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Biomedical subjects

G Mourad

Publications and source records attributed to G Mourad.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Actinomycosis after renal transplantation: apropos of 1 case and review of the literature].

Actinomycosis is a suppurative infection usually due to a facultative anaerobic bacteria, actinomyces israelii. This rare infection has been reported in immunocompetent individuals, with buccal or pharyngeal mucosal erosions. Paradoxically, few cases have been observed after solid organ transplantation: 2 cases after lung, 1 case after heart-lung transplantation and 1 case after renal transplantation. We report on a renal transplant recipient who developed a tongue and oropharynx suppurative abscess, looking like an epithelioma. Histological examination showed granulomatous inflammation with an angiofibroblastic reaction; few colonies of actinomyces were also observed by the pathologist. This lesion disappeared easily and totally after tetracycline treatment.

Actinomyces↗
PubMed2000

Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients.

INTRODUCTION: A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. METHODS: In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n = 40) or CsA (n = 38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. RESULTS: At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P = 0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. DISCUSSION: Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

Acute Disease↗
PubMed2000

Low dose antithymocyte globulins in renal transplantation: daily versus intermittent administration based on T-cell monitoring.

BACKGROUND: Despite the long history of use of antithymocyte globulins (ATG) in renal transplantation, ideal doses and duration of ATG administration based on the monitoring of T lymphocytes have yet to be defined. METHODS: Two immunosuppressive regimens based on low-dose rabbit ATG (Thymoglobuline; Imtix-Sang-stat, Lyon, France) were assessed during the first year after transplantation: daily ATG (DATG; n=23) where 50 mg of ATG was given every day and intermittent ATG (IATG; n=16) where similar doses of ATG were given for the first 3 days and then intermittently only if CD3+ T lymphocytes (measured by flow cytometry) were > 10/mm3. Both groups received steroids, azathioprine, and cyclosporine. RESULTS: ATG-induced depletion was similar for peripheral blood lymphocytes and T cells in both groups: it began at day 1 after transplantation, was submaximal at day 3, and reached maximum intensity between days 6 and 8, from which time cell counts progressively increased. However, T-cell depletion was still present at day 20. The total ATG dose per patient (381.5+/-121 vs. 564+/-135 mg/patient) and the mean cumulative daily dose of ATG (0.60+/-0.17 vs. 0.80+/-0.14 mg/kg/day) were significantly lower in the IATG group (P=0.0001 and 0.0006, respectively). The overlap of ATG and cyclosporine treatment was 6.7+/-3 vs. 7.4+/-4.3 days (P=NS), and the mean duration of ATG therapy was 11.3+/-3.2 vs. 11.6+/-2.7 days in the IATG and DATG groups, respectively (P=NS). ATG was given in an average of one dose every 1.6 days in the IATG group compared with one dose daily in the DATG group (P=7 x 10(-7)). There was no significant difference in renal graft function, the number of acute graft rejections, or ATG-related side effects and complications. Despite the daily immunological follow-up, there was a net saving of $760/patient in the cost of treatment in the IATG group. CONCLUSION: IATG had the advantage of a reduction in the dose of ATG and in the cost of treatment, while offering similar T-cell depletion and effective immunosuppression. This approach could be proposed as an induction protocol, particularly for patients with poor graft function in whom cyclosporine introduction has to be delayed or those with increased risk of cytomegalovirus infections or secondary malignancies.

Adult↗
PubMed2000

alpha2-Macroglobulin, the main serum antiprotease, binds beta2-microglobulin, the light chain of the class I major histocompatibility complex, which is involved in human disease.

beta(2)-Microglobulin, a 12 kDa protein forming part of the class I HLA (histocompatibility locus antigen) major histocompatibility complex, has been used as a prognosis factor for multiple myeloma and as a marker of renal function, and has been shown to be involved in the pathogenesis of dialysis-related amyloidosis. alpha(2)-Macroglobulin has the ability to bind a wide range of physiologically important molecules, thereby influencing their metabolic impact. In this study we show by Western blotting analysis that beta(2)-microglobulin binds to alpha(2)-macroglobulin in vitro. This binding was confirmed by BIAcore analysis, and was shown by ELISA to be concentration-dependent. The sequences of the binding peptides in the mature beta(2)-microglobulin molecule were identified by Spot multiple peptide synthesis and alpha(2)-macroglobulin binding studies. In conclusion, beta(2)-microglobulin interacts specifically with the universal antiprotease a(2)-macroglobulin. The identification of this interaction brings into question some of the axioms on the metabolism of beta(2)-microglobulin, and may help to explain the clinical findings observed in b(2)-microglobulin-related diseases.

Amyloidosis↗
PubMed2000

[Low-dose antithymocyte globulins in kidney transplantation: results of a protocol of intermittent administration].

BACKGROUND: Despite the long history of use of antithymocyte globulins (ATG) in renal transplantation, ideal doses and duration of ATG administration based on the monitoring of T lymphocytes have yet to be defined. METHODS: Two immunosuppressive regimens based on low dose rabbit ATG (thymoglobuline, Imtix-Sangstat, Lyon-France) were assessed during the first year post-transplant: daily ATG (n = 32) where 50 mg of ATG were given every day and intermittent ATG (n = 24) where similar doses of ATG were given for the first three days and then intermittently only if CD3+T lymphocytes (measured by flow cytometry) were > 10/mm3. Both groups received steroids, azathioprine and cyclosporin A (CsA). RESULTS: ATG-induced depletion was similar for PBL and T cells in both groups: it began at day one post-transplant, was submaximal at day 3 and reached maximum intensity between days 6 and 8 from which time cell counts progressively increased. However, T cell depletion was still present at day 20. The total ATG dose per patient (361 +/- 105 vs 556 +/- 119 mg/patient) and the mean cumulative daily dose of ATG (0.60 +/- 0.17 vs 0.80 +/- 0.14 mg/kg/d) were significantly lower in the IATG group (p = 0.0001, and 0.0006 respectively). The overlap of ATG and CsA treatment was 6.7 +/- 3 vs 7.4 +/- 4.3 days (p = ns) and the mean duration of ATG therapy was 12 +/- 3 vs 11 +/- 2.5 days in the IATG and DATG groups respectively (p = ns). ATG were given in an average of one dose every 1.6 days in the IATG group compared to one dose daily in the DATG group (p = 7 x 10(-7). There was no significant difference in renal graft function, the number of acute graft rejections or ATG related side effects and complications. Despite daily immunological follow-up, there was a net saving of 920 $/patient in the cost of treatment in the intermittent ATG group. CONCLUSION: Intermittent ATG had the advantage of a reduction in the dose of ATG and in the cost of treatment while offering similar T cell depletion and effective immunosuppression. This approach could be proposed as an induction protocol, particularly for patients with poor graft function in whom CsA introduction has to be delayed.

Adult↗
PubMed1999

Impaired lysosomal processing of beta2-microglobulin by infiltrating macrophages in dialysis amyloidosis.

BACKGROUND: Macrophages may participate in amyloid fibril formation by processing the protein precursor. Although this theory seems to apply for amyloidosis, in which proteolytic cleavage is a prerequisite for amyloid fibril formation, it has not been demonstrated for beta2-microglobulin (beta2m) amyloidosis. We aimed to establish the role played by macrophages in beta2m amyloidosis. METHODS: We used a double immunogold electron microscopy technique, including mouse antihuman CD68, rabbit antihuman beta2m, amyloid P component, and lysosome-associated membrane protein (LAMP-1) antibodies. Differential density labeling studies of beta2m and amyloid P component were performed extra- and intracellularly to assess protein processing by macrophages. RESULTS: The cells surrounding amyloid fibrils were found to be mostly CD68 positive, suggesting that they were of monocyte-macrophage lineage. Intracellular accumulation of amyloid fibrils was also observed; these fibrils were constantly surrounded by LAMP-1-linked gold particles, demonstrating that intracellular beta2m was almost exclusively lysosomal. The rough-surface endoplasmic reticulum was not labeled by beta2m antibody, suggesting that there was no active synthesis of beta2m by the cells. As a marker of endocytosis, protruded cytoplasmic processes in close relation with the intracellular accumulations of beta2m amyloid fibrils were observed. No difference in density labeling (extracellular vs. intracellular) was observed for beta2m, whereas intracellular P component labeling was significantly decreased. CONCLUSIONS: All of these data are strongly suggestive of phagocytosis and not synthesis of amyloid fibrils by macrophages. Further, they demonstrate an impaired lysosomal processing specific for beta2m, as other compounds of the amyloid fibrils (P component) are significantly cleared.

Aged↗
PubMed1999

[Risk factors of chronic rejection in kidney transplantation, results of a single center study].

Chronic rejection remains the single most important cause of renal allograft loss after the first year post-transplant. We performed a matched case control study within our cohort of 471 renal allograft recipients, comparing 66 patients with histologically proven chronic rejection with 66 controls. Analysis of immunological (transfusion, sensitisation, HLA matching, number of transplantation, number of acute rejections (AR), immunosuppression) and non-immunological (donors and recipients age and sex, CMV disease, post-transplant acute tubular necrosis, cold ischemia) factors which could predict the occurrence of chronic rejection (CR) was performed, using Wilcoxon rank test, Mac Nemar test and Cox model. Univariate analysis showed that potential risk factors for CR are: donor age > 45 years (p = 0.05), recipient age < 40 years (p = 0.008), CMV disease (p = 0.03), number of acute rejection episodes (p = 0.009), retransplantation (p = 0.002). Multivariate analysis showed that only the following factors significantly increased the risk of CR: AR episodes (p = 0.01) with an odds-ratio at 3.5 (95% CI = 1.3-3.9) for the second acute rejection episode and at 6.5 (95% CI = 1.5-29.4) for the third acute rejection episode, donor age > 45 years (p = 0.03) with an odds-ratio at 3.5 (95% CI = 1.1-10.6). Our data suggest that better matching at donor recipient age and more potent immunosuppressive protocols resulting in no acute rejection may improve the long term graft survival. They also show that the use of old donors (> 45 years), as a response to organ shortage is detrimental for long term renal function.

Adult↗
PubMed1998

Seasonal changes in blood pressure in patients with end-stage renal disease treated with hemodialysis.

BACKGROUND: Many factors contribute to the regulation of blood pressure. The role of climate has received relatively little attention. METHODS: During a four-year period, we determined the influence of climate on blood pressure in 53 patients with end-stage renal disease treated with hemodialysis. For each patient, blood pressure was measured before each of three dialysis treatments per week for an average of 31 months. The dose of dialysis (urea clearance multiplied by the length of dialysis and divided by the distribution volume of urea) and protein catabolism rate were assessed monthly. We then analyzed the monthly mean values for blood pressure, pulse, and body weight in relation to the monthly values for temperature, relative humidity, and atmospheric pressure recorded in Montpellier, France. RESULTS: The maximal monthly temperature varied from 10 degrees C in the winter to 31 degrees C in the summer, and the minimal monthly temperature from 1 degree to 20 degrees C. The mean (+/-SE) systolic and diastolic blood pressure was highest during the winter (153+/-3/82+/-2 mm Hg) and lowest during the summer (141+/-3/75+/-2 mm Hg). The seasonal pattern was evident throughout the four-year period. Blood pressure was correlated inversely with monthly maximal temperature (r= -0.65 and P<0.001 for systolic pressure; r= -0.71 and P<0.001 for diastolic pressure) and directly with minimal humidity (r=0.45 and P=0.002 for systolic pressure; r=0.43 and P=0.003 for diastolic pressure). Changes in protein catabolic rate, weight gain during dialysis, and dialysis dose were not related to changes in blood pressure. CONCLUSIONS: In patients with end-stage renal disease treated with hemodialysis, blood pressure varies seasonally, with higher values in the winter and lower values in the summer.

Blood Pressure↗