STAT-1 decoy oligonucleotide improves microcirculation and reduces acute rejection in allogeneic rat small bowel transplants.

During acute rejection leukocyte-endothelial cell interaction fuelled by costimulatory molecules such as the CD40/CD154 receptor/ligand dyad disrupts microcirculation of the small bowel. Downregulating endothelial CD40 expression by employing a decoy oligonucleotide (dODN) neutralizing the transcription factor signal transducer and activator of transcription-1 (STAT-1) may protect the graft. Therefore allogenic small bowel transplantation was performed in the Brown Norway to Lewis rat model. Graft vessels were pretreated with STAT-1 dODN, mutant control ODN (20 microM) or vehicle (n=8). CD40 antisense ODN and scrambled control ODN-treated transplants served as target control (n=3 each). Intravital microscopy, histology, immunohistochemistry and Western blot analyses were performed 7 days later. Functional capillary density, red blood cell velocity and perfusion index in STAT-1 dODN and CD40 antisense ODN-treated transplants were improved whereas stasis index was reduced. Leukocyte-endothelial cell interaction showed no difference. Histological parameters of rejection, infiltrating CD3-positive cells and apoptotic bodies were also reduced in STAT-1 dODN and CD40 antisense ODN-treated transplants 7 days post-transplantation. CD40 protein abundance was reduced to less than 10% of control in STAT-1 dODN-treated grafts. STAT-1 dODN blockade of CD40 expression improves mucosal perfusion, reduces graft rejection, T-cell infiltration and apoptosis in rat small bowel allografts during acute rejection.

Discriminant validity of the Wender Utah Rating Scale for attention-deficit/hyperactivity disorder in adults.

The authors examined the factor structure and discriminant validity of the Wender Utah Rating Scale (WURS) in adults seeking evaluation for attention-deficit/hyperactivity disorder (ADHD). Three factors (Dysthymia, Oppositional/Defiant Behavior, and School Problems) accounted for 59.4% of the variance. In a stepwise discriminant function analysis, age and childhood school problems emerged as significant variables. The classification procedure correctly classified 64.5% of patients. Among those who did not have ADHD, only 57.5% were correctly classified compared with 72.1% among those with ADHD. The WURS is sensitive in detecting ADHD, but it misclassifies approximately half of those who do not have ADHD.

Adult attention-deficit hyperactivity disorder: assessment guidelines based on clinical presentation to a specialty clinic.

Of 143 adults presenting for attention-deficit hyperactivity disorder (ADHD) evaluation, 46 (32%) clearly met diagnostic criteria, 46 (32%) clearly did not meet diagnostic criteria, and another 51 (36%) with current ADHD-like features did not meet criteria due to either a lack of childhood history and/or complicating severe psychiatric or substance abuse comorbidity. The three groups were similar in demographics, psychiatric diagnosis, psychiatric symptom severity, and functional impairment. Compared with the group not meeting ADHD criteria, patients with ADHD had more frequent histories of learning disability in childhood, poorer reading scores on the Wide-Range Achievement Test (WRAT), poorer scores on the Continuous Performance Test (CPT), and higher scores on the Wender-Utah Rating Scale (WURS) for ADHD. Patients in the ambiguous ADHD category had higher rates of current substance abuse than the other two groups. While this group resembled the non-ADHD group in having a low incidence of learning disability and normal reading scores, their poor performance on the CPT and high scores on the WURS more closely resembled those of ADHD patients. These findings suggest that there are a few rating scales, testing instruments, and lifetime history characteristics that help to clarify the difficult diagnostic distinction between adult patients who do and do not have ADHD.