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Introduction and aim. Procalcitonin is widely used as a biomarker to distinguish bacterial infections from other etiologies of systemic inflammation. Little is known about its value in acute liver injury resulting from intoxication with paracetamol.Material and methods. We performed a single-center retrospective analysis of the procalcitonin level, liver synthesis, liver cell damage and renal function of patients admitted with paracetamol-induced liver injury to a tertiary care children’s hospital. Children with acute liver failure due to other reasons without a bacterial or fungal infection served as the control group. Twelve patients with acute paracetamol intoxication and acute liver injury were compared with 29 patients with acute liver failure.Results. The procalcitonin levels were higher in children with paracetamol intoxication than in patients with acute liver failure without paracetamol intoxication (median 24.8 (0.01-55.57) ng/mL vs. 1.36 (0.1-44.18) ng/mL; p < 0.005), although their liver and kidney functions were better and the liver cell injury was similar in both groups. Outcome analysis showed a trend towards better survival without transplantation in patients with paracetamol intoxication (10/12 vs. 15/29). Within each group, procalcitonin was significantly correlated with alanine aminotransferase and aspartate aminotransferase but was not correlated with the International Normalized Ratio or paracetamol blood levels in the paracetamol group. In conclusion, paracetamol intoxication leads to a marked increase in procalcitonin serum levels, which are significantly higher than those seen in acute liver failure.Conclusion. The underlying mechanism is neither caused by infection nor fully explained by liver cell death alone and remains to be determined.

Multiple myeloma (MM) is frequently complicated by renal insufficiency, which is associated with an unfavorable prognosis. Serum cystatin C is a new and accurate marker of glomerular filtration rate. Global gene expression analysis has revealed serum cystatin C as one of the most highly upregulated genes in MM. Recent data have shown serum cystatin C as an independent prognostic marker in MM. To further elucidate the prognostic significance of serum cystatin C, we investigated pretreatment serum cystatin C levels in 68 newly diagnosed patients homogeneously treated with high-dose melphalan followed by autologous stem cell transplantation. Median serum cystatin C level in MM patients was significantly higher than in the 66 healthy controls (1.07 vs. 0.74 mg/L [p = 0.002]). Median serum cystatin C levels significantly increased with higher International Staging System (ISS) stages (stage I 0.72 mg/L; stage II 0.89 mg/L; stage III 1.28 mg/L; p < 0.0001). Higher serum cystatin C was positively correlated with higher serum levels of creatinine (r = 0.84; p < 0.0001), β2-microglobulin (r = 0.72; p < 0.0001), LDH (r = 0.43; p = 0.0003), white blood cell counts (r = 0.61; p < 0.0001) and calcium (r = 0.29; p = 0.016), and negatively correlated with lower serum albumin levels (r = 0.44; p < 0.0001) and hemoglobin levels (r = 0.31; p = 0.01). Using ROC analysis, patients with serum cystatin C levels ≥0.95 mg/L (n = 24) had a significantly shorter event-free survival (EFS) and overall survival (OS) than patients with serum cystatin C levels

Background: Serum creatinine (SCR) and blood urea nitrogen (BUN) determine the glomerular filtration rate (GFR) improperly in acute renal failure. Serum cystatin C (CYS) has the potential to be a more precise marker for GFR. The aim of this study was to compare the sensitivity of SCR, BUN and CYS with respect to the detection of acute renal failure in mice. Methods: In an ischaemia reperfusion (I/R) injury model, mice suffered 60-min left kidney ischaemia and right nephrectomy. In a nephrectomy model, mice were nephrectomized to a different extent: from unilateral (3/6Nx) to bilateral nephrectomy (BiNx). Blood samples were collected 2, 12 or 24 h post-op. Results:SCR,BUNandCYSincreasedsignificantlyinthe I/R-model in comparison to sham mice and 3/6Nx mice at 12 and 24 h post-op (SCR P = 0.009; BUN P < 0.001 and CYS P < 0.004). There were no significant differences in all three markers between 3/6Nx and sham-operated mice. In graded nephrectomy, BUN and CYS showed already significantly the loss of kidney in 4/6Nx mice 12 h postop [BUN (mg/dl): sham 26.4 ± 3.5, 4/6Nx 52.3 ± 13.4, P < 0.01; CYS (mg/l): sham 0.08 ± 0.03, 4/6Nx 0.15 ± 0.04, P < 0.01], whereas SCR was only significantly increasedin5/6NxandBiNxmice24hpost-op[SCR(mg/dl): sham 0.39 ± 0.05, 4/6Nx 0.52 ± 0.07, P = 0.13, 5/6Nx 1.00 ± 0.29, P < 0.01]. In the longitudinal experiment, CYS showed the renal damage significantly earlier and to a larger extent (2 h: SCR 57 ± 15%, BUN 40 ± 16%, CYS 295 ± 143%, P < 0.001). Conclusions: CYS can be used as a reliable and precise marker for renal function in mouse models. CYS is more sensitive than SCR, and it shows renal damage earlier than SCR and BUN.

We determined the prevalence and progression rate of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS (LCMGUS) in Germany utilizing the biobank of the population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45–75 years. To detect monoclonal proteins, standard serum electrophoresis was combined with parallel screening immunofixation using pentavalent antisera. Additionally, free light chains (FLC) were measured in all samples. Definition of MGUS included M-protein concentration, laboratory results, and disease history. LCMGUS was defined as abnormal FLC ratio, increase in FLC causing the abnormal ratio, and lack of intact immunoglobulin. One hundred sixty-five MGUS cases were identified among 4,702 screened samples (prevalence 3.5%, 95% confidence interval (CI) 3.0–4.1; median age 63 years, range 47–75 years; 103 (62%) male; IgG 59%, IgA 17%, IgM 17%, biclonal 4.8%, kappa 56%, and lambda 44%). Five cases progressed (0.6%/year, 95% CI 0.2–1.4). An abnormal FLC ratio was detected in 220 samples. Thirty-nine of these showed intact immunoglobulin. Thirty-four of the remaining met LCMGUS criteria (prevalence 0.7%, 95% CI 0.5–1.0). None of the LCMGUS cases progressed. We demonstrate a MGUS prevalence of 3.5% and a LCMGUS prevalence of 0.7% in the general population aged 45–75 years in Germany using a sensitive screening approach.

There is growing evidence that hepatitis-C virus (HCV) infection might cause peripheral neuropathy. We aimed to investigate the prevalence, clinical and electrophysiological features of sensory neuropathy in patients with cryoglobulin negative HCV infection. We studied 46 consecutive cryoglobulin negative HCV positive patients (24 of them with and 22 without neuropathic symptoms, NS) and compared to 28 age and gender matched controls. In all patients and controls, clinical neuropathy symptom (NSS) and neuropathy deficit scores (NDS) were assessed and standard nerve conduction velocity (SNCV) and pain related-evoked potentials (PREP) were recorded. Both, SNCV and PREP were abnormal in 13 NS positive patients (13/46, 28%). Abnormal PREP but normal SNCV were found in 5 (5/46, 11%) NS positive and in 2 NS negative patients (2/46, 4%). PREP abnormalities correlated positive with both clinical neuropathy scores (NSS r = 0.62; p < 0.001; NDS r = 0.57; p < 0.001), but not with the duration of the disease, current viral load, or the virus subtype. PREP abnormalities were more frequent (16/33, 48.5%) in HCV patients treated with interferon than in therapy naive patients (4/13, 30.8%); the difference was, however, not significant. In our present study (1) all virus subtypes are capable of inducing neuropathy, (2) no differences were found between interferon therapy and treatment naive patients, (3) the prevalence of peripheral sensory neuropathy including small sensory fibers (20/46, 43.5%) is higher than previously reported and (4) we found that detection of HCV associated neuropathy depends on the evaluation method.

Abstract 4037 Background: We utilized the biobank of the ongoing population-based, prospective Heinz Nixdorf Recall Study to determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) and a recently defined entity – light-chain MGUS (LCMGUS) – in the densely populated Ruhr area in Germany. Methods: The Heinz Nixdorf Recall study cohort comprises 4814 men and women from 3 large adjacent cities in Germany. Subjects were randomly selected from statutory lists of residence and gave informed consent. We screened serum samples from the baseline examination which took place from 2000 until 2003. Standard serum electrophoresis (SPE) was combined with parallel screening immunofixation electrophoresis (scIFE) using pentavalent antisera (Hydragel 12 IF, Penta-Kit, Sebia, Fulda, Germany). Where a monoclonal band was visible or suspected, confirmatory IFE followed. Free light-chain (FLC) κ and λ measurements were performed on a Dade Behring BNII automated nephelometer (Siemens, Germany) utilizing a commercially available kit (FREELITE, The Binding Site Ltd, Birmingham, UK). Definition of MGUS cases was based on common criteria including monoclonal protein concentration, laboratory results, and disease history. LCMGUS cases were defined as an abnormal FLC ratio, an increase in the FLC that caused the abnormal ratio and no detectable intact immunoglobulin (Dispenzieri et al. Lancet 2010: 1721-8). Age-standardization of prevalences was performed by direct standardization to the U.S. population 2000. Results: 165 MGUS cases were identified in a total of 4708 screened samples, translating into a prevalence of 3.5% (95% CI, 3.0 – 4.1). The median age of MGUS cases was 63 years (range 47 – 75), 103 (62%) were of male gender, and prevalence increased with age. The age-standardized prevalence was 3.9% (95% CI 3.2 – 4.5) which was significantly higher (p Conclusion: The higher MGUS prevalence of 3.9% in the Heinz Nixdorf Recall cohort compared to previous reports can be explained by the combined SPE + scIFE screening approach. Re-evaluation of the gels without the pentavalent tracks resulted in a prevalence similar to that reported for Olmsted County, Minnesota, U.S. The prevalence of the recently defined entity LCMGUS in the Heinz Nixdorf Recall cohort also compares favourably with the recently reported prevalence. Further characterization of MGUS and LCMGUS cases in the well-defined Heinz Nixdorf Recall cohort is the focus of ongoing analyzes. Disclosures: Eisele: Celgene: Research Funding. Dürig:Celgene: Research Funding.

The protein-kinase-C (PKC) family of iso-enzymes regulates mitogenic signal transduction in colorectal-cell lines. Its function in human colonic mucosal proliferation is controversial. Our study investigated the role of PKC with regard to proliferation and changes of PKC iso-enzyme expression in colonic biopsies compared with small adenomas. In short-term tissue-culture experiments of colonic mucosal biopsies, we found reduced S-phase labeling in the 2 apical compartments of longitudinally sectioned crypts when PKC was activated by 200 nM of the phorbol ester TPA (n = 8). Thus, PKC inhibited growth of differentiated colonocytes which may influence cell homeostasis in colonic crypts. Furthermore, we have determined the expression of PKCα, -β1, -β2, -δ and -ϵ in colonic adenomas smaller than 1 cm in diameter of 18 patients and found a significant increase of PKCα in the cytosolic fraction and decreased membrane levels of PKCβ2 in adenomas compared to normal, neighboring mucosa while protein levels of PKCβ1, -δ and -ϵ were not altered. Moreover PKCδ but not PKCα mRNA expression was significantly lowered in adenoma tissue in 7 patients, as determined by ribonuclease-protection analysis. Changes in the regulation patterns of PKC isoforms suggest a decreased activation state of PKC even in small adenomas. This is compatible with an anti-proliferative function of PKC serving to protect mucosa from expanding mutated cells. Int. J. Cancer 80:47–53, 1999. © 1999 Wiley-Liss, Inc.