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Biomedical subjects

Michael Wilschanski

Publications and source records attributed to Michael Wilschanski.

8 recordsLinked to original sources

Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates.

OBJECTIVE: To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense, thereby reducing both the incidence and severity of necrotizing enterocolitis (NEC) in preterm neonates. STUDY DESIGN: Neonates < or =1500 g birth weight were randomized to either receive a daily feeding supplementation with a probiotic mixture (Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus; Solgar, Israel) of 10(9) colony forming units (CFU)/day or to not receive feed supplements. NEC was graded according to Bell's criteria. RESULTS: For 72 study and 73 control infants, respectively, birth weight (1152 +/- 262 g vs 1111 +/- 278 g), gestational age (30 +/- 3 weeks vs 29 +/- 4 weeks), and time to reach full feeds (14.6 +/- 8.7 days vs 17.5 +/- 13.6 days) were not different. The incidence of NEC was reduced in the study group (4% vs 16.4%; P=.03). NEC was less severe in the probiotic-supplemented infants (Bell's criteria 2.3 +/- 0.5 vs 1.3 +/- 0.5; P=.005). Three of 15 babies who developed NEC died, and all NEC-related deaths occurred in control infants. CONCLUSION: Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population.

Administration, Oral↗

Relative expression and localization of the insulin-like growth factor system components in the fetal, child and adult intestine.

BACKGROUND: The insulin-like growth factors (IGFs) are important in the development and maintenance of the gastrointestinal tract. OBJECTIVES: To compare the expression of IGFs and their receptors in the stomach and duodenum of the fetus, the child and the adult. To identify the cells mainly responsible for the production of the members of the IGF system. METHODS: Tissue was obtained from fetus after abortion and from children and adults during diagnostic endoscopy and biopsy. The expression of the IGFs and their receptors was estimated by an RNAse protection assay and sections were stained with antisera to the components of IGF system. RESULTS: The tissues from the stomach and the duodenum expressed the two IGFs and their receptors at all stages of life. The fetal IGF receptors I and II, were approximately ten times higher than in the child and IGF-II was five times higher. Immunohistochemical staining showed the components of the IGF system to be localized to the gastric glands and to the basotlateral border of the gastric epithelial cells. In the duodenum, they were concentrated at the apical portion of the epithelial tissue. They could also be identified in ganglion cells and nerves. CONCLUSIONS: The IGFs and their receptors in the stomach and duodenum are expressed in all age groups and mostly are highest in the fetus. The IGF system proteins were located in the gastric glands and epithelium and in the apical portion of the villous epithelium of the duodenum.

Aborted Fetus↗

Treatment regimens for Helicobacter pylori infection in children: is in vitro susceptibility testing helpful?

BACKGROUND: Treatment regimens for Helicobacter pylori have variable success rates, and data comparing effectiveness with respect to strain sensitivity are relatively scarce. OBJECTIVE: To evaluate the efficacy of two treatment regimens for eradication of H. pylori and the impact of bacterial susceptibility testing. STUDY DESIGN: 265 children endoscopically diagnosed with H. pylori infection were randomly assigned to receive omeprazole + amoxicillin with clarithromycin or omeprazole + amoxicillin with metronidazole. Bacterial culture and susceptibility was performed in a subgroup. Eradication was assessed by C-urea breath test. RESULTS: Eradication was achieved in 73.4% by omeprazole + amoxicillin with metronidazole and in 62.6% by omeprazole + amoxicillin with clarithromycin (P = 0.078). H. pylori was cultured successfully in 105 patients. Resistance to metronidazole was detected in 31.4% of the isolates and resistance to clarithromycin in 15%. Eradication rate by omeprazole + amoxicillin with metronidazole for metronidazole-susceptible bacteria (N = 38) was 90%, and for resistant bacteria (N = 19) it was 42%. Only 75% of clarithromycin-sensitive strains were successfully treated by omeprazole + amoxicillin with clarithromycin, and none of the cases with clarithromycin-resistant strains responded to omeprazole + amoxicillin with clarithromycin treatment. CONCLUSION: There is a trend of greater efficacy of eradication with omeprazole + amoxicillin with metronidazole versus omeprazole + amoxicillin with clarithromycin therapy. Although resistance negatively influences eradication, first-line sensitivity-based treatment would be expected to improve this rate only slightly. Susceptibility testing should probably be reserved only for treatment failures.

Adolescent↗

Basic protocol for transepithelial nasal potential difference measurements.

Transepithelial nasal potential difference (NPD) measurements assess ion conductance in the upper respiratory epithelium. NPD is useful in assisting in the diagnosis of classical and atypical cystic fibrosis (CF) and of cystic fibrosis transmembrane regulator (CFTR)-related disorders, as well as for monitoring the effect of pharmacological agents and gene transfer approaches to correct the abnormalities of ion transport in CF. The article summarizes the objectives and the principle of NPD measurements, describes a hands-on protocol of the procedure and provides quality control measures, practical hints and troubleshooting.

Clinical Protocols↗

Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations.

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity. Aminoglycoside antibiotics can suppress premature termination codons, thus permitting translation to continue to the normal end of the transcript. We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels. METHODS: In a double-blind, placebo-controlled, crossover trial, patients with stop mutations in CFTR or patients homozygous for the DeltaF508 mutation received two drops containing gentamicin (0.3 percent, or 3 mg per milliliter) or placebo in each nostril three times daily for two consecutive periods of 14 days. Nasal potential difference was measured at base line and after each treatment period. Nasal epithelial cells were obtained before and after gentamicin treatment from patients carrying stop mutations, and the C-terminal of surface CFTR was stained. RESULTS: Gentamicin treatment caused a significant reduction in basal potential difference in the 19 patients carrying stop mutations (from -45+/-8 to -34+/-11 mV, P=0.005) and a significant response to chloride-free isoproterenol solution (from 0+/-3.6 to -5+/-2.7 mV, P<0.001). This effect of gentamicin on nasal potential difference occurred both in patients who were homozygous for stop mutations and in those who were heterozygous, but not in patients who were homozygous for DeltaF508. After gentamicin treatment, a significant increase in peripheral and surface staining for CFTR was observed in the nasal epithelial cells of patients carrying stop mutations. CONCLUSIONS: In patients with cystic fibrosis who have premature stop codons, gentamicin can cause translational "read through," resulting in the expression of full-length CFTR protein at the apical cell membrane, and thus can correct the typical electrophysiological abnormalities caused by CFTR dysfunction.

Administration, Intranasal↗

Helicobacter pylori genotypes in Israeli children: the significance of geography.

BACKGROUND: There is substantial genetic variation among different isolates of Helicobacter pylori, which may affect the clinical outcome. The aims of this study were to find the common H. pylori genotypes in Israeli children and to look for a possible genotype-phenotype correlation. METHODS: Ninety-eight H. pylori cultures were isolated from antral biopsy specimens of symptomatic Israeli children and were analyzed for vacA and iceA genotype and cagA and cagE status by polymerase chain reaction. RESULTS: cagA and cagE genes were present in only 25.5% and 24.5%, respectively. The common vacA genotype was s2m2, which was found in 65%. Eleven specimens (11%) contained multiple vacA genotypes. iceA1 was found in 37% and iceA2 in 52% of cases. Both iceA alleles were found in 11%. Increased prevalence of iceA1 and cagE were observed in children with duodenal disease, although it did not reach significance. CONCLUSIONS: The low prevalence of cagA and the high prevalence of vacA genotype s2m2 in Israeli pediatric patients are different from the genotype prevalence reported globally. However, similar findings have been reported in Egypt, indicating a possible geographic influence. There is a possible correlation between duodenal ulcer and cag E and ice A1 genotype, but the power of the study was too low to prove it.

Adolescent↗