Hideo Koh

Cigarette Smoking and the Association with Glomerular Hyperfiltration and Proteinuria in Healthy Middle-Aged Men

BACKGROUND AND OBJECTIVES Glomerular hyperfiltration and albuminuria accompanied by early-stage diabetic kidney disease predict future renal failure. Cigarette smoking has reported to be associated with elevated GFR in cross-sectional studies and with renal deterioration in longitudinal studies. The degree of glomerular hyperfiltration and proteinuria associated with smoking, which presumably is a phenomenon of early renal damage, has not been investigated in a satisfying manner so far. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 10,118 Japanese men aged 40 to 55 years without proteinuria or renal dysfunction at entry. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was defined as estimated GFR ≥117.0 ml/min per 1.73 m(2), which was the upper 2.5th percentile value of estimated GFR in the total population. Proteinuria was detected using standard dipstick. RESULTS During the 6-year observation period, there were 449 incident cases of glomerular hyperfiltration and 1653 cases of proteinuria. Current smokers had a 1.32-time higher risk for the development of glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than nonsmokers after adjustment for baseline age, body mass index, systolic and diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular leisure-time physical activity, and estimated GFR. Both daily and cumulative cigarette consumption were associated with an increased risk for glomerular hyperfiltration and proteinuria in a dose-response manner. CONCLUSIONS In middle-aged Japanese men, smoking was associated with an increased risk of glomerular hyperfiltration and dipstick proteinuria. Of importance, past smokers did not exhibit any increased risk for these conditions.

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma

BackgroundRecently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.MethodsWe retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.ResultsA multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.ConclusionOur data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.

Different immunoprofiles in patients with chronic myeloid leukemia treated with imatinib, nilotinib or dasatinib

Abstract Immunomodulation induced by dasatinib is reportedly related to better prognosis in chronic myeloid leukemia (CML). However, the underlying mechanism has not yet been fully elucidated. The immunoprofiles of 63 patients in the chronic phase of CML were evaluated during treatment with a tyrosine kinase inhibitor (imatinib, n = 36; nilotinib, n = 9; dasatinib, n = 18). The numbers of CD56 + CD57 + and CD3 + CD57 + cells increased significantly in the dasatinib group. The numbers of regulatory T-cells were comparable among the three groups. Dasatinib markedly enhanced natural killer (NK)-cell reactivity. Only one patient treated with dasatinib showed a slight cytomegalovirus (CMV) reactivation. In contrast, nilotinib suppressed NK-cell reactivity. Plasma levels of interleukin-8 (IL-8), interferon-γ inducible protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all three groups, and plasma levels of granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly elevated in the imatinib and dasatinib groups. Our results suggest the presence of a mechanism for dasatinib-associated immunomodulatory effects that is distinct from CMV reactivation and a decreased number of regulatory T-cells.

Relationship between drinking patterns and the risk of type 2 diabetes: the Kansai Healthcare Study

Background Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed. Methods Study participants included 10 631 Japanese men aged 40–55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was ≥7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires. Results During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4–7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1–2.0 or 2.1–4.0 US standard drinks per drinking day on 4–7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers. Conclusions More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4–7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers.

Serum levels of albumin-amyloid beta complexes are decreased in Alzheimer's disease

Decreased amyloid β (Aβ) clearance from the brain to blood might play a key role in the development of Alzheimers disease (AD). Aβ is normally bound to and transported by albumin in blood, thus possibly maintaining constant concentration of free Aβ in the blood. We therefore hypothesized that decreased blood levels of albumin‐Aβ complexes could be associated with decreased Aβ removal from the brain to blood, resulting in Aβ accumulation in the brain.

Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study

Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35–5.16) for tertile 2, and 5.08 (2.48–10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men.

Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation.

Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100–452 and 95–153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.

Dasatinib maintenance therapy after allogeneic hematopoietic stem cell transplantation for an isolated central nervous system blast crisis in chronic myelogenous leukemia.

A 22-year-old male with Ph-positive chronic myelogenous leukemia (CML) was started on treatment with imatinib. After 12 months of therapy, he achieved a complete cytogenetic response (CCyR). Although the CCyR persisted in his bone marrow, he developed an isolated CML blast crisis in his central nervous system (CNS) after 29 months of therapy. He underwent allogeneic hematopoietic stem cell transplantation (HSCT) following combination therapy with dasatinib, intrathecal chemotherapy and cranial irradiation. Subsequently, 168 days after allogeneic HSCT, he was started on dasatinib maintenance therapy to prevent a CNS relapse. Thirty-eight months after allogeneic HSCT, he has sustained a complete molecular response in both bone marrow and CNS. We believe dasatinib has the potential to prevent CNS relapse if used for maintenance therapy after allogeneic HSCT.

Serum butyrylcholinesterase and the risk of future type 2 diabetes: the Kansai Healthcare Study

Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross‐sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes.

Fatal BK virus pneumonia following stem cell transplantation

We report the case of a 39‐year‐old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV‐associated late‐onset hemorrhagic cystitis (HC) with long‐term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late‐onset HC, but BKV‐associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients.