Focal segmental glomerulosclerosis associated with polycythemia vera: report of a case and review of the literature.

A 69-year-old female with a 3-year history of polycythemia vera (PV) developed nephrotic syndrome. A renal biopsy showed focal and segmental glomerulosclerosis (FSGS). The patient was treated with prednisolone and myelosuppressive agents. Thereafter, parallel improvement of the two conditions was observed. After 4-year treatment, proteinuria disappeared. To our knowledge, there are five reported cases of FSGS associated with PV. Among them, three patients suffered from progressive azotemia. We suggest that steroid therapy with myelosuppressive agents can resolve the renal lesion in patients with PV.

Clinical application of the Personal Dialysis Capacity (PDC) test: serial analysis of peritoneal function in CAPD patients.

BACKGROUND: Peritoneal damage has been reported since the beginning of CAPD therapy. METHODS: To clarify the change of peritoneal function in CAPD patients, we used the Personal Dialysis Capacity (PDC) test in 22 patients with 49 serial studies and 14 patients with single studies. The data were expressed at the condition of 2.5% (2.27 g/dl of glucose), four times at 2,000 ml/day. RESULTS: In the mass analysis, the urea generation rate, creatinine generation rate, PNA/PCR, and water removal via the peritoneum (PD) were kept at the same level for almost eight years, and then gradually decreased. Urine volume and residual renal creatinine clearance (CCr) became zero at six years. On the other hand, PD CCr increased gradually with the time course of CAPD, and therefore the total CCr remained at the level of 6.0 ml/min even after six years. Weekly urea KT/V decreased gradually from almost 2.800 to 2.000. The protein loss remained approximately 7.0 g/day for the initial five years, then became 6.0 g/day, except in five patients who showed levels above 10.0 g/day on the first test of PDC. Weekly urea KT/V was correlated with residual renal CCr (P < 0.005), and significantly correlated with total CCr (weekly urea KT/V = -0.2798 + 0.3720 x total CCr; r = 0.915, P < 0.001). In the serial analysis, when the first and the last tests were compared, the urea generation rate increased significantly (mean +/- SD, 2.800 +/- 3.204 vs. 3.882 +/- 3.382; P < 0.0001); however, water removal via PD (1364 +/- 887 vs. 813 +/- 609; P = 0.021), total ultrafiltration (1762 +/- 841 vs. 1124 +/- 843; P = 0.042), and weekly urea KT/V (2.285 +/- 0.486 vs. 2.112 +/- 0.512; P = 0.026) decreased significantly. The delta water removal via PD/ duration became negative (-10.03 +/- 6.59 ml/week) in all 7 patients after more than four years, however, it was positive (+14.40 +/- 7.84 ml/week) in 6 of 10 patients after less than one year. CONCLUSION: These results suggest that water removal via PD increases within one year, then decreases after four years. The PDC test is useful to evaluate the change of peritoneal function in mass and serial analyses.

Serial alterations of glomerular matrix-degrading metalloproteinase activity in anti-thymocyte-induced glomerulonephritis in rats.

In the present study, we investigated the serial changes of glomerular metalloproteinase (GMP) activity in antithymocyte-induced glomerulonephritis (Thy.1 GN) in rats. GMP activity was determined by the measurement of EDTA-inhibitable gelatinolytic activity toward tritiated gelatin as substrate. Thy.1 GN was made by injection of antithymocyte serum into female Wistar rats and glomeruli were separated by a graded sieving method. Glomeruli were homogenized with sonication, and then the supernatant was used for the assay of GMP activity and substrate study. GMP activity was reduced on day 1 and at week 2 compared with controls, and returned to the control level by week 9. On light-microscopic examination, diffuse and focal glomerular ECM expansion were observed at weeks 2 and 4, respectively. These changes disappeared by week 9. With the use of several substrates labeled with tritium, GMP was observed to degrade type IV collagen, fibronectin and casein as well as gelatin, but not type I collagen. In conclusion, attenuated GMP activity may be one of the causes of glomerular ECM expansion in Thy.1 GN, because GMP was capable of degrading the components of glomerular ECM.

Crescentic glomerulonephritis accompanied by myeloperoxidase-antineutrophil cytoplasmic antibodies in a patient having myelodysplastic syndrome with trisomy 7.

A 63-year-old woman developed rapidly progressive glomerulonephritis syndrome with serum myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A renal biopsy showed diffuse crescentic glomerulonephritis. Immunofluorescence and electron microscopic studies showed no significant deposits in the glomeruli. The morphological findings were consistent with pauci-immune type crescentic glomerulonephritis. In addition, the patient had erythropoietin-resistant anemia and subsequent pancytopenia. Bone marrow was normocellular without an excess of blasts. However, multinuclear erythroblasts, hypersegmented neutrophils, and megakaryocytes without platelet formation were observed. Chromosome analysis of the bone marrow showed 47,XX,+7. This is the first case of MPO-ANCA-related crescentic glomerulonephritis in a patient with myelodysplastic syndromes (MDS). A possible relationship between MPO-ANCA and MDS is discussed.

Mouth and genital ulcers with inflamed cartilage (MAGIC syndrome): a case report and literature review.

A 39-year-old woman had relapsing polychondritis and Behçet's disease, which was described as mouth and genital ulcers with inflamed cartilage syndrome (MAGIC). Serologic human leukocyte antigen analysis showed A24 (9), A31 (19), B56 (22), B62 (15), Cw6, DR4, DR9. Human leukocyte antigen allele analysis revealed DRB1* 0406/0901, DQA1* 0301/0301, DQB1* 0302/0303, DPB1* 0201/0501 through determining the genotype using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Treatment with methotrexate (5 mg/week) and pentoxifylline (300 mg/d) was effective to control oral ulcers, erythema nodosum, and arthritis.

IgG subclasses in patients with membranoproliferative glomerulonephritis, membranous nephropathy, and lupus nephritis.

Primary glomerulopathy can be classified into seven essential patterns based on histopathological studies. The pathogenesis of membranoproliferative glomerulonephritis (MPGN), and membranous nephropathy (MN), which show glomerular IgG deposition and induce mainly nephrotic syndrome, is not known. To clarify the role of IgG subclass in glomerulonephritis, we compared serum concentrations of IgG subclasses, the ratio of serum IgG subclasses to total IgG (%IgG subclass), and glomerular deposition of IgG subclasses between 7 MPGN patients, 21 MN patients, and 9 lupus nephritis (LN) patients. Serum IgG subclasses and %IgG in all groups were almost within normal range based on the values in Japanese healthy adults. In the MPGN and MN groups, the IgG1 concentration was significant lower than that of the LN group (P < 0.001, P < 0.0001, respectively). The IgG2 concentration in the MPGN group decreased significantly compared with that in the LN group (P < 0.05). The %IgG2 of the LN group decreased significantly compared with that of the MN group (P < 0.05). The %IgG3 of the MPGN group was significantly higher that that of the MN group (P < 0.05). The glomerular immunofluorescent intensity of IgG1 and IgG2 were significantly stronger in the LN group than in the MPGN and MN groups (IgG1, P < 0.001, P < 0.01, respectively; IgG2, P < 0.0001, P < 0.0001, respectively). IgG3 in the MPGN and LN groups deposited significantly compared with that in the MN group (P < 0.0001, P < 0.01, respectively). The intensity of IgG4 in the MN group showed a significant difference compared with that in the MPGN and LN groups (P < 0.0001, P < 0.01, respectively). IgG3 is an important factor in the pathogenesis of primary MPGN, while IgG4 relates to glomerular IgG deposition in MN.

Clinicopathological analysis and therapy in hepatitis C virus-associated nephropathy.

We analyzed the clinicopathological features and therapy in 19 patients with kidney disease accompanied by hepatitis C viral infection, including 12 patients with mesangial proliferative glomerulonephritis (including eight with IgA nephropathy), six with membranoproliferative glomerulonephritis (MPGN), and one with membranous nephropathy. Persistent hematuria and/ or proteinuria (10 patients) was the most common finding, followed by nephrotic syndrome (8 patients). Cryoglobulinemia was detected in six of 19 patients examined (four of six patients with MPGN). Analysis of hepatitis C virus (HCV)-RNA genotype in 13 patients revealed that nine of them had type II genotype. All four patients with MPGN, who had serum positive for HCV-RNA, had type II genotype. Five patients were treated with interferon-alpha (IFN-alpha) without a demonstrable effect on renal impairment, whereas five of 11 patients treated with steroids showed improvement of the renal impairment. During the course of steroid therapy, the serum titer of HCV-RNA decreased in 5 of 7 patients. These observations suggest that HCV infection may be associated with several forms of glomerulonephritis. Type II HCV-RNA may have a strong association with MPGN in Japan. Steroid therapy is not contraindicated in patients with HCV-associated nephropathy if they are resistant to IFN-alpha treatment.

Late onset bone marrow transplant nephropathy.

We report a patient who exhibited proteinuria and renal failure 93 months after receiving an allogeneic bone marrow transplantation (BMT) from his HLA-identical brother. A renal biopsy specimen revealed segmental sclerosis, mesangiolysis, subendothelial lucency in the glomeruli, fibrosis and small round cell infiltration in the interstitium, and hyaline droplets in the intimal spaces of arterioles and small arteries. These histological findings were consistent with late onset BMT nephropathy. This nephropathy may represent a more serious problem in the near future in Japan, since the number of BMT performed has been increasing with the establishment of a bone marrow bank.

A combination of livedo racemosa, occlusion of cerebral blood vessels, and nephropathy: kidney involvement in Sneddon's syndrome.

A 59-year-old woman with retinal vein thrombosis and livedo racemosa had hematuria (4+) and proteinuria (1.7 g/day). Skin biopsy showed swollen blood vessel walls with infiltration of mononuclear cells, which were compatible with livedo racemosa (vasculitis). Magnetic resonance imaging (MRI) of the brain demonstrated multiple lacunar infarctions in the basal ganglia and white matter. Renal biopsy showed that small round cells had infiltrated into the interstitium, and a reticular structure was observed in the glomerular hilus. An amorphous substance composed of a single cell was present in the glomerular capillary lumen. Immunofluorescent study demonstrated the deposition of only IgA, in a segmental pattern differing from the diffuse global mesangial pattern seen in IgA nephropathy. After combined therapy including 40 mg/day prednisolone, 50 mg/day cyclophosphamide, antiplatelet drug, and anticoagulant was started, proteinuria and hematuria improved to 0.5 g/day and 2+, respectively, at the time of discharge. Sneddon's syndrome is a rare entity characterized by livedo racemosa and cerebrovascular lesions. In our patient with livedo racemosa, occlusion of cerebral blood vessels, and nephropathy with segmental immunoglobulin A (IgA) deposition, no antiphospholipid antibodies were detected on routine examination. Dermatologists, neurologists, psychiatrists, and nephrologists should be aware of the existence of Sneddon's syndrome with nephropathy (LI-O-N).

Right atrial myxoma with hypervascularity demonstrated by selective coronary angiography.

Cardiac myxoma is the commonest primary cardiac tumor, however, the incidence of right atrial myxoma is very rare. We reported a 71-year-old man with a right atrial myxoma, whose main complaint was fever of unknown origin. Definite diagnosis was confirmed by echocardiography and cineangiocardiography. Venacavogram revealed huge mass which occupied greater part of right atrial cavity. Coronary angiogram revealed the feeding artery arising from left coronary circumflex artery and the sign of hypervascularity. Open heart surgery was performed, and a 4.9 x 4.0 x 3.8 cm tumor was found in the right atrial cavity. Pathological examination showed the findings of myxoma. Postoperative clinical course was uneventful.

[Tolerance to a sustained release form of isosorbide dinitrate: comparison between 20 mg four times and 40 mg twice-daily administrations].

Attenuation of antianginal effects of oral isosorbide dinitrate in a sustained release from (ISDN-SR) were studied using the treadmill exercise test in eleven patients with stable exertional angina and a positive exercise test. We compared the four-time-daily administration of 20 mg with a twice-daily regimen of 40 mg for 10 days using the double-blind, crossover method. On the 1st day of the administration, with both regimens, the treadmill walking time, the time to 1mm and 2mm ST depression, and several hemodynamic parameters increased significantly. These improvements were reduced gradually on day 5 and day 10 after the administration. In the comparison between the four-time-daily and two-time-daily regimens, the former application showed clearer antianginal and hemodynamic effects than the latter regimen, but these effects were attenuated more markedly in the four-time daily administration. With both dosage regimens, the plasma ISDN concentrations increased gradually. With the long-term four-time-daily regimen, the time-to-time changes of the ISDN concentration were smaller each day. These data suggest that tolerance to oral ISDN-SR exists even if it is applied only two time daily, but its degree is less than when a four-time-daily dose in administered.

[Wrapping operation for Stanford type A acute dissecting aneurysms].

Four cases of Stanford type A acute aortic dissection were treated by wrapping operation. After careful dissection between the dilated ascending aorta and right pulmonary artery, 8 mm woven Dacron vascular prosthesis was passed around the aorta and tightened. Further enforcement wrapping was carried out using several prostheses from aortic root to the innominate artery. We call this technique "wrapping operation". Emergent operations were performed on all patients because of cardiac tamponade, 6.8-33 hours after the onset of dissection. Three patients are doing well 17-39 months after the operation, but only 1 patient died early postoperative period because of DIC and multiple organ failure. And 2 patients was showed closure of entry of the ascending aorta by the postoperative aortography. We think that the wrapping operation is a useful technique for the patients of ruptured Stanford type A acute dissecting aneurysms.

The efficacy of isoproterenol on quinidine induced torsade de pointes.

The efficacy of isoproterenol for torsade de pointes (TdP) was evaluated in 60 dogs. TdP was induced in 34 of 60 dogs (56.7%) after the administration of quinidine sulfate (30 mg/kg). The electrophysiologic effect of isoproterenol (0.5 micrograms/min) was studied in 9 dogs with quinidine induced TdP. Isoproterenol significantly shortened basic cycle length, corrected QT interval, effective refractory period (ERP) and dispersion of ERP and increased ERP/QT. Isoproterenol prevented the occurrence of TdP in all dogs. These findings suggest that isoproterenol decreases the dispersion of ventricular refractoriness and may be useful in the treatment of drug induced TdP.

[Efficacy of isoproterenol, magnesium sulfate and verapamil for torsade de pointes].

The efficacy of isoproterenol, MgSO4 and verapamil for torsade de pointes was evaluated in 60 dogs. Torsade de pointes was induced in 28 out of 60 dogs (46.7%) by ventricular stimulation after administration of quinidine sulfate (30 mg/kg). The electrophysiologic effect of isoproterenol (0.5 micrograms/min drip infusion) was studied in 9 dogs with torsade de pointes, in 9 dogs with MgSO4 (30 mg/kg), and in 10 dogs with verapamil (0.1 mg/kg bolus injection followed by 0.01 mg/kg/min drip infusion). If the first dose of these drugs was ineffective, ventricular stimulation was performed after the additional administration of the same dose. Isoproterenol significantly decreased QTc, ERP and dispersion of ERP but increased ERP/QT. MgSO4 significantly increased ERP and ERP/QT, however dispersion of ERP did not change. Verapamil induced no electrophysiologic changes in ventricular refractions . Isoproterenol prevented the occurrence of torsade de pointes in all dogs (100%), MgSO4 in 7 of 9 dogs (77.8%, 30 mg/kg in three and 60 mg/kg in four) and verapamil in 4 of 10 dogs (40%, 0.1 mg/kg in two and 0.2 mg/kg in two). These findings suggest that isoproterenol and MgSO4 increased ERP/QT, showing one of their antiarrhythmic effects. It also shows that isoproterenol and MgSO4 may be useful in the treatment of torsade de pointes.