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Biomedical subjects

M Aparicio

Publications and source records attributed to M Aparicio.

At least 73 records · Page 4Linked to original sources

Pharmacokinetics of rilmenidine in patients with chronic renal insufficiency and in hemodialysis patients.

The pharmacokinetics of rilmenidine (1 mg orally) was studied in 3 groups of patients with stable chronic renal insufficiency. This was an open, single-blind study following a single administration, and after 15 days of treatment. Group 1 included 11 patients with a creatinine clearance between 15 and 80 mL/min. Group 2 included 17 patients with a creatinine clearance < 15 mL/min. Group III included 10 hemodialysis patients. In patients with chronic renal failure, total plasma clearance and renal clearance of rilmenidine decreased; terminal half-life was 30-42 hours, which is clearly longer than previous values achieved in healthy volunteers. After repeated administration (1 mg daily in group 1, 1 mg every other day in group 2, 1 mg at the end of each dialysis session in group 3), the area under the curve was significantly increased, corresponding to drug accumulation. The steady state was reached after 6 days in patients in group 1 and after 8 days in patients in group 2. The pharmacokinetics of rilmenidine was linear since the terminal elimination half-life and renal clearance were not significantly different after single and repeated administration of rilmenidine. A positive correlation was found between rilmenidine total plasma clearance and creatinine clearance, and between rilmenidine renal clearance and creatinine clearance. Mean rilmenidine hemodialysance was 85 mL/min, that is, 26% of the rilmenidine renal clearance value achieved in healthy volunteers (330 mL/min). Thus, the following dosage schedule can be proposed. In patients whose creatinine clearance ranges between 15 and 80 mL/min, a 1 mg dose every day can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Mild phenotypic expression of alpha-N-acetylgalactosaminidase deficiency in two adult siblings.

Two adult siblings with an alpha-N-acetylgalactosaminidase deficiency are described. The patients' major features are massive lymphoedema and angiokeratoma corporis diffusum. Neurological evaluation performed in one of the patients was considered within normal limits. Blood type is A positive in each case. Ultrastructural examination of skin revealed numerous vacuoles in endothelial cells and pericytes. Fibroblast activity of alpha-N-acetylgalactosaminidase was decreased to 0.6-2% of mean normal value. Chromatography of urinary oligosaccharides showed abnormal bands identical to those excreted by two infantile patients with Schindler disease. The bands were identified as sialyloligosaccharides, and gas chromatography revealed the presence of N-acetylgalactosamine-rich compounds accounting for 30% of the total monosaccharide content of the oligosaccharide fraction. These findings confirm the heterogeneity of alpha-N-acetylgalactosaminidase deficiency and emphasize the need to consider this lysosomal storage disease in the differential diagnosis of patients with angiokeratoma.

Adult↗

Granulocyte activation and adhesion molecules during hemodialysis with cuprophane and a high-flux biocompatible membrane.

Hemodialysis with complement-activating membranes, such as cuprophane, induces neutropenia and expression of the granulocyte adhesion receptor Mac-1 (CD11b/CD18), while hemodialysis with noncomplement-activating membranes does not. Increased expression of CD11b by neutrophils may mediate cuprophane-induced leukopenia. However, the rebound granulocytosis that follows leukopenia is not fully understood. Ten patients on regular hemodialysis were included in a cross-over study. Hemodialysis was performed for 2 weeks with cuprophane and 2 weeks with polyamide, a high-flux noncomplement-activating membrane. At the end of each period, the following parameters were determined during a hemodialysis session: C5a concentration by enzyme immunoassay and the neutrophil expression of CD11b, LFA-1 (CD11a/CD18), and the antigen recognized by MoF11 (MoF11 Ag), a monoclonal antibody that recognizes activated neutrophils, by immunofluorescence flow cytometry. Hemodialysis with cuprophane induced an increase in C5a concentration and in the expression of CD11b and MoF11 Ag, which were maximal after 15 minutes of hemodialysis, at the nadir of neutropenia. CD11b expression was maintained throughout hemodialysis, despite the reversal of neutropenia. Conversely, after peak expression, C5a and MoF11 Ag decreased as the neutrophil count increased to baseline values. Polyamide hemodialysis did not induce variations in C5a concentration, nor in CD11b and MoF11 Ag expression. CD11a/CD18 expression remained stable during hemodialysis with both membrane types. Neutrophil activation, as determined by MoF11 Ag expression, was correlated with the evolution of neutrophil count and C5a concentration during cuprophane hemodialysis, while CD11b expression was not correlated with neutrophil count throughout dialysis. A decrease in neutrophil activation could explain in part the detachment of neutrophils previously bound to endothelium and, therefore, the reversal of neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phosphorus and protein restriction and parathyroid function in chronic renal failure.

Phosphorus retention as a result of chronic renal failure (CRF) induces secondary hyperparathyroidism (HPT II) while supplemented low-phosphorus low-protein diets (LPD) prevent it. The aim of this study was to assess in seven patients with advanced CRF and biological HPT II the effects of a LPD providing daily 5 to 7 mg/kg phosphorus, 0.4 g/kg protein, 300 mg calcium (Ca) and supplemented with amino acids, ketoacids, CaCO3 and vitamin D2, on the relationship between ionized Ca (iCa) and PTH concentrations. Hyper- and hypocalcemia were induced by CaCl2 and Na2-EDTA infusion. After three months of LPD, serum phosphorus decreased from 1.59 +/- 0.15 to 1.26 +/- 0.24 mmol/liter (mean +/- SEM, P < 0.02), basal PTH levels from 251 +/- 25 to 127 +/- 16 pg/ml (P < 0.03), while basal iCa and GFR did not vary. The sigmoidal PTH-calcium curve shifted downward with maximal PTH decreased from 482 +/- 86 to 319 +/- 60 pg/ml (P < 0.02) and minimal PTH from 35 +/- 4 to 21 +/- 4 pg/ml (P < 0.05). On the other hand, the slope of the % maximal PTH-iCa curve, which is an indicator of the sensitivity of the parathyroid cell to changes in iCa concentrations, did not vary significantly. The set point of Ca and calcitriol levels were not modified. These results demonstrate a direct inhibition of PTH secretion over a wide range of iCa concentration by LPD in patients with advanced CRF and mild HPT II over a three months period. This effect is independent of changes in plasma calcitriol levels.

Adult↗

Effects of a low-protein, low-phosphorus diet on metabolic insulin clearance in patients with chronic renal failure.

The metabolic clearance rate (MCR) of insulin was studied in 17 nondiabetic patients with advanced chronic renal failure (creatinine 479 +/- 15 mumol/L, glomerular filtration rate 14.6 +/- 2.9 mL/min) before and after 3 mo of a low-protein, low-phosphorus diet (LPD) providing daily per kilogram 0.3 protein of vegetal origin and 3-5 mg inorganic phosphorus. The energy supply (146 kJ.kg-1 x d-1) was furnished mainly by carbohydrates. The diet was supplemented with a mixture of essential amino acids and keto-analogues. The MCR of insulin was determined by using the euglycemic clamp technique. Before the diet the MCR of insulin was low (450 +/- 127 mL.min-1 x m-2) but increased significantly at the third month (568.8 +/- 148 mL.min-1 x m-2), reaching values close to the MCR of control subjects (630 +/- 135 mL.min-1 x m-2). Identical results have been described during hemodialysis of anephric patients, leading us to hypothesize that an LPD reduces the production of dialyzable factors that interfere with peripheral insulin metabolism.

Adult↗

[Comparison of different monitoring techniques for vascular access in chronic hemodialysis].

Aim of the study was to compare different techniques of monitoring for vascular accesses in our chronic hemodialysis patients. Twenty seven patients (14 men, 13 women) were investigated. The accesses studied consisted of 19 arteriovenous fistulas and 8 vascular protheses. Twenty-four were trouble free, venous pressure was high in two, one was difficult to puncture. Three measurements of recirculation percentage were made for each patient, as well as a color Doppler flow imaging, and a digital angiography of the access. Recirculation measurements were normal for all patients including those with functional abnormalities. A stenosis was found 9 times with the Doppler and 10 times by angiography, there being disagreement between the two techniques in one case. The location of the stenosis was the same in the 9 concordant cases. There was a very strong correlation between the degree of stenosis found using the two techniques (p < 0.0001). In conclusion, measurement of recirculation appears to us to be of no interest for verifying a vascular access. On the other hand, the color Doppler seems to be an excellent choice for detecting an abnormality. An arteriographic confirmation seems necessary before correction.

Adolescent↗

Plasma carnitine insufficiency and effectiveness of L-carnitine therapy in patients with mitochondrial myopathy.

Plasma carnitine "insufficiency," (plasma esterified carnitine to free carnitine ratio above 0.25) was found in 21 of 48 (43.8%) patients with mitochondrial myopathy, of whom 4 also showed both total and free carnitine deficiencies in plasma. In addition, plasma levels of SCAC and LCAC were higher in patients with mitochondrial myopathy than in controls (P < 0.001 and P < 0.01, respectively). Patients diagnosed as having plasma carnitine insufficiency or deficiency were treated with L-carnitine (50-200 mg/kg per day in four daily doses). Muscle weakness improved in 19 of 20 patients, failure to thrive in 4 of 8, encephalopathy in 1 of 9, and cardiomyopathy in 8 of 8 patients. Plasma carnitine "insufficiency" provides an additional clue to the diagnosis of mitochondrial myopathy and an indication for L-carnitine therapy.

Adolescent↗

Muscle carnitine deficiency and lipid storage myopathy in patients with mitochondrial myopathy.

Abnormal carnitine distribution in muscle was found in 22 of 77 patients (29%), with mitochondrial myopathy. Furthermore, total (TC) and free (FC) carnitine levels in muscle were lower in patients than in controls (P < 0.01). Muscle long-chain acylcarnitines (LCAC) were significantly increased in these patients (P < 0.01). Muscle carnitine deficiency was found in 31.5% of patients with lipid storage myopathy (LSM) and in 25.6% of patients with ragged-red fibers (RRF). Therefore, carnitine deficiency can be found in patients with mitochondrial myopathy even in the absence of LSM. Muscle levels of TC and FC were lower in patients with respiratory chain defects than in those with normal respiratory chain (P < 0.01). In contrast, LCAC levels were significantly increased (P < 0.05). Carnitine levels did not differ significantly, among patients with different respiratory-chain defects. Consequently, these patients, owing to their biochemical block, reduce progressively the muscle carnitine pool and subsequent LCAC rise, due to long-chain fatty acid (LCFA) accumulation.

Adolescent↗

[Rheumatoid purpura in adults. Retrospective study of 38 patients].

The authors report retrospectively 38 cases of Schönlein-Henoch purpura (20 males, 18 females; median age, 26 years). Skin (37/38) and joint (21/38) manifestations are similar to those seen in children. Gastro intestinal (22/38) manifestations are less complicated. Long term outcome of the disease depends on kidney's involvement (32/38) and is severe: chronic renal failure in 31%.

Adult↗

Tumor necrosis factor alpha in human kidney transplant rejection--analysis by in situ hybridization.

Macrophagic infiltration and necrosis of rejected kidney transplants represent two pejorative patterns. It has been assumed that the macrophagic toxicity is mediated partly by secretion of tumor necrosis factor alpha. On the other hand, TNF is also involved in many inflammatory and immunological phenomena. We thus evaluated the expression of TNF mRNA by in situ hybridization in 6 rejected kidney transplants using a radiolabeled TNF-c DNA probe. Then the synthesis of TNF alpha protein was studied by immunohistochemistry using an anti-TNF alpha antibody. In severely rejected kidney grafts, TNF mRNA is expressed in some monomorphic infiltrating cells, mostly located in the deepest part of the cortex and around the tubes. These cells do not bind other probes, such as dopa-decarboxylase DNA or preproenkephalin RNA. They are also recognized by a monoclonal antibody directed against TNF alpha. What is more, this antibody binds with some glomerular endothelial and tubular epithelial cells that do not express TNF mRNA. These cells are likely target cells for TNF. In the normal kidney, there are no cells expressing TNF-alpha mRNA.

Gene Expression↗

Effect of famotidine on renal transplant patients treated with ciclosporine A.

The influence of a 7-day course of 40 mg famotidine administered orally on the pharmacokinetics of ciclosporine A at steady-state has been investigated in 10 renal transplant patients. Famotidine did not appear to significantly alter the pharmacokinetics of ciclosporine A. This might be ascribed to the limited potential of famotidine for inhibiting microsomal enzyme function. Moreover, plasma creatinine concentrations and creatinine clearance remained stable. Our results suggest that famotidine has no noticeable interaction with ciclosporine A.

Adult↗

Effects of a low-protein diet on urinary glycosaminoglycan excretion in adriamycin-treated rats.

Adriamycin (ADR) induces glomerular damage in rats with persistent severe proteinuria which reaches a peak 15 days after a single 5 mg/kg intravenous (i.v.) injection. We studied in ADR-treated rats the effects of a low-protein (6%) diet (LPD) supplemented with keto acids on urinary protein and glycosaminoglycan (GAG) excretion and glomerular GAG contents. Animals were divided into three groups: group 1 was used as control, and groups 2 and 3 received a single i.v. injection of ADR; group 2 was fed a standard diet (21% protein) and group 3 an LPD. After ADR, group 2 developed heavy proteinuria and showed a progressive increase in urinary GAG excretion starting a few days after the beginning of proteinuria onset and persisting throughout the experiment. After ADR, group 3 (LPD treatment) did not develop proteinuria, and the level of urinary GAGs was comparable to that of controls. The glomerular GAG level in ADR-treated rats was greatly reduced as compared to controls; this decrease was partly eliminated in rats on an LPD. These results suggest that an LPD has a direct effect on cellular GAG production and turnover in ADR-induced glomerulonephritis.

Animals↗

[Protein metabolism during nephrotic syndrome. Experimental and clinical influence of dietary protein intake].

In adults, 12 to 14 g of albumin are synthesized daily. The same quantity is catabolized, essentially by the vascular endothelium and to a lesser degree in renal tubules. During nephrotic syndrome, contrary to what is observed in malnutrition conditions accompanied by hypoalbuminemia, hepatic synthesis is only moderately increased, whereas fractional catabolism is greater than normal. The increase in alimentary protein-intake, which has been proposed to restore the pool of albumin, raises hepatic albumin synthesis, but also its urinary losses, most likely by stimulation of the renin-angiotensin system. A reduction in protein rations lowers proteinuria and improves the hepatic abnormalities of nephrotic syndrome but its longterm nutritional consequences are poorly understood. The association of a converting enzyme inhibitor with a diet moderately restricted in protein content (1 g/kg/day) might constitute a therapeutic satisfactory solution.

Adult↗