In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit. (Blood. 2010; 116(18):3426-3430)

Background: The diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis requires demonstration of amyloid deposits in a tissue biopsy and amyloidogenic monoclonal light chains. The optimal strategy to identify the amyloidogenic clone has not been established. We prospectively assessed the diagnostic sensitivity of the serum free light chain (FLC) κ/λ ratio, a commercial serum and urine agarose gel electrophoresis immunofixation (IFE), and the high-resolution agarose gel electrophoresis immunofixation (HR-IFE) developed at our referral center in patients with AL amyloidosis, in whom the amyloidogenic light chain was unequivocally identified in the amyloid deposits. Methods: The amyloidogenic light chain was identified in 121 consecutive patients with AL amyloidosis by immunoelectron microscopy analysis of abdominal fat aspirates and/or organ biopsies. We characterized the monoclonal light chain by using IFE and HR-IFE in serum and urine and the FLC κ/λ ratio in serum. We then compared the diagnostic sensitivities of the 3 assays. Results: The HR-IFE of serum and urine identified the amyloidogenic light chain in all 115 patients with a monoclonal gammopathy. Six patients with a biclonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC κ/λ ratio (96% vs 76%). The combination of serum IFE and the FLC assay detected the amyloidogenic light chain in 96% of patients. The combination of IFE of both serum and urine with the FLC κ/λ ratio had a 100% sensitivity. Conclusions: The identification of amyloidogenic light chains cannot rely on a single test and requires the combination of a commercially available FLC assay with immunofixation of both serum and urine.

We analysed key biochemical features that reflect the balance between glycolysis and glucose oxidation in cybrids (cytoplasmic hybrids) harbouring a representative sample of mitochondrial DNA point mutations and deletions. The cybrids analysed had the same 143B cell nuclear background and were isogenic for the mitochondrial background. The 143B cell line and its rho(0) counterpart were used as controls. All cells analysed were in a dynamic state, and cell number, time of plating, culture medium, extracellular volume and time of harvest and assay were strictly controlled. Intra- and extra-cellular lactate and pyruvate levels were measured in homoplasmic wild-type and mutant cells, and correlated with rates of ATP synthesis and O2 consumption. In all mutant cell lines, except those with the T8993C mutation in the ATPase 6 gene, glycolysis was increased even under conditions of low glucose, as demonstrated by increased levels of extracellular lactate and pyruvate. Extracellular lactate levels were strictly and inversely correlated with rates of ATP synthesis and O2 consumption. These results show increased glycolysis and defective oxidative phosphorylation, irrespective of the type or site of the point mutation or deletion in the mitochondrial genome. The different biochemical consequences of the T8993C mutation suggest a uniquely different pathogenic mechanism for this mutation. However, the distinct clinical features associated with some of these mutations still remain to be elucidated.

a b s t r a c tSystemic cryostimulation is useful treatment, both in sport and medicine, during which human body is exposed to very low, cryogenic temperature (below À100°C). Although there exists some evidence of its beneficial effect in biological regeneration, so far it has not been unequivocally determined if the positive effect of repeated stimulations depends on their number in a series. The aim of this research was to estimate the influence of 5, 10 and 20 sessions of 3 min-long exposures to cryogenic temperature (À130°C) on the lipid profile in physically active men. Sixty-nine healthy volunteers participated in the study. The blood samples were taken in the morning, after overnight fasting, before the first cryostimulation session, and the following morning after the last one (5th,10th, 20th).In serum specimens the concentration of total cholesterol (TCh), HDL cholesterol and triglicerydes were determined using enzymatic methods. LDL cholesterol level was calculated using Friedewald formula. The changes in lipid profile (LDL decrease with simultaneously HDL increase) occurred after at least 10 sessions of cryostimulation.Ó 2010 Elsevier Inc. All rights reserved. IntroductionWhole-body cryostimulation in a cryogenic chamber uses very low temperatures (ranging from À100 to À160°C) over a short time span (1-3 min) to induce systemic physiological responses. It is based on the heat exchange between surfaces with different temperatures [30]. Heat is absorbed by cooled surface tissues from deeper situated tissues at the rate proportional to their difference in temperature.A desired response to a systemic effect of cryogenic temperatures (below À100°C) is a hyperaemic reaction (rebound effect), stimulatory in character. Exposure in cryogenic chamber, under a supervision of a physician and in compliance to commonly accepted rules concerning cryostimulation, is not harmful or dangerous to healthy individuals, although there exist several contraindications. Banfi et al. reported that whole-body cryotherapy is not deleterious to cardiac function in healthy individuals [1]. Documented analgesic, anti-inflammatory and antioedematous action reduces increased muscle tension and therefore cryotherapy has been increasingly often applied in sport and medicine, in combination with additional forms of treatment [13,14,25,34,36].It is postulated that cryostimulation mobilizes the white blood cells, particularly immunocompetent lymphocytes [4,15,21,22]. The effect on red blood cells has not been positively confirmed. Banfi et al. did not observe changes in the level of hematocrit, whereas red blood cells and mean corpuscular hemoglobin decreased after 5 cryostimulation sessions [2,3]. On the contrary, significant increase in erythrocytes count, hemoglobin concentration, hematocrit value and the mean corpuscular value (MCV) were reported by Stanek et al. [33].It is unclear how repeated cryostimulation influences the level of pro-inflammatory and anti-inflammatory mechanisms. There is a report of increased anti-inflammatory cy...