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Objective: In epidemiological and clinical studies, whole blood assay (WBA) has been used as a measure to characterize inter-individual differences in the cytokine response of individuals exposed to inflammatory agents, such as endotoxins. Several short-time repeatability studies have shown stable cytokine levels in individuals over periods of days, weeks or months, but little is known about the long-term stability of cytokine reactivity.Methods: We studied cytokine response levels in LPS-stimulated whole blood in a cohort of 193 farmers and agricultural industry workers at two time points with a five-year interval.Results: IL-10 and IL-1 beta responses measured with a five-year time interval showed a weak positive correlation (r = 0.22 and 0.27, respectively), whereas no correlation was observed for TNF alpha (r = 0.06). Cytokine reactivity measured repeatedly at the same time point showed high correlations (IL-10 r = 0.80, IL-1 beta r = 0.53 and TNF alpha r = 0.74), suggesting that the observed weak correlations over time are reflective of actual variations in cytokine reactivity over time.Conclusions: Repeatability of ex vivo cytokine reactivity showed to be differential for the measured cytokines, being more stable for IL-10 and IL-1 beta than for TNF alpha. However, in general, repeatability of ex vivo cytokine reactivity was weak, reflecting that cytokine reactivity can mostly be explained by (short term) intra-individual (immunological) or time varying environmental factors and less by genetic or other time-invariant factors. Therefore, WBA should be regarded as a viable tool to study relationships with current health status and exposure, and only partially as a predictor for a future response.

BACKGROUND: The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life. METHODS/DESIGN: 450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics. DISCUSSION: Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can restore the ecological balance of the microbiota and may mitigate potential negative effects on the developing immune system, when use of antibiotics cannot be avoided. TRIAL REGISTRATION: ClinicalTrials.gov NCT02536560 . Registered 28 August 2015.

Introduction Imbalance of the human gut microbiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, probiotic supplementation during infancy has been used for prevention of allergic diseases in infants, with variable success. However, not much is known about the long-term consequences of neonatal use of probiotics on the microbiota composition. The aim of this study was to assess the composition and microbial diversity in stool samples of infants at high-risk for atopic disease, from birth onwards to six years of age, who were treated with probiotics or placebo during the first year of life. Methods In a double-blind, randomized, placebo-controlled trial, a probiotic mixture consisting of B. bifidum W23, B. lactis W52 and Lc. Lactis W58 (Ecologic® Panda) was administered to pregnant women during the last 6 weeks of pregnancy and to their offspring during the first year of life. During follow-up, faecal samples were collected from 99 children over a 6-year period with the following time points: first week, second week, first month, three months, first year, eighteen months, two years and six years. Bacterial profiling was performed by IS-pro. Differences in bacterial abundance and diversity were assessed by conventional statistics. Results The presence of the supplemented probiotic strains in faecal samples was confirmed, and the probiotic strains had a higher abundance and prevalence in the probiotic group during supplementation. Only minor and short term differences in composition of microbiota were found between the probiotic and placebo group and between children with or without atopy. The diversity of Bacteroidetes was significantly higher after two weeks in the placebo group, and at the age of two years atopic children had a significantly higher Proteobacteria diversity (p < 0.05). Gut microbiota development continued between two and six years, whereby microbiota composition at phylum level evolved more and more towards an adult-like configuration. Conclusion Perinatal supplementation with Ecologic® Panda, to children at high-risk for atopic disease, had minor effects on gut microbiota composition during the supplementation period. No long lasting differences were identified. Regardless of intervention or atopic disease status, children had a shared microbiota development over time determined by age that continued to develop between two and six years.

Background: We previously demonstrated that probiotic prophylaxis, in patients with predicted severe pancreatitis, did not prevent infectious complications but unexpectedly increased the risk of bowel ischemia and mortality. The suggestion that these negative findings are only observed in the presence of organ failure at the start of probiotic treatment has not been confirmed. Methods: In a retrospective analysis, all patients with predicted severe acute pancreatitis without initial organ failure admitted to a medium care facility of a teaching hospital in Prague from January 2003 to December 2010 were included. All patients routinely received probiotic treatment with Probioflora. Total parenteral nutrition (TPN) was routinely started and shifted toward total enteral nutrition. Infectious complications, mortality and the incidence of bowel ischemia were recorded. Results: 99 consecutive patients, mean age 56 years, were included. Infectious complications occurred in 42 patients (42%), consisting of bacteremia (n = 40), pneumonia (n = 11) and infected necrosis (n = 11). Bowel ischemia was detected in two patients (2%). Overall mortality was 8%. Conclusion: In this retrospective study no apparent positive or negative impact of probiotic treatment with Probioflora was demonstrated when administered to patients with predicted severe acute pancreatitis without initial organ failure. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved

OBJECTIVE: To describe the increase of invasive Haemophilus influenzae type b (Hib) infections in The Netherlands before and after the introduction of Hib vaccination in 1993, and to hypothesise about possible explanations. DESIGN: Descriptive. METHOD: Data on the prevalence of invasive Hib infections, such as meningitis and epiglottitis, during 1990-2004 were obtained from The Netherlands Reference Laboratory for Bacterial Meningitis, which collects Hib isolates from spinal fluid and blood from across the country. RESULTS: The incidence of invasive Hib infections decreased substantially for a few years after 1993. The total number of isolates was at a minimum in 1999 (n = 12) and increased to 49 in 2004. The annual number of patients with vaccine failure was 5 or less during 1995-2001, but was between 10 and 15 from 2002 onwards. A definite explanation for the increase in the incidence of invasive Hib infections cannot be given. Improbable causes are a surveillance artefact, an impaired response to the vaccine due to vaccination-scheme changes or interaction with other vaccines, or selection of Hib variants that are less sensitive to the vaccine-induced immunity. It most likely involves secondary vaccine failure: Hib carriership is decreased by mass vaccination, whereupon natural boosting occurs less frequently later in life. Subsequently, immunity decreases and susceptibility to invasive infection increases. Careful surveillance of invasive Hib infections in The Netherlands remains important

Retrospective analysis of 33 patients with juvenile dermato/polymyositis showed 45% complete recovery, 26% remission (steroid dependent), 6% wheelchair-dependency, 3% deaths and 10% development of other connective tissue diseases after a mean follow up of 4 years. Patients who received 2 mg/kg of prednisone had the worst prognosis but since they apparently represent a subgroup it is questionable whether high dose prednisone was the cause of the poor prognosis. This subgroup is characterized by high CPK serum levels (a 10-fold increase or more) and an acute type of onset. An initial high ANA titer was found to predict the later development of other connective tissue disorders.

After immunization of carp with sheep red blood cells, the spleen accounts for only 5% of the total number of plaque-forming cells (PFC). In addition, thymus, peripheral blood and heart contained low numbers of PFC (< 0.5, 1 and 0.5%, respectively). Pronephros and mesonephros were the major antibody-forming organs (53 and 40% of total PFC, respectively). The temperature dependence of the antibody-forming cell response in spleen, pronephros and mesonephros as studied in animals kept at 12-24 degrees. Lowering temperatures induced a delay in the peak of the primary response but had no effect on the magnitude of the response. The temperature-peak day relationship indicated that there are steps in the primary immune response of carp differing in temperature sensitivity. The anamnestic character of the secondary response was clearly demonstrated at 24 and 20 degrees but lost at 18 degrees.

Dutch type periodic fever (DPF) is an autosomal recessive hereditary fever syndrome. Cases have been reported worldwide, the majority from France and The Netherlands. From infancy the patients suffer fever attacks that recur every 2-8 weeks, often precipitated by immunizations, infections or emotional stress. Fever lasts 2-7 days and can be accompanied by malaise, headache, diarrhea, abdominal pain, vomiting, skin rashes, arthralgia, arthritis, tender lymphadenopathy, hepatosplenomegaly, and oral and genital ulcers. Laboratory evaluation during fever shows granulocytosis and elevated acute phase reactants. DPF is caused by a deficiency of the enzyme mevalonate kinase (MK). Besides DPF, the spectrum of MK deficiency includes a severe phenotype, mevalonic aciduria (MA). MA patients have less residual MK activity, leading to substantially higher urinary mevalonic acid excretion than in DPF. Mevalonic aciduria is characterized by mental retardation and dysmorphic features in addition to the clinical features of DPF. At the genomic level, several mutations of varying severity have been identified. The DPF phenotype is caused by one particular mild missense mutation. Most patients are compound heterozygotes for this mutation and a more severe mutation. The mechanism by which MK deficiency leads to fever is not understood. The vast majority of DPF patients have persistently elevated serum IgD and can be classified as having hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Conversely, most HIDS patients have MK deficiency and hence DPF, but the two disorders do not overlap entirely