Treatment outcome in endodontics: the Toronto study--phases 3 and 4: orthograde retreatment

Outcome 4-6 years after retreatment was assessed for Phases 3 and 4 of the Toronto Study. Of 477 teeth retreated, 333 were lost to follow-up, 18 were extracted, and 126 (41% recall, excluding 124 discontinuers) were examined for outcome of healed (periapical index score, < or = 2; no signs or symptoms) or diseased. When pooled with Phases 1 and 2, 187 of 229 teeth (82%) were healed. Logistic regression identified significant (P < or = .05) preoperative outcome predictors: root filling quality (odds ratio [OR], 4.18; confidence interval [CI], 1.72-10.12; healed: inadequate, 88%; adequate, 66%), perforation (OR, 4.01; CI, 1.28-12.62; healed: absent, 87%; present, 56%), and radiolucency (OR, 3.33; CI, 1.19-9.36; healed: absent, 93%; present, 80%). In teeth with radiolucency, outcome predictors were number of treatment sessions (OR, 12.08; CI, 1.84-infinity; healed: one, 100%; > or = 2, 77%) and previous root filling quality (OR, 7.68; CI, 2.36-26.89; healed: inadequate, 86%; adequate, 50%). Outcome was better in teeth with inadequate previous root filling, without perforation and radiolucency. Suggested significance of number of treatment sessions in teeth with radiolucency requires validation from randomized controlled trials.     

Treatment outcome in endodontics: the Toronto study--phase 4: initial treatment

Outcome 4-6 years after initial treatment was assessed for Phase 4 (2000-2001) of the Toronto Study. Of 582 teeth treated, 430 were lost to follow-up (99 discontinuers, 331 dropouts), 15 were extracted, and 137 (32% recall minus 15 extracted teeth) were examined for outcome: healed (no apical periodontitis, signs, symptoms) or diseased. When pooled with Phases 1-3, 439 of 510 teeth (86%) were healed. Logistic regression identified 2 significant (P < or = .05) preoperative outcome predictors: radiolucency (odds ratio [OR], 2.86; confidence interval [CI], 1.56-5.24; healed: absent, 93%; present, 82%) and number of roots (OR, 2.53; CI, 1.25-5.13; healed: single, 93%; multiple, 84%). In teeth with radiolucency, intraoperative complications (OR, 2.27; CI, 1.05-4.89; healed: absent, 84%; present, 69%) and root-filling technique (OR, 1.89; CI, 1.01-3.53; healed: lateral, 77%; vertical, 87%) were additional outcome predictors. A better outcome was suggested for teeth without radiolucency, with single roots, and without mid-treatment complications. The predictive value of root-filling technique in teeth with radiolucency requires validation from randomized controlled trials.     

Generation of functional CD8+ T Cells by human dendritic cells expressing glypican-3 epitopes

Background

Glypican 3 (GPC-3) is an oncofoetal protein that is expressed in most hepatocellular carcinomas (HCC). Since it is a potential target for T cell immunotherapy, we investigated the generation of functional, GPC-3 specific T cells from peripheral blood mononuclear cells (PBMC).

Methods

Dendritic cells (DC) were derived from adherent PBMC cultured at 37°C for 7 days in X-Vivo, 1% autologous plasma, and 800 u/ml GM-CSF plus 500 u/ml IL-4. Immature DC were transfected with 20 μg of in vitro synthesised GPC-3 mRNA by electroporation using the Easy-ject plus system (Equibio, UK) (300 V, 150 μF and 4 ms pulse time), or pulsed with peptide, and subsequently matured with lipopolysaccharide (LPS). Six predicted GPC-3 peptide epitopes were synthesized using standard f-moc technology and tested for their binding affinity to HLA-A2.1 molecules using the cell line T2.

Results

DC transfected with GPC-3 mRNA but not control DC demonstrated strong intracellular staining for GPC-3 and in vitro generated interferon-gamma expressing T cells from autologous PBMC harvested from normal subjects. One peptide, GPC-3_522-530 FLAELAYDL, fulfilled our criteria as a naturally processed, HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitope: i) it showed high affinity binding to HLA-A2, in T2 cell binding assay; ii) it was generated by the MHC class I processing pathway in DC transfected with GPC-3 mRNA, and iii) HLA-A2 positive DC loaded with the peptide stimulated proliferation in autologous T cells and generated CTL that lysed HLA-A2 and GPC-3 positive target cells.

Conclusions

These findings demonstrate that electroporation of GPC-3 mRNA is an efficient method to load human monocyte-derived DC with antigen because in vitro they generated GPC-3-reactive T cells that were functional, as shown by interferon-gamma production. Furthermore, this study identified a novel naturally processed, HLA-A2-restricted CTL epitope, GPC-3_522-530 FLAELAYDL, which can be used to monitor HLA-A2-restricted CTL responses in patients with HCC. Further studies are required to investigate whether anti-GPC-3 immunotherapy has a role in the treatment of GPC-3 dependent tumours, such as HCC.     

The sit-to-stand technique for the measurement of dynamic cerebral autoregulation

Measurement of cerebral autoregulation is important for the evaluation and management of a number of clinical disorders that affect cerebral blood flow. We currently lack simple bedside measures that mimic common physiologic stresses. Therefore, we evaluated a new sit-to-stand technique as an alternative method to the frequently-used thigh-cuff technique in healthy volunteers. Continuous middle cerebral artery (MCA) blood flow velocities (BFV) and arterial blood pressure (ABP) were measured in response to standing from a sitting position, or rapid thigh-cuff deflation in 24 healthy subjects (50 +/- 22 y). Autoregulatory index (ARI) was calculated as the BFV response for step changes in ABP using a second-order differential equation with a set of parameters that can be used to grade the performance of autoregulation. Of these 24 subjects, 30% could tolerate only two thigh-cuffs and refused to proceed with the third cuff, whereas none of our subjects had any difficulty with performing the three sit-to-stand trials. The two techniques produced similar changes in mean ABP, but the times to nadir of the blood pressure and BFV were significantly faster for the thigh-cuff. The mean group ARIs were similar between the two techniques. Although between-subjects variability was higher for sit-to-stand ARIs, the within-subject sit-to-stand ARI variability was small. Thus, for the assessment of cerebral autoregulation, the sit-to-stand procedure is well tolerated and produces ARI values that have low within-subject variability. The sit-to-stand technique appears to be a suitable measure of individual ARI values for inferring dynamic cerebral autoregulation.     

Cerebral Hemodynamics during Coronary Artery Bypass Graft Surgery: The Effect of Carotid Stenosis

Carotid stenosis is a frequent coexisting condition in patients undergoing coronary artery bypass graft (CABG) surgery. The impact of carotid stenosis on cerebral perfusion is not fully understood. The purpose of this study was to determine the impact of carotid stenosis on cerebral blood flow velocity in patients undergoing CABG. Seventy-three patients undergoing CABG were prospectively recruited and underwent preoperative Duplex carotid ultrasound to evaluate the degree of carotid stenosis. Intraoperatively, transcranial Doppler ultrasound was used to record the mean flow velocity (MFV) within the bilateral middle cerebral arteries. In addition, during the period of cardiopulmonary bypass, regulators of cerebral hemodynamics such as hematocrit, partial pressure of carbon dioxide and temperature were recorded. The ipsilateral middle cerebral artery mean flow velocity was compared in arteries with and without carotid stenosis using a repeated measures analysis. Seventy-three patients underwent intraoperative monitoring during CABG and 30% (n = 22) had carotid stenosis. Overall, MFV rose throughout the duration of CABG including when the patient was on cardiopulmonary bypass. However, there was no significant MFV difference between those arteries with and without stenosis (F = 1.2, p = .21). Further analysis during cardiopulmonary bypass, demonstrated that hemodilution and partial pressure of carbon dioxide may play a role in cerebral autoregulation during CABG. Carotid stenosis did not impact mean cerebral blood flow velocity during CABG. The cerebrovascular regulatory process appears to be largely intact during CABG.     

A new variant of Vohwinkel syndrome: a case report

Vohwinkel syndrome (mutilating and diffuse palmoplantar keratoderma) is associated with various extracutaneous features including icthyosis and deafness. Its mode of inheritance is autosomal dominant with mutation in loricrin and Connexin 26 genes. Here we report a mutilating and focal palmoplantar keratoderma in two siblings with congenital hypotrichosis and probably autosomal recessive inheritance that appears to be a new variant of Vohwinkel syndrome.     

Applying conventional and saturated generalized gamma distributions in parametric survival analysis of breast cancer

Background: The generalized gamma distribution statistics constitute an extensive family that contains nearlyall of the most commonly used distributions including the exponential, Weibull and log normal. A saturatedversion of the model allows covariates having effects through all the parameters of survival time distribution.Accelerated failure-time models assume that only one parameter of the distribution depends on the covariates.Methods: We fitted both the conventional GG model and the saturated form for each of its members includingthe Weibull and lognormal distribution; and compared them using likelihood ratios. To compare the selectedparameter distribution with log logistic distribution which is a famous distribution in survival analysis thatis not included in generalized gamma family, we used the Akaike information criterion (AIC; r=l(b)-2p). Allmodels were fitted using data for 369 women age 50 years or more, diagnosed with stage IV breast cancer inBC during 1990-1999 and followed to 2010. Results: In both conventional and saturated parametric models,the lognormal was the best candidate among the GG family members; also, the lognormal fitted better thanlog-logistic distribution. By the conventional GG model, the variables “surgery”, “radiotherapy”, “hormonetherapy”, “erposneg” and interaction between “hormone therapy” and “erposneg” are significant. In the AFTmodel, we estimated the relative time for these variables. By the saturated GG model, similar significant variablesare selected. Estimating the relative times in different percentiles of extended model illustrate the pattern inwhich the relative survival time change during the time. Conclusions: The advantage of using the generalizedgamma distribution is that it facilitates estimating a model with improved fit over the standard Weibull or lognormaldistributions. Alternatively, the generalized F family of distributions might be considered, of which thegeneralized gamma distribution is a member and also includes the commonly used log-logistic distribution.     

Translation,cross-cultural adaptation,reliability and validity of the Persian version of the ACL-QOL questionnaire in patients with anterior cruciate ligament reconstruction

BackgroundQuality of life (QOL) measures can be used to make sound clinical decisions after reconstruction of the anterior cruciate ligament (ACL). The purpose of the present study was to translate and cross-culturally adapt the Anterior Cruciate Ligament Quality of Life (ACL-QOL) questionnaire into the Persian language and to evaluate its psychometric properties.MethodsThe process of translation and cross-cultural adaptation followed the World Health Organization method. One hundred and forty-five patients with ACL reconstruction (ACL-R) filled out the Persian versions of ACL-QOL and the SF-36 Questionnaire. The measurement properties of internal consistency, agreement, criterion validity, floor and ceiling effects were measured. 40 out of 145 patients with ACL-R completed the Persian version of the ACL-QOL questionnaire twice for the test-retest reliability.ResultsThe questionnaire had high internal consistency (Cronbach's α = 0.96). The intraclass correlation was excellent for reliability and agreement in five domains and overall score (ICC 0.87, 0.74, 0.90, 0.85, 0.81 and 0.89; p < 0.001). The standard error of measurement and the minimum detectable change were found to be 3.28 points and 9.9 points, respectively. There was a strong correlation between each item and the total score of the Persian version of ACL-QOL questionnaire. The questionnaire showed strong and moderate criterion validity (r = 0.61, r = 0.37) with SF-36 physical component score and mental component score, respectively. No ceiling and floor effects were observed.ConclusionsPersian version of the ACL-QOL questionnaire has acceptable reliability and validity and can be used in assessing Iranians quality of life after ACL reconstruction.     

White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies

Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural underpinnings of alcohol teratogenesis. This technique can detect alterations in white matter in neurodevelopmental disorders, such as fetal alcohol spectrum disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted on individuals with prenatal alcohol exposure (PAE). These studies confirm the widespread nature of brain damage in PAE by reporting diffusivity alterations in commissural, association, and projection fibers; and in relation to increasing cognitive impairment. Reduced integrity in terms of lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported more consistently in the corpus callosum, cerebellar peduncles, cingulum, and longitudinal fasciculi connecting frontal and temporoparietal regions. Although these interesting results provide insight into FASD neuropathology, it is important to investigate the clinical diversity of this disorder for better treatment options and prediction of progression. The aim of this review is to provide a summary of different patterns of neural structure between PAE and typically developed individuals. We further discuss the association of alterations in diffusivity with demographic features and symptomatology of PAE. With the accumulated knowledge of the neural correlates of FASD presenting symptoms, a comprehensive understanding of the heterogeneity in FASD will potentially improve the disease management and will highlight the diagnostic challenges and potential areas of future research avenues, where neural markers may be beneficial.     

Evaluating of Induction of Apoptosis by Cornus mass L. Extract in the Gastric Carcinoma Cell Line (AGS)

Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to thecure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction ofapoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGSand L929 cells were cultured and treated with different concentrations (0–10 mg/ml) of Cornus mass L. extract for 48and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantifiedat 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI anddouble staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed byANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviationamong various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line incomparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximatelyseveral-fold increased anti-cancer potency in AGS compared to L929 cells. The IC50 value in AGS cells (evaluatedafter 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p≤0.05). The analysis results of flow cytometryindicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Eachof our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferationin in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers.