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Biomedical subjects

B Flageul

Publications and source records attributed to B Flageul.

At least 91 records · Page 5Linked to original sources

Study of 39 documented relapses of multibacillary leprosy after treatment with rifampin.

Among 39 strains of Mycobacterium leprae isolated from patients with multibacillary leprosy who relapsed after treatment with rifampin (RMP), 22 strains were resistant to RMP and 17 were susceptible. All of the RMP-resistant strains were recovered from patients who had been treated with more than 50 doses of RMP, usually given as monotherapy. RMP-susceptible strains were recovered from only six patients who had received more than 50 doses of RMP, and from 11 patients who had received no more than seven doses. The median time to relapse after the beginning of RMP therapy was 9 years (range 1-12 years) among the patients harboring RMP-resistant strains of M. leprae, and the median time to relapse after discontinuation of RMP treatment was 7 years (range 1-11 years) among the patients harboring RMP-susceptible strains. These data suggest that monotherapy with more than a few doses of RMP can be responsible for the emergence of RMP-resistant strains of M. leprae, thus emphasizing the need to employ RMP only in combination with other effective drugs in the chemotherapy of multibacillary leprosy.

Animals↗

Cutaneous and plasma values of von Willebrand factor in AIDS: a marker of endothelial stimulation?

Patients infected by the human immunodeficiency virus (HIV) represent a model in which endothelial proliferation and/or damage are of concern. We studied Von Willebrand factor (VWF) plasma values as a presumed marker of endothelial proliferation in patients with the lymphadenopathy syndrome (LAS) (n = 45), AIDS-related Kaposi's sarcoma (KS) (n = 23), and AIDS opportunistic infections (n = 9), in comparison with normal controls (n = 19) and classical KS (n = 12). VWF was increased in AIDS patients with KS (p less than 10(-6)), in AIDS patients without KS (p less than 10(-7)), and to a lesser extent in classical KS (p less than 10(-3)) and LAS (p less than 10(-2] patients. To evaluate the diffusion of the vascular proliferation in HIV-infected patients, we studied the number of vessels within the superficial dermis of clinically uninvolved skin by an indirect immunoperoxidase method. We used an antibody directed against VWF in skin biopsies from 20 LAS patients and 10 AIDS-related KS patients compared to 11 controls and 10 classical KS patients. An increase in the number of blood vessels in normal skin was found in LAS (p less than 10(-2)), classical KS (p less than 0.05), and AIDS-related KS (p less than 10(-2]. Statistical studies and comparisons between plasma and cutaneous values of VWF indicate that plasma VWF is a good marker of endothelial damage but a poor marker of vascular proliferation in HIV-infected patients.

AIDS-Related Complex↗

Primary and secondary dapsone resistance of M. leprae in Martinique, Guadeloupe, New Caledonia, Tahiti, Senegal, and Paris between 1980 and 1985.

Primary and secondary dapsone resistance were studied among lepromatous patients living in Martinique, Guadeloupe, New Caledonia, Tahiti, Senegal, and Paris. Four hundred fifteen biopsies were taken from clinically active and bacteriologically positive (bacterial index greater than 2) patients in the 6-year period of 1980-1985. Among these, 280 biopsies that contained 5 x 10(4) acid-fast bacilli per ml with a morphological index of at least 0.10 were inoculated into the mouse foot pad, and 229 harbored infective Mycobacterium leprae. Among the 129 infective M. leprae isolated from new cases, 54% had some degree of dapsone resistance, a low degree being prominent in all cases. Among the 100 infective M. leprae isolated from relapsed cases, 79% had a high or an intermediate degree of dapsone resistance. The annual incidence of secondary dapsone resistance was estimated to be about 0.55% in Guadeloupe.

Dapsone↗

M. leprae and PPD-triggered T cell lines in tuberculoid and lepromatous leprosy.

Proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and bacillus Calmette Guerin-derived purified protein derivative (PPD) were studied in the presence or absence of interleukin 2 (IL 2) in high M. leprae responders (tuberculoid leprosy patients and healthy subjects) and low M. leprae responders (lepromatous leprosy patients). High responders in most cases developed a strong proliferative response to both antigens in the absence of IL 2. Additional IL 2 and restimulation with antigen plus autologous antigen-presenting cells (APC) allowed the derivation of antigen-specific T cell lines. The lines were assayed for proliferative responses to several mycobacterial antigens. Both PPD and M. leprae-triggered T cell lines exhibited a good proliferative response to either antigen and showed in addition a broad cross-reactivity with other mycobacteria, suggesting a preferential T cell response to epitopes shared by several mycobacterial species. Within the lepromatous group, 50% of the patients studied could mount a proliferative response to PPD antigen in the absence of IL 2, but none of them was able to do so with M. leprae antigen. The addition of IL 2 increased the number of positive responders to PPD in this group, and in some patients IL 2 was able to restore M. leprae reactivity as well, suggesting that IL 2 had overcome a suppressor mechanism. PPD and M. leprae-triggered T cell lines were obtained from these subjects (with IL 2 added from the beginning of the culture when required). M. leprae lines exhibited variable and unstable pattern of specificity, most lines exhibiting, at least transiently, a cross-reactive response to other mycobacteria, but some displaying only M. leprae-specific response. In contrast, PPD lines from these subjects consistently exhibited a good response to PPD, a lesser response to various other mycobacteria and no response to M. leprae, a pattern differing from that obtained with PPD lines of high M. leprae responders. Co-cultures of irradiated lepromatous PPD triggered T cell lines with fresh autologous PBMC non-specifically reduced the proliferative response of the latter to PPD, as well as to unrelated antigens. A similar suppression was also observed when PPD lines from one of the tuberculoid patients were assayed. PPD and M. leprae T cell lines from both high and low responders initially exhibited the same CD4+ CD8- phenotype. In all cases, antigenic specificity declined and could not be maintained after 5 to 8 wk of continuous culture, a change associated with the progressive appearance of CD8+ and Leu8+ cells.

Antigens, Surface↗

Captopril-induced lichen planus pemphigoides with pemphigus-like features. A case report.

We report a case of a bullous lichenoid eruption due to the intake of captopril. Clinical, histological, direct immunofluorescence and ultrastructural features were consistent with the diagnosis of lichen planus pemphigoides. In addition, the in vivo immunological study also revealed an intercellular fluorescence, similar to that seen in pemphigus. Complex drug-induced cutaneous reactions have been previously reported with other drugs, especially with D-penicillamine, which bears chemical similarities with captopril. However, such a drug-induced mixed pattern of lichen planus pemphigoides with pemphigus-like features has never been reported.

Autoantibodies↗

Antibodies to phenolic glycolipid-1 and to whole Mycobacterium leprae in leprosy patients: evolution during therapy.

Sera from 92 patients were tested by the ELISA method for the presence of IgM antibodies to phenolic glycolipid-1 (PGL-1) of Mycobacterium leprae, and of both IgM and IgG antibodies to the whole M. leprae bacillus. All untreated lepromatous patients exhibited high antibody levels in all three assays. A sharp decline of IgM antibodies to PGL-1 and whole M. leprae was observed during the first two years of therapy, while IgG antibodies to whole M. leprae showed a progressive decrease only over a number of years. Low titers of IgM antibodies to PGL-1 and IgG antibodies to whole M. leprae could be detected in about 50% and 75% of patients, respectively, after more than ten years of treatment, with only 15% showing persisting IgM antibodies to the whole bacillus. Antibody levels as measured by the three assays used were correlated with the bacterial index in patients treated for less than four years. In patients treated longer than four years, only IgM antibodies, whether directed to PGL-1 or to whole M. leprae, remained correlated to the bacillary load. Tuberculoid patients exhibited a different antibody pattern, showing a lower frequency (and lower levels) of antibodies of PGL-1 and of IgG antibodies to whole M. leprae than lepromatous patients, and no detectable IgM antibodies to the whole bacillus. IgG antibodies to whole M. leprae were more frequently noted than antibodies to PGL-1, the latter declining more rapidly during therapy.

Antibodies, Bacterial↗

Specificity study of PPD-reactive human T cell line and clones.

Peripheral blood mononuclear cells from a PPD-sensitive human subject, in vitro stimulated by PPD, could be maintained for several weeks in interleukin 2-containing medium, with regular reactivation with PPD and irradiated autologous mononuclear cells used as antigen-presenting cells. The proliferative response of this T cell PPD-reactive bulk culture could be stimulated to proliferate by PPD itself as well as by BCG and other mycobacteria. This T cell line comprised a majority of T cells expressing the OKT4+, OKT8- phenotype, and a minor proportion of T cells (8%) showing the OKT4-, OKT8+ phenotype. Two PPD-reactive clones, both OKT4+, were obtained from this line by the limiting dilution technique. Clone C9 was found to be highly specific of PPD and BCG, whereas clone A9 could be activated by four other species of mycobacteria. These data demonstrate the existence of species-specific and cross-reactive epitopes within PPD and prompt for the use of PPD-reactive clones as a tool for identification and purification of the molecules bearing these epitopes.

Cell Line↗

The cellular content of dermal leprous granulomas: an immuno-histological approach.

An indirect immunofluorescence technique with monoclonal antibodies has been used to identify T cells, T helper cells, T suppressor cells, and granulocytes in the dermal granulomas of 22 patients with leprosy. In tuberculoid leprosy, T helper cells predominated and T suppressor cells were located at the periphery of well-circumscribed granulomas. In lepromatous leprosy, the two subsets of T cells were numerous in treated patients. In ENL lesions, T cells were more numerous and T helper cells predominated. Enumerations of the T cell subsets in the dermis and in the blood showed similar changes, but these changes were quantitatively more marked in the dermal granulomas.

Adolescent↗

In vitro proliferative response to M. leprae and PPD of isolated T cell subsets from leprosy patients.

In vitro proliferative response to Mycobacterium leprae and PPD to T cell subsets, isolated by selective depletion procedure from peripheral blood using OKT4 or OKT8 monoclonal antibodies plus complement, was investigated in leprosy patients. Whole peripheral blood mononuclear cells (PBMC) developed a strong proliferative response to both M. leprae and PPD in most tuberculoid patients. This proliferation was confined to T cells, and concerned predominantly OKT4+ cells. Both antigens, however, induced a smaller, but significant proliferation oF OKT8+ cells. In lepromatous patients, proliferative response of whole PBMC incubated with M. leprae was in most cases unsignificant, at variance with PPD-induced proliferation, which was not significantly lower than that of PBMC from tuberculoid patients. In a majority of M. leprae non-responders, neither OKT4+ nor OKT8+ enriched PBMC developed a proliferative response to M. leprae. Unexpectedly in four M. leprae unreactive patients, control treatment of PBMC with complement alone restored a strong proliferative response to M. leprae. Taken together, these results suggest that in vitro unresponsiveness to M. leprae results at least in some patients, from an active suppressor mechanism but that the effector phase of such suppression does not directly involve OKT8+ T cells.

Adolescent↗

Mycobacterium leprae-reactive T-cell clones isolated from polar lepromatous and tuberculoid leprosy patients.

T-cell clones capable of mounting a proliferative response to Mycobacterium leprae were obtained in three leprosy patients (two polar lepromatous and one polar tuberculoid) either from M. leprae-activated or from protein-purified derivative-activated polyclonal T lymphoblasts. All these clones expressed the CD4 surface marker. Some of them proliferated to the antigen only in the presence of interleukin-2. A majority expressed cross-reactive responses to other mycobacteria. Clones obtained from the lepromatous patients did not differ in any of these features from those obtained from the tuberculoid patient. M. leprae-reactive clones obtained from one lepromatous patient displayed strong antigen-specific cytotoxicity toward autologous antigen-coated target cells. This phenomenon was not observed for any clone of the other lepromatous patient and was seen only for one clone in the tuberculoid patient.

Antigens, Bacterial↗

Anti-phenolic glycolipid-I (PGL-I) determination using blood collection on filter paper in leprosy patients.

The authors studied 70 leprosy patients and 20 normal individuals, comparing the traditional sera collection method and the finger prick blood with the conservation on filter paper for specific antibodies against the native phenolic glycolipid-I (PGL-I) from Mycobacterium leprae. The finger prick blood dried on filter paper was eluated in phosphate buffer saline (PBS) containing 0.5% gelatin. The classical method for native PGL-I was performed for these eluates, and compared with the antibody determination for sera. It was observed that there is a straight correlation comparing these two methods; although the titles found for the eluates were lower than those obtained for serology. This blood collection method could be useful for investigation of new leprosy cases in field, specially in contacts individuals.

Adolescent↗

[Lichen pemphigoid associated with developing hepatitis B in a child].

INTRODUCTION: Lichen planus pemphigoides is a rare acquired auto-immune bullous dermatosis which usually affects adults. Only four cases have been reported in children. We describe a new case of lichen planus pemphigoides in a child unusual by its association with an evolutive hepatitis B and by the occurrence of a lichen planus relapse. CASE REPORT: A 10-year-old African boy has been seen for a pruritic dermatosis with papular lichenoid lesions on the trunk and the limbs and blisters on the lower limbs, both arise on lichen planus lesions and normal skin. The diagnosis of lichen planus pemphigoides was confirmed by histology which showed the features of lichen planus on a papule and of a sub-epidermal split on a bulla and by direct and indirect immunofluorescent studies which revealed an IgG and C3 linear deposit at the dermo-epidermal junction and the presence of circulating IgG anti-basement membrane zone antibodies. Laboratory investigations showed an evolutive hepatitis B (HBsAg +). Healing was obtained by dapsone and topical steroid therapy. Eight months after withdrawal of treatment the patient presented a non-bullous relapse of lichen planus. The histology showed a typical aspect of lichen planus and the immunofluorescence studies were negative. The hepatitis B serology was unchanged. The lesions rapidly improved with topical steroid and coaltar. One year later the patient exhibited few slight lichen planus lesions on the limbs and the hepatitis B serology showed the onset of sero-conversion. DISCUSSION: Lichen planus and lichen planus pemphigoides are probably variants of the same disease. Their successive occurrence in our case report favours this hypothesis as does the association with an hepatitis B.

Administration, Cutaneous↗