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Biomedical subjects

S E Read

Publications and source records attributed to S E Read.

At least 37 records · Page 2Linked to original sources
PubMed1991

Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme.

Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.

Base Sequence↗
PubMed1991

Colchicine: a state-of-the-art review.

Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule-dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3',5'-adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half-lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine-induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long-term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Down's syndrome, the agent should not be used by pregnant women.

Amyloidosis↗
PubMed1991

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

AIDS-Related Complex↗
PubMed1990

Erythema infectiosum and pregnancy-related complications.

Erythema infectiosum, an acute, communicable viral disease with a highly distinctive exanthem, follows the usual course of a self-limiting benign disease. In pregnant women, however, it may be associated with fetal death and nonimmune hydrops fetalis. Because of the association of human parvovirus (HPV) B19 infection with fetal damage we reviewed the current knowledge of the clinical aspects of erythema infectiosum, focusing on pregnancy and fetal outcome, to determine the magnitude of fetal risk and offer recommendations for management. Among 180 infected pregnant women 44 fetal deaths (24%) occurred, 1 to 12 weeks after the infection was noted. Pregnant women should be advised that (a) because of the high prevalence (up to 65%) of anti-HPV B19 IgG antibody among adults most of them are not at risk and (b) if maternal infection does occur therapeutic abortion is not indicated since intrauterine infection causes fetal death more often than abnormal development. Infection should be suspected in pregnant women who exhibit the symptoms of erythema infectiosum with or without arthropathy. They should be monitored for an elevated serum alpha-fetoprotein level (indicating fetal aplastic crisis) and undergo serial ultrasonography for the detection of hydrops fetalis. Although the incidence of congenital malformation is no higher than the expected rate in the general population (3% to 5%), the precise incidence of fetal adverse outcomes remains unknown and requires investigation in larger, prospective studies.

Erythema↗
PubMed1990

Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease.

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Foscarnet therapy of cytomegalovirus retinitis in AIDS.

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Vancomycin-induced red man syndrome.

A total of 11 cases of red man syndrome collected among 650 children who had received vancomycin in our hospital between 1986 and 1988 (estimated prevalence 1.6%) were retrospectively analyzed. These 11 children were compared with 11 age-matched children who received vancomycin in whom red man syndrome did not develop. Of the patients with red man syndrome, 73%, and of the patients with no reaction, 45.4% received vancomycin for penicillin-resistant Staphylococcus epidermidis-positive cultures, or because of history of penicillin allergy. No difference was observed in the dose per kilogram given to both groups (12.9 +/- 3.5 mg/kg per dose in those with red man syndrome vs 12.3 +/- 6.9 mg/kg per dose in control children. The duration (mean +/- standard deviation) of vancomycin infusion was 45.9 +/- 16.7 minutes (range 10 to 90 minutes) in patients with red man syndrome and 54.5 +/- 7.6 minutes (range 45 to 65 minutes) in the control group (P = .07). In the 5 children with red man syndrome rechallenged with vancomycin, slower infusion rates prevented or reduced the syndrome, which emphasized the fact that the rate of administration is the important determinant of red man syndrome in susceptible cases. Clinically, the syndrome developed at the end of the infusion in most patients, but appeared as early as 15 minutes after initiation of the infusion. It was mostly manifested as a flushed, erythematous rash on the face, neck, and around the ears. Less frequently, the rash was distributed all over the body. Pruritus was usually localized to the upper trunk but was also generalized (2 of 11 children).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗
PubMed1989

Interferon-associated lymphocyte 2',5'-oligoadenylate synthetase in acute and chronic viral hepatitis.

Basal levels of the interferon-associated enzyme 2',5'-oligoadenylate synthetase were studied in lymphocytes of 46 patients with acute viral hepatitis and in 46 patients with chronic hepatitis B. Measurement of in vitro production of 2',5'-oligoadenylate synthetase following overnight incubation of lymphocytes with exogenous interferon was used to assess functional capacity of the lymphocyte interferon system. In acute hepatitis patients, an early but transient elevation of 2',5'-oligoadenylate synthetase was observed; the mean level at 1 week was significantly greater than the mean level at 4 weeks after the onset of their illness (p less than 0.01). Serial 2',5'-oligoadenylate synthetase levels did not identify those patients who were to progress to chronic hepatitis. Patients with chronic hepatitis B infection, regardless of background liver histology, generally had normal basal lymphocyte 2',5'-oligoadenylate synthetase levels. In both acute viral hepatitis and chronic hepatitis B, there was an inverse correlation between basal 2',5'-oligoadenylate synthetase level and 2',5'-oligoadenylate synthetase response to overnight incubation with interferon, a finding that suggested a transient down-regulation of interferon responsiveness. These findings provided no support for the hypothesis that there is an inherent or persistently induced deficiency in the interferon system in acute or chronic hepatitis B.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Kaposi's sarcoma and AIDS: a variable spectrum.

A cohort of 61 patients with Kaposi's sarcoma (KS) and AIDS was seen in the Oncology Unit of the Toronto General Hospital between 1982 and 1986. In an attempt to identify prognostic variables, laboratory and clinical parameters were examined using Kaplan-Meier estimates and the Cox Regression Model. All patients were male, median age 36 years (range 23-52). In 49 patients KS was diagnosed before any AIDS-associated opportunistic infection (OI). Three patients had concurrent KS and OI, and nine patients developed KS one or more months after an OI. Only 11 patients had stage I or II disease, 34 stage III, and 15 stage IV. Only 18 patients (30%) were asymptomatic. Twenty-six percent had fever, night sweats, or weight loss, 11% had minor opportunistic infections, and 33% had both symptom complexes. The median overall survival was 10.5 months. The survival of patients who received chemotherapy for their KS was not significantly different from the survival of non-treated patients (p = 0.7). Although significant differences in survival could not be seen between stages, patients with both systemic symptoms and minor opportunistic infections had significantly shorter survival (p = 0.03). Survival from the onset of KS was significantly shorter for patients who had experienced a previous OI, but their overall survival from the date of diagnosis of AIDS was not significantly different from those patients presenting with KS alone. When analyzed separately the laboratory parameters of hemoglobin (p less than 0.0001), absolute lymphocyte count (p = 0.03), platelet count (p = 0.04), and T4 level (p = 0.05) demonstrated a significant relationship with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1988

Combination chemotherapy and alpha-interferon in the treatment of Kaposi's sarcoma associated with acquired immune deficiency syndrome.

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2',5'-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks' duration) was seen in one patient and a partial response (of 14 to 44 weeks' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi's sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi's sarcoma associated with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Validity of sexual histories in a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition.

As part of a prospective study in Toronto, Canada of male sexual contacts of men with either acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition (primary cases), separate interviews were conducted in 1984-1985 with primary cases and their corresponding sexual contacts. Seventy-five primary cases and their corresponding sexual contacts were asked details concerning the sexual activities involved in their sexual encounters. Spearman correlation coefficients were calculated for the responses regarding frequency of various sexual activities between the primary case and his corresponding contact. Comparison of responses revealed good to excellent correlations for the majority of the sexual activities. Regression analysis of responses (dependent variable = contact's response; independent variable = primary's response) revealed the tendency for primary cases to report greater numbers of various activities than sexual contacts, as illustrated by regression coefficients that were consistently less than unity. Agreement between primary responses and sexual contact responses appeared to be affected by the time lapsed from the last sexual encounter with the contact and the date of the primary case's interview. No effect on agreement was observed when primary case diagnosis and the total number of other sexual partners of primary cases were considered. The authors conclude that such data can be captured with sufficient reliability and validity for use in epidemiologic investigations to assess the risk of acquisition of human immunodeficiency virus for the more common forms of sexual activity. However, some caution may be necessary in interpreting the results for some activities (anal digit insertion, anilingus) since agreement is less satisfactory for these activities.

AIDS-Related Complex↗
PubMed1988

Risk factors for HIV infection in male sexual contacts of men with AIDS or an AIDS-related condition.

A total of 246 healthy male sexual contacts of men with either acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition were recruited into a prospective study in Toronto, Canada between July 1984 and July 1985. At induction, data were collected on the sexual relationship between the contact and his primary case, sexual activities with other men, history of sexually transmitted diseases and other diseases, and use of recreational drugs. At recruitment, 144 sexual contacts had antibodies to human immunodeficiency virus (HIV); 102 of the contacts were seronegative at induction and at three months following recruitment. No association between HIV seropositivity and total number of sexual partners could be demonstrated. In univariate and multivariate analyses, receptive and insertive anal intercourse with the primary cases, and activities which either indicated or potentially caused anorectal mucosal injury (rectal douching, perianal bleeding, receipt of objects in ano, and receptive fisting) were strongly associated with HIV seropositivity. In the final multiple logistic regression model, two significant interaction effects were observed: the interaction between receptive anal intercourse and insertive anal intercourse and that between receptive anal intercourse and the anorectal mucosal injury index. These two interaction terms had negative regression coefficients which suggested that change in one sexual activity would not decrementally reduce risk of HIV infection without a comparable modification in the other activity. No association could be demonstrated between oral-genital and oral-anal sexual contact and odds ratios for these sexual activities declined to levels below 1.0 when adjusted for frequency of receptive anal intercourse.

3,4-Methylenedioxyamphetamine↗
PubMed1988

Downregulation of interferon alpha but not gamma receptor expression in vivo in the acquired immunodeficiency syndrome.

Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. In evaluating the role of IFN as therapeutic agents in AIDS, we investigated the expression of IFN alpha and gamma receptors on peripheral blood mononuclear cells (PBM) from patients with AIDS, ARC, and heterosexual control subjects using radioiodinated IFN alpha 2 and IFN gamma. The binding characteristics of the 125I-IFN alpha and gamma to PBM were analyzed to determine receptor numbers and dissociation constants. PBM from controls expressed 498 +/- 247 IFN alpha receptor sites/cell (n = 17). However, eight patients with ARC and seven patients with AIDS had a mean number of IFN alpha receptor/cell of 286 +/- 235 (P less than 0.05) and 92 +/- 88 (P less than 0.001), respectively. This was consistent with elevated levels of serum acid-labile IFN alpha and cellular 2-5A synthetase activity in patients. Treatment of PBM from the AIDS patients with exogenous IFN alpha in vitro resulted in minimal 2-5A synthetase induction in comparison to controls. In contrast, the expression of IFN gamma receptors in ARC (n = 5) and AIDS (n = 4) patients remained normal. Thus the decrease in IFN alpha receptor expression and consequent hyporesponsiveness to IFN alpha raises the question of the usefulness of IFN alpha therapy in end-stage AIDS. The normal expression of IFN gamma receptors in AIDS patients suggests that IFN gamma may prove useful in attempts to provide immune reconstitution.

2',5'-Oligoadenylate Synthetase↗