Difficult intubation assisted by three-dimensional computed tomography imaging of the pharynx and the larynx.
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Biomedical subjects
Publications and source records attributed to K Nakabayashi.
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In recent years, several laboratories have suggested that serum levels of antioxidant activity and redox balance are reduced in patients with chronic renal failure. Some clinical reports have also proposed that defective serum antioxidative enzymes may contribute to a certain uremic toxicity through peroxidative cell damage. A 48-year-old woman was referred to us from the surgical department of our hospital because of consciousness disturbance, pancytopenia and acute acceleration of chronic azotemia after postoperative radiation therapy. We diagnosed acute acceleration of chronic renal failure with severe acidemia and started hemodialysis therapy immediately. Two days after admission to our department, she developed upper abdominal sharp pain and bradyarrhythmia. Serum amylase activity was elevated markedly and the ECG finding showed myocardial ischemia. On the 24th hospital day these complications were treated successfully with conservative therapy and hemodialysis. We considered that radiation therapy in this patient with chronic renal failure evoked marked oxidative stress and that deficiency of transferrin played an important role in peroxidative cell damage.
A 34-year-old female patient was admitted to our hospital with a 1-year history of chronic congestive heart failure, massive proteinuria and tibial edema. On admission, she presented with hemolytic anemia, hepatomegaly, splenomegaly and renal impairment. Furthermore, the skin of her face, hand, forearm, lower extremities showed crust and bulla. Laboratory examination revealed a large amount of protoporphyrin in her blood and feces, but no increase in urine. Light microscopy of renal biopsy showed moderate chronic tubulointerstitinal disease and mild proliferation of mesangial cells. The prophyians are a group of compounds associated with involving the disturbance of various biosynthetic heme pathwas. Until now, the regulation of porphyrin and heme metabolism in the kidney have received relatively little attention as compared with those in liver and erythropoietic tissue. However, some recent reports have confirmed that proximal tubular cells may contribute to heme biosynthesis. It was strongly suggested that chronic tubulointerstitinal injury in this case might be directly induced by the disturbance of the biosynthetic heme pathway in the tubules.
In order to examine the clinical features of pulmonary involvement in patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA), 46 MPO-ANCA positive patients with collagen-vascular disease and glomerulonephritis were investigated. Twenty eight patients (60.8%) had pulmonary involvement without tumor and infection, 20 (43.5%) of MPO-ANCA positive patients had interstitial pneumonitis, 11 (23.9%) had pulmonary hemorrhage, 3 had asthma (6.5%) and 7 had both interstitial pneumonitis and pulmonary hemorrhage. Patients with pulmonary involvement were older (mean age 61.1) and they had higher inflammatory acute phase reactants and higher mortality (42.9%) than patients without pulmonary involvement. Pulmonary hemorrhage revealed on both lung fields in 10 patients, 7 patients required artificial respirator and 6 died. Titer of MPO-ANCA increased paralleled with progression of pulmonary hemorrhage. Interstitial fibrosis revealed predominantly lower and lateral side of the lung. It is suggested that MPO-ANCA may be closely related to the pathogenesis of pulmonary hemorrhage and interstitial pneumonia. Careful management is needed in patients with pulmonary involvement, especially pulmonary hemorrhage in patients with MPO-ANCA.
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Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.
IgG-class antibodies to double-stranded (ds) and single-stranded (ss) DNA in patients with collagen disease were measured by enzyme-linked immunosorbent assay (ELISA) using bacteriophage lambda DNA as the antigen. Moreover, avidity of IgG-class antibodies to both dsDNA and ssDNA in patients with systemic lupus erythematosus (SLE) was evaluated by ELISA as salt-dependent binding activities. The results are as follows: 1) Elevated IgG-class antibodies to dsDNA were largely restricted to patients with active SLE. Furthermore, the levels of IgG-class antibodies to dsDNA correlated with the disease activity of SLE. 2) Lupus nephritis (LN) patients with nephrotic syndrome (NS) or diffuse proliferative LN as determined by renal biopsy had high levels of IgG-class antibodies to both dsDNA and ssDNA. 3) LN patients with NS showed the highest means of avidity index of IgG-class antibodies to both dsDNA and ssDNA. These findings suggest that the present method of measuring IgG-class antibodies to dsDNA is useful for the diagnosis and management of patients with active SLE and that IgG-class antibodies to both dsDNA and ssDNA with high avidity may be an important factor in the pathogenesis of LN with NS.
Anti-MPO antibodies, serum MPO and cytokines were examined in 106 patients with glomerulonephritis. Twenty-three patients had anti-MPO antibodies and crescent formation; 17 had crescentic glomerulonephritis (CRGN) and the remaining 6 had focal segmental necrosis with less than 50% crescent formation in the observed glomeruli. Pauci-immune CRGN accounted for 28 of 43 CRGN cases. Anti-MPO antibody titers were significantly higher in the cellular crescent stage and their titers correlated well with the number of crescents. Clinical observation revealed that 11 of 18 patients with anti-MPO antibody-associated CRGN had a respiratory tract infection prior to the onset of overt glomerulonephritis. Serum MPO was detected in 20 of 23 patients with anti-MPO antibodies and the amounts of MPO were especially high in the cellular crescent stage and correlated with anti-MPO antibodies. TNF-alpha and IL-6 were also detected in the sera in parallel with the anti-MPO antibody titers. These data suggest that anti-MPO antibodies, TNF-alpha and IL-6, induced by the infection, may activate neutrophils and MPO itself released from neutrophils, may play an important pathogenetic role in glomerular capillary necrosis leading to CRGN.
In order to make an estimate of clinical significance of microalbuminuria (MAU) in patients with rheumatoid arthritis (RA), we studied MAU in 138 patients with RA without macroalbuminuria. MAU was assayed by double-antibody RIA in the ambulatory urine. Moreover, urinary (U) beta 2-microglobulin (BMG) and N-acetyl-beta-D-glucosaminidase (NAG) were simultaneously measured. The values for MAU/U-creatinine (U-Alb index) in patients with RA, osteoarthropathy (OA) and normal controls were 25.7 +/- 38.2, 11.4 +/- 11.5 and 7.7 +/- 3.5, respectively, and U-Alb indices in patients with RA were significantly higher than U-Alb indices in patients with OA and normal controls. Especially, in patients with RA receiving lovenzarit disodium and gold sodium thiomalate (GST), U-Alb indices were elevated. U-Alb indices were not correlated with clinical findings in RA. Also, U-Alb indices were not correlated with U-BMG indices and U-NAG indices in patients with RA. In serial measurements of U-Alb index, U-BMG index and U-NAG index in a patient with RA who developed massive macroalbuminuria during GST therapy, it was found that U-Alb index was elevated first, followed by U-NAG index and finally U-BMG index was elevated. These results indicate that U-Alb indices are elevated in patients with RA without macroalbuminuria, and serial measurements of MAU in patients with RA, especially receiving disease modifying antirheumatic drugs, are useful for the detection of subclinical glomerular injury.
A case of Goodpasture's syndrome with anti-myeloperoxidase (MPO) antibodies is reported. Histological examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular capillary walls and alveolar capillary walls by immunofluorescence microscopy. Not only anti-glomerular basement membrane (GBM) antibodies but also anti-MPO antibodies, an anti-neutrophil cytoplasmic antibody, were simultaneously detected in the serum. Although it is generally accepted that crescentic glomerulonephritis in Goodpasture's syndrome is mediated by anti-GBM antibodies, this case suggested that anti-MPO antibodies might also participate in the pathogenesis of crescentic glomerulonephritis and probably alveolar hemorrhage of Goodpasture's syndrome, especially with vasculitis.
We report a case of microscopic polyarteritis nodosa associated with myeloperoxidase-antineutrophil cytoplasmic autoantibodies (MPO-ANCA). A 38 year-old female was admitted to our hospital, because of proteinuria, recurrent pyrexia, polyarthralgia, abdominal pain and purpura. She had a history of severe pulmonary hemorrhage and 4 kg weight loss for 8 months. On admission perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MPO-ANCA was detected by enzyme linked immunosorbent assay. But anti-nuclear antibodies, immune complexes and anti-glomerular basement membrane antibodies were not detected. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. Skin biopsy revealed leukocytoclastic vasculitis. Diagnosis of microscopic polyarteritis nodosa was made by these clinical and histological evidence of vasculitis. As renal failure progressed after admission, corticosteroid and cyclophosphamide administration were started. Renal function and other symptoms improved paralleled with decreased MPO-ANCA titer to normal values. It is suggested that MPO-ANCA may be closely related to the pathogenesis of microscopic polyarteritis nodosa and it may be a good serological marker for diagnosis and disease activity of this disease.
Cisplatin (CDDP) is used widely in the treatment of a large number of carcinomas. The clinical use of cisplatin, however, can be complicated by myelotoxicity, intestinal toxicity and nephrotoxicity. We reviewed CDDP nephrotoxicity in 244 cases with primary lung cancer retrospectively. The enzyme histochemically localized in proximal tubular cells, N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (BMG), a low molecular weight peptide normally reabsorbed by the renal tubular cells that has been used as an indicator for renal proximal tubular damage, were measured. And fractional excretion of Na (FENa%) and serum magnesium (Mg) levels were also measured before and after CDDP administration serially. The following results were obtained; 1) Over 45% of patients with lung cancer showed transient hyperexcretion of urinary NAG and BMG after CDDP administration. And peak excretion of NAG and BMG appeared to occur within 36 hours after administration of CDDP. 2) Almost all cases with persistent azotemia after CDDP administration showed high values of FENa (%), in spite of gradual normalization of urinary NAG and BMG excretion. 3) Hypomagnesemia was a common complication of CDDP nephrotoxicity that might be caused by a defect in renal Mg reabsorption. CDDP-induced nephrotoxicity seemed to be initiated by an acute, mainly proximal tubular impairment that reflects alterations in excretion of urinary enzymes and low molecular weight protein. In cases with persistent azotemia after CDDP administration depressed renal function might be attributed to the impairment of proximal as well as distal tubular reabsorptive functions.
A 22 year old male of lupus nephritis associated with minimal change nephrotic syndrome was described. The patient was well until 4 years earlier, when Raynaud's phenomenon and photosensitivity developed. One week before admission, edema appeared suddenly and proteinuria was pointed out on July 28, 1990. On admission, his legs, ankles, and eyelids were edematous. There was no sclerodactylia, although Raynaud's phenomenon was positive when his hand disclosed to the cold. Urinalysis showed heavy albuminuria (10.4g/day), but urinary sediment showed no abnormality. Immunological examination showed positive antinuclear antibody, determination at a titer of 1: 160 with a speckled pattern. Anti-RNP and anti-Sm antibody were positive. However, neither anti-DNA antibody nor hypocomplementemia was detected. There was high concentration of serum IgE (2564IU/ml). Renal biopsy was performed. Light microscopic study showed slight increase of mesangial cells and matrix. Immunofluorescence study showed mesangial localization of IgG and C3. Electron microscopic study showed electron dense deposits only in the mesangial area. The diagnosis of lupus nephritis associated with minimal change nephrotic syndrome (MCNS) was made and administration of PSL was started. Proteinuria disappeared after 3 weeks and nephrotic syndrome remitted completely. The case of lupus nephritis associated with MCNS is very rare. Therefore, the relationship between amounts of proteinuria and various histological types of 67 cases with lupus nephritis which we experienced at our hospital was evaluated. Results showed that nephrotic range proteinuria was not present in mesangial lupus nephritis. So, it was concluded that if heavy albuminuria was found in mesangial lupus nephritis, we should consider the possibility of lupus nephritis associated with MCNS.
When men are exposed to a hyperbaric environment, urine flow increases. In order to elucidate the mechanism of this hyperbaric diuresis, a dry saturation dive experiment was carried out. Five male subjects were exposed to a 16-21 ATA (atmospheric pressure absolute) helium-oxygen (He-O2) environment for 4 days. Five blood samples were obtained in the early morning (0600-0630 h): once at predive 1 ATA air, 3 times at 16-21 ATA He-O2, and once at postdive 1 ATA air. Eight-hour timed urine samples, 0600-1400 h, 1400-2200 h, and 2200-0600 h (night urine), were collected throughout the experimental period. Urine flow markedly increased by the exposure to hyperbaria in the presence of constant creatinine clearance. The increase was mostly attributable to the urine flow during 2200-0600 h. The secretion of antidiuretic hormone (ADH) was suppressed at daytime and night during the exposure. On the other hand, the secretion of atrial natriuretic polypeptide (ANP) increased solely at night during hyperbaria and correlated with the increases of both the nocturnal urine flow and the nocturnal urinary excretion of sodium. These results suggest that both suppressed ADH secretion and stimulated ANP secretion cause hyperbaric diuresis.
We report a case of idiopathic crescentic glomerulonephritis with pulmonary hemorrhage associated with anti-myeloperoxidase antibodies (anti-MPO ab). A 74 year-old female was admitted to our hospital because of rapidly progressive glomerulonephritic syndrome and dyspnea with bloody sputum. On admission anti-MPO ab, one of anti-neutrophil cytoplasmic antibodies, were detected but anti-GBM antibodies and immune complexes were not detected. Renal biopsy showed crescentic glomerulonephritis and lung biopsy showed massive alveolar hemorrhage. Both tissue had pauci-immune deposit by immunofluorescence microscopy. Hemodialysis and steroid administration were started. Pulmonary hemorrhage was improved remarkably, but renal failure progressed rapidly to end stage kidney, then hemodialysis was continued. Although subsequent 3 years uneventful maintenance hemodialysis had been performed, she admitted to our hospital again because of progressive dyspnea with hemoptysis after upper respiratory tract infection. On admission anti-MPO ab were detected again and steroid administration was started. Pulmonary hemorrhage was improved with decreased anti-MPO ab titer. While tapering the dosis of steroid, anti-MPO ab again increased and pulmonary hemorrhage recurred. Although pulse methylprednisolone therapy and plasma exchange were performed, respiratory failure progressed rapidly and she died of sepsis. Postmortem examination showed no evidence of systemic vasculitis. In this case, titer of anti-MPO ab was associated with not only idiopathic crescentic glomerulonephritis but also with pulmonary hemorrhage. We tried to detect enzymatically active MPO in serum. Titer of serum MPO was also associated with disease activity and anti-MPO ab. It is suggested that both anti-MPO ab and serum MPO are closely related to the pathogenesis of idiopathic crescentic glomerulonephritis and pulmonary hemorrhage.
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Various peptide fragments related to eglin c, which consists of 70 amino acid residues, were synthesized by a conventional solution method and their inhibitory effects on leukocyte elastase, cathepsin G and alpha-chymotrypsin were examined. Among them, H-Arg-Glu-Tyr-Phe-OMe (eglin c 22-25) and H-Ser-Pro-Val-Thr-Leu-Asp-Leu-Arg-Tyr-OMe (eglin c 41-49) inhibited cathepsin G and alpha-chymotrypsin but not leukocyte elastase, while H-Thr-Asn-Val-Val-OMe (eglin c 60-63) inhibited leukocyte elastase but not cathepsin G or alpha-chymotrypsin, although eglin c potently inhibited leukocyte elastase, cathepsin G and alpha-chymotrypsin. These results indicated that the interaction sites of eglin c with leukocyte elastase, cathepsin G and alpha-chymotrypsin might be different.