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Biomedical subjects

P M Roger

Publications and source records attributed to P M Roger.

At least 37 records · Page 2Linked to original sources

Highly active anti-retroviral therapy (HAART) is associated with a lower level of CD4+ T cell apoptosis in HIV-infected patients.

HAART may increase CD4+ T cell counts despite a persistently detectable HIV load. The impact of HAART on apoptosis, which may play a role in the disease process in HIV-infected patients, has not been extensively studied. We performed a study to compare the level of spontaneous T cell apoptosis and anti-retroviral treatments in a cohort of HIV-1-infected patients. Data were obtained from a computerized medical record. Quantification of apoptotic cells was by cytofluorometric technique. From November 1995 to December 1997 we studied T cell apoptosis in 112 HIV-infected patients. Forty patients were classified A, 36 B and 36 C. Thirty patients were naive and 82 received an anti-retroviral treatment, 49 including a protease inhibitor (PI). The median plasma viraemia determined in 63 patients was 3.6 (range 1.3-5.6) log10. The median apoptotic cell count was 22% (range 2-73%) and 12% (range 2-60%) for CD4+ and CD8+ T cells, respectively. We did not observe any correlation between the HIV viraemia and the level of apoptosis of T cell subsets. Patients with HAART showed a lower percentage of apoptotic CD4+ T cells only: 16% (range 2-61%) versus 25% (range 5-73%) for patients receiving two nucleoside analogues (P = 0.02). This effect was significant in stage A patients and remained observable during the whole course of HIV disease. In conclusion, HAART, without any relation to plasma viraemia, is able to reduce apoptosis of CD4+ T cells.

Adult↗

Overexpression of Fas/CD95 and Fas-induced apoptosis in a patient with idiopathic CD4+ T lymphocytopenia.

The mechanisms of apoptosis have become better understood, in part with the discovery of Fas/CD95. We report the case of a patient characterized by a decreased CD4+ T cell count and an overexpression of Fas/CD95 resulting in apoptosis. A 54-year-old man presented with disseminated Mycobacterium xenopi infection. Analysis showed CD4+ T lymphopenia. Tests for human immunodeficiency virus (HIV) types 1 and 2 were negative. We compared the patient with eight healthy controls and five HIV-infected patients in terms of the expression of Fas/CD95 and Fas-mediated apoptosis of peripheral T lymphocytes. The percent of CD95+ cells in lymphocytes was 98% for the patient, and the mean percent of CD95+ cells in lymphocytes +/- SD for HIV-infected patients and healthy controls was 75% +/- 16% and 36% +/- 26%, respectively. The patient had a high level of spontaneous apoptosis, and apoptotic cells were all identified as being CD4+ T cells. Monoclonal antibodies to CD95 dramatically increased apoptosis of CD4+ T cells exclusively. CD4+ T lymphopenia observed in our patient correlated with an overexpression of Fas together with spontaneous and Fas-induced apoptosis.

Apoptosis↗

Efficacy and safety of an intravenous induction therapy for treatment of disseminated Mycobacterium avium complex infection in AIDS patients: a pilot study.

Monotherapy with macrolides for the treatment of disseminated Mycobacterium avium complex (MAC) bacteraemia leads to drug resistance and relapse of bacteraemia. Gastrointestinal intolerance is a common reason for treatment withdrawal of multidrug regimens. We have assessed the efficacy and safety of initial parenteral therapy together with a macrolide, for disseminated MAC infection, defined as two positive blood cultures, in AIDS patients. Patients received a daily infusion of amikacin 15 mg/kg + ethambutol 20 mg/kg + ciprofloxacin 400 mg/day, for 1 month, together with a macrolide by oral route. Fifteen patients were included and 13 (86%) achieved negative culture before the end of parenteral therapy.

AIDS-Related Opportunistic Infections↗

Gradient plate method to induce Streptococcus pyogenes resistance.

In recent years, increasing numbers of Streptococcus pyogenes (GAS) strains displaying resistance to macrolides have been reported in Finland, Japan, Asia and Spain. Antibiotic use has been shown to be a risk factor for infection with and carriage of drug-resistant streptococci. The aim of this study was to compare in-vitro development of resistance of streptococci to beta-lactams (penicillin, amoxycillin, cefotiam and cefuroxime) and erythromycin by serial passages in subinhibitory concentrations of antibiotics (subMICs) by gradient plate method. Three clinical strains of GAS were tested. Two were susceptible to erythromycin (MIC = 0.015 mg/L and 0.013 mg/L) and one resistant. Serial passages were performed daily by gradient plate method until a four-fold increase of the MIC was achieved. GAS variants obtained after serial passages in beta-lactams had MICs increased at least four-fold. They remained susceptible to these antibiotics. With erythromycin, final MICs reached intermediate and resistant level. Results obtained in this study with erythromycin are in good correlation with clinical studies showing that prior exposure to macrolides may help to facilitate the emergence of drug-resistant strains of streptococci.

Anti-Bacterial Agents↗

[Central apnea with consciousness impairment due to Listeria rhombencephalitis sequelae].

Listeria neuromeningitis presents as febrile rhombencephalitis in half the patients, often with persistent sequelae such as cranial nerve palsy. We report the case of a man who developed central apnea with simultaneous consciousness impairment subsequent to an infectious disease. Magnetic resonance imaging showed low signal intensities in T1 and T2, particularly in the medulla. Neither acidosis, hypoxia nor hypercapnea stimulated the respiratory centers during episodes of apnea; ventilation started again only with strong voluntary stimulation. Pons and medulla lesions of the reticular formation were probable as well as lesions of the automatic respiratory system and could explain the central origin of the apnea in this patient.

Cerebral Palsy↗

[Chronic sinusitis in patients infected by HIV: therapeutic strategies].

Chronic sinus pathology is a frequently encountered disease in HIV infected patients. The responsible bacterial agents and management are yet to be settled. The authors report the results of a retrospective study led in the unit of Head and Neck Surgery of the University Hospital of Nice. 25 patients where HIV holders and had a sinus pathology which had lasted more than 6 weeks, despite one or several antimicrobial drug administrations. Clinical and CT scan data are detailed as well as pathology results of the samples harvested during sinus surgery (bacteria free 32%, Pseudomonas aeruginosa 32%, Streptococcus pneumoniae 16%, Staphylococcus aureus 16%, Hemophilus influenzae 16%, anaerobic agents 16% and Toxoplasma gondii 4%). All patients underwent surgery (antral puncture with maxillary sinus drainage 17, functional endoscopic sinus surgery 8). Results where gathered at 4 months with 76% of relapse (100% in patients with less than 200/mm3 CD4 cells). In conclusion empiric antimicrobial drug therapy will be expected to be also effective on Pseudomonas aeruginosa, the surgical management being most often deceiving and leading to relapse especially when considering the frequency of bilateral morbidity and the level of CD4 cell below 200/mm3.

Adult↗

[Influence of HIV-related immunodeficiency on the histopathology of chronic hepatitis C].

OBJECTIVE: There is substantial evidence demonstrating the aggravating effect of human immunodeficiency virus (HIV) infection on the progression of chronic hepatitis C virus (HCV) infection. There is however, little data on the affect of certain factors which could affect liver pathology findings in patients with concomitant HIV infection such as the duration of HIV infection or T-cell subpopulation counts. We examined pathology findings in patients with concomitant HIV and HCV infections to determine the impact of immunodepression. PATIENTS AND METHODS: We reviewed liver pathology data collected in patients with concomitant HIV and HCV infections grouping patients according to severity of the liver pathology: group 1 = cirrhosis or active hepatitis; group 2 = minimally active hepatitis or histologically normal liver. Transparietal liver biopsies were obtained for the work-up of viral hepatitis or because of long-term unexplained fever or suspected lymphoma. Epidemiological and biological data were obtained from medical files. The duration of the liver disease was estimated from the date of exposure to risk of immunodepression as determined by the peripheral CD4+ and CD8+ counts. All pathology specimens were read by two pathologists who established the Knodell score for each patient. RESULTS: Fifty patients were included: 23 were classed in group 1 and 28 in group 2. The Knodell score was significantly different between the two groups, 11 +/- 4 and 4 +/- 3 respectively (p < 0.0001). Disease duration was similar for the two groups: mean 8 years. Mean CD4+ count was significantly higher in group 1: 312/mm3 versus 110/mm3 for group 2 (p = 0.0057); as was the mean CD8+ count (758/mm3 versus 360/mm3, p = 0.0013). For the entire study population, there was a significantly negative correlation (p < 0.05) between the Knodell score and the CD4+ count (r = 0.31) and for the CD8+ count (r = 0.41). CONCLUSION: HCV-related liver pathology in patients co-infected with HIV depends on the level of immunodepression. CD8+ counts are better correlated with pathology findings than with CD4+ counts.

Adult↗

Do viral load and CD8 cell count at initiation of tritherapy influence the increase of CD4 T-cell count?

BACKGROUND: Tritherapies including protease inhibitors improve clinical status and usually increase CD4 T cell count. However, the dissociation between the marked decreases in viral load and the incomplete restoration of CD4 cell counts with a three-drug combination has been reported. We assessed this potential difference among our patients. METHODS: Patients were enrolled when a protease inhibitor was prescribed to them for the first time. Using a computerized medical record (ADDIS), we retrospectively assessed a potential relationship between the increase in CD4 T cells (deltaCD4) at M3, M6 and variables including sex, age, CDC staging, protease inhibitor, prior antiviral therapy, CD8 and viral load at baseline. We used Epi-Info 6.4 and BMDP software. RESULTS: Data were analyzed on 154 patients. The median CD4 T cell count was 157 at baseline, 215 at month 3 and 202 at month 6. The median viral load was 52000 copies at baseline, 530 at month 3 and 500 at month 6. In a univariate analysis, a significant relationship was found between deltaCD4 and CD8 at baseline. A statistically significant negative correlation appeared between the CD8 cell count at baseline and deltaCD4 at M6 (r=-0.28, Pearson). Moreover, we found that there also was a relationship between deltaCD4 and viral load at baseline. There was a correlation between deltaCD4 at M6 and the viral load at M0 (r=0.37, Pearson). In a multiple regression model, after CD8 count at baseline had been accounted for, we found a significant correlation between deltaCD4 and viral load at baseline (multiple r=0.33 at M3, and 0.40 at M6). CONCLUSIONS: Patients with a low viral load do not benefit from as great an increase in CD4 T cell count as others when they receive a tritherapy including protease inhibitors. These results suggest that another mechanism rather than direct viral pathogenicity leads to CD4 T cell destruction. This mechanism may not be efficiently stopped by antiviral therapy, especially protease inhibitors.

Adult↗

[Lung cancer in patients infected with human immunodeficiency virus. Clinical course and therapeutic implications].

OBJECTIVES: HIV infection is associated with increased frequency of non-Hodgkin's lymphoma and Kaposi sarcoma. Like other malignancies, lung cancer has been described in HIV-infected patients although no evidence of a statistical correlation has been reported. PATIENTS AND METHODS: We performed a retrospective analysis of 15 HIV-infected patients with lung cancer. The patients were relatively younger (mean age 45 years) than is commonly found in lung cancer cohorts. RESULTS: The 15 patients had mild immunodepression (240 CD4+/mm3) and were in advanced clinical stage at diagnosis. Mean overall survival was 6 months and no clinical or biological prognostic factors were found. Death was usually due to infection, suggesting a synergetic effect between HIV and chemotherapy-induced immunodepression. CONCLUSION: We propose early antiretroviral therapy in cases of chemotherapy-treated HIV patients, even when commonly accepted immunological and/or clinical criteria are absent.

Adult↗

[Malaria attacks after returning from endemic areas. Failure or inadequate chemoprophylaxis?].

OBJECTIVE: Determine the causes of malaria attacks in subjects who have returned from endemic areas by assessing prescriptions for chemical prophylaxis and compliance. PATIENTS AND METHODS: All patients who developed a paroxysmal episode of malaria diagnosed at the University of Nice hospital in 1995 answered specific questions concerning their anti-malaria prophylaxis. RESULTS: Thirty-three patients were hospitalized for paroxysmal episodes of malaria in 1995. In 32 cases (97%) the attack resulted from either the lack of any prophylaxis (17 cases, 52%), inadequate prescription (11 cases, 12%) or poor compliance (4 cases, 12%). The prescribed chemical prophylaxis was not adapted to the chloroquinone-resistant area in 8 cases (24%) and medical recommendations concerning administration rules were inadequate in 3 cases (9%). Only one patient developed a paroxysmal episode despite correct compliance to a chloroquine-resistant zone-adapted well-conducted prescription. The cost of poor prophylaxis in terms of human suffering and financial cost was high for this preventable disease. Four patients had to be hospitalized in the intensive care unit and one died during hospitalization. The cumulative cost of hospitalization for these 33 cases was evaluated at 660,000 FF. CONCLUSION: Preventive measures for malaria must include better information for physicians on changing recommendations for chemical prophylaxis as well as better information for travelers provided by all those involved in organizing travel to endemic areas.

Adolescent↗