Use of cyclophosphamide and other immunosuppressive drugs in the treatment of patients with lupus nephritis.

UNLABELLED: Systemic lupus erythematosus (SLE) is a chronic relapsing systemic autoimmune disease; one of the most serious complications is renal involvement, which is occurring in almost 50% of all patients at the beginning of the disease. The aim of the present study was to compare renal function, proteinuria, activity markers and treatment regimen of active and inactive SLE patients with renal involvement. We analyzed the correlation of serum blood urea nitrogen, creatinine level, glomerular filtration rate, urine total protein/serum creatinine (uTP/creat), CRP to classic activity markers of SLE (serum complement 3, -4 level, anti-dsDNA antibody). Moreover we analyzed the treatment modalities of patients with lupus nephritis (LN). Data of 418 SLE patients were analyzed, out of these patients 128 had biopsy proven lupus nephritis or had more than 3 + proteinuria by urine dipstick analysis (30% of all cases). RESULTS: Data of 128 patients with lupus nephritis were analyzed (mean age 32.18 +/- 11.48 year, time between the diagnosis of SLE and LN was 2.78 +/- 4.59 year). 48% of patients had diffuse proliferative glomerulonephritis, 75% of them received cyclic cyclophosphamide treatment. UTp (total protein)/creatinine level was significantly higher in active LN group (p = 0.03), and correlated to erythrocyte sedimentation rate (p = 0.002, R = 0.52). Mean anti-dsDNA level of patients with active LN was significantly higher (p < 0.001). CONCLUSIONS: Patients with active lupus nephritis are at higher risk of developing renal failure, activity markers and urine protein are elevated in these patients as compared to inactive patients, early aggressive immunosuppressive treatment needs to be started to prevent end-stage renal failure.

Effect of drugs used in different type of myocardial infarction (STEMI or (NTEMI) on mortality.

We examined 416 patients with acute myocardial infarction. 249 patients had STEMI and 167 NSTEMI. 227 were men and 189 women. 142 men had STEMI and 85 men had NSTEMI. 107 women were diagnosed with STEMI and 82 with NSTEMI. 22.5% of patient with STEMI and 20.2% of patients with NSTEMI died (p = 0.58). We compared the effect of anticoagulant treatment, clopidogrel, salicylate, nitrate, beta-blocker, angiotensin-converting enzyme inhibitor, statin and trimetazidine therapy on mortality in function of the type of myocardial infarction. There were no differences between mortality of patients with STEMI and NSTEMI with respect of use of heparine, salicylate, nitrate, beta-blocker, ACE inhibitor, statin and trimetazidine. While examining the effect of clopidogrel, we observed a significantly lower mortality rate in patients with NSTEMI compared to the STEMI group (p = 0.005). These differences are due to the known variability in clopidogrel absorption and metabolism, which could be influenced by the type of myocardial infarction.

Serum and urinary cytokine levels of SLE patients.

Systemic lupus erythematosus (SLE) is a chronic, relapsing, polysystemic autoimmune disease with various clinical signs. The prognosis of SLE patients is influenced by neuropsychiatric and renal involvement. Lupus nephritis (LN) is present in 40-60% of patients. Classical laboratory parameters are not sensitive and specific in prediction renal flares, over the last few years there has been a growing interest in searching novel lupus biomarkers predicting future flares. Our goal was to detect serum and urinary level of cytokines in 36 patients with lupus nephritis (34 female and 2 male, mean age: 43.36 +/- 11.53 years), 23 patients with SLE without renal involvement (19 women and 4 men, mean age: 54 +/- 8.71) (both groups followed by the 3rd Department of Internal Medicine, Division of Clinical Immunology, University of Debrecen) and 30 healthy controls (23 female and 7 male, mean age: 45.5 +/- 12.4). Serum IL-1 (interleukin), IL-2 (both p < 0.05), IL-6, IL-13 and IFN-gamma (p < 0.001) levels were significantly higher in lupus nephritis patients, as compared to patients with SLE without renal involvement and healthy controls. Urinary level of IL-1 and TNF-alpha were significantly higher in SLE patients without renal disease (p = 0.012 and p < 0.001), while urinary IFN-gamma was significantly higher in LN patients (p = 0.002). Measurement of IL-6 level in SLE patients could help to predict future renal involvement of SLE patients.

Influence of statin treatment on mortality of patients with myocardial infarction.

Dyslipidaemia is a major risk factor of cardiovascular diseases, the role of serum total cholesterol (Chol) especially LDL-Chol is well established in the pathogenesis of atherosclerosis and ischemic heart disease. Use of cholesterol lowering drugs within the first 24 h of hospitalization for acute myocardial infarction (AMI) is associated with a lower rate of cardiogenic shock, arrhythmias, cardiac arrest and recurrent myocardial infarction. We assessed data of 416 patients admitted to hospital with AMI in a 2 year period (2001-2003) focusing on statin therapy. We have not found a correlation between serum lipid parameters and mortality of patients with AMI. Chronic statin treatment used before AMI (in 36 patients) did not influence mortality of patients. Chol level of patients with ST-elevation myocardial infarction (STEMI) was significantly higher (p = 0,043). Mortality of patients who did not receive statin treatment after AMI was significantly higher. These data highlight the importance of early aggressive statin treatment in patients with AMI and necessity of statins in patients with hypercholesterolaemia.

Does impairment of renal and hepatic function influence the metabolism of thrombolytics in patients with myocardial infarction?

Thrombolytic agents activate plasminogen and induce a systemic fibrinolytic and anticoagulant state. Two thrombolytic drugs are used frequently in practice: streptokinase (SK) and alteplase (t-PA). Streptokinase mainly undergoes renal elimination with a half-life of 11-17 min, while alteplase is eliminating by the liver with a half-life of 4-6 min. Our goal was to examine whether renal and hepatic function influence the elimination and metabolism of thrombolytics and the efficacy of percutaneous coronary intervention (PCI) after using alteplase or streptokinase. 416 patients with myocardial infarction (MI) were treated from January 2001 to December 2003 (228 male and 189 female). Alteplase was used in 9 men and 6 women (mean age: 53.88 +/- 9.61 vs. 65.33 +/- 9.87 years, p = 0.07). Patients who underwent rescue PCI after administration of alteplase had slightly higher hepatic enzyme levels/alanine transaminase (ALT): 47.85 vs. 41.4 U/l; gamma-glutamyl transpeptidase (GGT): 69.5 vs. 44.8 U/l/. All patients treated with alteplase survived, rescue PCI was done in 8 cases. Streptokinase was used in 36 men and 28 women (mean age: 63.33 +/- 10.51 vs. 63 +/- 12.03 years, p = 0.9). We did not find a difference between serum creatinine levels of patients who received streptokinase and underwent PCI as compared to those who had not. Rescue PCI was done in 16 cases. 12 patients died in this group. In conclusion we have not found a significant correlation between the use of the thrombolytics and hepatic or renal function; this could indicate that such a slight impairment of liver and renal function does not influence pharmacokinetic properties of thrombolytics.

Retrospective analysis of patients with lupus nephritis: data from a large clinical immunological center in Hungary.

The aim of this study was to review the development, histological type and outcome of 117 patients with lupus nephritis managed and followed by the Division of Clinical Immunology, 3rd Department of Internal Medicine, University of Debrecen, Debrecen, Hungary. The method used was a retrospective study in 117 patients with lupus nephritis followed between 1974 and 2004. The average occurrence of lupus nephritis was 3 (women) and 4.4 (men) years later after the diagnosis of systemic lupus erythematosus, 43 (46.2%) patients had class IV lupus nephritis. The initial therapy was intravenous cyclophosphamide treatment for 6 months in 37 (31.6%) patients. End-stage renal disease had developed in nine (7.6%) patients. The 5-year survival rate was 99.1%. Despite the well-known and proved risk factors like hypertension, high serum creatinine, renal failure at onset or membranous glomerulonephritis, the outcome of the disease in our patient population was more favourable than one would expect according to the data available in the literature. The authors would like to draw attention to the importance of systematic care of patients with systemic lupus erythematosus, which may lead to a better clinical outcome.

Metabolism of dynorphin A(1-13).

Dynorphin A(1-13), a tridecapeptide of the endogenous opioid peptides, has modest effects in reducing mild opiate withdrawal in humans. Previous studies revealed that dynorphin also potentiates the analgesic effect of morphine in morphine-tolerant rats and mice. The therapeutic potential of dynorphin A(1-13) is limited due to extensive metabolism by human metabolic enzymes resulting in an in vivo half-life of less than one minute. Chemical modifications of dynorphin A(1-13), such as N-methylation of Tyr1 and amidation of the C-terminus have been shown to be effective in protecting against the proteolytic enzymes in human plasma. This article is a general review of the metabolism of dynorphin A(1-13) in human plasma and CSF.