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Background Among infectious diseases, influenza is the most common cause of infection in Japan and worldwide. We aimed to evaluate the effect of influenza vaccination in kidney transplantation (KTx) recipients. Methods We retrospectively evaluated the records of 98 participants who underwent KTx at our institution between March 2009 and May 2016. All patients received tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone for maintenance immunosuppression after KTx. In accordance with the criteria of our institution, everolimus was administered for the maintenance of immunosuppression after KTx. We compared the rate of influenza infection during the 2016–2017 season (8 months, from October 2016-May 2017) between KTx patients treated with 1 or 2 doses of influenza vaccine (treatment group, n = 71) and KTx patients who did not receive a vaccine (nontreatment group, n = 27). Results Among patient characteristics, only the prevalence of diabetes mellitus differed significantly between the groups (treatment group: 9.9%, 7 of 71 patients; nontreatment group: 29.6%, 8 of 21 patients; P = .02). Influenza infection occurred at similar rates in the 2 groups (treatment group, 5.63% 4 of 71 patients; nontreatment group: 3.70%, 1 of 27 patients; P = .70). Conclusions Among KTx patients managed in our institution, treatment with 1 or 2 doses of influenza vaccine did not reduce the rate of influenza infection in the 2016–2017 season, suggesting that influenza vaccination may currently be ineffective in KTx patients.

Background In patients eligible for organ transplantation, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines specifically recommend avoiding red blood cell transfusions (RBCT) when possible to minimize the risk of allosensitization. Objective To assess the effect of perioperative RBCT on outcomes in living-related kidney transplantation (LRKT) recipients. Methods We retrospectively assessed 97 patients who underwent LRKT and whose data were evaluable at our institution between March 2009 and May 2016. We measured serum creatinine levels and calculated the estimated glomerular filtration rate (eGFR) at 3 months, 6 months, and 1 year after kidney transplantation (KTx). We evaluated the rejection rate within a year after KTx. We compared the renal function and rejection rate between those who received blood transfusions (n = 21) and those who did not (n = 76) during the perioperative period. Results Among patient characteristics, the rate of ABO-incompatible KTx and the mean hemoglobin levels before KTx differed significantly between the groups. The serum creatinine levels and eGFR within 1 year after KTx did not differ significantly between the two groups. The rejection rate in those who received blood transfusions and those who did not was 28.6% (6/21 patients) and 25.0% (19/76 patients) (P = .741), respectively. Conclusions We found that the rejection rate was slightly higher in patients who received perioperative RBCT than in those who did not, but the difference was not significant within a year after KTx. Perioperative RBCT may not affect renal function within a year after KTx.

This study revealed the time course of osteoporotic vertebral fracture by magnetic resonance imaging using a simple classification. Signal changes were associated with the compression degree and mobility of the fractured vertebral body. This classification showed sufficient reliability in categorizing magnetic resonance imaging findings of osteoporotic vertebral fractures. Magnetic resonance imaging (MRI) is useful in diagnosing osteoporotic vertebral fractures (OVFs). This study investigated the time course of OVFs by MRI using a simple classification. This multicenter cohort study was performed from 2012 to 2015. Consecutive patients with ≤2-week-old OVFs were enrolled in 11 institutions. MRI was performed at enrollment and at 1-, 3-, 6-, and 12-month follow-up. Signal changes on T1-weighted imaging (T1WI), T2WI, and short τ inversion recovery (STIR) were classified according to signal intensity. Height and angular motion of vertebral bodies were also measured. The 6-month follow-up was completed by 153 patients. At enrollment, fractured vertebrae signal changes were 43 % diffuse and 57 % confined low on T1WI; on T2WI, 56, 24, and 5 % were confined low, high, and diffuse low, respectively; on STIR, 100 % were high. On T1WI, diffuse low remained most common (90 % at 1 month and 60 % at 3 months) until 6 and 12 months, when most were confined low (54 and 52 %, respectively). On T2WI, confined low remained most common (decreasing to 41 % at 12 months). On STIR, high signal change was shown in 98, 87, and 64 % at 3, 6, and 12 months, respectively. At 3, 6, and 12 months, diffuse low signal change was associated with significantly lower vertebral height, and high signal change was associated with significantly greater angular motion. MRI signal changes were associated with the compression degree and angular motion of fractured vertebrae. This classification showed sufficient reliability in categorizing MRI findings of OVFs.

This study demonstrated the predictive values of radiological findings for delayed union after osteoporotic vertebral fractures (OVFs). High-signal changes on T2WI were useful findings.The purpose of the present study is to determine predictive radiological findings for delayed union by magnetic resonance imaging (MRI) and plain X-rays at two time points in the acute phase of OVFs.This multicenter cohort study was performed from 2012 to 2015. A total of 218 consecutive patients with OVFs ≤2 weeks old were enrolled. MRIs and plain X-rays were performed at the time of enrollment and at 1- and 6-month follow-ups. Signal changes on T1-weighted imaging (T1WI) were classified as diffuse low-, confined low-, or no-signal change; those on T2WI were classified as high (similar to the intensity of cerebrospinal fluid), confined low-, diffuse low-, or no-signal change. The angular motion of the fractured vertebral body was measured with X-rays.A total of 153 patients completed the 6-month follow-up. A high-signal change on T2WI was most useful in predicting delayed union. Sensitivity, specificity, and positive predictive values were 53.3, 87.8, and 51.6 % at enrollment and 65.5, 84.8, and 51.4 % at the 1-month follow-up, respectively. The positive predictive value increased to 62.5 % with observation of high- or diffuse low-signal changes at both enrollment and the 1-month follow-up. The cutoff value of vertebral motion was 5 degrees. Sensitivity and specificity at enrollment were 52.4 and 74.1 %, respectively.This study demonstrated the radiological factors predicting delayed union after an OVF. T2 high-signal changes showed the strongest association with delayed union. Consecutive MRIs were particularly useful as a differential tool to predict delayed union following OVFs.

Prediction of the timing of platelet recovery after chemotherapy and hematopoietic stem cell transplantation (HSCT) allows for optimal platelet transfusion. We assessed the clinical utility of the percentage value of the immature platelet fraction (IPF%) monitored using an XE-2100 automated hematology analyzer to predict the timing of platelet recovery after chemotherapy and HSCT. The IPF% was serially monitored in 31 patients with cancer who received 66 courses of chemotherapy and HSCT. In patients with cancer undergoing chemotherapy and HSCT, a transient increase in IPF% was observed 1-11 days prior to platelet recovery (>30 × 10⁹ /l). In patients undergoing chemotherapy with a peak IPF% >10%, platelet recovery occurred significantly earlier than in those with IPF% peak values ≤10% (median periods were 2 and 5 days; P 10% than in those with IPF% peak values ≤10% (median periods were 2 and 6 days). Thus, the IPF% peak value is a useful parameter for predicting the timing of platelet recovery after chemotherapy and HSCT and has the potential to facilitate optimal platelet transfusion.

Background: The effects of anti-hypertensive drugs on survival have not been examined in a large cohort of hemodialysis (HD) patients. Methods: We examined the relationship between blood pressure, anti-hypertensive drug therapy, and survival using the nationwide HD registry of the Japanese Society for Dialysis Therapy. Outcomes were confirmed using the coded ID numbers of the 2005 and 2006 registries. Logistic analyses were performed to determine the effect of anti-hypertensive drug therapy on survival. Results: A total of 163,668 patients (50.6% men; 31.5% with diabetes mellitus; mean age 63.6 years) on HD 3 times a week in 2005 were studied. Mean (SD) levels of systolic and diastolic blood pressure were 153.4 (24.1) and 78.7 (13.7) mm Hg, respectively, before the HD session. Two-thirds of the HD patients were prescribed anti-hypertensive drugs and the numbers of anti-hypertensive medications were: 1 in 26.8%, 2 in 24.4%, and 3 or more in 14.5% of the total patients. The 1-year mortality rate was 6.6% overall: 8.5% in patients not prescribed anti-hypertensive drugs and 5.6% among those prescribed anti-hypertensive drugs. The odds ratio (95% confidence interval) for the 1-year mortality rate was 0.724 (0.681–0.770, p < 0.0001) for patients prescribed anti-hypertensive drugs, after adjusting for age, sex, diabetes mellitus, body mass index, HD duration, serum albumin, and systolic blood pressure. Conclusion: Survival was better in patients prescribed anti-hypertensive drugs, particularly renin-angiotensin system inhibitors, than in those not prescribed anti-hypertensive drugs. The causality on this association remained to be determined and prospective studies on blood pressure target levels and the effects of anti-hypertensive drug class in HD patients are warranted.

Biogeochemical data from four sequential sediment traps deployed for one full year (April 1987–March 1988) at the shelf edge (200 m isobath) of the Canadian Beaufort Sea are presented. In addition, multi-traps and Kenney traps, which collect material suspended near the bottom, provided data from the inner shelf for short intervals in spring and summer. A novel aspect of this work is the discrimination of biogenic and terrigenous contributions to the total carbon using a relationship between terrigenous carbon and aluminum (Al). The vertical flux in the Beaufort Sea derives primarily from three sources: marine biological production, the Mackenzie River Plume, and coastal and seabed erosion. The material trapped at all shelf edge sites was predominantly biogenic and the seasonal fluxes of both biogenic and terrigenous matter varied with geographical location. In open-water conditions, deposition of terrigenous material can be attributed at various times and places to (1) transport by the Mackenzie Plume to the shelf edge during freshet; (2) resuspension of sediment during north-westerly gales; and (3) erosion of steep coastlines during south-easterly gales followed by northward transport. On the west side of the shelf, the biogenic and terrigenous fluxes were highest in summer and were primarily influenced by the Mackenzie River freshet, increased solar flux, available nutrients, sea ice break-up, and water column stability. On the east side of the shelf, biogenic and terrigenous fluxes were highest in the fall and the most important controlling factors were the extensive open water, intense resuspension events accompanying storms from the northwest, and the flow of the fresh, warm, turbid waters of Mackenzie River to the northeast. There was strong evidence of sediment transport in mid-water and bottom layers, but the mechanisms involved cannot be inferred from this study. Stable isotopes of carbon and nitrogen, C/N ratios, biogenic silica, and chlorophyll a measurements help to distinguish between marine autotrophic production and heterotrophic production, of which the latter appears to dominate in the fall and continue beneath the ice into the polar night. Al and iron correlate strongly and are primarily associated with the terrigenous fraction whereas calcium and phosphorus have both terrestrial and biogenic associations.

Objectives: Plasma-free amino acid (PFAA) profiles have been associated with a future risk of developing diabetes or cardiovascular disease in nondiabetic subjects. These PFAA alterations might predominantly result from the metabolic shift caused by insulin resistance and visceral fat deposition. The variety of PFAA profiles within diabetic subjects is not well researched. In this study, we focused on type 2 diabetic subjects and examined the association between PFAA profiles and insulin- and glucose-related variables. Methods: Fifty-one Japanese subjects diagnosed with type 2 diabetes were recruited from an outpatient clinic. The plasma concentrations of 21 amino acids; glucose-related markers including glucose, hemoglobin A1c (HbA1c), glycoalbumin and 1,5-anhydroglucitol; insulin-related markers including insulin, C-peptide, and the homeostasis model assessment of insulin resistance; and adipocytokines including adiponectin and leptin were determined. The association of PFAA and other metabolic profiles were analyzed, and stratified analyses of the PFAAs and clinical characteristics were performed according to the fasting plasma insulin and HbA1c levels. In addition, the PFAA indices that correlate to visceral fat obesity were evaluated. Results: Although strong correlations between PFAAs and glucose-related markers were not observed, several amino acids (branched-chain amino acids, tryptophan, alanine, tyrosine, glutamate and proline) and PFAA indices that evaluate visceral obesity were highly correlated with insulin-related markers and adiponectin (P Conclusions: The PFAA profiles in diabetic patients were strongly associated with hyperinsulinemia and hypoadiponectinemia, which might become risk evaluation factors for the development of cardiovascular diseases.

An extended time series of particle fluxes at 3800 m was recorded using automated sediment traps moored at Ocean Station Papa (OSP, 50°N, 145°W) in the northeast Pacific Ocean for more than a decade (1982–1993). Time-series observations at 200 and 1000 m, and short-term measurements using surface-tethered free-drifting sediment traps also were made intermittently. We present data for fluxes of total mass (dry weight), particulate organic carbon (POC), particulate organic nitrogen (PON), biogenic Si (BSi), and particulate inorganic carbon (PIC) in calcium carbonate. Mean monthly fluxes at 3800 m showed distinct seasonality with an annual minimum during winter months (December–March), and maximum during summer and fall (April–November). Fluxes of total mass, POC, PIC and BSi showed 4-, 10-, 7- and 5-fold increases between extreme months, respectively. Mean monthly fluxes of PIC often showed two plateaus, one in May–August dominated by 63 μm particles. Dominant components of the mass flux throughout the year were CaCO 3 and opal in equal amounts. The mean annual fluxes at 3800 m were 32±9 g dry weight g m −2 yr −1 , 1.1±0.5 g POC m −2 yr −1 , 0.15±0.07 g PON m −2 yr −1 , 5.9±2.0 g BSi m −2 yr −1 and 1.7±0.6 g PIC m −2 yr −1 . These biogenic fluxes clearly decreased with depth, and increased during “warm” years (1983 and 1987) of the El Nino, Southern Oscillation cycle (ENSO). Enhancement of annual mass flux rates to 3800 m was 49% in 1983 and 36% in 1987 above the decadal average, and was especially rich in biogenic Si. Biological events allowed estimates of sinking rates of detritus that range from 175 to 300 m d −1 , and demonstrate that, during periods of high productivity, particles sink quickly to deep ocean with less loss of organic components. Average POC flux into the deep ocean approximated the “canonical” 1% of the surface primary production.

We examined interannual variability in the 1965–1990 winter-summer differences in surface nitrate (ΔNO3) in the northeast subarctic Pacific Ocean (Station P, 50°N, 145°W). Increases in ΔNO3, of 30–70% above the mean value occurred during four events (1969, 1971-1972, 1979, 1983). The ΔNO3 time series was highly correlated (r = 0.86) with the spring-summer nitrate utilization rate from 1970 to 1980. The ΔNO3 time series was negatively correlated with the North Pacific index (NPI) (r = -0.72) and positively correlated with solar radiation in the spring (r = 0.48) and summer (r = 0.46). A simple ecosystem model forced with observed incident solar radiation and mixed-layer depth during the spring-summer period predicted increases in export production that were 50% of the observed increase for 1970–1972 and 1977–1979. Comparison between the ΔNO3 and sedimenting particulate organic nitrogen (PON) showed that the high ΔNO3 event of 1983 was associated with a dramatic increase in PON fluxes. A simple ecosystem model underpredicts observed interannual variations in export production, and this result combined with the observed PON fluxes suggests that a combination of increased phytoplankton production and increased f ratio produced the observed increase in ΔNO3. The increase in f-ratio implies a change in the community structure of the phytoplankton during the elevated ΔNO3 events that appears connected to changes in the NPI.

The effect of pravastatin, an inhibitor of p21ras isoprenylation, on hepatocarcinogenesis induced by N-nitrosomorpholine and on p21ras isoprenylation were investigated in male Sprague-Dawley rats. Rats received i.p. injections of pravastatin (10 and 20 mg kg(-1) body weight) every other day and, from the beginning of the experiment, were given drinking water containing N-nitrosomorpholine for 8 weeks. Visible white nodules and hepatic lesions staining positively for gamma-glutamyl transpeptidase or glutathione-S-transferase, placental type, were examined macroscopically or histochemically. In week 15, pravastatin at both dosages significantly reduced the incidence, number and volume of visible white nodules. Quantitative histological analysis also showed that prolonged administration of pravastatin at both dosages resulted in significant reductions in the number and percentage area of hepatic lesions positive for gamma-glutamyl transpeptidase and glutathione-S-transferase, placental type. Administration of pravastatin also significantly decreased the amount of membrane-associated p21ras in the tumour and the labelling index of neoplastic nodules and increased the apoptoic indices of neoplastic nodules. These findings indicate that pravastatin suppresses hepatocarcinogenesis and suggest that this effect might be related to pravastatin's inhibition of p21ras isoprenylation and its subsequent inhibition of cell proliferation and induction of apoptosis in neoplastic lesions. Images Figure 3 Figure 4 Figure 6 Figure 7 Figure 8

Background—An endoscopic procedure that uses a pH indicator called phenol red to assess Helicobacter pyloriinfected gastric mucosa has recently been developed. This test makes it possible to take biopsy specimens from H pylori infected areas.Aim—This test was applied to patients with early gastric cancers to clarify the role of H pylori in gastric carcinogenesis.Subjects—Sixty five patients with early gastric cancer (50 with differentiated adenocarcinoma and 15 with undifferentiated adenocarcinoma).Methods—Patients with early gastric cancer underwent the endoscopic phenol red test before their operation. In this test, areas infected with H pylori can be observed as “coloured” areas where phenol red was turned from yellow to red.Results—H pylori infection was significantly (p H pylori, but undifferentiated adenocarcinomas were frequently located in non-infected areas.Conclusion—H pylori may be a strong risk factor for differentiated early gastric cancer.

METHODS: Change in eGFR was estimated as % change from the first to last eGFR (CKD-EPI creatinine) in a 2-year baseline period. We modeled the hazard ratios (HRs) of subsequent mortality as a spline function of % change in eGFR after adjusting for age, sex, race, first eGFR, and co-morbid conditions. We used random effects meta-analyses to combine results stratified by first baseline eGFR (

Prediction of the timing of platelet recovery after chemotherapy and hematopoietic stem cell transplantation (HSCT) allows for optimal platelet transfusion. We assessed the clinical utility of the percentage value of the immature platelet fraction (IPF%) monitored using an XE-2100 automated hematology analyzer to predict the timing of platelet recovery after chemotherapy and HSCT. The IPF% was serially monitored in 31 patients with cancer who received 66 courses of chemotherapy and HSCT. In patients with cancer undergoing chemotherapy and HSCT, a transient increase in IPF% was observed 1-11 days prior to platelet recovery (30 × 10⁹ /l). In patients undergoing chemotherapy with a peak IPF%10%, platelet recovery occurred significantly earlier than in those with IPF% peak values ≤10% (median periods were 2 and 5 days; P0.05). Platelet recovery appears to occur earlier in patients undergoing HSCT with a peak IPF%10% than in those with IPF% peak values ≤10% (median periods were 2 and 6 days). Thus, the IPF% peak value is a useful parameter for predicting the timing of platelet recovery after chemotherapy and HSCT and has the potential to facilitate optimal platelet transfusion.

Summary Platelet number is often used as an indicator of the severity of liver disease. Although inadequate thrombopoietin production and decreased platelet production have been proposed as major causes of cirrhotic thrombocytopenia, the underlying mechanism has not yet been fully clarified. We examined whether the measurement of the immature platelet fraction (IPF) in thrombocytopenic patients with liver dysfunction is useful as a rapid and noninvasive method for the differential diagnosis of chronic liver diseases. We examined 20 liver cirrhosis patients, 56 patients with chronic hepatitis, 9 patients with fatty liver, and 86 patients without liver disease. The percentage value of IPF (IPF%) was measured using an XE-2100 multiparameter automatic hematology analyzer. Using a receiver operating characteristic curve, we found diagnostic significance of the absolute platelet count and the absolute number of the IPF between cirrhotic patients and noncirrhotic patients, and developed a powerful multivariate discriminant analysis (MDA) function based on the platelet count and the IPF%. The diagnostic accuracy obtained by the MDA function was superior to that obtained by the absolute number of platelets and the IPF. We therefore propose our IPF% measurement for the diagnosis of liver cirrhosis.

Evans syndrome is a rare autoimmune disorder with unknown aetiology. Although corticosteroids and/or intravenous immunoglobulin (IVIG) are commonly used in its treatment, no standard strategy has been established. We report here a 44-year-old male with refractory Evans syndrome combined with systemic lupus erythematosus (SLE) who responded well to rituximab. He was admitted to our hospital with severe bleeding caused by worsening of Evans syndrome. Despite treatment with a high-dose corticosteroid and IVIG, his thrombocytopaenia and haemolytic anaemia did not improve. We started rituximab at a dose of 375 mg/m(2) once a week for a total of two doses. There was significant improvement in his thrombocytopaenia and anaemia 1 month after administration of rituximab. Although the total immunoglobulin G (IgG) level did not change, the titres of platelet-associated IgG (PA-IgG) and of an indirect antiglobulin test (IAT) decreased under the treatment with rituximab. It is suggested that rituximab would be a powerful candidate in the treatment of refractory Evans syndrome by depleting abnormal clone-producing autoantibody.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever with serosal inflammation. FMF gene (MEFV) mutations have been identified primarily in patients from Mediterranean populations. Although several clinical cases have been reported in Japan, there have been few reports to date on mutation analysis. We studied FMF patients and their relatives to examine the clinical and genetic features of this disease in the Japanese population.Twelve Japanese FMF patients who met the Tel Hashomer criteria and a total of 17 relatives from 5 of 10 families underwent molecular genetic studies to detect MEFV mutations. The characteristics of these Japanese FMF patients and geno-phenotypical correlations were examined.Almost all of our patients had been suffering for a long time from fever of unknown origin and one patient also had systemic amyloidosis. In our 12 FMF patients, we detected the substitutions E84K, L110P, E148Q, R761H and M694I. We also newly diagnosed 2 relatives as having FMF based on clinical symptoms and the existence of FMF mutations. One patient was homozygous for E148Q, the patient with systemic amyloidosis was a homozygote for M694I and 4 patients from 3 families were compound heterozygotes for E148Q and M694I. Three patients in one family were compound heterozygotes for E148Q, L110P and M694I. There were 3 patients who were heterozygous for E84K, L110P-E148Q or M694I and had no other nucleotide changes in the exons of MEFV. On the other hand, 2 relatives who had never experienced symptoms of FMF were homozygous for L110P-E148Q as well as compound heterozygous for E148Q/E148Q-R761H. E148Q and M694I were the most frequently detected substitutions in our study.MEFV mutations occur in Japanese FMF patients though FMF is rare in Japan. The identification of MEFV mutations could be a reliable diagnostic test for FMF. The results of genetic analyses on 14 Japanese FMF patients in this study revealed that E148Q and M694I are frequent alleles.

Chronic kidney disease (CKD) is an important and leading cause of end-stage renal disease (ESRD) and moreover, plays a role in the morbidity and mortality due to cardiovascular disease, infection, and cancer. Anemia develops during the early stages of CKD and is common in patients with ESRD. Anemia is an important cause of left ventricular hypertrophy and congestive heart failure. Correction of anemia by erthyropoiesis-stimulating agent (ESA) has been shown to improve survival in patients with congestive heart failure. Anemia is counted as one of the non-conventional risk factors associated with CKD. Hypoxia is one of the common mechanisms of CKD progression. Treatment by ESA is expected to improve quality of life, survival, and prevent the CKD progression. Several clinical studies have shown the beneficial effects of anemia correction on renal outcomes. However, recent prospective trials both in ESRD and in CKD stages 3 and 4 failed to confirm the beneficial effects of correcting anemia on survival. Similarly, treatment of other risk factors such as hyperlipidemia by statin showed no improvement in the survival of dialysis patients. Given the high prevalence of anemia in ESRD and untoward effects of anemia in CKD stages 3 and 4, appropriate and timely intervention on renal anemia using ESA is required for practicing nephrologists and others involved in the care of high-risk population. Lessons from the recent studies are to correct renal anemia (hemoglobin10 g/dl not hemoglobinor =13 g/dl). Early intervention for renal anemia is a part of the treatment option in the prevention clinic. In this study, clinical significance of anemia management in patients with CKD is discussed.

To compare and contrast the gene expression of two LIM-homeobox type transcription factors, Lhx6 and L3/Lhx8, in secondary palate formation.In situ hybridization histochemistry with digoxygenin (DIG) labelled cRNA probes specific for Lhx6 and L3/Lhx8.Serial cryo-sections of embryonic day (E)13.5, 14.5, and 15.5 mice (C57BL/6).Comparison of the signal intensities of NBT/BCIP precipitate by alkaline phosphatase conjugated anti-DIG antibody.From E13.5 to E15.5, Lhx6 and L3/Lhx8 signals are detected in palatal mesenchyme, but the L3/Lhx8 signal is much more intense than the Lhx6 signal. In palatal epithelium, covering the mesenchyme, Lhx6 mRNA is transiently expressed at E14.5, while L3/Lhx8 mRNA expression is never detected throughout the development.Lhx6 and L3/Lhx8 functions may be partially redundant in the mesenchyme of the secondary palate, but not in the palatal epithelium.

Stroke is one of the leading causes of death in chronic dialysis patients. However, few epidemiological studies have reported on the demographics and long-term prognosis after stroke.We have observed the occurrence of stroke in the chronic dialysis population for the past 10 years in Okinawa, Japan. Definite cases of stroke were registered and categorized as cerebral haemorrhage (CB), cerebral infarction (CI), and subarachnoid hemorrhage (SAH).Among 3741 chronic dialysis patients (2073 men, 1668 women), 271 patients (164 men, 107 women) had strokes (CB 162, CI 97, SAH 12) at least once during the study period from 1 April 1988 to 31 March 1998. The total duration of observation was 15 pound 748.8 patient-years (males 8990.5, females 6758.3). The incidence of stroke per 1000 patient-years was 17.2 overall, 10.3 for CB, 6.2 for CI, and 0.8 for SAH. Twenty-four per cent of stroke cases occurred within 1 year of starting dialysis therapy, and 57.7% occurred within 5 years after the beginning of therapy. The mean (SD) age at onset of stroke was 59.8 (13.0) years overall, 57.2 (12.6) for CB, 65.0 (12.1) for CI, and 53.6 (13.0) years for SAH. The survival rates after stroke were 53.4% at 1 month, 43.5% at 6 months, 35.7% at 12 months, and 23.2% at 60 months. Patients with diabetes mellitus (DM) had higher incidence of CI and a poorer prognosis than those without DM.Incidence of stroke was high (17.2 per 1000 patient-years) in the dialysis population of our area and the long-term prognosis after stroke was poor.

Mortality from cardiovascular disease is high in chronic dialysis patients. We observed the occurrence of acute myocardial infarction (AMI) in the chronic dialysis population in Okinawa, Japan. A total of 3,741 chronic dialysis patients (2,073 men, 1,668 women) were followed up for 10 years from April 1, 1988, to March 31, 1998. Only definite cases of AMI were registered. Data were compared with AMI registry data obtained from the general population of the same district. The total duration of observation was 15,748.8 patient-years. During the study period, 61 patients (40 men, 21 women) had AMI. The incidence of AMI was 3.9/1,000 patient-years (men, 4.4/1,000 patient-years; women, 3.1/1,000 patient-years). Twenty-four percent of the AMI cases occurred at 12 months after starting dialysis therapy. Mean age at onset of AMI was 60.9 +/- 11. 4 (SD) years; 58.9 +/- 11.4 years in men and 64.7 +/- 10.7 years in women. Survival rates after AMI were 50.8% at 1 month, 45.0% at 6 months, 36.5% at 12 months, and 13.0% at 44 months. Patients with diabetes mellitus (DM) had a greater incidence of AMI and a worse prognosis than patients without DM. The long-term prognosis of AMI was poor in chronic dialysis patients.

We evaluated the usefulness of carcinoembryonic antigen (CEA) concentrations in colonic effluent as a high-risk marker for colorectal carcinoma (CRC). After 213 patients ingested 1,800 ml of a 5% isotonic solution of magnesium citrate, colonic effluent was collected from them before routine colonoscopy from February through June 1992. Of these patients, 27 who had undergone colonoscopy after a mean of 2.6 years were selected as subjects. The relationship between the CEA concentration in the colonic effluent and the occurrence of new colorectal tumors was examined. The CEA concentration in colonic effluent was adjusted on the basis of alkaline phosphatase activity. New colorectal tumors were noted significantly more frequently (P = .006) in patients with a high CEA level in colonic effluent (5 of 5; 100%) than in those with low a CEA level (6 of 22; 27%). The CEA concentration in colonic effluent is a simple and practical biomarker for identification of patients at high risk for CRC.

The effects of HGF on albumin gene expression in HepG2 human hepatoma cells and rat hepatocytes were investigated. HGF reduced the levels of albumin mRNA in HepG2 cells but the level was augmented in rat hepatocytes. By the transfection assay, HGF stimulated albumin promoter activity but repressed alpha-fetoprotein (AFP) enhancer activity regulating both AFP and albumin promoters in HepG2 cells. In contrast, HGF stimulated albumin promoter and AFP enhancer activities in rat hepatocytes. These results suggest that HGF elicits diverse responses of albumin gene expression in HepG2 cells and rat hepatocytes through the different biological actions on AFP enhancer in these cells.

To elucidate the effects of drug interactions on the urinary excretion of trientine in rats.Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brushborder membrane vesicles.Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide and furosemide, which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles.There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.

The effects of 1alpha-hydroxyvitamin D3[1alpha(OH)D3] and 1,25-dihydroxyvitamin D3[1,25(OH)2D3] on the incidence of colon tumors induced by azoxymethane and on the labeling index and angiogenesis of colon tumors were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 1alpha(OH)D3 and 1,25(OH)2D3 at lower and higher doses every other day for 45 weeks. Prolonged administration of both 1alpha(OH)D3 and 1,25(OH)2D3 at a higher dose significantly reduced the incidence of colon tumors in week 45. However, administration of 1alpha(OH)D3 or 1,25(OH)2D3 had little or no effect on the histologic type of colon tumors and cancers. Administration of 1alpha(OH)D3 and 1,25(OH)2D3 at higher doses significantly decreased the labeling index, the immuno-histochemical staining for vascular endothelial growth factor and microvessel counts in colon tumors. Our findings suggest that both 1alpha(OH)D3 and 1,25(OH)2D3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1alpha(OH)D3 and 1,25(OH)2D3 is the inhibition of angiogenesis as well as an anti-proliferative effect.

To elucidate the transport characteristics of the H+/dipeptide carrier that recognizes the orally active beta-lactam antibiotic ceftibuten, the uptake behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border membrane vesicles. The results show that 1) both the uptake of ceftibuten and that of Gly-Sar were dependent on an inwardly directed H+ gradient; 2) anionic compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even in the presence of 20 mM Gly-Sar. The results provide an evidence that several transporters with different features are potentially responsible for the uptake of beta-lactam antibiotics into the intestinal cells. It is suggested that the dianionic beta-lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H+-dependent transport systems for absorption.

Helicobacter pylori appears to play a major role in the development of gastric cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic effects of H. pylori has not been established. Ammonia, generated by urea from H. pylori, has been studied as a possible cause. However, the ammonia-monochloramine system has been shown to play a more important role in H. pylori-associated mucosal injury. Therefore, the effects of combined administration of monochloramine and methionine, singly or together, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without a subcutaneous injection of methionine, until the end of the experiment (week 52). Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers in week 52, whereas the concomitant administration of methionine with ammonium acetate and sodium hypochlorite significantly attenuated such enhanced gastric carcinogenesis. Spectrophotometric examination revealed that methionine scavenged monochloramine. Our findings suggest that H. pylori-associated gastric carcinogenesis may be mediated by monochloramine.

A patient with ABO blood group incompatibility who was treated by exchange transfusion is reported. A 63-year-old woman with blood group B type Rh (+) was accidentally transfused approximately 120 ml of A type Rh (+) packed red cells. She developed shock state, complaining chilliness, trepidation, nausea and vomiting just after the atypical blood transfusion. Fortunately, we could save her life without any complication by doing exchange transfusion in addition to anti-shock therapy and anticoagulant therapy preventing disseminated intravascular coagulation. The exchange transfusion was performed while monitoring central venous pressure. The total withdrawn blood reached 4300 ml, and 18 units of B type Rh (+) packed red cells, 10 units of AB type Rh (+) fresh frozen plasmas, 1250 ml of plasma protein fractions and 1750 ml of plasma expanders were infused with crystalloid fluid therapy. Although the amount of atypical blood transfusion to her was relatively small, it is considered that the exchange blood transfusion which seems to be only the fundamental therapy against atypical blood transfusion, took effect in saving her life without any complication.

The effect of body mass index (BMI) on the risk of developing end-stage renal disease (ESRD) has not been critically evaluated. To investigate this issue we used the registries of community-based mass screening and chronic dialysis programs. In 1983, a total of 101,516 subjects (47,901 men and 53,615 women) participated in a mass screening program in Okinawa, Japan. A total of 187 (101 men and 86 women) entered an ESRD program by March 31, 1994. Body mass index was calculated as weight in kilograms divided by the square of the height in meters. Subjects were categorized into six groups based on BMI:20.0, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, andor = 28.0 kg/m2. The cumulative incidence of ESRD, per 100,000 subjects was calculated in each BMI subgroup for men and women. In men, the cumulative incidence of ESRD increased with BMI, except in the range of 24.0 to 25.9 kg/m2. In women, the association between the cumulative incidence of ESRD and BMI was not clear, but was lowest in the range of 24.0 to 25.9 kg/m2. The adjusted odds ratio (95% confidence interval) was 0.99 (0.92 to 1.13) in men and 0.83 (0.72 to 0.96) in women.