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Deep learning (DL) algorithms are increasingly used in cardiac imaging. We aimed to investigate the utility of DL algorithms in de-noising transthoracic echocardiographic images and removing acoustic shadowing artefacts specifically in patients with congenital heart disease (CHD). In addition, the performance of DL algorithms trained on CHD samples was compared to models trained entirely on structurally normal hearts. Deep neural network based autoencoders were built for denoising and removal of acoustic shadowing artefacts based on routine echocardiographic apical 4-chamber views and performance was assessed by visual assessment and quantifying cross entropy. 267 subjects (94 TGA and atrial switch and 39 with ccTGA, 10 Ebstein anomaly, 9 with uncorrected AVSD and 115 normal controls; 56.9% male, age 38.9 ± 15.6 years) with routine transthoracic examinations were included. The autoencoders significantly enhanced image quality across diagnostic subgroups (p

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods...

Aims The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population. Methods and results Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients ( Conclusion Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.

Background Patients with coarctation of the aorta (CoA) are at increased risk of periprocedural and late neurological complications. Based on a nationwide inpatient dataset, we assessed the prevalence and risk factors for neurological complications in this cohort. Method and Results We included all CoA patients hospitalized in England between 1997 and 2015. The risk for procedural complications, subarachnoid bleeding and ischemic stroke were quantified, and risk factors investigated. Overall, 11,907 patients (60% male) with CoA were identified. The median age at first presentation was 0.6 years with a median follow-up period of 14.4 years. Throughout the study period, 8456 surgical or interventional procedures were performed in 6796 patients. The neurological complication rate for primary surgical or interventional repair in patients born after 1997 was 0.05% and 0.2%, respectively. During a total follow-up period of 146,295 patient-years, late neurological complications such as subarachnoid bleeding and cerebral infarction occurred in 225 patients (0.15%/patient-year). The median age for subarachnoid bleeding was 29 years and 57 years for ischemic stroke. While, arterial hypertension (p = .0014), current smoking (p = .02), dyslipidaemia (p = .007) and diabetes (p = .037) were significantly related to the risk of ischemic stroke, only arterial hypertension emerged as significant risk factor for subarachnoid bleeding. Conclusions Neurological complication during primary CoA repair are extremely rare in the current era. In contrast, many CoA patients are afflicted by late complications such as subarachnoid bleeding and ischemic stroke at a relatively young age, emphasizing the need for meticulous and pro-active blood pressure control and reduction of cardiovascular risk factors.

Objectives To analyze the timing of appearance of conduction abnormalities (CAs) after transcatheter aortic valve implantation (TAVI), to identify predictors of delayed CAs requiring pacemaker (PM) implantation and to provide guidance regarding the duration of telemetry monitoring. Background How long patients remain at risk of development of CAs requiring PM implantation after TAVI and for how long they should be monitored remains unclear but is crucial when considering early discharge. Methods Development of CAs was studied in 701 consecutive patients treated with Edwards Sapien 3 valves and monitored with telemetry for 7 days in a single center. After excluding valve-in-valve procedures and patients with previous PM, 606 patients remained for analysis. Predictors of CAs requiring PM and the time of onset of CAs were analyzed. Results Of 606 patients 76 (12.5%) required a PM after TAVI. CAs requiring PM implantation occurred after 48 h in 22.4% (17 patients) and in 10.5% (8 patients) even after 5 days. Of the patients who developed high grade CAs requiring PM after 48 h, 47.1% had no CAs prior to TAVI, and 23.5% had neither pre-existing CAs nor new-developed CAs within the first 48 h after TAVI. Conclusion After TAVI using a new-generation balloon-expandable valve, delayed development of CAs requiring PM implantation is not uncommon, even after 5 days. More importantly, 23.5% of patients eventually requiring a delayed PM implantation had still no CAs at 48 h after TAVI in this study. These results question the safety of early discharge and support ECG monitoring for a longer time period. The most optimal way to monitor these patients is yet to be determined.

Introduction Trans-lamina cribrosa pressure has been postulated to be a contributor in the development of a glaucomatous optic nerve versus optic nerve edema, depending on the pressure gradient. Uncertainty remains in the therapeutic outcome of adjusting this gradient. Case report We discuss a unique case of idiopathic intracranial hypertension presenting as asymmetric optic disc edema following trabeculectomy. It was treated via optic nerve fenestration due to the patient remaining symptomatic on maximum tolerated acetazolamide. Intraocular pressure stabilized into target range and the optic nerve edema resolved. Conclusions Rarely, intraocular pressure reduction can unmask elevated intracranial pressure, leading to optic nerve edema. Optic nerve sheath fenestration is a practical therapeutic modality to consider when treating this occurrence.

Background In patients with repaired Tetralogy of Fallot (ToF), implantable cardioverter defibrillators (ICD) are considered reasonable in selected adults with multiple risk factors for sudden cardiac death. Patients and methods We performed a retrospective cohort study of all 174 patients with repaired ToF who are followed at the University Hospital of Muenster. We analyzed data according to the risk score previously proposed by Khairy and coworkers and patient outcome. We analyzed data separately for patients without previous sustained ventricular tachycardia (VT) (risk stratification group, n = 157) and patients with VT/secondary prevention ICD (n = 17). Results In the risk stratification group, a mean of 4 ± 1 risk score parameters were available. All six risk parameters were known in 10%, five in 14%. Risk score increased with availability of parameters. 15 patients with secondary prevention ICD had a mean risk score of 6.3 ± 2.2 (range 2–10). 11 patients of the risk stratification group with primary prevention ICD had a mean risk score 5.8 ± 2.4 (range 3–8). During follow-up of up to 14 years, five patients died (3%): at age 58, two at 69 and two at 76 years. Conclusion In the majority of patients risk score variables were incomplete, severely limiting its applicability because the true score cannot be calculated. Risk scores were not different between patients with secondary prevention ICD and patients with ICD for primary prevention based on current guidelines. Standardization of follow-up and prospective evaluation of these standards in large prospective patient cohorts is desirable to improve risk stratification in patients with ToF.

Objectives: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. Methods: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = –1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. Results: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P

Background Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function and to predict outcome in repaired tetralogy of Fallot (ToF). We aimed to test the hypothesis that parameters of myocardial deformation on cardiac MRI (CMR) relate to symptoms and provide prognostic information in patients with repaired ToF. Methods and results We included 372 patients with ToF (median age 16 years; 55% male), recruited within a nationwide, prospective study. Longitudinal (LS), circumferential (CS) and radial global strain (RS) were analysed by CMR-based feature tracking (FT). A combined endpoint of death, successful resuscitation or documented ventricular tachycardia was employed. Parameters of global strain were associated with New York Heart Association (NYHA) class and symptomatic deterioration. During a median follow-up of 7.4 years, 20 events occurred. Left ventricular (LV) CS and right ventricular (RV) LS emerged as predictors of outcome, independent of QRS duration, LV/RV ejection fraction and volumes, NYHA class and peak oxygen uptake. In combination, these parameters also identified a subgroup of patients at significantly increased risk of adverse of outcomes (HR 3.3, p=0.002). Furthermore, LV LS, RS, CS and RV LS were related to the risk of death and nearly missed death (p Conclusions FT-CMR provides myocardial deformation parameters, easily derived from standard CMR studies. They relate to symptoms and clinical deterioration in patients with ToF. More importantly, they predict adverse outcome independent of established risk markers, and should be considered as a useful adjunct to established outcome predictors, especially in younger patients with ToF. Clinical trial registration number http://www.clinicaltrials.gov: NCT00266188; Results.

Mass gatherings are well-documented for their public health risks; however, little research has examined their impact on mental health or focused on young people specifically. This study explores risk and protective factors for mental health at mass gatherings, with a particular focus on characterising attendees with high levels of psychological distress and risk taking.Data collection was conducted in situ at "Schoolies", an annual informal week-long mass gathering of approximately 30,000 Australian school leavers. Participants were 812 attendees of Schoolies on the Gold Coast in 2015 or 2016 (74% aged 17 years old).In both years, attendee mental health was found to be significantly better than population norms for their age peers. Identification with the mass gathering predicted better mental health, and this relationship became stronger across the course of the mass gathering. Attendees with high levels of psychological distress were more likely to be male, socially isolated, impulsive, and in a friendship group where risk taking was normative.Mass gatherings may have a net benefit for attendee mental health, especially for those attendees who are subjectively committed to the event. However, a vulnerable subgroup of attendees requires targeted mental health support.

Objective Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) is associated with a poor clinical outcome and its assessment therefore crucial. Quantification of AR by transthoracic echocardiography (TTE), however, remains challenging in this setting. The present study used quantitative flow measurement by cardiac MRI (CMR) with calculation of regurgitant fraction (RF) for the assessment of AR and compared the results with TTE. Methods and results We included 65 patients with a mean age of 82.2±8.1 years (38 women) who underwent successful TAVI with Edwards SAPIEN valves (52 transfemoral, 13 transapical). The postinterventional degree of AR was assessed by CMR and by TTE. There was agreement between CMR and TTE with regards to the absence of severe AR. However, TTE significantly underestimated the presence of moderate AR classifying it to be mild in 38 and moderate in only 5 patients, whereas CMR found mild AR in 23 and moderate in 16 patients. Overall, there was only fair agreement between CMR and TTE regarding the grading of AR with a weighted κ of 0.33. The rate of detection of TTE for more than mild AR was only 19%. Conclusions Using CMR for the quantification of AR in a sizeable group of TAVI patients, we demonstrate a strong tendency of TTE to underestimate AR compared with CMR. Since higher AR severity on echocardiography has been associated with worse patient outcome, the potential incremental prognostic value of CMR should be studied prospectively in this setting.

Background: Left ventricular longitudinal strain (LV-LS) and strain rate (SR) are sensitive markers of early systolic dysfunction. Aim: To evaluate the feasibility of a novel, cardiac magnetic resonance (CMR) based method known as feature tracking (FT) for the assessment of strain and SR, and to compare the CMR based results to those obtained on standard transthoracic echocardiography (TTE) in healthy volunteers and in patients with left ventricular hypertrophy cardiomyopathy (HCM). Methods: Overall, 20 healthy volunteers (ten male, mean age 24 ± 3 years) and 20 consecutive patients with HCM (12 male, mean age 47 ± 19 years) were included. Longitudinal and circumferential strain and SR of the left ventricle were measured on CMR at 1.5 Tesla and TTE and interobserver variability was assessed. Results: FT measurements were feasible in all subjects. A good agreement between global LV-LS measured on CMR (controls: 20.8 ± 3.0; HCM: 17.6 ± 3.8) and TTE (controls: 19.4 ± 2.1; HCM: 16.6 ± 2.9) was found, while the agreement was worse for circumferential strain and all SR measurements. For the left and right ventricles, interobserver reproducibility was higher for strain measurements compared to SR. Coefficients of variation were lowest for LV-LS (13.2%) by CMR. Conclusions: FT analysis is a novel CMR based method for the analysis of myocardial strain and SR that is simple and correlates well with the echocardiographic measurements. Since CMR is unaffected by inadequate acoustic windows, FT may represent an attractive alternative to echocardiography in assessing the increasingly important parameters of myocardial deformation.

Predicting improvement of myocardial function after transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) remains a challenge. As ejection fraction (EF) may be of limited value in detecting early myocardial dysfunction and predicting outcome, we assessed the potential of echocardiographic longitudinal function in this setting.Left ventricular (LV) function was assessed using EF, mitral annular plane systolic excursion (MAPSE), peak longitudinal 2D strain (LS) and strain rate (SR) in101consecutive patients with severe symptomatic AS (age 81 ± 11 years) undergoing TAVI. Echocardiography and assessment of clinical status including NYHA functional class were performed prior and after intervention (median 70 days).Pre-interventional EF was 57 ± 17% and 32 patients (32%) had an EF50% while 58 patients (57%) were found to have an impaired LS. After TAVI there was no significant change in EF. In contrast, LS, SR and MAPSE improved significantly (-14.0 ± 4.4 vs. -15.5 ± 4.0%; p=0.007, 0.68 ± 0.24 vs. 0.78 ± 0.23/s, p=0.002; and 9.1 ± 3.2 vs. 10.2 ± 3.3mm, p=0.006, respectively). Receiver Operating Curve characteristic analysis identified a pre-TAVI LS-13.3% as the optimal cut-off value for predicting lack of LS recovery post TAVI. There was a marked improvement in NYHA FC after intervention (p=0.0002). Among the studied echocardiographic parameters LS change correlated closest with NYHA class improvement (r=0.42, p=0.0008).Overall, LS appears to be more sensitive for detecting early myocardial damage in patients with AS compared to conventional echocardiographic parameters. More importantly, pre-interventional LS may identify irreversible myocardial dysfunction and LS improvement correlates with symptomatic improvement after intervention.

We investigate the extent to which minority group members are surrounded by outgroup members in their immediate environment as a predictor of social dominance orientation. Using a large representative sample of New Zealanders, we found that minority group members in outgroup dense environments reported lower levels of social dominance orientation (Study 1). In studies 2 and 3, Asian Australian and Black American participants who were surrounded by outgroup members reported lower social dominance orientation. For majority group (White) participants there was no association between social dominance orientation and outgroup density. Study 4 explained the overall pattern: Black Americans surrounded by outgroup members perceived their group to be of lower status in their immediate environment, and through this, reported lower social dominance orientation. This article adds to growing literature on contextual factors that predict social dominance orientation, especially among minority group members.

People not only dehumanize others, they also dehumanize the self in response to their own harmful behavior. We examine this self-dehumanization effect across four studies. Studies 1 and 2 show that when participants are perpetrators of social ostracism, they view themselves as less human compared with when they engage in nonaversive interpersonal interactions. Perceived immorality of their behavior mediated this effect. Studies 3 and 4 highlight the behavioral consequences of self-dehumanization. The extent to which participants saw themselves as less human after perpetrating social ostracism predicted subsequent prosocial behavior. Studies 2 to 4 also demonstrate that consequences of self-dehumanization occur independently of any effects of self-esteem or mood. The findings are discussed in relation to previous work on dehumanization and self-perception. We conclude that in the context of immoral actions (self) dehumanization may be functional.

Echocardiographic parameters of ventricular deformation of the systemic right ventricle (sRV) predict adverse clinical outcome in patients after atrial repair of transposition of the great arteries (TGA). We assessed myocardial deformation on cardiac MRI (CMR) and correlated these with clinical and conventional CMR parameters in TGA patients.Retrospective analysis of CMR studies in 91 TGA patients (66% male; mean age 30.1±5.1years) at two tertiary adult congenital heart centers was conducted. Myocardial deformation was assessed by CMR-based feature tracking (FT), providing longitudinal (LS), radial (RS), and circumferential (CS) global strain for the sRV and the subpulmonary left ventricle. A subgroup of optimal TGA was defined (NYHA class I, NT-proBNP300pg/ml, max. exercise work load ≥100watt, no significant clinical events) as a reference cohort.There was a significant correlation between FT and conventional CMR parameters. Left ventricular ejection fraction (LVEF) correlated significantly with LV LS, RS, and CS (r between 0.24 and 0.34, p values between 0.03 and 0.005). sRVEF correlated with RV CS (r=0.56, p0.001), and RV RS (r=0.32, p=0.007). QRS duration showed a negative correlation with RV CS (r=-0.53, p0.001), LV RS (r=-0.34, p=0.008), and LV CS (r=-0.34, p=0.006). Reference values for the novel FT method in clinically optimal TGA patients are provided.Assessment of myocardial function using CMR-based FT is feasible in TGA patients. FT measurements related to important prognostic clinical parameters. Furthermore, we provide for the first time reference values for TGA patients in an optimal clinical status.

Many people like eating meat, but most are reluctant to harm things that have minds. The current three studies show that this dissonance motivates people to deny minds to animals. Study 1 demonstrates that animals considered appropriate for human consumption are ascribed diminished mental capacities. Study 2 shows that meat eaters are motivated to deny minds to food animals when they are reminded of the link between meat and animal suffering. Finally, Study 3 provides direct support for our dissonance hypothesis, showing that expectations regarding the immediate consumption of meat increase mind denial. Moreover, this mind denial in turn reduces negative affect associated with dissonance. The findings highlight the role of dissonance reduction in facilitating the practice of meat eating and protecting cultural commitments.

Purpose Percutaneous dilatational tracheotomy (PDT) is a well-established procedure in intensive care medicine. Several reports confirm a low acute and long-term complication rate. However, dilatational tracheotomy is still often postponed even in patients that are under ventilator support for more than 2 weeks. We present a retrospective study analyzing the subjective long-term results after percutaneous tracheotomy performed at our medical intensive care unit between 2002 and 2008. Methods We used a modified method described by Ciaglia for tracheotomy. We selected 649 patients eligible for the survey among those who had received PDT between 2002 and 2008 and had been dismissed from hospital alive. Results The return rate was 38.5% with 29.8% of the questionnaires being completed by the patients; in 32 cases, relatives reported of the patients' death. No patient experienced wound infection; none needed surgical wound revision. Dysarthria was reversible in all 16 cases; 2 patients reported a persistent hoarseness that was preexisting in both cases. One patient experienced a tracheal stenosis and received a tracheal stent; one other required a permanent tracheotomy because of a nonresectable granulation tissue. The overall rate of long-term complications associated with the long-term ventilation and the PDT was 1.8%. Conclusions Percutaneous dilatational tracheotomy is an easily performed, cost-saving method for long-term ventilated patients with a low rate of acute and long-term complications even in old and multimorbid internal medicine patients.

Background As a consequence of heterogeneous results of relatively small individual trials, the impact of congenital heart defects (CHD) and the effect of disease severity on patient reported outcome measures (PROs) of quality of life (QoL) remains uncertain. We aimed to systematically summarize QoL data in CHD patients using meta-analytic methods. Methods and results We performed a systematic review of the literature focusing on QoL in CHD. The search yielded 234 publications meeting the inclusion criteria, with a median of 88 patients per study (46% females, average age 24years). In total, QoL was reported using PROs in 47,471 CHD-patients. More than 95 different PROs were used to evaluate QoL. The most commonly used tool was the SF36 form (69 publications). Analysis of available quantitative QoL data from SF36 publications (n=4217 CHD patients) showed that QoL was reduced in patients with moderate or complex cardiac disease (e.g. relative physical functioning scores 0.96 [0.93–0.99] and 0.91 [0.88–0.95] compared with controls), while no such effect was evident in those patients with simple cardiac lesions. Similar results were found for the general health domain of the SF36 domain. Conclusions Despite the proliferation of QoL-studies in CHD no standardized approach for measuring and reporting QoL has emerged and the published results are heterogeneous. In aggregation, however, the results of this study suggest that QoL is impaired in moderate or complex CHD, while no such impact of CHD on QoL could be established — on average — in patients with simple defects.

Children and adolescents suffering from inflammatory bowel disease (IBD) are at risk of developing osteoporosis as a result of treatment with corticosteroids as well as of nonsteroidal factors like inflammation and malnutrition. To study the impact of these factors on development of osteopathy, we compared the rate of osteoporosis in steroid-naive and steroid-treated pediatric IBD patients.In 90 patients (50 girls) with IBD (34 steroid-naive, 53 steroid-treated, 3 not known) aged 8.8 to 19.2 (14.4 +/- 2.2) years and 52 controls (27 girls) aged 6.1 to 17.6 (12.9 +/- 3.0) years, bone mineral density (BMD) of the lumbar spine was assessed with dual energy x-ray absorptiometry. Areal BMD values were transformed into volumetric densities called bone mineral apparent density (BMAD) and expressed as standard deviation scores (SDS) on the basis of the BMAD values of the controls.The rate of osteoporotic patients (BMAD-SDS-2) was 8% in girls and 20% in boys. There was a similar proportion of osteoporosis in steroid-naive (12%) and steroid-treated (11%) patients. SDS of body height showed a significant positive correlation with BMD-SDS but not with BMAD-SDS in almost all patient subgroups, indicating an interfering dependency of BMD from bone size.The prevalence of osteoporosis in pediatric patients with IBD is approximately the same as in adult patients. Osteoporosis is already present before steroid treatment. Data of dual energy x-ray absorptiometry measurements should be transformed into volumetric parameters to compensate for short stature. Otherwise, a lot of growth-stunted patients may be falsely diagnosed as osteopenic.

Objective Previous studies have suggested endothelial dysfunction in adult patients after repair of aortic coarctation (CoA). It has been proposed to play a key role in the pathogenesis of arterial hypertension in the absence of re-coarctation. We aimed to assess the presence of endothelial dysfunction, the number of endothelial progenitor cells (EPC), and the levels of proinflammatory cytokines associated with endothelial injury in contemporary patients after CoA repair. Methods For this prospective observational study, 20 CoA patients and 22 healthy controls were recruited. Digital reactive hyperaemia was measured by peripheral arterial tonometry. Flow cytometry was used to quantify EPCs, and a comprehensive panel of laboratory markers of endothelial dysfunction was measured. Results Half the patients had known arterial hypertension requiring medical treatment. Indices of reactive hyperaemia showed no significant difference between CoA patients (1.96±0.32) and controlss (1.765±0.48) (p=0.82). Circulating EPCs, defined by the number of CD34 + , CD34 + /KDR + , CD34 + /AC133 + , CD34 + /AC133 + /KDR + or CD34 + /CD45 − labelled cells were equally not significantly different between the groups. Furthermore, plasma levels of inflammatory mediators and markers of endothelial function (IL-6, IL-8, ICAM1 and VCAM1) were not significantly different between the groups, as were vascular endothelial growth factor levels (p>0.05, for all). Conclusions By contrast with earlier reports, no clinically significant difference in endothelial function between adult patients with coarctation repair and healthy controls could be demonstrated. Therefore, endothelial dysfunction may not necessarily be present in this population. Further studies are required to identify mechanisms and to develop strategies to avoid arterial hypertension in these patients.

Background Echocardiographic upper normal limits of both main pulmonary artery (MPA) diameters (MPA-d) and ratio of MPA to aortic root diameter (MPA-r) are not defined in healthy adults. Accordingly, frequency of MPA dilatation based on echocardiography remains to be assessed in adults with Marfan syndrome (MFS). Methods We enrolled 123 normal adults (72 men, 52 women aged 42 ± 14 years) and 98 patients with MFS (42 men, 56 women aged 39 ± 14 years) in a retrospective cross-sectional observational controlled study in four tertiary care centers. We defined outcome measures including upper normal limits of MPA-d and MPA-r as 95 quantile of normal persons, MPA dilatation as diameters > upper normal limits, MPA aneurysm as diameters >4 cm, and indication for surgery as MPA diameters >6 cm. Results MPA diameters revealed normal distribution without correlation to age, sex, body weight, body height, body mass index and body surface area. The upper normal limit was 2.6 cm (95% confidence interval (CI) =2.44-2.76 cm) for MPA-d, and 1.05 (95% CI = .86–1.24) for MPA-r. MPA dilatation presented in 6 normal persons (4.9%) and in 68 MFS patients (69.4%; P 1.05 were equally frequent in 7 normal persons (5%) and in 8 MFS patients (10.5%; P = .161). MPA-r related to aortic root diameters (P = .042), reduced left ventricular ejection fraction (P = .006), and increased pulmonary artery systolic pressures (P = .040). No clinical manifestations of MFS and no FBN1 mutation characteristics related to MPA diameters. Conclusions We established 2.6 cm for MPA-d and 1.05 for MPA-r as upper normal limits. MFS exhibits a high prevalence of MPA dilatation and aneurysm. However, patients may require MPA surgery only in scarce circumstances, most likely because formation of marked MPA aneurysm may require LV dysfunction and increased PASP.

A tracer-kinetic study using 1-13C- and 15N-labeled L-methionine was conducted in order to measure the retention rate of free methionine added to commercially-produced soy-based infant formulas. Twelve male infants, fed on a soy formula, received a single-pulse labeling by oral administration of L-1-13C-methionine (5 mg/kg) and L-15N-methionine (10 mg/kg). The abundance of expired 13C-labeled CO2 was measured up to 7 h after administration at 15-, 30-, and 60-min intervals. Additionally, enrichment of total 15N and 15N in urinary ammonia were determined up to 48 h after administration. Retention rates of the labeled carboxyl group amounted to an average of 91.2% (SD 4.1) of the intake. A similar retention rate was measured for the 15N-label of methionine (90.0%, SD 4.3). The data point at the efficacy of methionine supplementation of soy-based infant formulas.

To translate the original English version of the Geriatric Oral Health Assessment Index (GOHAI) into Hindi and assess its validity and reliability for use among people in India.After translation into Hindi, a total of 385 participants aged 55+ demonstrated acceptable validity and reliability when used for people in India. Individual GOHAI items were recorded and summed as originally recommended. The questionnaire sought information about socio-demographic characteristics and self-reported perception of general and oral health. Clinical examination included assessment of periodontal status and number of decayed teeth, missing teeth, filled teeth and crowned teeth.Mean GOHAI score was 40.9 (SD, 10.6; range, 12-60). Cronbach's alpha for the GOHAI score was 0.88, indicating a high degree of internal consistency and homogeneity between the GOHAI items. The test-retest correlation coefficient for add-GOHAI scores was 0.72, indicating good stability. Add-GOHAI scores increased with poorer perceived general and oral health. Convergent validity, construct validity and discriminant validity of the GOHAI were demonstrated.It could therefore be used as a valuable instrument for measuring oral health-related quality of life for people in this region.

Short-term studies show that PPIs heal erosive esophagitis in children. There are no prospective studies that examine long-term maintenance therapy of erosive esophagitis in children with and without underlying GERD-predisposing disorders.To determine prospectively the dose of omeprazole needed to maintain remission of erosive oesophagitis and reflux symptoms in children.Patients aged 1-16 years with healed erosive reflux oesophagitis after omeprazole treatment (0.7-3.5 mg/kg/day) entered a 21-month maintenance phase where they initially received half the dose of omeprazole required to heal. Endoscopy was performed after 3, 12 and 21 months. The omeprazole dose was increased if erosive oesophagitis or reflux symptoms recurred.A total of 46 patients entered the study and 32 completed it. Of these, 17 (53%) remained on the maintenance dose, 12 (38%) returned to their healing dose and 3 (9%) ended the study on a dose higher than their healing dose. Three-quarters of the completers (24/32) had no erosive oesophagitis relapse. Four patients (13%) had relapse of only erosive oesophagitis, 4 (13%) had relapse of erosive oesophagitis and symptoms, and 10 (31%) had only symptomatic relapse. Of the 46 patients, 48% had GERD-predisposing disorders (neurological impairment or oesophageal atresia). Overall, 62.5% (5/8) of patients who had an erosive oesophagitis relapse had a GERD-predisposing disorder versus 33.3% (8/24) of those who did not.Remission of erosive oesophagitis is maintained with omeprazole treatment for at least 21 months in most children aged 1-16 years, and the drug is well tolerated. To maintain remission, some 60% of patients require more than half the dose required for healing. In children with GERD-predisposing conditions, GERD is often chronic and relapsing, and requires long-term management.

The case of an infant who had received EMLA(R) for local pain therapy after scalding to 5% of the body surface with boiling water is reported. Due to the application of EMLA(R) on the injured skin and exceeding the recommended doses of prilocaine and lidocaine the child developed symptomatic methemoglobinemia. During surgical wound dressing the boy showed cyanosis, decreased peripheral oxygen saturation and potentially suffered a general seizure. With a symptomatic therapy including mechanical ventilation and anticonvulsive drugs the methemoglobinemia normalized within 9 h. The child recovered without any neurological impairment after wound treatment was completed.

We studied 25 patients with gangrenous cholecystitis and observed a new sonographic finding--striated thickening of the gallbladder wall--and three patterns of pericholecystic fluid collections. Heterogeneous thickening of the gallbladder wall was characterized by either multiple striations (alternating hypoechoic and hyperechoic layers) or irregular mass-like protrusions projecting into the gallbladder lumen. We observed striated thickening far more frequently (in 10 of 25 patients) than other findings reported previously as being associated with gangrenous cholecystitis, such as intraluminal membranes (1 in 25 patients) and masslike protrusions into the gallbladder lumen (1 in 25 patients). Although the sensitivity and specificity of this finding cannot be determined by our study, we believe that mural striations in cases of acute cholecystitis should raise the question of gangrenous changes. Additionally, we found that two subtypes of pericholecystic fluid collections (types II and III) were associated with gallbladder wall perforation and abscess formation more frequently than type I collections.

Typical antipsychotic drugs, such as haloperidol and chlorpromazine, increase synthesis of the neuropeptide neurotensin (NT) in both the striatum and the nucleus accumbens, whereas atypical antipsychotic drugs, such as clozapine and olanzapine, do so only in the nucleus accumbens. By using in vivo microdialysis, we now report that acute administration of haloperidol, clozapine, or olanzapine failed to alter the release of NT in either the striatum or nucleus accumbens. In contrast, chronic administration of haloperidol for 21 days increased NT release in both the striatum and nucleus accumbens, whereas treatment for 21 days with the atypical antipsychotic drugs, clozapine or olanzapine, increased NT release selectively in the nucleus accumbens. These findings suggest that ( i ) increased NT mRNA expression and NT tissue concentrations are associated with increases in the extracellular fluid concentrations of the peptide and ( ii ) atypical antipsychotic drugs may exert their therapeutic effects and produce fewer side effects by virtue of their selectivity in limbic compared with striatal, target neurons.

The use of antibody microarrays continues to grow rapidly due to the recent advances in proteomics and automation and the opportunity this combination creates for high throughput multiplexed analysis of protein biomarkers. However, a primary limitation of this technology is the lack of PCR-like amplification methods for proteins. Therefore, to realize the full potential of array-based protein biomarker screening it is necessary to construct assays that can detect and quantify protein biomarkers with very high sensitivity, in the femtomolar range, and from limited sample quantities. We describe here the construction of ultramicroarrays, combining the advantages of microarraying including multiplexing capabilities, higher throughput, and cost savings with the ability to screen very small sample volumes. Antibody ultramicroarrays for the detection of interleukin-6 and prostate-specific antigen (PSA), a widely used biomarker for prostate cancer screening, were constructed. These ultramicroarrays were found to have a high specificity and sensitivity with detection levels using purified proteins in the attomole range. Using these ultramicroarrays, we were able to detect PSA secreted from 100 LNCaP cells in 3 h and from just four LNCaP cells in 24 h. Cellular PSA could also be detected from the lysate of an average of just six cells. This strategy should enable proteomic analysis of materials that are available in very limited quantities such as those collected by laser capture microdissection, neonatal biopsy microspecimens, and forensic samples.

The objective of the study was to determine the effect of nutrition level (NL, multiples of maintenance energy requirement) on the digestibility of nutrients for dairy cows regarding the energy supply of the animal. The digestion of nutrients and energy was investigated in two trials using lactating dairy cows. The NL varied from 2.7 to 5.0 using diets similar composition. In addition, sheep were given the same feed with a NL of 1.4. Digestibility of dry matter (DM) and all specific measures of dietary components declined significantly as NL increased. Digestibility of energy decreased by 4.1% for each increase in NL. The metabolizable energy, the ability to metabolize energy (metabolizable energy/gross energy), and the content of net energy for lactation (NE L ) per kilogram of DM intake were calculated for NL from 1 to 6 on the basis of these relationships and as well as the gross energy, methane energy, and urine energy. Accordingly the NE L content declined by 0.11 MJ/kg of DM intake or 1.6% as the NL increased by one unit. It means that the NE L requirement above the maintenance requirement increased by 0.07 MJ of NE L per kilogram of fat-corrected milk, if the NL increased by one unit.

The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics of a new infant formula containing partially hydrolyzed whey protein, modified vegetable oil with a high beta-palmitic acid content, prebiotic oligosaccharides, and starch.In a double-blind study, healthy formula-fed term infants aged younger than 2 weeks were randomized to receive either the new infant formula (NF) or a standard formula (SF) until the age of 12 weeks. Anthropometric measurements were taken at enrollment, 6 weeks, and 12 weeks. In a subsample of infants, blood samples were taken at 6 weeks and stool samples were taken at enrollment and 6 weeks. Blood samples were analyzed for biochemical measures of protein status and amino acids, and stools were analyzed for total bacteria and bifidobacteria. Mothers completed a feeding diary and questionnaire at 6 and 10 weeks.One hundred fifty-four infants were enrolled in the study; 102 completed the trial. The growth of infants in both formula groups was in line with published growth curves. During the first 6 weeks, NF girls gained more weight and head circumference than the SF girls. These velocity differences were not maintained throughout the 12-week study period. The NF stools had a higher proportion of bifidobacteria at 6 weeks compared with the SF stools, and they were softer. There were no clinically significant differences in the blood biochemical and amino acid values between groups. Both formulas were well tolerated by the infants.When compared with a standard infant formula, the new formula supported satisfactory growth, led to higher counts of bifidobacteria in the feces, produced blood bio-chemical values typical of formula-fed infants, and was well tolerated.

In the present study, extracellular concentrations of neurotensin were measured from the striatum, nucleus accumbens and the medial prefrontal cortex in the awake, freely moving rat. Using a highly sensitive solid phase radioimmunoassay, basal concentrations of neurotensin were 2–5 pg/sample. In each region, glutamate receptor agonists, N-methyl- d -aspartate (NMDA) and kainic acid, increased neurotensin release 2–3-fold. Preincubation with the Na+ channel blocker tetrodotoxin abolished the glutamate receptor agonist-induced increases except in the striatum following kainic acid infusion. These findings indicate that activation of glutamate receptors may indirectly stimulate neurotensin release.

Background: For indirect evaluation of pancreatic lipase activity in cystic fibrosis, different 13 C-labeled triglycerides may be used. Methods: Triglyceride oxidation in patients with cystic fibrosis was investigated after administration of different 13 C-labeled triglycerides by comparing 13 CO 2 breath exhalation. In the comparative study, five patients with cystic fibrosis (age, 8-15 years; body weight, 22.5-39.8 kg) were treated with Pangrol (individual dosages: 1-3 capsules per morning meal; Berlin-Chemie, Berlin, Germany). [1,1,1- 13 C 3 ]Glyceryl tripalmitate and [1,1,1- 13 C 3 ]glyceryl trioleate were administered as a single oral pulse at 8:00 A.M. (dosage, 4 mg/kg each) with the standard diet Fresubin (dosage, 10 ml/kg; Fresenius, Bad Homburg, Germany). Alternately, the same subjects were given the synthetic mixed triglyceride 1,3-distearyl, 2[ 13 C]octanoyl glycerol (dosage, 12.5 mg/kg) contained in the standard diet Nutri-Mix (dosage, 10 ml/kg; Nutricia, Zoetemeer, The Netherlands). Breath samples were taken in 15- and 30-minute intervals over 8 hours. The 13 CO 2 enrichment was measured by continuous-flow isotope ratio mass spectrometry. Results: After administration of the 13 C-labeled tripalmitin-triolein mixture and the mixed triglyceride, mean maximum 13 CO 2 enrichments were 4.70 and 7.37 δ over baseline, occurring at 7.0 and 3.5 hours, respectively. The corresponding percentage cumulative 13 CO 2 exhalations were 12.25% and 29.19%, respectively, and differed significantly in the five paired subjects (p = 0.003). Conclusions: After using different 13 C-labeled triglycerides the resultant 13 CO 2 exhalation reflected the triglyceride hydrolysis and subsequent oxidation. It is concluded that the different cumulative 13 CO 2 exhalations were mainly caused by the rate-limiting step of triglyceride hydrolysis to free fatty acids and 2-monoglycerides and by fat deposition. Noninvasive 13 C breath tests using different 13 C-labeled triglycerides can be used for evaluation of pancreatic lipase activity before and during enzyme supplementation.

Lymphotoxin-alpha (LT), also called TNF-beta, which belongs to the 'TNF family' was originally isolated from a lymphoblastoid cell line. LT enhances the proliferation of activated B cells and augments B cell proliferation induced by IL-2. It functions as an autocrine growth factor for EBV-infected B cell lines and has been implicated in the pathogenesis of B cell malignancies. We tested the expression of LT mRNA in B-CLL and found that LT was expressed in highly purified leukemic cells in 11 out of 11 patients examined. Regulation of expression of LT mRNA is aberrant in B-CLL cells, since LT mRNA expression was not detected in fresh peripheral blood mononuclear cells or B cells identified in seven out of seven normal individuals. In addition, LT mRNA expression was detected for up to 6 days in purified unstimulated in vitro cultures of B-CLL cells. Glucocorticosteroids, that have been effectively used in the treatment of lymphoid malignancies, were added to the cultures and abrogated the LT mRNA expression after an incubation time of 12 h. Addition of recombinant LT to cultures increased proliferation of B-CLL cells while proliferation of these cells was inhibited by antisense oligonucleotides against LT mRNA. B-CLL cells cultured with LT antisense oligonucleotides (asLT) as well as glucocorticoid-treated cells showed reduced viability and a DNA fragmentation ladder characteristic of apoptosis suggesting a relationship between down-regulation of LT mRNA expression and the induction of apoptosis. These studies support the role of LT in the growth regulation and development of B-CLL cells.

Rhabdomyolysis can be caused by aetiologic completely different factors. It can occur only few hours following beginning of enteritis and refusal of ingestion. We report the case of a 5 month old male infant, which showed the clinical characteristics of a hypertonic dehydration on admission to hospital. Serum levels of transaminases, creatinine, urea, lactated hydrogenase, creatine kinase and urinary excretion of myoglobin were highly elevated. Forced diuresis, compensation of acidosis and electrolyte disturbances could prevent the development of an acute renal failure--the most important complication of rhabdomyolysis. The boy could be discharged without any residuals of this episode of disease.

A male infant with obstructive uropathy developed yeast cell agglomerations which were detectable macroscopically and by image-generating techniques within both renal pelvises after Candida albicans infection of the urinary tract. Therapy with flucytosine induced excretion of 'fungal balls' via the urethra. Continuation of therapy with liposomal amphotericin B (AmBisome) prevented a relapse after development of fungal resistance against flucytosine. Sonographically or radiographically detectable formation of 'concrements' within the urinary tract of patients with an immature or compromised immune system and additional features such as obstructive urinary tract should suggest a localized or systemic mycosis, particularly in the context of long-term antibiotic treatment.

Tissue concentrations of the neuropeptide somatostatin and the specific activities of glutamic acid decarboxylase (GAD) were measured in several regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. By the beginning of the fourth postnatal week, these animals exhibited clinical signs of a mixed spastic/dyskinetic syndrome with visual deficits. At the onset of neurological impairment, a significant decrease in GAD activity was detected in the occipital cortex (48–49%) and striatum (45–50%) when compared to either normal or weight-matched controls. At one subclinical stage of toxicity, decreased GAD activity was detected only in the occipital cortex (29–30%). Tissue levels of somatostatin did not change significantly in the occipital cortex of methylmercury-treated animals at any stage of the experiment. However, somatostatin levels in the striatum were significantly reduced at the onset of neurological impairment (55–57%) and at one subclinical stage of toxicity (49–54%). Immunohistochemistry for somatostatin- and neuropeptide Y-immunoreactive neurons confirmed a marked loss of cells in the dorsolateral region of the striatum with atrophy of the surviving neurons. In the cerebral cortex of methylmercury-treated animals the morphology and distribution of somatostatin-positive neurons appeared normal. In view of the reported co-localization of GAD and somatostatin in some non-pyramidal neurons of the cerebral cortex, these results indicate that methylmercury-induced lesions of the developing cerebral cortex involve a subpopulation of GABAergic neurons which are not co-localized with somatostatin. In the striatum, where GAD and somatostatin are not co-localized within the same neurons, methylmercury-induced lesions involve both GABAergic and somatostatin-positive neurons.

The effects of oral administration of the neuroleptic, haloperidol, on regional brain concentrations of cholecystokinin (CCK) and neurotensin were examined in the rat. Both short-term (3 weeks) and long-term (8 months) haloperidol administration increased the concentration of CCK in the substantia nigra. While short-term administration significantly increased the concentration of CCK in the ventral tegmental area and decreased the concentration of CCK in the cortex, including the medial prefrontal cortex, these effects were not observed following long-term drug administration. In contrast, long-term, but not short-term, haloperidol administration decreased the concentration of CCK in the olfactory tubercle. Withdrawal from long-term haloperidol did not alter CCK concentrations in any of the brain regions examined. Short-term haloperidol administration significantly increased the concentration of neurotensin in the caudate-putamen. Both short- and long-term administration increased the concentration of neurotensin in the nucleus accumbens, but only the increased following long-term administration reached statistical significance. Withdrawal from long-term haloperidol administration slightly decreased the concentrations of neurotensin in the caudate-putamen and nucleus accumbens. These results indicate that dopamine receptor blockade can affect both CCK- and neurotensin-containing neural systems. Furthermore, these two neuropeptides are affected differently depending upon the duration of haloperidol administration and withdrawal from this drug. The results raise the possibility that chronic administration of haloperidol may be toxic to some neurotensin-containing neurons in the basal ganglia.

The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

The effects of caloric supplementation for pregnant women and children from an endemically malnourished population on children's school age behavior were examined. The child's abilities to respond to routinely stressful problem-solving situations and to interact appropriately with peers were the dependent variables. Seventy-eight boys and 60 girls in rural Guatemala received different amounts of food supplementation, pre- and postnatally, as part of the INCAP Longitudinal Study. Children were classified as High or Low Supplementation, based on supplemental caloric intake prenatally and from birth to four years. When measured at 6 to 8 yr, High Supplementation children showed more interest in and exploration of a novel environment, more involvement in a competitive game, greater persistence on a frustrating task, better motor impulse control, and greater initiative across several group tasks than did Low Supplementation children. In free play with peers, the High Supplementation children showed more frequent happy affect, social involvement, and moderate activity level, and were less frequently timid or anxious. Results are consistent with findings from studies on the effects of early undernutrition on infant behavior, and suggest that behavior impairments associated with early undernutrition have long-term consequences for the child's development.

Most neonatal Herpes-simplex-virus infections are the result of virus acquisition during passage through the birth canal. Transplacental transmission of HSV is seldom. The infection is mostly localized at the skin, eyes and central nervous system. The disseminated HSV-infection represents as the most severe clinical picture. It is reported about meningoencephalitis caused by HSV in 3 infants in the first weeks of life. The therapeutic success of antiviral chemotherapeutics depends very much on their application at an early stage of the disease, which can be recognized by cerebral sonography and detection of IgM-antibodies against HSV.

The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants.

Neuroleptics influence a variety of putative neurotransmitters in the basal ganglia, including somatostatin and substance P. Most studies have been performed in animals after only 3 or 4 weeks of neuroleptic administration and have seldom examined the effects of withdrawal. To understand better the effects of haloperidol on neuropeptide systems, the effects of short-term (3 weeks) and long-term (8 months) administration, as well as withdrawal from long-term administration of haloperidol, on somatostatin and substance P concentrations were examined in the rat. Short-term haloperidol significantly decreased the concentrations of somatostatin in the caudate-putamen, nucleus accumbens, and ventral tegmental area, and decreased the concentration of substance P in the substantia nigra and the nucleus accumbens. However, long-term administration only decreased the concentration of somatostatin in the nucleus accumbens. In addition, a slight reduction in the concentration of substance P in the medial prefrontal cortex was detected after long-term treatment. After withdrawal from long-term haloperidol administration the concentrations of these peptides did not differ from control values in any of the brain regions examined. These results confirm that dopamine receptor blockade can affect the somatostatin and substance P systems in the basal ganglia and indicate that during long-term administration (8 months) tolerance develops to some of the effects that are observed after shorter (3 weeks) treatment periods.

The effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) on the levels of the neuropeptides somatostatin and substance P, were examined in various brain regions of C57 mice. Two weeks after injections of MPTP (2 × 30, 2 × 40 and 2 × 50 mg/kg i.p.) a dose-dependent decrease in striatal catecholamine levels was observed. There was also a dose-dependent increase in nigral somatostain immunoreactivity and no reduction in striatonigral substance P levels. These results are in contrast with the changes observed in peptide levels in post-mortem Parkinson's brains.

This is an exploratory study of the emotional and social functioning of young children with a manic-depressive parent. Seminaturalistic observations and experimental manipulations of the affective environment were used to assess 2-year-old children's regulation of emotion, as well as their aggression, altruism, and affiliative interactions. Children with a bipolar parent sometimes showed heightened distress and preoccupation with the conflicts and suffering of others, especially disturbances in adults. These children had difficulty in maintaining friendly social interactions, in sharing, and in helping their playmates. They also had difficulty modulating hostile impulses; they showed more maladaptive patterns of aggression toward peers and adults. These interpersonal and emotional problems of offspring of manic-depressives were often similar to those problems of manic-depressives that have been implicated in the clinical literature as possibly associated with the transmission of the disorder. This apparent congruence of findings obtained from different disciplines employing very different research strategies and studying people of different ages, attests to the utility of an explicit interdisciplinary approach in the area of developmental psychopathology.

In 3 infants with meningoencephalitis caused by Herpes simplex viruses the findings of cerebral sonography corresponded with those of computerized tomography and electroencephalography. The therapeutic success of antiviral chemotherapeutics depends very much on their application at an early stage of the disease, which can be recognized by cerebral sonography.