Online access to NDT for developing countries

As editors we want as many people to have access to NDT as possible.The last 18 months have seen a number of experimental initiativesto test the technical and logistical     

Plasma kinetics of 125I-labelled amyloid P component in {beta}2M amyloidosis: A possible approach to quantitate disease activity

Dialysis amyloidosis is one of the most incapacitating complicationsof long-term dialysis treatment. Quantitative assessment ofamyloid deposition using radiolabelled tracers has been recentlyproposed but convincing evidence of its validity in uraemicpatients remains to be provided. We studied the plasma kineticsof i.v. administered ¹²⁵I-labelled serum amyloid P component(¹²⁵I-SAP) in 20 chronic haemodialysis patients compared withthose of nine healthy volunteers and three non-dialysed patientswith systemic amyloidosis. Plasma clearance of the tracer wasabnormal in 17 of 20 dialysis patients in whom plasma radioactivitydeclined in a bi-exponential mode, in contrast to the single-exponentialslope observed in all healthy controls. ¹²⁵I-SAP plasma half-lifeof the second component, probably reflecting metabolic clearance,was significantly prolonged in these dialysis patients comparedwith the healthy controls (35.3 versus 24.6 h, P<0.001).Among the long-term haemodialysis patients the calculated extravasculardistribution of ¹²⁵I-SAP was significantly greater in thosewith severe arthropathy than in asymptomatic patients. Thesefindings demonstrate for the first time that SAP clearance isdisturbed in haemodialysis patients due to both failing renalelimination and retention in extravascular sites. The extravasculardiffusion is greatly enhanced in patients with clinical evidenceof amyloidosis. Therefore the study of plasma ¹²⁵I-SAP kineticspromises to be a valuable tool to quantitate the extent of amyloidosis.     

The role of 5-HT in response inhibition and re-engagement

In animal and human research, the neurotransmitter serotonin (5-HT) has been implicated in inhibitory control. Using functional magnetic resonance imaging (fMRI), the present study investigated the acute effects of pharmacological modulation of the serotonergic system on brain activation during response inhibition and re-engagement in healthy human volunteers. In a randomized double-blind placebo-controlled cross-over design 14 men received either a single oral dose of the selective serotonin reuptake inhibitor (SSRI) escitalopram (10 mg) or a placebo. At the time of the expected plasma peak concentration, participants performed a stop–change task during fMRI. Escitalopram did not affect behavioural performance, since the main effect did not reveal significant differences between reaction times of go-, stop- or change-trials. During successful response inhibition, escitalopram, however, was associated with enhanced brain activation in right prefrontal cortex, right supplementary/pre-motor and bilateral cingulate cortex, and subcortical regions. During inhibition failures, escitalopram also modulated a broad network of brain regions, including anterior cingulate, right parietal cortex, right orbitofrontal cortex, and areas in right temporal cortex and subcortical regions. During response re-engagement escitalopram increased brain activation in right inferior frontal gyrus and precuneus as well as in left middle temporal gyrus. The results implicate the involvement of 5-HT in neural regulation of response inhibition and re-engagement. This study also provides evidence that 5-HT affects both action restraint and action cancellation through modulation of activation of brain areas. The results support the view for a fronto-striatal circuitry for response inhibition in conjunction with serotonin.     

Hypocalcaemic Effect of WR-2721, S-2 (3-Aminopropylamino) Ethyl-phosphorothioic Acid in an Anuric Haemodialysis Patient

The radio- and chemoprotective agent, S-2 (3-aminopropylamino)ethyl-phosphorothioic acid (WR 2721) has been reported to lowerhypercalcaemia in patients with cancer, probably by increasedrenal calcium excretion and decreased parathyroid hormone (PTH)secretion and bone calcium resorption. The present study reportsthe first clinical use of WR-2721 in an anuric haemodialysispatient with severe secondary hyperparathyroidism. The drugwas administered intravenously at different doses, i.e. 150,300, and 500 mg/m². The infusion was followed by a strikingdecrease of plasma immunoreactive (i) PTH within 30 min. Thenadir of the iPTH decrease was reached at 60 min and was followedby a steady return to previous values. Serum ionised calciumdecreased more progressively from 1.55 mmol/l initially to 1.30mmol/l at 4 h after the 300-mg dose, remained at that levelat 24 h, but rose again to pre-infusion values after 48 h. Theextent and duration of the decrease in plasma iPTH and ionisedcalcium were dose-dependent. The circulating iPTH at 24 h wasinversely related to the corresponding plasma ionised calciumconcentration and had risen above preinfusion values at thattime. Plasma concentrations of three other hormones, i.e. renin,insulin, and prolactin, were not affected by the administrationof WR-2721. In conclusion, WR-2721 can induce a decrease in serum ionisedcalcium in the absence of any excretory kidney function. Therapid effect of the drug on circulating iPTH supports the notionof an interference with PTH secretion or catabolism.     

Kinetics of erythropoiesis in dialysis patients receiving recombinant erythropoietin treatment

In eleven patients with uraemia on intermittent haemodialysis treatment, recombinant human erythropoietin (rHuEpo) was used at a dosage schedule of 100 IU/kg bodyweight thrice weekly. Erythrokinetic studies (blood volume, RBC survival and iron kinetics) were performed in nine cases before and after 6 months of treatment. The remaining two patients had only RBC and plasma volume determinations before and after treatment. Although total blood volume remained unchanged, RBC volume was increased in all cases. Red cell loss was not modified, and quantitative improvement of RBC production was noted in all cases. No qualitative defect of erythroid maturation or release was observed in the treated patients. In conclusion, rHuEpo treatment improves the anaemia of haemodialysis patients by normalising circulating RBC volume only through an increase in red cell production.