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Biomedical subjects

P L Page

Publications and source records attributed to P L Page.

At least 19 recordsLinked to original sources

Computer-based interview for screening blood donors for risk of HIV transmission.

OBJECTIVE: To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview. DESIGN: A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion. SETTING: The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital. SUBJECTS: Consecutive sample of 294 male and female blood donors 18 to 75 years of age. MAIN OUTCOME MEASURES: Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment. RESULTS: The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P less than .0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer. CONCLUSIONS: Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer-based screening is also acceptable to blood donors.

Adolescent↗

Reduced association between the Ii blood group and congenital cataracts in white patients.

The authors have identified a white patient with the red blood cell phenotype i, who also has congenital cataracts. However, in comparison with the strong association in Japanese patients between congenital cataracts and the i phenotype, the overall incidence of cataracts in white people with the i phenotype (three of ten people have congenital cataracts) is much lower. In addition, the authors studied the blood of 31 white patients with congenital cataracts and found no patients with the i phenotype. Thus, a close link between genes for these traits does not appear in most white patients with i red blood cell phenotypes.

Adult↗

Characterization of the spatial distribution of late ventricular potentials by body surface mapping in patients with ventricular tachycardia.

Low-level activity at the end of the QRS complex was analyzed from 63 thoracic leads in 15 normal subjects and in 21 patients with ventricular tachycardia (VT). The latter had old myocardial infarction and no conduction disturbances and had not been receiving antiarrhythmic drugs. In both normal subjects and patients with VT, isopotential maps of the time-averaged and filtered (25 Hz high-pass) electrocardiograms during the terminal portion of the QRS were dipolar, i.e., they showed single positive and negative regions. For patients with VT, the extrema were either distant, with one over the precordial area and the other over the back, or close together in the precordial region. In 10 patients, maps recorded after administration of antiarrhythmic drugs remained the same while QRS duration was prolonged. In six patients, maps recorded before antiarrhythmic surgery showed distant extrema for septal or posterobasal VT sites of origin and close extrema for anterior or posteroapical sites. Generally, QRS duration was reduced and maps were modified after surgery. Late potentials can be well detected with only three orthogonal leads because their distributions are dipolar, but maps provide additional information about their distribution, which may be related to conduction delay sites and possibly to VT sites of origin. Sources near the torso surface would produce close extrema, whereas deeper sources would produce distant extrema.

Adult↗

HTLV-III infection after bone marrow transplantation.

We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.

Acquired Immunodeficiency Syndrome↗

Microtopography of growth of normal and leukemic murine cells in diffusion-chamber cultures.

Histologic examination of "suspension" diffusion-chamber (DC) cultures of normal murine bone marrow cells demonstrates that hemopoietic cell growth in this system takes place in clonal form. Soon after implantation, marrow cells are arrayed on the filter membranes in a circumferential fashion adjacent to the surrounding lucite ring. Colonies of granulocytic cells soon form in this location and increase in size and number with increasing time of culture. Eventually cells begin to approach confluence over the entire filter membrane. Growth of C1498 murine acute myelogenous leukemic cells in DC cultures also takes place on the filter membranes and begins in a circumferential pattern. However, the leukemic cells grow diffusely and soon overspread the entire filter membrane, often growing several layers thick. Thus, although normal marrow cells are implanted into and are harvested from DC cultures in liquid-suspension form, they grow in a clonal pattern similar to that observed with the plasma-clot and fibrin-clot DC culture methods.

Animals↗

Linkage disequilibrium of HLA-SB1 with the HLA-A1, B8, DR3, SCO1 and of HLA-SB4 with the HLA-A26, Bw38, Dw10, DR4, SC21 extended haplotypes.

Homozygous typing cells from 13 normal HLA-A1, B8, Dw3, DR3 and five normal HLA-A26, Bw38, Dw10, DR4 individuals were typed for the following markers: HLA-SB, MB, MT; complement proteins BF, C2, C4A, C4B; and GLO. Ninety-one percent of A1, B8, Dw3, DR3 homozygous individuals (HI) tested were homozygous for BF*S, C2*C, C4A*QO, and C4B*1 (SCO1 complotype), which indicates that the SCO1 complotype is in linkage disequilibrium with the A1, B8, DR3 haplotype in randomly selected normal populations. Sixty-seven percent of HLA-A1, B8, Dw3, DR3, SCO1 positive HI also expressed SB1; since the frequency of SB1 in random Caucasian populations is 11.2%, this finding indicates that SB1 is in linkage disequilibrium with the A1, B8, DR3, SCO1 extended haplotype. All HI with the A26, Bw38, Dw10, DR4 haplotype were homozygous for both SC21 and SB4, suggesting that SC21 and SB4 should be included in the A26, Bw38, Dw10, DR4 extended haplotype. On the other hand, neither of the GLO markers were found in association with either haplotype. The results of this study indicate that HLA-SB is included in some extended haplotypes and may be important in these markers for diseases such as insulin-dependent diabetes mellitus. This study also demonstrated an apparent influence of HLA-SB on primary mixed lymphocyte culture (MLC) responses. The mean relative response of primary MLCs between individuals matched for HLA-A, B, D, DR, MB and MT but not SB was 40% of that for the MLCs with mismatched HLA-D, significantly higher than the MLCs matched for all HLA and complotypes.

Complement System Proteins↗

MHC determinants of response to Rh immunization.

The demonstration of immune response genes in man has been difficult, although there is evidence for genes linked to the MHC in mouse and guinea pig that control both the specificity and magnitude of immune responses. A number of features of the antibody response to the Rh D antigen, such as the failure of some individuals at risk to respond, the restricted immunoglobulin class, subclass, and light chain type of the antibody produced, and the presumed minor structural difference between Rh D antigen and its allelic product, all suggest that one or at most a few immune response genes are involved. Typing for the four MHC-linked complement genes BF, C2, C4A, and C4B was carried out in 52 independently ascertained Caucasian individuals with significant anti-D titers. A control population of 623 normal Caucasian chromosomes was also studied. In patients with anti-D antibodies, the frequency of BF F1 (0.04 vs 0.0064 for 623 chromosomes, p less than 0.003); of C4A 3 (0.769 vs 0.631, p less than 0.006); and of C4B Q0 (0.25 vs 0.104, p less than 0.00004) were all increased. These three alleles are found in the common complotype BF 8F1,C2 C,C2A 3, C4B Q0, and presumably represent a single extended haplotype of 6p associated with (and presumably containing a gene for) the immune response to RhD. This complotype has a 0.6% frequency in 623 normal control chromosomes, but is also increased in patients with insulin-dependent diabetes mellitus and with membranous glomerulonephritis.

Blood Group Incompatibility↗

Two classes of murine granulocyte progenitor cells expressed in plasma clot diffusion chamber cultures.

Two distinct classes of granulocyte progenitor cells present in normal mouse bone marrow are expressed sequentially in the vivo plasma clot diffusion chamber culture system. By several criteria, progenitor cells giving rise to granulocyte colonies on day 4 of culture (CFU-D4) are different from those giving rise to colonies on day 7 (CFU-D7). These differences include: cell cycle activity as measured by in vitro incubation with cytosine arabinoside, residual concentration in the bone marrow after in vivo treatment of donor mice with cytosine arabinoside or methotrexate, resistance to osmotic lysis, size as determined by velocity sedimentation, and the morphology of the granulocyte colonies to which these cells give rise. The CFU-D7 appears to represent an earlier progenitor cell than the CFU-D4 in the differentiation pathway of the granulocyte and is analagous in many respects to the BFU-E in the erythroid pathway.

Animals↗

Unregulated growth of murine leukemic cells and suppression of normal granulocyte growth in diffusion chamber cultures.

The patterns of proliferation of C1498 mouse acute leukemic cells have been studied using the diffusion chamber technique of cell culture. These malignant cells grow to the same maximal cell concentration irrespective of initial cell input. Leukemic cells proliferate equally well with or without the stimulus of prior host irradiation. When cells cultured for several days are diluted to the original input concentration and recultured, they rapidly proliferate back to maximal cell number. All of these findings are in sharp contrast to the behavior of granulocytes from normal mouse marrow grown in the same culture system. Co-culutre of equal numbers of normal marrow cells and leukemic cells results in virtually complete inhibition of normal marrow cells and leukemic cells results in virtually complete inhibition of normal granulocyte growth. These experiments provide a means of studying malignant growth of leukemic cells, as compared to the controlled growth and differentiation of normal granulocytes, and mechanisms by which leukemic cells suppress normal granulocyte development.

Animals↗

Effects of frequent and sustained plateletapheresis on peripheral blood mononuclear cell populations and lymphocyte functions of normal volunteer donors.

Per procedure, plateletapheresis may remove 2 X 10(9) to 3 X 10(9) white cells from the peripheral blood of a normal donor. To investigate the effects of frequent and sustained plateletapheresis, multiple peripheral blood tests were performed on 25 volunteer donors undergoing plateletapheresis an average of 72 times over periods of up to 8 years, and results were compared with 25 age- and sex-matched controls who had not undergone apheresis. In donors, significant decreases were observed in: 1) both absolute number and percentage of T4+ cells; 2) absolute number of both T8+ cells and Leu-7+ cells; 3) T4/T8 ratio; 4) responses to both pokeweed mitogen and alloantigens; and 5) IgG levels. Significant increases were observed in percentages of both B cells and monocytes, and responses to both phytohemagglutinin and Concanavalin A. Plateletapheresis removes a large number of T4 and T8 cells, a moderate number of B cells, and a smaller number of monocytes and Leu-7 cells. The results suggest that during vigorous plateletapheresis the replenishment to peripheral blood per month was less than 1.83 X 10(9) and 0.93 X 10(9) for T4 cells and T8 cells, respectively, greater than 0.27 X 10(9) and 0.62 X 10(9) for B cells and monocytes, respectively, and approximately 0.39 X 10(9) for Leu-7 cells. Although no clinical effect was noted, these data suggest that frequent and sustained non-lymphocyte sparing plateletapheresis is associated with changes in laboratory findings related to the immune system.

Adolescent↗