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Biomedical subjects

A Argiles

Publications and source records attributed to A Argiles.

At least 19 recordsLinked to original sources

Chronic kidney disease as cause of cardiovascular morbidity and mortality.

To make an evidence-based evaluation of the relationship between kidney failure and cardiovascular risk, we reviewed the literature obtained from a PubMed search using pre-defined keywords related to both conditions and covering 18 years (1986 until end 2003). Eighty-five publications, covering 552 258 subjects, are summarized. All but three studies support a link between kidney dysfunction and cardiovascular risk. More importantly, the association is observed very early during the evolution of renal failure: an accelerated cardiovascular risk appears at varying glomerular filtration rate (GFR) cut-off values, which were >/=60 ml/min in at least 20 studies. Many studies lacked a clear definition of cardiovascular disease and/or used a single determination of serum creatinine or GFR as an index of kidney function, which is not necessarily corresponding to well-defined chronic kidney disease. In six studies, however, chronic kidney dysfunction and cardiovascular disease were well defined and the results of these confirm the impact of kidney dysfunction. It is concluded that there is an undeniable link between kidney dysfunction and cardiovascular risk and that the presence of even subtle kidney dysfunction should be considered as one of the conditions necessitating intensive prevention of this cardiovascular risk.

Cardiovascular Diseases↗

[Sequential protocols with thymoglobuline and delayed introduction of calcineurin: effects on renal function in renal transplant recipients with non immunological risk and low risk of delayed graft function].

Induction therapy with thymoglobuline significantly decreases the risk of acute rejection, particularly in high immunological risk patients, in combined transplantations and in pediatric renal transplantation. After the introduction of cyclosporin in the 1980's and the recognition of its potential nephrotoxicity, induction therapy with delayed introduction of cyclosporin (sequential protocols) have became very popular in many transplant centers and are now used even in low-immunological risk patients. The aim of the present study was to assess the recovery of renal function in low-immunological risk patients receiving a sequential protocol versus those receiving a calcineurin inhibitor at day 1. Among patients receiving their first transplant in our center between January 1999 and June 2000, we selected 72 recipients with no immunological risk and no risk of delayed graft function (DGF). 35 patients (group I) have received a sequential protocol whereas 37 patients (group II) have received a calcineurin inhibitor (Neoral or prograf) at day 1. We analysed creatinine reduction ratio, 24-hour creatinine excretion on post-transplant day 2, and serum creatinine and creatinine clearance at day 15, 30, 45, 60 and 90 post-transplant. There was no difference between groups concerning demographic, immunological or surgical parameters. The percentage of patients with immediate graft function was similar between the two groups (10 versus 9). The number of patients requiring dialysis in the first post-transplant week was also similar (8/35 versus 6/37). The day serum creatinine reached 200 micromol/l was 15 +/- 11 versus 14 +/- 12 in groups I and II respectively. Serum creatinine and creatinine clearance were similar at all time intervals. CMV disease was significantly higher in the group 1 (42% versus 18.5%; p < 0.005). Our data suggest that in patients with low immunological risk and low-risk of DGF, introduction of calcineurin inhibitors as early as the post-transplant day 1 is not deleterious for renal function recovery. These data should be confirmed by a prospective randomised trial.

Adult↗

In vitro creation of amyloid fibrils from native and Arg124Cys mutated betaIGH3((110-131)) peptides, and its relevance for lattice corneal amyloid dystrophy type I.

BetaIGH3 protein has been recently involved in the pathogenesis of blinding corneal diseases, some of which have characteristic amyloid corneal deposits. The 124 codon of the betaig-h3 gene seems to be crucial for the amyloidogenicity of the protein product. We presently report an in vitro system that reproducibly forms amyloid fibrils from betaIGH3((110-131)) derived peptides. We also assessed the differences in fibril formation of two 22-amino acid peptides centered on the 124 residue: the native form and the Arg124Cys peptide (mutation linked to lattice corneal amyloid dystrophy type 1). After dialysis of Arg124Cys peptide against PBS 1/15 M pH 7.4 for 72 hours, Congo red staining and electron microscopy demonstrated the presence of abundant material fulfilling the criteria of amyloid. Quantitative analysis with thioflavine T fluorescence studies confirmed the high capacity of Arg124Cys peptide to form amyloid fibrils when compared to the native form.

Amino Acid Sequence↗

BIGH3 exon 14 mutations lead to intermediate type I/IIIA of lattice corneal dystrophies.

PURPOSE: To screen the BIGH3 gene in three unrelated families with lattice corneal dystrophy (LCD), two of which disclosed a particular phenotype. METHODS: Genomic DNA was extracted from peripheral leukocytes of the affected patients and their family members. The entire coding sequence of the BIGH3 gene was screened for mutations by means of transcript analysis on total RNA isolated from peripheral leukocytes by reverse transcription-polymerase chain reaction performed with primers designed for this study. Each mutation was confirmed at the genomic level, by using published primers. RESULTS: One family that had a typical form of LCD, had the described R124C mutation in the BIGH3 gene. Two families with atypical forms of LCD were negative for the previously known mutations of the gene. Direct sequencing of the BIGH3 mRNA in the latter two families allowed us to identify two mutations located in exon 14. They consist of a 9-bp insertion at position 18851886 and one missense mutation at position 1877 of the BIGH3 gene. Three new polymorphisms were also observed. CONCLUSIONS: Two mutations different from those linked to LCD have been found in clinically distinguishable forms of this disease, intermediate between LCDs types I and IIIA. The DNA segment comprising both alterations normally encodes for a highly conserved region of the fourth internal domain of the Betaig-h3 protein, suggesting that this region may be of functional and/or structural importance. The identification of new mutations by screening of the complete BIGH3 gene and the comparative analysis of the induced modifications in betaig-h3 protein should shed light in the understanding of the molecular mechanisms underlying LCDs resulting from mutations in the BIGH3 gene, and may help to explain their phenotypic heterogeneity.

Adult↗

On-line haemodiafiltration: state of the art.

Faced with the shortcomings of conventional dialysis on a long-term basis, as illustrated by the dialysis-related pathology, a need for a new strategy exists to improve the overall quality of treatment in end-stage renal failure (ESRF) patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic option to achieve this goal at the present time. By enhancing convective clearances through highly permeable membranes, HDF offers the greatest solute fluxes both for low and higher molecular weight uraemic toxins. As for example, in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h each, double-pool urea Kt/V achieved was 1.55+/-0.20 and beta2-microglobulin Kt/V was 0.91. By producing substitution fluid from fresh dialysate, the technique of HDF is simplified and becomes economically affordable. By improving the haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular patients to be treated more safely. By using bicarbonate-buffered infusate, HDF facilitates the correction of acidosis. Both by using ultrapure bicarbonate dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF introduces the first step for a full haemocompatibility concept. Finally, by giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid, HDF should introduce new therapeutic options such as a totally automated and feed-back-controlled machine. Today's on-line HDF is already a step forward to enhance the overall efficacy of renal replacement therapy and to improve the global care of ESRF patients.

Hemodiafiltration↗

Creatinine kinetic modelling: a simple and reliable tool for the assessment of protein nutritional status in haemodialysis patients.

While the mathematical modelling of urea kinetics is in wide use for evaluating treatment adequacy and protein nutrition in dialysis patients, the kinetics of creatinine generation in dialysis patients has been relatively unexplored. In this study creatinine kinetic modelling as a clinical tool was investigated in a group of 90 patients treated by haemodialysis (n = 20), haemodiafiltration (60), haemofiltration (7), or biofiltration (3) over a 6-36-month period. A single pool model of creatinine kinetics was employed to obtain monthly values of creatinine distribution space and creatinine appearance rate. Extrarenal creatinine degradation rate, estimated using a clearance of 0.038 l/kg/24 h as suggested by Mitch and co-workers, was added to creatinine appearance rate in urine and dialysate to calculate a corrected creatinine index (CI). Extrarenal degradation accounted for 12 +/- 2% of CI. CI was higher in males (22.4 +/- 4.5 mg/kg/24 h) than females (19.8 +/- 4.8) and decreased with age, falling off more sharply for the female group (CI = 29.9-0.185.age, R = 0.72) than the males (CI = 24.1-0.030.age, R = 0.31). CI was found to correlate strongly with protein catabolic rate determined by urea kinetic modelling (CI = 8.84 +/- 10.91.PCR). Low or reduced CI was associated in this study group with severe malnutrition status and high mortality rate. CI is suggested as a strong predictor of patient morbidity and mortality.

Creatinine↗

The effects of reprocessing high-flux polysulfone dialyzers with peroxyacetic acid on beta 2-microglobulin removal in hemodiafiltration.

The reuse of dialyzers is widely practiced, especially in the United States. Despite this, the effects of reuse on the efficacy of removal of solutes and more recently proteins such as beta 2-microglobulin (beta 2M) are the subject of much debate. There is considerable evidence to suggest that reuse after cleansing and sterilizing with formalin, with or without bleach, maintains dialyzer performance. In this study, we have examined peroxyacetic acid use as the cleansing and sterilizing agent using Renatron machines. We analyzed reuse in 24 patients using polysulfone membranes in a hemodiafiltration (HDF) unit over a 2-year period. The mean maximum number of uses achieved was 20.1 +/- 0.5. Several factors considered clinically to influence the number of reuses achievable (hemoglobin, white blood cell, and platelet levels, erythrocyte sedimentation rate [ESR], and fibrinogen and total protein levels) were found not to influence the maximum number of uses obtainable. We then assessed prospectively the performance of 26 polysulfone dialyzers after peroxyacetic acid reprocessing up to 20 times, particularly with regard to their ability to remove beta 2M. We report that this combination of polysulfone membranes reprocessed with peroxyacetic acid used for HDF up to 20 times exhibits a maintained high level removal of compounds beyond a molecular weight (MW) of 12,000. Any secondary membrane formation that occurs appears not to influence the subsequent removal of beta 2M. Thus, we would recommend the use of peroxyacetic acid for reprocessing dialyzers in a safe and efficacious manner.

Adult↗

Whole blood serotonin levels are markedly elevated in patients on dialytic therapy.

The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 +/- 54 mumol/l) chronic renal failure (270 +/- 46 micrograms/l) compared to 11 normals (163 +/- 17 micrograms/l, p less than 0.05; quoted normal range less than 300 micrograms/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 +/- 234 micrograms/l; cuprophane membranes, n = 6, 708 +/- 198 micrograms/l), hemodiafiltration (n = 12, 695 +/- 130 micrograms/l) and especially peritoneal dialysis (n = 6, 1,148 +/- 162 micrograms/l). All results were significant (p less than 0.01) compared to normals and compared to the nondialyzed group (p less than 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dialyzed patients.

Adult↗

Measurement of vascular access recirculation without contralateral venous puncture.

The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture.

Adult↗

High-molecular-mass proteins in haemodialysis-associated amyloidosis.

1. Protein constituents were determined in eight amyloid deposits from eight patients (five male and three female), 53 +/- 4 years of age, treated by haemodialysis for 9-20 years using only cuprophane membranes and operated for carpal tunnel syndrome. 2. Soluble proteins were removed by solubilization in phosphate-buffered saline after osmotic lysis. The proteins of the insoluble fibrils were characterized by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and two-dimensional gel electrophoresis, and immunologically identified by Western blotting. 3. In addition to beta 2-microglobulin, alpha 2-macroglobulin was identified in the fibrillar material. The presence of these two proteins in amyloid deposits was confirmed by immunofluorescent microscopic studies. 4. Our data confirm the presence of beta 2-microglobulin in haemodialysis-associated amyloidosis, and also suggest a possible role for alpha 2-microglobulin: it may protect beta 2-microglobulin from proteolytic digestion, leading to its accumulation in intact form and to amyloid fibril formation.

Amyloid↗

Contrasting effects of acute angiotensin converting enzyme inhibitors and calcium antagonists in transplant renal artery stenosis.

Deterioration of renal function is a major concern during treatment by converting enzyme inhibitors of hypertensive kidney recipients with transplant renal artery stenosis. However, there has been no assessment of the frequency of this complication and its specificity for converting enzyme inhibitors as compared to other antihypertensive drugs. The effect of acute administration of captopril on mean arterial pressure, glomerular filtration rate (GFR) (creatinine clearance) and effective renal plasma flow (clearance of 131I-hippuran) was assessed in eight hypertensive patients with transplant renal artery stenosis. Captopril induced a decrease in mean arterial pressure (128 +/- 6-121 +/- 7 mmHg) and a reduction in GFR (59 +/- 8-44 +/- 8 ml/min per 1.73 m2, P less than 0.05). The decrease in GFR was observed in seven out of eight patients and varied between 0% and 100% of the pre-captopril value. Effective renal plasma flow was maintained (157 +/- 47-141 +/- 24 ml/min per 1.73 m2) and filtration fraction decreased by 15 +/- 7%. The effect of captopril was compared to that of nifedipine (N = 20 mg) in four patients. Despite a larger decrease in mean arterial pressure (130 +/- 7-109 +/- 10 mmHg), no reduction in GFR was observed (68 +/- 13-71.4 +/- 8). Effective renal plasma flow was unchanged and filtration function slightly increased. Surgical or percutaneous transluminal angioplasty in five patients suppressed the captopril-induced decrease in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗