Total fat, fat distribution and blood pressure according to eating frequency in children living in southern Italy: the ARCA project

The relationships between eating frequency and adiposity and cardiovascular risk factors have been poorly investigated in children. To evaluate this issue, anthropometric indices and blood pressure (BP) were measured in 3668 children, aged 6-11 years. Meals/snack frequency, assessed by a questionnaire, was 'Low' in 332 (or=5/day) children. Body mass index (BMI) and waist circumference significantly decreased going up across meals/snacks categories (BMI=20.5+/-0.2, 19.7+/-0.1 and 18.8+/-0.1 kg/m2; waist=68.0+/-0.6, 66.6+/-0.3, 63.9+/-0.2 cm, for Low, Intermediate and High groups, respectively; M+/-s.e.; P<0.001 by ANCOVA trend analysis adjusted by age, sex, birth weight, physical activity, parental overweight and education level). BP decreased from Low to High group but differences were no longer significant after adjustment for BMI. In our sample of school children, the daily eating frequency was inversely associated with the degree of both total adiposity and central fat deposition.     

Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study

OBJECTIVE: The mechanisms underlying high blood pressure in the framework of metabolic syndrome (MS) are not clarified: we thus analyzed the relationship of MS and its components to renal tubular sodium handling among participants of the Olivetti Heart Study, an epidemiological investigation of a representative sample of adult white male population in southern Italy. METHODS: Proximal (FPRNa) and distal (FDRNa) fractional sodium reabsorption were estimated by the clearance of exogenous lithium in 702 participants aged 25-75 years examined in 1994-1995. Blood pressure and relevant anthropometric and biochemical variables were also measured. The diagnosis of MS was based on modified National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria. RESULTS: FPRNa, but not FDRNa, was directly associated with body mass index (BMI), waist circumference, diastolic pressure, serum triglyceride and uric acid, independently of age and of antihypertensive treatment. After adjustment for age, FPRNa, but not FDRNa, was significantly greater in individuals with MS, as compared to those without [77.6% (95% confidence interval = 76.7-80.1) versus 74.4% (73.7-75.1), P < 0.001]. A similar difference was observed after the exclusion of participants on current antihypertensive treatment (P = 0.018). In untreated individuals, a significant interaction was observed between obesity and insulin resistance as related to FPRNa (P = 0.002): the highest age-adjusted levels of FPRNa were detected in obese hypertensive and obese insulin-resistant participants. CONCLUSION: In this sample of an adult male population, MS was associated with an increased rate of FPRNa. This finding is relevant to the pathophysiology of MS and possibly to the prevention of its cardiovascular and renal consequences.     

Genetic evolution of gp41 reveals a highly exclusive relationship between codons 36, 38 and 43 in gp41 under long-term enfuvirtide-containing salvage regimen

OBJECTIVE: To analyse the genetic changes in the gp41 protein in HIV-infected patients with detectable plasma viraemia receiving a long-term salvage enfuvirtide regimen. METHODS: We studied 13 heavily antiretroviral-experienced patients receiving a salvage regimen containing enfuvirtide. Substitutions in gp41 were analysed by population-based sequencing at baseline and longitudinally after the initiation of enfuvirtide treatment. To investigate sequence evolution we also analysed multiple gp41 clones from four selected patients. A Fisher's two-tailed test was used to assess the distribution of resistance-associated mutations in the clonal sequences. RESULTS: Mutations at positions 36 and 38 in gp41 (HR1) emerged rapidly (median emerging time 10 weeks), but disappeared at subsequent timepoints in most of the patients. Amino acid changes did not accumulate over time, with no patient having more than two mutations in HR1 after 6 months of treatment. The mutation N43D was not observed together with changes at positions 36 or 38 in any patient. Clonal analysis showed that the three main gp41 resistance mutations were highly mutually exclusive (P < 0.001), being present in individual clones and constituting independent populations. CONCLUSION: Substitutions at positions 36 and 38 are rapidly selected but disappear thereafter in HIV-1-infected patients failing an enfuvirtide-containing salvage therapy. We found a highly exclusive relationship between the three main enfuvirtide resistance-associated mutations (amino acids 36, 38 and 43), suggesting that the genetic evolution of HIV-1 gp41 protein is a dynamic and much more complex process than previously though.     

Electrical impedance tomography: standardizing the procedure in pneumology

The following conditions are optimal for obtaining an adequate number of informative images by electric impedance tomography: a) patient seated or standing with hands at the nape of the neck; b) breathing at rest; c) recording of at least 300 images (at a frequency of 10 Hz), and d) readings taken at the sixth intercostal space.     

Transfusion risk in cancer patients with chemotherapy-induced anemia when initiating darbepoetin alfa therapy at a baseline hemoglobin level of <9?g/dL versus 9 to <10?g/dL versus ≥10?g/dL: an exploratory analysis of a phase 3 trial

Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia (CIA). Safety concerns have prompted changes to the ESA-product information, which now recommends initiating ESAs at hemoglobin (Hb) levels < 10 g/dL (US) or ≤ 10 g/dL (EU). The present exploratory analysis of a DA trial examined how baseline-Hb levels at ESA initiation affect transfusion rates, Hb response, and safety outcomes in CIA patients. Data were retrospectively analyzed from a phase 3 trial of CIA patients randomised to 500 mcg DA every 3 weeks (Q3 W) or to 2.25 mcg/kg DA weekly (QW) for 15 weeks. In the current analysis, data were reanalyzed by baseline-Hb categories of <9 g/dL (n = 126), 9 to <10 g/dL (n = 225), and ≥ 10 g/dL (n = 354). The Q3 W and QW groups were combined. Transfusion rates were highest in the <9 g/dL baseline-Hb group in all time periods examined. The Kaplan-Meier percentage (95% CI) of patients achieving Hb ≥ 10 g/dL was 68% (59, 78) and 88% (82, 92) in the <9 g/dL and 9 to <10 g/dL baseline-Hb groups, respectively. With lower baseline-Hb, incidence of a ≥ 1 g/dL-Hb rise in 14 days progressively decreased. Incidence of venous thromboembolic events was similar in all baseline-Hb groups and similar between patients with or without a ≥ 1 g/dL-Hb rise in 14 days. Overall, transfusion risk increased and Hb response decreased at lower baseline-Hb levels in this exploratory analysis. When following ESA-product information to initiate ESAs at Hb ≤ 10 g/dL, the greatest benefit may be achieved when initiating close to 10 g/dL. Prospective studies are needed to further examine this hypothesis.     

Preimplantation genetic diagnosis for inherited breast cancer: first clinical application and live birth in Spain

Carriers of a mutation in BRCA1/2 genes confront a high lifetime risk of breast and ovarian cancer and fifty percent probability of passing the mutation to their offspring. Current options for risk management influence childbearing decisions. The indications for preimplantation genetic diagnosis (PGD) have now been expanded to include predisposition for single-gene, late-onset cancer but few cases have been reported to date despite the favorable opinion among professionals and carriers. A 28-year-old BRCA1 mutation carrier (5273G>A in exon 19) with a strong maternal history of breast cancer and 2 years of infertility decided to pursue PGD to have a healthy descendent after an accurate assessment of her reproductive options. The procedure was approved by the national regulation authority and a PGD cycle was initiated. Four out of 6 embryos harbored the mutation. The two unaffected embryos were implanted in the uterus. A singleton pregnancy was achieved and a male baby was delivered at term. Consented umbilical cord blood testing confirmed the accuracy of the technique. Individualized PGD for inherited breast predisposition is feasible in the context of a multidisciplinary team.     

Glycine decarboxylase cleaves a "malignant" metabolic path to promote tumor initiation

Tumor-initiating cells (TICs) are thought to be critical for promoting tumorigenesis. In a recent Cell article, Zhang and colleagues found that non-small cell lung cancer TICs overexpress the metabolic enzyme glycine decarboxylase, which leads to increases in pyrimidine synthesis and is critical for proliferation and tumor initiation.