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Biomedical subjects

J Michel

Publications and source records attributed to J Michel.

At least 73 records · Page 4Linked to original sources

Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group.

BACKGROUND: A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

Adolescent↗

Diagnostic and therapeutic aspects of endoscopic retrograde cholangiography in papillomatosis of the bile ducts: analysis of five cases.

BACKGROUND: Biliary papillomatosis is an uncommon disease, the definitive diagnosis and treatment of which generally require surgery. In the present study, we described the diagnostic and therapeutic aspects of endoscopic retrograde cholangiography in five such patients. METHODS: Since 1982, five patients with biliary papillomatosis have been admitted to our unit. All these patients underwent endoscopic retrograde cholangiography. RESULTS: Endoscopic examination of the ampulla of Vater showed a dilated papillary orifice with mucin discharge in all five patients. Biliary papillomatosis was diagnosed from the following features: multiple filling defects in the lumen of the biliary system in four patients and several supple stenoses in one patient. Histologic examination of biliary specimens taken after endoscopic sphincterotomy showed typical lesions of papillomatosis in the five patients. Palliative endoscopic treatment was performed in three patients. CONCLUSION: This case series reports the typical endoscopic retrograde cholangiography and endoscopic biopsy findings in biliary papillomatosis. For inoperable patients, endoscopic palliative evacuation of mucus and debris and/or stent placement are of benefit.

Adenocarcinoma↗

Liver resection or transplantation for hepatocellular carcinoma? Retrospective analysis of 215 patients with cirrhosis.

BACKGROUND/AIMS: Currently, surgical treatment of hepatocellular carcinoma in patients with cirrhosis is not clearly defined. The objective of this study was, in patients with cirrhosis with hepatocellular carcinoma, to compare liver resection to transplantation assessed by patient survival and to determine whether the tumor recurrence might be influenced by prognostic factors. METHODS: We have gathered all the available data from six French Medical Universities, for 215 patients with cirrhosis with hepatocellular carcinoma surgically treated either by liver resection (102) or by transplantation (113). RESULTS: The overall 5-year survival rate was similar in the transplantation group and in the resection group (32% vs. 31%, p=0.7). However, the 5-year survival rate without recurrence was higher in the transplantation group than in the resection group (60% vs. 14%, p<0.001). Three independent prognostic factors influenced significantly the survival without recurrence: the surgical treatment by transplantation (p<0.001), the number of tumors (p<0.01) and the tumor size (p<0.001). With these factors we defined a prognostic index (Ip) which allowed assessment of the probability of survival without recurrence: Ip= (Xie. x 1.41)+(Nbr T. x 0.19)+(Size TV. x 0.16); Xie=surgical treatment (Xie=0 if transplantation, Xie=1 if resection), Nbr.T. and Size TV.=number of tumors and size of the most voluminous tumor, respectively, according to the histologic study. CONCLUSIONS: These results and this prognostic index are encouraging for liver transplantation as treatment of hepatocellular carcinoma in selected patients with cirrhosis.

Adult↗

Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the European Lung Cancer Working Party.

The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- (or carboplatin)-based combination regimens. Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991. All these trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or carboplatin). In this population of 1052 eligible patients, 752 were assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles. The predictive value of response to chemotherapy on survival (measured from the time of response assessment i.e. 12 weeks after registration in the trial) was studied by univariate analysis as well as by multivariate methods (adjustment of the impact of several covariates simultaneously on the dependent variable) with adjustment for the pretreatment prognostic variables. After three cycles of chemotherapy, the global estimated median survival time was 24 weeks with a 95% confidence interval of 22-25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discriminant marker (P < 0.0001) for further survival with estimated median survival times of 41 weeks (95% CI: 38-46) and 19 weeks (95% CI: 17-20), respectively, for the responding and non-responding patients. In a Cox regression model fitted to the data using a forward stepwise procedure, this variable was the first selected explanatory variable. Its effect was adjusted by the introduction in the model of initial disease extent, Karnofsky performance status, serum calcium level and white blood cell count. These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms (RECPAM) which led to a classification of the patients into three homogeneous subgroups. Our results, using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis, found an objective response to chemotherapy to be a predominant predictive factor for further survival, although it did not allow any conclusion about a causal relationship. The RECPAM results led to a classification of the patients into three subgroups which needs to be validated in other series.

Adult↗

Treatment of active gastroesophageal variceal bleeding with terlipressin or hemostatic balloon in patients with cirrhosis. A randomized controlled trial.

Gastroesophageal variceal bleeding due to portal hypertension should be treated by endoscopic sclerotherapy. This procedure, however, has some limitations. It has been established that vasoactive drugs are effective for controlling active variceal bleeding. We report the results of a randomized controlled trial comparing terlipressin to hemostatic tube (Linton-Michel tube) for the treatment of bleeding gastroesophageal varices in cirrhotic patients. Thirty-seven cirrhotic patients with a total of 40 episodes of gastroesophageal variceal bleeding were included in this trial. Patients were randomly assigned to intravenous terlipressin or Linton-Michel tube (LM tube), for 24 h. During this period, hemostasis was defined as obtaining of hemodynamic and hematocrit stabilization and/or absence of hematemesis or melena. Bleeding recurrence was assessed during a 1-month period after treatment. Twenty bleeding episodes were treated with terlipressin (Group I) and 20 with LM tube (Group II). Both groups of patients were similar in age, sex distribution, etiology of cirrhosis and degree of hepatic insufficiency. Bleeding was controlled in 70% of patients from Group I and in 95% from Group II (p < 0.05) during treatment. Bleeding recurred in 14% of patients in Group I vs. 36% in Group II 1 week following the treatment (p > 0.05) and in 16.6% in Group I vs. 83.3% in Group II 1 month after treatment (p < 0.05). Complications were more frequent in Group II than in Group I (65 vs. 15%, p < 0.05). Mortality rate was similar in both groups 1 month after treatment. In conclusion, hemostatic tubes were superior to terlipressin for the control of active gastroesophageal variceal bleeding within the first 24 h. Complications and bleeding recurrence were more frequent in patients treated by hemostatic tube within a period of 1 month after treatment. Mortality rate was similar in both groups of patients.

Adult↗

[Prognostic factors in advanced stage non-small cell bronchial cancer: experiences of the European Lung Cancer Working Party].

The European Lung Cancer Working Party has investigated prognostic factors for response, overall survival, long term survival in a population with advanced non small cell lung cancer registered in a clinical trial evaluating platinum derivatives-containing chemotherapy regimens. Various factors have been identified in multivariate analyses and were classified using RECPAM methodology. In addition to the clinical factors such as disease extent and performance status were shown, as significant predictors, rarely studied biological factors like pretherapeutic leucocyte and polynuclear levels. The obtention of an objective response to chemotherapy appeared to be a major prognostic factor for further survival.

Age Factors↗

[Painful rib syndrome (or Cyriax syndrome). Study of 100 patients].

OBJECTIVE: To analyse clinical expression and outcome of painful rib syndrome in a large series of 100 cases. METHODS: From 1978 to 1993, 100 consecutive patients with chronic anterior chest pain or supramesocolic abdominal pain of unknown origin underwent complete physical examination, laboratory tests and complementary explorations as required. RESULTS: Among the first 100 patients the sex ratio was 3.34 and mean age 50.6 years (21-80). Chronic pain had persisted for an average 41.2 months (15 days-30 years), predominantly on the right (81%) and exceptionally bilaterally (1%). No evidence of a cause could be identified from laboratory tests or complementary explorations. A past history of direct trauma was found in 71 patients and indirect trauma in 21. Seventy-three patients were given 1% lidocaine infiltrations (20 to 40 ml) including 14 who received 2 or 3 infiltrations. Six patients underwent surgical resection of a luxated cartilage with curative effect in 5. CONCLUSION: The diagnosis of painful rib syndrome is based solely on the presence of pain upon applying pressure to the anteroinferior border of the rib cage and is related to often neglected or forgotten trauma.

Adult↗

Quinazoline-2,4(1H,3H)-dione as a substitute for thymine in triple-helix forming oligonucleotides: a reassessment.

A major limitation in triple-helix formation arises from the weak energy of interaction between the third strand and the double-stranded target. We tried to increase the stacking interaction contribution within the third strand by extending the aromatic domain of thymine. We report here the use of 2,4-quinazolinedione as a substitute for thymine in the canonical TA*T triplet. The synthesis and the characterization of the quinazoline beta nucleoside Q and of its phosphoramidite derivative is described. Triple-helix- forming oligonucleotides incorporating Q have been prepared and their ability to form triplexes has been evaluated by UV-monitored thermal denaturation measurements. The introduction of one or multiple Q residues, either contiguous or remote from each other, slightly destabilized triple-stranded structures, whatever the nucleic acid base composition (pyrimidine or GT) of the third strand.

Drug Stability↗

Prognostic factors for response to chemotherapy containing platinum derivatives in patients with unresectable non-small cell lung cancer. (NSCLC).

PURPOSE: To identify pretreatment variables predicting response to platinum derivatives containing chemotherapy in patients with unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of the 7 consecutive clinical trials conducted by the European Lung Cancer Working Party between December 1980 and August 1991. All patients received a cisplatin or carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors including sex, age, histology, performance status, weight loss, type of lesions, extent of disease, main metastatic sites and several biological parameters, namely white blood cell count (WBC), neutrophil count, platelet count, hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On 1052 eligible patients. 107 were not assessable for response. The objective response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as statistically significantly associated with a higher objective antitumoral response rate the following characteristics: a normal platelet count, the absence of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a normal hemoglobinemia, an older age and a normal WBC count. On a restricted set of variables including data from 777 patients, a multivariate logistic regression model disclosed age and platelet count as significantly and independently related to response rate. CONCLUSION: Clinical and demographic characteristics of patients with unresectable NSCLC, as well as routine laboratory parameters, could not accurately predict response to chemotherapy in a population of patients selected for a clinical trial. Future studies on this subject should include more sophisticated variables as new biomolecular makers.

Adult↗

New staging system of the fifth Joint National Committee report on the detection, evaluation, and treatment of high blood pressure (JNC-V) alters assessment of the severity and treatment of hypertension.

The fifth Joint National Committee report on the detection, evaluation, and treatment of high blood pressure (JNC-V) introduced a new system of blood pressure classification that incorporated systolic blood pressure (SBP) and established new diastolic blood pressure (DBP) cut points. With the previous JNC classification, subjects were classified according to DBP alone. In this study, our purpose was to assess the effect of the new staging system on the assessment of hypertension severity and to determine whether' the new JNC-V staging system better identifies individuals at risk for hypertensive target-organ damage. We compared the assessment of hypertension severity using JNC-IV with that using JNC-V in 1158 subjects enrolled in the Harlem Hospital Hypertension Clinic database from 1975 to 1992. We used pretreatment DBP to classify subjects according to JNC-IV criteria. These subjects were reclassified into one of the four stages of JNC-V. The assessment of hypertension severity and prevalence of organ damage in subjects who remained in the same category of severity in both systems was compared with damage in subjects who were upstaged. With the JNC-V classification, 321 subjects remained in the same category, and 837 were upstaged. Six hundred and four subjects moved up because of the new cut points of DBP, and 275 were upstaged because of higher SBP. Upstaged subjects had more manifestations of hypertensive target-organ damage. With the new JNC-V classification system, hypertension is assessed as severe or very severe in more individuals than with JNC-IV. Subjects who are upstaged in JNC-V are more likely to have evidence of renal disease and other target-organ damage.

Adult↗

Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE AND METHODS: The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS: Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION: We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.

Adult↗

A fraction enriched in a novel glucocorticoid receptor-interacting protein stimulates receptor-dependent transcription in vitro.

Glucocorticoids influence numerous cell functions by regulating gene activity. The glucocorticoid receptor (GR) is a ligand-activated transcription factor and, like any other transcription factor, does not modulate gene activity just by binding to DNA. Interaction with other proteins is probably required to enhance the establishment of a functional transcription initiation complex. To identify such proteins, we analyzed the in vitro interaction of the glucocorticoid receptor bound to a double glucocorticoid response element with nuclear proteins and describe here three interacting proteins with different molecular weights. One of them, which we named GRIP 170 (GR-interacting protein), was purified and microsequenced, and it turned out to be an unknown protein. When tested in a cell-free transcription assay, the fraction highly enriched for GRIP 170 does not influence basal promoter activity but does enhance GR induction.

Carrier Proteins↗

[Secondary sclerosing cholangitis].

Secondary sclerosing cholangitis leads to slow and often irreversible destruction of the walls of both intra- and extrahepatic bile ducts. As for primary sclerosing cholangitis, clinical signs and laboratory findings reveal cholestasis. The diagnosis is confirmed by retrograde endoscopic cholangiography which shows narrowed bile ducts and rarefied ramifications of the intra-hepatic ductal system. Several causes have been identified including infectious causes with or without a relationship to bile duct obstruction and human immunodeficiency virus infection as well as ischaemic related causes after chemotherapy, arterial embolization or liver transplantation. Other causes include chemical aggression after treatment for hydatic cysts and post-surgical complications due to a damaged bile tract. Treatment is difficult and often dependent on the cause.

AIDS-Related Opportunistic Infections↗

Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.

Nowadays in many European heart centers the activation of the fibrinolytic system, always occurring during cardiopulmonary bypass, is routinely reduced by high-dose application of the proteinase inhibitor aprotinin (total of > 4 million KIU). In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin, particularly the protection of the myocardium during the ischemic period of aortic crossclamping. Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were randomly and in a double-blind fashion divided into two groups, one that received high-dose aprotinin therapy and one that received only saline solution. Markers such as troponin T, with high specificity for detection of myocardial ischemia and infarction, and markers with more general specificity such as creatine kinase, its isoenzyme, and lactate dehydrogenase showed significantly increased values after ischemia in both groups. In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group. Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury.

Aprotinin↗

Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party.

PURPOSE: This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group. PATIENTS AND METHODS: We included in the analysis all eligible patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party (ELCWP) during one decade. The patients were treated by chemotherapy regimens based on platinum derivatives. We prospectively collected 23 variables and analyzed them by univariate and multivariate methods. RESULTS: The global estimated median survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks. After univariate analysis, we applied two multivariate statistical techniques. In a Cox regression model, the selected explanatory variables were disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex. These results were confirmed by application of recursive partitioning and amalgamation algorithms (RECPAM), which led to classification of the patients into four homogeneous subgroups. CONCLUSION: We confirmed by our analysis the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of two methods: a classical Cox regression model and a RECPAM analysis. The classification of patients into the four subgroups we obtained needs to be validated in other series.

Algorithms↗

Induction chemotherapy with ifosfamide, etoposide, and anthracycline for small cell lung cancer: experience of the European Lung Cancer Working Party.

Prospective trials comparing drug analogues in the treatment of small cell lung cancer are rare. The European Lung Cancer Working Party has conducted a randomized trial with a primary end point of determining the effect on survival of maintenance chemotherapy and a secondary end point of comparing doxorubicin (45 mg/m2) with a bioequivalent epirubicin dose (60 mg/m2) in one set of patients, and a standard with a high epirubicin dose (60 v 90 mg/m2) in a second set of patients. Anthracycline was given on day 1 of induction chemotherapy in combination with ifosfamide (1.5 g/m2 intravenously days 1 through 3) and etoposide (80 mg/m2 intravenously days 1 through 3). Six courses were given at 3-week intervals. In all, 235 eligible previously untreated patients with pathologically proven small cell lung cancer were randomized: 106 to the comparison of doxorubicin and epirubicin and 129 to the comparison of standard-dose versus high-dose epirubicin. There was no difference between the regimens in terms of objective response rate or survival, and the regimen containing the lower (60 mg/m2) epirubicin dose was better tolerated, with fewer toxic deaths and less need for dose and schedule adjustments.

Adult↗