The aim of this study was to assess the therapeutic efficacy of osteopathic treatment in infants with postural asymmetry. A randomized clinical trial of efficacy with blinded videoscoring was performed. Sixty‐one infants with postural asymmetry aged 6 to 12 weeks (mean 9wks) were recruited. Thirty‐two infants (18 males, 14 females) with a gestational age of at least 36 weeks were found to be eligible and randomly assigned to the intervention groups, 16 receiving osteopathic treatment and 16 sham therapy. After a treatment period of 4 weeks the outcome was measured using a standardized scale (4–24 points). With sham therapy, five infants improved (at least 3 points), eight infants were unchanged (within 3 points), and three infants deteriorated (not more than −3 points); the mean improvement was 1.2 points (SD 3.5). In the osteopathic group, 13 infants improved and three remained unchanged; the mean improvement was 5.9 points (SD 3.8). The difference was significant (p=0.001). We conclude that osteopathic treatment in the first months of life improves the degree of asymmetry in infants with postural asymmetry.

In 75 gliomas and 31 meningiomas, mutations at the epidermal growth factor receptor (EGFR) gene locus were restricted to gliomas. The ligands of this receptor, epidermal growth factor and transforming growth factor alpha, lacked quantitative changes at their loci in gliomas and meningiomas. EGFR gene amplification occurred in astrocytomas, oligodendrogliomas, ependymomas and glioblastomas. The frequency of this mutation significantly increased with the malignancy grade and the patient's age. Especially in glioblastomas of individuals aged over 64 years, EGFR gene mutations were observed without chromosome-10-specific allele losses. This finding contradicts the hypothesis that deletion of one entire chromosome 10 regularly precedes EGFR gene amplification in primary glioblastomas of patients aged over 50 years. It was found that most individuals whose gliomas carry an EGFR gene mutation have a poor prognosis, comparable to that of glioblastoma patients even when the tumour is graded as benign.

Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential in vivo consequences of UGT1A gene variability in GS. Three hundred GS patients (UGT1A1*28 homozygous) and 249 healthy blood donors (HBD) were genotyped for UGT1A (UGT1A1*28, UGT1A3-66 T>C, UGT1A6*3a, UGT1A7*3) and transporter single nucleotide polymorphisms (SNPs) (SCLO1B1 p.V174A, SCLO1B1 p.N130D, ABCC2 p.I1324I, ABCC2-24 UTR) using TaqMan-5 0 -nuclease-assays. A humanized transgenic UGT1A-SNP and corresponding wildtype mouse model were established carrying the GS-associated UGT1A variant haplotype. UGT1A transcript and protein expression, and transcriptional activation were studied in vivo. Homozygous UGT1A1*28 GS individuals were simultaneously homozygous for UGT1A3-66 T>C (91%), UGT1A6*2a (77%), and UGT1A7*3 (77%). Seventy-six percent of GS and only 9% of HBD were homozygous for the variant haplotype spanning four UGT1A genes. SCLO1B1 and ABCC2 SNPs showed no differences. In transgenic humanized UGT1A SNP and wildtype mice this UGT1A haplotype led to lower UGT1A messenger RNA (mRNA) expression and UGT1A protein synthesis. UGT1A transcriptional activation by dioxin, phenobarbital, and endotoxin was significantly reduced in SNP mice. Conclusion: Our data redefine the genetic basis behind GS. In vivo data studying the genotype present in 76% of GS individuals suggest that transcription and transcriptional activation of glucuronidation genes responsible for conjugation and detoxification is directly affected, leading to lower responsiveness. This study suggests that GS should be considered a potential risk factor for drug toxicity. (HEPATOLOGY 2012;55:1912-1921

BackgroundReconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date.Design and MethodsIn a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer.ResultsCMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients.ConclusionsOur results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation.

Megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS), a rare condition that affects smooth muscle cells, is caused by biallelic null alleles in MYH11. We report on a girl with MMIHS in addition to growth hormone deficiency, central hypothyroidism and a tonically dilated pupil with accommodation deficit. Sanger sequencing and arrayCGH uncovered the novel heterozygous missense variant c.379C>T in MYH11 and a heterozygous 1.3 Mb deletion in 16q13.11 encompassing MYH11, respectively. Her mother carries the deletion, whereas her father is heterozygous for the c.379C>T p.(Pro127Ser) change. Proline 127 is crucial for the formation of the Adenosine triphosphate binding pocket of the MYH11 motor domain and molecular modeling indicated that p.Pro127Ser alters nucleotide binding properties. Thus, the unusual and complex clinical presentation of the patient results from compound heterozygosity for a 16p13.11 microdeletion including the entire MYH11 gene and a loss‐of‐function missense variant on the remaining MYH11 allele. In conclusion, we recommend genetic testing both for MYH11 sequence alterations and copy number imbalances in individuals with MMIHS and smooth muscle cell‐associated abnormalities in additional organs, that is, multisystemic smooth muscle dysfunction.