Search PubMed⌕ Search

Biomedical subjects

G Mourad

Publications and source records attributed to G Mourad.

162 records · Page 9Linked to original sources

[Renal response to acute expansion of the extracellular volume in renal transplant patients].

The response to acute isotonic saline loading (1 800 ml in 3 hours) was assessed in 12 normotensive and 11 hypertensive renal transplant recipients. Both groups had similar renal function, daily urinary excretion of sodium and doses of steroids. The natriuretic response to saline was not affected in hypertensive transplants and changes in blood pressure, renin and aldosterone were identical in both groups. Similar correlations between pre-saline fractional excretion of sodium (FENa+) and the FENa+ obtained during saline were obtained in normotensive and hypertensive patients. These results demonstrate that in renal transplant recipients of young donors no exaggeration of the response to saline occurs in hypertensive subjects thus suggesting that normal kidneys may carry their characteristics when transplanted in a new environment. The role of renal denervation remains unclear.

Adult↗

The natriuretic response to acute saline loading in normotensive and hypertensive renal transplant recipients.

The response to acute isotonic saline loading (1800 ml in 3 h) was assessed in 12 normotensive and 11 hypertensive renal transplant recipients. Both groups had similar renal function, daily urinary excretion of sodium and doses of steroids. The natriuretic response to saline was not affected in hypertensive transplants and changes in blood pressure, renin and aldosterone were identical in both groups. Similar correlations between presaline fractional excretion of sodium (FENa+) and the FENa+ obtained during saline were found in normotensive and hypertensive patients. These results demonstrate that recipients of renal transplants who are hypertensive do not show an exaggerated natriuresis in response to saline, thus suggesting that normal kidneys carry their characteristics when transplanted in a new environment. The role of renal denervation remains unclear.

Adult↗

[Immunologic selection of donors and recipients in renal graft: transplantation antigens ].

For the immunologic selection of donors and recipients in renal transplantation, several antigens must be considered: ABO and Lewis antigens identified by red cell typing, HLA-A, HLA-B and HLA-DR antigens identified by leucocyte typing and HLA-D antigens explored by mixed lymphocyte reaction (MLR). In renal grafts with living related donor, the best donor is ABO compatible, HLA-A and B identical, MLR negative with the recipient. In renal grafts with cadaver donor, the best recipient is ABO and Lewis compatible and must present the greatest number of HLA-A, B and DR identities with the donor. The number of cadaver donors is relatively small and the selected recipient does not however present a good HLA compatibility with his donor.

Blood Grouping and Crossmatching↗

[Reversible acute renal failure and nephrotic syndrome induced by fenoprofene ].

A 71-year old man experienced nephrotic syndrome and acute renal failure 13 months after the introduction of fenoprofen calcium, 900 mg/day, as treatment of right hip osteoarthritis. Clinical course and laboratory data were consistent with toxic nephropathy; kidney biopsy showed tubulo-interstitial nephritis with glomerular minimal change lesion. Renal function returned spontaneously to normal, after withdrawal of the drug. The clinical literature on nephrotic syndrome and reversible acute renal failure associated with non-steroidal anti-inflammatory drugs is reviewed.

Acute Kidney Injury↗

The V-twin system (Dade Behring Laboratories): a useful tool for immunosuppressive drug monitoring.

The predose trough cyclosporine (CsA) level (C0) was widely used to assess the possibility of drug nephrotoxicity. Owing to its potential limitation as an indicator of total drug exposure, 2-hour postdose (C2) monitoring has been considered to be a more accurate marker. The V-Twin analyzer (Vital SC, Netherlands) conceived for EMIT technologies (Dade Behring Laboratories) is proposed herein to determine CsA levels using a specific calibrator without any dilution, as well as tacrolimus (FK) and mycophenolate mofetil (MMF) levels. Both CsA (C0: n = 133 and C2: n = 55) and FK (n = 121) EMIT assays were compared to the RIA CsA assay (DiaSorin Laboratory) and to the MEIA tacrolimus assay (Abbott Laboratory), respectively. In addition, the feasibility of MMF EMIT assay was evaluated. Overall, 309 transplant patients were included in this study. For all parameters tested, total imprecision studies were lower than 10%, and the coefficient of linearity was r(2) > .99. For the CsA kit, the range of linearity was between 25 and 500 ng/mL for the C0 and 400 and 2000 ng/mL for the C2 assay. The values obtained were highly correlated with the RIA for the C0 levels (EMIT = 0.9 RIA+3.66; r = .97) and for the C2 levels (EMIT = 0.89 RIA-14.2; r = .956). Similar results were obtained with the EK EMIT kit, with a linearity range between 3 and 30 ng/mL, and a high concordance with the MEIA test (EMIT = 0.98 RIA+1.09; r = .96). Preliminary MMF results in 59 sera, containing from 0.1 to 30 microg/mL, showed that this examination could be included as a routine. The V-twin system is a useful tool for routine monitoring with a single method for C0 and C2 cyclosporine, tacrolimus, and mycophenolate levels.

Animals↗

Preliminary evaluation of a new chemiluminescence assay (Liaison Cyclosporine; DiaSorin Laboratories) allowing both C0 and C2 cyclosporine levels determination: comparison with RIA method.

Cyclosporine (CsA) monitoring is generally assessed by trough concentration determinations (C0). Recently, the 2-hour postdose CsA level (C2) has been proposed to be a better measurement to predict graft outcome and prevent toxicity. However, using the available methods, C2 determinations require external dilution, which impairs the precision and practicability of the assay. This study assessed the performance characteristics of a new competitive chemiluminescence immunoassay (CLIA, DiaSorin Laboratories, Anthony, France) for the determination of both C0 and C2 CsA concentrations in whole blood on a Liaison analyzer. The results were compared with the RIA method (DiaSorin) used in our laboratory as a reference technique. Analytical performances showed that the total intra-assay variation coefficients (CVs) on the CLIA Liaison ranged from 7.6% to 11.3%, while the between-day imprecision was 11% (15.2%, 11.5%, and 6.5%). The linearity of the method was estimated over the range of 30 to 2400 ng/mL as a correlation coefficient of r = .997. Recoveries, which were checked by adding pure CsA to CsA-free blood, showed a mean value of 86%. A total of 236 whole-blood samples (31% women, 69% men of mean age 45 +/- 17 years) were subjected to a comparative study of CLIA-CsA versus RIA (radioimmunoassay) values, yielding a correlation coefficient >0.90 (CLIA = 0.825RIA+21.611; r(2) > .90). In conclusion, the CLIA Liaison CsA kit represents an alternative to the radioisotopic method, which allows both C0 and C2 determinations without any preanalytical step. The chemiluminescence method demonstrated good analytical performance and practicability in routine use.

Adult↗

Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient.

Sirolimus is a new potent immunosuppressive drug used in organ transplantation; its major advantage is the absence of deterioration in renal function. Documented adverse effects include myelosuppression and hyperlipidemia. Recently several cases of sirolimus-associated interstitial pneumonitis have been reported, usually of mild severity. We report a new case that was complicated by a severe acute respiratory distress syndrome, which required several days of mechanical ventilation. No infectious or cardiogenic etiology was documented. Low sirolimus blood levels and acute CD4 lymphocytic alveolitis suggested an immune-related mechanism rather than a direct toxic effect of the drug. The patient recovered after discontinuation of sirolimus and the administration of corticosteroids.

Humans↗

Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes.

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to "reproduce" in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentration-dependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 microM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 microM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.

Blotting, Western↗

A portable artificial compact kidney: pack system.

To facilitate patients' movement, we developed a simplified portable haemodialysis system, using a sorbent cartridge (Organon Teknika) for regeneration of the dialysate. The whole system is in two parts: (1) a compact disposable container for dialysate recirculation with dialyser and blood and dialysate lines; (2) a dual functions circulatory assistance monitor. The pack system is easy to use: single-use; no water processing; no formalin processing; reliable for temporary use (because of its aluminium), providing excellent purification; compact and portable, it permits greater freedom for the patient, and with adequate dialysis.

Equipment Design↗