Diagnostic value of cerebral vasospasm by transcranial doppler ultrasound in Vietnamese patients with subarachnoid hemorrhage.

OBJECTIVE: Although the application of transcranial Doppler (TCD) ultrasonography in clinical diagnosis of cerebral vasospasm is popular in clinical practice in Vietnam, available evidence of the predictive value of vasospasm on TCD in the literature was mostly reported from large institutions in developed countries. Hence, this study was conducted to evaluate the value of TCD ultrasonography in the diagnosis of vasospasm in patients with subarachnoid hemorrhage (SAH) in Vietnam. PATIENTS AND METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between 2008 and December 2011. TCD and 64-slice computed tomographic angiography (CTA) were used to cerebral vasospasm in SAH patients. RESULTS: 316 patients were analyzed (mean age = 52.97±12.27 years, 52.2% males). There were statistically significant difference rates of the cerebral vasospasm by Hunt and Hess Classification and Fisher classification (p <0.01). The proportion of the patients with cerebral vasospasm who were diagnosed exactly by TCD was 95.2%, while the proportion of the patients without cerebral vasospasm diagnosed exactly was 91.5%. TCD predictive diagnostic value was the highest, with the sensitivity of 0.95 (95% CI: 0.91-0.98), specificity of 0.91 (95% CI: 0.85-0.96), positive predictive value of 0.94 (5% CI: 0.90-0.97) and negative predictive value of 0.93 (95 CI: 0.87-0.97). Hemiplegia was the clinical symptom with the highest diagnostic value with the sensitivity of 0.34 (95% CI: 0.27-0.41), specificity of 0.92 (95% CI: 0.86-0.96), positive predictive value of 0.86 (95% CI: 0.76-0.93) and negative predictive value of 0.49 (95% CI: 0.41-0.54). CONCLUSIONS: Evidence of vasospasm diagnosis on TCD ultrasonography was found with high accuracy. Current study enables to suggest the wide application of TCD in Vietnam health facilities from central to grassroots levels instead of the CTA use.

De novo AL amyloid in a renal allograft.

A 65-year-old woman developed nephrotic syndrome 7 years after receiving a cadaveric renal allograft. Renal biopsy and clinical laboratory evaluation revealed the underlying disease process to be AL amyloidosis. To our knowledge, this is the first reported case of de novo AL amyloid occurring in a renal allograft.

Glomerular basement membrane degradation by endogenous cysteine proteinases in isolated rat glomeruli.

Recent in vitro and in vivo studies suggest that cysteine proteinases may play an important role in degradation of the glomerular basement membrane (GBM) by renal glomeruli. However, little information is available concerning the cysteine proteinases present in glomeruli, the distribution of cysteine proteinases in other areas of the kidney, or the potential role of endogenous glomerular cysteine proteinases in GBM degradation. Using well characterized fluorogenic substrates, we have documented the presence of the cysteine proteinases, cathepsins B, H, and L, in glomeruli (0.45 +/- 0.06, 0.39 +/- 0.05, and 0.66 +/- 0.14 mU/mg protein, mean +/- SEM, N = 8) and other fractions prepared from normal rat kidney. The presence of cysteine proteinases in glomeruli was verified by fluorescence microscopy. For each proteinase, the activity was: proportional to the amount of tissue protein and time of incubation; dependent on the presence of exogenously added dithiothreitol; and completely inhibited by the specific cysteine proteinase inhibitor, E-64. The pH optimum for cathepsin B (substrate: Z-Arg-Arg-HNMec) and L (substrate: Z-Phe-Arg-HNMec in the presence of Z-Phe-Phe-CHN2) was approximately pH 6.0 for both glomeruli and renal cortex; while that for cathepsin H (substrate: Arg-HNMec) was approximately 6.5. Incubation of sonicated glomeruli with 3H-GBM under conditions optimal for cysteine proteinase activity (pH 4.5, 1 mM EDTA, and 1 mM dithiothreitol, 37 degrees C) resulted in significant GBM degradation as measured by the release of non-sedimentable (10,000 x g, 10 min) radioactivity or hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence suggesting a role for cathepsin L in an experimental model of glomerulonephritis.

We have utilized specific, irreversible inhibitors of cysteine proteinases to examine the role of renal cathepsin B and cathepsin L in the proteinuria which occurs in an experimental model of human glomerular disease. Administration of trans-epoxysuccinyl-L-leucylamido-(3-methyl)butane (Ep475) a specific, irreversible inhibitor of cysteine proteinases, including cathepsins B and L, significantly reduced proteinuria in rats with experimentally induced, neutrophil-independent, anti-GBM antibody disease (controls: 10 +/- 1 mg/24 h, N = 8; anti-GBM antibody disease: 203 +/- 30 mg/24 h, N = 8; anti-GBM antibody disease + Ep475: 112 +/- 13 mg/24 h, mean +/- SEM, N = 6, P less than 0.05). There was a marked reduction in the activity of both cathepsin B and cathepsin L in renal cortices obtained from Ep475-treated rats compared to either saline-treated controls or rats treated with anti-GBM IgG only. Administration of Z-Phe-Tyr(O-t-butyl)CHN2, a specific, irreversible cysteine proteinase inhibitor with a high degree of selectivity toward cathepsin L, also caused a reduction in anti-GBM antibody-induced proteinuria (90 +/- 18 mg/24 h, N = 6, P less than 0.05). This reduction in proteinuria was accompanied by a marked decrease (-84%) in the specific activity of renal cortical cathepsin L in Z-Phe-Tyr(O-t-butyl)CHN2-treated rats. However, cathepsin B activity was unchanged. There was no significant change in the renal anti-GBM antibody uptake, plasma urea nitrogen, or plasma creatinine values in the Z-Phe-Tyr(O-t-butyl)CHN2-treated rats compared to rats treated with anti-GBM IgG only or saline-treated controls. These data document the ability of cysteine proteinase inhibitors to decrease the proteinuria which occurs in a neutrophil-independent model of human anti-GBM antibody disease and suggest an important role for cathepsin L in the pathophysiology of the proteinuria which occurs in this model.

Osteopontin expression in human cyclosporine toxicity.

BACKGROUND: Osteopontin is a secreted phosphoprotein that has a number of diverse biological functions, including cell signaling, mediation of cell adhesion, migration, and chemoattraction of monocytes/macrophages. Up-regulation of osteopontin expression by proximal tubular epithelium has been demonstrated in both human and rodent models of renal injury in association with macrophage influx. METHODS: We studied the expression of osteopontin protein and mRNA in renal donor biopsies (N = 7) and renal transplant biopsies with cyclosporine A toxicity (N = 23) by immunohistochemistry and in situ hybridization. Serial tissue sections were immunostained with a monocyte/macrophage marker, CD68, to demonstrate the pattern of macrophage infiltration. RESULTS: Strong osteopontin expression was observed in the majority of pretransplant donor biopsies in the absence of any macrophage infiltration. In the biopsies with cyclosporine toxicity, osteopontin expression was widespread and demonstrated moderate immunohistochemical signal intensity that did not correlate with the number of interstitial macrophages present. CONCLUSIONS: Strong osteopontin protein and mRNA expression by tubular epithelium was observed in pretransplant donor biopsies and in biopsies with cyclosporine toxicity without an inflammatory cell infiltration. Therefore, osteopontin expression alone is insufficient to serve as the principal mediator of intrarenal monocyte/macrophage influx in the transplant setting.