Biomedical subjects
C Chatelain
Publications and source records attributed to C Chatelain.
[Combined renal and pancreas transplantation as treatment for chronic renal insufficiency of diabetic origin: a series of 50 consecutive transplantations].
STUDY AIM: The aim of this study was to report the results of 50 transplantations of kidney and pancreas performed in the same surgical centre for chronic renal insufficiency of patients with insulino-dependent diabetes. PATIENTS AND METHOD: From 1989 to 1999, 50 pancreatic transplantations were consecutively performed, 48 combined with a kidney transplantation and two in patients having a functioning kidney graft. The whole pancreas was transplanted in the right iliac fossa through an extraperitoneal approach with duodeno-vesical bypass of exocrine secretion. The kidney was transplanted in the left iliac fossa through a different extraperitoneal approach. Immunosuppression protocol included Azathioprine replaced by Mycophenolate Mofetil since 1996, associated with corticotherapy and Ciclosporine replaced by FK 506 since 1997. Recipients were 32 women and 18 men (mean age: 37 +/- 5 years) treated by insulinotherapy since 23 +/- 6 years and receiving 35 +/- 10 insulin units per day. Peptide C was 0.33 +/- 0.35 mg/mL and serum creatinin 726 +/- 260 mumol/L. RESULTS: One patient died on d10 from pulmonary artery thrombosis due to unknown drepanocytosis. The most frequent postoperative complications were leakage of duodeno-vesical anastomosis (n = 9) decreasing in frequency with experience, reoperated with preservation of the pancreatic graft in all cases and venous thrombosis of the pancreatic graft (n = 5) with a definitive loss of function. Secondary deaths occurred at 24, 36, 48, 50, 72 months with functioning grafts in two patients. With a mean 5-year follow-up, 44 patients were alive (88% of the whole series), 34 of them with two functional grafts (68% of the whole series) Sixteen pancreas grafts were lost: three by death of the patients, eight from surgical complications, four by rejection and one by transplantectomy of a functional graft. CONCLUSION: Combined kidney and pancreas transplantation is now very efficient in the treatment of diabetic renal insufficiency. Total pancreas transplantation through an extraperitoneal approach seems to be the safest method. A very strict selection of both donors and recipients is necessary.
[New therapeutic trends in benign hypertrophy of the prostate].
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Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension.
OBJECTIVES: To compare the efficacy and safety of Pygeum africanum extract, 50 mg twice daily and 100 mg once daily. METHODS: Patients with symptomatic benign prostatic hyperplasia (BPH) entered a 2-month randomized, parallel-group, double-blind, comparative phase (group A, 50 mg twice daily; group B, 100 mg once daily), followed by a 10-month, open phase (100 mg once daily). Main efficacy assessment parameters included International Prostate Symptom Score (IPSS), quality of life (QOL), and maximum urinary flow rate (Qmax). RESULTS: Two hundred nine patients completed the comparative phase in compliance with the protocol; 174 were included in the open phase. Both treatments had similar efficacy. IPSS (baseline 17 in both groups) improved by 38% in group A and 35% in group B. QOL improved by 28% in both groups. Qmax increased by 1.63 mL/s (16%) in group A and 2.02 mL/s (19%) in group B. After 12 months, the IPSS fell from 16 (baseline) to 9 (-46%). Half of the patients had an IPSS below 8. Mean Qmax increased by 1.65 mUs (15%). The safety profile was similar between groups and study phases. CONCLUSIONS: P. africanum extract at 50 mg twice daily and 100 mg once daily proved equally effective and safe at 2 months. Further improvements in efficacy with a satisfactory safety profile were documented after 12 months.
[Use of mycophenolate mofetil (MMF) in kidney transplantation: results of a single center trial].
Mycophenolate Mofetil (MMF) is a new immunosuppressant demonstrated to be effective at the dose of 2 to 3 g/day. The objective of this study was to determine whether MMF could be used at a lower dose with the same efficacy. Two patient groups were studied: 334 patients treated with azathioprine (AZA) and 60 patients treated MMF (at the dose of 750 mg/day, for patients receiving triple combination therapy or 1.5 g/day for those receiving two-agent combination therapy). The rest of the treatment was identical for the 2 groups. The main endpoint was the incidence of acute rejection at 3 months, which was 16% in the MMF group and 35% in the AZA group (p = 0.003). Multivariate analysis confirmed the impact of the type of purine synthesis inhibitor used (AZA or MMF, p = 0.007) on the acute rejection rate at 3 months. This study confirms the value of MMF, even at doses lower than those recommended in the international literature, with improved safety. MMF has now replaced azathioprine in our immunosuppressant protocols.
[How to plan the treatment of prostatic adenoma today?].
Surgical treatment, mainly transurethral resection of the prostate, still remains the reference treatment for benign prostatic hyperplasia (BPH). Two studies conducted in the Urology Department of the Pitié-Salpêtrière Hospital have tried to define certain characteristics of this surgery. The first study tried to evaluate the long-term outcome of patients operated for benign prostatic hyperplasia. Analysis of 881 replies to a questionnaire sent to 3,147 patients operated for BPH (between 1976 and 1989) assessed functional status (by Madsen's symptom score), quality of life (by Fowler's method), and sex life (by two specific questions), with a follow-up ranging from 5 to 14 years. At this follow-up, 90% of patients declared to be satisfied with their voiding status, 95% considered their quality of life to be excellent and about 50% had maintained a sex life. The second study was designed to evaluate the morbidity of this treatment in elderly patients. A group of 33 operated patients over the age of 80 was compared to a control group composed of 66 patients between the ages of 60 and 70 years, treated in a similar way, in the same centre and in the same year. Morbidity was higher in the first group, but age itself did not appear to constitute a poor prognostic factor for surgery; it only intervenes by allowing certain complications of benign prostatic hyperplasia (acute retention) to create emergency situations complicating the perioperative period. Following demonstration of the short-term and long-term efficacy of this conventional surgery, many new technologies were subsequently developed in order to reduce perioperative discomfort, anaesthetic requirements, duration of catheterization and hospital stay. Some of them constitute a new approach to endoscopic surgery, such as prostatic tissue vaporization techniques (electrovaporization, laser contact vaporization), which have a comparable efficacy to that of TURP, while reducing bleeding, catheterization time and hospital stay. However, the duration of postoperative irritative symptoms is much longer. Other techniques use a thermal effect to obtain coagulation necrosis of prostatic tissue, using various energy sources: microwaves (thermotherapy), laser (interstitial laser), radiofrequency waves (TUNA). These techniques are perfectly adapted to outpatient surgery with local or regional anaesthesia. They do not interfere with continence, sexual function, but may be followed by high dysuria or retention rates, with a variable cathererization time, sometimes several weeks. Finally, urethroprostatic stents are easy to insert, provide a solution in critical situations and have replaced old indwelling catheters. The current choice of treatment therefore comprises several approaches: more effective, but still purely symptomatic medical treatment, safe conventional surgery providing excellent long-term results, but generating a certain perioperative discomfort and a certain morbidity, or, on the contrary "minimally invasive" techniques, greatly simplifying the therapeutic procedure, but whose morbidity has not yet been determined and whose results are still uncertain.
A multivariate analysis of the survival of patients with aggressive lymphoma: variations in the predictive value of prognostic factors during the course of the disease. Groupe d'Etudes des Lymphomes de l'Adulte.
BACKGROUND: Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The International Prognostic Index (IPI) was recently developed to predict patient survival on the basis of pretreatment clinical features. However, classical multivariate regression models such as the IPI fail to detect time-dependent changes in the predictive value of covariates. In this study, an extension of the Cox proportional hazards model was used to determine whether the value of prognostic factors might decay over time. METHODS: A total of 1271 patients younger than 60 years, entered on the LNH-84 and LNH-87 studies of an ACVBP induction regimen (consisting of doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and IT methotrexate), were analyzed in terms of overall survival and monthly risk of dying. By a standard method, prognostic factors were identified in a training sample and confirmed in a validation sample. The independently significant covariates were then included in a step-function regression model (3-step) that permitted determination of their value in predicting the short term and long term survival of the entire population. RESULTS: During the entire follow-up period (median, 5.5 years), lactate dehydrogenase level, tumor stage, performance status, and number of extranodal sites remained independently predictive of overall survival. However, these covariates had nonproportional hazard functions. The study of their time-dependent effect with the 3-step model confirmed that they were predictive of overall survival during the short term follow-up period of 3 months to 2 years. However, during the induction period of 0-3 months and the long term follow-up period of 2-10 years, there was only 1 independently predictive factor for each of these periods: performance status and tumor stage, respectively. CONCLUSIONS: The IPI factors are relevant to short term follow-up and permit the selection of routine or experimental therapeutic regimens. In contrast, only performance status is predictive of a patient's ability to tolerate induction chemotherapy, and only tumor stage is predictive of long term survival.
Augmentation of the number of nucleolar organizer regions in human megakaryocyte cell lines after induction of polyploidization by a microtubule inhibitor.
BACKGROUND: Megakaryocyte polyploidization is an advantageous and regulated mechanism that leads to an increase in platelet production. In megakaryocytic cell lines, polyploidization can be obtained by using colchicine, an inhibitor of the tubulin spindle. The nucleolar organizer regions (AgNORs) are parts of nucleolar DNA transcribed into ribosomal RNA and are detected by the silver-staining technique. Their number is proportional to protein synthesis. RESULTS: To estimate protein synthesis in polyploid megakaryocytes, AgNORs are measured in three cell lines with megakaryocyte properties (DAMI, HEL and K562) after a 4-day culture in the presence or absence of colchicine. The mean number of AgNORs per cell was 16+/-4 (mean+/-SEM), 24+/-3 and 14+/-3 for DAMI, HEL and K-562 cell lines respectively. The addition of colchicine (10 ng mL[-1]) significantly increased the number of AgNORs per cell (DAMI 556%, HEL 338% and K-562 300% of controls, P < 0.05 using the t-test). Moreover, the number of nucleoles per cell after the addition of colchicine was augmented significantly (DAMI 246%; HEL 237% and K-562 148% of controls, P < 0.05 using the t-test). The total protein content estimated by Bradford's method increased significantly to 226%, 215% and 304% of controls in DAMI, HEL and K562 respectively (P < 005 using the t-test). After treatment with colchicine, the endomitotic index (EI) [mean of (log2 DNA content expressed in N)-1] measured by flow cytometry (and reflecting ploidy) increased to 234%, 255% and 301%, respectively, in DAMI, HEL and K-562 cell lines (P < 0.05 using the t-test). Concomitantly, the number of AgNORs per unit of DNA increased in the DAMI and HEL cell lines (P < 0.05 using the t-test) from 48+/-8 and 39+/-5, respectively, to 79+/-11 and 61+/-10. In contrast, the number of nucleoles and the total protein content per endomitotic index were not affected by colchicine (P > 0.05 using the t-test), but the number of nucleoles per endomitotic index of DAMI cells was affected. CONCLUSION: The increase in the number of the NORs induced by an agent known to stimulate polyploidization of megakaryocytic cell lines suggests that polyploidization occurs by a proportional increase in protein synthesis per DNA unit.
Induction and enhancement of normal human megakaryocyte polyploidization are concomitant with perturbation in the actin metabolism.
BACKGROUND: Megakaryocyte polyploidization results from the lack of cytoplasmic separation while the nucleus keeps dividing. METHODS: To investigate the role of actin in the megakaryocyte polyploidization, three human cell lines with megakaryocytic properties (DAMI, HEL and K562) were incubated in the presence of cytochalasin B, an inhibitor of actin polymerization. These data were then compared with normal megakaryocytes. RESULTS: Compared with control conditions, cells cultured in the presence of cytochalasin B revealed an augmentation of cell size and ploidy and an arrest of cell proliferation. The expression of platelet membrane glycoproteins Ib, IIb/IIIa, IIIa and thrombospondin and transferrin receptors was augmented after treatment with cytochalasin B. Physiologically, the role of actin in inducing polyploidization could be related to an imbalance between G- and F-actins. To test this hypothesis, we measured G-, F- and total actin in cytochalasin B-treated cells. Actin was found to be increased significantly in cytochalasin B-treated DAMI and HEL cell lines. In contrast, the G/F-actin ratio was not affected by cytochalasin B. To confirm these actin changes in physiological megakaryocytopoiesis, G- and F-actin contents were then estimated in normal megakaryocytes. The G- and F-actin contents of megakaryocytes from eight normal patients exponentially decreased from 2 to 128n, whereas the total actin content per cell kept increasing. The G/F ratio was unaffected. CONCLUSION: Polyploidization of human megakaryocytes results from either a diminution of actin synthesis or an increased actin turnover, which in turn possibly abrogates the formation of the actin cleavage furrow in telophasis.
Androgen deprivation for prostatic carcinoma: a rationale for choosing components.
Ever since prostatic carcinoma was discovered to be dependent on the hormone androgen for its proliferation, androgen deprivation has been the treatment of choice for advanced cases of prostate cancer. Originally, treatment was limited to surgical castration or estrogen therapy. However, the introduction of luteinizing hormone-releasing hormone analogues, antiandrogens, and newer treatment modalities, such as combined androgen blockade, has made choosing a treatment strategy more complex. Assuming that each modality is equally effective, emphasis should be placed on increasing patient tolerance and compliance by the use of long-acting, nontoxic treatments with simple dosing regimens and minimal side effects. This review focuses on the factors influencing the final choice of treatment strategy.
Analysis of megakaryocytes by flow cytometry.
A flow cytofluorometric measurement of megakaryocyte ploidy has been adapted from Tomer's method. Briefly, bone marrow is aspirated through a medium containing theophyllin, prostaglandin-E1 and other antiaggregant agents. Megakaryocytes-enriched buffy coats are recovered. Megakaryocytes are then stained for GP IIIa coupled with FITC and for DNA (propidium iodide). A Becton Dickinson FACScan flow cytometer is used for measuring the ploidy distribution of GP IIIa positive cells. The method we developed presents several advantages. Firstly, the time required is greatly decreased in comparison with other studies. Secondly, the washing steps are limited in number allowing a diminution of the cell loss. Thirdly, the method ensures a better megakaryocyte preservation. Finally, selection of megakaryocytes by ploidy and expression of GP IIIa can be made easily because of the simultaneity of the two stainings as well as by the use of a precise gating on the flow cytometer. Based on these results, we conclude that the present method provides a better means for the isolation and analysis of human normal megakaryocytes. This technique has been applied to the analysis of megakaryocyte populations from patients with abnormal platelet counts. In chronic myeloid leukemia patients, analysis of ploidy distribution shows a shift toward the low ploidy while in patients with immune thrombocytopenic purpura, polycythemia vera and essential thrombocythemia the ploidy distributions are shifted toward the high ploidy.
[Endoscopic surveillance of superficial papillary tumors of the bladder].
All cases of superficial bladder tumor treated in 1991 at the urology department of La Pitié hospital were reviewed to study the course of superficial bladder tumors with regard to the risk of muscle infiltration and the value of endoscopic follow-up. In 1991, 73 patients (63 men and 10 women) with a mean age of 64 years had TUR for superficial bladder tumor. Patients had repeated cystoscopy at 3 and 6 months and then on a yearly basis for 5 years. Fourty-eight patients had TIS tumors, and 19 patients had T1 tumors. Five patients were lost to follow-up. Sixty-eight patients were followed for 5 years. Of 48 patients with stage TIS tumors, 39 (81.5%) did not show any deterioration at histological examination, eight patients (16.5%) had infiltration of the lamina propria by tumor (pT1) and the tumor invaded muscle in one patient (2%). Of the 19 patients with stage T1 tumors at the first TUR eight (47%) had no pathologic deterioration, but nine (53%) developed muscle invasion (pT2). Two patients were lost to follow-up. Invasion of the lamina propria present at diagnosis or during the subsequent course is considered to be an indicator of high risk of progression to muscle invasive disease (over 50% of cases). The prognostic accuracy of both the grade and stage needs to be enhanced using molecular markers.
[Survival of patients with infiltrating tumors of the bladder treated with cystectomy].
We reviewed the results of infiltrating bladder cancer treated by radical cystectomy to evaluate survival. Between January 1989 and December 1992, a total of 58 consecutive cystectomies or anterior pelvectomies performed on 48 men and 10 women (mean age 63.2 years) in our department were retrospectively evaluated. Four patients were lost to follow-up and the mean follow-up was 72 months. Pathologic staging was as follows: stage pT0,A,1: 13.5%, stage pT2: 17.5%, stage pT3a: 12%, stage pT3b: 36%, stage pT4: 21%. The year probability of the overall survival was 60% for p T2-p T3a patients, 15% for pT3b patients, and 9% for pT4 patients, respectively. Overall, 53.5% of patients died of cancer, 7.5% of intercurrent disease, and 39% were alive. The cancer related death rate was 12% for pT2-pT3a patients, and 82% for pT3b-pT4 patients. The 5- year probability of specific survival was 80% for pT2-pT3a patients, 15% for pT3b patients, and 9% for pT4 patients, respectively. Infiltrating bladder cancer still has a high mortality rate. Radical cystectomy may be considered to be a curative procedure for stages pT2 and pT3a. Adjuvant chemotherapy and/or radiotherapy seem necessary at stages pT3b and pT4. Preoperative criteria need to be better defined to reduce understaging.
[S3 sacral neuromodulation in patients with chronic refractory miction disorders].
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Kidney transplantation in highly sensitized patients.
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A prospective study on efficacy and tolerance of antithymocyte globulin Fresenius versus thymoglobuline Merieux after renal transplantation.
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Results of kidney transplantation in nonresident patients: a retrospective study.
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Results of renal transplantation in patients with Schistosoma infection.
PURPOSE: We evaluated the results of renal transplantation in patients infected with Schistosoma haematobium, as well as the risks of urological complications and post-transplant reinfection. MATERIALS AND METHODS: The outcome of 20 kidney transplants was retrospectively studied. Based on our experience and review of the literature, our clinical practice to prevent urological complications consisted of antischistosomal chemotherapy given at the pre-transplant evaluation, with endovesical ureteroneocystostomy preferred in case of bladder calcifications. A Foley catheter was maintained for 10 days. A transurethral bladder neck incision was performed before removal of the Foley catheter when bladder neck sclerosis was present. RESULTS: The 1 and 2-year patient survival rate was 93%, and 1 and 2-year graft survival rates were 88 and 81%, respectively, which were not different from those of a cohort of 167 patients without schistosomal infection. Surgical complications included 2 postoperative hemorrhages, 2 urinary leaks and 1 nonschistosomal related ureteral stricture. Post-transplant schistosomal infection never occurred when antischistosomal chemotherapy was given at the pre-transplant evaluation. CONCLUSIONS: Patients with schistosomal infection are suitable recipients for kidney transplantation, although they are at risk for urological complications. Unlike other infectious diseases, such as tuberculosis, the risk of recurrence due to reactivation of chronically hosted pathogens seems to be low or absent in patients who received antischistosomal chemotherapy at the pre-transplant evaluation. Long-term urological followup is recommended, including urethrocystoscopy, because of the theoretically increased risk for bladder malignancy.