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Biomedical subjects

J L Nelson

Publications and source records attributed to J L Nelson.

At least 91 records · Page 5Linked to original sources

Core values in health care reform: a communitarian approach.

Controlling health care costs should allow the nation to provide more health services and higher quality care to more people. The authors are concerned, however, that many of the reform efforts will unwittingly undermine the culture of care in their pursuit of savings and access. This article is a plea to maintain the core moral values and the social and institutional commitments that are essential in the delivery of care, so that the health care community is not turned into a health industry. The authors' communitarian approach aims to preserve the balance between individual rights and social responsibilities, the moral integrity of a caring society, and the unique character of mutual trust between patients and health care personnel. They advocate an orientation toward preventing disease and promoting health, an imperative of reforming the violent, reckless, and costly aspects of American society, and a moral justification for cutting administrative waste, defensive medicine, and excessive profits rather than rationing beneficial and humane health services.

Child↗

Rheumatoid arthritis in Tlingit Indians: clinical characterization and HLA associations.

OBJECTIVE: To characterize the features of rheumatoid arthritis (RA) in Tlingit Indians, to identify the HLA-DR alleles associated with RA in the Tlingit, and to determine whether disease severity or specific clinical manifestations correlate with the presence of specific HLA antigens. METHOD: Thirty-seven Tlingit patients with RA and 75 controls were evaluated clinically; comparative HLA studies were carried out in 33 patients and 62 controls. RESULTS: The results of this clinical study of RA in the Tlingit confirms that the disease found in them is classical RA, characterized by an early age of onset, a high frequency of nodules, serum rheumatoid factor (RF) and antinuclear antibodies (ANA); an often severe clinical course, with a high frequency of erosive disease and frequent need for surgical joint repair, and an often positive family history. In Tlingit volunteers who did not have RA we also found an increased prevalence of RF and ANA. Neither HLA-DR1 nor DR4 was found to be associated with RA in the Tlingit. The commonest DR antigen in patients with RA was DR14. The most frequent DRB1 allele was DRB1*1402 (Dw16). CONCLUSION: The Tlingit population had a very high frequency of the DRB1*1402 allele, which shares key sequence homology with DRB1*0401 (Dw4) and DRB1*0101 (Dw1), associated with RA in other racial groups. No correlations were found between specific HLA-DRB1 alleles or combinations of alleles and specific disease features or severity.

Adult↗

Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis.

There is some evidence that sex hormones may influence the incidence of rheumatoid arthritis. Obesity has been found to increase endogenous estrogens, particularly among postmenopausal women. Although the association of endogenous hormones with smoking and alcohol use is less clear, we examined the relation of these three factors with rheumatoid arthritis in women. We conducted a population-based case-control study of rheumatoid arthritis in King County, WA, and Group Health Cooperative of Puget Sound. We compared 349 incident cases of rheumatoid arthritis with 1,457 controls selected by random digit dialing or by random selection from the enrollment files of Group Health Cooperative. We conducted personal interviews to collect data on weight, smoking, alcohol history, reproductive variables, and other demographic variables. Women with 20 or more pack-years of smoking had a relative risk of 1.5 [95% confidence interval (CI) = 1.0-2.0] compared with never-smokers. Post-menopausal women who averaged more than 14 alcoholic drinks per week had a reduced risk of rheumatoid arthritis (relative risk = 0.5; 95% CI = 0.2-1.7). Women in the highest quartile of body mass index had a risk of 1.4 (95% CI = 1.0-2.0) relative to women with lowest body mass index.

Adolescent↗

Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis frequently remits during pregnancy, for unknown reasons. Since an immune response to paternally inherited fetal HLA can occur during normal pregnancy and since rheumatoid arthritis is an autoimmune disorder with a known HLA class II antigen association, we tested the hypothesis that maternal-fetal disparity in HLA alloantigens might be associated with the pregnancy-induced remission of rheumatoid arthritis. METHODS: We studied 57 pregnancies of 41 women with rheumatoid arthritis, 18 prospectively and 39 retrospectively. Serologic and DNA techniques were used to study HLA class I and II antigens. For newborns, typing was performed from cord-blood samples obtained at delivery. For four young children, typing was performed from DNA extracted from hair samples. RESULTS: We found significantly more maternal-fetal disparity in HLA-DR and DQ antigens in pregnancies characterized by the remission or improvement of rheumatoid arthritis than in pregnancies characterized by active disease. Further studies using DNA-typing techniques to define allelic variants of HLA-DR and DQ antigens confirmed this observation. Maternal-fetal disparity in alleles of HLA- DRB1, DQA, and DQB occurred in 26 of 34 pregnancies characterized by remission or improvement (76 percent), as compared with 3 of 12 pregnancies characterized by active arthritis (25 percent) (odds ratio, 9.7; P = 0.003). The difference between the two groups was most marked for alleles of HLA-DQA. CONCLUSIONS: Amelioration of rheumatoid arthritis during pregnancy is associated with a disparity in HLA class II antigens between mother and fetus. These findings suggest that the maternal immune response to paternal HLA antigens may have a role in the pregnancy-induced remission of rheumatoid arthritis.

Alleles↗

Fecundity before disease onset in women with rheumatoid arthritis.

OBJECTIVE: To examine fecundity prior to disease onset in women with rheumatoid arthritis (RA). METHODS: Two hundred fifty-nine RA patients with an opportunity for pregnancy were compared with 1,258 control women as part of a prospective case-control study of recent-onset RA in women. RESULTS: A 12-month or longer interval to pregnancy was found in 42% of RA cases compared with 34% of controls (odds ratio = 1.44, 95% confidence interval 1.10, 1.91). This difference was not accounted for by an older age when attempting to become pregnant among the RA cases compared with the controls. The result was unrelated to rheumatoid factor or HLA-DR4 status. CONCLUSION: Women with RA were found to have decreased fecundity prior to disease onset, compared with control women.

Adolescent↗

Making peace in gestational conflicts.

Mary Anne Warren's claim that "there is room for only one person with full and equal rights inside a single human skin" ([1], p. 63) calls attention to the vast range of moral conflict engendered by assigning full basic moral rights to fetuses. Thereby, it serves as a goad to thinking about conflicts between pregnant women and their fetuses in a way that emphasizes relationships rather than rights. I sketch out what a 'care orientation' might suggest about resolving gestational conflicts. I also argue that the care orientation, with its commitment to the significance of the partial and the particular, cannot be absorbed within standard, impartialist moral theory.

Ethics, Medical↗

Metabolic and immune effects of enteral ascorbic acid after burn trauma.

A burned guinea-pig model (30 per cent BSA) was used to study the effect of vitamin C on immune and metabolic responses following burn trauma. Thirty-six guinea-pigs received identical enteral diets (175 kcal/kg) except for the amount of vitamin C. Groups I, II, III and IV were given formulae delivering no vitamin C, (1 RDA) 15 mg/kg/day, 75 mg/kg/day or 375 mg/kg/day, respectively. Resistance to infection was evaluated by injecting each animal with 0.1 ml of 1 x 10(9) Staph. aureus 502A subcutaneously on day 10. On day 14, Staph. aureus abscesses were excised and the numbers of viable colonies were determined. Results showed no statistical differences between groups in the clearance of Staph. aureus. From days 2 to 12, animals in groups I, II and III had body weights of approximately 97 per cent of preburn body weight. Animals in group IV, however, had a body weight gain, 102 per cent of preburn body weight on day 12. Animals in group IV also had significantly lower metabolic rates on day 12 as compared to the animals in the other groups. These results suggest that large amounts of vitamin C have beneficial effects on the maintenance of body weight and metabolic rate following burn trauma.

Animals↗

HLA antigens in Tlingit Indians with rheumatoid arthritis.

HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).

Adult↗

An analysis of transaction logs to evaluate the educational needs of end users.

End users at the University of Southern California (USC) have free access to the last ten years of MEDLINE through a local online system known as USCInfo. Librarians at USC Norris Medical Library provide documentation and offer formal and informal training on the use of the system to search MEDLINE. To assess the educational needs of the end users, 643 searches were analyzed. Although a high proportion (84%) of the searches were judged to be successful, the use of medical subject headings (MeSH) to obtain optimal results was low; only 20% of all successful subject searches employed MeSH. Also, the advanced features of the system were underutilized. While it is promising to learn that many end users are obtaining positive results, methods which will encourage end users improve their retrievals need to be developed.

Computer User Training↗

Role of the physician in encouraging use of advance directives.

Advance directives provide patients with the chance to tailor health care decisions to their own values even after they have lost the capacity to make decisions. Federal legislation enacted in 1990 and now effective will ensure widespread awareness of this opportunity. However, the extent to which advance directives actually contribute to improving patient care will depend much more on how physicians educate and counsel their patients than on what the law mandates.

Advance Directives↗

Pregnancy outcome in women with rheumatoid arthritis before disease onset.

Pregnancy outcome before disease onset was evaluated for women with rheumatoid arthritis (RA) and control women as part of a prospective case-control study of newly diagnosed RA. An analysis of women who were ever gravid revealed no statistically significant difference in any adverse pregnancy outcome between RA cases (n = 144) and controls (n = 605) including spontaneous abortions and stillbirths. Thus, in contrast to reports both of an increase of adverse pregnancy outcomes and a decrease in women who subsequently develop RA, we found no evidence for any difference in pregnancy outcome in the RA group.

Abortion, Spontaneous↗

The sequence specificity domain of cytosine-C5 methylases.

Prokaryotic DNA[cytosine-C5]methyltransferases (m5C-methylases) share a common architectural arrangement of ten conserved sequence motifs. A series of eleven hybrids have been constructed between the HpaII (recognition sequence: Cm5CGG) and HhaI (recognition sequence: Gm5CGC) DNA-methylases. The hybrids were over-expressed in E.coli and their in vivo methylation phenotypes investigated. Six were inactive by our assay while five of them retained partial methylation activity and full specificity. In all five cases the specificity matched that of the parent methylase which contributed the so-called variable region, located between conserved motifs VIII and IX. This was the only sequence held in common between the active hybrids and for the first time provides unequivocal evidence that the specificity determinants of the mono-specific m5C-methylases are located within the variable region. Correlation of the hybrid methylase structure with the efficiency of methylation suggests that conserved motif IX may interact with the variable region whereas motif X most probably interacts with the N-terminal half of the molecule.

Amino Acid Sequence↗

Rheumatoid arthritis in women. Incidence rates in group health cooperative, Seattle, Washington, 1987-1989.

As part of a prospective case-control study of newly diagnosed rheumatoid arthritis (RA) in women, we identified all cases of probable, definite, or classic RA diagnosed in 1987-1989 in 18-64-year-old women who were members of a health maintenance organization based in the Seattle, Washington area. Using both the 1958 and the 1987 American Rheumatism Association criteria for the diagnosis of RA and enrollment data from the health maintenance organization, we calculated the incidence by age and diagnostic class. Rates of RA incidence in women increased steadily with age. The incidence of probable, definite, or classic RA ranged from 13.1 per 100,000 person-years at risk for 18-29-year-old women to 82.1 per 100,000 person-years for 60-64-year-old women. The overall incidence rate, age-adjusted to the 1980 US female population, was 27.9/100,000 person-years. The overall incidence rate for definite/classic RA, age-adjusted to the 1980 US female population, was 23.9 per 100,000 person-years. When compared with adjusted rates of incidence of definite RA in Rochester, Minnesota, in 1950-1974, the incidence rates we found were 44.7% lower. Methodologic differences, changes in diagnostic criteria, and a declining incidence of RA among women over time may all be partial explanations for these results. The possible effects of reproductive factors, including oral contraceptives use, are discussed.

Adolescent↗

Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy.

It was found that the percentage of IgG-associated agalactosyl N-linked oligosaccharides (G0) falls during normal human pregnancy and rises to values higher than before conception following delivery (n = 10, 39-55 days after delivery). Serial bleeds from a normal pregnant woman showed a fall in the percentage G0 during gestation and a rapid rise post-partum. A similar study on a pregnant arthritic woman with a pathologically elevated percentage G0 also showed a fall in percentage G0 during pregnancy and a rapid rise post-partum. The changes in IgG glycosylation in the pregnant arthritic woman occurred simultaneously with the pregnancy-induced remission and post-partum recurrence of disease. A further seven pregnant women with rheumatoid arthritis were studied and analysis of their G0 values pre- and post-partum confirmed the result. In a further series of experiments using an animal model of rheumatoid arthritis, DBA/1 mice with collagen-induced arthritis were found to have elevated G0 levels compared with control mice. The percentage G0 was found to fall simultaneously with pregnancy-induced remission to the same value as non-arthritic pregnant mice. Post-partum recurrence of arthritis in these mice was also accompanied by a simultaneous and rapid rise in percentage G0. Pseudopregnancy did not result in a change in the percentage G0, confirming the effect of true pregnancy. Since the proportion of agalactosyl IgG is abnormally high in the serum of patients with rheumatoid arthritis these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying remission of arthritis in humans during pregnancy.

Acetylglucosamine↗

Dw14(DRB1*0404) is a Dw4-dependent risk factor for rheumatoid arthritis. Rethinking the "shared epitope" hypothesis.

HLA-DR4 has been shown to be associated with risk for developing rheumatoid arthritis (RA) in multiple populations and racial groups. The allelic variants of DR4 share the DR4 serologic specificity but differ by 1 to 3 amino acids in the third hypervariable region (positions 67 to 74) and at positions 57 and 86 of the DR beta 1 chain. We have examined DR4 variants in 61 DR4+ RA cases and 55 DR4+ healthy controls. Dw14 was not associated with RA risk in DR4 heterozygous (DR4,X) cases. Only 15% of DR4,X cases had the Dw14 allele compared with 28% of DR4,X controls. In homozygous (DR4,4) individuals who also expressed Dw4, however, Dw14 was associated with increased RA risk. Moreover, the relative risk for Dw4,Dw14 (16.1, p = 0.001) actually exceeded that of Dw4,Dw4 (2.2, p = ns). Thus Dw14 is not an independent risk factor for RA but is a synergistic risk factor for individuals who also have the Dw4 allele.

Alleles↗