KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops

ObjectivesUterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the most aggressive cervical cancer subtype. The successful treatment of some tumors, such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters the study of this receptor tyrosine kinase in other malignancies. In the present study, we intended to molecularly characterize KIT in ASC.MethodsIn a series of 30 cases, we studied KIT (CD117), KIT phosphorylated / activated form, as well as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for KIT gene amplification by Quantitative real-time PCR in CD117 positive cases.ResultsWe observed CD117 expression in ～ 13% of cases, with ～ 7% co-expressing SCF, which resulted in KIT phosphorylation/activation. No KIT activating mutations or gene amplification were found, despite the presence of 4q aneuploidy in one case.ConclusionsThis is the first study assessing KIT activation and molecular alterations in a large series of rare ASC. Our findings showed the absence of KIT molecular alterations and suggested the presence of KIT activation in a small proportion of cases through KIT/SCF co-expression.     

Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.     

Integrity situational judgement test for medical school selection: judging ‘what to do’ versus ‘what not to do’

Context

Despite their widespread use in medical school selection, there remains a lack of clarity on exactly what situational judgement tests (SJTs) measure.

Objectives

We aimed to develop an SJT that measures integrity by combining critical incident interviews (inductive approach) with an innovative deductive approach. The deductive approach guided the development of the SJT according to two established theoretical models, of which one was positively related to integrity (honesty–humility [HH]) and one was negatively related to integrity (cognitive distortions [CD]). The Integrity SJT covered desirable (HH‐based) and undesirable (CD‐based) response options. We examined the convergent and discriminant validity of the Integrity SJT and compared the validity of the HH‐based and CD‐based subscores.

Methods

The Integrity SJT was administered to 402 prospective applicants at a Dutch medical school. The Integrity SJT consisted of 57 scenarios, each followed by four response options, of which two represented HH facets and two represented CD categories. Three SJT scores were computed, including a total, an HH‐based and a CD‐based score. The validity of these scores was examined according to their relationships with external integrity‐related measures (convergent validity) and self‐efficacy (discriminant validity).

Results

The three SJT scores correlated significantly with all integrity‐related measures and not with self‐efficacy, indicating convergent and discriminant validity. In addition, the CD‐based SJT score correlated significantly more strongly than the HH‐based SJT score with two of the four integrity‐related measures.

Conclusions

An SJT that assesses the ability to correctly recognise CD‐based response options as inappropriate (i.e. what one should not do) seems to have stronger convergent validity than an SJT that assesses the ability to correctly recognise HH‐based response options as appropriate (i.e. what one should do). This finding might be explained by the larger consensus on what is considered inappropriate than on what is considered appropriate in a challenging situation. It may be promising to focus an SJT on the ability to recognise what one should not do.     

An Attempt to Stem the Tide: Exploring the Effect of a 90-Day Transitional Care Intervention on Readmissions to an Acute Male Psychiatric Unit in South Africa

Introduction

Pressure on inpatient beds often results in premature discharges, which may precipitate early readmission. This has prompted an increased interest in transitional care interventions to bridge the gap between in- and outpatient care to reduce such readmissions. Our study aimed to assess the effect of a Transitional Care Service (TCS) on readmission rates in a high pressure inpatient service which utilizes a premature discharge policy to address bed pressures.

Autoimmune polyendocrine syndrome type 1: case report and review of literature

Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome.     

The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy

To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.     

Autologous transplant: microbial contamination of hematopoietic stem cell products

Hematopoietic progenitor cells from peripheral blood (HPCPB) are commonly used for autologous and allogenic transplants in patients with most various onco-hematological diseases, and despite the utilization of sterile techniques during collection and processing of these products, bacterial contamination can occur. This study aimed to investigate the microbial contamination of HPCPB products. Microbial cultures of 837 HPCPB products between the year 2000 and 2009 were retrospectively analyzed to determine the incidence of culture positivity and identify the main organisms that cause contamination. The microbiological studies were performed with an automated system (BacT/Alert^® bioMérieux Corporate). Thirty-six (4.3%) of 837 microbial cultures were contaminated. Coagulase-negative Staphylococcus was the most frequent bacteria isolated from HPCPB products (20 [56%] of the 36 positive microbial cultures). Considering the 36 contaminated samples, 22 HPCPB products were infused and 14 discarded. Pre- and post-infusion antibiotic therapy of the patients transfused with contaminated products was established based on the isolated microorganism and its antibiogram. Microbial contamination rate of HPCPB products was low. Clinically significant outcomes after infusion of contaminated HPCPB products were not observed.     

Durability of the first combined antiretroviral regimen in patients with AIDS at a reference center in Belo Horizonte, Brazil, from 1996 to 2005

Finding a better first antiretroviral regimen is one of the strategies used to improve span and quality of life of HIV/AIDS patients. 891 patients were followed during 24 months or until interruption/abandonment of treatment, changing regimen or death. At the end of 6 months, 69% of the patients were still being treated with the first regimen, 54% at 12 months, 48% at 18 months and 39% at 24 months. AZT-3TC-EFV was the most prescribed regimen and with the lesser discontinuation. NNRTI regimens showed high effectiveness and durability compared to PI regimens. Irregular medication dispensation was the only risk factor for failure/interruption of treatment in multivariate analyses. Intolerance/adverse effects were mainly responsible for first regimen discontinuation, followed by abandonment/non-adherence and virologic failure. Results showed significant difference between causes of interruption of first HAART with higher percentage of intolerance/adverse effects with PI regimens and higher immunologic failure with NNRTI regimens. Even with the availability of more potent and tolerable drugs, lack of adherence to HAART and high level of adverse effects are still the most important barriers to prolonged success of treatment. This study adds relevant information about durability and effectiveness of HAART in the first decade of its use in Brazil.     

Dermographism and delayed pressure urticaria

There are few papers in the literature that describe pressure urticaria in the maxillofacial region. We present 2 cases and discuss the significance and principles of management. One case describes the diagnosis of pressure urticaria and the second describes the dental management of a patient with severe pressure urticaria.