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Biomedical subjects

B Lebeau

Publications and source records attributed to B Lebeau.

At least 19 recordsLinked to original sources

A monoclonal antibody specific to surface antigen on Candida krusei.

A monoclonal antibody (MAb; MAb 6B3) which reacts specifically with a cell wall antigen found in all strains or isolates of Candida krusei was developed. MAb 6B3 was extensively tested by immunofluorescence assay for cross-reaction with many Candida, Cryptococcus, Saccharomyces, Trichosporon, and Rhodotorula species and was found to react only with the species C. krusei. The specific epitope is expressed on the surface of fungal cells and appears to reside on a protein moiety. Taking into account the increasing importance of fluconazole-resistant strains in nosocomial fungal infections, the very high degree of specificity of this MAb for C. krusei could be useful for the routine detection of C. krusei in culture or in tissue samples.

Animals

Chromosome mapping and expression of the human interleukin-13 receptor.

Interleukin-13 (IL-13) is a cytokine secreted by activated T cells and shares most but not all biological activities with interleukin-4 (IL-4). Both cytokines play an important role as a switch factor directing synthesis of IgE; they act on monocytes and endothelial cells, but unlike IL-4, IL-13 does not act on T cells. These cytokines have both common and distinct components in their respective receptors. Based on sequence similarity shared by cytokine receptor family members, we have identified a cDNA encoding the human IL-13 receptor (IL-13R). This cDNA was used to examine the pattern of IL-13R mRNA expression by Northern blot analyses of poly(A)+ RNA purified from different human tissues and cell lines. Among several myeloma cell lines analyzed, the U266 cell line was the only one found to express IL-13R transcripts. This cell line is also the only one described as producing IgE. The IL-13R gene was mapped to chromosome Xq24 by in situ hybridization. Interestingly, this locus is near that of the CD40 ligand gene, the product of which is also involved, like IL-13, in proliferation and IgE isotype switching of human B cells. The human IL-13R gene maps between two cytokine receptor genes located on the chromosome arm Xq region: the interleukin-2 receptor gamma chain gene (Xq13.1) and the interleukin-9 receptor gene (Xq28). The lack of nucleotide sequence similarity suggests unrelated evolutionary pathways between these receptor genes.

Amino Acid Sequence

Reconstitution of two isoforms of the human interleukin-11 receptor and comparison of their functional properties.

Long-term stable Ba/F3 transfectants (B13R alpha1 and B13R alpha2) expressing two isoforms of the human IL-IIR alpha receptor (alpha1 full length or alpha2 lacking the cytoplasmic domain) in combination with human gp130 were established. IL-11R alpha1 and IL-11R alpha2 were each expressed and detected as three bands upon Western blot analysis, with apparent molecular masses in agreement with those of the polypeptide backbone (47 and 44 kDa, respectively) with no, one or two N-linked sugars. B13R alpha1 and B13R alpha2 bound IL-11-thioredoxin with similar efficiencies and proliferated with superimposable dose-response curves to IL-11, demonstrating that the intracellular domain of IL-11R alpha has no significant contribution on ligand binding and signaling. Analysis of a set of anti-human gp130 mAbs confirmed the similar responsiveness of B13R alpha1 and B13R alpha2 transfectants.

Animals

The efficacy of a combination of ondansetron, methylprednisolone and metopimazine in patients previously uncontrolled with a dual antiemetic treatment in cisplatin-based chemotherapy. The French Ondansetron Study Group.

BACKGROUND: Cisplatin is one of the most effective cytotoxic drugs used in the treatment of certain neoplasms, but is also one which most frequently induces nausea and vomiting. Combination of corticosteroids with ondansetron enables greater control of emesis than that obtained with ondansetron alone, but some patients still experience symptoms. The objective of this randomised, double-blind, multicentre, parallel group study was to examine the benefit of the addition of metopimazine (MPZ), a dopamine receptor antagonist, to the combination of ondansetron + methylprednisolone (O + M) in the prevention of cisplatin-induced nausea and vomiting in patients uncontrolled [i.e., at least one emetic episode (vomiting and/or retching) or moderate or severe nausea] during their previous course of cisplatin based chemotherapy, despite antiemetic treatment with a combination of a 5-hydroxytryptamine3 receptor antagonist (5HT3) with a corticosteroid. The impact of the treatment on the patients' quality of life was also evaluated using two specific questionnaires the FLIC (Functional Living Index for Cancer), and the FLIE (Functional Living Index for Emesis). PATIENTS AND METHODS: The intent-to-treat population consisted of 338 patients; 168 patients received the triple combination of ondansetron, methylprednisolone and metopimazine (O + M + MPZ), and 170 patients received ondansetron plus methylprednisolone (O + M). Tumour type was comparable in the two treatment groups, the most prevalent being lung cancer. Patients in group O + M + MPZ received ondansetron as an 8 mg intravenous injection prior to chemotherapy on day 1 followed by 8 mg tablets b.i.d. from D2 to D3, methylprednisolone as a 120 mg intravenous injection prior to chemotherapy on D1 and followed by 16 mg tablets b.i.d. from D2 to D3, and metopimazine as a 40 mg intravenous injection prior to chemotherapy on D1 and followed by 15 mg capsules b.i.d. on D2 to D3. Patients in group O + M received treatment with ondansetron and methylprednisolone as above. RESULTS: Analysis of the primary efficacy criterion (absence of emetic episode throughout the course of chemotherapy) revealed a success rate of 53% in the group receiving O + M + MPZ and 38% in the group receiving O + M (P = 0.008). Analysis of the secondary efficacy criteria (nausea grade, number of emetic episodes and global patient satisfaction on D1 and from D2 to D3) showed a statistically significant difference between the two groups, in favour of the O + M + MPZ treatment. The scores obtained with the FLIC and FLIE questionnaires did not reveal any significant differences between the two groups. Treatment was well tolerated in both groups. CONCLUSION: The study showed that the addition of MPZ to the combination O + M was an effective and well tolerated antiemetic treatment, with a 15% increase in efficacy compared to the combination in patients not controlled during their previous course of chemotherapy. The addition of metopimazine to existing regimens containing 5HT3 receptor antagonist and steroid combination should be considered for patients who fail on their previous course.

Adolescent

Long-term survivors of small-cell lung cancer (SCLC): a French multicenter study. Groupe d'Oncologie de Langue Française.

BACKGROUND: The aim of this study was to analyze SCLC patients beyond 30 months, particularly their outcome, their way of life, and factors which could influence relapses, second-primary cancers and death. PATIENTS AND METHODS: Between January 1986 and May 1995, 263 SCLC patients who survived longer than 30 months were included from 52 French institutions. The analysis was performed on the 155 cases confirmed by a pathologic review. RESULTS: Physical, mental and psychological states were considered as normal at 30 months in respectively 70.3%, 87.7% and 67.7% of patients, not influenced by prophylactic cranial irradiation, number of chemotherapy cycles, CCNU or cisplatin. Therapeutic sequelae were neurological impairment (13%), pulmonary fibrosis (18%) and cardiac disorders (11%) at 30 months. Return to work was possible for 40% of patients in the first two years following diagnosis. Among 43 relapsing patients, 33 benefited from a second-line treatment. Their median survival was 12 months since retreatment, and seven patients have survived again longer than 30 months. Age > 60 at the time of diagnosis was found as an independent factor increasing the risk of relapse beyond 30 months (OR = 2.46, IC 95% (1.16-5.26), P = 0.01). The risk of relapse became less than 10% beyond five years. Twenty patients (13%) developed a second primary cancer in a mean time of 58.6 months. The risk of second primary cancer was increased by a number of chemotherapy cycles > 6 (OR = 3.25, IC 95% (1.08-9.8) P = 0.02) and by an age > 60 (OR = 2.92, IC 95% (1.07-7.97), P = 0.03). Five- and 10-year survival rates were respectively 68% and 44%. In these patients having reached a 30-month survival, three independent factors were predictive of a survival longer than five years: age < or = 60 at the time of diagnosis (OR = 2.85, IC 95% (1.23-6.6), P = 0.01), chest radiotherapy (OR = 3.1, IC 95% (1.28-7.69), P = 0.006) and absence of relapse (OR = 4.5, IC 95% (1.75-12.5), P = 0.002). This study suggests that: 1) therapeutic sequelae are rather mild, allowing return to work in 40% of patients; 2) relapsing 30-month survivors can benefit from second-line treatment; 3) SCLC cure can be achieved with a 10-year follow-up.

Adult

Molecular typing of Aspergillus fumigatus strains by sequence-specific DNA primer (SSDP) analysis.

A PCR typing method has been developed and tested to investigate the polymorphism of clinical strains of Aspergillus fumigatus. Firstly, the DNA fragments from random amplified polymorphic DNA (RAPD) patterns of nine epidemiologically and geographically non-related monosporal strains of A. fumigatus were cloned and sequenced. The pairs of five sequence-specific DNA primers (SSDP), characteristic of the 5' and 3' extremities of the RAPD products, were then used in high stringency PCR to type 43 clinical strains of A. fumigatus from 13 patients, according to the presence or absence of a single amplified band. This original approach, which uses the advantages of PCR, has made it possible to overcome the difficulties resulting from the low stringency amplification. The SSDP analysis of 51 A. fumigatus strains (9 unrelated monosporal strains and 43 clinical strains from 13 patients) can be classed into 22 different types with a high reproducibility and a high level of discrimination (D = 0.96). The results suggest that seven lung transplant patients with necrotizing aspergillosis, bronchitis aspergillosis and bronchial colonization were infected by multiple strain genotypes, whereas three patients with invasive aspergillosis seem to have been infected by a single strain.

Aspergillosis

[A rare cause of Pierre Marie hypertrophic osteoarthropathy: subacute infectious endocarditis].

Secondary hypertrophic osteoarthropathy occurred in a patient with subacute endocarditis. Chest x-ray in this smoker with ethylic cirrhosis showed a pulmonary opacity. Clinical signs of osteoarthropathic inflammation resolved with antibiotics before surgical cure of the aortic insufficiency. The diagnosis was retained on the basis of outcome after antibiotic therapy and the absence of any other etiology, notably bronchogenic cancer. Endocarditis or infectious endarteritis should be entertained in case of hypertrophic osteoarthropathy in patients with an infectious syndrome. Pathogenic hypotheses are discussed. In congenital cardiopathies, intrapulmonary shunts, megacaryocytes and activation of the vascular-platelet endothelium unit may be involved. Bacterial factors and platelet aggregation could play a role in initiating hypertrophic osteoarthropathy in patients with infectious endocarditis.

Blood Platelets

[Second primary cancers after small-cell lung cancer].

The records of 1,371 patients with small cell carcinoma of the lung (SCLC) treated between 1983 and 1994, were reviewed for the occurrence of second primary malignancies (SPM). One was excluded for analysis because of insufficient data. Eight synchronous SPM (SSPM) and 8 metachronous SPM (MSPM) were identified, SSPM included non-small cell lung cancer in 6 patients, 1 head and neck cancer and 1 oesophageal cancer. Median survival after the diagnosis of SSPM was 6 months. The MSPM were detected between 1 and 6 years after the diagnosis of SCLC. MSPM included lung cancer (3 patients), gastrointestinal malignancies (2 patients), 1 hematologic malignancy, 1 prostatic cancer and 1 head and neck cancer. The median survival time after the diagnosis of MSPM was 4 months. Occurrence of SPM is a singular pattern of patients with SCLC. Tobacco consumption, genetic factors and carcinogenic effects of multimodality treatment are supposed mechanisms to explain SPM.

Adult

[Small-cell lung cancer: chemotherapy strategy].

Small-cell lung cancer, a malignant disease with an anatomological and clinical presentation quite different from other solid tumors, is highly sensitive to current polychemotherapy regimens. Definitive cure can be achieved in about 10% of the apparently localized forms and in under 5% of the disseminated forms with usual chemotherapy protocols. Definitive cure requires a rigorous strategy which should be carried out by well-trained teams in centers conducting clinical research since several points concerning the most adapted chemotherapy protocol remain to be determined. Several new drugs are proposed to investigators every year including both drugs with direct cytotoxicity as well as adjuvant treatments for chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

The human interleukin-11 receptor alpha gene (IL11RA): genomic organization and chromosome mapping.

The high-affinity receptor for interleukin-11 (IL-11) is composed of two subunits, IL-11 receptor alpha chain (IL-11R alpha) and gp130, the common subunit of the interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor, and oncostatin M receptors. The IL-11 receptor-specific alpha chain shares homologies with the alpha chain of the CNTF and IL-6 receptors. We isolated and characterized genomic DNA clones encompassing the entire coding sequence of the IL-11R alpha cDNA. The exon-intron organization of the IL-11R gene (HGMW-approved symbol IL11RA) is consistent with the predicted structure of the different domains of the IL-11R alpha protein, confirming evolutionary conservation at the level of gene organization among the hematopoietic cytokine receptor family. The IL-11R gene has been assigned to chromosome 9 band p13 by in situ hybridization using human IL-11R alpha cDNA as a probe. The fact that the ciliary neurotrophic factor (CNTFR) gene has recently been localized on this same band and the conserved genomic structure between IL-11R and CNTFR suggest that they may have evolved from a common ancestor.

Base Sequence

Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer.

Seventy-two patients with advanced stage IIIB (42%) or stage IV (58%) non-small cell lung cancer (median age 57 years, Karnofsky PS 60-100) were treated with mitomycin C (6 mg/m2, day 1), ifosfamide (1500 mg/m2, days 1-3), and cisplatin (30 mg/m2, days 1-3) every 4 weeks. The objective response rate was 37% in the overall population; 50% in stage IIIB patients and 29% in stage IV patients. Twenty four patients achieved partial response (33%) and three patients achieved complete response. Despite this relatively high objective response rate, the overall median survival time was 32 weeks. The median survival was significantly better in stage IIIB patients (55 weeks) than in stage IV patients (25 weeks) (P = 0.003). MIP regimen was permanently suspended in 14 patients because of toxic events. Seventeen patients developed grade III or IV febrile neutropenia and two patients died from sepsis. Two patients experienced acute mitomycin peumonitis. Despite increased doses of cisplatin and ifosfamide, compared with the original description for MIC chemotherapy, with probably higher toxicity, no apparent increased response rate or median survival was observed in this study. The MIP regimen could be tested in a randomized trial in comparison with other administration plans in a comparable population.

Adult

A laboratory validation study of the diagnostic mode of the Autoset system for sleep-related respiratory disorders.

We performed a validation study of the diagnostic mode of the Autoset system (ResMed, Australia) on a group of 44 snorers (10 women). We compared the result of the Autoset's automatic analysis of nasal airflow (using nasal prongs) to those of an in-laboratory polysomnographic study with a Fleisch facemask pneumotachograph. For the first 29 patients, the Autoset software was set to recognize only apneas; for the remaining 15, the software was modified to recognize both apneas and hypopneas. Relative to polysomnography, the Autoset overestimated the number of apneas. Oral breathing or displacement of the nasal prongs partially explained these differences. A significant correlation was found between the apnea indices (AI) assessed by the two methods (r = 0.98). For an AI of 20/hour the Autoset was 100% sensitive and 88% specific. The Autoset significantly underestimated the number of hypopneas compared to the polysomnograph with pneumotachograph (62.9 +/- 4.7 vs. 85.5 +/- 73.1, P = 0.04), although for an apnea-hypopnea index of 20, Autoset was 100% sensitive and 88% specific. The lack of linearity of Autoset's volume evaluation at low volumes could explain most of the differences. Our results indicate that the Autoset system, in its diagnostic mode, is a useful tool for identifying patients with significant obstructive sleep apnea syndrome. The system is less useful in patients with mild to moderate sleep disordered breathing, where it may give erroneous results.

Adult

Multicentric epidemiological study of Aspergillus fumigatus isolates by multilocus enzyme electrophoresis.

The genotypes of 63 isolates of Aspergillus fumigatus obtained from three hospitals in different geographical areas and of eight culture collection strains were determined by multilocus enzyme electrophoresis. Twelve of the 17 enzymatic loci studied were polymorphic, giving rise to 48 different electrophoretic types. The existence of fixed multilocus genotypes, significant heterozygote deficits and excesses at the different loci, and linkage disequilibria within subpopulations strongly suggests a clonal reproduction mode for A. fumigatus. Numerical analysis of the comparison and disposition of the different electrophoretic types demonstrates a significant genetic differentiation between the three sampling sites. However, no correlation could be found between geographical distances and genetic differentiation. On account of the multiple discriminatory markers, multilocus enzyme electrophoresis typing seems to be a very powerful tool for epidemiological and reproductive mode studies of A. fumigatus.

Aspergillosis

Comparison of the new API Candida system to the ID 32C system for identification of clinically important yeast species.

API Candida was evaluated in comparison with the ID 32C system for the identification of 619 yeast isolates. The sensitivity of API Candida for the identification of the 15 species it claims to identify with and without additional tests was 97.4% (593 of 609) and 75.2% (458 of 609), respectively. The API Candida system is easy to use and rapid (result in 18 to 24 h).

Candida

Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer.

Myelosuppression is the major dose-limiting toxicity of chemotherapy in small cell lung cancer (SCLC). The capacity of colony stimulating factors (CSFs) to stimulate granular neutrophil recovery may be of great value to prevent or cure febrile neutropenia and to increase dose-intensity. The aim of this review was to assess the current use of CSFs in SCLC on the basis of experimental and clinical data. Primary CSF administration has been shown to reduce the incidence of febrile neutropenia, hospital admission rate, and antibiotic use subsequent to cyclophosphamidedoxorubicin-high dose etoposide (CDE) chemotherapy, without improvement of survival or disease control. Primary CSF administration may be recommended when the expected incidence of febrile neutropenia is at least 40%. This benefit has not been established with less myelosuppressive regimens, such as cisplatin-etoposide (PE), which remains an alternative combination of SCLC when standard doses are used. A trial comparing high-dose CDE + CSF with PE would be of considerable interest. There is currently little clinical basis for the use of CSFs to increase chemotherapy dose-intensity, outside clinical trials. Peripheral blood progenitor cells mobilized with CSFs offer interesting prospects. Further studies, with later initiation, shorter duration or lower doses of CSFs, are warranted to improve the cost-effectiveness of CSFs. CSF therapy in addition to antibiotics is normally not justified in febrile neutropenia, except perhaps in selected patients with sepsis syndromes, hypotension or pneumonia.

Antineoplastic Agents