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Biomedical subjects

R Y Dodd

Publications and source records attributed to R Y Dodd.

At least 19 recordsLinked to original sources

Inactivation of microbial contaminants of blood components.

Despite the low risk of transfusion-transmitted infection currently present in the blood supply, processes to inactivate contaminating viruses and bacteria may improve the safety of transfusion even further. A variety of techniques, using both physical and chemical processes, are being explored. Particularly promising is adaptation of the solvent/detergent technique (already in use for plasma derivatives) to plasma for transfusion. Inactivation of viruses in cellular components may require a combination of techniques, possibly including leukocyte depletion filtration, photoactive compounds, and subsequent washing. Concerns about potential toxicity of the agents employed and retention of component efficacy after treatment and storage remain unresolved, however.

Bacteria

Factors influencing virus inactivation and retention of platelet properties following treatment with aminomethyltrimethylpsoralen and ultraviolet A light.

A wide variety of viruses are inactivated by psoralen compounds in the presence of ultraviolet A light (UVA). Use of aminomethyltrimethylpsoralen (AMT) and UVA is being evaluated as a method to inactivate viruses that may be present in platelet suspensions prepared for transfusion. Studies have been conducted to assess how variation in various environmental parameters influences the extent of viral inactivation and the retention of platelet properties. Most notably, it was determined that increasing levels of plasma progressively inhibited the inactivation of model viruses. As a result, experiments were routinely conducted at a plasma level of approximately 14.5%, using 40 micrograms/ml AMT, which was determined to be optimal when using this reduced plasma level. The reduced plasma level was achieved by dilution with a nonplasma medium that has been shown to be satisfactory for storage of platelets. Under these conditions, about 5 logs of vesicular stomatitis virus (VSV), pseudorabies, and phi 6 inactivation were achieved. Variation of platelet and leukocyte counts, within normal levels, had a minimal effect on extent of viral inactivation. Although oxygen level (mean levels, 97.9 mm Hg versus 19.2 mm Hg) had only a small influence on viral inactivation with 2.4, 4.8, and 7.2 J/cm2 of UVA (equivalent to 1-3 minutes of exposure), in vitro platelet properties, such as medium pH, morphology characteristics, and aggregation response, were better retained with a longer exposure time at the reduced oxygen level. With normal oxygen (97.9 mm Hg), platelet properties declined substantially relative to untreated controls (no UVA, no AMT) on exposure to 4.8 J/cm2. Our studies have identified two sets of conditions that provide about 5 logs of virus inactivation without extensively altering platelet in vitro properties.

Blood

Human immunodeficiency virus infection and indeterminate western blot patterns. Prospective studies in a low prevalence population.

Interpretation of human immunodeficiency virus (HIV) antibody results that are "indeterminate" rather than clearly positive or negative is problematic for the person delivering the result as well as for the individual being tested. To improve counseling messages for these individuals, we evaluated data collected from a well-characterized cohort of 387 blood donors who had been monitored for up to 2 years. We sought to determine if persons with indeterminate Western blot patterns were infected with HIV, and whether information derived from follow-up monitoring would assist in the development of counseling messages for persons on whom no follow-up information was available. Donors were studied by laboratory assays, clinical evaluation, and assessment of risk for HIV. The absence of HIV infection in 97 of 98 donors with indeterminate Western blot patterns was confirmed by clinical follow-up, Western blot assays of sequential samples, and negative gene amplification results. We propose supplemental guidelines to be used as an adjunct to existing interpretive criteria for counseling individuals when they first present with an indeterminate Western blot finding.

Acquired Immunodeficiency Syndrome

The western immunoblot procedure for HIV antibodies and its interpretation.

The Western blot is frequently used to confirm human immunodeficiency virus type 1 (HIV-1) screening tests as it permits the identification of antibodies to individual component polypeptides of HIV-1. The procedure is described and different criteria for evaluation of HIV-1 Western blots are compared. The significance and management of indeterminate blot patterns are discussed.

Blotting, Western

Exposure of patients to human immunodeficiency virus through the transfusion of blood components that test antibody-negative.

The risk of transmission of the human immunodeficiency virus to recipients of blood transfusions exists chiefly during the period between the time a donor is infected and the time he or she has a positive blood test for HIV antibodies. Estimating the chance that blood will be donated during this period is an effective way to define the risk of HIV infection from transfusion. Using this approach, and employing data from over 17 million American Red Cross blood donations, we estimate that during 1987 the most likely number of units of blood infected with undetected HIV that were transfused was 131 (range, 67 to 227). For a patient, the odds of contracting HIV infection were 1:153,000 per unit transfused. A patient who received the average transfusion (5.4 units) had odds of 1:28,000. The risk has been decreasing by more than 30 percent a year. We estimate that donor-recruitment practices plus careful education and screening are eliminating 49 of every 50 donors likely to be HIV-positive and that testing is 92 to 97 percent effective, for a combined effectiveness of 99.9 percent. The risk of undetected infectious units can probably be further reduced by transfusing fewer units and units from fewer donors, recruiting more women and fewer men as new donors, and encouraging more frequent donations from donors who have been tested repeatedly.

AIDS Serodiagnosis

Setting up an HIV screening program.

Human immunodeficiency virus-1 (HIV-1) screening programs currently are based primarily on the detection of specific HIV-1 antibodies by the commercially available enzyme immunoassay (EIA) combined with highly specific confirmation procedures. Factors to be considered in establishing a screening program include test performance characteristics, economy, confidentiality and notification procedures, legal and regulatory issues, proficiency and quality control measures, and laboratory safety. Commercial EIA screening in conjunction with a licensed Western blot assay permits the classification of all but a few serum samples into HIV-1-positive and HIV-1-negative categories. The occasional indeterminate results often can be resolved by following a defined retesting/resampling algorithm or by using research-level test procedures that may become available for diagnostic use in the future. Although screening of patient populations with an increased risk of HIV-1 exposure will improve the predictive accuracy of an initial screening assay, confirmation testing should nonetheless be performed for all EIA reactive sera regardless of the source. Local HIV-1 screening programs that meet minimum-volume requirements can result in considerable savings and flexibility for a moderate-size institution. However, before this type of program is undertaken, numerous technical and ethical considerations need to be addressed.

Algorithms

Transfusion and AIDS.

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Acquired Immunodeficiency Syndrome

Screening for hepatitis infectivity among blood donors. A model for blood safety?

The safety of blood and blood products is based on three interdependent activities: selection of safe donors, laboratory testing, and, where applicable, treatment of the product to reduce residual infectivity. Posttransfusion hepatitis has provided both the initial stimulus and the model for these procedures. The procedures have resulted in a progressive increase in the safety of the blood supply, which is continuing, as evidenced by a 50% decrease in the frequency of reported posttransfusion hepatitis over the past two years.

Blood Banks

Increased risk for lethal forms of liver disease among HBsAg-positive blood donors in the United States.

We have used a death-record search to define the frequency of lethal outcomes of hepatitis B virus infection among a population of more than 15,000 overtly healthy blood donors found positive in routine HBsAg testing. We have compared the study population with a control group of some 18,000 donors selected on the basis of a negative test result. The index and control groups were observed for periods reflecting a total of 55 and 59 thousand person-years, respectively. Twenty percent of the 134 deaths identified among HBsAg positive donors were in some way liver related, including seven deaths due to hepatitis, seven to cirrhosis and six to hepatoma. In contrast, only one of the 95 deaths in the control population was liver related, and was due to fatty degeneration of the liver. The majority (four) of the hepatoma deaths occurred among blacks, three of whom were less than 35 at the time of death. In contrast, deaths from cirrhosis were all among whites. We conclude that there is significant mortality associated with the HBsAg positive state, even though the affected individuals may be asymptomatic and well enough to give blood at some stage. We estimate the standardised mortality ratio for hepatoma among HBsAg-positive persons in the United States is at least 27, confirming the association observed in other populations. The risk for hepatoma among young, HBsAg positive black males appears to approach that reported for HBsAg positive males in Taiwan. Data on the feasibility of AFP testing for early detection of hepatoma are included and discussed.

Blood Donors

A test for human cytomegalovirus-specific immunoglobulins using a modification of a commercial test kit.

A technique (Ig-EIA) for the detection of CMV-specific IgG, IgM and IgA in human blood is described. Ig-EIA utilizes alkaline phosphatase-labeled goat anti-human IgG, IgM and IgA as a detection probe and CMV antigen-coated solid phase from commercial kits. Ig-EIA is compared to indirect fluorescent assay (IFA) and indirect hemagglutination (IHA) for sensitivity and specificity. On sequential samples of blood from a set of patients, Ig-EIA clearly demonstrated seroconversion in CMV-specific IgG and IgM. A test of 332 blood donors by Ig-EIA showed 177 (53%) had CMV-specific IgG and 17 (5%) had CMV IgM. Only two of the 17 donors with CMV IgM were nonreactive for CMV-IgG. The potential of CMV-IgM as an indicator of CMV infectivity is discussed.

Adult

Immunoglobulin level in donor blood reactive for antibodies to human immunodeficiency virus.

Blood samples from 98 asymptomatic volunteer blood donors, including 55 that were reactive for antibodies to human immunodeficiency virus (HIV) in Western blot (WB) assay, were tested for levels of immunoglobulin G (IgG), IgM, and titer of antibodies to HIV, cytomegalovirus, and herpes simplex virus. Levels of IgG were significantly elevated (P less than or equal to 0.001) in donors with specific anti-HIV reactivity. A total of 69% of donors with anti-HIV had IgG levels of greater than or equal to 12 mg/ml, and 44% had IgG levels of greater than or equal to 14.5 mg/ml. Levels of IgM were not significantly different among WB-reactive and nonreactive donors. The titer of anti-HIV was significantly (P less than 0.02) correlated with IgG levels among donors reactive in the WB assay. Elevation of IgG, however, was not significantly associated with the presence of anticytomegalovirus or anti-herpes simplex virus antibodies. The data show that elevation of IgG may represent an early manifestation of HIV infection before the development of clinical symptoms of acquired immunodeficiency syndrome.

Adolescent