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Biomedical subjects

E Dwyer

Publications and source records attributed to E Dwyer.

27 records · Page 2Linked to original sources

Definition of DRw10 by restriction fragment length polymorphism.

To better define the presence of the DRw10 haplotype which has sometimes proved difficult to type by using serologic reagents, Southern blot analysis was performed on seven DRw10 heterozygous individuals with rheumatoid arthritis. Using the restriction enzymes Taq I or BamH I, the restriction fragment length polymorphism (RFLP) pattern for the DRw10 haplotype was clearly distinguishable from that of other DR alleles. Digestion with Taq I revealed a unique DR beta/Taq I 12.20 fragment. A characteristic DR beta/Taq I 4.60 fragment was also present only in DRw10 and DR1 haplotypes. Digestion with the restriction enzyme BamH I revealed a DR beta/BamH I 5.07 fragment also present in DRw10 and DR1 haplotypes, and a DR beta/BamH I 4.30 fragment shared with the DRw52 and DR2 haplotypes but not found in DR1 haplotypes. The pattern was readily distinguished from those given by the haplotypes DR4, 7 and w9. Family studies of five individuals demonstrated appropriate segregation of the restriction fragments. In particular, segregation of DRw10 haplotypes from DR1 haplotypes was clearly shown in a family in which the DRw10 haplotype was associated with rheumatoid arthritis in two individuals. Southern blot analysis proved to be a useful alternative method for identifying the DRw10 allele in certain combinations where this allele has been difficult to define serologically.

Arthritis, Rheumatoid↗

Oral disopyramide therapy for obstructive hypertrophic cardiomyopathy.

Seven patients with obstructive hypertrophic cardiomyopathy (HC) were treated with oral disopyramide. Left ventricular outflow tract gradients were estimated using either Doppler or M-mode echocardiography. Gradients were measured before treatment, after acute and chronic dosing, after washout and after rechallenge. Disopyramide serum levels were measured at the time of echocardiography. With the first dose, mean outflow gradient decreased from 64 to 14 mm Hg (p less than 0.0001). This decrease in gradient was still present after long-term oral treatment 23 days later, with a mean gradient of 13 mm Hg (p less than 0.001). After withdrawal from the drug, gradient returned to the pretreatment value, 79 mm Hg. After rechallenge, the gradient once again declined to 30 mm Hg (p less than 0.001). High disopyramide serum levels correlated with lower outflow tract gradients, r = -0.77 (p less than 0.0001). Even at low therapeutic drug levels, there was a 49% reduction in outflow tract gradient. Four patients were symptomatically improved and have been maintained on disopyramide for greater than 1 year. In symptomatic patients, disopyramide acutely decreases obstruction and also provides sustained pharmacologic control of obstruction. Disopyramide should be considered as a good alternative to treatment with adrenergic blockers, calcium antagonists or surgery.

Aged↗

Hypotheses on the molecular basis of susceptibility to rheumatoid arthritis.

An interpretive summary of recent immunologic and molecular biologic data concerning the molecular basis of susceptibility of rheumatoid arthritis will be presented. The central point of view is taken that the MHC class II molecules encoding disease susceptibility function in a specific immune recognition event. This could involve an antigen "X" that currently eludes characterization or be directed to polymorphic determinants on the MHC molecule itself. The problem of understanding the meaning of the association of susceptibility to rheumatoid arthritis with diverse MHC alleles such as DR4 (Dw4 and Dw14) and DR1 is approached by detailed biochemical analysis that led to the identification of common stretches of amino acid sequence, presumably encoding conformationally equivalent structures. The sequence shared by the otherwise unrelated DR1 and DR4 haplotypes from residue 67 in the DR a chain that appears to confer susceptibility is Leu-X-X-Gln-Arg/Lys. Non-classic MHC polymorphisms related to disease susceptibility but not associated with particular alleles such as identified by Ab109d6 prove especially valuable in suggesting new directions for attempting to understand the significance of these associations. Consideration is given to the possibility that a family of either slightly different or identical conformations encoded in either cis or trans cumulatively confer the liability to develop rheumatoid arthritis. This implies a highly non-classic mode of inheritance. It seems reasonable to consider the pathogenesis of rheumatoid arthritis as evolving from a typical immune response based on a simple immune recognition event directed to a single antigen.

Antigens, Differentiation↗

Metabolic derangements in children requiring parenteral nutrition.

Intravenous alimentation is routinely used in many hospitalized pediatric patients, however, there are few reports of the nature and frequency of metabolic complications. In order to assess the frequency and nature of metabolic complications all children receiving parenteral nutrition from January 1, 1982 to December 31, 1982 were prospectively enrolled in the study. Data collection began with the institution of parenteral nutrition. Serum electrolytes, minerals, liver function tests, and renal function tests were followed weekly. A total of 201 patients received parenteral nutrition for 5378 days. Nutrition was delivered to 146 patients (4980 patient days) via a central line and 55 patients via a peripheral line (398 patient days). The sepsis rate was 3.7% in central lines used only for parenteral and 4.8% in multipurpose central lines. In general, complications were fewer in the patients supported peripherally. In patients supported centrally, hypoalbuminemia was the most commonly found abnormality followed by hypocalcemia, hypophosphatemia and hypomagnesemia, reflecting a malnourished state. One-third of the patients had abnormal liver function tests, and in half of those factors causing liver dysfunction other than parenteral nutrition were present. Abnormal renal function tests occurred in 10% of the patients. Thus, a high incidence of metabolic complications occurred in association with parenteral nutrition. Most were present during the initiation of parenteral nutrition, suggesting an abnormal metabolic state was present prior to the institution of parenteral nutrition. The frequency of low serum albumin and minerals is consistent with previous publications of the prevalence of malnutrition in hospitalized patients.

Adolescent↗