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Biomedical subjects

T I Evans

Publications and source records attributed to T I Evans.

13 recordsLinked to original sources
PubMed1999

HLA-DRB1 genotype influences risk for and severity of rheumatoid arthritis.

OBJECTIVE: To examine how HLA-DRB1 genotypes influence rheumatoid arthritis (RA) risk and clinical severity. METHODS: We performed polymerase chain reaction based DRB1 and tumor necrosis factor (TNF) genotyping of 309 Caucasian RA and 283 Caucasian control subjects. For risk analyses, we grouped the DRB1 alleles encoding each specific shared epitope: *0401 alone, *0404 with *0102, *0405 with *0408 and *0101, and *1001 alone. For estimates of RA outcome, we retrospectively obtained data regarding ARA classification criteria, age of disease onset and disease duration, number of slow acting antirheumatic drugs (SAARD) used, and rheumatoid factor (RF). RESULTS: Homozygous shared-epitope DRB1 genotypes, compound heterozygous genotypes, and simple heterozygous genotypes all conferred elevated relative risk (RR) for RA (RR 4.3, 11.7, and 3.5, respectively). However, compound heterozygous genotypes conferred more risk than either simple heterozygous genotype (RR 3.3, p = 0.004) or homozygous genotype (RR 2.8, p = 0.036). There was a trend toward more compound heterozygous genotypes in the male RA group than in the female RA group (p < 0.1), and male sex was associated with higher frequency of rheumatoid nodules (56 vs 35% for female RA). RA outcome was estimated by number of SAARD used; mean SAARD used was higher in male than in female RA (p < 0.01) and higher in genotypes containing one or 2 shared epitope DRB1 alleles than in those negative for shared epitope DRB1 alleles (p < 0.05). Analyses also suggested that shared epitope DRB1 genotype significantly influenced the occurrence of seropositive RA. Seropositive RA fraction was related to either number of shared epitope alleles (0, 1, or 2) represented in the DRB1 genotype, or, alternatively, to the combination of sex with shared epitope DRB1 genotype. The presence of one or 2 shared epitope DRB alleles influenced the occurrence of high titer seropositive RA as defined by sheep cell agglutination test (p < 0.01). TNFab microsatellite markers and TNF promoter polymorphisms did not influence SAARD number, seropositive RA, or high titer seropositive RA. CONCLUSION: Not all shared epitope DRB1 genotypes conferred the same relative risk, and the male RA group tended to have more compound heterozygous genotypes and more severe RA as indicated by rheumatoid nodules and SAARD usage. DRB1 genotypes with one or 2 shared epitope DRB1 alleles influenced the RA outcome as estimated by numbers of SAARD used and RF.

Alleles↗
PubMed1999

Tumor necrosis factor microsatellite markers TNFa5b5 and TNFa6b5 influence adverse reactions to parenteral gold in Caucasians.

OBJECTIVE: To investigate which HLA haplotypes identified by DRB1 or tumor necrosis factor (TNF) microsatellite markers are associated with adverse reactions to parenteral gold injections. METHODS: We retrospectively studied 193 Caucasian subjects with rheumatoid arthritis (RA) who had received parenteral gold injections from a university faculty outpatient practice (n = 163) and outpatient clinics at a Department of Veterans Affairs Medical Center (n = 30). DRB1 typing was done by several DNA based techniques. TNF microsatellite genotypes were derived by polymerase chain reaction amplification, sequencing-type gel electrophoresis, and silver staining. RESULTS: Seventy-six subjects had experienced adverse reactions to gold injections (other than nitritoid reactions), 18 of whom had 2 concurrent toxicities. The numbers with adverse reactions included: mucocutaneous (57), proteinuria (25), hematuria without proteinuria (5), thrombocytopenia (3), and miscellaneous (11). By frequency comparisons, no DR was associated with adverse reactions to parenteral gold (chi-squared 4.7, 6 df, NS). Specifically, there was no increased risk of proteinuria or mucocutaneous side effects in the DR3 positive RA group, almost all of whom had the DRB1 allele *0301. By logistic regression modeling controlling for sex and onset age, DR12 and the TNF microsatellite markers a5b5 and a6b5 were associated with mucocutaneous reactions (p < 0.05 for each). The odds ratios favoring mucocutaneous adverse reactions were 3.72 with TNFa5b5 and 2.03 with TNFa6b5. TNFa5b5 was commonly found on the HLA haplotypes bearing DRB1*0101, and TNFa6b5 was on the ones bearing DRB1 alleles of the DR1, DR2, DR3, DR5, or DR6 groups or the DRB1*0401 allele. CONCLUSION: HLA haplotypes conferring risk of gold induced mucocutaneous reactions were better identified by certain HLA class III markers, namely TNFa5b5 and TNFa6b5, than by any previously associated DR groups.

Antirheumatic Agents↗
PubMed1996

A comprehensive investigation of inpatient intravenous colchicine use shows more education is needed.

OBJECTIVE: To test the hypothesis that colchicine therapy for patients in whom treatment was guided by rheumatology consultation was more appropriately prescribed than therapy for patients not receiving consultation. METHODS: A retrospective chart review of all inpatients with acute crystal induced arthritis who received intravenous (iv) colchicine was performed to assess iv colchicine prescribing errors and any adverse outcomes of iv colchicine therapy. RESULTS: Errors in the prescribing of iv colchicine occurred in 5 of 19 patients (26%). A rheumatology consultation was not obtained in any of these cases. Overall, there was a significant increase in the prescribing error rate in the no-consultation versus the consultation groups (p = 0.045). These 5 errors did not lead to serious adverse outcomes, but leukopenia occurred in one patient and the white blood cell count decreased from 7.3 to 4.3 cells/mm3 in another patient. Leukopenia also occurred in 3 patients in whom iv colchicine was used appropriately. CONCLUSION: (1) Previously published guidelines for iv colchicine use appeared successful at preventing serious colchicine toxicity. (2) These guidelines do not protect against leukopenia occurring from colchicine use. (3) Rheumatology consultation may help prevent errors in the use of iv colchicine. (4) Further education is needed in the correct use of iv colchicine.

Adult↗
PubMed1995

The genotypic distribution of shared-epitope DRB1 alleles suggests a recessive mode of inheritance of the rheumatoid arthritis disease-susceptibility gene.

OBJECTIVE: To test whether the genotypic distribution of rheumatoid arthritis (RA)-associated DRB1 alleles suggests that the DRB1-associated disease-susceptibility gene has a recessive or additive (dominant) mode of inheritance. METHODS: Caucasian patients with RA and control subjects were recruited from a faculty outpatient practice. DRB1 typing was done by several DNA-based techniques: polymerase chain reaction (PCR), followed by dot-blot hybridization with sequence-specific oligonucleotides, conventional and PCR-based restriction fragment length polymorphisms (RFLPs), and a multiplex amplification-refractory mutation RFLP system. The genotypic distribution of shared-epitope DRB1 alleles was analyzed by antigen genotype frequency among patients. The analytical method postulates a linkage-disequilibrium model with a disease locus close to a marker locus and a marker allele in linkage disequilibrium with the disease-susceptibility allele. In this instance, the marker allele was defined alternatively by any DR4-group allele, by any DR4-group or DR1-group allele, by any DR4-group shared-epitope allele, by any DR4-group shared-epitope allele plus DRB1*0101, or by any shared-epitope DRB1 allele. Observed numbers were compared with those predicted for recessive mode or additive (dominant) mode of inheritance of the DRB1-associated RA disease-susceptibility gene. RESULTS: The genotypic distribution of shared-epitope DRB1 alleles (DRB1*0401, *0404, *0405, *0408, *0101, *0102, or *1001) fit that predicted for a recessive mode of inheritance and was significantly different from that predicted for an additive (dominant) mode. When the analysis was restricted to shared-epitope DR4 alleles alone (DRB1*0401, *0404, *0405, or *0408), the observed genotype numbers fit the recessive mode best. When DR1-group alleles were added to DR4-group alleles, or alternatively, when the major shared-epitope DR1 allele (*0101) was added to DR4-group shared-epitope alleles, there was a less significant deviation from the additive mode of inheritance. The reason for this was derived by comparison of observed genotype frequencies to those expected under Hardy-Weinberg equilibrium; there was a deficit of persons with DRB1*0401, *0101 and an excess of *0101,X. CONCLUSION: The genotypic distribution of shared-epitope DRB1 marker alleles suggests that the mode of inheritance of the DRB1-associated disease susceptibility gene must be recessive and not additive (dominant).

Adult↗
PubMed1994

Leukemic arthritis.

Leukemic arthritis (LA) is an uncommon complication of both acute and chronic leukemias. LA occurs in 12% to 65% of childhood leukemia cases and 4% to 13% of adult leukemia cases. Involved joints usually are warm, swollen, and tender. This arthritis often is pauciarticular and preferentially involves large joints. LA occurs at any time during the course of leukemia and may be the presenting manifestation. Therefore, LA should be considered in the differential diagnosis of both adult and childhood rheumatic diseases. Establishing a diagnosis may be difficult and usually requires tissue biopsy. Newer immunochemical methods may help in the diagnosis of LA by demonstrating leukemic cells in synovial fluid. Therapy for the underlying leukemia is the treatment of choice. Decreasing joint pain often is the first sign of a clinical response to chemotherapy. A case report is presented and the literature on the subject is reviewed.

Arthritis↗
PubMed1977

Problems in general anaesthesia. Geriatrics.

Elderly patients are at considerable risk during and following general anaesthesia due to the physiological changes which occur with age, the fact that they commonly undergo major surgery, and that there is a high incidence of associated cardiovascular and respiratory disease. This paper attempts to emphasize important points that the anaesthetist should be looking for, and to explain why. Pathological states, although common in this age group, will not be mentioned; the dicussion will apply only to healthy aged patients.

Aged↗
PubMed1977

Regional blocks and their difficulties. Spinal.

Low spinal analgesia remains a safe, reliable, simple and economical method for perineal surgery. If strict rules are followed during injection, and hypotension is sensibly managed, the technique is devoid of serious complications.

Anesthesia, Caudal↗