PubMed Health⌕ Search

Biomedical subjects

G Fredj

Publications and source records attributed to G Fredj.

At least 19 recordsLinked to original sources
PubMed1997

Study of the correlation between MEIA and ELISA methods for FK 506 determination in liver transplant recipients.

BACKGROUND AND OBJECTIVES: FK 506 is an immunosuppressive macrolide advocated for prevention of graft rejection. Plasma or blood FK 506 levels must be determined to strike a balance between FK 506 toxicity and graft rejection. The first aim of this study was to compare an automated microparticle enzyme immunosorbent assay (MEIA) method (on whole blood) with the reference enzyme-linked immunosorbent assay (ELISA) method (on plasma). A second aim was to compare the two methods for prediction of FK 506 nephrotoxicity. PATIENTS AND METHODS: Forty-seven patients were studied comprising 128 samples. All were treated with FK 506 on a compassionate basis. For each patient, the concentrations of FK 506 were determined in plasma by means of ELISA and in whole blood by MEIA. RESULTS: The repeatability and the reproducibility of these two methods were similar. The inter-patient correlation coefficient between MEIA and ELISA, determined on 128 samples from 47 liver recipients, was satisfactory (r = 0.82). From these 47 patients, the intra-patient correlation coefficients were calculated for 17 of them. The intra-patient correlation coefficients were between 0.63 and 0.98 for 15 patients, and between 0.26 and 0.55 in the remaining two cases. Mean creatinine plasma levels in the 55 samples below the median FK 506 value in the MEIA method and in the 55 with values above the median (120 and 134 mumol/litre, respectively) were significantly different (P < 0.05), as were those using the reference ELISA methods (115 and 139 mumol/litre, P < 0.01). In contrast, there was no significant difference between the mean creatinine plasma levels in the 55 samples with FK 506 levels below the median using both methods or between those above the median. CONCLUSION: The automated MEIA method, being simpler and more rapid than the ELISA method, should now be preferred for therapeutic monitoring of FK 506.

Adolescent↗
PubMed1994

FK 506 renal toxicity and lack of detectable cytochrome P-450 3A in the liver graft of a patient undergoing liver transplantation.

Many commonly used drugs are substrates for hepatic cytochrome P-450 3A in human beings, and its role in the metabolism of potentially toxic immunosuppressants has been highlighted (cyclosporine, FK 506). One hundred fifty human liver grafts were biopsied before and after liver transplantation, and levels of cytochromes P-450 3A, 1A2, 2D6 and 2C were estimated by means of the Western-blot technique and correlated with histological appearance, glycogen content and clinical course. In 15 of the grafts, cyclosporine oxidase was also measured, and in 12 of 15 recipients, urinary 6 beta-hydroxycortisol excretion was assayed. A wide range of cytochrome P-450 3A values were observed (25 to 366 arbitrary units/mg; mean, 105 +/- 63 arbitrary units/mg). In one graft (no. 730) no cytochrome P-450 3A was detectable on immunoblotting, despite increasing homogenate concentrations. In this sample, cytochromes P-450 1A2, 2D6, and 2C were present in normal ranges. Levels of cyclosporine oxidase and 6 beta-hydroxycortisol in the urine specimens of the recipient were found to be low. The recipient of graft 730 experienced reversible complications of FK 506 therapy despite adherence to the administration protocol and drug plasma level in the normal range. The subsequent appearance of the cytochrome P-450 3A was associated with the consequent tolerance of oral FK 506. The absence of detectable amounts of P-450 3A in one biopsy from a donated human liver graft dramatically emphasizes the extreme range of this enzyme levels and has important clinical implications.

Adolescent↗
PubMed1993

Relationship between graft cytochrome P-450 3A content and early morbidity after liver transplantation.

Cytochrome P-450 3A metabolizes CsA into several metabolites with very limited pharmacological activity and toxicity. In 40 liver donors, the relative concentrations of P-450 3A was assessed by immunoblot analysis using a specific monoclonal antibody exhibited a 10-fold variation (mean = 92 +/- 50 arbitrary units [AU]/mg) in levels. Problems consequent upon CsA usage (nephrotoxicity, neurotoxicity, and hypertension) occurred in 8 of 34 transplant recipients in the immediate postoperative period, and in these 8 patients the problems were always associated with low graft P-4503A levels (mean = 52 +/- 19 A.U./mg, P = 0.0003, cf. patients with no toxicity). Four of these patients had CsA levels that were also high, but 4 had CsA levels in the therapeutic range. Episodes of early graft rejection were related to higher P-450 3A levels (mean = 110 +/- 24 A.U./mg). Cytochrome P-450 3A levels were also found to be inversely related to CsA whole blood levels (assessed with a specific antibody 12 hr after the intravenous infusion of CsA at 1 mg/kg in the recipients (P < 0.02). Cytochrome P-450 3A can provide information that should allow individualized immunosuppression with CsA maintaining therapeutic levels but avoiding toxicity in susceptible individuals.

Adult↗
PubMed1992

Intratumor treatment of C3H mouse mammary carcinoma with 5-fluorouracil adsorbed on activated charcoal particles.

A dosage form comprising 5-fluorouracil (5-FU, 25 mg/ml) adsorbed on a suspension of micronized charcoal (100 mg/ml) 2-5 microns in diameter, adsorbing 5-FU in aqueous solution was studied for intratumor treatment of mammary carcinoma in animal experiments. An in vitro desorption method is described to determine the amount of 5-FU adsorbed on activated charcoal particles which would be released once the drug concentration decreased around the charcoal. In vivo results indicate that an intratumor injection of 5-FU adsorbed on activated charcoal particles is a highly effective method for achieving tumor regression without increasing toxicity.

Adenocarcinoma↗
PubMed1992

Open trial of tacrine therapy in 70 HIV-infected patients.

The purpose of this study consisted in following-up the biological and clinical parameters in HIV infected patients treated with tacrine (THA). THA (150-300 mg/d) was administrated to 70 patients (39 IVC I and 31 IVC II and III). Thirty-five were treated after discontinuation of AZT treatment and 35 as a first intention treatment. Thirty (43%) patients showed an increase in the CD4+ cell count by more than 50% relative to pretreatment levels and fifteen (21%) showed an increase of more than 25%. p24 antigenemia (Ag p24) became negative in eight of the twenty-seven patients who were initially positive, and decreased by 25 and 50% in nine and six patients, respectively. Ag p24 was therefore decreased in 80% of the patients. From a clinical point of view, there were two deaths (3%) and five opportunistic infections (7%). The treatment with THA was stopped in five patients because of side effects (nausea, rash). Neither hepatotoxicity, hematotoxicity, nor pancreatitis was observed during the THA treatment. In group II and III only two patients (6%) developed an opportunistic infection.

AIDS-Related Opportunistic Infections↗
PubMed1989

Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparison with cis-platinum and carboplatinum.

A new platinum complex, oxalatoplatin or l-OHP, which, at the same metal dose in experimental tests is as efficient as cisplatin, and is more so at a lower metal dose than carboplatin; which is as efficient in human tumors of the testis and ovary as these other analogs, and more so in melanoma and breast cancer; which is not nephrotoxic, cardiotoxic or mutagenic, and hardly hematotoxic and neurotoxic, is described and compared with the above-mentioned platinum complexes. Combined with 5Fu, it induces a high number of remissions in colorectal cancer, and has brought about cures in inoperable gastric cancers. Combined with carboplatin, it has resulted in a high proportion of cures in L1210-carrying mice, which no other two-by-two combination of these complexes has achieved.

Animals↗
PubMed1989

Tetrahydroaminoacridine in HIV infections. The THA Study Group.

On the basis of a similarity between certain neurological symptoms of AIDS and Alzheimer's disease, the authors studied the effects of tetrahydroaminoacridine (THA) in 9 patients with HIV infection. After 2 months of treatment, the preliminary results showed a significant increase in CD4 lymphocyte count as well as a decrease in p24 antigen level in 8 patients, of whom 4 became negative for the p24 antigen.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Clinical pharmacokinetics of cicletanine hydrochloride.

Results of the different pharmacokinetic studies performed with cicletanine, the first derivative of a new class of antihypertensive drugs, the furopyridines, are reviewed in this article. Pharmacokinetic studies with healthy subjects have shown that this drug is rapidly absorbed (time to Cmax about 0.65 h). It is strongly bound to plasma proteins (90%), with a volume of distribution of 37 l. The elimination half-life is between 6 to 8 h and elimination itself is mixed: renal and hepatic. The parameters are unchanged in young hypertensives. Pharmacokinetic studies in hepatic failure have shown that the mean retention time is about 6 h; the pharmacokinetic parameters are only slightly modified except in the case of cirrhosis with ascites and extra hepatic obstruction. The modification of pharmacokinetics in patients with renal failure is related to the severity of the condition. Small changes appear with moderate failure whereas important variations occur in severe renal failure.

Adult↗
PubMed1987

Changes in erythromycin pharmacokinetics induced by renal failure.

As erythromycin ototoxicity appears to be favored by renal insufficiency, its pharmacokinetics were assessed in chronic uremic patients treated by maintenance hemodialysis in comparison with normal subjects. Two groups of 8 patients each were studied, the first one on an interdialytic day, the second immediately after the end of an hemodialysis session. All subjects ingested a single dose of 1 gram of erythromycin ethylsuccinate. Times of peak serum concentration and biological half-lifes were similar in patients and in controls. Maximum serum concentrations and areas under the serum concentration time-curve were higher in patients than in controls whereas apparent oral clearances were lower in the former. The differences between the two groups of patients were not significant. These pharmacokinetic changes are suggestive of an enhanced bioavailability of erythromycin in chronic renal failure which might predispose uremics to the ototoxicity of the drug.

Adult↗