Cardiac MRI findings to differentiate athlete's heart from hypertrophic (HCM), arrhythmogenic right ventricular (ARVC) and dilated (DCM) cardiomyopathy.

To provide clinically relevant criteria for differentiation between the athlete's heart and similar appearing hypertrophic (HCM), dilated (DCM), and arrhythmogenic right-ventricular cardiomyopathy (ARVC) in MRI. 40 top-level athletes were prospectively examined with cardiac MR (CMR) in two university centres and compared to retrospectively recruited patients diagnosed with HCM (n = 14), ARVC (n = 18), and DCM (n = 48). Analysed MR imaging parameters in the whole study cohort included morphology, functional parameters and late gadolinium enhancement (LGE). Mean left-ventricular enddiastolic volume index (LVEDVI) was high in athletes (105 ml/m2) but significantly lower compared to DCM (132 ml/m2; p = 0.001). Mean LV ejection fraction (EF) was 61% in athletes, below normal in 7 (18%) athletes vs. EF 29% in DCM, below normal in 46 (96%) patients (p < 0.0001). Mean RV-EF was 54% in athletes vs. 60% in HCM, 46% in ARVC, and 41% in DCM (p < 0.0001). Mean interventricular myocardial thickness was 10 mm in athletes vs. 12 mm in HCM (p = 0.0005), 9 mm in ARVC, and 9 mm in DCM. LGE was present in 1 (5%) athlete, 8 (57%) HCM, 10 (56%) ARVC, and 21 (44%) DCM patients (p < 0.0001). Healthy athletes' hearts are characterized by both hypertrophy and dilation, low EF of both ventricles at rest, and increased interventricular septal thickness with a low prevalence of LGE. Differentiation of athlete's heart from other non-ischemic cardiomyopathies in MRI can be challenging due to a significant overlap of characteristics also seen in HCM, ARVC, and DCM.

Establishing a food list for a Total Diet Study: how does food consumption of specific subpopulations need to be considered?

A Total Diet Study (TDS) consists of selecting, collecting and analysing commonly consumed foods to obtain concentration data of different chemical compounds in foods as eaten. A TDS food list summarises the most consumed foods and represents the dietary habits of the general population of the country under study. The work reported here investigated whether TDS food lists that were initially designed for the whole population of the country under study also sufficiently cover the dietary pattern of specific subpopulations that are extra vulnerable for certain contaminants. The work was performed using data of three European countries: the Czech Republic, France and the UK. Each national food consumption database was combined with the corresponding national TDS food list (containing 336, 212 and 119 food items for the Czech Republic, France and the UK, respectively). The data were aggregated on the highest level of hierarchy of FoodEx-1, a pan-European food classification system, including 20 main FoodEx-1 groups. For the group 'milk and dairy products', the coverage of the consumption by the food list was investigated for more refined subgroups. For each food group or subgroup and country, the average percentage of coverage of the diet by the national TDS food list was calculated for different subpopulations, including children versus adults, women versus men, vegetarians versus non-vegetarians, and women of child-bearing age versus older women. The average diet of the different subpopulations was sufficiently covered by the food list of the Czech Republic and France. For the UK the average coverage was low due to a different food-coding approach and because food lists were not derived directly from national food consumption data. At the level of the 20 main food groups, differences between the subpopulations with respect to the average coverage of consumption by the TDS food list were minimal. The differences were more pronounced when looking in detail at the coverage of the dairy consumption. TDS food lists based on the mean consumption of the general population are also applicable to study the chemical exposure of different subpopulations, e.g. children, women of child-bearing age and vegetarians. This lowers the effort when performing a TDS.

Exploring the relationship between protein secondary structures, temperature-dependent viscosities, and technological treatments in egg yolk and LDL by FTIR and rheology.

Egg yolk and its main component, low-density lipoproteins (LDL), were consecutively pasteurised, optimally freeze-dried, and dispersed in various NaCl solutions (0-10%). Heat-induced changes in the protein secondary structures which accompanied viscosity-increasing aggregation processes were monitored using Fourier transform infrared spectroscopy (FTIR) to determine the intensities of intermolecular ß-sheets (1622 cm(-1)) and results were compared with the temperature-dependent viscosities. Considerable changes in secondary structures observed after reconstitution of freeze-dried LDL had no detectable effect on the characteristic heat-induced viscosity curves but suggest that LDL plays a particular role in the unwanted gel formation of egg yolk after conventional freezing. For all egg yolk samples and all NaCl-containing LDL samples, the sigmoidal changes in the absorbance units vs. temperature curves corresponded with the first increase in heat-induced viscosity. Both analytical methods showed that the presence of ionic strength caused a shift in curve progressions towards higher temperatures, indicating increased thermal stability.

[Prevalence of the metabolic syndrome and its risk factors: results of a large work-site health assessment]. / Prävalenz des Metabolischen Syndroms und seiner Risikofaktoren: Ergebnisse einer großen betrieblichen Gesundheitsuntersuchung.

BACKGROUND: Facing the demographic change, cardiovascular risk factors have been assessed within an occupational checkup to establish health programs. PATIENTS AND METHODS: From 2006 to 2007, anthropometric and blood parameters of 27 359 employees of a large company of the German automobile industry were collected aiming to determine the prevalence of metabolic syndrome (by NCEP ATP III) and its risk factors. Data from 3048 employees (fasting state) were analyzed (age: ∅ 39,4 ± 10,3 years, 81.4% males). RESULTS: The most common risk factors were hypertension ≥ 130/85 mmHg (men [m]: 74,4%, 95%-confidence interval [CI] 73-76%, women [w]: 47,1%, 95%-CI 43-51%), elevated triglycerides (≥ 150 mg/dl; m: 32,8%, 95%-CI 31-35%, w: 13,8%, 95%-CI 11-17%) and waist-circumferences (> 102 cm for men: 15,1%, 95%-CI 14-17%; > 88 cm for women: 16,9%, 95%-CI 14-20%). The prevalence of metabolic syndrome (≥ 3 risk factors) was 11,7% (95%-CI 12-15%; m: 12,7%, 95%-CI 11-14%, w: 7,4%, 95%-CI 6-10%) increasing with physical inactivity and rising age up to 20%. The prevalence of hypertension in young (< 20 years) and elder men (≥ 50 years) was similarly high (79,1%, 95%-CI 70-86% vs. 79,9%, 95%-CI 75-82%). CONCLUSION: The prevalence of metabolic syndrome in this sample is rather low, but 75% of the men and nearly 50% of the women had hypertension. Health programs should focus on this risk factor in particular.

Association of leptin and insulin with childhood obesity and retinal vessel diameters.

OBJECTIVE: Childhood obesity is associated with an impaired retinal microcirculation. The aim of the study was to investigate the association between specific obesity-related biomarkers, physical fitness and retinal vessel diameters in school children. DESIGN AND SUBJECTS: We studied 381 children aged 10-11 years (body mass index (BMI): 19.3±3.7 kg m(-2)) in a school-based setting. MEASUREMENTS: Anthropometric measurements and blood sampling were conducted using standard protocols for children. The serum biomarkers leptin, adiponectin, insulin as well as interleukin-6 (IL-6) were analyzed. Physical fitness was determined by a six-item-test battery and physical activity by use of a questionnaire. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and the arteriolar-to-venular diameter ratio (AVR) were assessed with a non-mydriatic vessel analyzer (SVA-T) using a computer-based program. RESULTS: Compared with normal weight children (n=254), obese children (n=39) showed higher leptin (P<0.001), higher insulin (P<0.001), higher IL-6 (P<0.001) and lower adiponectin levels (P=0.013). Obese children demonstrated wider CRVE (P=0.041) and lower AVR (P<0.001). Higher leptin levels were associated with wider CRVE (P=0.032) and lower AVR (P=0.010), that was BMI dependent. Insulin levels were associated with arteriolar (P=0.045) and venular dilatation (P=0.034) after adjustment for BMI. No significant associations between adiponectin levels, IL-6 levels, physical fitness or physical activity and retinal vessel diameter were observed. Lower leptin levels were independently correlated with higher physical fitness (r=-0.33; P<0.001). CONCLUSION: Leptin and insulin levels are associated with changes of the retinal microcirculation. Especially insulin seems to be a good target marker for the cardiometabolic risk assessment in children since elevated insulin levels are independently associated with microvascular end-organ alterations at an early stage. Lifestyle intervention studies are warranted to examine whether improvement of physical fitness or weight reduction can affect cardiometabolic risk markers and reverse alterations of the retinal microcirculation.

Retinal vessel diameter, obesity and metabolic risk factors in school children (JuvenTUM 3).

BACKGROUND: The prevalence of childhood obesity is high and its association with future cardiovascular disease in adulthood is well established. The cross-sectional data presented analyze the prevalence of obesity and the association between metabolic risk factors, physical inactivity and retinal vessel diameter in young school children. METHODS: The examination included 578 school children aged 11.1±0.6 years from secondary schools in the District of Munich, Germany. Anthropometric measurements and blood sampling were conducted using standard protocols for children. Physical activity was evaluated by use of a questionnaire. Retinal microvascular diameters and the arteriolar to venular ratio (AVR) were assessed with a non-mydriatic vessel analyser (SVA-T) using a computer-based program. RESULTS: In our population, 128 (22.2%) children were overweight (ow) or obese (ob). The mean retinal arteriolar and venular calibres were 208.0±15.6 µm and 236.2±16.2 µm, respectively, with a mean AVR of 0.88±0.01. Girls had significantly wider arteriolar and venular diameters compared to boys (p<0.001). ow and ob children had a lower AVR compared to normal weight (nw) children (mean(95% CI); nw: 0.89(0.88-0.89); ow: 0.87(0.86-0.88); ob: 0.85(0.83-0.87); p≤0.05). Wider venular diameters were independently associated with higher BMI and higher hsCRP. Blood pressure was associated with retinal vessel constriction. Higher physical inactivity and BMI were independently associated with a reduced AVR (p=0.032 and p<0.001, respectively). CONCLUSIONS: Cardiometabolic risk factors and physical inactivity are associated with retinal microvascular alterations in young children, comparable to associations in adults. Retinal vessel imaging seems to be a feasible assessment for the detection of microvascular impairments in children at risk of developing cardiovascular disease in adulthood.

Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY.

Patients with high-risk or advanced myeloid malignancies have limited effective treatment options. These include high-dose therapy followed by allogeneic hematopoietic cell transplantation (HCT). We report a single-institution, long-term follow-up of 96 patients, median age 50 (range, 20-60) years, who received HLA-matched related HCT between 1992 and 2007. All patients were treated with a uniform preparatory regimen intended to enhance the widely used regimen of BU and CY that included: BU 16.0 mg/kg (days -8 to -5), etoposide 60 mg/kg (day -4), CY 60 mg/kg (day -2) with GVHD prophylaxis of CsA or FK506 and prednisone. Disease status at transplantation was high-risk AML (n=41), CML in second chronic phase or blast crisis (n=8), myelofibrosis and myeloproliferative disorders (n=8), and myelodysplasia (n=39). Thirty-six percent (n=35) of patients received BM whereas 64% (n=61) received G-CSF-mobilized PBPC. With a median follow-up of 5.6 years (range, 1.6-14.6 years) actuarial 5-year OS was 32% (95% CI 22-42) and 5-year EFS was 31% (95% CI 21-41). Relapse rate was 24% (95% CI 15-33) at 2 and 5 years. Nonrelapse mortality was 29% (95% CI 20-38) at day 100 and 38% (95% CI 29-47) at 1 year. Cumulative incidence of acute (grade II-IV) and extensive chronic GVHD was 27% (95% CI 18-36) and 29% (95% CI 18-40), respectively. There was no statistically significant difference in OS (31 vs 32%, P=0.89) or relapse rates (17 vs 28%, P=0.22) for recipients of BM vs PBPC, respectively. These results confirm that patients with high-risk or advanced myeloid malignancies can achieve long-term survival following myeloablative allogeneic HCT with aggressive conditioning.

Water quality assessment of the Sinos River, Southern Brazil.

The Sinos River basin is located Northeast of the state of Rio Grande do Sul (29º 20' to 30º 10' S and 50º 15' to 51º20'W), Southern Brazil, covering two geomorphologic provinces: the Southern plateau and central depression. It is part of the Guaíba basin and has an area of approximately 800 km², encompassing 32 municipalities. The objective of this study was to monitor water quality in the Sinos River, the largest river in this basin. Water samples were collected at four selected sites in the Sinos River, and the following parameters were analysed: pH, dissolved oxygen, biochemical oxygen demand (BOD5), turbidity, fecal coliforms, total dissolved solids, temperature, nitrate, nitrite, phosphorous, chromium, lead, aluminum, zinc, iron, and copper. The results were analysed based on Resolution No. 357/2005 of the Brazilian National Environmental Council (CONAMA) regarding regulatory limits for residues in water. A second analysis was performed based on a water quality index (WQI) used by the Sinos River Basin Management Committee (COMITESINOS). Poor water quality in the Sinos River presents a worrying scenario for the region, since this river is the main source of water supply for the urban core. Health conditions found in the Sinos River, mainly in its lower reaches, are worrying and a strong indicator of human activities on the basin.

First wave of the influenza A/H1N1v pandemic in Switzerland.

AIM: To describe the disease burden, clinical pattern and outcome of influenza-related cases presenting to a Swiss Emergency Department (ED), during the first wave of the 2009 pandemic. METHODS: Retrospective analysis of prospectively collected data at the University Hospital of Basel, Switzerland. All patients presenting to the ED with influenza-like symptoms from June 1 to October 23, 2009, were studied. Rate of hospitalisation, demographic characteristics, symptoms, microbiological diagnoses and complications of influenza infection were analysed. RESULTS: One tenth (808 of 8356 patients) of all non-trauma ED presentations, during the study period, were a result of suspected influenza-related illness. Influenza A/H1N1v infection accounted for 5% of these presentations. Patients aged 50 years or less accounted for 87% of these presentations and for 100% of A/H1N1v infection. The highest detection rate of A/H1N1v-infection occurred in July, and the highest rate of clinical presentations occurred in August 2009. Underlying medical disease was observed in 14% of all patients. The presence of fever, cough and myalgia was the prime clinical predictor for the presence of A/H1N1v infection. 16% of patients with this triad suffered from A/H1N1v. CONCLUSION: Suspected A/H1N1v infection contributed to a considerable health care burden in Switzerland. However, the rate of true positivity was low (5%), hospitalisations rare (5%), and mortality did not occur. Therefore, the first wave of the A/H1N1v pandemic in Switzerland was rather media "hype" than real threat.

Dosimetria proposta para o tratamento por ultra-som: uma revisão de literatura / Dosimetry propost for the treated for ultrasound: a literature of the review

Um dos equipamentos termoterapêuticos utilizados para a produção do calor é o que utiliza princípios de ultra-som (US) produzindo calor profundo pela propagação das suas ondas mecânicas, que são essencialmente as mesmas das ondas sonoras, mas com uma frequência mais alta. O US é produzido por uma corrente alternada que flui por um cristal piezoelétrico, alojado em um transdutor. Os efeitos do US dependem de muitos fatores físicos e biológicos, tais como a iontensidade, o tempo de exposição, a estrutura espacial e temporal do campo ultra-sônico e o estado fisiológico do local a ser tratado. Este grande número de variáveis complica a compreensão exata do seu mecanismo de ação na interação com os tecidos biológicos. Os efeitos do US vem sendo investigados e descritos de maneira empírica através dos tempos e as opinio~es sobre as dosagens utilizadas para o tratamento diferem significativamente, existindo poucas evidências dos seus efeitos clínicos. Sendo assim, este trabalho tem como objetivo apontar, mediante uma revisão bibliográfica, se existem parâmetros físicos e biológicos para determinaçãoi das doses de US, quando utilizado para fins terapêuticos

Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML.

A total of 24 patients (median age 58; range, 27-71 years) with chronic myeloid leukemia (CML) in first chronic (CP1) (n=14), second chronic (n=4), or accelerated phase (n=6) who were not candidates for conventional hematopoietic cell transplantation (HCT), received nonmyeloablative HCT from HLA-matched siblings a median of 28.5 (range, 11-271) months after diagnosis. They were conditioned with 2 Gy total body irradiation (TBI) alone (n=8) or combined with fludarabine, 90 mg/m(2) (n=16). Postgrafting immunosuppression included cyclosporine and mycophenolate mofetil. All patients initially engrafted. However, 4 of 8 patients not given fludarabine experienced nonfatal rejection while all others had sustained engraftment. With a median follow-up of 36 (range, 4-49) months, 13 of 24 patients (54%) were alive and in complete remission. There were five (21%) deaths from nonrelapse mortality, one (4%) during the first 100 days after transplant. The proportions of grade II, III, and IV acute GVHD were 38, 4, and 8%, respectively. The 2-year estimate of chronic GVHD was 32%. The 2-year survival estimates for patients in CP1 (n=14) and beyond CP1 (n=10) were 70 and 56%, respectively. This study shows encouraging remission rates for patients with CML not eligible for conventional allografting.

Hematopoietic cell transplantation from related and unrelated donors after minimal conditioning as a curative treatment modality for severe paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a somatic mutation of the X-linked phosphatidylinositol glycan class A gene. Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning is the only curative treatment; however, it is associated with high treatment-related mortality. Here, we report on allogeneic HCT for PNH after minimal conditioning. Seven adult patients with high-risk PNH underwent peripheral blood HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m(2)/d on days -4 to -2 and 2 Gy of total body irradiation on day 0. After HCT, patients were given immunosuppressive therapy with oral cyclosporine starting on day -3 and mycophenolate mofetil starting on day 0. All 7 patients attained durable engraftment. After 28 days, a median of 77% (range, 53%-96%) T-cell donor chimerism was found in bone marrow and peripheral blood. T-cell chimerism increased to 91% (range, 76%-100%) on day +180 and to 100% in all surviving patients after 12 months. All 7 patients attained complete remissions of their disease. Four patients are alive 13 to 38 months after HCT. Three patients died of treatment-related mortality, 1 because of complications after acute pancreatitis and multiorgan failure, 1 because of infection related to chronic graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH.

HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals.

A highly conserved signaling property of Nef proteins encoded by human or simian immunodeficiency virus is the binding and activation of a PAK kinase whose function is unclear. Here we show that Nef-mediated p21-activated kinase (PAK) activation involves phosphatidylinositol 3-kinase, which acts upstream of PAK and is bound and activated by Nef similar to the manner of Polyoma virus middle T antigen. The Nef-associated phosphatidylinositol-3-PAK complex phosphorylated the pro-apoptotic Bad protein without involving the protein kinase B-Akt kinase, which is generally believed to inactivate Bad by serine phosphorylation. Consequently, Nef, but not a Nef mutant incapable of activating PAK, blocked apoptosis in T cells induced by serum starvation or HIV replication. Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis.

Non-myeloablative hematopoietic stem cell transplantation.

Conventional approaches to allogeneic stem cell transplantation have used toxic high-dose conditioning therapy in attempts to eradicate underlying diseases and achieve allogeneic engraftment. Preclinical studies and clinical observations have shown that to achieve engraftment conditioning regimens could be markedly reduced in intensity with reduction in treatment toxicities. The use of potent pre- and postgrafting immunosuppression facilitated stable mixed hematopoietic chimerism in a preclinical canine model. The initial clinical experiences with attenuated conditioning regimens have shown promise as a modality to achieve human stem cell transplantation with an improved safety profile. This may allow offering potentially curative hematopoietic stem cell transplantation (HSCT) to a more representative patient population (older and sicker) who are currently not eligible for such therapy. Obtaining a state of mixed hematopoietic chimerism could prove curative of the disease phenotype of various nonmalignant disturbances of the hematopoietic and immune systems. On the other hand, patients with hematopoietic malignancy will likely require conversion to full donor hematopoeisis by virtue of graft-versus-host (GVH) reactions directed against both recipient hematopoiesis and underlying malignancy. The infusion of additional donor lymphocytes has been proposed by many groups to augment graft versus tumor responses, but most likely more specific strategies will need to be developed to improve efficacy and avoid nonspecific GVH reactions.

Nonmyeloablative hematopoietic stem cell transplantation: transplantation for the 21st century.

Conventional approaches to allogeneic stem cell transplantation have used toxic high-dose conditioning therapy to achieve allogeneic engraftment and control of underlying disease. For engraftment purposes, preclinical studies and clinical observations have shown that conditioning regimens can be markedly reduced in intensity, resulting in reduced treatment toxicities. Preclinical canine studies demonstrated that the use of potent pre- and postgrafting immunosuppression allows for reduction in conditioning regimens while facilitating development of stable mixed chimerism. If attenuated conditioning regimens can be successfully translated to human stem cell transplantation, an improved safety profile will allow potentially curative treatment to a more representative patient profile not currently offered such therapy. Mixed chimerism could prove curative of disease phenotype of various nonmalignant disturbances of the hematopoietic and immune systems. For patients with hematopoietic malignancy, spontaneous conversion to full donor hematopoeisis after stem cell transplant may prove curative by virtue of graft versus host reactions directed against the malignancy, however infusion of additional donor lymphocytes may be needed to treat persistent disease.

Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation.

MSL-109 is a monoclonal antibody specific to the cytomegalovirus (CMV) glycoprotein H with high neutralizing capacity. In a prospective, randomized, double-blind study, allogeneic hematopoietic stem cell transplantation (HSCT) recipients with positive donor and/or recipient serology for CMV before transplantation received either 60 mg/kg MSL-109 (n = 59), 15 mg/kg MSL-109 (n = 60), or placebo (n = 60) intravenously every 2 weeks from day -1 until day 84 after transplantation. CMV pp65 antigenemia, CMV-DNA load in plasma, and viremia by culture were tested weekly. Primary end points were development of pp65 antigenemia at any level and/or viremia for which ganciclovir was given. There was no statistically significant difference in CMV pp65 antigenemia or viremia among patients in the 60-mg group (pp65 antigenemia, 47%; viremia, 15%), the 15-mg group (52%; 23%), and the placebo group (45%; 17%). There was also no difference in maximum levels of pp65 antigenemia, time to clearance of pp65 antigenemia after start of ganciclovir, CMV disease, invasive bacterial and fungal infections, time to neutrophil and platelet engraftment, acute graft-versus-host disease, days of hospitalization, and overall survival rate among the 3 groups. However, a subgroup analysis of CMV-seronegative recipients with a seropositive donor (D+/R-) showed a transiently improved survival rate by day 100 in MSL-109 recipients (mortality: 60-mg group, 1/13; 15-mg group, 1/12; placebo group, 6/10 [P = .02 for 60-mg versus placebo groups; P = .08 for 15-mg versus placebo groups]); by the end of follow-up, the difference was no longer statistically significant. The improved survival rate in D+/R- patients could not be attributed to a reduction in CMV disease; however, MSL-109 was associated with improved platelet engraftment and less grade III to IV acute graft-versus-host disease in this subgroup. In a subgroup analysis of CMV-seropositive recipients of MSL-109 (D+/R+ and D-/R+), overall mortality was increased compared to that of the placebo group (P = .12 for the 60-mg versus placebo groups, P = .05 for the 15-mg versus placebo groups, and P = .04 for the dose levels combined versus placebo). MSL-109 was well tolerated and no immune response to the drug was observed. Thus, MSL-109 was safe but did not reduce CMV infection in allogeneic HSCT recipients. The transient survival advantage seen early after transplantation in CMV D+/R- patients and the negative effect on survival in seropositive patients remain unexplained. Thus, there is no evidence that MSL-109 is beneficial in CMV-seropositive HSCT recipients.