Reliability of Lateral Cephalometric Radiographs in the Assessment of the Upper Airway in Children: A Retrospective study

ObjectivesTo test the reliability of Lateral cephalometric radiographs (LCRs) for use in the assessment of the upper airway, hyoid bone, soft palate, and tongue.Materials and MethodsThe records of 57 healthy Chinese children from a nonhospital population (mean age = 12.6 years, SD = 0.5, 28 males and 29 females) who received two consecutive LCRs in the natural head posture were retrospectively analyzed. Fifteen linear, angular, and area measurements were used to describe the airway, hyoid bone, soft palate, and tongue. The reliability between the two LCRs was assessed with the intraclass correlation coefficient (ICC) and F-test. Errors were estimated with the Dahlberg and Bland-Altman method, and intra- and inter-assessor agreements were determined.ResultsMeasurements of upper airway and hyoid bone had excellent method reliability, intra-assessor reliability, and inter-assessor reliability (ICC > 0.8). However, the method reliability and the inter-assessor reliability for soft palate and tongue was less favorable (ICC from 0.60 to 0.96). Soft palate area and thickness were the most critical parameters. Intra-assessor reliability was greater than both method reliability and inter-assessor reliability (which were similar).ConclusionsThe measurement of upper airway morphology, defined as the intramural space, and of the hyoid bone position were highly reliable on LCRs of children. However, the limited reliability in the assessment of tongue and soft palate area may compromise the diagnostic application of LCRs to these structures.     

Antibodies to Ro/La, Cenp-B, and snRNPs Antigens in Autoimmune Hepatitis of North America versus Asia: Patterns of Immunofluorescence, ELISA Reactivities, and HLA Association

To assess whether demography is one of theimportant factors determining antibody response tonuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La,snRNPs (A, 70K, B/B), and Cenp-B], weinvestigated 95 and 47 sera of autoimmune hepatitis (AIH) fromNorth America and Asia, respectively, byimmunofluorescent (IF) and recombinant ELISA.Correlations among nuclear IF patterns, ELISA, anddisease indices were analyzed. The frequency and titer of individualantibodies differed significantly between the groups.Patients with speckled patterns were younger in bothregions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2,and DR4 or DR3 or both in North America, and A2, B61,DQ7, and DR4 in Asia were predominant. In Asia, B61correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B/B. InNorth America, A1, B8, DR3 haplotype, and DQ2 correlatedwith antibodies to A and 70K. Anti-B/B and DR4 inNorth America, and A2 in Asia, were associated withconcurrent immunologic disorder. Individual ANA clusterscorrelated with individual HLA in the demography, anddifferent HLA alleles might determine disease expressionas well as different ANA being produced inAIH.     

The Reverse-Direction Method Links Mass Experimental Data to Human Diseases

Genome-wide analyses such as DNA microarray, RNA sequencing and RNA interference-based high-throughput screening are prevalent to decipher a biological process of interest, and provide a large quantity of data to be processed. An ultimate goal for researchers must be extrapolation of their data to human diseases. We have conducted functional genome-wide screenings to elucidate molecular mechanisms of the inflammation amplifier, a NFκB/STAT3-dependent machinery that potently drives recruitment of immune cells to promote inflammation. Using a public database of genome-wide association studies (GWAS), we recently reported the reverse-direction method by which our mass screening data were successfully linked to many human diseases. As an example, the epiregulin–epidermal growth factor receptor pathway was identified as a regulator of the inflammation amplifier, and associated with human diseases by GWAS. In fact, serum epiregulin levels were higher in patients with chronic inflammatory disorders. The reverse-direction method can be a useful tool to narrow mass data down to focus on human disease-related genes.     

Impact of CYP2C19 polymorphism on clinical outcome following coronary stenting is more important in non-diabetic than diabetic patients

Objective

The aim of this study was to examine the impact of CYP2C19 genotype on clinical outcome in coronary artery disease (CAD) patients with or without diabetes mellitus (DM).

Methods

CYP2C19 polymorphism and DM are associated with increased risk of cardiovascular events during antiplatelet therapy following stent implantation. Platelet reactivity during clopidogrel therapy and CYP2C19 polymorphism were measured in 519 CAD patients (males 70%, age 69 years) treated with stent placement. Patients were divided into two groups; DM (n = 249), and non-DM (n = 270), and clinical events were evaluated according to the carrier state, which included at least one CYP2C19 loss-of-function allele.

Results

The level of platelet reactivity and incidence of cardiovascular events were significantly different between Carriers and non-Carriers of the non-DM (platelet reactivity: 4501 +/− 1668 versus 3691 +/− 1714AUmin, P < 0.01; events, 32/178 versus 2/92, P < 0.01, respectively), however, there was no difference in clinical outcome in the DM group (events, 34/168 versus 14/81, respectively, P = 0.57). Multivariate analysis identified CYP2C19 loss-of-function allele carriage as an independent predictor of cardiovascular events in non-DM, but not in DM (non-DM, HR 7.180, 95% CI, 1.701 to 30.298, P = 0.007; DM, HR 1.374, 95% CI, 0.394 to 4.792, P = 0.618).

Conclusion

The impact of CYP2C19 polymorphism on clinical outcome seems to be more significant in non-DM compared with DM in patients with coronary stents.     

Chronic kidney disease status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation

Introduction

There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study.

Material and Methods

We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n = 154) and non-CKD (n = 177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status.

Results

The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P = 0.016) and non-CKD groups (34.3% versus 3.7%; P < 0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P = 0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P = 0.013) and there was no significant difference in the CKD group (log-rank test: P = 0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P = 0.043).

Conclusions

CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.     

A Paced Auditory Serial Addition Task evokes stress and differential effects on masseter-muscle activity and haemodynamics

This study aimed to determine autonomic and jaw-muscle activities, and haemodynamic responses, to acute experimental mental stress in humans. Eleven healthy men (25.2 ± 3.0 years of age) and five healthy women (23.0 ± 3.7 years of age) performed a standardized mental stress task, the Paced Auditory Serial Addition Task (PASAT). Autonomic function, such as heart rate variability (HRV), and haemodynamic changes were recorded simultaneously. The success rate of the PASAT decreased with increased pace and duration. Low-frequency (5.8 ± 1.1 ms(2)) and high-frequency (5.3 ± 0.6 ms(2)) components of HRV decreased during the PASAT (to 5.0 ± 0.9 ms(2) and 4.6 ± 1.1 ms(2), respectively) as an indication of acute stress. Oxygenated haemoglobin in the masseter muscle (14.6 ± 2.2 10(4) units mm(-3)) remained at an elevated level during the PASAT (15.5 ± 2.5 10(4) units mm(-3)), whereas deoxygenated haemoglobin (7.8 ± 2.3 10(4) units mm(-3)) showed a consistent decrease (to 6.8 ± 2.1 10(4) units mm(-3)). Total haemoglobin and jaw-muscle electromyographic (EMG) activity did not change during the PASAT. Thus, PASAT-induced mental stress changed the parasympathetic/sympathetic balance of the heart and had an acute influence on jaw-muscle haemodynamics, but not on jaw-muscle EMG activity. This non-invasive experimental set-up can be applied to study the effects of repeated or longer-lasting mental stress in order to further the understanding of pathophysiological mechanisms in craniofacial pain conditions.     

Successful Treatment of γ-Heavy-Chain Disease with Rituximab and Fludarabine

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ?-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgM? monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.