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Biomedical subjects

S Rasheed

Publications and source records attributed to S Rasheed.

At least 37 records · Page 2Linked to original sources
PubMed1996

Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone with zalcitabine in patients with acquired immunodeficiency syndrome-related lymphoma. Effect on human immunodeficiency virus and serum interleukin-6 levels over time.

BACKGROUND: Use of multiagent chemotherapy has been associated with complete remission (CR) in approximately 50% of patients with newly diagnosed acquired immunodeficiency syndrome (AIDS)-lymphoma, although additional AIDS-related complications may occur. Both chemotherapy and antiretroviral therapy were employed in an attempt to ascertain if the combination was safe, and associated with changes in human immunodeficiency virus (HIV) p24 antigen levels during the course of treatment. METHODS: Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone(M-BACOD) chemotherapy and zalcitabine (ddC) were employed in 28 patients. Since both vincristine and zalcitabine may cause peripheral neuropathy, a Phase I/II study design was employed. Serum was analyzed for immune complex dissociated (ICD) HIV p24 antigen and interleukin (IL)-6 levels during therapy. RESULTS: CR was achieved in 14 of 25 patients (56%), with partial response (PR) in 5 (20%). CRs were equivalent in patients with good or poor prognostic indicators, including a history of AIDS prior to lymphoma (CR = 60%); and/or CD4 lymphocytes < 200/mm3 (CR = 53%). Five patients with a CR subsequently relapsed (36%); median survival of CR patients was 29.2 months (4.1-61+), whereas that of all of the treated patients was 8.1 months. No significant peripheral neuropathy or other toxicity was observed. Serum ICD p24 antigen levels either fell (7/14) or remained consistently negative (2/14) in 9 of 14 patients (64%), whereas 36% experienced an increase. Elevated serum IL-6 levels at diagnosis were associated with systemic "B" symptoms (P = 0.023), whereas changes in IL-6 correlated with response to therapy over time (P = 0.006). CONCLUSIONS: Combination antineoplastic and zalcitabine antiretroviral therapy may be safely administered to patients with AIDS-related lymphoma, resulting in CR in 56%, lack of significant neurotoxicity, and favorable effect on HIV p24 antigen in 50%. Elevation of serum IL-6 is associated with systemic "B" symptoms, whereas changes in serum IL-6 may correlate with response.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Human T-cell lymphotropic virus types I and II infections in patients with leukaemia/lymphoma and in subjects with sexually transmitted diseases in Nigeria.

Serological assays that distinguish antibodies to human T-cell lymphotropic virus types I (HTLV-I) and type II (HTLV-II), and polymerase chain reaction (PCR) tests were used to investigate association of these two human retroviruses with several well-defined clinical conditions in Nigeria. We compared the frequency of HTLV-I and HTLV-II infections among patients with lymphopholiferative disorders (n=65), individuals with various sexually transmitted diseases (n=40), patients with genitals candidiasis (n=25) and apparently healthy individuals (n=60). Serological analysis of blood samples from all four groups showed that 10 of the 190 (5.3%) individuals tested were confirmed positive for the presence of antibodies to HTLV-I(6) or HTLV-II(4). Using the PCR technique, specific HTLV-I or HTLV-II sequences were amplified from the genomic DNA of 4 of 6 HTLV-I seropositive and 3 of the 4 HTLV-II seropositive individuals respectively. However, sequences of both viruses were amplified from the genomic DNAs of the remaining 3 seropositive individuals. Since one of the 5 sets of primer pairs [SK110(II)/SK111(II)], which is used for specific identification of HTLV-II did not amplify the target sequence from the genomic DNAs of any of the 4 HTLV-II confirmed seropositive individuals in this study, it suggested sequence diversity of these viruses in Nigeria. The virus-infected individuals identified in this study were one (1.5%) of the 65 patients with leukaemia/lymphoma (HTLV-I), 6 of 40 (15.0%) individuals (HTLV-I = 1 , HTLV-II = 3, HTLV-I/II = 2) with sexually transmitted diseases (STD), one of 25(4.0%) subjects with genital candidiasis for HTLV-I and 2 of 60 (33.3%) healthy individuals (one for HTLV-I and one for HTLV-I/II). There was a significant difference (P < 0.025) between the prevalence of HTLV-I/II infections among patients with lymphoma/leukaemia and those who attended STD clinic in Ibadan, Nigeria. This study also suggests that while HTLV-I and HTLV-II may be important sexually transmitted viruses, they may not be specific aetiological agents of the common lymphoproliferative disorders in Nigeria.

Adult↗
PubMed1996

Presence of cell-free human immunodeficiency virus in cervicovaginal secretions is independent of viral load in the blood of human immunodeficiency virus-infected women.

OBJECTIVE: The purpose of this study was to establish virologic or molecular criteria for evaluating the rate of transmission of human immunodeficiency virus type 1 and for defining the role of virus burden in the development of gynecologic diseases in human immunodeficiency virus-infected women. STUDY DESIGN: Paired samples of blood and cervicovaginal secretions from 63 human immunodeficiency virus-seropositive women were evaluated for cell-free and cell-associated virus load by several methods, including quantitative cultures and reverse transcription polymerase chain reaction. RESULTS: All women showed evidence of virus infection in both blood and cervicovaginal secretions by a combination of in vitro culture and molecular detection methods. The CD4+ cell counts in these women ranged from < 200/microliter to > 500/microliter. Blood plasma of 26% women (12/46) did not show detectable levels of human immunodeficiency virus ribonucleic acid by reverse transcription polymerase chain reaction (< 10(2)/100 microliters). These same women had significant amounts of human immunodeficiency virus in the cell-free cervicovaginal secretions (10(2) to 10(5) copies per 100 microliters). In contrast, 17% (8/46) women with significant quantity of human immunodeficiency virus ribonucleic acid in the blood plasma had negative results for human immunodeficiency virus in the cervicovaginal secretions. Further, treatment of women with the antiviral drug zidovudine did not change the human immunodeficiency virus-1 detection rate in plasma ribonucleic acid but showed significant reduction in the ability to detect human immunodeficiency virus ribonucleic acid in cell-free cervicovaginal secretions (p = 0.036). CONCLUSIONS: We conclude that the replication kinetics of human immunodeficiency virus in the blood and cervicovaginal cells are unrelated, independent events. Further, there is no correlation between the virus load or the CD4+ cell counts in the blood and the presence or absence of quantifiable human immunodeficiency virus in cervicovaginal secretions.

Antiviral Agents↗
PubMed1996

Isolation and characterization of a new subtype A variant of human immunodeficiency virus type I from Nigeria.

We have isolated a new variant of HIV-1 from Nigeria, Africa. The virus was recovered from the peripheral blood mononuclear cells (PBMCs) of an apparently healthy 23-year-old male from Ibadan, Nigeria. The in vitro studies indicated that the virus was highly cytopathic and replicated well in normal PBMCs, established T-cell lines and the monocytic cell line U937. The highest replicative titre of the virus was obtained in freshly isolated primary macrophage/monocyte cells which also showed the least cytopathology. Most other cultures showed single-cell cytolysis and giant cells, and syncytia were not induced in the HTLV-1 infected MT-2 cells. Since no HIV strain has been isolated from Nigeria, we obtained cDNA clones containing the env gene, to further characterize the Nigerian virus. Based on the DNA sequence analysis of 14 clones containing the coding region for its gp 120 protein, the Nigerian HIV isolate has been classified as HIV-1 subtype A. Only one subtype A virus from Rwanda has been characterized and this virus has not been shown to exhibit extreme cytopathicity in various cell types as was observed with the Nigerian strain. Further, the ability of this virus to grow well in lymphocytes, monocytes and macrophages and to exhibit cytopathicity without causing syncytia are uncommon properties distinguishing the Nigerian virus from other HIV-1 strains. Since most macrophage-tropic viruses have been associated with 'neurotropism', the isolation of an HIV-1 strain from the blood of an individual with no known neurological disorder indicates that this rapidly replicating cytopathic virus, with a broad host range, may play an important role in the pathogenesis of HIV disease. This represents the first report of an HIV-1 isolate from Nigeria.

Adult↗
PubMed1996

Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

Clinical Protocols↗
PubMed1996

Evaluation of an infectivity standard for real-time quality control of human immunodeficiency virus type 1 quantitative micrococulture assays. Participating Laboratories of The AIDS Clinical Trials Group.

Quantitative microculture assays of cryopreserved human immunodeficiency virus type 1-infected cell suspensions and culture supernatants were compared among seven assays sites. There was no significant change in titer during 1 year of storage. The overall standard deviation for infected cell suspensions was approximately 0.8 log10 virus titer. A method for detecting deviant assay results was developed and was used to identify two donor cell preparations (n = 54) that gave consistently low titers.

Cell Culture Techniques↗
PubMed1995

Evidence of serological cross-reactivities with human immunodeficiency virus types 1 and 2 and human T-lymphotropic virus types I and II in sera of pregnant women in Ibadan, Nigeria.

BACKGROUND: Our previous studies have indicated that the human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV) groups of retroviruses are endemic among various populations in Nigeria. These viruses are antigenically distinct and antibodies to HIV and HTLV do not cross-react, so we studied the prevalence of HIV-1, HIV-2, HTLV-I and HTLV-II antibodies in sera of pregnant women attending an antenatal clinic in Ibadan, Nigeria. METHODS: In all, 364 sera were screened using three different enzyme immunoassays, including those that distinguished HIV-1 antibodies from HIV-2, and HTLV-I antibodies from HTLV-II. All repeatedly reactive sera were confirmed by Western blots and synthetic peptide assays for the respective viruses. RESULTS: Overall, 71 sera (19.5%) had antibodies to HIV, HTLV or both groups of retroviruses. Most (95.8%) of the reactive samples were from women 20-29 years old. Two of five sera from individuals < 20 years old reacted for HIV antibodies while one serum from a 40 year old woman was reactive for HTLV-I antibodies. Of the 71 reactive sera, 29 (8%) had antibodies to HIV (HIV-1 = 14, HIV-2 = 9, HIV-1/2 = 6) and 42 samples (11.5%) showed antibodies to HTLV (HTLV-I = 20, HTLV-II = 14, HTLV-I/II = 8). Seven of 71 seropositive samples (9.8%) reacted for both HIV and HTLV antibodies in various combinations, including one serum that showed antibody reactivities to all four retroviruses (i.e. HIV-1, HIV-2, HTLV-I and HTLV-II). CONCLUSIONS: The high prevalence of antibodies to subtypes of the two entirely distinct retrovirus groups in young women has important implications for defining epidemiological patterns of diseases associated with co-infections with two or more retroviruses.

Adolescent↗
PubMed1995

Comparison of a rapid nonisotopic polymerase chain reaction assay with four commonly used methods for the early diagnosis of human immunodeficiency virus type 1 infection in neonates and children.

To initiate antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia, it is important to identify human immunodeficiency virus (HIV-1)-infected infants as soon after birth as possible. This study was undertaken to evaluate a novel 5-hour nonisotopic (NI) polymerase chain reaction (PCR) assay (Amplicor PCR; Roche Molecular Systems) and four other commonly used HIV-1 diagnostic tests including culture, oligonucleotide hybridization PCR, p24 antigen and immune complex-dissociated (ICD) p24 antigen tests and to determine the optimal age at which to perform these tests for the early and rapid diagnosis of HIV-1 in infants and children. We prospectively evaluated 225 infants and children, including 114 neonates, for HIV-1 infection. HIV-1 infection was defined as 2 positive HIV cultures. Of the 225 infants and children, 57 were infected, 138 were uninfected and 30 were of unknown (Centers for Disease Control and Prevention Classification P0) status. The sensitivity of NI PCR was 60% in cord blood, 40% at 0 to 2 days, 67 to 80% in the neonate (3 to 30 days) and 95 to 100% after 1 month of age. NI PCR was as sensitive as oligonucleotide hybridization PCR, culture, p24 antigen and ICD p24 antigen in the first 2 months of life and was more sensitive than p24 antigen or ICD p24 antigen thereafter. Specificity was 94% for cord blood and 99 to 100% for all age groups. The majority of HIV-1-infected newborns can be identified with NI PCR if testing is performed at birth and again between the third and fourth weeks of life. For older infants and children 2 NI PCR tests can correctly diagnose 98.5% of infected and uninfected infants and children. NI PCR of umbilical cord blood might also be useful as an initial screening test to identify infants who may be infected with HIV-1.

AIDS Serodiagnosis↗
PubMed1995

Geographical clustering of human T-cell lymphotropic virus type 1 infection in Honduras.

Geographical clustering of human T-cell lymphotropic virus type 1 (HTLV-1) infection has been identified in the nonmestizo communities in several cities along the Atlantic coast of Honduras. Of the 2,651 serum samples tested, 122 samples were repeatedly reactive for HTLV-1 antibodies in two different enzyme immunoassays and 3 were indeterminate. These sera did not react in the HTLV-2-specific antibody tests. The presence of HTLV-1 antibodies was confirmed by HTLV-1 immunoblots or Western blots (immunoblots), and the infection was verified by the detection of HTLV-1-specific genetic sequences in the cellular DNA by PCR. Genomic DNA from the peripheral blood mononuclear cells was first tested with generic primers and probes that identified both HTLV-1 and HTLV-2. Next, all DNA samples that showed HTLV reactivity were tested by PCR with specific primers and probes that distinguished HTLV-1 sequences from those of HTLV-2. Our results indicate that only HTLV-1 infection was present in the blood of both mestizo and nonmestizo residents of 15 cities in the Republic of Honduras. The overall prevalence of HTLV-1 infection in the nonmestizo population was 8.1% (95% confidence limit, 6.6 to 9.7%). The mestizo population residing in the same geographical vicinities showed a HTLV-1 antibodies in 0.5% of serum samples tested (95% confidence limit, 0.6 to 1.7%), indicating a significantly greater prevalence of HTLV-1 infection in the nonmestizo population than in the mestizo ethnic groups living in Honduras (P = 0.0001). Since no HTLV-2 antibody reactivity or HTLV-2-specific genetic sequences were detected by PCR with different primers and probes, it was concluded that HTLV-2 infection was not present in the Honduran population groups we tested. Our study also suggested an endemic nature for this virus because there was no difference in the prevalence rate of HTLV-1 antibodies in the nonmestizo community living in the coastal towns of Honduras between 1989 and 1993. This is the first report of HTLV-1 cluster identification in Honduras, Central America.

Adolescent↗
PubMed1995

Human immunodeficiency virus load. Quantitative assessment in semen from seropositive individuals and in spiked seminal plasma.

OBJECTIVE: To establish criteria for the quantitation of the human immunodeficiency virus (HIV) in seminal plasma, seminal cells and the whole semen of HIV-infected individuals. The reverse transcription polymerase chain reaction (RT-PCR), DNA-PCR and semen HIV culture assays were standardized by testing seminal plasma spiked separately with serial dilutions of cell-free and cell-associated HIV stocks of known titers. The standardized assays were then used to assess the quantity of virus in the freshly collected seminal cells and seminal plasma. RESULTS: Analysis of freshly collected peripheral blood mononuclear cells (PBMCs) and paired semen from HIV-seropositive men who had received antiviral drugs and/or immunemodulators indicated that HIV could be isolated from 42 of 55 (76%) samples of peripheral blood mononuclear cells (PBMCs) and 13 of 55 (24%) samples of ejaculates. Since no semen sample was culture positive in the absence of culturable HIV in PBMCs of the same individual, RT-PCR was 5-125 times more sensitive than cell cultures for the quantitation of HIV spiked in seminal plasma, freshly collected seminal fluid and whole semen. Further, HIV-RNA was detected in samples containing higher dilutions of virus from which HIV was not isolated by culture. CONCLUSION: We conclude that cell-free HIV is present in excess of the culturable virus in all specimens tested and that the high sensitivity of HIV-RNA detection is useful for quantitation of the virus directly in seminal fluid, seminal cells and whole semen.

Cell Survival↗
PubMed1994

Preliminary screening of methanolic extracts of Celastrus paniculatus and Tecomella undulata for analgesic and anti-inflammatory activities.

Flowers of Celastrus paniculatus and whole plant of Tecomella undulata were extracted individually in absolute methanol. Using the hot water tail immersion test in mice and carrageenan induced pedal edema in rats, both extracts were tested for their oral analgesic and anti-inflammatory potentials. Results showed that C. paniculatus had both analgesic and anti-inflammatory activities, while T. undulata had only analgesic potential when compared with aspirin.

Analgesics↗
PubMed1994

Serum p24 antigen level as an intermediate end point in clinical trials of zidovudine in people infected with human immunodeficiency virus type 1. Aids Clinical Trials Group Virology Laboratories.

Serum p24 antigen levels were examined in subjects from three clinical trials of zidovudine to determine whether the pattern of change in serum p24 antigen during the first 8-16 weeks of therapy was associated with human immunodeficiency virus type 1 (HIV-1) disease progression or death. Among 406 patients with AIDS and a first episode of Pneumocystis carinii pneumonia, 65% had measurable pretreatment concentrations of serum p24 antigen (> or = 10 pg/mL). Changes during treatment were not associated with reduced mortality. In 637 mildly symptomatic patients, 24% had measurable concentrations, and changes were marginally associated with increased time until more advanced disease. Among 683 asymptomatic patients, 18% had measurable concentrations, and changes were not associated with increased time until progression. Despite the small number of clinical events and the low rate of serum p24 antigen positivity in the latter two studies, pretreatment serum p24 antigen levels were predictive of clinical outcome; subsequent measurements appear to be of limited use in evaluating zidovudine therapy.

AIDS-Related Complex↗
PubMed1994

Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations.

Drug resistance conferred by specific human immunodeficiency virus type 1 (HIV-1) pol gene mutations has been associated with clinical progression in HIV-infected patients receiving anti-retroviral therapy. This study examined drug susceptibilities and pol mutations of HIV-1 strains from patients treated for 1 year with zidovudine, didanosine (ddI), or zidovudine and ddI. Ten (42%) of 24 patients receiving combination therapy versus 8/26 (31%) receiving only zidovudine had HIV-1 strains with phenotypic zidovudine resistance or a zidovudine resistance pol mutation at codon 215 (P = .6). In contrast, a ddI resistance mutation at codon 74 was less common among patients receiving combination therapy (2/24) than among those receiving ddI only (17/26; P < .001). Two patients receiving combination therapy developed resistance to zidovudine and ddI; they had HIV strains with amino acid mutations at codons 62, 75, 77, 116, and 151. Combination therapy with zidovudine and ddI selects for zidovudine-resistant HIV-1 strains lacking a ddI resistance mutation and for multidrug-resistant strains containing novel pol mutations.

Amino Acids↗
PubMed1994

Multicenter evaluation of quantification methods for plasma human immunodeficiency virus type 1 RNA.

Six procedures for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated by nine laboratories. The procedures differed in their sample volume and preparation of samples and methods of amplification and detection. Coded samples in a 10-fold dilution series of HIV-1-spiked plasma were correctly ranked by all six procedures. Subsequently, coded duplicate plasma samples from 16 HIV-1-infected patients were tested using a common set of standards. Several HIV-1 RNA procedures were sufficiently reproducible so that an empiric 4-fold change could be viewed as significant. HIV-1 RNA levels in the patients (up to 370,000 RNA copies/mL) correlated with proviral HIV-1 DNA and were inversely correlated with CD4 cell counts; HIV-1 RNA assays were more sensitive than plasma viremia, standard p24 antigen, or immune complex-dissociated p24 antigen assays. This study demonstrated that several HIV-1 RNA quantitative assays are ready for use in clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Optimization of quantitative culture assay for human immunodeficiency virus from plasma. Plasma Viremia Group Laboratories of the AIDS Clinical Trials Group (National Institute of Allergy and Infectious Diseases).

Experimental conditions essential to a simple, reproducible, quantitative human immunodeficiency virus plasma assay were determined. Five parameters were evaluated: length of culture, reproducibility, assay dilution schema, washing procedures, and anticoagulant usage. The recommended quantitative plasma assay utilizes undiluted citrated plasma cultured with peripheral blood mononuclear cells for 14 days with fivefold dilutions and a medium change on day 1 with no washing.

Blood↗
PubMed1994

Effects of gamma irradiation on the human immunodeficiency virus. A study in frozen human bone-patellar ligament-bone grafts obtained from infected cadavera.

We studied the effects of several different doses of gamma radiation, ranging from 20,000 to 40,000 gray (2.0 to 4.0 megarad), with respect to the inactivation of the human immunodeficiency virus in fresh-frozen, whole bone-patellar ligament-bone grafts. Although the International Atomic Energy Agency has recommended the use of 25,000 gray of gamma radiation for the sterilization of medical products, the dose required for the inactivation of the human immunodeficiency virus in frozen allografts has not been established. Using one of the most sensitive and specific tests for the detection of the human immunodeficiency virus, the polymerase-chain-reaction test, we found that doses of 20,000 or 25,000 gray of gamma radiation did not destroy the genes of the human immunodeficiency virus effectively; DNA of the virus was detectable in the DNA of bone-marrow tissue obtained from grafts treated with these doses. However, DNA of the human immunodeficiency virus was not detectable in the grafts treated with 30,000 or 40,000 gray of gamma radiation. We conclude that a dose of 30,000 gray of gamma radiation or more is necessary for the sterilization of a fresh-frozen bone-patellar ligament-bone allograft, so that it can be used for reconstructive procedures without the risk of transmission of the virus to the recipient.

Bone Transplantation↗