Successful treatment of recurrence of immunotactoid glomerulopathy in a kidney allograft recipient.
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Adult↗
Biomedical subjects
D Durand
Publications and source records attributed to D Durand.
Microgravity and hypergravity effects on fertilization of the salamander Pleurodeles waltl (urodele amphibian).
Effects of microgravity (microG) on fertilization were studied in the urodele amphibian Pleurodeles waltl on board the MIR space station. Genetic and cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that fertilization did occur in microG. Actual fertilization was demonstrated by the analysis of the distribution of peptidase-1 genes, a polymorphic sex-linked enzyme, in progenies obtained in microG. Further evidence of fertilization was provided by the presence of spermatozoa in the perivitelline space and in the fertilization layer of the microG eggs and by the presence of a female pronucleus and male pronuclei in the egg cytoplasm. Experiments in microG and in 1.4G, 2G, and 3G hypergravity showed for the first time that, compared to eggs in 1G, several characteristics of the fertilization process including the cortical reaction and the microvillus transformations were altered depending on the gravitational force applied to the eggs. Microvillus elevation, the most evident feature, was reduced on microG-eggs and amplified on eggs submitted to 2G and 3G. No lethal consequences of these alterations on the early development of microG-eggs were observed.
Animals↗
Change in backbone torsion angle distribution on protein folding.
Understanding protein folding requires the determination of the configurational space accessible to the protein at different stages in folding. Here, computer simulation analysis of small angle neutron scattering results is used to probe the change in the distribution of configurations on strong denaturation of a globular protein, phosphoglycerate kinase, in 4 M guanidine hydrochloride solution. To do this atomic-detail ensembles of the unfolded protein chain are modeled and their scattering profiles compared with the experiment. The local conformational statistics are found to strongly influence the experimental intensity at scattering vectors between 0.05 and 0.3 A(-1). Denaturation leads to a reduction in the protein atom-pair distance distribution function over the approximately 3-15 A region that is associated with a quantifiable shift in the backbone torsional angle (phi, psi) distribution toward the beta region of the Ramachandran plot.
Computer Simulation↗
Effects of milk diets containing beef tallow or coconut oil on the fatty acid metabolism of liver slices from preruminant calves.
Coconut oil (CO) induces a triacylglycerol infiltration in the hepatocytes of preruminant calves when given as the sole source of fat in the milk diet over a long-term period. Metabolic pathways potentially involved in this hepatic triacylglycerol accumulation were studied by in vitro methods on liver slices from preruminant Holstein x Friesian male calves fed a conventional milk diet containing CO (n 5) or beef tallow (BT, n 5) for 19 d. Liver slices were incubated for 12 h in the presence of 0.8 mm-[14C]oleate or -[14C]laurate added to the medium. Fatty acid oxidation was determined by measuring the production of CO2 (total oxidation) and acid-soluble products (partial oxidation). Production of CO2 was 1. 7-3.6-fold lower (P 0.0490) and production of acid-soluble products tended to be lower (P = 0.0625) in liver slices of CO- than BT-fed calves. Fatty acid esterification as neutral lipids was 2.6- to 3. 1-fold higher (P = 0.0088) in liver slices prepared from calves fed the CO diet compared with calves fed the BT diet. By contrast with what occurs in the liver of rats fed CO, the increase in neutral lipid production did not stimulate VLDL secretion by the hepatocytes of calves fed with CO, leading to a triacylglycerol accumulation in the cytosol. It could be explained by the reduction of fatty acid oxidation favouring esterification in the form of triacylglycerols, in association with a limited availability of triacylglycerols and/or apolipoprotein B for VLDL packaging and subsequent secretion.
Analysis of Variance↗
DNA packing in stable lipid complexes designed for gene transfer imitates DNA compaction in bacteriophage.
The structure of complexes made from DNA and suitable lipids (lipoplex, Lx) was examined by cryo-electron microscopy (cryoEM). We observed a distinct concentric ring-like pattern with striated shells when using plasmid DNA. These spherical multilamellar particles have a mean diameter of 254 nm with repetitive spacing of 7.5 nm with striation of 5.3 nm width. Small angle x-ray scattering revealed repetitive ordering of 6.9 nm, suggesting a lamellar structure containing at least 12 layers. This concentric and lamellar structure with different packing regimes also was observed by cryoEM when using linear double-stranded DNA, single-stranded DNA, and oligodeoxynucleotides. DNA chains could be visualized in DNA/lipid complexes. Such specific supramolecular organization is the result of thermodynamic forces, which cause compaction to occur through concentric winding of DNA in a liquid crystalline phase. CryoEM examination of T4 phage DNA packed either in T4 capsides or in lipidic particles showed similar patterns. Small angle x-ray scattering suggested an hexagonal phase in Lx-T4 DNA. Our results indicate that both lamellar and hexagonal phases may coexist in the same Lx preparation or particle and that transition between both phases may depend on equilibrium influenced by type and length of the DNA used.
Bacteriophage T4↗
Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group.
BACKGROUND: Sirolimus (rapamycin) is a potent immunosuppressant with a mechanism of action different from cyclosporine (CsA) or tacrolimus. METHODS: In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n=42) or sirolimus (n=41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. RESULTS: At 12 months, graft survival (98% sirolimus vs. 90% CsA), patient survival (100% vs. 98%), and incidence of biopsy-confirmed acute rejection (41% vs. 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P< or =0.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities reported significantly more often with sirolimus included hypertriglyceridemia (51% vs. 12%), hypercholesterolemia (44% vs. 14%), thrombocytopenia (37% vs. 0%), leukopenia (39% vs. 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/ml. Occurrence of cytomegalovirus was comparable (14% vs. 12%); incidences of herpes simplex (24% vs. 10%, P=0.08) and pneumonia (17% vs. 2%, P=0.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs. 33%). Two malignancies were observed with CsA and none with sirolimus. CONCLUSIONS: Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from CsA.
Adult↗
Kinetics of intracytoplasmic Th1 and Th2 cytokine production assessed by flow cytometry following in vitro activation of peripheral blood mononuclear cells.
BACKGROUND: Standard cytokine detection methods are unable to determine which cells are the producing cells. We report on the extent and under which conditions the multilabeling capability of flow cytometry (FCM) can bring new advances into the field. METHODS: Five different cytokines, interleukin-2 (IL-2), -4, -5, -10 and interferon-gamma (IFN-gamma), were assessed simultaneously under five ex vivo stimulation conditions in peripheral blood mononuclear cells from five healthy volunteers in a 5-day kinetic study. A second group of 35 volunteers was assessed for IFN-gamma and IL-2 production. RESULTS: This study showed that (a) intracytoplasmic cytokines were almost undetectable within unstimulated cells, (b) intracytoplasmic cytokines were detected only in CD69(+) T lymphocytes, and (c) intracytoplasmic IL-2 and IFN-gamma were dramatically upregulated after stimulation with phorbol myristate acetate (PMA)-ionomycin in a biphasic response or with PMA-phytohemagglutinin (one major peak only at 18 h) but to a lesser extent with other stimuli such as monoclonal antibodies. Th2 cytokines were detected at a later time point and at lower levels. PMA/ionomycin stimulation after 4 h and 18 h of culture in 35 other volunteers individualized several subgroups according to the frequency of IFN-gamma- or IL-2-producing cells--IFN-gamma delayed producers (n = 10/35), IFN-gamma low producers (n = 8/35), and IL-2 delayed producers (n = 16/35)--as opposed to IFN-gamma or IL-2 normal producers. CONCLUSIONS: FCM appears to be a good tool to examine cell cytokine status in pathology (allergy, autoimmune disease, etc.) provided that optimal stimulation conditions and multiple time-point cultures are used. It also seems to be a relevant method to define new Th subsets further.
Antigens, CD↗
Structural parameters involved in the permeation of propranolol HCl by iontophoresis and enhancers.
The purpose of this work was to study the effect of iontophoretic transport of Propranolol hydrochloride on the lipidic organization of the stratum corneum pretreated under passive or iontophoretic conditions by two model penetration enhancers, sodium lauryl sulfate and hexadecyl trimethylammonium bromide. Characterization of human stratum corneum was performed by X-ray diffraction, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and differential scanning calorimetry (DSC). The structural properties were compared with the iontophoretic permeability of propranolol hydrochloride on human stratum corneum. The iontophoretic fluxes of propranolol hydrochloride were effectively increased by two-fold in stratum corneum pretreated with sodium lauryl sulfate. In contrast, they were halved in stratum corneum pretreated with hexadecyl trimethylammonium bromide. These results could be related to changes in the electrical and structural properties of the stratum corneum after incorporation of these enhancers.
Adrenergic beta-Antagonists↗
Long-term impact of superinfection by hepatitis G virus in hepatitis C virus-positive renal transplant patients.
BACKGROUND: The hepatitis G virus (HGV) has been recently cloned. Studies in immunocompetent patients have shown that HGV superinfection in hepatitis C virus (HCV)-positive patients does not affect (i) clinical presentation, HCV RNA level, or response to interferon-alpha therapy; or (ii) the histopathologic severity and characteristics of chronic hepatitis. No data are currently available on the impact of HGV infection on liver histology of renal transplant (RT) patients although the reported prevalence of serum HGV RNA in this population is high, ranging from 14% to 55%. PATIENTS AND METHODS: We determined the prevalence of HGV infection in 103 HCV-positive RT patients for whom HGV RNA was retrospectively determined by reverse transcription-polymerase chain reaction before, at the time of, and after transplantation (last follow-up). We evaluated the impact of HGV on liver function tests, liver histology (by means of the Knodell score), and renal parameters such as the prevalence of acute rejection and renal function. RESULTS: A total of 29 (28%) of the HCV-positive RT patients had a positive HGV RNA (group 1). The mean duration of HGV infection was at least 119+/-64 months (range: 18-240 months). Group 1 patients were compared to the 74 HGV RNA-negative/HCV-positive RT patients (group 2). Liver histology showed a significantly lower degree of fibrosis in group 1 (0.4+/-0.5) than in group 2 (1+/-1.2; P=0.02); two patients from group 2 but none from group 1 had overt cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular destruction was not statistically different between the two groups. The number of patients who experienced at least one acute rejection episode was significantly higher in group 1 (69%) than in group 2 (42%; P=0.01). However, the multivariate analysis did not identify the presence of HGV RNA at the time of renal transplantation as an independent factor of acute rejection; conversely, (i) the occurrence of cytomegalovirus infection or disease and (ii) the duration of HCV infection significantly increased the likelihood of having acute rejection. CONCLUSIONS: This study shows that: (i) HGV infection was often present when the patients seroconverted for HCV, (ii) HGV RNA-positive/HCV-positive RT patients experienced acute rejection more frequently than HGV RNA-negative/HCV-positive RT patients, and (iii) HGV infection seems to have no detrimental effect upon liver enzymes or liver histology in HCV-positive RT patients.
Adult↗
Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat.
The aim of this study was to evaluate the protective or deleterious effects of endogenous nitric oxide (NO) on liver cells during hepatic ischemia-reperfusion (IR) in the rat. Injury to hepatocytes and endothelial cells was evaluated by determining cytolysis-marker activity in plasma (alanine transaminase [ALT]; aspartate transaminase [AST]) and plasma hyaluronic acid (HA) concentration. Clamping the hepatic pedicle for 45 minutes caused a significant increase in plasma AST and ALT activity after 30 minutes of reperfusion, which reached a maximum (+270% and +740%, respectively) after 6 hours of reperfusion. Plasma HA concentration was significantly higher (+130%) only after 6 hours of reperfusion. Administration of a nonselective NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine (L-NNA; 10 mg/kg iv), 30 minutes before IR, caused marked aggravation of postischemic liver injury, as shown by plasma ALT and AST activity and HA concentration. This deleterious effect was partially prevented by the simultaneous injection of L-arginine, the endogenous NO precursor (100 mg/kg iv). Interestingly, L-arginine alone limited postischemic damage (AST, -25%; ALT, -45%; HA, -21% vs. untreated IR rats at 6 hours reperfusion). Pretreatment with the Guanosine 3':5'-cyclic monophosphate-independent vasodilator, prazosin, partially reversed L-NNA effects, but it did not protect untreated IR animals. Pretreatment with aminoguanidine, a selective inhibitor of inducible NOS, did not aggravate hepatic IR injury. Thus, endogenous NO, probably produced by an early and transient activation of a constitutive NOS, protects both hepatocytes and endothelial cells against liver ischemia-reperfusion injury, and this effect is not entirely a result of vasorelaxation.
Animals↗
Evolution of the internal dynamics of two globular proteins from dry powder to solution.
Myoglobin and lysozyme picosecond internal dynamics in solution is compared to that in hydrated powders by quasielastic incoherent neutron scattering. This technique is sensitive to the motions of the nonexchangeable hydrogen atoms in a sample. Because these are homogeneously distributed throughout the protein structure, the average dynamics of the protein is described. We first propose an original data treatment to deal with the protein global motions in the case of solution samples. The validity of this treatment is checked by comparison with classical measurements of the diffusion constants. The evolution with the scattering vector of the width and relative contribution of the quasielastic component was then used to derive information on the amount of local diffusive motions and their characteristic average relaxation time. From dry powder to coverage by one water layer, the surface side chains progressively acquire the possibility to diffuse locally. On subsequent hydration, the main effect of water is to improve the rate of these diffusive motions. Motions with higher average amplitude occur in solution, about three times more than for a hydrated powder at complete coverage, with a shorter average relaxation time, approximately 4.5 ps compared to 9.4 ps for one water monolayer.
Animals↗
A new rejection criteria in the heterotopically placed rat heart by non-invasive measurement of Dp/Dtmax.
BACKGROUND: The heterotopic heart of rats has been a useful model in the evaluation of immunomodulatory protocols. Graft palpation usually determines the day of rejection. We present in this paper an original method of graft monitoring in allograft rejection. METHODS: Heterotopic cardiac abdominal transplantation was performed in Lewis isografts (n = 15) and in ACI to Lewis allograft (n = 15). A balloon connected to a measurement device was inserted in the left ventricle, and calculation of Dp/Dtmax was possible by recording the intra-left ventricular pressure. A ten-day follow-up was achieved with a daily comparison of palaption, ECG, and Dp/Dtmax. RESULTS: In transplanted hearts, Dp/Dtmax did not change in isografts but significantly decreased in allograft on posttransplantation Day 5 (PTD 5) vs PTD 0.1 and 3 (p < .01). Dp/Dtmax values on PTD 5 and 6 were also statistically significant in allograft vs isograft group (p < .01). Histological analysis at this time showed the occurrence of acute rejection in the allograft group. Graft palpation, and ECG remained normal until PTD 10 and no difference was observed between iso and allo groups. CONCLUSION: This study shows that daily measurement of Dp/Dtmax in heterotopic heart is made possible by our implantable system without interrupting the graft, and gives a more accurate definition of graft rejection than a combination of palpation and ECG. In addition, this method would seem desirable when differences in survival may be expected to be of lesser magnitude.
Abdomen↗
Differences in Type 1 and Type 2 intracytoplasmic cytokines, detected by flow cytometry, according to immunosuppression (cyclosporine A vs. tacrolimus) in stable renal allograft recipients.
Recent multicenter, randomized clinical trials have shown that in renal transplant patients tacrolimus (FK506) was more efficient than cyclosporine A (CsA) at preventing acute rejection. In order to try and evaluate whether this difference was related to a different in vivo T-cell suppression we assessed, in a prospective study, the frequencies of interleukin (IL)-2-, IL-4-, IL-5-, IL-6-, IL-10-, interferon-gamma (IFN-gamma)- and double-positive IL-2/IFN-gamma-producing whole T cells, CD4 + and CD8 + T-cell subsets by means of cytokine flow cytometry. This was performed after in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol myristate acetate (PMA) and ionomycin, in the presence of monensin, in 14 healthy volunteers (controls) and in 14 renal transplant patients. The immunosuppression of the latter was based either on CsA (n = 7) or on FK506 (n = 7). Cytokine-expressing T-cell frequencies were assessed immediately pretransplantation (DO), and subsequently 3 months (M3) and 6 months (M6) afterwards in fasting patients prior to the morning intake of the immunosuppressive drug. We found that at DO the frequencies of IL-2-(22 +/- 2% vs. 22.2 +/- 2%), IFN-gamma-(26 +/- 3% vs. 29 + 3.4%) and IL-4-(0.8 +/- 0.2% vs. 1.4 +/- 0.2%)-expressing T lymphocytes were not significantly different between the controls and the patients, respectively. Conversely, the frequency of IL-2/IFN-gamma double positive cells was higher in the latter (9.3 +/- 1.6%) than in the controls (5.6 +/- 0.8); p = 0.06. Finally, on D0 the frequencies of IL-5-, IL-6-, and IL-10-producing T lymphocytes were lower than 1%, in both groups, as well as after grafting, i.e. on M3 and M6. As compared to baseline (DO): (a) chronic immunosuppression significantly decreased the frequencies of IL-2-, IL-4- and IL-2/IFN-gamma-expressing T cells, whereas those of IFN-gamma, IL-5, IL-6, and IL-10 were not significantly affected; (b) the frequencies of cytokine-expressing T cells were not statistically different between M3 and M6; (c) the decrease in the frequencies of IL-2- and IL-2/IFN-gamma-expressing T cells affected CD4 + and CD8 + cells equally; (d) there was a marginal decrease in the frequency of IFN-gamma-expressing cells only in the CD4 + subset but not in the CD8 population; and (e) for CsA, but not for FK506, the frequency of the IL-2-expressing T cells was negatively correlated with the whole blood trough levels. When we compared the frequencies of cytokine-expressing cells in FK506- and CsA-treated patients, we found that the frequency of IL-2-expressing T cells was significantly lower with FK506 (10.9+/-1.61%) than with CsA (16.3 +/- 1.8%; p = 0.03), whereas the frequencies of the other cytokine-expressing cells were not statistically different between the two groups. In conclusion, our study clearly demonstrated that studied ex vivo, FK506 and CsA decrease the frequencies of cells expressing IL-2, IL-4 and IL-2/IFN-gamma in vivo but do not affect those expressing IFN-gamma. Meanwhile, the frequency of IL-2-producing T cells was more affected with FK506 than with CsA and was negatively correlated with the CsA trough level. Finally, our results regarding IL-2 might explain to some extent the higher efficiency of FK506 in vivo than CsA.
Adult↗
Bacterial contamination of hospital physicians' stethoscopes.
Because stethoscopes might be potential vectors of nosocomial infections, this study, conducted in a 450-bed general hospital, was devised to evaluate the bacterial contamination of stethoscopes; bacterial survival on stethoscope membranes; the kinetics of the bacterial load on stethoscope membranes during clinical use; and the efficacy of 70% alcohol or liquid soap for membrane disinfection. Among the 355 stethoscopes tested, 234 carried > or =2 different bacterial species; 31 carried potentially pathogenic bacteria. Although some bacteria deposited onto membranes could survive 6 to 18 hours, none survived after disinfection.
Bacteria↗
Apolipoprotein B production and very low density lipoprotein secretion by calf liver slices.
Secretion of triglycerides by the liver in ruminants as components of very low density lipoproteins particles is low as compared with that in primates or rodents. The rate-limiting steps for the hepatic export of very low density lipoproteins have been studied in liver slices to determine the origin of the low lipotropic capacity of calf liver compared to that of rat liver. The rates of production of apolipoprotein B (apo B) and albumin as well as the rate of secretion of VLDL-apolipoproteins were measured during 12-h incubation of liver slices in organo-culture using [35S]methionine-cysteine labeling. Hepatic apo B production was similar in the two animal species but the VLDL-apolipoprotein secretion rate for calf liver slices amounted to only 20% of that observed for rat liver slices. Although calf and rat liver slices synthesized similar amounts of total protein, the hepatic production of albumin, measured in cells and media, was much higher in calf than rat liver slices (around 2.7-fold), whereas the rate secretion of albumin was similar in the two species. Our results showed that the slow rate of secretion of VLDL by calf liver cells was not consecutive to a low rate of synthesis of apo B but rather to a defect in VLDL assembly and/or secretion.
Albumins↗
Predicting factors of long-term results of OKT3 therapy for steroid resistant acute rejection following cadaveric renal transplantation.
In this retrospective study, we evaluated the histological and biological predictors of long-term response of renal transplant (RT) patients treated with orthoclone OKT3 for steroid resistant acute rejection (AR). Seventy-three patients, aged 37 +/- 12 years, were included in this study between March 1987 and December 1996. All the patients but one had received sequential quadruple immunosuppression (polyclonal antilymphocyte globulins; steroids; azathioprine, and cyclosporin A). OKT3 (5 mg/day for 10 days) was administered for biopsy-proven steroid resistant AR i.e., after 3 consecutive pulses of methylprednisolone (10 mg/kg each). This was the first AR in 46 cases, the second AR in 22 cases and the third AR in 4 cases. Renal histology (Banff) showed borderline (BL) changes in 18 patients, grade I AR in 28 patients; grade II AR in 22 patients, and grade III AR in 5 patients. When treatment with OKT3 commenced (107 +/- 18 days post-transplantation) the mean serum creatinine (SCr) level was 325 +/- 195 micromol/l; this had decreased to 191 +/- 106 micromol/l by the end of OKT3 therapy. The immediate response to OKT3 therapy i. e., within the first month, was not dependent on the histological score. Twenty-six patients (35%) subsequently experienced at least one more AR episode of whom 4 were retreated with OKT3. The overall patient's survival was 94.5% at last follow-up. The overall cumulative graft survival was 64.5% at 2 years, 52.5% at 5 years, and 40.5% at 8 years. The graft survival (5 years) tended to depend on the initial histological score, i.e. BL 30%; grade I 66%; grades II and III 55.5% (p = 0.08). In a multiple logistic regression analysis we tried to identify independent factors that would predict that a graft would still be functioning at least 2 years after OKT3 therapy. We therefore analyzed the following parameters: donor and recipient's age; gender; cold ischemia time; HLA matching; panel reactive antibodies (PRA) prior to grafting; previous transplantation(s); total number of AR episodes; the time of onset of the AR treated by OKT3 compared to the other AR; the time of onset of the AR treated by OKT3; SCr levels at days 0, 10 and 30 after OKT3 therapy; histological score (Banff) i.e., the magnitude of AR and the presence or absence of chronic lesions. The only independent factors which would predict that a graft was still functioning 2 years after OKT3 therapy were: PRA <25% (Odds ratio (OR) 7.68 (1.15-51.3); p = 0.035); a grade I AR (OR 10.52 (1.18-93. 5); p = 0.035); SCr level 1 month after OKT3 therapy (OR 0.935 (0. 87-1.002); p = 0.05). HLA matching and the presence of histological chronic lesions were nearly significant (p = 0.06 and 0.09 respectively). In conclusion, this retrospective study shows that independent predictors of the long-term response to OKT3 therapy for AR in RT patients are the magnitude of pre-transplant PRA, the histological score, and the SCr level one month after OKT3 therapy.
Acute Disease↗
[Evaluation of the results of organ transplantation in France: is there a center effect?].
The evaluation of the results of organ allografts for each type of organ and for each center is one of the prioritary missions of the Etablissement français des Greffes (EfG). The objectives, the methodology and the results of this evaluation have been defined and discussed with all the organ transplantation teams, after a preliminary work of the Conseil Médical et Scientifique of the Etablissement. This paper describes the evaluation experiment conducted by the EfG between 1995 and 1998. The main objectives of this first phase of the evaluation project are the identification of centers with outside of the norm results and the study of the relationship between the number of transplants performed by each center and the quality of their results. The chosen quality indicators are the excess in the patients mortality rate, computed one year after the first transplantation, for vital organs, and in the one year kidney graft loss rate for kidney transplantation. The excess of mortality is defined as the difference between observed and expected mortality rates. The expected mortality rate is estimated, for each program, by a statistical model based on a set of patient specific risk factors. All the vital organ transplantation teams who have performed more than 10 transplants between 1991 and 1995, and all the kidney transplantation teams who have performed more than 15 transplants between 1991 and 1996 have been included in the study. The main results of this evaluation experiment are the following ones: even if the intercenter variability of the results was statistically significant, it remained of low magnitude, particularly for heart, liver and kidney transplantation. None of the evaluated centers presented results outside of the norm. The results were positively correlated to the number of transplants for liver and lung transplantation. This was not the case for heart and kidney transplantation; this relationship is difficult to analyze for heart-lung transplantation, due to the small number of centers included. Thanks to the data base constituted since 1959 by all the organ transplantation teams, and in spite of the partially retrospective nature of this study, which explains its limits, this evaluation experiment, opens a perspective of extension to other domains of public health. In the future, however, this kind of evaluation should be prospective; a project aimed to developing the evaluation of the results of organ transplant actions in real time was defined and is currently on-going.
France↗
[Long-term consequences of co-infection by hepatitis G virus in hepatitis c virus infected kidney transplant patients].
The objectives of this retrospective study were to determine the prevalence of hepatitis G virus (HGV) infection in hepatitis C virus positive (HCV+ve) renal transplant (RT) patients and to evaluate the impact of HGV both on liver function tests, liver histology tests and renal parameters such as the prevalence of acute rejection and renal function. Seventy-one HCV+ve renal transplant patients with a functioning graft for whom a post renal transplant liver biopsy was available, were included. Serum HGV RNA was assessed by reverse transcription polymerase chain reaction before, at the time of, and after renal transplantation. A total of 21 (30%) of the HCV+ve RT patients had a positive HGV RNA (Group 1); seventeen of these patients (81%) were already HGV RNA+ve when the most recent renal transplantation was performed. The other 4 patients became HGV RNA+ve following renal transplantation. The mean duration of HGV infection was at least 119 +/- 64 months (18-240). Patients in group 1 did not statistically differ from the 50 HGV RNA-ve/HCV+ve RT patients (Group 2) according to sex ratio; time on dialysis; number of blood transfusions; HLA matching; the duration of HCV infection; duration and type of immunosuppression or levels of liver enzymes i.e. aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase; serum HCV RNA concentration; or frequency of genotype 1b. However, Group 1 patients were statistically younger (41 +/- 10 y compared to 47 +/- 10 y; p = 0.016) than Group 2 patients. Liver histology showed a significantly lower degree of fibrosis in Group 1 (0.4 +/- 0.5) than in Group 2 (1 +/- 1.2; p = 0.02); two patients from Group 2 but none of Group 1 had overt cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular necrosis was not statistically different between the two groups. The number of patients who experienced at least one acute rejection episode was significantly higher in Group 1 (76.2%) than in Group 2 (46%; p = 0.02), although the difference was no longer significant in the multivariate analysis. In conclusion, this study shows that: i) HGV infection was often present when the patients seroconverted for HCV; ii) HGV RNA+ve/HCV+ve RT patients experience acute rejection more frequently than HGV RNA-ve/HCV+ve RT patients; iii) HGV infection seems to have no detrimental effect upon liver enzymes or liver histology in HCV+ve RT patients.
Adult↗