What is the correct management of stage i UPSC?

UPSC has been identified as a distinct variant of endometrial cancer and it has been reported to be associated with more aggressive behavior and a worse prognosis compared to endometrioid adenocarcinomas of the endometrium. Various studies have demonstrated survival rates of 15–51% for clinical stage I disease and 35–90% for surgical stage I/II disease. Aside from the very limited number of studies that incorporate comprehensive surgical staging, the majority of these reports used clinical parameters for staging or very limited surgical staging techniques and information.
A significant amount of controversy surrounds the optimal management of patients with stage I UPSC, and appropriate management of these patients has yet to be firmly established. The low incidence of this particular type of cancer, the variety of surgical interventions, and the wide variety of post-operative adjuvant therapies have made it extremely difficult to identify the optimal management of patients with UPSC. Prior to 2004, adjuvant treatment recommendations for surgical stage I UPSC were largely based on very small retrospective patient series (<20 patients), only a fraction of which included surgically staged patients. A recent publication reported the outcomes of surgical stage I UPSC patients from four institutions ⁽¹⁾ . Recurrence rates were lower than that published in previous studies, suggesting a potential benefit of comprehensive surgical staging in these patients. The risk of recurrence and mean overall survival were similar between surgical stage I UPSC patients who were managed conservatively versus those treated with adjuvant radiation therapy. Moreover, this study also suggests a potential benefit of adjuvant chemotherapy in these patients.     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

Anticerebellar antibodies--anti-Hu and anti-Yo--in the diagnosis of paraneoplastic neurologic syndromes]

The detection of antineuronal antibodies against cytoplasm and nuclei of Purkinje cells is considered to be an essential factor in the diagnosis of neurologic paraneoplastic syndromes. Published data rely on different immunological methods and relatively small numbers of patients. The clinical relevance of this phenomenon is not clear from the literature. A positive correlation between antibody detection and the appearance of neurologic paraneoplastic syndromes has been reported, but this finding has been questioned in critical reviews.     

Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy

Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.     

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.     

A survey of hospitals in New York State treating psychiatric patients with chemical abuse disorders.

Eighty-eight of 143 hospitals in New York State providing psychiatric inpatient treatment responded to a mailed questionnaire designed to determine the size of three subgroups of chemical abusers--alcohol abusers, drug abusers, and polychemical abusers--among inpatients with psychiatric diagnoses, as well as the availability of services for these patients. Data for New York City and its metropolitan area were analyzed separately. In 1987 almost one-third of psychiatric admissions both in and outside the metropolitan area had comorbid chemical abuse disorders. Seventy-five percent of patients in the metropolitan area with comorbid chemical abuse had a drug abuse disorder; in rural areas 88 percent of patients with chemical abuse disorders abused alcohol. Both hospital- and community-based aftercare services, especially in the metropolitan area, were less available to psychiatric patients with chemical abuse than to patients without these disorders.