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Biomedical subjects

H A Perkins

Publications and source records attributed to H A Perkins.

At least 19 recordsLinked to original sources

Declining efficacy of AIDS case list cross-referencing in human immunodeficiency virus look-back: 1981 through 1992.

BACKGROUND: The impact of AIDS case list cross-referencing in human immunodeficiency virus look-back was assessed. STUDY DESIGN AND METHODS: Post-1977 blood donations from former donors identified by 11 collaborating health departments as having developed AIDS have been traced at Irwin Memorial Blood Centers since 1983. To assess the changing efficacy of AIDS case list cross-referencing in identifying infected donors and recipients, trends in cases reported through December 1992 were analyzed. RESULTS: Previous donors (n = 638) were identified from 21,917 AIDS case listings, for an overall match rate of 2.9 percent. The rate of detection of previous donors from listings of AIDS cases declined from a peak of 5.3 percent in 1985 to 1.6 percent in 1992. Overall, 86 percent (1824/2122) of donations by persons later reported on AIDS case lists were made prior to January 1983 when risk exclusion measures were initiated. Of the 212 known infected recipients linked to AIDS case list donors, 87 (41%) were previously identified by other look-back approaches. The rate of identification of infected recipients detected exclusively through AIDS case listings declined from a mean of 21 per year from 1984 to 1987 to a mean of 3 per year from 1990 to 1992. No transmissions have been documented from donations prior to 1979. CONCLUSION: These findings demonstrate the declining yield of AIDS case list cross-referencing as a trigger for human immunodeficiency virus look-back. Continued reevaluation of look-back programs is essential so that their various components may be curtailed when justified.

Acquired Immunodeficiency Syndrome↗

Unrelated-donor marrow transplants: the experience of the National Marrow Donor Program.

As of December 1994, more than 3,000 marrow transplants had been accomplished using unrelated donors provided by the National Marrow Donor Program. With more than 1.5 million donors listed in the registry, over 60% of patients now find an HLA-A,B,DR phenotypic match at the initial search. The HLA types of these patients are biased toward the common Caucasian haplotypes, but the likelihood of identifying donors for non-Caucasian patients has improved with time. Analysis of the first 462 transplants showed disease-free survival (DFS) at 2 years to be approximately 40% in good-risk patients and 20% in poor-risk patients. Chronic myelogenous leukemia transplanted within the first year after diagnosis had 45% DFS. Some recent reports from individual transplant centers demonstrate results closer to those obtained with sibling donors, while a limited retrospective comparison suggests that unrelated-donor transplants are at least equivalent to and probably better than autologous transplants. A single HLA mismatch at A, B, or DR can be tolerated, but results are better with phenotypic identity. The most recent NMDP analysis has also identified younger donors and male donors as favorable variables in evaluating one-year survival of unrelated-marrow recipients.

Adolescent↗

Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners.

Using lookback procedures and other methods, we identified and then prospectively followed human immunodeficiency virus type 1 (HIV-1)-infected transfusion recipients and their sex partners to determine AIDS incidence and risks of heterosexual transmission of HIV-1. At enrollment, 7 of 32 (21.9%) female partners of male recipients were themselves infected with HIV-1, as compared with none of 14 male partners of female recipients (p = 0.08). No additional episodes of transmission were observed. The prevalence of advanced immunodeficiency at enrollment was similar in male and female recipients. Male recipients with advanced immunodeficiency (CD4+ lymphocyte count < or = 0.20 x 10(9)/L or a history of clinical AIDS) at enrollment were more likely to have infected their female partners (odds ratio = 7.9; p = 0.03) than men with neither condition. Similarly, AIDS-free survival, as estimated by the product-limit method, was lower among male transmitters than among male nontransmitters (p = 0.01). Transmission was not associated with frequency of unprotected vaginal intercourse. Our data suggest that HIV-1-infected men who develop immunodeficiency rapidly are more likely to infect their sex partners and that the greater efficiency of male-to-female HIV-1 transmission is not explained by a greater number of sexual contacts or more advanced immunodeficiency in index subjects.

Adult↗

The U.S. National Marrow Donor Program.

PURPOSE: The National Marrow Donor Program (NMDP) of the United States has nearly 650,000 unrelated potential marrow donors in its registry and > 1,225 marrow transplants have been performed. PATIENT AND METHODS: In 1991, 43% of patients who requested a search found at least one HLA-A-, -B-, -DR-identical donor in the files. The chance of finding a donor match is much better within one's own ethnic group. The individuals enrolled in the donor file are 67.0% white, 3.8% black, 3.0% Asian, 3.9% Hispanic, and 0.8% Native American. Therefore, patients who belong to ethnic minorities are at an obvious disadvantage in obtaining marrow donors. Because of this deficiency, the program has embarked on an aggressive campaign of recruitment of minority donors. RESULTS: Reciprocal search agreements with other countries have made another 200,000 potential donors available, but it is not likely that black patients will find help by this route. CONCLUSIONS: Several efforts are being made to speed up the search process and to ensure more accurate definition of identities. These efforts include prospective HLA-DR typing of donors in the file, storage of a sample of frozen blood from each donor to permit class II typing (HLA-DR, -DQ) by DNA techniques, and eliminating the mixed lymphocyte culture test as a requirement for designating a given donor as HLA identical.

Bone Marrow Transplantation↗

Safety of the blood supply.

This is a review of events when the medical community realized that AIDS was an infectious disease which might be transmitted by blood transfusions and the response by the various organizations and agencies to curb the potential spread of HIV via blood products. It became possible through a number of approaches to make the blood supply safe so that today the likelihood of transmission of HIV by blood transfusion is extremely unlikely.

Acquired Immunodeficiency Syndrome↗

The National Marrow Donor Program.

As the number of successful marrow transplants has increased, the lack of HLA-identical sibling donors for 60 to 70 percent of transplant candidates has become a serious problem. Pilot studies established that marrow transplantation between phenotypically HLA-identical, unrelated individuals can be accomplished successfully. Therefore, the National Marrow Donor Program was established to develop a large file of volunteer marrow donors and to serve as a center for the coordination of the donor search and donor-recipient matching processes. By November 1991, 63 months after the program was established, 457,205 potential marrow donors typed for HLA-A and -B antigens had agreed to be listed in the marrow donor registry. A donor search had been initiated for 8481 patients. At least one potential donor matched for at least three of the four HLA-A and -B antigens was located for 99.8 percent of patients. Among the 3156 searches that were completed, 940 (29.8%) resulted in a transplant. The median time in which to locate a matched donor, complete all predonation evaluations, and obtain donor consent was 208 days. The most common diagnosis in patients who underwent transplantation was chronic myelogenous leukemia (42.0%). When this analysis was completed in November 1991, the National Marrow Donor Program was operating a national network of 99 donor centers and 53 transplant centers. The donor file was increasing rapidly, and a follow-up system was in place to determine the effects of donation on the donors and the outcome in the patients who underwent transplantation. This national network of donor and transplant centers exists and is now facilitating unrelated-donor marrow transplants. The National Marrow Donor Program made it possible to locate donors for many patients in need of a transplant and helped to determine the role of unrelated-donor marrow transplants in the treatment of many diseases.

Blood Component Removal↗

Evaluation of screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells.

BACKGROUND: Reports of transmission of the human immunodeficiency virus type 1 (HIV-1) from transfusions of screened blood and reports of silent, antibody-negative HIV-1 infections in persons at high risk continue to foster concern about the safety of the blood supply. Previous estimates of the risk of HIV-1 range from 1 in 38,000 to 1 in 300,000 per unit of blood but are based on either epidemiologic models or the demonstration of seroconversion in recipients. METHODS: We isolated peripheral-blood mononuclear cells from blood that was fully screened and found to be seronegative, combined them into pools of cells from 50 donors, and tested them for HIV-1 by viral culture and the polymerase chain reaction, using protocols specifically adapted for this analysis. RESULTS: The 1530 pools of mononuclear cells were prepared from 76,500 blood donations made in San Francisco between November 1987 and December 1989. Of these pools, 1436 (representing 71,800 donations) were cultured successfully; 873 (43,650 donations) were evaluated by the polymerase chain reaction. Only one pool was confirmed as HIV-1--infected by both methods. After adjustment for sample-based estimates of the sensitivity of the detection systems using culture and the polymerase chain reaction, the probability that a screened donor will be positive for HIV-1 was estimated as 1 in 61,171 (95 percent upper confidence bound, 1 in 10,695). CONCLUSIONS: Silent HIV-1 infections are exceedingly rare among screened blood donors, so the current risk of HIV-1 transmission from blood transfusions, even in high-prevalence metropolitan areas, is extremely low.

Acquired Immunodeficiency Syndrome↗

Risk of human immunodeficiency virus (HIV) transmission by blood transfusions before the implementation of HIV-1 antibody screening. The Transfusion Safety Study Group.

Little information is available regarding the risk of human immunodeficiency virus type 1 (HIV-1) infection for patients transfused before routine anti-HIV-1 screening of blood donors was instituted in March 1985. A model was developed for estimating both the proportion and the number of transfusion recipients in the San Francisco Bay area who were infected by HIV-1 during each of the 7 years preceding routine donor screening for anti-HIV-1. The model is based on analysis of 1) donation histories of HIV-1-infected donors identified at the regional blood center; 2) HIV-1 seroprevalence estimates for homosexual and bisexual men in San Francisco; and 3) HIV-1 infection and survival rates for recipients traced by the Transfusion Safety Study and Irwin Memorial Blood Centers' Look Back Program. The incidence of transfusion-associated HIV-1 infection is estimated to have risen rapidly from the first occurrence in 1978 to a peak in late 1982 of approximately 1.1 percent per transfused unit. The decrease after 1982 coincided with the implementation of high-risk donor deferral measures. It is estimated that, overall, approximately 2135 transfusion recipients were infected with HIV-1 in the San Francisco region alone. This number suggests a higher prevalence of transfusion-associated HIV-1 infection than has been generally recognized and indicates the need for continued tracing of potentially exposed recipients. The data also strongly support the effectiveness of early donor education and self-exclusion measures and emphasize the importance of continued research and development in this area.

Acquired Immunodeficiency Syndrome↗

Differential reactions of HLA typing sera with cells homozygous for crossreacting antigens.

A large number of well-characterized HLA typing sera were used in a standard cytotoxicity technique to evaluate the frequency with which homozygous cells reacted to antisera directed against a crossreacting specificity. Four of 15 anti-HLA-A1 sera reacted with cells homozygous for HLA-A11 bet not with A11 heterozygotes. Similar dosage effects were noted with anti-A3 sera and A11 cells, with anti-A28 sera and A2 cells, with anti-A23 sera and A24 cells, and with anti-A24 sera and A23 cells. No dosage effects were seen with anti-A1 sera and A3 cells, with anti-A3 sera and A1 cells, and with anti-A11 sera and either A1 or A3 cells. Dosage effects were also not seen with anti-B51 or -B35 sera and cells containing antigens of the B5 crossreacting group. Dosage is a property of the individual serum and does not occur with all samples sharing the same primary specificity. As noted by red cell serologists, sera demonstrating dosage effects are common with some specificities but absent with others. The reactions noted may be a quantitative effect of epitopes present on certain antigens. Caution should be observed when interpreting an HLA phenotype that appears to contain two crossreacting antigens at the same locus, unless the sera used have been shown not to manifest dosage effects.

Blood Group Antigens↗

The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease.

Patients infected by the human immunodeficiency virus (HIV) as a result of blood transfusions are unique in that their dates of infection are well defined and their medical conditions before infection are known. To characterize the natural history of transfusion-associated HIV infection, we studied 694 recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of the recipients tested, 85 were seronegative, 116 were seropositive, and 19 had AIDS. Of 101 HIV-seropositive recipients followed for a median of 55 months after infection, 54 had Centers for Disease Control Class IV disease, including 43 with AIDS. Life-table analysis suggested that AIDS will develop in 49 percent of infected recipients (95 percent confidence limits, 36 to 62 percent) within seven years after infection. As compared with recipients without AIDS, the 43 recipients with AIDS had received more transfusions at the time of infection (median, 21 vs. 7; P = 0.01). HIV-infected blood donors in whom AIDS developed were grouped according to whether AIDS developed within 29 months (the median) after donation (Group 1) or 29 or more months after donation (Group 2). As compared with the 31 recipients of blood from Group 2 blood donors, the 31 recipients of blood from Group 1 donors were more likely to have AIDS four years after infection (49 percent vs. 4 percent; P = 0.005) and illnesses resembling acute retroviral syndrome (14 of 24 vs. 5 of 22; P = 0.03). We conclude that most recipients of HIV-infected blood become seropositive, that AIDS develops in about half these recipients within seven years, and that the risk may be higher when AIDS develops in the blood donor soon after donation.

Acquired Immunodeficiency Syndrome↗

Reduction of human immunodeficiency virus-infected cells from donor blood by leukocyte filtration.

Several filters for leukocyte removal were evaluated in terms of their ability to reduce the cell-associated human immunodeficiency virus (HIV) load in units of blood either inoculated in vitro with lymphocytes from a chronically infected cell line or collected directly from seropositive donors. Filtration of the experimentally inoculated units of blood resulted in a 5.9 log 10 mean reduction (95% confidence interval:7.4-4.5) of tissue culture infectious units (TCIU) as assayed by end-point titration using the coculture assay. Filtration of the units of blood from anti-HIV positive donors lowered the infectivity by over 2 logs, as detected by the coculture and polymerase chain reaction (PCR) techniques. However, residual cell-associated virus was detected in the majority of experiments. Clinical studies are warranted to determine if leukocyte filtration of blood will reduce the risk of transfusion transmitted viral infections.

Acquired Immunodeficiency Syndrome↗