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Biomedical subjects

J Suleiman

Publications and source records attributed to J Suleiman.

16 recordsLinked to original sources

A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients.

BACKGROUND: Severely immunocompromised individuals are highly susceptible to Candida infection of the esophagus. This randomized, double-blind study assessed the dose-response relationship of the new echinocandin antifungal, micafungin, compared with that of standard fluconazole treatment. METHODS: A total of 245 patients (age, > or =18 years) with a prior diagnosis of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection and esophageal candidiasis, confirmed by endoscopy and culture, were randomized to receive micafungin (50, 100, or 150 mg per day) or fluconazole (200 mg per day). Both agents were administered once per day by a 1-h intravenous infusion for 14-21 days. The primary efficacy end point was endoscopic cure rate, defined as endoscopy grade of 0 at the end of therapy. RESULTS: The endoscopic cure rate (grade 0) was dose-dependent with 50, 100, and 150 mg of micafungin per day at 68.8%, 77.4%, and 89.8%, respectively. Symptoms improved or resolved rapidly (3-7 days of treatment in the majority of patients). The endoscopic cure rate for 100 and 150 mg of micafungin per day (83.5%) was comparable to that for 200 mg of fluconazole per day (86.7%; 95% confidence interval for the difference in endoscopic cure rate, -14.0% to 7.7%). The overall safety and tolerability was acceptable, with no important differences between micafungin (all doses) and fluconazole. CONCLUSIONS: The dose-response findings demonstrate a greater efficacy with micafungin at 100 and 150 mg per day than at 50 mg per day. This study also indicates that the efficacy of micafungin (at dosages of 100 and 150 mg per day) was comparable to that of fluconazole, suggesting that micafungin represents a valuable new treatment option for esophageal candidiasis in HIV-positive patients.

AIDS-Related Opportunistic Infections↗

HTLV-I/HTLV-II coinfection in an AIDS patient from São Paulo, Brazil.

A serological survey for HTLV infection identified an AIDS patient with HTLV-I/HTLV-II dual seroreactivity. Two further sequential blood samples were collected (samples A and B) for PCR, restriction fragment length polymorphism (RFLP), and sequence analyses of HTLV-I and HTLV-II strains. PCR analyses confirmed dual infection in both samples. Restriction digests of the env region amplified from sample A showed the presence of an HTLV-IIa subtype; the HTLV-II provirus was found to be defective in the pol and env regions in the second sample from this patient. RFLP analysis of the HTLV-II LTR region of both samples confirmed this finding and identified an a5/bzl restriction type. Nucleotide sequence analyses revealed full homology in the HTLV-I env and LTR regions and in the HTLV-II LTR region between the two samples. These findings document the first case of an HTLV-I/HTLV-II coinfection that was fully confirmed and characterized by means of molecular analyses.

Acquired Immunodeficiency Syndrome↗

Trypanosoma cruzi meningoencephalitis in HIV-infected patients.

Five cases of Trypanosoma cruzi meningoencephalitis in HIV-infected patients are reported. All patients presented with mass lesions on head computed tomographic scan, trypanosomes in the cerebrospinal fluid and failure to respond to antitoxoplasmosis therapy. Benznidazole therapy was associated with clinical improvement in 1 patient. Another 4 patients had T cruzi identified in a peripheral smear. T cruzi needs to be considered in the differential diagnosis of HIV-infected patients with central nervous system mass lesions if they have a history of appropriate exposure.

AIDS-Related Opportunistic Infections↗

Sensitivity of two enzyme-linked immunosorbent assay tests in relation to western blot in detecting human T-cell lymphotropic virus types I and II infection among HIV-1 infected patients from São Paulo, Brazil.

We investigated the presence of human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II) infections, first searching for specific antibodies in 553 serum samples obtained from HIV-1-infected patients from São Paulo, Brazil. Sera were screened using two enzyme-linked immunosorbent assays (ELISAs): the ELISA-EM (ELISA HTLV-I/II, EMBRABIO, BR), which contains HTLV-I and HTLV-II lysates, and the ELISA-DB [ELISA HTLV-I/II, Diagnostic Biotechnology (DB), Singapore], which contains HTLV-I lysate, and HTLV-I and HTLV-II recombinant env proteins (MTA-1 and K55, respectively). Serum samples showing two positive and/or borderline results were confirmed by Western blot (WB 2.3, DB), which discriminates HTLV-I from HTLV-II. WB analyses disclosed 22 cases (4.0%) of HTLV-I and 34 (6.1%) of HTLV-II seroreactivity; 24 sera had indeterminate antibody profile (4.3%) and 2 specimens showed reactivity to both MTA-1 and K55 env proteins. Using stringent WB criteria and analyzing the population according to risk factors, the prevalence rates of HTLV-I and HTLV-II infections were 11.2% and 16.8% in i.v. drug users, 3.4% and 5.5% in heterosexual individuals, and 1.4% and 2.2% in homosexual/bisexual men, respectively. A comparison of ELISA and WB results disclosed that both ELISAs were highly sensitive in detecting HTLV-I antibodies, whereas the ELISA-DB showed 82% sensitivity and the ELISA-EM 100% sensitivity in detecting HTLV-II antibodies. PCR analyses conducted on 37 representative cells samples confirmed the presence of HTLV proviral DNA in the majority of concordant serological cases, except in one, which was HTLV-I infected and seroreacted with K55 protein of HTLV-II. Indeed, after PCR, one case of HTLV-I infection and HTLV-II coinfection, and 30% of WB-seroindeterminate or inconclusive cases infected with HTLV-II could be detected. Our data stress high prevalences of both HTLV-I and HTLV-II infections in HIV-1 coinfected i.v. drug users from São Paulo, and suggests that ELISA kits containing only K55 protein as the HTLV-II-specific antigen, may not have the appropriate sensitivity for the detection of HTLV-II infection in this geographic region, pointing out the need of improved screening tests to be used in Brazil.

Adolescent↗

Morphological features of the retinal pigment epithelium in the toad, Bufo marinus.

BACKGROUND: The toad's (Bufo marinus) retinal pigment epithelium (RPE) has been used in many studies as a model for understanding its role and interaction with the neural retina (NR). In this study, the fine structure of the RPE is described. METHODS: In vitro RPE-chorion preparations from the toad were studied after separation from the NR. Tissues were processed for light and electron microscopy. RESULTS: The RPE consists of a single layer of cells joined by a series of tight junctions forming part of the blood-retina barrier. These cells had minimal infolding of the basal membrane and numerous microvillous processes extending from the apical surface and surrounding photoreceptor outer segments. Internally, RPE cells display a large nucleus, numerous mitochondria located at the basal membrane, extensive smooth endoplasmic reticulum, myeloid bodies, phagosomes, scattered polysomes, large lipid droplets and melanin granules. Rough endoplasmic reticulum is relatively scarce within these cells. The choriocapillaris consists of large blood vessels facing Bruch's membrane. Bruch's membrane is typical of other vertebrates, being pentalaminate over the whole retina. The endothelium of the choriocapillaris facing Bruch's membrane is typically very thin but shows few fenestrations. CONCLUSIONS: Due to the ultrastructural similarities of toad RPE with that of mammals, it can serve as an excellent model for the study of retinal detachment/reattachment and their cellular and molecular mechanisms.

Adaptation, Ocular↗

Adenosine attenuates calcium paradox injury: role of adenosine A1 receptor.

The present study was conducted to test the hypothesis that adenosine attenuates the Ca2+ paradox (PD) injury via stimulation of adenosine A1 receptors linked to Gi proteins in the isolated rat heart. Treatment of adenosine reduced maximum lactate dehydrogenase release and ATP loss compared with regular Ca2+ PD. Recovery of mechanical activity after Ca2+ repletion was observed only in heart treated with adenosine before and during the Ca2+ PD. Significant preservation of myocytes was observed in adenosine-treated hearts compared with the regular Ca2+ PD. Adenosine exerted its effects in a dose-dependent manner, being maximum at 100 microM. The protective effects were mediated by adenosine A1 receptor activation since the adenosine A1 receptor agonist N6-phenylisopropyladenosine provided protection similar to adenosine-treated heart and was blocked by A1 receptor antagonist and pertussis toxin. This study suggests that protection by adenosine against the lethal injury of the Ca2+ PD is mediated by adenosine A1 receptor and a pertussis toxin-sensitive inhibiting G protein.

Adenosine↗

Ca2+ preconditioning elicits a unique protection against the Ca2+ paradox injury in rat heart. Role of adenosine. Fixed.

Repeated Ca2+ depletion and repletion of short duration, termed Ca2+ preconditioning (CPC), is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10 minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent rapid necrosis, and myocytes were severely injured. CPC hearts showed a remarkable preservation of cell structure; ie, 65% of the cells were normal in CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/- 0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted compared with the Ca2+ PD hearts (5.9 +/- 0.8 and 3.0 +/- 0.16 mumol/g dry weight, respectively). Addition of the adenosine A1 receptor agonist R-phenylisopropyl adenosine before and during Ca2+ PD provided protection similar to that in CPC hearts, whereas the nonselective adenosine A1 receptor antagonist, 8-(p-sulfophenyl)-theophylline, blocked the beneficial effects of CPC. CPC-mediated protection was aborted when hearts subjected to CPC were treated with pertussis toxin (the guanine nucleotide or G-protein inhibitor). The present study suggests that Ca2+ preconditioning confers significant protection against the lethal injury of Ca2+ PD in rat hearts. Cardioprotection appears to result from adenosine release during preconditioning and by Gi-protein-modulated mechanisms.

Adenosine↗

A rapid and reliable assay to enumerate CD4+ T lymphocytes in whole blood.

We compared the performance of a rapid and simple anti-CD4 antibody-coated microsphere assay with flow cytometry and immunofluorescence for quantitation of absolute count of CD4+ T lymphocytes. A longitudinal evaluation of CD4+ T lymphocytes by flow cytometry and microsphere assay in 10 human immunodeficiency virus (HIV)-seronegative and 59 HIV-seropositive individuals was conducted over a period of 9 months. Standard flow cytometry analysis was performed to establish the absolute CD4+ T-lymphocyte count. The microsphere assay uses whole blood; CD14+ and CD4+ cells are first blocked by small latex beads coated with anti-CD14 antibody, and remaining cells are stained with larger anti-CD4 antibody-coated beads. Cells rosetted with only anti-CD4 antibody-coated beads are counted with use of a hemacytometer. Immunofluorescence microscopy was performed by standard techniques with use of peripheral blood mononuclear cells. The predictive value for stratification of HIV-seropositive patients by CD4+ T-lymphocyte values of < 200/microliters was 95% when the microsphere method was compared with flow cytometry. A correlation coefficient of 0.91 between the two assay methods was demonstrated in 281 CD4+ T-lymphocyte tests for absolute count. Finally, the flow cytometry method yielded better results than did the microsphere assay and immunofluorescence microscopy, in descending order of accuracy. The microsphere method should be effective in determining absolute CD4+ T-lymphocyte count in developing countries where, for a variety of reasons, no other method can be reliably performed.

CD4 Lymphocyte Count↗

Isolation of Mycobacterium avium complex from bone marrow aspirates of AIDS patients in Brazil.

Mycobacterium avium complex (MAC) infection has not been reported as a major opportunistic infection among patients with AIDS in Latin America or Africa. In this study, 125 AIDS patients who had persistent fever, anemia, and leukopenia were examined among 2628 AIDS patients admitted to Instituto de Infectologia Emilio Ribas between May 1990 and April 1992. From the bone marrow aspirates of the 125 patients, MAC was isolated from 23 (18.4%) and Mycobacterium tuberculosis was isolated from 9 (7.2%). Between 1985 and 1990, only 11 MAC isolations among 60,000 cultures obtained from human immunodeficiency virus-seronegative patients were documented in São Paulo. Hence, the minimal estimated rate of MAC infection in AIDS patients in this city was 23/2628, or 0.88%. These findings suggest that MAC infection is an important opportunistic infection, especially among a subset of patients with AIDS in Brazil who have clinical characteristics and risk activities similar to those associated with MAC infections in North America and Europe.

AIDS-Related Opportunistic Infections↗

Genetic heterogeneity of the V3 region of the HIV-1 envelope glycoprotein in Brazil. Brazilian Collaborative AIDS Research Group.

OBJECTIVE: To examine the genetic heterogeneity of the V3 region of HIV-1 gp120 from 22 Brazilian HIV-1 specimens. DESIGN: Genetic heterogeneity was examined by DNA sequencing of the C2 V3 region of the HIV-1 envelope (env) gene from polymerase chain reaction (PCR)-amplified HIV-1 DNA. Deduced amino-acid sequences were compared to determine the extent of amino-acid conservation among the Brazilian specimens. Genetic similarity among and between the Brazilian specimens and other previously published HIV-1 isolates was analyzed by principal co-ordinate and DNA parsimony methods. METHODS: A 282 base pair (bp) region of a 1.5 kilo (k) bp PCR-amplified HIV-1 env fragment was sequenced by a Taq dye-labeled primer cycle sequencing reaction. Nucleotide sequences were used to analyze inter-specimen relationships based on overall nucleotide sequence similarity and DNA parsimony principles. RESULTS: Amino-acid comparison showed that 15 of the 35 (43%) residues of the V3 loop were conserved among the Brazilian specimens. Nine of the 22 (40%) Brazilian specimens contained the North American-European GPGR tetrapeptide motif, while eight (36%) contained the GWGR motif, previously reported in Japanese isolates. Principal co-ordinate analysis demonstrated that 19 of the 20 examined Brazilian HIV-1 specimens were more similar to North American and Haitian isolates than to African isolates. Similar results were also obtained by DNA parsimony analysis. CONCLUSION: The majority of the Brazilian specimens examined are more genetically related to North American and Haitian HIV-1 isolates than to African isolates. This finding and the presence of a GWGR V3 loop motif in some Brazilian isolates may be important for vaccine development.

Acquired Immunodeficiency Syndrome↗