Purpose Recently, a new enzyme immunoassay for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) has been reported. In this study, we proposed to account for feasibility of HBcrAg assay, and discuss the dynamics of HBV seen in patients following HBV-related living donor liver transplantation (LDLT).
Methods and results This study involved 12 patients; 11 patients had positive serum HBcrAg, and 6 patients had negative HBV-DNA. In the post-operation period, all cases were negative for HBV-DNA and HBsAg in sera under prophylaxis therapy. At post-operation, 5 of the 12 had positive serum HBcrAg, and at stable state, 6 had positive serum HBcrAg postoperatively. The mean levels of HBcrAg following LDLT were significantly lower than those seen in the preoperative-operation stage.
Conclusion This enzyme immunoassay is a readily utilizable marker of HBV replication in the post transplantation stage. Furthermore, the evaluation of HBV activity by HBcrAg assay must be studied to determine the appropriate prophylaxis for controlling replication of HBV following LDLT.

View full abstract

Aim Hepatocyte apoptosis is involved in the pathogenesis of liver diseases, while at the same time oxidative stress plays an important role in liver cell damage. This prompted us to evaluate the possible relationship between hepatocyte apoptosis and oxidative stress in patients with chronic hepatitis B.
Methods CHB patients were placed in groups A (ALT >40 IU/L) and B (ALT ≤40 IU/L). Healthy controls were considered as group C (all ALT ≤40 IU/L). Serum concentrations of α-tocopherol, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were determined and liver cell apoptosis was evaluated by using terminal deoxynucleotydil transferase-mediated d-UTP biotin nick-end labeling (TUNEL).
Results SOD, GSH-Px, and MDA did not differ between groups. α-Tocopherol was significantly decreased in groups A (p<0.01) and B (p<0.05) when compared with group C and it was negatively correlated with the apoptosis index (r=-0.575, p<0.01).
Conclusion Only the plasma concentration of α-tocopherol rather than the other oxidative stress markers changed significantly in patients with normal alanine aminotransferase levels (ALT <40 IU/L) when compared with healthy controls and correlated significantly with the apoptosis index, suggesting that α-tocopherol may be a possible marker to reflect liver cell damage, especially in the absence of serum aminotransferase elevation.

View full abstract

Objective To investigate the relationship between serum bilirubin and carotid atherosclerosis in patients with hypertension.
Patients and Methods Carotid artery ultrasonography was performed in 198 patients (104 males, average age of 65.6±7.1 years) with hypertension. Serum levels of bilirubin and C-reactive proteins (CRP) were measured at the same time.
Results Carotid atherosclerosis was detected in 133 patients, 87 of them had carotid artery plaque. The prevalence of stroke (20.3%) and myocardial infarction (13.5%) in the atherosclerosis group was higher than in the non-atherosclerosis group (9.2% and 6.2%, respectively, p<0.05). The average total serum bilirubin in the atherosclerosis group was lower than in the non-atherosclerosis group (12.8±1.3 vs 16.8±1.5 μmol/L, p<0.01), whereas the average serum of CRP was higher (4.1±1.1 vs 2.3±0.7 mg/L, p<0.01). After adjusting other factors such as age, total cholesterol, diabetes and systolic blood pressure, total serum bilirubin was negatively associated with carotid atherosclerosis in women and men, with odds ratios of 0.49 (95% CI, 0.28 to 0.71; p<0.01) and 0.66 (95% CI, 0.46 to 0.80; p<0.01). Serum CRP was positively correlated to carotid atherosclerosis, with odds ratios of 1.76 (95% CI, 1.36 to 2.04; p<0.01) in women and 1.95 (95% CI, 1.46 to 2.82; p<0.01) in men.
Conclusion Carotid atherosclerosis was associated with a high prevalence of stroke or myocardial infarction in hypertensive patients. Serum bilirubin was negatively associated with carotid atherosclerosis.

View full abstract

Background and Purpose We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in patients with acute ischemic stroke.
Methods We prospectively enrolled 335 consecutive patients (125 females; mean age, 72.3 years) with acute ischemic stroke within 24 hours of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization; and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis.
Results Death was observed in 20 (6.0%) patients. Frequencies of atrial fibrillation, cardioembolism, the use of diuretics before ischemic stroke, the use of digitalis before ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score on admission, glucose level, and D-dimer were significantly higher in the deceased group than in the survival group. On the other hand, albumin was significantly lower in the deceased group than in the survival group. The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (731.5±1,070.9 vs. 213.1±384.5 pg/mL, p=0.001). The optimal cut-off level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 240 pg/mL, 75.0% and 73.0%, respectively. Multivariate logistic regression analysis demonstrated that a NIHSS score of >13 (odds ratio [OR], 4.87; 95% confidence interval, 1.54 to 15.44, p=0.007) and plasma BNP level of >240 pg/mL (OR, 4.67; 95% confidence interval, 1.28 to 17.09, p=0.020) were independent factors associated with in-hospital death.
Conclusion The plasma BNP level on admission can predict in-hospital death in patients with acute ischemic stroke.

View full abstract

Objective LDL cholesterol is not usually considered as a component of metabolic syndrome (MetS) but rather it is associated with MetS components.
Methods Data from 2,449 men and 1,448 women were examined using receiver operating characteristic (ROC) curve for diagnosing MetS and correlation coefficients.
Results Blood levels of LDL cholesterol increased more steeply in women than in men as the number of MetS components increased. The area under ROC curve (AUC) and its 95% confidence interval (CI) of LDL cholesterol for diagnosing MetS were 0.57 and 0.53-0.60 in men and 0.66 and 0.61-0.71 in women. The optimal cut-off point (sensitivity; specificity) of LDL cholesterol was 127 mg/dL (0.50; 0.60) in men and 125 mg/dL (0.64; 0.61) in women. Correlations between LDL cholesterol and systolic blood pressure, diastolic blood pressure, gamma glutamyltransferase, and hemoglobin A1c were stronger in women than in men even after adjustment for age. The correlation between LDL cholesterol and blood pressure was significant in women, but not in men, even after adjusting for age.
Conclusion LDL cholesterol was more strongly associated with MetS in Japanese women than in men. The correlation between LDL cholesterol and blood pressure was significant in women, but not in men.

View full abstract

Objective The loss of podocytes has been reported to have a role in the onset and progression of diabetic nephropathy (DN). Although structural changes such as podocyte hypertrophy are considered to be associated with podocyte loss, the relationship has not been thoroughly investigated using human DN renal tissues.
Methods The subjects were 17 patients with DN diagnosed histopathologically by renal biopsy. Immunostaining was performed with antibodies for Wilm's tumor 1 (WT1) and synaptopodin (SPD), which are markers of podocytes, to determine the number of podocytes and assess podocyte hypertrophy.
Results The number of podocytes was decreased in DN patients compared with the controls. An inverse correlation was observed between the number of podocytes and both the urinary protein excretion and the extent of mesangial expansion. Podocyte hypertrophy was also more marked in DN patients compared with controls.
Conclusion Based on these results, podocyte loss and hypertrophy were suggested to be involved in the development and progression of human DN.

View full abstract

Objective To investigate the relationship between homeostasis model assessment for insulin resistance (HOMA-R) and urinary albumin excretion in Japanese and clarify gender difference in albuminuria-related insulin resistance.
Methods The subject group consisted of 752 Japanese who had no history of diabetes, hypertension or dyslipidemia. After anthropometric examination, fasting blood samples were obtained to determine plasma glucose (FPG), lipids and HOMA-R. The urinary excretion of albumin in the first void urine was expressed as the creatinine ratio (ACR, mg/gCr). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the formula for Japanese.
Results HOMA-R showed a significant correlation with ACR, and the correlation between HOMA-R and ACR was evident in the subjects with central obesity, whereas no significant correlation was found in the non-obese subjects. There was no correlation between HOMA-R and eGFR. HOMA-R increased according to the quintile of ACR and followed a significant trend. This association was obvious in males; however, in females there was no significant trend. Multiple regression analysis revealed that HOMA-R showed a significant correlation with age, waist circumference, blood pressure and serum triglyceride. In addition, ACR exhibited an independent association with HOMA-R. The association of HOMA-R and ACR was observed only in males, and was not present in females.
Conclusion Microalbuminuria is associated with insulin resistance in Japanese, where central obesity might play an essential role. This association is gender-specific suggesting the involvement of sex hormones in the pathogenesis of albuminuria-related insulin resistance.

View full abstract

Objective The progression of myelodysplastic syndrome to acute myeloid leukemia (MDS/AML) is generally incurable and its prognosis is extremely poor. It is important to determine the predictive factors of response and survival in diseases treated with chemotherapy.
Methods Twenty-nine patients who had been diagnosed of MDS/AML and had undergone chemotherapy between April 2001 and March 2008 were retrospectively analyzed.
Results Of the 29 patients, 21 patients had an abnormal karyotype. Among them, 13 had complex type abnormalities and/or monosomy 7. Twenty-four patients were administered a low-dose AraC containing regimen and 5 received an AML-like regimen as the initial chemotherapy. The responses were CR4/PR2/NR23. The response rate (RR) in the patients with a normal karyotype was significantly better than in those with an abnormal karyotype (62.5% vs. 4.8%, p=0.003). Univariate analyses showed that the hemoglobin level and cytogenetic abnormalities were factors that contributed to the overall survival.
Conclusion In MDS/AML, patients with a normal karyotype tended to have a better response to chemotherapy. The hemoglobin level and cytogenetic abnormalities were significant factors affecting the overall survival.

View full abstract

Objective Prediction of the prognosis of comatose survivors after cardiopulmonary arrest (CPA), so-called post-resuscitation encephalopathy (PRE), relies on neurological examination findings. Early laboratory indicators of poor prognosis (vegetative state/death) are not sensitive enough.
Methods We analyzed the results of magnetic resonance (MR) imaging with fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) in 22 consecutive patients with PRE. Clinical details such as arrest place and anoxia time along with neurological examination findings including items of Glasgow coma scale (GCS) and the Full Outline of UnResponsiveness (FOUR) score were determined. Receiver Operator Characteristics (ROC) curves were produced to determine prognostic yield of the parameters studied.
Results Prognosis was classified as 'poor' (Glasgow-Pittsburg Cerebral Performance —CPC-score 4 or 5) in 16 and 'better' (CPC score 1-3) in 6 patients. The lower limit of confidence interval (CI) of the area under the curve (AUC) of the ROC was higher than 0.5 for visual, motor and total scores of GCS and FOUR score. Presence of a lesion pattern of multilobar, or diffuse, cortical involvement, termed as "extensive cortical lesion pattern" in MR imaging was a very good predictor of poor prognosis with an AUC of ROC of 0,937. Sensitivity of GCS motor part score and MR was 87.5% (95% CI: 61.6%-92.6%). Motor part of the FOUR score has a slightly lower sensitivity (68.7% with 95% CI from 41.4% to 88.9%). Incorporating of MR to the motor scores (either GCS or FOUR score) improved sensitivity to 100 % (95% CI: 79.2%-100%). AUC of the ROC was 1.000 (95%CI: 0.844-1.000) for the combination of MR and GCS motor score.
Conclusion This study provides the preliminary evidence that MRI, when used in conjunction with a neurological examination, may have potential in terms of predicting outcome in patients with PRE.

View full abstract

N,N-dimethylformamide (DMF) is a solvent used extensively in the chemical industry. The main toxic effect reported after exposure to DMF is hepatotoxicity. We encountered four patients with liver injury due to DMF exposure; the severity of the liver injury was related to the exposure levels. After removal of exposure, all patients recovered without specific treatment. A careful evaluation of occupational history is necessary when liver dysfunction develops in industrial workers.

View full abstract

We report a 47-year-old man with cancer of unknown primary site in whom pancreatic cancer was confirmed at autopsy. Although a primary lesion was not confirmed, we planned to perform tumor marker-oriented chemotherapy because pancreatic cancer was suspected as the primary lesion based on tumor markers and pathological findings from metastatic lymph node. Neither S-1 nor gemcitabine was effective. However, gemcitabine combined with low-dose cisplatin therapy resulted in a marked decrease in the size of tumors. Microscopic examination at autopsy revealed poorly differentiated adenocarcinoma in the pancreatic head, although a pancreatic mass was not clear macroscopically.

View full abstract

An 80-year-old man presented with acute abdominal pain and hematemesis. He had a history of gastrojejunostomy 55 years previously. Ultrasonography (US) showed intragastric tublar images with peristalsis. Enhanced computed tomography (CT) demonstrated a dilated stomach with an intragastric filling by bowel loops suggestive of jejunogastric intussusception (JGI). Reduction of the JGI was immediately performed without resection of the intussuscepted intestine, and the patient was well postoperatively.
JGI is a rare life-threatening complication after gastric surgery. This complication may occur even 55 years after gastric surgery, and preoperative diagnosis is possible by US and CT findings.

View full abstract

We present a case of small pancreatic head cancer with pancreas divisum preoperatively diagnosed by pancreatic juice cytology. A 60-year-old woman was referred to our hospital for evaluation of a dilated main pancreatic duct (MPD). A small and poorly reproducible low-echoic lesion in the pancreas was suspected by ultrasonography (US) and endoscopic ultrasonography (EUS). Magnetic resonance cholangiopancreatography (MRCP) failed to visualize the ventral pancreatic duct, and the upstream dorsal pancreatic duct was dilated. Endoscopic retrograde cholangiopancreatography (ERCP) was indicative of pancreas divisum, and complete obstruction of the MPD in the pancreatic head was seen. Cytology of pancreatic juice obtained from the dorsal pancreas after minor papilla sphincterotomy revealed the presence of adenocarcinoma cells. Pancreatoduodenectomy was performed under the diagnosis of pancreatic head cancer with pancreas divisum. Histological examination revealed moderately-differentiated tubular adenocarcinoma 20 mm in diameter, located in the pancreatic head. Dilatation of the dorsal pancreatic duct is sometimes observed in cases with pancreas divisum without the presence of tumors. When pancreatic duct stenosis also exists in such cases, even if a tumor is not clearly visualized by diagnostic imaging, vigorous examinations such as pancreatic juice cytology are recommended to establish an accurate diagnosis.

View full abstract

Irritable urological symptoms with gross hematuria and bilateral lumbar pain developed when the patient received penicillin G for endocarditis. These symptoms were followed by renal insufficiency. A contrast-enhanced abdominal computed tomography (CT) scan revealed a thickened bladder wall, bilateral hydroureter and hydronephrosis, suggesting hemorrhagic cystitis complicated with urinary tract obstruction. Urine culture was negative. After discontinuation of penicillin G, all symptoms subsided and renal function recovered; hence, penicillin G seems to have been associated with hemorrhagic cystitis and acute kidney injury. Positive findings in the drug lymphocyte stimulation test (DLST) for penicillin G were consistent with this diagnosis.

View full abstract

Hyperparathyroidism is a rare cause of pancreatic inflammatory disease, however their causal relationship has been widely accepted. The appropriate therapy is less clear when patients with hyperparathyroidism-associated pancreatitis develop complications such as pseudocysts. We describe a 51-year-old woman with primary hyperparathyroidism who developed pancreatic pseudocysts extending into the mediastinum. After the correction of hyperparathyroidism by removal of a parathyroid adenoma, the pseudocysts were resolved and no additional treatment was necessary. In patients with primary hyperparathyroidism who develop uncomplicated pancreatic pseudocysts, surgical correction of primary hyperparathyroidism may precede the interventional treatment on the pancreas when possible.

View full abstract

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), such as gefitinib or erlotinib, is mainly metabolized in liver. To date, the safety data on administrating EGFR-TKI to patients with liver dysfunction is quite limited. Here, we administered gefitinib to two adenocarcinoma patients with liver cirrhosis, and one patient with EGFR gene mutation in exon 21 achieved long stable disease (SD) without any toxicity. Pharmacokinetic data of alternate days administration in these patients were similar to those of daily administration in patients with normal liver function. Although further studies are needed, a reduced dose of gefitinib might be feasible for patients with liver dysfunction.

View full abstract

Klinefelter's syndrome (KS) is a common cause of man infertility characterized by small testes, gynecomastia and hypogonadism. Deep vein thrombosis and thomboembolic events are frequent in these patients. Hormone imbalance and co-existent mutations in the coagulation system may be the primary factors in this hypercoagulable state. The increased thromboembolic risk in hypogonadic men has been explained by hypofibrinolysis due to androgen deficiency. Regarding the association between KS and congenital and acquired thrombophilias, to date, only three cases have been. Here, we present the youngest KS case with pulmonary thromboembolism with the heterozygous mutations in factor V Leiden and prothrombin genes, as detected by further tests. He had the previous diagnosis of diabetes mellitus and body mass index was 30 kg/m². Our report discusses the prothrombotic state in KS patients, with other possible causes for the young presentation and the importance of necessary tests in emergency service admissions with embolism.

View full abstract

An 80-year-old woman was referred to our hospital because of eosinophilia and thrombocytopenia. She presented with persistent pruritus and cough. Laboratory examinations showed persistent eosinophilia, and there was no underlying cause, consistent with hypereosinophilic syndrome (HES). After admission, she developed a neurological deficit, and microangiopathic hemolytic anemia. She was diagnosed with thrombotic thrombocytopenic purpura (TTP) and successfully treated with corticosteroids and plasmapheresis. Although TTP has been described in association with pregnancy, cancer, collagen diseases, infection, and drug intake, hypereosinophilia is not a well-documented cause of this disorder. To our knowledge, this is only the second case of TTP with HES, proved to be caused by ADAMTS13 inhibitor.

View full abstract

Although all-trans retinoic acid (ATRA) is widely used in acute promyelocytic leukemia (APL), there is little data as to whether or not ATRA is useful for patients with liver and renal failure. A 63-year-old APL patient, complicated by Child-Pugh class A liver cirrhosis and chronic renal failure (creatinine 3.2 mg/dL), was successfully treated with 45 mg/m²/day of ATRA. With three courses of chemotherapy, complete remission has been maintained for four years in this patient. Serum trough and maximum ATRA concentration, and the area under the curve (AUC) were not elevated. These observations suggest that full-dose ATRA therapy might be safely applicable to such a complicated case with APL.

View full abstract

A 53-year-old man was admitted with pancytopenia, fever and splenomegaly. Biochemistry showed increased ferritin levels. Bone marrow examination revealed increased erythrocytic precursors (94.9%) and active hemophagocytosis. Pure erythroid leukemia with hemophagocytic syndrome (HPS) was diagnosed. Induction chemotherapy comprising idarubicin and cytarabine was administered and steroid pulse therapy was added. Complete remission was attained, and HPS also improved. However, leukemia relapsed during chemotherapy and the patient died. This is the first report of pure erythroid leukemia complicated with HPS.

View full abstract

We report a patient that presented with the corticobasal syndrome (CBS), including progressive dementia, asymmetric parkinsonism associated with constructional and ideomotor apraxia, action myoclonus and focal hand dystonia. Magnetic resonance imaging of the brain revealed extensive ischemic lesions in both fronto-temporo-parieto-occipital lobes and steno-occlusion of the middle cerebral arteries, bilaterally. This case illustrates that extensive cortical vascular-ischemic lesions may present with symptoms mimicking the corticobasal syndrome.

View full abstract

A 59-year-old woman suffered from sudden onset of severe neck and back pain. She experienced right-side hemiparesis. Although the right-side hemiparesis soon disappeared, left-side hemiparesis developed. MRI of the brain was unremarkable. MRI of the cervical spine demonstrated hematoma in the left posterior epidural space at the C2/3 level. The spinal cord was compressed not only by a degenerative disc of the ventral region, but also by hematomas of the dorsal region. The unusual hemiparesis alternating from right-side to left-side in this case may have been caused by various factors, including cervical canal stenosis, the spread of hematoma, disturbance of blood flow, and distribution of stress and strain.

View full abstract

A 56-year-old previously healthy man was admitted to our hospital for disordered consciousness, anuria, and severe jaundice. The patient had not travelled recently, but he worked at a fish market in Tokyo. From his history and clinical observation we suspected Weil's disease and started the corresponding treatment. Leptospira infection was ultimately confirmed by a serological study. Our report raises the awareness that leptospirosis is not only a tropic disease, but also it can be a disease in an urban setting in Japan for people who are at risk of exposure.

View full abstract