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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 19 recordsLinked to original sources
PubMed2002

Calcium apatite crystals in synovial fluid rice bodies.

BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice bodies containing apatite clumps and examine their clinical pictures. METHODS: All synovial fluid analysis reports for 10 years were reviewed for rice bodies and eight patients were reported on. A series of patients with a variety of diseases with synovial fluid rice bodies found to contain calcific material is described. All were examined by compensated polarised light and alizarin red stain, and four were examined by electron microscopy. RESULTS: The eight patients all had alizarin red S chunks embedded throughout the rice body. Transmission electron microscopy disclosed the presence of a matrix of collagen, fibrin, and amorphous materials containing typical apatite crystals. Clinical diagnoses, radiographic findings, and leucocyte counts varied, but six of the eight patients had had previous repeated corticosteroid injections into the joints. CONCLUSION: Aggregates of apatites may be more common than previously recognised in rice bodies as they are not routinely sought. Whether they are a result of joint damage or depot steroid injections and whether that might contribute to further joint injury now needs to be investigated.

Anthraquinones↗
PubMed2001

Effects of stress management on pain behavior in rheumatoid arthritis.

OBJECTIVE: To examine the effects of stress management training on pain behavior exhibited by persons with rheumatoid arthritis (RA) and the relationship of change in pain behavior with certain patient characteristics as well as change in self-reported levels of pain. METHODS: Patients with RA (n = 131) were randomly assigned to 1 of 3 groups: a stress management group, an attention control group, or a standard care control group. The stress management and attention control groups received a 10-week intervention followed by a 15-month maintenance phase. RESULTS: The 3 groups did not differ significantly in the change in pain behavior at any of the assessment periods. However, persons with RA who had less disease activity tended to exhibit positive changes in pain behavior over time. Changes in self-reported pain were not significantly related to changes in pain behavior. CONCLUSION: The results indicate that stress management interventions do not reduce total pain behaviors exhibited by persons with RA. Changes in pain behaviors appear to be related to disease activity, age, and disease duration, but not to changes in self-reported measures of pain.

Arthritis, Rheumatoid↗
PubMed2001

Care of the dying: setting standards for symptom control in the last 48 hours of life.

The hospice model of care of the dying patient is regarded as a model of excellence; however, outcomes of this care have been poorly demonstrated. Integrated Care Pathways (ICPs) provide a method of recording and measuring outcomes of care. The ICP document replaces all previous documentation and is a multiprofessional record of patient care. The aim of this study was to implement an ICP in an inpatient hospice setting in order to set standards of care for symptom control in the dying phase of a patient's life. ICPs were analyzed from 168 inpatients who died over a one-year period. Symptoms of pain, agitation, and respiratory tract secretions (RTS) were monitored every four hours by nursing staff as either present or absent. For each symptom, 80% of patients had one episode or complete control of the symptom, 10% had two episodes, and 10% had three episodes or more recorded. As death neared, there was a statistically significant increase in the number of patients whose pain was controlled. The ICP has provided a means to measure symptom control in the dying patient and set standards of care, which is integrated into clinical practice.

Adult↗
PubMed2001

Treatment of systemic lupus erythematosus with bromocriptine.

Prolactin, a lactogenic hormone, is a cytokine and an important link between the immune and endocrine systems. Prolactin stimulated disease in autoimmune NZB/NZW mice. Treatment of the mice with the prolactin-lowering dopamine agonist, bromocriptine, suppressed anti-DNA and prolonged life spans. These findings have been applied to humans with systemic lupus erythematosus (SLE). An open-label study, a double blind study, and a study comparing bromocriptine to hydroxychloroquine provided evidence that bromocriptine therapy reduced flares and suppressed disease activity in SLE.

Animals↗
PubMed2001

Bromocriptine treatment of systemic lupus erythematosus.

Prolactin, a peptide hormone, acts as a cytokine. It has been hypothesized that bromocriptine, a dopamine analog that suppresses pituitary secretion of prolactin, suppresses circulating prolactin and, through this mechanism, has the potential to suppress autoimmune disease. This rationale has been applied to the treatment of systemic lupus erythematosus (SLE), a prototype autoimmune illness that occurs spontaneously in animal models such as the F1 hybrid NZBxNZW mouse, and in humans. Treatment with bromocriptine was effective in treating some induced and spontaneous autoimmune disease in experimental models. Bromocriptine did slow the course of SLE in NZBxNZW mice when treatment was started before the appearance of clinical disease. In addition, bromocriptine was effective in treating established disease in this model. In three separate clinical trials, bromocriptine showed evidence that it had a therapeutic effect in treating human lupus. Bromocriptine is currently considered an unproven therapy for SLE. Its use is entirely experimental. The fact that bromocriptine was effective in treating NZBxNZW mice, the beneficial therapeutic effects in human trials, and the low toxicity of the drug form a solid rationale for undertaking further therapeutic trials.

Animals↗
PubMed2001

Modulation of hormones in the treatment of lupus.

The etiologic enigma of systemic lupus erythematosus (SLE) has so far precluded a fully integrated approach to understanding and managing the disease. As new findings continue to uncover relationships between the endocrine system and the besieged immune system in lupus patients, however, researchers have an opportunity to rethink the direction of their investigative efforts. A successful approach to development of long-awaited new treatments may well include modulation of specific hormones. The peptide hormone prolactin may be associated with SLE disease activity. The dopamine agonist bromocriptine, which inhibits pituitary secretion of prolactin, has been shown in a variety of small animal and human trials to reduce disease activity in SLE. Continued research may show that it can be an attractive alternative or adjacent therapy in cases where hydroxychloroquine is contraindicated.

Animals↗
PubMed2001

False positive elevation of cardiac troponin I in seropositive rheumatoid arthritis.

Cardiac troponin I is a sensitive and specific biochemical marker for the diagnosis of acute myocardial injury. We describe a patient with seropositive rheumatoid arthritis (RA) in whom troponin I, measured with a microparticle enzyme immunoassay, was elevated falsely in the absence of acute myocardial infarction. Apparent elevation of troponin I concentration should be evaluated with care in patients with seropositive RA.

Aged↗
PubMed2000

Determination of hypericin and pseudohypericin in pharmaceutical preparations by liquid chromatography with fluorescence detection.

The quantification of the naphthodianthrones, hypericin and pseudohypericin, to which most St. John's wort pharmaceutical preparations are standardized, can be accomplished with a high degree of specificity and sensitivity with LC-fluorescence. Extraction into ethanol is rapid and recovers more than 95% of both pseudohypericin and hypericin following 1 h of sonication. This LC-fluorescence method can separate and detect both pseudohypericin and hypericin in the presence of other constituents in Hypericum perforatum with a greater degree of specificity than LC-UV at either 236 nm or 592 nm and may even be more specific than LC-MS if only the molecular ion is monitored. LC-fluorescence is also more sensitive than LC-UV at either 236 nm or 592 nm. The LC-fluorescence method can quantify on-column amounts of hypericin and pseudohypericin as low as 0.18 ng with less than 5% deviation from known and method replication error (reproducibility) less than 5.5%. Hypericin and pseudohypericin can be accurately and reproducibly quantified from capsules, tablets and tinctures of St. John's wort.

Anthracenes↗
PubMed2000

Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases.

PRL is capable of influencing immune responses and is a cytokine in all likelihood. Circulating PRL is elevated in a number of autoimmune diseases, and about 20% of SLE patients are hyperprolactinemic. The serum PRL concentration often does not reflect disease activity in SLE. The PRL-suppressing drug bromocriptine has been reported to benefit small numbers of patients with reactive arthritis and inflammatory eye disease, and bromocriptine may be beneficial in treating SLE. In NZB/NZW mice, bromocriptine was beneficial and prolonged life. Bromocriptine therapy favorably modified disease in human SLE. In a preliminary open-label study, SLE patients treated with bromocriptine for 6 months had significant improvement in disease activity. These responses were corroborated by masted therapeutic studies. Daily treatment with low-dose bromocriptine prevented lupus flares, and bromocriptine was as effective as hydroxychloroquine in treating active nonorgan-threatening disease. The reports of the efficacy of bromocriptine treatment of SLE are encouraging. Additional studies may confirm the findings reported in this review and may lead to further use of hormonal modification to treat lupus and other autoimmune diseases. For the present, it is important to understand that treatment with dopamine agonists such as bromocriptine is experimental and best confined to therapeutic trials. In the experience of the authors, bromocriptine should not be relied on to treat severe life-threatening autoimmune disease. If bromocriptine is used to treat SLE and is then discontinued, the patient should be observed carefully for rebound hyperprolactinemia and the development of a lupus flare. GnRH is produced by lymphocytes and exerts immunomodulatory actions. Thus, GnRH resembles a cytokine. GnRH can be shown to exert gender-restricted immune actions in vitro and in vivo. The authors' preliminary observations are consistent with the possibility that gender-related differences in expression of the GnRH receptor or in GnRH signal transducers may contribute to gender-related differences in immune responsiveness to GnRH. These differences in G proteins may contribute to the gender-related differences in immunity and expression of autoimmune disease.

Animals↗
PubMed2000

Air pollution exposure monitoring and estimation VII. Estimation of population exposure in a central European airshed.

In order to clarify the local variation in exposure and source-receptor relationships, a dispersion model for estimating air pollution concentrations was developed for a polluted area in the Czech Republic. Three models characterized by different spatial resolution were integrated into one modelling tool. A regional-scale dispersion model accounted for pollution contribution from sources outside the modelling area. Local- and urban-scale dispersion models were used to calculate local concentration distributions. Calculated concentration distributions were evaluated. Deviations between observed and calculated concentrations were not correlated in space, except in episodes, and concentrations measured at spatially representative stations were assimilated into the model results using statistical interpolation (simple kriging). The results indicated that centralized heating plants and local home heating were the most important sources for sulfur dioxide (SO2) pollution. Both high and low level sources may contribute to the accumulation of pollution concentrations in episodes. The measured concentrations were important for the description of distributions in episodes characterized by complex wind and dispersion conditions. The applicability of source oriented model calculations to correctly represent measured concentrations in the pollution episodes was limited due to the fact that meteorological conditions representative of high concentration episodes were characterized by very low wind speed and variable wind directions. About 8,000 individuals were given an exposure estimate representing contribution from local emissions, based on the estimated hourly outdoor exposure to SO2 at their home/work addresses in the 3 month study period in the autumn of 1991. The results showed that, for 5% of participants, the maximum hourly contribution of local emissions was over 380 microg m(-3). For the 3 month average, both large-scale and local-scale pollution contribute significantly. For primary compounds, such as SO2, steep gradients are observed in the vicinity of strong local sources. These gradients are important for exposure characteristics and health effect quantification, and often will not be captured by an existing monitoring network. The calculations can be extended to other periods or to different compounds.

Adolescent↗
PubMed2000

Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method.

The CYP3A4 enzyme contributes to the disposition of more than 60 therapeutically important drugs and displays marked person-to-person variability of the catalytic function. However, the extent of genetic contribution to variability in CYP3A4 activity remains elusive. Recently, we showed that a comparison of between- (SDb2) and within-person (SDW2) variances provides an estimate of the genetic component of variability in drug disposition. The aim of the present analysis was to assess the genetic control of CYP3A4 activity in vivo. A computerized literature search was conducted covering 1966 to September 1999 to identify studies reporting repeated administration of CYP3A4 substrates. The genetic contribution (rGC) to disposition of each CYP3A4 substrate was obtained by the formula (SDb2-SDW2)/SDb2. The rGC values approaching 1.0, point to overwhelming genetic control, whereas those close to zero suggest that environmental factors dominate. A total of 16 studies with 10 different CYP3A4 substrates were identified (n = 161 subjects). The rGC for hepatic CYP3A4 activity as measured by midazolam plasma clearance or the erythromycin breath test was 0.96 (0.92-0.98) (95% Cl) and 0.89 (0.65-0.98), respectively (P < 0.05). The point estimates of rGC for composite (hepatic + intestinal) CYP3A4 activity measured after oral administration of cyclosporine, ethinylestradiol, ethylmorphine, nifedipine and nitrendipine, ranged from 0.66-0.98 (median: 0.83) (P < 0.05). Cyclosporine data suggested a higher genetic control of CYP3A4 at night than during the day. These data indicate that further molecular genetic investigations are warranted to identify genetic variants at CYP3A4 or elsewhere in the genome which contribute to regulation of CYP3A4 activity.

Adolescent↗
PubMed2000

Mood states and disease activity in patients with systemic lupus erythematosus treated with bromocriptine.

We tested mood states in patients with systemic lupus erythematosus (SLE) treated with the prolactin-lowering drug, bromocriptine. Bromocriptine was given to seven patients in an open-label study to test its effects on active SLE. Two independent measures of SLE activity, the SLE Activity Measure (SLAM) and the SLE Disease Activity Index (SLEDAI), were scored and the Symptom Questionnaire (SQ) mood survey was administered at entry and at 6 monthly follow-up visits. The SLAM and SLEDAI scores improved significantly during treatment. Two of the four mood scales in the SQ (Anxiety Scale and Anger-Hostility Scale) showed significant improvement compared to the entry value at least once during treatment. Significant improvement was also observed in the Total Distress Score, which is the sum of the four scales and is a more sensitive measure of distress than the score of an individual scale. Depression, anxiety, somatic complaints, and total distress correlated positively with SLAM and/or SLEDAI scores. The Anxiety Scale and the Total Distress Score improved with treatment and did correlate positively with SLE activity. In contrast, the Anger-Hostility Scale improved with treatment but did not correlate with SLE activity.

Affect↗
PubMed2000

Immunization with a bacterial ATP-binding cassette transporter fragment suppresses autoimmunity and prolongs survival in MRL/lpr lupus-prone mice.

The present study was undertaken to better define the role of the U1 70 kDa antigen in a spontaneous murine model of systemic lupus erythematosus (SLE) by testing whether immunization with the U1 70 kDa polypeptide could alter the production of antibodies against U1 70 kDa or against other small nuclear ribonucleoproteins (snRNP), modify disease expression or alter survival. We found that, while immunization with a U1 70 kDa derived fusion protein (70 KFP) tended to delay the development of anti-snRNP antibodies in the sera of MRL/lpr mice, it had no effect on autoimmune-mediated renal disease or survival. Unexpectedly, it was found that MRL/lpr mice immunized with a 367 amino acid fragment of a bacterial ATP-binding cassette transporter, MFP, had prolonged survival compared to saline injection or U1 70 kDa immunization and that this was associated with a delay in the onset of SLE-like proliferative glomerulonephritis. This is the first study, to our knowledge, in which a bacterial ATP-binding cassette transporter was shown to be beneficial in treating a murine model of SLE. We report that MFP significantly prolonged longevity in the MRL/lpr murine model of SLE compared to saline injection or 70 KFP immunization and that improved survival was associated with a delay in the onset of SLE-like glomerulonephritis.

Albuminuria↗
PubMed2000

Neuropsychological deficit profiles in systemic lupus erythematosus.

Although neuropsychological deficits have been reported in several cognitive domains in patients with systemic lupus erythematosus (SLE), there is considerable variability in the literature about which neuropsychological domains are most affected. Similar to studies that demonstrated that specific profiles of neuropsychological deficits exist for those with traumatic brain injury (TBI; Johnstone, Hexum, & Ashkanazi, 1995), this study examined whether a specific pattern of deficits is present in SLE. By comparing reading scores (as estimates of premorbid ability) to tests of concurrent cognitive abilities (i.e., memory, attention, etc.), it was determined that SLE presents a profile distinct from TBI, with the most significant impairments noted in expressive language (Zdiff = -1.39), attention (Zdiff = -0.41), and speed of processing (Zdiff = -0.40). In contrast to TBI, no impairment was noted in intelligence, memory, or cognitive flexibility. Results suggest that memory problems reported by individuals with SLE may be related to inattention. Clinical implications are discussed.

Adult↗
PubMed2000

The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats.

In operant conditioning experiments, two methods are commonly used to motivate laboratory rats to perform designated tasks. The first is restricting food so that rats are forced to lose 20% of body weight within one week, followed by maintenance at 80% of the baseline weight for the remainder of the experiment. The second is restricting access to water to 15 min in each 24 h period. These methods are effective in motivating the animals. There is, however, little information available on the effects on performance in tests of behaviour that are not related to operant conditioning. In addition, it is not clear if these commonly used methods of food and water restriction will lead to physiological stress as indicated by an elevation of serum corticosterone. Male rats were either food-restricted to reduce and maintain their weight at 80% of baseline weight, or were restricted to 15 min access to water every 24 h. Activity in the open field was significantly greater in food-restricted rats than in water-restricted or control rats, but freezing behaviour was similar in all experimental groups. Food-restricted rats had a higher mean serum corticosterone level than water-restricted and control rats 37 days after the start of the experimental period. These data suggested that chronically restricting food and maintenance of body weight at 80% of baseline body weight led to significant behavioural changes and physiological stress. In contrast, water restriction did not lead to changes in behaviour or corticosterone levels. A second experiment was conducted to compare the effects of food restriction to 80% of baseline body weight, as described above, with a less stringent protocol in which test rats were initially reduced to 80% of baseline weight, but were then maintained at 80% of an ad libitum fed control rat's weight. Serum corticosterone levels and adrenal gland weights were measured after the initial week of forced weight loss and after maintenance for 21 days. Forced loss of 20% of body weight in the first week led to significantly increased serum corticosterone levels and adrenal gland weights compared to ad libitum fed controls. Serum corticosterone levels and adrenal gland weights in rats maintained at 80% of their initial body weight for 21 days remained higher than ad libitum fed control rats. However, rats maintained at 80% of an ad libitum fed control rat's weight did not differ from control rats in serum corticosterone levels or adrenal gland weights at the end of the 21-day study period. Adjustment of the feeding regimen in this manner eliminated physiological evidence of chronic stress.

Adrenal Glands↗