Dispensing filgrastim for outpatient use.
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Biomedical subjects
Publications and source records attributed to J McCullough.
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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.
Emergency CABG for failed coronary angioplasty was required in 3.3 percent of 1,625 consecutive patients undergoing angioplasties. Twenty-six percent of the patients died in the perioperative period. Efforts must be concentrated on identifying PTCA failure prior to cardiogenic shock.
Previous investigators have mentioned that human IgA is found in house dust. IgA has also been reported to be present on human skin and hence in human dander. If human dander is the primary source of food for house dust mites, a relationship would be expected between IgA and dust mite allergen (Der f I) concentrations. We wished to learn whether IgA was consistently detectable in house dust and whether IgA and dust mite allergen concentrations were related. Dust samples were collected from the bedrooms of infants enrolled in a prospective study designed to evaluate the relationship between early allergen exposure and childhood allergic disease. One hundred eighty samples were studied: 50 samples were the initial samples collected from the first 50 infants enrolled, 120 samples were monthly samples obtained from 10 other homes, and 10 additional samples were randomly selected for extraction in a nonprotein containing buffer to determine the percentage of total extractable dust protein contributed by IgA. Finally, nine commercial house dust extracts were studied to learn whether they were similar to the dust samples from study houses. Enzyme linked immunosorbent assays (ELISAs) were used to measure human IgA, human secretory IgA (sIgA) and Der f I concentrations in all of the dust extracts. We found that IgA was consistently present in house dust samples ranging from 3.2 to 2,396 micrograms of IgA per gram of dust. A strong correlation (r = .90) was found between IgA and sIgA concentrations. IgA constituted 0.27% to 6.04% of the total protein in dust samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Emergency CABG for failed coronary angioplasty was required in 3.3 percent of 1,625 consecutive patients undergoing angioplasties. Twenty-six percent of the patients died in the perioperative period. Efforts must be concentrated on identifying PTCA failure prior to cardiogenic shock.
Fel d I has been found in almost all houses investigated, including those in which cats have never been present. These observations have not been explained. We measured Fel dI in samples of carpet dust from ten newly built model homes, 14 occupied homes, six allergists' offices, five hospital corridors, and three shopping mall stores. We also measured Fel d I on T-shirts of persons with and without cats. Measurable amounts of Fel d I were found in all the dust samples. Fel d I found in older model homes exceeded that found in newer model homes (P < .05). The amounts of Fel d I found in allergists' offices, hospital corridors, and retail stores were similar to the amounts found in occupied homes without cats. Fel d I was found in all T-shirts sampled and increased with increasing exposure to cats. Our findings confirm and extend previous reports of the ubiquitous presence of cat allergen and are consistent with the hypothesis that Fel d I is carried into cat-free buildings on the clothing of people exposed to cats.
BACKGROUND: Cyclosporine is effective in the treatment of psoriasis; however, potentially serious side effects limit its long-term use. On the basis of the 36-hour psoriatic keratinocyte cell cycle, a new dosing regimen was investigated. OBJECTIVE: The purpose of this study was to evaluate a 36-hour weekly dosing schedule with cyclosporine for the treatment of psoriasis, in an attempt to decrease side effects while maintaining efficacy. METHODS: Fifteen patients were studied by means of oral doses of cyclosporine taken at 12-hour intervals for three doses per week during a 10-week period. The initial dose, 2.5 mg/kg/dose (7.5 mg/kg/wk), was increased every 2 weeks by 2.5 mg/kg/dose to a maximum of 10 mg/kg/dose. RESULTS: The average improvement as assessed by the Psoriasis Area and Severity Index for all 15 patients was 61%. Six patients had a more than 75% improvement, three patients improved 50% to 74%, and six patients improved less than 50%. Three patients dropped out because of adverse side effects, and three others completed the study at a reduced dose. CONCLUSION: It is concluded that, although effective, this dosing regimen may not have an advantage over daily dosing, given its side effect profile and the need to go to relatively high doses every 24 hours.
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In a clinical investigation, 103 Michigan residents with symptoms suggestive of allergic rhinitis or asthma were skin tested with olive (Olea europaea) pollen extract. Nineteen had positive reactions. Since the olive tree is not native to nor grown in Michigan, this study was undertaken to determine whether the skin test reactivity was the result of cross-reactivity among tree pollen allergens. ELISAs were developed to measure olive, ash (Fraxinus americana), privet (Ligustrum vulgare), and Russian olive (Elaeagnus angustifolia) specific IgE antibodies. Inhibition studies were performed to determine whether pollen extracts from each of these tree species could inhibit IgE antibody binding to olive extracts. Eleven of the 19 skin test-positive patients were olive-ELISA positive, eight either were ELISA-positive to ash, seven to privet and ten to Russian olive. There were significant correlations between the ELISA results to olive and each of the other three pollens. The inhibition studies demonstrated that all three of the tree pollens were capable of inhibiting the binding of IgE to olive extract in a dose-response fashion. IgE-immunoblot studies demonstrated several proteins common to olive, ash, and privet. Twelve of the olive skin test-positive patients were contacted and 75% were exposed to one or more of the studied trees in their yards. Five patients had traveled to areas where olive trees are grown. We conclude that there is a high degree of cross-reactivity among allergens from native Michigan trees and from olive trees. This cross-reactivity is the most likely reason for skin test reactivity to olive pollen extract in Michigan.
Antibodies to the neutrophil-specific antigens NA1 and NA2 are associated with alloimmune neonatal neutropenia (ANN), autoimmune neutropenia of childhood, and acute pulmonary transfusion reactions. These antigens have been found to be located on the neutrophil Fc-gamma receptor III (FcRIII). The mother of a child with ANN was found to lack both NA antigens and to produce an antibody that reacted with all normal neutrophils tested. We used maternal antibody and a CD16 monoclonal antibody (MoAb) that has specificity for FcRIII to immunoblot and immunoprecipitate neutrophil membranes of various NA phenotypes. Both antibodies immunoblotted an approximately 40- to 70-Kd glycoprotein (GP) on NA1, NA2-positive membrane, an approximately 40- to 55-Kd GP on NA1-homozygous membranes, and an approximately 55- to 70-Kd GP on NA2-homozygous membranes. Both antibodies also immunoprecipitated a 50- to 80-Kd GP from NA1, NA2-positive cells, a 50- to 60-Kd GP from NA1-homozygous cells, and a 55- to 80-Kd GP from NA2-homozygous cells. To further examine the specificity of the maternal antibody, sequential immunoprecipitation studies were performed using maternal antisera and a CD16 MoAb. After extracts of 125I surface-labeled neutrophils were precleared with maternal serum, CD16 MoAbs no longer immunoprecipitated any GP. Neither the CD16 MoAb nor a rabbit polyclonal antibody specific for FcRIII detected any GP in maternal neutrophil membranes by immunoblotting. Neutrophil FcRIII is a glycosyl-phosphatidylinositol anchored membrane GP as is decay accelerating factor and both are absent from neutrophils of patients with paroxysmal nocturnal hemoglobinuria (PNH). Maternal neutrophil membranes were probed with antibody specific for DAF and an 80-Kd GP was detected. This woman also has had no clinical evidence of PNH. These studies provide further evidence that the NA1 and NA2 antigens are on FcRIII and identify a healthy person whose neutrophils lack not only the neutrophil specific antigens NA1 and NA2 but multiple other epitopes of FcRIII and, therefore, likely lack FcRIII entirely.
Marrow transplants with phenotypically HLA-matched, unrelated donors have been used effectively to treat a number of diseases. Many blood centers have recruited HLA-typed apheresis blood donors into marrow donor registries. However, to build larger registries so that more patients may be treated with unrelated donor marrow transplants, whole blood donors and people who do not donate blood have been added to the registries. The marrow donor program at our blood center had 2844 potential donors, of whom 1725 were also apheresis donors, 608 were whole blood donors, and 511 were recruited from the general public as a result of community appeals for marrow donors for a specific patient. Over a 9-month period, 297 potential donors were asked to donate blood samples for HLA-DR typing or mixed lymphocyte culture (MLC) testing or to participate in an informational session, undergo a medical evaluation, and sign a statement indicating an intention to donate marrow for a specific patient. Overall, these requests were successfully completed by 75.5 percent of apheresis donors, 87.2 percent of whole blood donors, and 78.1 percent of the potential donors recruited through community appeals. Furthermore, there was no difference among the three groups in the portion of people who donated blood samples for HLA-DR typing or MLC testing. Fifteen of 18 apheresis donors who were found to match a specific donor signed a statement of intent to donate marrow, 2 apheresis donors were deferred for medical reasons, and 1 decided not to donate.(ABSTRACT TRUNCATED AT 250 WORDS)
Septicemia is a rare complication of blood transfusion. This is probably primarily due to the use of sealed disposable containers for blood collection and the storage of red cell-containing components at 4 degrees C. However, despite these measures, septicemia due to blood transfusion continues to occur. We report here a fatal case of Yersinia enterocolitica septicemia due to a contaminated unit of red cells which was collected from an apparently healthy, asymptomatic blood donor. The organism grows at cold temperature and multiplies during storage of red blood cell-containing components. Contaminated components do not show any visible abnormalities. The possibility of transfusion-transmitted Y. enterocolitica should be considered in patients who have symptoms of sepsis or shock following transfusion.
During the interval from January 1989 to March 1990, signs and symptoms of anaphylaxis developed in six patients during barium enema examinations in our institution. In all six cases the symptoms of anaphylaxis began during the procedure, usually within 10 min of starting the examination. The principal manifestation of anaphylaxis was severe hypotension, usually accompanied by edema and urticaria. The symptoms were considered potentially life threatening in all patients, and one patient died despite prompt recognition of the anaphylactic nature of the reaction and resuscitative efforts. Serum samples were obtained within a few hours of the reaction in two patients and at autopsy in the fatal case: all three samples showed elevated concentrations of mast cell tryptase, demonstrating the systemic release of anaphylactic mediators. In vitro tests demonstrated the presence of immunoglobulin E antibodies specific for latex allergens in five of the six cases. Further in vitro inhibition tests confirmed the specificity of the antibodies for latex allergens and demonstrated that similar allergens were found in both raw latex, latex gloves, and catheter balloons. Only one patient was willing to undergo a skin test, and her skin test was positive for extracts of latex products. After considering multiple possibilities, we conclude that the reactions associated with barium enemas observed in these six patients are most probably the result of latex allergy.
The desirable features for a screening assay to detect antibacterial antibiotics include 1) high specificity for the desired antibiotic type 2) high sensitivity 3) lack of interference by other compounds likely to be associated with the antibiotic of interest and 4) ease of operation to allow a large number of samples to be tested. These characteristics are largely found in screens employing strains carrying fusions between antibiotic induced promoters and the structural genes for Escherichia coli beta-galactosidase. Screens were designed based upon fusions with three antibiotic induced promoters: the tetracycline induced tetA/tetR promoter from transposon Tn10, the erythromycin induced promoter from the Staphylococcus aureus ermC erythromycin-resistance gene and the chloramphenicol induced promoter from the S. aureus cat86 chloramphenicol-resistance gene. Because there have been no reports of vancomycin induced resistance determinants, a Tn903 random gene fusion pool was screened to isolate a vancomycin induced gene fusion. This gene fusion was induced fairly specifically by glycopeptide antibiotics and the fusion was used as the basis for a glycopeptide screen.
From 1983 to 1987, cytomegalovirus seronegative allogeneic bone marrow recipients were randomized to receive screened cytomegalovirus (CMV) seronegative or unscreened blood products and 125 patients were available for analysis. CMV infection occurred in 18% of patients in the screened versus 38% in the unscreened blood product group. However, only two of 64 patients in the screened group and seven of 61 in the unscreened group developed culture or biopsy-proven CMV infections. Bone marrow donor CMV seropositivity was associated with an increased risk of developing CMV infection (21% with seronegative and 46% with seropositive donor), and CMV infection was not prevented by blood product screening if the bone marrow donor was sero = positive (62% for screened, 42% for unscreened group, p = 0.80). One year survival censored for relapse was 52% in the screened group versus 68% in the unscreened group (p = 0.08). Gram negative bacteremia complicated bone marrow transplantation (BMT) in 35% of patients receiving screened and 15% of those receiving unscreened blood products (p = 0.02). Relapse did not differ in the screened and unscreened groups. By multivariate analysis, high risk disease (p = 0.0002), CMV infection (p = 0.004), screened blood products group (p = 0.011), recipient age greater than 17 (p = 0.027), chronic graft-versus-host disease (p = 0.014) and gram negative bacteremia (p = 0.004) independently had a negative influence on survival. We conclude that blood product screening was effective in preventing CMV infections following BMT if both the recipient and bone marrow donor were CMV seronegative.(ABSTRACT TRUNCATED AT 250 WORDS)