Kaoru Yoshinaga

The role of macrophages in diabetic glomerulosclerosis

To elucidate the role of macrophages in diabetic glomerulosclerosis (DGS), an immunohistologic study was performed using monoclonal antibodies to common leukocyte antigen (DAKO-LC), T cells (T3), B cells (CD22), and macrophages (MAC 387, Leu-M5, and EBM-11). Kidney biopsy specimens were obtained from 28 patients with non-insulin-dependent diabetes mellitus. Cells were identified by a three-layer immunoperoxidase technique applied to cold ethanol-fixed, paraffin-embedded sections and quantitated as the number of cells per glomerular cross-sections and number of cells per square millimeter of glomerulus. The severity of the diffuse lesions in each glomerulus was graded semiquantitatively. The average grades for all the glomeruli were calculated and registered as an index of DGS for a biopsy specimen. There was no relationship between the index of DGS and the number of T or B cells. However, the number of macrophages and common leukocyte-positive cells increased significantly in the moderate stage of glomerulosclerosis compared with the mild or advanced stage. The results suggest that macrophages may transiently infiltrate during the moderate stage of diffuse DGS, contributing to irreversible structural damage.

Utility of automated brachial ankle pulse wave velocity measurements in hypertensive patients

BACKGROUND We examined whether pulse wave velocity (PWV), determined by brachial ankle arterial pressure wave measurements, using a newly developed, fully automated device could be a surrogate measure for carotid femoral PWV. METHODS & RESULTS This device (AT-form PWV/ABI, Nippon Colin, Komaki, Japan) can simultaneously monitor bilateral brachial and ankle pressure wave forms using the volume plethysmographic method, with two optional tonometry sensors for carotid and femoral arterial wave measurements. We examined the right brachial-right ankle PWV and left carotid-left femoral PWV in 89 normotensive and untreated hypertensive patients. The brachial ankle PWV correlated well with carotid femoral PWV (r = 0.755, P <.00001). The Bland-Altman plots of the two variables, however, showed a significant difference exists between the two techniques over the range of measurement. The within-observer and between-observer coefficients of variation of the brachial ankle PWV were 6.5% +/- 4.1% and 3.6% +/- 3.9%, respectively. To determine the factors affecting brachial ankle PWV, we studied treated and untreated hypertensive patients with World Health Organization stage I (n = 146), stage II (n = 74), or stage III (n = 54). In multiple regression analysis, age, brachial ankle PWV, and the presence of diabetes were significant predictors of the severity of hypertensive organ damage. Age, systolic blood pressure, and the stage of hypertensive organ damage were major determinants of brachial ankle PWV. CONCLUSIONS Although the brachial ankle PWV does not agree with the carotid femoral PWV, this parameter may yet become a new, useful measure for arterial stiffness. Further longitudinal studies are necessary to confirm the clinical significance of the brachial ankle PWV.

Clinical evaluation of semiautomatic and automatic devices for home blood pressure measurement: comparison between cuff-oscillometric and microphone methods.

The accuracy and reliability of blood pressure (BP) values were evaluated by comparing values obtained with eight automatic or semiautomatic devices designed for home BP measurement (four microphone devices based on the Korotkoff-sound technique and four cuff-oscillometric devices) with those obtained by the auscultatory method, using a standard mercury sphygmomanometer. Systolic blood pressure (SBP) values obtained using the microphone devices coincided well with those obtained by the auscultatory method. However, these devices produced a certain proportion of errors in the measurement of diastolic blood pressure (DBP), sometimes resulting in recordings at least 25mmHg higher than those obtained by the standard method. The most frequent causes of this phenomenon were an auscultatory (silent) gap and a weak Korotkoff sound after phase IV. A microphone device using a condenser microphone built into the manometer displayed comparatively good acoustic characteristics for determining DBP. All cuff-oscillometric devices demonstrated minimal mean differences and a constant s.d. of mean difference for DBP, with no great differences from the auscultatory method. However, mean differences and s.d.s in SBP measurements using cuff-oscillometric devices were relatively greater than those obtained using some of the microphone devices. Furthermore, the direction of the mean differences in measurements from those obtained with the auscultatory method differed. The error in relation to the auscultatory method tended to be reproducible in the same subjects with both the microphone and the cuff-oscillometric devices. These results indicate that practitioners should select the most appropriate method and/or device by taking into account the factors which may cause measurement error in relation to the auscultatory method in each subject, and should then evaluate, at least once, the difference in BP values obtained using the auscultatory method and using the device. In future, home blood pressure measurement devices for determination of SBP should employ a microphone method, while a method which combines a microphone with a cuff-oscillometric device, thereby compensating for the disadvantage of the Korotkoff-sound signal with the pulse wave signal, should be recommended for measurement of DBP.

Lipoprotein Glomerulopathy: Glomerular Lipoprotein Thrombi in a Patient With Hyperlipoproteinemia

An unusual nephropathy presumably induced by abnormal lipid metabolism is described in a 57-year-old woman who presented with proteinuria and edema. Histology at renal biopsy was characterized by marked dilatation of capillary lumina. Sudan staining and electron microscopy demonstrated lipid droplets occupying the capillary lumina. The patient had no particular clinical symptoms of lipidosis, but hyperlipoproteinemia similar to type III was suggested by lipid profiles. The nephropathy is thought to be an inherited disorder because proteinuria was detected in her sisters and similar renal histology and lipid profile were observed in one of her sisters. This is believed to be the first detailed report of glomerular lipoprotein thrombi.

LIPID-LOWERING EFFECT OF CARNITINE IN PATIENTS WITH TYPE-IV HYPERLIPOPROTEINÆMIA

Serum-lipid concentrations were determined in patients with type-IV hyperlipoproteinaemia treated with 900 mg/day oral DL-carnitine chloride. Serum-triglyceride was significantly reduced and concentrations continued to decline as carnitine administration continued. Total and esterified cholesterol concentrations did not change. Intravenous infusion of carnitine produced the same effects. The results suggest that carnitine is of value in the therapy of type-IV hyperliproteinaemia. Increased oxidation of free fatty acids in the tissues seems to account for the effects of carnitine on serum-lipid concentrations.

Circulating plasma kinin in patients with bronchial asthma

Bei 33 Patienten mit Asthma bronchiale von verschiedenem Erkrankungsgrade wurde der Kiningehalt im zirkulierenden Blut bestimmt. Erhöhte Blutkininwerte wurden in den Patienten gefunden, und zwar im allgemeinen mit der Schwere der Krankheit korrelierbar. Daraus folgt, dass das «Kinin» aetiologisch mit Asthma bronchiale verknüpft ist.

Glucose Tolerance and Insulin Secretion in Patients with Parathyroid Disorders: Effect of Serum Calcium on Insulin Release

To evaluate the role of serum calcium in human insulin secretion, insulin responses after a 100-g oral glucose load were studied in nine patients with primary hyperparathyroidism, five with idiopathic hypoparathyroidism, three with pseudohypoparathyroidism and one with normocalcemic secondary hyperparathyroidism. Glucose tolerance values in these disorders were almost normal. Insulin responses in primary hyperparathyroidism were increased, and those in idiopathic hypoparathyroidism and pseudohypoparathyroidism were reduced significantly as compared to normal subjects. Isulin response in secondary hyperparathyroidism was normal. The calculated insulin area during an oral glucose load was significantly correlated with serum calcium (5.1 to 12.2 mg per deciliter), and a linear relation was obtained (y = 1.59x - 3.3, r = 0.81, p less than 0.001), although a relation with the glucose area was not found. These observations indicate that serum calcium has an important effect on insulin secretion in parathyroid disorders.

Higher Brachial-Ankle Pulse Wave Velocity Is Associated with More Advanced Carotid Atherosclerosis in End-Stage Renal Disease

Brachial-ankle pulse wave velocity is a new measure of arterial stiffness. We examined whether higher brachial-ankle pulse wave velocity is associated with more advanced carotid atherosclerosis and left ventricular hypertrophy in patients with end-stage renal disease, and whether this effect would be mediated by the influence of wave reflection on central arterial pressure. In 68 patients with end stage renal disease, we examined blood pressures, brachial-ankle pulse wave velocity and the augmentation index of the left common carotid artery, a measure of the impact of wave reflection on the systolic peak in central arteries. The degree of carotid atherosclerosis was quantified by a plaque score and maximum intimal-medial thickness. Echocardiography was used to determine the left ventricular mass index. In simple regression analysis, brachial-ankle pulse wave velocity was correlated with both plaque score and maximum intimal-medial thickness (r=0.420, p<0.001 and r=0.452, p<0.0005, respectively) but not with left ventricular mass index. Multiple regression analysis was performed with the plaque score or maximum intimal-medial thickness as the dependent variable and brachial-ankle pulse wave velocity and known clinical risk factors as the independent variables. The brachial-ankle pulse wave velocity was an independent risk factor for both plaque score (β=0.006, p=0.004) and maximum intimal-medial thickness (β=0.008, p=0.04). Independent risk factors for left ventricular mass index were left ventricular diastolic dimension (β=3.509, p=0.000007) and augmentation index (β=0.580, p=0.04). The brachial-ankle pulse wave velocity was unrelated to augmentation index in patients with end stage renal disease. In conclusion, higher brachial-ankle pulse wave velocity was found to be a risk factor for carotid atherosclerosis in patients with end-stage renal disease; this effect was independent of the influence of wave reflection on central arterial pressure. The brachial-ankle pulse wave velocity was unrelated to left ventricular structure.

Colocalization of Corticotropin-Releasing Factor and Vasopressin in the Paraventricular Nucleus of the Human Hypothalamus

The anatomical relationship between corticotropin-releasing factor (CRF)-containing cells and arginine vasopressin (AVP)-containing cells in the human hypothalamus was investigated by immunocytochemistry. In the paraventricular nucleus of the hypothalamus (PVH), CRF-like immunoreactivity (CRF-LI) was present exclusively in parvocellular cells, while AVP-like immunoreactivity (AVP-LI) was present in both parvocellular and magnocellular cells. No CRF-immunoreactive neurons were observed in the supraoptic nucleus. All CRF-immunoreactive parvocellular cells in the PVH were also AVP immunoreactive. We confirmed the presence of AVP in the CRF-immunoreactive cells by using two kinds of anti-AVP antisera, one of which recognized the side chain of AVP while the other recognized the ring structure of AVP. Colocalization of CRF-LI and AVP-LI was observed not only in the same perikarya but also in the same nerve fibers of parvocellular cells. The present results raise the possibility that AVP and CRF may be secreted together into the human portal circulation.

Prognostic significance of the brachial–ankle pulse wave velocity in patients with essential hypertension: final results of the J-TOPP study

Brachial–ankle pulse wave velocity (baPWV) is a new tool for measuring arterial stiffness. The prognostic significance of this measure, however, is not fully established. We initiated a multicenter cohort study to examine the prognostic significance of baPWV in patients with essential hypertension in 2002. After baseline measurements were obtained, 662 previously untreated patients (mean age 60±12 years, mean blood pressure 156±19/94±12 mm Hg, 45% men) underwent long-term follow-up according to the current hypertension treatment guidelines. During the follow-up period (mean: 3 years, range: 3 months–8 years), 24 cardiovascular events were observed. The subjects were divided into high and low baPWV groups according to the median value (1750, cm s−1). Patients in the high baPWV group were older and had a lower body mass index, higher blood pressure, faster heart rate and higher fasting glucose and plasma creatinine concentrations compared with those in the low baPWV group. Cardiovascular morbidities per 1000 person-years for the high and low baPWV groups were 17.48 and 6.38, respectively (P<0.05), and the 8-year cardiovascular event-free survival rates were 78.2% and 93.5%, respectively (log-rank test, P=0.01). A multivariate Cox proportional hazard analysis showed that high baPWV compared with low baPWV was associated with a significantly poorer outcome (hazard ratio (HR) 2.97; 95% CI: 1.006–9.380). In conclusion, baPWV is an independent risk factor for future cardiovascular events in patients with essential hypertension.