Correction to: In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study.

The original article [1] contains errors in Table 1 affecting some of the presented oligonucleotide sequences and readthrough values in Table 1.

A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Nasal polyposis and cystic fibrosis(CF): review of the literature.

The aim of this study was to address whether NP might be a predictive factor for severity of CF. The authors collected data from the literature on NP as a unique or associated sign in CF and reviewed the clinical and molecular aspects of CF associated with NP. CF genotypes and clinical severity in NP(+) vs. NP(-) patients were reviewed, taking into account pulmonary function, frequency of P. aeruginosa lung infection, frequency of allergy, nutritional status, and exocrine pancreatic function. The CFTR gene was also analyzed in a patient with isolated severe NP as the unique feature of CF. This review of the literature showed a `milder` phenotype in `NP+` vs. `NP-` CF patients, contrasting with a marked association between NP and `severe` CF mutations. In addition, a complex genotype was identified, associating four heterozygous variants, namely p.Q493X (a severe mutation) on the paternal allele, and p.V562I, p.A1006E, and (TG)11(T)5 (IVS8-5T) on the maternal allele, in a case of CF presenting as isolated NP. The authors speculate that genetic/environmental factors associated with NP might attenuate the functional impact of `severe` CF mutations. The overrepresentation of CF carriers among patients with isolated NP also advocates the need for CFTR molecular screening in such populations for genetic counselling purposes.

[Cancer genetic predisposition: current events and perspectives in 2010]. / Prédispositions génétiques aux cancers: actualités et perspectives en 2010.

Studies performed during these last 30 years have had a major impact on the understanding of carcinogenesis. They have opened a new field: cancer genetic predisposition. At the present time, most of the cancer predispositions linked to the alteration of one gene, associated with a high risk of cancer and with a specific phenotype have been identified. About 70 genes have been identified and have led to genetic testing. The indication of genetic testing, the management of at risk patients require the establishment of guidelines. The next challenge is the identification of cancer susceptibility genes associated with low risk or modifying the effect of treatment.

[Isolated primary nocturnal enuresis: international evidence based management. Consensus recommendations by French expert group]. / Enurésie nocturne primaire isolée: diagnostic et prise en charge. Recommandations par consensus formalisé d'experts.

OBJECTIVE: The causes and treatment of isolated primary nocturnal enuresis (PNE) are the subject of ongoing controversy. We are proposing consensus practical recommendations, based on a formalised analysis of the literature and validated by a large panel of experts. METHODOLOGY: A task force of six experts based its work on the guide for literature analysis and recommendations and recommendation grading of the French Haute Autorité de Santé (formalized consensus process methodological guidelines) to evaluate the level of scientific proof (grade of 1 to 4) and the strength of the recommendations (grade A, B, C) of the publications on PNE. As a result of this, 223 articles from 2003 on were identified, of which only 127 (57 %) have an evaluable level of proof. This evaluation was then reviewed by a 19-member rating group. Several recommendations, poorly defined by the literature, had to be proposed by a professional agreement resulting from a consultation between the members of the task force and those of the rating group. For its final validation, the document was submitted to a reading group of 21 members working in a wide range of specialist areas and practices but all involved in PNE. RESULTS: The definition of PNE is very specific: intermittent incontinence during sleep, from the age of 5, with no continuous period of continence longer than 6 months, with no other associated symptom, particularly during the day. Its diagnosis is clinical by the exclusion of all other urinary pathologies. Two factors must be identified during the consultation: nocturnal polyuria promoted by excessive fluid intake, inverse secretion of vasopressin, snoring and sleep apnoea. It is sensitive to desmopressin; small bladder capacity evaluated according to a voiding diary and the ICCS formula. It may be associated with diurnal hyperactivity of the detrusor (30 %). It is resistant to desmopressin. Problems associated with PNE are: abnormal arousal threshold, attention deficit hyperactivity disorder (ADHD) (10 %), low self-esteem. The psychological component is not very significant. CONCLUSION: PNE is not psychological in origin. The management of this condition includes: evaluating the intrafamilial tolerance and the child's motivation, evaluating the rate, the volume of urine and wet nights using a diurnal and nocturnal diary; education (sufficient fluid intake at the start of the day, decrease in hyperosmolar intake in the evening, regular and complete urination); specific treatments: desmopressin for polyuric forms (expected success rate of 60-70 %), alarms for forms involving small bladder capacity (expected success rate of 60-80 %); alternative treatments and/or treatments combined with the preceding ones, for refractory forms: oxybutinin, tricyclic antidepressants (risk). Results obtained with hypnosis, psychotherapy, acupuncture, homoeopathy or chiropractic are not currently validated (insufficient level of proof).

Mutations of the noggin (NOG) and of the activin A type I receptor (ACVR1) genes in a series of twenty-seven French fibrodysplasia ossificans progressiva (FOP) patients.

Fibrodysplasia ossificans progressiva (FOP) is a rare but very severe disease, characterised by congenital malformations of the toes and by progressive heterotopic ossification of muscles and joints. Two genes, the noggin (NOG) gene and the activin A type I receptor (ACVRI) gene, are involved in FOP. In this study we have searched for the NOG and the 617G>A (ACVR1) mutations in a well characterized series of twenty-seven French FOP patients. Five NOG mutations (delta 42, 274G>C, 275G>A, 276G>A, and 283G>A) have been found in seven (26%) of our FOP patients. The 617G>A mutation in the ACVR1 gene is found in fourteen (52%) of the patients. With one exception (patient number 22), 617G>A and NOG mutations are mutually exclusive in patients. Mutations 274G>C, 283G>A and 617G>A segregate with the trait in five different FOP families, some members of them being partially affected by the disease.

Exhaled nitric oxide in cystic fibrosis: relationships with airway and lung vascular impairments.

A reduction of exhaled nitric oxide (NO) fraction and endothelial-mediated dysfunction have been reported in cystic fibrosis (CF). The aims of the present study were to search for relationships between flow-independent NO exchange parameters (bronchial NO flux (J'(aw,NO)) and alveolar NO concentration (C(A,NO))) and lung function tests characterising airflow limitation and pulmonary vascular bed (capillary blood volume and physiological dead space/tidal volume (V(D)/V(T)) ratio on exercise). In total, 34 patients (16 children, 18 adults) with CF, without resting pulmonary hypertension, underwent spirometry, exhaled NO measurement (multiple constant flow analytical method), gas transfer assessment (carbon monoxide and NO, allowing the calculation of capillary volume and membrane conductance) and a graded exercise test with oxygen uptake (V'(O(2))), carbon dioxide production (V'(CO(2))) and arterial blood gas evaluations. Both J'(aw,NO) and C(A,NO )correlated positively with airflow limitation. C(A,NO) correlated positively with capillary/alveolar volume. During exercise, criteria of mild pulmonary vascular disease were evidenced in some patients that participated in exercise limitation (negative correlation between physiological V(D)/V(T) and peak V'(O(2))). C(A,NO )at rest correlated positively with these parameters of wasted ventilation during exercise (physiological V(D)/V(T), minute ventilation (V'(E))/V'(CO(2)) at ventilatory threshold and V'(E)/V'(CO(2)) slope). Flow-independent exhaled NO parameters are linked to airway and early vascular diseases in patients with CF.

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.

[HHV-6 infection and acute lymphoblastic leukemia in a child]. / Infection à HHV-6 et leucémie aiguë lymphoblastique chez un enfant.

We report the case of a child who was infected by HHV-6 and who started an acute lymphoblastic leukemia two months later. This case reminds that an etiologic role have been suggested for many viral infections in some leukemias in childhood, particularly the human herpesvirus 6 (HHV-6).

[Cervical tumefaction in a teenager with cystic fibrosis]. / Tuméfaction cervicale chez une jeune fille atteinte de mucoviscidose.

Lobular emphysema and soft-tissue emphysema can exceptionally complicate malnutrition. We report the case of a teenager presenting malnutrition with cystic fibrosis and anorexia nervosa with soft-tissue emphysema.

Comprehensive analysis of CDKN2A (p16INK4A/p14ARF) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma.

OBJECTIVE: Comprehensive analysis of the 9p21 locus including the CDKN2A, ARF, and CDKN2B genes in 53 individuals from melanoma index cases considered to be at heightened risk of melanoma. METHODS AND RESULTS: Using a combination of DNA sequencing, gene copy number by real time quantitative PCR, linkage analysis, and transcript analysis in haploid somatic cell hybrids, we found no evidence for germline alteration in either coding or non-coding domains of CDKN2A and CDKN2B. However, we identified a p14ARF exon 1beta missense germline mutation (G16D) in a melanoma-neural system tumour syndrome (CMM+NST) family and a 8474 bp germline deletion from 196 bp upstream of p14ARF exon 1beta initiation codon to 11233 bp upstream of exon 1alpha of p16(INK4A) in a family with five melanoma cases. For three out of 10 families with at least three melanoma cases, the disease gene was unlinked to the 9p21 region, while linkage analysis was not fully conclusive for seven families. CONCLUSIONS: These data reinforce the hypothesis that ARF is a melanoma susceptibility gene and suggest that germline deletions specifically affecting p14ARF may not be solely responsible for NST susceptibility. Predisposition to CMM+NST could either be due to complete disruption of the CDKN2A locus or be the result of more complex genetic inheritance. In addition, the absence of any genetic alteration in 50 melanoma prone families or patients suggests the presence of additional tumour suppressor genes possibly in the 9p21 region, and on other chromosomes.

[Anti Pseudomonas aeruginosa antibiotic therapy in cystic fibrosis (exclusion of macrolides)]. / Stratégie antibiotique contre Pseudomonas aeruginosa dans la mucoviscidose (macrolides exclus).

Antibiotherapy is one of the main treatment in cystic fibrosis. Pseudomonas aeruginosa infection is one of the main causes of pulmonary degradation. The chronic sputum colonisation is characterized by the emergence of the mucoid phenotype, the formation of biofilm and the induction of excessive inflammatory response and consecutive tissue lesion. The choice of antibiotics depends on quantitative and qualitative analysis of sputum, bacteria resistance phenotypes and severity of infection. Treatment of P. aeruginosa is different in case of first colonization or chronic infection. In the first case, parenteral antibiotherapy (beta-lactams-aminoglycosids) followed by inhaled antibiotherapy may eradicate the germ. In the other case, superinfections can be treated with parenteral biantibiothérapy (beta-lactams or quinolons and aminoglycosides) during 15 to 21 days. This is associated with a better nutritional and respiratory status and a prolonged survival. Inhaled antibiotics between the courses have decreased the number of superinfections. This prolonged antibiotherapy must be monitored because of possible induction of bacterial resistance, nephrotoxicity and ototoxicity of aminosids and allergy to beta-lactams.

[Evaluation of patients' knowledge regarding counsels provided in case of chest pain after an acute myocardial infarction]. / Evaluation des conseils assimilés par les patients sur l'attitude recommandée en cas de douleur thoracique au décours d'un infarctus aigu du myocarde. Conseils ou patient après un infarctus du myocarde.

INTRODUCTION: an early call to the department of urgent medical assistance--Center 15 (SAMU-centre 15) is associated to shortest delays of reperfusion in case of myocardial infarction. However, patients are not always aware of this. OBJECTIVE: to assess the assimilated counsels by patients after an acute myocardial infarction. METHODS: from January 1998 to June 2004, patients managed by SAMU 93 and having benefited from thrombolytic therapy prior to hospitalization and/or primary angioplasty for a ST+ acute coronary syndrome with a confirmation of acute myocardial infarction during their hospital stay were prospectively enrolled into this study. A questionnaire was administered by phone from december 2003 to july 2005, assessing the knowledge about the necessity to alert SAMU-center 15 in case of chest pain and availability of medical files data. RESULTS: among the 976 patients: 111 (11%) were lost during follow-up, 162 (19%) were deceased when phone contact and 119 (12%) could not be interrogated. Among the 584 (60%) remaining subjects interrogated with a median follow-up period of 985 days (413-1596), 290 (50%) patients answered they received counseling, including 156 (27%) for taking nitrates, 19 (29%) stated they know that they should call SAMU-center 15. Patients with a high level of education and those treated by thrombolytic therapy prior to hospitalization were better informed; 464 (79%) patients declared having a prescription, 392 (67%) a hospital report, 406 (69%) an electrocardiogram, 227 (39%) a CD with their coronary angiography, and 79(14%) their medical file. CONCLUSION: the level of knowledge regarding the recommended attitude in case of chest pain is poor. The availability of medical data was better. Arch Mal Cceur

A new mutation of the noggin gene in a French Fibrodysplasia ossificans progressiva (FOP) family.

A new mutation of the Noggin gene in a French Fybrodysplasia ossificans progressiva (FOP) family: Fibrodysplasia ossificans progressiva (FOP) is a very rare disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of the muscles. We previously located a FOP gene in the 17q21-22 region and described several mutations of the noggin (NOG) gene (located in 17q22) in four FOP patients, including the G91C mutation which is transmitted dominantly in a Spanish FOP family. We describe in the present study a new mutation of the NOG gene in a French FOP family. This new mutation is a guanine to adenine change at nucleotide 283 (283G --> A) of the NOG gene, and is transmitted in the family (in the heterozygote form) by the affected mother to her two affected children. At the peptide level this mutation (A95T) substitutes an Alanine residue by a Threonine at position 95 of the Noggin protein. The Alanine mutated residue is located just adjacent to the myristoylation site of the protein, where all the mutations we described until now are located.

[Body temperature measurement in daily practice]. / La mesure de la température en pratique pédiatrique quotidienne.

The use of rectal mercury thermometer has long been the standard method for measurement of body temperature. The restriction of mercury use since 1996 has led to development of other devices. The liquid crystal strip thermometer held against the forehead has a low sensitivity. The single-use chemical thermometer measures oral temperature. Its accuracy must be evaluated. Infrared ear thermometers are routinely used because it is convenient and fast to use. However, numerous studies have shown that it does not show sufficient correlation with rectal temperature, leading to the risk to miss cases of true fever. Rectal temperature remains the gold standard in case of fever. Rectal temperature measurement with an electronic device is well correlated with the glass mercury standard. Galistan thermometer accuracy must be evaluated because of sterilization of the whole device, which is not the case for the electronic thermometer. A pediatric study is necessary to evaluate the performance of this device in comparison with the electronic thermometer.

Ratio of male to female births in the offspring of BRCA1 and BRCA2 carriers.

A recent report based on 68 families, including 17 with mutations in BRCA1, suggested that there was an excess of female offspring born to BRCA1 mutation carriers. We have examined the gender ratio among offspring of 511 mutation carriers from 116 BRCA1 families, 77 and 39 from Australia and the United States, respectively. We found no evidence for a significant deviation from the expected proportion of female offspring in the Australian pedigrees, but there was an excess of female offspring in pedigrees from the USA. Ascertainment bias probably explains this bias, rather than a link with X-chromosome inactivation as previously suggested, because the families from the USA were ascertained for the purposes of linkage studies whereas those from Australia were ascertained through Familial Cancer Clinics to which they had been referred for clinical genetic counseling and mutation testing.