Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC.

INTRODUCTION: Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question. OBJECTIVE: We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome. MATERIAL AND METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included. RESULTS: BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell's stage (p=0.85), mortality was higher in patients with a BSI (p=0.005). CONCLUSION: The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC.

Denaturing gradient gel electrophoresis of PCR-amplified gki genes: a new technique for tracking streptococci.

Viridans group streptococci (VGS) are a well-known cause of infections in immunocompromised patients, accounting for severe morbidity and mortality. Streptococcus mitis group species (Streptococcus mitis, Streptococcus pneumoniae, Streptococcus oralis) are among the VGS most often encountered in clinical practice. Identifying the portal of entry for S. mitis group strains is crucial for interventions preventing bacterial translocation. Unfortunately, tracking the source of S. mitis group strains is dependent on a combination of extremely laborious and time-consuming cultivation and molecular techniques (enterobacterial repetitive intergenic consensus-PCR [ERIC-PCR]). To simplify this procedure, a PCR analysis with newly designed primers targeting the household gene glucose kinase (gki) was used in combination with denaturing gradient gel electrophoresis (DGGE). This gki-PCR-DGGE technique proved to be specific for S. mitis group strains. Moreover, these strains could be detected in samples comprised of highly diverse microbiota, without prior cultivation. To study the feasibility of this new approach, a pilot study was performed. This confirmed that the source of S. mitis group bacteremia in pediatric patients with acute myeloid leukemia could be tracked back to the throat in five out of six episodes of bacteremia, despite the fact that throat samples are polymicrobial samples containing multiple S. mitis group strains. In contrast, using the classical combination of cultivation techniques and ERIC-PCR, we could detect these strains in only two out of six cases, showing the superiority of the newly developed technique. The new gki-PCR-DGGE technique can track the source of S. mitis group strains in polymicrobial samples without prior cultivation. Therefore, it is a valuable tool in future epidemiological studies.

Predictors of choosing life-long screening or prophylactic surgery in women at high and moderate risk for breast and ovarian cancer.

The aim of this study is to summarize published empirical data describing the predictors of adhering to screening practices and choosing to have prophylactic surgery in women at increased risk for breast and ovarian cancer. Pubmed, Psychinfo and Cinahl databases were searched to identify studies on the predictors of adherence to breast and ovarian cancer screening and predictors of having a prophylactic mastectomy or salpingo-oophorectomy. We found 37 empirical studies that met our inclusion criteria. The main predictors of the use of preventive measures are related to DNA test results, socio-demographic characteristics, and psychological outcome measures. It is concluded that there is no unequivocal relationship between age, education, risk perception, or anxiety and adherence to breast and ovarian cancer screening practices. Worrying about cancer is associated with a higher adherence to screening practices.

[Clinical reasoning and decision-making in practice. A young boy with fever, pancytopenia and an enlarged spleen]. / Klinisch denken en beslissen in de praktijk. Een jongetje met koorts, pancytopenie en een grote milt.

A 5-year-old boy presented with fever and fatigue after a holiday in northern Italy. On physical examination a marked splenomegaly was found. Laboratory investigations showed a pancytopenia as well as several markers suggesting an autoimmune disease. The splenomegaly and pancytopenia continued to progress despite treatment with prednisolone and intravenous immunoglobulins. One and a half years after presentation, the spleen had grown to such an extent that it was causing mechanical problems. Splenectomy was performed for diagnostic and therapeutic purposes. Histological investigation of the spleen showed amastigotes of Leishmania. PCR confirmed the diagnosis visceral leishmaniasis. Leishmaniasis is too often considered to be a tropical disease only. In recent years it has frequently been seen in southern European countries around the Mediterranean Sea.

Synthesis of a selectively protected trisaccharide building block of the capsular polysaccharide of Streptococcus pneumoniae types 6A and 6B.

4-Methoxybenzyl 2,4-di-O-benzyl-3-O-[2,4,6-tri-O-benzyl-3-O-(3,4,6-tri-O-benzyl-alpha-D- galactopyranosyl)-alpha-D-glucopyranosyl]-alpha-L-rhamnopyranoside (22), a building block for the alpha-D-Galp-(1----3)-alpha-D-Glcp-(1----3)-alpha-L-Rhap fragment of the capsular polysaccharides of Streptococcus pneumoniae types 6A and 6B [----2)-alpha-D-Galp-(1----3)-alpha-D-Glcp-(1----3)-alpha-L-Rhap-( 1----X)-D- RibOH-(5-P----]n (6A, X = 3; 6B, X = 4) has been synthesised. Ethyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-beta-D-glucopyranoside was coupled with 4-methoxybenzyl 2,4-di-O-benzyl-alpha-L-rhamnopyranoside in ether, using methyl triflate as promoter. The resulting alpha-D-Glcp-(1----3)-alpha-L-Rhap derivative was deallylated with KOBut in N,N-dimethylformamide followed by 0.1M HCl in 9:1 acetone-water. The product was coupled with 3,4,6-tri-O-acetyl-2-O-allyl-alpha,beta-D-galactopyranosyl trichloroacetimidate in ether, using trimethylsilyl triflate, to yield 19. Deacetylation, benzylation, and deallylation then gave 22.