Norio Wada

Importance of contralateral aldosterone suppression during adrenal vein sampling in the subtype evaluation of primary aldosteronism

Adrenal vein sampling (AVS) is the standard criterion for the subtype diagnosis in primary aldosteronism (PA). Although lateralized index (LI) ≥4 after cosyntropin stimulation is the commonly recommended cut‐off for unilateral aldosterone hypersecretion, many of the referral centres in the world use LI cut‐off of <4 without sufficient evidence for its diagnostic accuracy.

Step-up therapy with biphasic insulin aspart-70/30 : Sapporo 1-2-3 study

The effectiveness of BIAsp 30 step-up therapy in achieving glycemic control in Japanese patients with type 2 diabetes mellitus was investigated. Study subjects were 99 patients with type 2 diabetes mellitus aged over 20 years who were judged to require insulin therapy due to poor glucose control (HbA1c level of > or =7.5%). BIAsp 30 dosage was determined by the patients attending physician; coadministration of hypotensive agents and antilipemic agents was permitted, but OAD coadministration was limited to patients already receiving such drugs at the start of the study. Patients who did not achieve HbA1c <6.5% after 16+/-5 weeks with QD (Phase 1) were stepped up to BID (Phase 2). If patients still had not achieved HbA1c <6.5% after 16+/-5 weeks with BID, they were stepped up to TID (Phase 3). 55 of the 99 enrolled subjects completed the study and the rates of achievement of HbA1c <6.5% and HbA1c <7.0% were 45.5% and 74.5%, respectively. Of all registered subjects, 5.1% (5/99) achieved HbA1c <6.5% in QD, 19.5% (16/82) in BID, and 20.6% (7/34) in TID. Statistically significant reductions in HbA1c levels were recorded at the conclusion of each phase, with no incidents requiring intervention, indicating that BIAsp 30 step-up therapy is a safe, simple therapy that can be useful in achieving better glycemic control for Japanese patients with type 2 diabetes mellitus.

Problems in diagnosing atypical Gitelman’s syndrome presenting with normomagnesaemia

Objective  Gitelman’s syndrome, recognized as a variant of Bartter’s syndrome, is characterized by hypokalaemic metabolic alkalosis in combination with hypomagnesaemia and hypocalciuria. Overlapping biochemical features in Gitelman’s syndrome and Bartter’s syndrome has been observed. Here, we investigated the clinical, biochemical, and genetic characteristics of five, chronic, nonhypertensive and hypokalaemic Japanese patients.

Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism

Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154–69 920) in the higher side and 12 953 (range, 1866–36 190) pg/mL in the lower side (P<0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4–66.0] versus 17.3 [4.0–59.0] pg/mL per &mgr;g/dL; P<0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index ≥4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA.

Optimum position of left adrenal vein sampling for subtype diagnosis in primary aldosteronism

Although adrenal vein sampling (AVS) is the standard method for subtype diagnosis in primary aldosteronism (PA), protocol details including the sampling position in the adrenal vein are not standardized.

Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established.

Measurement of single low-density lipoprotein particles by atomic force microscopy

Background The size of lipoprotein particles is relevant to the risk of coronary artery disease (CAD). Methods We investigated the feasibility of atomic force microscopy (AFM) for evaluating the size of large low-density lipoprotein (LDL) and small dense LDL (sd-LDL) separated by ultracentrifugation. The measurements by AFM in tapping mode were compared to those by electron microscopy (EM). Results There was a significant difference in particle sizes determined by AFM between large LDL (20.6 ± 1.9 nm, mean ± SD) and sd-LDL (16.2 ± 1.4 nm) obtained from six healthy volunteers (P < 0.05). The particle sizes determined by EM for the same samples were 23.2 ± 1.4 nm for large LDL and 20.4 ± 1.4 nm for sd-LDL. The difference between large LDL and sd-LDL detected by EM was also statistically significant (P < 0.05). In addition, the particle sizes of each lipoprotein fraction were significantly different between AFM and EM: P < 0.05 for large LDL and P < 0.05 for sd-LDL. Conclusions AFM can differentiate between sd-LDL and large LDL particles by their size, and might be useful for evaluating risk for CAD.

Development of homogeneous assay for simultaneous measurement of apoE-deficient, apoE-containing, and total HDL-cholesterol

BACKGROUND Pathophysiological role for high-density lipoprotein (HDL) subclasses remains to be elucidated. Homogeneous assay for simultaneous measurements of apoE-deficient HDL-cholesterol (HDL-C), apoE-containing HDL-C, and total HDL-C is desired, because apoE plays important roles in lipid metabolism. METHODS The proposed assay consists of a primary reaction to remove non-HDL-C, a secondary reaction to measure apoE-deficient HDL-C, and a tertiary reaction to measure apoE-containing HDL-C. The assay is completed within 10 min. For control study, 13% polyethylene glycol precipitation assay and phosphotungstate-dextran sulfate-magnesium precipitation assay were carried out. RESULTS Good correlations between the control assays and the proposed assay was obtained in serum samples from patients without liver disease (n=33): r=0.987, 0.957, and 0.991 for apoE-deficient, apoE-containing, and total HDL-C, respectively. ApoE-containing HDL-C by the proposed method in healthy individuals (n=12) and patients with hyper-HDL-cholesterolemia (n=5) were 0.11±0.03 and 0.26±0.05 mmol/l (4.1±1.3 and 10.1±2.0 mg/dl), respectively. ApoE-containing HDL-C increased rapidly at >2.59 mmol/l (100 mg/dl) of total HDL-C, suggesting a unique regulating mechanism of apoE-containing HDL-C. CONCLUSIONS The established homogeneous assay might be useful for clinical and epidemiological studies on apoE-deficient and apoE-containing HDL subclasses.

Accuracy of adrenal computed tomography in predicting the unilateral subtype in young patients with hypokalaemia and elevation of aldosterone in primary aldosteronism

The current Endocrine Society Guideline suggests that patients aged <35 years with marked primary aldosteronism (PA) and unilateral adrenal lesions on adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS) before proceeding to unilateral adrenalectomy. This suggestion is, however, based on the data from only one report in the literature.

Novel monoclonal antibody recognizing triglyceride-rich oxidized LDLs associated with severe liver disease and small oxidized LDLs in normal subjects

Background Triglyceride-rich low-density lipoproteins (TG-rich LDLs) in the plasma of patients with severe liver disease are reported to change macrophages into foam cells in vitro. Methods Male BALB/c mice were immunized with TG-rich LDLs isolated from the plasma of a patient with severe liver disease. The resulting monoclonal antibody (G11-6) was used in a sandwich enzyme-linked immunosorbent assay (ELISA) in combination with polyclonal anti-apolipoprotein B antibodies. The time course of copper-mediated LDL oxidation was monitored using this ELISA. The results were compared with those of the two commercial ELISAs for oxidized LDLs using DLH or ML25, thiobarbituric acid reactive substances and the optical absorbance for the conjugated dienes generated in lipid peroxides. Furthermore, the lipoprotein fractions separated by gel filtration were tested with this ELISA in healthy volunteers (n = 11) and patients (n = 3) with liver disease. Results G11-6 reacted with oxidized LDLs during only the early phase of copper oxidation, being distinct from the other monoclonal antibodies and methods. G11-6 was confirmed to react with TG-rich LDLs in patients, while it reacted with small LDL particles in normal controls. Conclusions The monoclonal antibody G11-6 is useful for detecting oxidized small LDLs in normal controls and oxidized TG-rich LDLs in patients with severe liver disease.