Mutation analysis of the ATP7B gene in a new group of Wilson's disease patients: contribution to diagnosis.

Wilson's disease (WD), an autosomal recessive disorder of copper transport with a broad range of genotypic and phenotypic characteristics, results from mutations in the ATP7B gene. Herein we report the results of mutation analysis of the ATP7B gene in a group of 118 Wilson disease families (236 chromosomes) prevalently of Italian origin. Using DNA sequencing we identified 83 disease-causing mutations. Eleven were novel, while twenty one already described mutations were identified in new populations in this study. In particular, mutation analysis of 13 families of Romanian origin showed a high prevalence of the p.H1069Q mutation (50%). Detection of new mutations in the ATP7B gene in new populations increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

Field Marshall Wilson : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57056

A case of dissection of intracranial cerebral arteries with segmental mediolytic "arteritis".

The intravital diagnosis of intracranial arterial dissection is not always possible due to atypic and non-specific clinical and radiological presentations. The postmortem pathological examination of cerebral blood vessels is therefore necessary to establish or confirm the presence of a dissecting aneurysm of intracranial arteries. Most of the described cases showed no significant underlying vascular pathology. Here we present the case of a 24-year-old women who died 5 days after admission to the hospital for a rapidly developing right-sided hemisyndrome. Neuroradiological examination had revealed ill-defined bifrontal hypodense lesions and angiographic findings were compatible with a dissection of the left extracranial internal carotid artery with embolic subocclusion of both anterior cerebral arteries. The pathological evaluation ruled out a thromboembolic occlusion of cerebral arteries and an extracranial internal carotid artery dissection but showed an extended dissecting process of variable age in the anterior circulation of the circle of Willis. The dissected vessels showed pathological changes characteristic of segmental mediolytic "arteritis" [Slavin and Gonzalez-Vitale 1976]. To our knowledge this is the first report on intracranial arteries being affected by this pathologic entity. Our case illustrates the importance of a postmortem examination of dissecting aneurysms of intracranial arteries. Careful serial section studies of dissected intracranial arteries in young subjects should be performed and may allow for a better understanding of the vascular pathology underlying the dissection processus.

[Max Cyril] Morris sur Matchless [1000 cmc, concurrent de la course motocycliste Paris-Nice] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57950

La maladie de Wilson: un caméléon clinique auquel il faut penser [A primer on Wilson disease for the general practitioner].

Wilson disease (WD) is an inherited disorder of hepatic copper excretion leading to toxic accumulation of copper in the liver as well as the brain, cornea, and other organs. The defect is due to mutations of the copper-transporting ATPase ATP7B. Clinical manifestations are highly variable and comprise acute liver failure, chronic hepatitis and cirrhosis as well as neurological or psychiatric symptoms. The Kayser-Fleischer corneal ring is pathognomonic but absent in about 50% of patients with hepatic manifestations alone. A high index of suspicion in clinically compatible situations is key, with a combination of laboratory tests allowing the diagnosis of WD. Treatment is based on the use of chelating agents, D-penicillamine or trientine. Liver transplantation should be considered for patients with acute liver failure or advanced cirrhosis.

Common variants associated with plasma triglycerides and risk for coronary artery disease.

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Influence of preoperative leg pain and radiculopathy on outcomes in mono-segmental lumbar total disc replacement: results from a nationwide registry.

PURPOSE: Currently, many pre-conditions are regarded as relative or absolute contraindications for lumbar total disc replacement (TDR). Radiculopathy is one among them. In Switzerland it is left to the surgeon's discretion when to operate if he adheres to a list of pre-defined indications. Contraindications, however, are less clearly specified. We hypothesized that, the extent of pre-operative radiculopathy results in different benefits for patients treated with mono-segmental lumbar TDR. We used patient perceived leg pain and its correlation with physician recorded radiculopathy for creating the patient groups to be compared. METHODS: The present study is based on the dataset of SWISSspine, a government mandated health technology assessment registry. Between March 2005 and April 2009, 577 patients underwent either mono- or bi-segmental lumbar TDR, which was documented in a prospective observational multicenter mode. A total of 416 cases with a mono-segmental procedure were included in the study. The data collection consisted of pre-operative and follow-up data (physician based) and clinical outcomes (NASS form, EQ-5D). A receiver operating characteristic (ROC) analysis was conducted with patients' self-indicated leg pain and the surgeon-based diagnosis "radiculopathy", as marked on the case report forms. As a result, patients were divided into two groups according to the severity of leg pain. The two groups were compared with regard to the pre-operative patient characteristics and pre- and post-operative pain on Visual Analogue Scale (VAS) and quality of life using general linear modeling. RESULTS: The optimal ROC model revealed a leg pain threshold of 40 ≤ VAS > 40 for the absence or the presence of "radiculopathy". Demographics in the resulting two groups were well comparable. Applying this threshold, the mean pre-operative leg pain level was 16.5 points in group 1 and 68.1 points in group 2 (p < 0.001). Back pain levels differed less with 63.6 points in group 1 and 72.6 in group 2 (p < 0.001). Pre-operative quality of life showed considerable differences with an 0.44 EQ-5D score in group 1 and 0.29 in group 2 (p < 0.001, possible score range -0.6 to 1). At a mean follow-up time of 8 months, group 1 showed a mean leg pain improvement of 3.6 points and group 2 of 41.1 points (p < 0.001). Back pain relief was 35.6 and 39.1 points, respectively (p = 0.27). EQ-5D score improvement was 0.27 in group 1 and 0.41 in group 2 (p = 0.11). CONCLUSIONS: Patients labeled as having radiculopathy (group 2) do mostly have pre-operative leg pain levels ≥ 40. Applying this threshold, the patients with pre-operative leg pain do also have more severe back pain and a considerably lower quality of life. Their net benefit from the lumbar TDR is higher and they do have similar post-operative back and leg pain levels as well as the quality of life as patients without pre-operative leg pain. Although randomized controlled trials are required to confirm these findings, they put leg pain and radiculopathy into perspective as absolute contraindications for TDR.

Geological explorations in Central Borneo (1893-94) : Borneo expedition. english rev. ed. with an appendix on fossil radiolaria of Central-Borneo ([Reprod.]) / by Dr. G. A. F. Molengraaff,... ; by Dr. G. J. Hinde

Comprend : Description of fossil radiolaria from the rocks of Central Borneo, obtained by prof. Dr. G. A. F. Molengraaff in the dutch exploring expedition of 1893-94

The development of intercultural awareness and changes of beliefs: the effects of studying abroad on learners of English as a second language

The present study examines the development of interculturality and changes of beliefs, by analyzing 106 compositions produced by 53 advanced level university students of translation studies at a university in Spain before and shortly after a stay-abroad (SA) period. The study draws on data collected at two different times: before (T1) and after the SA (T3). In addition, we compared the results with the writings produced by a control group of 10 native English speakers on SA too. Data were collected by means of a composition which tried to elicit the learners’ opinion about cultural habits maintenance. The results reveal significant changes between T1 and T3 in the degree of better attitudes and intercultural acquisition.

Late bloomer or language impaired? Screening the speech of a Spanish-English bilingual toddler for early signs of language impairment

This case study presents corpus data gathered from a Spanish-English bilingual child with expressive language delay. Longitudinal data on the child’s linguistic development was collected from the onset of productive speech at age 1;1 until age 4 over the course of 28 video-taped sessions with the child’s principal caregivers. A literature review focused on the relationship between language delay and persisting disorders—including a discussion of the frequent difficulty in distinguishing between the two at early stages of bilingual development—is followed by an analysis of the child’s productive development in 2 distinct phases. An attempt is made to assess the child’s speech at age 4 for preliminary signs of SLI and to consider techniques for identifying ‘at risk’ bilingual children (that is, those with productive language delay, poor oral fluency, and family history of language problems) based on samples of recorded and transcribed speech.