytical controls should be performed in these patients independently of TPMT activity.     

Pharmacokinetics of tenofovir in breast milk of lactating rhesus macaques

To study tenofovir transfer into milk, two lactating macaques were given a subcutaneous dose of tenofovir (30 mg/kg of body weight). Peak concentrations and area under the curve values of tenofovir in milk were approximately 3 and approximately 20% of those detected in serum, respectively.     

A spatiotemporal statistical atlas of motion for the quantification of abnormal myocardial tissue velocities

In this paper, we present a new method for the automatic comparison of myocardial motion patterns and the characterization of their degree of abnormality, based on a statistical atlas of motion built from a reference healthy population. Our main contribution is the computation of atlas-based indexes that quantify the abnormality in the motion of a given subject against a reference population, at every location in time and space. The critical computational cost inherent to the construction of an atlas is highly reduced by the definition of myocardial velocities under a small displacements hypothesis. The indexes we propose are of notable interest for the assessment of anomalies in cardiac mobility and synchronicity when applied, for instance, to candidate selection for cardiac resynchronization therapy (CRT). We built an atlas of normality using 2D ultrasound cardiac sequences from 21 healthy volunteers, to which we compared 14 CRT candidates with left ventricular dyssynchrony (LVDYS). We illustrate the potential of our approach in characterizing septal flash, a specific motion pattern related to LVDYS and recently introduced as a very good predictor of response to CRT.     

Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF-alpha

Activation of inflammatory pathways may contribute to the beginning and the progression of both atherosclerosis and type 2 diabetes. Here we report a novel interaction between insulin action and control of inflammation, resulting in glucose intolerance and vascular inflammation and amenable to therapeutic modulation. In insulin receptor heterozygous (Insr+/-) mice, we identified the deficiency of tissue inhibitor of metalloproteinase 3 (Timp3, an inhibitor of both TNF-alpha-converting enzyme [TACE] and MMPs) as a common bond between glucose intolerance and vascular inflammation. Among Insr+/- mice, those that develop diabetes have reduced Timp3 and increased TACE activity. Unchecked TACE activity causes an increase in levels of soluble TNF-alpha, which subsequently promotes diabetes and vascular inflammation. Double heterozygous Insr+/-Timp3+/- mice develop mild hyperglycemia and hyperinsulinemia at 3 months and overt glucose intolerance and hyperinsulinemia at 6 months. A therapeutic role for Timp3/TACE modulation is supported by the observation that pharmacological inhibition of TACE led to marked reduction of hyperglycemia and vascular inflammation in Insr+/- diabetic mice, as well as by the observation of increased insulin sensitivity in Tace+/- mice compared with WT mice. Our results suggest that an interplay between reduced insulin action and unchecked TACE activity promotes diabetes and vascular inflammation.     

Prevalence of clinical isolates of Escherichia coli and Klebsiella spp. producing multiple extended-spectrum beta-lactamases

Eleven thousand two hundred seventy-two Escherichia coli, 1109 Klebsiella pneumoniae, 1124 Salmonella enterica, and 602 Klebsiella oxytoca unrelated clinical isolates were obtained between 2001 and 2004 in a university hospital in Salamanca, Spain. One hundred thirteen E. coli (1%), 32 K. pneumoniae (2.9%), 4 K. oxytoca (0.66%), and 5 S. enterica (0.44%) isolates produced extended-spectrum beta-lactamases (ESBLs). We obtained 42.2% of the ESBL-producing isolates from outpatients and 57.8% from inpatients. The most commonly detected ESBLs were CTX-M 14 (43.5% of ESBL-producing isolates), TEM-116 (22.1%), and SHV-2 (15.6%). A CTX-M 27-producing E. coli is 1st reported in Spain in this study. Two (20 isolates, 13%) or 3 (7 isolates, 4.5%) ESBLs were produced by 17.5% of ESBL-producing isolates (27 isolates). The most frequent combinations were CTX-M 14 + TEM-116 (5.7%), SHV-12 + TEM-116 (2.6%), and SHV-2 + CTX-M 14 + TEM-116 (2.6%). Clonal diversity was high even between isolates producing the same combinations of 2 or 3 beta-lactamases.