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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 37 records · Page 2Linked to original sources

Seropositive rheumatoid arthritis with dermatomyositis sine myositis, angioimmunoblastic lymphadenopathy with dysproteinemia-type T cell lymphoma, and B cell lymphoma of the oropharynx.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare lymphoproliferative disorder that often progresses to high grade T cell lymphoma. We describe a 63-year-old woman with longstanding seropositive rheumatoid arthritis who developed fever, cutaneous findings of dermatomyositis, a diffuse pruritic maculopapular rash, enlarged lymph nodes, polyclonal elevated serum gammaglobulins, and an IgG lambda paraprotein. Lymph node biopsies yielded tissue with characteristic changes of AILD and T cell lymphoma. Interleukin 6 (IL-6) was present during the early, active phase of disease, and circulating IL-6 and IL-2 were detected one month before tumor recurrence. Two years after AILD and T cell lymphoma were diagnosed, she developed a B cell lymphoma that involved the oropharynx.

Arthritis, Rheumatoid↗

Stress management in rheumatoid arthritis: what is the underlying mechanism?

OBJECTIVE: To test whether change in cognitive-behavioral variables (such as self-efficacy, coping strategies, and helplessness) is a mediator in the relation between cognitive behavior therapy and reduced pain and depression in persons with rheumatoid arthritis (RA). METHODS: A sample of patients with RA who completed a stress management training program (n = 47) was compared to a standard care control group (n = 45). A path analysis testing a model including direct effects of comprehensive stress management training on pain and depression and indirect effects via change in cognitive-behavioral variables was conducted. RESULTS: The path coefficients for the indirect effects of stress management training on pain and depression via change in cognitive-behavioral variables were statistically significant, whereas the path coefficients for the direct effects were found not to be statistically significant. CONCLUSION: Decreases in pain and depression following stress management training are due to beneficial changes in the arenas of self-efficacy (the belief that one can perform a specific behavior or task in the future), coping strategies (an individual's confidence in his or her ability to manage pain), and helplessness (perceptions of control regarding arthritis). There is little evidence of additional direct effects of stress management training on pain and depression.

Adaptation, Psychological↗

Tumor promotion resistant cells are deficient in AP-1 DNA binding, JunD DNA binding and JunD expression and form different AP-1-DNA complexes than promotion sensitive cells.

The JB6 cell culture model is used to identify molecular determinants of susceptibility to the promotion of neoplastic transformation. Clonal variants susceptible to transformation ('P+' cells) form numerous anchorage-independent colonies in soft agar upon treatment with the phorbol ester tumor promoter TPA, whereas resistant variants ('P-' cells) do not. We now report that there is significantly less binding of activator protein-1 (AP-1) to its DNA binding site in P- cells than in P+ cells. Gel supershift assays were performed to detect association of all seven AP-1 family members with their DNA binding site in TPA-treated and -untreated P+ and P- cells. Significantly lower DNA binding and protein expression of JunD were detected in P- cells than in P+ cells. c-Jun was detected in P+, but not P-, AP-1-DNA complexes, and c-Fos was detected in P-, but not P+, AP-1-DNA complexes. These and other phenotype-specific differences in abundance and composition of AP-1-DNA complexes may play a role in the resistance of P- cells to tumor promoter-induced transformation.

Base Sequence↗

Air pollution exposure monitoring and estimation. Part II. Model evaluation and population exposure.

The air pollution dispersion model EPISODE has been developed at the Norwegian Institute for Air Research (NILU) over the past several years in order to meet the needs of modern air quality management work in urban areas. The model has recently been used as a basis for exposure calculations of NOx and NO2 in order to assess the effects of different traffic diversion measures on health and well being for the residents in the Vålerenga-Ekeberg-Gamlebyen area in Oslo. Here we describe some results from the most recent evaluations of the model for NOx and NO2 at station Nordahl Brunsgate in Oslo for the period 1 October 1996-19 November 1996. In addition examples of population exposure calculations for Oslo performed during the winter period of 1995-96, are also presented.

Air Movements↗

Air pollution exposure monitoring and estimation. Part IV. Urban exposure in children.

In the winter of 1994, 2300 school-age children in Oslo participated in a panel study of the role of traffic pollution on the exacerbation of diseases of the respiratory system and other symptoms of reduced health and well being in children. The children filled out a diary daily with information for five time points over six weeks. In order to quantify exposure-effect relationships for the symptoms, individual exposure to NO2 and particulate matter (PM2.5) was estimated, using the DINEX method a combination of information from the diary as to the children's whereabouts during the five time points each day, coupled with continuous dispersion modelling. An individual exposure estimate for each time point for each child was defined. Individual exposure estimated using dispersion modelling can be used to examine patterns of exposure such as isolating geographic areas with higher concentrations or describing concentrations of pollution by time of day. The diary allowed the time-use of the children to be described.

Air Pollution↗

Air pollution exposure monitoring and estimation. Part V. Traffic exposure in adults.

In Oslo, traffic has been one of the dominating sources of air pollution in the last decade. In one part of the city where most traffic collects, two tunnels were built. A series of before and after studies was carried out in connection with the tunnels in use. Dispersion models were used as a basis for estimating exposure to nitrogen dioxide and particulate matter in two fractions. Exposure estimates were based on the results of the dispersion model providing estimates of outdoor pollutant concentrations on an hourly basis. The estimates represent concentrations in receptor points and in a square kilometre grid. The estimates were used to assess development of air pollution load in the area, compliance with air quality guidelines, and to provide a basis for quantifying exposure-effect relationships in epidemiological studies. After both tunnels were taken in use, the pollution levels in the study area were lower than when the traffic was on the surface (a drop from 50 to 40 micrograms m-3). Compliance with air quality guidelines and other prescribed values has improved, even if high exposures still exist. The most important residential areas are now much less exposed, while areas around tunnel openings can be in periods exposed to high pollutant concentrations. The daily pattern of exposure shows smaller differences between peak and minimum concentrations than prior to the traffic changes. Exposures at home (in the investigation area) were reduced most, while exposures in other locations than at home showed only a small decrease. Highest hourly exposures are encountered in traffic.

Adult↗

Air pollution exposure monitoring and estimation. Part VI. Ambient exposure of adults in an industrialised region.

This paper presents methodology and results of a dynamic individual air pollution exposure model (DINEX) that calculates the hourly exposure for each adult in a panel study. Each of over 260 participants, through the use of a diary, provided information used in the model to calculate his/her personal, individualised exposure. The participants filled out the diary daily, hour by hour, over two, two month periods. The exposure assessment model coupled the diary information and results of an indoor/outdoor measurement program, with the results of dispersion modelling on an hourly basis for an industrial area in Norway. The estimated air pollution concentrations from the dispersion model, based on continuous meteorological measurements, were calibrated with air pollutant concentrations measured continuously.

Adult↗

Modeling of P-glycoprotein-involved epithelial drug transport in MDCK cells.

P-glycoprotein (P-gp) on the apical membranes of epithelial cells is known as a drug efflux pump. However, unclear is its integral quantitative role in the overall epithelial drug transfer, which also involves distinct diffusion processes in parallel and sequence. We used a simple three-compartment model to obtain kinetic parameters of each drug transfer mechanism, which can quantitatively describe the transport time courses of P-gp substrates, digoxin and vinblastine, across P-gp-expressing MDCK cell monolayers grown on permeable filters. Our results show that the model, which assumes a functionally single drug efflux pump in the apical membrane with diffusion across two membranes and intercellular junctions, is the least complex model with which to quantitatively reproduce the characteristics of the data. Interestingly, the model predicts that the MDCK apical membranes are less diffusion permeable than the basolateral membrane for both drugs and that the distribution volume of vinblastine is 10-fold higher than that of digoxin. Additional experiments verified these model predictions. The modeling approach is feasible to quantitatively describe overall kinetic picture of epithelial drug transport. Further model refinement is necessary to incorporate other modes of drug transport such as transcytosis. Also, whether P-gp solely accounts for the pump function in this model awaits more studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin.

The oral anticoagulant warfarin is clinically administered as a racemic mixture of two enantiomers, (R) and (S). Many relevant drug interactions with warfarin have been attributed to the specific metabolic inhibition of the elimination of the more pharmacologically active (S)-enantiomer. To investigate reports that acetaminophen can potentiate the anticoagulant effect of warfarin, 20 healthy male volunteers were each given single oral 20 mg doses of racemic warfarin on three separate occasions: (1) alone, (2) after 1 day of acetaminophen (4 g/d), and (3) after 2 weeks of acetaminophen (4 g/d). The urinary excretion pattern of acetaminophen and its metabolites was not significantly altered over its course of administration. The (R)- and (S)-enantiomers of warfarin exhibited significantly different pharmacokinetic properties. However, acetaminophen did not alter the disposition of either (R)- or (S)-warfarin. All subjects exhibited a pharmacodynamic response to racemic warfarin. The response was not significantly altered in the presence of acute or chronic acetaminophen dosing, as assessed by prothrombin time and factor VII concentrations.

Acetaminophen↗

Refining the MAOI diet: tyramine content of pizzas and soy products.

BACKGROUND: Continuous refinement of the monoamine oxidase inhibitor (MAOI) diet has resulted in much reduced and simplified recommendations that attempt to balance safety and practicality. In the spirit of evidence-based practice, dietary restrictions should be based on carefully documented case reports and valid tyramine analyses. Residual concerns have focused on combination foods such as pizza and a variety of soy products. We determined the tyramine content of pizzas and a variety of soy products in order to refine dietary recommendations for use with MAOIs. METHOD: High-pressure liquid chromatography analysis of tyramine content was performed on a variety of pizzas, soy sauces, and other soybean products. A tyramine level of 6 mg or less was considered safe. RESULTS: No significant tyramine levels were found in any of the pizzas, including those with double pepperoni and double cheese. Marked variability was found in soy products, including clinically significant tyramine levels in tofu when stored for a week and high tyramine content in one of the soy sauces. CONCLUSION: Pizzas from large chain commercial outlets are safe for consumption with MAOIs. However, caution must be exercised if ordering pizzas from smaller outlets or gourmet pizzas known to contain aged cheeses. All soybean products should be avoided, especially soy sauce and tofu. Individualized counseling and continuous surveillance of compliance are still essential.

Acute Disease↗

Effects of prolactin in stimulating disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a chronic autoimmune illness, is influenced by hormones. High prolactin concentrations were associated with early death from autoimmune renal disease in NZB/NZW mice, an animal model of severe SLE. NZB/NZW mice that delivered and nursed pups and those that underwent pseudopregnancy had changes in serum IgG and autoantibodies. NZB/NZW mice treated with the prolactin-suppressing drug bromocriptine had prolonged lives. Elevated serum prolactin concentrations are reported in SLE patients of both sexes. We found four women with long-standing hyper-prolactinemia who developed SLE. A survey of premenopausal women whose sera were submitted for autoantibody testing showed that 20% with anti-ds-DNA antibodies also had high prolactin levels. Many hyperprolactinemic patients whose sera were referred to an endocrinology laboratory had positive FANA tests (women 33%, men 53%) but did not have SLE. Disease activity was suppressed in six of seven SLE patients treated with bromocriptine. All had elevated disease activity and five became unexpectedly hyperprolactinemic after treatment stopped. Manipulating serum prolactin affords a means of treating clinical SLE activity.

Bromocriptine↗

Stability of reconstituted indomethacin sodium trihydrate in original vials and polypropylene syringes.

The stability of reconstituted indomethacin sodium trihydrate 0.5 mg/mL in sterile water for injection for 14 days at either 2-6 degrees C or room temperature (21-25 degrees C) in the drug's original vial and in polypropylene syringes was studied. Twenty 1-mg vials of indomethacin sodium trihydrate were reconstituted with 2 mL of Sterile Water for Injection, USP. Solution from 10 vials was drawn into 20 1-mL disposable polypropylene syringes. Five vials and 10 syringes were stored at 21-25 degrees C, and the other 5 vials and 10 syringes were stored at 2-6 degrees C. Samples were taken on days 0, 1, 2, 4, 5, 7, 9, 12, and 14 and analyzed by liquid chromatography. Physical inspections and pH determinations were made as well. Throughout the study period, all solutions stored at 2-6 degrees C retained more than 95% of the initial indomethacin concentration. At room temperature, solutions stored in syringes retained more than 95% of the initial indomethacin concentration. Solutions stored in glass vials contained only 89.7% of the initial concentration on day 14. Solutions stored at room temperature in either syringes or vials had greater amounts of degradation products than solutions stored at 2-6 degrees C. Reconstituted indomethacin sodium trihydrate 0.5 mg/mL was stable for 14 days when stored in polypropylene syringes at 2-6 or 21-25 degrees C and in its original glass vials at 2-6 degrees C. When stored in the glass vials at 21-25 degrees C, the reconstituted drug was stable for 12 days.

Anti-Inflammatory Agents, Non-Steroidal↗

Age, depressive symptoms, and rheumatoid arthritis.

OBJECTIVE: To examine the relationship between age and depression in persons with rheumatoid arthritis (RA). METHODS: Two separate outpatient cohorts of persons with RA were studied. In both studies, the Center for Epidemiological Studies Depression Scale was administered to all subjects, and the prevalence of depressive symptoms was determined by age group. In the second study, data on additional measures of disease activity, pain, life stress, and coping were collected for use in multiple linear regression analyses. RESULTS: In both samples, a significant correlation between age and depression was found; younger persons (age < or = 45 years) with RA were significantly more depressed, even after controlling for potentially confounding variables such as sex, marital status, antidepressant medication, arthritis medication, functional class, and disease duration. CONCLUSION: The findings show that younger persons with RA are at higher risk for depressive symptoms than their older counterparts.

Adaptation, Psychological↗

Bone mineral density and biochemical markers of bone metabolism in ankylosing spondylitis.

OBJECTIVE: To determine (1) bone mineral density (BMD) of the axial and appendicular skeleton in men with moderate and severe ankylosing spondylitis (AS), and (2) associations between BMD and bone metabolism variables. METHODS: Nineteen men with AS and 19 healthy male controls were evaluated for osteoporosis by dual energy x-ray absorptiometry in both the hip and the lateral and posterior-anterior (PA) projections of the lumbar spine. Calcium homeostasis was evaluated by measuring minerals, calcitropic hormones, and markers of remodeling. Total testosterone levels were also measured. RESULTS: Osteopenia was noted in both the hip and spine of the subjects with AS. The lateral projection of L3 was a more sensitive indicator of the vertebral BMD compared to the PA projection. Calciuin homeostasis and testosterone levels were normal in subjects with AS. In most subjects, markers of bone formation and resorption were normal. CONCLUSION: BMD of subjects with AS is decreased, in spite of normal calcium homeostasis and bone remodeling indices.

Adult↗

Steady-state pharmacokinetics of propranolol enantiomers in healthy male volunteers.

OBJECTIVE: To describe the steady-state pharmacokinetics of (R)-, (S)- and racemic (rac) propranolol in 15 normotensive, male volunteers in a double-blind, randomized, 3-way, crossover study. METHODS: (R)-propranolol 80 mg, (S)-propranolol 80 mg, or rac-propranolol 160 mg was administered twice daily for 3 days. Multiple blood samples were collected for up to 12 hours on the fourth day to characterize the steady-state pharmacokinetic profile of each enantiomer. RESULTS: (R)-propranolol bound to plasma proteins to a lesser extent than (S)-propranolol when it was administered both as a racemic mixture (15.8% versus 13.0%) and as a pure enantiomer (15.8% versus 12.9%), respectively (p < 0.05). No stereoselective pharmacokinetic differences were observed between total (bound and unbound) and unbound (R)- and (S)-propranolol. The AUC(0-720) of (R)-propranolol was significantly higher when administered as a racemic mixture than when given as a pure enantiomer (p < 0.01), suggesting the disposition of (R)-propranolol may be influenced by (S)-propranolol. CONCLUSION: Stereoselective steady-state pharmacokinetic differences in AUC(0-720) were observed between (R)- and (S)-propranolol.

Adult↗