Allogeneic haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: outcome in a 20-year cohort

The curative potential of allogeneic haematopoietic stem cell transplant (allo HSCT) in chronic lymphocytic leukaemia CLL is established, with a demonstrated role for graft-versus-leukaemia and less certainty for other factors in determining outcome. The first two decades of CLL patients proceeding to allo HSCT at the Leukaemia/Bone Marrow Transplant Program of British Columbia (n = 49 consecutive, 1991-2009) were studied to clarify factors predicting outcome. The donor was related in 29 (59%) and unrelated in 20 (41%). Conditioning was reduced-intensity in 27 (55%) and myeloablative in 22 (45%). Thirty-one of 49 patients survive with median follow-up of 5 years (0·2-15). Cumulative incidence of non-relapse mortality; complete remission (CR); clearance of fluorescence in situ hybridization (FISH) abnormality and progression at 10 years was 36%; 69%; 55% and 22%. Overall survival (OS) was 63% at 2 years; 55% at 5 years and beyond. Factors predicting OS (P value by log rank <0·05) were: comorbidity index <3, FISH rank (Dohner) and 17p deletion, alemtuzumab pre-HSCT, achievement of CR post-HSCT, donor chimerism >90%, clearance of FISH abnormality post-HSCT and absence of high-grade (3-4) graft-versus-host disease. Results from this province-wide, two-decade cohort demonstrated that a substantial proportion of patients with high-risk CLL become long term disease-free survivors.     

Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic

An Autism Spectrum Disorder (ASD) diagnosis is often used to access services. We investigated whether ASD diagnostic outcome varied when DSM-5 was used compared to ICD-10R and DSM-IV-TR in a clinical sample of 150 intellectually able adults. Of those diagnosed with an ASD using ICD-10R, 56 % met DSM-5 ASD criteria. A further 19 % met DSM-5 (draft) criteria for Social Communication Disorder. Of those diagnosed with Autistic Disorder/Asperger Syndrome on DSM-IV-TR, 78 % met DSM-5 ASD criteria. Sensitivity of DSM-5 was significantly increased by reducing the number of criteria required for a DSM-5 diagnosis, or by rating ‘uncertain’ criteria as ‘present’, without sacrificing specificity. Reduced rates of ASD diagnosis may mean some ASD individuals will be unable to access clinical services.     

Hashimoto's thyroiditis presenting as bilateral knee arthropathy

Hashimoto's thyroiditis is an autoimmune disease associated with antimicrosomal antibodies. Thyroid failure from any cause can lead to hypothyroidism which has numerous manifestations, including rheumatic. Rheumatic or musculoskeletal symptoms may be the initial presentation of hypothyroidism. A case is described in which knee pain was the presenting symptom in a patient with Hashimoto's thyroiditis without any other sign or symptom of hypothyroidism. Synovial fluid was non-inflammatory and lab tests were consistent with hypothyroidism secondary to Hashimoto's thyroiditis. The non-inflammatory arthralgia and arthritis, stiffness and musculoskeletal signs of hypothyroidism were completely reversible with adequate thyroid replacement hormone. Knee effusions are a common sign in hypothyroidism with a sluggish bulge sign, which is due to highly viscous synovial fluid. Purpose of this case is early diagnosis and treatment of hypothyroidism by primary care physicians, which can probably prevent many patients from developing polyarthritis associated with hypothyroidism.     

Increased drinking stimulated by exposure to lithium-conditioned taste cues: Effects of conditioning trials and drug dose

Rats first received differential conditioning in which the oral infusion of one flavored solution (the CS+) was followed by lithium injection and the oral infusion of a different solution (the CS?) was followed by no drug treatment. The intake of a novel palatable flavor was then measured after infusion exposure to either the lithium-conditioned CS+, the taste of tap water, or the CS?. Exposure to the CS+ stimulated more drinking than comparable exposure to tap water following 2–8 differential conditioning trials (Experiment 1), following conditioning with lithium doses of 0.75–3.0 mEq/kg (Experiment 2), and in comparison with both exposure to water and exposure to the CS? (Experiment 3). However, the phenomenon was not closely related to the degree of aversion subjects acquired to the lithium-paired taste solution. These results indicate that a complete characterization of the changes in drinking which are elicited by lithium-conditioned stimuli requires recognition of not only the suppression of intake commonly observed in the presence of the conditioned stimuli, but also the enhancement of intake evident as an after-effect of the lithium-conditioned stimuli.     

[H]-dynophin A (1–8): Degradation profile and binding characteristics in brain homogenates

[³H]-Dynorphin A (1–8) was degraded in brain homogenates at 25° and even at 0°C. The peptidase inhibitors bestatin and captopril almost completely protected[³H]-dynorphin A (1–8) from degradation at 0°C but had only little effect on binding at this temperature. At 25°C, the binding of [³H]-dynorphin A (1–8) was markedly improved by addition of bestatin, captopril and L-leucyl-L-arginine, which afforded some, but not complete protection from degradation. The results of saturation binding assays at 25°C in the presence of the peptidase inhibitors were variable. However, it was found from saturation binding assays at 0°C that the maximum binding capacity for [³H]-dynorphin A (1–8) at the κ-site is similar to that of [³H]-(−)-bremazocine and [³H]-dynorphin A (1–9).     

Steroid-refractory ulcerative colitis treated with corticosteroids,metronidazole and vancomycin: a case report

Background  

Increasing evidence elucidating the pathogenic mechanisms of ulcerative colitis (UC) has accumulated and the disease is widely assumed to be the consequence of genetic susceptibility and an abnormal immune response to commensal bacteria. However evidence regarding an infectious etiology in UC remains elusive.     

Field contamination of the starfish Asterias rubens by metals. Part 2: Effects on cellular immunity

To study the effects of metals on starfish in field conditions, immune responses were measured in starfish from natural populations along a metal pollution gradient (long-term contamination) and in starfish that were transferred up the gradient (short-term contamination). Coelomic amoebocyte concentration (CAC) and production of reactive oxygen species (ROS) by amoebocytes were measured in two varieties of Asterias rubens occurring in the fjord: The black variety which lives only in the low salinity upper waters (22-26/1000) and the red variety which live both in the upper layer and in the deeper layer characterized by a salinity close to that of seawater (30/1000). The studied immune responses were stimulated in starfish living along the metal pollution gradient according to the contamination of these starfish by cadmium. However, the sensitivity of these responses toward metals appeared to be strongly modulated by the salinity stress. In red starfish living at 30/1000 and transferred up the contamination gradient, the immune responses were inhibited and closely followed the short-term accumulation of metals in the animal organs. Starfish transferred down the gradient did not recover normal immune responses in the short-term and appeared highly sensitive to caging stress. It is suggested that the impact of metals on the immune responses of A. rubens in field conditions occurs in three phases. Short-term inhibitory effects are exerted by a direct action of metals on the immune cells and are followed by a recovery due to the induction of protective mechanisms. Eventually, when these mechanisms are overwhelmed by a long-term contamination, indirect and durable stimulatory effects on the immune responses appear due to a global disruption of the animal physiology.