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Biomedical subjects

R Y Dodd

Publications and source records attributed to R Y Dodd.

At least 73 records · Page 4Linked to original sources

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↗

Antibodies to delta antigen in asymptomatic hepatitis B surface antigen-reactive blood donors in the United States and their association with other markers of hepatitis B virus.

A total of 1,915 sera collected in 1979 from asymptomatic hepatitis B surface antigen (HBsAg) carriers were tested for delta antigen, antibody to delta antigen (anti-delta), hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) in addition to HBsAg and its subtypes. These sera represented blood donated by volunteers to 49 of 57 regions of the American Red Cross located in nine geographic regions of the United States and Puerto Rico. A total of 72 (3.8%) sera had anti-delta activity while none had a detectable level of delta antigen. A significantly higher (p less than 0.01) prevalence of anti-delta (12.1%) was found in San Jose, California (Pacific Region); on the other hand, the East South Central region covering Alabama, Kentucky, Mississippi and Tennessee had a significantly lower (p less than 0.05) prevalence (1.4%) of anti-delta when compared with all other regions combined. Anti-delta was, however, detected in all regions of the United States and in Puerto Rico. The cause of significant differences in the prevalence of anti-delta was not clear. The distribution of anti-delta was not associated with age, sex or blood type of the donor. Sixty-nine of 70 samples with anti-delta were found among the 1,527 samples that had either HBeAg or anti-HBe. And among 149 that lacked both HBeAg and anti-HBe, only one sample had anti-delta. The difference is statistically significant (p less than 0.05). The presence of anti-delta was not associated with HBsAg/ad (2.7%) or HBsAg/ay (4.6%).

Adolescent↗

Transfusion-associated AIDS: serologic evidence of human T-cell leukemia virus infection of donors.

An assay for antibodies to membrane antigens of cells infected by human T-cell leukemia virus was used to examine serum from persons who donated blood to 12 patients with acquired immunodeficiency syndrome (AIDS) associated with blood transfusions. The occurrence of positive results in the assay was significantly greater among donors to the AIDS patients (9 of 117; 7.7 percent) than among random donors (1 of 298; 0.3 percent). Of 12 sets of donors examined, 9 sets included a donor whose serum gave positive results for the presence of the antibodies. In six of these nine sets, the seropositive donor was an individual who was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used.

Acquired Immunodeficiency Syndrome↗

Hepatitis-associated markers in the American Red Cross blood donor population. V. Prevalence of antibodies to core antigen in three blood services regions.

A total of 20,643 samples of blood donated to three American Red Cross Blood Service regions were tested for antibodies to hepatitis B core antigen (anti-HBc) in order to evaluate and understand its significance and implications. All 20,643 samples were non-reactive for hepatitis B surface antigen (HBsAg) when screened at the regions. Overall, 2.2% of all samples were found to have anti-HBc, and a total of 16 had anti-HBc in the absence of antibodies to surface antigen (anti-HBs) activity. 1 of the 16 samples with anti-HBc in the absence of anti-HBs was found to have HBsAg when tested by a sensitive procedural modification of the Austria II test. Samples with low levels of anti-HBc activity were significantly more likely to be negative for anti-HBs.

Antibodies, Viral↗

Reducing the incidence of non-A,non-B post-transfusion hepatitis by testing donor blood for alanine aminotransferase: economic considerations.

Recent studies have established a relation between elevated alanine aminotransferase levels in donor blood and the incidence of non-A, non-B hepatitis in recipients of such blood. Routine testing of donor blood for alanine aminotransferase activity in order to reduce hepatitis is not currently supported, largely because the results of such testing are unknown. We assessed the potential economic benefits of screening donor blood for alanine aminotransferase as a means to reduce post-transfusion hepatitis. Benefits, defined as the expected costs of hepatitis potentially avoided, ranged from $898 to $31,629 per 1000 blood units collected. This wide range reflected lack of information about the natural history of non-A, non-B hepatitis. Costs were defined as the direct costs of testing and the indirect costs associated with loss of blood product, additional donor recruitment, and informing donors of their abnormal aminotransferase levels; costs ranged from $3,151 to $4,003 per 1000 units. Our results suggest that if prospective studies demonstrate that exclusion of blood with elevated aminotransferase levels decreases non-A, non-B hepatitis in recipients, the net economic impact may be positive. However, because of major uncertainties about the medical consequences of non-A, non-B hepatitis, the benefit estimates are so broad that they preclude a definitive policy decision.

Alanine Transaminase↗

Inactivation of DNA-polymerase associated with hepatitis B virus.

The effects of heat, sodium hypochlorite, diethyl ether, and ethyl alcohol on the activity of DNA polymerase (DNA-P) associated with hepatitis B virsus (HBV) in serum were evaluated. The response of DNA-P to heating at 60 degrees C for 15, 30, 45, 60, 90, 120, 180, and 240 minutes was studied and the data suggested that there may be two types of DNA-P. The majority of DNA-P was type 'a', and it showed a one log reduction (D60) at 60 degrees C in 36 minutes, while the remaining activity was type 'b' that showed a one log reduction (D60) in 340 minutes. Treatment of DNA-P with sodium hypochlorite at concentrations of 250 and 500 parts per million (ppm) of available chlorine resulted in a 20 to 25% reduction in DNA-P activity within one minute. Complete loss in detectable DNA-P activity occurred within one minute when available Cl- was 2500 ppm or greater. Various concentrations of ethyl alcohol (ranging from 10 to 70%) caused gradually increasing inactivation of DNA-P activity in ten minutes at 4 degrees C. Ninety percent inactivation occurred with 60% alcohol. Overnight treatment of DNA-P-reactive material with diethyl ether at 4 degrees C led to loss of detectable activity. A reduction in the titer of HBsAg was found following treatment with alcohol or ether. The possible use of DNA-P assay as an indicator of the rate of inactivation of HBV is proposed.

DNA-Directed DNA Polymerase↗

Alanine aminotransferase levels among volunteer blood donors: geographic variation and risk factors.

The incidence of elevated levels of alanine aminotransferase (ALT) in the serum of volunteer blood donors from different geographic areas of the United States was evaluated. Five regional blood collection centers participated by collecting samples randomly from volunteer blood donors. Serum samples were centrally tested for elevated ALT levels, and a sociodemographic questionnaire was sent to donors with elevated ALT levels and to a randomly selected group with normal levels. Significant regional variation was found in the incidence of elevated ALT levels. Age, sex, and the use of alcohol were all significantly associated with elevated ALT levels. These preliminary data are important in the consideration of a program to screen blood donors for elevated ALT levels in serum.

Adult↗

Hepatitis-associated markers in the American Red Cross volunteer blood donor population. IV. A comparison of HBV-associated serologic markers in HBsAg-positive first-time and repeat blood donors.

The present study was undertaken to determine whether there were any differences in the distribution of hepatitis B virus-(HBV) associated serologic markers among hepatitis B surface antigen-(HBsAg) positive first-time and repeat blood donors. The markers examined in samples from 412 newly identified HBsAg-positive donors (254 first-time and 158 repeat) included HBsAg titer and subtype, HBeAg/anti-HBe, and anti-HBc. Repeat donors were more frequently HBeAg-positive (25.9%) than were first-time donors (17.7%). Anti-HBc and anti-HBe were observed more often among first-time (99.6 and 76%) than repeat (91.8 and 60.8%) donors. No differences were found in the mean HBsAg titer nor in the subtype distribution in the two populations. The frequency of HBeAg positivity and the mean HBsAg titer in blood were significantly lower among first-time donors aged 30 or older as compared to those younger than 30. Such age-related tendencies did not occur among the repeat donors. The profiles of HBV makers suggest that the HBsAg-positive first-time donor group consists predominantly of long-term HBsAg carriers who may have acquired HBV at an early age, while the HBsAg-positive repeat donors have newly acquired infections.

Adolescent↗