Familial cryptic translocation (2;17) ascertained through recurrent spontaneous abortions

We report a young woman who presented with a reproductive history of three recurrent spontaneous abortions (RSA) and two neonatal deaths. Comparative genomic hybridization (CGH) was used to determine the chromosomal composition of the patient's last miscarriage. It showed the presence of monosomy for the distal end of chromosome 2 long arm (segment 2q37.2 to qter) and trisomy for the distal end of chromosome 17 long arm (segment 17q25 to qter). The mother was found to be a carrier for a cryptic translocation between chromosomes 2 and 17 long arms by fluorescence in situ hybridization using a subtelomeric probe for 17q. Retrospective CGH analysis on one baby who died neonatally showed that he had inherited the maternal translocation in the same unbalanced state as the last pregnancy loss. His detailed postmortem examination is reported.     

Rapid detection of 17p11.2 rearrangements by FISH without cell culture (direct FISH,DFISH): a prospective study of 130 patients with inherited peripheral neuropathies

Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with pressure palsies (HNPP) are two frequent hereditary motor and sensory neuropathies. CMT is characterized by slowly progressive weakness and atrophy, primarily in peroneal and distal leg muscles. The most frequent form, CMT1A, is due, in most cases, to the duplication of a 1.5 Mb region on chromosome 17p11.2 containing the peripheral myelin protein 22 gene (PMP22). The phenotype seems to result from dosage of the PMP22 gene. This hypothesis is reinforced by the existence of HNPP, which is clinically characterized by various recurrent truncular palsies or sensory loss precipitated by minor trauma, which is caused by deletion of the same 1.5 Mb region in 17p11.2. In clinical practice, the detection of the duplication or the deletion in 17p11.2, which permits a positive diagnosis, is still performed by time consuming methods (Southern blot or various combinations of molecular tools). We developed a method for the rapid detection of 17p11.2 rearrangements, using "direct FISH" and PRINS analyses, which does not require cell culture. In a prospective study of 92 patients with CMT and 38 with suspected HNPP, we compared this new technique to classical strategies like Southern blot. The results demonstrate the high sensitivity and specificity of the new FISH technique for the diagnosis of CMT1A and HNPP. Moreover, because of its simplicity and rapidity, this technique provides a useful alternative to the molecular approaches that have been used to diagnose segmental aneusomies, especially in the case of duplications that often go undetected.     

Outer membrane protein A renders dendritic cells and macrophages responsive to CCL21 and triggers dendritic cell migration to secondary lymphoid organs

Outer membrane protein A (OmpA) is a class of bacterial cell wall protein that is immunogenic without adjuvant. As specific immune responses are initiated in the lymph nodes (LN, we analyzed the effect of the OmpA from Klebsiella pneumoniae (KpOmpA) onchemokine/ chemokine receptor expression by APC and on cell migration to the LN. Upon contact with KpOmpA, human immature DC and macrophages acquire CCR7 expression and responsiveness to CCL21. In parallel, CCR1 and CCR5 expression is down-regulated and CXCL8, CCL2, CCL3 and CCL5 production is up-regulated. Mice injected subcutaneously with KpOmpA present a transient inflammatory reaction at the site of injection accompanied by an enlargement of the draining LN with a higher proportion of DC and macrophages. Lastly, when exposed to KpOmpA prior injection, DC but not macrophages migrate to the draining LN. In conclusion, KpOmpA confers a migratory phenotype to DC and triggers their migration to the regional LN. This property contributes to explain how innate cells initiate adaptive immune response upon recognition of conserved bacterial components and also why OmpA is immunogenic in the absence of adjuvant.     

General practitioners' fear-avoidance beliefs influence their management of patients with low back pain

The objectives of this cross-sectional study conducted in primary care practice in France were to describe general practitioners' (GPs) fear-avoidance beliefs about low back pain (LBP), investigate the impact of these beliefs on their following guidelines for bed rest, physical activities, and sick leave, and uncover factors associated with GPs' fear-avoidance beliefs. A total of 864 GPs completed a 5-part self-administered questionnaire. Parts 1, 2, and 3 concerned demographic, professional data, and personal history of back pain, respectively. Part 4 dealt with GPs' education about LBP and practice for LBP. Part 5 assessed GPs' fear-avoidance beliefs on the Fear-Avoidance Beliefs Questionnaire (FABQ). GPs' mean age was 48.2+/-7.0 years, 80% were male, 88% had been practicing for more than 10 years, and 52% reported a previous personal episode of acute LBP. Forty-six percent had participated in an educational session on LBP during the last 3 years. Mean scores for the FABQ Phys and Work were 9.6+/-4.8 and 17.5+/-6.7, respectively. Sixteen percent of participants had high rating on the FABQ Phys (FABQ Phys score>14). FABQ Phys score was associated with recommendation of bed rest or rest during sick leave (p<0.0001) for acute LBP and less advice to maintain maximum bearable physical activities (p<0.001) for chronic LBP. FABQ Work score was associated with prescribing sick leave during painful periods (p<0.005) for acute LBP and less advice to maintain maximum bearable physical activities (p<0.001) for chronic LBP. GPs' fear-avoidance beliefs about LBP negatively influence their following guidelines concerning physical and occupational activities for patients with LBP.     

DFNB40, a recessive form of sensorineural hearing loss, maps to chromosome 22q11.21-12.1

We report on a novel localization for a recessive form of deafness (DFNB), by linkage analysis in an Iranian consanguineous family. Affected individuals suffer from prelingual profound sensorineural hearing loss. Genome-wide analysis led to the characterization of a new locus, DFNB40, which maps to an approximately 9 Mb interval between markers D22S427 and D22S1144 at chromosome 22q11.21-12.1. Maximum lod score of 3.09 was obtained with D22S1174. Since the Bronx waltzer (bv) mouse mutant, characterized by waltzing behavior, deafness, and degeneration of cochlear inner hair cells, has been mapped to the syntenic region on murine chromosome 5, we suggest that DFNB40 and bv may result from orthologous gene defects.     

Prospective, double-blind, randomized trial of equimolar mixture of nitrous oxide/oxygen to prevent pain induced by insertion of venous access ports in cancer patients

BACKGROUND: To assess the efficacy of equimolar mixture of nitrous oxide/oxygen (EMNO) to prevent pain induced by venous access ports (VAPs) implantation in cancer patients. PATIENTS AND METHODS: In a randomized, double-blind study on an adult population not knowing the effects of EMNO, cancer patients were randomly assigned to breath via a facial mask, EMNO or a placebo mixture comprising 50% oxygen and 50% nitrogen. The primary end-point was the patients' assessment of the severity of pain evaluated using a visual analog scale (VAS, 0 to 100) and the proportion of patients suffering pain in each group. The secondary criteria were side effects, tolerability of EMNO, and the level of satisfaction of both the patients and the medical team. RESULTS: Eighty-three adults (42 in the EMNO group and 41 in the placebo group) were included. VAPs were implanted in the jugular vein in 95% of patients. In the placebo group, 78% of the patients declared that they found VAP implantation painful vs. 34% in the EMNO group (p=0.001). The severity of the pain was reduced by 50% in the EMNO group in comparison with placebo (p=0.0125). Although the median time to perform implantation was strictly identical in both groups (20 min), the estimated duration of surgery seemed longer to patients in the control group. Patient and investigator satisfaction indexes were >90% in both groups. CONCLUSION: EMNO provides an effective solution for the prevention of pain during placement of VAPs.     

Executive functioning in children with autism and Tourette syndrome

The main aims of this study were to investigate if children with high-functioning autism (HFA) and children with Tourette syndrome (TS) can be differentiated in their executive functioning (EF) profile compared to normal controls (NCs) and compared to each other and to investigate whether children with HFA or children with TS and a comorbid group of children with both disorders are distinct conditions in terms of EF, Four groups of children participated in this study: HFA, TS, comorbid HFA + TS, and a NC group. All children were in the age range of 6 to 13 years. The groups were compared on five major domains of EF: inhibition, visual working memory, planning, cognitive flexibility, and verbal fluency. Children with HFA scored lower than NC children on all the EFs measured. Children with TS and NC children showed the same EF profile. The HFA group scored lower than the TS group for inhibition of a prepotent response and cognitive flexibility. Children with HFA performed poorer than children with comorbid HFA + TS on all functions, with the exception of inhibiting an ongoing response, interference control, and verbal fluency. Children with TS and children with comorbid HFA + TS could not be differentiated from one another in terms of EF. This study indicates that EF deficits are highly characteristic of children with HFA in comparison to children with TS and NC. The results suggest that for the comparison between HFA and TS groups, it is important to take into account comorbidity. A reevaluation of the EF hypothesis in children with TS is suggested.