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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 73 records · Page 4Linked to original sources
PubMed1996

The making of a user friendly MAOI diet.

BACKGROUND: Many monoamine oxidase inhibitor (MAOI) diets are considered to be excessively restrictive and founded on poor scientific evidence. We present a safe and practical MAOI diet based on the related clinical and analytic data. METHOD: We used a critical review of the literature and our own tyramine assay results to categorize foods to be restricted absolutely, taken in moderation only, or unrestricted. RESULTS: We recommend that users avoid aged cheese; aged or cured meats (e.g., air-dried sausage); any potentially spoiled meat, poultry, or fish; broad (fava) bean pods; Marmite concentrated yeast extract; sauerkraut; soy sauce and soy bean condiments; and tap beer. Wine and domestic bottled or canned beer are considered safe when consumed in moderation. Other foods not mentioned are considered unrestricted. CONCLUSION: The concerns about perpetuating an overly restrictive MAOI diet include the avoidance by prescribers of a potentially useful treatment option, excessive limitations on lifestyle for patients, and increased risk to patients secondary to noncompliance with the diet. We propose an MAOI diet that has a solid scientific and clinical basis and that is, above all, practical.

Acute Disease↗
PubMed1996

Accelerated progressive systemic sclerosis in a patient with hypothenar hammer syndrome.

We describe the first case of hypothenar hammer syndrome followed by accelerated systemic sclerosis (SSc). A sawmill worker with repeated wrist trauma presented with bilateral digital ischemia and fingertip ulcerations. Hypothenar hammer syndrome involving both hands was diagnosed based on classic angiographic studies showing occlusion of the ulnar arteries at the level of the hamate and occlusions of multiple digital arteries. He also had minimal digital swelling, telangiectatic lesions on the fingers, and a positive FANA test. Resected ulnar arteries showed clearcut changes compatible with both microtrauma and SSc. After surgical repair of both ulnar arteries, he rapidly developed severe SSc with significant cardiopulmonary involvement.

Angiography↗
PubMed1995

The clenched fist syndrome. A psychiatric syndrome mimicking reflex sympathetic dystrophy.

We describe a patient with swelling and pain in his right hand, which persisted for 1 year after minimal trauma. We think this represents a case of "clenched fist syndrome," a conversion disorder with unique somatic features that is easily mistaken for reflex sympathetic dystrophy syndrome. Included is a comparison of other psychological illnesses in which unusual physical findings involve the hand.

Diagnosis, Differential↗
PubMed1995

Effects of stress management on clinical outcomes in rheumatoid arthritis.

OBJECTIVE: To examine the effects of stress-management training on clinical outcomes in persons with rheumatoid arthritis (RA). METHODS: Patients with RA (n = 141) 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 the attention control groups received a 10-week intervention followed by an additional 15-month maintenance phase. RESULTS: The stress management group showed statistically significant improvements on measures of helplessness, self-efficacy, coping, pain, and health status. Selected beneficial effects were still detectable at the 15-month followup evaluation. CONCLUSION: The data indicated that stress management interventions are capable of producing important clinical benefits for persons with RA.

Adaptation, Psychological↗
PubMed1995

Differential effects of CD4+ T cell depletion on inflammatory central nervous system disease, arthritis and sialadenitis in MRL/lpr mice.

Autoimmune MRL/lpr mice were treated for 12-14 weeks with anti-CD4 monoclonal antibody to define the role of CD4+ T cells in the pathogenesis of the inflammatory central nervous system (CNS) lesions, arthritis and sialadenitis characteristic of the strain. Anti-CD4 therapy effectively prevented the development of CNS lesions and arthropathic changes. Marked depletion of CD4+ T cells was documented in the mononuclear cells infiltrating the major salivary glands but the severity of sialadenitis was significantly increased by chronic anti-CD4 immunotherapy. This dissociation between beneficial and harmful effects of anti-CD4 treatment in the MRL/lpr mouse suggests that the net regulatory effect of CD4+ T cells on the underlying autoimmune-mediated inflammatory process may be positive or negative depending on the organ system involved. The pathogenetic mechanisms of inflammation and tissue destruction in this model of systemic autoimmune disease are in some instances target organ-specific.

Animals↗
PubMed1995

Abnormal serum transaminases following therapeutic doses of acetaminophen in the absence of known risk factors.

J.M., a healthy, 25-year-old male, volunteered for a study involving warfarin and acetaminophen. Acetaminophen 1 g four times a day was started for 21 days. Liver function tests taken at regular intervals for the first 12 days were unremarkable. On day 18, however, aspartate aminotransferase (AST) was 527 IU/liter and alanine aminotransferase (ALT) was 166 IU/liter. Acetaminophen was discontinued and serum transaminase levels returned to baseline levels two weeks later (AST = 26, ALT = 20). Analysis of J.M.'s urine samples over the first 18 days showed excretion patterns of glucuronide, sulfate, and glutathione derived cysteine and mercapturic acid conjugates were similar to the other subjects in the study. Acetaminophen causes hepatotoxicity in overdose or malnourished or alcoholic patients, none of which applied to our subject. Differences in metabolic activation and capacity for glutathione synthesis can predispose individuals given therapeutic doses of acetaminophen to adverse effects. Failure to detoxify a highly reactive metabolite, formed by P-450 metabolism, via glutathione conjugation is responsible for the development of acute hepatic necrosis. Accumulation of the toxic metabolite due to depleted glutathione stores may have occurred with prolonged high dosing in our subject and been responsible for his abnormal rise in liver enzymes.

Acetaminophen↗
PubMed1995

Aberrant hormone balance in fetal autoimmune NZB/W mice following prenatal exposure to testosterone excess or the androgen blocker flutamide.

F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive models of the human disease systemic lupus erythematosus. In this study, NZB/W fetuses produced by pregnant NZB mice were compared with F1 C57BL/6 x DBA/2 (C57/DBA2) hybrid fetuses produced by nonautoimmune C57BL/6 females. Dams of both strains were treated with testosterone or the androgen blocker flutamide to alter the hormonal environment in late gestation. Hormonal changes in male fetuses carried by treated dams were of interest because hormonal manipulation using either testosterone or flutamide has been shown to increase longevity in male NZB/W offspring. Testosterone-implanted NZB dams developed the expected elevations in circulating maternal testosterone, whereas C57BL/6 dams treated with either testosterone or flutamide had elevated maternal serum testosterone concentrations. The treatment-induced changes in circulating testosterone in NZB dams and C57BL/6 dams were not reflected in serum from 18-day NZB/W or C57/DBA2 fetuses. Male NZB/W offspring from untreated control NZB dams had unexpectedly high levels of serum estradiol and alpha fetoprotein and relatively low extractable testicular testosterone, compared with nonautoimmune male control fetuses. Maternal testosterone treatments produced a significant decrease in serum estradiol in NZB/W male fetuses, and placental testosterone content was also reduced. Our findings suggest that placental androgen control is regulated differently in the autoimmune NZB-NZB/W vs. the nonautoimmune C57BL/6-C57/DBA2 maternal-placental-fetal unit.

Androgen Antagonists↗
PubMed1995

Relative value of femoral and lumbar bone mineral density assessments in patients with ankylosing spondylitis.

The objective of this study was to examine the relative sensitivity of femoral and lumbar bone mineral density (BMD) measurements in patients with ankylosing spondylitis (AS) and to identify the most appropriate test site for detection of osteopenia in these patients. Fourteen patients with ankylosing spondylitis had femoral and lumbar bone mineral density studies using dual energy x-ray absorptiometry. Significant osteopenia was found in 93% of patients when the femoral hip was examined and in 29% of patients when the lumbar region was examined. Moreover, femoral measurements exhibited greater severity of osteopenia than lumbar measurements when average T and Z scores were compared. Bone loss was most marked at Ward's triangle and the neck of the femur. When the lumbar measurements are insensitive and inappropriate, femoral neck and Ward's triangle measurements provide a more reliable indication of the presence and severity of osteopenia in patients with AS. Interpretation of BMD at the trochanter and intertrochanter, as well as total hip BMD, yielded no additional information in the diagnosis of osteopenia.

Absorptiometry, Photon↗
PubMed1995

Efficacy of bromocriptine in an open label therapeutic trial for systemic lupus erythematosus.

OBJECTIVE: To investigate the efficacy of bromocriptine in suppressing active systemic lupus erythematosus (SLE) in a therapeutic trial. METHODS: We conducted an open label investigation of bromocriptine treatment in 7 patients with active non-life threatening SLE. Patients received bromocriptine daily during the treatment phase of 6 to 9 months and were followed for 5 months after bromocriptine was discontinued. Disease activity was assessed by determination of the SLE activity Measure (SLAM) and the Toronto SLE Disease Activity Index (SLEDAI). Serum prolactin concentrations and a battery of serologic and urine tests were obtained at baseline and at monthly intervals during and after bromocriptine treatment. RESULTS: Serum prolactin concentration was suppressed from (mean +/- SEM) 11.2 ng/ml +/- 1.9 to 3.1 ng/ml +/- 1.7 after 6 months of bromocriptine treatment. The mean pretreatment SLAM score was 11.3 +/- 0.9;6 months of bromocriptine treatment significantly decreased the mean SLAM score to 6.0 +/- 1.6 (p = 0.03 compared to pretreatment measure). The mean SLEDAI score decreased from 16.0 +/- 2.0 to 5.9 +/- 0.8 (p = 0.02) during the same period. Bromocriptine treatment was associated with transient suppression of anti-dsDNA, and serum cholesterol was reduced significantly through the treatment period. After bromocriptine was discontinued, all patients had increased disease activity associated with rising serum prolactin concentrations. CONCLUSION: These findings justify controlled trials to study the efficacy of bromocriptine in treating patients with active SLE.

Adult↗
PubMed1994

Evaluation of memory, learning ability, and clinical neurologic function in pathogen-free mice with systemic lupus erythematosus.

OBJECTIVE: To determine if neurologic impairment is related to progressive autoimmune disease in 3 murine models of systemic lupus erythematosus (SLE): MRL/lpr, NZB, and NZB/WF1. METHODS: Sensorimotor function, learning, and memory were tested within strains at specific ages, before and after the appearance of SLE. These parameters were also compared between strains for young and older lupus mice and their congenic controls with reduced autoimmune disease (MRL/lpr versus MRL/+; NZB versus NZB/xid). RESULTS: Abnormal neurologic features were present at a much higher frequency in MRL/lpr mice than in age-matched MRL/+ control mice, and sensorimotor function deficits were also seen in NZB/WF1 mice. Strains that develop lupus showed deficits on a water-escape, distal cue discrimination task and on a food-rewarded, proximal cue discrimination task, but the cognitive impairments were not global. CONCLUSION: MRL/lpr, NZB, and NZB/WF1 mice differed in terms of which behaviors were impaired as well as when those impairments appeared.

Age Factors↗
PubMed1994

Hyperprolactinemia in male NZB/NZW (B/W) F1 mice: accelerated autoimmune disease with normal circulating testosterone.

It has been proposed that the immunostimulatory hormone, prolactin, is associated with flares of systemic lupus erythematosus (SLE). In autoimmune female NZB/NZW F1 (B/W) mice with accelerated lupus-like disease, hyperprolactinemia accelerated autoimmunity. The current study explored effects of moderate and severe hyperprolactinemia in male B/W mice, which have late-onset SLE. Autoimmune disease in B/W males was assessed by measurement of anti-DNA antibodies (anti-DNA), gp70-anti-gp70 immune complexes (gp70IC), IgM, IgG, and renal function. Serum testosterone concentrations were assayed serially. All mice were necropsied when moribund. Hyperprolactinemic B/W males were characterized by premature appearance of anti-DNA and gp70IC and elevation of IgM and IgG. Hyperprolactinemia accelerated mortality with vasculitis and renal disease compared to control mice. Serum testosterone concentrations were not suppressed. In male B/W mice, chronic hyperprolactinemia stimulated autoimmune disease activity; the deleterious effects of prolactin were not mediated through suppression of the immunoprotective hormone, testosterone. This observation supports the proposed association between elevated prolactin levels and exacerbations of SLE.

Animals↗
PubMed1994

Idiopathic focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus: an unusual combination.

Renal involvement is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Histologic examination of renal tissue using light microscopy, immunofluorescent staining, and electron microscopy permit identification of glomerular immune complex deposits in virtually all patients with SLE. We report a patient who fulfilled four American College of Rheumatology criteria for the classification of SLE whose clinical course was consistent with SLE, yet whose renal failure resulted from focal glomerulosclerosis that was not mediated by immune complexes. The characteristics of this case of focal glomerulosclerosis that differentiate it from healed focal proliferative glomerulonephritis are discussed.

Biopsy↗
PubMed1994

Pharmacokinetic and pharmacodynamic interactions during multiple-dose administration of nisoldipine and propranolol.

OBJECTIVES: The pharmacokinetic and pharmacodynamic interactions after 7 days of oral treatment with nisoldipine (10 mg twice daily) and propranolol (80 mg twice daily) were investigated in a partially randomized, placebo-controlled crossover study of 12 healthy volunteers. METHODS: At the end of each treatment period, pharmacokinetic parameters were measured, along with blood pressure, heart rate, cardiac function, systemic hemodynamics, plasma catecholamines, forearm blood flow, and apparent hepatic blood flow (estimated by the clearance of indocyanine green dye). RESULTS: After 7 days of treatment with nisoldipine and propranolol, neither drug altered the other's bioavailability or elimination parameters, and propranolol did not change the area under the plasma concentration-time curve of nisoldipine's metabolite, N-9425. Nisoldipine alone increased apparent hepatic blood flow and forearm blood flow compared with the other treatment groups but, with the addition of propranolol, both of these parameters were similar to those in the placebo group. Changes in the other hemodynamic parameters were consistent with the known effects of these drugs, and no differences in plasma catecholamine levels were detected. CONCLUSIONS: In contrast to the findings with single-dose treatment, administration of the combination of nisoldipine and propranolol for 7 days is not associated with any measurable kinetic interactions, although significant hemodynamic interactions do occur.

Adult↗
PubMed1994

Primary antiphospholipid antibody syndrome and microscopic polyarteritis in the puerperium: a case report.

The primary antiphospholipid antibody syndrome (PAPS) and systemic lupus erythematosus (SLE) may occur in women of reproductive age, and both syndromes have been reported to exacerbate during periods of hormonal flux such as oral contraceptive administration, pregnancy, or the puerperium. These disorders have features which cause them to resemble other multisystem diseases. PAPS and SLE must be differentiated from preeclampsia with HELLP syndrome and thrombotic thrombocytopenic purpura occurring during pregnancy. These four disorders differ in prognosis and required therapies. We report an instructive case of PAPS in a patient who developed microscopic polyarteritis with significant glomerulonephritis following prostaglandin-induced delivery of a stillborn fetus. We compare the manifestations of PAPs, SLE, HELLP, and thrombocytopenic purpura, and discuss the possible role of hormonal imbalance as a precipitating event.

Adult↗
PubMed1994

Chemotherapy waste reduction through shelf-life extension.

Minimization of total drug expenditures within the health care system, without affecting patient outcome has become a rational goal in today's economic, environment. The objective of this study was to observe the effect of extending the shelf-life for three chemotherapy medications, [doxorubicin, epirubicin and mitoxantrone] on wastage of these medications. Prior to and following the introduction of new, longer, shelf-lives for these three medications, prospective, non-randomized, unblinded four-month chemotherapy wastage audits for all chemotherapy medications were completed at 18 institutional sites within Ontario (six Ontario Cancer Treatment and Research Foundation clinics, ten Ontario hospitals and two preparation sites in a large cancer treatment centre). Data were provided by 18 sites in 1989 but from only 12 sites in 1990. Ten of the 12 sites extended their shelf-lives for each of doxorubicin, epirubicin and mitoxantrone, and on average, waste at these sites was reduced to less than 1% of the 1989 total for epirubicin, less than 15% for doxorubicin and 35% for mitoxantrone. Many sites eliminated waste entirely for these drugs. For sites which did not extend their shelf-lives, the waste remained unchanged. We conclude that appropriate extension of the shelf-life for chemotherapy medications can reduce waste, and is a relatively simple method of reducing expenditures without affecting health outcomes or adding additional complications to IV chemotherapy.

Analysis of Variance↗
PubMed1994

Longstanding hyperprolactinemia associated with systemic lupus erythematosus: possible hormonal stimulation of an autoimmune disease.

OBJECTIVE: To describe 4 women in whom hyperprolactinemia was associated with the development of systemic lupus erythematosus (SLE). METHODS: Clinical assessment and followup (2 cases). Chart review and interviews with the attending rheumatologist (2 cases). Detailed review and reassessment of multiple imaging studies of the pituitary. RESULTS: One patient had idiopathic hyperprolactinemia, and 3 had pituitary microadenomas. Serum 17 beta-estradiol concentrations were normal in all women, but serum testosterone was suppressed in 2. SLE flares occurred in 2 individuals, one and 6 months after bromocriptine therapy was discontinued, and reinstitution of bromocriptine therapy in a patient who refused corticosteroids resulted in resolution of her SLE disease activity. CONCLUSION: Hyperprolactinemia, which has the potential to exacerbate autoimmunity, may coexist with SLE. In these instances, bromocriptine may afford therapeutic benefit.

Adult↗
PubMed1994

Accelerated deaths from systemic lupus erythematosus in NZB x NZW F1 mice treated with the testosterone-blocking drug flutamide.

In the New Zealand black (NZB) x New Zealand white (NZW) (B/W) mouse model of systemic lupus erythematosus (SLE), females die prematurely and males have late onset of disease. It has been proposed that testosterone protects B/W mice from rapidly progressive SLE. The mechanisms of androgenic suppression of the immune system, however, are not understood. We tested the hypothesis that testosterone exerts protective effects in males through classic receptor-mediated actions. Flutamide, a potent and specific androgen receptor blocker, was administered continuously to B/W mice from 6 weeks of age, and the animals were monitored in a longevity study. Our supposition that flutamide treatment would accelerate disease was upheld in female B/W mice. In females, flutamide clearly accelerated mortality and reduced longevity to (median) 30 weeks as compared with 37 weeks in controls (p = 0.003). In male B/W mice, mortality was identical in treated and control animals in the early phase of the study, and deleterious effects of treatment were apparent only after the first year of treatment. Flutamide-treated males had significant elevation of serum testosterone, but their atrophied seminal vesicles strongly suggested that peripheral androgen effects were blocked. Albuminuria, blood urea nitrogen, and anti-DNA antibodies were not altered by flutamide in females or males. The receptor-mediated effects of androgens on murine autoimmune disease were dependent on gender and were noted primarily in females and in males that survived past 1 year of age.

Albuminuria↗