Myeloperoxidase Antineutrophil Cytoplasmic Antibody-Associated Renal-Limited Vasculitis in a Young Adult Woman.

Antineutrophil cytoplasmic antibody (ANCA)-associated renal-limited vasculitis (RLV) is a minor subtype of small vessel vasculitis characterized by the inflammation of blood vessels, tissue damage, and loss of renal function localized in the kidney without systemic involvements. Here, we report a case of myeloperoxidase (MPO) ANCA-associated RLV in a young adult woman in Japan presenting chronic hematuria and newly overt proteinuria. Percutaneous renal biopsy revealed focal fibro-cellular crescent glomerulonephritis and the absence of other small vasculitides, tubular atrophy, and interstitial fibrosis. Therapeutic intravenous methylprednisolone pulse followed by oral prednisolone was administered as a remission induction. The patient's serum MPO-ANCA level gradually decreased, coinciding with dramatic changes in proteinuria and hematuria after therapeutic glucocorticoid administration. Renal function was maintained within the normal range, and disease activity was well-tolerated throughout the follow-up period for more than 14 weeks. While the incidence of RLV is rare among younger patients, it occurs with asymptomatic hematuria and proteinuria, which is important in differentiating RLV from typical glomerulonephritis. The overall prognosis of ANCA-associated RLV potentially depends on the severity of extrarenal involvements. Early diagnosis, appropriate treatment, and regular maintenance are essential for controlling and treating RLV. Due to the nontypical case presented here, further investigation is recommended to improve the diagnosis strategies and treatment options for this disease.

Association between high normal-range thyrotropin concentration and carotid intima-media thickness in euthyroid premenopausal, perimenopausal and postmenopausal women.

OBJECTIVE: There are currently no established cutoff levels for thyrotropin (TSH) within the reference intervals associated with carotid atherosclerosis to prevent the onset of cardiovascular diseases. The present study aimed to determine the TSH cutoff level associated with carotid maximum intima-media thickness (max IMT) in euthyroid premenopausal, perimenopausal and postmenopausal women. STUDY DESIGN: We conducted a cross-sectional study of 468 euthyroid women who had not been treated for or diagnosed with cardiovascular diseases and/or metabolic disorders among 1221 Japanese women who participated in a comprehensive medical examination at the Hidaka Hospital, Japan. Participants' weight, blood pressure, plasma glucose, serum lipoprotein, free thyroxine and TSH were measured and an interview about menstruation was conducted. Carotid ultrasonography was performed to determine max IMT. RESULTS: Max IMT significantly increased stepwise as menopausal status progressed (p < 0.001). Serum TSH levels were significantly higher in participants with carotid plaques, defined as max IMT ≥1.1 mm (p = 0.038), and were independently associated with the presence of carotid plaque using multivariate logistic regression analysis (ß =1.218, p = 0.036). In postmenopausal women, significantly higher carotid max IMT values were observed in women with serum TSH ≥2.5 µIU/mL compared with women with concentrations <2.5 µIU/mL (p = 0.018) without elevated total cholesterol and low-density lipoprotein cholesterol concentrations. These differences were not observed in premenopausal women. CONCLUSIONS: Laboratory finding of serum TSH concentration ≥2.5 µIU/mL may be useful to assess risk of atherosclerosis, especially in postmenopausal women.

Re-expansion pulmonary edema after thoracentesis for iatrogenic pneumothorax and severe subcutaneous emphysema.

Subclavian central venous catheterization can cause severe complications, including tension pneumothorax, subcutaneous emphysema, and pneumomediastinum. Re-expansion pulmonary edema after thoracentesis is a life-threatening complication.

Non-alcoholic Fatty Liver Disease Is a Risk Factor for Type 2 Diabetes in Middle-aged Japanese Men and Women.

Objective Emerging studies have focused on the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM in a Japanese middle-aged health check population. Methods We conducted a 10-year observational study in a health checkup population of middle-aged Japanese men and women at Hidaka Hospital from 2004 to 2013. We excluded cases with an alcohol intake exceeding 20 g/day and those with impaired glucose tolerance. The remaining 1,544 men and 864 women were classified into fatty liver and non-fatty liver groups based on the findings of abdominal ultrasonography. Both groups were followed for the development of diabetes. A multiple regression analysis was performed for each variable to predict the risk of future diabetes. Results The median age of the participants was 46.0 years at the entry, and the follow-up period was 10 years. The incidence of diabetes in the fatty liver group was 12.5% (29/232) in men and 26.3% (10/38) in women, whereas the incidence of diabetes in the non-fatty liver group was 2.5% (34/1,312) in men and 1.8% (15/826) in women. The relative risk of diabetes associated with fatty liver was 4.8 [95% confidence interval (CI) 3.0-7.8, p<0.0001] in men and 14.5 (95% CI 7.0-30.1, p<0.0001) in women. Conclusion NAFLD was a significant predictor for future diabetes in a Japanese middle-aged health check population, especially in women.

Lipoprotein lipase does not increase significantly in the postprandial plasma.

BACKGROUND: Previous reports have shown that lipoprotein lipase (LPL) activity significantly increases in the postprandial plasma associated with the increase of TG-rich lipoproteins. Therefore, we have reexamined those relationships using newly developed LPL assay with the different kinds of food intake. METHODS: Standard meal (n=81), 50g of fat (n=54), 75g of glucose (n=25) and cookie (25g fat and 75g carbohydrate fat) (n=28) were administered in generally healthy volunteers. Plasma LPL, HTGL and TC, TG, LDL-C, HDL-C, RLP-C and RLP-TG were determined at subsequent withdrawal after the food intake. RESULTS: Plasma TG, RLP-C and RLP-TG were significantly increased at 8PM (2h after dinner of standard meal) compared with 8AM before breakfast within the same day. Also those parameters were significantly increased in 2-6h after fat load. However, the concentrations and activities of LPL and HTGL did not significantly increase in association with an increase in the TG and remnant lipoproteins. Also LPL concentration did not significantly increase after glucose and "cookie test" within 4h. CONCLUSION: No significant increase of LPL activity was found at CM and VLDL overload after different kinds of food intake when reexamined by newly developed assay for LPL activity and concentration.

Relationships between blood rheology and age, body mass index, blood cell count, fibrinogen, and lipids in healthy subjects.

We investigated the relationships between blood rheology assessed by microchannel method and the various hemorheologic factors in healthy subjects. One hundred seventy-six healthy volunteers (90 men and 86 women, mean age; 32.9+/-11.3 years) were participated in this study. Body weight, body mass index, red blood cell count, hematocrit, hemoglobin, white blood cell count, and platelet count, plasma fibrinogen, and fasting serum lipid and lipoprotein concentrations were measured. In order to assess blood rheology, blood passage time was determined by a microchannel method (Micro Channel Array Flow Analyzer). Age, body mass index, red blood cell count, hematocrit, hemoglobin, white blood cell count, total cholesterol, low-density lipoprotein cholesterol, and triglyceride were positively correlated with blood passage time in all subjects, respectively (p<0.01) and high-density lipoprotein cholesterol was inversely correlated with blood passage time (p<0.01). However, platelet count, and fibrinogen were not correlated with blood passage time. The present study showed that increased age, body mass index, red blood cell count, white blood cell count, total cholesterol, low-density lipoprotein cholesterol, and triglyceride and decreased high-density lipoprotein cholesterol were associated with impaired blood rheology measured by microchannel method in healthy subjects, suggesting that aging, obesity, erythrocytosis, leukocytosis, and dyslipidemia may be related to hemorheological disorders. This microchannel method may be useful to study blood rheology which may be associated with various risk factors of cardiovascular disorders.

[Present state of outpatient consultation in Gunma University Hospital].

We started outpatient consultation by clinical laboratory physicians in Gunma University Hospital in June, 2002. Three days a week, five clinical laboratory physicians examine outpatients or answer questions concerning laboratory tests in an outpatient consulting room. The number of outpatients referred has gradually increased since we started this consultation. Among the wide rage of cases examined, there have been many preoperative patients with eye disorders from the Department of Ophthalmology. There are some advantages of our outpatient consultation. For example, we are able to give patients a detailed and unrushed explanation of their laboratory data, and close cooperation with clinical laboratory technicians enables physicians to perform quick and smooth echo-guided fine needle aspiration cytology of thyroid nodules. We hope that our consulting work by clinical laboratory physicians will become widely known to patients and doctors.

Dual mechanism of the potentiation by glucose of insulin secretion induced by arginine and tolbutamide in mouse islets.

Glucose induces insulin secretion (IS) and also potentiates the insulin-releasing action of secretagogues such as arginine and sulfonylureas. This potentiating effect is known to be impaired in type 2 diabetic patients, but its cellular mechanisms are unclear. IS and cytosolic Ca(2+) concentration ([Ca(2+)](i)) were measured in mouse islets during perifusion with 3-15 mmol/l glucose (G3-G15, respectively) and pulse or stepwise stimulation with 1-10 mmol/l arginine or 5-250 micromol/l tolbutamide. In G3, arginine induced small increases in [Ca(2+)](i) but no IS. G7 alone only slightly increased [Ca(2+)](i) and IS but markedly potentiated arginine effects on [Ca(2+)](i), which resulted in significant IS (already at 1 mmol/l). For each arginine concentration, both responses further increased at G10 and G15, but the relative change was distinctly larger for IS than [Ca(2+)](i). At all glucose concentrations, tolbutamide dose dependently increased [Ca(2+)](i) and IS with thresholds of 25 micromol/l for [Ca(2+)](i) and 100 micromol/l for IS at G3 and of 5 micromol/l for both at G7 and above. Between G7 and G15, the effect of tolbutamide on [Ca(2+)](i) increased only slightly, whereas that on IS was strongly potentiated. The linear relationship between IS and [Ca(2+)](i) at increasing arginine or tolbutamide concentrations became steeper as the glucose concentration was raised. Thus glucose augmented more the effect of each agent on IS than that on [Ca(2+)](i). In conclusion, glucose potentiation of arginine- or tolbutamide-induced IS involves increases in both the rise of [Ca(2+)](i) and the action of Ca(2+) on exocytosis. This dual mechanism must be borne in mind to interpret the alterations of the potentiating action of glucose in type 2 diabetic patients.

The elevation of glutamate content and the amplification of insulin secretion in glucose-stimulated pancreatic islets are not causally related.

Glucose increases insulin secretion by raising cytoplasmic Ca(2+) ([Ca(2+)](i)) in beta-cells (triggering pathway) and augmenting the efficacy of Ca(2+) on exocytosis (amplifying pathway). It has been suggested that glutamate formed from alpha-ketoglutarate is a messenger of the amplifying pathway (Maechler, P., and Wollheim, C. B. (1999) Nature 402, 685-689). This hypothesis was tested with mouse islets depolarized with 30 mm KCl (+ diazoxide) or with a saturating concentration of sulfonylurea. Because [Ca(2+)](i) was elevated under these conditions, insulin secretion was stimulated already in 0 mm glucose. The amplification of secretion produced by glucose was accompanied by an increase in islet glutamate. However, glutamine (0.5-2 mm) markedly augmented islet glutamate without affecting insulin secretion, whereas glucose augmented secretion without influencing glutamate levels when these were elevated by glutamine. Allosteric activation of glutamate dehydrogenase by BCH (2-amino 2-norbornane carboxylic acid) lowered islet glutamate but increased insulin secretion. Similar insulin secretion thus occurred at very different cellular glutamate levels. Glutamine did not affect islet [Ca(2+)](i) and pH(i), whereas glucose and BCH slightly raised pH(i) and either slightly decreased (30 mm KCl) or increased (tolbutamide) [Ca(2+)](i). The general dissociation between changes in islet glutamate and insulin secretion refutes a role of beta-cell glutamate in the amplification of insulin secretion by glucose.

Signals and pools underlying biphasic insulin secretion.

Rapid and sustained stimulation of beta-cells with glucose induces biphasic insulin secretion. The two phases appear to reflect a characteristic of stimulus-secretion coupling in each beta-cell rather than heterogeneity in the time-course of the response between beta-cells or islets. There is no evidence indicating that biphasic secretion can be attributed to an intrinsically biphasic metabolic signal. In contrast, the biphasic rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) induced by glucose is important to shape the two phases of secretion. The first phase requires a rapid and marked elevation of [Ca(2+)](i) and corresponds to the release of insulin granules from a limited pool. The magnitude of the second phase is determined by the elevation of [Ca(2+)](i), but its development requires production of another signal. This signal corresponds to the amplifying action of glucose and may serve to replenish the pool of granules that are releasable at the prevailing [Ca(2+)](i). The species characteristics of biphasic insulin secretion and its perturbations in pathological situations are discussed.