Family-based and case-control studies reveal no association of lipocalin-type prostaglandin D2 synthase with schizophrenia.

Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia.     

Diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia.

AIMS--(1) To assess the diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia (HCL); (2) to compare the immunostaining of bone marrow biopsy specimens with bone marrow and peripheral blood cytospins; (3) to evaluate the sensitivity of the different markers used; (4) to identify the ultrastructural localisation of DBA.44 in HCL variant. METHODS--Immunoenzymatic staining procedures, immunoperoxidase and immunoalkaline phosphatase, were used with a panel of monoclonal antibodies directed to HCL associated antigens. Ultrastructural immunostaining was performed using colloidal gold conjugated antibodies. RESULTS--HCL showed strong cytoplasmic reactivity for CD22, CD25, CD103, DBA.44, kappa, or lambda light chains. Peripheral blood diagnostic hairy cells were found in all the cases with absolute counts ranging from 0.11 x 10(9)/l up to 6.4 x 10(9)/l and values increasing with the size of the spleen. A median of 36.5% of leukaemic cells was found in bone marrow aspirates and 70% in bone marrow trephine specimens. The monoclonal antibodies CD22 and DBA.44 showed the highest and the lowest percentage of positive hairy cells, respectively; this difference was statistically significant (p = 0.0025). Ultrastructural immunolabelling with DBA.44 showed a cytoplasmic membrane localisation of the antigen in one case of HCL variant. CONCLUSIONS--(1) Immunocytochemistry is a useful technique which enhances the accuracy of diagnosis in HCL; (2) peripheral blood immunocytochemistry is recommended because it highlights hairy cells in all cases; (3) CD22 appears to be the most sensitive of the markers tested; (4) ultrastructural analysis is a useful tool in selected cases of HCL variant.     

Teaching and training in the psychiatric-psychosomatic consultation-liaison setting

BACKGROUND: The consultation-liaison (C-L) psychiatrist is in an opportune position to undertake the tasks of education, training and assessment of performance as regards future physicians, psychiatrists, specialists in other branches and nurses. This paper describes the education and training programme in the Psychiatric-Psychosomatic C-L Service of Modena University Hospital. DESCRIPTION OF THE PROGRAMME: This programme consists of the following main activities: (1) daily group-case supervision, performed by the full-time psychiatrist together with the psychiatry residents of the C-L staff; (2) a bimonthly quality management meeting, which is part of a European project of measurement and improvement of quality of service; (3) weekly lectures on selected topics; (4) monthly tutorials in research techniques; (5) bimonthly presentations of literature reviews; (6) weekly clinical case conferences, which are the nucleus of the curriculum and which focus on the following main topics: 'the patients', 'the intervention' and 'the group', and (7) liaison meetings requested by non-psychiatric departments. CONCLUSIONS: A common denominator seen throughout the teaching and training activities of such a programme is the attitude of openness and effort toward integration which should be the C-L psychiatrist's distinguishing mark, in the context of the general hospital.     

Noninvasive measurement of human forearm oxygen consumption by near infrared spectroscopy

Summary This study reported on the application of near infrared spectroscopy (NIRS) to noninvasive measurements of forearm brachio-radial muscle oxygen consumption ( O₂) and recovery time (t _r) in untrained volunteers. Seven healthy subjects were submitted to four consecutive protocols involving measurements made at rest, the induction of an ischaemia, and during a maximal increase of metabolic demand achieved with and without vascular occlusion. Two isometric maximal voluntary contractions (MVC) of 30-s duration were executed with and without vascular occlusion and a 50% MVC lasting 125 s was also performed. The protocols were repeated on 2 different days. The results showed that, during vascular occlusion at rest, the time to 95% of the final haemoglobin (Hb) + myoglobin (Mb) desaturation value was independent of O₂. The MVC, performed during vascular occlusion, caused complete Hb + Mb desaturation in 15–20 s, which was not followed by any further desaturation when the second contraction was performed. No difference was found between O₂during MVC with and without vascular occlusion. A consistent difference was seen between O₂measured during occlusion at rest and O₂measured during MVC with and without occlusion. During prolonged exercise (125 s) Hb + Mb desaturation was maintained for the whole contraction period. The results of this study show that O₂can be measured noninvasively by NIRS. The O₂during MVC was very similar both in the presence and absence of blood flow limitation in most of the subjects tested. This would suggest that muscle O₂might be accurately evaluated dynamically without cuff occlusion.     

Age-dependent changes in CXC chemokine ligand 10 serum levels in euthyroid subjects.

Circulating levels of cytokines are deeply influenced by aging, and few data about serum chemokines are available. The aim of this study was to evaluate the influence of aging on circulating CXCL10. One hundred forty healthy subjects (70 males and 70 females), 10-79 years of age, underwent fasting plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and CXCL8 serum assay. Thyroid hormone testing for thyroid-stimulating hormone (TSH), antithyroglobulin (AbTg), and antithyroperoxidase (AbTPO) autoantibodies and thyroid ultrasonography were performed in all subjects to exclude the presence of clinical or subclinical thyroid disease. Serum CXCL10 levels were assayed in all subjects and found to be increased in 14 of 70 females (20%) and in 4 of 70 males (5.7%) (p = 0.01). In a multiple linear regression model including age, body mass index (BMI), systolic and diastolic blood pressure, glycemia, total cholesterol, HDL, LDL, triglycerides, TSH, AbTPO, AbTg, and CXCL8, only age was significantly related to CXCL10 [C.R. 1.30 (0.28-2.33), p = 0.001]. No relationship was present between CXCL8 serum levels and age, suggesting a specificity of CXCL10 elevation as a function of age. Results of this study, performed in healthy subjects on an age gradient, demonstrate an increase in serum CXCL10 with advancing age overall in females, supporting the hypothesis of enhanced Th1 immune responses in aging.     

ATP receptors and giant cell formation

We have investigated the role of the purinergic P2X7 receptor in the formation of multinucleated giant cells in human monocyte/macrophage cultures stimulated with either concanavalin A or phytohemagglutinin. Macrophage fusion can be blocked by a P2X7-selective pharmacological antagonist or by a mAb directed against the extracellular P2X7 domain. Furthermore, macrophage cell clones expressing high P2X7 levels spontaneously fuse in culture, whereas macrophage clones lacking P2X7 are unable to fuse. Our findings suggest that the newly identified purinergic P2X7 receptor plays a central role in the complex chain of events leading to generation of macrophage-derived giant cells.     

Serious childhood respiratory infections and asthma in adult life. A population based study. ECRHS Italy. European Community Respiratory Health Survey.

BACKGROUND: A number of epidemiologic studies have tried to establish whether respiratory tract infections in early childhood cause obstructive pulmonary disease in adult life. OBJECTIVE: To determine whether reported serious respiratory infection before the age of 5 years (SRI) is a significant risk factor for subsequent development of bronchial asthma and/or bronchial hyperresponsiveness in adults. METHODS: We investigated a random population sample of 1,104 subjects (aged 20 to 40 years), participating in the European Respiratory Health Survey in Italy. Bronchial response to methacholine and answers to a standardized questionnaire were analyzed. RESULTS: The prevalence of SRI (ie, a positive response to the question "Have you ever had a serious respiratory infection before the age of 5 years?") was significantly higher in the subjects with a positive family history of allergic diseases than in those with a negative one (O.R. 1.89; 95% C.I. 1.24 to 2.87, P < .01). No relationship was found between SRI and current adult asthma; however, asthma in the past was found in 20.5% of the SRI positive subjects and in 9.1% of SRI negative subjects (O.R. 2.47; 95% C.I. 1.47 to 4.15, P < .05). No difference in the response to methacholine and in FEV1, FEV1/FVC values was found between SRI positive and SRI negative subjects. CONCLUSIONS: We suggest that a positive family history of atopy is associated with a significantly higher prevalence of SRI. Furthermore our results indicate that exposure to SRI is a risk factor for asthma in the past (ie, asthma in childhood and adolescence) but not for adult asthma or for the development of bronchial impairment in adult life.     

Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction

Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.     

Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features

Summary: CD40 is a member of the tumor necrosis factor receptor family, which is expressed by a variety of cells including B cells, macrophages, dendritic cells, and other nonimmune cell types. CD40 activation is critical for B‐cell proliferation, immunoglobulin (Ig)‐isotype switching, and germinal center formation. In physiological conditions, the activation of CD40 occurs by binding to its natural ligand, CD154, which is expressed on activated T cells. The in vivo critical role of CD40–CD154 interaction on B‐cell differentiation and isotype switching is provided by the discovery that mutations in either CD40 or CD154 gene cause the hyper IgM syndrome, termed HIGM3 or HIGM1, respectively, characterized by very low levels of serum IgG, IgA, and IgE, with normal or elevated IgM, associated with a defective germinal center formation. Originally considered humoral primary immunodeficiencies, the clinical features and the defect of T‐cell priming, resulting from a defective T–B cell or dendritic cell interaction, is now considered as combined immunodeficiencies. In this article, we present a comprehensive overview of the clinical, genetic, and immunological features of patients with hyper IgM syndrome due to CD40 mutations.