Biomedical subjects

Robert J Williams

Publications and source records attributed to Robert J Williams.

At least 19 recordsLinked to original sources

PubMed2006

Does learning about the mathematics of gambling change gambling behavior?

The present research examined the influence of improved knowledge of odds and mathematical expectation on the gambling behavior of university students. A group of 198 students in an introductory statistics class received instruction on probability theory using examples from gambling. A comparison group of 134 students received generic instruction on probability, and another group of 138 students in classes on unrelated topics received no mathematical instruction. Students receiving the intervention demonstrated superior ability to calculate gambling odds as well as resistance to gambling fallacies 6 months after the intervention. Unexpectedly, this improvement in knowledge and skill was not associated with any decreases in actual gambling behavior. The implication of this research is that enhanced mathematical knowledge on its own may be insufficient to change gambling behavior.

Adult↗

PubMed2006

Serotonin transporter expression is not sufficient to confer cytotoxicity to 3,4-methylenedioxymethamphetamine (MDMA) in vitro.

There is much evidence from animal studies that the recreational drug MDMA is a selective toxin which damages serotonin nerve terminals and axons. These in vivo studies show that an interaction between MDMA and the serotonin transporter protein (SERT) is the .rst step in toxicity. To further our understanding of the biochemical processes of MDMA toxicity we wished to use an in vitro model for toxicity. We produced two COS-7 cell lines with different levels of expression of recombinant rat SERT, as determined by 5-HT uptake assays, and compared them to human SERT expressing JAR cells and to untransfected COS-7 cells which do not express SERT. Cultured cells were exposed to MDMA (0.1 microM-1 mM) for 24 or 48 h at 37 degrees C before assessing cytotoxicity by LDH release and MTT turnover. Only at the highest concentration used, 1 mM, was MDMA cytotoxic, and this toxicity was found in all cell lines. Cytotoxicity caused by 48 h exposure to 1 mM MDMA at 37 degrees C was not related to the level of SERT expression, not blocked by the SERT-blocking drugs paroxetine or fluoxetine and not enhanced, in JAR cells, by forskolin preincubation that increased 5-HT uptake capacity by 50%. We conclude that SERT expression is not sufficient to confer MDMA toxicity to cell lines. Therefore SERT-expressing cell lines do not offer a simple model system to elucidate the mechanisms underlying MDMA toxicity.

Animals↗

PubMed2005

Neuroleptic and benzodiazepine use in long-term care in urban and rural Alberta: characteristics and results of an education intervention to ensure appropriate use.

OBJECTIVES: To examine the use of psychotropic drugs in 24 rural and urban long-term care (LTC) facilities, and compare the effect of an education intervention for LTC staff and family members on the use of psychotropic drugs in intervention versus control facilities. METHODS: Interrupted time series with a non-equivalent no-treatment control group time series. Data on drug use were collected in 24 Western Canadian LTC facilities (10 urban, 14 rural) for three 2-month time periods before and after the intervention. Pharmacy records were used to collect data on drug, class of drug, dose, administration, and start/stop dates. Chart reviews provided demographics, pro re nata (prn) use, and indications for drug use. Subjects comprised 2443 residents living in the 24 LTC facilities during the 1-year study. An average of 796.33 residents (32.7%) received a psychotropic drug. An education intervention on psychotropic drug use in LTC was offered to intervention physicians, nursing staff, pharmacists and family members. RESULTS: Approximately one-third of residents received a psychotropic drug during the study, often for considerable lengths of time. A minority of psychotropic drug prescriptions had a documented reason for their use, and 69.5% of the reasons would be inappropriate under Omnibus Budget Reconciliation Act (OBRA) legislation. Few psychotropic drug prescriptions were discontinued or reduced during the study. More urban LTC residents received neuroleptics and benzodiazepines than their rural counterparts (26.1% vs. 15.7%, and 18.0% vs. 7.6%, respectively). The education intervention did not result in any significant decline in the use of these drugs in intervention facilities. CONCLUSION: The results suggest substantial use of psychotropic drugs in LTC, although rural LTC residents received approximately half the number of psychotropic drugs compared with urban residents. A resource-intensive intervention did not significantly decrease the use of psychotropics. There is a need for better monitoring of psychotropic drugs in LTC, particularly given that voluntary educational efforts alone may be ineffective agents of change.

Aged↗

PubMed2005

Antipsychotic drug use in Canadian long-term care facilities: prevalence, and patterns following resident relocation.

BACKGROUND AND AIMS: Data on antipsychotic use were collected in two Canadian long-term care (LTC) facilities. During the one-year study, residents in one facility were relocated to a new facility, allowing examination of the changes in antipsychotic use associated with relocation. METHOD: A comparative descriptive design was used. Pharmacy and chart data on antipsychotic use were gathered for three separate one-month periods during one year. Data were collected both in a facility experiencing relocation of all residents to a new facility, and in a facility not undergoing relocation. The three one-month data collection periods covered a one-month period before the relocation, immediately after the relocation, and six months after the relocation. RESULTS: In the facility not experiencing relocation, an average of 31.3% of all residents were receiving antipsychotics. Residents in this facility received antipsychotics for an average length of 0.81 years, and 20.8% of all antipsychotic prescriptions reflected dose reductions within six months of the start of the prescription. Only 8.1% of prescriptions had accompanying documentation on the behavioral indication for the use of antipsychotics. A total of 73.4% of all antipsychotics were 'atypical' antipsychotics, and 13.5% of all antipsychotic prescriptions were written as 'p.r.n.' (as needed). While the use of antipsychotics remained relatively constant in the non-relocation facility (between 30.3% and 33.1% of all residents), the percentage of residents receiving antipsychotics in the facility experiencing a relocation climbed significantly; from 21.5% six months before the move, to 32.6% immediately after the move, to 36.9% six months after the move. CONCLUSION: These findings, when compared with the U.S. standards on antipsychotic use (OBRA), suggest the need for additional research on antipsychotic use in Canadian LTC facilities.

Adaptation, Psychological↗

PubMed2005

Bandaging technique after knee replacement.

BACKGROUND: Firm bandaging of the knee following knee replacement may prevent bleeding into the joint by a tamponade effect. We studied the pressure required to achieve tamponade, and then clinically compared the use of a compression bandage with the use of a standard crêpe bandage, with or without a drain. METHOD: Transducers were used to measure the pressure achieved on the surface of the knee under different bandages, and within the knee following release of the tourniquet. We prospectively compared 3 series of 50 patients each: (1) with compression bandaging from toes to mid-thigh, (2) with crêpe bandage from mid-calf to mid-thigh alone, or (3) with crêpe bandage and suction drain. RESULTS: The pressure within the joint at which tamponade occurs is 52-62 mm Hg. The pressure on the skin under a properly applied compression bandage is between 28 and 32 mm Hg, and this controls bleeding within the joint. Patients treated with compression bandaging recovered more quickly from the operation, had a shorter hospital stay, and a greater range of flexion on discharge. They had no swelling of the limb, rarely suffered a tense hemarthrosis, and had fewer complications. INTERPRETATION: The use of a compression bandage incorporating the foot and calf following knee replacement surgery, without the use of drains, confers specific advantages over the use of a crêpe bandage alone.

Aged↗

PubMed2005

Validity of adolescent self-report of substance use.

The validity of self-report of substance use was examined in 367 adolescents referred for a substance use assessment between 1996 and 2000. Referrals came from a wide variety of sources, including pediatricians, the courts, and social services, as well as their parents. Average age of the sample was 15, 52% were male, and 82% were Caucasian. Adolescents were first asked about the details of their substance use by a clinician using a structured interview with established reliability and validity (Adolescent Drug and Alcohol Diagnosis). They were subsequently asked to provide a urine sample, a requirement they were unaware of when being interviewed about their substance use. If the urine sample was deemed valid by the laboratory technician, it was analyzed by means of fluorescence polarization immunoassay and paper chromatography. If positive screens were obtained for any substance, the sample was subjected to gas chromatographyl mass spectrometry for confirmation and quantification. Biochemical test results were compared to self-report. Overall, 28% (96/338) of the self-reports were not corroborated by urinalysis. In adolescents who reported nonuse of a substance, 26% (56/219) had a positive urinalysis. More surprisingly, 34% (40/119) of adolescents reporting substance use in the urinalysis detection window had a negative urinalysis. The present study found self-report of substance use in adolescents to only have fair validity. It is recommended that biochemical corroboration be routinely used for this population.

Adolescent↗

PubMed2005

Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons.

The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.

Alkaline Phosphatase↗

PubMed2005

Promoting alcohol abstinence among pregnant women: potential social change strategies.

Fetal Alcohol Syndrome Disorder (FASD) is one of the most preventable sources of developmental abnormalities, and has a singular cause-alcohol consumption during pregnancy. Estimates for the costs of treatment of a single case of FASD range often above one million dollars. The primary strategy for prevention currently centers on no alcohol consumption during pregnancy. However, a sizeable number of North American women currently drink during pregnancy. A literature review examined the behavior of maternal alcohol consumption in order to understand the rationale associated with drinking. Generally, it appears that pregnant women differ by their alcohol consumption habits and their reasons to drink. In an attempt to eliminate FASD, we review a number of educational, legal, and community-based programs that have been used to promote abstinence and examine where they have been successful. Unfortunately, social marketing strategies have received less attention. Several potential applications of social marketing directed to drinking-during- pregnancy campaigns are suggested, and possible contributions to the overall effort are explained.

Adult↗

PubMed2004

Zinc-histidine complex protects cultured cortical neurons against oxidative stress-induced damage.

The levels of zinc in the brain are directly affected by dietary zinc and deficiency has been associated with alcohol withdrawal seizures, excitotoxicity, impaired learning and memory and an accelerated rate of dysfunction in aged brain. Although zinc is essential for a healthy nervous system, high concentrations of zinc are neurotoxic, thus it is important to identify the most effective forms of zinc for treatment of conditions of the central nervous system. Accumulating evidence suggests that zinc-histidine complex (Zn(His)(2)) has greater biological potency and enhanced bioavailability compared with other zinc salts and also has antioxidant potential. Therefore, in this study we investigated the ability of zinc-histidine to protect cultured cortical neurons against hydrogen peroxide-induced damage. Pre-treating neurons for 18 h with subtoxic concentrations of zinc-histidine (5-25 microM) improved neuronal viability and strongly inhibited hydrogen peroxide-induced (75 microM, 30 min) cell damage as assessed by MTT turnover and morphological analysis 24h later. Low concentrations of zinc-histidine were more neuroprotective than zinc chloride. There was evidence of an anti-apoptotic mechanism of action as zinc-histidine inhibited hydrogen peroxide-induced caspase-3 activation and c-jun-N-terminal kinase phosphorylation. In summary, zinc supplementation with zinc-histidine protects cultured neurons against oxidative insults and inhibits apoptosis which suggests that zinc-histidine may be beneficial in the treatment of diseases of the CNS associated with zinc deficiency.

Animals↗

PubMed2004

Flavonoids: antioxidants or signalling molecules?

Many studies are accumulating that report the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids, and their in vivo metabolites, do not act as conventional hydrogen-donating antioxidants but may exert modulatory actions in cells through actions at protein kinase and lipid kinase signalling pathways. Flavonoids, and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), tyrosine kinases, protein kinase C (PKC), and mitogen activated protein kinase (MAP kinase) signalling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as antioxidants or modulators of cell signalling, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anticancer agents, cardioprotectants, and inhibitors of neurodegeneration

Antioxidants↗

PubMed2004

Expression of SOD1 G93A or wild-type SOD1 in primary cultures of astrocytes down-regulates the glutamate transporter GLT-1: lack of involvement of oxidative stress.

Glutamate excitotoxicity is implicated in the aetiology of amyotrophic lateral sclerosis (ALS) with impairment of glutamate transport into astrocytes a possible cause of glutamate-induced injury to motor neurons. It is possible that mutations of Cu/Zn superoxide dismutase (SOD1), responsible for about 20% of familial ALS, down-regulates glutamate transporters via oxidative stress. We transfected primary mouse astrocytes to investigate the effect of the FALS-linked mutant hSOD1(G93A) and wild-type SOD1 (hSOD1wt) on the glutamate uptake system. Using western blotting, immunocytochemistry and RT-PCR it was shown that expression of either hSOD1(G93A) or hSOD1wt in astrocytes produced down-regulation of the levels of a glutamate transporter GLT-1, without alterations in its mRNA level. hSOD1(G93A) or hSOD1wt expression caused a decrease of the monomeric form of GLT-1 without increasing oxidative multimers of GLT-1. The effects were selective to GLT-1, since another glutamate transporter GLAST protein and mRNA levels were not altered. Reflecting the decrease in GLT-1 protein, [3H]d-aspartate uptake was reduced in cultures expressing hSOD1(G93A) or hSOD1wt. The hSOD1-induced decline in GLT-1 protein and [3H]d-aspartate uptake was not blocked by the antioxidant Trolox nor potentiated by antioxidant depletion using catalase and glutathione peroxidase inhibitors. Measurement of 2',7'-dichlorofluorescein (DCF)-induced fluorescence revealed that expression of hSOD1(G93A) or hSOD1wt in astrocytes does not lead to detectable increase of intracellular reactive oxygen species. This study suggests that levels of GLT-1 protein in astrocytes are reduced rapidly by overexpression of hSOD1, and is due to a property shared between the wild-type and G93A mutant form, but does not involve the production of intracellular oxidative stress.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Inhibiting Src family tyrosine kinase activity blocks glutamate signalling to ERK1/2 and Akt/PKB but not JNK in cultured striatal neurones.

Glutamate receptor activation of mitogen-activated protein (MAP) kinase signalling cascades has been implicated in diverse neuronal functions such as synaptic plasticity, development and excitotoxicity. We have previously shown that Ca2+-influx through NMDA receptors in cultured striatal neurones mediates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt/protein kinase B (PKB) through a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. Exposing neurones to the Src family tyrosine kinase inhibitor PP2, but not the inactive analogue PP3, inhibited NMDA receptor-induced phosphorylation of ERK1/2 and Akt/PKB in a concentration-dependent manner, and reduced cAMP response element-binding protein (CREB) phosphorylation. To establish a link between Src family tyrosine kinase-mediated phosphorylation and PI 3-kinase signalling, affinity precipitation experiments were performed with the SH2 domains of the PI 3-kinase regulatory subunit p85. This revealed a Src-dependent phosphorylation of a focal adhesion kinase (FAK)-p85 complex on glutamate stimulation. Demonstrating that PI3-kinase is not ubiquitously involved in NMDA receptor signal transduction, the PI 3-kinase inhibitors wortmannin and LY294002 did not prevent NMDA receptor Ca2+-dependent phosphorylation of c-Jun N-terminal kinase 1/2 (JNK1/2). Further, inhibiting Src family kinases increased NMDA receptor-dependent JNK1/2 phosphorylation, suggesting that Src family kinase-dependent cascades may physiologically limit signalling to JNK. These results demonstrate that Src family tyrosine kinases and PI3-kinase are pivotal regulators of NMDA receptor signalling to ERK/Akt and JNK in striatal neurones.

Animals↗

PubMed2004

Effect of compression on blood flow in lower limb wounds.

Blood flow is believed to be a key parameter in the formation and management of lower limb wounds. Patients with venous leg ulcers (VLUs) have high venous pressures, due to the partial or complete failure of calf muscle pump, which in turn disturbs the local blood flow within the lower limb. Compression has currently been the mainstay for treatment of VLUs and is thought to restore valvular competence and reduce or suppress superficial and deep venous reflux. Efficacy and assessment of compression therapy can be understood in a better way by measuring blood flow in lower limbs. Publications applicable to the effects of compression on lower limb blood flow parameters are summarised. However, they have shown varying results due to the different methodology and assessment techniques used. This article seeks to explore the methods of assessment of blood flow in the lower limb associated with wound management and compression in particular and provides suggestions for future explorations.

Bandages↗

PubMed2004

Analysis of skin wound images using digital color image processing: a preliminary communication.

This article presents the use of digital image processing using hue, saturation, and intensity measurements as a technique for the color analysis of chronic wounds on the skin. An adaptive spline technique was used to segment the wound boundary in the images of venous leg ulcers. This technique was further used to approximate the position of venous leg ulcers. The amount of slough within the wound site was quantified using the software developed and was compared with a grading system based on visual inspection by an experienced clinician, and the results were compared by deriving Kappa (K) statistic. There was moderate agreement over all grades between the computer and clinician. At lower grades 1 and 2, there was excellent agreement. The results from this preliminary study suggest that this analytical technique has the potential to image process chronic skin wounds.

Journal Article↗

PubMed2003

Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability.

Much recent interest has focused on the potential of flavonoids to interact with intracellular signaling pathways such as with the mitogen-activated protein kinase cascade. We have investigated whether the observed strong neurotoxic potential of quercetin in primary cortical neurons may occur via specific and sensitive interactions within neuronal mitogen-activated protein kinase and Akt/protein kinase B (PKB) signaling cascades, both implicated in neuronal apoptosis. Quercetin induced potent inhibition of both Akt/PKB and ERK phosphorylation, resulting in reduced phosphorylation of BAD and a strong activation of caspase-3. High quercetin concentrations (30 microM) led to sustained loss of Akt phosphorylation and subsequent Akt cleavage by caspase-3, whereas at lower concentrations (<10 microM) the inhibition of Akt phosphorylation was transient and eventually returned to basal levels. Lower levels of quercetin also induced strong activation of the pro-survival transcription factor cAMP-responsive element-binding protein, although this did not prevent neuronal damage. O-Methylated quercetin metabolites inhibited Akt/PKB to lesser extent and did not induce such strong activation of caspase-3, which was reflected in the lower amount of damage they inflicted on neurons. In contrast, neither quercetin nor its O-methylated metabolites had any measurable effect on c-Jun N-terminal kinase phosphorylation. The glucuronide of quercetin was not toxic and did not evoke any alterations in neuronal signaling, probably reflecting its inability to enter neurons. Together these data suggest that quercetin and to a lesser extent its O-methylated metabolites may induce neuronal death via a mechanism involving an inhibition of neuronal survival signaling through the inhibition of both Akt/PKB and ERK rather than by an activation of the c-Jun N-terminal kinase-mediated death pathway.

Animals↗

PubMed2003

Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites.

Understanding the cellular effects of flavonoid metabolites is important for predicting which dietary flavonoids might be most beneficial in vivo. Here we investigate the bioactivity in dermal fibroblasts of the major reported in vivo metabolites of quercetin, i.e. 3'-O-methyl quercetin, 4'-O-methyl quercetin and quercetin 7-O-beta-D-glucuronide, relative to that of quercetin, in terms of their further metabolism and their resulting cytotoxic and/or cytoprotective effects in the absence and presence of oxidative stress. Uptake experiments indicate that exposure to quercetin led to the generation of two novel cellular metabolites, one characterized as a 2'-glutathionyl quercetin conjugate and another product with similar spectral characteristics but 1 mass unit lower, putatively a quinone/quinone methide. A similar product was identified in cells exposed to 3'-O-methyl quercetin, but not in the lysates of those exposed to its 4'-O-methyl counterpart, suggesting that its formation is related to oxidative metabolism. There was no uptake or metabolism of quercetin 7-O-beta-D-glucuronide by fibroblasts. Formation of oxidative metabolites may explain the observed concentration-dependent toxicity of quercetin and 3'-O-methyl quercetin, whereas the formation of a 2'-glutathionyl quercetin conjugate is interpreted as a detoxification step. Both O -methylated metabolites conferred less protection than quercetin against peroxide-induced damage, and quercetin glucuronide was ineffective. The ability to modulate cellular toxicity paralleled the ability of the compounds to decrease the level of peroxide-induced caspase-3 activation. Our data suggest that the actions of quercetin and its metabolites in vivo are mediated by intracellular metabolites.

Chromatography, Liquid↗

PubMed2003

Parental awareness of adolescent substance use.

Parental awareness of adolescent substance use was investigated in a high school sample of 985 adolescents and their parents. Only 39% of parents were aware their adolescent used tobacco, only 34% were aware of alcohol use, and only 11% were aware of illicit drug use. There were no variables that differentiated aware from unaware parents for all substances. Greater parental awareness of alcohol and tobacco use occurred with older adolescents. High adolescent ratings of family communication combined with low parental ratings of family communication were also associated with greater parental awareness of alcohol and tobacco use. Better school grades predicted greater awareness of alcohol and illicit drug use. Single parents and blended families were more aware of tobacco and illicit drug use.

Adolescent↗

PubMed2003

Negative perceptions about self-control and identification with gender-role stereotypes related to binge eating, problem drinking, and to co-morbidity among adolescents.

PURPOSE: To examine the role of both positive and negative styles of self-control, and gender-role stereotypes in binge eating and problem drinking. METHOD: Participants were 428 adolescent boys and 555 girls from predominantly Anglo-Australian backgrounds who attended regional state schools in New South Wales, Australia. Students completed standardized questionnaires that assessed problem drinking, binge eating, self-control styles, and identification with gender-role stereotypes. ANOVA and post hoc Tukey tests were conducted to examine differences among adolescents who reported problems in binge eating, drinking, and both domains. RESULTS: Adolescents who reported eating and drinking problems also reported a high negative and a low positive sense of self-control coupled with self-identification with the traits that typically describe negative dimensions of gender-role stereotypes. Regardless of gender, problem drinking was mainly related to traits of negative masculinity (bossy, noisy aggressive, etc.) whereas binge eating was mainly related to negative femininity (shy, needs approval from others, etc.). Participants who reported eating and drinking symptoms recorded low scores on positive control, high scores on negative control, and also high scores on the negative dimensions of masculinity and femininity. SUMMARY: A negative and passive style of self-control coupled with an identification with negative dimensions of gender summarizes the type of self-regulation that is implicated in both binge eating and problem drinking, and co-morbid symptoms. There is a need for interventions working toward a more balanced gender self-concept and a positive sense of self-control.

Adolescent↗