RESUMEN

The aim of this study is to describe childhood cancer incidence and survival in the French islands of Reunion and Mayotte for the period 2005-2011. Data were taken from the population-based Cancer Registry of Reunion Island. All incident cases of malignant tumours and benign tumours of the Central Nervous System diagnosed between 2005 and 2011 in children under the age of 15 and living in Reunion or Mayotte were included. A total of 236 cases were registered (176 in Reunion, 60 in Mayotte). Age-standardised incidence rates (ASRs, world standard) for all cancers were 125.0 and 101.8 per million for Reunion and Mayotte, respectively. ASRs for the main cancer groups were lower than those described in mainland France for the same period. The 5-year overall survival rate for all patients was 78.5% (95%CI 71.9- 83.7), slightly lower than that reported in mainland France.

Asunto(s)

Asunto(s)

RESUMEN

Apart from the high frequency of the delta F508 mutation (81.81%) in Breton cystic fibrosis chromosomes, one mutation, 1078 del T, is also observed frequently (4.96%) in this group, in comparison with the rest of the French where it occurs with a frequency of 0.57%. These two mutations account for more than 86.5% of the total CF mutations identified on Breton chromosomes. We have conducted an unblinded retrospective analysis of 25 patients with the 1078 del T mutation and compared their phenotypes with those of a group of 70 delta F508 homozygous patients. Both groups of patients had the same ethnic origin and were regularly attending the same CF centre in Brittany, which makes this sample highly homogeneous despite the small size. The 1078 del T mutation appeared to be associated with severe presentation of the disease with, however, a trend to reduced mortality and less Pseudomonas aeruginosa colonisation.

Asunto(s)

RESUMEN

We have screened the 27 exons of the cystic fibrosis transmembrane conductance regulator gene in 87 non-delta F508 chromosomes of Breton origin using the combined techniques of denaturing gradient gel electrophoresis and direct sequencing. By this process, we have detected a new missense mutation, G91R, which results in an arginine for glycine at codon 91. Three affected patients with a delta F508/G91R genotype are pancreatic sufficient. Such observations could facilitate a better understanding of the functional importance of different regions of the encoded product and of the pathogenesis of the disease.

Asunto(s)

RESUMEN

In a retrospective study of 206 patients with cystic fibrosis (CF), five cases of CF arthritis were recorded. This is a frequency of 2.5% and of 4.5% in patients aged over 10. Four patients had episodic arthritis, which was related to the course of pulmonary disease in two cases. In three patients, synovial fluid examination revealed minimal evidence of inflammation. In one of these three cases, synovial biopsy revealed a mild and non-specific synovitis. The fifth patient had chronic arthropathy and was positive for rheumatoid factor, but did not fulfil the criteria for rheumatoid arthritis. There were no radiographic abnormalities in any of these cases. CF arthritis is a rare syndrome of unknown pathogenesis.

Asunto(s)

RESUMEN

Arthritis in mucoviscidosis has been described as aseptic arthritis with the picture of oligo or polyarticular intermittent rheumatism, independent of the pulmonary course of the disease, often accompanied by skin signs, sometimes in the form of vasculitis, and without radiological signs. Chronic forms with the presence of rheumatoid factor and/or radiological signs have also been described. The authors found 4 cases of arthritis (incidence 2%) in a retrospective study of 208 patients with mucoviscidosis. These included one case of typical intermittent rheumatism, one of chronic arthritis of the wrist with positive rheumatoid factor, one case associated with purpura, the course of which was linked to pulmonary secondary infections, and one case of polyarthritis with spinal pain which was difficult to classify. Arthritis in mucoviscidosis appears to be a clinically heterogeneous entity, the pathophysiology of which could involve various immune reactions, secondary to a chronic bacterial stimulus of bronchopulmonary origin.

Asunto(s)

RESUMEN

We report here the spontaneous in vitro transformation of blood monocytes into fibroblasts, in a patient suffering from cystic fibrosis (CF). The blood monocytes with this capacity express HLA-DR specificity. Monocytes were identified by non-specific esterase activity and by immunofluorescence using monoclonal antibodies against monocytes/macrophages antigens. Neo-fibroblasts were identified by electron microscopy and immunofluorescence using monoclonal antibodies against a cytoplasmic enzyme specifically involved in the synthesis of collagen. The secretion of collagen was evidenced using antibodies against type I collagen. Both monocytes/macrophages and neo-fibroblasts express the monocytic and the fibroblastic markers and synthesize type I collagen. This transformation observed in vitro might mimick the process of fibrosis development which takes place in vivo, particularly in pancreatic acini, lungs and intestine of patients with CF. Interestingly, the whole process in vitro is inhibited when T lymphocytes are properly stimulated by IL2. In addition, both monocytes and neo-fibroblasts secrete high quantities of uromodulin-like glycoprotein. The significance of this finding is discussed in relation to the thick mucus secretion which characterizes the disease. In addition, from a fundamental point of view, it confirmed in a large series of patients that this observation may have significant implications, since CF mutation impairs the gene coding for cAMP-regulated Cl- channel and that it has been proposed that uromodulin might be implicated in Cl- transport. Therefore the question of the relationships between uromodulin and the cAMP-regulated Cl- channel arises.

Asunto(s)

RESUMEN

The cystic fibrosis locus was mapped on the long arm of the chromosome 7 in 1985. It has recently been cloned and a three base pair deletion has been recognized as the mutation associated with the majority of CF chromosomes (delta F508). CF haplotypes previously defined with tightly associated DNA markers were analysed using PCR (Polymerase Chain Reaction) and allele specific oligonucleotides to determine the presence or absence of this mutation. This mutation was found on 80% of our CF chromosomes and associated predominantly with the B haplotypes. The detection of this mutation is now a major improvement for carrier detection and prenatal diagnosis of the disease.

Asunto(s)

RESUMEN

Retrospective analysis of 63 patients with mucoviscidosis (age: 11 to 21 years), treated with pefloxacine, shows the occurrence of arthropathies ascribed to pefloxacine in 9 patients (age: 9 to 20 years), or 14% of the patients under treatment. The dose of pefloxacine was normal (9 to 16 mg/kg/day) in all cases, except one case of overdose (29 mg/kg/day). Mechanical arthralgias, affect the knees, elbows and wrists, resulting in functional discomfort, and frequently accompanied by mechanical synovial extravasation. They always subside after pefloxacine is discontinued. The role of age is essential as the incidence of arthropathies reaches 45% when pefloxacine is first administered between the ages of 15 and 20 years. Retrospective analysis of 37 patients with mucoviscidosis (age: 2 to 20 years), treated with ofloxacine, failed to show any joint complication. In this study, the best joint tolerance of ofloxacine, compared with pefloxacine is statistically significant. Arthropathies induced by pefloxacine represent an original entity which seems related to the cartilage toxicity of quinolones, observed in animal experiments, during growth.

Asunto(s)

RESUMEN

UNLABELLED: Cefsulodin is a third generation cephalosporin with specific antipseudomonas activity. We used cefsulodin in combination with aminoglycosides in 15 cystic fibrosis patients treatments. There were 13 children or adolescents, 4 to 19 years old with chronic Pseudomonas aeruginosa lung infections: 9 patients had acute exacerbations of infection with occasionally important respiratory insufficiency and 5 patients had a regimen of regular treatment every 3 months. Cefsulodin was given after record of bacterial sensitivity to antibiotics, at the mean posology of 100 mg/kg, IV, tid. The combination with aminoglycosides was systematic: tobramycin (6 mg/kg/day), netilmicin (6 mg/kg/day) or amikacin (30 mg/kg/day). Duration of treatment was 9 to 15 days. RESULTS: --clinical improvement in all patients, important in 13 patients and moderate in 2 patients;--respiratory function improvement in 11 patients;--pulmonary radiography improvement in 10 patients;--Pseudomonas were eradicated in 8 patients but temporarily and were found after treatment in 7 patients, 5 with lower number, 2 with higher number. Clinical and biological tolerance was excellent. The present study shows the interest of cefsulodin use in combination with aminoglycosides in this pathology.

Asunto(s)

RESUMEN

We used 5 polymorphic probes strongly linked to the gene of cystic fibrosis (CF) to perform the genotypical study of 48 families with at least one child presenting with the disease. The last Km19 and XV2c probes showed a very important linkage imbalance with the CF gene (allele 2 = 6.6 kb of Km19/Pstl, chi 2 = 56; allele 1 = 2.1 kb of XV2c/Taql, chi 2 = 21). These two markers define a B haplotype which confers a relative risk of 55 to be gene carrier. From these data, the predictive value for an individual presenting with this haplotype to be heterozygous was computed to be 1/5. Presently, the risk of 1/20 for a randomized subject to be gene-carrier should be reexamined after study of this genotype. These results are very important practically, as they modify the classical data of genetic counselling concerning cystic fibrosis for the couples with a risk higher than 1/4.

Asunto(s)

RESUMEN

The gene for cystic fibrosis is located on the long arm of chromosome 7 at 7q31. The close linkage between the disease locus and several DNA markers allowed a study of the DNA restriction polymorphism pattern in 30 Breton families. The frequency of the haplotypes indicated by the probes pJ 3.11, met H and met D was established reaching a 66.6% informativity for the families studies. The complete informativity of a family allows for detection of heterozygous brothers and sisters, uncles and aunts and for antenatal screening on trophoblast biopsies in case of further pregnancies.

Asunto(s)

Asunto(s)

RESUMEN

Incidence of cystic fibrosis has been estimated in three adjacent geographic areas of Brittany: North Finistere, South Finistere and Morbihan. This incidence is respectively 6.0 x 10(-4), 4.8 x 10(-4), 2.9 x 10(-4) in these three areas. A significant difference between North Finistere and Morbihan was found. Without proofs in favor of natural selection, genetic drift seems to be a possible explanation of this variation. Moreover, as in other studies, a genetic heterogeneity of the disease was not shown.

Asunto(s)

RESUMEN

The biologic effects of a purified long-acting porcine calcitonin (pTCT) were investigated in 45 children without any known renal, skeletal, endocrine, or metabolic disorder. pTCT was given as a single im injection at dose levels varying from 1 to 150 MRC u/1.73 m2. Administration of the highest dose was followed by a decrease in serum calcium and phosphorus concentrations and in tubular reabsorption of phosphorus, serum calcium and phosphorus concentrations and in tubular reabsorption of phosphorus. Mean maximal variation of serum calcium was -- 13.8 +/- 2.1 mg/l in children less than 3 years old, versus -- 8.2 +/- 0.9 mg/l (p less than 0.01) in older ones. Such an age-related differences was not observed for the hypophosphatemic action of pTCT. In 40 subjects aged 3 to 14 years the threshold for pTCT hypocalcemic activity was between 1 and 5 MRC u/1.73 m2. No significant differences in the effects on serum calcium of either 10, 25, 75 or 150 MRC u/1.73(2) m could be found. The threshold for pTCT hypophosphatemic activity was between 10 and 25 MRC u/1.73 m2 with, similary, no dose-response relationship for doses varying from 25 to 150 MRC u/1.73 m2. The present data demonstrate the high sensitivity of children, especially those younger than 3 years, to pTCT; furthermore, the lack of a dose-response relationship indicates that the pharmacological use of pTCT in pediatrics at doses higher than 10 to 25 MRC u/1.73 m2 is unnecessary.

Asunto(s)

RESUMEN

In 94 children suffering from cystic fibrosis, no abnormal frequencies of HLA markers of the A and B locus were observed in comparison with the distribution of these antigens in control series. Furthermore, the HLA genotypes of seven pairs of diseased sibs are incompatible with the hypothesis of a closed linkage between CF--an autosomal recessive transmitted disease--and HLA.

Asunto(s)

RESUMEN

Cystic fibrosis in the northern sector of the French "département" of Finistère is 1:1787 live births. Within this sector a concentration of the disease was found in a small area. The minimal frequency in this area, from 1946 to 1972, was calculated as 1 per 377 live births, the gene frequency being 0.0515. Genealogic analysis, going back to the beginning of the 18th century, showed a relationship between 8 of the 10 families to which the patients belonged. The origin of the deleterious genes may be explained by a least five primary ancestral couples living in the 18th century. Random drift is the most probable explanation for the concentration of cystic fibrosis in this region.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)