Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

BACKGROUND: Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed multispecies probiotics reduces bacterial translocation or improves outcome in a rat model of acute pancreatitis. METHODS: Male Sprague-Dawley rats were allocated into 3 groups: (1) controls (sham-operated, no treatment), (2) pancreatitis and placebo, and (3) pancreatitis and probiotics. Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Daily probiotics or placebo was administered intragastrically from 5 days prior until 7 days after induction of pancreatitis. Tissue and fluid samples were collected for microbiologic and quantitative real-time PCR analysis of bacterial translocation. RESULTS: Probiotics reduced duodenal bacterial overgrowth of potential pathogens (Log(10) colony-forming units [CFU]/g 5.0 +/- 0.7 [placebo] vs 3.5 +/- 0.3 CFU/g [probiotics], P < .05), resulting in reduced bacterial translocation to extraintestinal sites, including the pancreas (5.38 +/- 1.0 CFU/g [placebo] vs 3.1 +/- 0.5 CFU/g [probiotics], P < .05). Accordingly, health scores were better and late phase mortality was reduced: 27% (4/15, placebo) versus 0% (0/13, probiotics), respectively, P < .05. CONCLUSIONS: This experiment supports the hypothesis that modification of intestinal flora with multispecies probiotics results in reduced bacterial translocation, morbidity, and mortality in the course of experimental acute pancreatitis.     

Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody

Allergic bronchopulmonary aspergillosis (ABPA) can cause severe worsening of the respiratory condition in patients with cystic fibrosis. Treatment can result in steroid dependency and serious adverse events. A dramatic and rapid improvement of respiratory symptoms and lung function after a single dose of anti-IgE antibody (omalizumab) in a 12-year-old girl with cystic fibrosis and ABPA is described. This is the first report of this experimental treatment. It suggests an important role for IgE in the pathogenesis of ABPA and offers new therapeutic possibilities.     

Fatal cerebral and cerebellar hemorrhagic infarction after thoracoscopic microdiscectomy. Case report

The authors present a rare case of fatal cerebral and cerebellar hemorrhagic infarction following an uneventful thoracoscopic microdiscectomy. They hypothesize that this complication was associated with cortical venous thrombosis secondary to intracranial hypotension, which was caused by an unnoticed leak of cerebrospinal fluid (CSF) into the thoracic cavity. Cortical venous thrombosis and intrathoracic CSF were confirmed at autopsy. The former disorder is the most severe manifestation of the pathophysiological mechanism occurring to a lesser degree in patients affected by mild intracranial hypotension, and occurs more frequently in these patients. Intracranial hypotension (of an orthostatic nature or not) must be considered in the differential diagnosis of every patient who complains of headaches after thoracoscopic or open transthoracic microdiscectomy.     

Absence of Neisseria meningitidis Serogroup C-Specific Antibodies during the First Year of Life in The Netherlands: an Age Group at Risk?

In The Netherlands, a single meningococcal serogroup C conjugate (MenCC) vaccination is administered to children at the age of 14 months. Here, we report the levels of MenC polysaccharide-specific antibodies in children at birth and at 3, 11, and 12 months of age and the presence of functional antibodies at 11 months of age, before infants receive their MenCC immunization. We observed a rapid decline in polysaccharide-specific antibodies after birth and no induction of naturally elicited polysaccharide-specific antibodies. Furthermore, at 11 months of age, no bactericidal antibodies are observed. These data indicate that these infants may be at risk in the period prior to MenCC immunization, if Neisseria meningitidis serogroup C starts to (re)circulate.Childhood immunization programs are initiated to prevent infectious diseases in children. Most countries have designed their own national immunization program (NIP), and great variations exist among different countries (7). Immunization of children at 14 months of age with the meningococcal serogroup C conjugate (MenCC) vaccine (NeisVac-C; Baxter, IL) was introduced in The Netherlands in 2002. The choice to administer the vaccine to children at this age was based on programmatic and economical reasons. In The Netherlands, only two immunizations at once are accepted by the public. This fact, taken together with the economical impact, indicated that the best opportunity to include a new vaccine in the NIP was at 14 months of age (10). Furthermore, epidemiological data supported the introduction of the MenC vaccine as a single dose with a catch-up campaign (10). Other countries in Europe adapted the United Kingdom schedule, in which immunization at first was offered at 2, 3, and 4 months of age (14). Currently, the MenCC immunization program in the United Kingdom has been changed to a schedule of administration at 3, 4, and 12 months of age (1).In addition to the introduction of the MenCC vaccine for children at 14 months of age, a catch-up program in which all children and adolescents up to 19 years of age were offered a single immunization (vaccine coverage of 94%) was carried out in The Netherlands (15). This vaccination strategy led to an almost complete disappearance of MenC disease in children, with only a few cases occurring in unvaccinated individuals, indicating a large herd immunity effect and virtually no circulation of MenC in the community (3). Given this immunization strategy, it is important to monitor the prevalence of antibodies among those age groups who may be at risk because they are not eligible to receive a MenCC vaccination yet. In the Dutch situation, these are mainly children under 14 months of age.In the present study, we evaluated the prevalence of MenC polysaccharide (PS)-specific antibodies and the serum bactericidal antibody (SBA) activities in populations of infants at various time points during the first year of life. Cord blood samples (n = 41) and serum samples from children at the ages of 3 months (n = 70) and 12 months (n = 38) were obtained from a study that investigated the influence of probiotics on eczema and allergies in 2004 and 2005 (ISRCTN00200954). Serum samples from infants at the age of 11 months (n = 103) were obtained from a study which investigated the serological responses following the replacement of a whole-cell pertussis vaccine by different acellular pertussis vaccines in the period from 2004 to 2007 (ISRCTN97785537). For all participating children, informed consent to use serum samples for further research was obtained from the parents.MenC PS-specific immunoglobulin G (IgG) antibodies are quantified using a fluorescent-bead-based multiplex immunoassay (4). Standardized reference serum CDC 1992 (National Institute for Biological Standards and Control, Potters Bar, United Kingdom) was used in this assay. The lower limit of quantitation for MenC antibodies is assigned at 0.01 μg/ml. The levels of MenC-specific functional antibodies in 103 serum samples from the 11-month-old age cohort were determined by an SBA assay using baby rabbit complement (Pel-Freeze Incorporated, Rodgerson, AZ) (12). The target strain for the assay was C11 (phenotype C:16:P1.7-1,1). SBA titers are expressed as the reciprocal of the final serum dilution yielding 50% killing at 60 min. For statistical purposes, SBA titers of <4 were assigned a value of 2. Antibody concentrations in serum samples were calculated as geometric mean concentrations (GMC) or geometric mean titers, with 95% confidence intervals (95% CI).Overall, cord blood samples showed a MenC PS-specific IgG GMC of 0.25 μg/ml. Antibodies declined to levels of 0.10 and 0.09 μg/ml at 3 and 12 months of age, respectively (Table ​(Table1).1). Paired cord blood and 3-month samples from 26 infants and paired 3- and 12-month samples from 17 infants were available (Fig. ​(Fig.1).1). The data indicate that, during the first year of life, MenC PS-specific IgG antibodies are not elicited by natural contact.Open in a separate windowFIG. 1.Concentrations of MenC PS-specific IgG in cord blood samples and in samples from infants at 3 and 12 months of age. Paired cord blood and 3-month samples from 26 infants and paired 3- and 12-month samples from 17 infants were available. Paired samples are indicated by solid lines.

TABLE 1.

MenC PS-specific IgG concentrations and SBA titers in infants during the first year of life

Interleukin-8 CSF levels predict survival in patients with leptomeningeal metastases

Median survival of patients with leptomeningeal metastases (LM) is 4 to 6 months, with a few long-term survivors. Current prognostic factors for survival have limited value. The authors measured the CSF levels of nine inflammatory proteins in 57 patients with LM and determined their prognostic value. High interleukin (IL)-8 CSF levels predicted short-term survival independently. The data indicate that IL-8 CSF levels may serve as a prognosticator in patients with LM, but prospective validation is needed.     

Response to pneumococcal vaccination in mannose‐binding lectin‐deficient adults with recurrent respiratory tract infections

Mannose‐binding lectin (MBL)‐deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL‐deficient patients with recurrent respiratory tract infections (RRTI). The response to pneumococcal vaccination in MBL‐deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL‐deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL‐deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL‐deficient and ‐sufficient patients with RRTI. Eighteen MBL‐deficient and 63 MBL‐sufficient adult patients with RRTI were all vaccinated with the 23‐valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL‐sufficient and ‐deficient patients. Forty‐three MBL‐sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL‐deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL‐sufficient and ‐deficient patients. In conclusion, our study suggests that MBL‐deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL‐sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL‐deficient patients with RRTI.     

Differential expression of type I insulin-like growth factor receptors in different stages of human T cells

Insulin-like growth factor I (IGF-I) has been implicated to play a regulatory role in T cell development and in T cell function. We investigated the expression of type I IGF receptors on human peripheral T cells related to the maturation and activation stage using the type I IGF receptor-specific monoclonal antibody αIR3. It appeared that 87% of the CD4⁺CD45RA⁺ cells and 66% of the CD8⁺CD45RA⁺ cells were αIR3⁺, whereas only 37% of the CD4⁺CD45RO⁺ cells and 38% of the CD8⁺CD45RO⁺ cells bound αIR3. We also found that the fraction of αIR3⁺ cells within in vivo or in vitro activated (HLA-DR⁺) T cells is markedly lower than in nonactivated (HLA-DR^?) cells. In vitro phytohemagglutinin-activated T cells and CD4⁺CD45RO⁺ cells activated with recall antigens also contained less αIR3⁺ cells (1–6%) than nonactivated cells (30–54%).