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Background: Whole blood (WB) is carried by special operations forces as part of a remote damage control resuscitation strategy. The effects of an underwater mission on the quality and coagulation profile of WB were simulated by exposure to hyperbaric pressures in a chamber. Methods: WB units collected in CPDA‐1 were exposed to three different combinations of hyperbaric pressure and duration of exposure: Group A 153.52 kPa (15.24 msw; 1.52 atm) for 4 h; n = 9, Group B 506.63 kPa (50.29 msw; 5.00 atm) for 1 h; n = 9, Group C 153.52 kPa (15.24 msw; 1.52 atm) for 1 h; n = 7. The following parameters were measured on each unit: prothrombin time/international normalized ratio, activated partial thromboplastin time, thromboelastography and concentration determinations of platelets, lactate, fibrinogen, and lactate dehydrogenase. Each sample underwent baseline, prepressurization, immediate postpressurization, and 6 h postpressurization laboratory testing. Results: Six hours following hyperbaric exposure, the lactate concentration in group C was higher than prepressurization measurement and the platelet concentration in Group A was lower than prepressurization measurement. There were no changes in any of the other analyzed biochemical, coagulation and thromboelastogram parameters following exposure to hyperbaric stress. Discussion: These data suggest that pressurization of WB up to 5 atm did not impact parameters tested. Changes observed in lactate and platelet count need further study, as well as complementary testing of red blood cell integrity. Further investigation of the hyperbaric extremes is necessary to determine if there is a damage inducing pressure to which WB should not be exposed. [ABSTRACT FROM AUTHOR]

Silybum marianum (L.) Gaertn. (Asteraceae), commonly known as milk thistle, is a botanical natural product used to self‐treat multiple diseases such as Type 2 diabetes mellitus and nonalcoholic steatohepatitis (NASH). An extract from milk thistle seeds (achenes), termed silymarin, is comprised primarily of several flavonolignans. Systemic concentrations of these flavonolignans can influence the potential biologic effects of silymarin and the risk for pharmacokinetic silymarin‐drug interactions. The aims of this research were to determine the roles of organic anion transporting polypeptides (OATPs/Oatps) in silymarin flavonolignan disposition and in pharmacokinetic silymarin‐drug interactions. The seven major flavonolignans from silymarin were determined to be substrates for OATP1B1, OATP1B3, and OATP2B1. Sprague Dawley rats were fed either a control diet or a NASH‐inducing diet and administered pitavastatin (OATP/Oatp probe substrate), followed by silymarin via oral gavage. Decreased protein expression of Oatp1b2 and Oatp1a4 in NASH animals increased flavonolignan area under the plasma concentration‐time curve (AUC) and maximum plasma concentration. The combination of silymarin inhibition of Oatps and NASH‐associated decrease in Oatp expression caused an additive increase in plasma pitavastatin AUC in the animals. These data indicate that OATPs/Oatps contribute to flavonolignan cellular uptake and mediate the interaction between silymarin and NASH on pitavastatin systemic exposure. [ABSTRACT FROM AUTHOR]

Background and purpose: Better understanding the incidence, predictors and mechanisms of early neurological deterioration (END) following intravenous thrombolysis (IVT) for acute stroke with mild symptoms and isolated internal carotid artery occlusion (iICAo) may inform therapeutic decisions. Methods: From a multicenter retrospective database, we extracted all patients with both National Institutes of Health Stroke Scale (NIHSS) score <6 and iICAo (i.e. not involving the Willis circle) on admission imaging, intended for IVT alone. END was defined as ≥4 NIHSS points increase within 24 h. END and no‐END patients were compared for (i) pre‐treatment clinical and imaging variables and (ii) occurrence of intracranial occlusion, carotid recanalization and parenchymal hemorrhage on follow‐up imaging. Results: Seventy‐four patients were included, amongst whom 22 (30%) patients experienced END. Amongst pre‐treatment variables, suprabulbar carotid occlusion was the only admission predictor of END following stepwise variable selection (odds ratio = 4.0, 95% confidence interval: 1.3–12.2; P = 0.015). On follow‐up imaging, there was no instance of parenchymal hemorrhage, but an intracranial occlusion was now present in 76% vs. 0% of END and no‐END patients, respectively (P < 0.001), and there was a trend toward higher carotid recanalization rate in END patients (29% vs. 9%, P = 0.07). As compared to no‐END, END was strongly associated with a poor 3‐month outcome. Conclusions: Early neurological deterioration is a frequent and highly deleterious event after IVT for minor stroke with iICAo, and is of thromboembolic origin in three out of four patients. The strong association with iICAo site—largely a function of underlying stroke etiology—may point to a different response of the thrombus to IVT. These findings suggest END may be preventable in this setting. [ABSTRACT FROM AUTHOR]

Climate change is altering biogeochemical, metabolic, and ecological functions in lakes across the globe. Historically, mountain lakes in temperate regions have been unproductive because of brief ice‐free seasons, a snowmelt‐driven hydrograph, cold temperatures, and steep topography with low vegetation and soil cover. We tested the relative importance of winter and summer weather, watershed characteristics, and water chemistry as drivers of phytoplankton dynamics. Using boosted regression tree models for 28 mountain lakes in Colorado, we examined regional, intraseasonal, and interannual drivers of variability in chlorophyll a as a proxy for lake phytoplankton. Phytoplankton biomass was inversely related to the maximum snow water equivalent (SWE) of the previous winter, as others have found. However, even in years with average SWE, summer precipitation extremes and warming enhanced phytoplankton biomass. Peak seasonal phytoplankton biomass coincided with the warmest water temperatures and lowest nitrogen‐to‐phosphorus ratios. Although links between snowpack, lake temperature, nutrients, and organic‐matter dynamics are increasingly recognized as critical drivers of change in high‐elevation lakes, our results highlight the additional influence of summer conditions on lake productivity in response to ongoing changes in climate. Continued changes in the timing, type, and magnitude of precipitation in combination with other global‐change drivers (e.g., nutrient deposition) will affect production in mountain lakes, potentially shifting these historically oligotrophic lakes toward new ecosystem states. Ultimately, a deeper understanding of these drivers and pattern at multiple scales will allow us to anticipate ecological consequences of global change better. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibition may be a promising new treatment modality for inflammatory (skin) diseases. However, little is known about direct effects of kinase inhibitors on keratinocyte differentiation and function as well as skin barrier formation. Objective: Our aim was to address the direct impact of kinase inhibition of the JAK1/3 pathways by tofacitinib on keratinocyte immune function and barrier formation in atopic dermatitis (AD) and psoriasis. Methods: 3D skin equivalents of both diseases were developed and concurrently pretreated with tofacitinib. To induce AD, 3D skin equivalents were stimulated with recombinant human IL‐4 and IL‐13. Psoriasis‐like conditions were induced by incubation with IL‐17A, IL‐22 and tumour necrosis factor α (TNFα). The activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT6 was assessed by Western blot analysis. Microarray analysis and quantitative real‐time PCR were used for gene expression analysis. Results: Tofacitinib pretreatment preserved epidermal morphology and reduced STAT3 and STAT6 phosphorylation of AD‐like and STAT3 phosphorylation of psoriasis‐like culture conditions in 3D skin models compared to sham‐controls. Filaggrin expression was fully maintained in the AD‐like models, but only partially in psoriasis‐like conditions after pretreatment with tofacitinib. In addition, tofacitinib upregulated DSC1, FLG and KRT1. Using gene expression analysis, downregulation of POSTN and IL24 was observed in AD‐like conditions, whereas downregulation of IL20 and IL1B was observed in psoriasis‐like conditions. Conclusion: JAK1/3 inhibition counteracted cytokine‐induced AD‐ and psoriasis‐like epidermal morphology and enhanced keratinocyte differentiation in 3D skin models. This effect was more pronounced in the AD‐like models compared to the psoriasis‐like 3D skin models. [ABSTRACT FROM AUTHOR]

Objective: Intra-abdominal adhesions are associated with an increased risk of complications during repeat Cesarean section (CS), such as bladder and bowel injury, hemorrhage, infection and hysterectomy. We present a simple sonographic marker, the 'sliding sign' of the uterus, for the prediction of intra-abdominal adhesions in the third trimester of pregnancy in women undergoing repeat CS.Methods: This was a prospective observational study of pregnant women with a history of at least one Cesarean delivery evaluated by transabdominal ultrasound during the third trimester of an ongoing pregnancy. In order to diagnose intra-abdominal adhesions, we assessed a sonographic sign, the sliding of the uterus under the inner part of the fascia of the abdominal muscles during deep breathing. Women were considered to be at high risk for severe adhesions if uterine sliding was absent and at low risk in the presence of obvious or moderate uterine sliding. A comparison between sonographic findings and intra-abdominal adhesions observed during surgery was performed.Results: Of the 63 patients with one or more previous CS examined, 59 completed the study and underwent CS at our institution. In 16 of the 19 cases assigned to the high-risk group for severe adhesions due to absence of sliding of the uterus, the suspicion was confirmed at surgery. The prediction of low risk for adhesions was confirmed in 35 out of 40 patients. The sensitivity and specificity of the sliding sign in predicting presence of intra-abdominal adhesions in women undergoing repeat CS were 76.2% and 92.1%, respectively. Inter- and intraobserver correlation using Cohen's kappa coefficient were 0.52 and 0.77, respectively.Conclusion: Our data show that a simple sonographic sign might be able to discriminate between high and low risk for intra-abdominal adhesions in patients with a history of Cesarean delivery. This technique may aid clinical decisions in patients undergoing repeat CS. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Summary: Background: Minimal hepatic encephalopathy (HE) and HE grade 1 (HE1) according to the West Haven criteria have recently been grouped as one entity named—covert HE‐ (CHE). Data regarding the impact of CHE on health‐related quality of life (HRQoL) and sleep quality are controversial. Aim: First, to determine whether CHE affects HRQoL and sleep quality of cirrhotic patients and second, whether minimal HE (MHE) and HE1 affect HRQoL and sleep quality to a comparable extent. Methods: A total of 145 consecutive cirrhotic patients were enrolled. HE1 was diagnosed clinically according to the West Haven criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to detect MHE. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL and Pittsburgh Sleep Quality Index (PSQI) was applied to assess sleep quality. Results: Covert HE was detected in 59 (40.7%) patients (MHE: n = 40; HE1: n = 19). Multivariate analysis identified CHE (P < 0.001) and female gender (P = 0.006) as independent predictors of reduced HRQoL (CLDQ total score). CHE (P = 0.021), low haemoglobin (P = 0.024) and female gender (P = 0.003) were identified as independent predictors of poor sleep quality (PSQI total score). Results of CLDQ and PSQI were comparable in patients with HE1 and MHE (CLDQ: 4.6 ± 0.9 vs 4.5 ± 1.2, P = 0.907; PSQI: 11.3 ± 3.8 vs 9.9 ± 5.0, P = 0.3). Conclusion: Covert HE was associated with impaired HRQoL and sleep quality. MHE and HE1 affected both outcomes to a comparable extent supporting the use of CHE as a clinically useful term for patients with both entities of HE in clinical practice. [ABSTRACT FROM AUTHOR]

Assess the value of 3rd trimester uterine artery (UtA) Doppler for predicting adverse outcomes in placental intrauterine growth restriction (IUGR). Results Of 1600 patients with EFW < 10th centile, 98 pregnancies met criteria for placental IUGR, 55 of which had abnormal UtA Doppler. [Extracted from the article]

Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high-fat (HF) diet for 2 hours a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2-hour scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs 24 hours ad libitum feeding on the same HF diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine-and amphetamine-regulated transcript, pro-opiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), as well as enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain, were measured by in situ hybridisation. Mice fed ad libitum on a HF diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, although they did not appear to be related to feeding behaviour in the schedule-fed groups (ie, the large, binge-type meals) and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by nonhomeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, although it still leaves open the fundamental question about the underlying mechanisms of meal feeding. [ABSTRACT FROM AUTHOR]

Linear growth failure can be caused by many different genetic abnormalities. In many cases, the genetic defect affects not only the growth plate, causing short stature but also other organs/tissues causing additional clinical abnormalities. A 10-year old boy was evaluated for impaired postnatal linear growth (height 113.3 cm, −4.6 SDS), a bone age that was delayed by 5 years, dysmorphic facies, cognitive impairment, and central nervous system anomalies. His younger brother, presented only with growth failure at 10 months of age. Exome sequencing identified compound heterozygous variants in the gene encoding RNA polymerase III transcription initiation factor 90 kDa subunit ( BRF1) in both affected siblings: a missense mutation (c.875 C > G:p. P292R) and a frameshift mutation (c. 551delG:p. C184Sfs). The frameshift mutation is expected to lead to nonsense-mediated mRNA decay ( NMD) and/or to protein truncation. Expression of BRF1 with the P292R missense mutation failed to rescue yeast lacking BRF1. The findings confirm a previous report showing that biallelic mutations in BRF1 cause cerebellar-facial-dental syndrome. Our findings also help define the growth phenotype, indicating that the linear growth failure can become clinically evident before the neurological abnormalities and that a severely delayed bone age may serve as a diagnostic clue. [ABSTRACT FROM AUTHOR]

The article presents a case study of three white patients with Brooke–Spiegler syndrome (BSS) who were initially diagnosed both clinically and histopathologically. Topics include mutation analysis of the cylindromatosis (CYLD) gene, which revealed three splice site mutations and assessment of the expression of CYLD in normal human epidermal keratinocytes (NHEK), leucocytes and peripheral blood mononuclear cells (PBMC) by quantitative reverse transcriptase (qRT)-PCR.

Metal ornaments from Únětice ( Mierczyce, Tomice, Jordanów and Opatowice) and Urnfield culture ( Szprotawa, Żarek and Wrocław Żerniki) sites in south-west Poland are made of bronze of varying composition, with the exception of the early Bronze Age Przecławice site, where the copper items are found in graves from stages III/ IV. The combined XRF and electron microprobe study of 37 ornaments (mostly pins) shows that those excavated from Únětice culture graves usually consist of cored dendrites, plus a Sb-rich phase in some. The copper objects from Przecławice correspond in composition to the East Alpine Copper or to the Ösenring copper and were produced from fahlore. Those from the Urnfield culture sites consist of homogeneous bronze. The Únětice culture ornaments were produced with little control of the effect of varying bronze composition on its microstructure. The results of XRF analyses of heterogeneous metal artefacts vary depending on the proportion of phases in the analysed site, and should be combined with micrometre-scale analytical data and microstructural information yielded by electron microprobe methods. The same refers to deeply weathered or corroded objects made of homogeneous metal, which contain irregularly dispersed decomposition products. [ABSTRACT FROM AUTHOR]

Background National population-based medical registries in Denmark offer a unique opportunity to study eosinophilic oesophagitis (EoE) epidemiology. Aim To determine the incidence and prevalence of EoE in Denmark, and evaluate whether an increase in endoscopy with biopsy activity explains changes in these trends. Methods The Danish National Pathology Registry, Danish National Patient Registry and Danish Registry of Medicinal Product Statistics were queried from 1997 to 2012. Using an EoE case-finding algorithm validated for Danish patients, EoE cases were identified during each year of the study period; we also identified all patients with oesophageal eosinophilia. Using the known population of Demark, the annual incidence and prevalence of EoE were determined. We also determined the number of oesophageal biopsies performed each year in Denmark, and compared the change in the incidence rate to the change in biopsy rate. Results Between 1997 and 2012, 1708 patients had oesophageal eosinophilia, of whom 844 met the case definition of EoE. There were seven new cases of EoE in 1997 and 145 new cases in 2012, corresponding to a 19.5-fold increase in incidence (0.13/100 000 to 2.6/100 000). There were 769 total cases in 2012 (prevalence of 13.8/100 000). Over the same time frame, the oesophageal biopsy rate increased only 1.9 fold, from 91.1/100 000 to 175.3/100 000. Conclusions The incidence and prevalence of EoE markedly increased in Denmark over the past 15 years. This increase far outpaced the increase in oesophageal biopsy utilisation, indicating that changes in the frequency of EoE are not due to changes in biopsy rates alone. [ABSTRACT FROM AUTHOR]

The effect of a cord entanglement on perinatal outcomes, such as fetal demise, Caesarean section rate and low Apgar score is controversial. The aim of this study was to evaluate the impact of cord entanglement on perinatal outcomes. Umbilical cord entanglement around various fetal body parts is usually an incidental diagnosis during delivery. [Extracted from the article]

We have developed an immunochromatographic test for the diagnosis of peste des petits ruminants ( PPR) under field conditions. The diagnostic assay has been tested in the laboratory and also under field conditions in Ivory Coast, Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The specificity was 95% over all nasal and ocular samples. The test detected as little as 103 TCID50 (50% tissue culture infectious doses) of cell culture-grown virus, and detected virus isolates representing all four known genetic lineages of peste des petits ruminants virus. Virus could be detected in swabs from animals as early as 4 days post-infection, at a time when clinical signs were minimal. Feedback from field trials was uniformly positive, suggesting that this diagnostic tool may be useful for current efforts to control the spread of PPR. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2012; 35: 165-174 Summary Background Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. Aim To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time-varying drug exposure ascertainment. Methods We conducted this population-based cohort study in Western Denmark (population 3 million) using medical databases. We identified all 13 001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders. Results During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0.47 (95% CI: 0.42-0.53) among PPI non-users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91-1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR = 1.24 (95% CI: 0.97-1.58) for clopidogrel users and 1.26 (95% CI: 0.97-1.63) for clopidogrel non-users]. Conclusions The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 901–907 Background The risk of dying from gastric cancer appears to have increased among consecutive generations born during the 19th century. Aim To follow the time trends of hospitalization for gastric cancer and test whether they confirm such increase. Methods Inpatient records of the last two centuries from four hospitals in Scotland and three US hospitals were analysed. Proportional rates of hospitalization for gastric cancer, gastric ulcer and duodenal ulcer were calculated during consecutive 5-year periods. Results The data from all seven cities revealed strikingly similar patterns. No hospital admissions for gastric cancer or peptic ulcer were recorded prior to 1800. Hospital admissions for gastric cancer increased in an exponential fashion throughout the 19th and the beginning of the 20th century. In a majority of cities, the rise in hospitalization for gastric cancer preceded a similar rise in hospitalization for gastric ulcer. Hospitalization for these two latter diagnoses clearly preceded hospitalization for duodenal ulcer by 20–40 years. Conclusions The occurrence of gastric cancer, gastric ulcer and duodenal ulcer markedly increased during the 19th century. Improvements in hygiene may have resulted in the decline of infections by other gastrointestinal organisms that had previously kept concomitant infection by Helicobacter pylori suppressed. [ABSTRACT FROM AUTHOR]

Background Soluble immune receptors (SIRs) have been proposed as biomarkers in patients with atopic dermatitis (AD). However, their clinical applicability in affected children has rarely been studied. Objective To assess the diagnostic usefulness of serum SIRs in childhood AD by correlating the obtained receptor profiles with serological parameters and clinical features such as age, AD phenotype and disease severity. Methods We investigated 100 children with AD. The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic protein (ECP) were determined using sera of all children. The clinical phenotype was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of allergen-specific IgE antibodies. Results A total of 55 male and 45 female children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed significant age-dependency. At a mean SCORAD of 40 (range 8–98), none of the evaluated SIRs was correlated to disease severity. In all, 73% of patients suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs differed significantly between ADe and ADi patients, while tIgE and ECP levels were elevated in the ADe subgroup. Conclusion The current study provides evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum concentrations of all investigated SIRs did not significantly correlate with disease severity in children with AD and were not differentially expressed in patients of different AD phenotypes. Therefore, we believe that the studied SIRs cannot be regarded as clinically useful biomarkers for the assessment of childhood AD. [ABSTRACT FROM AUTHOR]

Background: The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction’s phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation. Objective: The aim of this study was to assess drug-specific cytokine production by means of flow cytometry as an alternative nonradioactive approach which may be more appropriate for routine testing and may provide in addition more information about the pathophysiology of the reaction than proliferation-based assays, like the LTT. Method: Peripheral blood mononuclear cells of 19 patients were incubated with culprit drugs ( n = 28) or irrelevant antigens ( n = 10). Ten healthy persons served as controls for all different drugs ( n = 15). Intracellular interleukin (IL)-5, interferon (IFN)-γ and IL-10 production was investigated using flow cytometry. Accuracy of the flow cytometry test system was confirmed using different statistical tests, i.e. receiver operating characteristic curve and Mann–Whitney rank test. In addition, drug-specific secretion of IL-5, IL-2 and IFN-γ were analysed using enzyme-linked immunosorbent assay (ELISA). Results: Drug-specific cytokine production could be demonstrated in 75% of the patients using flow cytometry and in 79% using ELISA respectively. Combining ELISA and flow cytometry increased the sensitivity to 100%. Analysis of involved T-cell subsets [e.g. CD4+ or CD8+; T helper (TH) 1 or TH 2] allowed characterization of the in vitro lymphocyte reactivity pattern. Conclusions: Analysis of drug-specific cytokine production by means of flow cytometry proved a useful and reliable approach for the in vitro detection and characterization of drug hypersensitivities. [ABSTRACT FROM AUTHOR]

Background: Component-resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray-based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. Methods: We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed. Results: We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component-resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods. Conclusions: Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double-blind, placebo-controlled food challenges in most cases. [ABSTRACT FROM AUTHOR]

Preventing death and limiting handicap from ischaemic stroke are major goals that can be achieved only if the pathophysiology of infarct expansion is properly understood. Primate studies showed that following occlusion of the middle cerebral artery (MCA)––the most frequent and prototypical stroke, local tissue fate depends on the severity of hypoperfusion and duration of occlusion, with a fraction of the MCA territory being initially in a ‘penumbral’ state. Physiological quantitative PET imaging has translated this knowledge in man and revealed the presence of considerable pathophysiological heterogeneity from patient to patient, largely unpredictable from elapsed time since onset or clinical deficit. While these observations underpinned key trials of thrombolysis, they also indicate that only patients who are likely to benefit should be exposed to its risks. Accordingly, imaging-based diagnosis is rapidly becoming an essential component of stroke assessment, replacing the clock by individually customized management. Diffusion- and perfusion-weighted MR (DWI-PWI) and CT-based perfusion imaging are increasingly being used to implement this, and are undergoing formal validation against PET. Beyond thrombolysis per se, knowledge of the individual pathophysiology also guides management of variables like blood pressure, blood glucose and oxygen saturation, which can otherwise precipitate the penumbra into the core, and the oligaemic tissue into the penumbra. We propose that future therapeutic trials use physiological imaging to select the patient category that best matches the drug's presumed mode of action, rather than lumping together patients with entirely different pathophysiological patterns in so-called ‘large trials’, which have all failed so far.British Journal of Pharmacology (2008) 153, S44–S54; doi:10.1038/sj.bjp.0707530; published online 26 November 2007 [ABSTRACT FROM AUTHOR]

The Food Quality Protection Act (FQPA) was enacted in August 1996 and required the US Environmental Protection Agency (EPA) to reassess all existing and new crop protection active substances using a new set of health and environmental standards to further protect infants and children. The initial fear that many minor or specialty crop use registrations would be lost without adequate replacements has largely been overcome by an aggressive programme by the International Research Project no. 4 (IR-4) in partnership with the EPA and the crop protection industry to register new, safer, reduced risk products for specialty crop pest control needs. Since the FQPA, the EPA has approved over 5600 new specialty crop uses resulting from IR-4 residue programmes. This amounts to about 56% of the over 10 000 clearances received by the IR-4 programme in its 43 year history and about 50% of all new uses granted by the EPA since FQPA. The positive outcomes from these efforts have been partially negated by the lack of tolerances or Maximum Residue Levels (MRLs) in countries to which US produce is exported. This has forced some US specialty crop growers to continue to use older, less desirable products. IR-4 has been addressing this challenge by cooperating in the NAFTA (North American Free Trade Agreement) countries with Agriculture and Agri-Food Canada's Pest Management Centre and Health Canada's Pest Management Regulatory Agency to harmonize MRLs through joint projects and regulatory reviews. IR-4 has also provided leadership for the International Crop Grouping Consulting Committee to harmonize specialty/minor crop groupings and representative crops for residue studies with the long-term goal being to globally harmonize MRLs. [ABSTRACT FROM AUTHOR]

Background Stomach pain and discomfort have been reported since antiquity. Aim To follow the time trends since the 18th century of dyspepsia, gastric ulcer, duodenal ulcer, and benign oesophageal disease to test when dyspepsia started to become a major clinical problem. Methods The annual in- and out-patient records of the last three centuries from the Scottish Royal Infirmaries of Edinburgh, Aberdeen, Glasgow and Dundee were analysed. In addition, dispensary attendances, clinicians' casebooks, students' notebooks and medical texts have been scrutinized for historic statistics of upper gastrointestinal disease. Results Dyspepsia was first recorded in the 1750s and increased markedly subsequently. Such dyspepsia persisted after gastric and duodenal ulcers appeared in the late 19th century and then declined again in the late 20th century. Non-ulcer dyspepsia has remained the commonest diagnosis made after endoscopy for stomach pain in the beginning of the 21st century. Conclusion The current commonest diagnosis of stomach pain, dyspepsia dates from the mid-18th century. Any explanations of its causation need to consider this timing. [ABSTRACT FROM AUTHOR]

Background Case reports have suggested that the use of newer cyclo-oxygenase-2 selective inhibitors may cause acute pancreatitis, but there has been no formal study of the association. Aim To assess the relationship between the use of cyclo-oxygenase-2 inhibitors and other non-steroidal anti-inflammatory drugs, and risk of acute pancreatitis. Methods A population-based case–control study was conducted using hospital discharge and prescription data from Denmark. Using conditional logistic regression with adjustment for multiple covariates, we estimated the relative risk of acute pancreatitis for use of the cyclo-oxygenase-2 inhibitors celecoxib and rofecoxib and for other non-steroidal anti-inflammatory drugs. Results A total of 3083 cases of acute pancreatitis and 30 830 population controls were identified. For current use the relative risk estimate for celecoxib was 1.4 (95% CI: 0.8–2.3) and for rofecoxib was 1.3 (95% CI: 0.7–2.3). The overall relative risk for other non-steroidal anti-inflammatory drugs was 2.7 (95% CI: 2.4–3.0) with a substantial variation in risk between the individual drugs. The highest relative risk was for diclofenac (odds ratio 5.0, 95% CI: 4.2–5.9) and the lowest for naproxen (odds ratio 1.1, 95% CI: 0.7–1.7). Conclusion Cyclo-oxygenase-2 selective inhibitors are associated with a lower risk of acute pancreatitis than most other non-steroidal anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Prior studies suggest that histamines may modulate the development of colorectal neoplasia. To assess whether histamine receptor antagonist use was associated with adenoma formation. Patients ( n = 2366) were drawn from three adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of adenoma(s) and were deemed free of remaining lesions; they were followed with surveillance colonoscopy. Medication use was assessed by questionnaire. Adjusted risk ratios for adenoma formation related to histamine receptor antagonist use (histamine H1 and H2 receptor, H1RA and H2RA) were determined using log linear models. In pooled analyses, H1RA exposure was not associated with subsequent adenoma risk (RR = 1.10; 95% CI 0.97–1.25) or multiple adenoma formation (RR = 0.85; 95% CI 0.67–1.07). H2RA use also was not associated with adenoma (RR = 0.90; 95% CI 0.77–1.06), or multiple adenoma (RR = 0.77; 95% CI 0.57–1.04) in the pooled analyses, but H2RA users in the first trial had a decreased risk of adenoma (RR = 0.70; 95% CI 0.48–1.03) and multiple adenoma (RR = 0.31; 95% CI 0.12–0.79). H2RA use was associated with reduced risk for adenoma in one trial, but not in the pooled analyses. Further study would be warranted before undertaking randomized trials of H2RAs for adenoma chemoprevention. [ABSTRACT FROM AUTHOR]

Since the publication of the first EFNS task force reports in 1997, a total of 20 evidence-based guidelines for the treatment and management of neurological diseases have been published by the EFNS (). In 2001, recommendations for the preparation of neurological guidelines were issued by the EFNS Scientific Committee (Eur J Neurol 2001; 8: 549–550). These have now been updated and revised. More unified criteria for standards of reporting are set up which include classes of scientific evidence and predefined levels of recommendation. These criteria as well as others listed below should be used for all working groups that aim at recommending treatment, diagnostic procedures or other interventions within the framework of the EFNS. [ABSTRACT FROM AUTHOR]

This report discusses a biopsy proven case of cerebral amyloid angiopathy, with additional prominent vascular inflammatory features, characterized by a rapidly progressive dementia and leukoencephalopathy, where the clinical and radiological abnormalities resolved rapidly with minimal therapeutic intervention. We propose the term cerebral amyloid inflammatory vasculopathy (CAIV) to describe this condition. [ABSTRACT FROM AUTHOR]

Summary Background : Although dyspepsia has been described for thousands of years, few studies have analysed its incidence before the 19th century when peptic ulcer first became a major dyspepsia-producing disease. Methods : The incidence of alimentary disease around 1800 was examined in three private practices for the fee-paying middle class and in five public dispensaries for the poor in London, as well as in one dispensary in New York. Results : The proportions of attendances for alimentary disorders were identical, 16%, in each of the three groups. Diarrhoea and dysentery were twice as common in the London dispensary than in private practice, presumably because of poor sanitation. Dyspepsia showed a similar incidence in the London dispensary and private practice, but was only half as common in New York. Worms were three times more common in dispensary patients in New York than in London. The incidence of diarrhoea and dyspepsia indicated no significant time trends over 43 years. None of the alimentary causes of death showed peptic ulcer at necropsy, and both haematemesis and intestinal haemorrhage were rare. Conclusions : Around 1800, the infrequent deaths from alimentary conditions suggested that the ulcer epidemic had not yet started. Instead, it is probable that the dyspepsia was similar to the non-ulcer dyspepsia of today. [ABSTRACT FROM AUTHOR]

Background: Immune hemolytic anemia has been associated with the administration of various antibiotics, including cephalosporins. Presented here is a patient who developed severe acute hemolysis while receiving ceftizoxime (Ceftizox, Fujisawa USA), a third-generation cephalosporin. This is the fourth reported case of hemolysis in association with ceftizoxime. In the previous cases, ceftizoxime was shown to induce hemolysis by the immune-complex mechanism. However, in one of those reports, the concentration of drug used to treat the target RBCs in vitro may not have been optimal.Case Report: The patient's antemortem blood samples were analyzed retrospectively for drug-dependent antibodies by the drug-adsorption and immune-complex methods. Antibody class and titer were evaluated.Results: The patient's sample agglutinated RBCs coated with ceftizoxime as well as uncoated RBCs in the presence of ceftizoxime. The antibodies to ceftizoxime were IgM and IgG.Conclusion: This is the first report on both the immune-complex and drug-adsorption mechanisms of ceftizoxime-induced hemolysis. The differential diagnosis of a falling Hct in a patient receiving antibiotics should include drug-related hemolysis; once this diagnosis is considered, management includes the appropriate serologic workup, immediate cessation of the implicated drugs, and possible transfusion support. [ABSTRACT FROM AUTHOR]

In the international neurological literature, neuroimaging research plays an important role. Neuroimaging techniques are also of steadily increasing importance for clinical diagnosis and treatment monitoring. Therefore, neuroimaging research activities were surveyed by a questionnaire, which was completed by 100 neurological centres across Europe. It showed that most groups use magnetic resonance imaging (MRI), fMRI, computerized tomography (CT) and single photon emission computerized tomography (SPECT). Positron emission tomography (PET) and ultrasound are also employed by nearly half of the centres. Neuroimaging research involves co-operation amongst typically five to 10 disciplines. Cerebrovascular disease, dementia, cognitive disorders, epilepsy, movement disorders, brain tumours and multiple sclerosis are frequently being studied. Many groups rely on small budgets, have few full-time scientists and limited access to expensive resources. There is little exchange of scientists amongst laboratories. It was felt that funding and co-operation needed improvement in order to maintain a high standard in neuroimaging research. [ABSTRACT FROM AUTHOR]

It has been suggested that the long-term discount rate for environmental goods should decrease at longer delays. One justification for this suggestion is that human judgments support it. This article presents an experiment showing that judgments concerning discount rates are internally inconsistent. These results point to potential problems with the use of judgments referenda for determining discount rates in cost-benefit analyses. [ABSTRACT FROM AUTHOR]

One hundred twenty-two members (experts) of the Society for Risk Analysis completed a mailed questionnaire and 150 nonexperts completed a similar questionnaire on the World Wide Web. Questions asked included those about priorities on personal and government action for risk reduction, badness of the risk, number of people affected, worry, and probabilities for self and others. Individual differences in mean desire for action were largely explained in terms of worry. Worry, in turn, was largely affected by probability judgments, which were lower for experts than for nonexperts. Differences across risks in the desire for action, within each subject, were also determined largely by worry and probability. Belief in expert knowledge about the risk increased worry and the priority for risk reduction. A second study involving 91 nonexperts (42 interviewed and 49 on the Web) replicated the main findings for nonexperts from the first study. Interviews also probed the determinants of worry, attitudes toward government versus personal control, and protective behaviors. [ABSTRACT FROM AUTHOR]

Abstract The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well-known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age- and sex-matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III-R criteria, and 10 age- and gender-matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C-flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger’s and Covi’s scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F-values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety-score–PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across-group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety. [ABSTRACT FROM AUTHOR]

Presents evidence that cytochrome P450-dependent metabolism is involved in the formation of nominal antigen. Examples of specific immunological reactions to small molecular weight compounds on the level of T-lymphocytes; Presence of cytochrome P450 isoenzymes in antigen presenting cells.

The article focuses on a study on the impact of water redistribution, land cover and temperature on ecosystem process on ecosystem in the South Platte Basin. It is noted that the changes in plant productivity and vegetation-related hydrological processes were compared using the RHESSys model. The study found that in the mountain vegetation, the effect of temperature changes on productivity and water fluxes was stronger while land cover change exerted more control over annual plant productivity.