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Biomedical subjects

S B Moore

Publications and source records attributed to S B Moore.

At least 37 records · Page 2Linked to original sources

Corrective and preventive action.

Recognized principles of quality management include a component for process improvement, comprised largely of corrective and preventive action taken in response to identified problems. The importance of identifying and investigating problems has been clearly established in transfusion medicine. Such problems can be identified in the following ways: error, incident, and accident reports; adverse reaction reports; customer complaints; process indicator measurements; results of proficiency testing; and results of internal or external audits, inspections, or assessments. Responses to reported events can be remedial, in which the symptom is addressed, or corrective, in which the underlying cause is addressed with the intent to prevent recurrence. If identified problems or their root causes are trended to look for patterns or problems not yet occurring are anticipated, the action taken is proactive and considered preventive. Methods to trend events, monitor processes, and perform root cause analysis are discussed as well as use of the following process improvement 'tools': control charts, flowcharting, the 'repetitive why', cause-and-effect diagram, and Pareto analysis.

Consumer Behavior↗

Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions.

BACKGROUND: An increasing incidence of delayed hemolytic and delayed serologic transfusion reactions (DHTRs/DSTRs) has been seen at the Mayo Clinic since 1978. Recently, the average length of stay (LOS) for inpatients and the average number of red cell transfusions per inpatient (TPI) decreased, and the albumin and papain technique for RBC antibody detection was replaced by a polyethylene glycol technique. These changes may have affected the incidence of DHTRs/DSTRs. STUDY DESIGN AND METHODS: The diagnoses of DHTR and DSTR made at the Mayo Clinic from 1993 through 1998 were reviewed. These data were compared with previously published Mayo Clinic data from 1980 through 1992. The LOS for inpatients and the average TPI were also obtained from hospital data. RESULTS: The incidence of DHTR/DSTR increased from 1 in 1899 in 1980 through 1992 to 1 in 1300 in the 1993 through 1998 period (p < 0.05). Similarly, DSTR increased from 1 in 2990 in 1980 through 1992 to 1 in 1612 in the 1993 through 1998 period (p < 0.05). The incidence of DHTR showed a trend toward decrease, from 1 in 5405 in 1980 through 1992 to 1 in 6715 in 1993 through 1998. No alloantibody specificities were statistically associated with DHTRs in 1993 through 1998, unlike in the 1980 through 1992 period. Moreover, the incidence of Jka antibodies increased in 1993 through 1998, while the incidence of other alloantibodies remained stable. Average LOS and TPI declined by 24.5 percent and 8.8 percent, respectively, between the two periods. CONCLUSION: Recently, a trend toward a decrease in the incidence of DHTR and a significant increase in DSTRs has occurred at the Mayo Clinic. These changes are most likely due to a combination of factors, including a decrease in average LOS and the adoption of the polyethylene glycol antibody detection system.

Antibody Specificity↗

Host- and disease-specific factors affecting steatosis in chronic hepatitis C.

BACKGROUND/AIM: Steatosis is commonly present in chronic hepatitis C. Our aim was to evaluate host- and disease-specific factors associated with its occurrence. METHODS: Histologic findings in 60 patients were correlated with body mass index, human leukocyte antigens, and other conventional parameters. Comparisons were made with 41 patients who had nonalcoholic steatohepatitis and 18 patients who had chronic hepatitis B. RESULTS: Patients with chronic hepatitis C and steatosis had lower serum concentrations of gamma-globulin (p=0.01) and immunoglobulin G (p=0.05) than their counterparts without steatosis, and they had a lower frequency of antinuclear antibodies (19% versus 52%, p=0.01). They also had a higher mean body mass index (p=0.002) and a greater frequency of risk factors for steatosis (70% versus 34%, p=0.009). These risk factors, however, occurred more commonly in patients with nonalcoholic steatosis (p=0.007). Furthermore, fat deposition occurred more often in chronic hepatitis C than in chronic hepatitis B (52% versus 22%, p=0.03), despite comparable metabolic findings. The degree of steatosis in chronic hepatitis C was not associated with individual metabolic features. CONCLUSIONS: Steatosis in chronic hepatitis C is mainly a viral effect, and host-dependent metabolic factors may potentiate the manifestation. Fat deposition is associated with less immunoreactivity and it may connote a distinctive pathogenic mechanism.

Adult↗

The association between HLA class I alleles and measles vaccine-induced antibody response: evidence of a significant association.

While the Moraten strain measles vaccine is an excellent, safe, and immunogenic vaccine, vaccine failure occurs, presumably when an individual develops an inadequate immune response. In this study, we examined the association of HLA class I genes and measles vaccine-induced antibody levels. We found that the allele distribution of HLA-B alleles differed between non-responders and hyper-responders (p = 0.002). Several class I alleles were associated with non-response (HLA-B13, -B44, and -C5); whereas several other alleles were associated with hyper-response (HLA-B7 and -B51). In addition, non-responders were more likely to be HLA-B homozygous than normal responders (odds ratio 2.1), and more likely to be homozygous than hyper-responders (odds ratio 3.7, p = 0.031 Mantel-Haenzel for trend). Finally, we found evidence of an allele dose-response phenomenon for HLA-B7. We conclude that there are important associations between class I HLA genes and measles antibody levels following immunization.

Adolescent↗

Immune phenotype of chronic liver disease.

Immune disorders in chronic liver disease may reflect common host propensities or disease-specific factors. Our aim was to determine the principal bases for these expressions. Four hundred fifty-one patients with various chronic liver diseases were assessed prospectively for concurrent immune disorders. Individuals with immune diseases were more frequently women (73% vs 60%, P = 0.02) and they had HLA DR4 more often than counterparts with other HLA (46% vs 23%, P = 0.000008). The association between HLA DR4 and immune disease was apparent within individual liver diseases and within different categories of liver disease. Women with HLA DR4 had a higher frequency of immune disease than women without HLA DR4 (52% vs 22%, P < or = 0.000001), and they also had immune diseases more commonly than DR4-positive men (52% vs 31%, P = 0.03). DR4-positive men, however, had higher frequencies of immune disease than DR4-negative men, especially in the nonimmune types of liver disease (26% vs 4%, P = 0.002). We conclude that HLA DR4 and female gender constitute an immune phenotype that is an important basis for autoimmune expression in chronic liver disease.

Autoantibodies↗

Serum platelet antibody testing: evaluation of solid-phase enzyme immunoassay and comparison with indirect immunofluorescence.

We compared the ability of solid-phase enzyme immunoassay (SPEIA) with that of indirect immunofluorescence to detect serum platelet antibodies by parallel testing five sets of serum specimens: (1) 12 monospecific HLA class I specimens with defined specificities, (2) 4 HPA-1a specimens, (3) 164 sequential unselected specimens sent to our laboratory for serum platelet antibody testing, (4) specimens from 15 consecutive patients sent for indirect immunofluorescence testing alone, and (5) specimens from 19 consecutive patients sent for both indirect and direct immunofluorescence testing. In addition, specimens of HLA sera were tested by standard complement-dependent lymphocytotoxicity. Solid-phase enzyme immunoassay was consistently more sensitive than indirect immunofluorescence for all 12 HLA specimens and more sensitive than complement-dependent lymphocytotoxicity for 11 of 12 specimens. Similarly, SPEIA was more sensitive than indirect immunofluorescence for all four HPA-1a serum specimens by one to three dilutions. In the nine presumed autoimmune cases (group 5), results were positive with SPEIA in one case; no positive results were noted with indirect immunofluorescence. The solid-phase enzyme immunoassay test permits ready differentiation between alloantibodies directed to HLA and those directed to platelet-specific glycoproteins.

Antigens, Human Platelet↗

Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study.

BACKGROUND: The major histocompatibility complex (MHC) has been consistently associated with susceptibility to MS and the course of several other human autoimmune diseases. A putative association between the course and severity of MS and the MHC remains controversial. METHODS: DR and DQ genotyping by either restriction fragment length polymorphism or sequence-specific PCR-based typing in 119 patients representing 73.4% of the population with MS evaluated in a cross-sectional disability survey and 100 healthy controls from Olmsted County, Minnesota. RESULTS: We found a positive association between MS susceptibility and the DR15-DQ6 and DR13-DQ7 haplotypes, and we found a negative association with the DR1-DQ5 haplotype. We found a trend to a positive association of primary progressive MS with DR4-DQ8 and DR1-DQ5 and an association of "bout onset" MS with DR17-DQ2. We did not find an association with disease severity, as defined by EDSS/duration. CONCLUSION: Lack of consistency between different studies may be due to regional variation in MS and limitations of power but likely indicate a minor effect of MHC class II genes on the course and severity of MS.

Adult↗

HLA antibody screening: comparison of a solid phase enzyme-linked immunoassay with antiglobulin-augmented lymphocytotoxicity.

BACKGROUND: IgG antibodies to HLA class I antigens can cause hyperacute rejection of renal allografts. Screening of sera from such transplant candidates is laborious, time-consuming, and expensive when performed by sensitive antihuman globulin-augmented lymphocytotoxicity (AHG-CDC). METHODS: Because 60-70% of our transplant screens are negative, we evaluated a solid phase enzyme-linked method (EIA) as a potential prescreen by parallel testing 215 sera by AHG-CDC and by EIA. This EIA method is designed to detect only IgG antibodies, and all positive AHG-CDC sera were retested after dithiothreitol treatment. RESULTS: There was 96.2% concordance between the tests for IgG antibodies. Seven sera (3.25%) were positive by EIA alone, and one (0.46%) was negative by EIA alone. The EIA method was also less costly ($15.00 versus $105.00) and less time consuming (hours versus days) than AHG-CDC panel testing for large numbers of sera. CONCLUSIONS: We conclude that this EIA method is simple, sensitive, objective, and cost effective as a prescreen for HLA class I antibodies.

Cytotoxicity Tests, Immunologic↗

Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis.

Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB1*0301, DRB3*0101, DRB1*0401, and DRB4*0103, whereas the DRB1*1501 allele may protect from the disease. Our aim was to determine if these alleles or others influence clinical manifestations and prognosis. Eighty-six white patients were evaluated prospectively for immune features and outcomes. Class I alleles were determined by microlymphocytotoxicity, and class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes or sequence-specific primers. One hundred two white, normal subjects were typed in the same fashion. Patients with concurrent immunologic diseases were more commonly positive for DRB4*0103 than patients without these features (68% vs. 38%, P = .01). DRB1*0301 (86% vs. 45%, P = .008) and the DRB1*0301-DRB3*0101 haplotype (79% vs. 42%, P = .02) occurred more commonly in patients who deteriorated during corticosteroid therapy. In contrast, DRB1*0401 and the DRB1*0401-DRB4*0103 haplotype were associated with a lower frequency of death from liver failure or the need for transplantation than patients with other alleles (0% vs. 37%, P = .03). Patients with DRB1*0301 differed from those with DRB1*0401 in that they were younger and failed treatment more commonly (27% vs. 5%, P = .04). We conclude that alleles associated with susceptibility to type 1 autoimmune hepatitis also influence its clinical features and prognosis. DRB4*0103 is associated with concurrent immune diseases, DRB1*0301 with a poor treatment response, and DRB1*0401 with a lower frequency of hepatic death or transplantation.

Adolescent↗

Length of survival after perioperative transfusion.

To describe the post-transfusion survival of an entire, geographically defined population, we observed all residents of a US county who underwent perioperative transfusion before and after the introduction of a large autologous transfusion programme. We enrolled 444 and 1540 county residents, transfused in 1981 and in 1986-88, respectively. Complete follow-up (until death or for 5 years) was available on 1960 patients (98.8%). Of patients transfused in 1986-88, 67.6% were alive at 5 years, having survived for a mean (+/- SE) period of 46.15 (+/- 0.575) months. The survival statistics were 66.2% and 46.09 (+/- 1.047) months, respectively, for patients transfused in 1981 (P = 0.8424). Transfusion in 1986-88 vs. 1981 (with 615 [40%] vs. six [1.3%] patients receiving some autologous blood) did not have an effect on survival (P = 0.3892), following adjustment for age, gender, transfusion dose, receipt of a single-unit transfusion and transfusing surgical service. We conclude that the survival of an entire, geographically defined transfused population is substantially longer than that reported previously for patients referred to tertiary-care medical centres. The aggregate 5-year survival of patients transfused in 1981 and in 1986-88 does not differ, despite differences in patient case-mix and in perioperative transfusion practice, particularly as it relates to autologous blood usage.

Adolescent↗

Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis.

BACKGROUND & AIMS: In a recent study, we suggested that susceptibility to type 1 autoimmune hepatitis is associated with a six-amino acid motif, LLEQKR, within the DR beta polypeptide, but these data are in conflict with contemporary reports from Japan and Argentina. The purpose of the present study was to reexamine this question in a large independent cohort of patients. METHODS: Eighty-six North American white patients and 102 control subjects were studied. HLA class I antigens were determined serologically, and the DRB1, DQA1, DQB1, and DPB1 genes and the DRB3/4/5 subtypes were determined by high-resolution genotyping. RESULTS: The greatest risk was associated with DRB1*0301 (corrected probability [Pc] = 0.00003; relative risk [RR] = 4.58), and a secondary association with DRB1*0401 was identified (Pc = 0.000132; RR = 5.97). Protection from disease was associated with the DRB5*0101-DRB1*1501 haplotype (Pc = 0.021; RR = 0.3). However, further analysis indicated that a lysine residue at position 71 of the DR beta polypeptide may be the most important determinant of disease susceptibility (P = 0.0000003; RR = 8.6, increasing to RR = 16.38 with four lysine residues). CONCLUSIONS: DRB1*0301 and DRB1*0401 are confirmed as the principal susceptibility alleles for type 1 autoimmune hepatitis, and these data support the hypothesis that a lysine residue at position 71 of the DR beta-polypeptide chain may be the major risk factor.

Adult↗

Antagonists of cyclic nucleotide phosphodiesterase (PDE) isozymes PDE 3 and PDE 4 suppress lymphoblastic response to HLA class II alloantigens: a potential novel approach to preventing allograft rejection?

As a potential novel approach to preventing renal allograft rejection, we investigated whether the proliferative response of lymphocytes to mismatched HLA class II antigens in mixed lymphocytic culture (MLC) can be suppressed by antagonists of cyclic nucleotide phosphodiesterase (PDE) isozymes. Cilostamide, an antagonist of isozyme PDE3 and, to an even greater extent, in combination with rolipram, an antagonist of isozyme PDE4, markedly suppressed (delta = -60%; p < 0.01) the mitogenic proliferative response of lymphocytes in MLC to HLA-DR alloantigens from unrelated donors. These observations suggest that the selective PDE isozyme antagonists might have potential as novel drugs in "signal transduction-targeted" pharmacotherapy of renal transplant rejection.

3',5'-Cyclic-AMP Phosphodiesterases↗

Genetic distinctions between types 1 and 2 autoimmune hepatitis.

OBJECTIVES: Our aim was to determine whether alleles affecting susceptibility to type 1 autoimmune hepatitis in the United States occur as commonly in German patients with type 2 disease. METHODS: DNA specimens from 12 German patients with type 2 autoimmune hepatitis were tested for class II alleles of the major histocompatibility complex by polymerase chain reaction using sequence specific primers. Eighty-six American patients with type 1 disease and 102 Caucasoid normal subjects from the United States were tested in a similar manner. RESULTS: American patients with type 1 autoimmune hepatitis had DRB1*03 alleles more commonly than the German patients with type 2 disease (51% vs 17%, p = 0.03) and DRB1*0301 occurred more frequently in the type 1 patients (51% vs 17%, p = 0.03). The frequency of DRB1*04 alleles was also higher in the type 1 patients after exclusion of the DR1*03 alleles (64% vs 20%, p = 0.01). In contrast, patients with type 2 disease more commonly had DRB1*07 (p = 0.003), DRB1*15 (p = 0.004), and DQB1*06 (p = 0.0004). DRB1*07 (p = 0.005), DRB4*01 (p = 0.03), and DQB1*06 (p = 0.03) also occurred more frequently in the type 2 patients from Germany than in the normal subjects from the United States, although none of these frequencies were statistically significant by an adjusted p value. CONCLUSIONS: German patients with type 2 autoimmune hepatitis do not have the same susceptibility alleles as American patients with type 1 disease. Regional differences in prevalence may reflect the genetic profiles of the populations at risk.

Adult↗

Do cold agglutinins have any impact on the outcome of liver transplantation?

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.

Agglutinins↗

Genetic predispositions for immunological features in chronic liver diseases other than autoimmune hepatitis.

BACKGROUND/AIMS: Human leukocyte antigens DR3 and DR4 influence susceptibility for type 1 autoimmune hepatitis and affect its immunological manifestations. We aimed to determine if autoimmune features in patients with chronic liver diseases other than autoimmune hepatitis are associated with these same antigens. METHODS: One hundred and seventy-eight patients were evaluated. Class II typing was performed by restriction fragment length polymorphism in all patients and 80 normal subjects. RESULTS: One or more autoantibodies, including antinuclear antibodies (28%), smooth muscle antibodies (8%), thyroid antibodies (18%) and antimitochondrial antibodies (13%), were found in 92 patients (52%). Concurrent clinical diseases of an immunological nature were recognized in 53 patients (30%). Patients with antinuclear antibodies had a higher frequency of the A1-B8-DR3 haplotype than patients without these antibodies (27% versus 12%, p = 0.04) and patients with concurrent immunological diseases had a higher frequency of HLA DR4 than patients without this antigen (51% versus 26%, p = 0.003). Patients with antinuclear antibodies were more commonly DR3 positive than normals (35% versus 16%, p = 0.03) and patients with concurrent immunological diseases were more commonly HLA DR4 positive than normals (51% versus 30%, p = 0.02). CONCLUSIONS: We conclude that the clinical expression of antinuclear antibodies is associated with the A1-B8-DR3 haplotype and the presence of concurrent immunological diseases is related to the DR4 antigen. These clinical manifestations have a genetic basis that is not disease-specific.

Adult↗

DR human leukocyte antigens and disease severity in chronic hepatitis C.

BACKGROUND/AIMS: Immune mechanisms may modulate disease severity in chronic hepatitis C and the DR human leukocyte antigens may affect these mechanisms. Our aims were to evaluate the association between the DR antigens and disease severity at presentation and to seek correlation between these antigens, disease severity and autoantibodies in this condition. METHODS: Sixty-four patients were assessed prospectively and classified as having mild, moderate and severe disease by clinical, laboratory and histologic criteria. Fourteen DR antigens were determined by restriction fragment length polymorphism or polymerase chain reaction-sequence specific primers. Eighty normal subjects were typed in a similar fashion. RESULTS: Patients with mild (16), moderate (32) and severe (16) disease at presentation were indistinguishable from each other and from normal subjects by the frequencies of each DR antigen. Subsets of patients with different laboratory and histological findings had DR frequencies comparable to those without these findings and to those of normal subjects. Patients with autoantibodies and/or concurrent immunologic diseases had mild (19% versus 32%, p = 0.4), moderate (50% versus 50%) and severe (31% versus 18%, p = 0.4) disease as commonly as other patients. The frequencies of the DR antigens were similar in each category of disease severity. Patients with autoimmune features differed from patients without these features (3% versus 32%, p = 0.002) and normal subjects (3% versus 25%, p = 0.003) by having a lower frequency of HLA DR1. CONCLUSIONS: The DR antigens are not associated with any index of disease severity at presentation. Immunologic manifestations do not identify patients with a different disease severity or a distinctive genetic predisposition for disease activity. The presence of DR 1 is associated with a lower frequency of immune manifestations.

Antibodies, Antinuclear↗