Biomedical subjects
J McCullough
Publications and source records attributed to J McCullough.
A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant.
We performed a prospective, randomized trial in CMV seronegative marrow recipients to determine if filtered blood products were as effective as CMV-seronegative blood products for the prevention of transfusion-transmitted CMV infection after marrow transplant. Before transplant, 502 patients were randomized to receive either filtered or seronegative blood products. Patients were monitored for the development of CMV infection and tissue-documented CMV disease between days 21 and 100 after transplant. Infections occurring after day 21 from transplant were considered related to the transfusion of study blood products and, thus, were considered evaluable infections for the purpose of this trial. In the primary analysis of evaluable infections, there were no significant differences between the probability of CMV infection (1.3% v 2.4%, P = 1.00) or disease (0% v 2.4%, P = 1.00) between the seronegative and filtered arms, respectively, or probability of survival (P = .6). In a secondary analysis of all infections occurring from day 0 to 100 post-transplant, although the infection rates were similar, the probability of CMV disease in the filtered arm was greater (2.4% v 0% in the seronegative arm, P = .03). However, the disease rate was still within the prestudy clinically defined acceptable rate of < or = 5%. We conclude that filtration is an effective alternative to the use of seronegative blood products for prevention of transfusion-associated CMV infection in marrow transplant patients.
Unrelated donor bone marrow transplantation: influence of HLA A and B incompatibility on outcome.
We have studied the outcome of 211 consecutive unrelated donor (URD) bone marrow transplants (BMT) performed at the University of Minnesota (Minneapolis, MN) between May 1985 and December 1992. Ninety patients (43%) received marrow matched serologically at HLA A, B, and DR loci; 86 (41%) received marrow with a major and 32 (15%) marrow with a minor serologic mismatch at the HLA A or B locus. Multivariate analysis revealed that older age had an adverse effect on survival. In younger (age less than 18 years) recipients, survival after fully matched (A, B, and DR sub-type) or major mismatched (A or B locus), DR subtype-matched donor BMT was not significantly different (P = .4; survival: 53% v 41%, respectively, at 3 years). For adults, survival after matched donor BMT was significantly better than that with mismatched donors (P < .01; survival: 30% v 10%, respectively, at 3 years). Formal quality of life assessment by telephone interview demonstrated similar functional status in survivors of URD and related donor (RD) BMT at least 2 years post-BMT. URD BMT provides effective therapy for a variety of lethal hematopoietic diseases that rivals outcome of RD transplant in some cases. Use of URD marrow with a major mismatch at one HLA A or B locus is well tolerated in young, but not in older, recipients. These observations should be used to improve donor selection and counseling for URD BMT candidates.
Genetic and biochemical analysis of Cdc42p function in Saccharomyces cerevisiae and Schizosaccharomyces pombe.
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Determination of ABO glycosyltransferase genotypes by use of polymerase chain reaction and restriction enzymes.
BACKGROUND: The molecular basis of red cell ABO group antigens has been determined. The genes encoding the group A and B glycosyltransferases and a nonfunctional group O transferase have been cloned and sequenced. All three genes were similar. When compared to the nucleotide sequence of the A gene, the O gene has a one-base deletion that leads to a frame shift and results in a nonfunctional protein. The B gene differs from the A gene at seven nucleotides. STUDY DESIGN AND METHODS: Techniques using polymerase chain reaction and restriction enzymes to determine ABO transferase genotypes from white cell DNA were modified. Nucleotide sequence differences within the genes were analyzed by the application of selected restriction enzymes. Restriction enzymes Asp718 and BstEII were used to analyze the genes at nucleotide 258, and BssHII and Kas I were used to analyze the genes at nucleotide 523. ABO red cell phenotypes were compared in 60 unrelated individuals with ABO transferase genotypes. The ABO phenotypes and genotypes of individuals from two different families were also analyzed to determine if this method could distinguish individuals who were homozygous for A or B transferase genes from those who were heterozygous. RESULTS: The phenotypes and genotypes were consistent for all unrelated individuals, and within the families, heterozygous individuals could be distinguished from homozygous individuals. Nevertheless, two individuals from one family were found to have a group A red cell phenotype, but when the transferase genes were analyzed at nucleotide 523 with enzymes BssHII and Kas I, both A and B transferase genes were detected. Further analysis of the transferase genes at nucleotide 700 by using restriction enzymes Alu I and Hpa II and those at nucleotide 793 by using enzyme BstNI found that both transferase genes in the two individuals were similar to the A transferase gene. CONCLUSION: An A allele of the group A glycosyltransferase was detected that had the same sequence as the B gene at nucleotide 523 but was identical to the A gene at positions 700 and 793. The identification of this variant gene makes genotyping at nucleotide 523 unreliable. However, analysis of the genes at other sites of nucleotide variation may accurately identify phenotypes.
The new generation of blood components.
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Rat reproductive performance following photodynamic therapy with topically administered Photofrin.
A rat animal model was used for comparing the photodynamic efficacy of two formulations of topically administered Photofrin in the uterus: 0.7 mg/kg Photofrin and 0.7 mg/kg Photofrin + 4% Azone, a penetration-enhancing agent. Uterine structure and reproductive performance were evaluated following illumination with 80 J/cm2 of 630 nm light. Fluorescence microscopy was employed to determine drug localization in frozen uterine sections at various times after drug administration. Functionality studies demonstrated a significant reduction in the number of implantations per treated uterine horn compared to controls. The mean number of implantations decreased systematically on increasing the interval between Photofrin administration and light application. At 72 h, 0.88 +/- 0.52 gestational sacs per rat were recorded with Photofrin therapy, compared with 8.1 +/- 1.12 (P = 0.01) on the untreated side, indicating nearly complete loss of reproductive capability. Similar results were achieved after only 3 h treatment with Photofrin + Azone (0.38 +/- 0.26 sacs per rat versus 7.5 +/- 1.07 on the untreated side; P = 0.01). This indicates that the effect of Photofrin can be enhanced either by extending the drug incubation period from 3 to 72 h or by adding the penetration-enhancing drug Azone. Fluorescence pharmacokinetic studies suggest that both forms of topically administered Photofrin are diffusely distributed throughout the endometrium at virtually the same rate. However, Azone may enhance the selectivity of photodynamic therapy by facilitating drug targeting to critical endometrial structures.
The changing activities of a regional marrow donor program.
BACKGROUND: A regional marrow donor program was established in 1982. Following the establishment of the National Marrow Donor Program (NMDP) in 1987, the activities of this regional program changed. STUDY DESIGN AND METHODS: To better understand the changes that occurred in the regional marrow donor program, its donor recruitment and marrow collection activities through 1991 were studied retrospectively. Data analyzed included the total number of potential donors, the number and types of potential donors recruited each year, the number of searches performed, the number of samples collected for HLA-DR typing and mixed lymphocyte culture testing, and the number of transplants in both programs from 1987 through 1991. Statistical analysis was performed by using chi-square. RESULTS: Initially, only persons who donated platelets by apheresis were enrolled into the program. In 1986, the regional program's first drive to recruit people who were not apheresis donors occurred. The number of such drives increased each year, and in 1991, 12 drives occurred, which resulted in the recruitment of 1313 potential marrow donors. From 1987 to 1991, the number of potential donors in the regional program grew from 3252 to 9146, but the proportion of apheresis donors in the program decreased. In 1987, 91.9 percent of marrow donors at the regional center had been apheresis donors, but in 1991, 41.7 percent had been apheresis donors. The number of marrows donated at the regional center increased from 11 in 1987 to 29 in 1989, but then fell to 24 per year in 1990 and 1991. The decrease in the number of donations at the regional program was due to the rapid growth in the NMDP file of potential marrow donors and the selection of donors whose HLA antigens were more compatible with those of the transplant recipients. In 1989, the regional program contained 4.6 percent of all HLA-A,B-typed and 11.2 percent of all HLA-A,B,DR-typed potential donors in the NMDP and collected 15.3 percent of all marrows. However, in 1991, the regional program contained 2.0 percent of HLA-A,B-typed donors and 4.1 percent of HLA-A,B,DR-typed donors and collected 5.3 percent of marrows. In 1987, 18 percent of the people who donated marrow at the regional center were phenotypically HLA-A,B,DR identical with the recipient, but in 1991, 92 percent of donor-recipient pairs were phenotypically HLA-A,B,DR identical. CONCLUSION: Recruitment activities became an increasingly larger part of the Regional Marrow Donor Program's activities. Increasing the size of the file of potential donors was necessary to maintain a constant number of donations. Persons who were not regular blood donors were an important part of the marrow donor program.
Granulocyte transfusions: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation.
BACKGROUND: A retrospective study was conducted to evaluate the efficacy of granulocyte transfusions in neutropenic patients with fungal infections following bone marrow transplantation. STUDY DESIGN AND METHODS: Systemic fungal infection was detected in 87 patients during the first 100 days following bone marrow transplantation; 50 received granulocytes in addition to appropriate antifungal agents. The median age was 17 years in the transfused patients (range, 1.5-57) and 35 years in the nontransfused patients (range, 0.8-50). Granulocyte transfusions were given on a daily to twice-daily basis. To evaluate their responses, patients were categorized by infection type (candidal [n = 38] vs. noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n = 57]). Resolution of infection was defined as the resolution of signs and symptoms and negative cultures and/or histopathology. RESULTS: No benefit of granulocyte transfusions could be shown in the resolution of infection in patients with either invasive noncandidal infection (29% in the transfused patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56% vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was seen in the resolution of infection in the transfused (25.9%) and nontransfused (50%) patients (p > 0.1); nor was any difference between the transfused and nontransfused patients evident in the duration of febrile episode associated with the fungal infection. Granulocyte transfusions were well tolerated, with the only complications being fever in 12 patients (24%), chills in 10 (20%), and respiratory distress in 2 (4%). Despite attempts to stratify by infection type, invasiveness, and marrow recovery, it was not possible to show any benefit of granulocyte transfusions in this group. CONCLUSIONS: It is likely that only through a prospective randomized trial can the question of the efficacy of granulocyte transfusions in treating fungal infections be conclusively answered.
Statistics in articles published in TRANSFUSION.
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Collection and use of stem cells; role of transfusion centers in bone marrow transplantation.
Marrow transplantation is increasing, hematopoietic stem cells are being obtained from a wider variety of donors, and the cells almost always undergo some processing steps. These activities, along with the hematologic complexities of marrow transplant patients, create many varied opportunities for blood centers.
Proposed policies and procedures for the establishment of a cord blood bank.
To carry out cord blood transplants from allogeneic unrelated donors, cord blood stem cell banks must be established. This report proposed the policies and procedures that can be used to establish cord blood banks. The areas covered include donor consent and suitability criteria; infectious and genetic disease testing; collection, processing, and preservation of the cord blood; retention of specimens for special testing; confidentiality; documentation and record keeping; establishment of a quality control program; and related regulatory issues. There are no technologic impediments to establishing cord blood banks. Agreement on some standard policies and procedures would facilitate exchange of cord blood stem cells among transplant centers and should increase the number of transplants that can be done.
Leiomyomatosis peritonealis disseminata (LPD) with associated endometriosis: a case report.
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The nation's changing blood supply system.
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Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program.
BACKGROUND AND METHODS: Allogeneic bone marrow transplantation is curative in a substantial number of patients with hematologic cancers, marrow-failure disorders, immunodeficiency syndromes, and certain metabolic diseases. Unfortunately, only 25 to 30 percent of potential recipients have HLA-identical siblings who can act as donors. In 1986 the National Marrow Donor Program was created in the United States to facilitate the finding and procurement of suitable marrow from unrelated donors for patients lacking related donors. RESULTS: During the first four years of the program, 462 patients with acquired and congenital lymphohematopoietic disorders or metabolic diseases received marrow transplants from unrelated donors. The probability of engraftment by 100 days after transplantation was 94 percent, although 8 percent of patients later had secondary graft failure. The probability of grade II, III, or IV acute graft-versus-host disease was 64 percent, and the probability of chronic graft-versus-host disease at one year was 55 percent. The rate of disease-free survival at two years among patients with leukemia and good prognostic factors was 40 percent and among patients at higher risk, 19 percent. Twenty-nine percent of the patients with aplastic anemia were alive at two years, and the rate of two-year disease-free survival among patients with myelodysplasia was 18 percent. For patients with congenital immunologic or nonimmunologic disorders, the probability of survival was 52 percent. CONCLUSIONS: The National Marrow Donor Program has benefited a substantial number of patients in need of marrow transplants from closely HLA-matched unrelated donors and has facilitated the recruitment of unrelated donors into the donor pool and the access to suitable marrow.
Anaphylaxis after ingestion of beignets contaminated with Dermatophagoides farinae.
A 48-year-old man was evaluated for anaphylaxis associated with ingestion of beignets prepared from a commercial mix. Microscopic examination of the patient's beignet mix revealed live Dermatophagoides farinae. Another unopened box from the same source was not infested. Skin test results to aeroallergens and foods, including all beignet mix ingredients, were positive only to D. farinae and D. pteronyssinus extracts. Skin prick test results to an infested mix extract (1:5 wt/vol) were also positive, but no reaction was observed with noninfested mix extract. ELISA inhibition studies demonstrated significant inhibition of the patient's serum binding to D. farinae strips by infected mix extract. Parallel inhibition curves were produced by the infested mix extract and a commercial D. farinae extract. Noninfested mix extract showed no inhibition. RAST analysis with beignet mix discs showed significant binding of the patient's serum IgE to infested mix discs but not to noninfested mix discs. RAST inhibition studies revealed more than 86% inhibition of binding of the patient's IgE to infested mix discs by infested mix extract and D. farinae extract. No inhibition was observed with noninfested mix or 5% fetal calf serum-phosphate-buffered saline. We conclude that the allergen to which the patient reacted was most likely D. farinae and that ingestion of D. farinae may cause anaphylaxis in sensitive persons.
Dispensing filgrastim for outpatient use.
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Standards for bone marrow donation.
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