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Biomedical subjects

P Merville

Publications and source records attributed to P Merville.

At least 19 recordsLinked to original sources
PubMed2006

[Lymphoma with initial renal involvement: four cases].

PURPOSE: To present a comprehensive description of the clinical features of patients with renal manifestations during lymphoma. METHODS: Retrospective review of medical records from all patients diagnosed with lymphoma associated with kidney involvement in our hospital between 1996 to 2004. Four cases were identified and analysed. RESULTS: Four patients presented a non-Hodgkin's lymphoma. One patient showed intravascular large B-cell lymphoma, revealed by proteinuria. Another patient had a nephrotic syndrome, and two had a renal mass. Renal histology allowed diagnosis of lymphoma in 3 cases. CONCLUSION: The diagnosis of lymphoma associated with renal involvement is rather difficult, and more specifically in case of intravascular large B-cell lymphoma, or even primary renal lymphoma. We present here a comprehensive review of the literature and we discuss pathogenesis of these conditions.

Aged↗
PubMed2006

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

Adrenal Cortex Hormones↗
PubMed2005

[First case in the world of autoreplantation of a limb associated with oral administration of an immunosupressant agent (FK 506-Tacrolimus)].

This is the case of the replantation of the upper limb of a sixty year old woman. The nature of the traumatism is an avulsion of the upper limb, at the junction of the middle third and the lower third of the humerus, which has a very bad prognosis. The originality of this report is the administration of Tacrolimus (immunosuppressive molecule) in an autotransplant. Tracolimus stimulates the nerve growing back, as already demonstrated in the animal and the fetus. In this preliminary report, the use of Tacrolimus over one year showed exceptional results. Indeed, the autors noticed clinical signs of intrinsic reinervation of the hand in the territory of the ulnar and median nerve. This has been confirmed with the use of electromyography. This is, as far as we know, the first observation of such results with adults and when the level of amputation is located so high. The authors think that the use of Tacrolimus should be tested in numerous cases of nerve lesions with bad prognosis such as high ulnar nerve lesions, serious plexus suffering or even in spinal cord trauma.

Administration, Oral↗
PubMed2004

An unusual endocarditis-induced crescentic glomerulonephritis treated by plasmapheresis.

A 58-year-old man presented with fever and a rapidly progressive glomerulonephritis. An infective endocarditis due to Streptococcus parasanguis was diagnosed. A renal biopsy revealed type III pauci-immune crescentic glomerulonephritis. As first-line therapy, antibiotics were administered alone. Faced to the unsuccessful anti-infective approach, corticosteroid therapy was added as a second-line therapy. Finally, plasmapheresis introduced as the third-line therapy, significantly improved renal function. This case is an original type III rapidly progressive glomerulonephritis, since ANCA were repeatedly found negative. In very few cases, plasmapheresis was successfully used for the treatment of infective endocarditis-induced crescentic glomerulonephritis. The pathophysiology and the potential efficiency of plasmapheresis are discussed.

Endocarditis, Bacterial↗
PubMed2004

[Immune dysfuntion of uremic patients: potential role for the soluble form of CD40].

Immune deficiency is one of the numerous physiological alterations associated with chronic renal failure. Recurrent bacterial infections, diminished vaccinal response or beta2-microglobuline amyloïdosis are some common features of clinically well known dysregulations of uraemic immune functions. During the last ten years, our knowledge concerning the molecular and cellular effectors involved in the immune response has considerably progressed. Recent data clearly demonstrated that despite their activated phenotype, the effector capacity of the immune cells are severely hampered. Of interest, those abnormalities are not corrected by haemodialysis which sometimes even accentuate them. However, the presence of uraemic toxins in the serum of chronic renal failure patients jeopardise the determination of the factors responsible for the alteration of immune response in those patients. Among those molecules, the soluble form of CD40 (sCD40), which seric levels are dramatically increased, seems to play a crucial role. A better understanding of the molecular and cellular actors involved in the immune disorders of uraemic patients should allows the emergence of new immuno-intervention strategies and improve haemodialysis traitement.

Antigens, CD↗
PubMed2001

Functional quantification of cyclosporine A and FK506 in human whole blood by flow cytometry, using the green fluorescent protein as an interleukin-2 reporter gene.

The concentration of the immunosuppressive drugs cyclosporine A (CSA) and FK506 in biological fluids is routinely determined by antibody-based assays, which for several reasons do not give accurate information on the actual level of immunosuppression in the patient. To alleviate this problem, we developed a functional reporter gene assay which uses the enhancer fragment of the interleukin-2 promoter region driving the expression of the green fluorescent protein (GFP). This construct was stably transfected in the Jurkat human T lymphoblastoid cell line. Upon stimulation of the cell recipient, the GFP was produced and evaluated by flow cytometry. Immunosuppressants acting via inhibition of interleukin-2 synthesis, such as CSA or FK506, inhibited the production of GFP in a dose-dependent manner. This assay can be performed within a working day with a good reproducibility and was more sensitive than the antibody-based assays, since its detection limit was as low as 10 ng/ml for CSA and 0.5 ng/ml for FK506. We used it for the follow up of drug level present in the blood of transplanted patients, and compared the results with those obtained with the antibody-based assay routinely carried out in our hospital. The conclusions suggest that this assay is a valuable alternative to the presently available assays for the measurement of the immunosuppressive activity found in body fluids.

Antibodies, Monoclonal↗
PubMed2001

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Adult↗
PubMed2001

Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role.

gammadelta T cells undergo massive expansion in the peripheral blood of renal transplant recipients who are infected with cytomegalovirus (CMV). In a 3-year prospective study, the relationship between the evolution of CMV infection and the kinetics of gammadelta T cell amplification was followed for 10 months after transplantation. Patients with late gammadelta T cell expansion (>/=45 days) had significantly longer (P<.0001) and higher (P<.0003) pp65 antigenemia and more-symptomatic CMV disease than did patients with early expansion. Analysis of data for each patient showed that gammadelta T cell expansion is concomitant with the resolution of CMV infection and disease, regardless of the CMV serologic status of donor and recipient before transplantation. These observations point to gammadelta T cell percentage determination as a new, rapid, and reliable prognosis factor to predict the resolution of CMV infection and strongly suggest that gammadelta T cells play a protective role against CMV infection.

Adult↗
PubMed2001

Long-term (> or =20 yr) status of 14 cadaveric kidney-transplant recipients.

The aim of this study was to analyze the status of patients with a successful long-term (> or =20 yr) kidney graft. Nineteen (8.1%) of the 234 recipients who received a cadaveric kidney transplant between 1968 and 1978 in our center are still alive 21.7+/-1.6 yr (mean+/-standard error of the mean) later with a functioning allograft. Function, including measurement of the renal functional reserve (RFR), histological status, and morbidity were evaluated. Fourteen patients agreed to participate in this study. Their current immunosuppressive regimens combined prednisone (P)+azathioprine (AZA) (n=9), P+AZA+cyclosporine (CsA) (n=3) or P+CsA (n=2). Although they described their quality of life as good, 10 patients had mild hypertension, 5 developed 10 malignancies (9 cutaneous), 5 had replicative hepatitis, 8 had osteopenia, and 6 had cataracts, but none had diabetes mellitus. Proteinuria was detected in 6 patients, but was always less than 1 g/d. Mean serum creatinine was 1.28+/-0.28 mg/dL and glomerular filtration rate was 54.5+/-5.3 mL/min/1.73 m2. RFR was present for 4 patients with a mean value of +14.8+/-1.9 mL/min. Their functional status was not correlated with the histological lesions observed in concomitant transplant biopsies. Kidney grafts are able to function well even more than 20 yr post-transplantation, with some having a RFR whose significance remains unknown. Morbidity is of minor clinical severity, but could be further reduced with optimized management. Moreover, transplantation is much less costly than hemodialysis.

Adult↗
PubMed2000

New molecular assays to predict occurrence of cytomegalovirus disease in renal transplant recipients.

Thirty renal transplant recipients, after transplantation, were tested weekly with the following assays: cytomegalovirus (CMV) antigenemia (pp65 Ag), plasma qualitative Amplicor CMV (P-AMP), plasma and peripheral blood leukocyte quantitative Amplicor CMV monitor (P- and PBL-CMM), peripheral blood leukocyte (PBL) quantitative Quantiplex bDNA CMV, version 2.0 (bDNA), and whole-blood Nuclisens pp67 CMV (pp67). Eleven patients developed symptomatic CMV disease, and 7 developed asymptomatic CMV infection. For prediction of CMV disease, the sensitivity, specificity, and positive and negative predictive values, respectively, were as follows: 100%, 63%, 61%, and 100% for pp65 Ag; 100%, 42%, 50%, and 100% for bDNA; 91%, 47%, 50%, and 90% for PBL-CMM; 55%, 74%, 55%, and 74% for P-AMP; 55%, 74%, 55%, and 74% for P-CMM; and 64%, 79%, 64%, and 79% for pp67. First positive results in PBL were obtained 9-10 days before symptoms of CMV disease, compared with 5-6 days in plasma and 0 days in whole blood. PBL assays appear to be more appropriate than plasma assays when pre-emptive therapy is required to prevent the rapid progression from the first detection of the virus to CMV disease.

Adult↗
PubMed1999

Implication of gammadelta T cells in the human immune response to cytomegalovirus.

In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates. This in vitro expansion was inhibited by anti-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.

Adolescent↗
PubMed1999

Reduced parathyroid functional mass after successful kidney transplantation.

BACKGROUND: Chronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function. METHODS: The kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions. RESULTS: The mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 +/- 54 pg/ml before KT to 70 +/- 12 pg/ml six months later (P < 0. 005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 +/- 91 to 220 +/- 30 pg/ml (P = 0.03) and from 25 +/- 6 to 15 +/- 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve. CONCLUSION: Improvement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass.

Adult↗
PubMed1999

Major expansion of gammadelta T lymphocytes following cytomegalovirus infection in kidney allograft recipients.

In normal persons, circulating gammadelta T cells comprise a minor cell subset (0.5%-6% of total lymphocytes). gammadelta T cells were studied in the context of therapeutic immunosuppression in transplanted patients. Flow cytometry detected an expansion of gammadelta T cells in 31 of 205 renal allograft recipients and in 2 of 41 uremic patients but in none of 45 healthy subjects. Univariate statistical analysis identified cytomegalovirus (CMV) infection (P<. 001), second graft (P<.001), and antithymocyte globulin treatment (P=.01) as three variables associated with high levels (>=6%) of circulating gammadelta T cells in allograft recipients. Multivariate analysis further indicated that CMV infection was the only independent parameter associated with >6% gammadelta T cells. gammadelta T cell expansion directly followed CMV infection and was never observed in persons who did not develop CMV infection. Thus gammadelta T cells may represent a first-line defense mechanism against CMV infection in a person whose alphabeta T cell response has been weakened by immunosuppression.

Adolescent↗