Cartilage hair hypoplasia with cutaneous lymphomatoid granulomatosis

Cartilage–hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short‐stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi‐allelic RMRP gene mutation. At 13 years, the patient developed an Epstein–Barr virus (EBV)‐driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV‐associated low‐grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV‐associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV‐associated cutaneous malignancy in CHH.     

Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.     

Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database

Lung - Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and...     

Using Interpretation Bias Modification to Reduce Anger in Veterans with Posttraumatic Stress Disorder: A Pilot Study

Difficulty controlling anger is the most commonly reported reintegration concern among veterans with posttraumatic stress disorder (PTSD). One of the mechanisms associated with problematic anger is a tendency to interpret ambiguous interpersonal situations as hostile, known as the hostile interpretation bias (HIB). A computer-based interpretation bias modification (IBM) intervention has been shown to successfully reduce HIB and anger but has not been tested in veterans with PTSD. The current study was a pilot trial of this IBM intervention modified to address problematic anger among veterans with PTSD. Veterans with PTSD and a high level of anger (N = 7) completed eight sessions of IBM treatment over the course of 4 weeks. Participants completed self-report questionnaires at pre- and posttreatment assessment visits, as well as a treatment acceptability interview at posttreatment. Veterans experienced large reductions in hostile interpretation bias and anger from pre- to posttreatment, ds = 1.03–1.96, although these estimates may be unstable due to the small sample size. The feasibility for recruitment, retention, and treatment completion were high. Questionnaire and interview data demonstrated that most participants were satisfied with the treatment and found it helpful and easy to use. Overall, IBM for anger was feasible and acceptable to veterans with PTSD and was associated with reductions in hostile interpretations and self-reported anger outcomes. Further research examining this approach is warranted.     

Delivering Prolonged Exposure Therapy via Videoconferencing During the COVID-19 Pandemic: An Overview of the Research and Special Considerations for Providers

Leveraging technology to provide evidence-based therapy for posttraumatic stress disorder (PTSD), such as prolonged exposure (PE), during the COVID-19 pandemic helps ensure continued access to first-line PTSD treatment. Clinical video teleconferencing (CVT) technology can be used to effectively deliver PE while reducing the risk of COVID-19 exposure during the pandemic for both providers and patients. However, provider knowledge, experience, and comfort level with delivering mental health care services, such as PE, via CVT is critical to ensure a smooth, safe, and effective transition to virtual care. Further, some of the limitations associated with the pandemic, including stay-at-home orders and physical distancing, require that providers become adept at applying principles of exposure therapy with more flexibility and creativity, such as when assigning in vivo exposures. The present paper provides the rationale and guidelines for implementing PE via CVT during COVID-19 and includes practical suggestions and clinical recommendations.     

Membrane glycoproteins and platelet cytoskeleton in immune complex- induced platelet activation

To clarify the mechanism of platelet activation by immune complexes and the possible involvement of surface glycoproteins (GPs), we studied platelet activation induced by heat-aggregated IgG (HAG). We examined the effects of monoclonal antibodies (MoAbs) against GPIb, GPIIb/IIIa, and the Fc receptor on resting platelets and on platelets stimulated by HAG. HAG increased the cytosolic ionized calcium concentration ([Ca2+]i) and stimulated protein (P47 and P20) phosphorylation, phosphatidic acid (PA) synthesis, serotonin secretion, and platelet aggregation. IV.3, an anti-Fc gamma RII receptor MoAb, inhibited HAG binding to platelets and all subsequent platelet responses. Like IV.3, MoAbs against GPIIb/IIIa (Tab, 10E5, AP-3) or GPIb (AP-1, 6D1) strongly inhibited platelet activation by HAG. However, while anti-GPIIb/IIIa MoAbs inhibited binding of IV.3 and HAG to platelets, anti-GPIb MoAbs had little effect on platelet binding of IV.3 or HAG. These observations suggest a close topographical and functional association of GPIIb/IIIa with Fc gamma RII in the platelet response to HAG. Cytochalasin B, an inhibitor of actin polymerization, also inhibited platelet activation but not HAG or IV.3 binding. Measurement of the fluorescence of 7-nitrobenz-2-oxa-1,3-(NBD)-phallacidin, a specific marker for filamentous actin (F-actin), showed that both cytochalasin B and AP-1 blocked the increase of F-actin induced by HAG. The common effects of anti-GPIb MoAbs and of cytochalasin B suggest that unlike the activity of GPIIb/IIIa, the ability of anti-GPIb to inhibit the activation of platelets by immune complexes is associated with perturbation of the cytoskeleton.     

Rejection is less common in children undergoing liver transplantation for hepatoblastoma

To compare the incidence of acute histologically proven rejection in children who have had a liver transplant for hepatoblastoma with a control group of children transplanted for biliary atresia (EHBA). A retrospective case notes based study was performed. Twenty patients were identified with hepatoblastoma who were transplanted at a single unit between 1991 and 2008. These were matched as closely as possible for age, gender, year of transplant and type of immunosuppression used to the control group transplanted for biliary atresia (n = 60). There was a significant decrease in rate of acute rejection as assessed by the rejection activity index (RAI) in the hepatoblastoma group (75% vs. 50%, respectively, p < 0.04). Chronic rejection was rare in both groups, but twice as common in the biliary atresia group. Equal levels of immunosuppression were achieved in both groups. Renal function was noted to be reduced one yr post‐transplant in both groups, as previously reported. A modified immunosuppression regimen could be considered in children with hepatoblastoma undergoing liver transplantation.     

Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.

The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mice was found to produce a disseminated pattern of leukaemia similar to that seen in man. The intravenous injection of 10(7) HSB-2 cells was associated with a universally fatal leukaemia. Histopathological examination of animals revealed the spread of leukaemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to the ribosome-inactivating protein saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. When SCID mice were injected with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous dose of 10 micrograms of immunotoxin there was a significant therapeutic effect evidenced by the numbers of animals surviving in the therapy group compared with untreated controls (chi 2 = 5.348, P = 0.021). These results demonstrate the useful application of human leukaemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 immunotoxin in human T-ALL.