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Biomedical subjects

R R Redfield

Publications and source records attributed to R R Redfield.

At least 91 records · Page 5Linked to original sources
PubMed1987

Diagnosis of human immunodeficiency virus infection by immunoassay using a molecularly cloned and expressed virus envelope polypeptide. Comparison to Western blot on 2707 consecutive serum samples.

To detect human immunodeficiency virus (HIV) antibodies in a simple enzyme-linked immunoassay (CBre3-EIA), we used an Escherichia coli-expressed polypeptide antigen, representing the carboxy-terminal third of the external membrane glycoprotein gene fused with the amino-terminal half of the transmembrane glycoprotein gene. Over a 3-month period, 2707 consecutive serum samples referred for confirmatory testing for human T-lymphotrophic virus type III (HTLV-III) antibodies were evaluated by both Western blot and CBre3-EIA. On a single determination for each sample, the CBre3-EIA was found to have an estimated sensitivity (99.9%) and specificity (99.1%) similar or superior to the more cumbersome Western blot method. This study shows that all HIV-seropositive subjects have antibodies to the virus envelope protein; no other virus antigens are required for construction of highly sensitive immunoassays.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS.

In a study of genetic variation in the AIDS virus, HTLV-III/LAV, sequential virus isolates from persistently infected individuals were examined by Southern blot genomic analysis, molecular cloning, and nucleotide sequencing. Four to six virus isolates were obtained from each of three individuals over a 1-year or 2-year period. Changes were detected throughout the viral genomes and consisted of isolated and clustered nucleotide point mutations as well as short deletions or insertions. Results from genomic restriction mapping and nucleotide sequence comparisons indicated that viruses isolated sequentially had evolved in parallel from a common progenitor virus. The rate of evolution of HTLV-III/LAV was estimated to be at least 10(-3) nucleotide substitutions per site per year for the env gene and 10(-4) for the gag gene, values a millionfold greater than for most DNA genomes. Despite this relatively rapid rate of sequence divergence, virus isolates from any one patient were all much more related to each other than to viruses from other individuals. In view of the substantial heterogeneity among most independent HTLV-III/LAV isolates, the repeated isolation from a given individual of only highly related viruses raises the possibility that some type of interference mechanism may prevent simultaneous infection by more than one major genotypic form of the virus.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Defective regulation of Epstein-Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders.

Patients with the acquired immunodeficiency syndrome (AIDS) acquire undifferentiated B-cell lymphomas that are similar to African Burkitt's lymphoma and contain Epstein-Barr virus (EBV). Using an in vitro assay system that measures a complex of cellular responses to EBV-infected lymphocytes, we found that B cells from 7 patients with AIDS and from 10 patients with AIDS-related disorders produced abnormally low numbers of immunoglobulin-secreting cells (P less than 0.001 as compared with normal controls) and that T-cell suppression, which was greater than 80 percent in EBV-seropositive normal controls, was absent. Instead, the patients' T cells markedly increased immunoglobulin production induced by EBV. In further studies, we determined that the mean frequency of circulating EBV-infected B cells capable of spontaneous outgrowth in vitro was 13 per 10(6) B cells in 7 patients with AIDS and 21 per 10(6) B cells in 10 patients with AIDS-related disorders--figures that were significantly higher than the mean in normal controls (P less than 0.001). Thus, patients with AIDS or AIDS-related disorders may be predisposed to the development of EBV-containing lymphomas, because they have a profound defect of T-cell immunity to EBV and abnormally high numbers of EBV-infected B cells in the circulation.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Clinical pharmacokinetics of suramin in patients with HTLV-III/LAV infection.

Suramin has been reported to inhibit the reverse transcriptase activity of a number of retroviruses and to reduce the in vitro infectivity and cytopathic effect of HTLV-III/LAV, the etiologic agent of acquired immune deficiency syndrome (AIDS). The clinical pharmacokinetics of suramin were investigated as part of a pilot study to evaluate the safety and efficacy of this drug for the treatment of patients with diseases caused by HTLV-III/LAV. A dose of suramin 6.2 g was given intravenously over a five-week period to four patients. After the last dose, the plasma half-life of suramin was 44 to 54 days. This is among the longest half-lives reported for any therapeutic substance given to humans. Total plasma levels of suramin were greater than 100 micrograms/mL for several weeks. In vitro activity of suramin was found at concentrations as low as 50 micrograms/mL. Metabolites were not found in plasma, and urinary excretion accounts for elimination of most of the drug. Suramin is approximately 99.7% bound to plasma proteins. The results from these initial clinical pharmacokinetic studies might assist the design of further therapeutic trials of suramin, especially the selection of frequency of dosing and adjustments for renal impairment.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Acquired immunodeficiency syndrome: epidemiology and significance for the obstetrician and gynecologist.

A retrovirus, variously named human T-lymphotropic virus type III or lymphadenopathy-associated virus, is now recognized as the etiologic agent of the acquired immunodeficiency syndrome. As of January, 1986, more than 16,000 cases of acquired immunodeficiency syndrome have been reported, and it is estimated that greater than or equal to 1 million Americans are now infected with human T-cell lymphotropic virus/lymphadenopathy-associated virus. Most cases of overt acquired immunodeficiency syndrome still fall within well-defined "high-risk groups," that is, homosexual or bisexual men, intravenous drug users, recipients of transfused blood or blood components, and persons with hemophilia. Also at risk are heterosexual partners of persons who have overt acquired immunodeficiency syndrome or who are at risk for acquired immunodeficiency syndrome, as are children born to mothers who either have acquired immunodeficiency syndrome or are members of a "high-risk group." Transmission of the virus may occur via sexual contact, via parenteral exposure to contaminated blood products, or from an infected mother to her child. Of special concern to the practicing obstetrician are recent reports suggesting bidirectional heterosexual transmission, transmission via artificial insemination, and perinatal transmission. In addition, the isolation of human T-cell lymphotropic virus/lymphadenopathy-associated virus from human breast milk raises concerns regarding potential transmission by this route.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Occupational and geographic risk factors for hepatitis B among US Army enlisted personnel during 1980.

Hepatitis B hospitalization rates for US Army enlisted personnel were determined by occupation and geographic area for 1980. The only group in the US Army currently recommended to receive hepatitis B vaccine is medical personnel regularly exposed to blood. Other groups of Army personnel, specifically those working in areas of high hepatitis B endemicity, have been thought to be at higher risk. Therefore, this work was undertaken to document hospitalization rates for all personnel using occupational blood exposure criteria as well as geographic area of assignment as risk factors for hepatitis B. The hospitalization rates underestimate true rates of hepatitis B incidence by a wide margin, and therefore were not used to calculate specific costs and specific benefits for a new vaccination strategy. In spite of this limitation, these data were useful for calculating relative risk, attributable risk, and amount of vaccine preventable disease. The risk of hospitalization for blood-exposed employees was consistently higher than that for non-blood-exposed personnel. The magnitude of the relative risk for blood exposure may be as high as 3.8 times or as low as 1.2 times, depending on which occupational comparison group is used. The relative risk of hospitalization in South Korea vs. the United States was 3.1 (p less than 0.0001), that for Europe vs. the United States, 2.1 (p less than 0.0001). Of all occupational and geographic risk comparisons, assignment to South Korea carried the highest attributable risk: 225 per 100,000. The amount of vaccine preventable disease in personnel assigned to South Korea was similar to that in occupationally blood-exposed employees (5.5 vs. 5.2 hospitalized cases per 1,000 vaccinees) after prorating exposure to risk based on average number of days of exposure to risk over three years. These data support the argument that geographic factors are as important as occupational blood exposure in defining risk of hepatitis B hospitalization among the US Army enlisted personnel.

Blood↗
PubMed1986

Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus.

Patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) have hyperimmunoglobulinemia and increased numbers of circulating immunoglobulin-secreting cells. In this paper, we studied the basis for this B cell hyperactivity. Limiting dilution studies of B cells from seven patients with ARC and four with AIDS revealed that some B cells spontaneously produced antibodies to human T cell lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV) (39:10(6) and 7:10(6) B cells, respectively), suggesting that chronic antigenic stimulation by HTLV-III/LAV was one contributing factor. The patients also had an increased number of spontaneously outgrowing B cells than did normals (6:10(6) vs. less than 2:10(6) B cells), suggesting that they had an increased number of Epstein-Barr virus (EBV)-infected B cells. However, fewer B cells from patients were immortalized by exogenously added EBV than were B cells from normals. In additional studies, HTLV-III/LAV induced immunoglobulin secretion (mean 2,860 ng/ml) by peripheral blood mononuclear cells from normals; this HTLV-III/LAV-induced immunoglobulin secretion required the presence of both B and T cells. Thus, antigenic stimulation by HTLV-III/LAV, increased numbers of EBV-infected B cells, and HTLV-III/LAV-induced T cell-dependent B cell activation all contribute to the B cell hyperactivity in patients with HTLV-III/LAV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Clinical evaluation of low-dose intradermally administered hepatitis B virus vaccine. A cost reduction strategy.

High cost and limited availability of the current hepatitis B virus vaccine lead to underutilization. To address this problem, we performed a vaccine trial comparing the currently recommended regimen of 20 micrograms of hepatitis B surface antigen (HBsAg) intramuscularly on days 0, 30, and 180, with a more economical regimen of 2 micrograms of HBsAg intradermally on days 0, 30, and 180. This trial was performed in 50 seronegative health care workers to assess the immunogenicity and local reactogenicity of both vaccine regimens. We found no significant difference in seroconversion between the intradermal group (96%) and the intramuscular group (100%). Mean ratios of test sample value to mean negative control value for antibody to HBsAg at 360 days were not significantly different (intradermal group, 84 +/- 26; intramuscular group, 120 +/- 22). Reactions in both groups were minor. Although the optimal dose of HBsAg was not investigated, our data demonstrate that 0.1 mL of inactivated hepatitis B virus vaccine (Heptavax-B) intradermally is immunogenic in healthy adults. Vaccination by this regimen can broaden hepatitis B virus disease prevention.

Adult↗
PubMed1985

Heterosexually acquired HTLV-III/LAV disease (AIDS-related complex and AIDS). Epidemiologic evidence for female-to-male transmission.

Thirty-seven percent (15/41) of patients with human T-cell lymphotropic virus type III (HTLV-III) disease (acquired immunodeficiency syndrome [AIDS] or AIDS-related complex) sequentially evaluated at Walter Reed Army Medical Center, Washington, DC, acquired this infection from a partner(s) of the opposite sex. Demographic features of these 15 patients (ten males and five females) differed substantially from those for patients reported to the Centers for Disease Control. Heterosexual contact with partners who developed AIDS or who were at risk for AIDS was confirmed in six patients. The remaining nine patients had multiple (greater than 50) heterosexual partners and/or sexual contact with prostitutes. The method of sexual activity did not appear to be related to disease acquisition; however, this study clearly demonstrated that receptive anal intercourse was not a requirement. The observations reported herein provide further epidemiologic evidence to support the occurrence of bidirectional heterosexual transmission (both male to female and female to male) of HTLV-III infection and disease.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effects of suramin on HTLV-III/LAV infection presenting as Kaposi's sarcoma or AIDS-related complex: clinical pharmacology and suppression of virus replication in vivo.

Suramin was given to ten outpatients with acquired immunodeficiency syndrome (AIDS) presenting as Kaposi's sarcoma (KS) or as an AIDS-related complex (ARC). Side-effects associated with the administration of 6.2 g of suramin over 5 weeks included fevers, rashes, urinary abnormalities, and transient rises in hepatic aminotransferases. Peak serum levels of over 100 micrograms/ml were attained. There was evidence of HTLV-III infectivity and replication in lymphocytes from four patients before therapy. The detectable virus level fell in each case by the time of the last dose, and in three cases it became undetectable at the end of therapy. In each case, viral replication was again detected in the weeks or months following the administration of suramin. Despite this in-vivo virustatic effect, no significant clinical or immunological improvement was observed using this short-term regimen. However, the results provide a rationale for investigating longer-term regimens.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Frequent transmission of HTLV-III among spouses of patients with AIDS-related complex and AIDS.

Seven cases of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) associated with human T-cell leukemia (lymphotropic) virus (HTLV)-III infection were documented in married males whose family members consented to medical evaluation. Five spouses also had evidence of HTLV-III infection documented by isolation of virus and by detection of serum antibody directed against viral structural proteins. Three of the five HTLV-positive spouses also had clinical evidence of ARC. The remaining four spouses were clinically healthy. Eleven children (between 14 months and 13 years of age) were also evaluated for evidence of disease and exposure to HTLV-III. Only one 14-month-old child was seropositive for antibody to HTLV-III. These data support the opinion that close household contact to patients with ARC or AIDS is not an efficient mechanism for virus transmission, while demonstrating that HTLV-III can be transmitted by repeated heterosexual contact.

Acquired Immunodeficiency Syndrome↗