Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population.

OBJECTIVE: Congenital dislocation of the hip (CDH) is a multifactorial disease which involves genetic factors that are still unidentified. Recently, a functional polymorphism (rs143383) of the 5'-untranslated region of GDF5 (Growth/Differentiation Factor 5) - previously reported to be associated with osteoarthritis - has been associated with CDH in a Chinese population. The aim of our study was to determine whether GDF5, known to be involved in bone, joint and cartilage morphogenesis, is also associated with CDH in Caucasians. DESIGN: We genotyped three tagSNPs (rs224334, rs143384, rs143383) in 239 cases and 239 controls from western Brittany (France) where CDH is frequent, and tested the association using both single-locus and haplotype-based approaches. RESULTS: The most significant association was observed with rs143384. The T allele of this SNP was overrepresented in cases (65.9% vs 55.9%, P=0.002). Under a recessive model, carriers of the TT genotype had a 1.71-fold higher risk of developing CDH than carriers of the other genotypes (OR(TT vs CT+CC)=1.71, 95% CI: [1.18-2.48], P=0.005). At a nominal level, the association was also significant with rs143383 (OR(TT vs CT+CC)=1.52, 95% CI: [1.05-2.19], P=0.026). The haplotype carrying the susceptibility alleles of these SNPs was also more frequent in cases (65.9% vs 55.9%, OR=1.53, 95% CI: [1.18-1.98], P=0.002). CONCLUSION: This study reports, for the first time, the association between GDF5 polymorphisms and CDH in Caucasians, and points out another polymorphism of interest that requires further investigation. Reduction in GDF5 expression might lead to developmental deficiency of ligaments and capsule in hip joint, and therefore contribute to CDH pathogenesis.

Do HOXB9 and COL1A1 genes play a role in congenital dislocation of the hip? Study in a Caucasian population.

OBJECTIVE: Congenital dislocation of the hip (CDH), which is one of the most common congenital skeletal disorders, corresponds to an abnormal seating of the femoral head in the acetabulum. It is commonly admitted that CDH presents a genetic component. However, little is known about the genetic factors involved. This study aimed to determine the role of two potential candidate genes on chromosome 17 in CDH: HOXB9 (involved in limb embryonic development) and COL1A1 (involved in joint laxity). METHOD: We set up a case-control association study (239 cases and 239 controls) in western Brittany (France) where CDH is particularly frequent. The set of informative single nucleotide polymorphisms (SNPs) in each gene was selected using Tagger and genotyped using the SNaPshot method (n=2 and n=10, respectively). The association was tested both through single-locus and haplotype-based analyses, using SAS and Haploview softwares. In addition, we carried out the transmission disequilibrium test (TDT) with the same polymorphisms from a sample of 81 trios (i.e., 81 patients included in the case-control study and their both parents). RESULTS: The case-control study revealed no significant association between CDH and the tagSNPs selected in both HOXB9 and COL1A1. Moreover, the TDT did not reveal distortion in allelic and haplotype transmission of the studied markers. CONCLUSION: Our study did not support an association between HOXB9 and COL1A1 and CDH in our population. These negative findings were obtained by population- and family-based designs. Analysis of the genetic component of CDH should focus on other candidate genes.

Effects of two wheat cultivars on physico-chemical properties of wheat flours and digesta from two broiler chicken lines (D+ and D-) differing in digestion capacity.

1. The current experiment is the second part of a study about the effects of wheat quality on digestibility of pelleted diets for broiler chickens. In the first part, it was shown that a hard cultivar resulted in a negative effect on starch digestibility in two divergent lines of chickens (D+ and D-) selected for digestion capacity. The aim of this second part was to investigate the reasons for this negative effect of a hard cultivar (Baltimor) compared to a soft one (Scipion) in D+ and D- lines. 2. Proventriculus pepsin activity and pancreas proteolytic and amylolytic activities were estimated in 4 pools of birds: 'D+ line (Baltimor fed)', 'D+ line (Scipion fed)', 'D- line (Baltimor fed)' and 'D- line (Scipion fed)'. Results suggested the greatest amount of pepsin units per g BW for D+ birds and the lowest amount of pancreas proteolytic units per g BW for D+ birds fed Scipion wheat. Pancreas showed very similar alpha-amylase activities among treatments. 3. In vitro hydrolyses of wheat gluten proteins with proventriculus extracts from pools of D+ and D- birds did not show any differences between hard and soft cultivars, whatever the origin of pools. 4. Pepsin hydrolysis of fine (300 to 425 microm) and coarse (1180 to 1600 microm) fractions from wheat flours (Baltimor or Scipion) showed that the 30 min proteolysis rate was highest for the fine fraction in both cultivars. No difference was observed with extended hydrolysis time. 5. In vitro digestion simulation of whole wheat flours confirmed the results previously obtained in vivo, with a negative effect of hard cultivar on starch digestion rate and no effect on protein digestion. 6. Laser particle size analyses showed that ileum digesta from birds fed with hard wheat cultivar showed the highest proportion of coarse particles. 7. Microscopic analyses of D+ ileum digesta revealed that the concentration of undigested starch granules in the subaleurone area of wheat bran particles was the highest with hard cultivar. 8. The results suggested that physical entrapment of starch granules in coarse particles was a major explanation for decreased starch digestibility values in chickens fed hard wheat diets.

Rheological characterization of pharmaceutical powders using tap testing, shear cell and mercury porosimeter.

Most of the pharmaceutical processes involved in the manufacturing of so lid dosage forms are connected with powder flow properties, at least for some of the intermediate steps. Powder flow characteristics are commonl y investigated by various measurements, such as handling angles, tap tes ting, shear cell measurements, etc. All these approaches allow the calc ulation of indices characterising powder flowability. Unfortunately, th ese methodologies are highly product consuming, which is a limitation in the first steps of a novel drug development, when only a small amount of product is available. The use of mercury porosimetry to evaluate compre ssibility and flow properties of powders could be a new and alternative approach to obtain insight in the rheological properties of granular med ium by the interpretation of the first part of programs (low pressures) . We have developed such an evaluation and compared the results obtaine d with those given by tap testing and shear cell measurements, applied t o four excipients for direct tabletting and three different drugs. Merc ury porosimetry turned out to be a sensitive technique, able to providequantitative information about powder flow properties, complemen ted by an evaluation of particles micro porosity and size distribution, in a single step. These characterisations are obtained with only approx imately 250mg of bulk powder compared to high quantities ( >100g) needed for other methods.

[Results of the orthopedic treatment of scoliosis in children under 7 years of age. Apropos of 75 cases]. / Résultats du traitement orthopédique dans les scolioses de l'enfant de moins de 7 ans. A propos de 75 cas.

Seventy five children suffering from scoliosis under the age of 7 years have been treated by the authors. The treatment was commenced before the age of 4 in infantile scoliosis and before the age of 6 in juvenile scoliosis. It was based on the use of the Milwaukee brace used directly in cases of angulation less than 50 degrees and preceded by a plaster cast in other cases. The treatment was continuous with sometimes a few hours of freedom from bracing. Occasionally the treatment had to be stopped. The development of the curve was very variable. The authors have distinguished seven different types of development. The prognosis was therefore difficult to establish and was mainly based on the specific features of the progress of the curve. At puberty, deterioration was often seen despite bracing and there were many indications for spine fusion.

[Kyphosis caused by severe spondylodiscitis in newborn infants and young children]. / Les cyphoses par spondylodiscite grave du nourrisson et du jeune enfant.

The authors report their experience of 12 discitis occurring in the new born and in young children. Pyogenic infections were found with general septicemia in the new born children. The onset of cases of Pott's disease occurred later. Anterior destruction of several vertebrae accounted for severe kyphosis which were found on clinical examination. Conservative immobilisation of the kyphosis during growth does not prevent any increase in deformity before puberty with the possible onset of neurological symptoms. The only possible treatment is surgical with anterior arthrodesis of the damaged region together with a corrective osteotomy followed as soon as possible by posterior arthrodesis. If, unfortunately the patient is seen later in the course of the disease, the possibility of corrective osteotomy will depend on the degree of kyphosis and the neurological symptoms.