A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population.

Familial focal epilepsy with variable foci (FFEVF) is a heterogeneous epilepsy syndrome originally described in the French-Canadian (FC) population. Mutations in DEPDC5 have recently been identified in multiple cases of FFEVF as well as in a wide spectrum of other familial focal epilepsies. In this study, we aimed to determine the frequency of mutation of this gene in our large cohort of FC individuals with FFEVF, as well as familial and sporadic cases with focal epilepsy. We report a recurrent p.R843X protein-truncating mutation segregating in one large FFEVF and two small focal epilepsy FC families. Fine genotyping suggests an ancestral allele. A new p.T864M variant, predicted to be disease-causing, was also identified in a small FC family. Overall, we identified DEPDC5 mutations in 5% of our familial and sporadic focal epilepsy cases (4/79). Our results support the view that mutations in the DEPDC5 gene are an important cause of autosomal dominant focal epilepsies in the FC population, including a founder mutation that is specific to this population. These findings may facilitate molecular diagnosis in clinical practice.

Discovery and validation of serum biomarkers expressed over the first twelve weeks of Fasciola hepatica infection in sheep.

Serum biomarkers associated with Fasciola hepatica infection of Corriedale sheep were analysed during the first 12 weeks of infection using surface-enhanced laser desorption ionisation time of flight mass spectrometry (SELDI-TOF MS). In the discovery phase of analysis, pooled sera collected at week 0 and at each week p.i. to week 12 were fractionated by anion-exchange chromatography and the protein mass fingerprints obtained in individual fractions were in the M/z range 1.5-150 kDa. A total of 2302 protein clusters (peaks) were identified that varied between time-points following infection with peaks increasing or decreasing in intensity, or showing transient variation in intensity, during the 12 weeks of parasite challenge. In the validation phase, candidate biomarkers in sera of individual sheep at weeks 3 and 9 p.i. were analysed, identifying 100 protein peaks, many of which are small peptides <10 kDa in size: 54% of these peaks were up-regulated in intensity at week 3 or 9 p.i. Twenty-six biomarkers were chosen for further study, ranging in size from 1832 to 89,823 Da: six biomarkers were up-regulated at weeks 3 and 9 p.i., 16 biomarkers were up-regulated only at week 9 p.i. and four biomarkers were down-regulated at week 9 p.i. Two biomarkers up-regulated at week 9 were identified as transferrin (77.2 kDa) and Apolipoprotein A-IV (44.3 kDa), respectively. The results show that the interaction between the host and F. hepatica is complex, with changes in biomarker patterns beginning within 3 weeks of infection and either persisting to weeks 9-12 or showing transient changes during infection. Identification of biomarkers expressed during ovine fasciolosis may provide insights into mechanisms of pathogenesis and immunity to Fasciola and may assist in the rational development and delivery of vaccines.

A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps atrophy maps to 11p13-p12.

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of pathologies. We have identified a cohort of 14 French-Canadian patients from eight different families displaying a novel form of LGMD with an autosomal recessive inheritance. These patients share some features with previously described cases of 'quadriceps myopathy' that evolved into an LGMD. All demonstrate quadriceps femoris asymmetrical atrophy. Creatine kinase values were variable from normal to 6000 U/l. Clinical evaluations and MRI studies demonstrate a variable intrafamilial and interfamilial phenotype. Asymmetrical muscle involvement was clinically observed and confirmed by imaging. MRI studies suggest that the hamstrings and the adductor magnus are the first limb muscles to demonstrate fatty infiltration. Muscle pathology shows no sign of active inflammation but increased endomysial connective tissue associated with basal lamina duplication and collagen disorganization. A genome-wide scan using the two largest families uncovered linkage to marker D11S1360 on chromosome 11p12 [multipoint logarithm of the odds (LOD) score of 2.78]. Further genotyping for the eight families confirmed linkage to this new LGMD locus (multipoint LOD score of 4.56). Fine mapping subsequently defined a less than 3.3 cM candidate interval on 11p13-p12. Haplotype analysis of carrier chromosomes suggests that the most frequent mutation may account for up to 81.3% of French-Canadian mutations. In this study, we describe the chromosomal locus of a new form of recessive LGMD with prominent quadriceps femoris atrophy.

Ferrofluidic adaptive mirrors.

A magnetic liquid mirror based on ferrofluids was demonstrated. Magnetic liquid mirrors represent a major departure from solid mirror technology. They present both advantages and disadvantages with respect to established technologies. Stroke (from a fraction of a wave to several hundreds of micrometers), cost (a few dollars per actuator), and scalability (hundreds of thousands of actuators) are the main advantages. Very large mirrors having diameters of the order of a meter should be feasible. There are a few disadvantages. The most important disadvantage is the time response, which is of the order of a few milliseconds. Although this time response could be further decreased with additional technical developments, it is unlikely to match the speed of solid mirrors. The technology is still in its infancy, and considerable work must still be done. However, the advantages are such that the technology is worth pursuing.

A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33-34.

Recessive ataxias are a heterogeneous group of diseases. We identified a group of 23 French-Canadian cases belonging to 17 families affected by an autosomal recessive spastic ataxia associated with frequent white matter changes. The fact that 59% of these families have a genealogical relationship to the Portneuf County of Quebec suggests that this is a new form of ataxia with a regional founder effect. All cases present with cerebellar ataxia and spasticity. There is great intrafamilial and interfamilial variability, as illustrated by the spectrum of age of diagnosis (range: 2-59 years, mean: 15.0) and the presence of white matter changes on MRI in 52.4% of cases. The more severe cases have spasticity from birth, scoliosis, dystonia and cognitive impairment and were considered cases of cerebral palsy. Brain MRI constantly shows cerebellar atrophy, which in some cases may be associated with cortical atrophy, leucoencephalopathy and corpus callosum thinning. A genome wide scan uncovered linkage of three families to marker D2S2321 localized on chromosome 2q33-34. Linkage analysis confirmed that all families are linked to the same region [multipoint log of the odds (LOD) score of 5.95]. Haplotype analysis and allele sharing suggest that one common mutation may account for 97% of carrier chromosomes in Quebec. The uncovering of the mutated gene may point to a common pathway for pyramidal and cerebellar degeneration as both are often observed in recessive ataxias and complicated paraplegias.

Ultrasonography of chronic inflammatory bowel diseases.

Advances in the understanding of bowel appearances with high-resolution sonography have led to consideration of this technique as an important tool for bowel disease assessment. Ultrasonography may display the transformation of the intestinal wall from normal to pathological state in inflammatory diseases. Furthermore, intestinal ultrasonography may serve as a diagnostic clue if typical patterns of the bowel wall are demonstrated. Thus, Crohn's disease, ulcerative colitis, diverticulitis, or infectious ileocolitis may be specifically demonstrated in the majority of cases. Besides showing the parietal signs of inflammation, ultrasonography also shows the perigut abnormalities and may demonstrate complications such as fistulas and abscesses. Finally, with the help of Doppler, some additional information may be obtained about the activity of chronic inflammatory diseases. In clinical practice, used in combination with other imaging modalities, such as CT or endoscopy, bowel ultrasonography appears to be a non-invasive and effective diagnostic tool for the diagnosis and follow-up of Crohn's disease and ulcerative colitis.

[Maternal anemia in the southeast and northeast regions of New Brunswick and the impact on hematological parameters and the growth of the newborn]. / Anémie maternelle dans les régions du sud-est et du nord-est du Nouveau-Brunswick et impact sur les paramétres hématologiques et la croissance du nouveau-né.

The prevalence of anaemia remains a major nutritional problem in industrialized countries. The aim of this study was to compare the prevalence of maternal anaemia in southeastern and northeastern areas of New Brunswick and to identify a potential interaction between maternal haematologic indices and the growth, hemoglobin (Hb) and hematocrit (Ht) of newborns. In this retrospective study, 952 obstetric and paediatric records, including 654 from the southeastern area (Greater Moncton) and the rest from the northeastern area (Acadian Peninsula) of New Brunswick, were investigated. The prevalence of maternal anaemia was 21.4% in the Greater Moncton area, compared to 11.5% in the Peninsula. The majority of anaemic women suffered from a light form of anaemia, mainly in the third trimester. Immediately after delivery, 52% of women from Greater Moncton and 40% from the Acadian Peninsula had Hb below normal. A positive correlation was observed between maternal Hb and newborn Hb and between maternal Ht and newborn Hb. Results indicate that maternal anaemia is prevalent in both areas under study and confirm the importance of implementing effective prevention measures.

Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people.

BACKGROUND: The administration of many drugs concurrently to elderly patients is a well-known problem in geriatrics and involves numerous risks. One way to reduce polypharmacy is to provide information to physicians in order to modify their prescribing practices. The main objective of this study was to evaluate the impact of an intervention program that targeted physicians with the aim of reducing the number of potentially inappropriate prescriptions (PIPs) given to elderly patients. METHODS: A randomized controlled trial was carried out among community-dwelling elderly people in Sherbrooke, Que. The participants were 266 patients over 75 years of age (experimental group: n = 136, control group: n = 130). A team comprising 2 physicians, a pharmacist and a nurse reviewed the list of drugs and the diagnoses of a subgroup of the experimental group in a case conference. Suggestions were formulated and mailed to the patients' physicians together with relevant scientific documentation justifying the recommendations. The main outcome measure was the number of PIPs. RESULTS: The mean number of PIPs per patient declined by 0.24 in the experimental group (n = 127) and by 0.15 in the control group (n = 116). The decline in PIPs was even larger in the experimental group that had case conferences (n = 80), in which the mean number of PIPs per patient declined by 0.31. However, this difference between the experimental group and the control group was not statistically significant in the intent-to-treat analysis. The number of drugs prescribed was not modified by the intervention, nor were the results of the global assessment of the patients' drug profiles. INTERPRETATION: This study suggests that the intervention program had no effect on the prescribing of PIPs.

Early diet influences hepatic hydroxymethyl glutaryl coenzyme A reductase and 7alpha-hydroxylase mRNA but not low-density lipoprotein receptor mRNA during development.

Plasma cholesterol levels increase after birth, and to a greater extent in breast-fed versus formula-fed infants. This increase is believed to be due to the high fat and cholesterol content of the infant diet, but little is known about the effects of early diet on the expression of proteins involved in regulating cholesterol metabolism. This study examined changes in the expression of hepatic proteins regulating cholesterol metabolism during development. Newborn piglets were fed sow milk or one of four formulas for 18 days. The formulas had similar levels of palmitic acid (16:0) as in milk, supplied as palm olein oil with 16:0 esterified predominantly to the sn-1,3 position or as synthesized triglyceride (TG) with 16:0 esterified mainly to the sn-2 position of glycerol, each with no cholesterol (<0.10 mmol/L) or 0.65 mmol/L cholesterol added. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of mRNA levels was used to assess the effects of diet on hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, low-density lipoprotein (LDL) receptor, and 7alpha-hydroxylase (C7H). LDL receptor mRNA levels showed no appreciable difference between milk- and formula-fed piglets. However, the levels of HMG-CoA reductase and C7H mRNA were higher (P < .05) in all formula-fed versus milk-fed piglets, irrespective of the formula TG source or cholesterol content. The lower levels of HMG-CoA reductase and C7H mRNA in milk-fed piglets were accompanied by higher (P < .05) plasma total, high-density lipoprotein (HDL), and apolipoprotein (apo) B-containing cholesterol. These studies show that the levels of hepatic HMG-CoA reductase and C7H mRNA, but probably not LDL receptor mRNA, are altered by early diet.

[The contribution of ultrasonography to various pathologies of the small intestine]. / Apport de l'echographie aux differentes pathologies de l'intestin grele.

Ultrasonography has progressively become an easily available non expensive imaging modality for the study of the small intestine. It has no secondary effects and is comforting for the abdominal radiologist. Further, as ultrasonography does not require special preparation nor contrast administration in the intestine or vascular system, no delay is caused if other imaging modalities (such as CT or angiography) have to be performed. This report covers the most common pathologic conditions in the small bowel and does not consider enteroliths, foreign bodies nor mucoviscidosis.

Crescent-shaped necrosis: a new imaging sign suggestive of stromal tumor of the small bowel.

We report three cases of unsuspected stromal tumors of the small bowel (STSB). These cases were diagnosed preoperatively by sonography, the imaging was completed for some with barium studies, computed tomography, magnetic resonance imaging, or angiography. To our knowledge, the use of this noninvasive technique for detecting this type of tumor has not been described in the literature. Moreover, we believe that some sonographic findings such as crescentic tumoral necrosis may appear highly suggestive of STSB.

Disability: the place of judgement in a world of fact.

Ways of viewing disability, of developing research questions, of interpreting research results, of justifying research methodology, and of putting policies and programmes in place are as much about ideology as they are about fact. It is important to recognize how significant this is to research generally and to the field of intellectual disability in particular. The roots of scientific and socio-economic justification for the allocation of research funding, and of political (or state) action based on research findings can be found in identifiable and shifting ideological frameworks. Therefore, to understand the field, it is useful to explore the social and scientific formulations of disability which underpin the research agenda, and the ways of knowing disability.

Sonographic detection of ingested foreign bodies in the inferior vena cava.

Ingested foreign bodies usually proceed uneventfully through the intestinal tract; complications rarely occur. The wide variety of clinical presentations they produce often make the diagnosis difficult. We report two cases of sonographic detection of foreign bodies in the inferior vena cava, namely one toothpick and one small (chicken?) bone, which probably caused a duodenocaval fistula. Both patients were initially investigated for recurrent septic episodes, weight loss, and deterioration of general condition.

Delayed peritoneal and retroperitoneal abscesses caused by spilled gallstones: a complication following laparoscopic cholecystectomy.

Many complications following laparoscopic cholecystectomy have been reported. We report a case of delayed peritoneal and retroperitoneal abscesses caused by spilled gallstones from a laparoscopic cholecystectomy performed 1 year earlier. This diagnosis was suggested only at sonography because the aggressive behavior of the lesions containing nonopaque gallstones suggested, by computed-tomography scan, peritoneal metastatic disease.

Cystic lymphangioma of the colon: ultrasonographic and computed tomographic features.

Cystic lymphangioma is a rare benign tumour of the gastrointestinal tract. The authors describe a 52-year-old woman with cystic lymphangioma in the ascending colon. Ultrasonographically, the lesion was compressible and anechoic and showed posterior acoustic enhancement. Doppler analysis showed no flow within the lesion. On computed tomography the lesion appeared as a focal thickening of the colonic wall with attenuation values of 6 to 10 Hounsfield units. The lesion extended along the wall and did not invade the adjacent fat. It could not be located during endoscopy or laparotomy and was eventually located for resection with intraoperative ultrasonography.

Sonographic appearance of primary small bowel carcinoid tumor.

BACKGROUND: To assess the value of sonography in the diagnostic work-up of small bowel carcinoid tumors and characterize their sonographic appearance. METHODS: We retrospectively reviewed the sonographic findings (size, shape, echogenicity, contour, location, wall thickening, serosal transgression, vascularity) of all cases of carcinoid tumors investigated between January 1988 and January 1993. Six tumors, in five patients with histologic proof, were analyzed and, when possible, correlation with pathological or surgical results was made. RESULTS: In four out of five cases, the tumor was not suspected clinically prior to sonography; in one case, a small synchronous lesion was only found at surgery. Its sonographic appearance was a hypoechoic, homogenous, predominantly intraluminal mass with smooth intraluminal contour and attached to the wall by a broad base with interruption of the submucosa and thickening of the muscularis propria in all cases. There were signs of serosal transgression in four cases, puckering and retraction in two cases, hypervascularity in two cases, and mesenteric involvement in three cases. All lesions were located in the ileum and the mean diameter was 22 x 17 mm. CONCLUSION: Ultrasonography was useful in the detection of primary carcinoid tumors of small bowel. Their sonographic characteristics were described and some of them were highly suggestive of the diagnosis.

Sonographic detection of peritoneal carcinomatosis: a prospective study of 37 cases.

BACKGROUND: The use of sonography as an accurate modality to detect peritoneal carcinomatosis in patients with or without known malignancy was investigated. METHODS: Using ultrasound, we prospectively diagnosed peritoneal carcinomatosis in 37 patients. Findings such as liver metastases, adenomegalies, ascites and gallbladder wall thickness were first assessed. Then high resolution sonography detected omental, mesenteric, serosal and peritoneal involvement, the latter presenting as a nodule or an interruption of the anterior hyperechoic peritoneal line. Percutaneous biopsy under sonographic guidance of detected lesions, surgery or autopsy confirmed the peritoneal carcinomatosis. Sonographic search for the primary neoplasm was simultaneously done. RESULTS: Carcinomatosis was proven in all 37 cases. Omental involvement was found in 36 cases (97%), serosal implants in 7 cases (19%), mesenteric involvement in 6 cases (16%), peritoneal implants in 20 cases (54%). Interruption of the anterior peritoneal line was found in 6 cases (16%), liver metastasis in 14 cases (38%), lymphadenopathies in 9 cases (24%), and significant ascites in 18 cases (49%). Gallbladder wall thickness was not a useful criterion since 12 patients (32%) had previous cholecystectomy. Biopsy of detected lesions was performed in 21 cases with 100% positive results for malignant cells. Sonography detected the primary tumor in 16 (57%) out of 28 patients without known malignancy. CONCLUSION: Sonography was very useful for prospective detection of peritoneal carcinomatosis and the omental abnormality was the single most useful sign. Furthermore, sonographic findings, confirmed by percutaneous biopsy, prevented 24 unnecessary exploratory laparotomies.

Colonic bull's-eye lesions in histiocytosis X.

A 27-year-old woman with known pulmonary, cutaneous and osseous histiocytosis X presented with vague abdominal pain. Double-contrast barium enema examination revealed multiple colonic bull's-eye lesions. Biopsy showed histiocytic infiltration similar to that already described at other sites in this patient (the lungs and bone). To the authors' knowledge, this case represents the first radiologic description of this manifestation of histiocytosis X. Though rare, it should be considered in the differential diagnosis of colonic bull's-eye lesions.