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Biomedical subjects

B Leng

Publications and source records attributed to B Leng.

At least 37 records · Page 2Linked to original sources

Foscarnet decreases HIV-1 plasma load.

OBJECTIVE: To evaluate the effect of foscarnet on HIV-1 replication in vivo. PATIENTS AND METHODS: Seventeen AIDS patients with cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV) infection, Kaposi's sarcoma (KS), or a combination of these were treated with foscarnet. HIV RNA quantification (bDNA 2.0, Chiron, Emeryville, CA, U.S.A.), CMV pp65 antigenemia (Argene Biosoft, Varilhes, France), and CMV viremia were determined before and during therapy. RESULTS: Four patients had CMV retinitis (1 with KS), 2 patients had CMV pneumonia (1 with KS), 1 patient had CMV cholecystitis, 2 patients had VZV infection (1 with KS), 1 patient had HSV-2 infection, and 7 patients had KS alone. The decrease in HIV-1 load was -0.73 +/- 0.39 log copies/ml (p = 2.10(-6)) after 3 days of treatment and -1.15 +/- 0.49 log copies/ml (p < 10(-7)) after 10 days of treatment, compared with day 0. Furthermore, reduction of HIV-1 plasma load during foscarnet therapy did not depend on the presence or absence of CMV disease or on a positive pp65 antigenemia at day 0. CONCLUSION: We observed decreased HIV-1 plasma load in all patients treated with foscarnet, regardless of presence or absence of clinical or biologic CMV infection. This decrease supports the proposition that foscarnet anti-HIV-1 activity may be of clinical importance.

Acquired Immunodeficiency Syndrome

Autoantibodies directed against phospholipids or human beta 2-glycoprotein I in HIV-seropositive patients: relationship with endothelial activation and antimalonic dialdehyde antibodies.

BACKGROUND: We investigated the possible role of antiphospholipid (APA) and anti-human 2-glycoprotein I (beta2-GPI) antibodies (Ab) in thrombosis and atherosclerosis in human immunodeficiency (HIV)-positive patients, in whom they seem to be more frequent. METHODS: We measured APA and anti-beta2-GPI Ab in 58 HIV-positive patients together with markers of disease progression, circulating beta2-GPI, plasma lipids, biological markers of endothelial activation and integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion molecule 1) and with antimalonic dialdehyde antibodies (anti-MDA Ab). RESULTS: We found a 41% frequency of IgG APA in the HIV-positive patients. APA IgMs were rarely positive (7%), and anti-beta2-GPI IgGs were positive in 3-4% patients. There was no correlation between APA or anti-beta2-GPI Ab and the presence of opportunistic infections. Although plasma thrombomodulin, von Willebrand factor and vascular cell adhesion molecule 1 were significantly increased in the HIV-positive patients, APA was correlated only with vascular cell adhesion molecule 1, suggesting that APAs are correlated with endothelial activation but not with vascular endothelial lesions. A correlation between APA and anti-MDA IgG was demonstrated using multivariate analysis (r=0.542, P < 0.0001), suggesting a relationship between the targets of these antibodies. Finally, IgG APAs are frequent in HIV infection but are not correlated with biological markers of endothelial injury. CONCLUSION: Our results do not support a role for APA or anti-beta2-GPI in HIV-associated silent vascular endothelial damage. However, the role of these autoantibodies in clinically relevant thrombotic events should be investigated in HIV-positive patients.

Adult

[Exudative enteropathy in disseminated lupus erythematosus. Report of 3 cases and review of the literature].

Protein-losing enteropathy (PLE) is characterized by loss of essentially protein substances into the gastrointestinal tract. Few reports of PLE supervening in patients who have systemic lupus erythematosus (SLE) have appeared in the literature. We report three new cases. All three were women who had a severe form of SLE involving several organs. PLE was diagnosed on the basis of an increased clearance of alpha 1 antitrypsin. The severeness of the clinical picture in all three patients justified the use of immunosuppressive agents (corticosteroids and pulse cyclophosphamide therapy) which were effective. These cases are compared to the 24 previously reported. The frequency of PLE during an SLE flare-up is probably underestimated. It should be looked for in SLE patients who have edema by means of the simple alpha 1 antitrypsin test. PLE is often found in severe clinical forms of SLE and should be managed using corticosteroids either alone or in association with immunosuppressive drugs.

Adult

[Scleroderma renal crisis. 7 cases and review of the literature].

We report a series of seven patients who had scleroderma renal crisis. Their primary clinical and laboratory features along with the details of their management were compared with those of similar cases from the literature. The seven patients died within one to four months of the diagnosis with a pattern of acute renal failure, left ventricular failure and malignant hypertension. Histopathologic examination was performed in four of the patients, in two of whom it revealed thickening of the wall of the interlobular arteries related to the scleroderma, and in the other two patients nonspecific lesions of malignant hypertension. This histopathologic particularity led us to propose, on the basis of multiple renal biopsies performed in patients with scleroderma, a lesion chronology of the kidney in patients with scleroderma. Nevertheless, the triggering factors and pathophysiologic mechanisms of scleroderma renal crisis remain unclear and its prognosis is severe. Early treatment with angiotensin-converting enzyme inhibitors and other vasodilatators administered intravenously can prevent death and dialysis.

Acute Kidney Injury

[Lichenoid paraneoplastic pemphigus in low-grade nodular lymphoma].

BACKGROUND: The precise diagnostic criteria for paraneoplastic pemphigus defined by Anhalt are not always present. In many cases, the clinical and histological features are misleading. CASE REPORT: We observed a case of paraneoplastic pemphigus in a 60-year-old man followed for low-grade inactive nodal lymphoma. The clinical course was long. The main features were lichenoid cutaneous and mucosal lesions without bullae. The only histology finding was basal vacuolization, lymphocyte infiltration and suspended keratinocyte necrosis without acantholysis. This clinical and pathological situation continued for one year. Just a few days prior to the patient's death, the clinical situation suddenly worsened with major bullae involving most of the skin surface and mucosal areas including the esophagus and respiratory tract. Cyclosporine and bolus injections of corticosteroids did not prevent the fatal outcome. DISCUSSION: This unusual lichenoid presentation has not been previously described. Associated skin erosions usually occur early in the disease course. The long lichenoid presentation for several months without acantholysis emphasizes the difficulties encountered in the diagnosis of paraneoplastic pemphigus. This diagnosis should be entertained in cancer patients who develop lichenoid lesions.

Biopsy

Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia.

The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti-platelet antibodies directed against the major platelet membrane glycoproteins (GP IIb-IIIa, GP Ib-IX, GP Ia-IIa and GP IV) in patients where SLE and APAS were associated or not with thrombocytopenia. Results were compared with a series of 26 ITP patients, 46% of whom were shown to possess anti-platelet antibodies directed against one or more of the platelet surface glycoproteins. When APAS was associated with thrombocytopenia, 7/10 patients possessed antibodies against GP IIb-IIIa and/or GP Ib-IX. For SLE patients with thrombocytopenia, 6/10 patients were shown to have antiplatelet antibodies against GP IIb-IIIa, GP Ib-IX or GP IV. In contrast, for APAS (n=11) and SLE patients (n=11) without thrombocytopenia, only one patient had an antibody directed against GP IIb-IIIa and one patient had an antibody to GP IV. Our results suggest that antibodies directed against major platelet membrane glycoproteins may play a role in the thrombocytopenia that is seen during SLE and APAS.

Adolescent

Alteration of arterial distensibility in systemic sclerosis.

OBJECTIVES: To evaluate the distensibility of large arteries in patients with systemic sclerosis (SSc). DESIGN: Prospective case-control study including unselected patients with SSc. SETTING: One cardiology and two internal medicine units in a teaching hospital. SUBJECTS: Eighteen patients with SSc and controls matched for age, sex, height, weight and 24-h ambulatory blood pressure (BP). INTERVENTION: The timing of Korotkoff's sounds (QKD interval), a newly described noninvasive ambulatory method was used to measure arterial distensibility during 24 h. MAIN OUTCOME MEASURES: Two endpoints were used: QKD 100-60 (normalized for a heart rate of 100 beats min-1 and a systolic BP of 100 mmHg) and the slope of QKD against pulse pressure. RESULTS: The patients with SSc had a lower slope of QKD against pulse pressure than the controls (median 0.55, range 0-1.21, versus 0.92, range 0.5-1.34, respectively; P = 0.003), and a lower QKD 100-60 (medians/ranges respectively 191 [162-216] and 203 [169-231]: P = 0.01). CONCLUSIONS: These results indicate that arterial distensibility of large arteries is decreased in SSc.

Adult

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