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ABSTRACT: OBJECTIVE: Intravenous cyclophosphamide (IV CYC) in combination with high doses of corticosteroids is considered the "gold standard" of therapy for lupus nephritis (LN). However, the optimal dose of corticosteroids needed has not been defined. We evaluated the efficacy of a monotherapy with IV CYC in patients with a first episode of LN (duration ≤ 6 months). METHODS: Forty patients with LN received IV CYC (12 pulses). Prednisone alone was administered and dose-adjusted to control extrarenal manifestations. Response after 24 months was defined as normalization of creatinine level, inactive urinary sediment, and proteinuria ≤ 0.2 g/day [complete response (CR)] or ≤ 0.5 g/day [partial response (PR)]. RESULTS: CR was achieved in 25 (62.5%) and PR in 8 (20%) patients. Mean starting dose of prednisone was 23.9 ± 23.8 mg/day. In a posthoc analysis, we separately analyzed patients initially treated with prednisone doses ≥ 20 mg/day (Group A, n = 19) or < 20 mg/day (Group B, n = 21). CR was achieved in 52.6% (Group A) versus 71.4% (Group B; p = 0.37); and PR in 26.3% versus 14.3%, respectively (p = 0.58). During longterm followup (10.4 ± 3.1 yrs), 37.8% experienced a renal flare. Thirty patients (81%) still have normal renal function. Renal outcome was irrespective of initial prednisone doses (p = 0.46, Pearson chi-square test of independence). CONCLUSION: Our rates of CR and PR and longterm outcomes were comparable with rates after treatment with a combination of IV CYC with high doses of corticosteroids. These data warrant randomized controlled trials evaluating different doses of corticosteroids in LN.
The Journal of Rheumatology 09/2012; · 3.69 Impact Factor
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ABSTRACT: To analyse if defensins, immunomodulatory peptides involved in angiogenesis and elevated in the sera of systemic lupus erythematosus (SLE) patients, relate to cardiovascular disease in SLE.
Serum levels of the defensins human beta defensin 2 (hBD2) and human neutrophil peptide (HNP) of 72 SLE patients were determined by ELISA at baseline. Cardiovascular risk factors and the occurrence of cardiovascular events (CVE: stroke, claudication, angina pectoris, myocardial infarction) were recorded over 6 years. Intima media thickness of the carotid arteries (CIMT) was measured by ultrasound in 42 patients at baseline and at 4 years. Normally distributed log-transformed defensin levels (log-hBD2 and log-HNP) were used for statistical analysis.
SLE patients who experienced a CVE had significantly higher log-hBD2 values and a likelihood-ratio for CVE of 2.23 when levels increased above 3.3 log(ng/ml). Using binary logistic regression analysis, log-hBD2 significantly contributed to a model also incorporating the number of traditional cardiovascular risk factors (dyslipidemia, hypertension, positive family history, age, smoking) as explanatory variables for the incidence of cardiovascular events. Moreover, SLE patients with progressive CIMT showed increased log-hBD2 and log-HNP values. Both defensin-levels also showed some correlation to the plaque stadium at baseline (hBD2: r2 0.10; HNP r2 0.12). Neither log-hBD2 nor log-HNP were correlated to traditional cardiovascular risk factors.
HNP and especially hBD2 may be indicators of progressive cardiovascular disease in SLE.
Clinical and experimental rheumatology 03/2012; 30(3):364-70. · 2.15 Impact Factor
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ABSTRACT: Defensins are highly conserved peptides with antimicrobial and immunomodulatory functions. Due to their chemotactic properties on mononuclear cells, including dendritic cells and macrophages, defensins may contribute to granuloma formation in Wegener's granulomatosis (WG). In order to explore whether these peptides might be involved in WG pathogenesis, sera of patients were screened to detect altered defensin levels. For this purpose, serum and EDTA-blood of patients with WG (n = 17; aged 54.8 ± 15.5 years) and age- and sex-matched healthy controls (n = 24; aged 55.5 ± 16.8 years) were collected. Levels of neutrophil α-defensins (human neutrophil peptides, HNP) and β-defensin (hBD) 2 and 3 in serum were measured by ELISA. By this means, WG patients displayed higher serum levels of hBD2 and HNP when compared to controls. Furthermore, serum hBD2 was raised in patients with meningeal granulomas (n = 4) or in those undergoing treatment with cyclophosphamide (n = 4). In order to detect whether increased gene expression in polymorphonuclear cells is responsible for the elevated defensin levels, real-time polymerase chain reaction with gene-specific primers was performed. Expression of specific mRNA in polymorphonuclear cells was observed for HNP only, but did not parallel HNP serum levels, suggesting that degranulation rather than increased gene expression may be responsible for increased HNP serum levels in WG. In conclusion, elevated serum levels of HNP and hBD2 in WG patients suggest a role for both defensins in WG pathogenesis.
Rheumatology International 12/2010; 31(9):1251-4. · 1.88 Impact Factor
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The Journal of Rheumatology 08/2008; 35(7):1419. · 3.69 Impact Factor
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ABSTRACT: In the diagnosis of giant cell arteritis (GCA) with aortic involvement, (18)F-FDG PET has been demonstrated to be a powerful tool. No other imaging method is able to directly detect acute inflammation within the aortic wall. However, because GCA is a rare PET indication, the assessment of GCA with (18)F-FDG PET remains difficult and highly dependent on the experience of the investigator. This study aimed to semiquantify the relationship between aortic and liver uptake and to introduce a receiver operating characteristic (ROC)-based cutoff ratio to allow investigator- and experience-independent GCA diagnosis with optimal sensitivity and specificity. Ratios of aortic wall uptake versus liver uptake were calculated in a group of GCA patients and a control group. These data were assessed in an ROC analysis, and finally, a cutoff-ratio-optimizing strategy was applied.
Twenty-three patients with initially suspected GCA (18 positive for GCA criteria, 5 negative) and 36 matched controls were included. The control subjects underwent PET for oncologic diagnostics. None had intrathoracic or hepatic disease or therapy-related tracer accumulation. Additionally, physiologic liver metabolism was ensured by the presence of normal liver enzymes. After defining regions of interest over the thoracic aorta and the liver, we calculated maximal standardized uptake value ratios. Sensitivities and specificities for cutoff ratios from 0.1 to 2.5 were estimated and were ultimately used to assess an optimal cutoff ratio for separating GCA patients from controls. To further investigate the usefulness of the resulting cutoff ratio, we tested it in a second control group with changed hepatic metabolism and elevated liver enzymes.
ROC analysis revealed optimal selectivity for a cutoff ratio of 1.0. This ratio led to a sensitivity of 88.9%, a specificity of 95.1%, and an accuracy of 94.4%. When this aorta-to-liver ratio was applied to the control group with pathologic liver metabolism, the resulting specificity was 95.6%.
The (18)F-FDG PET region-of-interest analysis with aorta-to-liver maximal standardized uptake value ratios is a reliable, investigator-independent indicator of GCA not affected by minor inflammation-associated changes in hepatic metabolism. Our results for a cutoff ratio of 1.0 prove that (18)F-FDG PET is a method of high sensitivity and specificity for GCA-related large-vessel inflammation.
Journal of Nuclear Medicine 08/2008; 49(7):1107-13. · 6.38 Impact Factor
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Oliver Sander
Evidence-based medicine 09/2007; 12(4):106.
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ABSTRACT: Verbindliche Richtlinien zur Begutachtung von Kollagenosen sind nicht verfügbar. Der Artikel gibt dafür am Beispiel des systemischen
Lupus erythematodes einen Leitfaden unter Berücksichtigung publizierter Daten, der aktuellen Therapie und Prognose von Kollagenosen.
Neben Tabellen mit Graduierungsvorschlägen werden Interpretationshilfen gegeben und Beispiele gezeigt.
Guidelines for assessments of connective tissue diseases in social jurisdiction and for insurance are not available in Germany.
This article is a guideline reflecting published data, modern therapy and actual prognosis. In addition, help for interpretation
and examples are given.
Zeitschrift für Rheumatologie 11/2002; 61(6):652-660. · 0.46 Impact Factor
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Oliver Sander
ACP journal club 140(3):71.
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Oliver Sander
ACP journal club 139(2):46.
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Oliver Sander
ACP journal club 142(1):9.
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Oliver Sander
ACP journal club 138(1):21.
