Takaharu Matsuda

Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure

Background/Aim: Intima media thickness (IMT) and stiffness of the carotid arteries is related to coronary artery disease, and chronic renal failure patients are at high risk for such diseases. An oral adsorbent, AST-120 (Kremezin; Kureha Chemical Industry, Tokyo, Japan), can delay the progression of chronic renal failure in undialyzed uremic patients. The aim of the present study was to determine whether AST-120 affects carotid artery IMT and pulse wave velocity (PWV) in patients with chronic renal failure not undergoing dialysis. Methods: Fifty patients with non-diabetic chronic renal failure were randomly divided into two groups: 30 patients (18 men and 12 women; mean age 53.5 years; mean serum creatinine 3.2 mg/dl) who were given AST-120 (6.0 g/day) and 20 patients (12 men and 8 women; mean age 52.0 years; mean serum creatinine 3.5 mg/dl) who were not given AST-120. Thirty healthy age-matched subjects (18 men and 12 women; mean age 51.5 years; mean serum creatinine 0.9 mg/dl) were also included. The treatment period was 24 months. IMT and arterial stiffness were measured before and after treatment. Results: The slope of the reciprocal serum creatinine concentration over time became significantly less steep in the AST-120 group than in the non-AST-120 group (p < 0.001). Before treatment, carotid artery IMT differed little between the AST-120 group (0.90 ± 0.22 mm) and the non-AST-120 group (0.88 ± 0.20 mm). IMT in these two groups was significantly greater than IMT in the control group (0.64 ± 0.14 mm) (p < 0.01). Carotid IMT in the AST-120 group decreased slightly but not significantly to 0.84 ± 0.20 mm after 12 months and then significantly after 24 months to 0.78 ± 0.18 mm (p < 0.05). Carotid IMT in the non-AST group showed little change throughout the experimental period. PWV differed little between the AST-120 group (1,980 ± 330 cm/s) and the non-AST group (1,940 ± 360 cm/s) before treatment. PWV values in these two groups were significantly greater than PWV in the control group (1,280 ± 240 cm/s) (p < 0.01). After 12 and 24 months, PWV in the AST-120 group decreased significantly to 1,840 ± 280 cm/s (p < 0.05) and to 1,780 ± 260 cm/s (p < 0.05), respectively; however, PWV in the non-AST group showed a slight increase during the experimental period. Conclusion: The data suggest that AST-120 may reduce arterial stiffness and IMT in non-diabetic chronic renal failure patients before dialysis.

Histopathologic characteristics of autoimmune pancreatitis based on comparison with chronic pancreatitis.

Objectives: To clarify the histopathologic characteristics of autoimmune pancreatitis (AIP), based on comparison with both chronic alcoholic pancreatitis (CAP) and chronic obstructive pancreatitis (COP). Methods: Three AIP patients, 17 CAP patients, and 19 COP patients were studied histopathologically. Results: There was a dense lymphoplasmacytic infiltrate, especially within and around the pancreatic ducts, and fibrosis associated with AIP, while there was fibrosis accompanied by mild inflammatory infiltration in both CAP and COP. Inter- and intralobular fibrosis admixed with acinar atrophy was observed in both AIP and COP, while interlobular fibrosis combined with a “cirrhosis-like” appearance was found in CAP. Obliterative phlebitis was found in AIP, while thrombosis of the splenic vein was exhibited in CAP. Conclusion: Autoimmune pancreatitis was histologically characterized by dense lymphoplasmacytic infiltrate combined with fibrosis, acinar atrophy, obliterative phlebitis, and ductal involvement.

Case of combined adrenal cortical adenoma and myelolipoma

We report a case of myelolipoma 10u2003mm in size within a functional cortical adenoma that was 33u2003×u200322u2003×u200317u2003mm in size. A 29‐year‐old woman was referred to hospital for transient hypertension. A right adrenal tumor was detected by computed tomography (CT) scan and magnetic resonance imaging (MRI). Her cortisol levels indicated a loss of the normal diurnal pattern, and urinary 17‐hydroxycorticosteroids was elevated. She underwent a right adrenalectomy under the diagnosis of adrenal adenoma with Cushings syndrome. The tumor was fairly well encapsulated by a thin layer of connective tissue. The major tumor portion was composed of two distinct cell types, clear cells and eosinophilic cells, arranged in an alveolar structure. These findings were representative of cortical adenoma. The adrenal cortical adenoma centrally included well‐demarcated adipose tissue admixed with scattered islands of myelopoietic elements: erythroblasts, myeloid cell series and lymphocytic cells, which was eventually recognized as myelolipoma. Recently, adrenal myelolipoma has commonly been found because of the ease of detecting it as an incidentaloma by CT scan or MRI. However, the present adrenal myelolipoma case is uncommon because it is combined with a functioning cortical adenoma. Only six similar cases have previously been reported in English and Japanese publications. Furthermore, in the present case, the myelolipoma formed a tumor nodule, and to our knowledge, this is the first reported case of a radiographically recognizable tumor nodule. We discuss the etiology of myelolipoma and suggest that myelolipoma can develop in the course of endocrine hyperfunction.

Effect of polymyxin B-immobilized fiber on bone resorption in patients with sepsis

ObjectiveTo analyze the effects of polymyxin B-immobilized fiber (PMX-F) on bone resorption in septic patients.Design and settingObservational prospective study in intensive care units of a general hospital.Patients and participants25 patients with severe sepsis and 20 healthy controls.Measurements and resultsSeptic patients were randomly assigned to two groups: PMX-F treatment group (n=15) and conventional treatment group (n=10). Total pyridinium crosslink pyridinoline (PYD) and deoxypyridinoline (DPD) in urine were determined by modified high-performance liquid chromatography. Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products to urinary creatinine (NOx/Cr). Plasma endotoxin levels were determined by endospecy test. The blood albumin, ionized calcium, and parathyroid hormone were also measured. PMX-F treatment was performed twice separated by 24xa0h. Urinary NOx/Cr, PYD/Cr, and DPD/Cr were significantly increased in septic patients compared with those in healthy controls. Blood ionized calcium in septic patients was lower than in healthy controls, while parathyroid hormone levels in septic patients were higher than in healthy controls (P<0.01). PMX-F treatment reduced plasma endotoxin, urinary NOx/Cr, PYD/Cr, DPD/Cr, and serum parathyroid hormone levels and increased blood ionized calcium significantly; however, conventional treatment did not affect these levels.ConclusionsSeptic patients increased nitric oxide production and bone resorption, and PMX-F treatment is effective in reducing nitric oxide levels and bone resorption markers.

Silent cerebral infarction in patients with type 2 diabetic nephropathy. Effects of antiplatelet drug dilazep dihydrochloride

To determine whether diabetic nephropathy is a risk factor for silent cerebral infarction and whether antiplatelet drug dilazep dihydrochloride decreases the occurrence of silent cerebral infarction in type 2 diabetes patients with microalbuminuria.

Effects of polymyxin B immobilized fiber on urinary N-acetyl-β-glucosaminidase in patients with severe sepsis

Severe sepsis is known to cause multiple organ failure, including renal dysfunction. During sepsis, endotoxin targets the renal proximal tubular cells, the function of which can be evaluated on the basis of urinary N-acetyl-&bgr;-glucosaminidase (NAG). We investigated whether urinary NAG activity is altered in patients with severe sepsis and whether treatment with polymyxin B immobilized fibers (PMX-F) affects this activity. Subjects of this study were 120 patients with severe sepsis and 60 healthy volunteers matched for age and gender. Patients were randomly assigned to one of two treatments: PMX-F treatment (n = 70) or conventional treatment (n = 50). The plasma endotoxin level was significantly reduced, from 34.6 ± 10.2 to 6.8 ± 2.4 pg/ml (p < 0.01) in patients treated with PMX-F, and the urinary NAG/creatinine ratio was reduced from 46.5 ± 26.8 U/gm to 18.6 ± 13.6 U/gm (p < 0.01). The plasma endotoxin level and urinary NAG/creatinine ratio were unchanged in patients who received conventional treatment. The increased urinary NAG/creatinine ratio in patients with severe sepsis may reflect proximal tubular dysfunction. PMX-F is effective in reducing proximal tubular dysfunction, in part owing to reduced plasma endotoxin levels.

Effect of Granulocyte and Monocyte Adsorption Apheresis on Urinary Albumin Excretion and Plasma Endothelin-1 Concentration in Patients with Active Ulcerative Colitis

Background/Aim: Increases in microalbuminuria and endothelin (ET-1) are involved in the development of ulcerative colitis (UC) and in its progress. Because granulocyte and monocyte adsorption apheresis has proven to be useful in the treatment of UC, we examined whether urinary albumin excretion and plasma ET-1 concentrations are altered and whether granulocyte and monocyte adsorption apheresis affects the concentrations of these two factors in patients with active UC. Methods: Twenty patients with active UC and 20 age-matched healthy volunteers (our hospital staffs) were included in this study. UC patients were randomly divided into two treatment groups: a granulocyte and monocyte adsorption treatment group (n = 10) and a conventional treatment group (n = 10). The urine albumin/creatinine ratio, plasma ET-1 concentration and tumor necrosis factor (TNF)-α were determined before and after treatment and compared between 2 treatment groups. The 10 adsorption treatment patients underwent 5 consecutive weekly apheresis sessions, each of 60 min duration at a flow rate of 30 ml/min. Results: The urine albumin/creatinine ratio in UC patients (6.4 ± 2.2 mg/mmol) were higher than that in healthy subjects (1.0 ± 0.7 mg/mmol, p < 0.01). In addition, the plasma ET-1 level in UC patients (3.5 ±1.5 pg/ml) was higher than that in healthy subjects (0.8 ± 0.4 pg/ml, p < 0.01). Plasma TNF-α was detected in UC patients (18.8 ± 8.4 pg/ml), but not in healthy subjects. The urine albumin/creatinine ratio was highly correlated with the plasma ET-1 level (r = 0.62; p < 0.01) and plasma TNF-a level (r = 0.66, p < 0.01). Granulocyte and monocyte adsorption apheresis reduced the urine albumin/ creatinine ratio from 6.6 ± 2.4 to 1.8 ± 0.6 mg/mmol (p < 0.01), reduced the plasma ET-1 level from 3.7 ± 1.6 to 1.4 ± 0.6 pg/ml (p < 0.05) and reduced the plasma TNF-α from 19.2 ± 8.6 to 3.8 ± 1.2 pg/ml (p < 0.01). Conventional treatment did not affect these factors. Conclusion: Our data suggest that increases in the urine albumin/creatinine ratio, ET-1 and TNF-α play an important role in active UC and that granulocyte and monocyte adsorption apheresis is effective in ameliorating such increases.