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Biomedical subjects

B Leng

Publications and source records attributed to B Leng.

At least 55 records · Page 3Linked to original sources

Improving the cytogenetic response to interferon alpha by zidovudine (AZT) in an HIV-positive chronic myelogenous leukemia patient.

An asymptomatic HIV-positive patient with Philadelphia chromosome positive chronic myelogenous leukemia (CML) was treated by interferon-a (IFN-a) for four years. A sustained hematological response and major cytogenetic response were achieved. However, a complete cytogenetic remission (100% Ph-negative cells) was observed when zidovudine (AZT) was introduced as treatment for HIV-related immunodepression. Moreover, this complete cytogenetic remission was confirmed by quantitative PCR showing decreased BCR-ABL rearrangement at very low level. As, there are some in vitro reports demonstrating a synergistic antiproliferative effect of IFN-a and zidovudine, we discuss the possibility of synergistic effects between AZT and IFNa in the treatment of CML.

Adult↗

[Rheumatoid purpura in adults. Apropos of 40 cases].

Fourty cases of Henoch-Schönlein purpura in adults (21 females, 19 males--age 39 years) are reviewed [departments of nephrology (28 cases) and internal medicine (12 cases)]. Dermatological manifestations occur in 39 cases and are similar to those seen in children. Gastrointestinal involvement (23 cases) usually takes the form of abdominal pains or diarrhea; gastrointestinal haemorrhages are rare. These symptoms are less severe than in children in this review as in the literature. Joint manifestations (22 cases) disappear without sequelae. The outcome of the disease depends on the nephropathy, present in 33 patients (82.5%) (all of those of the department of nephrology (100%) and 42% of those of the department of internal medicine). In one third of cases, renal manifestation appears after the onset of the disease (until 24 months). As in the children, haematuria and proteinuria are quasi constant. The renal histopathology is a focal and segmental proliferative glomerulonephritis in 58%, with IgA deposition in the mesangium (16/21 cases). Treatment regimen includes steroïds (10 cases), combination of steroïds with immunosuppressive agents (8 cases), steroïds-immunosuppressive drugs-plasma exchange (2 cases), dapsone (1 case). Of the 26 patients followed for 27 months, 11 are in clinical remission, 7 have persistent proteinuria or hematuria, and 8 have chronic renal failure after 3 months to 13 years. In this review, renal insufficiency, hypertension and young age predict a poor outcome. This severe outcome is probably explained by the fact that most of our patients referred to renal units. Unlike in the children, in which the affection is usually an acute illness, Henoch-Schönlein purpura in the adults seems to be a chronic disease, with prognosis depending on the nephropathy.

Adolescent↗

The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene.

To investigate the effects of selenium or beta-carotene supplementation in human immunodeficiency virus (HIV)-infected patients, who are known to have deficiencies of selenium and vitamin A, we evaluated the blood enzymatic antioxidant system, including superoxide dismutase (SOD), selenodependent glutathione peroxidase (GPX), and catalase (Cat); glutathione (GSH) status; and plasma selenium concentration. The placebo group consisted of 18 HIV-infected patients with no supplementation, the selenium group was composed of 14 patients receiving oral selenium treatment, and the beta-carotene group comprised 13 patients receiving oral beta-carotene supplementation. All groups were studied for 1 y. At the beginning of the study, a significantly higher SOD activity (P < 0.001) was observed in all HIV-infected patients compared with uninfected control subjects, and GPX activity at baseline was higher in the placebo (P < 0.004) and selenium (P < 0.014) groups than in the control subjects. These higher enzyme activities could be related to an increased synthesis of these enzymes in erythrocyte precursors under oxidative stress. Moreover, we observed significantly lower GSH values in all HIV-infected patients than in control subjects at the beginning of the study (P < 0.001). After selenium or beta-carotene supplementation, no significant difference was observed for SOD activity compared with baseline. On the contrary, GPX activity increased significantly after selenium treatment (P < 0.04 between 3 and 6 mo), whereas a slight increase was found after beta-carotene treatment. Similarly, a significant increase in GSH values was observed at 12 mo compared with baseline both after selenium supplementation (P < 0.001) and beta-carotene supplementation (P < 0.01). Because GPX and GSH play an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water, selenium supplementation could be of great interest in protecting cells against oxidative stress. The lower efficiency of beta-carotene could be attributed to the seriousness of the pathology at the time of recruitment into the beta-carotene group.

Acquired Immunodeficiency Syndrome↗

Activity of rifabutin, clarithromycin, ethambutol, sparfloxacin and amikacin, alone and in combination, against Mycobacterium avium complex in human macrophages.

Disseminated infection with Microbacterium avium complex (MAC) in patients with AIDS is currently treated with a combination of antimycobacterial agents in order to prevent the selection of resistant mutant strains. Although clinical and microbiological responses can generally be achieved within a few weeks, relapses are common and require modification of the combination regimen or identification of effective alternate therapies. In this study we investigated the activities of rifabutin 0.5 mg/L, sparfloxacin 1 mg/L, clarithromycin 4 mg/L, amikacin 16 mg/L and ethambutol 2 mg/L, alone and in combination, against nine strains of M. avium isolated from the blood of patients with AIDS in order to identify regimens with the greatest therapeutic potential. Macrophages derived from human monocytes were infected with M. avium and inoculated with a single drug or a combination of drugs; cfu counts were performed at 0, 4 and 7 days after infection. At day 4 and at day 7, the combination of rifabutin, clarithromycin, amikacin and sparfloxacin displayed the highest degree of activity. However, the activity did not differ significantly from that of the combination of rifabutin, clarithromycin and ethambutol. The results of this study confirm the activity of combinations including rifabutin and clarithromycin (+/- ethambutol) in human monocyte-derived macrophages and suggest potentially useful associations in incorporating sparfloxacin and amikacin.

Amikacin↗

Comparative uptake of sparfloxacin and ciprofloxacin into human THP 1 monocytic cells.

The uptake of sparfloxacin (CAS 11542-93-9) by human monocytes was studied by comparison with ciprofloxacin (CAS 86393-32-0). The human monocytic THP 1 cells were incubated with the antibiotics for 2 h. Entry of antimicrobials into the cells was determined by means of a velocity gradient centrifugation technique and HPLC assay. Antibiotic uptake was expressed as the ratio of the intracellular to the extracellular drug concentration (IC/EC). Quinolones enter readily in monocytic cells but sparfloxacin is taken up more rapidly than ciprofloxacin. At steady-state the IC/EC ratio of sparfloxacin (9.07) is higher than IC/EC of ciprofloxacin (4.29). Characterization of quinolone uptake suggests that these drugs penetrate throughout the THP 1 membrane by passive diffusion. However, the results of the present study indicate that additional mechanisms may contribute to intracellular accumulation of ciprofloxacin and sparfloxacin. Gemfibrozil, an inhibitor of organic anion transport, increases the accumulation of ciprofloxacin but does not modify IC/EC of sparfloxacin. It can be concluded that human monocyte-like cells have functional organic anion transporters and that this way of secretion is quinolone selective.

Anti-Infective Agents↗

[Pseudolymphoma induced by carbamazepine. Apropos of 2 cases].

We present two pseudolymphoma occurring 8 days and 1 month after carbamazepine introduction. Both patients present fever, rash, generalized lymphadenopathy and hepatosplenomegaly in the second case. Hematologic abnormalities included anemia, eosinophilia, hepatic cytolysis. Histologic evaluation of a lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture mimicking a lymphoma. Gene rearrangement studies proved the benign nature of the proliferation. Carbamazepine-induced lymphoproliferative disorders are relatively rare with only 38 observations published. The pathogenesis is uncertain. Immune dysregulation is probable. Morphologic and immunophenotypic data must be completed by gene rearrangement studies. Corticoid therapy is useless. The evolution is favorable after the cessation of carbamazepine.

Adult↗

Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides.

Malondialdehyde (MDA), a peroxidative end-product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA-modified proteins may exist in systemic diseases, and that autoantibodies to MDA-modified structures might reflect this oxidative process. Autoantibodies to MDA-modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA-modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0.702, P = 0.0001), anti-nuclear antigen autoantibodies (ANA, r = 0.4, P = 0.029), IgG anti-cardiolipin (r = 0.558, P = 0.03) and the steroid drug regimen (r = 0.52, P = 0.004). Autoantibodies to MDA-modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.

Adult↗

Detection of Toxoplasma gondii by PCR and tissue culture in cerebrospinal fluid and blood of human immunodeficiency virus-seropositive patients.

To investigate whether both tissue culture and PCR on a sequence from the repetitive rDNA could contribute to the diagnosis of toxoplasmosis, blood samples and, if they were available, cerebrospinal fluid (CSF) and aqueous humor samples from 72 human immunodeficiency virus-seropositive patients with suspected toxoplasmosis were prospectively tested. For 10 patients with fever of unknown origin but without confirmed toxoplasmosis, no Toxoplasma gondii was detected. For two patients with confirmed toxoplasmic uveitis, only PCR of aqueous humor samples was positive. Of 60 patients (48 with CSF samples) with neurological signs, 25 (from 13 of whom CSF samples were available) had confirmed cerebral toxoplasmosis and 10 had a positive PCR of CSF and/or blood samples, while for 1 patient culture of the CSF sample was also positive. Unlike tissue culture, PCR of rDNA is of value for the detection of cerebral toxoplasmosis in human immunodeficiency virus-seropositive patients, provided that both CSF and blood samples are available (sensitivity, 76.9%; specificity, 100%).

Adolescent↗

Asymptomatic atherosclerosis in HIV-positive patients: A case-control ultrasound study.

Atherosclerosis has been reported in some HIV-positive subjects without any known risk factor. The purpose of the present study was to investigate cervical arteries, abdominal aorta and femoral arteries by B-mode ultrasonography and doppler in 30 HIV-positive subjects matched to 18 controls for sex, age, tobacco consumption and arterial hypertension. Although no haemodynamically or clinically relevant lesions were found, plaques occurred more often in patients than in controls (11 patients, 36.7% vs. 2, 11.1%; P = 0.05). Compared to the HIV-positive patients without plaques, those with plaques had a tendency to have decreased lower HDL cholesterol, higher tobacco consumption and lower CD4-cell count (77 +/- 85/mm3 vs. 220 +/- 202/mm3). The patients with plaques (but not those without plaques) had lower HDL cholesterol than controls (P = 0.03). Asymptomatic atherosclerosis seems to be more frequent in HIV-positive patients and is associated to lower HDL cholesterol.

Adult↗

[Primary prophylaxis against cerebral toxoplasmosis. Efficacy of folinic acid in the prevention of hematologic toxicity of pyrimethamine].

OBJECTIVES: Cerebral toxoplasmosis is the most frequent opportunistic infection in patients with acquired immune deficiency syndrome in France. We evaluated the effect of adding folic acid to the standard treatment (including pyrimethamine) on preventing induced cytopenia in order to determine the optimal dose. METHODS: From January to September 1990, pyrimethamine (50 mg 3 times per week) was given as primary prophylaxis against toxoplasmosis to 30 patients who were positive for human immunodeficiency virus (CDC classes II or II, CD4 counts < 200/mm3). The patients were randomly divided into three groups given 5, 25 and 0 mg folic acid 3 times per week. Associated treatments were the same in all patients (zidovudine 600 mg/d, pentamidine isethionate aerosol, 300 mg, once a month). Blood cell counts and lymphocyte subset counts were made on days 0, 30, 90 and 180. RESULTS: Two patients were lost to follow-up and between day 90 and 180, 3 were excluded due to other opportunist infection and 1 due to zidovudine induced anaemia. Between the groups, there was no difference in haemoglobin level or cell counts on day 0. No haematologic toxicity was observed at day 90. Haemoglobin was significantly reduced in the control group (0 mg folic acid) on day 180 (mean haemoglobin on day 180, 13.8, 13.1 and 12.1 g/dl in groups 1, 2 and 3 respectively). No variation in polynuclear neutrophil counts was observed. CONCLUSION: These findings suggest that folic acid has a moderate beneficial effect on preventing haematologic disease in patients treated with pyrimethamine. There was no observed dose effect.

AIDS-Related Opportunistic Infections↗