IL-6 Expression in Neurons of Transgenic Mice Causes Reactive Astrocytosis and Increase in Ramified Microglial Cells but no Neuronal Damage

Growing evidence suggests that aberrant production of inflammatory cytokines within the central nervous system (CNS) contributes to the development of pathological conditions. To test the cause—effect relationship between the overproduction of interleukin-6 (IL-6) in the CNS and the onset of neuropathological changes, we have generated transgenic mice in which human IL-6 expression has been targeted to the neurons by using the rat neuron-specific enolase promoter. These mice develop reactive astrocytosis and an increase in ramified microglial cells but do not show histological or behavioural signs of neuron damage at the light microscope level. We thus conclude that a constant release of human IL-6 by neuronal subpopulations in mice is sufficient to activate cells potentially capable of modulating the local immune response, but at the same time is compatible with normal neuron functions.     

Proposal for a standardized interpretation of the atopy patch test in children with atopic dermatitis and suspected food allergy

The interpretation of the atopy patch test (APT) to foods is not standardized. This study aimed to validate the reading of the APT in terms of the diagnostic accuracy of individual skin signs. Eighty-seven children (mean age 2.4 +/- 2.5 yr, range 0.5-13.5; 57 male) with atopic dermatitis (AD) and suspected food allergies underwent APT to cow's milk, hen's egg, wheat and soy. Twelve-millimetre Finn chambers were applied for 48 h, and results were read after 48 and 72 h. Skin changes were graded for erythema, induration, papule formation and 'crescendo' phenomenon (increase of skin sign severity from 48 to 72 h). Food allergy was assessed by double blind, placebo-controlled food challenges (DBPCFC). Sensitivity, specificity and predictive values were calculated for each skin signs in relation to challenge outcome. Of 165 DBPCFC children, 75 (45%) were positive. The combination of any skin induration plus papules (seven or more), or of moderate erythema plus any induration plus seven or more papules had a positive predictive value (PPV) and specificity for the challenge outcome of 100%; however, the sensitivity was low (8% and 15%). The best diagnostic accuracy for single signs was found for induration beyond the Finn chamber margin (PPV 88%, specificity 99%, sensitivity 9%) and presence of at least seven papules (PPV 80%, specificity 96% sensitivity 21%). Presence of both induration and of at least seven papules at 72 h were the APT skin signs with the greatest diagnostic accuracy for food allergy in children with AD.     

Left Ventricular Volume Reduction for End-Stage Heart Disease

Abstract Partial left ventriculectomy (PLV) was recently introduced for end-stage dilated cardiomyopathy to improve ventricular function. Since November 1996 we have performed PLV in 14 patients; preoperatively 4 patients had idiopathic dilated cardiomyopathy and 10 had ischemic dilated cardiomyopathy. 57.1% of patients were in New York Heart Association functional Class IV. The mitral valve was replaced in 11 patients. Postoperative echocardiography showed a reduction of left end-diastolic diameter (55.4 ± 5.4 mm) and an increase in forward ejection (cardiac index from 2.19 ± 0.571 min/m² to 2.67 ± 0.931/min/m²). The 30-day mortality was 28.6% and 20-month survival was 57.2%. Only one patient was not in NYHA functional class due to postoperative progressive mitral incompetence. Prognostic factors should be identified to avoid early failure. However, even if the mortality rate for PLV high, this operation is a valid choice for the treatment of end-stage dilated cardiomyopathy.     

Evidence for Modulation of Melatonin Secretion in Men With Benign and Malignant Tumors of the Prostate: Relationship With the Pituitary Hormones

The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle-stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean-cosinor method, and linear correlation coefficients between the five hormones were calculated for each group. Melatonin showed significant circadian rhythms in young men and patients with BPH and PCi but not in patients with PC. Twenty-four-hour mean concentration (mesor) and amplitude were significantly increased in patients with PCi as compared to patients with PC. Prolactin showed significant circadian rhythms in young men and in patients with BPH, whereas patients with PCi and PC appeared to have ultradian variations. Growth hormone did not show significant rhythms in any of the groups; the mesors were elevated in all tumor groups as compared to young men. Gonadotropin mesors were elevated in all tumor patients as compared to young men; rhythms were not detected. Carcinoma patients showed different interhormonal correlations than all other groups. These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer.     

The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low-dose immunosupressive regimen

Krampe K, Briem-Richter A, Fischer L, Nashan B, Ganschow R. The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low-dose immunosupressive regimen.
Pediatr Transplantation 2010: 14: 67–71. © 2009 Wiley Periodicals, Inc.
Abstract:  The incidence of CMV infection following pediatric Ltx is particularly high, which can be attributed to the increased number of patients at high risk for primary infection (donor CMV+, recipient CMV−). Current approaches to cope with this complication producing post-operative morbidity include prophylactic or preemptive ganciclovir therapy. As the risk for symptomatic CMV infection is directly correlated with the intensity of immunosuppression, the aim of our study was to assess the value of IVIG in order to protect children receiving low-dose immunosuppression from CMV disease. Twenty-eight consecutive children (median age 62.2 months) at high risk prospectively received three infusions of IVIG on days four, 14, and 28 post-transplant and were monitored for six months post-Ltx. Immunosuppression consisted of cyclosporine (initial trough levels 170–200 μg/L) and prednisolone (starting dose 15 mg/m²) as well as basiliximab induction therapy. Patient survival was 100% and graft survival was 92.9%. Two subjects developed laboratory findings of CMV infection (8%) and one child suffered from tissue invasive CMV disease (4%). Three patients were excluded from the study because of protocol violations. We conclude that there was a low incidence of CMV disease among a prospective cohort receiving low-dose immunosuppression and a standard IVIG product.     

In vivo stratum corneum distribution of lidocaine, assessed by tape stripping, from a new bioadhesive film

Background/purpose: The aim of this work was to study the in vivo performance of an innovative drug-delivery system, denominated Patch-non-Patch^®, using the tape-stripping technique.
Methods: The stratum corneum distribution of lidocaine, chosen as the model drug, was studied on human volunteers, using the tape-stripping technique. The amount of lidocaine recovered in tape strips was quantified using high-pressure liquid chromatography.
Results: When lidocaine was included in the film, the model drug was found in the stratum corneum already after 5 min of contact time. The increase in the application time increased lidocaine recovery in the stratum corneum, although only the extreme application times (5–10 min and 24 h) were significantly different. The profile of lidocaine recovered in the stratum corneum from the film was comparable with that obtained from the equivalent water solution, confirming the conclusion of in vitro permeation data that the film does not reduce lidocaine mobility inside the film and its partitioning into the stratum corneum.
Conclusion: The bioadhesive film studied in this work seems to be an effective system for the delivery of drugs to the skin.     

Association of moderate coffee intake with self-reported diabetes among urban Brazilians

Coffee has been associated with reductions in the risk of non-communicable chronic diseases (NCCD), including diabetes mellitus. Because differences in food habits are recognizable modifying factors in the epidemiology of diabetes, we studied the association of coffee consumption with type-2 diabetes in a sample of the adult population of the Federal District, Brazil. This cross-sectional study was conducted by telephone interview (n = 1,440). A multivariate analysis was run controlling for socio-behavioural variables, obesity and family antecedents of NCCD. A hierarchical linear regression model and a Poisson regression were used to verify association of type-2 diabetes and coffee intake. The independent variables which remained in the final model, following the hierarchical inclusion levels, were: first level-age and marital status; second level-diabetes and dyslipidaemias in antecedents; third level-cigarette smoking, supplement intake, body mass index; and fourth level-coffee intake (≤100 mL/d, 101 to 400 mL/day, and >400 mL/day). After adjusting hierarchically for the confounding variables, consumers of 100 to 400 mL of coffee/day had a 2.7% higher (p = 0.04) prevalence of not having diabetes than those who drank less than 100 mL of coffee/day. Compared to coffee intake of ≤100 mL/day, adults consuming >400 mL of coffee/day showed no statistically significant difference in the prevalence of diabetes. Thus, moderate coffee intake is favourably associated with self-reported type-2 diabetes in the studied population. This is the first study to show a relationship between coffee drinking and diabetes in a Brazilian population.     

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.