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PubMed2002

Facilitating children's understanding of misinterpretation: explanatory efforts and improvements in perspective taking.

The authors investigated children's understanding of how mistaken beliefs can arise through misinterpretation of ambiguous information. Children (N = 91), aged 4 to 5 years, were given pre- and posttests on their ability to infer a puppet's interpretation of a restricted-view drawing after the puppet had been led to an erroneous expectation about the drawing's identity. Before the posttest, the children received either self-explanation training or other-explanation training in which they explained the source of their own or a puppet's misinterpretations of drawings; a control group received no training. The children who received training improved from pre- to posttest, and those who had practiced explaining misinterpretations by referring to previously viewed pictures or to features of a target picture showed the greatest improvement. These results indicate that learning to explain misinterpretations can help children recognize situations in which misinterpretations are likely to occur.

Child, Preschool↗
PubMed2006

Assessment of the quality of interaction in distance learning programmes utilizing the Internet or interactive television: perceptions of students and lecturers.

WebCT, a web-based virtual learning environment (VLE) and Interactive TV (ITV) are relatively new technologies that are used to deliver distance education at the Faculty of Health Sciences, Stellenbosch University. This study explores how effective current approaches to instructional design and interaction have been in utilizing these two technologies to support interaction and what lessons can be learnt. Five focus-group interviews were held with students and lecturers to assess the perceived quality of student-lecturer/student-student interactions. All students were invited to complete a questionnaire at the end of every module to assess their perceptions of interaction. Interaction was highly valued by students and lecturers participating in distance-learning programmes utilizing either VLE or ITV. Students rated courses using both technologies as moderately interactive. Significant differences between VLE and ITV were detected in student-lecturer and student-student interactions, use of additional modes of communication, instructional design, technological interactivity and social rapport activities. The groups did not differ across a number of likely barriers to interaction and both also reported the need for more flexible and better paced instructional designs.

Adult↗
PubMed2006

Nature-inspired indolyl-2-azabicyclo[2.2.2]oct-7-ene derivatives as promising agents for the attenuation of withdrawal symptoms: synthesis of 20-desethyl-20-hydroxymethyl-11-demethoxyibogaine.

Microwave assisted Diels-Alder cycloaddition of 5-Br-N-benzylpyridinone (2) with methyl acrylate is described to gain an easy access to 7-bromo-2-benzyl-3-oxo-2-aza-5 or 6-carbomethoxy bicyclo[2.2.2]oct-7-enes (3)-(6). The preparation of the ibogaine analogue 20-desethyl-(20-endo)-hydroxymethyl-11-demethoxyibogaine (17) is described by stereoselective hydrogenation of the C(7)-C(8) double bond. Biological evaluation showed an interesting in vitro binding profile toward dopamine transporter, serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl 7-indolyl-2-aza-bicyclo[2.2.2]oct-2-ene (14). The simplification of the ibogaine structure appears as a promising approach toward the design of compounds that could reduce the withdrawal symptoms.

Animals↗
PubMed2006

Influence of high-carbohydrate mixed meals with different glycemic indexes on substrate utilization during subsequent exercise in women.

BACKGROUND: Few data exist on the metabolic responses to mixed meals with different glycemic indexes and their effects on substrate metabolism during exercise in women. OBJECTIVE: We examined the effects of preexercise mixed meals providing carbohydrates with high (HGI) or low glycemic index (LGI) on substrate utilization during rest and exercise in women. DESIGN: Eight healthy, active, eumenorrheic women [aged 18.6 +/- 0.9 y; body mass: 59.9 +/- 7.1 kg; maximal oxygen uptake (VO(2)max): 48.7 +/- 1.1 mL . kg(-1) . min(-1)] completed 2 trials. On each occasion, subjects were provided with a test breakfast 3 h before performing a 60-min run at 65% VO(2)max on a motorized treadmill. Both breakfasts provided 2 g carbohydrate/kg body mass and were isoenergetic. The calculated GIs of the meals were 78 (HGI) and 44 (LGI). RESULTS: Peak plasma glucose and serum insulin concentrations were greater after the HGI breakfast than after the LGI breakfast (P < 0.05). No significant differences in substrate oxidation were reported throughout the postprandial period. During exercise, the estimated rate of fat oxidation was greater in the LGI trial than in the HGI trial (P < 0.05). Similarly, plasma free fatty acid and glycerol concentrations were higher throughout exercise in the LGI trial (P < 0.05). No significant differences in plasma glucose or serum insulin were observed during exercise. CONCLUSION: Altering the GI of the carbohydrate within a meal significantly changes the postprandial hyperglycemic and hyperinsulinemic responses in women. A LGI preexercise meal resulted in a higher rate of fat oxidation during exercise than did an HGI meal.

Adipose Tissue↗
PubMed1995

Identification and quantitation of ibogaine and an o-demethylated metabolite in brain and biological fluids using gas chromatography-mass spectrometry.

This report describes a sensitive method for quantitating ibogaine and a single major metabolite in biological fluids and brain tissue. We identified the metabolite as 12-hydroxy-ibogamine (12-OH-ibogamine or noribogaine) by full-scan, electron-impact gas chromatography-mass spectrometry (GC-MS). Ibogaine, 12-OH-ibogamine, and o-(methyl)-ibogaine-d3 (ibogaine-d3) internal standard were isolated by solvent extraction under basic conditions. The resulting organic extract was evaporated to dryness, and the residue was derivatized at room temperature with ethyl iodide in the presence of trimethyl anilinium hydroxide in dimethyl sulfoxide. The reaction was terminated by acidification and washed with organic solvents to remove impurities. The aqueous phase was then alkalinized and reextracted. The organic extract was concentrated and analyzed by GC-MS. Quantitation was based upon the ratios of the molecular ions at m/z 310 for ibogaine, m/z 313 for ibogaine-d3, and m/z 324 for 12-OH-ibogamine ethyl ether. The limit of detection was 5 ng/mL for both ibogaine and derivatized 12-OH-ibogamine, and limits of quantitation were between 5 and 10 ng/mL for all matrices tested. Calibration curves were linear in the range of 3-1000 ng/mL or ng/g for both analytes.

Administration, Oral↗
PubMed1996

Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca.

Harmine, harmaline, tetrahydroharmine (THH), and N,N-dimethyltryptamine (DMT) were quantitated in plasma from 15 healthy male volunteers after the ingestion of ayahuasca, a beverage that has been used for religious purposes in Brazil since pre-Columbian times. A growing awareness of the interest in this ancient shamanistic practice in modern urban cultures and the widespread popular dissemination of the inebriant effects and type and sources of the plant admixtures used to prepare the beverage have provided additional impetus for this study. The three harmala alkaloids were quantitated from protein-precipitated plasma by high-performance liquid chromatography using fluorescence detection. Recovery from blank human plasma was quantitative, and the limit of quantitation (LOQ) was below 2 ng/mL of plasma for each of the harmala alkaloids. Standard concentrations ranged from 10 to 250 ng/mL for harmine and THH and from 1.0 to 25.0 ng/mL for harmaline, respectively. Linearity was observed for harmine, harmaline, and THH within these respective ranges. The highest concentrations of harmala alkaloids in human plasma were found to be 222.3 ng/mL for harmine, 134.5 ng/mL for THH, and 9.4 ng/mL for harmaline. DMT was quantitated by gas chromatography using nitrogen-phosphorus detection after liquid-liquid extraction with diphenhydramine as an internal standard. DMT recovery was quantitative, and the limit of detection and LOQ were 0.5 and 5 ng/mL, respectively. Linearity for DMT was observed from 5 to 1000 ng/mL. The one-step extraction method for DMT and the protein precipitation method for the three harmala alkaloids afford rapid, sensitive, and quantitative analyses of these alkaloids with minimal analyte loss. The analytical methods also may be applicable to other matrices, including whole blood and urine samples and homogenized tissue specimens. These are the first reported observations of DMT and harmala alkaloids in plasma after ritual ingestion of ayahuasca.

Administration, Oral↗
PubMed2003

Pediatric sibling donors of successful and unsuccessful hematopoietic stem cell transplants (HSCT): a qualitative study of their psychosocial experience.

OBJECTIVE: To examine the psychosocial impact of pediatric hematopoietic stem cell transplants (HSCTs) on sibling donors, particularly in unsuccessful HSCTs. METHODS: Fifteen sibling HSCT donors, 8 who had participated in successful transplants, and 7 whose recipient sibling died, were interviewed (M age = 19.6 years at time of interviews, and 13.3 years at time of sibling's HSCT). Grounded theory methodology was used to derive themes from interviews. RESULTS: Siblings in the unsuccessful transplant group reported greater negative impact and feelings of guilt following the HSCT and were less likely to experience positive psychological effects. Both groups reported that informed consent involved "no choice" and that psychological aspects of the procedure outweighed physical aspects. CONCLUSIONS: Some themes differentiated sibling donors of successful and unsuccessful transplants, while others were common to both groups. All emergent themes reinforced the importance of providing sibling donors with developmentally appropriate, accurate information and long-term psychological support.

Adolescent↗
PubMed1994

Localization of muscarinic receptor subtypes in brain stem areas regulating sleep.

Muscarinic cholinergic receptors (mAChRs) within the pontine brain stem play a key role in generating rapid eye movement (REM) sleep. Using an in vitro autoradiographic technique that permits selective labeling of mAChR subtypes by radioligand binding, this study provides the first quantitative map of mAChR subtypes in cat brain stem areas important for REM sleep generation. M1, M2 and M3 mAChR subtypes were distributed heterogeneously throughout the brain stem. For all 3 mAChR subtypes, the greatest levels of binding were found in the dorsal raphe and locus coeruleus, and the least amount of binding was in the reticular formation. These findings are consistent with data from in vivo studies showing that multiple mAChR subtypes are involved in REM sleep generation.

Animals↗
PubMed1995

The serotonin agonist m-chlorophenylpiperazine (mCPP) binds to serotonin transporter sites in human brain.

The serotonin (5-HT) agonist m-chlorophenylpiperazine (mCPP) is commonly used as a neuroendocrine challenge agent in humans, and it is well accepted that its mechanism of action involves direct stimulation of postsynaptic 5-HT receptors. In the present work, we demonstrate that mCPP also displays appreciable affinity (IC50 = 230 nM) for 5-HT transporters labeled by [125I]3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([125I]RTI-55) in human occipital cortex. These data agree with reports that show mCPP increases extracellular 5-HT in rat brain via a mechanism involving 5-HT transporters. Our results indicate that mCPP may exhibit a presynaptic 5-HT action in man, and studies utilizing mCPP to assess 5-HT receptor sensitivity should be interpreted with caution.

Adult↗
PubMed1996

Altered dopamine transporter densities in alcohol-preferring vervet monkeys.

Altered dopamine (DA) transporter densities have been implicated in mechanisms of vulnerability and relapse in human alcoholics. The regional distribution and density of the DA transporter was studied in alcohol-preferring vervet monkeys to investigate baseline status and regulation of the DA transporter at different stages of chronic alcohol drinking. Combined ligand binding and in vitro autoradiography of the cocaine congener [125I]RTI-55 (beta-CIT) demonstrated a significant increase in DA transporter densities in abstinent alcohol-preferring monkeys over those in alcohol-avoiding monkeys. Chronic alcohol consumption down-regulated DA transporter densities, and this effect was reversed by acute withdrawal. These results demonstrate that the DA transporter is regulated by alcohol exposure and suggest that increased DA transporter densities may be a phenotypic marker of alcohol preference in vulnerable monkeys.

Alcohol Drinking↗
PubMed1998

Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding.

Noribogaine is formed in vivo by the O-demethylation of the indole alkaloid ibogaine. We report here that noribogaine acts as a full agonist at the mu-opioid receptor. Noribogaine-stimulated guanylyl 5'gamma-[35S]thio]triphosphate ([35S]GTPgammaS) was studied in rat thalamic membranes to measure activation of guanine nucleotide binding proteins (G-proteins) in the presence of excess GDP. Noribogaine caused a 170% increase above basal [35S]GTPgammaS binding at sub-micromolar effective concentrations (EC50) in a naloxone-sensitive manner, confirming that this effect was an opioid receptor-mediated process. The level of intrinsic activity for noribogaine in these assays was comparable to the full agonists DAMGO and morphine. In contrast, ibogaine had no significant effect on [35S]GTPgammaS binding over a similar concentration range. The efficacy of noribogaine as a full mu-opioid agonist may explain ibogaine's ability to block the acute signs of opiate withdrawal and its suppressive effects on morphine self-administration.

Animals↗
PubMed1998

Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals.

The presence of diffuse or primitive senile plaques in the neocortex of cognitively normal elderly at autopsy has been presumed to represent normal aging. Alternatively, these patients may have developed dementia and clinical Alzheimer disease (AD) if they had survived. In this setting, these patients could be subjects for cognitive or pharmacologic intervention to delay disease onset. We have thus followed a cohort of cognitively normal elderly subjects with a Clinical Dementia Rating (CDR) of 0 at autopsy. Thirty-one brains were examined at postmortem according to Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria and staged according to Braak. Ten patients were pathologically normal according to CERAD criteria (1a). Two of these patients were Braak Stage II. Seven very elderly subjects exhibited a few primitive neuritic plaques in the cortex and thus represented CERAD 1b. These individuals ranged in age from 85 to 105 years and were thus older than the CERAD la group that ranged in age from 72 to 93. Fourteen patients displayed Possible AD according to CERAD with ages ranging from 66 to 95. Three of these were Braak Stage I, 4 were Braak Stage II, and 7 were Braak Stage III. The Apolipoprotein E4 allele was over-represented in this possible AD group. Neuropsychological data were available on 12 individuals. In these 12 individuals, Possible AD at autopsy could be predicted by cognitive deficits in 1 or more areas including savings scores on memory testing and overall performance on some measures of frontal executive function.

Aged↗
PubMed1998

Intraneuronal ApoE in human visual cortical areas reflects the staging of Alzheimer disease pathology.

Alzheimer disease (AD) is marked by progressive loss of cortical neurons with associated cognitive decline. Multiple genetic and environmental factors likely contribute to this progressive loss. Such genetic factors include the polymorphic locus (APOE) that encodes apolipoprotein E (apoE). In order to investigate a possible correspondence between cellular localization of apoE and the neuropathology of AD, we examined the distribution of apoE-immunoreactive neurons in visual cortical areas with different apparent susceptibility to AD neuropathology (areas 17-primary sensory, 18-secondary sensory, and inferior temporal-association cortex) at different stages of AD pathology as described by Braak and Braak. We found that intraneuronal apoE was present at all these stages, however, only in visual cortical regions known to be vulnerable to AD. In the late stages, the laminar distribution of apoE-immunoreactivity matched the distribution of other markers of AD pathology, especially modified tau. These data support previous findings that intraneuronal apoE in neocortex is common in aged, nondemented controls and demonstrate that it may be more common in regions at risk for AD pathology. Thus, intraneuronal accumulation of apoE may be an attribute of cortical neurons that are more vulnerable to age-related injury with the presence of apoE antedating the classical indices of late-onset AD pathology.

Aged↗
PubMed1996

Detection of HIV-1 DNA in needle/syringes, paraphernalia, and washes from shooting galleries in Miami: a preliminary laboratory report.

Shared use of injection equipment (needle/syringes), registering, booting, and backloading are practices among injection drug users (IDUs) that increase the risk for transmission of human immunodeficiency virus type 1 (HIV-1). The sharing of injection paraphernalia (including cookers and cottons) and washwater for rinsing used needle/syringes and dissolving drugs could be potential sources for secondary transmission of HIV-1. Laboratory rinses were made from needle/syringes, cottons, and cookers obtained from shooting galleries, and washwaters were obtained from shooting galleries in Miami. Three rinses were analyzed and antibodies to HIV-1 proteins were detected by using Western blot and HIV-1 DNA was detected by using nested polymerase chain reaction (PCR) specific for the gag and envelope genes of HIV-1. Antibodies to HIV-1 proteins were detected in 12 (52%) of 23 rinses from visibly contaminated needle/syringes, in three (18%) of 17 rinses from cottons, in three (14%) of 21 rinses from cookers, and in one (6%) of 17 washwaters. No antibodies were detected in laboratory rinses from visibly clean needles. Using nested PCR followed by Southern blot confirmation of the amplified targets, HIV-1 gag gene DNA was detected in 16 (84%) of 19 and envelope gene DNA in 17 (85%) of 20 laboratory rinses from visibly contaminated needle/syringes. We detected gag and envelope gene DNA, respectively, in three (27%) and four (36%) of 11 cottons, in six (46%) and seven (54%) of 13 cookers, and in five (38%) of 13 and in 10 (67%) of 15 washwaters from shooting galleries. No HIV-1 DNA was detected in laboratory rinses from visibly clean needles. These results indicate that HIV-1 might be present in contaminated cottons, cookers, and washwaters as well as in contaminated needle/syringes at shooting galleries. Reduction of risks of exposure to HIV-1 among IDUs may require modification of behaviors that are ancillary to the act of injection, such as the use of common cookers, cottons, and washwater.

Blotting, Southern↗
PubMed2005

Intraobserver reliability of the Teller Acuity Card procedure in infants with perinatal complications.

PURPOSE: Intraobserver test-retest reliability of the Teller Acuity Card (TAC) procedure for estimating grating acuity was assessed in 79 infants who had been treated in a neonatal intensive care unit for preterm birth and/or other perinatal complications. METHODS: Subjects were tested monocularly at one or more of four different age intervals that ranged between 2.5 and 18.5 mo corrected age. Testers were masked to the location and spatial frequency of the grating on each card. RESULTS: Of the intraobserver test-retest scores, 91% differed by no more than one octave and 68% differed by no more than 0.5 octave. Intraobserver agreement was similar to that reported previously for healthy, preterm infants. Reliability was uniform between infants of differing levels of risk for abnormal visual development but bore effects of low tester ratings of confidence. CONCLUSIONS: The results demonstrate the reliability of the TAC procedure but suggest that test sessions should be repeated when tester confidence in validity of results is low.

Gestational Age↗
PubMed2004

National Association of Medical Examiners position paper on the certification of cocaine-related deaths.

The National Association of Medical Examiners Committee on Cocaine-related Deaths recommends that the following guidelines be applied in the process of documenting, interpreting, and certifying potential cocaine-related fatalities. The committee cautions that the investigation of any drug-related death requires a complete investigation of the circumstances of death, the death scene, and past medical history. It is also necessary to have the results of the forensic toxicological analysis and those of a complete forensic autopsy examination prior to formulating an opinion as to the cause and manner of death. Cocaine should be considered the underlying cause of the death when 1 or more of the following is true: (1). the circumstances surrounding the death can be associated with an acute cocaine exposure and there are no supervening causes of death; (2). the immediate cause of death is directly due to a readily identifiable mechanism or disease such as a gunshot wound or a stroke, yet the acute use of cocaine was the direct underlying cause of the trauma or the disease process; and (3). chronic cocaine use leads to a disease that results in an ultimately fatal pathologic process leading to organ injury and death. The committee further cautions that reported drug levels may not directly relate to the toxic or lethal effects of the drug upon the patient. These guidelines are intended for use by practicing medical examiners and physicians who certify drug deaths, as well as providing education tools for students.

Autopsy↗