Yasushi Kamiya

Aortitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody: report of three cases

We recently experienced three cases of aortitis syndrome that were associated with perinuclear antineutrophil cytoplasmic antibody (ANCA). In the three cases, roentgenographic examination revealed the typical appearance of stenosis or occlusive subclavian arteries. In addition, two cases showed a thickened thoracic aorta wall and the remaining case had irregular stenosis of both common iliac arteries. All three cases had persistently increased ESR and CRP over the years. These findings suggested the diagnosis of aortitis syndrome. ANCA tests were performed because of rapidly progressive glomerulonephritis symptoms in two patients and marked excretion of beta(2)-microglobulin in urine in one patient. The test showed P-ANCA in all three patients, with two patients identified as anti-MPO antibody and the third patient as non-MPO antibody. The implication of ANCA in the pathogenesis of aortitis syndrome is presumed to be: ANCA, which plays an important role in the pathogenesis of small vessel vasculitis, induces vasculitis of the vasa vasorum in the aorta or main branches (or both) and this pathologic process results in the pathogenesis of aortitis syndrome.

Atypical Takayasu arteritis: late onset and arthritic manifestations: report of two cases.

We recently experienced two cases of Takayasu arteritis rendered atypical by late onset (over 60 years of age) of disease, involvement of distal branch arteries, and association with rheumatoid arthritis. In both cases, roentgenologic examination revealed typical appearance of the abdominal aorta and stenosis of the subclavian artery entirely compatible with Takayasu arteritis. In addition, Case 1 had occlusive lesions of the superficial femoral arteries and Case 2 manifested occlusion of the axillary artery. Laboratory findings showed increased ESR and CRP but negative HLA B52 locus. Both cases showed arthritis symptoms with swelling, pain, and tenderness in joints. Case 1 did not manifest erosive lesions and positive RA test; Case 2 showed roentgenologic erosive lesions in hand joints with positive RA test. A surgical specimen from the femoral artery of Case 1 showed lesions suggesting Takayasu arteritis. Based upon these findings, we diagnosed the two patients as having atypical Takayasu arteritis with late middle age onset and arthritic manifestations.

Simultaneous Inhibition of Renal Phospholipase A2 and Glutathione Synthesis by Manoalide and DL-Buthionine Sulfoximine Induces Acute Tubular Dysfunction in Rats

We have previously demonstrated that gentamicin-induced acute renal failure is mediated by the consumption of renal glutathione (GSH) and accumulation of oxidized phospholipids in tubular epithelial cells as a result of inhibition of phospholipase A2 (PLA2) activity. Based on these results, we tested the hypothesis that the simultaneous inhibition of PLA2 and GSH synthesis induces acute renal failure similar in characteristics to gentamicin-induced acute renal failure. Male Sprague-Dawley rats kept under standard laboratory conditions were administered 3 mmol/kg of DL-buthionine sulfoximine (BSO; γ-glutamylcysteine synthetase inhibitor) and 30 μg/kg of manoalide (PLA2 inhibitor), following which significant elevations in serum creatinine and urinary lysosomal enzyme levels (elevation of N-acetyl-β-D-glucosaminidase activity) were observed. The renal tissue GSH content was reduced in the group that received both BSO and manoalide as compared with the group that received manoalide alone. The renal tissue GSH content was also reduced in the group that received BSO alone. The renal tissue concentration of 2-thiobarbituric-acid-reactive substances increased rapidly, followed by an increase in renal tissue total phospholipid concentration in the group that received both BSO and manoalide. In contrast, the activity of PLA2 in renal tissue decreased in the group that received both BSO and manoalide as compared with the groups that received BSO alone or physiological saline. In conclusion, concomitant administration of BSO and manoalide induces renal tubular damage and acute renal failure in rats, similar in characteristics to gentamicin-induced nephrotoxicity, whereas administration of BSO or manoalide alone did not. These results suggest that both inhibition of PLA2 and GSH depletion are necessary for the induction of acute renal failure.

Clinical Characterization of Acute Renal Failure in Multiple Organ Dysfunction Syndrome

BackgroundAcute renal failure frequently occurs as a complication of multiple organ dysfunction syndrome (MODS). Various forms of therapy for MODS, including endotoxin absorption and anticytokine therapy, have been attempted.MethodsWe retrospectively studied the pathophysiologic characteristics of acute renal failure in 152 MODS patients examined in our department over the past 5 years. The diagnosis of MODS was based on the criteria of the Japanese Association for Critical Care Medicine. The diagnosis of systemic inflammatory response syndrome (SIRS) and sepsis was conducted in accordance with the definition proposed at the 1992 Consensus Conference of the American College of Chest Physicians/ Society of Critical Care Medicine.ResultsAcute renal failure occurred as a complication of secondary MODS with a high frequency of 76.3% (116/152 patients). Significant associations have been found between the respective frequencies of acute renal failure and disseminated intravascular coagulation occurring as complications of SIRS. An increase in the number of cases undergoing continuous hemodiafiltration was noted, in an attempt to improve the survival rate of MODS complicated with acute renal failure.ConclusionAcute renal failure seen in secondary MODS is thought to be derived from a pathogenesis differing from that of conventional intrinsic acute renal failure, such as ischemic and nephrotoxic forms. Acute renal failure associated with secondary MODS appears to be a disease entity that arises as a sequela of SIRS, similar to disseminated intravascular coagulation.

A Case of Partial Carnitine Palmitoyltransferase Deficiency in a Patient Undergoing Chronic Hemodialysis

A 71-year-old male undergoing hemodialysis for chronic renal failure presented with proximal muscle weakness. He had normal levels of serum creatine phosphokinase. The results of nerve conduction velocity studies and a needle-exploration electromyogram were normal. Ultrasonography revealed adenomatous enlargement of the parathyroid glands, and he had marked elevation of the serum parathormone level. The level of serum free carnitine before hemodialysis was significantly lower than normal, while the acyl/free ratio was high. However, the muscle carnitine content was within the normal range. Interestingly, partial inactivation of carnitine palmitoyltransferase activity in the muscle was observed in association with the elevation of the serum parathormone level. Uremic myopathy in this case may be caused not only by abnormal carnitine metabolism but could also be attributable to the partial carnitine palmitoyltransferase deficiency associated with secondary hyperparathyroidism.