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PubMed2003

Post menopausal hormone replacement therapy and risk of acute myocardial infarction--a case control study of women in the East Midlands, UK.

AIMS: To examine the relationship between hormone replacement therapy (HRT) and acute myocardial infarction (AMI) adjusting for coronary risk factors and social and behavioural confounders that might indicate a healthy user effect and could account for the discrepancy between randomized and observational studies of HRT use. METHODS: A case-control study of 864 women aged between 35-65 suffering an AMI with two age matched community controls from the same geographical area. Information was collected by interview and from general practitioner records. Conditional logistic regression was used to calculate odds ratios (OR) adjusted for diabetes, hypertension, smoking, alcohol, social class, family history and a health conscious behaviour score. RESULTS: HRT use was recorded for 34% of non-fatal AMI cases and 39% of controls with the adjusted OR for ever-use of HRT versus never-use being 0.74 (95% CI 0.55-0.99). The pattern of risk of AMI was similar for oestrogen only and combined HRT. During the first 12 months of HRT use there was a small increase in risk of AMI with the adjusted OR being 1.14 (0.72-1.80). HRT use for 13-60 months was associated with a small reduction in AMI risk (adjusted OR 0.85, 0.55-1.29). Only HRT used for >60 months was associated with a substantial risk reduction (adjusted OR 0.42, 0.24-0.73). Data for deceased cases and controls showed a similar pattern. CONCLUSIONS: HRT use whether as oestrogen only or combined hormones was only associated with a significant reduction in risk when used for greater than 60 months. These findings could reflect a dual effect of HRT on AMI risk by prothrombotic and anti-atherogenic mechanisms. Neither oestrogen only or combined HRT can be recommended for prevention of coronary artery disease.

Adult↗
PubMed2003

Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe.

OBJECTIVE: To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. METHODS: Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. RESULTS: The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7%, respectively. HIV-infected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96, 95% confidence interval (CI): 2.42-6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74, 95% CI: 1.34-16.78) and preterm delivery (OR = 4.10, 95% CI: 2.17-7.75), respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09, 95% CI: 6.50-15.65; HIV: OR = 3.16, 95% CI: 1.80-5.54) and very low birth weight (malaria: OR = 5.04, 95% CI: 1.00-25.43; HIV: OR = 10.74, 95% CI: 2.12-54.41), low Apgar score (malaria: OR = 4.45, 95% CI: 1.42-13.94; HIV: OR = 5.94, 95% CI: 1.66-21.30), and fetal growth restriction (malaria: OR = 3.98, 95% CI: 2.51-6.30; HIV: OR = 4.07, 95% CI: 2.40-6.92). Dual infection with malaria and HIV was associated with increased risk of maternal, perinatal, and early infant death. CONCLUSIONS: Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist.

Abortion, Spontaneous↗
PubMed1999

HAV and HEV infection in hospitalised hepatitis patients in Alexandria, Egypt.

A total of 202 serum and stool samples from acute hepatitis patients attending the Fever Hospital of Alexandria, Egypt, have been studied to reveal markers of hepatitis virus infection. Anti-HAV IgM were detected in 21 out of 202 sera (10.4%), whereas 201 sera (99.5%) had anti-HAV IgG. The first age attack was in the class-age 0-9 years with 64.7% of anti-HAV IgM positive sera. Among 202 patients, anti-hepatitis E IgG (sample/over cut off > 1.0) was identified in 90 patients (44.5%). The anti-HEV seropositivity ranged from 17.6% to 60.0% in the different age groups, with the highest level in the class-age 20 29 years. Anti-hepatitis E IgM were identified in 49 patients with the first age attack in the class-age 10-19 years (39.4%). HAV RNA was identified by nested PCR in 7 samples out of 15, whereas HEV RNA was present in 4 out of 75 stool samples. Direct DNA sequence of the latter PCR products confirmed the presence of the HEV genome; comparison of the sequences of the isolates from Egypt with those in data banks revealed the highest homology to the Burma strain. Our data confirm that HAV and HEV are common causes of acute sporadic hepatitis in Alexandria but with different peak age positivity. Occasionally, but not infrequently, dual infections (HAV-HEV and HEV-enteric viruses) were also found. The risk analysis indicates that patients living in rural areas are exposed to a higher risk of hepatitis E infection compared to the urban population, whereas the presence of anti-HEV IgG was significantly associated with consumption of common village water and use of indoor dry pit and oral therapy for schistosomiasis.

Adolescent↗
PubMed2002

Visual-vestibular interactions in postural control during the execution of a dynamic task.

The purpose of this experiment was to determine the interaction between visual and vestibular information during the transition from quiet standing to the completion of a forward step. Six subjects were asked to take one step forward at the sound of an audio tone, with their eyes open or closed, and terminate the step in a standing position. During stimulation trials, galvanic vestibular stimulation (GVS) was delivered 1500 ms before the auditory cue. GVS was delivered at an intensity three-fold that of each subject's quiet stance threshold with either stimulus right, left or no stimulation. Force data were collected from three forceplates for the calculation of centre of pressure (CoP), and kinematic data were used to calculate centre of mass (CoM) and body trajectories. In quiet stance all subjects responded to the GVS perturbation by demonstrating upper body segment roll and whole body sway towards the anode electrode. Unexpectedly, in the presence of vision during quiet stance, the upper body roll response was not attenuated, even though the CoP sway patterns were reduced when vision was available. During the initiation phase of the step, despite ongoing GVS stimulation, there were no significant effects seen in CoM, CoP or upper body roll responses. During step execution, however, both CoM displacement and upper body roll demonstrated significant effects and both responses were significantly reduced when subjects' eyes were open. Analysis of the medio-lateral CoP integrals also indicated a strong stimulation effect between conditions late in the execution phase, which were largely attenuated with vision. The results suggest that the importance of visual and vestibular information varies depending on the phase of the task. In addition, the different integration between visual and vestibular input during quiet standing suggests a dual role for vestibular information. We propose that vestibular information in quiet standing has a role in maintaining whole body postural stability, as well as playing an integral role in the alignment of the body segments in preparation for proper movement execution. Vision was demonstrated to differentially attenuate these responses based on the phase of the task. Thus, visual and vestibular information appear to be integrated differently across the different phases of a forward-stepping task.

Acoustic Stimulation↗
PubMed2001

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis.

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline (Pyr), deoxy-pyridinoline (DPyr) and N-telopeptide of type 1 collagen (NTX) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGFbeta2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX) as well as bone resorptive cytokines (IL-11,TGFbeta2). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis.

Adult↗
PubMed2000

Synkinetic blepharoclonus.

OBJECTIVES: To analyze the clinical data and test results collected in a group of patients exhibiting eyelid-closure blepharoclonus (BLC) on clinical neurologic examination. MATERIALS AND METHODS: Thirty-five patients were referred for neurologic evaluation for reasons other than BLC. Clinical electrophysiologic evaluations, including cranial nerve testing and electromyograms, were done according to standards. All patients had neuroimaging studies, including brain magnetic resonance imaging and head computerized tomography, or both, and many had electroencephalograms. Additional tests were done based on the patient's symptoms or reasons for referral. RESULTS: Eight patients had reflex BLC. Two cases were precipitated by vertical gaze; one of these patients had hereditary palmoplantar keratoderma and cataplexy, and the other patient had Ehlers-Danlos syndrome and familial BLC. Other precipitants included speech in four cases, postural changes in two cases, and light stimulation in one case. Two patients had generalized myoclonus independent of their BLC, two patients had a history of sleep myoclonus, and several patients had BLC-associated facial myoclonus. One patient had BLC-associated myoclonus of the right shoulder. Synkinetic cranial movements were detected in 11 patients (four oculofacial, three oculopterygoid, one oculolingual, two dual cases, and one case of imitation synkinesis.) Three patients had familial BLC, seven patients had congenital developmental disorders, six patients had synkinetic tremors, and six patients had restless feet. Some indication of peripheral neuropathy was evident in eight patients. CONCLUSIONS: Eyelid-closure BLC is an underrecognized, sporadic or familial, mostly benign, chronic eyelid-movement disorder that may be associated with tremors, myoclonus, cranial synkinesis, and restless feet. Reflex mechanisms may be identified in some patients. Gaze-induced BLC seems to have the greatest clinical relevance. In the current series, there were no examples of posttraumatic BLC, multiple sclerosis, hydrocephalus, or blepharospasm conditions previously reported to be associated with BLC. No electroencephalographic abnormalities were recorded during BLC, ruling out eyelid-closure epilepsy.

Adolescent↗
PubMed2006

Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis approach.

BACKGROUND: Schizophrenia is a debilitating chronic mental illness. However, the annual prevalence of schizophrenia is not well understood because of under-representation of schizophrenia patients in epidemiological surveys. This study used multiple administrative claims databases to estimate the annual prevalence of diagnosed schizophrenia in the USA. METHOD: The annual prevalence of diagnosed schizophrenia in the USA was estimated for different health insurance coverage groups. The prevalence for privately insured individuals was calculated from an administrative claims database of approximately 3 million privately insured beneficiaries covering the period 1999-2003. The prevalence for Medicaid enrollees was calculated from California Medicaid claims covering the period 2000-2002. The prevalence for Medicare and Medicaid/Medicare dual eligibles was estimated using a combination of both databases. Published statistics were used to estimate the prevalence of schizophrenia in the uninsured and veteran populations and to weight the prevalence rates obtained to the population of the USA. RESULTS: The 12-month prevalence of diagnosed schizophrenia in the USA in 2002 was estimated at 5.1 per 1000 lives. The Medicaid population was identified with the highest prevalence rate among the populations studied. Sensitivity analyses taking into consideration the Veterans Affairs population only changed the estimate slightly to 5.3 per 1000 lives. CONCLUSION: Analyses of administrative claims data contribute to the understanding of the prevalence of diagnosed schizophrenia.

Adolescent↗
PubMed2000

The 5HT(1B) receptor agonist, CP-93129, inhibits [(3)H]-GABA release from rat globus pallidus slices and reverses akinesia following intrapallidal injection in the reserpine-treated rat.

This study examined whether activation of 5HT(1B) receptors in the rodent globus pallidus (GP) could reduce GABA release in vitro and reverse reserpine-induced akinesia in vivo. Microdissected slices of GP from male Sprague Dawley rats (300-350 g) were preloaded with [(3)H]-GABA. During subsequent superfusion, 4 min fractions were collected for analysis of release. The effects of the 5HT(1B) receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3, 2-b]pyrid-5-one (CP-93129), on 25 mM KCl-evoked release were examined using a standard dual stimulation paradigm. Male Sprague Dawley rats (270 - 290 g), stereotaxically cannulated above the GP, were rendered akinetic by injection of reserpine (5 mg kg(-1) s.c.). Eighteen hours later, the rotational behaviour induced by unilateral injection of CP-93129 was examined. CP-93129 (0.6-16.2 microM) produced a concentration-dependent inhibition of 25 mM KCl-evoked [(3)H]-GABA release reaching a maximum inhibition of 52.5+/-4.5%. The effect of a submaximal concentration of CP-93129 (5.4 microM) was fully inhibited by the 5HT(1B) receptor antagonist, isamoltane (10 microM). Following intrapallidal injection, CP-93129 (30-330 nmol in 0.5 microl) produced a dose-dependent increase in net contraversive rotations reaching a maximum of 197+/-32 rotations in 240 min at 330 nmol. Pre-treatment with isamoltane (10 nmol in 1 microl) inhibited the effects of a submaximal dose of CP-93129 (220 nmol) by 84+/-6%. These data suggest that at least some 5HT(1B) receptor function as heteroreceptors in the GP, reducing the release of GABA. Moreover, CP-93129-mediated activation of these receptors in the GP provides relief of akinesia in the reserpine-treated rat model of PD.

Animals↗
PubMed2005

Inhaled beclomethasone dipropionate acutely stimulates dose-dependent growth hormone secretion in healthy subjects.

STUDY OBJECTIVES: It is well known that systemic administration of corticosteroids has a dual effect on growth hormone (GH) secretion in man: acute systemic administration stimulates GH release, whereas chronic administration consistently blocks it. In this study, we evaluate whether administration of inhaled corticosteroids could acutely stimulate GH secretion, and whether this effect could be dose related. DESIGN: Double-blind, placebo-controlled, crossover study. PARTICIPANTS: Eight normal male volunteers all recruited at our institution. INTERVENTIONS: Administration of increasing doses of inhaled beclomethasone dipropionate (BDP; range, 50 to 1,500 mug) or placebo. MEASUREMENTS AND RESULTS: Blood samples for GH determinations were collected at - 15, 0, 60, 120, 180, 240, 300, and 360 min in relation to BDP or placebo administration. The results of this study show a peak GH secretion at 240 min after the administration of BDP at doses > 100 microg. The comparisons among the peaks obtained with increasing doses showed a dose-response effect on GH secretion, starting from 100 to 1,000 microg. BDP 1,500 microg did not induce a peak significantly different from that obtained with 1,000 microg. When we calculated the GH response to BDP as an area under the curve (micrograms per liter x 6 h), the data confirmed that GH secretion was elicited in a dose-related manner. CONCLUSIONS: Our data show that inhaled BDP at dose > 100 microg acutely stimulates GH secretion in a strictly dose-dependent manner. We propose this test as a surrogate for systemic absorption and as a valuable test to compare systemic effects among different inhaled steroids.

Administration, Inhalation↗
PubMed1992

Characteristics and distribution of nuclear medicine physicians.

OBJECTIVES: The authors examined the characteristics and distribution of physicians certified by The American Board of Nuclear Medicine (ABNM). METHODS: Three thousand seven hundred twenty-nine physicians were certified by the ABNM by 1989, and information on 3,389 physicians was obtained for this study from available databases. RESULTS: The age distribution shows 24% (793) of patients were 60 years of age or older; 17% (560) were 55 to 59 years of age; and 21% (714) were 50 to 54 years of age. The average rate of physicians certified by the ABNM was 67.8 annually over the most recent 5 years. Those physicians with additional board certification in radiology, internal medicine, and pathology also were examined. The radiology/nuclear medicine group demonstrated the largest change, with 56.7% having dual certification in the initial 6 years of the ABNM and only 26.4% in the most recent 6 years. The ratio of state population to the number of certified nuclear medicine physicians within the state was found to vary from 30,000:1 in the District of Columbia to 370,000:1 in New Hampshire. CONCLUSIONS: There will be a decline, and possibly a shortage, of comprehensively trained nuclear medicine physicians over the next 10 to 20 years. There is also a decreasing trend of American Board of Radiology (ABR) certification associated with ABNM certification. In addition, there is an uneven distribution of ABNM-certified physicians.

Age Factors↗
PubMed1999

Reliability and validity of body composition measures in female athletes.

The purpose of this investigation was to determine the reliability and validity of bioelectrical impedance (BIA) and near-infrared interactance (NIR) for estimating body composition in female athletes. Dual-energy X-ray absorptiometry was used as the criterion measure for fat-free mass (FFM). Studies were performed in 132 athletes [age = 20.4 +/- 1.5 (SD) yr]. Intraclass reliabilities (repeat and single trial) were 0.987-0.997 for BIA (resistance and reactance) and 0.957-0.980 for NIR (optical densities). Validity of BIA and NIR was assessed by double cross-validation. Because correlations were high (r = 0.969-0.983) and prediction errors low, a single equation was developed by using all 132 subjects for both BIA and NIR. Also, an equation was developed for all subjects by using height and weight only. Results from dual-energy X-ray absorptiometry analysis showed FFM = 49.5 +/- 6.0 kg, which corresponded to %body fat (%BF) of 20.4 +/- 3.1%. BIA predicted FFM at 49.4 +/- 5.9 kg (r = 0.981, SEE = 1.1), and NIR prediction was 49. 5 +/- 5.8 kg (r = 0.975, SEE = 1.2). Height and weight alone predicted FFM at 49.4 +/- 5.7 kg (r = 0.961, SEE = 1.6). When converted to %BF, prediction errors were approximately 1.8% for BIA and NIR and 2.9% for height and weight. Results showed BIA and NIR to be extremely reliable and valid techniques for estimating body composition in college-age female athletes.

Absorptiometry, Photon↗
PubMedDate not supplied

Transient puffs of trace organic emissions from a batch-fed waste propellant incinerator.

Emissions data have been obtained from a waste propellant incinerator. The incinerator is a dual fixed hearth, controlled air incinerator equipped with acid gas and particulate scrubbing. "Puffing" has been evident in this waste propellant incinerator by spikes in the CO concentration. Transient puffs of organics may travel down the combustion chambers and lead to stack emissions. The major conclusions from this study are that (1) transient puffs are formed due to the semi-batch feed nature of the combustion process (causing a local oxygen deficiency) and high water content of the desensitized propellant; (2) in batch-fed combustors, puffs can contribute to most of the organic emissions (which are relatively low) measured with US EPA sampling and analytical methods; (3) it is estimated that batch-fed combustion contributes up to 7-18 times more emissions than steady-state combustion will generate; (4) by applying dispersion analyses to determine the amount of oxygen deficiency in the flame zone, the combustion zone concentration of CO during batch-fed operation could be as high as 160,000 ppm, compared to a measured peak stack concentration of 1200 ppm CO; and (5) an organic sample is collected and averaged over at least a 2-h period that smooths out the transient peaks of organics emissions during batch-fed operation. For emissions that are associated with long-term potential health impacts, this is an appropriate sampling method. However, if a compound has a short-term potential health impact, it may be important to measure the time-resolved emissions of the compound.

Journal Article↗
PubMed2003

Part one: Restoring patients to health outcomes and indicators of advanced nursing practice in adult critical care.

The key characteristics of advanced nursing practice have been a subject of international debate over the past decade. To address this debate, a grounded theory study was undertaken by one of the authors which sought to identify the key characteristics of advanced nursing practice in adult critical care. The outcome of the main study was a theory of legitimate influence in which enhancing patient stay and improving patient outcome represented the dual purpose of advanced nursing practice in critical care. Fundamental to these factors is strategic activity. This encompasses improving patient care, facilitating continuity of care and engaging in patient education. The outcome of these strategic activities can be evaluated through evidence of eased transition across complex hospital networks, patient satisfaction and enabling of independence. The findings reflect a change in the focus and delivery of care to the critically ill and their relatives by nurses practising at an advanced level. In the second paper of this series, the intervening conditions that affect the expression of legitimate influence will be discussed.

Adult↗
PubMed2005

A dynamical analysis of tennis: concepts and data.

This research reported here draws on self-organization theories and dynamical system models to investigate the collective behaviour of tennis players. In tennis, the unceasing to-and-fro displacements of a player about a "home" reference position, located in the middle of the baseline, are akin to those of an oscillator, and the reciprocal attending of both players establishes an informational linkage. Thus, theoretically, the displacement of the two players can be analysed as a system formed by two coupled non-linear oscillators. In such a system, relative phase has been shown to be an adept measure of the temporal synchronization between the oscillators. We hypothesized that relative phase is a relevant collective variable to characterize the relative motion of tennis players. Four players were videotaped and their displacements analysed. The results revealed just two stable patterns of synchronization, in-phase and anti-phase, as the players moved in the same or opposite directions, respectively. Moreover, relative phase showed two types of evolution within trials: either it remained stable at in-phase or anti-phase, or it exhibited transitions between these two modes. In accordance with our hypothesis, the results identified relative phase as a pertinent collective variable to represent both invariance and change in the relative displacements of tennis players. Such a finding opens new avenues for investigating dual sports.

Biomechanical Phenomena↗
PubMed2003

Combination treatment of PKD utilizing dual inhibition of EGF-receptor activity and ligand bioavailability.

BACKGROUND: We have previously demonstrated an essential role for increased epidermal growth factor receptor (EGFR) activity in mediating renal cyst formation and biliary ductal ectasia (BDE) in murine models of autosomal-recessive polycystic kidney disease (ARPKD) such as the BPK mouse. The current study was designed to determine (1). if treatment with a second-generation inhibitor of EGFR tyrosine kinase activity, EKB-569, was effective in treatment of ARPKD; (2). if tyrosine kinase inhibitor therapy used in combination with pharmacologic reduction of the availability of transforming growth factor-alpha (TGF-alpha), using WTACE2, could provide improved therapeutic efficacy and/or decrease potential toxicity; and (3). if effectiveness of treatment could be monitored noninvasively in murine ARPKD models by use of serial ultrasonography. METHODS: BPK litters were treated with EKB-569 by intraperitoneal injection from postnatal day 7 to postnatal day 21. EKB-569's effectiveness alone or in combination with WTACE2 was measured by reduction in kidney weight/body weight ratios, morphometric renal cystic index, and evaluation of renal function. Renal ultrasound was performed on normal and cystic animals, under different therapeutic regimens, utilizing a 15 mHz linear array transducer, and ultrasound data were compared with histology and renal functional data. RESULTS: Treatment of BPK mice with EKB-569 alone resulted in a marked reduction of kidney weight/body weight ratios, dramatically reduced collecting tubule cystic index, as well as BDE, and improved renal function. The combined treatment with EKB-569 and WTACE2 permitted a 67% reduction in EKB-569 dosage necessary to achieve results equivalent to those produced with EKB-569 alone. Untreated cystic animals died of renal failure, on average, at postnatal day 24 with a collecting tubule cystic index of 4.8, significant BDE, and maximal urine osmolarity of 361 mOsm. Cystic animals treated with EKB-569 and WTACE2 to postnatal day 21 were alive and well with normal renal function, a reduced collecting tubule cystic index of 1.7 (P < 0.02), improvement in BDE, and a threefold increase in maximum urinary concentrating ability (P < 0.01). Renal ultrasound could reliably detect cystic kidneys as early as postnatal day 7 and the natural history as well as effects of therapeutic intervention were clearly delineated by ultrasound evaluation. CONCLUSION: This study demonstrates that in murine ARPKD (1). EKB-569 is as effective as first-generation EGFR tyrosine kinase inhibitors in reducing cyst formation and preserving renal function; (2). combination therapy with EKB-569 and WTACE2 provides maximum efficacy in improving renal and biliary abnormalities, at lower doses, thereby minimizing potential toxicity; and (3). renal ultrasound provides a simple, reliable, noninvasive method of following natural history and effect of treatment regimens.

Aminoquinolines↗
PubMed2005

Species differences in the elimination of a peroxisome proliferator-activated receptor agonist highlighted by oxidative metabolism of its acyl glucuronide.

A species difference was observed in the excretion pathway of 2-[[5,7-dipropyl-3-(trifluoromethyl)-1,2-benzisoxazol-6-yl]oxy]-2-methylpropanoic acid (MRL-C), an alpha-weighted dual peroxisome proliferator-activated receptor alpha/gamma agonist. After intravenous or oral administration of [14C]MRL-C to rats and dogs, radioactivity was excreted mainly into the bile as the acyl glucuronide metabolite of the parent compound. In contrast, when [14C]MRL-C was administered to monkeys, radioactivity was excreted into both the bile and the urine as the acyl glucuronide metabolite, together with several oxidative metabolites and their ether or acyl glucuronides. Incubations in hepatocytes from rats, dogs, monkeys, and humans showed the formation of the acyl glucuronide of the parent compound as the major metabolite in all species. The acyl glucuronide and several hydroxylated products, some which were glucuronidated at the carboxylic acid moiety, were observed in incubations of MRL-C with NADPH- and uridine 5'-diphosphoglucuronic acid-fortified liver microsomes. However, metabolism was more extensive in the monkey microsomes than in those from the other species. When the acyl glucuronide metabolite of MRL-C was incubated with NADPH-fortified liver microsomes, in the presence of saccharo-1,4-lactone, it underwent extensive oxidative metabolism in the monkey but considerably less in the rat, dog, and human liver microsomes. Collectively, these data suggested that the oxidative metabolism of the acyl glucuronide might have contributed to the observed in vivo species differences in the metabolism and excretion of MRL-C.

Animals↗
PubMed2001

Dual Tobacco use among Native American adults in southeastern North Carolina.

OBJECTIVE: While patterns of smokeless tobacco (ST) use and cigarette smoking are well documented, the epidemiology of simultaneous use of both tobacco products is less well studied, particularly among Native American populations. This study examines correlates of dual tobacco use among Lumbee Indian adults in southeastern North Carolina. METHODS: A telephone survey among 400 adult Lumbee Indians in Pembroke, North Carolina, collected information on demographics, current tobacco use, amounts of tobacco used, and tobacco related attitudes. RESULTS: Total of 241 (60.3%) individuals did not currently use tobacco, 104 (26%) currently smoked, 74 (18.5%) currently used ST, and 19 (4.8%) used both products. Thus, 19 of 104 (18.3%) current smokers and 19 of 74 (25.7%) current ST users reported dual tobacco use. Compared to exclusive users of either tobacco product, dual tobacco users were intermediate in age and frequency of church attendance, had lower levels of education, and were the highest proportion of subjects reporting no friends and few close relatives. There was no difference by gender or marital status by tobacco use categories. While exclusive cigarette smokers reported smoking more cigarettes per day than dual tobacco users, overall, dual tobacco users had higher estimated daily nicotine exposure levels. Logistic regression analysis showed that younger age and infrequent church attendance predicted exclusive cigarette smoking, while older age and less education predicted exclusive ST use. Dual tobacco use was predicted only by less education. CONCLUSIONS: Simultaneous use of ST and cigarettes is comparatively more common among Lumbee Indian adults than the general population and has an epidemiology distinct from either exclusive cigarette smoking or ST use. These data are the first to explore social support as well as tobacco-related attitudes among dual tobacco users in a Native American population. Recognition of these patterns of dual tobacco use would be important in any future tobacco intervention among Lumbee Indian adults.

Adult↗
PubMed2006

American Indian adolescents in substance abuse treatment: diagnostic status.

The goal of this study was to describe the prevalence of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) psychiatric disorders among a sample of American Indian (AI) adolescents in residential substance abuse treatment. Data on 89 AI adolescents admitted to a tribally operated residential substance abuse treatment program were collected. Participants reported using a mean of 5.26 substances; 20% percent met DSM-IV criteria for four or more substance use disorders. Marijuana abuse/dependence was the most common substance use disorder (84.3%). Eighty-two percent met criteria for at least one DSM-IV nonsubstance use disorder, the most common of which was conduct disorder (74.2%). These results suggest strong diagnostic parallels between these AI adolescents and their non-AI counterparts who have participated in similar studies, including the considerable diagnostic complexity that was common among the participants in this study. These diagnostic patterns suggest that emerging practices for treating substance-abusing adolescents that have been developed for use with non-AI adolescents warrant consideration for use with AI youths.

Adolescent↗