Incomplete genotypic resistance to nonnucleoside reverse transcriptase inhibitors in patients treated with nevirapine: a potential interest in clinical practice.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M Duong
Publications and source records attributed to M Duong.
Increased prevalence of subclinical hypothyroidism in HIV patients treated with highly active antiretroviral therapy.
Explore the source record for details and available documents.
Adult↗
Hepatitis B virus seroconversion in HIV-HBV coinfected patients treated with highly active antiretroviral therapy.
Explore the source record for details and available documents.
Adult↗
[Congenital tracheobiliary fistula].
A case of congenital bronchobiliary fistula in a three-year old girl is reported. The patient was born after 40 weeks of gestation and referred due to a long history of respiratory tract problems. Bronchoscopy disclosed a third opening at the level of the carina. The opening was cannulated with an X-ray positive catheter, and a fistula crossing the diaphragm and communicating with the left hepatic duct was found. Cholescintigraphic examination (HIDA-scanning) confirmed the presence of the fistula, but found no evidence of abnormalities in the rest of the biliary system. The thoracic portion of the fistula was excised through a right side thoracotomy. The postoperative course was uncomplicated. HIDA-scanning one month after the operation showed normal uptake, and the girl's symptoms had disappeared.
Biliary Fistula↗
HIV-1 protease inhibitors induce an increase of triglyceride level in HIV-infected men without modification of insulin sensitivity: a longitudinal study.
We investigated longitudinally the effect of protease inhibitors (PI) on insulin sensitivity, glycemia, and serum lipids in HIV-infected patients. Ninety-one consecutive patients treated with PI for at least 12 months were included in this study. Fasting glycemia, lipid profile, insulinemia, CD4 T lymphocytes, and plasma HIV-1 RNA were performed at baseline and on PI therapy. Insulin sensitivity and insulin secretion were measured by the homeostasis model assessment (HOMA MODEL) using the fasting glucose and insulin concentrations. Triglycerides (+ 0.34 mmol/l, SD = 1.07, p = 0.001) and cholesterol (+ 1.07 mmol/l, SD = 1.21, p= 0.001) significantly increased on PI therapy. Fasting glycemia, insulin sensitivity, and insulin secretion were not modified after PI therapy. PI therapy significantly increased body mass index (0.35 kg/m2, p < 0.05). Serum lipid changes correlated with changes in the CD4+ cell count. Lipodystrophy was observed in 40.6% of patients treated with PI. Our longitudinal study found that PI therapy had no major impact on fasting glycemia, insulin sensitivity, and insulin secretion. These findings are not consistent with previous cross-sectional studies, which did not include baseline measurements before PI initiation. However, we observed a similar profile of lipid changes induced by PI therapy. These results suggest that PI could be responsible for the development of hypertriglyceridemia by a mechanism independent of insulin resistance which remains to be elucidated.
Adult↗
Recurrent NNRTI-induced hepatotoxicity in an HIV-HCV-coinfected patient.
Explore the source record for details and available documents.
Adult↗
[Discontinuing protease inhibitor treatment of HIV-1 patients for intolerance. Longitudinal study of 309 patients].
OBJECTIVES: Determine the frequency and nature of interruptions in HIV-1 protease inhibitor treatment in HIV-infected patients. PATIENTS AND METHODS: A longitudinal study included patients treated with antiretroviral protocols including at least one antiprotease and followed from 1 March 1996 through 1 March 1998. RESULTS: Among the 309 patients followed for the duration of the study, 137 (44.3%) interrupted their antiprotease treatment at least once. Withdrawal was warranted by therapeutic failure in 49.6% of the cases and by drug intolerance in 45.4%. Drug intolerance concerned 37%, 36.7%, 5.7% and 2.9% of the patients taking ritonavir, indinavir, nelfinavir and saquinavir respectively (p < 106). Multivariate analysis demonstrated that saquinavir was significantly associated with better tolerance and with efficacy at least as good as ritonavir or indinavir. The most frequent cause for interrupting treatment were digestive disorders for ritonavir (20% of the treated patients) and lithiasic manifestations for indinavir (9.4%). The ritonavir-hepatitis C association appeared to predispose to drug-induced perturbed liver tests. CONCLUSION: Drug intolerance is a frequent cause of treatment interruption. Therapeutic success in HIV infection requires improved efficacy but also better tolerated antiretorviral drugs, particularly antiretroviral drugs.
Adult↗
Transmission of afferent information from urinary bladder, urethra and perineum to periaqueductal gray of cat.
The micturition reflex pathway is a supraspinal pathway. Anatomical tracing evidence is compatible with an involvement of the periaqueductal gray (PAG) in the ascending limb of this reflex. We tested the involvement of the PAG in receiving urinary tract- or perineum-related information and attempted to characterize this ascending path in terms of what type of information is being conveyed. Electrical stimulation of the pelvic nerves, which carry afferent information from the urinary bladder, evoked maximum field potentials in the caudal third of the PAG, primarily in the dorsal part of the lateral PAG and in the ventrolateral PAG. Since the regions activated by pelvic nerve stimulation differed from those activated by stimulation of the sensory pudendal or superficial perineal nerves, it is possible that specific pathways for different nerve inputs to the PAG exist. Sacral spinal cord neurons ascending to the PAG were identified by antidromic activation and then tested for inputs from pelvic, sensory pudendal or superficial perineal nerves. Of 18 units identified, only five received inputs from any of the peripheral nerves tested and only two projecting neurons received a pelvic nerve input. Thus the PAG may receive inputs from bladder and perineum, but the small proportion of cells with direct projections to the PAG receiving inputs from our test nerves implies that the major part of this pathway is not directly related to lower urinary tract function.
Afferent Pathways↗
Comparison of molecular changes in cervical intraepithelial neoplasia in HIV-positive and HIV-indeterminate subjects.
OBJECTIVE: HIV infection is associated with an increased incidence of cervical malignancy and its precursor lesions (CIN, cervical intraepithelial neoplasia) compared with the general population. We studied the molecular abnormalities in the development of HIV-associated CIN and compared them with those present in CINs arising in HIV-indeterminate subjects ("sporadic CIN"). METHODS: We investigated the presence of human papilloma virus (HPV) sequences, loss of heterozygosity (LOH), and microsatellite alterations (MAs) at five 3p chromosomal regions using 17 polymorphic markers in precisely microdissected archival tissues from 16 HIV-positive CINs and compared them with those present in 39 sporadic CINs. RESULTS: HPV sequences were detected in 36 of 55 (66%) CIN lesions, and high-risk oncogenic strains (HPV 16 and 18) accounted for 15 of them. No differences in the HPV frequencies were found between HIV-associated and sporadic CINs. Allelic losses at one or more chromosome 3p regions were frequently detected in CIN lesions (49%). The overall frequency of 3p LOH and the frequencies at all individual regions were similar in HIV-associated and sporadic CINs. The frequency of MA present in the HIV-associated CIN cases (0.093) was sixfold greater than in sporadic CINs (0.014; P = 0.0001). At least 1 MA was present in 11 (69%) of 16 HIV-associated vs. 5 of 39 (13%) sporadic CIN (P = 0.0006). Molecular changes were independent of the presence of HPV sequences. CONCLUSION: Chromosome 3p deletions are frequently detected in the precursor lesions of cervical carcinoma (CIN) and there are no differences in the 3p LOH frequencies between HIV-associated and sporadic CIN lesions. Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated CIN. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated neoplasias.
DNA Probes, HPV↗
Development of a new experimental model of penicillin-resistant Streptococcus pneumoniae pneumonia and amoxicillin treatment by reproducing human pharmacokinetics.
The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log(10) CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log(10) CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log(10) CFU/ml, P < 10(-6)) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.
Amoxicillin↗
Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients?
OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. DESIGN: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l. CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.
Adult↗
Myocardial tissue engineering with autologous myoblast implantation.
OBJECTIVE: Implanting myoblasts derived from autologous skeletal muscle, that is, satellite cells, for myocardial replacement has many advantages when compared with implanting either fetal cardiac myocytes (ethical and donor availability issues) or established cell lines (oncogenicity). Furthermore, autologous myoblasts do not require immunosuppression. The feasibility of satellite cell differentiation into muscle fibers, after implantation into the myocardium, was confirmed by means of a unique cell-labeling technique. METHODS: Myoblasts (satellite cells) isolated from the skeletal muscle of adult rats are labeled with 4',6-diamidino-2-phenylindone, which binds to DNA and to the protein tubulin to form a fluorescent complex, and implanted into the left ventricular wall of isogenic rats. The specimens are harvested 1 to 4 weeks after myoblast implantation. Histologic sections are examined under a fluorescent microscope. RESULTS: The labeling efficiency of satellite cells with 4',6-diamidino-2-phenylindole is nearly 100%. In 4 specimens, the progressive differentiation of implanted myoblasts into fully developed striated muscle fibers can be observed. CONCLUSION: Our earlier studies of autologous myoblast implantation into the cryoinjured myocardium of dogs suggested that these cells could differentiate into cardiac myocytes. However, it had been difficult to firmly establish these findings with the use of cell markers, thereby proving that the neomyocardium had indeed been derived from the implanted myoblasts. In this study, using 4',6-diamidino-2-phenylindole as a satellite cell marker, we were able to demonstrate that the implanted satellite cells did in fact differentiate into fully developed, labeled muscle fibers. Because of the obvious advantages of using autologous donor myoblasts, the clinical application of this approach may provide a novel strategy for the future management of heart failure.
Animals↗
Kinetic study of host defense and inflammatory response to Aspergillus fumigatus in steroid-induced immunosuppressed mice.
The sequential pathogenesis of pulmonary aspergillosis was studied and the role of inflammatory cytokines in host response to Aspergillus fumigatus was characterized in immunocompetent and immunosuppressed mice. Two distinct phases were observed in immunocompetent mice: First, an intense clearance of A. fumigatus occurred, possibly through alveolar macrophages and recruited neutrophils (PMNL), accompanied by rapid release of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1beta, and second, cellular and fungal debris were cleaned by recruited monocytes, cytokine production rapidly decreased, and pneumonia self-healed. In contrast, cortisone-treated animals had, first, an altered clearance of conidia and delayed cytokine production and inflammatory cell recruitment; second, an invasive process in lungs, recruitment of PMNL, and release of IL-6 and IL-1beta; and third, widespread tissue necrosis, sustained release of IL-6 and IL-1beta, further increases in PMNL trafficking but no monocyte recruitment, respiratory failure, and 100% mortality within 5 days. These insights may be useful in the development of new treatment strategies for pulmonary aspergillosis.
Adrenal Cortex Hormones↗
Experimental efficacy of combined ceftriaxone and amoxycillin on penicillin-resistant and broad-spectrum cephalosporin-resistant Streptococcus pneumoniae infection.
The activity of amoxycillin and ceftriaxone, alone and in combination, was tested against four strains of penicillin-resistant pneumococci in vitro and in an animal model. Three of the strains were also resistant to third-generation cephalosporins. Fractional inhibitory concentration indexes for combined amoxycillin and ceftriaxone were measured by the Etest method and were considered additive (1.2; 1.1; 1.3 and 1.3 for the four strains). Twenty-four hour time-kill curves for two strains showed that the combination was additive or synergic for concentrations up to the MIC of the single drugs. The efficacy of these antibiotics alone and in various combinations against strains 16089 and 11724 were investigated in vivo using prolonged (48 h) experimental fibrin clot infection in rabbits. The bacterial reductions (delta log10 cfu/g) obtained for all the antibiotic combinations tested were significantly higher than those of the single drug regimens. The in-vivo efficacy of amoxycillin was significantly correlated with the time for which its concentration was above the MIC and that of ceftriaxone was correlated with its maximal concentration. From these findings, we concluded that, at concentrations easily achievable in humans, the combination of amoxycillin and ceftriaxone was strongly synergic against infection due to penicillin- and cephalosporin-resistant pneumococci.
Amoxicillin↗
Immunomodulating effects of HMR 3004 on pulmonary inflammation caused by heat-killed Streptococcus pneumoniae in mice.
We investigated the influence of HMR 3004, a new ketolide antibiotic, on the pulmonary inflammation induced by heat-killed fluorescein isothiocyanate-labeled Streptococcus pneumoniae. HMR 3004 downregulated (P < 0.05) the pneumococcus-induced release of interleukin-6 (IL-6), IL-1beta, and nitric oxide in bronchoalveolar lavage fluid. The drug limited (P < 0.05) neutrophil recruitment to lung tissues and alveoli but did not interfere with phagocytosis. HMR 3004 totally abrogated lung edema. By reducing inflammation in addition to possessing antimicrobial properties, HMR 3004 may participate in improving the outcome of bacterial pneumonia.
Adjuvants, Immunologic↗
Non-Hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus.
A case of HIV-associated cardiac non-Hodgkin's lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune deficiency syndrome-defining condition in the majority. Patients were referred with nonspecific clinical findings including dyspnea and tachycardia, but rapid progression of cardiac dysfunction was frequent after symptoms appeared. Echocardiography constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had disseminated diseased at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high-grade subtypes. Prognosis of HIV-associated cardiac NHL is generally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HIV-associated patients are typically high-grade and often disseminate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival under systemic chemotherapy.
Adult↗
In-vivo activity and tolerance of conventional formulation versus fat emulsion formulation of amphotericin B in experimental disseminated candidiasis in neutropenic rabbits.
Amphotericin B can cause significant toxicity but this can be reduced by direct dilution into a fat emulsion (Intralipid). To investigate the potential use of amphotericin B diluted in Intralipid, a study was made of its activity in the treatment of subacute disseminated candidiasis in persistently granulocytopenic rabbits, compared with the same dose of amphotericin B diluted in dextrose. Amphotericin-B-fat emulsion was at least as effective as amphotericin-B-dextrose. Amphotericin-B-fat emulsion was significantly more effective than amphotericin-B-dextrose therapy in reducing candida colony counts in both kidney and liver tissues (P < 0.05). Furthermore, amphotericin-B-fat emulsion was found less toxic on the renal function than conventional amphotericin B (P < 0.05). From these experimental results, we conclude that amphotericin-B-fat emulsion (Intralipid) was at least as effective and less toxic than conventional amphotericin B.
Amphotericin B↗
Renal failure after treatment with ritonavir.
Explore the source record for details and available documents.
Acute Kidney Injury↗