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Context: To identify VA and non-VA Emergency Department (ED) and hospital utilization by veterans with spinal cord injury and disorders (SCI/D) in California. Design: Retrospective cohort study. Setting: VA and Office of Statewide Health Planning and Development (OSHPD) in California. Participants: Total 300 veterans admitted to the study VA SCI/D Center for initial rehabilitations from 01/01/1999 through 08/17/2014. Interventions: N/A. Outcome Measures: Individual-level ED visits and hospitalizations during the first-year post-rehabilitation. Results: Among 145 veterans for whom ED visit data available, 168 ED visits were identified: 94 (55.2%) at non-VA EDs and 74 (44.8%) at the VA ED, with a mean of 1.16 (±2.21) ED visit/person. Seventy-seven (53.1%) veterans did not visit any ED. Of 68 (46.9%) veterans with ≥ one ED visit, 20 (29.4%) visited the VA ED only, 34 (50.0%) visited non-VA EDs only, and 14 (20.6%) visited both VA and non-VA EDs. Among 212 Veterans for whom hospitalization data were available, 247 hospitalizations were identified: 82 (33.2%) non-VA hospitalizations and 165 (66.8%) VA hospitalization with a mean of 1.17 (±1.62) hospitalizations/person. One hundred-seven (50.5%) veterans had no hospitalizations. Of 105 veterans with ≥ one hospitalization, 58 (55.2%) were hospitalized at the study VA hospital, 15 (14.3%) at a non-VA hospital, and 32 (30.5%) at both VA and non-VA hospitals. Conclusion: Non-VA ED and hospital usage among veterans with SCI/D occurred frequently. The acquisition of non-VA healthcare data managed by state agencies is vital to accurately and comprehensively evaluate needs and utilization rates among veteran populations.

In order to improve the quality of life of dialysis patients, our group have been developing an implantable hemofiltration device (IHFD) composed of multiple layers of dialysis membranes and microfluidic channels. To improve the hemodialysis performance of IHFD, preventing the negative filtration, which is caused by the oncotic pressure of blood, is mandatory. In this study, we fabricated IHFDs with five different microchannel designs and experimentally investigated the performance of each device in in vitro experiment. In addition, the successful IHFD was further evaluated by ex vivo experiments with a beagle dog. The experiments verified the effectiveness of the microchannel design, which will be used for the IHFD for in vivo experiments with pigs in the future.

BACKGROUND Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P

Interferential current therapy is a noninvasive therapy using simultaneously two or more medium-frequency currents passing through tissue. By controlling the interfered area of the current flows, selective stimulation is possible in target muscles, including deep muscles. However, controlling the interfered area or the intensity of the current precisely is still lacking. Using simulations based on a biological model of the thigh as well as electrical muscle stimulation (EMS) experiments, we investigated the influence of electrode area ratio in changing the interfered area of the currents. Simulation and experiments were conducted under the same conditions, whereby current signals were applied through electrodes placed on the quadriceps and hamstring with an electrode area ratio of either 1:1 or 3:1. A comparison of the simulation results showed that the interferential current density decreased near the larger area electrode but increased near the smaller area electrode. In addition, the EMS experiment also showed that the quadriceps were stimulated using electrodes in a 1:1 area ratio, and the hamstrings were stimulated using electrodes in a 3:1 area ratio. These results demonstrated the possibility of controlling the area application of interferential current through electrode area patterning.

Major depressive disorder (MDD) affects up to 17% of the population, causing profound personal suffering and economic loss. Clinical and preclinical studies have revealed that prolonged stress and MDD are associated with neuronal atrophy of cortical and limbic brain regions, but the molecular mechanisms underlying these morphological alterations have not yet been identified. Here, we show that stress increases levels of REDD1 (regulated in development and DNA damage responses-1), an inhibitor of mTORC1 (mammalian target of rapamycin complex-1; ref. 10), in rat prefrontal cortex (PFC). This is concurrent with a decrease in phosphorylation of signaling targets of mTORC1, which is implicated in protein synthesis-dependent synaptic plasticity. We also found that REDD1 levels are increased in the postmortem PFC of human subjects with MDD relative to matched controls. Mutant mice with a deletion of the gene encoding REDD1 are resilient to the behavioral, synaptic and mTORC1 signaling deficits caused by chronic unpredictable stress, whereas viral-mediated overexpression of REDD1 in rat PFC is sufficient to cause anxiety- and depressive-like behaviors and neuronal atrophy. Taken together, these postmortem and preclinical findings identify REDD1 as a critical mediator of the atrophy of neurons and depressive behavior caused by chronic stress exposure.

To determine the effectiveness of a melatonin agonist for treating sleep disturbances in individuals with tetraplegia.Placebo-controlled, double-blind, crossover, randomized control trial.At home.Eight individuals with tetraplegia, having an absence of endogenous melatonin production and the presence of a sleep disorder. Interventions Three weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover, randomized order) with 2 weeks of baseline prior to and 2 weeks of washout between active conditions.Change in objective and subjective sleep.Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale, SF-36.We observed no consistent changes in either subjective or objective measures of sleep, including subjective sleep latency (P = 0.55, Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35, Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or objective sleep efficiency (P = 0.78, Friedman test). There were significant increases in both objective total sleep time (P0.05, Friedman test), subjective time in bed (P0.05, Friedman test), and subjective sleep quality (P0.05, Friedman test), although these occurred in both arms. There were no significant changes in any of the nine SF-36 subscale scores (Friedman test, PsBonferroni adjusted α of 0.005).In this pilot study, we were unable to show effectiveness of pharmacological replacement of melatonin for the treatment of self-reported sleep problems in individuals with tetraplegia. Trial Registration ClinicalTrials.gov # NCT00507546.

Many patients with hypertension have difficulty achieving their target blood pressure (BP). Therefore combination therapy, for example with an angiotensin II receptor blocker (ARB) and a diuretic, may be recommended. We previously evaluated the efficacy and safety of losartan (LOS) 50 mg - hydrochlorothiazide (HCTZ) 12.5 mg, as well as its effect on the plasma concentration of B-type natriuretic peptide (BNP, a prognostic marker for cardiovascular events), in patients with hypertension uncontrolled by ≥3 months of ARB-based therapy. The present subanalysis used data from patients who received LOS-based therapy before switching to LOS-HCTZ. Efficacy, safety, and changes in blood biochemical variables including BNP were evaluated. After excluding 4 patients with protocol violations, data from 35 patients (aged 36-79 years, mean 63 years; 66% male) were used in the safety analysis. The efficacy analysis used data from the 30 patients who were followed up for 12 months. Systolic/diastolic BP decreased from 156±12/87±11 mmHg at baseline to 125±11/73±10 mmHg at 12 months (p0.001). After 12 months, half of the patients achieved their target BP as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2004. In 12 patients with baseline plasma BNP concentration ≥20 pg/mL, BNP decreased from 78.3±18.8 pg/mL to 57.3±17.7 pg/mL (p0.01). 3 patients experienced adverse events, one of which was cardiovascular. LOS-HCTZ is efficacious, has a good safety profile, and decreases plasma BNP concentration.

Objectives To compare the interface pressure during posture changes and exercise between elastic stockings and bandages. Methods Using a pressure transducer (air pack-type analyzer), the interface pressures associated with three different elastic stockings and three different elastic bandages were measured during supine resting, standing and exercise in 15 healthy volunteers. Results Short-stretch bandages showed a significantly higher static stiffness index value, which is defined as the pressure difference between lying and standing, than long-stretch bandages and short-stretch stockings ( P < 0.001). Furthermore, short-stretch bandages showed a significantly greater pressure difference between muscle contraction and relaxation in both tip-toe and knee-bending exercises than long-stretch bandages and short-stretch stockings ( P < 0.001). Conclusion Short-stretch bandages can be expected to have more pronounced benefits for augmenting muscle pump than long-stretch bandages and short-stretch stockings.

The reliability and validity of assessments and diagnoses made via home telehealth was measured in 42 patients with spinal cord injury. Two telehealth modalities were investigated: telephone-only contact and videoconferencing. The results were compared with a reference (gold-standard) method, the in-person assessment and diagnosis of skin integrity and pressure ulcers. The agreement on the presence of a pressure ulcer was excellent for both telephone and videoconferencing approaches (92% for telephone, 97% for videoconferencing). The diagnoses of the stage of pressure ulcer (on an ordinal scale of 0–4) made via telephone and videoconferencing showed substantial to almost perfect agreement with the in-person diagnoses (Spearman's rho of 0.76 and 0.83, respectively). There was a tendency for the measurements of wound volume to be somewhat larger in the telephone and videoconferencing modalities compared to those made in-person. Bland-Altman plots showed that videoconferencing gave substantially narrower 95% limits of agreement. The findings of the study indicate that telephone contact can be a useful tool for identifying the presence of a pressure ulcer, but videoconferencing is required to obtain an evaluation reasonably close to that of a home visit.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed.Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p 0.05, p 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000).Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD.

Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown.We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT.Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1.Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.

Major depressive disorder (MDD) is a debilitating and widespread illness that exerts significant personal and socioeconomic consequences. Recent genetic and brain-imaging studies suggest that bicaudal C homolog 1 gene (BICC1), which codes for an RNA-binding protein, may be associated with depression. Here, we show that BICC1 mRNA is upregulated in the dorsolateral prefrontal cortex and dentate gyrus of human postmortem MDD patients. We also show that BICC1 is increased in the prefrontal cortex and hippocampus in the rat chronic unpredictable stress (CUS) model of depression. In addition, we show in vivo that a single acute antidepressant dose of ketamine leads to a rapid decrease of BICC1 mRNA, while in vitro, we show that this is likely due to neuronal activity-induced downregulation of BICC1. Finally, we show that BICC1 knockdown in the hippocampus protects rats from CUS-induced anhedonia. Taken together, these findings identify a role for increased levels of BICC1 in the pathophysiology of depressive behavior.

Cyclin-dependent kinase 5 regulates numerous neuronal functions with its activator, p35. Under neurotoxic conditions, p35 undergoes proteolytic cleavage to liberate p25, which has been implicated in various neurodegenerative diseases. Here, we show that p25 is generated following neuronal activity under physiological conditions in a GluN2B- and CaMKIIα-dependent manner. Moreover, we developed a knockin mouse model in which endogenous p35 is replaced with a calpain-resistant mutant p35 (Δp35KI) to prevent p25 generation. The Δp35KI mice exhibit impaired long-term depression and defective memory extinction, likely mediated through persistent GluA1 phosphorylation at Ser845. Finally, crossing the Δp35KI mice with the 5XFAD mouse model of Alzheimer’s disease (AD) resulted in an amelioration of β-amyloid (Aβ)-induced synaptic depression and cognitive impairment. Together, these results reveal a physiological role of p25 production in synaptic plasticity and memory and provide new insights into the function of p25 in Aβ-associated neurotoxicity and AD-like pathology., National Institutes of Health (U.S.) (Grant R01 NS051874), National Institutes of Health (U.S.) (Grant F31GM80055-03), Howard Hughes Medical Institute

We document the rst case of a patient who manifested systemic lupus erythematosus (SLE) complicated with multicentric reticulohistiocytosis (MRH). Neither intravenous steroid nor cyclophosphamide (CY) pulse therapies were fully effective against multiple MRH-related tumors that appeared on the left ankle joint and interphalangeal joints of both hands. In contrast, treatment with cyclosporin A (CyA) resulted in a marked regression of these nodules within one month, together with a complete remission of both MRH and lupus nephritis. We propose CyA as an alternative choice for the treatment of MRH.

A specific stain using violet polymethine dye (VPM stain) for megakaryocytes was first developed by Kass (1995). We have modified this method for practical use in bone marrow specimens. The modified VPM stain labels megakaryocytes very well, while other marrow cells are poorly colorized. This staining procedure was more stable, and its color intensity was finer and clearer than the original. Using this stain, morphologic classification of megakaryocytes in bone marrow specimens from 11 normal and 8 myelodysplastic syndrome (MDS) patients was performed. Many megakaryocytes observed in MDS patients were juvenile compared with normal subjects according to their morphology. Blasts from acute megakaryoblastic leukemia (M7) and from a megakaryoblastic cell line (Mo7e) were also clearly stained with our method. This staining method is practical and very useful for rapid identification of megakaryocyte distribution and morphology.

CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1β and TNF-α; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.

BackgroundMutations in endothelin 3 (EDN3) and endothelin B receptor (EDNRB) genes cause terminal colonic aganglionosis in mice, and mutations in these genes have also been linked to the terminal aganglionosis seen in human Hirschsprung’s disease. However, details of EDN3 expression during embryogenesis are lacking, and consequently the cellular mechanism by which EDN3 regulates innervation of the terminal gut is unclear.AimsTo localise the expression of EDN3 and EDNRB in the embryonic mouse gut.MethodsExpression of EDN3 and EDNRB mRNA was analysed by reverse transcription polymerase chain reaction and in situ hybridisation.ResultsHigh levels of EDN3 mRNA expression were restricted to mesenchymal cells of the caecum before and after the arrival of neural crest cells. In contrast, EDNRB expression along the gut displayed a time dependent pattern similar to those of the protein tyrosine kinase ret and the neural crest cell marker PGP9.5.ConclusionsMesenchymal cells of the caecum express high levels of EDN3 mRNA during embryogenesis and hence the production of EDN3 at the caecum is likely to act on neural crest cells as a paracrine factor necessary for subsequent innervation of the terminal gut.

To determine the origin of the increased serum ferritin that occurs in adult Still's disease (ASD), we analyzed subunits of the serum ferritin as follows. Gel filtration with Sepharose CL-6B demonstrated that the molecular weight of serum ferritin was about 490 kDa. Western blot analysis revealed only L-subunits (molecular weight 19 kDa) in patients with serum ferritin levels higher than 1,000 ng/ml. Patients with serum ferritin levels higher than 1,000 ng/ml, however, showed G-subunits (molecular weight 23 kDa) in addition to the L-subunits. When concanavalin A (Con-A) Sepharose 4B was used in an absorption test, the percentage absorption was extremely low in the patients with serum ferritin levels higher than 1,000 ng/ml. Isoferritin patterns of the patients determined by chromatofocusing revealed traces of acidic ferritin. The findings suggested that glycosylated ferritin does not account for the major portion of the increased serum ferritin.

Stress is a common occurrence in everyday life and repeated or traumatic stress can be a precipitating factor for illnesses of the central nervous system, as well as peripheral organ systems. For example, severe or long-term psychological stress can not only induce depression, a leading illness worldwide, but can also cause psychosomatic diseases such as asthma and rheumatoid arthritis. Related key questions include how psychological stress influences both brain and peripheral systems, and what detection mechanisms underlie these effects? A clue is provided by the discovery of the pathways underlying the responses to host “danger” substances that cause systemic diseases, but can also contribute to depression. The inflammasome is a protein complex that can detect diverse danger signals and produce the accompanying immune-inflammatory reactions. Interestingly, the inflammasome can detect not only pathogen-associated molecules, but also cell damage-associated molecules such as ATP. Here, we propose a new inflammasome hypothesis of depression and related comorbid systemic illnesses. According to this hypothesis, the inflammasome is a central mediator by which psychological and physical stressors can contribute to the development of depression, and as well as a bridge to systemic diseases. This hypothesis includes an explanation for how psychological stress can influence systemic diseases, and conversely how systemic diseases can lead to psychiatric illnesses. The evidence suggests that the inflammasome may be a new target for the development of treatments for depression, as well as psychosomatic and somato-psycho diseases.

Atrophy of neurons and gross structural alterations of limbic brain regions, including the prefrontal cortex (PFC) and hippocampus, have been reported in brain imaging and postmortem studies of depressed patients. Preclinical findings have suggested that prolonged negative stress can induce changes comparable to those seen in major depressive disorder (MDD), through dendritic retraction and decreased spine density in PFC and hippocampal CA3 pyramidal neurons. Interestingly, recent studies have suggested that environmental and pharmacological manipulations, including antidepressant medication, exercise, and diet, can block or even reverse many of the molecular changes induced by stress, providing a clear link between these factors and susceptibility to MDD. In this review, we will discuss the environmental and pharmacological factors, as well as the contribution of genetic polymorphisms, involved in the regulation of neuronal morphology and plasticity in MDD and preclinical stress models. In particular, we will highlight the pro-depressive changes incurred by stress and the reversal of these changes by antidepressants, exercise, and diet.

To image truly contiguous CT sections without breath-holding, we developed a respiratory-gating device combined with ultrafast CT. The purpose of this study was to evaluate the utility of this system, especially focusing on the contiguity of the images.In 37 patients, we obtained respiratory-gated scans and breath-hold scans with 6-mm collimation and 6-mm incrementation (19 patients) and with 3-mm collimation and 3-mm incrementation (18 patients). We compared these two sets of images with respect to quality and contiguity. In nine patients who could not hold their breath because of dyspnea or infancy, we obtained only respiratory-gated scans with 3-mm collimation and 3-mm incrementation. Our respiratory-gating device was composed of a commercial ECG and respiratory monitor, a triggering device, an original amplifier, and an original switching unit. It was designed to control the scan timing of an ultrafast CT scanner at a user-selected level of the respiratory curve obtained with transthoracic impedance plethysmography.The respiratory-gated images were equal in quality to the breath-hold images in 31 of the 37 patients who had both sets of images. In 15 of 19 patients who had 6-mm-thick sections and in 11 of 18 patients who had 3-mm-thick sections, satisfactory contiguous images of bronchi and pulmonary vessels were obtained. Additionally, in seven of the nine patients who could not hold their breath, satisfactory contiguous sections were obtained.The respiratory gating system combined with ultrafast CT can provide contiguous CT scans without breath-holding or patients' cooperation. The procedure could improve the diagnostic accuracy of CT, especially in severely ill patients, infants, and senile patients.

We examined whether second-line multi-agent chemotherapies are of any value for carboplatin/paclitaxel (TC)-refractory ovarian cancer.Subjects included 60 patients with ovarian, peritoneal, or tubal carcinoma who received second-line platinum-based combination chemotherapy. Thirty-nine were treated with irinotecan/cisplatin or nedaplatin and 21 with docetaxel/cisplatin shortly after TC failure. Patients were divided between those who were refractory to initial platinum-based chemotherapy (n = 29, Group A) and those who were platinum-sensitive (n = 31, Group B). Efficacy and safety of the combination chemotherapies were compared between the two groups.Response to the combination chemotherapy was 10.3% in Group A and 41.9% in Group B. Median time to disease progression was 4.02 months and 7.21 months, respectively (p = 0.006), and median survival time was 7.89 months and 9.23 months, respectively (p = 0.003). There was no difference in response between the two regimens. Grade 3-4 hematologic toxicities were more frequent with the docetaxel regimen.The choice between agents for second-line chemotherapy for TC-refractory ovarian cancer should be based on whether the cancer was previously platinum-sensitive. With a history of such response, multi-agent chemotherapies are worth considering after TC failure. With no previous response, the expected efficacy of second-line multi-agent chemotherapy is low, suggesting the use of monochemotherapy.

Aim To evaluate multi-detector computed tomography (MDCT) findings of intraductal papillary neoplasm of the bile duct (IPNB), a neoplasm that is considered to be the biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. Materials and methods Two radiologists retrospectively evaluated multiphase contrast-enhanced CT images with 0.5 or 1 mm collimation in 37 consecutive patients with resected IPNB diagnosed by a single pathologist. The CT findings were correlated with the pathological findings concerning invasion of the surrounding organs and vessels. Results All patients showed bile duct dilatation. An intraductal mass was detected in 36 patients and the following findings were observed: extensive infiltration along the bile duct more than 20 mm ( n = 32), compared with normal hepatic parenchyma, isodense or hyperdense during the late arterial phase ( n = 31), not hyperdense during the portal-venous and delayed phases ( n = 36), and intense enhancement rim at the base of the mass during the portal-venous or delayed phase ( n = 27). Parenchymal invasion of the surrounding organs was seen in eight of 16 tumours showing irregular or bulging margins. Vascular invasion was false positive in four of eight tumours. Conclusions IPNB exhibits relatively characteristic findings with multiphase contrast-enhanced examination using MDCT. A tendency to overestimate invasion of the surrounding organs and vessels was seen.

Objective To evaluate the reliability of a newly developed stiffness-determining device, composed of a leg mannequin and air-pack type analyser, for measuring the interface pressure. Method The correlation of stiffness values obtained employing the Hohenstein method and this new method was investigated using 17 different brands of medical elastic compression stocking. Results A significant correlation in stiffness values using the two methods was obtained ( P < 0.01). When this new method was applied to the bandages, the stiffness was significantly correlated with the initial pressure when assessing both short-stretch and long-stretch bandages. On the comparison of stiffness values between elastic stockings and bandages with the same initial pressure, the short-stretch bandages showed a predominantly higher value than long-stretch bandages and stockings ( P < 0.01). Conclusion The reliability of this new method, which can be easily applied to not only elastic stockings but also elastic bandages, was verified. In clinical practice, the compression pressure should be selected in consideration of the prospective stiffness.

The canine is frequently used as a model for human hip arthroplasty research. In order to better understand the appropriateness of the canine as a model for human total hip replacement studies, the external morphology of canine and human femurs were examined and compared. Several differences were found between canine and human femora, including angular measurements, anterior bow, and femoral head position relative to the femoral diaphysis. In addition, the human femur was noted to undergo age-related changes in several of the measured parameters. The canine femur did not exhibit any age-related changes in the measured parameters. This study suggests that there are limitations to the use of the canine model in human hip arthroplasty research, and that discretion must be exercised when attempting to extrapolate results from a canine study to the human clinical condition. © 1993 John Wiley & Sons, Inc.

Objectives To compare the interface pressure during rest and exercise among various kinds of arm sleeves. Methods The interface pressure underneath nine different arm sleeves was measured during 10 maximal opening and closing movements of fingers using a pressure transducer (Air Pack Type Analyser) in 16 healthy volunteers. Furthermore, in order to evaluate the characteristics of each arm sleeve, the extensibility, stiffness and thickness were determined in vitro by several apparatuses. Results There was a significant correlation between stiffness and extensibility. The stiffness was significantly correlated with the pressure difference between muscle contraction and relaxation during exercise. The higher the value of stiffness, the greater the pressure amplitude during exercise. Conclusion Short-stretch arm sleeves characterized with a high level stiffness, including thick round- and flat-knitted arm sleeves, are more beneficial for the augmentation of muscle pumping than long-stretch arm sleeves, in the same way as short-stretch bandages or stockings applied to the leg.

Type I collagen, the major organic component of human dentin, plays an important role in regulating the mechanical strength of dentin. Collagen in dentin can be strengthened by heating. We hypothesized that UV irradiation could produce similar strengthening effects and might maintain the strength of dentin after rehydration. Beam-shaped dentin specimens from the crowns of human third molars were subjected to flexural testing. Flexural strengths were two and three times greater than those in the control group after 5 minutes’ UV irradiation and heating to 140°C, respectively. After 30 days of rehydration, the heated specimens reverted to their original strength, whereas the UV specimens were 69% stronger than the original. Raman spectra of dental collagen were unchanged after heating, whereas several peaks, including a C-C bond in a proline ring, were amplified by UV irradiation. It is concluded that dentin strengthened by UV irradiation retains strength after rehydration because of chemical changes in collagen.

When recording with a palm electrode, a premotor potential (PMP) precedes the compound muscle action potential evoked from the second lumbrical muscle following median nerve stimulation. The origin of the premotor potential has remained uncertain. The aim of this study was to determine whether the PMP-2L is a SNAP derived from antidromically activated digital sensory branches of the median nerve.We recorded three active electrodes were placed over the second lumbrical muscle, the third lumbrical muscle, the fourth lumbrical muscle by multi-channel recordings.PMPs are recorded only over the median digital sensory branches after stimulating the median nerve, while they are recorded only over the ulnar branch after stimulating the ulnar nerve.We conclude that the origin of the PMP is a SNAP arising from antidromically activated digital sensory branches.

The aim of this study was to assess the effects of the reconstructed thickness of axial images on image quality of CT pancreatic arteriography with 16-channel multislice CT. In 31 consecutive patients, raw data of arterial-phase scanning with 0.5 mm collimation were reconstructed in the following three ways: 0.5 mm thickness (effective thickness of 0.75 mm) at 0.4 mm intervals in Group 1; 1 mm thickness at 0.5 mm intervals in Group 2; and 2 mm thickness at 1 mm intervals in Group 3. For the visualization of major arteries and small arteries of the pancreatic head, four blinded readers independently performed side-by-side comparison of the CT arteriographic images generated from each axial dataset for the same patient using a three- dimensional volume-rendered technique. In all comparisons using a continuous rating scale, CT arteriographic images generated from thinner axial images were found to be significantly superior (p,0.01). The difference was more pronounced for small arteries. The degree of degradation from Group 1 to Group 2 was markedly smaller than that from Group 1 to Group 3 or from Group 2 to Group 3. For small arteries, paired images were assigned a grade of ''almost equivalent'' in 73%, 6% and 15% of the comparison between Group 1 and Group 2, Group 1 and Group 3, and Group 2 and Group 3, respectively. We concluded that the image quality of CT pancreatic arteriography, especially for small arteries, can be improved by reconstructing axial images with thinner thickness from the data obtained with submillimetre collimation.

An 82-year-old man was referred to our hospital because of progressive heart failure. He had Parkinson's disease and had been treated with cabergoline during the preceding 4 years and 8 months. Echocardiography revealed severe mitral regurgitation through retracted mitral leaflets with incomplete coaptation. Heart failure persisted despite pharmacologic therapy, so the mitral valve was surgically replaced with a biological valve. Histologic analysis showed fibrous thickened mitral chordae with myxoid degeneration. These characteristics of the mitral valve of our patient are similar to the valvular heart disease described with the use of cabergoline. Clinicians must be care of valvular heart disease whenever they treat Parkinson's disease patients with cabergoline.

Hyaline vascular type Castleman's disease (HVCD) is a benign cause of lymph node hypertrophy which radiologically resembles tumours such as paraganglioma and lymphoma. However, a distinguishing pathological characteristic of HVCD is the presence of central stellate fibrosis. Since conventional CT and MRI scans failed to differentiate areas of fibrosis, three-phase dynamic CT was performed on a patient who was thought to have HVCD. The images showed central fibrosis and consequently the correct pre-operative diagnosis of HVCD was made.

Focal fatty infiltration of the liver (FFIL) is a frequently encountered entity. It sometimes, however, mimics liver tumour on ultrasonography (US) and/or computed tomography (CT). Though scintigraphic studies have been utilized to differentiate this disorder from tumours in such cases, there have been four exceptional false positive cases of FFIL reported with accumulation defects on Tc-99m colloid scan. We performed a Tc-99m-GSA SPECT on a patient with possible FFIL that showed a defect on Tc-99m colloid scan to see if it could provide diagnostic usefulness for FFIL. Tc-99m-GSA showed no uptake and could not differentiate FFIL from tumours in this case.

Intrapancreatic accessory spleen (IPAS) is a mass that can mimick a neoplastic mass in the pancreas. As it poses no clinical problem no treatment is required. Unfortunately almost all the reported cases of IPAS have been misdiagnosed and unnecessary surgery performed. We performed contrast-enhanced ultrasound (CEUS) in a patient with IPAS for a research purpose, and confirmed that CEUS is useful for diagnosing this entity.

The primary transmitter deficit is cholinergic in Alzheimer's disease (AD), and the amygdala receives a major cholinergic projection from the nucleus basalis of Meynert (Ch4), which may play an important role in the retention of affective conditioning and/or memory consolidation. We measured brain acetylcholinesterase (AChE) activity in 54 patients with AD and in 22 normal controls by positron emission tomography and N-[(11)C]methylpiperidin-4-yl acetate to characterize the cholinergic pathology in AD. The k(3) values were calculated as an index of AChE activity in a three-compartment model analysis using the metabolite-corrected arterial input function. The k(3) values were highly significantly reduced by 20% in the cerebral neocortex (P0.0001 in the two-tailed t test), 14% in the hippocampus (P0.001), and 33% in the amygdala (P0.0001) in AD patients compared with normal controls. The k(3) values were significantly correlated with the Mini-Mental State Examination scores in both the cerebral cortex (P0.001) and the amygdala (P0.05) in AD patients, supporting the cholinergic hypothesis of cognitive dysfuncion in AD. Further studies are required, however, to elucidate the specific role of the cholinergic deficit in the amygdala in the emotional and behavioral symptoms in AD.

A case is reported of glioblastoma multiforme (GM) of the cerebellum associated with an intracerebellar hemorrhage. A 54-year-old male was admitted to our hospital with sudden onset of headache and nausea. CT scan showed right intracerebellar hemorrhage. The patient received conservative therapy and was discharged without any neurological deficits. However a second cerebellar hemorrhage attacked him ten days after discharge. His level of consciousness deteriorating, he underwent suboccipital craniectomy and the hematoma with the surrounding elastic tissues was excised. There were no findings suggesting hemorrhage within the tumor on the preoperative neuroimagings, but histological examination confirmed GM with massive hemorrhage. To our knowledge, only 2 cases of cerebellar GM with massive hemorrhage have been reported in the literature. Our case indicates cerebellar GM should be taken into account as a possible cause of cerebellar hemorrhage.

Annotation and database system of full-length cDNA sequences was developed. As the components of the system, ORF annotation system, functional annotation system based on database search results, mapping annotation system, and integrated retrieval and display system were developed. In the ORF annotation system integrated analyses using conventional tools are performed and useful retrieval interface using motif list are introduced. In the functional annotation system based on database search results, a new method that characterizes a given unknown cDNA was developed by using a profile of similarity level over words appearing in sequence database entries. In the mapping annotation system, we linked by similarity searches full-length cDNA sequences with database DNA sequences that are already mapped on chromosomes. By using these links, full-length cDNAs can be retrieved by the retrieval condition of physical mapping information. Genetic disease information mapped on the physical mapping site can also be displayed by this system. Furthermore, we constructed an integrated database system for these analyzed data, and thus enabled annotation and selection of full-length cDNAs from points of both gene function and mapping information.

A 36-year-old woman admitted to our hospital because of numbness in the left limbs and weakness in the right arm, and was subsequently given a diagnosis of intramedullary spinal cord metastases from lung cancer. The patient had lung adenocarcinoma with metastases to the brain, spine and lymph nodes. Occipital craniotomy, radiation therapy and chemotherapy were performed on the lesions in the year following June 1994. In June 1995, however, she complained of numbness in the left limbs and weakness in the right arm. Compatible with her neurological manifestation, MRI demonstrated tumors in the right side of the cord at the spinal level of C3-4 and C7-Th1, both of which were of high density in T2-enhanced conditions with enhancement by gadolinium-diethylenetriamine pentaacetic acid. No invasion from spinal metastasis was detected by CT, scintigraphy or MRI. We therefore diagnosed her manifestation as Brown-Séquard syndrome caused by intramedullary spinal cord metastatic tumors of lung adenocarcinoma. In order to avoid paraplegia and dysfunction of the bladder and bowel, radiation therapy of the cord lesions with total dose of 44 Gy was performed. Her neurologic manifestation was improved, restoring her quality of life, as the tumor size estimated by MRI decreased. Four months later, however, she died of lung adenocarcinoma that developed accompanied with severe peritonitis carcinomatosa and multiple metastases.

Splenosis is autotransplantation of splenic tissue that usually follows traumatic rupture of the spleen and/or splenectomy. We report a case of retroperitoneal splenosis. The correct diagnosis was made noninvasively with Tc-99m heat-damaged red blood cell scintigraphy. Surgical treatment, which was not necessary in this patient, could be avoided by splenic scintigraphy.

Recent improvements in imaging techniques have made it possible to improve the diagnostic accuracy for detection, staging, and indicating surgical resectability of pancreatic cancer. The latest advance in the computed tomography technique, is the introduction of subsecond multislice helical scanning that improves z-axis resolution in the reformatted images and three-dimensional rendering with a large volume data. Magnetic resonance imaging provides versatile information including magnetic resonance cholangiopancreatography that allows noninvasive delineation of the pancreatic and biliary duct systems. The presence of pancreatic cancer may best be evaluated by dynamic computed tomography or dynamic magnetic resonance imaging with administration of intravenous contrast material. Both computed tomography and magnetic resonance imaging are valuable for the preoperative assessment of local invasion and vascular involvement. Multislice helical computed tomography is currently considered as the best single modality for the diagnosis of pancreatic cancer as it provides excellent image quality. When advanced magnetic resonance imaging equipment is used as a primary modality, in the future, it may have a possibility to replace other imaging modalities.

We report a 73-year-old woman with intravascular malignant lymphomatosis (IML) who showed generalized telangiectasia as well as various neurological symptoms. In July 1998, she developed fever, dizziness, and confusion followed by left hemiparesis, and was admitted to our hospital on August 11, 1998. Laboratory tests indicated a normochromic normocytic anemia, thrombocytopenia, elevated serum lactic dehydrogenase (LDH), C-reactive protein (CRP), and cerebrospinal fluid protein. Magnetic resonance imaging (MRI) of the brain revealed an infarct-like lesion in the left frontal lobe and multiple white matter lesions. After admission, her neurological status deteriorated and lapsed into coma and quadriplegia. At the end of September 1998, generalized telangiectasia appeared, and she was diagnosed as IML on skin biopsy. Although combination chemotherapy failed to improve her neurological symptoms, telangiectasia disappeared in a few days, and the infarct-like lesion on MRI decreased in size. Serum LDH, CRP, and thrombocyte counts were normalized. Autopsy findings revealed perivascular clustering of B cell type lymphoma cells in the left frontal lobe where abnormal signal intensity was found on MRI, as well as the spleen and the bone marrow. This case emphasizes the importance of early diagnosis and treatment in IML.

A 25-year-old woman was admitted to our hospital with goiter. The diagnosis was Grave's disease. Diagnostic transthoracic echocardiography revealed a hyperdynamic stage of the heart with right ventricular dilation. Doppler echocardiography showed mild to moderate tricuspid regurgitation and elevated systolic right ventricular pressure. Right heart catheterization revealed high cardiac output (9.49 l/min) and pulmonary hypertension (57 mmHg) with increased pulmonary vascular resistance and total pulmonary resistance. No intracardiac shunts were detected. Since neither thiomazole nor propylthiouracil was effective and both caused side effects, she underwent subtotal thyroidectomy. After the surgery, pulmonary hypertension improved and cardiac output normalized, but without normalization of pulmonary vascular resistance and total pulmonary resistance. Reversible pulmonary hypertension may occur in patients with hyperthyroidism. Increased pulmonary blood flow and sustained high pulmonary artery resistance were suspected as the causes of pulmonary hypertension. In addition, pulmonary endothelial dysfunction as a result of sustained increased pulmonary blood flow could be another cause of pulmonary hypertension.

Eosinophilic pustular folliculitis (EPF) is characterized by erythematous patches of large follicular papules and pustules involving mainly the face. Although various treatments have been attempted for EPF, including systemic and topical steroid, diaphenylsulphone, colchicine, minocycline as well as UVB phototherapy, there is no consensus on the first choice of treatment. We report a typical case and summarize 25 patients with EPF treated in our hospital between 1978 and 1998. Indomethacin was most frequently used (12/25) and showed clinical improvement in the majority of the cases (11/12). The effect of indomethacin was usually observed within 1--2 weeks after initiation of treatment. Decrease of peripheral blood eosinophils accompanied the clinical improvement. Thus, indomethacin should be considered as a first choice of treatment for EPF.

After the advent of DSM-III, operational diagnostic criteria, along with the classification of disorders using such criteria, received considerable attention, and many studies on the reliability and validity of psychiatric diagnosis were conducted worldwide. Operational methodology was applied to diagnosis and classification, especially, in the area of research, and has contributed greatly to advances in reliable and refined clinical research. Such methodology, however, has not necessarily been accepted as a guiding principle in the area of clinical practice by all psychiatrists. Rather, some psychiatrists, especially more experienced psychiatrists, took a somewhat negative attitude toward the use of operational methodology. The author contends that one of the causes for the relatively poor acceptance of operational methodology in the area of clinical practice lies in the "classification model" view of diagnosis that forms the implicit background for the methodology. From a clinical perspective, it is not from the "classification model" basis but rather, from the "decision-making model" basis that the actual process of clinical diagnosis in psychiatry is explained properly. This is a very important point, because the latter model is potentially more useful both to psychiatric patients and to researchers in psychiatry than the former model. There have been however, few reports in psychiatry that highlight the importance of this model as the clinical framework. The author analyzes the limitations of the "classification model" view, and then, based on this analysis, lists prerequisites that a model for the framework of clinical practice should possess. The prerequisites listed are: that clinical information not sufficient to meet the disease criteria should be used as effectively as possible, that diseases low in probability but high in seriousness should be considered by clinicians in the differential diagnoses; that diagnosis should be readily changed when necessary; that the component of benefit to the patient should be included in the model; and that the relationship between nosological definition of diseases and practical diagnostic criteria should be explained explicitly. In addition, the author emphasizes that psychiatric diagnosis involves "decision-making under the condition of incomplete information", because most psychiatric diseases are still of unknown etiology. With all these conditions in mind, the author contends that the Bayesian statistical model of decision-making is suited to the frame of reference, and that it should replace the classification model as a guiding principle. This model can integrate various aspects of psychiatric clinical activities systematically and explicitly. A case is presented to illustrate the model in a clinical context. The author points out problems to be solved in current psychiatry from the perspective of the Bayesian model of decision-making. Finally, limitations of the Bayesian model view are discussed.

A combined aortectomy was performed on a patient with recurrence of sigmoid colon cancer in the paraaortic lymph nodes. The 48-year-old woman was found to have tumor recurrence in the lymph nodes in the area between the aortic bifurcation and the paraaortic area, accompanied by left hydronephrosis, four years after surgery for sigmoid colon cancer (H0, P0, ss, n3, stage IIIb). No metastasis to distant areas was detected at that time. The woman thus underwent a reoperation. Intraoperatively, the aortic bifurcation and the lymph nodes were seen as a mass. The mass involved the left common iliac vein and the left ureter, as well. Therefore, we resected the area from the aortic bifurcation to the bilateral common iliac arteries, the left common iliac vein, the left ureter and the left kidney en bloc, and replaced them with a Y-shaped graft. One year after the reoperation, a tumor metastasis to the liver was detected, and a partial hepatectomy was performed. At present, the patient is being managed at our outpatient clinic. The results suggest that extended resection, involving the aorta as well, is sometimes useful when dealing with tumor recurrence in the paraaortic lymph nodes, unaccompanied by blood-borne metastasis.

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.

We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD.

Evolution of Ig V gene segments are generally characterized by (a) evolution by "the birth and death process" and (b) diversifying selection. However, the detailed evolutionary pattern of V gene segments varies among species due to the fact that the humoral immune system itself has changed during vertebrate evolution. The change in somatic diversification system coupled with the change in lymphocyte development has imposed a significant impact on the evolution of Ig genes. In order to understand the evolution of immunological genes it is important to view it in the context of the evolution of the entire immune system itself.