ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia

Chronic myelomonocytic leukaemia (CMML) is a haematological disease currently classified in the category of myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) because of its dual clinical and biological presentation. The molecular biology of CMML is poorly characterized. We studied a series of 53 CMML samples including 31 cases of myeloproliferative form (MP-CMML) and 22 cases of myelodysplastic forms (MD-CMML) using array-comparative genomic hybridisation (aCGH) and sequencing of 13 candidate genes including ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, PTPN11, RUNX1, TET2 and WT1. Mutations in ASXL1 and in the genes associated with proliferation (CBL, FLT3, PTPN11, NRAS) were mainly found in MP-CMML cases. Mutations of ASXL1 correlated with an evolution toward an acutely transformed state: all CMMLs that progressed to acute phase were mutated and none of the unmutated patients had evolved to acute leukaemia. The overall survival of ASXL1 mutated patients was lower than that of unmutated patients.     

Cognitive vulnerability to anxiety: A review and an integrative model

Consistent research evidence supports the existence of threat-relevant cognitive bias in anxiety, but there remains controversy about which stages of information processing are most important in the conferral of cognitive vulnerability to anxiety. To account for both theoretical and empirical discrepancies in the literature, an integrative multi-process model is proposed wherein core assumptions of dual-systems theories from social and cognitive psychology are adapted to explain attentional and interpretive biases in the anxiety disorders. According to the model, individual differences in associative and rule-based processing jointly influence orientation, engagement, disengagement, and avoidance of threat-relevant stimuli, as well as negatively-biased interpretation of ambiguous stimuli in anxious populations. By linking anxiety-related symptoms to basic principles of information processing, the model parsimoniously integrates different kinds of cognitive biases in anxiety, providing a useful framework for future research and clinical intervention.     

Acute appendicitis in children: evaluation with US

During a 4-month period, high-resolution ultrasonography (US) was used to prospectively evaluate 70 children with clinically suspected acute appendicitis. Thirty-five US scans showed a noncompressible appendix with maximal outer diameters greater than 6 mm. This finding was considered positive for the diagnosis of acute appendicitis. Thirty-one of these 35 patients had acute appendicitis documented by surgical and pathologic findings. The remaining four patients were observed, and their symptoms resolved. Thirty-five patients had US scans considered negative for appendicitis. Seventeen of these patients had US findings positive for other conditions including mesenteric adenitis, ileitis, intussusception, Crohn disease, and Burkitt lymphoma. In this series US enabled diagnosis of acute appendicitis with a sensitivity of 94%, a specificity of 89%, and a predictive accuracy of 91%. Diagnosis of acute appendicitis can be made with US with the same accuracy in children as has been previously reported in series of adult patients. The use of US in clinically ambiguous cases may allow earlier diagnosis, prevention of perforation, and decreased complications in the pediatric patient with acute appendicitis.     

Coxiella burnetii seroprevalence of shepherds and their flocks in the lower Saint-Lawrence River region of Quebec, Canada.

OBJECTIVE: To determine the seroprevalence of Coxiella burnetii among the shepherds and their sheep in the lower Saint-Lawrence River region (LSLRR) of Quebec, Canada. DESIGN: A prospective human-animal comparative study was conducted with 81 shepherds from 46 farms and a control group matched for sex and age. All participants answered a standardized questionnaire to evaluate their risk factors for Q fever, including a specific section on the work practices of the shepherds. All human subjects had a blood sample taken for serology to phase I and phase II antigens of C burnetii performed by indirect immunofluorescence assay. At each participating farm, seven to nine sheep had blood samples taken for C burnetii serology to be assessed by the complement fixation test. RESULTS: The seroprevalence to C burnetii was higher in the group of shepherds (28.4%) than the control group (1.2%) (P<0.005). Among the group of shepherds, spending more than 5 h/week in the sheep barn (P=0.06) and buying and/or trading sheep within the past six months (P=0.004) were associated with positive C burnetii serology. A total of 137 of 334 sheep (41%) were seropositive for C burnetii. These positive sheep were distributed in 41 of the 46 flocks (89%). No correlation could be demonstrated between a serology for C burnetii in the herds and the shepherds. CONCLUSION: Q fever is highly prevalent in the LSLRR of Quebec, affecting 89% of the flocks and 28% of the shepherds. Shepherds in this region are at increased risk for C burnetii infection in comparison to the general population.     

Intrinsic Organization and Connectivity of Intrastriatal Striatal Transplants in Rats as Revealed by DARPP-32 Immunohistochemistry: Specificity of Connections with the Lesioned Host Brain

Intrastriatal grafts of tissue obtained from the striatal or neocortical primordia of rat fetuses have been studied with respect to their intrinsic organization and connectivity using antibodies to DARPP-32 in combination with acetylcholinesterase (AChE) histochemistry, tyrosine hydroxylase (TH) immunocytochemistry, and anterograde and retrograde axonal tracing techniques. The striatal grafts were characterized by distinct patches of DARPP-32-immunoreactive neurons, which were identical to the densely AChE-positive patches stained in adjacent sections from the same specimens. The non-patch areas possessed only few DARPP-32-positive neurons and contained only sparse AChE-positive fibres. The cortical grafts, by contrast, contained no neurons with clear-cut DARPP-32-positivity and they exhibited a sparse, evenly distributed AChE fibre network, similar to that seen in the non-patch areas of the striatal grafts. The host dopaminergic afferents, as revealed by TH immunostaining, had grown selectively into the DARPP-32-positive patches in the striatal grafts, where they formed a dense terminal network around the DARPP-32-positive cell bodies. The non-patch areas, as well as the cortical grafts, received only sparse TH innervation. By contrast, the host cortical afferents, labelled by Phaseolus vulgaris leucoagglutinin from the host frontal cortex, were seen to extend into both the patch and non-patch areas of the striatal grafts. Transplant neurons projecting into the host brain were labelled by Fluoro-Gold injections into the ipsilateral host globus pallidus. These injections labelled large numbers of medium-sized neurons within the striatal grafts and the vast majority of them (over 85%) were confined to the DARPP-32-positive patches. Similar Fluoro-Gold injections labelled only few graft neurons in the cortical grafts. The results indicate that the striatal grafts are composed of a mixture of striatal and non-striatal tissue, and that the striatal graft compartment selectively establishes afferent and efferent connections with the host nigro-pallidal system. These graft connections demonstrate a remarkable specificity in the formation of graft - host connectivity. The results, moreover, suggest that developmental properties of the grafted striatal primordium are retained and expressed in the implanted cell suspension, and that the neuronal systems of the lesioned adult host brain, at least to some extent, remain responsive to growth regulating mechanisms normally operating during ontogenetic development.     

Peritonitis in continuous ambulatory peritoneal dialysis: impact of a compulsory switch from a standard to a Y-connector system in a single North American Center.

One hundred one continuous ambulatory peritoneal dialysis (CAPD) patients from a single North American center were analyzed in a retrospective and cross-over study for peritonitis rates using a standard system (Travenol System II) or a Y-shaped disconnect-disinfectant system (Travenol O-set). Twenty-one of 34 patients using the standard set (group I) had 53 episodes of peritonitis in 508 patient-months or one episode per 9.6 patient-months. Nine of 17 patients switching from the standard to the disconnect-disinfectant system (group II) experienced 22 episodes of peritonitis in 275 patient-months or one episode per 12.5 patient-months on the standard set, while six patients had 10 episodes of peritonitis in 275 patient-months or one episode per 27.5 patient-months on the disconnect-disinfectant system (P less than 0.04). Twenty-eight of 67 new CAPD patients starting on the disconnect-disinfectant system (group III) had 37 episodes of peritonitis in 1,086 patient-months or one episode per 29.4 patient-months (P less than 0.01 v group I). Exit-site infections (ESI) occurred in 35.3% of patients using the standard set versus 34.3% of those using the O-set. The presence of an ESI was not associated with a higher risk of peritonitis, but modified the bacteriological profile of subsequent peritonitis episodes in patients using the O-set, favoring the organisms isolated from the exit site. Decreases in peritonitis rates with the O-set were due to a reduction of peritonitis episodes secondary to most bacterial agents and not only to skin organisms. Diabetics using intraperitoneal insulin had similar peritonitis and ESI rates as nondiabetics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptive reaction of nigral neurons following lesion of their ventromedial-thalamic projection field

The response of reticulata-nigral neurons to injury of their ventromedial-thalamic (VM) projection was studied in the rat, by the autoradiographic [14C]deoxyglucose method. Electrolytic lesion of the VM induced reversible: reticulata hypoexcitability; and hyporesponsiveness of areas receiving reticulata efferents, to nigral electrical stimulus. The results suggest that distal axonal injury (in the VM) induces reversible rearrangement of functional properties in the nigral parent cells and their uninjured collaterals, as a retrograde reaction.