Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice

T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation.     

Corticomotoneuronal dysfunction in ALS patients with different SOD1 mutations.

OBJECTIVE: To examine corticomotoneuronal function in amyotrophic lateral sclerosis (ALS) patients carrying superoxide dismutase 1 (SOD1) mutations using peristimulus time histograms (PSTH). METHODS: Six I113T, 3 A4V, one G41D and one G114A patient were studied along with 21 healthy control subjects. Analyses included comparison with previously reported data from 8 D90A homozygous and 12 sporadic ALS (SALS) patients examined by the authors using identical methodology. RESULTS: Cortical threshold was significantly reduced in A4V patients (41.3%) compared to I113T (58%), SALS (57%) and D90A (71%) patients, as well as healthy controls (49.7%). Estimated excitatory postsynaptic potentials (EPSPs) were significantly larger in A4V patients (4.39 mV) compared to healthy controls (2.95 mV), I113T (2.71 mV) and SALS (2.39 mV) patients. Clinical features and PSTH parameters in I113T were similar to SALS, however, PSTH primary peaks (PP) were significantly more dispersed, 9.5 ms compared to 4ms in SALS. PSTHs from single G41D and G114A patients were unremarkable, apart from large EPSP amplitudes in the G114A patient. CONCLUSIONS: ALS patients with A4V and I113T SOD1 mutations have distinctive corticomotoneuronal changes that are different from those in D90A homozygous and SALS patients. SIGNIFICANCE: PSTH studies should be considered for future in vivo studies of SOD1 pathophysiology in ALS.     

Combining treatment for written and spoken naming.

Individuals with left-hemisphere damage often have concomitant impairment of spoken and written language. Whereas some treatment studies have shown that reading paired with spoken naming can benefit both language modalities, little systematic research has been directed toward the treatment of spelling combined with spoken naming. The purpose of this study was to examine the therapeutic effect of pairing a lexical spelling treatment referred to as Copy and Recall Treatment (CART) with verbal repetition of target words. This approach (CART + Repetition) was compared with treatment using verbal repetition without the inclusion of orthographic training (Repetition Only). Two individuals with moderate aphasia and severe impairment of spelling participated in the study using a multiple baseline design across stimulus sets and treatment conditions. Both participants improved spelling of targeted words as well as spoken naming of those items, but improvement in spoken naming was marked for one individual in the CART + Repetition condition, while the other participant made smaller gains in spoken than written naming irrespective of treatment condition. Consideration of the participant profiles suggested that CART + Repetition provides greater benefit when there is some residual phonological ability and the treatment serves to stimulate links between orthography and phonology.     

What should nurse teachers be doing? A preliminary study

There is little doubt that the role of the nurse teacher is complex and multifaceted in nature. The apparently conflicting demands of NHS trusts and education in the United Kingdom, at the time of integration of nurse education into the higher education sector, further complicates the role. This recognition underlines the need to capture and measure key aspects of nurse teacher function in order to maximize educational gain. Using a comprehensive literature review, focus group discussions and a small number of individual semi-structured interviews, this preliminary study explored the issue of teacher workload, from the perspective of the principal stakeholders in nurse and higher education. Competing research and clinical practice objectives for nurse teachers are identified against a background of changing health care provision, reduced availability of placements and an increased need for evidence-based practice.     

Successful Treatment of Kasabach-Merritt Syndrome with Prednisone and Epsilon-Aminocaproic Acid

The Kasabach-Merritt syndrome is characterized by thrombocytopenia and localized coagulopathy associated with a hemangioma. Most techniques applied to eradicate the tumor or accelerate its involution (surgery, radiation therapy, embolization) are invasive and require transfusion of large amounts of blood products. In some cases, medical treatment is the only alternative. Efficacy of steroids and antifibronolytic agents has already been described, but even this approach is associated with the administration of blood products. We report two cases of infants with Kasabach-Merritt syndrome associated with cardiac and hepatic hemangiomas. At admission, both had signs of cardiac failure. They were successfully treated with prednisone and epsilon-aminocaproic acid (EACA). Blood products were not required once the diagnosis was made. These observations have important implications for the management of patients with Kasabach-Merritt syndrome because they show that even in severe cases blood transfusions can be avoided by the use of prednisone and EACA.     

Prevalence of mental illness and its impact on the use of home care and nursing homes: a population-based study of older adults in Manitoba.

OBJECTIVES: To determine the prevalence of mental illness in older adults and its effect on home care and personal care home (PCH) use. METHODS: Using nonidentifying administrative records (fiscal years 1997-1998 to 2001-2002) from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy, we determined the 5-year period prevalence for individuals aged 55 years and over (119 539 men and 145 752 women) for 3 mental illness categories: cumulative mental disorders (those having a diagnosis of depression, anxiety disorder, personality disorder, schizophrenia, and [or] substance abuse), any mental illness, and dementia. We calculated age-specific and age-adjusted rates of home care and PCH use and the prevalence of mental illness in PCH residents. RESULTS: From the group aged 55 to 59 years to the group aged 90 years or older, the prevalence of mental illness increased with the population's age. The prevalence of any mental illness rose from 32.4% to 45.0% in men and from 42.6% to 51.9% in women, and dementia prevalence rose from 2.0% to 33.6% in men and from 1.3% to 40.3% in women. The age-adjusted annual rates of open home care cases per 1000 population aged 55 and older varied by mental illness grouping (no mental disorder, 57 for men and 91 for women; cumulative mental disorders, 162 for men and 191 for women; dementia, 300 for men and 338 for women). The age-adjusted rates of PCH use per 1000 population aged 75 years and older also varied by mental illness grouping (no mental disorder, 53 for men and 78 for women; cumulative mental disorders, 305 for men and 373 for women; dementia, 542 for men and 669 for women). Among patients admitted to (or resident in) a PCH in 2002-2003, 74.6% (87.1%) had a mental illness, and 46.0% (69.0%) had dementia. CONCLUSIONS: Mental illness affects the use of home care and nursing homes profoundly. Individuals with dementia used home care at 3 times the rate of those having no mental illness diagnosis, and they used PCHs at 8 times the rate.     

The effects of norepinephrine transporter inactivation on locomotor activity in mice.

BACKGROUND: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. RESULTS: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.