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Biomedical subjects

B Charpentier

Publications and source records attributed to B Charpentier.

At least 91 records · Page 5Linked to original sources

Recurrence of immunoglobulin A nephropathy after renal transplantation in the cyclosporine era.

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Schönlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.

Adult↗

Spondylodiskitis due to Candida albicans: report of two patients who were successfully treated with fluconazole and review of the literature.

We report the cases of two patients with spondylodiskitis due to Candida albicans who were successfully treated with fluconazole. On the basis of findings from these cases and a review of 52 mycologically proven cases in the literature, we describe the main characteristics of candidal spondylodiskitis. In 60% of the cases, candidal spondylodiskitis was a late complication of candidemia (mean delay, 5.2 months) it was determined to be a complication on the basis of the results of previously positive blood cultures (19 cases), and it was presumed to be a complication in iv drug addicts (12 cases). As spondylodiskitis can be a late complication of candidemia, all episodes of candidemia should be treated with systemic antifungal agents. Clinical and radiological signs of candidal spondylodiskitis were nonspecific. Any bone or joint symptoms in a patient who has had candidemia should be considered to be of fungal origin at the time of presentation. The definitive diagnosis of candidal spondylodiskitis was made on the basis of the results of percutaneous puncture in 26 of 30 cases. The overall prognosis for patients with candidal spondylodiskitis was good, with the full recovery rate ranging from 67% to 100%. The preliminary results of treating candidal spondylodiskitis with triazole derivatives, particularly fluconazole, were satisfactory; there was excellent tolerance of this drug.

Antifungal Agents↗

[Double kidney-total pancreas transplantation with bladder reimplantation. 25 cases].

Twenty five double kidney-pancreas transplantations were performed according to the total pancreas transplantation technique with drainage of exocrine secretions into the bladder via a vesicoduodenostomy. 72% of kidney-pancreas grafts were functional at one year and 59% were functional at four years. The authors observed a slightly higher rejection rate (0.56 versus 0.34) and a higher incidence of urinary tract infection (60% versus 35%) following double pancreas and renal transplantation than after isolated renal transplantation. Complications were rare: two venous thromboses and two cases of urethritis requiring of rediversion of the duodenum into the intestine. These good results, comparable to those reported in the international registry, reflect the value of the pancreatic and renal transplantation technique using a total pancreas drained into the bladder. It would probably be preferable to transplant patients earlier, when chronic renal failure secondary to insulin-dependent diabetes induces end-stage renal failure and the need for haemodialysis.

Adolescent↗

Occurrence and treatment of kidney graft lithiasis in a series of 1500 patients.

In a series of 1500 patients transplanted between 1976 and 1992, 12 patients presented urinary calculi. The symptoms presented included obstructive anuria in 3 patients and abdominal pain in 1 patient. There were 8 asymptomatic patients. The risk factors were mainly hyperparathyroidism and non-absorbable sutures. The occurrence of renal graft calculi is now ten times less frequent than in the 1980s. In all, 5 of the patients were treated using incisional surgery, 5 with ESWL and 4 using ureteroscopy; a double J stent was inserted for the 3 cases of obstructive anuria. Nine patients are currently calculus-free and 2 have relapsed. One asymptomatic patient was not treated. The renal function of these 12 patient was not modified and no hypertension was noted after treatment. Calculi are generally asymptomatic when they are diagnosed by ultrasonography and in our experience they can be treated using ESWL or by ureteroscopy. In our opinion all patients can be treated successfully but with a high rate of relapse if the causal factors are not treated.

Adult↗

Insertion of a double pigtail ureteral stent for the prevention of urological complications in renal transplantation: a prospective randomized study.

PURPOSE: Urologists successfully use ureteral stents to protect the ureterovesical anastomosis in nontransplant patients. MATERIALS AND METHODS: We determined the value of ureteral stents in transplant patients. The frequency of urological complications (leaks, obstructions and urinary tract infections) was compared in a prospective randomized series of 194 kidney transplantations (97 with and 97 without a double pigtail ureteral stent). RESULTS: In the stent group 1 patient had a urinary leak and 35 had urinary tract infections (including 2 cases of Corynebacterium cystitis). In the no stent group 6 patients had urinary leaks, 4 had obstructions and 32 had urinary tract infections. The 1-year patient and graft survival rates were similar in both groups, and renal function at 1 year was also similar (229 versus 208 mumol./l. creatinine in the stent and no stent groups, respectively). A small number of stent related complications occurred (2 stent breakages and 1 stent migration). No stones formed in any case. CONCLUSIONS: Ureteral stent insertion significantly decreases the rate of vesicoureteral leakage and obstruction in renal transplantation.

Adult↗

Intramolecular structure in yeast introns aids the early steps of in vitro spliceosome assembly.

rp5l B pre-mRNA, like many Saccharomyces cerevisiae primary transcripts, contains a secondary structure within its intron sequence. The structure is required for optimal in vivo splicing efficiency and includes two complementary regions near the 5' splice site and the branchpoint (UB1 and DB1, respectively). An intron-containing RNA was probed in vitro with RNase T1 and dimethyl sulfate (DMS), and is folded as expected. We have also examined in vitro splicing of rp5l B pre-mRNA, by analyzing the formation of splicing complexes as well as splicing products. Similar analyses were done with mutant pre-mRNAs containing shortened or lengthened UB1/DB1 base pairing regions. Our experiments indicate that the secondary structure acts at an early step of spliceosome assembly to aid the formation of U1 snRNP-containing commitment complexes. pre-mRNAs were probed with DMS in vivo and the folding takes place inside cells. The effect of the different UB1/DB1 interactions on in vivo splicing efficiency was also analyzed. The results are consistent with the idea that the intramolecular interaction takes place prior to or at the beginning of spliceosome assembly.

Base Sequence↗

[Significance of organ donor characteristics in renal function at 1 month: reflection on the allocation of renal transplant].

In a series of 731 kidneys taken from brain-dead donors for renal transplantation, 652 were grafted, and the renal function at 1 month is known for 490 of them. The results show that some donor-related factors influence the outcome of the transplant. In particular, haemodynamic instability refractory to medical treatment is responsible for a 50 mumol increase of serum creatinine one month after transplantation and the use of UW solution during organ collection is responsible for an improvement of serum creatinine compared to other preservation solutions. Haemodynamic instability is a criterion which must be added to those already demonstrated in donors, such as the cause of death, age and sex. The authors propose that donor-related factors be taken into account in the allocation of organs in the same way as immunological factors which, at the present time, constitute the only criterion for kidney allocation.

Adolescent↗

[Impact of weight difference between donor and recipient on the function of the transplanted kidney].

OBJECTIVE: The objective of this retrospective study was to determine whether the difference between the donor's weight (wd) and the recipient's dry weight (wr) could influence the function of renal transplants. METHODS: Between 1987 and 1994, 185 patients with a mean age of 43.3 years +/- 12 were transplanted with a locally harvested cadaver kidney, corresponding to 120 men (42.2 years +/- 1.4) and 65 women (45 years +/- 12.8). The weight variation between donors and recipients (wd - wr) was 0.06 for men and 0.22 for women. The serum creatinine of recipients at 1 year was 147 mumol +/- 41.7. We used analysis of variance for univariate statistical analysis and multiple linear regression for multivariate analysis. RESULTS: On univariate analysis, the serum creatinine at 1 and 2 years was significantly higher (p < 0.02 and p < 0.035 respectively) when the donor's weight was 10% lower than the recipient's weight. Multivariate analysis, taking into account the donor's age and sex and the recipient's serum creatinine, confirmed the influence of the donor-recipient weight difference on serum creatinine at 2 years (p0.03), but also the role of the donor's age at 1 and 2 years (p < 0.0001 and p < 0.0004, respectively). CONCLUSION: In our study, the donor-recipient weight difference was a factor influencing the recipient's serum creatinine at 2 years. The donor's age also influences the recipient's serum creatinine, 1 and 2 years after renal transplantation.

Adolescent↗

Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes.

The retinoic acid receptors (RARs) transduce retinoid dependant gene regulation, and many biological effects of retinoids are mediated through binding and activation of three closely related receptor subtypes (RAR alpha, RAR beta, and RAR gamma). In order to investigate the role of receptor subtypes, we have carried out a chemical synthesis program to seek selective retinoids for these receptors. We measured receptor binding affinity using recombinant RAR alpha, -beta, and -gamma proteins and assessed cellular differentiating activity in F9 murine teratocarcinoma cells (F9 cells). This research has identified the 4-substituted-3-(1-adamantyl)phenyl moiety as a new pharmacophore which can replace the beta-cyclogeranylidene ring of the naturally occurring all-trans-retinoic acid. Two chemical series derived from the general structures 6-(3-tertioalkylphenyl)-2-naphthoic acid (series I) and 4-[(E)-2-(3-tertioalkylphenyl)propenyl]benzoic acid (series II) were developed. In particular, we have obtained the RAR gamma selective derivatives 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthoic acid (7) [Ki(RAR alpha) = 6500 nM, Ki(RAR beta) = 2480 nM, Ki(RAR gamma) = 77 nM] and 4-[(E)-2-[3-(1-adamantyl)-4-hydroxyphenyl]propenyl]benzoic acid (19) [Ki(RAR alpha) = 1,144 nM, Ki(RAR beta) = 1245 nM, Ki(RAR gamma) = 53 nM]. In series I, the presence of a phenol group, irrespective of the nature of tertioalkyl group, imparted at least partial RAR gamma selectivity, whereas in series II, the presence of both adamantyl and phenol groups is needed to confer RAR gamma selectivity. The RAR gamma selective ligands induce differentiation in F9 cells (7, AC50 = 33 nM; 19, AC50 = 66 nM). From series I, a mixed RAR beta-gamma agonist with potent cellular differentiating activity was selected for development as a topical antiacne agent, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (5, CD 271) [Ki(RAR alpha) = 1100 nM, Ki-(RAR beta) = 34 nM, Ki(RAR gamma) = 130 nM, AC50(F9) = 37 nM]. Finally, from series II, we have obtained a weak antagonist in the F9 cellular differentiation assay, 4-[(E)-2-(3-tert-butyl-4-hydroxyphenyl)propenyl]benzoic acid (15, IC50 = 700 nM).

Animals↗

Five years' experience at one centre with protein A immunoadsorption in patients with deleterious allo/autoantibodies (anti-HLA antibodies, autoimmune bleeding disorders) and post-transplant patients relapsing with focal glomerular sclerosis.

Protein A is extracted from a strain of Staphylococcus aureus and binds specifically to the constant domains of immunoglobulins and possibly to fibronectin. It has already been shown that concentrations of all IgG isotypes (except IgG3) are efficiently decreased by immunoadsorption (IA) on protein A linked to sepharose beads. This system has been developed by Cobe-Excorim Co. to either remove IgG in some instances where they wil be harmful, i.e. allo- and autoantibodies inducing pathological conditions (autoimmune diseases, haematological disorders with allo/autoantibodies, anti-HLA antibodies in sensitized patients awaiting organ transplantation) or treat several immunological diseases with unknown pathogenesis. In our unit, 20 patients with high titres of anti-HLA panel-reactive antibodies, four patients with haematological disorders (haemophilia with anti-VIII antibodies and Glanzmann diseases) and three patients with post-transplant focal glomerular sclerosis (FGS) underwent IA over the past 5 years. Infectious complications were not observed after IA and the procedure was always well tolerated. In spite of the use of adjunctive immunosuppressive therapy with prednisone and cyclophosphamide, and although the reduction in serum IgG was close to 90%, the de novo synthesis of allo- and autoantibodies was important after IA procedures. In the cases of removal of anti-HLA antibodies, patients with a pre-IA antibody titre which was > 1:128 clearly did not benefit from the technique and other immunological criteria were not predictive of efficacy. Fourteen patients were transplanted, four with a well-matched kidney with both pre- and post-IA negative cross-matching, and 10 with a positive historical cross-match with the donor.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticoagulants↗

Combined liver and kidney transplantation in patients with chronic nephritis associated with end-stage liver disease.

A variety of renal diseases can be associated with end-stage liver diseases requiring orthotopic liver transplantation (OLT), including cirrhosis-associated glomerulonephritis (GN), and nephropathy unrelated to the liver disease. A retrospective survey showed that nine patients undergoing liver transplantation in our centre had histologically proven GN or interstitial nephritis with renal failure and/or nephrotic-range proteinuria, and experienced severe complications post-OLT since nephrotoxic immunosuppressive drugs (CsA and FK506) could not be adequately given. Four of the nine patients died. Therefore, combined liver-kidney transplantation has been suggested as first choice treatment in such patients. From January 1990 to February 1994, in patients with end-stage liver disease referred for OLT, and who presented with unexplained renal function impairment and/or significant proteinuria, severe nephropathy was confirmed by renal biopsy in nine: four mesangiocapillary GN with immune deposits, one membranous nephropathy, two diabetic glomerulosclerosis and two interstitial nephritis. All underwent liver transplantation immediately followed by kidney transplantation. The postoperative period was uneventful, and neither death nor renal failure were recorded. Combined transplantation resulted in all patients in the normalization of renal function, and in the disappearance of proteinuria within the first postoperative month. From 6 months to 4 years post-transplant, the renal function remained within normal ranges in all patients. Routine renal transplant biopsy was performed in two patients with pre-transplant cirrhosis-associated GN, and showed no evidence of recurrence of the original nephropathy. We conclude that combined liver-kidney transplantation is an adequate therapeutic option in patients with end-stage liver disease associated with advanced kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗