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Deep learning technology is rapidly advancing, and is now used to solve complex problems. induced pluripotent stem cells (iPSCs) can be used for several purposes such as regenerative medicine, disease modeling study and drug screening. It is inevitable to identify iPSC-derived differentiated cells in microscopy for any use. Here, we used deep learning to establish an automated method to identify endothelial cells derived from iPSCs, without the need for immunostaining or lineage tracing.

Aim: Despite the significant advances in chemotherapy, the prognosis of unresectable or recurrent gastric cancer is still very poor. Given that older adults are likely to have a number of concomitant diseases and an impaired major organ function, cancer chemotherapy in elderly patients requires particular caution. We examined what factors are associated with the overall survival of gastric cancer patients undergoing chemotherapy., Methods: A retrospective chart review of gastric cancer patients receiving oral fluoropyrimidines (N=130) was performed at Nagoya Memorial Hospital over 9 years. The overall survival was calculated from the beginning of chemotherapy until death or the most recent date of follow-up. The Kaplan-Meier method was used to plot survival curves, which were compared using the log-rank test. A multivariate analysis was performed using stepwise Cox proportional hazards models. A comprehensive geriatric assessment was conducted for the elderly patients. The chart review was approved by the ethics committee of Nagoya Memorial Hospital., Results: The objective response rate and overall survival did not differ markedly between the patients < 75 years (N=64) and those ≥ 75 years of age (N=28). The addition of lentinan significantly prolonged the survival of the stage 4 gastric cancer patients. In a multivariate analysis of those ≥ 75 years of age, the only independent prognostic factor for the survival was the functional capacity, as measured by the TMIG Index of Competence., Conclusions: This comprehensive geriatric assessment was useful for predicting the longevity of patients with stage 4 gastric cancer ≥ 75 years of age.

Adult skeletal muscle has its own stem cell population known as satellite cells. After muscle injury, quiescent satellite cells are activated and then proliferate and differentiate into mature skeletal muscle to ensure that muscle function is recovered. In our screen for myocyte differentiation-promoting factors, we noted markedly elevated expression of granulocyte-colony stimulating factor receptor(G-CSFR, encoded by csf3r)in the skeletal muscle developing area. Furthermore, G-CSFR was transiently expressed in regenerating myocytes of adult injured skeletal muscle, and extrinsic G-CSF supported short-term and long-term muscle regeneration in mouse model of skeletal muscle injury.

Microsemi LC-767CRP (LC-767, Horiba, Ltd.) is capable of simultaneous measuring of complete blood count (CBC) including 3-part differentials (3-part Diff.) of white blood cells (WBC) and C-reactive protein (CRP) in 4 minutes. Data obtained using LC-767 were intra-assay-reproducible (n = 10, CV = 0.6-4.0% for CBC, 0.6-2.5% for 3-part Diff. and 2.8-7.7% for CRP). They also showed the good linearity, no definite carry-over and the excellent correlations with routine instruments in our institution. Concerning CRP, the minimal detectable concentration revealed < 0.1 mg/dL, and prozone was observed in the sample containing > 30 mg/dL of CRP. LC-767 showed better correlation with a routine instrument in monocyte percentage than LC-667, probably due to modification of the hemolysis solution ratio and diluent temperature. In conclusion, LC-767 provided accurate CBC and CRP results, and showed improvement in CRP linearity and monocyte percentage compared with LC-667. LC-767, which is equipped with a bar-code reader with easy accessibility to electronic medical record, is suitable as the next-generation point of care testing model in the era of information and network-oriented medicine.

Severe oral mucositis induced by cancer chemotherapy can cause intolerable pain and increase the risk of systemic infections, necessitating dose reduction and discontinuation of antineoplastic agents. Moreover, this adverse effect may have an impact on patient nutrition and quality of life. An effective and prophylactic intervention should be useful for alleviating this complication. Because Nagoya Memorial Hospital has neither a dentistry nor an oral surgery department, we collaborated with dental associations near the hospital. First, we performed a questionnaire survey on the present status of the members of the local dental associations. The survey showed that 86% of the community dentists were interested in communicating with our hospital. In addition, they agreed to provide us with information on their specialty and status of amenities. In discussion with the community dentists, we decided on fax-based communication for collaboration to improve the quality of oral management in cancer patients. Three seminar series were conducted to share updated information on cancer treatment and enhance communication between the medical doctors and the dentists. Our hospital has registered 129 community dentists and enrolled 81 cancer patients in this medical and dental cooperation initiative.

We collected the different volumes of venous blood(60 microL, 125 microL, 250 microL and 500 microL) into micro sample cups from respective volunteer to compare complete blood count (CBC) among 4 sample volumes, and found that 60 microL of sample volume seemed enough for CBC measurement using Microsemi LC-667 CRP (Horiba Co.). Subsequently, we measured CBC using 60 microL of peripheral blood after combining one of the 3 capillary tubes (heparin coated, EDTA coated and plain) with either EDTA coated or plain micro sample cups to examine the effect of anticoagulants contained into these commercially available maneuvers for capillary blood sampling. When we used the plain micro sample cup, platelet aggregation and false increase of white blood cell(WBC) count were observed irrespective to the combination of capillary tubes. We also tried whether commercially recommended volume (250 microL) of sample could be obtained by either fingertip or earlobe puncture from volunteers, and found that 7 of 16 fingertip and only 1 earlobe punctures could achieve sufficient volume. Whereas, at least 60 microL of sample were available more than 80% of volunteers by both methods, and CBC data obtained from these lesser samples obtained by fingertip puncture showed no statistically significant differences when compared with those of conventional venous samples (2 mL). From these findings, we concluded that at least 60 microL of capillary blood obtained from fingertip then collected into EDTA coated micro sample cup was enough to measure CBC using Microsemi LC-667 CRP.

Rebamipide, a cytoprotective agent, has been suspected to attenuate oral mucositis through anti-inflammatory potentials and induction of endogenous prostaglandin synthesis. This prospective study was designed to assess the clinical efficacy of rebamipide gargle against oral mucositis, which is induced by fluoropyrimidines in patients with stomach and colorectal cancer. We first conducted a pilot study on gargle flavors, because the solution in this agent has a strong and bitter after taste. Nine kinds of flavors were prepared, and six characteristics were evaluated by ten volunteers: sourness, bitterness, sweetness, remain, after taste, and hard to drink. We determined the contents of rebamipide using HPLC, which showed stability in an acidic condition. Finally, we decided that 100% Pokka Lemon should be used as the flavor of the rebamipide solution. A clinical study was then started to compare the preventive effects rebamipide gargle and placebo have on stomatitis, quality of life (QOL), and the therapeutic effects of chemotherapy.

We examined the basic performance of "Microsemi LC-667CRP" (LC-667, HORIBA, Ltd.) which has been newly developed as compact laboratory instrument capable of simultaneous measuring of complete blood count (CBC) including 3-part differentials of white blood cells (WBC) and C-reactive protein (CRP) using whole blood anticoagulated with ethylenediaminetetraacetic acid (EDTA). We found that CBC and CRP were intra-assay-reproducible (n = 10, CVs < 5.0%). They also showed the good linearity and no definite carry-over. Concerning the WBC differentials, percentage of monocytes (MON%) showed less intra-assay reproducibility compared with those of granulocytes (GRA%) and lymphocytes (LYM%). We also evaluated the correlation of values obtained by LC-667 and routinely used instruments in our institute. Concerning the CBC and WBC differentials, excellent correlations were found between LC-667CRP and XE-2100 (SYSMEX CORPORATION) except MON%. In addition, whole blood CRP as well as plasma and serum CRP measured by LC-667 also showed the good correlations with serum CRP measured by 7600 (Hitachi High Technologies Corporation). From these findings, LC-667 was revealed to produce the clinically reliable data using only 18 microL of sample volume in 4 minutes. Point of care testing (POCT) has been developed as the laboratory system performed at or near the site of patient to reduce the turn around time. Therefore, LC-667 seemed useful in POCT for the patients with acute inflammatory disease especially in pediatrics.

The prevalence of depression has been reported to be higher in cancer patients, especially those of advanced stage, compared to normal controls. However, depression is often under-recognized in clinical oncology settings. And this psychological problem is not routinely assessed even in patients with inoperable metastatic cancer who often have psychological disorders. Psychological distress including depression, is affected by physical, psychosocial, and clinical factors. In order to detect psychiatric problems at the early stage, we assessed the mental conditions of 47 inpatients with metastatic gastric and colorectal cancerusing the Japanese version of Zung's Self Rating Depression Scale(SDS)and analyzed the relationships between these factors and SDS scores. While SDS scores of our patients did not differ according to their gender, age, performance status (PS), ortypes of patients' character, they were significantly higher in Group B(cancer patients with palliative care alone), compared to Group A(those receiving chemotherapy)(p<0. 001). As the disease in the four identical patients progressed to the terminal stage, their scores were significantly increased, respectively(p<0. 05). These results suggest that psychological intervention should be more critical for terminally ill patients without any indication of chemotherapy.

Methicillin-resistant Staphylococcus aureus (MRSA), a well-known causative multidrug-resistant pathogen responsible for nosocomial and community-acquired infections, particularly in blood stream infection, often proves difficult and expensive to treat. Despite the need for rapid, accurate MRSA detection for treatment and infection control, conventional testing including culture, have sensitivity and turn-around time (TAT) problems. We evaluated BD GeneOhm MRSA Detection Kit rapid detection performance directly from positive blood culture using real-time PCR. The kit recognizes, a specific part of the staphylococcal cassette chromosome mec (SCCmec) gene, not a mecA gene. Compared to conventional culture in 138 samples with gram stains showing gram-positive cocci (GPC) clusters, the kit's sensitivity was 100%, specificity 97.3%, positive predictive value 90% and negative predictive value 100%. Three of the 27 MSSA isolates found was false-positive, indicating that the kit detected SCCmec/orfX region sequences lacking mecA. Coupled with direct tube coagulase testing to rapidly differentiate MRSA from methicillin-susceptible S. aureus (MSSA) could provide optimum treatment through appropriate antibiotic use. The kit thus appears to be useful in rapidly diagnosing MRSA from blood culture, improving the prognosis and reducing medical cost.

The microbiology laboratory of our university hospital aims to provide accurate and rapid microbiological results and useful information for healthcare workers involved in both the treatment of infectious diseases and infection control. For this purpose, we have been running a microbiology laboratory open 365 days a year since 2005. Before starting this laboratory, we formulated both a precise procedural manual and educational program to increase the number of microbiological technologists from 4 to 8 persons and improve their skills. Moreover, we reviewed the reporting system. As a result, we could report positive blood cultures up to 1.4 days earlier than previously possible, and significantly improved the prognosis of MRSA bacteremia patients by the early treatment of anti-MRSA antimicrobials within 48 hours after positive blood culture. In addition, the rate of MRSA/Staphylococcus aureus decreased to 35.8%. It is essential for the treatment of infectious diseases and infection control to accept only appropriate specimens and report the results rapidly and accurately.

Sensory information of various modalities is integrated in the amygdala, where the emotional information is subsequently generated. The resultant emotional information is then sent to the widespread cortical and subcortical areas. This output to the cortex is directed to the prefrontal cortex and the medial temporal lobe, a memory system, and modulates the higher cortical functions as well as the learning and memory. The output to the subcortical structures is directed to the hypothalamus and brainstem, and the autonomic, hormonal and behavioral responses are elicited as the expression of the emotional response. Taking into account the above mentioned emotional system, the examination of somatotopic representation in the amygdala and related structures is very difficult. However, recent studies have elucidated the somatotopic representation of the amygdalar output system in the brain of rhesus monkey. The lateral basal nucleus of the monkey amygdala was proved to project to the cingulate motor cortex M3, and the target cortical neurons project somatotopically to the facial nucleus in the brain stem. Accordingly, the amygdala-cingulate cortex-facial nucleus system is involved in the emotional expression by the facial movement. This system might be involved in the pathophysiology of temporal lobe epilepsy and the facial expression of patients with Parkinson disease. Furthermore, the amygdala-cingulate cortex projection develops from adolescence to adulthood and reflects the emotional maturation and the development of social adaptation.

Methicillin-resistant Staphylococcus aureus (MRSA) is well known to be a causative pathogen of skin and soft tissue or blood stream infections, and also to be a nosocomial drug-resistant bacteria in healthcare settings. Although a rapid and accurate detection of MRSA is indispensable for infection control, the conventional tests including culture method have some problems of sensitivity, procedure time, and so on. We evaluated the performance of the rapid detection assay of MRSA (BD GeneOhm MRSA Detection Kit) directly from specimens by a real-time PCR. The principle of this kit is characterized by recognizing not a mecA gene, but a specific part of SCCmec gene. Limits of detection of this method was 810 CFU/mL. Compared to the results of mecA PCR assay in 105 clinically isolated samples, the sensitivity, specificity, positive predictive value and negative predictive value were 100%, 97.4%, 98.5% and 100%, respectively. One of the 38 mecA negative isolates was found to be a positive result, this finding suggested that this method detect sequences of SCCmec/orfX region lacking of mecA. Because of the rapid turn-around time and the excellent negative predictive value, this method appears to be a useful tool for rapid diagnosis of MRSA.

The goal of our microbiology laboratory is to provide an accurate microbiological result and a useful information for every healthcare workers (HCWs). For this purpose, we were trying to do several activities, such as improving the work-flow of microbiology testings, starting 365-day-open microbiology tests, providing some training courses of microbiology and sending many useful informations about infectious diseases and infection control. Before these activities, we needed another 5 microbiology technicians beside 3 technicians and had started the program to educate them. We have successfully finished it and enabled all plans begin in April, 2005. Since then we are open for 365 days and also sending HCWs many newsletters for performing effective microbiological testings via the intra-network system and having lectures for both doctors and nurses, especially for new resident doctors at the orientation. We had also the training course for certified infection control nurses and accepted two technicians from Africa, who came to study a basic microbiology via JICA. These activities have enabled every technician not only to report and analyze microbiological test result effectively but also to improve writing and presentation skills. Through these activities all technicians have realized that accurate and rapid information from a microbiology laboratory is a key to treat patients with infectious diseases and improve their prognosis. It is suggested that skill-up of technicians lead to report an accurate result in microbiology and at the same time improve the attitude for their job.

Oxaliplatin (L-OHP) has been established as a key drug for advanced colorectal cancer, and combination therapy with 5-FU/Leucovorin (LV)(FOLFOX regimen) is commonly used in Europe and the US. A phase I study of modified (m) FOLFOX 6 therapy was conducted to determine the recommended dose (RD) of 5-FU infused for 46 hours. Inclusion criteria were unresectable advanced colorectal cancer,measurable lesions, performance status (PS; ECOG) 0-2, age 20-75 years, and adequate organ functions. L-OHP and l-LV was administered over 2 hours and followed by bolus injection and continuous infusion of 5-FU for 46 hours every 2 weeks. Two cycles of mFOLFOX 6 therapy were performed. Doses of L-OHP, l-LV, and bolus injection of 5-FU were fixed at 85 mg/m(2), 200 mg/m(2), and 400 mg/m(2), respectively. The dose of continuous infused 5-FU was escalated from 1,600 mg/m(2), (level 1), 2,000 mg/m(2), (level 2), 2,400 mg/m(2), (level 3), and 2,800 mg/m(2), (level 4). RD was determined in a dose escalation manner, and safety was evaluated according to NCI-CTC Ver 2.0. A total of 13 patients were enrolled. Male/female=7/6, PS 0/1/2=2/4/7, mean age 64 years (range 55-75). Thrombocytopenia was not observed, and grade 2 of neutropenia and peripheral neuropathy was observed in 4 and 6 out of 13 patients. No dose-limiting toxicity (DLT) was observed at level 1 (n=3), 2 (n=4), and 3 (n=4), but at level 4 (n=2), 2 patients experienced DLT; grade 3 easy fatigue and anorexia required treatment delay over 7 days. Level 3 was therefore determined as RD. A phase II study is ongoing to evaluate the efficacy of mFOLFOX 6 therapy.

In an attempt to assist the clinical physicians at the outpatient clinics in Kyoto Prefectural University Hospital, we opened the laboratory consultation office in January 2005. This office is staffed by one medical technologist from 9 am to 4 pm on weekdays. The technologist shows the laboratory examination result of respective patient, and then explains the significance of reference interval using the personal computer. Additional explanation such about the mechanism of abnormal result or the general interpretation of diagnostic tests is also performed according to the patients' demands. Whereas, as the major premise, the consulting technologist never comments to the patients on the clinical relevance between their laboratory results and their own disease courses. Until March 2006, 1,430 outpatients have visited the office in total, resulting in 6.1 patients/day as mean value. Almost all of the visitors (97.9%) wanted to listen to the meaning of liver function test, which was followed by renal function test (95.3%). Consulting time required for respective patient has been quite variable from 10 to 120 minutes (30 minutes/patient as mean). The questionnaire survey after consultation revealed that all of the visitors felt satisfactory for consultation, and wanted to revisit to our laboratory consultation office. We believe that the laboratory consultation office contributes as a new medical service of our hospital to outpatients.

Acute myocardial infarction, as a result of coronary malperfusion caused by acute type A aortic dissection, has been identified as one of significant factors relating to operative mortality. This complication could be diagnosed with a combination of electrocardiography and echocardiography in acute phase. However, the indication of coronary angiography and/or intervention has been controversial as it is time-consuming and renders additional stress to a critical patient requiring an emergency operation. We report a case of myocardial infarction successfully treated with percutaneous transluminal coronary angioplasty (PTCA) at first, after that, recognition of dissection of aorta necessitated subsequent surgical therapy. In this particular case, coronary intervention in advance proved to be mandatory.

Aneurysm of the ductus arteriosus in the adults is rare. A 60-year-old male with no symptoms was admitted to our hospital. 3 D-CT scans and aortograms indicated a diagnosis of aneurysm of the ductus arteriosus. Operation was done through median sternotomy with the aid of partial cardiopulmonary bypass. The saccular aneurysm was located between the aortic isthmus and the left pulmonary artery. The aneurysm was resected and closed a patch. The post-operative course was uneventful.

We examined a disparity in D-arabinitol values between two commercial assay kits, LABOFIT and ARABINITEC-AUTO. The determined values by the former were increased by 26%(y = 0.2643x) because of concomitant D-mannitol, whereas those by our newly developed ARABINITEC-AUTO was increased only by 2%(y = 0.0242x). Of 109 samples, 5 samples were found to contain more than 100 mumol/l of D-mannitol. A clear relation(r = 0.89) was noted between the degree of disparity between measurements by the two methods and D-mannitol concentrations in samples. Thus, we have proved that the disparity is mainly caused by D-mannitol.

The retrospective study was aimed at assessing the usefulness of the application of the criteria of SIRS for identifying a subset of patients with higher mortality in 22 cases (21 patients) of liver cirrhosis with upper gastrointestinal hemorrhage (GIH) and 16 cases (14 patients) of liver cirrhosis with hepatocellular carcinoma with upper GIH. The following results were obtained; (1) The incidence of SIRS on upper GIH was 66%. (2) The mortality rate in patients with SIRS on GIH was significantly higher than in patients with non-SIRS on GIH in 60 days after GIH was significantly higher than in patients with non-SIRS on GIH in 60 days after GIH (50% vs. 8%; p < 0.01). (3) The rate of patients who met four criteria of SIRS on GIH or during admission and of patients whose durations of SIRS was over 5 days was significantly higher in the died patients with SIRS on GIH than in the survived patients with SIRS on GIH (67% vs. 0%; p < 0.01, 67% vs. 0%; p < 0.01, respectively). These results suggested that the application of the criteria of SIRS was useful for identifying a subset of patients with higher mortality in chronic liver disease with GIH.

Although the inhibition of nitric oxide (NO) synthesis is known to induce systemic hypertension, the underlying mechanisms mediating this type of hypertension are incompletely understood. In the present study we investigated the influence of sodium intake on the pressor effect of long-term administration of the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 16 mg/dl in drinking fluid for 8 weeks), in conscious Sprague-Dawley rats. Urinary excretion rates of catecholamine during NO synthesis inhibition were also examined. Long-term administration of L-NAME produced a sustained elevation in tail-cuff pressure without altering urine flow, or sodium excretion rate. L-NAME-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites, NO2- and NO3-, and was aggravated when rats drank 0.9% saline in place of tap water. Thus, inhibition of NO synthesis resulted in a rightward shift of the pressure natriuresis relationship and a significant decrease in the slope of this relationship. Urinary excretion of epinephrine and norepinephrine, but not that of dopamine, in L-NAME-treated rats significantly increased within the first week of the study when compared with those observed in control rats. A natriuretic index of the sympathetic nervous system, the ratio of dopamine to norepinephrine excretion, was significantly less in L-NAME-treated rats than in control rats. After 8-week treatment with L-NAME, renal morphologic evaluation revealed significant narrowing and obliteration of the arterioles. L-arginine (2 g/dl in drinking fluid) completely reversed the elevation of blood pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment after 3 weeks of concomitant administration. These results suggest that the inhibition of chronic NO synthesis produces sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

In spite of continuing development in transfusion medicine, homologous transfusion accompanies risks and problems, such as viral infection, alloimmunization, transfusion associated GVHD and immunosuppressive reactions. To avoid these risks of homologous transfusion, autologous blood transfusion has been introduced as the safest blood transfusion. Here, methods of predeposit autologous blood transfusion and its clinical usefulness are described. There are two methods for predeposit autologous transfusion; Liquid preservation and frozen preservation. The merit of the former is easy and economical, but 3 units (1200 ml) will be maximum volume to collect in 3 weeks before surgery. While frozen preservation, patient can predeposit the necessary amount of blood without affecting their preoperative condition, as we can set the intervals of blood collections more than 3 weeks, and blood can be stored up to 10 years. However this method requires equipment and cost more.

We have performed bronchial artery embolization (BAE) in patients with hemoptysis using a superselective catheter system and a permanent-emboli coil. We performed an investigation because major complications were observed. Of a total of 57 BAE using this system, 7 cases of major complications as detachment of the large vessel were found. Although BAE using this system is effective because permanent emboli can be selectively in-dwelled in abnormally developing vessels, detachment of vessels were developed in 7 cases. They are found more frequently for embolization of the left bronchial artery and full attention should be paid to this phenomenon when performing this surgery.

Mitral regurgitation caused by papillary muscle rupture after acute myocardial infarction has poor prognosis, and it is the usual course for such cases in cardiogenic shock to be performed early mitral valve replacement. However, we recently experienced a case of successful scheduled mitral valve replacement for mitral regurgitation caused by rupture of the posterior papillary muscle after acute inferior myocardial infarction. The patient was a 63-year-old woman who admitted to a hospital with back pain and dyspnea and was diagnosed as pulmonary edema due to mitral regurgitation after acute myocardial infarction. She was treated with dopamine and diuretic agents effectively, but not weaned from these drugs. Then, she was transferred to our hospital. At the admission, she was in the NYHA class II due to mitral regurgitation and inferior myocardial infarction with papillary muscle rupture revealed by transesophageal echocardiography. Cardiac catheterization demonstrated total occlusion of the proximal right coronary artery (segment #2) and mitral regurgitation in Sellers III. The patient underwent a successful scheduled mitral valve replacement with SJM 27M concomitant with coronary artery bypass grafting 47 days after the onset of acute mitral regurgitation. There are few reports that successful surgical treatment for papillary muscle rupture was done more than 4 weeks after the onset of mitral regurgitation in Japan.

A 64-year-old woman complaining of severe lumbar pain was admitted to our hospital because of the finding of pre-existing mitral valve regurgitation on examination. Laboratory data revealed the proximal type of renal tubular acidosis, renal glucosuria, phosphaturia, generalized aminoaciduria and low-molecular-weight proteinuria. She did not have any cause of these tubular dysfunctions, and was diagnosed as adult idiopathic Fanconi syndrome. Dual energy X-ray absorptiometry (DEXA) revealed a reduction of bone mineral density in the lumbar spine to about 65% of the age-and gender-matched control value. Alkali agents (sodium citrate and potassium citrate), calcium lactate and 1 alpha-hydroxyvitamin D3 were administered. Bone mineral density estimated with DEXA improved with a reduction of serum alkali phosphate and disappearance of lumbar pain, and was restored to 82% of the age-and gender-matched control value after about 30 months of treatment. DEXA is useful for the long-term follow-up study of bone mineral density in a patient with Fanconi syndrome.

We examined the effects of histamine H2-receptor antagonists on the phosphorus binding ability of phosphate binders. Serum calcium, phosphorus, ALP, PTH and arterial blood pH and bicarbonate were measured during treatment with histamine H2-receptor antagonists accompanied by calcium carbonate in sixteen patients undergoing maintenance hemodialysis. Seven patients receiving histamine H2-receptor antagonists without calcium carbonate were selected as controls. In the sixteen patients receiving calcium carbonate, serum calcium, ALP, PTH and arterial blood pH and bicarbonate were not significantly altered during treatment with histamine H2-receptor antagonists, but serum phosphorus levels increased significantly after four (5.6 +/- 1.1 mg/dl) and eight weeks (5.9 +/- 0.8 mg/dl) of treatment as compared with that before treatment (4.8 +/- 1.2 mg/dl). Furthermore, serum phosphorus levels decreased significantly eight weeks after the discontinuation of treatment with histamine H2-receptor antagonists. In the seven control patients there were no statistical differences in serum calcium and phosphorus levels measured before and after treatment with histamine H2-receptor antagonists. In seven other patients receiving histamine H2-receptor antagonists with calcium carbonate, calcium carbonate was replaced with calcium lactate as the phosphate binder after four weeks of treatment with histamine H2-receptor antagonists. With the 4-week administration of histamine H2-receptor antagonists accompanied by calcium carbonate, the serum phosphorus level increased, similarly to that of the first study (from 6.3 +/- 0.9 to 7.1 +/- 0.5 mg/dl). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly (6.3 +/- 0.2 and 6.0 +/- 0.9 mg/dl after four and eight weeks, respectively, despite continued administration of histamine H2-receptor antagonists). These results suggest that histamine H2-receptor antagonists significantly affect the phosphorus binding ability of calcium carbonate, but not of calcium lactate. Although the exact mechanism remains obscure, one possible explanation may be related to the rise in pH of the gastric juice. Careful observation of changes in the serum phosphorus level is required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphate binder in such hemodialysis patients.

Monosodium 2-[(R*s,9S*)-(4-methoxy-6,7,8, 9-tetrahydro-5H-cyclohepta-[b]pyridin-9-yl)sulfinyl]-1H-benzimidazole (3A), a novel antiulcer agent previously reported by us, was found to be easily decomposed in weakly acidic solutions. In order to improve the stability of the parent compound, 3A, the preparation of 1-substituted benzimidazoles (4A) was attempted. However, the inhibitory effect of 4A against gastric acid secretion was less potent than that of 3A. Then 3A was solvated by EtOH or H2O to afford 5A or 6A, respectively. On the other hand, an another diastereoisomer, (R*s,9R*)-3B, was not solvated by EtOH or H2O under the same conditions. The thus obtained solvates (5A, 6A) are much more stable than that of 3A. The antiulcer activities of 5A and 6A were found to be similar to that of the parent compound (3A). Consequently, 6A was selected as an antiulcer agent for the development.

An immortalized neural cell line V1 was transplanted stereotaxically into the cerebellum and hippocampus of developing and adult mice, and the mode of migration, differentiation and arrangement of the grafted cells were examined by labeling the grafted cells with DiI (1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine perchlorate) and immunohistochemical staining. This cell line was established by transduction of the temperature-sensitive allele tsA58 of SV40 large T antigen oncogene into mouse hypothalamic cells. Grafted cells did not show any tumorigenicity for a long time. Some of the cells grafted into the neonatal cerebellum and hippocampus were arranged along the host cortical layer and showed neuronal or glial differentiation according to the grafted site. The cells grafted into adult cerebellum also showed migration and arrangement along the host cortical layer as well as morphological differentiation into glial cells in a manner similar to that of transplantation to the neonate. On the other hand, the cells grafted into the adult hippocampus made only clusters without forming an organized arrangement. These findings suggest that the grafted cells are integrated into the developmental processes of the host brain, and the mode of differentiation and arrangement of the grafted cells depends on the microenvironment of the different developmental stages of the host brain. The involvement of host blood vessels and astroglial framework in the migration and arrangement of the grafted cells was also suggested. Furthermore, these findings suggest the plasticity of the host brain in response to the grafted cells and the possibility of reconstructing the host brain with this multipotential neural cell line.

Various cell adhesion molecules and neurotrophic factors are involved in cell migration, axonal elongation and synaptogenesis during the development of neural networks. The developmental mechanisms of neural networks were investigated in the mouse cerebellar system in relation to the neuron-glia interactions and the expression of cell adhesion molecules. Radial migration of Purkinje cells in the cerebellar primordium is guided by contact with radial glial processes, and expression of the neuron-glia cell adhesion molecule tenascin is involved in this process. Purkinje cell migration is obstructed in the reeler mutant mouse, and the disorganized arrangement of radial glial processes is considered to be responsible for this defect. Pontine nuclei and inferior olivary nuclei constitute the cerebellar afferent system, and these neurons are generated from the rhombic lip which is originated from the alar plate of the metencephalon in common with the cerebellar primordium. Pontine nuclei migrate tangentially from the rhombic lip under the pia mater, and the binding sites for peanut lectin are specifically expressed on the migratory route. Thy-1 molecule, a member of the immunoglobulin superfamily is expressed transiently in the synaptogenesis between the cerebellar afferent fibers and their target neurons in the developing cerebellar cortex. The homophilic binding activity of this molecule is considered to be involved in the recognition between presynaptic terminals and postsynaptic structures.

The patient was a 47-year-old female who had undergone hypophysectomy due to Cushing's syndrome when 46 years old. In April 1992, about 1 month after the operation, chest CT-scan revealed a lesion of 8 x 8 mm in size in the right upper lobe. A high value of serum ACTH was obtained from the A3b wedge blood by cardiac catheterization. She was operated on suspicion of ACTH releasing lung tumor. During the operation, it was histologically diagnosed as lung carcinoid by a frozen section of the lesion. In addition, ACTH of the blood obtained from the right superior pulmonary vein was as high as 37,300 pg/ml, but that in the right main pulmonary artery or the radial artery was 850-970 pg/ml. Right upper lobectomy with dissection of mediastinal lymph nodes was so performed. Post-operative value of serum ACTH was significantly decreased. She was in good course, and is still asymptomatic 8 months after the operation.

Since April 1989, we have been using autologous blood donation in order to avoid homologous blood transfusion as much as possible. To determine the factors which influence the necessity for homologous blood transfusion as well as autologous blood donation. Of them 77.6% (group 1) required autologous blood only, but others needed homologous blood transfusion as well as autologous blood. Using an invert analysis, preoperative factors that showed significant differences were age, body weight, number of autologous blood donations, amount of donated autologous blood, preoperative Hb and Ht. Among operative factors, aortic cross clamping time, cardiopulmonary bypass time, amount of concentrated blood from CPB circuit, amount of transfused autologous blood and amount of drainage demonstrated significant differences between groups. Univariately significant factors were studied by multivariate discriminant analysis. Total amount of drainage proved to be the best contributor of non-homologous blood transfusion surgery, followed by preoperative Hb, body weight, amount of concentrated blood from CPB circuit and amount of donated autologous blood in order of contribution Understanding these factors, homologous blood transfusion requirement may be greatly reduced. This is thought to be the largest series of autologous blood donation in Japan.

Postoperative right ventricular function was evaluated serially by thermodilution techniques (REF-1, Edwards Laboratories) in patients who underwent aorto-coronary bypass surgery with uneventful postoperative recovery. The patients were divided into three groups depending on the location of critical stenosis of the right coronary artery. The stenosis was proximal to the right ventricular branch in group I (n = 13), distal to the right ventricular branch but proximal to the acute marginal branch in group II (n = 13) and distal to the acute marginal branch in group III (n = 11). Control (n = 20) consisted of the patients with no significant stenosis of the right coronary artery. Cardiac index, intracardiac pressures and amount of cathecolamin used during postoperative course showed no significant differences among the groups including control. With the use of cathecolamine after surgery, right ventricular ejection fraction (RVEF) rose and right ventricular volumes (RVEDV and RVESV) decreased in all the groups except for group I. These values in group I were unchanged. Thus, there were significant differences in RVEF, RVEDV and RVESV between group I and control. These results mean that right ventricular dysfunction may remain even long after occlusion of the proximal right coronary artery.

Dietary Ca is an important modulator of arterial blood pressure in humans and rats. Since the kidney plays a key role in the pathogenesis of hypertension, the effect of a low Ca diet (0.01%Ca) on blood pressure and pressure natriuresis response was studied in Sprague-Dawley rats. In addition, a possible role of the renin-angiotensin system in the development of hypertension and an altered pressure natriuresis response resulting from low dietary Ca intake was investigated. In the low Ca diet group, systolic blood pressure determined by the tail-cuff method was significantly higher than in the normal Ca diet group (1.1%Ca) 1 week after the diet (113.0 +/- 7.1 vs. 105.0 +/- 9.5 mmHg, p < 0.05). Furthermore, low dietary Ca treatment significantly inhibited the water and sodium excretory responses to acute elevation of renal perfusion pressure. Treatment with an inhibitor of angiotensin converting enzyme, captopril (30 mg/kg/day), attenuated both the development of hypertension and the reduced pressure natriuresis response observed in Ca-deficient rats. Although plasma renin activity was not different between the low and normal Ca diet groups after the 2-week dietary regimen, the pressor response to angiotensin II injection was significantly greater in the low Ca diet group. These results indicate a possible involvement of the renin-angiotensin system in the development of hypertension and the inhibitory effects of the pressure natriuresis response caused by low dietary Ca intake, via enhanced sensitivity to angiotensin II.

From Oct. 1987 to Apr. 1992, coronary artery bypass grafting (CABG) was performed in 33 patients who had a history of previous cerebral infarction. Two patients associated with severe carotid disease underwent combined carotid endarterectomy and CABG. There have been no perioperative cerebral complications. On the other hand, in 199 patients without a history of previous cerebral infarction, three patients (1.5%) suffered perioperative cerebral infarction. In two of these patients, the etiology was felt to be calcific and atherosclerotic debris from the ascending aorta and in the remaining patient, to be arterial hypotension during cardiopulmonary bypass. In conclusion, no direct relationship has been found between previous cerebral infarction and incidence of perioperative cerebral complications.

The importance of the distribution of intrarenal blood flow in the regulation of various renal functions, such as urine concentration and sodium excretion, has been well recognized. However, there have been no reliable methods to measure local flow in the kidney in vivo. The present study demonstrated the usefulness of contrast ultrasonography combined with injection of sonicated 5% albumin for assessment of the distribution of renal cortical blood flow in eleven mongrel dogs. The left kidney was displayed by tomographic echography, and microbubbles of sonicated albumin were injected into the abdominal aorta above the left renal artery. Video density time curves were generated and fitted to a time-intensity curve. Intrarenal infusion of acetylcholine (4.0 micrograms/kg/min) increased renal blood flow (RBF) from 2.5 +/- 0.3 to 4.6 +/- 1.0 ml/min/g kwt (p < 0.01), and norepinephrine (0.5 microgram/kg/min) decreased RBF from 2.5 +/- 0.3 to 1.2 +/- 0.5 ml/min/g kwt (p < 0.01). There were significant positive correlations between percent change in RBF and peak intensity and area under the curve, which were calculated with a time-intensity curve. Furthermore, the inner/outer renal cortex ratio of peak intensity significantly increased during acetylcholine infusion (0.72 +/- 0.11 vs 0.86 +/- 0.09; p < 0.01), whereas no significant change was observed during norepinephrine infusion. These results suggest that renal contrast ultrasonography may be useful for real-time assessment of the distribution of renal cortical blood flow in vivo.

To determine the role of endothelium-derived nitric oxide (EDNO) in mediating the natriuretic response to acute extracellular volume expansion (ECVE) with isotonic saline (3% of body weight per hour), the diuretic and natriuretic responses to ECVE were studied in anesthetized Sprague-Dawley rats during the intravenous infusion of an EDNO synthesis inhibitor, NW-nitro-L-arginine methyl ester (L-NAME). Intravenous infusion of L-NAME at the dose of 5 micrograms/kg/min significantly inhibited the diuresis and natriuresis in response to ECVE by 58% and 67%, without altering arterial pressure, effective renal plasma flow, glomerular filtration rate and basal excretory function. This inhibitory effect of L-NAME on the diuretic and natriuretic responses to ECVE was attenuated by the infusion of the EDNO synthesis precursor, L-arginine (1mg/kg/min), but not by D-arginine. In addition, pretreatment with 0.3 mg/kg of the angiotensin II receptor antagonist, L-158,809, normalized the diuretic and natriuretic responses to ECVE in L-NAME-treated rats, suggesting an angiotensin-II-dependency of the reduced renal excretory response to ECVE during EDNO synthesis inhibition. Neither L-arginine nor L-158,809 alone significantly altered the renal excretory response to ECVE compared with vehicle-treated control rats. These results suggest that EDNO might play an important role in the regulation of sodium and water excretion during ECVE, and indicate a possible interaction between EDNO and angiotensin II on the renal excretory function.

It has been described that a rapid worsening in renal function is uncommon in the elderly patient with lupus nephritis. We report a case of a 76-year-old man with rapidly progressive lupus nephritis. On admission, laboratory studies revealed massive proteinuria, telescoped urine, thrombocytopenia and azotemia. Hypocomplementemia and the positive presence of anti-DNA antibody and lupus anticoagulant were also noted. Because of a rapid deterioration of renal function, he was started on a regimen of steroid pulse therapy and plasmapheresis. Serum levels of complements gradually increased after initiation of these treatments, and three weeks later, improvements of renal function and nephrotic syndrome were obtained. A renal biopsy specimen taken five months after admission showed diffuse membranous glomerulonephritis. In addition, we examined renal arterial blood flow with Doppler ultrasound, and significant improvements of the velocity and pulsatility were observed during recovery of the renal function.

Infarction of the right ventricle occurs with acute inferior myocardial infarction and results in a unique syndrome, characterized by distended neck vein, hypotension, heart block and spontaneous recovery in right ventricular function with time. We performed aorto-coronary surgery for four patients with right ventricular infarction. Three of them had emergency surgery. Surgical indications were refractory angina pectoris in two and cardiogenic shock in one. Postoperative courses in these patients were stormy and two died. Low output syndrome rarely improved with volume load alone and required inotropic and vasoactive drugs. Antiarrhythmic therapy including artificial pacing was especially important in keeping IABP support effectively. Remaining case, on the other hand, were conservatively supported by IABP and drug therapy through the first two weeks after infarction and then operation was done for unstable angina. Postoperative course in this patient was uneventful. In conclusion, delayed surgical intervention may be considered in patients with right ventricular infarction if their hemodynamic condition in the early stage of infarction can be conservatively managed.

A 50-year-old woman was admitted to the intensive care unit 40 min after the onset of severe chest and back pain with consciousness loss. Emergency computed tomography and aortography demonstrated an acute type A dissection without opacification of the false lumen. The patient was initially treated with antihypertensive drugs. Recurrent back pain and bilateral pleural effusion appeared 3 days after onset of the pain. Both the right radial and carotid pulses were reduced. Emergent operation was performed when computed tomography and aortography repeated 5 days after onset of the pain demonstrated the intimal flap in the ascending aorta with the opacified false lumen. The site of intimal tear in the proximal arch was resected and a 26 mm Dacron graft was inserted during deep hypothermia and circulatory arrest. The postoperative course was uneventful.

It is considered that cell adhesion molecules play important roles in the host-graft interaction during the reconstruction of the injured nervous system by neural transplantation. In this article, we report the expression of such molecules during the migration and differentiation of donor Purkinje cells in the adult rat cerebellum. Cerebellar primordium at the 14th day of gestation was transplanted into the adult rat cerebellum. Purkinje cells which had migrated from the grafted tissue into the host molecular layer were identified immunohistochemically with anti-spot 35 antibody, a specific marker for Purkinje cells in the cerebellum, as well as by labeling them with bromodeoxyuridine at their final mitotic period. In the grafted site, transient expression of a neuron-glia cell adhesion molecule, tenascin, was detected immunohistochemically. This molecule was expressed in the host tissue adjacent to the migratory Purkinje cells as well as within the donor immature tissue. Tenascin was not detected in the host tissue far distant from the grafted tissue. In considering the expression of tenascin in the migratory process of Purkinje cells during cerebellar development, this molecule induced in the host tissue may be involved in the migration of donor Purkinje cells.

We reported two cases of successful combined carotid endarterectomy and coronary artery bypass grafting. The first case was a 60-year-old male who had unstable angina pectoris and a history of two times of cerebral infarction. He was revealed to have severe stenosis of left internal carotid artery as well as diffuse stenosis of right and left coronary arteries. The second case, 67-year-old male with a history of cerebral infarction, was admitted because of anterior myocardial infarction. Coronary angiography revealed left main trunk disease and carotid angiography also revealed critical stenosis of bilateral internal carotid arteries. We discussed the management of the patients having coexistent such coronary and carotid artery disease.

We studied on coagulation and fibrinolysis systems during pregnancy by measuring plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), fibrinogen/fibrin degradation products (FDP), plasminogen (PLG) and antithrombin III (AT-III). Ninety seven pregnant, 5 post-delivery and 32 nonpregnant women aged from 20 to 52 years old were included in this study. Plasma concentrations of TAT and PIC in nonpregnant women were 3.38 +/- 1.02 micrograms/l and 0.65 +/- 0.24 micrograms/ml, respectively. TAT gradually increased with the progression of pregnancy and rapidly decreased after the delivery. Whereas PIC and AT-III concentrations did not change significantly during pregnancy. Fibrinogen, PLG and FDP concentrations changed similarly as TAT. Eight pregnants whose plasma PIC concentrations elevated more than 1.0 micrograms/l were further examined. In 6 women out of them (71.5%), FDP concentrations were elevated. In this particular group of subjects, however, they delivered normally without complications such as toxemia. These observations suggest that, at least, a hypercoagulative state progresses with pregnancy, being normalized after the delivery. Although we could not find the relationship between the hypercoagulation and clinical complications such as thrombosis and toxemia of pregnancy, present findings suggest that special caution should be paid on the pregnants whose TAT and FDP levels are elevated.

Of 167 patients, who underwent cardiac surgery using topical ice slush, 21 (12.6%) were found to have phrenic nerve palsy postoperatively. In addition, two patients showed severe epigastric discomfort, such as nausea, vomiting and gastric distension. These symptoms were consistent with so called "gastric ileus", first reported by Spencer et al. The injury of thoracic vagi induced by topical ice slush might be related to the development of this complication.

Four phenolic metabolites of (+-)-3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2- a]pyridine-3-spiro-4'-piperidino)propyl]-10,11-dihydro-5H-dibenz [b,f]azepine (mosapramine), a new antipsychotic drug, were synthesized in order to determine their chemical structures. Pharmacological activities of the three main metabolites were compared with those of mosapramine. The activities of the metabolites were far less potent than those of mosapramine.

The phasic renal arterial blood flow velocity was measured using a Doppler-Based Toshiba SSH-160A scanner in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Renal arterial blood flow at the renal hilum was visualized with color Doppler ultrasound, and the velocity waveform was obtained by pulsed Doppler ultrasound. The velocity waveform was then analyzed to give the peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of Tc-99m DTPA, also correlated well with these parameters. These findings suggest that renal arterial blood flow as detected by Doppler ultrasound may be useful for the noninvasive, direct, rapid, and simple evaluation of renal hemodynamics and renal function, although various modifying factors also need to be considered.