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D K Miller

Publications and source records attributed to D K Miller.

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

Chronic cadmium exposure attenuates conditioned place preference produced by cocaine and other drugs.

Adult male rats were exposed ad lib for 40 days to 100 ppm dietary cadmium chloride (group cadmium) or an identical diet with no added cadmium (group control). Conditioned place preference (CPP) was conducted in a two-chamber apparatus in which all drugs were paired with the least-preferred side as determined by a pretest. In Experiment 1, animals received 0, 2.5, or 5 mg/kg cocaine HCl (IP) for 4 days and vehicle only for 4 days. Control animals showed a place preference for the drug side at 2.5 and 5 mg/kg, while the cadmium-exposed animals showed a preference at 5 mg/kg only. In Experiment 2, animals received 0, 5, or 10 mg/kg of the D1/D2 dopamine receptor agonist apomorphine HCl (SC) for 4 days and vehicle only for 4 days. Control animals showed a place preference at 5 and 10 mg/kg, while metal-exposed animals showed a preference at 10 mg/kg only. To determine the possible effects of alterations of learning mechanisms by cadmium, a conditioned place aversion (CPA) procedure was employed for Experiment 3. Animals received 0, 10, or 40 mg/kg lithium chloride (IP) for 4 days or vehicle only for 4 days. Control animals showed a significant place aversion at 40 mg/kg, while cadmium-exposed animals did not. These findings are discussed within a framework of possible metal-induced disturbance of neurochemical function and/or associative processing.

Animals↗
PubMed1999

The effects of cadmium contamination on the discriminative stimulus properties of cocaine and related drugs.

Rats were exposed to a diet containing 100 ppm cadmium chloride or a control diet. At 52 days of exposure, rats were trained to discriminate between saline and 5 mg/kg cocaine injections. After acquisition training, successive substitution tests were conducted using cocaine, the indirect dopamine agonist d-amphetamine, the mixed D1-D2 agonist apomorphine, SKF 38393 and SKF 82958 (both preferential D1 agonists), quinpirole (a preferential D2 agonist), GBR 12909 (a dopamine reuptake inhibitor), procaine (a local anesthetic), and morphine (an opiate). The results showed that cadmium-exposed rats were slower to acquire the saline-cocaine discrimination than controls. Moreover, cadmium contamination reduced substitution when apomorphine, SKF 82958, and GBR 12909 were presented during generalization testing. Also, cadmium exposure blocked tolerance to cocaine that was evident in control rats following 14 days of exposure to 60 mg/kg/day cocaine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Reported and measured physical functioning in older inner-city diabetic African Americans.

BACKGROUND: The impact of diabetes on disability and physical functioning in older African Americans and potential causes of the excessive disability associated with diabetes in other studies have been inadequately investigated. METHODS: A population-based survey was performed comparing 116 self-reported diabetic inner-city African Americans aged 70 years and older to 522 nondiabetic persons from the same population. A subsample (n = 168) received a physical examination focused on body habitus, upper and lower body strength, balance, and timed physical performance tasks. Blood tests were obtained from 173 subjects. RESULTS: Diabetic individuals reported worse general health (p = .01), instrumental activities of daily living (p = .02), and modified versions of the Rosow-Breslau scale (p<.001) and the Stanford Health Assessment Questionnaire (p = .002). Diabetic persons also reported more falls (0.59 per person vs. 0.20, p = .019) and injurious falls (12% vs. 6%, p = .025). There were minimal differences in the strength, balance, and timed performance measures (analyzed separately by gender). In multivariable analyses, impairments in visual function and pain and light touch perception appeared to explain some of the association between diabetic status and poor general health, disability, and falls, with lesser contribution from the number of medical problems, number of medications, and glycemic control. CONCLUSIONS: Older inner-city diabetic blacks demonstrated worse general health, excess disability, and more falls compared to controls, although deficits in strength, balance, and timed performance could not be demonstrated. The cause of decreased functional status in diabetic elders deserves additional investigation, focusing especially on sensory function, glycemic control, and contribution from specific medical problems and medications.

Accidental Falls↗
PubMed1999

Activation of apoptosis and its inhibition.

The induction of apoptosis, or controlled cell death, by various stimuli has been shown to activate a cascade of endoproteases, called caspases, that cleave numerous cellular proteins necessary for cellular homeostasis. This review discusses this family of proteases together with a variety of mammalian and viral regulatory proteins that act to control this activation.

Animals↗
PubMed1999

Anorexia of aging, leptin, and the Mini Nutritional Assessment.

In this chapter we have reviewed the evidence for physiological anorexia of aging and stressed that its pathophysiology involves both central and peripheral mechanisms. Early satiation in the older person appears to involve signals predominantly arising in the stomach. The increased feeling of satiety in older persons is mainly related to changes in the central feeding drive, in particular a decrease in the opioid rewarding properties for fatty foods. Increased cytokines, secondary to inflammatory conditions which are common in old age, may further increase the anorexia seen in older persons. Leptin, the fat hormone, is an excellent indicator of fat mass in women, in whom leptin concentrations correlate with the MNA. In men, testosterone inhibits leptin, and the fall in testosterone with age results in an increase in leptin concentrations. In males the MNA is not related to leptin concentrations. Finally, we have examined the interrelation of two nutritional screening indices, MNA and SCALES. The two indices were well correlated and were both predictive of poor basic function. We conclude that the MNA is an excellent predictor of nutritional status. These findings suggest that malnutrition is a major predictor of frailty or the "failure to thrive" syndrome in older persons. Depression is a major cause of poor nutritional status in older persons.

Aged↗
PubMed1999

Serosurvey for selected disease agents in white-tailed deer from Mexico.

Serum samples from 350 white-tailed deer (Odocoileus virginianus texanus) collected in March 1994 from northeastern Mexico were tested for the prevalence of antibody activity against five infectious diseases of ruminants. The prevalence rate was 81% for bluetongue virus (BTV) of all serotypes, 72% for epizootic hemorrhagic disease virus (EHDV), 3% for Borrelia burgdorferi, 69% for Anaplasma marginale, and 0% for Brucella abortus, B. melitensis, and B. ovis. These are diseases that affect domestic ruminants, and deer may act as a reservoir of infection. In addition, if deer are translocated, they may introduce pathogens to formerly disease-free areas. The high seroprevalence of BTV and EHDV cannot be related to the presence of hemorrhagic disease in the deer in this region. This is the first report to indicate the presence of B. burgdorferi infection of deer in Mexico. Despite the high prevalence of A. marginale titers, it is uncertain that deer play a role in the epizootiology of cattle anaplasmosis in the region. Apparently, white-tailed deer are unimportant in the epizootiology of brucellosis of both cattle and goats in northeastern Mexico.

Anaplasma↗
PubMed1999

Diabetes mellitus among ethnic seniors: contrasts with diabetes in whites.

Diabetes mellitus is one of the most common chronic diseases affecting older persons in the United States. It occurs in 18% of persons between 65 and 75 years of age and in as many as 40% of persons over 80 years of age. The prevalence of diabetes mellitus varies considerably by ethnic group and is higher among most minority groups in the United States than among non-Hispanic white persons. Published data also show increased complications and mortality rate from diabetes in the minority groups. In this article, we review the current literature on the prevalence, complications, and mortality-rate effects of diabetes mellitus and the results of interventions in three major minority groups in the United States, namely African Americans, Hispanic Americans, and Native Americans. Recent studies of diabetes mellitus in Mexican seniors also are described. Our review focuses primarily on patients with non-insulin-dependent diabetes mellitus, because by far this is the most prevalent type in older persons.

Aged↗
PubMed1998

Characterization and quantitation of NF-kappaB nuclear translocation induced by interleukin-1 and tumor necrosis factor-alpha. Development and use of a high capacity fluorescence cytometric system.

A new quantitative cytometric technique, termed the ArrayScanTM, is described and used to measure NF-kappaB nuclear translocation induced by interleukin (IL)-1 and tumor necrosis factor-alpha (TNFalpha). The amount of p65 staining is measured in both the nuclei defined by Hoechst 33342 labeling and in the surrounding cytoplasmic area within a preselected number of cells/well in 96-well plates. Using this technique in synchronously activated human chondrocytes or HeLa cells, NF-kappaB was found to move to the nucleus with a half-time of 7-8 min for HeLa and 12-13 min for chondrocytes, a rate in each case about 4-5 min slower than that of Ikappa Balpha degradation. IL-1 receptor antagonist and anti-TypeI IL-1 receptor antiserum on the one hand and anti-TNFalpha and monoclonal anti-TNF receptor 1 antibodies on the other hand could be shown to respectively inhibit IL-1 and TNFalpha stimulation in both cell types. In contrast, a polyclonal anti-TNF receptor 1 antiserum exhibited both a 50% agonism and a 50% antagonism to a TNFalpha stimulation in a dose-dependent fashion, indicating that subtle functional responses to complex agonist and antagonist stimuli could be measured. The effects of different proteasome inhibitors to prevent Ikappa Balpha degradation and subsequent NF-kappaB translocation could also be discriminated; Leu-Leu-Leu aldehyde was only a partial inhibitor with an IC50 of 2 microM, while clastolactacystin beta-lactone was a complete inhibitor with an IC50 of 10 microM. The nonselective kinase inhibitor K252a completely inhibited both IL-1 and TNFalpha stimulation in both cell types with an IC50 of 0.4 microM. This concentration, determined after a 20-min stimulation, was shown to be comparable with that obtained for inhibition of IL-6 production induced by a 100-fold lower IL-1 and TNFalpha concentration measured after 17 h of stimulation. These results suggest that the ArrayScanTM technology provides a rapid, sensitive, quantitative technique for measuring early events in the signal transduction of NF-kappaB.

Biological Transport↗
PubMed1998

Effects of (-)-ephedrine on locomotion, feeding, and nucleus accumbens dopamine in rats.

The intent of the present study was to determine the effects of systemic injections of the sympathomimetic agent ephedrine (EPH) on extracellular dopamine (DA) levels within the rat nucleus accumbens (NAC) and to compare these effects with those of EPH on locomotion and on feeding. In experiment 1, adult male rats were prepared with an indwelling 3 mm microdialysis probe positioned within the NAC. The rats were injected (i.p.) with vehicle, 5, 10, or 20 mg/kg (-)-EPH with dialysates collected every 20 min for 100 min after drug injection. Systemic injections of 5, 10 or 20 mg/kg (-)-EPH significantly enhanced extracellular levels of NAC DA over baseline by 79%, 130%, and 400%. Systemic injection of 20 mg/kg EPH significantly reduced NAC levels of DOPAC and HVA by 37% and 31%. The effects of EPH on brain dopamine activity were stereospecific given that an additional group of rats injected with 20 mg/kg (+)-EPH exhibited smaller changes in NAC DA (< 25%), DOPAC (< 10%), and HVA levels (< 20%) than did rats injected with 20 mg/kg (-)-EPH. In experiment 2, adult male rats were injected (i.p.) with 0, 5, 10, or 20 mg/kg (-)-EPH prior to placement in automated activity chambers. Total distance traveled was significantly increased by 10 and 20 mg/kg (-)-EPH, but not by 5 mg/kg (-)-EPH. In experiment 3, adult male rats were injected (i.p.) with 0, 2.5, 5, or 10 mg/kg (-)-EPH or with 0, 2.5, 5, or 10 mg/kg (+)-EPH prior to a 30-min feeding test. Although each EPH enantiomer decreased feeding, (-)-EPH was more potent in feeding suppression than was (+)-EPH. The present results suggest that EPH may alter locomotion and feeding via an indirect action on brain dopamine activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Repeated administration of ephedrine induces behavioral sensitization in rats.

Systemic injection of the sympathomimetic agent ephedrine (EPH) stimulates locomotion in drug-naive rats, an effect that may be dependent on the enantiomer of EPH employed [(-)-EPH or (+)-EPH]. The present experiments examined the effects of repeated EPH exposure on locomotion in rats to assess whether these treatments result in drug tolerance or sensitization. In experiment 1, adult male rats were injected once daily with 0, 10, 20, or 40 mg/kg (-)-EPH (IP) on each of 11 days. Locomotor activity was assessed for 60 min after drug injection. Acute exposure to (-)-EPH treatment increased locomotion for animals receiving 20 or 40 mg/kg, and this effect was augmented after 11 days of drug administration. A vehicle-only injection was given to all animals on day 12 to determine the influence of environmental cues on sensitization. On day 13, all rats were injected with 10 mg/kg cocaine HCl to assess whether repeated (-)-EPH exposure produced a cross-sensitization to cocaine (10 mg/kg, IP). Only rats treated repeatedly with 40 mg/kg (-)-EPH exhibited increases in cocaine-stimulated locomotion relative to saline-treated rats. In experiment 2, repeated exposure to (+)-EPH, 40 mg/kg, but not 20 mg/kg, increased activity and demonstrated the development of sensitization. Cross-sensitization to cocaine (10 mg/kg, IP) was not evident following treatment with either concentration of (+)-EPH. There was no evidence that contextual events alone played a role in the effects observed here.

Animals↗
PubMed1998

Prevalence and causes of undernutrition in medical outpatients.

PURPOSE: To assess the prevalence, common causes, and frequency of recognition and treatment of undernutrition in older and younger medical outpatients using a cross-sectional survey design with 2-year follow-up of undernourished subjects. PATIENTS AND METHODS: Charts of 1017 adult patients attending a hospital outpatient department were reviewed for the presence of undernutrition, and 85 patients meeting inclusion criteria for undernutrition were evaluated and followed for 2 years. An initial evaluation focused on nutritional, cognitive, and affective status and on nutritional attitudes using two subscales of the EAT-26 eating disorder inventory. After 2 years, initial data plus outpatient records were evaluated by 2 independent reviewers to determine a primary cause of undernutrition and to assess the recognition and treatment of undernutrition by the primary physician. RESULTS: Undernutrition was identified in 46 (11%) and 44 (7%) of older and younger subjects respectively; odds ratio (OR) (95% [confidence interval (CI)]) for older versus younger=1.65 (1.06 to 2.51). The primary cause of undernutrition differed between age groups but was deemed treatable in nearly 90% of all subjects. Undernutrition was recognized in 19 (43%) older subjects and 5 (12%) younger subjects (OR=5.47 [1.87 to 16.0]), and appropriate intervention(s) were instituted in 6 (14%) and 2 (5%) of older and younger subjects, respectively (OR=3.08 [0.668 to 14.21]). Older subjects scored higher on the EAT-26 oral control subscale than did younger subjects (4.7 versus 2.5, P=0.004) but similarly on the EAT-26 dieting subscale (5.2 versus 6.3, P=0.332); these relationships did not change with control for potentially confounding variables. CONCLUSIONS: In this study, undernutrition was relatively common, usually amenable to treatment, but frequently undetected and undertreated in both older and younger medical outpatients. Older undernourished subjects exhibited higher oral control needs than younger persons, which may have implications for the pathophysiology and treatment of their malnutrition. Further improvement in detection and intervention is warranted in both younger and older age groups.

Adult↗
PubMed1998

Predilection for frailty remedial strategies among black and white seniors.

BACKGROUND: Frailty prevention and remedial programs based on exercise, hormone replacement, and vitamin supplementation are becoming available for use with older patients, but success of these programs depends largely on seniors' willingness to participate. METHODS: We evaluated preferences for specific aspects of these programs using a sample of 359 older persons recruited from potential delivery sites. Main effects and subgroup analyses were done. RESULTS: Subjects preferred stretching, chair-based, walking, and dynamic balance exercises over lifting weights, dancing, hormone and vitamin therapy; exercising alone in their own homes over exercising in groups; and vitamins over hormones. Preferences were affected to some extent by sex, race, recruitment site, and functional status. However, subjects' willingness even to consider exercise was rarely as high as the desired levels of participation set forth in Healthy People 2000. CONCLUSIONS: Physicians and public health authorities need to educate older persons about effective methods to prevent or treat frailty.

Accidental Falls↗
PubMed1998

Decreasing hospitalization rates for older home care patients with symptoms of depression.

OBJECTIVE: To target medically ill older home care patients with symptoms of depression in order to reduce their rate of hospitalization. DESIGN: A case-control study. SETTING: A private, nonprofit home care organization, the Visiting Nurse Association of St. Louis. PARTICIPANTS: Home care patients 65 years of age and older with symptoms of depression who were participants of a Total Quality Management (TQM) intervention (n = 81) were compared with an historical control of home care patients 65 years of age and older with symptoms of depression (n = 69). INTERVENTION: Utilization of TQM principles to develop a plan including: (a) an educational seminar on depression for home care staff involved in the project; (b) letters to physicians introducing the TQM project; (c) use of the Geriatric Depression Scale (GDS) for screening; (d) recommendation to the primary physician of a home social service (SS) consultation for patients with a GDS of 10 to 14; (e) recommendation to the primary physician of three interventions for patients with a GDS > or = 15: home SS consultation + mental health (MH), or gerontological nurse (GN) consultation + antidepressant medication (a pharmacotherapeutic algorithm sent by facsimile to the primary physician upon request). OUTCOME MEASURES: Hospitalization rates of the control group compared with the TQM intervention group, the degree to which part (e) of the plan was implemented, and the effect this had on hospitalization rates. RESULTS: The TQM intervention patients had a higher mean age than the historical control patients but were not different in percent female, percent white race, percent with a caregiver in the home, functional status, and in 15 of 16 diagnostic categories. Overall, the TQM intervention group had a hospitalization rate of 23.5% (19/81) compared with a rate of 40.6% (28/69) for the historical control group (P = .024). For part (e) of the plan (56/81 patients had a GDS > or = 15), 29/56 (52%) received the recommended SS consultation, 50/56 (89%) received the recommended MH or GN consultation, and 32/56 (57%) received antidepressant medication. One type of intervention did not seem to lower hospitalization rates more than another although having received the MH or GN visits approached significance (12/50, 24%; P = .052) when compared with the control group. CONCLUSIONS: Utilization of TQM principles and the development of an intervention such as the one described here can decrease hospitalization rates for medically ill older home care patients with symptoms of depression.

Aged↗
PubMed1998

The effect of aging on bone mineral metabolism and bone mass in Native American women.

OBJECTIVE: To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women. DESIGN: A cross-sectional study. SETTING: The Sac and Fox Nation in rural Oklahoma MEASUREMENTS: Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry. PARTICIPANTS: A total of 77 Native American women aged 19 to 85 years. RESULTS: Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P < .05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P < .001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P < .001). BMD was lower (P < .001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (r > or = -0.48, P < .001) and body mass index (BMI) (r > or = 0.41, P < .005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P < .05) and femoral (r = .41, P < .01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P < .05) in premenopausal Native American women, and lower (P < 0.05) in postmenopausal subjects, compared with white women. CONCLUSIONS: In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

Adult↗
PubMed1997

IL-1 beta-converting enzyme (ICE) is present and functional in human alveolar macrophages: macrophage IL-1 beta release limitation is ICE independent.

Tissue macrophages readily produce intracellular pro-IL-1beta in response to stimuli such as LPS, but are limited in mature IL-1beta release compared with blood monocytes. The mechanism of this IL-1beta control may provide important insights into the physiology of IL-1beta at the tissue level. Since it has been hypothesized that IL-1beta processing by the IL-1beta-converting enzyme (ICE) regulates IL-1beta release, we compared human alveolar macrophages and human blood monocytes for relative ICE expression and activation. Using immunoblots and enzyme-linked immunoassay for ICE, we demonstrate that alveolar macrophages do not differ from blood monocytes in antigenic p45 ICE. Furthermore, an indirect assay for functional ICE documents similar ICE activities in both monocytes and alveolar macrophages, i.e., similar concentrations of soluble synthetic ICE inhibitor (IC50 values of 0.3 +/- 0.01 and 0.6 +/- 0.2 microM, respectively) are required to block mature IL-1beta generation. However, as has been reported for THP-1 myelomonocytic cells, neither alveolar macrophages nor blood monocytes contain directly quantifiable levels of functional ICE forms (p22/p20 and p10) when assayed by immunoblots or by a sensitive capture ELISA that uses an irreversible, biotinylated ICE inhibitor. These findings document that the macrophage limitation in mature IL-1beta release is not due to a lack of ICE or to an inability to activate ICE. Finally, using a staged release assay, the time to half-maximum mature IL-1beta release is significantly depressed in macrophages compared with that in monocytes. Taken together, these findings suggest that macrophage IL-1beta export is regulated independently of ICE activation.

Adenosine Triphosphate↗
PubMed1997

Chronic cadmium exposure attenuates the conditioned reinforcing properties of morphine and fentanyl.

Adult male rats were exposed ad libitum for 40 days to 100 ppm cadmium chloride through their diet, or an identical diet with no added cadmium. Conditioned place preference (CPP) was conducted in a 2-chamber apparatus in which all drugs were paired with the least-preferred side as determined on a pre-test. In Experiment 1. control and cadmium-exposed rats received 0, 0.6, 1.25, 2.5, or 5 mg/kg morphine sulfate (i.p.) for 4 days, and vehicle only for 4 days. Control animals showed a preference for the drug-paired side at 1.25, 2.5, and 5 mg/kg while the cadmium-exposed rats showed a preference at 5 mg/kg only. In Experiment 2, rats were implanted with cannulae into the lateral ventricles and 0, 2, 5 micrograms morphine sulfate was administered intracerebroventricularly (i.c.v.). An attenuation by cadmium again was observed, as control animals showed a place preference at 2 and 5 micrograms and cadmium-exposed animals showed preference at 5 micrograms only. In Experiment 3, increasing doses of the mu-opioid receptor agonist fentanyl (0, 0.0004, 0.004, and 0.04 mg/kg) were systemically administered (s.c.) and rats tested for CPP. While cadmium animals showed place preference only at 0.04 mg/kg, control animals showed preference at 0.0004, 0.004, and 0.04 mg/kg. These findings are discussed within the framework of metal-induced disturbance of neurochemical function and/or associative processing, and the implications that such disturbances may have for drug seeking and taking.

Animals↗