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The aim of this study was to evaluate the inflammatory/nutritional index in patients with colorectal cancer. A total of 600 patients with pStage Ⅱ-Ⅲ colorectal cancer who underwent radical resection at our hospital between January 2008 and September 2022 were retrospectively reviewed. Onodera's prognostic nutritional index(OPNI), CRP-to-albumin ratio, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio were measured preoperatively. Clinical and pathological data were assessed using univariate and multivariate analysis to determine prognostic factors for overall survival(OS), relapse-free survival(RFS)and post-relapse overall survival (PROS). Moreover, these patients were divided into high and low groups based on OPNI, these survival outcome for OS, RFS and PROS were assessed using Kaplan-Meier analysis with the logrank test. In multivariate analysis, the independent prognostic factors were gender, age, OPNI, histological type, pStage for OS, gender, OPNI, venous invasion and pStage for RFS, and OPNI, histological type and resection of recurrent site for PROS. In Kaplan-Meier analysis, patients in the low OPNI group had significant poor prognosis for OS, RFS and PROS. OPNI is a useful prognostic factor in colorectal cancer.

The problem of high-dose psychotropic polypharmacy has been pointed out for a longtime in schizophrenia, being referred to at the Annual Meeting of the Society in 2011. The fre- quency of high-dose psychotropic polypharmacy is much higher in Japan compared with other countries. The polypharmacy rate is about 65% for anti-psychotic drugs, and rates of high- dose antipsychotics are 30% or higher. The rates of combination therapy using anti-Parkinson drugs, anti-anxiety drugs/sleeping pills, and mood stabilizers with antipsychotics have also been reported to be 30-80% or higher. In 2014, a reduction of medical fees for multi-drug prescriptions of psychotropic drugs was made, but it is still too early to assess its impact. Against this background, we introduced the Guidelines for Pharmacological Therapy of Schizophrenia, created by The Japanese Society of Neuropsychopharmacology. We describe how high-dose psychotropic polypharmacy has been used to treat schizophrenia in Japan in these guidelines, being the first evidence-based guidelines using the Minds method. Further- more, a schizophrenic case with cognitive decline who received polypharmacy is presented. In addition, the EGUIDE project for the purpose of education and dissemination of these guide- lines is considered. It is our hope that patients with schizophrenia can receive more appropriate treatment.

A biomarker is defined as a biological indicator of normal or pathological processes, and a pharmacological response to a therapeutic intervention, whose characteristics can be measured and evaluated objectively. In medicine and health, biomarkers can be paraphrased as diagnostic methods objectively conducive to treatment. Here, we discuss biomarkers of schizophrenia as a representative mental illness, whose research has advanced compared with that of other disorders. Schizophrenia is a syndrome with a typical course and symptoms. Its pathophysiology and pathogenesis have not been elucidated (medically however, its underlying biological mechanisms are assumed to be present. That is, in biomarker discovery, when the pathogenesis and cause are elucidated, the patient group would not consiste of schizophrenia but, it is a new disease of "x x disease." For example, neurosyphilis is exogenous psychosis, by finding a biomarker of syphilis spirochete, a new disease concept of neurosyphilis could be distinguished from the schizophrenia). In this way, it can be said that biomarker research is essential for the development of new diagnostic and treatment methods for mental illness. There are several biomarker research methods such as genetic analysis, biological sample analysis, cognitive analysis, neurophysiology, neuroimaging, animal models, and post-mortem brain analysis. Further, studies have been made, however, biomarkers that can explain all of schizophrenia has not been found yet. As schizophrenia is assumed to be a heterogenous syndrome, it is believed that the etiology varies. Thus, there is a possibility that targeting schizophrenia as a whole will make it difficulty to find biomarkers for patients with schizophrenia. It is considered that appropriate subgroup analysis is needed. In order to overcome it, amount-of-resources strategy to find patients by using large of samples has been made mainly in Europe and the United States. In Japan, we have used sub-group analysis strategy to elaborate this issue such as the use of an intermediate phenotype. It is not possible to research a similar strategy, because of the limited funds and manpower in Japan compared to U. S. and Europe. As nationwide research organizations in Japan, such as IGC (Imaging genetics consortium), combination analysis of genetics and neuroimaging and COCORO (Cognitive genetics collaborative research organization), combination analysis of genetics and cognitive function, have been established, the development of biomarkers for mental illnesses is expected in the near future.

We report a case of non-curatively resected esophageal cancer with no recurrence biweekly treated with postoperative docetaxel/nedaplatin combined chemotherapy. A 59-year-old woman underwent non-curative resection with esophagectomy for advanced esophageal cancer with direct invasion to the descending aorta in August, 2007. Postoperatively, she was treated biweekly with docetaxel/nedaplatin combined chemotherapy 32 times. In this period, there was no finding in the enhanced CTs, and clinically she was free from recurrence. The quality of life of this patient was also good. Thus, postoperative biweekly docetaxel/nedaplatin combined chemotherapy could be effective for advanced esophageal cancer after non-curative surgery and might be promising for long-term survival. This combined chemotherapy could be carried out on an outpatient basis, and the quality of life could also be preserved. More experience must be accumulated using this chemotherapy.

The dysbindin-1 gene (DTNBP1: dystrobrevin binding protein 1) has been identified as a susceptibility gene for schizophrenia. Genetic variations of DTNBP1 were reported to be associated with several intermediate phenotypes such as general cognitive ability, memory, and regional brain activation and cortical volume. In studies on postmortem brain tissue, decreased expression levels of dysbindin-1 were shown in patients with schizophrenia. Risk genetic variation of dysbindin for schizophrenia was associated with reduced expression of dysbindin in human brains. These data indicate that the dysbindin-1 gene may confer susceptibility to schizophrenia through reduced expression and that sandy mice lacking dysbindin-1 protein could be a unique animal model of schizophrenia. Sandy mice were less active, had heightened anxiety-like response, demonstrated deficits in social interaction and showed impaired long-term memory retention and working memory. Sandy mice demonstrated lower levels of dopamine, but not glutamate, in restricted brain regions. Several neuronal functions of dysbindin were reported, such as neurotransmitter release, direct interaction with presynaptic molecules, neuroprotection, cytosckeletal organization, and gene expression. To investigate dysbindin function in the brain could shed light on the etiology of schizophrenia and lead us to new hypotheses, novel diagnostic tools, and more effective therapies for the disorder.

We report a case of non-curatively resected gastric cancer successfully treated with postoperative continuous chemotherapy, resulting in long-term survival of 19 months. A 75-year-old woman underwent non-curative resection with total gastrectomy for advanced gastric cancer with peritoneal metastasis in June, 2005. Postoperatively, at first, she received oral administration of S-1. However, due to grade 2-3 nausea and anorexia, the dose of S-1 was reduced. After four courses, the value of the tumor markers increased. Next, we chose sequential methotrexate and 5-fluorouracil therapy, but no decrease tumor markers could be obtained. Then, 9 months after surgery, biweekly paclitaxel (PTX) chemotherapy was performed. The value of the tumor markers gradually decreased or stopped increasing, and PTX was administered 18 times. In this period, the quality of life of this patient was good. Eighteen months after surgery, the value of the tumor markers increased again, and S-1 and CPT-11 combination therapy was chosen. However, the patient died of brain infarction 19 months after surgery. Thus, continuous and persevering chemotherapy could be effective for advanced gastric cancer with peritoneal metastasis and may be promising for long-term survival.

The patient was a 87-year-old woman diagnosed as type 2 advanced colon cancer in the ascending colon. The patient underwent right hemicolectomy. The pathological diagnosis showed poorly-differentiated adenocarcinoma, si, ly2, v1, n0 (0/41) and Stage IIIa. The postoperative course was uneventful, and she was discharged on POD 23. But a left submandibular lymph node enlarged rapidly within two months after the operation. Aspiration cytology of the lymph node indicated poorly-differentiated adenocarcinoma, and she was diagnosed as recurrent colon cancer. Combined chemotherapy of 5-FU (200 mg/day/po) and PSK (3.0 g/day/po) was started as palliative chemotherapy. The metastatic lymph nodes were reduced in size within two months after the treatment. Oral administration of 5-FU+PSK succeeded without serious adverse effects or worsening of quality of life. Ten months later, no recurrence was detected on physical examination or computed tomography. We conclude that palliative oral (5-FU+PSK) chemotherapy is useful for recurrent colon cancer in the elderly because of its excellent safety and effectiveness.

The development of diagnostic markers for earlier and more reliable diagnosis of Alzheimer disease (AD) is essential, particularly because therapeutic medication is available for AD. Cerebrospinal fluid (CSF) is a useful source of diagnostic information. Previously we found the increase of total tau protein in CSF in normal pressure hydrocephalus patients, and others reported the increase also in corticobasal degeneration and frontotemporal dementia. To differentiate the AD from other diseases, further approach was employed and oxidized protein in CSF was investigated. Heat stable fractions of CSF were analyzed on the content of carbonyl residues, which are derivatives of protein oxidization. The result suggests that protein oxidation is highly involved in AD and that this method might be useful to differentiate AD from other neurological disease.

We report a case of severe rhabdomyolysis associated with Salmonella encephalopathy. A 3-year-old girl was admitted to our hospital because of status convulsives and unconsciousness. She was diagnosed as having Salmonella encephalopathy with rhabdmyolysis, and was treated by mild hypothermia and mechanical ventilation. Five days later she developed anuria with increased serum levels of myoglobin, CK and creatinine. And the diagnosis of acute renal failure was made. Peritoneal dialysis was begun from 6 days after admission. Hyperinfusion, the usual therapy of rhabdomyolysis, was not performed. She survived showing gradual improvement of renal function and consciousness. In a case of rhabdomyolysis complicating a neurologic disorder, a well-known poor prognostic factor, priority should be given to brain protection rather than to symptomatic treatment of rhabdomyolysis.

Recent surgical nutrition includes the management of mediator to induce the stress response and immune function. N-3 polyunsaturated fatty acid (n-3 PUFA) were reported to increase the survival rate, and to improve the nutritional and immune status of septic or burned animals. N-3 PUFA also inhibited the proliferation and metastasis of cancer, and improved the cancer cachexia. N-3 PUFA decreased the production of cytokine and eicosanoid originated from n-6 PUFA, and reduced the inflammatory and stress response. Cell-mediated immunity was suppressed with the reduction of cytokine. But in the stressed state, N-3 PUFA ameliorated the stress induced immunosuppression. Alteration of transcription of cytokine mRNA, changes of membrane fluidity, and reduced expression of adhesion molecule were proposed to interpret these effects. In conclusion, n-3 PUFA can be applied for the surgical patients, especially for the critically ill patients.

Eleven inoperable patients with advanced esophageal carcinoma were treated with chemotherapy (carboplatin, 5-FU, vindesine) and concomitant radiotherapy. Two patients (T2) received this treatment due to their poor general condition and refusal of operation, and 9 patients for infiltration of tumor into the adjacent organs (T4). Administration of carboplatin (30 mg/body) and 5-FU (250 mg/body) together with radiotherapy (1.8 Gy/d) for 5 days a week was performed. This chemoradiation therapy was carried out for 5 consecutive weeks. In addition, vindesine (1-3 mg/body) was administered in the 1st and 4th week. After evaluation, endoscopic balloon dilatation was performed in 6 patients with stenosis of the esophagus. The general response rate was 80%. CR was noted in 2 patients of T2 but 1 patient of T4 developed severe leucopenia and immunosuppression, and died of septic MOF. All but the MOF case could take enough food orally following the endoscopic dilatation. The 1-year survival rate in the T4 group (45%) was significantly better than the non-treatment group (0%). In conclusion, this treatment is beneficial for patients with inoperable esophageal carcinoma to obtain a satisfactory QOL and survival rate.

A Japanese girl developed tonic spasms in series at two months after birth. When she was admitted at 4 months, she had generalized muscle hypotonia and could not control her head. She had atotal agenesis of the corpus callosum on MRI, reticulo-lacunitis revealed by ophthalmologic examination, and hypsarrhythmia in EEG. Brain stem auditory evoked potentials and flash-visual evoked potentials exhibited abnormally asymmetrical findings. The cortical components of somatosensory evoked potentials were not elicited on admission, but some components became to be recognized on median nerve stimulation in accordance with improvement of EEG findings after various therapeutic trials. We concluded that these neurophysiological examinations were useful to investigate the abnormal lesions of the central nervous system in patients with Aicardi syndrome.

Effect of insulin-like growth factor-I (IGF-I) on protein metabolism was investigated in burned rats receiving TPN. Twenty-six male SD rats were divided into two groups. IGF-I was administered to group IGF (IGF-I group, n = 14), but not to group C (Control group, n = 12). Loss of body weight after burn in group IGF was significantly lower than group C (p < 0.01). Cumulative nitrogen balance for 2 postburn days in group IGF was significantly higher than group C (p < 0.01). Rate of whole body protein turnover, synthesis and breakdown increased significantly in group IGF compared with group C. On the other hand, blood glucose was decreased significantly in group IGF (p < 0.05). Water balance made no significant difference between two groups. In group IGF, weight of the spleen, kidney, small intestine and colon increased significantly. Fractional synthesis rate and protein content of mucosa of the small intestine were significantly higher in group IGF than group C. From the histological point of view, mucosal layer was thickened and hyperplastic. Catabolism and surgical diabetes are caused in the surgical stress, and the administration of IGF-I are thought to be effective for improvement of those conditions. And IGF-I has the most remarkable effect on the small intestine of all organs studied in our experiment.

Adequate requirements of energy and protein in post operative total parenteral nutrition (TPN) were determined by studying the effects of energy and protein dose on nitrogen retention at varying levels of surgical stress assessed by urinary excretion of total catecholamines. Fifty-two patients received esophagectomy (severe stress), and gastric or colorectal operations (moderate stress) fed exclusively by TPN perioperatively were divided into 6 groups according to the dose level of protein and energy; Group I: 40 kcal, 1.0 g.protein/kg.day (9 patients), Group II: 40 kcal, 1.5 g.protein/kg.day (11 patients), Group III: 40 kcal 2.0 g.protein/kg.day (8 patients), Group IV: 40 kcal, 3.0 g.protein/kg.day (7 patients), Group V: 30 kcal, 2.0 g.protein/kg.day (11 patients), and Group VI: 50 kcal, 2.0 g.protein/kg.day (6 patients). Daily nitrogen balance (NB) and urinary excretion of total catecholamines (U-CA) were determined everyday pre- and post-operatively. Significantly negative correlations between U-CA and NB were observed. Statistically significant differences among the correlations of all groups were recognized. In moderate stress, increasing dose of protein and energy improved NB, and positive NB was achieved when 1.5-2.0 g.protein/kg.day with 35-40 kcal/kg.day was provided. Protein dose exceeding 3.0 g/kg.day caused the rise of BUN. In severe stress, such as following esophagectomy, NB was not improved by increasing dose of nutrients.

Insulin (INS) has been known to be absorbed through the intestine in small amounts and to decrease blood sugar (BS) levels. However, stable control of BS has not been attained by intestinal intake of INS. To elucidate the possibility of a surgical approach to control hyperglycemic states, Thiry-Vella loops or upper jejunal loop fistulae were constructed in mongrel dogs in hyperglycemic states. Hyperglycemic states (around 400mg/dl) were induced by injecting streptozotocin. Lente insulin was administered every day to control hyperglycemia, except for the days for studies. As we confirmed that co-administration of aprotinin (TR) or nafamostat mesilate (FT) was necessary, to decrease BS by infusing INS into the intestinal loops, safe and effective dose levels were determined by series of preliminary infusion studies in the intestinal loops of diabetic dogs. By continuous infusion of these doses into the jejunal loop fistulae, a long term stable blood sugar control was attained in the diabetic dogs as long as 7 days. These results suggest that continuous infusion of INS with antiproteolytic adjuvants like TR or FT into the isolated small intestinal loop can control BS in hyperglycemic states.

In order to clarify the metabolism of Lipoprotein X (Lp-X) induced by intravenous Intralipid 10%, in vitro experiments using purified Lp-X from the sera of the patients receiving Intralipid 10% were carried out. 1) Lp-X or high density lipoprotein (HDL) was incubated with J-774 macrophages laden with [3H] cholesterol. Marked extraction of cholesterol from macrophages by Lp-X as well as HDL was observed. 2) [3H] cholesterol labelled Lp-X or oxidized LDL (o-LDL) was incubated with J-774 macrophages. Incorporation of Lp-X into macrophages was negligible comparing to o-LDL. 3) [3H] cholesterol labelled Lp-X, low density lipoprotein (LDL), or HDL was incubated with Hep G2 cells was less than LDL, but similar to that of HDL. These results indicated that Lp-X extracted cholesterol from peripheral tissues during its formation, and it was not catabolized by the scavenger pathway, but catabolized by the LDL pathway of hepatocytes.

The effects of human growth hormone (HGH) on protein metabolism were investigated. In the experimental study, thirty one male SD rats receiving TPN were divided into 2 groups (control group & HGH group). Cumulative nitrogen balance after burn in HGH group was significantly higher than in control group. (p less than 0.05) Rates of whole body protein turnover (Q), together with those of synthesis (S) and breakdown (B) were significantly higher in HGH group than in control group. (p less than 0.01) Nitrogen balance significantly correlated with urinary total catecholamine excretion in both groups. (p less than 0.01) The difference of correlations of nitrogen balance to urinary total catecholamine excretion between two groups was statistically significant (p less than 0.01) when compared by analysis of covariance. In the clinical study, 12 patients after sub-total esophagectomy receiving TPN were divided into 2 groups (control group & HGH group). Cumulative nitrogen balance after operation in HGH group was significantly higher than in control group. (p less than 0.01) Q,S, and B were higher in HGH group than in control group. Increase of S was statistically significant. (p less than 0.01). These results indicate that HGH may be greatly beneficial in improving protein metabolism in the surgically stressed state.

This study was performed to elucidate adequate energy and amino acid (AA) requirements for TPN patients after abdominal surgery. The effects of AA formula, rich in BCAA (30% BCAA), as a nitrogen source and the carbohydrate mixture of glucose, fructose, and xylitol (GFX = 4:2:1), on nitrogen sparing were also studied. Forty-nine patients having undergone major abdominal surgeries, were divided into 5 groups. The regimens were as follows: G1: 40kcal/kg, standard amino acid (21% BCAA) 1.5g/kg. day, G2: 40kcal/kg, 30% BCAA 1.5g/kg.day, G3: 30kcal/kg, 21% BCAA 1.5g/kg.day, G4: 30kcal/kg, 30% BCAA 1.5g/kg.day, G5: 40kcal/kg, 21% BCAA 1.5g/kg.day. Glucose was the sole carbohydrate energy source in G1 through G4. In G5, GFX was used. (1) Accumulated nitrogen balances during the week immediately after operation were significantly higher in G1 and G2 where higher energy intakes were administered than G3 and G4. (2) The nitrogen balances during the 2nd or 3rd postoperative days in G2 or G4, using 30% BCAA as a nitrogen source, were higher than in G1 or G3 respectively. (3) The changes in serum rapid turnover proteins were not significantly different among these groups. (4) The accumulated nitrogen balance in G5 tended to be higher than that of G1. These results indicate that BCAA rich amino acid formula will induce a more favorable nitrogen sparing effect than a conventional AA formula on TPN patients under surgical stress.

We employed latamoxef (LMOX) as antibiotic therapy subsequent to the performance of appendectomies in children. Fifteen patients, consisting of 8 cases of catarrhal appendicitis and 7 cases of gangrenous appendicitis, were administered LMOX at 50 mg/kg/day, while 13 patients with peritonitis due to a perforated appendix were treated with a dosage of 90 mg/kg/day. Both of these dosages were administered in 3 equally-divided doses, as one shot intravenous injections. All of the cases of catarrhal and gangrenous appendicitis showed good, steady recovery after the surgery, and there were no instances of complications. With regard to the 13 cases of perforating appendicitis, a clinical efficacy of at least "good" was obtained in 12 patients, for an efficacy rate of 92.3%. In addition, bacteriologically, 35 out of 36 strains that were isolated initially could no longer be detected after the LMOX therapy, indicating an eradication rate of 97.2%. Complications consisted of 1 case of dehiscence of the wound, and 1 case of adhesive ileus. Comparison of the values of the laboratory tests before and after the LMOX therapy revealed no development of abnormalities. Moreover, with regard to side effects, with the exception of 1 case of transient diarrhea, there were no side effects which presented clinical problems. It was found that the causative microbes involved in these cases of appendicitis--especially in the perforative appendicitis cases--were Gram-negative bacilli such as E. coli, and an anaerobic bacterium, B. fragilis.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was conducted to clarify the mechanisms underlying the loss of body nitrogen after trauma. Six patients who underwent abdominal surgery and six for control were studied. The measurement of whole body protein turnover was made on the third and tenth postoperative day during TPN with constant infusion of [15N] glycine according to Picou and Taylor-Roberts. The measurement was also made on six control patients during TPN in non-stressed state. The rates of whole body protein turnover (Q), synthesis (S) and breakdown (B) were calculated from the plateau 15N enrichment of urinary total N, which was analyzed with a mass spectrometer. The values were compared with control and the changes in the individual patients were examined by a paired t-test. Immediately after operation, Q and B were significantly elevated (p less than 0.05 and p less than 0.02, respectively), and reduced with the improvement of N-balance after recovery from stress by 0.95 +/- 0.21 and 0.61 +/- 0.13 g X protein/kg X day, respectively. The changes in Q and B were statistically significant (p less than 0.005 and p less than 0.005, respectively). Whereas, no tendency of alteration in S was found throughout the study. It is concluded that protein turnover rate increases in surgical stress, and that the increased protein catabolism rather than the alteration in synthesis could account for the postoperative nitrogen losses.

This study was conducted to understand the mechanisms underlying the loss of body nitrogen after surgical trauma. Thirteen patients who underwent moderate to severe abdominal surgery and six for control were studied. The measurement of whole body protein turnover was made on the third and tenth postoperative day during isonitrogenous and isocaloric TPN using the constant infusion method of [15N] glycine. Nitrogen balance was improved markedly in 6 patients, who received moderate surgical procedures (group I). However the balance was still negative at the tenth postoperative day in 7 patients, who received severe surgery with some critical complications (group II). A significant increase in whole body protein breakdown on the third postoperative day in groups I and II were found (p less than 0.02, p less than 0.001, respectively). Breakdown was higher in group II than in group I (p less than 0.02). Whole body protein synthesis tended to increase on the third postoperative day in group II, but was within the normal range in group I. In conclusion, the change of whole body protein turnover was different depending upon the severity of stress. Protein synthesis unchanged in moderate stress, but tended to increase in severe stress with a greater increase of breakdown.