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Biomedical subjects

A Guerci

Publications and source records attributed to A Guerci.

16 recordsLinked to original sources

All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases.

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course ("4 + 7" course), then three "2 + 5" DNR + Ara C courses and maintenance chemotheapy. However, the "4 + 7" course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the "4 + 7" course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the "4 + 7" course. Four patients did not receive this course but received the subsequent "2 + 5" courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis

Acute haematogenous osteomyelitis of the patella revealed by a pathological fracture in multiple myeloma.

A 57-year-old man was followed up for multiple myeloma with no lytic bone lesions. During a septicaema, he presented with a pathological fracture of the patella. Despite a poor haematological status, he received surgical treatment, which allowed diagnosis of haematogenous osteomyelitis of the patella. The outcome was favourable, with a 6-week plaster immobilization after cerclage and 4 months of intravenous antibiotic therapy. This case emphasizes the fact that one well-known cause of bone lesions may lead to an erroneous diagnosis. The successful clinical course suggests that accurate therapeutic management may be discussed in haematological malignancies when intensive-care support is available.

Acute Disease

Flow cytometric analysis of the cell cycle in chronic gastritis.

Flow cytometric cell cycle analysis was recorded in gastric biopsy specimens from patients with normal gastric mucosa (GM), superficial gastritis (SG) and chronic atrophic gastritis (CAG). Cell-cycle analysis showed significantly higher percentages of cells in S- and S+G2/M-phase in CAG than in SG and normal GM (P < 0.0001). Moreover, CAG with severe or moderate atrophy showed significantly higher percentages of cells in S-phase (P < 0.05) and S+G2/M-phase (P < 0.02) than CAG with mild atrophy in antrum. In fundus, even if this increase was observed, it did not reach statistical significance. Consideration of concomitant pathologic findings such as oesophagite, gastric or duodenal ulcer, duodenite or benign polyp allowed a better differentiation of CAG both in antrum and in fundus. Significantly higher S-phase was observed in CAG with severe or moderate atrophy than in CAG with mild atrophy (P < 0.05). No statistically significant results were observed in patients with normal gastric mucosa or chronic gastritis and a concomitant pathologic finding.

Cell Cycle

Time-variations of pretreatment peripheral blood S + G2/M-phase size determined by flow cytometry in adult acute myeloid leukaemia.

The circadian and seasonal variations of pretreatment proliferative activity of peripheral blood (PB) as PB S + G2/M-phase size was determined by flow cytometry in 61 adult patients with acute myeloid leukaemia (AML). Pretreatment PB S-phase (p less than 0.002), G2 + M-phase (p less than 0.008) and S + G2/M-phase size are statistically correlated to the time of sampling, with the highest phase size at the end of the day. Time-variations of the blast cell count are slightly significant (p = 0.049). Cytological diagnosis-related differences in S + G2/M-phase (p less than 0.003) and white blood cell count (p less than 0.04) time-variations are observed. For all patients, no seasonal variations can be drawn, but in AML 1 (p less than 0.029) and AML 4-5 patients (p less than 0.003), the circadian variations of S + G2/M are affected by the seasons. The present results suggest that time may be taken into account in the monitoring of chemotherapy in acute leukaemia.

Adult

Prognostic significance of peripheral blood S + G2/M phase size in adult acute non-lymphoblastic leukaemia.

Flow cytometric analysis of peripheral blood (PB) S + G2/M phase size was performed in 73 adult patients with untreated acute non-lymphoblastic leukaemia, to assess whether the results may correlate to response rate and patient prognosis. All patients were treated with the same induction chemotherapy regimen: ARA-C alone or in combination with an anthracycline antibiotic. Pretreatment PB S + G2/M phase size is significantly correlated to induction response rate (p less than 0.02), duration of response (p less than 0.02) and duration of survival. Patients with low PB S + G2/M phase size experience a longer survival, in patients over and below 50 yr (p less than 0.001). Lastly, early deaths tend to be more frequent in the high median age and high PB S + G2/M phase size group. Our study suggests that PB S + G2/M phase size has prognostic significance in obtaining response and duration of survival.

Adult

Flow cytometric analysis of DNA content differences in blood samples obtained by leucoconcentration.

The leucoconcentration technique allows rapid obtainment of cellular suspensions from total blood or bone marrow for flow cytometric analysis. The technique is based on picric acid in ethyl alcohol fixation and saponin red cell lysis, followed by mithramycin staining for DNA. It gives a good resolution of DNA distributions that allow detection of slight variations in DNA content. These results were obtained with cellular suspensions differing only in one X or Y chromosome (male, female, Klinefelter and Turner syndromes). In these studies the ratio of the DNA content of X and Y chromosomes agrees with the chromosomal mass ratio already reported by other authors, but the "absolute values" are 10-fold more compared to these same works. Our conclusion is that leucoconcentration technique followed by DNA staining with mithramycin increases the difference in the dye's penetration and binding between X and Y chromosomes.

DNA

[Flux cytometry of the cellular cycle of leukemic cells of the blood].

The coordination of flux cytometry and of a techniques of leukoconcentration allowed to determine the cellular cycle of nucleated cells of circulating blood, without logs nor enrichment of cellular type on a definitive moment. The study of acute leukemias allow to conclude that: 1) it exists in peripheral blood a synthetic activity of ADN bound to the presence of leukemic or blastic cells; 2) this activity allows to appreciate the spontaneous variations of synthesis and the incidence of chemotherapy.

Adult

Technique and staining optimization leucoconcentration.

In cytometric clinical application, it is important to obtain cell suspensions rapidly with as little cytological alteration as possible. A procedure has been achieved to prepare cell suspensions for flow cytometric analysis. The leucoconcentration technique, first described by Herbeuval for cytologic analysis, has been modified to be applied in cytometry. This technique involves Saponin lysis of red cells of peripheral blood or bone marrow samples that have been previously fixed with picric acid alcohol solution. Cells in suspension are not shifted and tinctorial affinity is not modified. Then cells have been stained with Mithramycin. Each parameter defined by Crissman has been analyzed to define the best staining conditions. The availability of Leucoconcentration with Mithramycin-DNA-staining permits determination of cell cycle with a fine resolution.

Bone Marrow Cells

Schwann cell marker defined by a monoclonal antibody (224-58) with species cross-reactivity. I. Cellular localization.

We have demonstrated by indirect immunofluorescence the cellular localization of a monoclonal antibody (mAb 224-58), produced after immunization of a mouse with human central nervous system (CNS) myelin. Serologically, mAb 224-58 was found to be specific for 3'-sulfomonogalactosylglycolipids, namely 3'-sulfogalactosylceramide (SGC) and 3'-sulfogalactosyl 1-O-alkyl ether 2-O-acylglycerol (seminolipid). This mAb did not bind to SGC-containing tissues such as kidney, liver, spleen, or brain, nor to muscle. However mAb 224-58 did stain positively mouse, rat, and human peripheral nerve sections. In these latter sections, mAb 224-58 was bound to Schwann cell bodies and processes. The specificity of mAb 224-58 for Schwann cells was ascertained on teased rat sciatic nerves and rat Schwann cell cultures. Cells positive for mAb 224-58 were also positive for laminin, and negative for Thy 1-1 antigens both in teased fibers and Schwann cell cultures. In addition, in teased nerve preparations, mAb 224-58-positive cells were also galactosylceramide (GalC)- and SGC-positive. Isolated Schwann cells also expressed 224-58 antigen, even after prolonged time in culture. On testis sections, which contain both SGC and seminolipid, the SGC-positive cells, i.e., the spermatogonia, were always 224-58-negative. But the other germinal cells were 224-58-positive. This suggests that although 224-58 does not discriminate between SGC and seminolipid in serological tests, these lipids in their naturally occurring membrane acquire a spatial configuration that renders them distinguishable to their respective antibody.

Animals

Schwann cell marker defined by a monoclonal antibody (224-58) with species cross-reactivity. II. Molecular characterization of the epitope.

A monoclonal antibody (mAb) designated 224-58 (IgM-kappa) has been raised by fusion of Sp2/0-Ag14 mouse hybridoma cell line with spleen cells of a mouse immunized with human brain myelin. This mAb binds specifically to mouse, rat, and human Schwann cells membrane. Serological tests showed that mAb 224-58 reacted with total lipid extract, but not with total protein extract of human myelin. Combination of ELISA, complement fixation, and immunoautoradiographic detection on silica gel TLC allowed us to determine that mAb 224-58 reacted with sulfomonogalactolipids, namely 3'-sulfogalactosylceramide (SGC) and 3'-sulfogalactosyl 1-O-alkyl-ether 2-O-acylglycerol (seminolipid). The fine molecular structure of the epitope recognized by mAb 224-58 was established by studying the cross-reactivity of this mAb toward closely related sulfolipids and by comparing its reactivity after submitting either purified sulfolipids or total lipid extracts to various chemical and enzymatic treatments. The lipidic hapten-binding site to mAb 224-58 is dependent on (1) the sulfoester on carbon 3 of the galactose molecule, (2) the osidic bond, and (3) the carbonyl group of the fatty acid. Interestingly enough, neither the amide bond and the long-chain base nor the OH group of the fatty acid belongs to the antigenic determinant recognized by mAb 224-58.

Animals

Depigmenting procedures and drugs employed by melanoderm populations.

The "fashion" of lightening the skin represents a very serious problem because it involves the melanoderm populations, not only in Africa, but in the world, undermining their physical integrity and psychological equilibrium. The diffusion of the skin-whitening practice is much more intense in the areas where there are inter-relations between Blacks and Whites. Among the drugs used, mercury prevails under the form of biioduro salts in aseptic soaps; hydroquinone taken in form of per os pills, and cortisoides. The resource of using traditional skin-bleaching plants seems frequent, but the information we tried to gather from informants has been very scarce.

Africa

[1 alpha 25-dihydroxyvitamin D3 (calcitriol) and malignant hemopathies. Decreased serum levels in acute leukemia: preliminary results].

We used the Amersham radioimmunological method to measure plasma 1 alpha 25-dihydroxyvitamin D3 (calcitriol) levels in patients presenting with one of the following diseases: (i) non-acute myelodysplastic syndrome (39 cases); (ii) acute myeloid leukaemia in blastic phase (43 cases) or in complete remission (15 cases) and (iii) acute lymphoid leukaemia in blastic phase (11 cases). All patients had normal metabolic functions. Compared with our standard laboratory values (15-35 pg/ml), the results of these assays were related to the type of pathology or, in patients with acute myeloid leukaemia, to the stage of the disease (p less than 0.001). Moreover, the mean plasma calcitriol values differed according to the type of pathology (p less than 0.003). Patients with acute myeloid leukaemia in blastic phase had a low level of calcitriol as compared with controls (p less than 0.05) and with patients with acute myeloid leukaemia in complete remission (p less than 0.001) whose calcitriol levels were never low. In contrast, there was no significant difference between controls and patients with myelodysplastic syndrome or acute lymphoid leukaemia in blastic phase. This study demonstrates the usefulness of plasma calcitriol assays in malignant blood diseases where low values in certain types of leukaemia would incite to include calcitriol in therapeutic regimens.

Acute Disease

[Realization of an assisted system for medical decision and follow-up in hematologic diseases treated with sequential chemotherapy].

The follow-up of patients treated with sequential chemotherapy in internal medicine departments with special interest in haematology imposes a heavy burden on the entire treating staff. The chances of errors, notably in medical prescriptions and care, are not negligible, and these errors result in iatrogenic complications, readmissions and prolonged stays in hospitals. Designing a medical decision and therapeutic follow-up aid system should be time-saving for the staff and ensure good quality and safe prescriptions as well as reliable therapeutic evaluations and better hospital management. The system described here is developed on 4D Macintosh computer which handles a relational data-base. It includes the data-base, i.e. a knowledge-based system devised by the expert clinician containing "declarative" data and deduced rules which represent the expert's reasoning and determine the action to be taken, and the interface between them. The system easily accepts many parameters, thereby enabling medical knowledge and therapeutic attitudes to be updated.

Decision Making, Computer-Assisted