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Biomedical subjects

Jean-Luc Pellegrin

Publications and source records attributed to Jean-Luc Pellegrin.

29 records · Page 2Linked to original sources

Severe prolonged red blood cell aplasia and thrombocytopenia induced by parvovirus B19 infection in a patient with sarcoidosis.

We describe an acromegalic patient who developed a parvovirus B19 (PVB19) infection concomitantly with sarcoidosis, which was complicated by chronic red blood cell aplasia and severe thrombocytopenia, despite disappearance of the virus from serum and the production of high levels of specific polyclonal antibodies to PVB19. Mitogen stimulation of the patient's peripheral blood mononuclear cells induced oversecretion of interferon-gamma (IFN-gamma). Because hematopoietic suppression by IFN-gamma has been reported, a possible mechanism underlying reticulocytopenia and thrombocytopenia could involve IFN-gamma.

Adult↗

Crow-Fukase (POEMS) syndrome: a study of peripheral nerve biopsy in five new cases.

The pathogenesis of Crow-Fukase (POEMS) syndrome is not well known, and in some cases, a definite diagnosis is difficult to establish. Nerve fibers have been studied in about 120 peripheral nerve biopsies (PNBs), and a mixture of axonal and demyelinating lesions were found in most of them. We report five new cases of Crow-Fukase (POEMS) syndrome with ultrastructural examination of their PNBs. In every case, there were features of axonal degeneration and primary demyelination. Interestingly, uncompacted myelin lamellae (UMLs) were present in every case at a percentage of 1-7. The association of UML and Crow-Fukase (POEMS) syndrome was described 20 years ago but was only reported in a few studies and found in 31 of 41 cases. In fact, this association is very significant because apart from Crow-Fukase (POEMS) syndrome, UMLs can only be found with such a frequency in rare cases of Charcot-Marie-Tooth disease type 1B. UML was also reported in acute and chronic inflammatory demyelinating polyneuropathies but at a much lower percentage. Moreover, in our five cases, UML was frequently associated with a decrease in the number of intra-axonal filaments, and this finding raises the problem of relationships between myelin formation and neurofilaments. So far, glomeruloid hemangiomas present in the dermis of some patients are considered as the only specific criteria of Crow-Fukase (POEMS) syndrome, but we think UML can also be regarded as highly suggestive of this entity on condition that a thorough ultrastructural examination of a PNB is performed.

Aged↗

Borna disease virus RNA in immunocompromised patients in southwestern France.

Borna disease virus (BDV) is a neurotropic RNA virus with a wide host range. Human infections, although controversial, have been described in Europe, Asia, and the United States. The present study investigated the existence of BDV infections in immunocompromised human beings, namely, 82 human immunodeficiency virus (HIV)-infected and 80 therapeutically immunosuppressed patients. BDV p40 RNAs were detected in peripheral white blood cells with reverse transcription-nested PCR and hybridization in, respectively, 11 (13.41%) and 1 (1.25%) of the two groups of patients. BDV p24 RNAs were identified in only one of those. BDV RNA was detected in the absence of any neuropsychiatrical illness, suggesting that BDV infections may occur in asymptomatic carriers. The severity and particularity of cellular immunosuppression could explain the significantly increased detection of BDV RNA in HIV-infected patients.

Base Sequence↗

Predictive value of provirus load and DNA human immunodeficiency virus genotype for successful abacavir-based simplified therapy.

Of 75 human immunodeficiency virus (HIV) type 1-infected patients successfully responding to 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus 1 protease inhibitor (PI), 55 started a simplified abacavir (ABC)-based triple NRTI regimen. Influences of DNA load and DNA reverse-transcriptase (RT) mutations on virological responses were assessed at month 6 after initiation of therapy. Baseline heterogeneity was observed: peripheral blood mononuclear cell (PBMC) genotyping showed 31% RT mutations with 1-5 NRTI-related mutations, 78% protease mutations had 1-5 PI-related mutations; and HIV-1-DNA levels were 1.8-3.5 log(10) copies/10(6) PBMC. Outcomes for 49 patients on a regimen of 2 NRTIs plus ABC were as follows: 22 successes, 10 blips ("blip" defined as intermittent plasma HIV-1 RNA levels between 50 and 100 copies/mL and a return to an undetectable level), and 17 failures, whereas, for patients continuing on a regimen of 2 NRTIs plus 1 PI, there were 19 successes and 1 blip. Previous treatment regimens, baseline provirus level, and PBMC genotype predicted virological outcome.

Acquired Immunodeficiency Syndrome↗

Gammadelta T lymphocytosis associated with granulomatous disease in a patient with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of immunodeficiency syndromes that involves defective production of specific antibodies and decreased serum concentrations of > or =1 immunoglobulin isotype. We describe a patient with an atypical case of CVID who had extensive granulomatous lesions that were partially attributable to mycobacterial infection. In the peripheral blood, there was a massive increase in the number of double-negative CD3+ T cells that expressed the gammadelta T cell receptor.

Adult↗

Virologic response to nelfinavir-based regimens: pharmacokinetics and drug resistance mutations (VIRAPHAR study).

OBJECTIVE: To assess the impact of HIV-1 protease and reverse transcriptase (RT) mutations, and pharmacokinetic parameters on virological responses to nelfinavir (NFV)-containing highly active antiretroviral therapy. DESIGN: Naive or antiretroviral-experienced HIV-1-infected subjects were included in a non-randomized, observational cohort study and received two nucleoside RT inhibitors + NFV (750 mg three times per day or 1250 mg twice per day). Virologic success was defined as a virus load < 50 copies/ml for > 6 months. METHODS: RT and protease genes were sequenced at baseline and at the time of virological failure. Plasma NFV trough concentration (Cmin), maximum concentration (Cmax), and AUC0-tau at steady-state were subjected to population pharmacokinetic analysis. RESULTS: Patients (n = 154) enrolled between November 1998 and February 2000 started a twice per day (n = 84) or three times per day (n = 70) NFV-based regimen as first- (n = 48) or second-line therapy when protease inhibitor-naive (n = 64) or -experienced (n = 42). Median follow-up duration was 16 months. Virologic failure occurred in 88 patients. No significant differences were observed between twice per day and three times per day regimens. According to multivariate analysis, NFV Cmin and Cmax, CD4 cell count, number of baseline RT + protease gene mutations, D67N, M184V, T215F/Y in RT, and M36I in protease, were independent factors that were significantly predictive of failure. At failure, L10I, D30N, M36I, V77I, N88S/D or L90M protease mutations had emerged since baseline. Pharmacokinetic parameters were similar in patients with or without emergence of these neo-mutations. The more discriminating NFV Cmin efficacy-threshold was estimated to be 1 mg/l. CONCLUSIONS: Our data confirm the association among individual pharmacokinetic parameters, genotype pattern and virological response to NFV-containing regimens.

Adult↗

Reversible myelofibrosis induced by tuberculosis.

Tuberculosis and myelofibrosis are reported in conjunction often enough to raise the possibility that a relationship exists between the 2 entities. However, whether tuberculosis stimulates a secondary fibrotic reaction or develops in patients who have preexisting myeloproliferative disorders is not clear. We describe the case of a 28-year-old man in whom myelofibrosis disappeared completely after administration of antituberculous treatment, which suggests that a causal relationship exists between the 2 disease entities.

Adult↗

Increased soluble and platelet-associated CD40 ligand in essential thrombocythemia and reactive thrombocytosis.

CD40 ligand (CD40L) is expressed on activated CD4(+) T lymphocytes and at the activated platelet surface. A circulating soluble form of CD40L (sCD40L) is generated by the way of a proteolytic cleavage. We measured sCD40L in the plasma of either healthy subjects; patients with inflammatory disorders and low, normal, or high platelet count (reactive thrombocytosis); or patients with essential thrombocythemia (ET). A tight correlation was found between the platelet count and plasma sCD40L. ET patients had the highest levels of sCD40L. Platelet-associated CD40L was increased in ET and reactive thrombocytosis, conditions associated with increased platelet regeneration. Platelet-associated CD40L was released upon platelet activation. In conclusion, platelets appear as a reservoir of CD40L that may be a major contributor to circulating sCD40L. Platelet-associated CD40L may be a potential marker of platelet regeneration.

Adult↗

Evaluation of cardiovascular risk factors in HIV-1 infected patients using carotid intima-media thickness measurement.

BACKGROUND: Highly active antiretroviral therapies (HAART) in HIV-infected patients are often associated with lipodystrophy syndrome and metabolic disorders. Atherogenic lipid profile could expose these patients to atheromatous cardiovascular disease. We describe carotid artery intima-media thickness (IMT), a surrogate marker of atherosclerosis, according to HIV status, antiretroviral treatment, lipodystrophy and conventional cardiovascular risk factors. METHOD: In a multicenter prospective cohort study we have surveyed HIV-infected subjects with a carotid IMT measurement by B-mode ultrasonography. We collected information on lipodystrophy clinical manifestations, age, gender, body mass index (BMI), smoking habits, alcohol intake, systolic blood pressure, HIV transmission category, AIDS stage, type and duration of HAART, CD4+ cell count, plasma HIV-1 RNA, glucose, insulin, total cholesterol and homocysteine. RESULTS: Four hundred and twenty-three HIV-infected patients were studied. The median carotid IMT measurement was 0.54 mm (range: 0.50-0.60). Lipodystrophy syndrome was diagnosed in 161 HIV-infected patients (38.1%). In univariate linear regression, IMT was significantly higher (P<0.05) with older age, male gender, higher body mass index, higher waist-to-hip ratio, increased systolic blood pressure, total cholesterol, glucose disorders and homocysteine, regular smoking and alcohol consumption, lipodystrophy and HAART. In a multivariate analysis, the effect of lipodystrophy and HAART disappeared after adjustment for other cardiovascular risk factors. CONCLUSIONS: It was concluded that only conventional cardiovascular risk factors are independently associated with increased IMT in HIV-infected patients.

Adult↗