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Biomedical subjects

J Michel

Publications and source records attributed to J Michel.

At least 19 recordsLinked to original sources
PubMed1995

[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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

Transcriptional regulation of differentiation, selective toxicity and ATGCAAAT binding of bisbenzimidazole derivatives in human melanoma cells.

To study the relationship between the structure of minor groove ligands and their affinity for specific DNA sequences that regulate gene transcription, three analogues of the A-T-specific DNA minor groove ligands Hoechst 33258 and Hoechst 33342 were synthesized with 5, 8 or 12 carbons in an aliphatic chain attached to the phenolic oxygen of the molecule. There was a striking bimodal relationship between toxicity to HeLa cells and the lipophilicity of the five analogues, toxicity being low for the compounds with a free hydroxyl (Hoechst 33258) or a 12-carbon substituent, yet high for the 5-carbon analogue. Selective killing of human melanoma cells compared with normal fibroblasts was observed for the Hoechst analogue with a 12-carbon chain attached. Hoechst 33258 itself was selectively toxic for the MM96E melanoma cell line compared with other cell lines, induced a highly dendritic morphology, increased tyrosinase activity and tyrosinase mRNA but decreased the level of gp75 (TRP-1) mRNA; message for a third pigment gene, Pmel-17, was unchanged. Tyrosinase activity was decreased in the resistant A2058 melanoma cell line and transcription was affected to a lesser extent than in MM96E. Expression of gp75 protein and two intermediate filament proteins was inhibited by Hoechst 33258 in MM96E cells. There was no major difference in the amount of 125I-Hoechst 33258 taken up by sensitive and resistant cells. Of the five derivatives studied, the parent drug Hoechst 33258 and the 2-carbon analogue (Hoechst 33342) were found to have the most inhibitory effect on affinity of octamer binding proteins for the ATGCAAAT consensus sequence found in the promoter region of certain genes associated with proliferation and differentiation. In contrast to Distamycin A (also an A-T-specific minor groove ligand), Hoechst 33258 displaced proteins already bound to the octamer motif. The G-C ligand chromomycin A3 exhibited a different spectrum of cell toxicity and tyrosinase stimulation compared with Hoechst 33258. Chromomycin A3 but not Hoechst 33258, strongly inhibited the zinc-dependent transcriptional activity of the sheep metallothionein-Ia promoter in reporter gene assays of transfected cells. Since the six metal-responsive elements of the promoter are GC-rich, this provides independent evidence for the sequence-specificity of transcriptional inactivation by one of these drugs in melanoma cells. Overall, the results suggest that Hoechst 33258 acts by inhibiting the transcription of specific genes, cell lines evidently differing in the accessibility to drugs of certain A-T-rich sequences.

Base Sequence↗
PubMed1994

Dose-finding study of tropisetron in cisplatin-induced nausea and vomiting.

BACKGROUND: The purpose of these two studies was to define the optimal therapeutic dose of the 5-HT3 receptor antagonist tropisetron (Navoban, ICS 205-930) in cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: In two multicentre, dose-finding studies of tropisetron in the prevention of cisplatin-induced emesis, cancer patients naïve to chemotherapy or who had not vomited previously were randomly assigned to tropisetron 5, 10, 20 or 40 mg (study I, 143 patients) or 2 or 5 mg (study II, 74 patients), administered as a single intravenous dose over 15 minutes just before the start of chemotherapy. RESULTS: In study I total control of acute symptoms (no nausea and no vomiting) was achieved in, respectively, 66%, 50%, 64% and 50% in the 5-, 10-, 20- and 40-mg groups of patients. A total absence of vomiting alone was seen in, respectively, 71%, 51%, 61% or 58% of patients. None of the differences were statistically significant. In study II there was total acute control in 57% of patients in the 2-mg group and 63% in the 5-mg group (p = NS). Total or major control of vomiting (< or = 2 emetic episodes) was the primary endpoint in study II and was seen in 68% of patients for the 2-mg and 86% for the 5-mg group (p = 0.055). In this study failures ( > 3 vomiting) were rescued with a second infusion of tropisetron (5-mg fixed dose). Three of 8 rescue infusions administered in the 2-mg group prevented further vomiting whereas none of 5 were successful in the 5-mg group during course 1 of chemotherapy. The most frequently reported adverse effects (over all three courses) were headache (6.0% of 217 patients) hypertension (3.7%) and diarrhoea (2.8%). None of the 25 deaths which occurred during the two studies were attributable to tropisetron. CONCLUSIONS: Thus, a single dose of tropisetron provides 24-hour protection against cisplatin-induced nausea and vomiting and is well tolerated. These studies do not allow a firm conclusion but suggest that 2 mg may be subtherapeutic and that 5 mg is as effective as higher doses.

Adult↗
PubMed1992

Courvoisier's sign revisited: two patients with palpable gallbladder.

More than a century ago, Courvoisier published his observation on the significance of a palpable gallbladder in the differential diagnosis of obstructive jaundice. We have described two patients with newly described conditions--AIDS-associated cholangiopathy and diet-induced cholecystitis--who had a palpable gallbladder and have discussed possible pathogenetic mechanisms.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Characterization of substance P-like immunoreactivity and tachykinin-encoding mRNAs in rat medullary thyroid carcinoma cell lines.

Rat thyroid tissue and three rat medullary thyroid carcinoma cell lines, 6-23, WE4/2, and CA77, have been examined for substance P (SP) and SP-like peptide expression. Analysis by combined HPLC and radioimmunoassay revealed the presence of SP in thyroid and 6-23 cell extracts. The presence of SP-encoding mRNAs was also detected in 6-23 cells by solution hybridization-nuclease protection analysis. SP-encoding mRNA expression was increased (fourfold) by maintaining the 6-23 cells in low serum (2%) for 4 or 10 days. The 6-23 cells also expressed other SP-like immunoreactive species, which were chromatographically and immunologically distinct from established tachykinin peptides. WE4/2 cells did not contain SP but did display SP-like immunoreactivity (SPLI), which migrated like the unidentified SPLI in 6-23 cells. CA77 cells did not contain SP or SP-encoding mRNA but did contain SPLI that migrated identically to the unidentified SPLI in the other cell lines. This novel SPLI was detected with an antiserum directed against the SP carboxyl terminus and to a lesser extent with an antiserum directed against the neurokinin A carboxyl terminus, but it showed minimal cross-reactivity using an antiserum directed against the midportion of SP. Treatment with 50 mM KCl resulted in secretion of this SPLI from CA77 cells. Gel filtration analysis demonstrated that this novel SPLI had an apparent molecular weight of approximately 1,000. These results are discussed in terms of cell lines that express tachykinin peptides and in terms of the molecular nature of the new SPLI detected in CA77 cells.

Animals↗
PubMed1992

Frequent loss of heterozygosity on chromosome 18 in ovarian adenocarcinoma which does not always include the DCC locus.

Inactivation of the DCC gene on chromosome 18 owing to loss of heterozygosity is a common finding in colorectal cancer. Because both ovarian and colon cancer are features of Lynch syndrome II, which has been provisionally mapped to chromosome 18, we hypothesized that loss of heterozygosity at the DCC locus may also occur in ovarian neoplasia. Fifty-two sporadic ovarian adenocarcinoma tumours were analysed by Southern blotting for loss of heterozygosity (LOH) at six chromosome 18 loci. Overall, tumours from 31 patients (60%) showed allelic loss at one or more of these loci. A similarly high level of LOH, 66%, was found at D17S5 (17p13.3). In contrast, moderate levels of LOH, of 31%, 39% and 33%, were found at MYCL1 (1p32), D1S57 (1p) and D14S20 (14q32.33) respectively. However, analysis of partial chromosome deletions in 11 patients indicates that the smallest region of overlap appears to exclude the DCC gene but to be between the D18S5 and D18S11 loci. This suggests that another locus, as well as or apart from DCC, may be involved.

Adenocarcinoma↗
PubMed1991

Intraoperative valvuloplasty in calcific aortic stenosis: a study comparing the mechanism of a novel expandable device with conventional balloon dilatation.

In selected patients with calcific aortic stenosis, balloon valvuloplasty is an intermediate alternative to surgery. The effect of balloon valvuloplasty to increase valve area, however, is limited and the restenosis rate is high during follow-up. To improve the results and reduce the complication rate, a new device for valvuloplasty of calcific aortic stenosis was developed. This system consists of three expandable prongs mounted on a freely movable catheter tip. To evaluate the efficacy of this new device, valvuloplasty was performed in 10 patients with severe aortic stenosis intraoperatively just prior to valve replacement. Comparison was made with the results of conventional balloon dilatation performed in an additional 20 patients during surgery. Using the new device, the relative orifice area increased from 10 +/- 3% before to 20 +/- 6% following intervention. However, in only one patient was a considerable increase of static valve area (greater than 15%) found. The results were comparable to the effect of conventional balloon dilatation, which led to an increase of orifice area from 12 +/- 7% to 24 +/- 10%. With both systems, the best results were achieved in patients with aortic stenosis and significant commissural fusion. In contrast, in bicuspid or tricuspid valves without fused commissures the effect of the intervention was limited. Because complete obstruction of the aortic valve does not occur during dilatation, this new device might be superior to conventional balloon dilatation. Preselection of patients according to the morphology of the valve seems mandatory to improve the success and reduce the complication rate of valvuloplasty in aortic stenosis.

Aged↗
PubMed1990

Experience of the Belgian Society of Medical Oncology with single-administration 5 g/m2 ifosfamide with mesna as second- or third-line therapy in advanced breast cancer.

In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits.

Adult↗
PubMed1990

Sigma receptors modulate the hypothalamic-pituitary-adrenal (HPA) axis centrally: evidence for a functional interaction with NMDA receptors, in vivo.

The present report investigates the modulation of the hypothalamic-pituitary-adrenal (HPA) axis in the rat by sigma receptors, using a selective ligand, (+) pentazocine, and comparing the effects with (+) SKF 10, 047. Both compounds stimulate ACTH release potently after central and peripheral administration. These effects are centrally mediated, since they did not release ACTH from anterior pituitary primary cultures. The effects are not blocked by naloxone, but are blocked by the NMDA antagonist, CPP, indicating a centrally mediated functional interaction between NMDA and sigma receptors, in vivo.

Adrenocorticotropic Hormone↗
PubMed1990

A randomized study comparing etoposide and vindesine with or without cisplatin as induction therapy for small cell lung cancer. EORTC Lung Cancer Working Party.

We conducted a randomized trial testing etoposide (120 mg/m2 d1-3) + vindesine (3 mg/m2 d1) with or without cisplatin (60 mg/m2 d1) in patients with SCLC. A total of 8 courses were given at 3-week intervals. 221 patients were registered and 201, 95 in the CEV arm and 106 in the EV arm, were eligible for survival analysis. 183 patients were evaluable for response: 74% had an objective response (OR) with CEV versus 55% with EV (p = 0.01). Complete response rates were, respectively, 21% and 13% (NS). In patients with limited disease (LD), OR rates were 72% and 61% (NS), and 76% and 48% in extensive disease (ED) (p = 0.01). There was no statistically significant difference in survival between the two regimens (p = 0.745, log rank test). Median survival for EV and CEV were, respectively, 40 and 45 weeks, and two-year survivals were 11% and 9%; in patients with LD, the corresponding figures were 14% and 16% (NS) and in those with ED, 8% and 3% (NS). Disease extent (LD vs ED), Karnofsky performance status and loss of body weight were significant prognostic factors for survival; age, sex, type of treatment and type of lesion were not. The CEV regimen was not significantly more myelotoxic than EV but was associated with more severe nausea, vomiting and alopecia. In conclusion, the addition of cisplatin to the EV regimen, a combination reported to be easily manageable, was associated with a significantly higher OR rate but survival was not significantly improved.

Adult↗