Unexpected extradermatological findings in 31 patients with xeroderma pigmentosum type C

Background Xeroderma pigmentosum type C (XP‐C) is a rare, autosomal, recessive condition characterized by the association of various clinical manifestations mostly involving the skin and eyes. Objectives To evaluate the clinical manifestations in a homogeneous, genetically characterized cohort of patients with XP‐C. Methods All patients with XP‐C, which was confirmed genetically or by unscheduled DNA synthesis, from the registry of our department and from the French association of patients ‘Les Enfants de la Lune’ were contacted. During a planned consultation, clinical information was collected using a standardized case‐record form. Results In total, 31 patients were seen. The mean age at diagnosis was 2·95 years; skin symptoms started at a mean age of 1·49 years. Among the patients, 52% had relatively short stature, with a height‐for‐weight z‐score below ?1 SD; 62% showed pyramidal syndrome and 45% had photophobia and/or conjunctivitis. Four patients had several pyogenic granulomas. Twenty‐four patients (77%) had skin cancer. The mean age of onset of the first skin cancer was 4·76 years (range 2–14·5 years). Basal‐cell carcinoma was the most frequent cancer. Melanomas were rare and mostly desmoplastic. Multinodular thyroid was the most frequent internal tumour. Conclusions Our data highlight several new aspects of XP‐C. Patients with XP‐C are at risk of developing pyogenic granulomas, desmoplastic melanomas and multinodular thyroid. Involvement of the central nervous system is frequent, but its mechanism remains unclear. The relatively short stature of the patients needs further investigation in order to be explained. XP‐C is not only a cancer‐prone disorder but is also a polysystemic disorder.     

Impairment of testicular endocrine function after lead intoxication in the adult rat

To clarify the mechanism of the action of lead on male reproductive function, adult male rats were injected intraperitoneally (i.p.) with lead acetate (8 mg/kg/day of lead), 5 days a week for 35 days. Despite this high dose, germ cells and Sertoli cells did not appear to be major targets of lead. However, lead determination in the reproductive organs showed that the accessory sex glands are such a target. Epididymal function was unchanged. In lead-exposed rats, plasma and testicular testosterone dropped by about 80%, but plasma luteinizing hormone (LH) only dropped by 32%. After luteinizing hormone releasing hormone (LHRH) stimulation of the pituitary, the plasma LH level reached the control one, but plasma testosterone remained significantly reduced by 37%. The sharp decrease in the testosterone: LH ratio in lead-exposed rats, combined with the significant reduction of intertubular tissue volume in the testes, indicate impaired Leydig cell function.     

Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A, P14ARF or cdk4 genes

In familial cutaneous malignant melanoma (CMM), disruption of the retinoblastoma (pRB) pathway frequently occurs through inactivating mutations in the p16 (p16INK4A/CDKN2A/MTS1) gene or activating mutations in the G1-specific cyclin dependent kinase 4 gene (CDK4). Uveal malignant melanoma (UMM) also occurs in a familial setting, or sometimes in association with familial or sporadic CMM. Molecular studies of sporadic UMM have revealed somatic deletions covering the INK4A-ARF locus (encoding P16INK4A and P14ARF) in a large proportion of tumours. We hypothesized that germline mutations in the p16INK4A, p14ARF or CDK4 genes might contribute to some cases of familial UMM, or to some cases of UMM associated with another melanoma. Out of 155 patients treated at the Institut Curie for UMM between 1994 and 1997, and interviewed about their personal and familial history of melanoma, we identified seven patients with a relative affected with UMM (n = 6) or CMM (n = 1), and two patients who have had, in addition to UMM, a personal history of second melanoma, UMM (n = 1), or CMM (n = 1). We screened by polymerase chain reaction single-strand conformation polymorphism the entire coding sequence of the INK4A-ARF locus (exon 1alpha from p16INK4A, exon 1beta from p14ARF, and exons 2 and 3, common to both genes), as well as the exons 2, 5 and 8 of the CDK4 gene, coding for the functional domains involved in p16 and/or cyclin D1 binding. A previously reported polymorphism in exon 3 of the INK4A-ARF locus was found in one patient affected with bilateral UMM, but no germline mutations were detected, either in the p16INK4A, p14ARF or CDK4 genes. Our data support the involvement of other genes in predisposition to uveal melanoma.     

Field 2. Epidemiology (medical errors and patient adverse events). French-speaking Society of Intensive Care. French Society of Anesthesia and Resuscitation

Iatrogenic pathology is currently a serious problem. Intensive care units (ICU) are wards with a high risk of occurrence of adverse events (AE) related to the care and medical errors. The incidence of AE in ICU varies from 3 to 31% according to the publications. These variations are mainly due to the methodology of data collection. The latter is essential. The indicators must be standardized (consensual definitions), and easily collected. The method of collection must be ideally prospective, nonpunitive, confidential, independent within a compliant team, and realized with the participation of various actors not only of the unit but also external (biologists, pharmacists). The risk factors of AE in ICU are known: old age and high severity scores at admission, with medical and nurse workload more important. AE are associated with an increased patients' morbidity in ICU with no evident causality. The over cost related to AE in ICU was quantified to 3961 dollars in the United States. The mortality of patients with an AE is higher but no study showed to date that AE constituted an independent risk factor of mortality in ICU. Some AE are preventable (from 28 to 84% according to studies). Therefore, the implementation of procedures of security (PS) is capital. Many methods often easy to implement exist such as in care, structural and managerial procedures. The development of a safety culture in hospitals and other delivery care settings is essential. It is the first essential step in a better comprehension of the health care professionals and the public opinion.     

Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling

BACKGROUND: Mutations in the cystic fibrosis (CF) transmembrane conductanceregulator (CFTR) gene have been widely detected in infertilemen with congenital bilateral absence of the vas deferens (CBAVD).Despite extensive analysis of the CFTR gene using varied screeningmethods, a number of cases remain unsolved and could be attributableto the presence of large gene rearrangements, as recently shownfor CF patients. METHODS: We carried out a complete CFTR gene study in a group of 222CBAVD patients with strict diagnosis criteria and without renalanomaly, and searched for rearrangements using a semi-quantitativeassay in a subgroup of 61 patients. RESULTS: The overall mutation detection rate was 87.8%, and 82% of patientscarried two mutations. Ten out of the 99 different mutationsaccounted for 74.6% of identified alleles. Four large rearrangementswere found in patients who already carried a mild mutation:two known partial deletions (exons 17a to 18 and 22 to 23),a complete deletion and a new partial duplication (exons 11to 13). The rearrangements accounted for 7% of the previouslyunknown alleles and 1% of all identified alleles. CONCLUSIONS: Screening for rearrangements should be part of comprehensiveCFTR gene studies in CBAVD patients and may have impacts ongenetic counselling for the patients and their families.