Studies on the procoagulant activity of human amniotic fluid. I. Stability and coagulation factor requirements

A fraction of human amniotic fluid possessing procoagulant activity was purified 35-70 fold by gel filtration on Sepharose 4B. The activity eluted in the void volume indicating a particle size in excess of 5 X 10(6) daltons. The amniotic fluid factor (AFF) activity is stabilized on storage in the presence of Ca++ ions which could not be replaced by Mg++. Addition of phospholipids resulted in accelerated loss of activity. Steps taken to remove factor VII did not affect the activity, but factor X and V are required.     

Leptospirosis and acute renal failure--clinical experiences and a review of the literature.

About 50 cases of leptospirosis are diagnosed each year in the United Kingdom, with an overall mortality of 5%. Renal failure, in association with jaundice, is commonly held responsible for this figure. Over a period of 18 years, 6 cases of leptospirosis complicated by renal failure were treated at the Royal Air Force Renal Unit; there were 4 survivors. The 2 deaths occurred before the unit policy of daily haemodialysis and total parenteral nutrition, and were both from haemorrhagic complications. The authors believe that patients with leptospirosis and progressive renal impairment should be managed in renal units experienced in the management of the hypercatabolic patient, and that this should improve their prognosis.     

Clinical features and outcome of patients with both ANCA and anti-GBM antibodies

BACKGROUND: Patients have been described who have both anti-neutrophil cytoplasm antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies. We have attempted to define the true prevalence of such "double positive" patients, and describe in detail their clinical features and outcome. METHODS: We have reviewed all serologic assays performed between 1990 and 2000 in a single institution, and the case notes of patients having sera positive for both ANCA and anti-GBM antibodies. During this time 20,392 sera were initially tested for ANCA, and 4808 sera tested for anti-GBM antibodies. RESULTS: Five percent of all ANCA-positive serum samples were also positive for anti-GBM antibodies, and 32% of all anti-GBM positive samples had detectable ANCA. Of 27 patients with both antibodies, 82% had anti-myeloperoxidase specific P-ANCA. Pulmonary hemorrhage occurred in 44%. Renal biopsy showed extensive glomerular cellular crescents in most patients. Patient and renal survival rates were 52% and 26%, respectively, at one year. Sixty-eight percent of patients were dialysis-dependent at presentation, and none of these recovered renal function, despite immunosuppression with or without plasma exchange. CONCLUSION: Serologic evidence of double positivity for both ANCA and anti-GBM antibodies is common in patients with either antibody. In our study these patients have a poor prognosis when presenting with severe disease and initially behave more like anti-GBM disease than vasculitis. Recovery from severe renal failure is rare.     

Treatment with an antibody to VLA-1 integrin reduces glomerular and tubulointerstitial scarring in a rat model of crescentic glomerulonephritis

The alpha 1 beta 1 integrin (VLA-1) is a major collagen/laminin receptor that regulates fibroblast proliferation and mesangial cell migration and cell contraction. We have examined the effect of an antibody to VLA-1 in crescentic glomerulonephritis. Nephrotoxic nephritis was induced in Wistar-Kyoto rats and rats were given monoclonal antibody to VLA-1 (Ha31/8), 2.5 mg/kg, on alternate days. Antibodies were given from day -1 to day 10 or from day 14 to day 28. Treatment from day -1 to day 10, during the early inflammatory phase of nephrotoxic nephritis, had no effect on albuminuria or glomerular crescent formation. In the delayed treatment experiment, all rats developed florid crescentic glomerulonephritis, and control rats showed marked glomerular and tubulointerstitial scarring at day 32. VLA-1 expression, by immunohistochemistry, was increased in glomeruli and around tubules. Proteinuria did not differ between groups. In anti-VLA-1-treated rats, serum creatinine was significantly lower at day 32 (P = 0.002) and renal survival was significantly better (P = 0.045). Both glomerular and interstitial scarring were significantly less at day 32 in rats given anti-VLA-1 (P = 0.002). Deposition of ED(A) fibronectin, a marker of new matrix synthesis, and of type IV collagen, were reduced in glomeruli and interstitium in anti-VLA-1-treated animals (P = 0.0006). Expression of alpha-smooth muscle actin, a marker of myofibroblasts, showed no significant difference. Expression of matrix metalloproteinase-9 was increased in the glomeruli of rats treated with anti-VLA-1. We conclude that VLA-1 mediates both glomerular and interstitial fibrosis in crescentic glomerulonephritis and that neutralization of VLA-1, which enhanced expression of matrix metalloproteinase-9, is a possible therapeutic strategy in progressive renal scarring.     

筛查和诊断糖尿病的新观点

美国约有30％的糖尿病患者（约620万人）被漏诊。超过25％的新诊断糖尿病患者已经患有糖尿病视网膜病变或出现微量白蛋白尿，这意味着患者在2型糖尿病发病和确诊之间被“忽视”了7年。有时发现在糖尿病前期，即空腹血糖（FPG）略有偏高（IFG，空腹血糖受损）或口服葡萄糖耐量试验（OGTT）略有偏高，甚至已存在微血管和大血管并发症。     

Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies.

To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry. Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine less than 500 mumol/liter (N = 17), or greater than 500 mumol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow-up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases.