Cognitive function of patients with brain tumor in pre- and postoperative stage

BACKGROUND: Nobody knows whether cognitive dysfunction affects survival. Furthermore, it is unknown whether the dysfunction is caused by the tumor itself or by its treatment. METHODS: Patients with 20 gliomas (LGG, 7; MG, 13 [AG, 4; GM, 9]) in the right brain (nondominant) and 11 gliomas (LGG, 1; MG, 10 [AG, 6; GM, 4]) in the left brain (dominant) were studied. Thirty-four patients with meningioma were also studied. Cognitive function was evaluated by the 3MS examination, and propriety of radical resection of tumor was reviewed. RESULTS: Cognitive function pre-Op and post-Op was normal in patients with LGG and MGs in the right brain but decreased before an Op in all patients with MG in the left brain, and they did not normalize after Op. In patients with MG in left brain, the test of temporal and spatial orientation, first recall, similarities, 4-legged animals, mental reversal, and writing decreased after Op. Cognitive hypofunction before or after Op did not correlate with tumor malignancy and degree of tumor resection. CONCLUSION: Firstly, radical Op should aim at improvement of cognitive function for patients with glioma in the right brain, and for patients with glioma in the left brain, QOL should be thought about without expecting improvement of cognitive function. Secondly, improvement of cognitive function cannot be anticipated in patients with meningioma in the left brain. Aged patients older than 75 years require carefulness in Op. Then, damage of the cingulated gyrus and corpus callosum should be avoided in the left brain. This study emphasizes that clinicians should be careful in the evaluation of cognitive function in glioma and meningioma treatment.     

Involvement of ST1B subfamily of cytosolic sulfotransferase in kynurenine metabolism to form natriuretic xanthurenic acid sulfate

Natriuretic substances are a group of molecules affecting sodium homeostasis in the body. Recently, two new molecules having natriuresis effects, xanthurenic acid 8-O-beta-d-glucoside and xanthurenic acid 8-O-sulfate (XA sulfate), have been isolated from human urine. In the present study, we have investigated the sulfation of xanthurenic acid (XA) in mouse tissues to assess the contribution of specific sulfotransferases (STs) to the reaction. Cytosols from tissues of both sexes of C57BL/6N mice (liver, stomach, jejunum, colon, and kidney) were capable of forming XA sulfate, with various K(m) values. Jejunum cytosol showed the lowest K(m) value, and its V(max)/K(m) value was much greater than those of other tissues. The kinetic analyses with recombinant mouse (m) STs (Sult1a1, Sult1b1, Sult1c2, and Sult1d1) showed the lowest K(m) value for mSult1b1, and the value was comparable with that for jejunum cytosol. The highest expression of mSult1b1 in small intestine was confirmed at the mRNA and protein levels. mSult1b1 is thus suggested as a major enzyme responsible for XA sulfation in jejunum. Similar to mSult1b1, human SULT1B1 and rat Sult1b1 mediated XA sulfation efficiently. Thus, XA is likely to be an endogenous substrate for ST1B members. In contrast to XA, an XA-related compound, kynurenic acid strongly inhibited mSult1b1-mediated sulfations, with IC(50) values at a micromolar range. These results indicate the functional role of ST1B subfamily of ST in XA sulfate formation in the body.     

Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

PURPOSE: The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. MATERIALS AND METHODS: CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). RESULTS: On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median +/- SD, 16.0 +/- 3.7 vs. 8.0 +/- 1.4 months; p < 0.05). CONCLUSIONS: We conclude that in patients with advanced pancreatic cancer, CTAI with systemic chemotherapy appeared to be effective and may prolong their survival. The development of a reservoir port system allowing for the homogeneous distribution of anticancer drugs is necessary to improve the prognosis of patients with advanced pancreatic cancer.     

Action of GLP-1 (7-36) amide and exendin-4 on Suncus murinus (house musk shrew) isolated ileum

Glucagon-like peptide-1 (GLP-1) receptor agonists have been reported to modulate gastrointestinal motility but the mechanism is essentially unknown. In the present studies, we investigated the potency and mechanism of action of GLP-1 receptor ligands on the isolated ileum of Suncus murinus, an insectivore used in anti-emetic research. Ileal segments were mounted in organ baths containing Kreb's solution. Cumulative concentration-response curves to GLP-1 (7-36) amide (0.1-300 nM) and exendin-4 (0.1-100 nM) were constructed in the absence and presence of exendin (9-39) amide (0.3-3 nM). GLP-1 (7-36) amide and exendin-4 induced concentration-dependent contractions yielding pEC50 values of 8.4+/-0.2 and 8.4+/-0.4, respectively. Exendin (9-39) antagonized the action of both agonists in a non-competitive reversible manner, with apparent pKB values of 9.5 and 9.7, respectively. Tetrodotoxin (1 microM), atropine (1 microM) and hexamethonium (500 microM) were used to determine the contractile mechanism of action of exendin-4. Tetrodotoxin and atropine significantly antagonized (P<0.01) the contractile action of exendin-4 (10 nM); hexamethonium (500 microM) had no action. These studies suggest that GLP-1 receptor agonists contract the ileum indirectly via postganglionic enteric neurones and an involvement of muscarinic receptors. These studies provide information relevant to the use of this species to estimate the therapeutic indexes of GLP-1 receptor agonists.     

Reference serum cystatin C levels in Japanese children

Background  

Single measurements of serum cystatin C (cysC) concentration have generally been used to determine glomerular filtration rate (GFR) in adults. Since GFR varies to some extent among children, we attempted to determine reference serum cysC concentrations for Japanese children.     

Phylogenetic analysis of dengue viruses isolated from imported dengue patients: possible aid for determining the countries where infections occurred

BACKGROUND: Molecular epidemiology of dengue viruses in endemic countries have been reported, but few were reported on the imported dengue cases among travelers. We analyzed dengue viruses isolated from imported dengue cases in Japan who were infected while traveling in endemic regions of the world. METHOD: We sequenced the complete envelope (E) gene of 33 dengue virus strains isolated from patients returning from Asia, Oceania, South Pacific islands, and South America to Japan where no domestic dengue virus infection occurs. We then performed phylogenetic analysis to define the geographic origin of isolated viruses. Moreover, we compared the genomes of isolated dengue viruses with those of the strains already deposited in the GenBank database. RESULT: The isolates are clustered into expected genotypes, confirming that the viruses originated from the visited countries. When patients visited more than one country during a single trip, the countries where the infection occurred were also determined for four of the six patients. There were three isolates, which were different genotypes from those previously isolated in visited countries. CONCLUSIONS: The study demonstrates that many dengue virus strains are introduced into Japan and that phylogenic analysis of isolated dengue viruses is a unique technique to determine the countries where infection occurred. Travelers carry viruses and provide important and unique information for clarifying dengue virus trait and its dissemination.     

Bi-weekly administration of gemcitabine plus vinorelbine in elderly patients with advanced non-small-cell lung cancer: multicenter phase II trial

PURPOSE: Gemcitabine (GEM) and vinorelbine (VNR) have demonstrated activity as a first-line treatment in elderly patients with advanced non-small-cell lung cancer (NSCLC). We conducted a multicenter phase II trial to evaluate the efficacy and toxicity of bi-weekly administration of GEM plus VNR in elderly patients with advanced NSCLC. PATIENTS AND METHODS: Forty-six chemotherapy-naive elderly (age: >or=70 years) NSCLC patients were enrolled. Patients were eligible if they had histologically or cytologically confirmed unresectable NSCLC with measurable and/or assessable disease. Patients received GEM (1000 mg/m2) and VNR (25 mg/m2) every 2 weeks. RESULTS: The objective response rate of this treatment was 22.7% (95% confidence interval (CI), 10.3-35.1%), median survival time was 310 days, and median time to progression was 133 days. The one-year survival rate was 40.9% (95% CI, 26.3-55.4%), and most adverse events were mild. Only three (6.8%) patients needed to omit GEM because of grade 4 neutropenia or due to physician judgment. No patients suffered treatment-related death. CONCLUSIONS: Bi-weekly administration of GEM plus VNR in elderly patients was an effective, feasible and well-tolerated treatment schedule.     

Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome

Gitelman’s syndrome is an autosomal recessive disorder marked by salt wasting and hypokalaemia resulting from loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter. Gitelman’s syndrome is usually distinguished from Bartter’s syndrome by the presence of both hypomagnesaemia and hypocalciuria. Although recent advances in molecular genetics may make it possible to both diagnose and differentiate these diseases, the phenotypes sometimes overlap. Here we report two sporadic cases of Gitelman’s syndrome and two novel genotypes of SLC12A3. Patient 1 was a compound heterozygote with a known missense mutation, L849H, and a novel mutation, R852H in exon 22. Patient 2 was homozygous for the missense mutation L849H. To our knowledge, this is the first report of a patient homozygous for 849H. Interestingly, both patients were affected with autoimmune thyroid disease. Patient 1 was affected with Hashimoto’s disease, and Patient 2 was affected with Graves’ disease. The symptoms of Patient 2 were more serious than those of Patient 1. Although the patients both carried the 849H allele (Patient 1 as a heterozygote and Patient 2 as a homozygous), their clinical symptoms differed. The difference in the clinical features may have been due both to phenotypic differences and the fact that Gitelman’s syndrome is a complicated disorder.