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Background Cancer chemotherapy is associated with a variety of side effects/adverse events. It is very important that patients adhere to the planned chemotherapy regimen, which necessitates a minimum of side effects and that these side effects be kept under control. We have investigated patients’ concerns and symptoms during chemotherapy with the aim to seek solutions that will improve patients’ quality of life during chemotherapy. Methods Forty-nine patients with malignant diseases on parenteral antineoplastic agents were sequentially enrolled in this study. These patients completed a questionnaire consisting of 42 items related to non-physical concerns and 52 items of physical symptoms related to chemotherapy. Each patient was also asked to select the three items among these 94 items which affected him/her the most. Results The median age of the cancer patients was 62 years and the male-to-female ratio was 18:31. Among the non-physical concerns, the most frequently chosen concern was ‘affects my family or partner,’ followed by anxiety related to treatment. Regarding the physical symptoms, the most frequent complaints were fatigue, alopecia and constipation, while the most troublesome symptoms were nausea, poor taste and paresthesia. Overall, the most frequently expressed concerns were ‘affects my family or partner’ and anxiety related to treatment. Male patients suffered most from fever, fatigue and nausea, and female patients complained more of poor taste and gastrointestinal problems. Conclusion Patient perceptions of adverse events associated with cancer chemotherapy apparently have changed from physical symptoms to non-physical concerns. In our patient cohort ‘affects my family or partner’ was the most important concern. One important point to note is that female patients often complained of poor taste because this meant they were unable to cook well. Electronic supplementary material The online version of this article (doi:10.1007/s10147-017-1117-y) contains supplementary material, which is available to authorized users.

The current study aimed to compare cytology using SurePathBetween January 2014 and December 2016, 57 patients underwent endoscopic retrograde cholangiopancreatography for the diagnosis of biliary disease. Biliary cytological samples were processed using SP-LBC and subsequently BTH was performed. A final diagnosis was confirmed by surgery (23 malignant cases) and clinical follow-up (34 benign and malignant cases): 18 extrahepatic cholangiocarcinoma; 17 intrahepatic/hilar cholangiocarcinoma (intra/H-CC); eight other malignant disease; and 14 benign biliary disease. The diagnoses made using SP-LBC and BTH were classified into four categories: (1) benign; (2) indeterminate; (3) suspicious for malignancy/malignant; and (4) inadequate. In addition, diagnostic accuracy was compared between SP-LBC and BTH.Although 23% (13/57) of BTH samples were classified as inadequate, all SP-LBC cases were classified as adequate. Among 43 malignant cases, 11 normal, four indeterminate and 28 suspicious for malignancy/malignant were found using SP-LBC (26%, 9% and 65%, respectively), in contrast to 10 inadequate, nine normal, 10 indeterminate and 14 suspicious for malignancy/malignant observed using BTH (23%, 21%, 23%, and 33%, respectively). The identification of malignant cells was strikingly different between SP-LBC and BTH. Furthermore, limited to intra/H-CC, accuracy was significantly higher using SP-LBC than using BTH (P .001).SP-LBC of the biliary tract is a useful and reliable method for diagnosing biliary malignant disease and has an advantage over BTH for detecting malignant cells and accurately diagnosing intra/H-CC.

Background Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). Methods FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).

The GAC→AAC mutation at codon 178 (D178N) of prion protein (PrP) gene ( PRNP ) results in 2 distinct clinicopathologic phenotypes dependent on codon 129 polymorphism of the mutant allele: fatal familial insomnia (FFI) with methionine encoded in codon 129 and familial Creutzfeldt-Jakob disease (CJD) with valine.1,2 However, some D178N patients who had homozygosity for methionine at codon 129 (D178N-129MM) were reported recently to have the CJD phenotype.3–5 The cause for these clinicopathologic diversities is unclear. We report a Japanese son–mother pair who presented with FFI and CJD phenotypes. ### Case reports. #### Patient 1 (proband). A 54-year-old man, born to nonconsanguineous parents, developed dysphagia and loss of appetite. Later, he showed peculiar movement in sleep, followed by insomnia and hypersomnolence. Diplopia, intention tremor, ataxic gait, sleep apnea, fluctuant low-grade fever, tachycardia, hyperhidrosis, constipation, and impotence also followed. He was admitted to hospital 7 months after the onset of symptoms. Neurologic examination showed mild memory disturbance, cerebellar ataxia, myoclonus, brisk deep tendon reflexes, sleep apnea, and dysautonomia. He did not show akinetic mutism. He moved continuously during sleep. EEG showed no periodic synchronous discharge (PSD), and polysomnography showed loss of deep sleep and marked reduction of REM sleep. Brain MRI showed only mild atrophy. In the cerebral cortex and thalamus, hypoperfusion and hypometabolism were detected by SPECT with 99mTc-ECD and PET with 18F-2-fluorodeoxy-d-glucose. He died 13 months after the onset of symptoms. PRNP analysis, with informed consent, on leukocyte DNA showed D178N-129MM. Histologic examination showed spongiform changes limited to the cingulate gyrus and subiculum, and severe neuronal loss and fibrillary gliosis in the centromedian and dorsomedial nucleus of the thalamus and in the inferior olivary nucleus (figure, A, D, and G). Immunohistochemical analysis showed no pathologic PrP (PrPSc) deposition in the cerebral cortex, thalamus, or inferior olivary nucleus. Western blot analysis (WB) showed very …

Summary A new type of inherited chondrodysplasia is described in Japanese Brown cattle, but the basic defects of the epiphyseal growth plate (EGP) in the limb long bones, and proliferation and differentiation of the chondrocytes in the EGP, are not yet understood. In the present study, the EGPs of the limb long bones in eight cases of chondrodysplasia and four normal (control) cattle were examined histologically and immunohistochemically. In the control cattle, proliferative chondrocytes (PCs) and hypertrophic chondrocytes (HCs) were arranged in columns parallel to the long axis of the bone, and HCs were situated on the metaphyseal side of the EGP. In all the affected cattle, many chondrocytes with a hypertrophic appearance were detected in the inner areas of the central portion of the EGP. The PC columns were short and arranged irregularly. Bone tissue and small blood vessels were found frequently in these areas. Six affected cattle showed complete EGP-closure. Backscattered electron (BSE) imaging showed that the calcified cartilage matrix was restricted to the lower region of the hypertrophic zone (HZ) of the EGP in the control cattle, while the calcified cartilage matrix and bone tissue were scattered in the inner areas of the EGP in all the chondrodysplastic cattle. Immunohistochemistry revealed type X collagen in the HCs and cartilage matrix of the HZ in the control cattle. In all the affected cattle, type X collagen was detected in apparently hypertrophic chondrocytes in the inner areas of the EGP. Type II collagen was detected in the entire EGP in all the affected cattle, as in the controls. BrdU (5-bromo-2’-deoxyuridine), injected intravenously 1 h before euthanasia was detected in many PCs in the EGP in the control cattle; none, however, was detected in the central portion of the EGP in any affected animal. These observations indicate that differentiation into HCs and calcification of cartilage matrix occur in the inner areas of the central portion of the EGP in chondrodysplasia of Japanese Brown cattle. Differentiation into the HCs at this abnormal site may be caused by the inadequate proliferation and disorganization of the PCs. Premature EGP-closure, observed commonly in chondrodysplasia of Japanese Brown cattle, was thought to be caused by replacement of the calcified cartilage in the inner areas of the EGP by bone tissue.

The aim of this study was to assess the immunomodulatory effect of KC-1317 (a symbiotic mixture containing Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria, and lactose mixture) supplementation in immune-compromised but otherwise healthy elderly subjects. A liquid formulation of KC-1317 was administered in a randomized controlled trial (RCT) fashion to healthy volunteers (65-79 years) previously selected for low natural killer (NK) cell activity, and this parameter was checked at the completion of the study. A significant improvement in NK cell activity of KC-1317 consumers was observed as compared to placebo at the end of 2 months. Although preliminary, these beneficial immune-modulatory effects of KC-1317 in aged individuals might indicate its employment within a wider age-management strategy.

We built an in-house oligonucleotide array on which 394 genes were selected based on our Serial Analysis of Gene Expression (SAGE) data and previously reported array data and listed several genes related to cancer progression. Among these, we focused on SEC11A, which encodes the SPC18 protein. SEC11A mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric cancer (GC) tissue samples. Expression and distribution of SPC18 protein were investigated by immunohistochemical analysis in two independent GC cohorts (Hiroshima cohort, n=99 and Chiba cohort, n=989). To determine the effect of SPC18 on cell viability and invasiveness in vitro, MTT and Boyden chamber invasion assays were performed. To evaluate the influence of SPC18 on cell growth in vivo, GC cells were injected into severe combined immunodeficiency mice. Levels of TGF-α and EGF in media from the GC cells were measured by enzyme-linked immunosorbent assay (ELISA). Studies in human tissue revealed overexpression of SEC11A mRNA in 40% of 42 GC samples by qRT-PCR. Immunohistochemical analysis of SPC18 revealed that 26 and 20% of GC cases were SPC18-positive in the Hiroshima and Chiba cohorts, respectively. In both cohorts, the Kaplan-Meier analysis showed poorer survival in SPC18-positive GC cases than in SPC18-negative GC cases. Forced expression of SPC18 activates GC cell growth in vitro and in vivo. The levels of TGF-α in culture media from GC cells were reduced by knockdown of SPC18. These results indicate that SPC18 contributes to malignant progression through promotion of TGF-α secretion in GC.

We report one case of parkinsonism induced by cisapride and one case of Parkinson's disease whose symptoms were worsened by cisapride. Case 1. A 75-year-old female who had suffered from constipation and loss of appetite, was treated with cisapride for her gastro-intestinal symptoms. One year later, she developed progressive parkinsonian gait, cogwheel rigidity She showed parkinsonian gait, cogwheel rigidity and slowness in motion. Two months after cisapride was discontinued, her parkinsonism and depression disappeared. Case 2. A 66-year-old female with Parkinson's disease was given cisapride for constipation. Two months after starting cisapride, her akinesia and rigidity deteriorated gradually, and she became bed-ridden with dysphagia and dyspnea. After cisapride was discontinued, her parkinsonian symptoms improved gradually, and she became ambulant three months later. Cisapride is a benzamide derivative with a prokinetic action. Experimental studies have revealed that it has indirect cholinomimetic effects and potentially stimulates the gastrointestinal motor activity without blocking dopamine receptors or activating muscarinic cholinergic receptors. However, the present cases showed that cisapride could be a dopamine receptor blocker, and either induce or worsen parkinsonism. Therefore, cisapride should be avoided or very carefully used in parkinsonian patients and old people.

An 8-year-old girl with preexisting chronic renal failure (CRF) due to bilateral renal hypoplasia presented with edema, gross hematuria and acute deterioration of renal function. The diagnosis of poststreptococcal acute glomerulonephritis (PSAGN) was made based on clinical presentation, red blood cell casts, low level of C3 and elevated antistreptolysin 0 titer. Her course was prolonged with serum creatinine increased from the baseline level of 1.1 mg/dl to 2.2 mg/dl, returning toward the baseline level (1.2 mg/dl) after one month. Serum creatinine then started to increase again. The slope of creatinine clearance over time became steeper after the episode of PSAGN. A severe course of PSAGN and subsequent deterioration of renal function have previously been reported in patients with diabetic nephropathy or focal glomerulosclerosis. The present case along with a literature review suggests that individuals with fewer nephrons are at higher risk of severe course and outcome of PSAGN. Conversely, patients with severe PSAGN may be born with fewer nephrons due to low birth weight, unrecognized renal hypoplasia or other unknown causes.

Syphilitic cardiovascular disease has become a rarity today. It most commonly affects the ascending aorta and aortic arch. A case is reported of a 50-year-old female with a ruptured syphilitic ascending aortic aneurysm who underwent an emergency operation. The patient was emergently admitted with complaint of severe dyspnea, circulatory shock due to cardiac tamponade was observed in the emergency room. Bentall's procedure was performed. Intraoperative findings showed multi-cystic dilatation of an aortic root. Penetration was existed on right side posterior wall of an aortic root. Postoperative pathological examination of the aneurysmal wall revealed the characteristic finding of syphilitic aortitis. The postoperative course was uneventful and the patient has been doing well at period of 3 years after operation.

We report a case of a 28-year-old female who underwent an extracardiac Fontan procedure. The subject was diagnosed as an atrioventricular septal defect (Rastelli classification: type C), a double outlet right ventricle, pulmonary artery stenosis, a hypoplasty of left ventricle, total anomalous venous return (Darling: Ib + IIb), and atrial flutter. She underwent a Blalock shunt and an aorto-pulmonary shunt at the ages of 3 and 9 years, respectively. Under a total CPB, an extracardiac total cavo-pulmonary connection (TCPC), using a 26 mm Hemashield graft, was completed. The postoperative course was uneventful. The complicated atrial anatomy and atrial arrhythmia indicated TCPC in this adult patient.

With this tissue engineering (TE) technique, the peripheral pulmonary artery was successfully reconstructed, using the patient's own venous cells in a 4-year-old girl, 2 years after Fontan procedure. A 4-year-old girl was given a diagnosis of single right ventricle, double-outlet right ventricle and pulmonary atresia. She underwent left modified Blalock-Taussig shunt at a month old, pulmonary artery angioplasty at a year and 3 months old, and bidirectional cavopulmonary shunt at 2 years and a month old. She underwent again pulmonary artery angioplasty and Fontan operation at 3 years and 3 months. An angiographical examination 7 months after the operation revealed total occlusion of the right intermediate pulmonary artery. TE technique using autologous cells was indicated. The application of this procedure was approved by the ethical committee in Tokyo Women's Medical University. The patient's parents were thoroughly informed and signed a consent form. Approximately 2 cm of the peripheral vein was explanted under sterile conditions. The tissue was minced, placed in tissue culture dishes and cultured at 37 degrees C, 100% humidity and a 5% CO2 atmosphere for almost a month. The number of cells substantially increased to reach 12 millions for almost a month. The culture medium was changed every 3 days. The polymer tube that served as a scaffold for cells was composed of the copolymer of PCL-PLA (50:50) with reinforcement by woven PGA. The polymer conduit, 10 mm in diameter, 20 mm in length and 1 mm in thickness, was designated to biodegradate within 8 weeks. The number of seeded cells was approximately a million/cm2. The graft transplantation was performed 10 days after seeding cells. The occlusive right intermediate pulmonary artery was reconstructed with the TE vessel graft under extracorporeal circulation with a pump-oxygenator. The patient followed a satisfactory postoperative course. The postoperative angiography demonstrated that the graft was not constricted and dilated but that it preserved good patency. Long-term follow-up are necessary. We plan to continue to use the TE technique using autologous cells in the low pressure system like venous or pulmonary circulation. Because our results even in early experimental phase were valuable and promising, we believe that the TE approach may play an important role in the near future as an another alternative, together with transplantation and artificial organ, especially in the field of cardiovascular surgery that mostly needs replants.

Recurrent breast cancer has a very poor response rate to chemotherapy. To understand the degree of acquisition of multidrug resistance in recurrent disease, 24 recurrent breast tumors and 127 primary tumors were evaluated and compared for chemosensitivity in the histoculture drug response assay (HDRA). The evaluation rate was 98.8%. The HDRA utilizes 3-dimensional culture of human tumors on collagen-gel rafts. Doxorubicin (DXR), 5-fluorouracil (5-FU) and mitomycin C (MMC) were tested as standard agents and cisplatin (CDDP) as a candidate agent on surgical specimen of breast cancer in the HDRA. In vitro drug exposure in the HDRA was for 7 days. At the end of the assay, tumor response was assessed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The mean inhibition rates of primary tumors vs. recurrent tumors were 57.9% and 38.6% for DXR (p0.0005); 59.9% and 42.8% for MMC (p0.01); 49.0% and 33.4% for 5-FU (p0.01); and 34.5% and 16.0% for CDDP (p0.005), respectively. The recurrent cases were pretreated clinically with CAF (cyclophosphamide, DXR and 5-FU), CEF (cyclophosphamide, epirubicin and 5-FU) or CMF (cyclophosphamide, methotrexate and 5-FU). In the CAF and CEF group, the HDRA sensitivity to CDDP was significantly lower in recurrent disease (p0.005) than that of primary breast cancer suggesting that one agent can induce resistance to another. This is further suggested by the fact that 64.7% of the recurrent cases were resistant to all 4 agents tested as opposed to 27% of the primary cases and that only 5.9% of the recurrent cases were sensitive to three or more agents as opposed to 18% of the primary cases. The correlation of the HDRA results to clinical outcome in the study was 80.0% with 15 cases evaluated consisting of 5 true positives, 3 false positives, 7 true negatives and no false negatives. Thus, the HDRA gives useful clinical information, in particular for the specific individualized treatment design necessary to overcome the multidrug resistance problem of recurrent breast cancer.

An 87-year-old female in shock was referred to our hospital. Emergency chest computed tomography and echocardiography showed a dissecting aneurysm of the ascending aorta and remarkable epicardial effusion. She was diagnosed as having rupture of Stanford type A acute aortic dissection with cardiac tamponade and an emergency operation was performed. While anesthesia was administered, cardiac arrest occurred and the chest was opened. We managed to establish an extra-corporeal circulation and performed graft replacement of the ascending aorta with GRF glue. The patient followed a satisfactory postoperative course and was discharged from the hospital at the 48th postoperative day. The proper indication for operation and minimally invasive procedure enabled us to operate on the elderly patient.

The study was carried out to collect basic data on exposure of mucous cells of the large intestine to mutagens by investigating the genotoxicity of fecal samples from the urban population. Simultaneously, relations with food intake (food groups and nutritive components), lifestyle factors and fecal metal content was investigated.A total of 199 self-collected fecal samples from middle aged healthy volunteer living in urban areas of Osaka city were freeze-dried and ground in a mill. The mutagenicity of aqueous extracts of the ground samples was measured by the umu-test. Metal content of the feces was analysed by atomic absorption spectrophotometlly. On the day previous to the feces collection, the contents of meals were recorded and confirmed by interview with a dietitian. Quantification of nutritive components was carried out using the 4th edition of the Japan Food Standard Vomposition Table.Mutagenicity of feces was higher in males than in females, and in those aged 40-49 years than 50-69 years in males but not females. Large differences were found for content of 8 metals in the feces; concentrations were in the decreasing order of calcium, potassium, magnesium, sodium, zinc, iron, manganese and copper, the highest being 20.4 mg for calcium and the lowest was 53.5 micrograms for copper. Between the metal contents and mutagenicity, values for zinc and iron showed positive correlations and for sodium a negative correlation under S9(+) conditions. A weak but significant correlation was observed between the numbers of cigarettes smoked per day and S9 (+) mutagenicity. However we could not find any relation with food groups or nutritive components.It is well known that human feces contain many mutagens and carcinogens and that these can act directly on the mucous membrane of large intestine. Therefore, it is very important to estimate exposure levels. From the present data we can conclude that relations between mutation-activity of the feces and diet are complex. Their elucidation will require a large number of volunteers who have similar living conditions to obtain appropriate data.

The perioperative treatment of open heart surgery cases with preoperative pulmonary embolism is controversial. A 40-year-old woman, who had undergone mitral valve replacement with a bioprosthetic valve 16 years earlier, showed severe heart failure, right pulmonary embolism diagnosed by pulmonary perfusion scan in the subacute stage, and prosthetic valve regurgitation. Preoperative catheterization showed severe pulmonary hypertension of 122 mmHg, equal to the systemic pressure. Pulmonary angiography showed right peripheral pulmonary embolism without main pulmonary artery embolism. Prosthetic valve replacement with a BICARBON 27 M and tricuspid annuloplasty were performed, with thrombolytic therapy before and after operation without thrombectomy, because of pulmonary hypertension attributed to prosthetic valve regurgitation. Pulmonary perfusion scan and angiography showed improvement of pulmonary embolism after treatment. Postoperative catheterization showed good results, with right and left pulmonary artery pressure of 43/16(23) and 39/15(24) mmHg, mean pulmonary capillary wedge pressure of 4 mmHg, and cardiac index of 4.96 l/min/m2. It is important to make an early diagnosis of pulmonary embolism and treat the major cause of pulmonary hypertension in cases of cardiac valve disease with pulmonary hypertension.

Tumor-infiltrating lymphocytes, particularly CD8(+) T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8(+) but also CD4(+) T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8(+) T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8(+) T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.

A 73-year-old woman underwent docetaxel therapy for lung metastasis from breast cancer after having received CAF therapy. Because of the progressive disease due to secondary resistance to docetaxel, the patient was given three courses of paclitaxel therapy (60 mg/m2, day 1, 8, 15 and 22, repeated every 6 weeks). The paclitaxel therapy brought about no adverse effects and a 51%-reduction in the size of the metastatic lung tumor (PR). Although the duration of the response to the paclitaxel therapy was limited to about one month due to progression of a brain metastasis, paclitaxel therapy may be effective against docetaxel-resistant breast cancer.

The prevalence of viral hepatitis in Japan were very high as peak HBsAg positive rate of 2-3% and HBsAb positive rate of 25% of peoples born in the 1930th and 1940th. But recently in Japan hepatitis A has completely eradicated and hepatitis B and C were seldom seen in our pediatric clinics. Many strategies were done beginning from sterilized water service to introduction of HCV-Ab screening system for blood transfusion in 1989. Many efforts had combined to get final success. The historical views of epidemics of viral hepatitis and maneuvers to improve were introduced here.

We evaluated arterial infusion chemotherapy for unresectable metastatic liver tumor using FDG-PET and CT. A 72-year-old female patient with multiple metastatic liver tumors of rectal cancer was treated by arterial infusion chemotherapy. The tumor size decreased by chemotherapy, but there was a high uptake lesion of FDG. Three months later, tumor ingrowth was detected. FDG produces images of regional glycolytic activity, and it is a useful method of assessment of tumor viability after chemotherapy in patients with cancer.

Intraductal papillary mucinous tumors of the pancreas have been recognized as a distinct clinical entity. However, their biological behavior has not been clearly defined. The aim of this study was to examine the prognosis of this tumor, to clarify the biological behavior and determine the most appropriate treatment.Correlations between prognosis of operated cases and histopathologic features were investigated.In 105 patients with characteristic clinical features of intraductal papillary mucinous tumors, the lesions were classified as hyperplasias in 21%, intraductal tumors in 48% and invasive carcinomas in 31%. Minimal invasion was apparent in 25%, lymph node metastasis in 21%, and fistula formation in 31% of the invasive lesions. Non-invasive and minimally invasive intraductal papillary mucinous tumors were essentially free from risk of tumor recurrence. Other invasive intraductal papillary mucinous tumors showed a significantly poor prognosis.Because of the variation in pathological characteristics, patient outcome and the possibility of differential diagnosis, the treatment might be recommended as follows: the case of hyperplasia can be followed-up with close surveillance. Non-invasive and minimally invasive intraductal papillary mucinous tumors should be operated with function-preserving minimal pancreatectomy. For patients with invasive intraductal papillary mucinous tumors evident with preoperative imaging modalities, radical operations with lymph node dissection might be needed.

We examined the chemosensitivity of non-small cell lung cancer (NSCLC) tissues to CDDP, 5-FU, ADM, MMC, ETP and SN38 using histoculture drug response assay (HDRA). One-hundred and thirty surgical specimens from NSCLC patients who were not given preoperative chemotherapy were used. The inhibition indexes of CDDP, 5-FU, MMC, ADM, ETP and SN38 were 39.1 +/- 18.2%, 48.0 +/- 19.7%, 63.3 +/- 17.7%, 47.6 +/- 22.0%, 36.9 +/- 21.1%, and 37.9 +/- 25.2%, respectively. Inhibition indexes were above the cutoff level, i.e., 'judged sensitive,' in 40 cases (31.3%) for CDDP, 34 cases (27.4%) for 5-FU, 54 cases (44.3%) for MMC, 36 cases (33.0%) for ADM, 29 cases (29.8%) for ETP, and 34 cases (37.4%) for SN38, respectively. In almost one-third of patients, the inhibition indexes of all drugs were under cutoff levels. Correlations between in vitro chemosensitivity data and patient responses to chemotherapy were obtained from 16 evaluable patients, and a 44.4% true positive rate and a 100% true negative rate were observed. Our results with HDRA for NSCLC showed a high incidence of intrinsic multidrug resistance. HDRA may help doctors to avoid non-effective chemotherapy for NSCLC patients.

A 66-year-old woman developed a bone metastasis from breast cancer to the sternum in September, 1997. She received alendronate therapy, consisting of biweekly intravenous administrations of 10 mg-alendronate 6 times and monthly 20 mg-alendronate infusions 15 times. The first alendronate administration markedly alleviated her bone pain. She obtained complete pain relief after the 4th alendronate infusion. However, an elevation of tumor marker levels in serum without any pain increase forced us to treat her with medroxyprogesterone acetate and doxifluridine in addition to the alendronate therapy. With these therapies, she has shown an objective response (PR) of the bone metastasis for 8 months. In conclusion, alendronate therapy was effective against bone pain due to metastasis of breast cancer.

We investigated the chemosensitivity of anticancer agents against primary (230 patients, 268 tumors) and recurrent breast cancer (40 patients, 51 tumors) using histoculture drug response assays (HDRA) of surgical specimens. Of the 40 recurrent breast cancer patients, 26 were pretreated with anthracycline. The efficacy of the agents was assessed according to an inhibition index of optical density detected by an ELISA reader. The inhibition rate of docetaxel against recurrent tumors was similar that against primary ones, although the rates of adriamycin, 5 fluorouracil, mitomycin and cisplatin against recurrent tumors were significantly lower than those against primary ones. The clinical response of docetaxel was also evaluated in ten patients with recurrent breast cancer. Of the ten patients with recurrent breast cancer, eight were pretreated with anthracycline, and seven showed a partial response. These results indicate that docetaxel is effective against recurrent breast cancer, even anthracycline-resistant breast cancer.

The molar ratio of branched-chain amino acids to tyrosine (BTR) correlates well with the Fischer ratio, and can be measured in a short period of time. It is regarded as the method of analysis that will eventually replace the Fischer ratio. But clinical significance of BTR in terms of acute liver disorders has not been examined thoroughly as of yet. In this study, we measured BTR of 34 patients with acute hepatitis, and examined the transition of the acute period of acute hepatitis and its recovery process. Thirty-four patients diagnosed with acute viral hepatitis became subjects of examination (16 patients of A type, 15 patients of B type, 1 patient of C type, 2 patients of non-A, non-B, non-C type). Out of the 34 patients, 11 were in serious stages (HPT under 40%), including 3 in fulminant condition. By using preserved serum obtained during the acute period (within 1 week of the highest transaminase value), recovery period (within 4 weeks), and treatment period (3 months and later), measurements were conducted with Diacolor:BTR (enzymatic analysis, ONO Pharmaceutical Co., Ltd.), and the results were compared with those of 50 healthy subjects (25 men, 25 women). BTR correlated well with the Fischer ratio for chronic hepatic patients, and with albumin (Alb), PT, and ICGR15 as well, proving that it is useful as an indicator of hepatic reserve ability. But BTR has not been thoroughly examined as it relates to acute liver disorders. In this study, BTR fell in the acute period, correlating with the serious period, proving that it is a useful indicator. For acute liver damage, BTR supports conventional indicators (Alb, Ch-E, HGF, etc.) for assessing serious damage. Also, it has been suggested that measuring the passage of BTR could be the indicator of true recovery, including amino acid metabolism for liver disorders.

To assess the safety of rapid infusion of incadronate and its efficacy against bone metastasis of breast cancer, we conducted a trial using incadronate therapy for breast cancer patients with bone metastasis. Of the 12 patients, 6 had undergone pamidronate or alendronate therapy. Rapid infusion of incadronate consisted of administration of 10 mg incadronate diluted in 100 ml saline in 30 minutes, and was repeated every two weeks. Each patient underwent 2 to 20 incadronate administrations. With the incadronate therapy, no patients showed hypocalcemia, but 3 patients showed asymptomatic hypophosphoremia. Of the 11 patients with bone pain, 5 patients (45%) experienced pain relief. A decrease in tumor marker levels in serum was found in 5 (56%) of the 9 patients with elevated marker levels. The side effects of incadronate administration were general fatigue (25%), pyrexia (17%) and transient pain increase (17%), but no renal dysfunction was found. In conclusion, rapid infusion of incadronate was a safe treatment and the incadronate therapy was effective against bone metastasis of breast cancer.

Since 1969, community-based stroke prevention programs have been conducted in N town, Kochi prefecture. To clarify factors related to participation in medical checkups including social networks, a cross-sectional questionnaire survey was performed on 6,704 residents aged 40 and over in N town in 1996. 1. Location of the workplace, types of medical insurance and interest in health were significantly associated with participation in medical checkups. 2. Participation in medical examinations provided at the workplace was significantly, inversely related with participation rates in community checkups in the group aged 40 to 59 years. 3. Low independence level in daily activities was inversely associated with participation rates for medical checkups in groups aged 60 years and older. 4. Visiting medical facilities was inversely associated with the participation rate for medical checkups in female groups. 5. The group with the highest social networks score (5 points) had the highest participation rate for medical checkups. After adjusting for other participation related factors, social networks scores had a significantly positive association with the participation rate for medical checkups provided by the Health Services for the Elderly Act.

Cormorants feed by feet-propelled diving. How cormorants optimize foraging is of a particular interest in relation to the understanding of the feeding strategies of diving birds, as well as within the debate about cormorants' impact on sustainable resources. Using microdata loggers that recorded diving depth, we investigated the foraging strategy of males and females of subantarctic cormorants, which inhabit cold regions, and of Japanese cormorants, which live in the northern temperate zone. For both species, males and females daily spent the same amount of time submerged, and apparently captured the same amount of fish. However, males dived deeper and longer, which could be explained by their 15-20% larger body mass and may minimize potential competition for food.

To evaluate the efficacy of docetaxel therapy against anthracycline-resistant breast cancer, twenty patients were treated with docetaxel. Of the 20 patients pretreated with anthracycline, 17 were clinically anthracycline-resistant and the remaining three were refractory to anthracycline on histoculture drug response assay. Nine patients had loco-regional recurrence and 11 had distant +/- loco-regional recurrence. Docetaxel (49-60 mg/m2) was administered every 4 weeks, and was infused 1-13 times (median; 3 times). Of the 19 evaluable patients, eight (42%) showed partial response with the docetaxel therapy. Durations of the response ranged from 1 to 8 months (median; 4 months). Major adverse effects of the therapy were alopecia, neutropenia, and leucocytopenia. Hypersensitivity reaction was observed in one case. In addition, severe adverse effects such as grade 2 pneumonia and grade 4 diarrhea were found in one patient each. In conclusion, although the adverse effects are not negligible, docetaxel therapy is effective against anthracycline-resistant breast cancer.

To measure N-acetyl-beta-D-glucosaminidase (NAG) activity in urine of cows with renal diseases and to correlate values for NAG activity with renal lesions.8 lactating Holstein cows and a Japanese Shorthorn cow, all of which had renal disease.Urine samples were collected, and urinary NAG activity and creatinine concentration were measured. The NAG activity was expressed as units per gram of creatinine (NAG index). Cows were euthanatized, necropsy was performed, and correlations between results for urinary NAG index and histopathologic findings for the kidneys were evaluated.The NAG activity and NAG index in urine samples obtained from cows with interstitial nephritis were high, ranging from 4.2 to 13.6 U/L and 3.5 to 23.0 U/g, respectively. A cow with renal amyloidosis also had high values for urinary NAG activity and NAG index. Histologic examination of the kidneys revealed various kinds of parenchymal lesions. However, urinary NAG index in cows with enzootic bovine leukosis was low.Cows with renal diseases had high urinary NAG indexes that correlated well with their renal lesions, except for cows with enzootic bovine leukosis. Therefore, measurement of NAG index in urine samples has the potential to provide new perspectives on clinical diagnosis of renal disease in cattle.

Three parturient cows in lateral recumbency which were moaning and had tachycardia, arrhythmia and dyspnoea were thoroughly examined. They were hypocalcaemic (0.70-1.27 mmol/litre) and were euthanased within four days, because they failed to respond to calcium treatment. By light microscopy the most characteristic pathological changes in the heart were necrotic changes scattered throughout the myocardium. Electron microscopy revealed abnormalities in the myocytes which were characterised by focal myofibrillar lysis, irregular splitting, streaming and spreading of the Z band and myofibrillar disarray.

From January 1986 to May 1998, 45 lung cancer patients with chest wall invasion (P3) underwent resection (40 male, 5 female), (median age 63.2 yrs (30-79)). Histological types were squamous cell carcinoma in 20, adenocarcinoma in 14, large cell carcinoma in 7, adenosquamous cell carcinoma in 2, and unknown in 2. Operative methods of lung resection were total pneumonectomy in 2, bilobectomy in 3, lobectomy in 38, and partial lung resection in 2. Resection was regarded as complete in 35 and incomplete in 10 patients. Thirty one patients had negative lymph nodes (N0), 9 had peribronchial or hilar lymph node metastases (N1), and 5 had mediastinal lymph node metastases (N2). The extent of tumor invasion to chest wall was P3a (invasion within parietal pleura) in 11, P3b-c (invasion to intercostal muscle) in 16, P3d (invasion to rib) in 18, patients. 5-year survival rate was totally 19.7%. Cisplatin based chemotherapy and concurrent thoracic radiation following surgery (CCRT) was performed in latest nine P3d cases. Partial response was observed in 5 of 9 cases (response rate 56%) and viable tumor cell in the primary site was not seen histologically in 5 of 9 cases. Three year survival rate was 46.9% for CCRT(+) 11.1% for CCRT(-). Acturial 5-year survival rate in P3a-d was 19.76%. P3d cases had poor survival, but CCRT improved prognosis of P3d cases.

We conducted an epidemiological study of survival and disability in stroke in three Japanese communities to seek community strategies for improvement in survival and disability.A total of 297 first-ever strokes were identified between 1988 and 1992 in three rural communities (total population = 47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of daily living by sex, age-group and stroke subtypes. Successful review of computed tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and the data were used for subtype analyses.For all strokes (n = 297) survival rates were 85% for 30 day, 70% for one year, 62% for three year. The rates tended to be lower in women than in men. The rates were lowest in ages less than 60 at thirty day, and in ages 80 and older at the end of the first and third year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage and cortical cerebral infarction had lower survival rates than intracerebral hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80 in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar infarction. The proportion of stroke survivors who need assistance from others in the first and third years tended to be higher in women than in men. The proportion was higher in older patients than in the younger, and higher for intracerebral hemorrhage with ventricular rupture and cortical cerebral infarction than in other subtypes of stroke. From logistic regression analysis, the odds ratio for disability in the first year was 6.55 for ages 80 and older compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage with ventricular rupture, 4.53 for cortical cerebral infarction compared with lacunar infarction. In the third year the odds ratio was significant for ages 70-79, and decreased for intracerebral hemorrhage with ventricular rupture (odds ratio = 2.98), and increased for cortical cerebral infarction (odds ratio = 6.06).Survival and disability in stroke depended on age and stroke subtypes. Even after age adjustment, stroke subtypes with large cerebral involvement had worse prognosis than stroke subtypes. Community-based hypertension control programs are important to prevent any subtypes of stroke. Stroke subtypes as well as age should be taken into account to develop effective care and medical treatments for strokes.

To determine the relationship between preservation of the mastoid mucosa during ear surgery and retraction of the attic or posterior wall of the external auditory canal (EAC) and mastoid aeration after surgery.Retraction of the posterior EAC wall and mastoid aeration were evaluated after surgery in 48 individuals (50 ears) with cholesteatoma, adhesive otitis media, or chronic suppurative otitis media, in whom the posterior bony EAC walls were removed with or without preservation of mucosa and reconstructed with soft tissues alone (EAC skin and temporal fascia) during surgery.Postoperative computed tomography showed that in ears with notable retraction of the posterior EAC wall appearing like an open mastoid cavity, there was no air in the mastoid, whereas in ears with no or only slight retraction there was computed tomographic evidence of mastoid aeration. Second, notable retraction of the posterior EAC wall occurred in a significantly smaller percentage of ears in which at least the epitympanic mucosa had been able to be preserved during surgery than in those that had undergone removal of all mucosa (mastoidectomy).These results indicate that 1) preservation of epitympanic mucosa during surgery is an important factor for prevention of retraction of the posterior EAC wall and for reaeration of the mastoid after surgery, and 2) the intact canal wall technique seems to be indicated whenever at least the epitympanic mucosa can be preserved, and when no mucosa can be preserved the canal wall down procedure seems to be indicated.

To measure urine N-acetyl-beta-D-glucosaminidase (NAG) activity of healthy cattle, using 3 substrates (4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide, sodio-m-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminid e, and p-nitrophenyl-N-acetyl-beta-D-glucosaminide), and to determine the relations between the obtained values and age and sex of cattle.50 healthy lactating Holstein-Friesian cows and 10 healthy Holstein-Friesian steers.Untimed urine samples were collected, and urine NAG activity was measured, using the 3 aforementioned methods. Urine creatinine concentration also was measured, and NAG activity was expressed as units per gram of creatinine (NAG index). Correlations between urine NAG activity and age and sex of cattle were investigated. Furthermore, correlations among data obtained by each of the 3 methods were determined.Urine NAG activity in cows measured by each of the 3 methods was3.0 U/L. Urine NAG activity in steers was significantly higher than that in cows. However, there was no significant difference between the sexes in NAG index. There were no significant differences in mean values of NAG activity and index among cows of various age groups. Individual values of urine NAG activity determined by each method correlated significantly with each other.Urine NAG activity and NAG index of healthy cattle will be useful for determining diagnostic criteria of renal disease in cattle.

Parasagittal surface coil magnetic resonance imaging (MRI) of the internal auditory canal and the inner ear was performed in patients with otoneurological diseases. T2-weighted fast spin-echo sequences, plain and enhanced T1-weighted sequences were used to examine the inner ear and the individual nerves in the internal auditory canal. Normal parasagittal images of the inner ear and the internal auditory canal and 4 patients with otoneurological disorders are presented. Precise location of the acoustic tumor was visualized and postoperative status of the internal auditory canal and the inner ear was assessed by the present method. The cochlear nerve was not identified in a patient with long-standing unilateral deafness. A follow-up study with MRI was performed in a patient with Meniere's disease who underwent endolymphatic-mastoid shunt surgery, showing gradual postoperative shrinkage of the shunted endolymphatic sac. The present method provides a new approach to the assessment of otoneurological disorders.

An auditory-evoked magnetic field was recorded before and during tinnitus remission induced by an intravenous lidocaine injection. One and 4 kHz probe tones were presented monaurally in four tinnitus patients, and the responses were recorded using a 122-channel magnetometer. Three normal volunteers were also examined as controls. In tinnitus patients, the N100 m peak became sharper, while there was no marked change except for slight reduction in amplitude in normal subjects. Tinnitus remission by lidocaine may be related to attenuation of a masking-like effect of tinnitus on the sound-evoked responses.

To study the effects of oral administration of bovine lactoferrin (LF) on intractable stomatitis in feline immunodeficiency virus (FIV)-positive and FIV-negative cats, and phagocytosis of neutrophils in healthy and ill cats, simultaneously.7 ill cats with diagnosis of intractable stomatitis (4 FIV positive and 3 FIV negative) and 7 healthy, FIV-negative cats.LF (40 mg/kg ot body weight) was applied topically to the oral mucosa of cats with intractable stomatitis daily for 14 days and improvement of clinical signs of disease (pain-related response, salivation, appetite, and oral inflammation), expressed by scoring from 1 to 4, were evaluated. Assay of neutrophil phagocytosis was examined before and 2 weeks after starting LF treatment, using nonopsonized hydrophilic polymer particles (2 microns).Oral administration of LF improved intractable stomatitis in all 4 respects. Phagocytic activity of neutrophils increased after LF treatment. This effect was observed in healthy and ill (FIV positive and FIV negative) cats.Oral administration of LF improved intractable stomatitis and concurrently enhanced the host defense system. Topical application of LF to oral mucous membrane is useful as a treatment for intractable stomatitis even in FIV-positive cats.

Infectious diseases caused by methicillin-resistant Staphylococcus aureus, MRSA, and Candida albicans are often serious in compromised hosts. We enumerated MRSA and C. albicans on denture surfaces and in saliva samples from 29 adults. Staphylococcus species, MRSA, and methicillin-resistant Staphylococcus epidermidis, MRSE, were detected on 17, 3, and 1 of the 29 denture surfaces, respectively. C. albicans were detected on 22 denture surfaces. All saliva samples from patients whose dentures carried Staphylococcus species and C. albicans were also found to contain both microorganisms. Adherence of isolated 3H labeled cells of MRSA and C. albicans to resin beads and saliva-coated resin beads was examined. Cells of both microorganisms adhered in significantly higher numbers to saliva-coated resin beads than to resin beads. The hydrophobicity of the MRSA isolated from denture surfaces varied from strain to strain; that of C. albicans strains was moderately high. The zeta potentials of MRSA isolates and of C. albicans isolates determined in KCI buffer were significantly low. The potential of the resin beads decreased after treatment with saliva. Two out of 5 MRSA strains were found to be inhibited in growth by oral Streptococcus, Actinomyces, and gram-negative bacterial strains, suggesting that some oral bacterial species play a role in inhibiting the colonization of Staphylococcus species. No isolates of C. albicans were inhibited in their growth by any of the oral bacteria tested. Isolates of MRSA and C. albicans coaggregated with Porphyromonas gingivalis and Fusobacterium nucleatum strains. Using denture cleaners every night for 2 weeks did not reduce numbers of Staphylococcus species or C. albicans organisms in saliva.

We studied the relationship of serum levels of human hepatocyte growth factor (hHGF) to causative viruses and clinical features in 63 patients at our hospital with serologically diagnosed acute viral hepatitis. Serum levels of hHGF were not correlated with the type of hepatitis virus (A, B, and C) during the acute phase (p0.60) but were correlated with results of the hepaplastin test (p0.01). Furthermore, the difference in serum levels of hHGF between severe (levels on hepaplastin test40%) and nonsevere cases of hepatitis was significant (p0.001), and serum levels of hHGF became normal as levels of alanine aminotransferase decreased. However, serum levels of hHGF in prolonged cases of hepatitis (time until normalization of alanine aminotransferase13 weeks) tended to be slightly lower than in nonprolonged cases (p0.47). These results suggest that serum levels of hHGF are useful to determine the prognoses of patients with severe hepatitis and to estimate the time until liver damage heals.