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Biomedical subjects

C Michelet

Publications and source records attributed to C Michelet.

At least 19 recordsLinked to original sources
PubMed2003

[Cutaneous metastatic Crohn's disease].

INTRODUCTION: Cutaneous metastatic Crohn's disease is a granulomatous inflammation of the skin that is noncontiguous to the gastrointestinal tract. CASE REPORT: A 42-year-old man with Crohn's disease is admitted for antibiotic resistant erysipela-like dermo-hypodermitis. The presence of granulomatous lesions on skin biopsy, the absence of any infectious agent identified despite extensive investigations and the dramatic improvement observed with corticosteroid eventually lead to the diagnosis of cutaneous metastatic Crohn's disease. CONCLUSION: During Crohn's disease, biopsy should be considered for every undiagnosed skin lesion as the characteristics of cutaneous metastatic Crohn's disease are not specific. The presence of a non caseous granulomatous dermal infiltration suggests the diagnosis and should make consider the initiation of corticosteroid and the discontinuation of others inappropriate therapeutics (i.e. surgical treatment, antibiotics).

Adult↗
PubMed2002

Detection of herpesvirus genomes by polymerase chain reaction in cerebrospinal fluid and clinical findings.

BACKGROUND: The viruses of the Herpesviridae family, in particular herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and human herpesvirus 6 (HHV-6), are responsible for numerous infections of the central nervous system (CNS). These infections manifest as diverse clinical signs, many of which are not specific. The diagnosis of these infections is necessary to make it possible to adapt treatment appropriately, as treatment is specific for the particular virus concerned. OBJECTIVES: To apply a polymerase chain reaction (PCR) technique for the diagnosis in a single reaction of the six herpesviruses most frequently detected in the cerebrospinal fluid (CSF) and to analyse clinical events in patients presenting positive results in PCR for herpesviruses. STUDY DESIGN: We studied 141 patients, from whom 180 CSF samples were collected. The clinical files of the patients were consulted retrospectively, and a list of clinical signs was recorded. After testing by targeted PCR, at the clinician's demand, we tested these samples by herpes consensus PCR, which detects six herpesviruses (HSV-1, HSV-2, CMV, EBV, VZV, HHV-6), in a single PCR. RESULTS: Targeted PCR tests identified 25 CSF samples (13.9%), corresponding to 18 patients (12%), as positive. The herpes consensus PCR test detected 49 samples (27.2%) as positive, resulting in the identification of 54 individual viruses (four samples displayed co-infection) from 39 patients (27%). 130 CSF samples, from 101 patients, tested negative by both techniques. 23 HIV-positive patients (30.6%), three HIV-negative immunocompromised patients (27%), and 14 immunocompetent patients (25%) were CSF PCR-positive. In HIV-positive patients, CMV was the virus most frequently identified (13%), followed by EBV (10.6%), VZV (5.3%) and finally HSV-1 and HSV-2 (both 1.3%). We did not detect HHV-6 in any of these samples. We detected only HSV-2, EBV and VZV in the 11 HIV-negative immunocompromised patients. CSF samples of immunocompetent patients contained mostly VZV (9%) and HSV-1 (7.3%). CONCLUSIONS: The herpes consensus PCR for a given virus was more sensitive than the standard, targeted PCR used in our laboratory. The clinical signs presented by patients infected with HSV-1, HSV-2 and CMV were similar to those reported in previous studies. For VZV, we report the possibility of mild, transient cerebral viral reactivation. Our data on the detection of EBV by PCR suggest that the PCR test is of predictive value for cerebral lymphoma in immunocompromised patients. The possible role of HHV-6 in a subacute neurological disorder merits further investigation.

Adolescent↗
PubMed2001

Ritonavir-saquinavir dual protease inhibitor compared to ritonavir alone in human immunodeficiency virus-infected patients.

The objective of this study was to evaluate the antiretroviral efficacy and safety of ritonavir (600 mg twice a day [b.i.d.])-saquinavir (400 mg b.i.d.) compared to ritonavir (600 mg b.i.d.) in patients pretreated and receiving continued treatment with two nucleoside analogs. The study was placebo controlled, randomized, and double blind. Inclusion criteria included protease inhibitor naive status and a viral load of >10,000 copies/ml. The main end point was viral load at week 24. Forty-seven patients were included (25 given ritonavir and 22 given ritonavir-saquinavir) and monitored until week 48. At inclusion, 23% had had at least one AIDS-defining event. Previous treatment durations (mean and standard deviation) were 42 +/- 25 and 37 +/- 23 months, viral loads were 4.75 +/- 0.62 and 4.76 +/- 0.50 log(10) copies/ml, and CD4 cell counts were 236 +/- 126 and 234 +/- 125/mm(3) in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, viral loads were 2.81 +/- 1.48 and 2.08 +/- 1.14 log(10) copies/ml (P = 0.04) and CD4 cell counts were 330 +/- 151 and 364 +/- 185/mm(3) (P = 0.49) in the ritonavir and ritonavir-saquinavir groups, respectively. Similar results were observed at week 48. Moreover, at week 48, 40 and 68% (P = 0.05) and 28 and 59% (P = 0.03) of patients achieved viral suppression at below 200 and 50 copies/ml in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, six patients in the ritonavir group but only one in the ritonavir-saquinavir group had key mutations conferring resistance to protease inhibitors. Clinical and biological tolerances were similar in both groups. In nucleoside analog-pretreated patients, ritonavir-saquinavir has higher antiretroviral efficacy than and is as well tolerated as ritonavir alone.

Adult↗
PubMed2000

[Renal failure during treatment with Ambisome].

BACKGROUND: Although renal function is generally unaffected by liposome formulations of amphotericin B-deoxycholate, there is nevertheless a risk. CASE REPORTS: Two patients immunodepressed patients treated for candidosis involving the mouth and esophagus unresponsive to local care and flucanazol developed renal failure when given the liposome formulation of amphotericin B-deoxycholate (AmBisome). In one with normal renal function prior to treatment, moderate impairment was observed after initiating AmBisome. In the second patient, impaired renal function worsened after initiating treatment with amphotericin B-deoxycholate then progressed to very severe renal failure after switching to AmBisome. CONCLUSION: The indication for AmBisome (amphotericin B-deoxycholate treatment in patients with active renal impairment) must not overshadow the risk of worsening renal function under treatment.

Adult↗
PubMed1999

Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene expression after 1 year of highly active antiretroviral therapy.

OBJECTIVES: To examine T-cell repertoire modifications, the evolution of T-helper (TH)1/TH2 cytokine imbalance and modifications in chemokine receptor expression when the viral load is decreased by 2-3 log10 copies/ml under highly active antiretroviral therapy (HAART). DESIGN: Sixteen patients previously treated with zidovudine and lamivudine, with CD4 cells below 300 x 10(6)/l and viraemia above 30000 copies/ml were treated by saquinavir and ritonavir together with both reverse transcriptase (RT) inhibitors (ANRS 069 trial). T-cell repertoire, chemokine receptor and lymphokine expression were studied from peripheral blood mononuclear cells sampled at weeks 0, 24 and 48. METHODS: T-cell repertoire study was carried out using the Immunoscope method. Interleukin (IL)-12 receptor beta2, CC-chemokine receptor (CCR)-3, CXC-chemokine receptor-4 and CCR-5 expression in CD4+ cells was measured by kinetic quantitative PCR and IL-2, IL-4, IL-10, IL-13, interferon (IFN)-gamma were measured using a quantitative RT-PCR assay with homologous internal standards. RESULTS: Repertoire alterations were more frequent in CD4- than in CD4+ cells and persisted despite undetectable viraemia. Increased CCR-3 expression and spontaneous IFN-gamma as well as mitogenic induced IL-13 were observed at baseline and decreased slightly under HAART. CONCLUSION: The CD8+ cell repertoire alterations were profound, whereas the CD4+ cell alterations were moderate and both persisted unchanged under HAART. The TH1/TH2 imbalance was more related to TH2 over-expression than to TH1 deficiency and persisted for at least 1 year under HAART.

Adult↗
PubMed1999

Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group.

OBJECTIVE: To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults. DESIGN: Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30. RESULTS: Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion. CONCLUSION: Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae.

Adult↗
PubMed1999

Safety and efficacy of ritonavir and saquinavir in combination with zidovudine and lamivudine.

BACKGROUND: Ritonavir is a potent inhibitor of cytochrome P4503A4 that strongly increases saquinavir bioavailability. In this study we assessed the safety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine and lamivudine who were protease inhibitor naive and who had a CD4 cell counts below 200/mm3. METHODS: In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48. RESULTS: Sixteen patients were included in the study. Previous nucleoside analog treatment duration was 48+/-22 months (mean +/- SD). Two patients quit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusion and week 48, plasma viremia varied from 4.87+/-0.43 to 3.00+/-1.29 log10 copies/mL and CD4 cell counts ranged from 98+/-61 to 250+/-139/mm3. Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) had viral loads below 50 copies/mL. A single key mutation that conferred ritonavir resistance I84V and V82A/V developed in two patients. A mutation at codon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was observed. CONCLUSION: Ritonavir and saquinavir in combination are quite well tolerated and induce a high and sustained antiretroviral efficacy. A four-drug combination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Comparative efficacies of antibiotics in a rat model of meningoencephalitis due to Listeria monocytogenes.

The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of trovafloxacin with TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the cerebrospinal fluid was cultured to document meningitis, and the treatment was started. Treatment was instituted for 48 h, and efficacy was evaluated 24 h after administration of the last dose. All tested treatment regimens exhibited significant activities in brain, liver, and blood compared to infected rats receiving saline (P < 0.001). In the brain, amoxicillin plus gentamicin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 +/- 0.5 log10 CFU/ml for amoxicillin-gentamicin, 5.0 +/- 0.4 log10 CFU/ml for trovafloxacin, and 5.8 +/- 0.5 log10 CFU/ml for TMP-SMX; P < 0.05). In liver, amoxicillin-gentamicin and trovafloxacin were similarly active (2.8 +/- 0.8 and 2.7 +/- 0.8 log10 CFU/ml, respectively) but more active than TMP-SMX (4.4 +/- 0. 6 log10 CFU/ml; P < 0.05). The combination of trovafloxacin with TMP-SMX did not alter the antibacterial effect in the brain, but it did reduce the effect of trovafloxacin in the liver. Amoxicillin-gentamicin was the most active therapy in this study, but the activity of trovafloxacin suggests that further studies with this drug for the treatment of Listeria infections may be warranted.

Animals↗
PubMed1999

Amplification of the six major human herpesviruses from cerebrospinal fluid by a single PCR.

We used a novel type of primer system, a system that uses stair primers, in which the primer sequences are based on consensus sequences in the DNA polymerase gene of herpesvirus to detect herpesviruses by PCR. A single PCR in a single tube detected the six major herpesviruses that infect the central nervous system: herpes simplex virus type 1 (HSV-1), and type 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and human herpesvirus 6 (HHV-6). We used the technique to analyze 142 cerebrospinal fluid (CSF) samples that had been stored at -80 degrees C and compared the results with those obtained previously for the same samples by standard, targeted PCR. Four hundred one targeted PCR tests had been run with the 142 samples to detect HSV-1, HSV-2, CMV, and VZV; screening for EBV and HHV-6 was not prescribed when the samples were initially taken. Eighteen CSF samples tested positive by classic targeted PCR. The herpesvirus consensus PCR detected herpesviruses in 37 samples, including 3 samples with coinfections and 17 viral isolates which were not targeted. Two samples identified as infected by the targeted PCR tested negative by the consensus PCR, and eight samples that tested positive by the consensus PCR were negative by the targeted PCR. One hundred three samples scored negative by both the targeted and the consensus PCRs. This preliminary study demonstrates the value of testing for six different herpesviruses simultaneously by a sensitive and straightforward technique rather than screening only for those viruses that are causing infections as suggested by clinical signs.

Consensus Sequence↗
PubMed1998

Efficacy and safety of stavudine and didanosine combination therapy in antiretroviral-experienced patients.

OBJECTIVES: To assess the efficacy, tolerance, and safety of combination antiretroviral therapy with didanosine and stavudine in HIV-infected patients with CD4+ cell counts > 100 x 10(6)/l and HIV plasma RNA > 10(4) copies/ml previously treated with other antiretroviral agents for at least 3 months. DESIGN: In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (200 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Patients for whom the first regimen had led to undetectable HIV RNA levels were offered a second 6-month course of treatment; those who had achieved insufficient immunological and virological gains in the first 6 months were given a new combination. METHODS: Primary evaluation of efficacy was based on viral load measured by branched DNA second-generation testing (lower limit of detection, 500 copies/ml) and CD4+ cell counts; secondary evaluations included AIDS-defining events and clinical side-effects. RESULTS: Sixty-five patients with median prior antiretroviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 198 x 10(6)/l and median plasma HIV RNA was 80000 copies/ml (4.9 log10 copies/ml). In this heavily pretreated population, an increase in the mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In addition, rapid and prolonged antiviral activity was seen, with a mean maximal decrease of 1.1 log10 copies/ml at week 4, a mean decrease of 0.89 log10 copies/ml at week 24, and a plasma RNA viraemia < 500 copies/ml achieved in 14% of patients at week 24. CONCLUSIONS: Combination therapy with stavudine and didanosine is safe and leads to a sustained antiviral effect, even in patients with prolonged prior antiretroviral exposure and low CD4+ cell counts.

Adult↗
PubMed1998

Opportunistic infections occurring during highly active antiretroviral treatment.

OBJECTIVE: To analyse the characteristics of opportunistic infections in patients receiving highly active antiretroviral treatment (HAART). DESIGN AND METHODS: A retrospective study performed in seven hospitals, included all patients starting treatment by ritonavir or indinavir between 26 March and 31 December 1996. Patients were evaluated for the development of AIDS-defining events. Clinical evaluation, plasma HIV-1 RNA quantification, CD4 cell count were recorded at baseline and at the onset of the event. RESULTS: Four hundred and eighty-six patients were included: 44.2% had a CD4 cell count below 50 x 10(6) cells/l. Fifty clinical events were recorded in 46 patients with a mean follow-up of 6.1 months, of which 34 events (68%) were observed during the first 2 months of HAART. Eighteen of these occurred despite a reduction of viral load by at least 1.5 log10) and a 100% increase of the CD4 cell count compared with that at the onset of the event, corresponding to 11 cytomegalovirus infections, five mycobacterial infections, one case of cryptococcosis, and one case of Varicella-Zoster virus-related acute retinal necrosis. Among the 16 events observed after the second month, six occurred despite a marked biological improvement, corresponding to a recurrence in five of six patients who had stopped their maintenance therapy. Events were one cytomegalovirus infection, two mycobacterial infections, one episode of oesophageal candidiasis and one cryptococcal meningitis. CONCLUSION: In patients at high risk of developing an opportunistic infection prior to the institution of a HAART regimen, prophylaxis should not be discontinued during the first 2 months of treatment, and maintenance therapy should be carried on despite a significant increase in the CD4 cell count.

AIDS-Related Opportunistic Infections↗
PubMed1998

The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) in the course of subacute bacterial endocarditis with glomerular involvement, coincidence or association?

Antineutrophil cytoplasmic antibodies positivity with cytoplasmic pattern (C-ANCA) and proteinase-3 (PR-3) specificity was found in two patients with both subacute bacterial endocarditis (SBE) and glomerular involvement. Renal biopsy showed membranoproliferative glomerulonephritis in one case and focal segmental glomerulonephritis in the second case. Immunofluorescence study showed granular immune deposits in both cases evocating immune complex glomerulonephritis. Renal and biological manifestations disappeared with clinical improvement secondary to antibiotherapy. Physicians have to consider the possible occurrence of such C-PR-3 ANCA, claimed to be specific markers for Wegener's granulomatosis, in infectious diseases such as SBE. Hence we focus on the necessity of performing a renal biopsy with light microscopy and immunofluorescence studies in all patients with ANCA associated glomerular disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Longitudinal study of HIV-specific cytotoxic lymphocytes in HIV type 1-infected patients: relative balance between host immune response and the spread of HIV type 1 infection.

To evaluate the contribution of a specific cytotoxic response in the control of HIV infection in relation to clinical status, we performed serial analysis of anti-Env and anti-Gag cytotoxic activity in 13 infected individuals over a 6- to 10-year period, using cryopreserved peripheral blood mononuclear cells (PBMCs). Autologous EBV-transformed B cell lines infected in vitro with recombinant vaccinia viruses expressing HIV-1 env and gag genes were used as targets. Without any stimulation of the effector cells, we were able to show an anti-HIV cytotoxic activity in the PBMCs of 12 of 13 HIV-1-infected patients, consistent with chronic immune activation in HIV infection. Different patterns of HIV-specific cytotoxic activity were observed, and the extent of this cytotoxic response varied between the clinically defined groups of individuals. No direct relationship was observed with the number of CD4 and CD8 lymphocytes during the observation period. However, patients who remained asymptomatic had a more vigorous cytotoxic response than patients with clinical deterioration during the observation period, and a significant difference was observed for HIV Gag-specific CTL activity. From these data, we suggest that the HIV-specific cytotoxic response has a protective role in the course of HIV infection.

B-Lymphocytes↗