A randomised controlled trial to test the feasibility of a collaborative care model for the management of depression in older people

BACKGROUND: Depression is the most common mental health disorder in people aged over 65 years. Late-life depression is associated with chronic illness and disability. AIM: To investigate the feasibility of a collaborative care model for depression in older people in a primary care setting. DESIGN OF STUDY: Randomised controlled trial with 16-weeks follow up. SETTING: A primary care trust in Manchester. METHOD: Participants were 105 people aged 60 years or older who scored 5 or more on the Geriatric Depression Scale; 53 were randomly allocated to an intervention group and 52 to a usual care group. The intervention group received care managed by a community psychiatric nurse who delivered an intervention comprising a facilitated self-help programme with close liaison with primary care professionals and old-age psychiatry according to a defined protocol. The usual care group received usual GP care. A nested qualitative study explored the views of the health professionals and patients regarding the acceptability and effectiveness of the intervention. RESULTS: The main outcome measure was recovery from depression. Patients in the intervention group were less likely to suffer from major depressive disorder at follow up compared with usual care (0.32, 95% confidence = interval = 0.11 to 0.93, P = 0.036). The qualitative component of the study demonstrated the acceptability of the intervention to patients. CONCLUSION: A model of collaborative care for older people with depression, used in a primary care setting with a facilitated self-help intervention is more effective than usual GP care. This study demonstrates that the implementation of a collaborative care model is feasible in UK primary care and that the intervention is effective and acceptable to patients.     

TNF revisited: TNF-independent antitumor activity in sera of mice sensitized with Propionibacterium acnes and challenged with lipopolysaccharide

Sera of mice sensitized with bacteria and subsequently challenged with lipopolysaccharide promote hemorrhagic necrosis of tumors in vivo and display cytotoxic activity against tumor cells in vitro, which has been attributed to the induction of tumor necrosis factor (TNF). Here, we describe the induction of a previously unrecognized antitumor activity in such sera, which is distinct from TNF but displays tumor-specific cytocidal activity in vitro as well as potent tumor-regressing activity in vivo. Biochemical analysis of this activity yielded a molecular mass of approximately 150 kDa, closely resembling a novel tumoricidal factor of murine macrophages (Mphi) termed MTC 170 (Mphi tumor cytotoxin, approximate molecular mass 170 kDa), which we have previously proposed to constitute a major effector pathway for the destruction of tumor cells by activated Mphi.     

Engineering porcine arteries: effects of scaffold modification

Techniques have been developed to culture bovine or porcine vascular cells on polyglycolic acid (PGA) scaffolds to form engineered vessels. Previously, it was shown that smooth muscle cells (SMCs) that were in close proximity to PGA remnants after 8 weeks of culture had lower expression of SMC markers of differentiation and were more mitotic compared with SMCs that were distant from polymer residuals. Modifications of PGA were explored as a means to minimize residual polymer fragments after culture. To hasten degradation, polymer was treated with heat, NaOH, or gamma-irradiation. Differential scanning calorimetry, mass and tensile strength degradation, and inherent viscosity were used to assess polymer characteristics. When polymer was maintained in aqueous conditions, tensile strength of treated PGA degraded to zero within 3 weeks for each treatment. Engineered vessel constructs cultured on NaOH and gamma-treated polymer displayed smooth muscle alpha-actin throughout the vessel wall. Scaffold treatment impacted graft morphology, cellular differentiation, and mechanical integrity.     

Uncovering novel inter- and intrachromosomal chromosome 1 aberrations in follicular lymphomas by using an innovative multicolor banding technique

Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21), which is the initial genetic perturbation in this disease. Additional genetic mutations are required to generate a fully malignant phenotype. Secondary chromosomal alterations seen in FL include prominent involvement of chromosome 1 in the form of balanced or unbalanced translocations, insertions, deletions, and duplications involving both the p and q arms. We investigated a diagnostically well defined set of 55 t(14;18)-positive FL cases with complex karyotypes by means of multicolor karyotyping. Sixteen cases showed involvement of chromosome 1 and were analyzed in further detail by a novel multicolor banding technique for this chromosome. We defined three groups showing varying complexity of chromosome 1 alterations. The first group revealed simple translocations, such as t(1;2), t(1;6), t(1;8), and t(1;17), involving breakpoints on either the p or the q arm of chromosome 1. The second group showed more complex rearrangements with translocations, insertions, regional duplications, and involvement of more than one partner chromosome with either the p or the q arm of chromosome 1. The third group was defined by highly complex rearrangements involving translocations, regional duplications, amplifications, and intrachromosomal band relocations affecting the entire chromosome 1. All three groups shared interchromosomal rearrangements of chromosome 1 with chromosome 8, often involving the MYC protooncogene site, amplification involving region 1q21-q31, and deletion involving region 1p36. Thus, the use of sophisticated multicolor molecular cytogenetic assays in the investigation of malignant lymphoma allows precise characterization of chromosomal alterations and will provide a better understanding of their biology.     

Mode of delivery and risk of developing allergic disease

The aim of this study was to quantify the relationship between mode of delivery and subsequent incidence of allergic disease. The analysis is based on data derived from a birth cohort of 24,690 children who contributed data to the West Midlands General Practice Research Database. We found no convincing evidence to suggest that babies born by caesarean, forceps, or breech delivery had an increased risk of developing allergic disease.     

Immunohistochemical localization of pepsinogen A and C containing cells in Barrett's oesophagus

Summary No data are available on the localization of Pepsinogen A (PGA=PG I) and Pepsinogen C (PGC=PG II) positive cells in Barrett's epithelium. Endoscopic biopsy specimens were taken from the columnar epithelium from 23 patients (n=93), and in addition from the cardia from eight healthy control subjects (n=38). The tissue was stained by the immunoperoxidase technique with specific anti-pepsinogen antisera, and double immunostained for PGA and PGC. In the Barrett's epithelium PGA was found in 28 out of 93 biopsy specimens (30.1%) and PGC in 55 out of 93 (59.1%). Chief cells always stained both for PGA and PGC, while clear mucous cells were often PGA– and PGC+. PGA+ and PGC+ cells were found each in 100% of the biopsy specimens with fundic type epithelium, in 21.7% and 70.7% of biopsy specimens with junctional type, in 0% and 26.1% of biopsy specimens with specialized epithelium and in 12.5% and 43.5% of biopsy specimens with mixed junctional/specialized features respectively. Dysplastic epithelium stained always negatively with both anti-pepsinogen antisera. In most control cardia biopsy specimens PGA as well as PGC were demonstrable; occasionally clear mucous glands were PGA– and PGC+.It is concluded that pepsinogen-containing cells can be accurately identified in the Barrett's epithelium; their presence seems related to the histological cell type. Identification of pepsinogen positive cells may contribute to a more accurate morphological classification of the Barrett's epithelium.Presented in part at the Annual Meeting of the American Gastroenterological Association, San Francisco, May 1986     

Hepatic gluconeogenesis and Krebs cycle fluxes in a CCl4 model of acute liver failure

Acute liver failure was induced in rats by CCl4 administration and its effects on the hepatic Krebs cycle and gluconeogenic fluxes were evaluated in situ by 13C NMR isotopomer analysis of hepatic glucose following infusion of [U-13C]propionate. In fed animals, CCl4 injury caused a significant increase in relative gluconeogenic flux from 0.80+/-0.10 to 1.34 +/-0.24 times the flux through citrate synthase (p<0.01). In 24-h fasted animals, CCl4-injury also significantly increased relative gluconeogenic flux from 1.36+/-0.16 to 1.80+/-0.22 times the flux through citrate synthase (p<0.01). Recycling of PEP via pyruvate and oxaloacetate was extensive under all conditions and was not significantly altered by CCl4 injury. CCl4 injury significantly reduced hepatic glucose output by 26% (42.8+/-7.3 vs 58.1+/-2.4 micromol/kg/min, p=0.005), which was attributed to a 26% decrease in absolute gluconeogenic flux from PEP (85.6+/-14.6 vs 116+/-4.8 micromol/kg/min, p<0.01). These changes were accompanied by a 47% reduction in absolute citrate synthase flux (90.6+/-8.0 to 47.6+/-8.0 micromol/kg/min, p<0.005), indicating that oxidative Krebs cycle flux was more susceptible to CCl4 injury. The reduction in absolute fluxes indicate a significant loss of hepatic metabolic capacity, while the significant increases in relative gluconeogenic fluxes suggest a reorganization of metabolic activity towards preserving hepatic glucose output.     

Predicting protein cellular localization using a domain projection method

We investigate the co-occurrence of domain families in eukaryotic proteins to predict protein cellular localization. Approximately half (300) of SMART domains form a "small-world network", linked by no more than seven degrees of separation. Projection of the domains onto two-dimensional space reveals three clusters that correspond to cellular compartments containing secreted, cytoplasmic, and nuclear proteins. The projection method takes into account the existence of "bridging" domains, that is, instances where two domains might not occur with each other but frequently co-occur with a third domain; in such circumstances the domains are neighbors in the projection. While the majority of domains are specific to a compartment ("locale"), and hence may be used to localize any protein that contains such a domain, a small subset of domains either are present in multiple locales or occur in transmembrane proteins. Comparison with previously annotated proteins shows that SMART domain data used with this approach can predict, with 92% accuracy, the localizations of 23% of eukaryotic proteins. The coverage and accuracy will increase with improvements in domain database coverage. This method is complementary to approaches that use amino-acid composition or identify sorting sequences; these methods may be combined to further enhance prediction accuracy.     

Activated T-Lymphocytes Express Occludin, a Component of Tight Junctions

T-lymphocytes routinely traffic from the lymphoid and vascular compartments to the tissues during immune surveillance and inflammatory responses. This egress occurs without compromising endothelial barrier, which is maintained by tight junctions (zonula occludens). We report that T-lymphocytes up-regulate the expression of occludin, a major component of the tight junction in response to stimulation with phorbol ester (PMA) + calcium ionophore, CD3 antibody or T-cell receptor (TCR) antibody. Only activated T-lymphocytes express occludin; this adhesion molecule is nearly absent in resting T-lymphocytes. By immunofluorescence, occludin is seen in lymphocyte aggregates, but does not appear to mediate aggregation since only 50% of the cells in these clusters express occludin. Occludin is expressed between 8 and 24 h following stimulation, and persists for at least 48 h. These data indicate that activated T cells produce occludin which may regulate lymphocyte adhesion and trafficking.     

Studies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89.6P challenge in DNA/MVA-vaccinated macaques

Here, we study immune responses in four DNA/MVA-vaccinated macaques following an SHIV-89.6P challenge and a subsequent CD8 cell depletion. Both post-challenge and post-depletion peaks of viremia contracted with the expansion, or re-emergence, of CD8 T cells. Post-depletion, CD8 cells expanded in the presence of higher levels of neutralizing Ab and CD4 help than post-challenge and had superior maturational characteristics as measured by expression of the anti-apoptotic protein Bcl-2, the IL-7 receptor CD127 and co-production of IFN-gamma and IL-2. Pre-challenge and pre-depletion titers of neutralizing Ab correlated inversely with peaks of viremia and directly with peaks for anti-viral CD4 cells. Thus, our results reveal CD8 cells playing a central role, and neutralizing Ab, a supporting role in SHIV-89.6P control. They also suggest a dynamic relationship between neutralizing Ab, antigen load and anti-viral CD4 cells in the maturation of high-quality anti-viral CD8 T cells.