ISSN:1660-8151    

DOI:10.1159/000190218

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Mycophenolate Mofetil (MMF), the morpholinoethyl ester of the active compound mycophenolic acid, is a new immunosuppressive agent which blocks the de novo synthesis of guanine nucleotides. As this pathway is essential for purine synthesis of both T and B lymphocytes, the blocking effect on cell division is lymphocyte-selective with little effect on the division of other cell types. In three recent randomized multicenter trials, MMF in conjunction with ciclosporin and steroids has been shown to reduce the incidence of early acute rejection after renal transplantation by almost 50%. The toxicity profile is comparable to that of azathioprine but with a significantly higher efficacy. Major side effects are gastrointestinal with a slight increase of the incidence of mainly viral (CMV) infections. In contrast to ciclosporin and FK-506, MMF is not nephrotoxic. Future studies have to show whether the use of MMF in combination with other immunosuppressants may allow to reduce the doses of the most toxic ones. In addition, long-term studies are needed to prove its potential protective effect on the occurrence of chronic rejection as suggested by several experimental studies and by its effect on the incidence of acute rejection.

ISSN:1660-8151    

DOI:10.1159/000190219

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:1660-8151    

DOI:10.1159/000190220

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Lupus anticoagulant (LA), anticardiolipin (aCL), and/or antiphospholipid (aPL) antibodies are the hallmarks of the antiphospholipid syndrome, characterized by widespread thrombosis. The syndrome has been described as primary or secondary when aCL/aPL are the only classes of detectable autoantibodies or occur in the context of systemic lupus erythematosus (SLE) or SLE-like disease. However, since LA/aCL/aPL have been extensively looked for, it has become evident that they may also be detected in the absence of any clinical correlation with thrombosis. In particular, among SLE patients, these antibodies mean a high risk of thrombosis only in a small subset, sharing clinical features with primary antiphospholipid syndrome. As laboratory examination is still unable to distinguish between high-risk and non-high-risk antiphospholipid antibodies, it is crucial to have some reasonable criteria able to guide the day-to-day clinical practice. We attempt to trace the following guidelines: (1) distinguish between transient and persistent LA/aCL/aPL results; (2) do not forget the LA phenomenon in the era of aCL/aPL; (3) maintain a strict communication with the laboratory; (4) exclude other causes of primary coagulation abnormalities; (5) look at the time of appearance of LA/aCL/aPL with respect to thrombosis; (6) analyze any possible laboratory clue putatively useful to distinguish between ‘rouge’ and ‘non-rouge’ LA/aCL/aPL; (7) look for signs of widespread noninflammatory vasculopathy; (8) do not engage a war to the knife against LA/aCL/aPL by immunosuppressive th

ISSN:1660-8151    

DOI:10.1159/000190221

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The study was devised to explore the effects of an acute oral protein load on renal hemodynamic response in patients with IgA nephropathy (IgAN). The study was performed in 10 proteinuric IgAN patients (800 ± 300 mg/day) and in 20 healthy controls (matched by sex, age, BMI, BSA, plasma creatinine, plasma urea, urinary urea and protein intake). Blood pressure and creatinine clearance were nearly identical in the two groups. GFR. and RPF, measured as the clearance of inulin and of p-aminohippurate (PAH) were studied before and after a meat meal which provided 2 g of protein/kg BW. Following the protein load, renal reserve, percent renal reserve and postmeal cumulative changes of GFR were not significantly different in IgAN and controls. Filtration fraction (FF) at baseline was significantly higher (p < 0.01) in IgAN than in controls (25.5 ± 1.41 vs. 19 ± 2%). Postmeal hyperemia and hyperfiltration did not affect FF in either group. Filtration capacity in IgAN was lower (p < 0.02) than in controls (117 ± 5.6 vs. 137.9 ± 7.0ml/min × 1.73 m2), whereas the percent of filtration capacity utilized at rest was identical in controls and in IgAN. Creatinine clearance overestimated GFR in IgAN. The data indicate that renal hemodynamic response to proteins in IgAN is n

ISSN:1660-8151    

DOI:10.1159/000190222

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Insulin-dependent diabetes mellitus (IDDM) patients may have an increased intrarenal angiotensin II activity. In diabetic patients, captopril increases the renal hemodynamic response to an amino acid infusion. We investigated the effects of two salt diets on arterial pressure and renal response to a protein load in 10 normotensive (blood pressure < 140/90 mm Hg) IDDM patients (aged 30 ± 3 years) who had diabetes for 7 ± 4 years and normoalbuminuria levels [albumin excretion rate 4.8 (2.5-19.1) μg/min]. After 1 week of normal (≈100 mmol/day; ≈100 mEq/l) and 1 week of high (≈300 mmol/day; ≈300 mEq/l) salt intake, renal hemodynamic studies were performed at baseline and after a protein load (meat meal) of 100 g/l.73 m2. The mean 24-hour urinary sodium excretion levels were 99 ± 27 and 293 ± 80 mmol (mEq) with normal and high salt intake, respectively. No significant changes were seen in plasma sodium and glucose control with the normal and high salt diets, respectively: plasma sodium 135 ± 3 vs. 137 ± 1 mmol/l (mEq/l), (p = 0.08) and glycated hemoglobin 9.1 ± 1.9 vs. 9.4 ± 2.1% (p = 0.36). The body weight (70.9 ± 12 vs. 71.8 ± 13 kg; p = 0.015) was significantly higher with a high salt diet. The mean arterial pressure was similar with both diets (normal vs. high salt diet 91 ± 9 vs. 89 ± 6 mm Hg, p = 0.25). The plasma renin concentration [28 ± 15 vs. 16 ± 6μU/ml(168 ± 90 vs. 96 ± 36 pmol/l), p = 0.013] and angiotensin II [8.8 ± 4.4 vs. 6.4 ± 3.5 pg/ml (0.052 ± 0.025 vs. 0.038 ± 0.021 nmol/l), p = 0.016] were significantly lower with the high salt diet. Following protein loading, the glomerular filtration rate increased with both diets: normal salt diet 114 ± 26 vs. 128 ± 30ml/min/1.73 m2(1.9 ± 0.43 vs. 2.13 ± 0.50ml/s/1.73 m2), p = 0.04; high salt diet 118 ± 23 vs. 127 ± 29 ml/min/1.73 m2 (1.97 ± 0.38 vs. 2.12 ± 0.48 ml/s/1.73 m2), p = 0.13. The change in renal plasma flow was similar to that of the glomerular filtration rate with normal and high salt intake, respectively: 566 ± 94 vs. 617 ± 142 ml/min/1.73m2 (9.44 ± 1.57 vs. 10.29 ± 2.37 ml/s/173m2), p = 0.0017; 572 ± 125 vs. 600 ± llθml/min/l.73 m2 (9.54 ± 2.08 vs. 10.00 ± 1.83 ml/s/1.73 m2), p = 0.057. In this subset of normotensive normoalbuminuric IDDM patients, a high salt intake did not promote an exaggerated renal response to the protein load desp

ISSN:1660-8151    

DOI:10.1159/000190223

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Hemodialysis with new cuprophane membranes upregulates expression of granulocyte adhesion molecules and activates 5-lipoxygenase as reflected by the enhanced generation of leukotriene B4 (LTB4). We assessed the role of 5-lipoxygenase activity in hemodialysis-induced upregulation of the granulocyte adhesion molecules, CD lib and CD 18, and granulocyte adhesion to human umbilical vein endothelial cells in an ex vivo dialysis model. 5-Lipoxygenase was effectively inhibited by preincubation of human whole blood with the speciñc inhibitor, BAY XI00 5. Dialysis with new cuprophane but not with new acrylonitrile membranes significantly upregulated expression of CD1 lb and CD 18 by 6-fold and 4-fold, respectively. Inhibition of 5-lipoxygenase did not affect the expression of CD1 lb and CD 18 during dialysis with either of the two membranes. In contrast to the enhanced expression of CD1 lb and CD 18, adhesion of granulocytes to human umbilical vein endothelial cells did not increase during dialysis, nor was it affected by BAY XI005. These data indicate that ex vivo dialysis with cuprophane membranes upregulates expression of CD1 lb and CD 18 on granulocytes independent of the activation of 5-lipoxygenase

ISSN:1660-8151    

DOI:10.1159/000190224

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

To clarify the in vivo involvement of cellular adhesion molecules and cytokines in human glomerulonephritis, we have investigated the glomerular and interstitial expression of intercellular adhesion molecule 1 (ICAM-1) in 69 kidney biopsy specimens by immunohistochemical methods and its correlation with serum bioactive tumor necrosis factor alpha (TNF-α) and soluble ICAM-1 (sICAM-1) levels in 43 cases. In normal controls, glomerular ICAM-1 expression and serum TNF-α and sICAM-1 levels showed a mean score of 1.0 (n = 7) and were 12.1 ± 1.5 and 187 ± 5 ng/ml (mean ± SEM, n = 25), respectively. ICAM-1 was positive in 68 kidneys except in 1 patient with membranous nephropathy at various degrees in glomeruli and in 72% of peritubular capillaries or venules in the interstitium. Serum-bioactive TNF-α levels increased in the patients with IgA nephropathy, purpura nephritis, and lupus nephritis (LN) (18.9 ± 4.1, 32.6 ± 13.3, and 20.9 ± 3.5 pg/ml) and were positively correlated with the grade of glomerular ICAM-1 expression (n = 43, r = 0.57, p < 0.001), endocapillary proliferation with exudative lesions (r = 0.72, p < 0.001) and hematuria (r = 0.62, p < 0.001). Serum sICAM-1 levels were elevated in patients with LN and purpura nephritis and decreased from 312 ± 40 to 226 ± 21 ng/ml after methylprednisolone pulse therapy in LN (n = 9, p = 0.0285). sICAM-1 levels were positively correlated with the grade of interstitial ICAM-1 expression (r = 0.46, p 210 ng/ml) showed high odds ratios in the interstitial ICAM-1-positive cases and systemic vasculitides such as purpura nephritis and LN (6.00, p = 0.0355; 6.50, p = 0.0216, respectively). These results suggest that bioactive TNF-α might relate to glomerular ICAM-1 expression associated with endocapillary lesions in human glomerulonephritis and that sICAM-1 levels may be used as a clinical marker to assess interstitial lesions in human nephritis and systemic v

ISSN:1660-8151    

DOI:10.1159/000190225

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Objective: Indexes of myocardial ischemia and vasoconstrictive hormonal release were evaluated in order to investigate the difference between essential hypertension and hypertension during chronic renal failure. Background: Arterial hypertension induces several cardiovascular alterations that reflect themselves either on the heart and/or on the coronary blood flow enhancing the cardiovascular risk. Since chronic renal failure can influence the neuroendocrine response, various mechanisms involved in hypertension during chronic renal failure are still unclear. High endothelin 1 (ET-1) levels have been found both in arterial hypertension and during chronic renal failure. Interestingly, either ET-1 or catecholamines seem also to be implied in the pathogenesis of myocardial ischemia. Methods: 20 hypertensive uremic and 20 essentially hypertensive patients underwent echocardiographic wall motion and wall thickening analysis performed at baseline and immediately after the end of exercise. Simultaneously, myocardial perfusion was evaluated by 99mTc-MIBI-SPECT. In addition, plasma norepinephrine and ET-1 concentrations were measured at baseline and at peak exercise. Results: The segmental radionuclide analysis showed a greater ischemic degree in hypertensive uremic patients. Yet, we were able to identify one or more regions of the left ventricle in which both systolic thickening measurements and wall motion after exercise were impaired. After exercise, wall thickening impairment was correlated with both wall motion abnormalities (r = 0.72, p < 0.01) and MIBI ischemic grade (r = 0.82, p < 0.001). Basal and after-exercise plasmatic norepinephrine and endothelin levels were higher in hypertensive uremic than in essentially hypertensive patients. Moreover, there was a significant correlation between increments in norepinephrine concentration and MIBI perfusion defects, and between the increment in ET-1 concentration and both MIBI perfusion defects, or kinetic alterations assessed by wall motion as well as by wall thickening. Conclusions: This is the first cross-sectional study in which a higher degree of myocardial ischemia has been observed in hypertensive uremic patients combined with an enhanced plasma release of both norepinephrine and ET-1. This phenomenon may contribute to enhance the cardiovascular risk of these patients.

ISSN:1660-8151    

DOI:10.1159/000190226

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We reevaluated the distribution of anionic sites in the glomerular basement membrane with ruthenium red, alcian blue, cationic ferritin, polyethyleneimine, and cationic colloidal gold. Without the accentuation by the metal staining with uranyl acetate and lead citrate, we observed the existence of anionic sites throughout all the layers of the glomerular basement membrane with a similar reticular pattern and the structural difference between the lamina rara and lamina densa, indicating that the lamina rara is an acutal structural element.

ISSN:1660-8151    

DOI:10.1159/000190227

出版商:S. Karger AG    

年代:1997

数据来源: Karger