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Biomedical subjects

E A Walker

Publications and source records attributed to E A Walker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Costs of health care use by women HMO members with a history of childhood abuse and neglect.

BACKGROUND: Early childhood maltreatment has been associated with adverse adult health outcomes, but little is known about the magnitude of adult health care use and costs that accompany maltreatment. We examined differences in annual health care use and costs in women with and without histories of childhood sexual, emotional, or physical abuse or neglect. METHODS: A random sample of 1225 women members of a health maintenance organization completed a 22-page questionnaire inquiring into childhood maltreatment experiences as measured by the Childhood Trauma Questionnaire. Health care costs and use data were obtained from the automated cost-accounting system of the health maintenance organization, including total costs, outpatient and primary care costs, and emergency department visits. RESULTS: Women who reported any abuse or neglect had median annual health care costs that were $97 (95% confidence interval, $0.47-$188.26) greater than women who did not report maltreatment. Women who reported sexual abuse had median annual health care costs that were $245 (95% confidence interval, $132.32-$381.93) greater than costs among women who did not report abuse. Women with sexual abuse histories had significantly higher primary care and outpatient costs and more frequent emergency department visits than women without these histories. CONCLUSION: Although the absolute cost differences per year per woman were relatively modest, the large number of women in the population with these experiences suggests that the total costs to society are substantial.

Adolescent↗
PubMed1999

Naltrexone and beta-funaltrexamine antagonism of the antinociceptive and response rate-decreasing effects of morphine, dezocine, and d-propoxyphene.

RATIONALE: Patterns of competitive and insurmountable antagonism provide important data to guide the classification and characterization of different types of opioid agonists as well as infer the mechanism of action for agonists. OBJECTIVE: Experiments with the competitive antagonist, naltrexone, and the insurmountable antagonist, beta-funaltrexamine (beta-FNA), were conducted to determine whether the antinociceptive and rate-decreasing effects of the opioid agonists dezocine and d-propoxyphene are 1) mediated through muu opioid receptors in rats, and 2) differ from morphine with respect to relative efficacy. METHODS: The rat tail-withdrawal assay was used to measure antinociception and a fixed ratio 20 (FR20) schedule of food delivery was used to measure rate suppression. RESULTS: Naltrexone (0.01-1.0 mg/kg) was approximately equipotent as an antagonist of the antinociceptive and rate-decreasing effects of both morphine and dezocine and as an antagonist of the antinociceptive effects of d-propoxyphene. Naltrexone failed to block the rate-decreasing effects of d-propoxyphene. beta-FNA (5 and 10 mg/kg) also antagonized the antinociceptive and rate-decreasing effects of morphine and dezocine as well as the antinociceptive effects of d-propoxyphene. beta-FNA failed to produce a dose-dependent antagonism of the rate-decreasing effects of d-propoxyphene. CONCLUSIONS: These data suggest that the antinociceptive effects of morphine, dezocine, and d-propoxyphene and the rate-decreasing effects of morphine and dezocine are mediated through mu opioid receptors. Overall, high doses of beta-FNA produced a greater degree of antagonism of the behavioral effects of dezocine than morphine or d-propoxyphene, confirming other reports that dezocine is a lower efficacy agonist than morphine. Additionally, the degree of antagonism produced by beta-FNA was greater for the antinociceptive effects of all three compounds than for the rate-decreasing effects.

Animals↗
PubMed1999

Adult health status of women with histories of childhood abuse and neglect.

PURPOSE: Several recent studies have found associations between childhood maltreatment and adverse adult health outcomes. However, methodologic problems with accurate case determination, appropriate sample selection, and predominant focus on sexual abuse have limited the generalizability of these findings. SUBJECTS AND METHODS: We administered a survey to 1,225 women who were randomly selected from the membership of a large, staff model health maintenance organization in Seattle, Washington. We compared women with and without histories of childhood maltreatment experiences with respect to differences in physical health status, functional disability, numbers and types of self-reported health risk behaviors, common physical symptoms, and physician-coded ICD-9 diagnoses. RESULTS: A history of childhood maltreatment was significantly associated with several adverse physical health outcomes. Maltreatment status was associated with perceived poorer overall health (ES = 0.31), greater physical (ES = 0.23) and emotional (ES = 0.37) functional disability, increased numbers of distressing physical symptoms (ES = 0.52), and a greater number of health risk behaviors (ES = 0.34). Women with multiple types of maltreatment showed the greatest health decrements for both self-reported symptoms (r = 0.31) and physician coded diagnoses (r = 0.12). CONCLUSIONS: Women with childhood maltreatment have a wide range of adverse physical health outcomes.

Adult↗
PubMed1999

Discriminative stimulus effects of nalbuphine in nontreated and morphine-treated pigeons.

In the present study, the stimulus effects of the low efficacy agonist nalbuphine were examined under two conditions: nontreated and morphine treated. In the first experiment, five pigeons were trained to discriminate among 3.2 mg/kg morphine, 5.6 mg/kg nalbuphine, and saline. Nalbuphine produced nalbuphine-like responding. Low doses of morphine produced nalbuphine-like responding, whereas high doses produced morphine-like responding. Naltrexone produced saline-like responding and reversed the stimulus effects produced by the training doses of morphine and nalbuphine. Five different pigeons were treated daily with 10 mg/kg morphine (i.m.) and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine and saline. In these pigeons, morphine produced morphine-like responding and nalbuphine produced nalbuphine-like responding. Morphine abstinence produced nalbuphine-like responding that was reversed by morphine. Additionally, naltrexone produced nalbuphine-like responding. These data suggest that the discrimination between morphine and nalbuphine in the nontreated and morphine-treated pigeons may be based on the relative efficacy differences between morphine, a higher efficacy mu-agonist, and nalbuphine a lower efficacy mu-agonist.

Analgesics, Opioid↗
PubMed1999

Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care.

OBJECTIVE: The authors' goal was to determine whether improved outcomes from enhanced acute-phase (3-month) treatment for depression in primary care persisted. METHOD: They conducted a 19-month follow-up assessment of 156 patients with major depression in the Collaborative Care intervention trials, which had found greater improvements in treatment adherence and depressive symptoms at 4 and 7 months for patients given enhanced acute-phase treatment than for patients given routine treatment in a primary care setting. Sixty-three of the 116 patients who completed the follow-up assessment had received enhanced treatment, and 53 had received routine treatment in primary care. The Inventory for Depressive Symptomatology and the Hopkins Symptom Checklist were used to measure depressive symptoms. Automated pharmacy data and self-reports were used to assess adherence to and adequacy of pharmacotherapy. RESULTS: At 19 months, the patients who had received enhanced acute-phase treatment did not differ from those who had received routine primary care treatment in clinical outcomes or quality of pharmacotherapy. CONCLUSIONS: Even though enhanced acute-phase treatment of depression in primary care resulted in better treatment adherence and better clinical outcomes at 4 and 7 months, these improvements failed to persist over the following year. Continued enhancement of depression treatment may be needed to ensure better long-term results.

Adult↗
PubMed1999

Constitutive expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in a transformed human proximal tubule cell line: evidence for direct regulation of vitamin D metabolism by calcium.

Circulating levels of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) are dependent on activity of the renal mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase). Production of 1,25-(OH)2D3 occurs predominantly in the renal proximal tubule, with 1alpha-hydroxylase activity being impaired in renal insufficiency and renal disease. The expression and activity of 1alpha-hydroxylase are tightly regulated in response to serum levels of PTH, calcium, phosphate, and 1,25-(OH)2D3 itself. As a consequence of this, the characterization of 1alpha-hydroxylase in human renal tissue has proved difficult. In this study we have characterized constitutive 1alpha-hydroxylase expression in a simian virus 40-transformed human proximal tubule cell line, HKC-8. Initial analyses of [3H]25-hydroxyvitamin D3 (25OHD3) metabolism in these cells using straight and reverse phase HPLC revealed product peaks that coincided with authentic 1,25-(OH)2D3 as well as 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3). Enzyme kinetic studies indicated that the Km for synthesis of 1,25-(OH)2D3 in HKC-8 cells was 120 nmol/liter 25OHD3, with a maximum velocity of 21 pmol/h/mg protein. This activity was inhibited by treatment with ketoconazole, but not diphenyl phenylenediamine. RT-PCR analysis of RNA from HKC-8 cells revealed a transcript similar in size to that observed in keratinocytes and primary cultures of human proximal tubule cells, and protein was detected by Western blot analysis. Synthesis of 1,25-(OH)2D3 was up regulated by treatment with forskolin (10 micromol/liter, 24 h) and was down-regulated by 1,25-(OH)2D3 (10 nmol/liter, 24 h). 1Alpha-hydroxylase activity in HKC-8 cells was also sensitive to the concentration of calcium. Cells grown in low calcium (0.5 mmol/liter) showed a 4.8-fold induction of 1alpha-hydroxylase, whereas treatment with medium containing high levels of calcium (2 mmol/liter) significantly inhibited 1,25-(OH)2D3 production. These data suggest that direct effects of calcium on proximal tubule cells may be an important feature of the regulation of renal 1,25-(OH)2D3 production.

24,25-Dihydroxyvitamin D 3↗
PubMed1999

Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in the human kidney.

The secosteroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a vital role in calcium metabolism, tissue differentiation, and normal bone growth. Biosynthesis of 1,25(OH)2D3 is catalyzed by the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase). Although activity of this enzyme has been described in several tissues, the kidneys are recognized to be the principal site of 1,25(OH)2D3 production. To date, enzyme activity studies using vitamin D-deficient animals have suggested that 1alpha-hydroxylase is expressed exclusively in proximal convoluted tubules. With the recent cloning of 1alpha-hydroxylase, specific cRNA probes and in-house polyclonal antiserum have been used to determine the distribution of 1alpha-hydroxylase along the human nephron. Immunohistochemistry and in situ hybridization studies indicated strong expression of 1alpha-hydroxylase protein and mRNA in the distal convoluted tubule, the cortical and medullary part of the collecting ducts, and the papillary epithelia. Lower expression was observed along the thick ascending limb of the loop of Henle and Bowman's capsule. Weaker and more variable expression of 1alpha-hydroxylase protein and mRNA was seen in proximal convoluted tubules, and no expression was observed in glomeruli or vascular structures. These data show for the first time the distribution of alpha1-hydroxylase expression in normal human kidney. In contrast to earlier enzyme activity studies conducted in vitamin D-deficient animals, our data indicate that the distal nephron is the predominant site of 1alpha-hydroxylase expression under conditions of vitamin D sufficiency.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1999

The effect of health education on the rate of ophthalmic examinations among African Americans with diabetes mellitus.

OBJECTIVES: This study evaluated a multicomponent educational intervention to increase ophthalmic examination rates among African Americans with diabetes. METHODS: A randomized trial was conducted with 280 African Americans with diabetes, enrolled from outpatient departments of 5 medical centers in the New York City metropolitan area, who had not had a dilated retinal examination within 14 months of randomization (65.7% female, mean age = 54.7 years [SD = 12.8 years]). RESULTS: After site differences were controlled, the odds ratio for receiving a retinal examination associated with the intervention was 4.3 (95% confidence interval = 2.4, 7.8). The examination rate pooled across sites was 54.7% in the intervention group and 27.3% in the control group. CONCLUSIONS: The intervention was associated with a rate of ophthalmic examination double the rate achieved with routine medical care.

Adult↗
PubMed1998

In vivo apparent affinity and efficacy estimates for mu opiates in a rat tail-withdrawal assay.

Experiments in a rat tail-withdrawal assay tested the hypothesis that the magnitude and pattern of antagonism of mu opiate agonists by the insurmountable mu opioid antagonist clocinnamox are inversely related to agonist efficacy. In addition, these experiments examined whether this antagonism could be quantified to yield apparent affinity and efficacy estimates for the pharmacological characterization of five opiate agonists. Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Morphine required a higher dose of clocinnamox for a 50% reduction in maximal antinociceptive effect than did buprenorphine or GPA 1657. In contrast, no dose of clocinnamox tested decreased the %MPE for etonitazene or etorphine. These data suggest a rank order of relative efficacy of etonitazene > or = etorphine > morphine > or = GPA 1657 > or = buprenorphine. Similarly, numerical analysis of these data yielded the following apparent affinity and efficacy estimates: etonitazene (0.38 mg/kg, 128); etorphine (0.68 mg/kg, 125); morphine (50 mg/kg, 38), GPA 1657 (6.6, 39); and buprenorphine (0.042 mg/kg, 2.2). These data illustrate that in vivo affinity and efficacy estimates for a number of agonists are remarkably similar across different methods of analysis and are useful for drug classification.

Algorithms↗
PubMed1998

A randomized, double-blind crossover trial of sertraline in women with chronic pelvic pain.

The efficacy of antidepressants as analgesics for a range of chronic pain problems is well documented. However, a controlled trial of an antidepressant for women with chronic pelvic pain has not yet been published. We randomized 23 women from a general gynecology clinic to either double-blind sertraline or placebo. Measures of psychological function, pain, and functional disability were taken at baseline and 6 weeks. After a 2-week washout, the groups were crossed-over and the same measures were done over the next 6 weeks. There were no significant improvements in pain or functional disability noted on sertraline compared to placebo. Studies involving larger samples of patients are needed to confirm these findings.

1-Naphthylamine↗
PubMed1998

Impact of improved depression treatment in primary care on daily functioning and disability.

BACKGROUND: Few data are available regarding the impact of improved depression treatment on daily functioning and disability. METHODS: In two studies of more intensive depression treatment in primary care, patients initiating antidepressant treatment were randomly assigned to either usual care or to a collaborative management programme including patient education, on-site mental health treatment, adjustment of antidepressant medication, behavioural activation and monitoring of medication adherence. Assessments at baseline as well as 4 and 7 months included several measures of impairment, daily functioning and disability: self-rated overall health, number of bodily pains, number of somatization symptoms, changes in work due to health, reduction in leisure activities due to health, number of disability days and number of restricted activity days. RESULTS: Average data from the 4- and 7-month assessments in both studies, intervention patients reported fewer somatic symptoms (OR 0.68, 95% CI 0.46, 0.99) and more favourable overall health (OR 0.50, 95% CI 0.28, 0.91). While intervention patients fared better on other measures of functional impairment and disability, none of these differences reached statistical significance. CONCLUSIONS: More effective acute-phase depression treatment reduced somatic distress and improved self-rated overall health. The absence of a significant intervention effect on other disability measures may reflect the brief treatment and follow-up period and the influence of other individual and environmental factors on disability.

Absenteeism↗
PubMed1998

Clocinnamox antagonism of the antinociceptive effects of mu opioids in squirrel monkeys.

The opioid agonists morphine, etorphine, buprenorphine and U50,488 were examined alone and in combination with the insurmountable opioid antagonist clocinnamox (C-CAM) in squirrel monkeys responding under a schedule of shock titration. In this procedure, shock intensity increased every 15 sec from 0.01 to 2.0 mA in 30 increments. Five lever presses during any given 15-sec shock period produced a 15-sec timeout, after which shock resumed at the next lower intensity. When given alone, each of these agonists increased the median intensity at which the monkeys maintained shock [median shock level (MSL)]. At the highest dose examined alone, each agonist produced maximal increases in MSL and, except buprenorphine, decreased response rates. C-CAM dose-dependently antagonized the effects of morphine, etorphine and buprenorphine on MSL. In the presence of the higher C-CAM doses, etorphine, morphine and buprenorphine did not produce maximal effects on MSL. The effects of U50,488 were not systematically altered when tested in combination with the highest C-CAM dose. In general, C-CAM was more potent and the duration of antagonism was slightly longer against buprenorphine than against morphine and etorphine. Quantitative analysis of these data according to an extended model of yielded the following apparent affinity and efficacy estimates, respectively: etorphine (0. 085 mg/kg, 117); morphine (49 mg/kg, 24) and buprenorphine (0.62 mg/kg, 7.1). Determination of the individual q values over time indicated that the receptor population recovers more quickly after C-CAM antagonism of etorphine than from C-CAM antagonism of either morphine or buprenorphine. These data suggest that C-CAM functions as a long-lasting antagonist of mu opioid agonist actions in a shock titration procedure and yields estimates of relative intrinsic efficacy with the rank order of etorphine > morphine > buprenorphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Medically unexplained symptoms in primary care.

Fourteen common physical symptoms are responsible for almost half of all primary care visits. Only about 10% to 15% of these symptoms are found to be caused by an organic illness over a 1-year period. Patients with medically unexplained symptoms are frequently frustrating to primary care physicians and utilize medical visits and costs disproportionately. This paper will review the relationship between psychological distress and the decision to seek medical care for common physical symptoms such as fatigue and headache. Evidence will be presented demonstrating that an increasing number of medically unexplained symptoms over a patient's lifetime correlate linearly with the number of anxiety and depressive disorders experienced, the score on the personality dimension of neuroticism, and the degree of functional impairment. Several scales measuring somatization and hypochondriasis are recommended for primary care and medical specialty patients.

Comorbidity↗
PubMed1997

Tolerance and cross-tolerance to morphine-like stimulus effects of mu opioids in rats.

The purpose of these experiments was to examine the relationship of agonist relative efficacy to the pattern of tolerance and cross-tolerance to the morphine-like stimulus effects of three opioid agonists. Rats were trained to discriminate 3.2 mg/kg morphine from saline under fixed-ratio 15 schedule of food reinforcement. Morphine, nalbuphine, and fentanyl produced dose-dependent increases in morphine-like stimulus effects and decreases in response rates. Repeated treatment with 20 mg/kg per day morphine increased the ED50 for stimulus control by fentanyl, morphine, or nalbuphine two-, four-, or 40-fold, respectively. Repeated treatment with 64 mg/kg per day nalbuphine increased the ED50 for stimulus control for morphine by two-fold, but lower or higher treatment doses had no significant effect. Treatment with 100 mg/kg per day nalbuphine increased the ED50 for nalbuphine by six-fold. Repeated treatment with 0.22 mg/kg per day fentanyl increased the ED50 for stimulus control by fentanyl or morphine by approximately two-fold. Comparisons among treatment conditions suggested that magnitude of tolerance to morphine-like stimulus effects did not vary as an inverse function of the relative efficacy of the agonist used for repeated treatment. Rather repeated morphine and fentanyl treatments produced comparable tolerance, whereas repeated nalbuphine treatment did not evoke substantial tolerance. Comparisons within treatment conditions, however, suggested that magnitude of tolerance may vary inversely with relative efficacy of the agonist tested for morphine-like stimulus effects. During treatment with morphine or fentanyl, greater tolerance was observed to the morphine-like stimulus effects of the lower efficacy agonist relative to the higher efficacy agonist.

Analgesics, Opioid↗
PubMed1997

Predictors of physician frustration in the care of patients with rheumatological complaints.

Recent studies of the doctor-patient relationship have shown that certain patients are perceived as frustrating or difficult by their doctors; however, little is known about the characteristics of these patients that elicit this dissatisfaction. As part of a larger study of rheumatology clinic patients with fibromyalgia or rheumatoid arthritis (N = 68) we used stepwise multiple regression to select the factors most associated with physician frustration while controlling for the effects of other variables. Variable domains included demographics, psychiatric diagnoses, personality factors, functional disability, disease state, and trauma history. These domains as well as individual variables within these domains were systematically evaluated for their unique contribution to the prediction of physician frustration as measured by the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ). Initial bivariate correlates of physician frustration included marital status, current dysthymia and agoraphobia, lifetime panic disorder and obsessive-compulsive disorder, adult rape and physical abuse, somatization disorder, physical and social disability, the presence of fibromyalgia, as well as neuroticism, illness impact, and perceived loss of control. The best multivariable model for estimating frustration magnitude included somatization disorder, perception of lack of control over illness, and a lifetime history of obsessive-compulsive disorder. These factors explained 48% of the variance in DDPRQ score. Physicians in this study were most frustrated with patients who had ongoing preoccupation with multiple medically unexplained physical symptoms as well as the perception of greater impact and lack of control over their illness. These findings suggest that treatment of somatization in patients with chronic symptoms may decrease physician frustration.

Adult↗
PubMed1997

Does the study of victimization revictimize the victims?

Although the number of questionnaire surveys examining the sequelae of prior sexual and physical victimization has increased over the last decade, little attention has been given to understanding the impact of such studies on participants. As part of a larger study of long-term effects of prior sexual and physical victimization, 500 randomly selected women in an HMO received a comprehensive questionnaire including multiple symptomatic distress measures and several items inquiring into previous history of sexual, physical, and emotional abuse and neglect. They also completed a short rating scale asking about their reactions to completing the questionnaire. Despite the sensitive content, the women who participated generally found the experience to be a positive one. Only a small number of women were more upset than they had anticipated, but the vast majority felt they would have completed the survey even if they had known in advance how they would feel. The subset of women who did express distress was significantly different from the group that did not, with respect to other measures of symptomatic distress and trauma exposure. These data suggest that surveys that inquire into prior episodes of childhood victimization are generally well tolerated by women who participate, and that, although a small number may be disturbed by these investigations, in general, adverse reactions may be less common than previously anticipated.

Adult↗