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Biomedical subjects

F Clément

Publications and source records attributed to F Clément.

At least 37 records · Page 2Linked to original sources

Clonality of cold agglutinins in patients with hemolytic anemia: an analysis by high-resolution two-dimensional gel electrophoresis.

High-resolution two-dimensional gel electrophoresis (2-DGE) was used to analyse plasma samples and partially purified cold agglutinins (CA) obtained from two selected patients. Both presented an acute hemolytic anemia with CA of high thermal amplitude, normal immunoglobulin levels, no detectable paraproteinemia, and no clinical evidence of a malignant B-cell disorder. The electrophoretograms of their plasma showed evident alternations of the "normal" protein profile, which were directly related to hemolysis (absence of the spots of haptoglobin and in one case of those of hemopexin), but no monoclonal gammopathy. The electrophoretograms of their purified CA revealed two clearly different spot patterns respectively corresponding to a monoclonal IgM and to polyclonal IgM. These results show that the clonality of CA associated with hemolytic anemia can be easily determined by 2-DGE. This technique may be very useful to discriminate chronic cold agglutinin disease in the early phase from "parainfectious" CA.

Adult↗

[The treatment of acute lymphatic leukemia in adults: pilot project with intensive early therapy without a maintenance phase].

Acute lymphoblastic leukemia (ALL) is conventionally treated in three phases: remission induction, consolidation and maintenance. In adults initial remission rates of nearly 80% can be achieved. The 3 to 5 year leukemia free survival is 20 to 40%. Most relapses occur during maintenance, despite continuous therapy for 2 to 3 years. The value of maintenance therapy following intensive induction in adults is not documented. In this pilot study we treated 34 patients with ALL in five Swiss centers between 1986 and 1989 with intensive induction/consolidation therapy alone. Three induction/consolidation courses were applied: course I, 43 days, consisting of daunomycin, vincristine, prednisone, methotrexate, L-asparaginase and intrathecal CNS prophylaxis; course II, 6 days, consisting of high dose cytosine arabinoside and VP-16; course III, three non randomized arms, either allogeneic or autologous bone marrow transplantation (BMT) or high dose cyclophosphamide and repeated intrathecal therapy alone. 32 patients (94%) reached complete remission (CR): 24 after course I (71%), 7 after course II (cumulative 91%) and one after course III only (cumulative 94%). 3 patients had early, relapses before course III, 3 died of infection, and 2 of graft-versus-host disease. One patient had refractory leukemia in all three courses. 26 patients (76%) were in CR after completion of therapy. 16 relapsed within 1 to 17 months (median 5). 10 patients are free of disease after 10 to 44 months (median 24): 5 had had allogeneic BMT, 3 autologous BMT and 2 cyclophosphamide in course III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Genotypic and phenotypic evidence of T-cell leukemia in a patient successfully treated by interferon-alpha for typical hairy cell leukemia.

A 53-year-old man was diagnosed to have typical hairy cell leukemia. Immunophenotyping of frozen splenic tissue showed clonality of hairy cells for mu lambda, confirmed by the corresponding immunoglobulin gene rearrangements. The patient was successfully treated with interferon-alpha (IF-alpha). In the fifth year of treatment with IF-alpha the morphology of peripheral blood mononuclear cells (PBMC) and of bone marrow infiltration changed with the appearance of numerous small to intermediate shaped lymphocytes of a T-helper phenotype. Frank leukemia, resistant to IF-alpha treatment and ultimately aggressive chemotherapy, developed. Emergence of this second clonal disease was confirmed by rearrangement studies performed on PBMC; rearrangements of both alleles of the TCR beta were identified, whereas the JH and lambda IVS genes were in germline configuration. The outgrowth of a second, malignant T-cell clone paralleled by the disappearance (down-regulation?) of the initial B-cell clone while under cytokine treatment is consistent with the possibility that IF-alpha favoured the emergence of this second clone.

Bone Marrow↗

[Achondrogenesis. Ultrasonic diagnosis and clinical and anatomopathologic comparison].

The authors report two cases of achondrogenesis, the first of which was diagnosed in utero. Ultrasonographic abnormalities suggested the diagnosis, which was confirmed radiographically. The diagnosis of achondrogenesis in utero made it possible to avoid a Cesarian. It is always difficult to extract the malformed fetus. The histopathology findings make it possible to codify this rare type of congenital and lethal chondrodysplasia. Achondrogenesis is probably inherited in a recessive and autosomic fashion.

Achondroplasia↗

[Monoclonal gammopathies of undetermined significance called "MGUS"].

While the discovery of a monoclonal gammopathy in the blood of a patient sometimes leads to the diagnosis of multiple myeloma, immunocytoma or other B-cell lymphoproliferative syndromes, "secondary" monoclonal dysproteinemia is seldom considered. In most cases "monoclonal gammopathy of undetermined significance" (MGUS) is diagnosed. After ten years about 25% of these cases evolve to true multiple myeloma or Waldenström's disease. Other MGUS usually remain asymptomatic, though sometimes a complication such as amyloidosis or cryoglobulinemia may occur as a result of the "perverse" effect of the monoclonal protein. Some cases are described.

Aged↗

Restriction map of mycobacteriophage D29 and its deletion mutant F5.

A physical map of mycobacteriophage D29 was constructed, including positions for 25 restriction sites for 9 endunocleasic enzymes. D29 DNA contains about 48 150 bp. Analysis of a deletion mutant (F5) has allowed to determine the location of two non essential regions in the genome, allowing further insertion of foreign genes and construction of cosmids.

Chromosome Deletion↗

Methionine as methyl-group donor in the synthesis of Mycobacterium avium envelope lipids, and its inhibition by DL-ethionine, D-norleucine and DL-norleucine.

The radioactivity from 3H-methyl methionine was rapidly incorporated into the surface lipids of Mycobacterium avium. The transmethylation reaction was efficiently inhibited by DL-ethionine, D-norleucine and DL-norleucine. The structure of the outerlayer of the M. avium envelope was profoundly altered in the bacteria treated with DL-norleucine.

Cell Wall↗

[Distribution of bacteriophage types of Mycobacterium tuberculosis in France].

The bacteriophage typing of M. tuberculosis enables separation of the strains of the species according to their sensitivity to certain bacteriophages. A relationship has been observed between the geographical origin of patients and the distribution of the phage types of their strains. This study related to a sample of 450 strains isolated between 1978 and 1987 in patients of French origin coming from different regions in France. An analysis of the data provided by the study indicates that the distribution of the 5 phage types, A, AX, I, B, and C is relatively homogenous in the different regions with a predominance of the phage type A and B. The mean percentage of the lysotypes A, AX, I, B and C in the country as a whole are 43%, 15%, 7%, 30% and 5% respectively. Only in region 3 (Haute and Basse Normandie), 8 (Provence-Côte-d'Azur) and 9 (Rhône-Alpes) is there any perceptible deviation from this distribution. This study also underlines the contribution that can be provided by this type of information in the epidemiology of tuberculosis.

Bacteriophage Typing↗

Studies on clofazimine-resistance in mycobacteria: is the inability to isolate drug-resistance mutants related to its mode of action?

This study showed that clofazimine was not radiomimetic, it was not a mutagenic compound, it was not an inducer of prophage-lambda, and it did not eliminate plasmids from appropriate host bacteria. The drug caused an effective inhibition of the growth of Mycobacterium aurum, and also inhibited the growth cycle of the mycobacteriophage D29. Cross-resistance between clofazimine, streptomycin and rifampicin could not be demonstrated. Drug-resistance mutants towards clofazimine could not be isolated, and it was found that the existing clofazimine-resistant strains of Mycobacterium tuberculosis were rather susceptible organisms requiring clofazimine in their growth medium to maintain their drug-resistance. Ultrastructural studies showed that clofazimine did not act by cell wall lysis, nor did it act on bacterial ribosomes. Higher concentrations of the drug resulted in bacterial plasmolysis. These findings are discussed in the light of its known properties and proposed mode of action.

Clofazimine↗

Structure of the cell envelope of Mycobacterium avium.

In this report the cell wall of Mycobacterium avium is shown as a triple-layered structure where the outermost layer was stained by the ruthenium red staining for polysaccharides. The outermost layer hindered the diffusion of chemotherapeutic agents across the wall thus causing multiple drug-resistance by exclusion. The concerted electron microscopy and chemical analysis of chloroform-methanol and Triton X-100 extracts indicated that the outer layer was made of diverse amphiphil glycolipids (mycosides C, glycolipids, peptidolipids, phospholipids) that formed a matrix in which proteins were embedded. The examination of a spontaneous rough mutant indicated that mutations blocking the synthesis of one or several of the amphiphils must leave unsubstituted mycolic acid residues, thus causing surface hydrophobicity and roughness. Judging from our data, a model describing the overall cell envelope of M. avium was proposed. From the comparative analysis of M. avium, its spontaneous rough mutant, and its spheroplasts, some of the functions of the outermost layer were disclosed.

Antigens, Bacterial↗

[Propofol and thoracic surgery].

20 patients undergoing thoracic surgery were studied. Before anaesthesia either a catheter was placed in the intercostal space, at the same level as the thoracotomy (16 patients) or an epidural catheter was inserted if there was a contraindication of intercostal blockade (4 patients). Marcaine 0.5--was injected. Anaesthesia was induced with propofol 2.5 mg.kg-1, vecuronium 0.1 mg.kg-1, dextromoramide 50 mcg.kg-1. It was maintained with propofol 9 mg.kg-1.h-1 for 30 mn, then 4.5 mg.kg-1.h-1 for following hours (by a syringe pump) and vecuronium 0.1 mg.kg-1.h-1. Cardio vascular effects were studied only in the 16 patients with intercostal blockade: during induction bradycardia in 3 patients, and systolic arterial pressure (S.A.P.) decrease of 30% in 8 patients were observed. After the incision, heart rate and S.A.P. became steady. The average duration of anaesthesia was 214 min +/- 74. The time from the end of propofol infusion to the moment of extubation was 15.4 min +/- 33 and the time to recover all mental faculties was 46 mn +/- 11. 30 min after the end of anaesthesia the maxima minute ventilation was equal to the post operative value at 48 H. Propofol anaesthesia allows a fast awakening, without cumulative effects.

Anesthesia Recovery Period↗

[Treatment of multiple myeloma].

Multiple myeloma comprises widely varying clinical varieties of a more or less evolutive character. Establishment of an effective therapeutic plan requires inter alia an analytical study of tumor mass (stages) and cytokinetics. Thus, "indolent", "slow" or "aggressive" myelomas have been reported. 19 consecutive symptomatic patients (12 with stage II, 6 with stage III) have been treated, with overall 5-year survival of 42%. In the light of these observations and the recent literature it appears essential to adopt a flexible therapeutic approach which allows a rapid switch from simple chemotherapy to heavy polychemotherapy when necessary, or postponement of treatment or halting of chemotherapy under selected conditions.

Drug Therapy, Combination↗

Action of colistin (polymyxin E) on the lytic cycle of the mycobacteriophage D29 in Mycobacterium tuberculosis.

The antibiotic colistin (polymyxin E) inhibited the lytic cycle of the mycobacteriophage D29 in the tubercle bacilli, but not the D29 adsorption. The protein and nucleic acid synthesis in D29-infected bacteria were not affected significantly. The inhibitory activity was reversed by washing off the antibiotic, and by addition of Ca++, but not in media made iso-osmotic by addition of NaCl or sucrose. Transmission electron microscopy revealed an asymmetric to symmetric transition in the staining profile of the cytoplasmic membrane. Though no mature phage particles were ever observed in colistin-treated, D29-infected tubercle bacilli, loosely arranged aggregates resembling phage proheads were occasionally found. Judging from the above data, it was concluded that colistin inhibited D29 lytic cycle by causing molecular displacements in the inner leaflet of the cytoplasmic membrane, and consequently, the binding sites for D29 structural proteins were not available.

Adsorption↗