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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

At least 127 records · Page 7Linked to original sources

Risk of extramedullary relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia with leukemia cutis.

Leukemia cutis (LC) is a rare feature of acute myeloblastic leukemia (AML). Little information is available regarding its prognostic influence on post-transplant outcome. In our institution, 202 patients with AML received an allogeneic HLA-identical marrow transplant from related donors between March 1982 and January 1994. Thirteen patients had prior leukemic involvement of the skin (leukemia cutis or LC group) while 189 patients did not (non-LC group). There was a higher incidence of patients with the M4-M5 FAB subtypes in the LC group (83%) as compared to the non-LC group (33%). In addition, the percentage of patients transplanted in relapse was also higher in the LC group (69 vs 15%). While there were no differences observed in the rates of relapse post-transplant in the LC and non-LC groups when matched for stage of disease at transplant, the sites of relapse differed markedly. Five of six relapses in the LC group involved extramedullary sites as compared to only six of 38 relapses in the non-LC group (P = 0.002), with a 6-year probability of extramedullary relapse of 38.5% in the LC group as compared to 3.9% in the non-LC group. This increased probability of extramedullary relapse was independent of the FAB morphology (50 vs 2% for patients with the M4-M5 subtypes in the LC and the non-LC group respectively) and of disease status at the time of transplant. Moreover, only three relapses post-transplant involved the skin, all of which were in the LC group, with a probability of skin relapse of 23.1% in this group. Patients with AML and leukemia cutis have a remarkable propensity to relapse in extramedullary sites following marrow transplantation. These relapses occur in the skin as well as other organs. Further investigations are needed to understand the biological basis of this clinical feature.

Adult↗

Prevalence of hepatitis G virus RNA in a monocentric population of French haemophiliacs.

Hepatitis G virus (HGV) and hepatitis GB virus (GBV-C) have been reported as possible causes of non-A-E transfusional hepatitis. To assess the prevalence of hepatitis G virus infection in haemophiliacs we retrospectively investigated the presence of viral RNA in 92 patients with and without HCV infection. HGV/GBV-C RNA was reverse transcribed and amplified with primers from the 5' non-coding region of the genome. RNA was detected in 16/92 patients (17.4%). Restriction enzyme analysis revealed that the 16 patients belonged to the HGV-like genotype. Serology with E2-specific antibodies demonstrated that HGV viraemia underestimates previous infection by HGV. 33 patients were positive for HGV; all but two have cleared HGV RNA. 47/92 patients had a marker of prior infection by HGV. No difference between HGV RNA positive and negative patients was observed concerning age, diagnosis, HIV and HCV status. Previous HBV infection correlated with the frequency of HGV infection. There was no difference in alanine aminotransferase levels between HGV positive and negative patients. All 18 patients exposed to only virally inactivated plasma-derived concentrates were negative for both HGV RNA and anti E2 antibodies. Prior exposure to untreated concentrates correlated with HGV viraemia (P=0.03), HGV seropositivity (P=0.0002), and markers of HGV infection (P<0.0001). In haemophiliacs with a past exposure to non-inactivated concentrates, persistence of HCV RNA (53/74 patients) was more frequent than HGV RNA persistence (16/74 patients) although HGV viraemia is more frequent than HCV viraemia in blood donors. This may be related to a greater ability of individuals to clear HGV infection and suggests that hepatitis G virus infection in multi-transfused patients has a better outcome than infection with other blood-borne viruses.

Adolescent↗

Adult granulosa-cell tumor of the ovary: a retrospective study of 45 cases.

This study describes 45 cases of adult granulosa-cell tumors seen in our institution between 1976 and 1993. The median age was 46.5 years (12-77) and 18 women were postmenopausal. Vaginal bleeding was present in one-third of cases; other complaints were abdominal pain (28%) and the presence of a pelvic mass (47%). The tumor size was variable (<3 cm to 30 cm, median 11.5 cm). FIGO stages were: stage I: 30 (73%) (19 Ia, seven Ic, four I unknown); stage II: seven (17%) (two IIa, five IIC); stage III: three (7%) (one IIIb, two IIIc). Two adenocarcinomas and 13 cases of hyperplasia were found in 25 endometrial samples available. The initial therapy for all the cases was surgery, consisting in 34 patients of hysterectomy, bilateral salpingo-oophorectomy, +/- tumor resection. Sixteen patients received adjuvant therapy as well: chemotherapy (CT) alone for 12, radiotherapy (RT) alone for two, and CT + RT for two patients. Among the 39 patients who achieved a complete response after initial therapy, 15 patients have relapsed (pelvic recurrences) (38.5%) including six stage Ia (three received only conservative surgery). All the recurrent tumors were resected and 14/15 had CT (13/14 with cisplatin). The overall survival rate was 77.2% at 5 years, 66.5% at 10 years, and 41.2% at 20 years. A statistically significant difference was found between the survival of patients with stage Ia disease (75% at 10 and 15 years) and that of other patients (60% at 10 years, and <50% at 15 years). Serum estradiol and serum inhibin were measured in some patients and the results are described.

Journal Article↗

Automatic washer disinfector for flexible endoscopes: a new evaluation process.

BACKGROUND AND STUDY AIMS: Many automatic washer disinfectors for flexible endoscopes have been marketed and offered as an alternative method of preventing infections, but they are frequently unsatisfactory. There is therefore clearly a need to test prototypes prior to marketing, following an evaluation process that is sufficiently reliable and rigorous to guarantee the efficacy of the decontamination processes. MATERIALS AND METHODS: The present study describes an experimental method based on the follow-up of the decontamination of a Tygon tube, the internal surface of which was contaminated by a bacterial biofilm. This method is proposed as a preliminary test for evaluating washer disinfectors. RESULTS: An analysis of the results obtained after technical modifications of the first prototype of the Fibro-Cleaner showed that complementary activities of each successive cycle phase allow a reduction in the number of adherent bacteria of more than 8 log per cm2 of support. With the three different biofilms tested (Escherichia coli, Pseudomonas aeruginosa mucoid and Staphylococcus aureus), no microorganisms were recovered from the support at the end of the decontamination process. CONCLUSIONS: The experimental protocol suggested here seems to be well suited for assessing washer disinfectors during the development phase of the prototype, as well as for comparative studies.

Biofilms↗

Use of amplification and sequencing of the 16S rRNA gene to diagnose Mycoplasma pneumoniae osteomyelitis in a patient with hypogammaglobulinemia.

A splenectomized patient with hypogammaglobulinemia who was hospitalized because of a high-grade fever subsequently developed osteomyelitis. Although pus cultures were repeatedly sterile, polymerase chain reaction (PCR) analysis with use of 16S rRNA gene primers with a broad specificity detected bacterial DNA in pus samples. Subsequent nucleotide base determination of the amplified DNA demonstrated that the detected DNA was derived from Mycoplasma pneumoniae. The results were confirmed by a PCR assay with use of M. pneumoniae-specific primers. Our findings confirm the usefulness of 16S rRNA gene amplification and analysis in the rapid and specific diagnosis of infectious osteomyelitis and reaffirm the role of such methods in detecting fastidious or uncultivable pathogens.

Adult↗

Analysis of UVB-modulated gene expression in human keratinocytes by mRNA differential display polymerase chain reaction.

Ultraviolet (UV) light is the most important environmental insult to skin. Even a single exposure to UVB radiation can result in inflammation and may also lead to DNA damage and apoptosis in the acute response of the cutaneous tissue. To elucidate the complex alterations of gene expression in human keratinocytes underlying these UV responses we took advantage of differential display polymerase chain reaction (DD-PCR) technology's ability to detect qualitative and quantitative changes in gene expression in more than two cell populations simultaneously. We demonstrate that low-dose UVB (100 Jm-2) leads to both induction and downregulation of different genes during the 24 h after irradiation in a time-dependent manner. In addition to the identification of known genes as possible effectors or targets in the UV response of human keratinocytes, we here identify a new sequence that is negatively regulated by UVB irradiation and was termed HUR 7 (HaCaT UV repressed). In general our results showed that DD-PCR is a useful tool in the analysis of quantitative changes of mRNA levels in human keratinocytes after UV irradiation. The identification of new UVB-repressed genes offers the opportunity to identify unrecognized molecular mechanisms in the UV response of human cells.

Blotting, Northern↗

In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

Animals↗

Influence of trophic conditions on exopolysaccharide production: bacterial biofilm susceptibility to chlorine and monochloramine.

This study examines the controversial efficacy of chlorine and monochloramine against biofilms that differ in their extracellular polysaccharide (EPS) content. The results point out a net variability of bacterial biofilm susceptibility according to the nutrients present. Chlorine and monochloramine showed an equal biocidal activity on lactose medium-grown E. coli ATCC 10536 and glycerol-ammonium nitrate medium-grown nonmucoid Pseudomonas aeruginosa biofilms. In contrast, the effect of monochloramine is greater compared with that of chlorine on E. coli and mucoid P. aeruginosa biofilms grown in sucrose and glycerol-ammonium nitrate media, respectively. In these culture conditions, treatment with 25 mg monochloramine/L for 2 h reduced culturable cells by 4.5 logs (99.997%) for E. coli and about 3 logs (99.87%) for mucoid P. aeruginosa while the similar treatment with chlorine reduced culturable cells in these biofilms by 2.2 logs (99.4%) and 1 log (10%), respectively. The decrease of chlorine disinfection efficacy on sucrose and glycerol-ammonium nitrate medium-grown biofilms is postulated to be linked to the higher polysaccharide production observed in these media. It seems likely that monochloramine produces a high leakage of material absorbing at 260 nm from sucrose medium-grown E. coli biofilm, which could indicate its better penetration into biofilms.

Biofilms↗

Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children's Leukemia Cooperative Group.

PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS: This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS: All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.

Antimetabolites, Antineoplastic↗

Late effects of allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: the impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

PURPOSE: To evaluate growth, thyroid function, puberty, cardiac function, and the incidence of cataracts in children who received allogeneic bone marrow transplantation (BMT) for acute myeloblastic leukemia (AML) in first complete remission (CR) after a preparation with or without total-body irradiation (TBI). PATIENTS AND METHODS: Among 45 children studied, 26 received busulfan-cyclophosphamide (Bu-Cy) in preparation for transplantation and 19 received TBI. TBI was fractionated in nine cases and delivered as a single dose in 10. Four children in the Bu-Cy group and none in the TBI group had received prior cranial radiation. The mean follow-up duration after BMT was 5.9 years for the whole group. RESULTS: The mean cumulative changes in height SD score (SDS) were -0.86 at 3 years and -1.56 at 5 years in the TBI group, whereas these changes were only -0.05 and -0.17 in the Bu-Cy group (P < .01 at 3 and 5 years). The 6-year probability of hypothyroidism was 9% +/- 8% in the Bu-Cy group and 43% +/- 15% after TBI (P < .02). Pubertal development after Bu-Cy was assessable in two girls and five boys: both girls had primary ovarian failure, whereas Leydig cell function appeared to be preserved in the five boys. One child who had received anthracycline when he was less than 1 year old developed cardiac dysfunction 4 years after Bu-Cy. The 6-year probability of cataracts was 70% +/- 13% in the TBI group and 0% after Bu-Cy. CONCLUSION: The use of Bu-Cy represents an alternative transplant cytoreductive regimen for children with AML in first CR, which can reduce the risk of posttransplant growth impairment, thyroid dysfunction, Leydig cell damage, and the incidence of cataracts.

Adolescent↗

Absence of LKM-1 antibody reactivity in autoimmune and hepatitis-C-related chronic liver disease in Sweden. Swedish Internal Medicine Liver club.

BACKGROUND: Type-2 autoimmune hepatitis is a subgroup of chronic hepatitis characterized by the presence of liver/kidney microsomal autoantibodies type 1 (LKM-1). A frequent association with chronic hepatitis C suggests that hepatitis virus might trigger autoimmune reactivity. LKM-1-positive chronic hepatitis is not uncommon in southern Europe but is rarely seen in the USA and the UK. The prevalence in Scandinavia is hitherto unknown. METHODS: We used an automated prototype LKM-1 immunometry-based assay (IMx) to detect LKM-1 antibodies in sera from 350 Swedish patients with chronic liver diseases (100 with primary biliary cirrhosis, 80 with primary sclerosing cholangitis, 100 with hepatitis C, and 70 patients with various forms of chronic hepatitis, including 36 autoimmune cases), and from 17 children with autoimmune hepatitis. Sera reactive in the IMx assay were subjected to immunofluorescence testing. RESULTS: No clearly LKM-reactive sera were detected. Serum samples from 29 patients were borderline reactive in the IMx assay but tested negative in the confirmatory immunofluorescence test. Positive tests in the former assay were likely caused by reactivity against microsomal antigens other than LKM-1/cytochrome P450IID6. CONCLUSIONS: LKM-1-positive type-2 autoimmune hepatitis is very rare in Sweden. Furthermore, chronic hepatitis C did not trigger this type of autoimmune reactivity in our patients, probably owing to genetic insusceptibility.

Adolescent↗

In vivo infusion of anti-LFA-1 and anti-CD2 antibodies prevents graft failure after HLA partially incompatible bone marrow transplantation in children with high risk acute lymphoblastic leukaemia.

Bone marrow transplantation (BMT) from matched sibling donors is the therapy of choice for children with high-risk acute lymphoblastic leukaemia in children. It is however not available to more than two-thirds of patients who lack a matched donor. Here, we review the outcome of 28 patients with high-risk ALL who were transplanted in France with alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives. For these patients, we tested the possibility to prevent T-depleted marrow graft rejection by infusing in vivo two monoclonal antibodies directed against adhesion receptors i.e., LFA-1 and CD2. Two previous multicenter trials in children transplanted with partially incompatible bone marrow for inborn errors of metabolism showed their efficacy in this setting. Twenty eight patients were enrolled in this study and followed for a median of 4.4 years. Bone marrow engraftment occurred in 81% of the evaluable patients. Post-transplantation leukaemic relapse was the most frequent cause of death in this group of patients, and occurred in 39% of patients. The second most frequent complication was infectious disease, while an EBV-induced B-lymphocyte proliferative disorder occurred in four patients. In conclusion, T-cell-depletion combined with infusion of anti-LFA-1 and anti-CD2 antibodies is efficient in preventing graft failure and GVHD in this group of children with high-risk leukaemia undergoing partially incompatible BMT. The overall DFS is not improved in contrast to what has been previously observed in patients with immunodeficiencies transplanted with a similar rejection prophylaxis. Other approaches are therefore needed aiming either at preserving donor T-cell mediated immunity or accelerating immune reconstitution.

Antibodies, Monoclonal↗

[Current treatment of malignant epithelial tumors of the ovary].

Surgery is the essential element of staging and treatment of malignant ovarian tumours. Regardless of the stage, it must include peritoneal cytology, hysterectomy with bilateral adnexectomy, omentectomy, pelvic and lumbo-aortic lymphadenectomy, appendicectomy and multiple peritoneal biopsies. In stage I tumours, in young women desiring a subsequent pregnancy, preservation of the uterus and contralateral ovary can be proposed. In stages II, III and IV, the therapeutic strategy consists of primary surgery and systematic chemotherapy (6 cycles). Radical surgery is essential in these cases, as the size of the residual tumour at the end of operation constitutes the major prognostic factor. To optimize the quality of tumour debulking, the maximum of visible carcinomatous nodules must be resected with, if necessary, gastrointestinal resections. The value of second-look surgery, after 6 cycles of chemotherapy, is currently controversial: it is only indicated in the context of randomized trials. Borderline malignant ovarian tumours have a good prognosis regardless of their stage. Surgery can very often be conservative, particularly in young women. Adjuvant chemotherapy has been shown to be effective in these tumours. Many studies are underway to define the value of new cytostatic molecules and "interval" surgery (intercalated between several courses of chemotherapy).

Adult↗

Extensive cytoreductive surgery in advanced ovarian carcinoma.

From June 1985 to June 1993, 152 patients with advanced ovarian cancer were treated with maximum cytoreductive surgery, and six to nine cycles of platinum-based chemotherapy. Six patients had stage IIIA-B disease, 101 stage IIIC, and 45 stage IV. Twenty-two tumors were grade 1. 58, grade 2. and 72, grade 3. Eighty-four patients (55%) presented with bulky tumors (> 10 cm in diameter). Optimal cytoreductive surgery (diameter of largest residual mass < 2 cm) was performed in 138 patients (91%). Fifty patients (33%) developed postoperative complications; 38 patients (25%) required a second laparotomy within a few days. Two postoperative deaths occurred. Overall 2-year and 4-year survival rates were 56% and 28%, respectively. There was a clear relationship between residual tumor and survival: the 2-year survival rate was 80% in the absence of residual tumor vs. 22% when the residuum exceeded 2 cm in diameter. The 2-year survival rate was 49% for tumor nodules < 2 cm in diameter. In a multivariate analysis of various risk factors (grade, stage, lymph node metastases, residual tumor, and age), the one that correlated most with survival was residual tumor. Despite a high morbidity rate, this modality of treatment, with the presence of optimal and aggressive perioperative measures in terms of intensive care unit and post-operative follow-up, offers an encouraging if not promising strategy for increased chances of survival in advanced ovarian cancer.

Adult↗

[Negative second-look laparatomy in ovarian cancers. Survival analysis and prognostic factors from 64 cases treated at the Gustave Roussy Institute].

This study describes 64 cases of ovarian adenocarcinoma seen in the Gustave-Roussy Institut between 1978 and 1988 and who had a negative second-look laparotomy. The median age was 51 years (30-74). FIGO stages were: I: 7 (11%); II: 3 (5%); III: 39 (61%); IV: 3 (5%); and undetermined: 12 (19%). There were 53% of serous type, 14% of endometrioid type, 13% of undifferencied type, 8% of clear cells type, 3% of mucinous type, and 9% of mixed type tumors. There were 50% of grade 3 tumors. Initial debulking surgery was as complete as possible in 59 patients, with a residual tumor after surgery superior or equal to 2 cm in 25 patients. Post second-look surgery treatment (n = 57) consisted of chemotherapy (CT) alone in 22 patients (34%), radiotherapy (RT) alone in 31 patients (49%), and CT associated with RT in 4 patients (6%). Median follow-up is 100 months. The overall survival rates at 3 and 5 years were respectively 86 and 81%, and disease free survival rates 70 and 61%. Among the 64 patients, 26 relapsed (39%). Median time to relapse was 96 months. There is a statistical difference in the survival between patients who had no or inferior to 2 cm residual tumor and others. Residual tumor was the only factor to be significant in univariate and multivariate analysis of survival.

Adenocarcinoma↗

[Celioscopic ovariectomy. Retrospective study of 56 ovariectomies].

OBJECTIVE: To describe a technique of laparoscopic oophorectomy, and evaluate its feasibility, limits and complications. DESIGN: We performed a retrospective study of 34 patients who underwent laparoscopic oophorectomy, from 1 December 1992 to 28 February 1995. SETTING: Centre Hospitalier Intercommunal, Créteil, and Institut Gustave Roussy, Villejuif. SUBJECTS: Mean age was 58 years (range: 42 to 74 years). In post-menopausal patients with ovarian cyst, a systematic oophorectomy was performed (33 patients). Among post-menopausal women, a systematic contro-lateral oophorectomy was done in 77% of cases. Castration was preconized in one woman with previous breast carcinoma. TECHNIC: Removal of the ovary was performed by dessication and division of the utero-ovarian junction and of the mesovarium. RESULTS: Among the 34 women, 32 (94%) had an exclusive laparoscopic procedure, 2 had laparo-conversion. The reasons of laparo-conversion were the presence of adhesions in one case and presumption of ovarian malignancy (Border-line ovarian tumor) in the other case. For the 32 women with laparoscopic treatment, 22 (65%) had bilateral oophorectomy. Per-operative complication rate was 6.2% (an epigastric vessel injury in one case and an hemorrhage during laparoscopic adhesiolysis in an other case). The post-operative time was uneventful. CONCLUSION: This technique of laparoscopic oophorectomy is simple, rapid and has a low rate of per and post-operative complications. In addition, this technique has the advantage to prevent the risk of ureteral injury.

Adult↗