PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

OBJECTIVE: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. METHODS: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. RESULTS: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. CONCLUSIONS: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutationsjournal articleresearch support, non-u.s. gov't2012 Nov 202012 10 17importedComment in : Paroxysmal disorders associated with PRRT2 mutations shake up expectations on ion channel genes. [Neurology. 2012

Comparison of ochratoxin A and deoxynivalenol in organically and conventionally produced beers sold on the Belgian market.

Beer was chosen as a cereal-derived and homogeneous product for a comparison of organic and conventional production methods in terms of mycotoxin contamination levels. Ochratoxin A (OTA, a storage mycotoxin) and deoxynivalenol (DON, a field mycotoxin) were assessed by HPLC in organically and conventionally produced beers sold in Belgium. Immunoaffinity column (OchraTest and DONPrep) purification was used prior to HPLC analysis. For in-house validation, recovery experiments, carried out with the spiked beers in the ranges of 50-200 ng OTA l-1 and 20-100 microg DON l-1, led to the overall averages of 91% (RSD = 10%, n = 9) and 93% (RSD = 5%, n = 27), respectively. Organic beers collected during 2003-2004 were more frequently OTA-contaminated (95%, n = 40) than their conventional counterparts (50%, n = 40). Conventional beers were OTA-contaminated at a mean concentration of 25 ng l-1 (range: 19-198 ng l-1), while organic beers contained a mean level of 182 ng l-1 (range: 18-1134 ng l-1). High OTA contamination above the limit of 200 ng l-1 (up to 1134 ng l-1) occasionally occurred in organically produced beers. A complementary survey performed with the same brands in 2005 did not confirm this accidental presence of excessive OTA loads (range: 3-67 ng l-1 for 10 conventional beers and 19-158 ng l-1 for 10 organic beers). Establishing a maximum of 3 microg OTA kg-1 in malt, the application of the regulation EC No. 466/2001 (entered in force before the last sampling) may be related to the observed improvement. The overall incidence of DON was 67 and 80% in conventional and organic beers, respectively. DON concentrations ranged from 2 to 22 microg DON l-1 (mean = 6 microg DON l-1) in conventional beers, while organic beers ranged from 2 to 14 microg DON l-1 (mean=4 microg DON l-1). Thus, DON in beers does not appear to be a major matter of concern. From the statistical tests, it was concluded that the variation between different batches was significant (P < 0.0001), in contrast to that observed between different brands, showing a lack of homogeneity in the raw materials. This occurs either in organically or in conventionally produced materials. Considering these results, an optimized frequency of controls according to European Regulations EC No 466/2001 and EC No 856/2005 should be recommended to reject the irregular batches

Novel familial cases of ICCA (infantile convulsions with paroxysmal choreoathetosis) syndrome

International audienc

Novel familial cases of ICCA (infantile convulsions with paroxysmal choreoathetosis) syndrome

International audienc

Fluid management and risk factors for renal dysfunction in patients with severe sepsis and/or septic shock

Introduction: The causative role of new hydroxyethyl starch (HES 130/0.4) in renal dysfunction frequency (a > 50% increase in serum creatinine or need for renal replacement therapy (RRT)) remains debated. Using the database of a multicenter study focusing on patients with severe sepsis and septic shock, the present study aimed at identifying factors associated with the occurrence of renal dysfunction. Methods: Among the 435 patients in a multicenter study of patients with severe sepsis and septic shock in 15 Southern French ICUs, 388 patients surviving after 24 hour, without a history of renal failure were included. Factors associated with renal dysfunction and RRT were isolated using a multivariate analysis with logistic regression. Results: Renal dysfunction was reported in 117 (33%) patients. Ninety patients required RRT. Among study participants, 379 (98%) were administered fluids in the first 24 hours of management: HES 130/0.4 only (n = 39), crystalloids only (n = 63), or both HES 130/0.4 and crystalloids (n = 276). RRT was independently associated with the need for vasopressors and the baseline value of serum creatinine in the first 24 hours. Multivariate analysis indicated that male gender, SAPS II score, being a surgical patient, lack of decrease in SOFA score during the first 24 hours, and the interventional period of the study were independently associated with renal dysfunction. Mortality increased in the presence of renal dysfunction (48% versus 24%, P < 0.01). Conclusions: Despite being used in more than 80% of patients with severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first 24 hours of management was not associated with the occurrence of renal dysfunction

Who should receive antibiotic prophylaxis before ERCP?

Infectious complications after endoscopic retrograde cholangiopancreatography (ERCP) are rare but can be major. The role of antibiotic prophylaxis in this setting is not clear and clinical practice varies widely. In this Practice Point commentary, I discuss the findings and limitations of a study by Cotton and colleagues, which investigated a sequential quality improvement approach over 11 years for antibiotic prophylaxis of infection after ERCP. The authors made several changes in practice over the study period leading to a dramatic reduction in use of antibiotics. In the final phase, antibiotics were given only to 26% of patients, but this group probably represents those patients who really benefit from prophylaxis. The study by Cotton et al. underlines that the findings of randomized, controlled trials should be adopted in practice, but that findings should be critically analyzed with selective changes in practice taken over time on the basis of clever analysis of clinical studies and local practice.CommentJournal ArticleSCOPUS: no.jinfo:eu-repo/semantics/publishe

Omalizumab Protects against Allergen-Induced Bronchoconstriction in Allergic (Immunoglobulin E-Mediated) Asthma

<p>Background: Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pretreatment immunoglobulin E (IgE)</p>

Radiospectroscopical search for molecule delivery and induced chemistry in the Earth atmosphere during the Leonids meteor shower

International audienc

Radiospectroscopical search for molecule delivery and induced chemistry in the Earth atmosphere during the Leonids meteor shower

International audienc