Psychological screening and the success of donor insemination

In a previous case series, a psychologist‘s rating ofcouples’ emotional adjustment and readiness for donorinsemination was predictive of pregnancy rates. We attemptedto replicate this finding with an extended series of 120 consecutivecouples in which each spouse filled out questionnaires whenevaluated for donor insemination. The Stress and InfertilityQuestionnaire measured specific attitudes and anxieties aboutdonor insemination. The Brief Symptom Inventory assessed psychologicaldistress. The Dyadic Adjustment Scale measured marital happiness.A psychologist used these questionnaires to rate the couple‘soverall adjustment in regard to donor insemination. Those couplesrated as distressed had a session of psychological counselling.Outcome was reviewed at a mean of 20 months after evaluation,with categories of pregnancy, continuing donor insemination,failure to begin the programme, or dropped out. For the 120couples overall, psychological factors did not predict pregnancyoutcome. Younger age of the wife did predict higher pregnancyrates     

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.     

Adenoviral transfer of the murine oncostatin M gene suppresses dextran-sodium sulfate-induced colitis.

The use of biologics has promising potential in the treatment of inflammation. Studies with cultured cells and mouse models of disease have ascribed proinflammatory and anti-inflammatory functions to oncostatin M (OSM) and the related cytokine, interleukin-6 (IL-6). Here, we examined the effect of systemic administration of adenoviral (Ad) vectors encoding either murine OSM (AdMuOSM) or murine IL-6 (AdMuIL-6) in a mouse model of colitis. BALB/c mice were treated with a 5-day course of 4% dextran-sodium sulfate (DSS) water with or without administration of adenoviral vectors (i.p. or i.m. at 10(7) plaque-forming units [pfu]) given as a cotreatment or therapy. The deletion variant of the adenovirus served as a control for adenoviral infection. Colitis was assessed by (1) morphology (damage score, macrophage infiltration, apoptosis) and (2) function (myeloperoxidase activity and Ussing chamber analysis of epithelial ion transport). Infection with adenovirus alone did not affect colonic form or function. AdMuOSM (either i.p. or i.m.) significantly reduced the severity of the DSS-induced colitis. There was less damage, reduced macrophage infiltration, fewer apoptotic bodies, and a significant improvement in stimulated ion transport in colonic tissues from the treated mice. No benefit of AdMuIL-6 treatment was observed in this model system. Thus, systemic administration of AdMuOSM given as a cotreatment and to a lesser extent as a therapy was found to be of benefit in DSS-induced colitis, a murine model of inflammatory bowel disease (IBD).     

GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies

A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABAA receptor delta subunit, affects GABA current amplitude consistent with a model of polygenic susceptibility to epilepsy in humans. We have found a GABRD Glu177Ala variant which is heterozygously associated with generalized epilepsy with febrile seizures plus. We also report an Arg220His allele in GABRD which is present in the general population. Compared with wild-type receptors, alpha1beta2Sdelta GABAA receptors containing delta Glu177Ala or Arg220His have decreased GABAA receptor current amplitudes. As GABAA receptors mediate neuronal inhibition, the reduced receptor current associated with both variants is likely to be associated with increased neuronal excitability. Since delta subunit-containing receptors localize to extra- or peri-synaptic membranes and are thought to be involved in tonic inhibition, our results suggest that alteration of this process may contribute to the common generalized epilepsies.     

Preoperative chemoradiotherapy alters the expression and prognostic significance of adhesion molecules in Barrett's-associated adenocarcinoma

A variety of prognostic markers have been related to decreased patient survival in patients with epithelial malignancies. These include expression of the homotypic adhesion molecule E-cadherin (ECAD) and the hyaluronic acid receptor CD44. Expression of ECAD and CD44 was evaluated in Barrett's-associated adenocarcinoma (BAd) from 67 patients. Expression was determined by immunoperoxidase staining and graded semiquantitatively based on the proportion of positively stained cells. These data were then correlated with clinical and pathological parameters, including the presence or absence of chemoradiotherapy (chemrad) and patient survival. There were 56 men and 11 women (mean age, 62 years). Thirty-nine (58%) patients received preoperative chemrad. ECAD expression was detected in all (100%) tumors. The ECAD staining grade did not correlate with other pathological features of the tumors. However, ECAD staining was significantly increased in BAd of patients who received chemrad (P = .003), in comparison with those who did not, and in individual patients when prechemrad biopsies and postchemrad resection specimens were compared (P = .04). In terms of prognosis, increased ECAD expression was associated with shortened patient survival only in BAd patients who had received chemrad (univariate analysis of chemrad patients with stage I and II BAd, P = .02). ECAD expression was not significantly associated with survival in BAd patients who did not receive chemrad. CD44 expression was detected in 88% of cases. CD44 expression did not correlate with any of the pathological features of the tumors or with chemrad status. Increased expression of CD44 was significantly associated with shortened patient survival in chemrad patients only (univariate analysis P = .03, multivariate analysis P = .04), although a strong trend was observed when all patients were analyzed regardless of chemrad status (P = .07). The results of this study indicate that chemrad alters the expression of ECAD in BAd. Thus, the prognostic utility of ECAD expression must be evaluated in the context of chemrad status. CD44 also may be a valuable prognostic marker in BAd.     

Immunological mechanisms in the maintenance of pregnancy

Mmammalian pregnancy involves prolonged, intimate interactions between genetically dissimilar organisms. This dissimilarity evokes an immunological response in the gravida which promotes placental implantation and fetal viability. The nature of the immunological reactions, the factors moderating these responses and the signficance of abnormalities in the responses are discussed.     

Prevention of spinal cord injury: an elementary education approach.

Spinal cord injury (SCI) results in permanent paralysis and most often happens to teenagers and young adults. High risk behaviors are most often the cause; therefore these injuries are often preventable. In response to a gap in existing prevention programs, an elementary age SCI prevention program was developed, designed for implementation by teachers. Evaluation was carried out via a quasi-experimental pre-post comparison group design. Experimental students demonstrated significantly improved knowledge of SCI and its prevention. Similar changes in self-reported safety belt use were not noted. Development of the curriculum, related grant activities, and plans for national dissemination are described.     

Association study of a SNAP‐25 microsatellite and attention deficit hyperactivity disorder

Several lines of evidence implicate synaptosomal‐associated protein of 25 kDa (SNAP‐25) in the etiology of attention deficit hyperactivity disorder (ADHD). Most notably, the coloboma mouse mutant, considered to be a good animal model of hyperactivity, has a deletion spanning this gene. Introducing a SNAP‐25 transgene into these animals alleviates hyperlocomotion. We have identified a novel microsatellite repeat in SNAP‐25 located between the 5′UTR and the first coding exon, and tested for association with ADHD. Case‐control analyses suggest there may be a role of this polymorphism in ADHD, with one allele over‐represented in controls and another over‐represented in probands. Within‐family tests of linkage and association confirmed these findings. Further work is needed to ascertain the role of SNAP‐25 in ADHD and assess the functional significance of this polymorphism. © 2002 Wiley‐Liss, Inc.     

Endoscopic ultrasound-guided fine-needle aspiration cytology of peripheral nerve-sheath tumors

Endoscopic ultrasound (EUS) has allowed for the fine-needle aspiration and diagnosis of many different gastrointestinal neoplasms, including mesenchymal tumors. Although most mesenchymal tumors of the gastrointestinal tract are gastrointestinal stromal tumors (GISTs), other mesenchymal tumors, including neural tumors, do occur. Proper diagnosis and differentiation of these tumors from GISTs are important because of their different prognoses and treatment regimens. We encountered three peripheral nerve-sheath tumors of the gastrointestinal tract aspirated by EUS (two schwannomas and a granular-cell tumor). We report on the endoscopic ultrasound, cytologic, histologic, and immunohistochemical findings of these cases.