Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia

It is currently not known which level of pentagastrin-stimulated calcitonin serum concentration indicates medullary thyroid carcinoma in patients with chronic kidney disease (CKD). We examined CKD stage 3–5 patients who had total thyroidectomy because of a pentagastrin-stimulated calcitonin concentration greater than 100pg/ml, and tested the diagnostic performance of basal and pentagastrin-stimulated calcitonin levels for differentiating medullary thyroid carcinoma and C-cell hyperplasia in this patient population. A total of 180 CKD patients presented with an elevated calcitonin level and had a pentagastrin stimulation test. Forty patients showed a maximum pentagastrin-stimulated calcitonin concentration greater than 100pg/ml, and 22 patients had a total thyroidectomy. Seven of these 22 patients presented with a medullary thyroid carcinoma, all other patients showed C-cell hyperplasia. Patients with medullary thyroid carcinoma showed higher unstimulated (212pg/ml (36–577) vs 42pg/ml (17–150); P<0.001) and higher maximum pentagastrin-stimulated calcitonin concentrations (862pg/ml (431–2423) vs 141pg/ml (102–471); P<0.001) as compared to patients with C-cell hyperplasia. The sensitivity (100%) and specificity (93%) estimates suggested that a maximum pentagastrin-stimulated calcitonin concentration greater than 400pg/ml indicates the presence of medullary thyroid carcinoma in patients with CKD. Receiver-operating characteristic (ROC) analysis revealed an area under the ROC plot of 0.99 for maximum pentagastrin-stimulated calcitonin concentrations. A maximum pentagastrin-stimulated calcitonin concentration greater than 400pg/ml appears to be a clinically meaningful threshold for thyroidectomy

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients.BackgroundCurrently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B12, folate, or total homocysteine (tHcy).MethodsIn a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B12, folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.ResultsThe allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N = 72) or homozygosity (N = 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B12 (P = 0.33) or tHcy (P = 0.70), but a borderline association with higher folate concentrations was detected (Δfolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P = 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B12 concentrations.ConclusionHigher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B12 in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

Bernd Muehling1, Alexander Oberhuber1, Hubert Schelzig1, Gisela Bischoff1, Nikolaus Marx2, Ludger Sunder-Plassmann1, Karl H Orend11Department of Thoracic and Vascular surgery; 2Department of Internal Medicine, University of Ulm, Ulm, GermanyBackground and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL).Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter.Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter.Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated.Keywords: biomarkers, aneurismal disease, statin therap

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients.BackgroundIron deficiency and anemia are commonly encountered in patients with autoimmune diseases undergoing immune apheresis. This makes erythropoietin and iron substitution necessary in most patients. However, intravenous iron therapy may result in an increase of potentially toxic nontransferrin-bound iron.MethodsWe examined the effect of 50 mg or 100 mg of iron (III) sucrose on bleomycin-detectable iron (BDI) in immune apheresis patients. Six patients with autoimmune disorders and normal kidney function were enrolled. Before and after the injection of 50 mg or 100 mg of iron (III) sucrose, BDI was measured in serum samples at five different time points.ResultsThere was no BDI traceable before injection of iron (III) sucrose. BDI was present in serum of all patients after the administration of 100 mg of iron (III) sucrose in concentrations up to 0.49 μmol/L. In contrast, only one patient showed BDI at a concentration of 0.16 μmol/L after the administration of 50 mg of iron (III) sucrose.ConclusionWe conclude that if parenteral iron is administered after apheresis treatment, despite the equal tolerability, use of 50 mg of iron (III) sucrose is superior to 100 mg of iron (III) sucrose in avoiding the formation of potentially toxic nontransferrin-bound iron

Mutation (677C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients

Mutation 677C to T in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients. Hyperhomocysteinemia is frequent in hemodialysis patients and represents an independent risk factor for vascular disease in these patients. Elevated total homocysteine (tHcy) plasma levels can result from defective remethyla-tion of Hcy to methionine due to decreased activity of the enzyme methylenetetrahydrofolate reductase (MTHFR). A genetic aberration in the MTHFR gene (677C to T substitution) has been shown to result in reduced MTHFR activity. We tested the hypothesis that elevation of tHcy plasma levels in hemodialysis patients is influenced by the 677C to T mutation of the MTHFR gene and examined the relation of the genotype with tHcy, folate and vitamin B12 plasma levels in these patients. The allelic frequency of the MTHFR mutation was evaluated in 203 patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in 69 age- and sex-matched healthy control subjects. The allelic frequency of the 677C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus 35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/−) genotype was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level in hemodialysis patients was 28.7 ± 11.0 µuunol/liter versus 10.0 ± 3.0 µmol/liter in control subjects. The mean tHcy levels were 36.4 ± 13.4 µmol/liter in (+/+) patients and 12.2 ± 4.5 /mol/liter in (+/+) controls, 28.7 ± 10.8 µmol/liter in (+/−) patients and 9.9 ± 2.7 µmol/liter in (+/−) controls and 25.4 ± 8.5 µmol/liter in (−/−) hemodialysis patients versus 9.7 ± 2.8 µmol/liter in (−/−) controls. There was no significant difference of folate and vitamin B12 concentrations in patients and controls with different MTHFR genotypes. Analysis of covariance including age, gender, folate concentrations, vitamin B12 levels, albumin and creatinine as covariables revealed a significant influence of the (+/+) genotype, albumin and folate status on tHcy levels in hemodialysis patients. Together, our data demonstrate that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of uremia or folate status, but is also genetically determined by the (+/+) MTHFR genotype. The presence of the 677C to T mutation in the MTHFR gene does not appear to represent a risk factor for development of end-stage renal disease

How organizational cognitive neuroscience can deepen understanding of managerial decision-making:a review of the recent literature and future directions

There is growing interest in exploring the potential links between human biology and management and organization studies, which is bringing greater attention to bear on the place of mental processes in explaining human behaviour and effectiveness. The authors define this new field as organizational cognitive neuroscience (OCN), which is in the exploratory phase of its emergence and diffusion. It is clear that there are methodological debates and issues associated with OCN research, and the aim of this paper is to illuminate these concerns, and provide a roadmap for rigorous and relevant future work in the area. To this end, the current reach of OCN is investigated by the systematic review methodology, revealing three clusters of activity, covering the fields of economics, marketing and organizational behaviour. Among these clusters, organizational behaviour seems to be an outlier, owing to its far greater variety of empirical work, which the authors argue is largely a result of the plurality of research methods that have taken root within this field. Nevertheless, all three clusters contribute to a greater understanding of the biological mechanisms that mediate choice and decision-making. The paper concludes that OCN research has already provided important insights regarding the boundaries surrounding human freedom to act in various domains and, in turn, self-determination to influence the workplace. However, there is much to be done, and emerging research of significant interest is highlighted

Intravenous iron increases labile serum iron but does not impair forearm blood flow reactivity in dialysis patients

Intravenous iron increases labile serum iron but does not impair forearm blood flow reactivity in dialysis patients.BackgroundThere are concerns about adverse vascular effects of intravenous iron by inducing oxidative stress. We therefore examined the effect of a single high dose of intravenous iron on endothelial function and biochemical markers of iron homeostasis.MethodsIn a randomized, placebo-controlled, double-blind, parallel-group study, forearm blood flow (FBF) was assessed by strain-gauge plethysmography in 38 peritoneal dialysis patients before and after a single intravenous infusion of 300mg iron sucrose.ResultsIron infusion increased total (Δ 601 μg/100mL, CI 507, 696) and non-transferrin-bound iron (Δ 237.2 μmol/L, CI 173.6, 300.8) approximately 10-fold, as well as redox-active iron nearly five-fold (Δ 0.76 μmol/L, CI 0.54, 0.98). After iron infusion basal FBF was 59% higher than after placebo. FBF response to acetylcholine before and after iron infusion was 263 ± 32% and 310 ± 33%, corresponding to 304 ± 43% and 373 ± 29% in the placebo group, respectively. Before and after iron or placebo infusion, glyceryl-trinitrate increased resting FBF to 232 ± 22% and 258 ± 21% in the iron group, and to 234 ± 18% and 270 ± 30% in the placebo group. L-N-monomethyl-arginine decreased FBF to 70 ± 4% and 72 ± 3% before and after iron, and to 74 ± 4% and 73 ± 4% before and after placebo infusions, respectively. Despite higher basal FBF after iron infusion, absolute and relative FBF changes in response to vasoactive substances were not significantly different between iron and placebo groups.ConclusionOur data suggest that 300mg intravenous iron sucrose has a vasodilatory effect, but does not impair vascular reactivity in dialysis patients, despite a significant increase in non-transferrin-bound and redox-active iron

Single-dose testosterone administration increases men’s preference for status goods

In modern human cultures where social hierarchies are ubiquitous, people typically signal their hierarchical position through consumption of positional goods—goods that convey one’s social position, such as luxury products. Building on animal research and early correlational human studies linking the sex steroid hormone testosterone with hierarchical social interactions, we investigate the influence of testosterone on men’s preferences for positional goods. Using a placebo-controlled experiment (N = 243) to measure individuals’ desire for status brands and products, we find that administering testosterone increases men’s preference for status brands, compared to brands of similar perceived quality but lower perceived status. Furthermore, testosterone increases positive attitudes toward positional goods when they are described as status-enhancing, but not when they are described as power-enhancing or high in quality. Our results provide novel causal evidence for the biological roots of men’s preferences for status, bridging decades of animal behavioral studies with contemporary consumer research

Effect ofMTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients

Effect ofMTHFRgenotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients.BackgroundThe total homocysteine (tHcy) plasma level, which is partly determined by theMTHFR 677C→T genotype, may be associated with vascular disease. We prospectively examined the influence ofMTHFR genotypes (677C→T, 1298A→C) and tHcy plasma concentration on all cause mortality and graft outcomes of renal transplant recipients.MethodsBaseline tHcy plasma levels of 189 patients (three groups with either theMTHFR 677CC, CT or TT genotype, including 63 patients in each group, were matched for age, gender, body mass index and creatinine clearance at baseline), were obtained between September 1996 and May 1997. Follow-up data (time until return to dialysis therapy, time and cause of death) were collected from April to June 1999. Kaplan-Meier survival estimations were calculated and plotted, the groups (threeMTHFR 677C→T genotype groups, or threeMTHFR 1298A→C genotype groups, or two groups with tHcy plasma levels above/below 15 μmol/L) were compared by log-rank test. Age, gender, body mass index (BMI), time since transplantation, serum creatinine, creatinine clearance, combinedMTHFR 677C→T/1298A→C genotypes, tHcy, folate and vitamin B12 plasma levels were evaluated with regard to graft and patient survival in a multivariate Cox-proportional hazard regression model.ResultsDuring the follow-up period of 2.26 ± 0.66 years, 9 patients died (5 in the TT, 2 in the CT and 2 in the CC genotype group;P = 0.34) and 22 returned to dialysis treatment (7 in the TT, 9 in the CT and 6 in the CC genotype group;P = 0.65). There was also no influnce ofMTHFR 1298A→C genotypes (AA genotype, 114 patients; AC genotype, 64 patients; CC genotype, 11 patients) on patient or graft survival (P = 0.7087 andP = 0.1633, respectively). Two of 93 patients with a tHcy plasma level ≤15 μmol/L died, in contrast to 7 of 96 patients in the low tHcy > 15 μmol/L group,P = 0.0778. Two patients in the low tHcy group had to return to dialysis, in contrast to 20 patients in the high tHcy group (P = 0.0001). In the multivariate model there was no significant predictor of patient survival, and the serum creatinine was the only predictor of graft survival (P < 0.0001).ConclusionsIn summary, our study shows that neitherMTHFR 677C→T/1298A→C genotypes nor hyperhomocysteinemia are independently associated with patient or graft survival following kidney transplantation