Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

Impact of demographic, environmental, and lifestyle factors on vitamin D sufficiency in 9084 Japanese adults.

BACKGROUND: Little is known about correlates of vitamin D status in Asian populations. In this study, we established the prevalence of vitamin D sufficiency in the Murakami region (latitude N38°13') in Niigata, Japan, and examined demographic, environmental, and lifestyle factors that might be associated with vitamin D sufficiency, with the aim of clarifying the relative contributions of previously described determinants of vitamin D status as well as identifying new determinants in this Japanese population. METHODS: This study involved a cross-sectional analysis of baseline data obtained from a cohort study conducted in 2011-2013. Participants were 9084 individuals aged between 40 and 74 years who provided blood samples for the determination of plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained from 8498 participants, with some missing values regarding different lifestyle factors. Multiple logistic regression analysis was used to obtain odds ratios for vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration ≥ 75 nmol/L. RESULTS: The prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D concentration ≥ 75 nmol/L) was 9.1%, and significant associations were observed with male gender (P<0.0001; OR=2.37, 95% CI: 1.84-3.05), older age (P for trend <0.0001), lower BMI (P for trend <0.0001), higher METs score (P for trend=0.0138), higher vitamin D intake (P for trend=0.0467), summer season (P for trend <0.0001), longer duration outdoors (P for trend=0.0026), no sunscreen use (P=0.0135; OR=1.40, 95% CI: 1.07-1.82), higher salmon consumption (P for trend <0.0001), higher alcohol consumption (P for trend <0.0001), and lower coffee consumption (P for trend=0.0025). Unlike other populations previously reported, vitamin D sufficiency was associated with older age. CONCLUSIONS: The prevalence of vitamin D sufficiency (i.e., 25[OH]D ≥ 75 nmol/L) was low (9.1%) in this Japanese population. A number of demographic, environmental, and lifestyle factors are associated with vitamin D sufficiency, and thus lifestyle modification may present an opportunity to achieve vitamin D sufficiency.

Long-term effects of the Niigata-Chuetsu earthquake in Japan on acute myocardial infarction mortality: an analysis of death certificate data.

OBJECTIVE: To determine if the Niigata-Chuetsu earthquake of October 2004 increased long-term mortality from acute myocardial infarction (AMI). DESIGN: A comparative study of mortality rates before and after the earthquake, as well as between the disaster and control areas, by analysing death certificate data from 1 October 1999 to 30 September 2007. SETTING: The disaster area and a control area in Niigata Prefecture (n = 2 448 025 in 1 October 2004) in Japan. POPULATION: The total population of Niigata Prefecture observed for five years (12 333 429 person-years) before and three years (7 279 076 person-years) after the earthquake. MAIN OUTCOME MEASURES: Mortality from AMI (ICD-10, I21 and I22). RESULTS: Overall mortality rates from AMI five years before and three years after the earthquake in the disaster area were 47.3 and 53.9 per 100 000 person-years, respectively. Change (+6.6 or +14.0%) was significantly different (p = 0.0008), compared to the control area, where mortality rates were 42.5 and 42.6 per 100 000 person-years, respectively, and was not significantly different (p = 0.9028). In men, a change in AMI mortality before and after the earthquake in the disaster area was +7.1 per 100 000 person-years (+13.4%, p = 0.0172), and +2.0 (+4.2%, p = 0.2362) in the control area. In women, a change in AMI mortality in the disaster area was +6.2 per 100 000 person-years (+14.9%, p = 0.0184) and -1.6 (-4.2%, p = 0.2735) in the control area. CONCLUSIONS: The Niigata-Chuetsu earthquake significantly increased long-term mortality from AMI in both men and women. Clinicians and policymakers in public health must recognise the need for long-term prevention of AMI in earthquake disaster areas.

Palladium-catalyzed cross-coupling reaction of triarylbismuths with aryl halides and triflates.

[reaction: see text] Palladium-catalyzed cross-coupling reaction of triarylbismuths with aryl bromides, iodides, and triflates proceeded efficiently in the presence of K(2)CO(3) or CsF.

Diagnostic application of CD44 variant expression in pancreatic juice for detection of pancreatic neoplasm.

Recently, increased and disorganized expression of CD44 variant exons (CD44v) has been demonstrated in several types of human malignancy. We tried to investigate CD44v expression in pancreatic juice from patients who underwent endoscopic retrograde pancreatography. We analyzed 24 patients with pancreatic neoplasms diagnosed histologically (adenocarcinoma, 17; adenoma, 7) and 15 patients with non-neoplastic lesions. The expression of CD44v mRNA in pancreatic juice was detected by using the reverse-transcription polymerase chain reaction technique followed by Southern hybridization with exon-specific probes. Of 17 patients with adenocarcinoma, 14 (82%) showed expression of CD44v6 mRNA and 11 (65%) showed expression of CD44v2 mRNA. Of 7 patients with adenoma, 6 (86%) were positive CD44v6 mRNA expression and 2 (29%) for CD44v2 mRNA expression; while, out of 15 patients with non-neoplastic lesion, 5 (33%) showed positive findings for CD44V6 mRNA and 3 (20%) for CD44v2 mRNA. Comparing of diagnostic accuracy among CD44v6, CD44v2 and cytological examination, the sensitivities for adenocarcinoma were 82%, 65% and 41% respectively. However, the specificity was lower in CD44v6 (50%), CD44v2 (77%) than in cytology (100%), because CD44v was positive in adenoma cases and normal cases. A combination of RT-PCR analysis for the expression of CD44v with cytological examination in the pancreatic juice may increase the accuracy of diagnosis for pancreatic cancer.

Clinicopathological factors predicting outcome after resection of mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis for patients with intrahepatic cholangiocarcinoma differs according to macroscopic type. The identification of clinical and pathological features that predict outcome in patients with mass-forming intrahepatic cholangiocarcinoma is required in order to determine optimal surgical strategies for patients with this type of tumour. METHODS: The details of 35 patients with resected mass-forming intrahepatic cholangiocarcinomas were analysed retrospectively. Univariate analysis of potential prognostic factors was performed. RESULTS: The cumulative survival rate at 1, 3 and 5 years after operation was 58, 33 and 33 per cent respectively. Patients with stage II tumours had a better outcome than those with advanced stage tumours. By univariate analysis, lymphatic invasion, lymph node metastasis, intrahepatic satellite lesions and microscopic resection margin involvement were found to be highly significant variables and were identified as possible risk factors for a poor outcome after operation. CONCLUSION: When frozen-section examination of lymph nodes reveals negative nodal metastasis, extensive anatomical hepatic resection is indicated for mass-forming intrahepatic cholangiocarcinomas. Intraoperative frozen-section examination of the resection margin to confirm the absence of cancer cells is recommended.

Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial.

BACKGROUND: Interferon therapy decreases the incidence of hepatocellular carcinoma in patients with chronic hepatitis C. OBJECTIVE: To evaluate effects of interferon-alpha on recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. DESIGN: Randomized, controlled trial. SETTING: University hospital, medical center, and affiliated hospital in Osaka, Japan. PATIENTS: 30 men were randomly allocated after resection to the interferon-alpha group (n = 15) or the control group (n = 15). INTERVENTION: Patients in the interferon-alpha group received interferon-alpha, 6 MIU intramuscularly daily for 2 weeks, then three times weekly for 14 weeks, and finally twice weekly for 88 weeks. MEASUREMENTS: Recurrence rates after resection. RESULTS: Recurrent tumors were detected in 5 patients in the interferon-alpha group and in 12 control patients. The recurrence rate was significantly lower in the interferon-alpha group than in the control group (P = 0.037). CONCLUSION: Postoperative interferon-alpha therapy appears to decrease recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.

Erythrocytosis caused by an erythropoietin-producing hepatocellular carcinoma.

A case of erythrocytosis caused by a hepatocellular carcinoma (HCC) that produced erythropoietin (Epo) is described. A 64-year-old man, with a huge HCC tumor in the right lobe of the liver, showed a high concentration of hemoglobin and increased levels of serum Epo, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II). Right lobectomy of the liver was performed. Histological findings of the specimen showed a moderately differentiated HCC. The existence of Epo was confirmed immunohistochemically only in the tumor tissue and not in the normal liver tissue. Erythrocytosis disappeared and the serum levels of Epo, AFP, and PIVKA-II returned to the normal range after the operation. Within 2 months after the operation, recurrent tumors appeared in the remnant liver, and the patient died 13 months after the operation.

Influenza vaccination levels and influenza-like illness in long-term-care facilities for elderly people in Niigata, Japan, during an influenza A (H3N2) epidemic.

Surveys on influenza vaccination and illness in long-term-care facilities in Niigata Prefecture during an influenza A (H3N2) epidemic revealed that >20% of facilities had outbreaks and >10% of residents experienced influenza. Outbreaks and number of cases were significantly reduced by vaccination, which should be strongly recommended for institutionalized elderly people.

Prevalence of anorexia nervosa and bulimia nervosa in a geographically defined area in Japan.

OBJECTIVE: Little has been understood regarding the frequency of eating disorders in Japan. This study was designed to identify the prevalence of anorexia nervosa (AN) and bulimia nervosa (BN) in Japan. METHOD: We asked doctors in all of the relevant medical facilities (130 hospitals and 1,326 clinics) in Niigata Prefecture to report patients with DSM-IV-diagnosed eating disorders who appeared or were admitted between 20-24 October 1997. The response rate was 94.4%. RESULTS: The estimated point prevalences of AN and BN were 4.79 and 1.02, respectively, per 100,000 females. Specifically for the age group of 15-29 years, the prevalence of AN was 17.10 and that of BN 5.79. DISCUSSION: The prevalence of AN and BN in Japan is lower than that for European Caucasian populations. This result may be due to cultural and ethnic differences and/or it may be a transient phenomenon.

Relationship between breast milk feeding and atopic dermatitis in children.

OBJECTIVE: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR] = 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR = 1.14, 95% CI; 0.95-1.35) showed odds ratios that were higher than unity without statistical significance. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders.

Successful treatment of a hepatic abscess that formed secondary to fish bone penetration by percutaneous transhepatic removal of the foreign body: report of a case.

We describe herein the case of a hepatic abscess that developed secondary to fish bone penetration which was successfully treated without laparotomy. A 61-year-old man was admitted to our hospital with a high fever that had persisted for 2 weeks in spite of medication. Abdominal ultrasonography (AUS) and computed tomography (CT) of the abdomen revealed a hepatic abscess with a linear calcified foreign body and gas. Percutaneous abscess drainage was performed under ultrasonographic guidance. After drainage, the patient became afebrile, and AUS and CT findings demonstrated that the abscess cavity had decreased in size, but still contained the foreign body. Under ultrasonographic guidance and fluoroscopy, we inserted endoscopic forceps into the sinus tract and succeeded in removing the foreign body from the liver. It was found to be a fish bone that was 2.8 cm long and 0.3 cm wide.

Serum endothelin-1 and hepatocyte growth factor levels in patients with obstructive jaundice.

BACKGROUND/AIMS: Endothelin-1, a potent vasoconstrictive peptide, is known to modulate changes in local circulation. Additionally, hepatocyte growth factor, a potent mitogen for hepatocytes, is increased in various liver diseases. The present study examined changes in serum endothelin-1 and hepatocyte growth factor levels in patients with obstructive jaundice before and after percutaneous transhepatic cholangio drainage. METHODOLOGY: Endothelin-1 and hepatocyte growth factor levels were measured by enzyme-linked immunosorbent assay using sera from 16 patients with obstructive jaundice before and after percutaneous transhepatic cholangio drainage. RESULTS: Serum endothelin-1 levels decreased rapidly in the good bilirubin decrease group after biliary drainage. Endothelin-1 levels decreased 1 week after drainage but then increased gradually in the worse bilirubin decrease group. Serum hepatocyte growth factor levels decreased gradually after biliary drainage, and were higher in the worse bilirubin decrease group than in the good bilirubin decrease group throughout the study. CONCLUSIONS: These results suggest that endothelin-1 may be associated with the microcirculatory disturbance in obstructive jaundice and prolonged cholestasis. Measurement of hepatocyte growth factor levels in patients with obstructive jaundice before percutaneous transhepatic cholangio drainage may be an early clinical predictor of the subsequent rate of decrease of the serum bilirubin concentration.

Portal serum human hepatocyte growth factor levels after partial hepatectomy.

BACKGROUND/AIMS: We investigated whether or not hepatocyte growth factor increases in portal serum via an endocrine mode after partial hepatectomy in humans. METHODOLOGY: Portal blood was sampled through a catheter inserted through the umbilical vein to the portal trunk during surgery in 17 patients. Serum human hepatocyte growth factor levels were determined by enzyme-linked immunosorbent assay. RESULTS: Human hepatocyte growth factor levels were higher in portal than in peripheral serum throughout the study. Portal and peripheral serum human hepatocyte growth factor levels without complications increased rapidly and reached a maximum level 1 day after partial hepatectomy. The maximal level of portal and peripheral serum human hepatocyte growth factor was 1.20 and 1.00 ng/ml, respectively. In the case of hepatic failure after partial hepatectomy, portal and peripheral serum human hepatocyte growth factor levels markedly increased and reached 9.31 ng/ml and 6.78 ng/ml 2 days before death, respectively. CONCLUSIONS: These results suggest that hepatocyte growth factor increases in portal serum via an endocrine mode after partial hepatectomy in humans. Furthermore, measurement of the portal and peripheral serum human hepatocyte growth factor levels may be useful for the clinical evaluation of patients with post-operative hepatic failure.

Magnetic resonance cholangiography in hepatolithiasis.

OBJECTIVES: Our objective was to examine the usefulness of magnetic resonance cholangiography in hepatolithiasis. METHODS: Ten patients with hepatolithiasis were studied by ultrasonography, computed tomography, direct cholangiography, and magnetic resonance cholangiography to detect stones and to determine the morphological features of the bile ducts. In nine patients who underwent surgery, dilation and stenosis of the bile ducts were confirmed by intraoperative cholangioscopy, pathology, or both. RESULTS: Stones were demonstrated in seven patients by ultrasonography, in eight by computed tomography, in seven by direct cholangiography, and in all by magnetic resonance cholangiography. The locations of stones were identified in four patients by ultrasonography, in seven by computed tomography, in six by direct cholangiography, and in nine by magnetic resonance cholangiography. Among nine patients with dilation of the bile ducts, the dilation was shown by ultrasonography in seven, by computed tomography in eight, by direct cholangiography in six, and by magnetic resonance cholangiography in eight. Among seven patients with stenosis of the bile ducts, this stenosis was shown by direct cholangiography in four and by magnetic resonance cholangiography in six. Ultrasonography and computed tomography did not show the stenosis. Sensitivity for detection of biliary stenosis was significantly higher in magnetic resonance cholangiography. CONCLUSIONS: This study shows that magnetic resonance cholangiography not only detects stones, but can also delineate detailed information on the bile ducts, which is useful in the planning of treatment for hepatolithiasis.

[Risk factors for gallbladder cancer in Chilean females].

A case-control study of gallbladder cancer was conducted with 90 Chilean cases registered at one hospital in Santiago city, Chile from January, 1992 to August, 1994. Controls were selected among outpatients of the hospital who received abdominal echography. Each case was assigned 2 age- and sex-matched controls; either with or without gallstone(s). Study subjects were all directly interviewed by well-trained medical students. The present study focused on 74 female pairs and the following findings were obtained: 1) Odds Ratio(OR)s were significantly high for education years less than or equal to 6, body mass index greater than or equal to 24.0, constipation, and consumption of egg, fried meals, green and red chili. Chili pepper consumption of both types in cases showed significantly elevated risks with higher frequency. 2) While high ORs were observed, biliary symptoms such as dyspepsia and past history of cholelithiasis were strongly involved with present gallstone(s) and may not be independent factors for gallbladder cancer. 3) Significantly low ORs were seen for past history of intestinal parasitosis and surgical operation, hormone therapy, all industrial workers and workers in clothes & textile industry. However results may be influenced by more years of education or recall bias. 4) When a conditional logistic model was applied and controls with gallstone(s) were taken as reference, those with the habit of constipation showed a significantly high risk of 2.10 (95% CI: 1.01-4.38), and the consumers of red chili with a frequency > or = 1 time/day had elevated risks of 2.16 (1.27-3.66) vs those < 1 time/day and 4.66 (1.63-13.40) vs non-consumers, respectively. From the above results, the occurrence of gallbladder cancer in Chilean females may be related to constipation and chili pepper consumption, based on the presence of gallstone(s). Further investigations are needed to elucidate whether these are actual risk factors or whether only a false association was detected.

Mirizzi syndrome caused by xanthogranulomatous cholecystitis: report of a case.

Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder. In severe cases, inflammation extends to adjacent structures, and XGC is sometimes confused with a malignant neoplasm. We recently diagnosed XGC as the preoperative cause of Mirizzi syndrome in a patient based on the clinical course. The patient was admitted because of obstructive jaundice, with gallbladder carcinoma as the suspected cause. The gallbladder was swollen with gallstones and the serum level of carbohydrate antigen 19-9 (CA19-9) was 3070 U/ml at admission. A percutaneous transhepatic cholangiodrainage (PTCD) was done, and the common hepatic duct as well as the right and left hepatic ducts were found to be obstructed. Later, the CA19-9 level and swelling of the gallbladder decreased and the obstruction of the bile ducts disappeared. A cholecystectomy was performed and the intraoperative pathohistological diagnosis of chronic cholecystitis was made from frozen sections. The pathohistological diagnosis of XGC was made from paraffin-embedded sections. Mirizzi syndrome such as that seen in our patient is a rare complication of XGC. XGC occasionally causes extensive inflammation; thus, performing a conventional cholecystectomy can be unsafe. However, in our opinion, a total, not subtotal, cholecystectomy should be done whenever possible because the incidence of gallbladder carcinoma accompanied with XGC is higher than that with ordinary cholecystitis or gallstones.