Serum-Mediane von Placentaprotein-Markern: Relevanz der Unterschiede zwischen spontanen und nach-in-vitro-Fertilisation eingetretenen Schwangerschaften für das fetale Trisomie-Screening.

Trisomy-21 (Down syndrome) is the most frequent chromosomal abnorm- ality but only one third of cases would be detected by amniocentesis based on maternal age alone. Serum screening tests in the early second trimester increase the detec- tion rate to 60-65%, and more recently it was found that such screening was also possible in the first trimester by quantifying a diffe- rent panel of markers. The concen- trations of these placental proteins are strongly dependent on gestatio- nal age; thus control medians must be established and precise dating is essential. Serum chorionic gonado- trophin (HCG) levels were recently found to be increased in IVF preg- nancies compared to spontaneous gestations, leading to a falsely ele- vated trisomy screening risk. The aim of this preliminary study was to find out whether, in the first-trime- ster screening, the markers similarly differed between IVF and spontane- ous pregnancies which would call for the establishment of separate normal medians for IVF patients. We compared 24 pregnancies ob- tained after ovarian stimulation and IVF with six women after thawed embryo transfer (unstimulated cycle) and 63 gestation- and maternal-age matched spontaneously pregnant controls. A single serum was ob- tained between 6 and 16 weeks of gestation and various placental protein levels determined by im- munometric assays. Serum levels of pregnancy-associated plasma protein A (PAPP-A), which is the major marker in the first-trimes- ter screening test, were reduced in IVF pregnancies: after 9 weeks of gestation, multiples of median (MoMs) ranged between 0.23 and 3.58 (logarithmic mean 0.743). For the frozen/thawed transfers, this value was 1.08. In the 9-12 week group containing 6 cases of IVF, three thawed transfers and 25 con- trols, PAPP-A was significantly redu- ced in the stimulated compared to the nonstimulated cycles. In the late first and early second trimester the difference was not significant in our small group but the trend persisted. Pregnancies after IVF will thus show an increased incidence of false positive results in fetal trisomy-21 screening, and special medians should be established for these pati- ents.

European Cardiovascular Magnetic Resonance (EuroCMR) registry--multi national results from 57 centers in 15 countries.

BACKGROUND: The EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting. Furthermore, interim analysis of the specific protocols should underscore the prognostic potential of CMR. METHODS: Multi-center registry with consecutive enrolment of patients in 57 centers in 15 countries. More than 27000 consecutive patients were enrolled. RESULTS: The most important indications were risk stratification in suspected CAD/Ischemia (34.2%), workup of myocarditis/cardiomyopathies (32.2%), as well as assessment of viability (14.6%). Image quality was diagnostic in more than 98% of cases. Severe complications occurred in 0.026%, always associated with stress testing. No patient died during or due to CMR. In 61.8% CMR findings impacted on patient management. Importantly, in nearly 8.7% the final diagnosis based on CMR was different to the diagnosis before CMR, leading to a complete change in management. Interim analysis of suspected CAD and risk stratification in HCM specific protocols revealed a low rate of adverse events for suspected CAD patients with normal stress CMR (1.0% per year), and for HCM patients without LGE (2.7% per year). CONCLUSION: The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.

Thoracic fat volume is independently associated with coronary vasomotion.

PURPOSE: Thoracic fat has been associated with an increased risk of coronary artery disease (CAD). As endothelium-dependent vasoreactivity is a surrogate of cardiovascular events and is impaired early in atherosclerosis, we aimed at assessing the possible relationship between thoracic fat volume (TFV) and endothelium-dependent coronary vasomotion. METHODS: Fifty healthy volunteers without known CAD or major cardiovascular risk factors (CRFs) prospectively underwent a (82)Rb cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, and MBF response to cold pressor testing (CPT-MBF) and adenosine (i.e., stress-MBF). TFV was measured by a 2D volumetric CT method and common laboratory blood tests (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hsCRP) were performed. Relationships between CPT-MBF, TFV and other CRFs were assessed using non-parametric Spearman rank correlation testing and multivariate linear regression analysis. RESULTS: All of the 50 participants (58 ± 10y) had normal stress-MBF (2.7 ± 0.6 mL/min/g; 95 % CI: 2.6-2.9) and myocardial flow reserve (2.8 ± 0.8; 95 % CI: 2.6-3.0) excluding underlying CAD. Univariate analysis revealed a significant inverse relation between absolute CPT-MBF and sex (ρ = -0.47, p = 0.0006), triglyceride (ρ = -0.32, p = 0.024) and insulin levels (ρ = -0.43, p = 0.0024), HOMA-IR (ρ = -0.39, p = 0.007), BMI (ρ = -0.51, p = 0.0002) and TFV (ρ = -0.52, p = 0.0001). MBF response to adenosine was also correlated with TFV (ρ = -0.32, p = 0.026). On multivariate analysis, TFV emerged as the only significant predictor of MBF response to CPT (p = 0.014). CONCLUSIONS: TFV is significantly correlated with endothelium-dependent and -independent coronary vasomotion. High TF burden might negatively influence MBF response to CPT and to adenosine stress, even in persons without CAD, suggesting a link between thoracic fat and future cardiovascular events.

Objectifying psychomental stress in the workplace--an example.

BACKGROUND: Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. DESIGN: Repeated measurements observational cohort study (before and after intervention). SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2 h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. MAIN RESULTS: Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (p = 0.0009), but not in team A (p = 0.464). The control situation showed no difference between teams and study periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.

Impact of physical activity on energy balance, food intake and choice in normal weight and obese children in the setting of acute social stress: a randomized controlled trial.

BACKGROUND: Psychological stress negatively influences food intake and food choices, thereby contributing to the development of childhood obesity. Physical activity can also moderate eating behavior and influence calorie intake. However, it is unknown if acute physical activity influences food intake and overall energy balance after acute stress exposure in children. We therefore investigated the impact of acute physical activity on overall energy balance (food intake minus energy expenditure), food intake, and choice in the setting of acute social stress in normal weight (NW) and overweight/obese (OW/OB) children as well as the impact of psychological risk factors. METHOD: After receiving written consent from their parents, 26 NW (BMI < 90(th) percentile) and 24 7-to 11-year-old OW (n = 5)/OB (n = 19, BMI ≥ 90(th) percentile) children were randomly allocated using computer-generated numbers (1:1, after stratification for weight status) to acute moderate physical or to sedentary activity for 30 min. Afterwards, all children were exposed to an acute social stressor. Children and their parents completed self-report questionnaires. At the end of the stressor, children were allowed to eat freely from a range of 12 different foods (6 sweet/6 salty; each of low/high caloric density). Energy balance, food intake/choice and obesity-related psychological risk factors were assessed. RESULTS: Lower overall energy balance (p = 0.019) and a decreased choice of low density salty foods (p < 0.001) in NW children compared with OW/OB children was found after acute moderate physical activity but not sedentary activity. Independent of their allocation, OW/OB children ate more high density salty foods (104 kcal (34 to 173), p = 0.004) following stress. They scored higher on impulsive behavior (p = 0.005), restrained eating (p < 0.001) and parental corporal punishment (p = 0.03), but these psychological factors were not related to stress-induced food intake/choice. Positive parenting tended to be related to lower intake of sweet high density food (-132 kcal, -277 to 2, p = 0.054). CONCLUSIONS: In the setting of stress, acute moderate physical activity can address energy balance in children, a benefit which is especially pronounced in the OW/OB. Positive parenting may act as a protective factor preventing stress-induced eating of comfort food. TRIAL REGISTRATION: clinicaltrials.gov NCT01693926 The study was a pilot study of a project funded by the Swiss National Science Foundation (CRSII3_147673).

Gender, age, and body surface area are the major determinants of ascending aorta dimensions in subjects with apparently normal echocardiograms.

BACKGROUND: Limited data have been published on the normal size of the ascending aorta (AA) measured using transthoracic echocardiography (TTE). METHODS: AA diameters were measured in 1799 patients with normal cardiac findings on TTE and compared with the diameters of the sinus of Valsalva (SoV). RESULTS: Mean diameters in men and women, respectively, were 3.4 and 3.1 cm for the SoV and 3.2 and 3.0 cm for the AA. The sizes of the SoV and the AA showed strong correlations with age, age squared, and body surface area. The 5th and 95th percentile curves for the SoV and AA showed faster growth of diameters in early adulthood compared with old age. The dimensions of the SoV were larger than those of the AA (mean differences, 0.19 cm in men and 0.08 cm in women), and the difference between the SoV and AA was negatively correlated with age. CONCLUSION: The findings of this study stress the importance of indexing dimensions of the SoV and the AA to age and body surface area separately for men and women.

Bruce Treadmill Test in Children : First Normal Values for Children from Western Europe : P67

Introduction: One of the main goals for exereise testing in children is evaluation of exercise capacity. There are many testing protocols, but the Bruce treadmill protocol is widely used among pediatrie cardiology centers. Thirty years ago, Cuming et al. were the first to establish normal values for children from North America (Canada) aged 4 to 18 years old. No data was ever published for children from Western Europe. Our study aimed to assess the validity of the normal values from Cuming et al. for children from Western Europe in the 21 st century. Methods: It is a retrospective cohort study in a tertiary care children's hospital. 144 children referred to our institution but finally diagnosed as having a normal heart underwent exercise stress testing using the Bruce protocol between 1999 and 2006. Data from 59 girls and 85 boys aged 6 to 18 were reviewed. Mean endurance time (ET) for each age category and gender was compared with the mean normal values fram Cumming et al by an unpaired t-test. Results: Mean ET increases with age until 15 years old in girls and then decreases. Mean endurance time increases continuouslY'from 6 to 18 years old in boys. The increase is more pronounced in boys than girls. In our study, a significant higher mean ET was found for boys in age categories 10 to 12, 13 to 15 and 16 to 18. No significant difference was found in any other groups. Conclusions: Some normal values from Cuming et al. established in 1978 for ET with the Bruce protocol are probably not appropriate any more today for children from Western Europe. Our study showed that mean ET is higher for boys from 10 to 18 years old. Despite common beliefs, cardiovascular conditioning doesn't seem yet reduced in children from Western Europe. New data for Bruce treadmill exercise. testing for healthy children, 4 to 18 years old, living in Western Europe are required. .

p53 Mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients.

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation, we postulated that p53 mutations in normal tissue samples of patients bearing a single primary tumor could have a clinical value as a biomarker for the risk of developing second primary tumors. Thirty-five patients presenting with a single primary tumor were followed-up for a median of 51 months (range 1 month to 10.9 years) after biopsies of histologically normal squamous cell mucosa had been analyzed for p53 mutations with a yeast functional assay at the time of the primary tumor. During this follow-up, recurrences and non-sterilization of the primary tumor, occurrence of lymph node metastases, and of second primary tumors were evaluated. Sixteen (45.7%) patients were found to have p53 mutations in their normal squamous cell mucosa, and 19 (54.3%) patients showed no mutation. No relationship was found between p53 mutations and the occurrence of evaluated events during follow-up. Notably, the rate of second primary tumors was not associated with p53 mutations in the normal squamous mucosa. The correlation between p53 mutations in histologically normal mucosae and the incidence of second primary tumors is generally low. The benefit of analyzing p53 mutations in samples of normal squamous cell mucosa in every patient with a primary tumor of the head and neck is doubtful.

The Aspergillus fumigatus septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.

Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi. The requirement of septins for virulence has been demonstrated in the human pathogenic yeasts Candida albicans and Cryptococcus neoformans, as well as the plant pathogen Magnaporthe oryzae. Aspergillus spp. contains five genes encoding for septins (aspA-E). While the importance of septins AspA, AspB, AspC, and AspE for growth and conidiation has been elucidated in the filamentous fungal model Aspergillus nidulans, nothing is known on the role of septins in growth and virulence in the human pathogen Aspergillus fumigatus. Here we deleted all five A. fumigatus septins, and generated certain double and triple septin deletion strains. Phenotypic analyses revealed that while all the septins are dispensable in normal growth conditions, AspA, AspB, AspC and AspE are required for regular septation. Furthermore, deletion of only the core septin genes significantly reduced conidiation. Concomitant with the absence of an electron-dense outer conidial wall, the ΔaspB strain was also sensitive to anti-cell wall agents. Infection with the ΔaspB strain in a Galleria mellonella model of invasive aspergillosis showed hypervirulence, but no virulence difference was noted when compared to the wild-type strain in a murine model of invasive aspergillosis. Although the deletion of aspB resulted in increased release of TNF-α from the macrophages, no significant inflammation differences in lung histology was noted between the ΔaspB strain and the wild-type strain. Taken together, these results point to the importance of septins in A. fumigatus growth, but not virulence in a murine model.

Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity.

Ambulatory blood pressure measurement and antihypertensive therapy.

The traditional basis for assessing the effect of antihypertensive therapy is the blood pressure reading taken by a physician. However, several recent trials have been designed to evaluate the blood pressure lowering effect of various therapeutic agents during the patients' normal daytime activities, using a portable, semi-automatic blood pressure recorder. The results have shown that in a given patient, blood pressure measured at the physician's office often differs greatly from that prevailing during the rest of the day. This is true both in treated and untreated hypertensive patients. The difference between office and ambulatory recorded pressures cannot be predicted from blood pressure levels measured by the physician. Therefore, a prospective study was carried out in patients with diastolic blood pressures that were uncontrolled at the physician's office despite antihypertensive therapy. The purpose was to evaluate the response of recorded ambulatory blood pressure to treatment adjustments aimed at reducing office blood pressure below a pre-set target level. Only patients with high ambulatory blood pressures at the outset appeared to benefit from further changes in therapy. Thus, ambulatory blood pressure monitoring can be used to identify those patients who remain hypertensive only when facing the physician, despite antihypertensive therapy. Ambulatory monitoring could thus help to evaluate the efficacy of antihypertensive therapy and allow individual treatment.

Extensor carpi ulnaris (ECU) subsheath: Normal MRI appearance and findings in athletic injuries : 40

Purpose: First, to report ECU subsheath's normal MRI appearance and the findings in athletic injuries. Second, to determine the best MRI sequence for diagnosis. Methods and materials: Sixteen patients (13 males, 3 females, mean age 30.3 years) with ECU subsheath's athletic injuries sustained between January 2003 and June 2009 were retrospectively reviewed. Wrist MRI studies were performed on 1.5-T units and consisted of at least transverse T1 and STIR sequences in pronation, and FS Gd T1 in pronation and supination. Two radiologists assessed the following items, in consensus: injury type (A to C according to Inoue), ECU tendon stability, and associated lesions (ulnar head oedema, extensor retinaculum injury, ECU tendinosis and tenosynovitis). Then, each reader independently rated the sequences' diagnostic value: 0 = questionable, 1 = suggestive, 2 = certain. Follow-up studies were present in 8 patients. ECU subsheath's normal visibility (medial, central and lateral parts) was retrospectively evaluated in 30 consecutive control MRI studies. Results: FS Gd T1 sequences in supination (1.63) and pronation (1.59) were the most valuable for diagnosis, compared to STIR (1.22) and T1 (1). The study group included 9 type A, 1 type B and 6 type C injuries. There were trends towards diminution in pouches' size, signal intensity and enhancement in follow-up studies, along with tendon stabilization within the ulnar groove. In control studies, ECU subsheath's visibility in medial, central and lateral parts were noted in 66.7-80%, 63.3-80% and 30-50% respectively. Conclusion: ECU subsheath's athletic injuries are visible on 1.5-T MRI studies. FS Gd T1 sequences in supination and pronation are the most valuable.

Long-term fluctuation of relative afferent pupillary defect in subjects with normal visual function.

PURPOSE: To determine whether the relative afferent pupillary defect (RAPD) remains constant over time in normal subjects. METHODS: Seventeen normal subjects were tested with infrared pupillography and automated perimetry in four sessions over 3 years. The changes in RAPD and visual field asymmetry between testing sessions were compared. RESULTS: The range of RAPD was 0.0 to 0.3 log unit, and the difference in the mean deviation between the eyes on automated static perimetry was 0 to 3 dB. Eight subjects repeatedly had an RAPD in the same eye. There was no correlation between the RAPD and the visual field asymmetry at the same visit. Changes in the magnitude of the RAPD between any two sessions were typically small (median, 0.08 log unit; 25th percentile, 0.04 log unit; 75th percentile, 0.15 log unit). CONCLUSIONS: Some normal subjects may show a persistent but small RAPD in the absence of detectable pathologic disease. Therefore, an isolated RAPD in the range of 0.3 log unit that is not associated with any other significant historical or clinical finding should probably be considered benign.