Comparison of different methods of CAIX quantification in relation to hypoxia in three human head and neck tumor lines.

PURPOSE: In head and neck cancer, it has been shown that hypoxic tumors respond poorly to therapy. Methods to identify hypoxic tumors are, therefore, of importance to select patients for oxygenation modifying or other intensified treatments. The aim of this study was to compare tumor cell hypoxia assessed by the hypoxic cell marker pimonidazole (PIMO) with expression of the endogenous hypoxia-related marker carbonic anhydrase IX (CAIX) in three human head and neck tumor lines. MATERIAL AND METHODS: Forty-five tumors of three human head and neck tumor lines, SCCNij3, SCCNij59 and MEC82, xenografted in athymic mice, were used. CAIX was quantified by biodistribution (% injected dose/g tumor) after injecting 3-5 microl 111In-labeled G250 mouse antibody 3 days prior to euthanizing. In a tissue section from the same tumor, fractions of tumor area positive for PIMO, CAIX and Hoechst 33342 (perfusion marker) were assessed after immunohistochemical staining, using a digital image analysis system. RESULTS: SCCNij3 and MEC82 were relatively hypoxic tumor lines with fractions of tumor area positive for pimonidazole of 0.16 and 0.15, respectively. SCCNij59 was a better-oxygenated tumor line with a PIMO-fraction of 0.03. The three tumor lines showed different levels and patterns of CAIX immunohistochemical staining, but only in MEC82 there was a good correlation between PIMO-fraction and CAIX-fraction (r2=0.92, P<0.0001). Correlations between 111In-G250 uptake and CAIX-fraction or PIMO-fraction within tumor lines were weak or absent. CONCLUSIONS: Assessment of CAIX expression depends largely on the techniques and tumor lines used. Furthermore, the immunohistochemical staining pattern of CAIX relative to PIMO differs between human tumor lines of similar anatomical origin. Therefore, the use of CAIX as endogenous marker of tumor hypoxia remains questionable.     

Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients.

PURPOSE: To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. RESULTS: The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. CONCLUSION: We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.     

Management of metastatic disease of other bones

Metastases to the scapula and distal sites on the upper and lower extremities are infrequent. Although these metastases tend to occur in patients with advanced disease, a distal metastasis is occasionally the sole metastatic location. Distal metastases do not pose an immediate threat to a patient's life; however, they may cause significant pain and disability. Appropriate management can considerably enhance function, quality of life, and, occasionally, survival. Seven cases of distal metastasis are presented in this article with discussion of operative and nonoperative approaches to management.     

Executive function and general intellectual functioning in dyskinetic cerebral palsy: Comparison with spastic cerebral palsy and typically developing controls

AimTo comprehensively describe intellectual and executive functioning (EF) in people with dyskinetic cerebral palsy (DCP), by comparing their performance with that of: 1) age- and sex-matched typically developing controls (TDC); and 2) participants with spastic cerebral palsy (SCP) matched for age, sex, term/preterm and gross motor function classification system (GMFCS).MethodThis cross-sectional study was conducted by the University of Barcelona in collaboration with five institutions. Participants were people with DCP (n = 52; 24 females, median age 20.5 y: 5mo, interquartile range [IQR] = 13.75 y: 7mo; GMFCS I–V). As comparison groups, participants with SCP (n = 20; 10 females, median age = 20.5 y: 5.5mo, IQR = 13.75 y 9mo; GMFCS I–V) and TDC (n = 52; 24 females, median age = 20 y: 4mo, IQR = 12 y 7mo) were included. Intelligence and EF were assessed using common tests in all participants.ResultsBoth CP groups had lower intelligence than TDC and performed poorer in almost all EF tasks. Intelligence was higher in DCP than SCP (z = ?2.51, p = 0.01). Participants with DCP also performed significantly better in goal-setting tasks (z = 2.27, p = 0.03) and information processing (z = ?2.54, p = 0.01) than those with SCP.ConclusionPeople with DCP present lower general intellectual functioning and poorer EF across multiple domains than typically developing controls. People with DCP have higher general intellectual functioning and better EF than people with SCP when levels of motor severity are similar.     

Bacterial leakage in root canals filled with AH Plus and dentine bonding agents

Objective. The aim of this study was to compare the efficacy of different dentine adhesives in delaying the coronal bacterial leakage of Enterococcus faecalis in filled root canals. Materials and methods. Ninety-five lower incisors of patients >65 years of age were instrumented using the ProTaper® system and were irrigated with 1 mL of 2.5% sodium hypochlorite (NaOCl) alternated with 1 mL 17% EDTA between each file change. Final irrigation was performed with 5 mL of 17% EDTA and then flushed with 5 mL of distilled water. The teeth were randomly divided into five experimental groups (n = 15/group) and one of the following dentine adhesives was applied: (1) AdheSE®; (2) Excite® DSC; (3) Clearfil^? Protect Bond; (4) One Coat 7.0; or (5) Control group without adhesive. After filling the root canals, the samples were mounted on a double chamber device to evaluate the bacterial filtration of E. faecalis during a period of 240 days. The results underwent non-parametric Kaplan-Meier survival analysis and comparisons among groups were done using the Log-Rank test. Results. At 240 days, E. faecalis was detected in samples of all groups in the lower chamber. The highest survival value was obtained by One Coat 7.0, giving statistically significant differences from the other groups, whereas Clearfil^? Protect Bond, AdheSE® and Excite® DSC showed similar behaviours, likewise similar to the Control group. Conclusions. One Coat 7.0 adhesive system provides the longest survival value to delay E. faecalis coronal leakage in filled root canals.     

Patterns in the prevalence of diabetes and incidence of diabetic complications in people with and without an intellectual disability in Dutch primary care: Insights from a population-based data-linkage study

AimsTo conduct an epidemiological analysis of patterns observed in diabetes care provided to individuals with and without intellectual disabilities (ID) in primary care settings.MethodsAn ID-cohort (N = 21,203) was compared with a control group of similar age and sex from the general Dutch population (N = 267,628). Distinctive data for diabetes (both type 1 and type 2) and related complications were retrieved from national databases.ResultsThe prevalence of diabetes was higher in people with ID than in the general population (9.9% versus 6.6%). Largest differences were seen in younger age groups. Women with ID had diabetes more often than men with ID. Complications were less common in people with ID than in the general population (IR 58.6 vs. 70.4). In particular, cardiological complications were noted less, while surgical interventions and hospitalization occurred more often.ConclusionsAlthough diabetes was 1.5 times more prevalent in people with ID than in other people, related complications were less common, followed different patterns and were more severe than in the general population. Future research is needed to understand of the underlying causal mechanisms and to lower the risk of severe diabetic complications among people with ID.     

Workplace learning through collaboration in primary healthcare: A BEME realist review of what works,for whom and in what circumstances: BEME Guide No. 46

Background: Changes in healthcare practice toward more proactive clinical, organizational and interprofessional working require primary healthcare professionals to learn continuously from each other through collaboration. This systematic review uses realist methodology to consolidate knowledge on the characteristics of workplace learning (WPL) through collaboration by primary healthcare professionals.

Methods: Following several scoping searches, five electronic bibliographic databases were searched from January 1990 to December 2015 for relevant gray and published literature written in English, French, German and Dutch. Reviewers worked in pairs to identify relevant articles. A set of statements, based on the findings of our scoping searches, was used as a coding tree to analyze the papers. Interpretation of the results was done in alternating pairs, discussed within the author group and triangulated with stakeholders’ views.

Results: Out of 6930 references, we included 42 publications that elucidated who, when, how and what primary healthcare professionals learn through collaboration. Papers were both qualitative and quantitative in design, and focused largely on WPL of collaborating general practitioners and nurses. No striking differences between different professionals within primary healthcare were noted. Professionals were often unaware of the learning that occurs through collaboration. WPL happened predominantly through informal discussions about patient cases and modeling for other professionals. Any professionals could both learn and facilitate others’ learning. Outcomes were diverse, but contextualized knowledge seemed to be important.

Discussion/conclusions: Primary care professionals’ WPL is multifaceted. Existing social constructivist and social cognitivist learning theories form a framework from which to interpret these findings. Primary care policy makers and managers should ensure that professionals have access to protected time, earmarked for learning. Time is required for reflection, to learn new ways of interaction and to develop new habits within clinical practice.