Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.     

Experience and outcomes of stepping stones triple P for families of children with autism

This study investigated the experience and perceived outcomes of a behavioural family intervention, standard stepping stones triple P (SSTP), for parents of children with autism. An indepth, prospective, mixed-methods, multiple case-study design was employed. Parent participants and SSTP practitioners took part. Participation in SSTP was consistently associated with improved parental self-efficacy, and was also associated with improved parental psychological well-being and decreased perceived need for behavioural services for some families. Three key themes emerged from the qualitative interview data, reflecting changes attributed to participation in SSTP: (1) changes in the “attribution of cause” of misbehaviour, (2) “Who's the boss?” reflecting a change to parents feeling more in charge of their child's behaviour, daily routines and choices, and (3) “Rewarding is rewarding!” reflecting appreciation of a positive approach to behaviour management. Practitioners discussed their impressions of appropriate participants, timing, structure, and session preferences for SSTP, and implications related to the professional qualifications of practitioners delivering SSTP. Clinical implications for the use of SSTP with families of children with autism are discussed.     

Somatosensory stimulation interventions for children with autism: literature review and clinical considerations

BACKGROUND: There is considerable evidence that children with autism experience sensory dysfunction, which can affect their ability to participate in functional activities. Occupational therapists frequently recommend somatosensory stimulation interventions to mitigate sensory dysfunction and improve a child's ability to function. PURPOSE: This paper examines the rationale and evidence supporting somatosensory stimulation interventions for children with autism. METHOD: A comprehensive review of the literature specific to somatosensory stimulation was conducted, resulting in six published studies that addressed interventions feasible within a child's daily routine. DISCUSSION: Although research related to somatosensory stimulation interventions is becoming more rigorous, empirical support remains limited; therefore, when these interventions are implemented, they should be systematically evaluated. PRACTICE IMPLICATIONS: To help occupational therapists recommend interventions with confidence, strategies are provided to (1) utilise best practices to intervene in an area in which evidence is limited, and (2) help expand the evidence base through clinical research.     

Chronic physical illnesses,mental health disorders,and psychological features as potential risk factors for back pain from childhood to young adulthood: a systematic review with meta-analysis

To report evidence of chronic physical illnesses, mental health disorders, and psychological features as potential risk factors for back pain in children, adolescents, and young adults. This systematic review and meta-analysis included cohort and inception cohort studies that investigated potential risk factors for back pain in young people. Potential risk factors of interest were chronic physical illnesses, mental health disorders (e.g. depression, anxiety), and other psychological features (e.g. coping, resistance). Searches were conducted in MEDLINE, Embase, CINAHL, and Scopus from inception to July 2019. Nineteen of 2167 screened articles were included in the qualitative synthesis, and data from 12 articles were included in the meta-analysis. Evidence from inception cohort studies demonstrated psychological distress, emotional coping problems, and somatosensory amplification to be likely risk factors for back pain. Evidence from non-inception cohort studies cannot distinguish between risk factors or back pain triggers. However, we identified several additional factors that were associated with back pain. Specifically, asthma, headaches, abdominal pain, depression, anxiety, conduct problems, somatization, and ‘feeling tense’ are potential risk factors or triggers for back pain. Results from the meta-analyses demonstrated the most likely risk factors for back pain in young people are psychological distress and emotional coping problems. Psychological features are the most likely risk factors for back pain in young people. Several other factors were associated with back pain, but their potential as risk factors was unclear due to risk of bias. Additional high-quality research is needed to better elucidate these relationships. These slides can be retrieved under Electronic Supplementary Material.     

Surgical ventricular reconstruction and subendocardial resection for the treatment of refractory ventricular tachycardia

We describe a case of 64-year-old female patient with ventricular tachycardia intractable to medical treatment and acute heart failure following myocardial infarction. Emergency surgical ventricular reconstruction and subendocardial resection was undertaken. We discuss the option of surgical intervention in this difficult and unusual clinical scenario.     

Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells

Using two different approaches, we have investigated the types of G proteins coupled to CC chemokine receptors. First, permeabilization of interleukin-2-activated natural killer (IANK) cells with streptolysin-O and introduction of anti-G protein antibodies inside these cells resulted in the following. (1) Anti-G(s), anti-G(o), and anti-G(z) inhibited the migration of IANK cells in response to macrophage- inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), or regulated on activation normal T cell expressed and secreted (RANTES). (2) Anti-Gi inhibited their migration in response to MCP-1 or RANTES but not in response to MIP-1 alpha. Second, incubation of IANK cell membranes with anti-G protein antibodies before incubating with (gamma-35S) GTP or (gamma-32P) GTP, resulted in the following. (1) Anti-G(s), anti-G(o), or anti-G(z) inhibited GTP binding and GTPase activity in the presence of MIP-1 alpha, or RANTES. (2) Anti- G(i) inhibited GTP binding and GTPase activity in the presence of MCP-1 or RANTES but not in the presence of MIP-1 alpha. The inhibitory effect of anti-G protein antibodies was reversed upon incubating these antibodies with their respective synthetic peptides before addition to IANK cell membranes. These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i).     

Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.     

Identification of a second transforming gene, rasn, in a human multiple myeloma line with a rearranged c-myc allele

Multiple myeloma is a disease characterized by a long, slowly progressive phase and a final, more aggressive one. Little is known about the mechanism of transformation of myeloma cells, although the clinical characteristics of the disease suggest a multi-step process. Recently, a myeloma cell line, NCI-H929, was isolated from a patient with aggressive preterminal disease and found to have a rearranged myc allele. This myeloma cell line has been further characterized in a focus formation assay to determine whether its unusual growth characteristics were associated with a second activated transforming gene. We now report that the NCI-H929 myeloma cell line has an activated rasn allele in addition to a rearranged myc allele. This is the first identification of an activated transforming gene in a multiple myeloma cell line; furthermore, the characterization of two independently activated oncogenes in this B cell malignancy has implications for both the pathogenesis and evolution of the disease.     

Prevalence of cluster headache in the Republic of Georgia: results of a population-based study and methodological considerations

We present a study of the general-population prevalence of cluster headache in the Republic of Georgia and discuss the advantages and challenges of different methodological approaches. In a community-based survey, specially trained medical residents visited 500 adjacent households in the capital city, Tbilisi, and 300 households in the eastern rural area of Kakheti. They interviewed all ( n  = 1145) biologically unrelated adult occupants using a previously validated questionnaire. The household responses rates were 92% in Tbilisi and 100% in Kakheti. The survey identified 32 persons with possible cluster headache, who were then personally interviewed by one of two headache-experienced neurologists. Cluster headache was confirmed in one subject. The prevalence of cluster headache was therefore estimated to be 87/100 000 (95% confidence interval < 258/100 000). We used a conservative approach, which has an obvious advantage of high-quality data collection, but is very demanding of manpower and time.