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Biomedical subjects

G Mourad

Publications and source records attributed to G Mourad.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Morbidity of percutaneous biopsy of kidney transplants (Vim-Silverman and Tru-cut needles)].

OBJECTIVES: To evaluate the morbidity of renal transplant biopsies performed after simple ultrasonographic identification of the transplants, using a Vim-Silverman or Tru-cut needle. METHODS: From January 1987 to April 1991, 360 renal transplant biopsies were performed after simple ultrasonographic identification of the transplants, using a Vim-Silverman (n = 204) or Tru-cut (n-156) needle. In 221 transplants, these biopsies were performed because of a rise of serum creatinine (n = 319) or proteinuria (n = 17) or were even performed systematically (n = 24). One to 5 (mean = 1.6) transplant biopsies were performed systematically and the interval between renal transplantation and biopsy varied between 3 days and 11 years. RESULTS: 290 biopsies (80.6%) allowed the analysis of a minimum of 3 glomeruli (mean = 9.3). The yield of the Vim-Silverman needle was significantly greater than that of the Tru-cut model (p = 0.02). 147 biopsies (50.7%) demonstrated acute or chronic rejection, 57 (19.7%) revealed cyclosporin nephrotoxicity, 41 (14.1%) showed acute tubular necrosis and 14 (4.8%) showed glomerulopathy, while 31 (10.7%) were strictly normal. The morbidity of these biopsies was reflected by 37 complications (10.3%), including 30 minor and 7 major complications (2 cases of haemoperitoneum, 4 cases of obstructive anuria and 1 arteriovenous fistula). However, only one case required transplantectomy. These problems were significantly more frequent following inadequate biopsies (< 3 glomeruli, purely medullary, extra-renal). CONCLUSION: Despite the considerable risk of iatrogenic lesions, these biopsies were justified by their potential diagnostic and therapeutic benefit. The prophylaxis of complications of this procedure is based on strict respect of blood pressure and haematological criteria and on real-time ultrasound monitoring of the biopsy and miniaturization of the trocars. The treatment of severe complications has been greatly improved by the development of endourology and interventional radiology, but surgery, and especially transplantectomy, is still occasionally required.

Adolescent↗
PubMed1994

CDR-grafted OKT4A monoclonal antibody in cynomolgus renal allograft recipients.

In an attempt to improve therapeutic efficacy and limit antimurine responses to the IgG2a monoclonal antibody OKT4A, humanized complementarity determining region (CDR)-grafted OKT4A mAbs (IgG1 and IgG4 isotypes) were developed from the murine molecule. Preclinical evaluation was undertaken in 12 cynomolgus renal allograft recipients (IgG1, n = 7; IgG4, n = 5). Control animals received either no therapy (n = 2) or OKT3 (n = 2). The mAbs were given as a single 10-mg/kg bolus on the day of transplantation or as multiple 1-mg/kg doses. Mean allograft survival (+/- SEM) was 9 +/- 0.7 days in control animals; 45.2 +/- 6.0 days, P = 0.002 (single dose, n = 5), and 39 +/- 5.0 days, P = 0.053, (multiple doses, n = 2) in IgG1-treated animals; and 35.3 +/- 7.2 days, P = 0.034, (single dose, n = 3) and 15.5 +/- 6.5 days, P = .251 (multiple doses, n = 2) in IgG4-treated animals. Whereas IgG4-treated animals showed coating of peripheral blood CD4+ T cells, significant CD4+ T cell depletion was observed in IgG1-treated animals. These results confirm the retained immunosuppressive efficacy of humanized OKT4A antibodies. In contrast to murine mAbs, the use of these agents would not preclude sequential treatment with mAbs directed against different epitopes. The fact that rejection can occur despite peripheral blood CD4+ cell depletion suggests that indefinite control of allograft rejection in primates may require more intensive therapy than has proved effective in rodent models.

Animals↗
PubMed1994

Intragenic recombination in the CSR1 locus of Arabidopsis.

Four classes of herbicides are known to inhibit plant acetolactate synthase (ALS). In Arabidopsis, ALS is encoded by a single gene, CSR1. The dominant csr1-1 allele encodes an ALS resistant to chlorsulfuron and triazolopyrimidine sulfonamide while the dominant csr1-2 allele encodes an ALS resistant to imazapyr and pyrimidyl-oxy-benzoate. The molecular distance between the point mutations in csr1-1 and csr1-2 is 1369 bp. Here we used multiherbicide resistance as a stringent selection to measure the intragenic recombination frequency between these two point mutations. We found this frequency to be 0.008 +/- 0.0028. The recombinant multiherbicide-resistant allele, csr1-4, provides an ideal marker for plant genetic transformation.

Acetolactate Synthase↗
PubMed1994

Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages.

Dialysis-related amyloidosis is a type of amyloidosis which had beta 2-microglobulin as the major protein constituent and occurs predominantly in haemodialysis patients. Its prevalence is very high with increasing time on dialysis treatment and its pathogenesis is not completely understood. While remarkable progress has been made in the identification of the components of the deposits, there are no reports characterizing the cells surrounding the amyloid fibrils. To characterize the cellular composition of the amyloid material, specimens from seven patients treated by maintenance haemodialysis were studied with immunoperoxidase labelling using monoclonal antibodies to leukocytes (CD3, CD14, CD68, CD4, CD8, CD45). The results were very reproducible for the seven deposits assessed: Of the 182 +/- 26 leukocytes/0.2 mm2 of amyloid tissue expressing the 71.5-CD45 marker (common leukocyte), 91 +/- 6% were CD68 (KP1) positive (monocyte macrophage). No CD3-positive cells (T-cell marker) were found in six of the seven patients, with only 1.6% in the remaining one. The present study shows that although amyloidosis has classically been considered as an acellular pathology, clearly there are cells surrounding amyloid fibrils. Strikingly, these cells are almost exclusively macrophages; there are no lymphocytes or granulocytes. The putative role of macrophages in the pathogenesis of beta 2-microglobulin amyloidosis remains to be established. However, the identification and quantitation of the cells surrounding the amyloid deposits may be important for subsequent studies to elucidate amyloid pathogenesis and particularly protein-cell interactions.

Adult↗
PubMed1994

Antilymphocyte globulins versus OKT3 as prophylactic treatment in highly sensitized renal transplant recipients.

Monoclonal antibodies were proposed as an effective prophylactic immunosuppressive treatment in highly sensitized patients (HSP). In this study we compared the results obtained in HSP treated with OKT3 or antilymphocyte globulins (ALG). From January 1989 to January 1993, 38 transplantations were performed in patients with high panel reactive antibodies (PRA > 50%). The group comprised 22 women and 16 men, mean age 45 +/- 2 (23-67) years; ten were second grafts and two were third grafts. Peak PRA was > or = 80% in 24 sensitized patients and 50-80% in 14 sensitized patients. Patients were randomly assigned to either prophylactic OKT3 (n = 15) or ALG (n = 23). Oral cyclosporin A (10 mg/kg) was started at day 8 in the OKT3 group and when the serum creatinine level decreased to 200 micromol/l in the ALG group. OKT3 was systematically withdrawn on day 10 but ALG was stopped only when total blood cyclosporin A concentration reached 150-200 ng/ml. In both groups, azathioprine (150 mg/day) and prednisolone were given. During the first months, 6/15 grafts were lost in the OKT3 group (three hyperacute rejections, one renal vein thrombosis, one steroid-resistant rejection, one death); in the ALG group 4/23 grafts were lost (one hyperacute rejection, two steroid-resistant rejections, one death). Side effects were significantly more frequent in the OKT3 group than in the ALG group. After 12 months of follow up, the graft survival was 71% (27/38) and did not significantly differ (log-rank test, NS) between the OKT3 (60%, 9/15) and the ALG group (78%, 18/23). We conclude that the use of the monoclonal antibody OKT3 as a prophylactic agent in HSP does not improve the early graft survival when compared with prophylactic ALG. Polyclonal antibodies, which react with many epitopes and are much better tolerated seem to offer a good strategy for induction therapy in this population.

Adult↗
PubMed1994

[Kidney transplantation in patients more than 60 years old. Analysis of results apropos of 57 patients].

From April 1988 to August 1993, 57 elderly recipients more than 60 years old (mean age 64 +/- 3 years, 35 males, 22 females) underwent cadaveric renal transplantation. The pretransplant screening included immunological and viral status and urological examination; cardiovascular risk factors were systematically estimated by medical history, physical examination, echocardiography, femoral arterial doppler, and myocardial stress thallium imaging. A coronarography was performed if myocardial ischemia was evidenced. Patients free of cardiovascular diseases or after correction of vascular and/or coronary lesions were included in the waiting list. A sequential immunosuppression regimen including azathioprine, prednisolone anad antilymphocyte globulins was given in all patients. Oral cyclosporin A (5-8 mg/kg/day) was started when serum creatinine level decreased to 200 mumol/l; antilymphocyte globulins were stopped when whole trough blood cyclosporin level reached 150-200 ng/ml. After 24 months of follow-up, the patient survival rate of elderly recipients was significantly lower than the survival rate observed in patients less than 60 years old (90% vs 97%; p < 0.005); the deaths were related to cardiovascular complications in 3 cases and to infectious diseases in 3 cases. No abdominal complications were observed in our series. The graft survival was identical in both groups (81% vs 82% at 2 years), and we observed a low incidence of acute rejection (23%) in the elderly group. The graft function, as determined by serum creatinine level, is significantly correlated with the donor age (p < 0.05). We conclude that the patients more than 60 years old, free of ischemic coronary disease or after correction of such a lesion could be safely transplanted.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Cytomegalovirus-specific in vitro antibody production by peripheral blood lymphocytes from renal transplant recipients with CMV infection.

Cytomegalovirus-specific in vitro antibody production (CMV-IVAP) by peripheral blood lymphocytes (PBL) was investigated in 12 renal transplant recipients. CMV-IVAP, CMV-serology, and viral cultures were carried out weekly during at least 8 weeks after transplantation. Nine episodes of CMV infection occurred in eight patients. CMV-IVAP was positive in eight episodes; IgG and/or IgA and/or IgM antibodies reacting with several CMV polypeptides were secreted by PBL. In two patients with primary CMV infection, only IgA antibodies were detected. Cytomegalovirus cultures were positive in eight episodes and serological evidence of CMV infection was obtained in five episodes. In one case, CMV-IVAP was observed before CMV isolation and in another case, before serological evidence of CMV infection. Our study indicates that CMV-IVAP could represent an additional tool for the diagnosis of CMV infection. Our study indicates that CMV-IVAP could represent an additional tool for the diagnosis of CMV infection in renal transplant recipients.

Adult↗
PubMed1993

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants.

The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Serum alpha 2-macroglobulin in haemodialysis patients: baseline and kinetic studies.

The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of beta 2-microglobulin (beta 2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha 2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and alpha 2M, beta 2M and alpha 1 antitrypsin were determined along with the routine biological analysis of these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both groups. The serum alpha 2M and beta 2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum alpha 2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P < 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloidosis↗
PubMed1993

[Post-transfusional anti-HLA hyperimmunization: importance of erythropoietin].

The use of erythropoietin (Epo) in chronic renal failure patients improves anemia and avoids iterative transfusions. As a consequence, a significant decrease of anti-HLA antibodies might be observed. From 31.12.1985 to 30.07.1991, among the 61 highly sensitized patients (pts) waiting for renal transplantation at our institution, 23 (7 men, 16 women, mean age 43.3 +/- 2.3 years) were treated with Epo during 21.4 +/- 1.7 months. After introduction of Epo, the mean number of transfusions significantly decreased from 35 +/- 8 to 0.5 +/- 0.4 (p < 0.0001) and the Panel Reactive Antibodies decreased from 88.1 +/- 1.7 to 18.8 +/- 5.6% (p < 0.0001). HLA antibodies totally disappeared in 12 patients, decreased more than 30% in 9 patients and remained stable in the 3 others. Renal transplantation was performed in 9 patients; 4 with a negative cross-match in both historical and current sera and 5 with a negative current cross-match but with a positive historical cross-match. 6/9 patients are doing well with a good graft function; 2 patients returned to hemodialysis for rejection and 1 patient died with a functioning kidney. Since Epo permits the transfusion withdrawal, its introduction in chronic renal failure treatment suppresses both the main factor of immunisation and one of the most important mechanisms of persistence of antibodies.

Adult↗
PubMed1993

Early systemic and renal responses to nephrectomy in normotensive kidney donors.

The present studies were designed to assess the effect of uninephrectomy (UNX) on arterial pressure and renal excretory function in normal subjects. Baseline values of arterial pressure, renal function, parameters of the renin-angiotensin and renal kallikrein-kinin systems and the response to acute saline loading (VE, 1800 ml in 3 h) were estimated in 18 kidney donors prior to and 1 year following UNX. Within the follow-up period of 14 +/- 1 months mean arterial pressure (MAP) increased by 7 +/- 2 mmHg, creatinine clearance decreased by 38 +/- 4%, plasma renin activity (PRA) decreased, urinary kallikrein remained unchanged, and the renal response to VE was blunted. According to individual changes in MAP associated with UNX, subjects were classified as responders (R, increase in MAP > or = 10%, n = 8) and non-responders (NR, n = 10). Age, incidence of a family history of hypertension, decrease in creatinine clearance, and predonation PRA, urinary kallikrein, and the natriuretic response to VE were similar in the two groups. However, following UNX, PRA decreased whereas 24-h urinary sodium and thus sodium intake increased only in the R group. In conclusion, in normotensive subjects a 50% reduction in renal mass may result in a consistent increase in MAP and sometimes the development of de novo hypertension (4/18 subjects). Baseline characteristics as well as the predonation renal response to VE do not provide a means of detecting kidney donors in whom arterial pressure will increase consistently after UNX.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗