Neonatal herpes simplex virus infections in Switzerland: results of a 6-year national prospective surveillance study.

A large variation in neonatal herpes incidence is observed in USA and Europe. Better knowledge of neonatal herpes epidemiology is important to inform local prevention strategies. Between 2002 and 2008, the Swiss Paediatric Surveillance Unit reported prospectively proven neonatal herpes simplex virus infections. During the study period seven cases were declared, for an incidence of 1.6/100,000 (95% CI 0.64-3.28/100,000) live births. This is one of the lowest incidences of neonatal herpes reported.

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability. Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of >50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (>3 yrs of intensive care vs. <3 yrs, 4.1 vs. 4.95 nmol/L, p < .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with >8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p < .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.

Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions.

The purpose of this work was to develop and optimize a simple and suitable method to detect the potential inhibitory effect of drugs and medicines on alcohol dehydrogenase (ADH) activity in order to evaluate the possible interactions between medicines and alcohol metabolism. Commonly used medicines that are often involved in court litigations related with driving under the influence of alcohol were selected. Alprazolam, flunitrazepam and tramadol were tested as drugs with no known effect on ADH activity. Cimetidine, reported previously as having inhibitory effect on ADH, and 4-methylpyrazole (4-MP), a well known ADH inhibitor, were tested as positive controls. Apart from 4-MP, tramadol was identified as having the higher inhibitory effect with an IC50 of 44.7×10(-3)mM, followed by cimetidine (IC50 of 122.9×10(-3)mM). Alprazolam and flunitrazepam also reduced liver ADH activity but to a smaller extent (inhibition of 11.8±5.0% for alprazolam 1.0mM and 34.5±7.1% for flunitrazepam 0.04mM). Apart from cimetidine, this is the first report describing the inhibitory effect of these drugs on ethanol metabolism. The results also show the suitability of the method to screen for inhibitory effect of drugs on ethanol metabolism helping to identify drugs for which further study is justified.

Depistage mutationnel des genes de la peripherine/RDS, rhodopsine et ROM-1 dans 69 cas index de retinite pigmentaire et autres dystrophies retiniennes [Mutational screening of peripherin/RDS genes, rhodopsin and ROM-1 in 69 index cases with retinitis pigmentosa and other retinal dystrophies]

PURPOSE: Phenotypic, genetic and molecular characterization of 69 index patients with retinitis pigmentosa (RP) and various inherited retinal diseases. PATIENTS AND METHOD: patients went through complete ocular examination and blood samples were drawn for mutational screening of three candidate genes: rhodopsin (RHO), peripherin/RDS, and ROM-1. RESULTS: the most frequent type of RP among our population was the autosomal dominant (43.6%). Three RHO mutations were found among the RP patients. A RDS mutation was detected in three unrelated families segregating dominant macular dystrophy. DISCUSSION AND CONCLUSIONS: 18% of the autosomal dominant RP patients presented a RHO mutation; RDS R172W mutation was present in 25% of the dominant macular dystrophies.

Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats.

Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.

Sources d'exposition aux phtalates dans une unité de soins néonatals [Phthalate exposure in the neonatal intensive care unit].

There are growing concerns on long-term health consequences, notably on fertility rates, of plasticizers such as phthalates. While di(2-ethylhexyl)phthalate (DEHP) is currently used in several medical devices, newborns in the neonatal intensive care unit are both more exposed and more vulnerable to DEHP. The objectives of this study were to identify, count, and describe possible sources of DEHP in a neonatal care unit. Our method consisted in the listing and the inspection of the information on packaging, complemented by contact with manufacturers when necessary. According to the results, 6% of all products and 10% of plastic products contained some DEHP; 71% of these involved respiratory support devices. A vast majority of the items showed no information on the content of DEHP. Further research is needed, particularly to determine the effects of such an early exposure and to study and develop safer alternatives.

Dépistage du cancer de la prostate: utilité, buts et perspectives en 2010 [Prostate cancer screening: utility, goals and perspectives in 2010].

According to recent results of a sub-group of 20,000 patients from the ERSPC study, prostate cancer screening significantly increases disease specific survival for men with a life expectancy of 15 years. However presently, only 20% of prostate biopsies lead to the diagnosis of cancer. This low yield may be increased by using new tools on their way to validation, such as the blood and urinary markers p2-PSA and PCA3, so as MRI and tridimensional computerized echography. Finally, the tumours detected must be managed with subtlety, since a third of them are not overtly aggressive clinically. Hence, a significant proportion of such tumours may not need immediate curative intent treatment, and can be followed up in an active surveillance protocol.

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes.

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (ICa). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of ICa. This study provides the first direct and unequivocal evidence for MR function in the heart.

Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature.

BACKGROUND: The A3243G point mutation in mitochondrial DNA (mtDNA) is associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both MELAS and MIDD patients can present with visual symptoms due to a retinopathy, sometimes before the genetic diagnosis is made. CASE PRESENTATION: Patient 1: 46 year-old woman with diabetes mellitus and hearing loss was referred for an unspecified maculopathy detected during screening evaluation for diabetic retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed bilateral macular and peripapillary hyperpigmented/depigmented areas.Patient 2: 45 year-old woman was referred for recent vision loss in her left eye. History was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited several nummular perifoveal islands of retinal pigment epithelium atrophy and adjacent pale deposits in both eyes.Retinal anatomy was investigated with autofluorescence, retinal angiography and optical coherence tomography. Retinal function was assessed with automated static perimetry, full-field and multifocal electroretinography and electro-oculography. Genetic testing of mtDNA identified a point mutation at the locus 3243. CONCLUSION: Observation of RPE abnormalities in the context of suggestive systemic findings should prompt mtDNA testing.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Temporal evolution of MR perfusion in neonatal hypoxic-ischemic encephalopathy

PURPOSE: To illustrate the evolution of brain perfusion-weighted magnetic resonance imaging (PWI-MRI) in severe neonatal hypoxic-ischemic (HI) encephalopathy, and its possible relation to further neurodevelopmental outcome. MATERIALS AND METHODS: Two term neonates with HI encephalopathy underwent an early and a late MRI, including PWI. They were followed until eight months of age. A total of three "normal controls" were also included. Perfusion maps were obtained, and relative cerebral blood flow (rCBF) and cerebral blood volume (rCBV) values were measured. RESULTS: Compared to normal neonates, a hyperperfusion (increased rCBF and rCBV) was present on early scans in the whole brain. On late scans, hyperperfusion persisted in cortical gray matter (normalization of rCBF and rCBV ratios in white matter and basal ganglia, but not in cortical gray matter). Diffusion-weighted imaging (DWI) was normalized, and extensive lesions became visible on T2-weighted images. Both patients displayed very abnormal outcome: Patient 2 with the more abnormal early and late hyperperfusion being the worst. CONCLUSION: PWI in HI encephalopathy did not have the same temporal evolution as DWI, and remained abnormal for more than one week after injury. This could be a marker of an ongoing mechanism underlying severe neonatal HI encephalopathy. Evolution of PWI might help to predict further neurodevelopmental outcome.