Significant association of poor glycemic control with increased resistance in efferent arterioles--study of inulin and para-aminohippuric acid clearance in humans.

AIMS: To examine whether glomerular hemodynamic parameters in humans are associated with glycemic control indices, by simultaneously measuring clearance of inulin (Cin) and para-aminohippuric acid (CPHA). METHODS: Thirty-one subjects (age 55.4±14.7 years; 15 men and 16 women; 21 diabetics and 10 non-diabetics) were enrolled. Cin and CPAH were measured simultaneously. Afferent arteriolar resistance (Ra), efferent arteriolar resistance (Re), glomerular hydrostatic pressure (Pglo) and glomerular filtration fraction (FF) were calculated according to Gomez' formula. RESULTS: FF correlated significantly and positively with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and glycated albumin (GA) (r=0.396, p=0.0303; r=0.587, p=0.0007; r=0.525, p=0.0070, respectively). Pglo correlated significantly and positively with FPG, HbA1c and GA (r=0.572, p=0.0008; r=0.535, p=0.0019; r=0.540, p=0.0053, respectively). Although there was no significant correlation between Ra and glycemic control indices, Re correlated significantly and positively with HbA1c and GA (r=0.499, p=0.0043; r=0.592, p=0.0018, respectively). FF, Pglo and Re were associated significantly with HbA1c and GA after adjustment for age. CONCLUSIONS: These results demonstrate, in humans, that poor glycemic control is associated with increased Re, but not Ra. It is suggested that increased Re causes increased Pglo, leading to increased FF. Thus, hemodynamic abnormalities with poor glycemic control may be related to glomerular hypertension in humans.

Reduction of whole PTH/intact PTH ratio as a predictor of bone metabolism in cinacalcet treatment of hemodialysis patients with secondary hyperparathyroidism.

UNLABELLED: In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker. INTRODUCTION: Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients. METHODS: Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT. RESULTS: Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks. CONCLUSION: W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption.

Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients.

AIM: Vascular calcification, which significantly increases cardiovascular and other causes of mortality, is highly prevalent in hemodialysis patients. The aim of the present study was to examine the association between serum magnesium levels and vascular calcification in hemodialysis patients. METHODS: 390 nondiabetic patients on maintenance hemodialysis (226 males and 164 females, 59 +/- 13 years) were examined. Hand roentgenography was performed in each patient, and visible vascular calcification of the hand arteries was evaluated. Blood was drawn to measure serum calcium, phosphate, magnesium and intact parathyroid hormone levels. RESULTS: There were 52 patients (38 males and 14 females) with vascular calcification, and 338 (188 males and 150 females) without. Serum phosphate was significantly higher in the former compared with the latter group (p < 0.005); serum intact parathyroid hormone was significantly higher (p < 0.05), whereas serum calcium was not statistically different between the two groups. Serum magnesium was significantly lower in patients with vascular calcification than in those without (2.69 +/- 0.28 vs. 2.78 +/- 0.33 mg/dl, p < 0.05). Multivariate logistic regression analysis revealed that serum magnesium concentration was a significant independent factor associated with the presence of vascular calcification in hemodialysis patients (odds ratio 0.28, 95% CI 0.09 - 0.92/1 mg/dl increase in serum magnesium, p = 0.036) after adjustment for age, gender, duration of hemodialysis, calcium, phosphate and intact parathyroid hormone concentrations. CONCLUSION: Hypomagnesemia is significantly associated with the presence of vascular calcification of the hand arteries, independent of serum calcium and phosphate levels. These results suggest that higher serum magnesium concentrations may play an important protective role in the development of vascular calcification in hemodialysis patients, and that magnesium concentration of dialysis fluid may be reconsidered in view of preventing vascular calcification in hemodialysis patients.

Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients.

INTRODUCTION: Fibroblast growth factor (FGF) 23 is a recently identified circulating factor that regulates phosphate (Pi) metabolism. Since the derangement of Pi control is an important risk factor for vascular calcification, we investigated the importance of plasma FGF-23 in the development of vascular calcification in the aorta and peripheral artery in hemodialysis patients with and without diabetes mellitus (DM). METHODS: Male hemodialysis patients with DM (n=32) and without DM (n=56) were examined. Plasma samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Roentgenography of the aorta and hand artery was performed, and visible vascular calcification was evaluated by one examiner, who was blinded to the patient characteristics. RESULTS: In the 56 non-DM hemodialysis patients, vascular calcification was found in the hand artery in 5 patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and 21 (65.6%) had vascular calcification of the hand artery and aorta, respectively. Multiple regression analyses performed separately in the non-DM and DM patients showed that the plasma FGF-23 level, CaxPi product, and body weight are independent factors significantly associated with hand-artery calcification and that diastolic blood pressure is associated with aorta calcification in non-DM patients. In DM patients, the plasma FGF-23 level and hemodialysis duration emerged as independent factors associated with hand-artery calcification and diastolic blood pressure was associated with aorta calcification. The independent association of the plasma FGF-23 level with hand-artery calcification was retained in both non-DM and DM patients when adjusted for the CaxPi product. CONCLUSION: Our findings show that the plasma FGF-23 level is an independent factor negatively associated with peripheral vascular calcification in the hand artery, but not in the aorta, in both male non-DM and DM hemodialysis patients, even when adjusted for the CaxPi product. This study raises the possibility that the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial calcification in male hemodialysis patients, independent of its regulatory effect on Pi metabolism.

Different risk factors for peripheral vascular calcification between diabetic and non-diabetic haemodialysis patients--importance of glycaemic control.

AIM/HYPOTHESIS: Although derangements of calcium and phosphate control have been emphasized as important risk factors for vascular calcification in non-diabetic haemodialysis patients, similar risk factors for diabetic haemodialysis patients are not known. We compared factors affecting peripheral vascular calcification between haemodialysis patients with and without diabetes. METHODS: We examined 421 patients on maintenance haemodialysis. There were 89 patients with Type II (non-insulin-dependent) diabetes mellitus (53 men and 36 women, 62+/-10 years old) and 332 patients without diabetes (192 men and 140 women, 59+/-13 years old). Hand roentgenography was carried out, and visible vascular calcification of the hand arteries was evaluated. RESULTS: There were 42 diabetic patients and 45 non-diabetic patients with vascular calcification. The prevalence of vascular calcification in diabetic patients (47.1%) was higher than in non-diabetic patients (13.6%) ( p<0.001). In multivariate logistic regression, the main factors affecting vascular calcification in non-diabetic patients were advanced age, longer duration of haemodialysis, increased phosphate concentrations, male gender, and lower predialysis diastolic pressure. In diabetic patients, predictors for vascular calcification were higher values of HbA(1C) and longer duration of haemodialysis. In diabetic patients, a 1% increase in HbA(1C) increased the risk of calcification by 2.1-fold (95% CI 1.282-3.575, p=0.0029). CONCLUSION/INTERPRETATION: We have shown that poor glycaemic control, rather than calcium and phosphate concentrations, is a predictor of peripheral vascular calcification in diabetic patients on haemodialysis. This study emphasizes that glycaemic control remains critical even in diabetic patients with end-stage renal disease.

Renal insufficiency accelerates atherosclerosis in patients with type 2 diabetes mellitus.

Diabetes mellitus is a strong risk factor for the progression of atherosclerosis. In patients with chronic renal failure on hemodialysis, advanced atherosclerosis is reported to be present. We examined how renal insufficiency affects intima-medial thickness (IMT) of the carotid and femoral arteries in patients with type 2 diabetes mellitus. IMT was measured by B-mode ultrasonography in 115 patients with type 2 diabetes mellitus (65 men, 50 women; 58 +/- 13 years old). The IMT of the carotid and the femoral artery of patients with creatinine clearance less than 80 mL/min (n = 55) were significantly greater than those of patients with creatinine clearance 80 mL/min or greater (n = 60; P < 0.01 and P < 0.05). Linear regression analyses showed that there was a significant negative correlation between creatinine clearance and IMT of the carotid artery (r = -0.330; P < 0.001) and femoral artery (r = -0.336; P < 0.001). Multiple regression analyses revealed that age and creatinine clearance significantly and independently affected the IMT of the carotid artery (R(2) = 0.176; P < 0.0001), and age, duration of diabetes, and smoking affected the IMT of the femoral artery (R(2) = 0.287; P < 0.0001). These findings show that decreased renal function accelerates atherosclerosis in patients with type 2 diabetes mellitus and that chronic renal failure is a significant, independent risk factor for carotid atherosclerosis in these patients.

Correlation between peritoneal mesothelial cell cytology and peritoneal histopathology with respect to prognosis in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a serious complication seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We have previously reported that mesothelial cells in effluent dialysate significantly increased in size as the duration of CAPD progressed. In this study, we investigated the relationship between mesothelial cytology, histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients. METHODS: When peritoneal dialysis catheters were inserted (n = 7) or removed (n = 27), a peritoneal biopsy was performed and results compared with mesothelial cytology in effluent dialysate. RESULTS: A significant positive correlation was noted between the duration of CAPD and the surface area of peritoneal mesothelial cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in peritoneal sclerosis (n = 9; 584 +/- 97 microm(2)) was significantly greater than in peritoneal fibrosis (n = 14; 389 +/- 26 microm(2), p < 0.05), pathologic acute peritonitis (n = 3; 223 +/- 10 microm(2), p < 0.005), and normal peritoneum (n = 7; 247 +/- 12 microm(2), p < 0.001). The surface area in sclerosing peritonitis (n = 1; 1,200 microm(2)) was greater than that of all the others. Giant cells were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with peritoneal sclerosis, although they were found in only 1 of 14 patients with peritoneal fibrosis and in none of those with pathologic acute peritonitis or normal peritoneum. As the surface area of mesothelial cells increased to more than 400 microm(2) and giant cells appeared in the effluent, the frequency of peritoneal sclerosis and/or clinical SEP increased. CONCLUSION: An increase in the mesothelial cell surface area and the emergence of giant cells in the effluent indicate advanced peritoneal histopathology, and may be useful indicators to determine appropriate timing of discontinuation of CAPD to prevent the development of SEP.

Modulation by cAMP of 1alpha,25-dihydroxyvitamin D3 sensitivity of murine erythroleukemia cells.

As we previously reported, 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) dose-dependently inhibited not only proliferation of undifferentiated murine erythroleukemia (MEL) cells but also activin A-induced erythroid differentiation of MEL cells. However, the effect of 1,25(OH)2D3 on MEL cell proliferation was significantly greater by one order of magnitude than that on differentiation (IC(50): 9.2 vs 0.8 nM, respectively). The response of activin A-treated mature MEL cells to 1,25(OH)2D3 in the induction of 1,25(OH)2D3-24-hydroxylase (24-OHase) activity, a rapid effect of 1,25(OH)2D3, was enhanced to the same degree as in untreated immature cells, suggesting that differences in capacity of cells to inactivate 1,25(OH)2D3 did not contribute to augmentation of 1,25(OH)2D3 effect in activin A-treated mature cells. Furthermore, neither the number nor the affinity of vitamin D receptors (VDR) differed significantly between activin A-treated cells and untreated immature cells. The intracellular cAMP level, which affects 1,25(OH)2D3-mediated induction of 24-OHase activity, was significantly less in activin A-treated mature cells than in immature MEL cells. The addition of dibutyryl cAMP (dbc AMP) to activin A-treated MEL cells dose-dependently attenuated 1,25(OH)2D3-mediated induction of 24-OHase activity, finally to a level comparable to that of the untreated cells at the final concentration of 100 nM dbcAMP, while dbcAMP itself by 100 nM did not affect MEL cell differentiation by 24 h. In summary, we have shown for the first time that 1,25(OH)2D3 exerted its effect on leukemia cells at physiological concentration and that the magnitude of this effect depended on the changes in intracellular cAMP level through stages of differentiation, suggesting that the cAMP-protein kinase A system may be useful as a target for clinical application of vitamin D analogs by improving the sensitivity of leukemic cells to 1,25(OH)2D3.

Hypertrophic pachymeningitis with anti-neutrophil cytoplasmic antibody (p-ANCA), and diabetes insipidus.

We treated a patient with idiopathic cranial hypertrophic pachymeningitis and elevated serum titer of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactive against myeloperoxidase. This 67-year-old man showed multiple cranial nerve-palsies, central diabetes insipidus (DI), and an intrasellar mass. DI and intrasellar mass had been present for 3 years, and DI had been well controlled by intranasal desmopressin. His nerve-palsies were most likely caused by thickened dura matter detected by the brain MRI. Granuloma may develop in the sella, and MRI findings in our patient are compatible to it. Corticosteroid and oral cyclophosphamide therapy improved his neurological symptoms and serum p-ANCA level with showing good correlation. DI improved temporally for 2 months. Few other cases of hypertrophic pachymeningitis with elevated p-ANCA have been reported, however the etiology is unknown. As p-ANCA antibodies have been detected in many of vasculitides, microvasculitis may be involved in some cases of idiopathic hypertrophic pachymeningitis.

Alphav integrin regulates TNF-alpha-induced nitric oxide synthesis in rat mesangial cells--possible role of osteopontin.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) induces nitric oxide (NO) synthesis in rat mesangial cells (MCs). We previously demonstrated that osteopontin (OP), a matrix protein that mainly interacts with the alphav integrin family, increased time-dependently by TNF-alpha stimulation at gene and protein levels. The regulation of NO synthesis by integrins or matrix proteins is unclear. METHODS: We examined whether integrin, especially alphav integrin, regulates NO synthesis in rat MCs and whether OP, an alphav integrin ligand, has an effect on TNF-alpha-induced NO synthesis. Furthermore, OP and inducible NO synthase (iNOS) gene expression was examined by Northern blotting. RESULTS: TNF-alpha increased NO synthesis in MCs in a time-dependent manner. Synthetic GRGDSP peptide, which is known to inhibit various integrins that interact with RGD-containing extracellular matrices, increased TNF-alpha-induced NO levels in a dose-dependent manner. Cyclical RGD peptide, the specific inhibitor of alphav integrin, also exhibited a dose-dependent effect of increasing NO levels, while GRGESP peptide, which has very low affinity to integrins, had no effect. In addition, NO synthesis was found to be significantly reduced when MCs were plated on OP-coated dishes compared to type I or IV collagen-coated dishes. Furthermore, anti-OP antibody increased NO synthesis in MCs. iNOS mRNA levels were increased by TNF-alpha, and were abruptly diminished after OP mRNA was significantly induced. CONCLUSIONS: The present study demonstrated the involvement of alphav integrin in TNF-alpha-induced NO synthesis in rat MCs, and the possible role of OP was suggested in the mechanism. TNF-alpha and extracellular matrices can co-operate to regulate the behaviour of MCs at least partly through NO synthesis, which may participate in the course of glomerular diseases.

A case of membranous glomerulonephritis associated with gastric cancer.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.

Idiopathic portal hypertension associated with high serum titer of autoantibodies and liver dysfunction.

Idiopathic portal hypertension (IPH) is a condition marked by unexplained portal hypertension. Although a number of immunological abnormalities occur in patients with IPH, liver function is usually normal. We experienced an unusual case of IPH in a 49-year-old woman, who had pronounced splenomegaly. Laboratory data revealed pancytopenia, hypergammaglobulinemia, and liver dysfunction. Antinuclear antibodies were positive, with high titer at 1280 dilutions of sera. LE cell phenomena were also positive. Histological examination of biopsied liver showed only mild changes, but portal venous pressure was markedly elevated, at 38 cm H2O. This case was thus characterized by both a high serum titer of autoantibodies and liver dysfunction.

Amyloid goiter: radiological study in a case presenting hypothyroidism.

We report herein a case of amyloid goiter associated with rheumatoid arthritis in which hypothyroidism was observed. A 52-year-old housewife who had suffeed from rheumatoid arthritis for 15 years was referred to our hospital because of general fatigue. On admission, a large goiter was observed. Laboratory data showed primary hypothyroidism. Renal biopsy and gastric mucosa biopsy showed amyloid deposition of AA-type. Thyroid biopsy showed massive amyloid involvement. Although the findings of iodine-123 scintigraphy, technetium-99m pertechnetate scintigraphy, computed tomography and magnetic resonance image studies were similar to those for goiter associated with chronic thyroiditis, tallium-201 chloride scintigraphy gave a differing result, demonstrating absent uptake at 3 hours in this case. Replacement therapy with levothyroxine relieved the symptoms. This case was unusual in that amyloid goiter presented clinically as hypothyroidism. Absence of tallium-201 chloride uptake at 3 hours may be a diagnostic specificity for amyloid goiter in differentiating its hypothyroidism from that caused by chronic thyroiditis.

Heat-insoluble cryoglobulin in a patient with essential type I cryoglobulinemia and massive cryoglobulin-occlusive glomerulonephritis.

We report a case of type I essential cryoglobulinemia with massive cryoglobulin-occlusive glomerulonephritis, in which the clinical course and the physical characteristics of the cryoglobulin were unusual. Nine years before appearance of cryoglobulin, this 54-year-old man noted edema and purpura of the lower extremities. Renal biopsy performed 2 years later showed large amounts of amorphous, weakly eosinophilic, weakly periodic acid-Schiff (PAS)-positive materials occluding the glomerular capillaries. Immunostaining showed the material to be weakly immunoglobulin (Ig) G positive, and electron microscopy showed homogeneous, electron-dense deposits. Nephrotic syndrome and azotemia did not respond to steroid treatment, and dialysis was begun 5 years after the biopsy. A small amount of cryoglobulin was first detected 2 years later, 9 years after the onset of disease. The cryoglobulin had a white gelatinous appearance, was resistant to resuspension, and did not redissolve when rewarmed to 37 degrees C. Immunoelectrophoresis of the cryoglobulin, which partially dissolved at 54 degrees C, showed it to be composed of monoclonal IgG-kappa and a small amount of albumin. We consider that the unusual physical characteristics of the cryoglobulin in this case precipitated a massive cryoglobulin-occlusive glomerulonephritis, which progressed to end-stage renal failure in the absence of significant cryoglobulinemia during the initial onset of disease.

Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells.

Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia.

Acute renal failure associated with minimal change nephrotic syndrome in an elderly adult.

We report a 66-year-old man with minimal change nephrotic syndrome (MCNS) that was associated with reversible acute renal failure (ARF) caused by acute tubular necrosis (ATN). He had a subacute onset of proteinuria and progressive azotemia. Hemodialysis (HD) was required to improved azotemia. Renal biopsy revealed minor glomerular abnormalities associated with ATN. While continuing HD, steroid therapy was started, which subsequently allowed the patient to be weaned from HD and relieved from NS. In this patient, histological examination and clinical course suggested that ATN was probably induced by hypovolemia due to MCNS.

Effect of aminohydroxypropylidene diphosphonate on the bone metabolism of patients with parathyroid adenoma.

Aminohydroxypropylidene diphosphonate (APD), a potent inhibitor of bone resorption, is used to control hypercalcemia in various diseases. It is less effective, however, in the management of hypercalcemia induced by primary hyperparathyroidism. We investigated the effect of APD on the bone metabolism of five patients with parathyroid adenoma. Before parathyroidectomy, 30 mg of APD was administered intravenously. Serum calcium decreased in all cases one to two days after APD administration, although it did not decrease to the normal range. Serum phosphorus also decreased. Urine calcium and hydroxyproline excretion, markers of osteoclasts activity, decreased dramatically. Serum alkaline phosphatase (ALP) and osteocalcin, markers of osteoblast activity, decreased after APD administration. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D (1,25[OH]2D) increased. These results indicate that APD is partially effective in the management of preoperative serum calcium level in patients with parathyroid adenoma. As osteoclasts activity is inhibited by APD, osteoblasts activity is also suppressed. Elevation of PTH and 1,25(OH)2D after APD-induced decrease in serum calcium level may explain the partial and limited effect of APD on lowering serum calcium in patients with parathyroid adenoma.

[A case of dextrocardia concomitant with tetralogy of Fallot, patent ductus arteriosus and bronchiectasia].

We report a case of dextrocardia concomitant with tetralogy of Fallot (TOF), patent ductus arteriosus (PDA), bronchiectasia, and pulmonary tuberculosis. A 24-years-old man without surgical operation for TOF, whose diagnosis had been made at infancy, was admitted to the Osaka City University Hospital because of massive hemoptysis. The diagnosis of pulmonary tuberculosis was made. He received anti-tuberculotic drugs and bronchial arterial embolization improved his symptoms. A case of mirror-image dextrocardia concomitant with TOF, PDA, and bronchiectasia, as seen in our case, has a low incidence rate, and, moreover, such a case concomitant with pulmonary tuberculosis is rarer still.

Effect of uremic serum on 1,25-dihydroxyvitamin D3-induced differentiation of human promyelocytic leukemia cell, HL-60.

The mechanism by which resistance to 1,25-(OH)2D3 occurs in patients with chronic renal failure was studied. 1,25-(OH)2D3 causes the induction of differentiation and of 1,25-(OH)2D3-24-hydroxylase activity in the mitochondria of the human promyelocytic leukemia cell line, HL-60, via a steroid hormone-receptor mechanism. Treatment of these cells with 10(-8) M 1,25-(OH)2D3 for 5 days in a medium containing 10% uremic serum from 4 patients with chronic renal failure resulted in maturation of the cells amounting to 30.3 +/- 18.7 (mean +/- SD) and 32.5 +/- 11.2% maturation by the nitroblue tetrazolium reduction assay and the nonspecific esterase assay, respectively. These values were significantly lower than those obtained with 10% normal serum from 3 normal controls (66.6 +/- 12.8 and 58.3 +/- 10.9%, p < 0.02). The occurrence of resistance to 1,25-(OH)2D3 in uremic serum-treated cells was also confirmed when the effect of 1,25-(OH)2D3 was assessed by the induction of the cell's ability to hydroxylate the C-24 position of 1,25-(OH)2[3H]D3. Treatment of HL-60 cells with a mixture of 5% uremic plus 5% normal serum impaired 1,25-(OH)2D3-induced cell differentiation to the levels as those in 10% uremic serum, strongly suggesting the occurrence of a substance(s) having 1,25-(OH)2D3-inhibitory activity in the uremic serum. A significant reduction in 1,25-(OH)2D3 receptor levels was observed in uremic serum-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)