Children's dental health: British expatriate residents in Tokyo, Japan

AIM: To identify in expatriate British parents resident in Tokyo, Japan, their levels of dental health knowledge, patterns of dental health behaviour, and caries status of their children compared to Japanese children. METHODS: 223 parents with children at one school were asked to complete a structured questionnaire. Data were collected on: parental knowledge and behaviours with respect to caries prevention, and sweet consumption of the children. The caries status of the children was established by a clinical examination, using standard criteria. RESULTS: The questionnaire response rate was 66.8%. The mean age of the children was 7.6 years (range 3-11 years). The responses related to 51 British, 21 Japanese, and 20 children who had British and Japanese mixed parents. 33% of British and none of Japanese children had sweet foods frequently. Fluoridated toothpaste was used by 67% of British and 10% of Japanese children. British parents knew about dental caries more than Japanese. 13% of British and 38% of Japanese children were found in the higher caries experience group. CONCLUSION: Parental access to information in the UK and to fluoridated toothpaste in Japan could have helped to prevent dental caries in these expatriate British children.     

Curative resection of hilar cholangiocarcinoma in a 25-year-old woman: report of a case

A 25-year-old woman was referred to our hospital with persistent upper abdominal pain. Preoperative imaging studies revealed a hilar bile duct stricture with portal venous encasement, and the patient underwent curative resection involving extended left hepatectomy and segmental portal vein resection. The pathological findings demonstrated a well-differentiated tubular adenocarcinoma of the bile duct with regional lymph node metastasis (stage IIIB according to the UICC TNM classification), as well as the overexpression of p53 proteins and the K-ras gene mutation in tumor cells. The patient has shown no evidence of recurrence in the 10 months since the operation. Although there are several reports of relatively young adults with cholangiocarcinoma, the majority of such patients demonstrate either an anomalous arrangement of the pancreaticobiliary duct system or primary sclerosing cholangitis. The absence of any morphological abnormalities in this patient’s biliary system implicates de novo carcinogenesis as the most likely cause of the cholangiocarcinoma.     

Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid

This study aimed to develop breakpoints of carbapenems for intraabdominal infections, based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target site. Imipenem, meropenem, and doripenem were each administered to 8-11 patients before abdominal surgery, and venous blood and peritoneal fluid samples were obtained. The drug concentrations in plasma and peritoneal fluid were determined and analyzed using population pharmacokinetic modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation was performed to estimate the probabilities of attaining the bacteriostatic and bactericidal targets (20% and 40% of the time above the minimum inhibitory concentration [MIC], respectively) in peritoneal fluid. The bacteriostatic and bactericidal breakpoints were defined as the highest MIC values at which the bacteriostatic and bactericidal probabilities in peritoneal fluid were 80% or more. The breakpoints for the minimum and maximum approved dosages of each drug were identical for imipenem, meropenem, and doripenem, and some of these values varied with dosing interval and infusion time. Site-specific PK-PD-based breakpoints are proposed here for the first time, and should help us to select appropriate carbapenem regimens for intraabdominal infections.     

Quantitative evaluation of ventricular dilatation using computed tomography in infants with congenital cytomegalovirus infection

Background

Infants with congenital cytomegalovirus infection (CCMVI) may develop brain abnormalities such as ventricular dilatation, which may potentially associate with sensorineural hearing loss. There is currently no recognized method for quantitative evaluation of ventricle size in infants with CCMVI. Our objectives were to establish a method for quantitative evaluation of ventricle size using computed tomography (CT) in infants with CCMVI, and determine a cut-off value associated with abnormal auditory brainstem response (ABR) early in life.

Design/Subjects

This study enrolled 19 infants with CCMVI and 21 non-infected newborn infants as a control group. Infants with CCMVI were divided into two subgroups according to ABR at the time of initial examination: normal ABR (11 infants) or abnormal ABR (8 infants). Ventricle size was assessed by calculating Evans’ index (EI) and lateral ventricle width/hemispheric width (LVW/HW) ratio on brain CT images, and was compared among groups. A cut-off ventricle size associated with abnormal ABR was determined.

Results

EI and LVW/HW ratio were significantly higher in the CCMVI with abnormal ABR group than the control and CCMVI with normal ABR groups. Cut-off values of 0.26 for EI and 0.28 for LVW/HW ratio had a sensitivity of 100% and 100%, respectively, and a specificity of 73% and 91%, respectively, for association with abnormal ABR.

Conclusions

We established a method for quantitative evaluation of ventricle size using EI and LVW/HW ratio on brain CT images in infants with CCMVI. LVW/HW ratio had a more association with abnormal ABR in the early postnatal period than EI.     

On the monitoring of dabigatran treatment in “real life” patients with atrial fibrillation

Introduction

The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients.

Material and methods

Ninety AF patients (68 ± 9 years, 67% men, mean CHADS₂ score 1.5) were treated with dabigatran 150 (n = 73) or 110 mg BID (n = 17). Trough plasma concentrations of total and free dabigatran by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to indirect measurements by Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as PT-INR and aPTT.

Results

Total plasma dabigatran varied 20-fold (12–237 ng/mL with 150 mg BID) and correlated well with free dabigatran (r² = 0.93). There were strong correlations between LC-MS/MS and HTI or ECA (p < 0.001) but these assays were less accurate with dabigatran below 50 ng/mL. The aPTT assay was not dependable and PT-INR not useful at all. There were weak correlations between creatinine clearance (Cockcroft-Gault) and LC-MS/MS, HTI and ECA (p < 0.001 for all). A high body weight with normal kidney function was associated with low dabigatran levels.

Conclusions

HTI and ECA reflect the intensity of dabigatran anticoagulation, but LC-MS/MS is required to quantify low levels or infer absence of dabigatran. Most real life patients with a normal creatinine clearance had low dabigatran levels suggesting a low risk of bleeding but possibly limited protection against stroke.     

Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology

Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.     

Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer

Background

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.

Methods

The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.

Results

Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).

Conclusions

Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.     

Pathophysiology of flow impairment during carotid artery stenting with an embolus protection filter

Objective

Carotid artery stenting (CAS) is a well-accepted treatment for atherosclerotic stenosis of carotid arteries. Since the occurrence of distal embolization with CAS is still a major concern embolus protection devices (EPD) are usually employed during the procedure. We examined two types of embolus protection filters (Angioguard XP (AG); Filterwire EZ (FW)) and evaluated the function. Thus, the filter was examined postoperatively and the cause of intraoperative flow impairment was evaluated.

Materials and methods

CAS was performed for 54 patients with carotid artery stenosis (55 lesions: 25 AG; 27 FW; 3 others). After completing CAS the filter membrane was stained with hematoxylin-eosin (HE) solution and removed from the filter strut. Once mounted on a glass slide the filter was evaluated under a microscope. The area occupied with debris was measured and the relationship to intraoperative flow impairment was evaluated. Furthermore, the relationship between perioperative ischemic complications and intraoperative flow impairment was statistically analyzed.

Results

Microscopic observation of the slide revealed the pore density of the FW was 1.5 times higher than that of the AG and the filter area of the FW was 2.5 times wider than than the AG. HE staining facilitated characterization of the debris composition. The area occupied with debris was significantly more in the AG (0.241?±0.13 cm²) than in the FW (0.129?±0.093 cm²). Thus, fibrin was significantly more precipitated in the AG. Flow impairment occurred in 6 AG cases (24.0 %) and 4 FW cases (14.8 %). It was induced by filter obstruction in the AG and by vasospasms in the FW. Three cases treated with AG (12.0 %) were complicated with cerebral infarction and all of them were related to flow impairment. One FW case (3.7 %) was complicated with cerebral infarction in presence of preserved flow throughout the intervention.

Conclusion

Filter function is different according to each design. The cause of flow impairment was attributable to filter obstruction in the AG group and to vasospasms in the FW group. Filter obstruction tends to result in cerebral infarction.