TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma.

BACKGROUND: Tripartite motif-containing 27 (TRIM27) has been implicated in the progression of various cancers. However, the role of TRIM27 in sinonasal mucosal melanoma (SNMM) remains poorly understood. MATERIALS & METHODS: We retrospectively examined 28 patients with SNMM treated with between 2003 and 2021. We undertook immunohistochemical analysis of TRIM27, Ki-67, and p-Akt1 expression in SNMM tissues. We also investigated the relationship between TRIM27 expression and clinical characteristics, prognosis, Ki-67 as a tumor growth potential marker, and p-Akt1 as one of the prognostic factors in mucosal melanoma. RESULTS: TRIM27 expression was significantly higher in T4 disease than in T3 disease and was higher in stage IV than in stage III. Patients with high-TRIM27 SNMM had a significantly poorer prognosis in terms of overall survival (OS) and disease-free survival.There was also a significantly higher rate of distant metastasis. Univariate analysis for OS revealed that TRIM27 and T classification were significant poor prognostic factors. In addition, the Ki-67 positive score and the p-Akt1 total staining score were significantly higher in the high-TRIM27 group than in the low-TRIM27 group. CONCLUSIONS: High TRIM27 expression in SNMM was associated with advanced T classification, poor prognosis and distant metastasis. We suggest that TRIM27 has potential as a novel biomarker for prognosis in SNMM.

Swelling of Doubly Magic

Interaction cross sections for ^{42-51}Ca on a carbon target at 280 MeV/nucleon have been measured for the first time. The neutron number dependence of derived root-mean-square matter radii shows a significant increase beyond the neutron magic number N=28. Furthermore, this enhancement of matter radii is much larger than that of the previously measured charge radii, indicating a novel growth in neutron skin thickness. A simple examination based on the Fermi-type distribution, and mean field calculations point out that this anomalous enhancement of the nuclear size beyond N=28 results from an enlargement of the core by a sudden increase in the surface diffuseness of the neutron density distribution, which implies the swelling of the bare ^{48}Ca core in Ca isotopes beyond N=28.

Zinc-depletion associates with tissue eosinophilia and collagen depletion in chronic rhinosinusitis.

BACKGROUND: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro. METHODOLOGY: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts. RESULTS: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion. CONCLUSIONS: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.

Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

Background: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Patients and methods: Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Results: Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. Conclusions: The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. Registered clinical trial number: UMIN000010507.

Integrating quantitative morphological and intratumoural textural characteristics in FDG-PET for the prediction of prognosis in pharynx squamous cell carcinoma patients.

AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region.

BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). METHODS: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). RESULTS: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions. CONCLUSION: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

Phase I safety and immunogenicity study of a Brazilian serogroup B vaccine.

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 µg, 25 µg and 50 µg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.

Long-term outcome after endoscopic resection in patients with hypopharyngeal carcinoma invading the subepithelium: a case series.

Patients with early stage hypopharyngeal carcinoma can be treated with endoscopic resection. However, strict indication for endoscopic resection in cases of hypopharyngeal carcinoma is unclear. In this paper, we evaluated the long-term outcome after endoscopic resection in patients with hypopharyngeal carcinoma invading the subepithelium. Among 16 patients with hypopharyngeal carcinoma who underwent endoscopic resection, eight patients who were histologically confirmed to have tumors with shallow invasion of the subepithelium were studied. Depth of tumor invasion in the subepithelium in those patients ranged from 300 to 720 microm (mean +/- SD, 490 +/- 140 microm). During a median follow-up period of 40 months, none of the eight patients had local recurrence or metastasis. Kaplan-Meier estimates of relapse-free survival rates at 5 years in the eight patients were 100 %. The results of this study suggest that hypopharyngeal carcinoma with slight invasion to the subepithelium can be successfully treated by endoscopic resection.

Automated discrimination between very early Alzheimer disease and controls using an easy Z-score imaging system for multicenter brain perfusion single-photon emission tomography.

BACKGROUND AND PURPOSE: In Alzheimer disease (AD), a peculiar regional cerebral blood flow (rCBF) abnormality has been reported in the posterior cingulate gyri and precunei, even at a very early stage. We performed a multicenter brain perfusion single-photon emission tomography (SPECT) study to evaluate the discrimination ability of an easy Z-score imaging system (eZIS) with a common normal data base between patients with very early AD at the stage of mild cognitive impairment and age-matched healthy controls. MATERIALS AND METHODS: For a multicenter study, SPECT images of 40 patients with AD and 40 healthy volunteers were acquired from 4 gamma camera systems in 4 different institutions. Systematic differences of SPECT images between gamma cameras were corrected by using conversion maps calculated from the SPECT images of the same brain phantom. Receiver operating characteristic (ROC) analysis was performed to discriminate patients and controls by using a Z-score in the volume of interest (VOI), which had been defined as a region related to AD in subjects other than those in a multicenter study. RESULTS: Bilateral posterior cingulate gyri, precunei, and parietal cortices were defined as a VOI showing rCBF reduction in very early AD. A new indicator of rCBF abnormality in the VOI provided 86% accuracy for distinction of AD and healthy controls in the multicenter study. The area under the ROC curve was 0.934. CONCLUSION: Because an eZIS can use a common normal data base by converting site-specific SPECT data to the core data, the eZIS was useful for automated diagnosis of very early AD in routine studies in multiple institutions.

Reduction of blood eosinophil counts in eosinophilic chronic rhinosinusitis after surgery.

OBJECTIVE: This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery. METHODS: Blood eosinophil numbers and serum interleukin-5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed. RESULTS: Blood eosinophil numbers and serum interleukin-5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 ± 26.1 vs 443.9 ± 76.6 cells/µl, p < 0.05), and decreased significantly after surgery (825.7 ± 26.1 vs 76.7 ± 25.8 cells/µl, p < 0.05). CONCLUSION: Blood eosinophil numbers may reflect disease severity in eosinophilic chronic rhinosinusitis patients and their prognosis after surgery.

Usefulness of Pseudocontinuous Arterial Spin-Labeling for the Assessment of Patients with Head and Neck Squamous Cell Carcinoma by Measuring Tumor Blood Flow in the Pretreatment and Early Treatment Period.

BACKGROUND AND PURPOSE: For the assessment of the treatment response in non-surgical treatment, tumor blood flow provides the functional information of the tumor which is different from the morphological information such as tumor volume. The purpose of this study was to evaluate the diagnostic value of tumor blood flow values obtained by pseudocontinuous arterial spin-labeling in patients with head and neck squamous cell carcinoma. MATERIALS AND METHODS: Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods in all the patients, and the percentage change of tumor blood flow between the two was calculated. At the early treatment period, based on their tumor volume reduction rate, we divided the patients into stable disease and partial response groups for a subgroup analysis. The local control or failure was confirmed either by histopathology or by radiologic evaluation within the follow-up. RESULTS: Pretreatment tumor blood flow in patients in the failure group was significantly lower than that in patients in the local control group. In the subgroup analysis of patients with stable disease, the percentage change of tumor blood flow was significantly larger (due to the tumor blood flow increase from pretreatment value) in the local control group than in the failure group. In addition, in patients with a partial response, the percentage change of tumor blood flow was significantly smaller (due to the tumor blood flow decrease from the pretreatment value) in the local control group than in the failure group. The accuracy for determination of the local control group or the failure group in pretreatment tumor blood flow was 0.83 and that in the combination use of the percentage change of tumor blood flow and tumor volume in the early treatment period was 0.93. CONCLUSIONS: Tumor blood flow obtained by pseudocontinuous arterial spin-labeling can be useful for the determination of local control. The combined use of the percentage change of tumor blood flow and tumor volume had particularly high diagnostic accuracy.

Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS.

Differentiation of squamous cell carcinoma and inverted papilloma using non-invasive MR perfusion imaging.

OBJECTIVES: To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity. METHODS: We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IP in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T2 weighted images was determined in all patients. As a subgroup analysis, patients with IP were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IP and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed. RESULTS: The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 ± 33.1, 77.8 ± 31.5, 109.4 ± 16.7 and 58.8 ± 19.9 ml 100 g⁻¹ min⁻¹, respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IP and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings. CONCLUSIONS: The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity.

Age related change in the frequency of ara C-induced chromosome aberrations in human peripheral blood lymphocytes.

1-beta-D-Arabinofuranosylcytosine (ara C) has been known to inhibit repair replication in the G1 phase of cell cycle and to convert certain types of DNA damage into chromosome-type exchanges: e.g., dicentric or ring chromosomes. It is then considered to be a useful cytogenetic method to investigate the frequency of ara C-induced dicentric and ring chromosomes (dic and ring) for estimating cellular DNA damage or capacity to repair it. Peripheral blood lymphocytes from donors ranging from newborn to 91 years old were treated with 10 microM ara C in their G1 phase and the resulting disc and ring were observed to investigate whether age-related change in peripheral lymphocytes would be present in the amount of spontaneous DNA damage or in the capacity to repair it. Chromatid-type (Ct) aberrations and sister chromatid exchanges (SCEs) were also scored for additional cytogenetic indices of DNA damage in the lymphocytes. The results showed that the frequency of dic and ring had a negatively linear correlation with the logarithm of the age of the blood donors, but that the frequencies of Ct aberrations and SCEs were not influenced by the age. The present study suggests the presence of age-related change in the amount or in the capacity to repair certain types of DNA damage in the G1 phase of human peripheral lymphocytes. Other possible explanations for the present results are also discussed.

Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation.

BACKGROUND: At many lung transplant centers, right heart catheterization and transthoracic echocardiogram are part of the routine pre-transplant evaluation to measure pulmonary pressures. Because decisions regarding single vs bilateral lung transplant procedures and the need for cardiopulmonary bypass are often made based on pulmonary artery systolic pressures, we sought to examine the relationship between estimated and measured pulmonary artery systolic pressures using echocardiogram and catheterization, respectively. METHODS: We retrospectively reviewed all patients in our program who had measured pulmonary hypertension (n = 57). Patients with both echocardiogram-estimated and catheterization-measured pulmonary artery systolic pressures performed within 2 weeks of each other were included (n = 19). We analyzed results for correlation and linear regression in the entire group and in the patients with primary pulmonary hypertension (n = 8) and pulmonary fibrosis (n = 8). RESULTS: In patients with primary pulmonary hypertension, pulmonary artery systolic pressure was 94 +/- 27 and 95 +/- 15 mm Hg by echocardiogram and catheterization, respectively, with r(2) = 0.11; in patients with pulmonary fibrosis, 57 +/- 23 and 58 +/- 12 mm Hg with r(2) = 0.22; and in the whole group, 76 +/- 29 and 75 +/- 23 mm Hg with r(2) = 0.50. Thirty-two additional patients had mean pulmonary artery systolic pressure = 48 +/- 16 mm Hg by catheterization but either had no evidence of tricuspid regurgitation by echocardiogram (n = 22) or the pulmonary artery systolic pressure could not be measured (n = 10). CONCLUSIONS: In patients with pulmonary hypertension awaiting transplant, pulmonary artery systolic pressures estimated by echocardiogram correspond but do not serve as an accurate predictive model of pulmonary artery systolic pressures measured by catheterization. Technical limitations of the echocardiogram in this patient population often preclude estimating pulmonary artery systolic pressure.

Clinicopathological study of fatal myocardial sarcoidosis.

Presented here was an outline of fatal myocardial sarcoidosis in Japan based on 42 autopsy cases. The incidence, clinical features, pathological findings (particularly the distribution of sarcoid lesions in various organs, and gross as well as histological patterns have been reviewed. The ratio of fatal myocardial sarcoidosis to the total number of sarcoidosis deaths is higher than that of other countries and it appears characteristic of Japanese sarcoidosis that the disease occurs here predominantly after the fourth decade in females. Only 12% of myocardial sarcoidosis cases are diagnosed exactly. Conduction disturbances and dysrhythmias due to myocardial damage are its most common manifestations. The modes of presentation or cardiac death are sudden death, 16 cases (41%); congestive heart failure, 9 cases (23.1%); Adams-Stokes syndrome, except sudden death, 7 cases (17.9%); death due to dysrhythmia, 6 cases (15.4%); and 2 pacemaker deaths among the application of pacemakers, 7 cases. As for the ECG findings, A-V block and bundle-branch block was observed in most cases and ectopic beats were also frequently observed. The difficulty in exact diagnosis of myocardial sarcoidosis appears to be due to the frequency of lack of manifestation of systemic sarcoidosis as well as insidious cardiac involvement. The gross findings on myocardial lesions showed 3 patterns and each of the localized patterns corresponded to the histological extension. The conglomerate-band-like pattern corresponded to expansive invasion, the dendrite pattern to interstitial extension. The histological findings on the myocardial lesions were classified into four types: 1) exudative type, 2) granuloma type, 3) combined type of granuloma and fibrosis, 4) fibrotic type. Two extreme cases showed the exudative and fibrotic type, respectively, and were discussed.

Standardization of the clinical diagnosis of the dementia syndrome and its subtypes in a cross-national study: the Ni-Hon-Sea experience.

BACKGROUND: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan. METHOD: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises. RESULTS: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia. CONCLUSIONS: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.

Distribution of capsular types and antimicrobial susceptibility of invasive isolates of Streptococcus pneumoniae in Colombian children. Pneumococcal Study Group in Colombia.

Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in the developing world. This study describes the type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional initiative designed to determine the ideal serotype composition of a protein polysaccharide pneumococcal conjugate vaccine for use in children less than 5 years old in Latin America. In Colombia, during the study period, centres in Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%), 19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and 3.1% showing high level resistance. Among DSP isolates, 23% were also resistant to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the isolates that have DSP. Penicillin resistance was associated with types 23F (53.8%) and 14 (25.6%). These data provides information on capsular types prevalent in Colombia that will not only allow the formulation of an ideal vaccine for the region but also reinforce the need for ongoing regional surveillance.