Biomedical subjects
M Phillips
Publications and source records attributed to M Phillips.
John Lykoudis and peptic ulcer disease.
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Simultaneous detection of C282Y and H63D hemochromatosis mutations by dual-color probes.
BACKGROUND: Hemochromatosis is a common genetic disease, affecting one in every 200 individuals in the United States. A PCR assay was designed using fluorescent melting curve analysis to simultaneously detect the G845-->A (C282Y) and C187-->G (H63D) mutations. The G845-->A and C187-->G loci are distinguished by color, and mutant alleles are distinguished from wild type by probe melting temperature (Tm). METHODS AND RESULTS: The probe sets used two fluorophore pairs, fluorescein with LCRed 640 for G845-->A and fluorescein with LCRed 705 for C187-->G. The probes, complementary to the mutant allele, dissociate from the product at specific Tms. Wild-type alleles form mismatches with the probes, reducing the Tms by 6 degrees C (G845-->A) and 10 degrees C (C187-->G). One of 133 samples had a Tm shift 4 degrees C less than the wild-type Tm for the G845-->A locus. Sequencing confirmed the sample to be homozygous for G845-->A and heterozygous for a C-->A substitution at position 842 (C842-->A), substituting lysine for threonine. CONCLUSIONS: Multiplexing by color and Tm allows for simultaneous genotyping of each mutation. A novel base-pair alteration was detected in cis with a G845-->A mutation.
Ultra Flat Gold Surfaces for Use in Chemical Force Microscopy: Scanning Probe Microscopy Studies of the Effect of Preparation Regime on Surface Morphology.
The preparation of ultra flat gold surfaces for use in chemical force microscopy (CFM) has been studied. The surfaces were studied in terms of substrate effects by comparing mica, Si (110) wafer and glass slides. The effect of different annealing regimes was also investigated. Measurements on these surfaces were made by both atomic force microscopy (AFM) (in contact and tapping mode) and by scanning tunneling microscopy (STM). The films contain different morphologies with respect to grain size and topography. Calculations of surface roughness present values less than 2.5 nm for all surfaces studied, making the choice of the "flattest" surface difficult if based on criteria of surface roughness alone. Additionally, it is shown that different acquisition parameters can produce dissimilar images that have stability and reproducibility.
The process of relapse in severely dependent male problem drinkers.
AIMS: The aim of the study was to investigate factors hypothesized to influence the relapse process, with a focus on the role of self-efficacy, alcohol dependence and cognitive functioning. DESIGN: The study was conducted in the context of a controlled trial of a relapse prevention programme. Subjects were assessed prior to treatment, at immediate conclusion of treatment and at 6- and 12-month follow-up. SETTING: The study was conducted in an Alcohol Treatment Unit (ATU) in Scotland. PARTICIPANTS: Subjects were 60 male problem drinkers who were patients at the ATU. They were heavy drinkers, with corresponding high levels of alcohol dependence and alcohol-related harm. MEASUREMENTS: The independent variables were post-treatment self-efficacy, alcohol dependence, cognitive functioning, level of depression and alcohol consumption prior to admission to treatment. The dependent variables were post-treatment drinking behaviour and functioning and time to lapse and relapse. FINDINGS: Although the methodology does not allow identification of causality, support was found for the hypothesis that post-treatment self-efficacy was an intervening variable between treatment and outcome. Higher post-treatment self-efficacy predicted better outcome at 6-month follow-up and was associated with a reduced risk of lapse and relapse over the 12-month follow-up. Poorer cognitive functioning was significantly associated with being categorized as a problem drinker at 6-month follow-up and with higher risk of a lapse over the 12-month follow-up. Level of alcohol dependence did not predict outcome. CONCLUSIONS: It was concluded that post-treatment self-efficacy rating is a predictor of treatment outcome and time to lapse and relapse and that cognitive functioning is a predictor of treatment outcome and time to lapse.
Early results from a school alcohol harm minimization study: the School Health and Alcohol Harm Reduction Project.
AIMS: The School Health and Alcohol Harm Reduction Project aims to reduce alcohol-related harm by enhancing students' abilities to identify and deal with high-risk drinking situations particularly likely to be encountered by young people. DESIGN: The SHAHRP study has adopted a quasi-experimental research design, incorporating intervention and control groups and measuring change over a 3-year period. SETTING: The study is set in metropolitan, government secondary schools (13-17-year-olds) in Perth, Western Australia. The 14 schools involved in the SHAHRP study represent approximately 23% of government secondary schools in the Perth metropolitan area. PARTICIPANTS: The sample was selected using cluster sampling, with stratification by socio-economic area, and involves over 2300 intervention and control students from junior secondary schools. Seventy-three per cent (73.7%) of students completed surveys at both baseline and first follow-up. INTERVENTION: The intervention incorporated evidence-based approaches to enhance potential for behaviour change in the target population. The intervention is a curriculum-based programmeme with an explicit harm minimization goal and will be conducted in two phases over a 2-year period. MEASURES AND FINDINGS: The early results of the study demonstrate initial knowledge and attitude change, predicted by the students' involvement in the intervention. A surprising impact of the first phase of SHAHRP was the significant difference in alcohol consumption and harms between control and intervention groups, with the SHAHRP group demonstrating a significantly lower increase in alcohol consumption than the control group. Students who were supervised drinkers at baseline and who received the SHAHRP intervention were overwhelmingly represented in the change results. CONCLUSIONS: Results from phase one of the SHAHRP study suggest that classroom-based alcohol education programmemes can reduce harm, particularly in students who are supervised drinkers prior to the intervention.
Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress.
Reactive oxygen species (ROS) are toxic byproducts of mitochondrial energy production that inflict oxidative stress, a constant barrage of damage to DNA, proteins, lipids, and other biologically important molecules. Oxidative stress has been implicated as a pathologic mechanism in aging and in several diseases. We developed a display of apparent new markers of oxidative stress in human beings, the breath methylated alkane contour (BMAC). The BMAC is a three-dimensional display of C4 to C20 alkanes and monomethylated alkanes in breath, with x-axis = carbon chain length, z-axis = methylation site, and y-axis = alveolar gradient (relative abundance in breath minus relative abundance in room air). In 102 normal human subjects of 9 to 89 years of age, alveolar gradients of components of the BMAC increased significantly with age. The mean alveolar gradient of all components of the BMAC varied from negative in the youngest quartile (ages 9 to 31 years) to positive in the oldest quartile (ages 74 to 89 years)(P < 2.10(-9)). These findings were consistent with an increase in oxidative stress with advancing age, although an age-related decline in clearance by cytochrome p450 may have contributed. The BMAC provides a display of apparent new markers of oxidative stress with potential applications in aging research, clinical diagnosis, pharmacology, and toxicology.
Effect of age on the profile of alkanes in normal human breath.
Ethane and pentane in breath are markers of oxidative stress, produced by ROS-mediated lipid peroxidation of n-3 and n-6 polyunsaturated fatty acids (PUFAs), but little is known about other n-alkanes in normal human breath. We investigated the spectrum of alkanes in normal human alveolar breath, and their variation with age. Fifty normal humans were studied (age range 23-75, median 35). Volatile organic compounds (VOCs) in alveolar breath were captured on sorbent traps and assayed by gas chromatography and mass spectroscopy. Alveolar gradients (concentration in breath minus concentration in ambient room air) of alkanes were determined. C4-C20 alkanes were observed in breath and room air. Their mean alveolar gradients were negative from C4 to C12 and positive from C13 to C20. The mean alveolar gradients of four alkanes (C5-C8) were significantly less negative in the older subjects (p < 0.05). There were no significant differences between males and females. Normal human breath contained a spectrum of alkanes which may include new markers of oxidative stress. The mean rate of clearance (via cytochrome p450) exceeded the mean rate of synthesis (by ROS-mediated oxidative stress) for C4-C12 alkanes, while synthesis was greater than clearance for C13-C20 alkanes. The elevated alkane profile in older subjects was consistent with an age-related increase in oxidative stress, though an age-related decline in alkane clearance rate may have contributed.
A comparison of substance use between female inmates and female substance misusers in treatment.
Recent literature documents extensive substance misuse histories among US female prison inmates. The primary purpose of the present study was to determine whether histories of personal and familial substance misuse distinguished female inmates from substance misusers in treatment. After accounting for drug-related offences, we hypothesized that the inmates would have more extensive histories of personal and familial substance misuse and that they would have initiated substance use at an earlier age. Contrary to our expectations, the two samples were similar on many measures of alcohol and drug use. Similarly, differences in family histories of substance misuse were not in the predicted direction. As hypothesized, however, the inmates did report earlier age at onset of drinking. Of particular clinical relevance was the finding that, despite similar alcohol consumption levels, inmates reported fewer alcohol-related adverse medical, legal, and psychosocial consequences than did the treatment sample.
The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions.
Although high-functioning individuals with autistic disorder (i.e. autism and Asperger syndrome) are of normal intelligence, they have life-long abnormalities in social communication and emotional behaviour. However, the biological basis of social difficulties in autism is poorly understood. Facial expressions help shape behaviour, and we investigated if high-functioning people with autistic disorder show neurobiological differences from controls when processing emotional facial expressions. We used functional MRI to investigate brain activity in nine adults with autistic disorder (mean age +/- standard deviation 37 +/- 7 years; IQ 102 +/- 15) and nine controls (27 +/- 7 years; IQ 116 +/- 10) when explicitly (consciously) and implicitly (unconsciously) processing emotional facial expressions. Subjects with autistic disorder differed significantly from controls in the activity of cerebellar, mesolimbic and temporal lobe cortical regions of the brain when processing facial expressions. Notably, they did not activate a cortical 'face area' when explicitly appraising expressions, or the left amygdala region and left cerebellum when implicitly processing emotional facial expressions. High-functioning people with autistic disorder have biological differences from controls when consciously and unconsciously processing facial emotions, and these differences are most likely to be neurodevelopmental in origin. This may account for some of the abnormalities in social behaviour associated with autism.
Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage.
The role of focal brain damage as a trigger for autoimmune inflammation in multiple sclerosis (MS) is unclear. In this study we examine mechanisms by which experimental autoimmune encephalomyelitis (EAE) is enhanced by focal brain damage. EAE was produced in Lewis rats by footpad inoculation; focal brain damage, in the form of a cortical cryolesion (cryolesion-EAE), was induced 8 days post-inoculation (d.p.i.). The distribution of inflammation and chemokine production in cryolesion-EAE and EAE-only were compared. Inflammation in the brain, measured by immunocytochemistry for T lymphocytes (W3/13) and microglial activation (MHC class II -OX6), was significantly enhanced in cryolesion-EAE 11-15 d.p.i. (p < 0.01-0.05) but by 20-40 d.p.i., equated with EAE-only. Inflammation in cryolesion-EAE related to breakdown of the blood-brain barrier (BBB) at the site of the cryolesion and also to the corticospinal tracts and thalamus, reflecting the afferent and efferent neuronal connections with the cryolesioned cortex. Semiquantitative RT/PCR dot-blot hybridization assay showed a 6-fold increase in mRNA for specific chemokines in the brain in cryolesion-EAE at 9 d.p.i. (MCP-1) and 11 d.p.i. (MCP-1 and MCP-5) with no significant increase in RANTES, GRO-alpha, or MIP-1alpha. By 14 d.p.i., the levels of MCP-1 and MCP-5 mRNA equated with EAE-only animals. These results suggest that enhancement and location of autoimmune inflammation in the brain following focal cortical injury initially involve chemokines such as the macrophage chemoattractants MCP-1 and MCP-5, and the activities of afferent and efferent neuronal connections with the site of damage. By analogy, similar factors may modulate or reactivate autoimmune inflammation in MS.
Identifying patients "at risk" for alcohol withdrawal syndrome and a treatment protocol.
Alcohol abuse and alcohol dependence are common problems. It is estimated that more than 10 million Americans have problems with alcohol dependence that adversely affect their lives and the lives of their families. Many of these patients, if hospitalized, have the potential to experience symptoms of alcohol withdrawal. Major alcohol withdrawal symptoms may include seizures and the development of delirium tremens. Obtaining an alcohol consumption history is a critical component to identifying patients at risk and determining the appropriate treatment plan for potential alcohol withdrawal. A protocol was established for identifying and treating patients at risk for alcohol withdrawal. The initiation of the treatment protocol is history- and symptom-based; treatment is symptom-triggered on the basis of frequent objective assessments. The purpose of the protocol is to prevent and control withdrawal symptoms without heavily sedating or hindering a patients' neurological assessment.
Disease and injury among veterinarians.
OBJECTIVE: To identify occupational causes of disease and injury in veterinarians and their staff. DESIGN: A self-administered questionnaire was mailed to all of the 160 registered veterinary practices in Western Australia. RESULTS: Injuries accounted for most workers' compensation claims over a 12-month period with 31% of respondents losing a total of 360 work days with a mean of 13.3 days whereas non-occupational diseases such as influenza accounted for 408 work days lost. Over a 10-year period, 71% of respondents had been injured. The major physical injuries were dog and cat bites, cat scratches, scalpel blade cuts and back injuries from lifting heavy animals. Exposure to chemicals such as flea rinses, formalin, glutaraldehyde, x-ray developers and gaseous anaesthetics were reported to cause headache, nausea and allergies. Thirty percent of respondents did not have extractor fans for scavenging waste anaesthetic gases. The study showed high use of radiography (94%) for diagnostic purposes with 24% of respondents believing radiation exposure is a major occupational health and safety issue. Stress, drug abuse, suicide and burglary were also reported. Despite a high awareness of zoonotic diseases, there were very few reports of these. CONCLUSION: Injuries and other occupational hazards reported together with work days lost demonstrate a need for improving the working environment of veterinarians and their staff and the development of comprehensive health and safety programs.
Predicting the outcome of therapy for pulmonary tuberculosis.
Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses (> 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.
Characteristics of American-Indian clients seeking inpatient treatment for substance abuse.
OBJECTIVE: The current study was conducted as a preliminary examination of substance use and some of its correlates in nonreservation-residing American Indians. METHOD: A group of 522 American-Indian (AI) subjects (473 men) were compared with two sets of geographic controls: (1) an equal number of African Americans (AA) and (2) an equal number of European Americans (EA). All received treatment in the same facilities over the same time period. RESULTS: Contrary to expectations, the ethnic/racial groups were remarkably similar on a number of alcohol use variables, including the amount consumed in the 6 months prior to treatment and the number of previous treatments. Among those self-reporting as problem drinkers, there were group differences in the age of first drink (AA mean = 13.54, AI mean = 12.24 and EA mean = 11.71) and first drunk (AA mean = 15.80, AI mean = 14.23 and EA mean = 14.08) and the number of alcohol-related problems (AA mean = 7.52, AI mean = 8.49 and EA mean = 8.46). On these measures, AI and EA subjects did not differ whereas AA subjects reported a later age of onset and fewer negative consequences. EA and AI male subjects reported marijuana as their most frequently used "other" drug, whereas AA male subjects listed stimulants as their primary drugs. Regardless of ethnic/racial group, women did not differ on their drug(s) of choice, reporting stimulants as the most frequently abused drug (after accounting for alcohol use). CONCLUSIONS: This preliminary study is remarkable for the observed similarities among groups. Future studies using more rigorous sampling are needed to provide clarification of this preliminary study.
Explicit and implicit neural mechanisms for processing of social information from facial expressions: a functional magnetic resonance imaging study.
The processing of changing nonverbal social signals such as facial expressions is poorly understood, and it is unknown if different pathways are activated during effortful (explicit), compared to implicit, processing of facial expressions. Thus we used fMRI to determine which brain areas subserve processing of high-valence expressions and if distinct brain areas are activated when facial expressions are processed explicitly or implicitly. Nine healthy volunteers were scanned (1.5T GE Signa with ANMR, TE/TR 40/3,000 ms) during two similar experiments in which blocks of mixed happy and angry facial expressions ("on" condition) were alternated with blocks of neutral faces (control "off" condition). Experiment 1 examined explicit processing of expressions by requiring subjects to attend to, and judge, facial expression. Experiment 2 examined implicit processing of expressions by requiring subjects to attend to, and judge, facial gender, which was counterbalanced in both experimental conditions. Processing of facial expressions significantly increased regional blood oxygenation level-dependent (BOLD) activity in fusiform and middle temporal gyri, hippocampus, amygdalohippocampal junction, and pulvinar nucleus. Explicit processing evoked significantly more activity in temporal lobe cortex than implicit processing, whereas implicit processing evoked significantly greater activity in amygdala region. Mixed high-valence facial expressions are processed within temporal lobe visual cortex, thalamus, and amygdalohippocampal complex. Also, neural substrates for explicit and implicit processing of facial expressions are dissociable: explicit processing activates temporal lobe cortex, whereas implicit processing activates amygdala region. Our findings confirm a neuroanatomical dissociation between conscious and unconscious processing of emotional information.
Chronic disease self-management: improving health outcomes.
Chronic disease has become pandemic in the United States, and estimates are that it will affect 148 million people by the year 2030. Patients with chronic illnesses cost the health care system over three times more than individuals without chronic conditions. The US Department of Veterans' Affairs (VA) Sunshine HealthCare Network, composed of VA health care facilities in Florida and Puerto Rico, recognized that the needs of its increasing number of veterans with chronic diseases were unmet by traditional medical interventions. The Network implemented a chronic disease self-management pilot program to evaluate its value for the veteran population. Results of the pilot indicate that this program will make a positive, lasting change in the health status and quality of life for veterans with chronic disease.