Overweight, obesity and body fat composition in spanish adolescents. The AVENA Study

OBJECTIVE: To describe the prevalence of overweight and obesity in the Spanish adolescent population and its relationship with the socioeconomic status, and to assess their body fat composition and compare these results with previous data from our own country. DESIGN: Cross-sectional multicenter study conducted in five Spanish cities (Granada, Madrid, Murcia, Santander and Zaragoza) in 2000-2002. SUBJECTS: 2,320 adolescents with complete set of anthropometric measurements, 1,192 boys and 1,128 girls. MEASUREMENTS: Body mass index calculated from weight and height measurements, and body fat percentage calculated from skinfold thickness measurements. RESULTS: Overweight + obesity prevalences were 25.69 and 19.13% in boys and girls, respectively. Overweight + obesity prevalence increased in boys from high to medium-low socioeconomic status categories (p = 0.015); meanwhile, there was not a significant effect of socioeconomic status in girls. In males, overweight + obesity prevalence changed from 1985 to 2000-2002 from 13 to 35% and in females from 16 to 32%. The rate of change in overweight + obesity prevalences seems to increase in the last years; from 0.88 (1985 to 1995) to 2.33%/year (1995 to 2000-2002) in males and from 0.5 (1985 to 1995) to 1.83%/year (1995 to 2000-2002) in females. The rate of body fat percentage increase was similar between 1980 and 1995 and between 1995 and 2000-2002: 0.26 and 0.23%/year, respectively, at 13 years of age, and 0.16 and 0.17%/year, respectively, at 14 years of age. CONCLUSION: We observed elevated overweight and obesity prevalences in Spanish adolescents, similar to those observed in other European countries. There is a significant inverse relationship between socioeconomic status and overweight + obesity, but only in boys. The rate of change in overweight prevalence in Spanish adolescents seems to increase, and the rate of increase of body fat percentage seems to be similar as in previous years.     

Management and Outcome of Patients Admitted With Tricuspid Regurgitation in France

BackgroundGrowing evidence shows a major outcome impact and undertreatment of tricuspid regurgitation (TR), but large and comprehensive contemporary reports of management and outcome at the nationwide level are lacking.MethodsWe gathered all consecutive patients admitted with a diagnosis of likely functional TR in 2014-2015 in France from the Programme de Médicalisation des Systèmes d’Information national database and collected rate of surgery, in-hospital mortality, 1-year mortality, or heart failure (HF) readmission rates.ResultsIn 2014-2015, 17,676 consecutive patients (75 ± 14 years of age, 51% female) were admitted with a TR diagnosis. Charlson index was ≥ 2 in 56% of the population and 46% presented with HF. TR was associated with prior cardiac surgery, ischemic/dilated cardiomyopathy, or mitral regurgitation in 73% of patients. Only 10% of TR patients overall and 67% of those undergoing mitral valve surgery received a tricuspid valve intervention. Among the 13,654 (77%) conservatively managed patients, in-hospital mortality, 1-year mortality, and 1-year mortality or HF readmission rates were 5.1%, 17.8%, and 41%, respectively, overall, and 5.3%,17.2%, and 37%, respectively, among those with no underlying medical conditions (8-fold higher than predicted for age and gender).ConclusionsThis nationwide cohort of patients admitted with TR included elderly patients with frequent comorbidities/underlying cardiac diseases. In patients conservatively managed, mortality and morbidity were considerably high over a short time span. Despite this poor prognosis, only 10% of patients underwent a tricuspid valve intervention. These nationwide data showing a considerable risk and potential underuse of treatment highlight the critical need to develop strategies to improve the management and outcomes of TR patients.     

Two acquired immunodeficiency syndrome-associated Burkitt's lymphomas produce specific anti-i IgM cold agglutinins using somatically mutated VH4-21 segments

We analyzed the reactivity and the structure of the VH and VL segments of two IgM monoclonal antibodies (MoAbs) produced by spontaneously in vitro outgrowing cell lines, HBL-2 and HBL-3, established from two acquired immunodeficiency syndrome (AIDS) patients with Epstein-Barr virus (EBV)-negative Burkitt's lymphoma (BL). These B-cell clones were representative of the respective neoplastic parental clones, as determined by immunophenotypic and molecular genetic analysis. The IgM MoAbs were highly specific for the i determinant on red blood cells (cold agglutinins), but bound none of the other eight self and nine foreign antigens (Ags) tested, including those most commonly recognized by natural antibodies or autoantibodies. Structural analysis showed that the IgM MoAb VH segment sequences were 93.5% and 84.2% identical with that of the germline VH4-21 gene, which encodes the vast majority of cold agglutinins that are specific for the i/l carbohydrate Ag and are produced under chronic lymphoproliferative conditions. The HBL-2 MoAb VH4-21 gene segment was juxtaposed with 20P3 and JH6 genes and paired with a V lambda 1 segment, the sequence of which was 95.5% identical to that of the germline Humlv117 gene; the HBL-3 MoAb VH4-21 gene segment was juxtaposed with DXP'1 and JH5 genes and paired with a V lambda 1 segment, the sequence of which was 86.7% identical to that of the germline Humlv1L1 gene. The high degree of conservation of the VH4-21 gene in the human population, the nature of the nucleotide differences in the expressed VH4-21 segments, and the presence of nucleotide substitutions in the HBL-2 and HBL-3 IgM MoAb JH and/or J lambda segments suggested that the MoAb V segments underwent a process of somatic hypermutation. This was formally shown in the HBL-3 MoAb VH segment, by differentially targeted polymerase chain reaction amplification of the HBL-3 MoAb-producing cell genomic DNA. In addition, cloning and sequencing of the genomic DNA from fibroblasts of the same patient whose neoplastic B cells gave rise to the HBL-3 cell line yielded a germline copy of the VH4-21 gene. Thus, the expression of VH4-21 gene products may be involved in a self Ag-driven process of clonal B-cell expansion and selection associated with BL in these AIDS patients.     

BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death [published erratum appears in Blood 1994 Jun 15;83(12):3835]

Apoptosis is the major form of cell death associated with the action of chemotherapeutic agents on tumor cells, and therefore the expression of genes that interfere with apoptosis can have important consequences for the efficacy of therapeutic approaches. Here we show that K562, a chronic myelogenous leukemia (CML) cell line expressing the BCR-ABL fusion protein, are resistant to the induction of apoptosis by a number of agents and conditions. Antisense oligodeoxynucleotides corresponding to the translation start of bcr downregulate bcr-abl protein in these cells and render them susceptible to induction of apoptosis by chemotherapeutic agents or serum deprivation. Expression of a temperature sensitive v-Abl protein reverses the effects of the antisense oligonucleotides, such that the cells remain resistant to apoptosis at the permissive temperature. These data indicate that bcr- abl acts as an anti-apoptosis gene in CML cells and suggests that the effect is dependent on the abl kinase activity in this chimeric protein. Inhibition of bcr-abl to render CML cells susceptible to apoptosis can be combined with therapeutic drugs and/or treatment capable of inducing apoptosis to provide an effective strategy for elimination of these cells.     

Assessment of cyclosporine pharmacokinetic parameters to facilitate conversion from C0 to C2 monitoring in heart transplant recipients

BACKGROUND: Cyclosporine (CsA) 2-hour postdose (C2) monitoring is recommended to assess CsA exposure and predict clinical outcomes among heart transplant recipients. We correlated pharmacokinetic parameters and clinical outcomes in stable long-term heart transplant recipients monitored with C0 to develop an algorithm to convert patients from C0 to C2 monitoring. METHODS: Paired CsA C0-C2 measurements and serum creatinine levels were obtained from 35 heart transplant recipients more than 2 years posttransplantation (mean 8.8+/-4.7 years). RESULTS: The mean CsA dose and C0, C2, and C0/C2 ratio were 85+/-23 mg/12 hours, 123+/-41 ng/mL, 572+/-274 ng/mL and 4.8+/-2.1, respectively. C0 correlated weakly with C2 (r=.42, P=.011). The CsA dose correlated better with C2 (r=.58; P<.001) than with C0 (r=.37; P=.026). A good correlation was noted between C2 and the C2/C0 ratio (r=.73; P<.001), but none between C0 and the C2/C0 ratio. A borderline significant inverse correlation was noted between C0 and the worst endomyocardial biopsy score (r=-.34; P=.045), whereas none was noted with C2. Serum creatinine level did not correlate with either C2 or C0. Among patients with C0 within our target of 100 to 150 ug/L, six had C2 above 300 to 600 ug/L as suggested by the literature. CONCLUSIONS: In long-term heart transplant recipients, we could not identify a single pharmacokinetic parameter that could be used to develop an algorithm to convert from C0 to C2 monitoring; however, C2 may be better than C0 for identifying patients at risk of overexposure to CsA.     

Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

Background

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition.

Materials and methods

We investigated the effect of two dual PI3K/mTOR (both mTORC1 and mTORC2) inhibitors, NVP-BEZ235 and NVP-BGT226, on SQ20B laryngeal and FaDu hypopharyngeal cancer cells characterised by EGFR overexpression, on T24 bladder tumor cell lines with H-Ras mutation and on endothelial cells. Analysis of target protein phosphorylation, clonogenic survival, number of residual ??H2AX foci, cell cycle and apoptosis after radiation was performed in both tumor and endothelial cells. In vitro angiogenesis assays were conducted as well.

Results

Both compounds effectively inhibited phosphorylation of Akt, mTOR and S6 target proteins and reduced clonogenic survival in irradiated tumor cells. Persistence of DNA damage, as evidenced by increased number of ??H2AX foci, was detected after irradiation in the presence of PI3K/mTOR inhibition, together with enhanced G2 cell cycle delay. Treatment with one of the inhibitors, NVP-BEZ235, also resulted in decreased clonogenicity after irradiation of tumor cells under hypoxic conditions. In addition, NVP-BEZ235 blocked VEGF- and IR-induced Akt phosphorylation and increased radiation killing in human umbilical venous endothelial cells (HUVEC) and human dermal microvascular dermal cells (HDMVC). NVP-BEZ235 inhibited VEGF-induced cell migration and capillary tube formation in vitro and enhanced the antivascular effect of irradiation. Treatment with NVP-BEZ235 moderately increased apoptosis in SQ20B and HUVEC cells but not in FaDu cells, and increased necrosis in both tumor and endothelial all cells tumor.

Conclusions

The results of this study demonstrate that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.     

Early postoperative anticoagulation after mechanical valve replacement: a Canadian survey

BACKGROUND AND AIM OF THE STUDY: The optimal approach to anticoagulation during the early postoperative period after mechanical valve replacement, by which early thromboembolism is prevented without bleeding complications, is not yet known. The study aim was to examine the practice patterns of Canadian cardiac surgeons with regard to early postoperative anticoagulation after mechanical valve implantation. METHODS: A questionnaire was sent to 100 Canadian cardiac surgeons in July 2004, and 57 responses were received. Data were collected regarding the approaches to early postoperative anticoagulation following uncomplicated isolated mechanical aortic valve replacement (AVR) and mitral valve replacement (MVR). RESULTS: Heparin was administered routinely after AVR and MVR by 63% and 68% of surgeons, respectively. This was most commonly initiated on postoperative day (POD) 1, and given either subcutaneously (AVR, 28%; MVR, 25%) or intravenously (AVR, 33%; MVR, 42%). Alternatively, low-molecular-weight heparin was used by 21% and 23% of surgeons after AVR and MVR, respectively. Oral warfarin was usually started on POD 1 (72% and 68%, respectively), with 40% prescribing an initial dose between 2.5 and 5.0 mg, and 51% administering between 5.1 and 7.5 mg. When heparin was not used, oral anticoagulation was more often administered earlier (AVR, p = 0.003; MVR, p = 0.006), but not at higher doses (AVR, p = 0.07; MVR, p = 0.2). Following surgery, aspirin was prescribed by 61% and 65% of surgeons after AVR and MVR, respectively. CONCLUSION: The study results highlighted a significant variability in the management of early postoperative anticoagulation after mechanical valve implantation. The clinical impact of these findings is unknown, and can only be assessed through a prospective trial.