Search PubMed⌕ Search

Biomedical subjects

J P Jais

Publications and source records attributed to J P Jais.

At least 19 recordsLinked to original sources

An oligonucleotide microarray for mouse imprinted genes profiling.

Genomic imprinting is an epigenetic phenomenon unique to mammals that causes some genes to be expressed according to their parental origin. It results in developmental asymmetry in the function of the parental genomes. We describe here a method for the profiling of imprinted genes based on the development of a mouse imprinting microchip containing oligonucleotides corresponding to 493 genes, including most of the known imprinted genes (IG = 63), genes involved in epigenetic processes (EPI = 15), in metabolism (= 147), in obesity (= 10) and in neurotransmission (= 256) and housekeeping reference genes (= 2). This custom oligonucleotide microarray has been constructed to make data analysis and handling more manageable than pangenomic microarrays. As a proof of concept we present the differential expression of these 493 genes in different tissues (liver, placenta, embryo) of C57BL6/J mice fed different diets. Appropriate experimental strategies and statistical tools were defined at each step of the data analysis process with regard to the different sources of constraints. Data were confirmed by expression analyses based on quantitative real-time PCR. These oligochips should make it possible to increase our understanding of the involvement of imprinted genes in the timing of expression programs, tissue by tissue, stage by stage, in response to nutrients, lifestyles and other as yet unknown critical environmental factors in a variety of physiopathological situations, and in animals of different strains, ages and sexes. The use of oligonucleotides makes it possible to expand this microchip to include the increasing number of imprinted genes discovered.

Animals↗

Impact of different gases and pneumoperitoneum pressures on tumor growth during laparoscopy in a rat model.

BACKGROUND: The influence on intraperitoneal tumor growth of the choice of gas and pneumoperitoneum pressure during laparoscopy is still unknown. This study compared tumor growth after laparoscopy with different gases and pneumoperitoneum pressures in an immunodeficient model. METHODS: In an initial experiment, 60 nude rats were randomly allocated to undergo laparoscopy at different pneumoperitoneum pressures (gasless, 4 mmHg, or 8 mm Hg.) In a second experiment, 23 nude rats were randomly allocated to undergo laparoscopy with different gases (carbon dioxide or helium). Surgery was carried out 7 days after intraperitoneal injection of IGR-OV1 cells. The rats were killed 7 days after surgery. Tumor growth was assessed by the weight of the omental metastasis. For statistical analysis, we used analysis of variance (ANOVA). RESULTS: Mean omental weight was similar for all groups, regardless of the pneumoperitoneum pressure (p = 0.86) or the type of gas (p = 0.80). CONCLUSION: Physical parameters of gas have a limited impact on tumor growth.

Animals↗

Peritoneal closure reduces port site metastases: results of an experiment in a rat ovarian cancer model.

BACKGROUND: The arm of this study was to assess the role of peritoneal closure in the prevention of port site metastasis after carbon dioxide (CO2) CO2 pneumoperitoneum. METHODS: We developed a xenograft ovarian cancer model by intraperitoneal injection of 27 106 IGR-OV1 line cells in nude rats Seven days after the inoculation, the animals underwent a CO2 pneumoperitoneum. At the end of the procedure, port sites were randomly closed either with suture of peritoneum (n = 14, group A) or without suture of peritoneum (n = 12, group B). The rats were killed 7 days after surgery and their port site scars were resected. Tumor implantation was assessed by a pathologist who was blinded to the type of wound closure. RESULTS: The animals in group B were significantly more likely to have at least one port site metastasis frequent (seven of 12, or 58.3%) than those in group A (two of 14, or (14.3%) (p = 0.037). Port sites with metastases were seen more frequently in group B (eight of 24, or (33.3%) than in group A (three of 28, or 10.7%) (p = 0.046). CONCLUSIONS: Our results shows that peritoneum closure decreases the risk of port site metastasis.

Animals↗

Lipodystrophic syndromes and hyperlipidemia in a cohort of HIV-1-infected patients receiving triple combination antiretroviral therapy with a protease inhibitor.

OBJECTIVES: To assess the frequency and features of lipodystrophic syndromes in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) with a protease inhibitor (PI), and examine whether clinical and biologic abnormalities are always associated in these conditions. METHODS: Retrospective-prospective single-center observational study of 175 patients. Comparisons for continuous variables by t-test and paired t-test, and Kaplan-Meier analysis of time to onset of lipodystrophy were performed. RESULTS: In all, 51 patients (29%) had morphologic changes, after a mean HAART duration of 20.0 +/- 6.1 months, and were categorized into pure lipoatrophy (n = 16), mixed syndrome (truncal fat accumulation and face or limb lipoatrophy) (n = 30) or pure truncal fat accumulation (n = 5). Because of the small number, the latter group was not analyzed statistically. No differences were found among patients with lipoatrophy, mixed syndrome, or no lipodystrophy, in terms of gender, CD4 count, and HIV RNA plasma load at time of HAART initiation, nor in response to treatment. Patients with a mixed syndrome were older. Patients with lipoatrophy had longer duration of HIV disease, pre-HAART exposure to nucleoside analog therapy, and HAART. Baseline and pre-HAART fasting triglyceride levels were higher in patients who developed lipoatrophy, whereas weight and fasting cholesterol were higher in patients who developed a mixed syndrome. After 12 and 24 months on HAART, triglycerides and cholesterol rose significantly in all patients, independently of lipodystrophy, whereas these parameters were not increased during nucleoside analog therapy. CONCLUSIONS: Nucleoside analog exposure appears as a risk factor for lipoatrophy. Age and nutritional status (reflected by baseline weight, triglycerides and cholesterol) may influence the evolution to lipoatrophy or a mixed syndrome. Hyperlipidemia is observed in the absence of lipodystrophy and depends on PI exposure.

Adult↗

The use of frailty models in genetic studies: application to the relationship between end-stage renal failure and mutation type in Alport syndrome. European Community Alport Syndrome Concerted Action Group (ECASCA).

BACKGROUND: Alport syndrome (AS) is a severe hereditary disease usually transmitted as an X dominant trait and involving a mutation of the COL4A5 gene. It leads to end-stage renal failure (ESRF), but this progression is heterogeneous. Mutations of the COL4A5 gene have been characterised in numerous families using molecular biology. Our objective was to evaluate the interfamilial heterogeneity of the disease and to study relationships between mutation types and progression to ESRF in the European Community Alport Syndrome Concerted Action group (ECASCA) registry database. METHODS: We used the frailty model framework. Frailty models have been developed to analyse censored data with non-independent observations. Random effects are introduced in a Cox proportional regression model to take into account the intracluster correlations. In this study, ESRF is considered a censored event and the intrafamilial correlations are taken into account in the frailty models. RESULTS: These approaches allow us to demonstrate the existence of an interfamilial heterogeneity; the role of the mutation type explains the interfamilial variability. In particular, the results suggest that some mutation types are associated with a higher risk of ESRF for males. CONCLUSIONS: This study shows the importance of characterising the mutation at the molecular level in genetic studies, to understand the relationship between genotype and phenotype. The frailty models constitute an attractive approach in this context, when the phenotype is characterised by a censored end-point.

Alleles↗

[Methodology for analyzing censored correlated data: application of marginal and frailty approaches in human genetics. The European Community Alport Syndrome Concerted Action Group (ECASCA)].

BACKGROUND: Statistical analysis for correlated censored data allows to study censored events in clustered structure designs. Considering a possible correlation among failure times of the same group, standard methodology is no longer applicable. We investigated proposed models in this context to study familial data about a genetic disease, Alport syndrome. Alport syndrome is a severe hereditary disease due to abnormal collagenous chains. Renal failure is the main symptom of the disease. It progresses toward end-stage renal failure (IRT) according to a high time variability. As shown by genetic studies, mutations of COL4A5 gene are involved in the X-linked Alport Syndrome. Due to the large range of the mutation types, the aim of this study was to search for a possible genetic origin of the heterogeneity of the disease severity. METHODS: Marginal survival models and mixed effects survival models (so-called frailty models) were proposed to take into account the possible non independence of the observations. In this study, time until end-stage renal failure is a rightly censored end point. Possible intra-familial correlations due to shared environmental and/or genetic factors could induce dependence among familial failure times. In this paper, we fit marginal and frailty proportional hazards models to evaluate the effect of mutation type on the risk of IRT and an interfamilial heterogeneity of failure times. RESULTS: In this study, the use of these models allows to show the presence of an interfamilial heterogeneity of the failure times to IRT. Moreover, the results suggest that some mutation types are linked to a higher risk of fast evolution to IRT, which explains partially the interfamilial heterogeneity of the failure times. CONCLUSIONS: This paper shows the interest of marginal and frailty models to evaluate the heterogeneity of censored responses and to study relationships between a censored criterion and covariables. This study puts forward the importance of characterizing the mutation at a molecular level to understand the relationship between genotype and phenotype.

Data Interpretation, Statistical↗

Gibbs sampler for the logistic model in the analysis of longitudinal binary data.

Logistic mixed-effects models constitute a natural framework to study longitudinal binary response variables when the question addressed with the data is related to covariate effects within persons. However, the computations of the likelihoods are generally tedious and require the resolution of integrals which have no analytical solution. In this paper, we study a logistic mixed-effects model in a Bayesian framework and use the Gibbs sampler to overcome the current computational limitations. From a study of side-effects occurring during plasma exchanges, we explore the issues of bayesian formulation, model parametrization, choice of the prior distributions, diagnosing convergence, comparison between models and model adequacy. Finally, we show that a Bayesian random-effects model is useful to facilitate prediction.

Bayes Theorem↗

Anti-B-cell monoclonal antibody treatment of severe posttransplant B-lymphoproliferative disorder: prognostic factors and long-term outcome.

B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus-transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti-B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti-B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti-B-cell MoAb therapy: multivisceral disease (P </= .005), central nervous system involvement (P </= .05), and late onset of BLPD (P </= .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti-B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD.

Adolescent↗

Ten-year results of a strategy combining three cycles of ABVD and high-dose extended irradiation for treating Hodgkin's disease at advanced stages.

BACKGROUND: The treatment of Hodgkin's disease (HD) at advanced stages relies mainly upon multi-agent chemotherapies (CT), while the role of radiation therapy has not been definitely identified. The aim of this report is to analyze the 10-year results of a prospective study including 133 patients with HD clinical stages (CS) IIIA to IVB treated by three monthly courses of ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine) followed by high-dose subtotal or total lymphoid irradiation [(S)TLI]. PATIENTS AND METHODS: From 1 October 1981 to 30 September 1988, 133 adult patients with HD CS IIIA (45), IIIB (33), IVA (seven) and IVB (48) were entered in the non-randomized multicentric prospective trial POF81/34. The number of involved nodal areas (NINA), and the number of visceral sites (NVIS) involved were registered in all patients; patients with bulky mediastinal tumor (BuMT) (mediastinal mass ratio > or = 0.45) were also identified. All patients received three monthly cycles of ABVD. Patients in complete remission (CR) or partial remission (PR) after completion of CT received a (S)TLI including the spleen (involved sites 40 Gy, non-involved 30 Gy); initially involved lung(s) and liver received 18 and 20 Gy, respectively; and patients not in CR or PR after CT or RT received salvage treatments. Univariate and multivariate analyses were performed to identify the factors contributing significantly to the prognosis; initial characteristics, as well as status after the three cycles of CT, were entered in the model. RESULTS: Of the 133 patients, 74 (55.6%) entered in CR after CT and 116 (87.2%) after completion of radiation therapy. Ten-year freedom from progression (FFP), freedom from tumor mortality (FFTM) and survival rates were 70.4%, 78.9% and 70.6%, respectively. According to univariate analysis the NVIS (< or = one vs. > or = two) was the only initial factor simultaneously influencing 10-year FFP (73.9% vs. 38.2%) FFTM (82.5 vs. 34.1%) and survival (73.5% vs. 17.3%) rates; on the other hand, the NINA (< or = four vs. > or = five) influenced FFP (81.4% vs. 60.7%) and FFTM rates (87.3% vs. 71.4%) while symptoms (A vs. B) influenced FFP (80.7% vs. 63.3%) and survival (82.8% vs, 61.2%) rates. Finally, age (< 40 vs. > or = 40) influenced survival rate only (79.2% vs. 50%). According to multivariate analysis, NVIS and NINA had an independent impact on FFP and FFTM, while survival was modified by the NVIS and age. The post-CT status (CR vs. no CR) had a major impact on FFP (85.3% vs. 64.9%) FFTM (92.1% vs. 63.3%) as well as on survival (78.6% vs. 54.7%) rates in both univariate and multivariate analyses. Complications of therapy were mainly due to RT: 11 patients acquired second malignancies, six developed lung fibrosis or severe pulmonary infections, three developed intestinal obstructions and six developed angina pectoris or carotid stenosis. CONCLUSIONS: Tumor burden (identified by the number of involved nodal areas and the number of visceral sites) and the response to initial CT were the two independent factors influencing the outcome of this group of 133 patients with HD, CSIII and IV treated by three cycles of ABVD followed by high-dose [(S)TLI].

Adult↗

Adaptation of the rectal wall to distension in children with constipation.

OBJECTIVE: To determine whether there is significant change in the tension-length relationship of the digestive smooth-muscle mechanical function in constipation in children and to examine a new method of analysis of the mechanical properties of the rectal wall. DESIGN: Case-control study. PARTICIPANTS: Thirty children with constipation and 30 control children who did not have constipation. INTERVENTION: Rapid distension of the rectal wall by inflation of a rectal balloon with air. MAIN OUTCOME MEASURES: The in vivo rectal pressure-volume P[t,V] curve was determined according to the quasilinear viscoelasticity law. The recorded pressure was defined as the product of 2 functions: the elastic response P0[V] and the reduced relaxation function G[t], a normalized function of time such that P[t,V] = P0[V] x G[t]. Analysis of variance with repeated measures and modelling (linear for P0[V] and exponential plus constant term for G[t] were used for data analysis. RESULTS: The quasilinear viscoelastic law can be applied to the in vivo determination of the mechanical properties of the rectal wall in controls and in children with constipation. The elastic response was similar in the 2 groups. The reduced relaxation function was significantly different between the 2 groups, with the absence of an asymptotic value in the group with constipation (p < 0.01). CONCLUSION: Distension of the rectal wall with the use of an air-inflated balloon, with this type of interpretation according to the viscoelastic law, is useful in the analysis of chronic constipation.

Adaptation, Physiological↗

TCR alpha beta gene usage for myelin basic protein recognition in healthy monozygous twins.

The pathogenic role of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) has been suggested by the encephalitogenicity of MBP-specific T cells in experimental allergic encephalomyelitis (EAE). In humans, extensive analysis of TCRs involved in MBP recognition has led to conflicting results, varying from an intra- and/or interindividual restriction to high diversity in TCRAV/TCRBV gene usage. We previously established MBP-specific T cell lines (TCLs) from healthy monozygous twins and characterized their fine epitope specificity. In this study, we report on the TCR alpha beta gene usage of 52 of these MBP TCLs that are specific for epitopes recognized by both co-twins within the same pair. High overall diversity in the TCR alpha and TCR beta genes used for recognition of this self-Ag, MBP, was observed. Variable genes belonging to 19 different TCRAV and 16 different TCRBV subfamilies are expressed by the 52 TCLs herein studied. In co-twins, TCLs utilized genes belonging to common TCRAV and/or TCRBV gene subfamilies in 7 of 13 instances of shared epitope recognition. Statistical analysis of intrapair concordance for TCR gene usage for the recognition of a given peptide did not show any significant deviation from values that would be anticipated in the absence of genetic background effect.

Amino Acid Sequence↗

Talking effect and white coat phenomenon in hypertensive patients.

Both white coat effect (the tendency of blood pressure to rise during a medical visit) and talking effect were analyzed in 42 patients with essential hypertension. Blood pressure was measured during the clinic visit and over the subsequent 24-hour ambulatory period, with the physician performing 49 +/- 4 measurements for each patient. Three silent periods and two talking periods (stress and relaxation) were randomly allocated in a crossover design and studied, using analysis of variance. During the initial 11-minute silent period, systolic/diastolic blood pressures increased by 6 mm Hg/5 mm Hg. During the subsequent talking periods, these variations were significantly greater: +22 mm Hg/+17 mm Hg. Measures of systolic/diastolic blood pressure were higher during stressful talking than during relaxed talking. The talking and its emotional contents seemed to explain 70% of the white coat phenomenon. To minimize the white coat phenomenon in the clinic, physicians, nurses, and clinicians are advised to measure blood pressure during an initial period of silence.

Communication↗

Mediastinal tumor size and response to chemotherapy are the only prognostic factors in supradiaphragmatic Hodgkin's disease treated by ABVD plus radiotherapy: ten-year results of the Paris-Ouest-France 81/12 trial, including 262 patients.

PURPOSE: To identify prognostic factors in 262 patients with supradiaphragmatic Hodgkin's disease (HD), clinical stages (CS) I and II, prospectively treated between 1981 and 1988 according to the Paris-Ouest-France (POF) 81/12 protocol by three 1-month cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus methylprednisone (ABVD-MP) followed by subtotal nodal irradiation (RT). PATIENTS AND METHODS: The size of mediastinal tumor (MT) was measured in all patients: 66 did not have MT (NoMT); 105 had a small-size MT (SSMT), ie, mediastinal mass ratio (MMR) less than 0.33; 58 had a medium-size MT (MSMT), ie, MMR > or = 0.33 and less than 0.45; and 33 had a bulky MT (BuMT), ie, MMR > or = 0.45. All patients received three cycles (CS IA, one cycle only) of ABVD-MP; patients in partial remission (PR) or complete remission (CR) after chemotherapy (CT) received supradiaphragmatic RT (involved fields, 40 Gy; adjacent fields, 30 Gy) plus lumboaortic and splenic RT (30 Gy); patients not in CR or PR after CT received salvage CT. RESULTS: Two hundred seventeen patients (82.8%) entered CR after CT and 258 (98.5%) after RT. Ten-year freedom-from-progression (FFP) and survival rateswere 88.6% and 89.4%, respectively. According to univariate analysis, MT size and post-CT status were the only factors to influence both FFP and survival. For patients with NoMT or SSMT, those with MSMT, and those with BuMT, FFP rates were 94.1%, 87.0%, and 63.0% (P < .001), respectively, while corresponding survival rates were 92.6%, 87.2%, and 78.2% (P < .05). FFP rates were significantly different between the patients who achieved CR and those who did not achieve CR after CT: 94.6% versus 65.3% (P < .001); corresponding survival rates were 89.9% and 73.7% (P < .01). Multivariate analysis confirmed that MT size and post-CT status were the only two prognostic factors for FFP; for survival, the same two characteristics, as well as age (< 40 v > or = 40 years), significantly affected prognosis. We were thus able to identify three groups. The 33 patients (12.6%) with a BuMT had 10-year FFP and survival rates of 63.0% and 78.2%, respectively. Of 229 patients without BuMT, the 195 who attained CR after CT had an optimal prognosis (FFP, 96.6%; survival, 93.6%), while those who failed to achieve CR after CT had an intermediate prognosis (FFP, 68.8%; survival, 77.6%). CONCLUSION: These results demonstrate the independent impact on HD prognosis of tumor burden and post-CT status.

Adolescent↗

Infradiaphragmatic Hodgkin's disease: long term results of combined modality therapy.

Hodgkin's disease (HD) confined below the diaphragm accounts for less than 5% of all patients with HD. Although the major characteristics of this presentation appear established, optimal modalities of treatment still remain difficult to define. From April 1972 to October 1988, 28 patients with newly diagnosed infra-diaphragmatic HD, clinical stages I or II have been treated with 3 successive prospective protocols combining initial chemotherapy and radiotherapy (40 gy). This series of patients accounted for 4,3% of patients with HD limited to clinical stages (CS) I and II. Overall survival and freedom from relapse at 15 years were 74,4% and 73% respectively, without significant differences between clinical stages I and II, presence or absence of B symptoms or histologic subtype. There is only a trend (p < 0,10) in favour of patients younger than 40 years. In all 7 clinically staged IA patients no relapses were seen and combined treatment does not appear to be better than inverted Y irradiation alone. On the other hand initial chemotherapy seems necessary in patients with CS II A and B since 15 of our 21 patients are alive in first CR whereas the crude rate of transdiaphragmatic nodal relapses may reach up to 53% following radiotherapy alone.

Adolescent↗

[Internet, a new resource for anatomopathology?].

The Internet network is the largest computer network in the world. It can be accessed by a telephone line and a modem. Its different functions are the electronic mail (e-mail), the discussion forums ("newsgroups"), the transfer of files and the navigation between "hypertext" pages ("World Wide Web"). This network offers multiple services for pathology: access to databases, consultation of image banks or electronic journals, teleteaching, informations about congresses and societies, participation to thematic forums. We have connected to this network on October 1995 a french-english web site called "Anapath Web" (http://www.anapath.necker.fr) devoted to pathology. Its purpose is to collect information useful to pathologists and to develop specific applications. We are conceiving several projects for teleteaching.

Computer Communication Networks↗

Long-term follow-up of HIV positive asymptomatic patients having received cyclosporin A.

The data of the 27 asymptomatic HIV-1 seropositive patients with CD4+ cell count between 300 and 600/microliters treated by Cyclosporin A (CSA) (7.5 mg/kg/day) in our institution between October 1985 and 1987 were reviewed in October 1993. Hemoglobin concentration, platelet count, total lymphocytes, CD4+ and CD8+ cell counts and serum core protein p24 antigenemia, as well as creatininemia measured before CSA onset, at CSA cessation and twice a year were recorded as well as clinical signs and CSA toxicities. In October 1993 median duration of CSA treatment was 11 months, median follow-up after CSA cessation was 45 months and median total follow-up was 67 months. Toxicities of CSA were those commonly encountered in other pathologies. Under CSA no patient progressed toward clinical AIDS (1987 definition). The mean CD4+ cell count of the 27 patients remained unchanged (gain of 1 cell/year) under CSA treatment, while it decreased at a rate of 50 cells/year after CSA cessation (p < 0,005). On the other hand CSA treatment had no significant impact on the evolution of total lymphocyte count, CD8+ cell counts, and P24 antigenémia.

Adult↗

Survival modelling in kidney transplantation: hazard rates of graft loss. Transplant Working Group of the Registry Committee of the European Dialysis and Transplantation Association-European Renal Association (EDTA-ERA).

Mathematical modelling of survival data provides long-term projection of graft survival and allows evaluation of the impact of several variables on graft outcome. We analysed 52,315 first cadaveric grafts performed between 1971 and 1985 and reported to the EDTA Registry. We quantified the risk of graft loss using the hazard rates. The hazard function provides the magnitude of the risk of graft loss at a given time post-transplantation. For the 1971 and the 1985 cohorts, the risk of graft loss at 1 month posttransplantation was 143 and 53 per 1000 patient-months, respectively. At 1 year it was 5 and 2.4 per 1,000, respectively. The hazard function thus allowed quantification of the magnitude of the risk of graft loss and its evolution along with time. At 5 years posttransplantation, the risk of graft loss was close to 1 per 1,000, whatever the cohort considered, quantifying the lack of improvement of graft losses in the long term since the early 1970s. It was also possible to evaluate the composition of the risk and to explore the respective influence of graft failure and of patient death.

Aged↗

Radioiodine therapy of the autonomous thyroid nodule in patients with or without visible extranodular activity.

UNLABELLED: Patients with an autonomously functioning thyroid nodule (ATN) may be present with various clinical, biochemical and scintigraphic features. To optimize 131I dose planning and treatment timing in these patients, relationships between dosimetric data and clinical follow-up events must be established. METHODS: We retrospectively reviewed the records of 88 patients who received 131I (intended dose of 80 Gy) for an ATN, of whom 39 had evidence of extranodular activity (ENA) and 76 presented with overt thyrotoxicosis. In all of the patients, dosage calculation was monitored to estimate precisely both beta and gamma absorbed doses received by the ATN and the nodule-free lobe. The mean duration of follow-up was 75 mo (max 180) and always included biochemical thyroid tests. Finally, we compared the dosimetric profiles of four dosage schemes which had been normalized by simulation to ensure that the same absorbed dose threshold value was always delivered to the ATN. RESULTS: About 75% of the patients were cured at 6 mo for a mean 305 MBq administered. The absorbed doses delivered to the nodule-free lobe ranged from 12% (no ENA) to 86% (ENA) of the values delivered to the ATN, mainly in the form of beta irradiation. Life-table estimates for hypothyroidism and death were 9.6% and 22% at 75 mo, respectively. Hypothyroidism mainly developed in patients with nonsuppressed TSH levels but regardless of ENA, which often accounted for multifocal disease. CONCLUSION: We suggest that fixed doses bordering on 370 MBq are advizable in younger individuals and in patients with mild thyrotoxocosis, while 555 MBq-740 MBq can be administered in other patients and that ENA indicates multifocal autonomy in patients with toxic ATN and is a further indication for radioiodine treatment which should be begun as soon as possible to avoid the development of cardiac complications.

Aged↗