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Although most patients in the intensive care unit (ICU) receive antibiotics, little is known about patterns of antibiotic use in ICUs in Japan. The objective of this study was to evaluate the pattern of antibiotic use in ICUs. A nationwide one-day cross-sectional surveillance of antibiotic use in the ICU was conducted three times between January 2011 and December 2011. All patients aged at least16 years were included. Data from 52 ICUs and 1148 patients were reviewed. There were 1028 prescriptions for intravenous antibiotics. Of 1148 patients, 834 (73%) received at least one intravenous antibiotic, and 575 had at least one known site of infection. Respiratory and intra-abdominal infections were the two most common types. Of 1028 prescriptions, 331 (34%) were for surgical or medical prophylaxis. Excluding prophylaxis, carbapenems were the most commonly prescribed agent. Infectious disease consultations, pre- and post-prescription antimicrobial stewardship, and ICU-dedicated antibiograms were available in 44%, 52%, 77%, and 21% of the ICUs, respectively. In logistic regression analysis adjusting for patient characteristics, treatment in a university hospital (adjusted odds ratio, 1.72; 95% CI, 1.05–2.84; P = 0.033) and an open ICU (adjusted odds ratio, 2.30; 95% CI, 1.02–5.17; P = 0.044) were significantly associated with greater likelihood of carbapenem use. An increase in the number of closed ICUs and more intensive care specialists may reduce carbapenem use in Japanese ICUs. Large-scale epidemiological studies of antimicrobial resistance in the ICU are needed.

Purpose To evaluate whether white matter tracts within the Papez circuit are altered in patients with unilateral hippocampal sclerosis (HS). Methods Twenty patients with histologically proven unilateral HS and 20 age-matched controls were studied with a 3 T Epilepsy-dedicated MRI protocol including a MPRAGE sequence for hippocampus volumetry and a diffusion tensor imaging (DTI) sequence (61 diffusion-encoding directions, 2 × 2 × 2 mm3 voxels) for diffusion tensor tractography (DTT). An energy-based global tracking algorithm was used to calculate streamline counts (SC) and fractional anisotropy (FA) of cingulate, fornix, and mammillo-thalamic tracts, respectively. Results Sclerotic hippocampi were significantly smaller compared to the contralateral side and to age-matched controls. Cingulum SC but not FA were reduced on the hippocampal sclerosis (258 + 81.0) and contralateral side (271 + 85.6) compared to age-matched controls (447 + 138). Conclusion Focusing on white matter tracts of the Papez circuit we showed that in patients with intractable temporal lobe epilepsy unilateral hippocampal sclerosis is associated with a bilateral reduction of cingulum association fibers projecting from the cingulate gyrus to the parahippocampal gyrus.

Objectives Focal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of medically intractable epilepsy. FCDs are characterized by local architectural disturbances of the neocortex and often by a blurred gray-white matter boundary indicating abnormal white matter myelination. We have recently shown that myelination is also compromised in the gray matter of dysplastic areas, since transcripts encoding factors for oligodendrocyte differentiation and myelination are downregulated and myelin fibers appear fractured and disorganized. Methods Here, we characterized the gray matter-associated myelination pathology in detail by in situ hybridization, immunohistochemistry, and electron microscopy with markers for myelin, mature oligodendrocytes, and oligodendrocyte precursor cells in tissue sections of FCD IIa and control cortices. In addition, we isolated oligodendrocyte precursor cells from resected dysplastic tissue and performed proliferation assays. Results We show that the proportion of myelinated gray matter is similar in the dysplastic cortex to that in controls and myelinated fibers extend up to layer III. On the ultrastructural level, however, we found that the myelin sheaths of layer V axons are thinner in dysplastic specimens than in controls. In addition, the density of oligodendrocyte precursor cells and of mature oligodendrocytes was reduced. Finally, we show for the first time that oligodendrocyte precursor cells isolated from resected dysplastic cortex have a reduced proliferation capacity in comparison to controls. Significance These results indicate that proliferation and differentiation of oligodendrocyte precursor cells and the formation of myelin sheaths are compromised in FCD and might contribute to the epileptogenicity of this cortical malformation.

Objective Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). Methods Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer-specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region. Results We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer-specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32-positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin- and Calretinin-positive interneurons in layers II and III were not different from controls, whereas Parvalbumin-expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4-positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b. Significance The application of a broad panel of markers defining layer-specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin-positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition.

To compare the performance of machine learning using multiparametric magnetic resonance imaging (mp-MRI) and positron-emission tomography (PET) to distinguish between uterine sarcoma and leiomyoma.This retrospective study was approved by the institutional review board and informed consent was waived. Sixty-seven consecutive patients with uterine sarcoma or leiomyoma who underwent pelvic 3 T MRI and PET were included. Of 67 patients, 11 had uterine sarcomas and 56 had leiomyomas. Seven different parameters were measured in the tumours, from T2-weighted, T1-weighted, contrast-enhanced, and diffusion-weighted MRI, and PET. The areas under the receiver operating characteristic curves (AUC) with a leave-one-out cross-validation were used to compare the diagnostic performances of the univariate and multivariate logistic regression (LR) model with those of two board-certified radiologists.The AUCs of the univariate models using MRI parameters (0.68-0.8) were inferior to that of the maximum standardised uptake value (SUVmax) of PET (0.85); however, the AUC of the multivariate LR model (0.92) was superior to that of SUVmax, and comparable to that of the board-certified radiologists (0.97 and 0.89).The diagnostic performance of the machine learning using mp-MRI was superior to PET and comparable to that of experienced radiologists.

We investigated the correlation between class II HLA epitope mismatch and antibody-mediated rejection (AMR) episodes in kidney transplant recipients. In patients with AMR, epitope mismatch was also examined for each class II HLA mismatch to determine development of de novo donor-specific antibodies (DSAs).We conducted a retrospective study of 167 kidney recipients. The numbers of eplet mismatches were compared between those with (n = 12) and without (n = 155) AMR, and the numbers of eplet mismatches for each type of mismatch in class II HLA among the AMR patients was also compared.Twelve AMR episodes were diagnosed. The total number of eplet mismatches in AMR patients with either HLA-DR or HLA-DQ was greater than those in non-AMR patients (P = .0085 and P = .0041, respectively), though the incidence of HLA class II (DRB1 + DQB) mismatch was not significantly different between the groups (P = .095). The rate of non-AMR status in patients with ≥15 was lower than those with 15 HLA class II (DR or DQ) eplet mismatches (P = .0299 and P = .0128, respectively). Twelve AMR patients had 30 HLA-DRB1/3/4/5 and 32 HLA-DQA/B mismatches. In both HLA-DR and -DQ, de novo DSAs developed against HLAs in association with a greater number of eplet mismatches (P = .0046 and P = .0044, respectively).Class II HLA eplet mismatch is a risk factor for de novo DSA and AMR in kidney transplantation recipients. Furthermore, the number of HLA class II eplet mismatches has greater significance as a risk factor than the number of conventional HLA class II mismatches.

Objective The stereotactic suboccipital-transcerebellar approach is widely regarded as technically demanding requiring substantial modifications of the standard stereotactic methods thus often making a transfrontal approach preferable. In this comprehensive series we aim to present our experience with the stereotactic suboccipital-transcerebellar approach to lesions of the brainstem or cerebellum using two standard stereotactic systems. Patients and Methods In the period of 2000–2015 overall 80 patients (mean age 43.95 ± 23.76 years) with lesions of the brainstem or cerebellum underwent stereotactic surgery for diagnostic or therapeutic purposes via a suboccipital approach. In 59 patients stereotactic surgery was performed using the Riechert-Mundinger Stereotactic Frame, the Leksell Stereotactic Frame was used in 21 patients. For both frames standard systems were used without modification. Retrospective analysis of intraoperative stereotactic technique, achievement of the predefined surgical objectives and perioperative complications was carried out. Results In this series, the stereotactic suboccipital-transcerebellar approach proved to be feasible with two standard stereotactic systems. Using either frame the predefined surgical objective was achieved in 90.0%. A verified neuropathological diagnosis was obtained in 89.6%. Minor transient perioperative complications occurred in 8.75%. There was no surgery-related permanent morbidity or mortality. Conclusion In this comprehensive series the stereotactic suboccipital-transcerebellar approach using a standard stereotactic system proved to be a favorable stereotactic approach with a high diagnostic success rate and no surgery-related permanent morbidity.

Background To clarify the patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy. Methods From January 1999 to March 2012, 577 patients underwent laparoscopic or laparoscopy-assisted gastrectomy for curative resection of gastric cancer. Recurrence patterns were classified as locoregional, hematogenous, peritoneal, distant lymph node and mixed. Recurrence patterns and time to recurrence were retrospectively examined and risk factors for recurrence were analyzed. Results Recurrence occurred in 28 (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%), hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to recurrence was 384 days (range 83–1497 days). Recurrence was detected within a year in 13 cases (46.4%), within two years in 21 (75%), and within three years in 25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of operation, tumor depth, and lymph node classification as risk factors for recurrence. Multivariate analysis indicated tumor depth and lymph node classification as risk factors of recurrence. Conclusions Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are similar to those after open gastrectomy, with no peculiarities specific to laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed according to the present inclusion criteria, follow-up can be similarly performed as for open gastrectomy.

Focal cortical dysplasias (FCDs) are local malformations of the human neocortex with strong epileptogenic potential. To investigate the underlying pathomechanisms, we performed a whole human transcriptome screening to compare the gene expression pattern of dysplastic versus nondysplastic temporal neocortex. Tissue obtained from FCD IIIa cases (mean age 20.5 years) who had undergone surgical treatment, due to intractable epilepsy, was compared with nondysplastic specimens (mean age 19.9 years) by means of Affymetrix arrays covering 28 869 genes. We found 211 differentially expressed genes (DEX) among which mainly genes important for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa. These findings were confirmed as functionally important by Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis. The reduced expression of myelin-associated transcripts was confirmed for FCD Ia, IIa, and IIIa by real-time RT-qPCR. In addition, we found that the density of myelin basic protein mRNA-expressing oligodendrocytes and of 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive myelin fibers was significantly reduced in dysplastic cortex. Moreover, high-resolution confocal imaging and 3D reconstruction revealed that the myelin fiber network was severely disorganized in dysplastic neocortex, indicating a disturbance of myelin sheath formation and maintenance in FCD.

Purpose: To examine the efficacy of UFT, an oral 5-fluorouracil derivative agent, as post-operative adjuvant therapy for pathologic (p-) stage I non-small-cell lung cancer (NSCLC), because a previous randomized study had suggested it was efficacious for early-stage NSCLC patients. Patients and methods: Patients with completely resected p-stage I, adenocarcinoma or squamous cell carcinoma were eligible. A total of 332 patients were randomized to the surgery-alone group (control group) and the treatment group (UFT 400 mg/m 2 for 1 year after surgery, UFT group) after stratification by the histologic types. Results: For all patients, the 5- and 8-year survival rates for the UFT group were 82.2% and 73.0%, and those for the control group were 75.9% and 61.2%, respectively; no statistically significant improvement of survival was achieved by UFT administration (P = 0.105). For Ad patients, the 5- and 8-year survival rates of the UFT group (n = 120) were 85.2% and 79.5%, respectively, which seemed better than those of the control group (n = 121) (79.2% and 64.0%, respectively; P = 0.081). For squamous cell carcinoma patients, there was also no difference in survival between the control group (n = 48) and the UFT group (n = 43) (P = 0.762). For all pT1 patients, the 5- and 8-year survival rates of the UFT group were 83.6% and 82.1%, respectively, significantly better than those of the control group (77.9% and 57.6%, respectively, P = 0.036); UFT was not significantly effective for pT2 patients. For pT1 adenocarcinoma patients, UFT administration markedly improved the survival (P = 0.011). Conclusion: Post-operative UFT administration did not significantly improve post-operative survival of p-stage I NSCLC patients. Subset analyses suggested that UFT might be effective in pT1N0M0 adenocarcinoma patients.

Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO (-/-) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26.7+/-1.9 g vs 26.1+/-0.8 g and 28.8+/-1.4 g vs 26.9+/-1.0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P

This report describes three patients who developed cytomegalovirus infection 4 months after high-risk donor+/recipient−(D+/R−) kidney transplantation, despite treatment with valgancyclovir (VGCV) for 3 months at low dose (450 mg/d).

Objective Osteoclasts may be involved in the process of rheumatoid bone destruction. To test this hypothesis, we developed an in vitro model of bone destruction by osteoclast-like cells derived from cultured rheumatoid synovial tissue without using any inducers. Methods Synovial tissues were obtained from rheumatoid arthritis and osteoarthritis patients and tissue pieces of about 2 mm(3) that contained synovial lining were cultured. Multinucleated cells derived from cultured synovial tissues were studied cytochemically and morphologically for osteoclast-specific markers. Results Fibroblast-like and macrophage-like cells from the tissue pieces proliferated in the coexistence of lymphocytes. After 14 days of culture, multinucleated cells with tartrate-resistant acid phosphatase activity appeared. These cells expressed vacuolar H(+)-ATPase, the vitronectin receptor and cathepsin K. Although binding of (125)I-labelled salmon calcitonin was very low, the cells contained ringed structures of F-actin and showed strong bone-resorbing activity on ivory slices. Proliferation of macrophage-like cells and formation of multinucleated cells continued during 6 months of culture in the presence of fibroblast-like cells. The bone-resorbing activity of multinucleated cells derived from rheumatoid synovial tissue was much higher than that of cells from osteoarthritis synovial tissue, and was related to the disease activity of rheumatoid arthritis. Conclusion Our culture system reproduced in vitro the process of bone destruction by rheumatoid synovium, including the proliferation and fusion of precursor cells, polarization, activation and bone tissue resorption. This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction.

Objective: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. Methods: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. Results: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR]= 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR=1.14, 95% CI;0.95-1.35) showed odds ratios that were higher than unity without statistical significance. Conclusion: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders. J Epidemiol, 2000 ; 10 : 74-78

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone. © 1999 Cancer Research Campaign

Summary. In southwestern China, small but substantial numbers of patients with acute hepatitis were found without known hepatropic viral infections (hepatitis A, B, C, D or E, cytomegalovirus, Epstein-Barr virus) and were receiving no hepatotoxic drugs. Prevalence of antibodies, both neutralizing and specific immunoglobulin (Ig)M and IgG, to Hantaan virus were evaluated in a cohort of 136 such patients: 83 were of unknown aetiology, 53 had known viral hepatitis and 59 healthy subjects acted as controls. The results showed that the incidence of neutralizing antibody to Hantaan virus in acute hepatitis patients with non-hepatitis A-E virus infections (13 of 83) was significantly higher than in those with A-E infections (0 of 53, P

Some of cases suffering from subarachnoid hemorrhages (SAHs) in grade V on World Federation of Neurologic Surgeons (WFNS) grading can gain a good prognosis. The outcome of patients of SAH in grade V on WFNS grading in their institute was here investigated.Between April 2007 and July 2012, consecutive 37 patients had SAH diagnosed on CT scan and were classified in grade V on WFNS grading in Kosei General Hospital. There were seventeen male and twenty female patients. We were assigned to patients with spontaneous respiration and without oculomotor palsy (N group, N.=11), and patients with oculomotor palsy (O group, N.=26). Patients were evaluated by mRS.The prognosis in N group was significantly better than in O group (P0.001).Surgical treatments should be considered for SAH patients without oculomotor palsy. It is necessary to make subgroups in grade V on WFNS grading in order to decide operative indication and evaluate the treatment results of SAH in grade V.

1. A controlled-release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease. 2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan-induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives. 3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5-aminosalicylic acid and acetyl-5-amino-salicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine. 4. The present study indicates that slow release 5-amino-salicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan-induced colitis in the rabbit.

Folk wisdom suggests that chicken extract is useful for recovery from physical and mental fatigue. To explore this question, the physiological effect of Brand's Essence of Chicken (BEC), a popular chicken extract used as a traditional remedy, was assessed during recovering from mental stress. We quantitated the blood levels of stress-related substances, and examined the task performance and subjects' mood states during mental workloads. Subjects were 20, healthy male students who have never tasted BEC. They took two bottles of BEC or a placebo (70 ml/bottle) daily in the morning for 7 days. On the final experimental day, two mental workload tests were performed: (A) a mental arithmetic test (MAT; 1600 trials of two or three figure-addition or subtraction for 40 min). (B) a short-term memory test (SMT; 20 trials of memorizing 9 digit numbers). Blood was collected before and after each workload task. After the mental workload, the recovery of mean cortisol level of subjects who consumed BEC was significantly faster than that for those consuming the placebo. The task performance of subjects performing the MAT and SMT was also improved with BEC consumption compared with placebo. According to the profile of mood state questionnaire, subjects felt more active and less fatigued during the workload when they took BEC regularly. We conclude that the extract of chicken has the potential to metabolize stress-related substance in blood and to promote recovery from mental fatigue.

The outcomes of video-assisted thoracoscopic lobectomy for clinical stage I non-small cell lung cancer (NSCLC) patients with comorbidities were examined to determine the technical feasibility and safety of this procedure.Between January 2002 and December 2007, 111 consecutive patients with suspected stage I lung cancer, who individually had one or more comorbidities cited in the modified Kaplan-Feinstein Index, were scheduled for a video-assisted thoracoscopic lobectomy. The demographic, perioperative, and outcome variables were assessed.One hundred of 111 patients had non-small cell lung cancer. Ninety-nine patients underwent successful video-assisted thoracoscopic lobectomies, while there was one conversion because of a hemorrhage from the pulmonary artery in the early stage. Including this one conversion, no patients required a blood transfusion during surgery or postoperatively. There were no intraoperative or in-hospital deaths. No complications occurred in 78 (78.8%) of 99 patients. Only one patient (1.0%) with a Kaplan-Feinstein Index Score of severe grade contracted pneumonia indicating grade 3 (severe), whereas the remaining 20 patients had grade 1 (mild) or 2 (moderate) complications. At a median follow-up of 40 months, the overall 3-year survival rates for postoperative stage IA (N.=52); IB (N.=26); and II or more (N.=21) were 100%; 78%; and 71%, respectively.A video-assisted thoracoscopic lobectomy is therefore considered to be a feasible and safe procedure for clinical stage I NSCLC even in patients with comorbidities.

Objective: To characterize Alexander disease (AxD) phenotypes and determine correlations with age at onset (AAO) and genetic mutation. AxD is an astrogliopathy usually characterized on MRI by leukodystrophy and caused by glial fibrillary acidic protein ( GFAP ) mutations. Methods: We present 30 new cases of AxD and reviewed 185 previously reported cases. We conducted Wilcoxon rank sum tests to identify variables scaling with AAO, survival analysis to identify predictors of mortality, and χ 2 tests to assess the effects of common GFAP mutations. Finally, we performed latent class analysis (LCA) to statistically define AxD subtypes. Results: LCA identified 2 classes of AxD. Type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, failure to thrive, paroxysmal deterioration, and typical MRI features. Type II is characterized by later onset, autonomic dysfunction, ocular movement abnormalities, bulbar symptoms, and atypical MRI features. Survival analysis predicted a nearly 2-fold increase in mortality among patients with type I AxD relative to those with type II. R79 and R239 GFAP mutations were most common (16.6% and 20.3% of all cases, respectively). These common mutations predicted distinct clinical outcomes, with R239 predicting the most aggressive course. Conclusions: AAO and the GFAP mutation site are important clinical predictors in AxD, with clear correlations to defined patterns of phenotypic expression. We propose revised AxD subtypes, type I and type II, based on analysis of statistically defined patient groups.

To clarify the clinical manifestations of adult-onset Alexander disease (AOAD) in Japanese patients with glial fibrillary acidic protein (GFAP) gene mutations. Twelve patients of AOAD with GFAP mutations detected in our centre were examined for neurological and magnetic resonance imaging (MRI) findings. Major symptoms were pyramidal and bulbar signs. In addition, three patients presented abnormal behaviour and/or memory disturbance. Two of the three patients also had Parkinsonism and had been diagnosed with fronto-temporal dementia or progressive supranuclear palsy until GFAP mutations were detected. Abnormalities of the medulla oblongata and cervical spinal cord were observed on MRI in all patients. Patients presenting with pyramidal and/or bulbar signs with abnormalities of the medulla oblongata and cervical spinal cord on MRI should be considered for GFAP analysis as this is the typical presentation of AOAD. Abnormal behaviour and cognitive disorders including deterioration of memory were rare symptoms but could be an obstacle to diagnosing Alexander disease.

Zebrafish kidney marrow (ZKM), which is equivalent to the haematopoietic bone marrow of mammals, produces all major blood cell types, which morphologically resemble their mammalian counterparts. To be able to exploit the advantages of zebrafish genetics for analysis of the general mechanisms controlling self-renewal, proliferation and lineage decisions of vertebrate haematopoetic cell populations, it is essential to develop a simple surgical technique in order to identify, dissect and take out the ZKM without contamination with other surrounding tissues and cells. However, the size of adult zebrafish is small (average size: 2.5 cm) and the ZKM is an extremely protected organ and not easy to localize, which makes this procedure a great microsurgical challenge. Here we report a new microsurgical technique to identify, localize and dissect ZKM in adult zebrafish using a new approach. The potential advantages of this technique are summarized here: it allows purity of the sample, which is critical for performing flow cytometry analysis and/or cell number count; it enables visualization of the ZKM without a parenchimal incision, which simplifies the further dissection; the learning curve is short, requiring only basic microsurgical skills, and it is reliable and highly reproducible. To further characterize the kidney marrow cells obtained by this technique, we performed histology, flow cytometry, cytospin experiments and cell counts.

Background: Nodal status has been reported to be one of the most important factors affecting survival in patients with lung cancer. For determining treatment strategy, accurate evaluation of nodal status is expected. Purpose: To evaluate the accuracy of 18F-2-deoxy-fluoro-D-glucose (FDG) positron emission tomography (PET) for diagnosing nodal status in lung cancer patients with pathologically proven N1 (pN1) lymph node metastases, in comparison with that of computed tomography (CT). Material and Methods: Nineteen pN1 patients with primary lung cancer undergoing preoperative CT and FDG-PET were investigated. The diagnosis was confirmed by surgery in all patients. Lymph nodes were considered to be positive when uptake higher than the surrounding mediastinum level was visually observed. Radiological and pathological correlation was investigated, and the association between FDG uptake and the size of metastatic nodes was evaluated. Results: Of the 19 pN1 patients, nodal stage determined by FDG-PET was cN0 in eight, cN1 in four, cN2 in six, and cN3 in one. Thus, FDG-PET provided correct N-staging in 21%, under-staging in 42%, and over-staging in 37%. FDG-PET could not depict pN1 lymph node in six (32%) of 19 patients. In two patients (11%), mild symmetrical hilar and mediastinal accumulation was found and considered as benign physiological uptake. In six patients (32%), the ipsilateral mediastinal uptake was depicted and diagnosed as cN2. One patient was diagnosed as cN3 because of FDG accumulation at the supraclavicular fossa. On CT, nodal staging was cN0 in nine, cN1 in six, and cN2 in four. CT staging was therefore correct in 32%, underestimated in 47%, and overestimated in 21%. Conclusion: The diagnostic accuracy of FDG-PET (21%) was low and similar to that of CT (32%); under- and over-diagnosis were found in similar proportions. The limitation of FDG-PET should be recognized when nodal staging might alter the therapeutic strategy in patients with primary lung cancer.

Cerebral vasoreactivity (CVR) in the major cerebral arteries evaluated by transcranial Doppler sonography has shown some correlation with CVR in the brain tissue measured by other neuroradiological modalities. To clarify vasoreactive differences in the brain tissue and the major cerebral arteries, we have evaluated the relationship of acetazolamide (ACZ) CVR between transcranial ultrasonic power harmonic imaging (PHI) and color Doppler sonography (CDS), in cases ofparenchymal pathology with and without occlusive vascular lesions.The subjects were 31 stroke patients with intraparenchymal pathologies, 15 with (occlusive group) and 16 without (non-occlusive group) occlusive carotid and/or middle cerebral artery lesions. CVR based on values before/after ACZ (angle-collected CDS velocity in the middle and posterior cerebral arteries, PHI contrast area size, peak intensity, time to peak intensity), and correlation of CVR between PHI and CDS were compared between the side with and without lesions in both groups.(a) PHI CVR tended to be more disturbed than CDS CVR. CVR side differences were not significant. (b) CVR correlations between PHI and CDS were always lower in the pathological sides.CVR in brain tissue evaluated by PHI is susceptible to disturbance in comparison with CDS, due to both parenchymal and vascular occlusive pathologies.

The atypical antipsychotic drug, zotepine, is effective in treatment of schizophrenia and acute mania, but the incidence of seizures during treatment is higher than with other antipsychotics. In addition, the mechanisms underlying the clinical actions of zotepine remain uncharacterized.The effects of intraperitoneal administration of zotepine and haloperidol on the extracellular levels of noradrenaline, dopamine, 5-HT, GABA, and glutamate in the medial prefrontal cortex (mPFC) were compared. Neuronal activities induced by each drug in the ventral tegmental area (VTA), locus coeruleus (LC), dorsal raphe nucleus (DRN) and mediodorsal thalamic nucleus (MTN) were also analysed.Haloperidol did not affect extracellular neurotransmitter levels in the mPFC. In contrast, zotepine activated neuronal activities in all nuclei and increased the extracellular levels of noradrenaline, dopamine, GABA, and glutamate in the mPFC, but not 5-HT levels. The zotepine-stimulated neuronal activity in the VTA, LC, DRN and MTN enhanced the release of dopamine, noradrenaline, 5-HT, glutamate and GABA in the mPFC, although the enhanced GABAergic transmission possibly inhibited noradrenaline, dopamine and 5-HT release. The other afferent to mPFC, which releases dopamine and noradrenaline, was partially insensitive to GABAergic inhibition, but possibly received stimulatory AMPA/glutamatergic regulation from the MTN.Our results indicated that the positive interaction between prefrontal catecholaminergic transmission and AMPA/glutamatergic transmission from MTN might explain the regulatory effects of zotepine on neurotransmitter release. A mechanism is suggested to account for the pharmacological profile of this atypical antipsychotic and for its pro-convulsive action.

In a preliminary study, we noticed that alpha 2 activity in the frontal regions was suppressed less in schizophrenic patients than in other patients during the discriminative tasks. This was confirmed with 37 schizophrenic and 16 nonschizophrenic patients under the treatment of neuroleptics, 15 nonmedicated schizophrenic patients and 32 normal controls. The EEGs in eye-closed resting and during the auditory and visual discriminative tasks were recorded. Alpha 2 power values of the frontal, central, parietal, occipital and temporal regions in every subject group were processed by cluster analysis. During the discriminative tasks, the frontal regions were the most isolated cluster in schizophrenic patients and, in the normal and medicated nonschizophrenic groups, the frontal regions were incorporated in a different cluster. The same result was obtained by different statistical analyses of F-alpha 2 power ratio. The relative abundance of alpha 2 power value shifts from the occipital to the frontal regions during the discriminative tasks in schizophrenic patients. The weakened suppression of alpha 2 waves in the frontal regions by the discriminative tasks in schizophrenic patients supports the hypofrontal hypothesis of schizophrenia.

Hashimoto's and Graves' diseases represent the main two types of autoimmune thyroid disease. The combination of these two is well known. However, occurrence of Graves' disease after primary hypothyroidism is rare. We report seven patients with hypothyroidism due to Hashimoto's disease, who developed Graves' disease with hyperthyroidism. We also report one patient with hypothyroidism due to Hashimoto's disease, who continued to be hypothyroid even in the presence of TSAb (thyroid stimulating antibody). These patients were divided into three groups according to the changes in thyroid function and clinical course: (1) transient hyperthyroidism due to Graves' disease following hypothyroidism; (2) persistent hyperthyroidism due to Graves' disease following hypothyroidism; and (3) persistent hypothyroidism with positive TSAb. Such changes in thyroid function and clinical course seem to be decided by three factors: (1) TSAb and (2) TSBAb (thyroid stimulation blocking antibody) activities in the blood and (3) the responsiveness of the thyroid gland to TSAb. Seven patients had hyperthyroidism, when they had TSAb, which stimulated the thyroid gland; one of these seven patients had TSBAb during the hypothyroid state and TSAb during the hyperthyroid state, indicating that the alterations in the thyroid state related to the balance between the activities of TSAB and TSBAb. Another patient continued to be hypothyroid despite the presence of TSAb; his thyroid gland was not palpable and could not respond to TSAb.

Pulmonary sequestration is a rare malformation of the respiratory tract. We here report an adult case of intralobar pulmonary sequestration with aberrant artery of the right lower lobe. A 20-year-old man admitted to our hospital with a chest discomfort. Chest computed tomography (CT), angiography, and scintigraphy showed abnormal findings of the right lower lobe with an aberrant artery. Under the diagnosis of pulmonary sequestration, video-assisted thoracoscopic surgery (VATS) lobectomy was performed. VATS is useful for the operation of pulmonary sequestration.

A case of large ameloblastoma of the mandible with severe hypoproteinemia is reported. The patient, a 53-year-old man, had a large swelling (14 × 11 × 10 cm) from the right cheek to the submandible causing severe hypoproteinemia. The tumor was removed when the serum protein level had recovered to 5.3 g/dl following administration of 50 ml of 20% albumin for 4 days. After the operation, his hypoproteinemia, which was thought to be caused by leakage of plasma through the oral fistula of the ameloblastoma, rapidly improved. This article describes preoperative and postoperative findings and the clinical course of the patient.

To confirm the reliability of a refill kinetic method of ultrasonic harmonic perfusion imaging (HPI) capable of quantifying separate parameters of microvascular blood flow velocity and volume in brain tissue, we evaluated acetazolamide (ACZ) cerebrovascular reactivity by transcranial HPI in comparison with Doppler sonography (TCD). Methods. HPI during continuous Levovist infusion with changing pulsing intervals (t) and TCD time-averaged maximum velocity (TAMX) in the middle and posterior cerebral arteries were evaluated before and after ACZ administration in 12 patients, 8 without and 4 with a temporal skull defect. Plateau value (A) and rise rate (beta) of intensity (I) represented by HPI time-intensity curves of I(t) = A(1 - e(-beta*t)) were analyzed on the axial diencephalic plane.1) A significantly decreased in proportion to the region of interest location depth only in the intact skull cases. 2) Despite inter- and intra-individual data scattering, in correspondence with TAMX increases after ACZ, significant beta increases were more frequently identified than increases of A.Cerebral vasoreactivity analysis utilizing refill kinetics of transcranial HPI can potentially provide separate quantification based on microvascular blood velocity and volume (capillary patency) with consideration of depth-dependant ultrasound attenuation. This should be suitable for bedside evaluation of neurointensive care patients.

The survival time of patients with unresectable malignant biliary stenosis and the patent period of metallic biliary stents are different in each disease. The efficacy of the covered metallic stent was analyzed according to the primary disease.Seventy-three patients with bile duct carcinoma (12 cases), gallbladder carcinoma (22 cases), and pancreas carcinoma (39 cases) were retrospectively enrolled. Covered metallic stents were used in 42 patients and uncovered metallic stents in 31 patients. The patency of covered stents was compared with that of uncovered stents for each disease.The patent rate at 6 months after insertion was 80.6% (95% CI [72.6%, 88.6%]) for the covered stent, and 49.5% (95% CI [37.6%, 61.4%]) for the uncovered stent. The mean patent periods of the covered stent and the uncovered stent were 14.6 and 27.6 months for bile duct carcinoma (p=0.424), 12.7 and 3.0 months for gallbladder carcinoma (p=0.003), and 11.9 and 9.6 months for pancreas carcinoma (p=0.919), respectively.The covered metallic stent was the most effective in patients with gallbladder carcinoma.

This study was intended to examine whether serum IGF-I concentration is appropriate for use as a physiological predictor for genetic improvement of meat production and meat quality traits in pigs. Heritabilities and genetic correlations were estimated for these traits. The Duroc breed used in this study was selected for seven generations for average daily BW gain (DG) from 30 to 105 kg of BW, loin-eye muscle area (EM), backfat thickness (BF), and intramuscular fat (IMF) content. Serum IGF-I concentration of boars and gilts at the fourth generation of selection and that of boars, gilts, and barrows from the fifth to seventh generations of selection were measured at 8 wk (IGFI-8W) for 832 animals and again at the time they reached 105 kg of BW (IGFI-105KG) for 834 animals. A multivariate REML procedure was used to estimate genetic parameters with a model incorporating generation of selection, sex, common environmental effect of litter, and individual additive genetic effects. Heritability estimates for IGFI-8W and IGFI-105KG were 0.23 +/- 0.02 and 0.26 +/- 0.03, respectively. The estimates of common environmental effect for IGFI-8W and IGFI-105KG were 0.20 +/- 0.02 and 0.03 +/- 0.01, respectively. Positive genetic correlations were estimated between IGFI-8W and DG (0.26 +/- 0.08), EM (0.22 +/- 0.10), and IMF (0.32 +/- 0.10). Moreover, the positive genetic correlation between IGFI-105KG and EM was 0.42 +/- 0.08. These results indicate that serum IGF-I concentration at an early stage of growth was effective for prediction of IMF, but it was not a reliable physiological predictor of genetic merit of meat production traits.

Objective: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). Background: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. Methods: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. Results: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. Conclusions: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.

To clarify the clinical variability, including central nervous system (CNS) involvement, in X-linked Charcot-Marie-Tooth disease (CMTX) patients.We clinically, pathologically and genetically studied six CMTX patients with distinct symptoms and four different GJB1 mutations.One patient with Val63Ile had deafness, low intelligence, saccadic eye movement, upper extremity distal dominant muscle weakness and normal sensation. Another patient with Glu186Lys had severe sensorineural deafness at the age of 6 years, but did not develop muscle weakness until the age of 20 years. Two patients with Arg22Gln had typical CMT1A-like clinical features, no CNS symptoms and obvious onion bulb formations. Two siblings with deletion of the entire GJB1 gene had mild to moderate lower extremity muscle weakness and sensory disturbance without CNS involvement.These findings suggest that some gain of function mutations of GJB1 may be related to CNS symptoms because the patients with GJB1 deletion only had peripheral neuropathy, although other unknown associated factors may contribute to their clinical phenotypes.

Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.

To clarify the relationship between mitochondrial DNA (mtDNA) sequence variations and phenotypes in patients with A3243G mutation.We studied whole mtDNA sequences in two families with A3243G mutation and characteristic clinical features. Two brothers in Family 1 had shown thiamine deficiency and mitochondrial myopathy without central nervous system involvement. In Family 2, a 16-year-old woman showed the symptoms of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Her mother had had diabetes mellitus and died at the age of 42. The proportion of A3243G mtDNA in blood was 87 and 89% in the patients of Family 1, and 25% in the patient and less than 5% in the mother of Family 2.The mtDNA analysis revealed the following homoplasmic substitutions: T1520C and C12153T found only in Family 1, and A15954G found only in Family 2. These substitutions were not detected in seven other MELAS patients or in 50 controls.These substitutions might be specific to these families and could be one of the factors that modulate their clinical features together with the A3243G mutation.

The effect of 450 mg/day propafenone for two weeks on premature ventricular contractions (PVCs) was studied in combination with an assessment of heart rate (HR) dependency of PVCs using Holter ECG monitoring in patients with more than 720 PVCs per day. The PVC-HR correlation was classified into positive (P), bidirectional (B), and flat and negative (FN) correlation groups. The positive group included only patients in whom PVC frequency increased with a heart rate increase, while the bidirectional group included patients with PVCs whose frequency increased at low heart rates and decreased at high heart rates. The FN group contained both flat (PVC frequency was almost fixed regardless of heart rate changes) and negative (PVC frequency decreased as heart rate increased) correlations. The effectiveness of propafenone was 70% in the positive group and 50% in the nonpositive group which included both bidirectional (67%) and FN (0%) groups, using a70% PVC reduction as a criterion of efficacy. From this, we concluded that propafenone is effective in patients showing either positive or bidirectional PVC-HR correlation. The coupling interval (CI) of PVCs was also prolonged by propafenone as a whole. The present study suggests that there are differences in the mechanism of PVC development in patients with flat or negative correlation and those with a positive or bidirectional correlation. Thus, this type of analysis contributes to an understanding of the action of antiarrhythmic agents, and may allow the prediction of their efficacy on PVCs.

To clarify the phenotypic varieties in Machado-Joseph disease (MJD).We studied a 64-year-old man with ataxia, retinal degeneration and dementia neurologically, ophthalmologically and genetically.The patient noted dysesthesia of his hands at age 57 and later had memory disturbance. He had gait disturbance and needed a wheelchair at age 64. His total IQ was 61 on the WAIS-R. He had loss of central vision, ophthalmoplegia, hearing impairment, dysarthria, truncal and limb ataxia, sensory disturbance, and mild weakness of the extremities. Electrophysiologically he was suspected to have polyneuropathy. Brain MRI showed marked atrophy of the cerebellum and pons with mild cerebral atrophy. Ophthalmologic evaluation revealed multiple chorioretinal atrophy. Expanded CAG repeat numbers in MJD1 were 64.These findings indicate that the clinical features of MJD might cover a wider spectrum than previously expected, though it is possible that these complications, namely retinal degeneration and dementia, were incidental findings in this patient.

To evaluate the role of inflammatory cells in acute lung injury induced by Candida sepsis, we investigated the time course of cell counts in bronchoalveolar lavage (BAL) fluid, the lung wet-to-dry weight (W/D) ratio and the CFU of Candida after a Candida infection. Male BALB/c mice were injected intravenously with 107 CFU of Candida albicans. They were sacrificed by exsanguination 0, 6, 12, 18, and 24 h after infection. The lung W/D ratio was determined in order to assess the severity of pulmonary edema. BAL was performed 3 times with 0.5 ml of sterile saline. The lung W/D ratio increased significantly 24 h after the injection of Candida, and the neutrophil counts in the BAL fluid increased significantly 12, 18, and 24 h after Candida injection. To assess the effect of neutrophils on Candida-induced acute lung injury, we investigated that of neutrocytosis and neutropenia on cell counts in BAL fluid, of the W/D ratio, and of the CFU of Candida in the lung 24 h after infection. We created neutrocytotic mice using G-CSF, and neutropenic mice with cyclophosphamide. Peripheral neutrophil counts decreased significantly in cyclophosphamide-treated mice, and increased significantly in G-CSF-treated mice. The lung W/D ratio increased significantly in cyclophosphamide-treated mice. Neutrophil counts in BAL fluid increased significantly in G-CSF-treated mice, and decreased significantly in cyclophosphamide-treated mice. The CFU of Candida in the lung decreased significantly in G-CSF-treated mice, and increased significantly in cyclophosphamide-treated mice. We concluded that neutrophils play a protective role in Candida albicans-induced acute lung injury.

We present a 73-year-old man with probable dementia with Lewy bodies(DLB). At 65 years of age, he gradually developed bradykinesia, gait disturbance and mild amnesia. At 71 years of age, he noted resting tremor in bilateral hands, and amnesia and disorientation were exacerbated. He was diagnosed as having parkinsonism and took L-dopa/carbidopa at 100 mg/day. Since he developed hallucination and abnormal behavior 2 days after the initiation of the drug, he stopped taking L-dopa and was admitted to our hospital. A neurological examination on admission revealed moderate amnesia, disorientation, finger agnosia, constitutional apraxia, mask-like face, cogwheel rigidity, resting tremor in bilateral hands, and bradykinesia. Brain MRI showed mild brain atrophy, and single photon emission computerized tomography(SPECT) showed diffuse moderate hypoperfusion in bilateral cerebral cortex. As he had fluctuating cognitive dysfunction and parkinsonism, he was diagnosed to have probable DLB. As his dementia was exacerbated by trihexyphenidyl, an anti-cholinergic agent, at 2 mg/day, we treated him with donepezil, an anti-choline esterase agent, at 3-5 mg/day. His parkinsonism, including rigidity and bradykinesia, was markedly improved his dementia, consisting of amnesia and disorientation. Electroencephalography (EEG) improved in the organization of the dominant rhythm. The SPECT improved in the blood perfusion of the bilateral frontal lobe as well as cognitive function and parkinsonism were maintained by donepezil for 6 months after discharge. A therapeutic efficacy of donepezil for DLB has recently been reported. It is notable that donepezil was beneficial not only for cognitive dysfunction but also for parkinsonism in the present case with probable DLB.

We studied the effect of myocardial ischemia and diabetes mellitus (DM) on the myocardial fatty acid metabolism using 123I-BMIPP myocardial scintigraphy.We performed 123I-BMIPP myocardial scintigraphy in 50 patients with myocardial ischemia and without DM (AP), in 30 patients with myocardial ischemia and DM (AP + DM), 12 patients with DM and without myocardial ischemia (DM), and in 10 normal subjects (N). Myocardial uptake rate of 123I-BMIPP was obtained using the time activity curve. Myocardial washout rate of 123I-BMIPP was calculated using the polar images of early and delayed SPECT images.Myocardial uptake rate of 123I-BMIPP (%) were AP: 4.9 +/- 0.6, AP + DM: 5.5 +/- 0.5, DM 5.7 +/- 0.5 and N: 5.0 +/- 0.4. 123I-BMIPP myocardial uptake rate was increased in AP + DM and DM. 123I-BMIPP myocardial washout rate (%) were AP: 30.2 +/- 4.3, AP + DM: 24.5 +/- 3.9, DM: 16.1 +/- 2.8 and N: 19.4 +/- 3.2. 123I-BMIPP myocardial washout rate was increased in AP and AP + DM. 123I-BMIPP myocardial washout rate was increased particularly in patients with multi-vessels disease. 123I-BMIPP myocardial washout rate was decreased in DM.The present study suggested that diabetes mellitus increased myocardial fatty acid uptake and decreased myocardial fatty acid washout, and that myocardial ischemia increased myocardial fatty acid washout.

A 62-year-old male presented to our hospital with jaundice. On the abdominal ultrasound and abdominal CT, there was evidence of multiple, massive liver metastases with dilatation of intrahepatic bile ducts, thickened wall of the stomach from the body to the antrum, direct invasion to the pancreas, multiple lymph node metastases, and ascites. We believed it was Stage IV and too far advanced for surgery. Therefore, ST-1 60 mg bid was started, and CDDP 50 mg was infused in the seventh week. On the follow-up CT and ultrasound three months later, the thickening of the gastric wall and the lymph node metastasis had improved and the border between the stomach and the pancreas had become clearer. The liver metastases seen on both lobes had decreased significantly both in size and number. The dilatation of the intrahepatic bile ducts disappeared, and the liver function normalized. No side effects were evident during the treatment with the medications.

Various electrocardiographic and physiologic tests have been developing for almost 100 years since Einthoven established the standard 12 lead electrocardiogram(ECG) system. Recently, interest has focused on the new developing parameters associated with cardiac ventricular repolarization, such as transmural dispersion of repolarization, T wave alternans and QT dispersion. QT dispersion, measured as interlead difference of QT interval, has been suggested to reflect regional variation of ventricular repolarization. However, still unsolved basic problems give difficulties for clinical acceptance of this parameter. On the other hand, it is generally accepted that heart rate variability obtained from Holter ECG is useful tool to assess the autonomic tone. Head-up tilt test is a valuable diagnostic tool to identify patients with neurally mediated syncope and also useful for assessment of reflex cardiac autonomic function, such as baroreflex sensitivity. The number of electrophysiologic study(EPS) dramatically increased together with increase of radiofrequency catheter ablation. A new three-dimensional nonfluoroscopic electroanatomical mapping system(CARTO) is an exciting development in catheter ablation treatment. Transtelephonic ECG and its computer-assisted answering system are also useful for diagnose and treatment in the patients of paroxysmal cardiac symptoms.

Missense mutations in the calcium-sensing receptor (CaSR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were studied, and we found a novel CaSR missense mutation with polymerase chain reaction single-strand conformational polymorphism analysis. The mother, grandmother, and aunt of the baby all had FHH. A heterozygous missense mutation in exon 6 that substitutes a glutamic acid for the glycine at codon 557 (Gly557Glu), which corresponds to the extracellular domain of CaSR, was identified and shown to cosegregate with the disease. Identification of the mutation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH.

The tumor-rejection antigen SART3 possesses two antigenic epitopes (SART3(109-118) and SART3(315-323)) capable of inducing HLA-A24-restricted and tumor-specific CTLs. To determine its safety and ability to generate antitumor immune responses, 12 patients with advanced colorectal cancer were administered s.c. vaccinations of these peptides. No severe adverse events were associated with the vaccinations. Significant levels of increased cellular immune responses to both HLA-A24+ colon cancer cells and the vaccinated peptide were observed in the postvaccination peripheral blood mononuclear cells in 7 of 11 and 7 of 10 patients tested, respectively, and the higher responses were observed in those patients vaccinated with the highest dose (3 mg/injection) of the peptides. These results encourage further development of SART3 peptide vaccine for colorectal cancer patients.

A 50-year-old male patient with no symptoms was admitted to our hospital for further evaluation of a right superior mediastinal mass shadow found in chest radiographs during a health examination. Computed tomographic (CT) scans demonstrated a middle mediastinal mass of 4 cm in diameter surrounded by the SVC, the ascending aorta and the trachea at the subaortic level. Routine examination disclosed no metastatic or primary lesion elsewhere. A surgical biopsy resulted in a diagnosis of neuroendocrine carcinoma of unknown primary organ. The patient was given 1 course of chemotherapy with CAV-PE, but little effect was seen. However, when a PE regimen combined with thoracic radiation was used, the tumor shrank to half of its size. After the patient subsequently received high-dose treatment with Etoposide, CT imaging and cytologic analysis revealed multiple metastases to the subcutaneous tissue, both adrenal glands and the liver. Lung lesions also spread aggressively, and the patient died of metastasis. Although neuroendocrine carcinomas can arise from the systemic neuroendocrine cells including those in the mediastinum, their appearance in the middle mediastinum is rarely reported.

TS-1 is a novel oral formation of 5-fluorouracil, developed using tegafur and two biochemical modulations. We report the case of a patient with multiple lymph node metastases from gastric cancer that markedly responded to TS-1. A 70-year-old man suffering from hematemesis was admitted to our hospital. Computed tomography showed advanced gastric cancer with huge lymph node metastases. After non-curative operation, he received adjuvant chemotherapy with TS-1 for 12 weeks. CT revealed that almost complete reduction of the metastatic nodes was obtained. No serious adverse reactions were observed.