Masticatory Behavior Change with a Wearable Chewing Counter: A Randomized Controlled Trial.

Because a relationship has been reported between masticatory behavior, obesity, and postprandial blood glucose, it is recommended to chew well and take a longer time to eat. The purpose of this study was to examine the possibility of changing masticatory behavior using a small ear-hung wearable chewing counter, which can monitor masticatory behavior without disturbing daily meals. In total, 235 healthy volunteers participated in a 4-wk randomized controlled trial and were divided into 3 groups. All participants were instructed about the importance of mastication at the first visit. During the intervention, group B used the chewing counter without an algorithm during each meal (notification of the number of chews after meal), and group C used the chewing counter with a masticatory behavior change algorithm (setting a target value and displaying the number of chews in real time). Group A was set as the control group. The number of chews and the meal time when consuming 1 rice ball (100 g) were measured before and after the intervention using the chewing counter, and the rate of change in these values was evaluated. Participants also provided a subjective evaluation of their changes in masticatory behavior. The number of chews and the meal time of 1 rice ball increased significantly in groups B and C compared with before the intervention, and the rate of change was significantly higher in group C than in group A and group B. In addition, the subjective evaluation of the change in the number of chews was highest in group C. Self-monitoring of masticatory behavior by providing a target value and the degree of achievement for the number of chews using a wearable chewing counter with a behavioral change algorithm could promote effective change in masticatory behavior and lead to an increased number of chews. (Trial ID: UMIN000034476).

Imaging Differences between Neuromyelitis Optica Spectrum Disorders and Multiple Sclerosis: A Multi-Institutional Study in Japan.

BACKGROUND AND PURPOSE: Both clinical and imaging criteria must be met to diagnose neuromyelitis optica spectrum disorders and multiple sclerosis. However, neuromyelitis optica spectrum disorders are often misdiagnosed as MS because of an overlap in MR imaging features. The purpose of this study was to confirm imaging differences between neuromyelitis optica spectrum disorders and MS with visually detailed quantitative analyses of large-sample data. MATERIALS AND METHODS: We retrospectively examined 89 consecutive patients with neuromyelitis optica spectrum disorders (median age, 51 years; range, 16-85 years; females, 77; aquaporin 4 immunoglobulin G-positive, 93%) and 89 with MS (median age, 36 years; range, 18-67 years; females, 68; relapsing-remitting MS, 89%; primary-progressive MS, 7%; secondary-progressive MS, 2%) from 9 institutions across Japan (April 2008 to December 2012). Two neuroradiologists visually evaluated the number, location, and size of all lesions using the Mann-Whitney U test or the Fisher exact test. RESULTS: We enrolled 79 patients with neuromyelitis optica spectrum disorders and 87 with MS for brain analysis, 57 with neuromyelitis optica spectrum disorders and 55 with MS for spinal cord analysis, and 42 with neuromyelitis optica spectrum disorders and 14 with MS for optic nerve analysis. We identified 911 brain lesions in neuromyelitis optica spectrum disorders, 1659 brain lesions in MS, 86 spinal cord lesions in neuromyelitis optica spectrum disorders, and 102 spinal cord lesions in MS. The frequencies of periventricular white matter and deep white matter lesions were 17% and 68% in neuromyelitis optica spectrum disorders versus 41% and 42% in MS, respectively (location of brain lesions, P < .001). We found a significant difference in the distribution of spinal cord lesions between these 2 diseases (P = .024): More thoracic lesions than cervical lesions were present in neuromyelitis optica spectrum disorders (cervical versus thoracic, 29% versus 71%), whereas they were equally distributed in MS (46% versus 54%). Furthermore, thoracic lesions were significantly longer than cervical lesions in neuromyelitis optica spectrum disorders (P = .001), but not in MS (P = .80). CONCLUSIONS: Visually detailed quantitative analyses confirmed imaging differences, especially in brain and spinal cord lesions, between neuromyelitis optica spectrum disorders and MS. These observations may have clinical implications.

Relationship between Eustachian tube dysfunction and otitis media with effusion in radiotherapy patients.

OBJECTIVE: This study evaluated the relationship between radiation and Eustachian tube dysfunction, and examined the radiation dose required to induce otitis media with effusion. METHODS: The function of 36 Eustachian tubes in 18 patients with head and neck cancer were examined sonotubometrically before, during, and 1, 2 and 3 months after, intensity-modulated radiotherapy. Patients with an increase of 5 dB or less in sound pressure level (dB) during swallowing were categorised as being in the dysfunction group. Additionally, radiation dose distributions were assessed in all Eustachian tubes using three dose-volume histogram parameters. RESULTS: Twenty-two of 25 normally functioning Eustachian tubes before radiotherapy (88.0 per cent) shifted to the dysfunction group after therapy. All ears that developed otitis media with effusion belonged to the dysfunction group. The radiation dose threshold evaluation revealed that ears with otitis media with effusion received significantly higher doses to the Eustachian tubes. CONCLUSION: The results indicate a relationship between radiation dose and Eustachian tube dysfunction and otitis media with effusion.

Re-evaluating Cut-off Points for the Expansion of Deceased Donor Criteria for Kidney Transplantation in Japan.

BACKGROUND: A shortage of donors poses a serious problem for organ transplantation around the world. In response, the concept of the expanded criteria donor (ECD) has been defined to include donors with traditionally less favorable characteristics. That definition has now been accepted and is being applied in kidney transplantation in the United States and Europe. However, the ECD has not yet been defined for deceased donor kidney transplantation in Japan. PATIENTS AND METHODS: We analyzed data on graft survival and relevant risk factors in patients who received deceased donor kidney transplants through the East Japan Branch of the Japan Organ Transplant network (n = 1051). Recipients were divided into two groups: the standard-function group (estimated glomerular filtration rate [eGFR] ≥20 mL/min/1.73 m2; n = 906) and the poor-function group (eGFR <20 mL/min/1.73 m2; n = 145; Cox proportional hazards regression analysis; P < .0001). RESULTS: The 10-year survival rate was significantly lower in the poor-function group than in the standard-function group (85.5% vs 22.5%; P < .0001). The two groups differed significantly in recipient and donor risk for graft failure. Recipient risk factors were length of time on dialysis before renal transplantation and incidence of acute rejection after transplantation. Donor risk factors were donor category (heart death), age, history of hypertension, presence of cerebrovascular disease, mean urine output, and donor creatinine level immediately before donor nephrectomy, total ischemic time, and warm ischemic time. CONCLUSION: Data from deceased donor transplantation should be analyzed in depth to determine which factors influence renal function after transplantation. In addition, ECD standards should be reconsidered for use in a Japanese context.

Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials.

PURPOSE: The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. METHODS: Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. RESULTS: pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. CONCLUSION: This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC.

Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds in humans.

OBJECTIVE: Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. MATERIAL AND METHODS: One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. RESULTS: Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. CONCLUSIONS: The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders.

Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer.

BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

Long insular artery infarction: characteristics of a previously unrecognized entity.

BACKGROUND AND PURPOSE: The infarctions arising in the long insular arteries of the M2 segment have been poorly described in the past. The purpose of this study was to investigate the incidence, clinical characteristics, and pathogenesis of long insular artery infarcts. MATERIALS AND METHODS: Patients with acute isolated infarcts in territories of the long insular arteries and lenticulostriate arteries were retrospectively reviewed. The long insular artery territory was defined as the area above the lenticulostriate artery territory at the level of centrum semiovale. On the coronal section, it lies between the tip of the anterior horn and the top of the superior limb of the insular cleft. Clinical features and prevalence of embolic sources were compared between the 2 groups. RESULTS: Of 356 consecutive patients with acute ischemic stroke, 8 (2.2%) had a long insular artery infarct (long insular artery group) and 50 (14.0%) had a lenticulostriate artery infarct (lenticulostriate artery group). There were no differences in age, sex, prevalence of risk factors, neurologic deficit, or incidence of lacunar syndromes between these groups. Abrupt onset was more common in the long insular artery than in the lenticulostriate artery group (P = .004). The prevalence of embolic high-risk sources (eg, atrial fibrillation) was not significantly different between these groups, but the combined prevalence of all embolic sources, including moderate-risk sources, was significantly higher in the long insular artery group (P = .048). CONCLUSIONS: Isolated infarction caused by long insular artery occlusion is not rare. Abrupt onset is more common for long insular artery infarction, and this finding could be attributed to the higher incidence of an embolic etiology as the pathogenesis of infarction.

Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease.

The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted whole-genome exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N=13), I-II (N=20), III-IV (N=19) and V-VI (N=19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N=30), and in patients with late-onset AD (N=37), dementia with Lewy bodies (N=17) and Parkinson disease (N=36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Protein-protein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.

Robot hand with soft tactile sensors and underactuated control.

We developed a robot hand with three fingers and controlled them using underactuated control to obtain a more flexible grip. With underactuated control, we can flexibly operate an artificial robot hand and reduce the number of actuators. The robot fingers had three joints to imitate human fingers. One finger was driven by one wire and one servo motor for bending and by three torsion springs for extension. We also developed a soft tactile sensor having three pneumatic sensors and mounted it on front of each robot fingers. We obtained the following information from our experimental examinations of the robot hand. It adaptively grasped an object by underactuated control. The soft tactile sensor deftly touched an object, and the data showed the contact position with. By analyzing the data from tactile sensors, we obtained the rough information of the object's shape.

Growth of Japanese breastfed infants compared to national references and World Health Organization growth standards.

AIM: The aim of this study was to compare the growth of Japanese infants that were exclusively breastfed to those of national references and World Health Organization (WHO) standards. METHODS: Mothers, who delivered a normal term baby and had been exclusively breastfeeding for at least 4 months, were enrolled. The lengths, body weights and head circumferences of 647 children, aged 0-24 months, were obtained and compared to national references and WHO standards. RESULTS: Comparisons of the national references for both length and body weight indicated that breastfed infants were significantly shorter and lighter almost throughout the first 24 months. Conversely, head circumferences of breastfed infants were significantly larger at 1 and 6 months of age in boys and 6 months in girls. Compared to WHO standards, similar trends to the comparisons with national references were found. CONCLUSION: There were significant differences identified between the growth of breastfed infants and existing national references and WHO standards.

Factors related to postoperative delirium in patients with lower limb ischaemia: a prospective cohort study.

OBJECTIVES: To preoperatively determine candidates at definitive risk of postoperative delirium (POD), we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery. DESIGN: A prospective cohort study. PATIENTS AND METHODS: 299 patients (age ≥ 60 years) who underwent bypasses in 1995-2006 were enrolled. Cognitive impairment was assessed by the Revised Hasegawa Dementia Scale, the Confusion Assessment Method was also used, and severity was graded as Grade I-III (mild to severe) based on the Delirium Rating Scale. All patients were followed for 3 years. RESULTS: POD occurred in 88 patients (29%), with a median age of 75 (10) years (IQR). Onset was 2 (1) days postoperatively, and a duration of 2 (2) days was observed. POD was hyperactive in 89% and was Grade I, II, and III in 11%, 68%, and 21% respectively. Multiple logistic regression analysis identified the following risk factors for POD: age ≥ 72 years (<0.0001), end-stage renal failure (0.001), multiple occlusive lesions (<0.0001), cognitive impairment (0.003), and critical limb ischaemia (0.034). The 3-year survival rate was similar when comparing POD and non-POD patients (84% vs. 88%, NS). CONCLUSIONS: This study identified 5 risk factors for POD in patients undergoing bypasses for limb ischaemia. Long-term outcomes were similar when comparing the patients who experienced POD with those who did not.

Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers.

BACKGROUND: We established the cell cycle profiling (C2P) assay for specific activity (SA; activity/expression) of cyclin-dependent kinases (CDKs). C2P risk score (C2P-RS) based on CDK1 and CDK2 SAs was significantly associated with relapse in breast cancer (BC). This study was conducted to investigate the predictive value of C2P-RS for neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Among 124 eligible patients, 122 were treated with weekly paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide (P-FEC) and 2 were treated with paclitaxel monotherapy. C2P-RS was determined via C2P using frozen biopsy samples before NAC. RESULTS: Negative estrogen receptor (ER), negative progesterone receptor (PR), positive human epidermal growth factor receptor 2 (HER2), high Ki-67 expression and intermediate + high C2P-RS were significantly associated with high pathological complete response (pCR) rates compared with positive ER (30% versus 9%), positive PR (25% versus 6%), negative HER2 (34% versus 11%), low Ki-67 expression (24% versus 7%) or low C2P-RS (24% versus 9%), respectively. The combination of C2P-RS and Ki-67 had a stronger impact on pCR than each parameter alone, and a multivariate analysis showed that the combination was an independent predictor of pCR (odds ratio 3.3, 95% confidence interval 1.1-9.5). CONCLUSIONS: C2P-RS was significantly associated with pCR after P-FEC and may be a useful predictor for chemotherapy in BCs.

Phase II trial of preoperative chemotherapy for breast cancer: Japan Breast Cancer Research Network (JBCRN)-02 trial.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In our previous study, biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were essential predictors of the effectiveness of NAC to help individualize treatment. This study examined the effect of NAC on the disease-free survival (DFS) of breast cancer patients. Furthermore, the study was expanded by adding Ki-67 as a biological marker, and examined the correlation between Ki-67 and the prognosis. PATIENTS AND METHODS: Between September 2005 and September 2007, 43 patients with breast cancer received NAC and surgery. Four cycles of DC (doxorubicin: 60 mg/m(2) and cyclophosphamide: 500 mg/m(2)) were administered intravenously (i.v.) on day 1 every 21 days, followed by 12 cycles of paclitaxel i.v. (80 mg/m(2)) every 7 days, prior to surgery. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoint was DFS; the pCR rate was estimated for each groups stratified by the presence or absence of different factors (PcR, ER/PgR, and Ki-67). RESULTS: The clinical response (cCR+cPR) rate was 81.0%, and the pCR rate was 25.6%. The pCR rate was 75, 50, 9 and 0% in HER2(+)/ER(-), HER2(+)/ER(+), HER2(-)/ER(-), and HER2(-)/ER(+) patients, respectively. The 4-year DFS rate was estimated at 78% for all patients. The HER2 status was an independent predictor of pathological complete response (pCR). The DFS rate of patients with lower Ki-67 values (<15%) was higher than that of patients with higher Ki-67 values (≥15%). The treatment-related adverse events were manageable: the majority were mild, but five patients experienced grade 3 (neutropenia and sensory neuropathy) adverse events. CONCLUSION: DC followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. HER2 overexpression may be a good predictive marker of pCR, and the Ki-67 value after NAC may be a prognostic factor for DFS.

MR imaging of ventral thalamic nuclei.

BACKGROUND AND PURPOSE: The Vim and VPL are important target regions of the thalamus for DBS. Our aim was to clarify the anatomic locations of the ventral thalamic nuclei, including the Vim and VPL, on MR imaging. MATERIALS AND METHODS: Ten healthy adult volunteers underwent MR imaging by using a 1.5T whole-body scanner. The subjects included 5 men and 5 women, ranging in age from 23 to 38 years, with a mean age of 28 years. The subjects were imaged with STIR sequences (TR/TE/TI = 3200 ms/15 ms/120 ms) and DTI with a single-shot echo-planar imaging technique (TR/TE = 6000 ms/88 ms, b-value = 2000 s/mm(2)). Tractography of the CTC and spinothalamic pathway was used to identify the thalamic nuclei. Tractography of the PT was used as a reference, and the results were superimposed on the STIR image, FA map, and color-coded vector map. RESULTS: The Vim, VPL, and PT were all in close contact at the level through the ventral thalamus. The Vim was bounded laterally by the PT and medially by the IML. The VPL was bounded anteriorly by the Vim, laterally by the internal capsule, and medially by the IML. The posterior boundary of the VPL was defined by a band of low FA that divided the VPL from the pulvinar. CONCLUSIONS: The ventral thalamic nuclei can be identified on MR imaging by using reference structures such as the PT and the IML.

Opening velocity, a novel parameter, for finger tapping test in patients with Parkinson's disease.

OBJECTIVES: A new system consisting of an accelerometer and touch sensor was developed to find objective parameters for the finger tapping (FT) test in patients with Parkinson's disease (PD). METHODS: We recruited sixteen patients with PD and thirty-two age-matched healthy volunteers (HVs). By using this new system, various parameters related to velocity, amplitude, rhythm and number in the FT test were measured in patients with PD and examined in comparison with those of HVs on the basis of the Unified Parkinson's Disease Rating Scale (UPDRS) FT score. RESULTS: The new system allowed us to measure fourteen parameters of FT movement very easily, and a radar chart showed obvious differences in most of these parameters between HVs and patients with PD. Principal component analysis showed that fourteen parameters were classified into three components: (1) both mean and standard deviation (SD) of both amplitude and velocity, (2) number of FT for 60s and mean FT interval, and (3) SD of FT interval. The first (velocity- and amplitude-related parameters) and third (rhythm-related parameters) components contributed to discrimination of PD from HVs. Maximum opening velocity (MoV) was the best of these parameters because of its sensitivity and association with the UPDRS FT score. CONCLUSIONS: A novel system for the FT test, which is compact, simple and efficient, has been developed. Velocity- and amplitude-related parameters were indicated to be valuable for evaluation of the FT test in patients with PD. In particular, we first propose that MoV is a novel marker for the FT test.

Prediction of disease-associated single nucleotide polymorphisms using virtual genomes constructed from a public haplotype database.

OBJECTIVES: Simultaneous dealing of hundreds of thousands of single nucleotide polymorphisms (SNPs) in genome-wide association studies is laborious. The aim of our study is to develop a method to decrease the number of candidate SNPs prior to the genotyping of study subjects. METHODS: We created virtual genotype data on case and control subjects from data of the International HapMap Project by using haplotype-based simulation method. We repeated virtual case-control association studies and selected candidate SNPs. We applied the selected SNPs to previously published genetic case-control studies. Sensitivity to detect association with causative genes using our method was compared to the original studies and results using tag SNPs. RESULTS: We found a discrete distribution pattern of SNPs, which was able to produce significant results in case-control association studies. The number of candidate SNPs that we selected was 24.7% of the number of the original set of SNPs. We applied this method to previously published genetic case-control studies and found that the use of candidate SNPs improved the sensitivity for detecting significant alleles, both compared to the original studies and to the use of tag SNPs. The results were not affected by the difference of the diseases and genes involved. CONCLUSIONS: Our simulation-based approach has advantages of reducing costs and improving performance to detect significant alleles. This method can be used without considering the specific disease and genes involved.

Incidental acute infarcts identified on diffusion-weighted images: a university hospital-based study.

BACKGROUND AND PURPOSE: Pathogenesis of leukoaraiosis is incompletely understood and accumulation of small infarctions may be one of the possible sources of such white matter lesions. Thus, the purpose of this study was to identify the rate of incident infarction as depicted on diffusion-weighted images (DWIs) obtained from a general patient population. MATERIALS AND METHODS: During the 4-year study period, a total of 60 patients (36 men and 24 women) had an incidental DWI-defined infarction without overt clinical symptoms suggestive of a stroke or a transient ischemic attack. All of the MR images were obtained by using a similar protocol on 2 identical 1.5T whole-body scanners. The patient's vascular risk factors, as well as the presence of white matter lesions (WMLs) on MR imaging and atheromatous changes on MR angiography, were assessed retrospectively. The incidental DWI-defined infarcts were also characterized in terms of their lateralization, lobe, and specific location. RESULTS: A total of 16,206 consecutive brain MR images were done during the study period; the overall incidence of incidental infarcts was 0.37%. Most of these patients with an incidental infarct had vascular risk factors and WMLs on MR images. Most of these patients (80%) had a single lesion on DWI. A total of 88 lesions were identified; most were located in the white matter of the supratentorial brain, primarily in the frontoparietal lobes. There were also lesions involving the brain stem (n = 2). The lesions involving cerebrum were more commonly located in the right side (right to left = 52:34). CONCLUSION: Small, DWI-defined acute brain infarctions can be found incidentally in an asymptomatic population; this finding may account, at least in part, for the pathogenesis of WMLs identified on MR imaging.

Economic impact of extended treatment with peginterferon alpha-2a and ribavirin for slow hepatitis C virologic responders.

It is difficult to achieve a sustained virologic response from antiviral therapy for genotype 1 hepatitis C virus-infected patients without a sufficient virologic response in the early weeks after treatment. However, a recent study has reported on the effectiveness of an extended course of treatment with peginterferon alpha-2a plus ribavirin for slow virologic responders. The aim of this study was to evaluate the economic impact of an extended course of treatment. A Markov cohort model of hepatitis C was designed in order to demonstrate the clinical states, based on the assigned transition probabilities over 30 years. The slow virologic responders treated with an extended 72-week course of therapy could increase by 0.55 the quality-adjusted life years (=15.35-14.80) and reduce the lifetime cost by $2762 (=71 559-69 438) in comparison with those treated by the standard 48-week course. One-way sensitivity analyses did not change the cost-effectiveness. Therefore, the extended 72 weeks of treatment with peginterferon alpha-2a plus ribavirin for slow virologic responders could be cost-effective in comparison with the standard 48 weeks of treatment.

Association of GSTP1 expression with resistance to docetaxel and paclitaxel in human breast cancers.

AIMS: It has been reported that glutathione S-transferase P1 (GSTP1) expression is implicated in resistance to taxanes (docetaxel and paclitaxel) in human breast cancer cells in vitro. In the study presented here, we examine whether GSTP1 expression is associated with resistance to docetaxel or paclitaxel in human breast cancers. We also investigated the relationship between GSTP1 methylation status and response to these taxanes. MATERIAL AND METHODS: Sixty two primary breast cancer patients were treated with docetaxel or paclitaxel as primary systemic treatment (PST). GSTP1 expression was detected immunohistochemically and the hypermethylation status GSTP1 gene was identified with a methylation specific primer assay. RESULTS: The mean tumor reduction rate for all patients (n=62) was significantly (p<0.001) higher in GSTP1 negative (0.73+/-0.04; mean+/-standard error) than GSTP1 positive (0.31+/-0.09) tumors. The subset analysis showed that the mean reduction rate was significantly (p=0.005) higher in GSTP1 negative (0.59+/-0.06) than GSTP1 positive (0.11+/-0.13) tumors in the docetaxel group as well as in the paclitaxel group (p=0.006; GSTP1 negative tumors: 0.84+/-0.05; GSTP1 positive tumors: 0.56+/-0.08). On the other hand, GSTP1 methylation showed no significant association with the reduction rate. CONCLUSION: Our present study has suggested that GSTP1 protein expression, but not GSTP1 methylation status, might be associated with response to docetaxel and paclitaxel. This suggests that GSTP1 immunohistochemical expression might be a potentially clinically useful predictive factor for response to docetaxel and paclitaxel.