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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 19 recordsLinked to original sources
PubMed2003

Improvement of asthma control with a breath-actuated pressurised metred dose inhaler (BAI): a prescribing claims study of 5556 patients using a traditional pressurised metred dose inhaler (MDI) or a breath-actuated device.

A relationship has been reported between sub-optimal inhaler technique and control of asthma symptoms. Randomised controlled trials and systematic reviews may fail to accurately represent this relationship, by excluding patients who are unable to correctly use the reviewed devices. Breath actuated inhalers (BAIs) are reported to be easier to use than metered dose inhalers (MDIs). This study uses a large primary care medical record database (DIN-LINK) to examine the 'real-life' clinical effectiveness of a BAI vs. traditional MDIs. A comparison is made between the quantity of asthma-related medication (beta2 agonist, oral steroids and antibiotics) and healthcare resource use required by children (0-12 years) and adults (13+ years) using either the BAI or an MDI over a 12-month period. Out of 5556 new asthma patients who met the inclusion criteria, 306 used a BAI and 5250 used a traditional MDI. Children and adults using the BAI received fewer prescriptions for all three medication types than those using a traditional MDI (children: beta2 agonists -18% P=0.036, oral steroids -88% P<0.05, antibiotics -68% P<0.05 and adults: beta2 agonists -10.9% P=0.179, oral steroids -51.2% P<0.05, antibiotics -19.5% P=0.276). All prescription results reached statistical significance, with the exception of beta2 agonist and antibiotic prescription numbers for adult patients. Children and adults using the BAI required less GP consultations for asthma (children -30.3%, P<0.05 and adults -22.9%, P<0.05) and less GP consultations for respiratory infections than those using a traditional MDI (children -35.2%, P=0.001 and adults -10.4%, P=0.236). Adults using the BAI required less outpatient appointments than adults using an MDI (-43.7%, P=0.166). All non-prescription resource results reached statistical significance with the exception of GP consultations for respiratory infections and outpatient visits in the adult group. In conclusion, children and adults using the BAI appear to have better asthma control than children and adults using an MDI as evidenced by fewer relief medication prescriptions and less healthcare resource use.

Administration, Inhalation↗
PubMed2003

A qualitative study of Australian GPs' attitudes and practices in the diagnosis and management of attention-deficit/hyperactivity disorder (ADHD).

BACKGROUND: The importance of general practice involvement in the care of attention-deficit/ hyperactivity disorder (ADHD) is increasing due to the rising numbers of patients who present with the disorder. It has been suggested by consensus bodies that GPs should be identifying and referring patients at the severe end of the ADHD spectrum and managing those with less severe symptoms. However, GPs' views of their role in ADHD care are unknown. OBJECTIVE: Our aim was to explore the attitudes and practices of Australian GPs towards the diagnosis and management of ADHD. METHODS: We conducted a series of focus groups to explore GPs' beliefs regarding the causes of ADHD, their perceived role in ADHD diagnosis and management and their views on the role of behaviour therapies and pharmacotherapies in ADHD management. The subjects were 28 GPs in six focus groups. RESULTS: GPs in this study did not want to be the primary providers of care for patients with ADHD. Participants indicated a preference to refer the patient to medical specialists for diagnosis and treatment of ADHD, and expressed low levels of interest in becoming highly involved in ADHD care. Concerns about overdiagnosis and misdiagnosis of the disorder, diagnostic complexity, time constraints, insufficient education and training about the disorder, and concerns regarding misuse and diversion of stimulant medications were the reasons cited for their lack of willingness. CONCLUSIONS: The Australian GPs in this study identify a role for themselves in ADHD care which is largely supportive in nature, and involves close liaison with specialist services.

Adult↗
PubMed2003

Evaluating integrated urban water systems alternatives for Brisbane, Australia.

The Brazil Development Study investigates the feasibility of alternative approaches to providing sustainable water services to a 226 ha mixed residential and industrial greenfield development within the city of Brisbane, Australia. The alternatives include techniques such a the use of rainwater tanks, water use efficiency, a local wastewater treatment plant for recycling of reclaimed water and composting toilets amongst others. This paper evaluates a series of urban development scenarios against the objectives of the study. The insights gained into the drivers for cost and environmental impact for this particular site are discussed as well as a number of issues of concern and challenges to Council and the community.

Cities↗
PubMed2002

CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours.

We have recently shown that the CHEK2*1100delC mutation acts as a low penetrance breast cancer susceptibility allele. To investigate if other CHEK2 variants confer an increased risk of breast cancer, we have screened an affected individual with breast cancer from 68 breast cancer families. Five of these individuals were found to harbour germline variants in CHEK2. Three carried the 1100delC variant (4%). One of these three individuals also carried the missense variant, Arg180His. In the other two individuals, missense variants, Arg117Gly and Arg137Gln, were identified. These two missense variants reside within the Forkhead-associated domain of CHEK2, which is important for the function of the expressed protein. None of these missense variants were present in 300 healthy controls. Microdissected tumours with a germline mutation showed loss of the mutant allele suggesting a mechanism for tumorigenesis other than a loss of the wild type allele. This study provides further evidence that sequence variation in CHEK2 is associated with an increased risk of breast cancer, and implies that tumorigenesis in association with CHEK2 mutations does not involve loss of the wild type allele.

Adult↗
PubMed2001

The patient-physician relationship. Teaching the human dimensions of care in clinical settings.

Despite repeated calls to emphasize the humanistic dimensions of care during medical education, these are few known techniques for effective teaching of humanism. We describe the barriers that inhibit humanistic teaching and suggest pragmatic teaching methods to overcome such barriers and teach humanistic care in clinical settings. We began by asking participants at a conference on patient-physician communications sponsored by the American Academy on Physician and Patient in June 1998, "What can we do in the patient's presence to improve and teach the human dimensions of care? Please provide one or more examples of approaches you found to be effective." We augmented this information with suggestions from a number of colleagues in other settings. In a series of iterations, we analyzed all their suggestions to identify key teaching methods. We found that barriers to teaching humanism largely consist of elements of the informal and hidden curricula in medical schools. We then defined methods to help teachers overcome these barriers. Specific methods fall into the 3 categories of taking advantage of seminal events, role modeling, and using active learning skills. We believe that formal courses and other well-motivated endeavors that take place away from patients fail to foster humanistic care. In contrast, we present pragmatic teaching methods that can be used in the fast-paced setting of the clinical environment.

Education, Medical↗
PubMed2001

The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants.

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal fatty acid-binding protein polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or microsomal triglyceride transfer protein mass and activity. Similarly, the alanine to threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis.

Absorption↗
PubMed2001

Prenatal diagnosis of suprasellar arachnoid cyst and postnatal endoscopic treatment.

Arachnoid cysts are benign developmental anomalies that occur in the cerebrospinal axis in relation to the arachnoid membrane. An antenatal ultrasound scan first raises the suspicion of arachnoid cysts, but misdiagnoses have been reported. Confirmatory antenatal magnetic resonance imaging (MRI) is very useful to delineate anatomical detail and help in correct diagnosis. This helps proper counselling and treatment planning. Controversy also surrounds the surgical management, in terms of both the indications and the procedures employed. We report the successful endoscopic treatment, in a neonate, of an arachnoid cyst diagnosed by antenatal ultrasound and MRI. In this case accurate diagnosis and detailed assessment led to objective counselling and helped to optimise neonatal management.

Adolescent↗
PubMed2001

Mesotrione: a new selective herbicide for use in maize.

Mesotrione is a new herbicide being developed for the selective pre- and post-emergence control of a wide range of broad-leaved and grass weeds in maize (Zea mays). It is a member of the benzoylcyclohexane-1,3-dione family of herbicides, which are chemically derived from a natural phytotoxin obtained from the Californian bottlebrush plant, Callistemon citrinus. The compound acts by competitive inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), a component of the biochemical pathway that converts tyrosine to plastoquinone and alpha-tocopherol. Mesotrione is an extremely potent inhibitor of HPPD from Arabidopsis thaliana, with a Ki value of c 6-18 pM. It is rapidly taken up by weed species following foliar application, and is distributed within the plants by both acropetal and basipetal movement. Maize is tolerant to mesotrione as a consequence of selective metabolism by the crop plant. Slower uptake of mesotrione, relative to susceptible weed species, may also contribute to its utility as a selective herbicide for use in maize.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed2001

In vitro inhibition studies of phytoene desaturase by bleaching ketomorpholine derivatives.

The herbicidal activities of homochiral steroisomeric 5-methy1-2-(3-trifluoromethybenzyl)-3-keto- morpholine derivatives were investigated in vitro as inhibitors of phytoene desaturase, a key enzyme in carotenoid biosynthesis. It was demonstrated that ketomorpholines are classical bleaching compounds which directly inhibit phytoene desaturase, accumulating phytoene at the expense of colored carotenoids. Ketomorpholines interact with phytoene desaturase in a noncompetitive manner with respect to phytoene. A structure-activity investigation for in vitro inhibition of phtoene desaturase activity revealed that the relative and absolute stereochemistry is important for optimum inhibition for the 5-methyl derivatives, and that the distance of the phenyl group from the ketomorpholine ring is critical for the inhibitory potential. The average herbicidal score on 7 weeds and the in vitro I(50) values related very well with the exception of two compounds. It was postulated that the discrepancies may possibly occur through modification in plants to compounds that are either more or less active herbicides.

Carotenoids↗
PubMed2001

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women.

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women Fifteen healthy premenopausal female volunteers underwent weekly nipple aspiration of ductal fluid from both breasts during two menstrual cycles to investigate the variability of the cellular profile of the ductal fluid. Ductal fluid was successfully obtained using breast massage and nipple-areolar suction from 247/280 (89%) breasts. 83% of samples available for cytological analysis were cellular and 30% of cellular aspirates contained ductal epithelial cells identified using standard morphological criteria. No significant variation in cell number or cell type was identified during the menstrual cycle. All samples tested had an 'H' score of zero for oestrogen receptor. Seven out of 14 women expressed the proliferation marker Mcm-2 in the cells of at least one of the specimens, with no evidence of a menstrual cycle influence on expression. In conclusion, the cellular profile of breast ductal fluid did not vary consistently during the menstrual cycle, permitting future breast cancer screening studies incorporating serial nipple aspirations to be performed independent of the phase of the cycle.

Adult↗
PubMed2001

Rectal temperature measurement results in artifactual evidence of selective brain cooling.

Selective brain cooling (SBC) is defined as a brain temperature cooler than the temperature of arterial blood from the trunk. Surrogate measures of arterial blood temperature have been used in many published studies on SBC. The use of a surrogate for arterial blood temperature has the potential to confound proper identification of SBC. We have measured brain, carotid blood, and rectal temperatures in conscious sheep exposed to 40, 22, and 5 degrees C. Rectal temperature was consistently higher than arterial blood temperature. Brain temperature was consistently cooler than rectal temperature during all exposures. Brain temperature only fell below carotid blood temperature during the final few hours of 40 degrees C exposure and not at all during the 5 degrees C exposure. Consequently, using rectal temperature as a surrogate for arterial blood temperature does not provide a reliable indication of the status of the SBC effector. We also show that rapid suppression of SBC can result if the animals are disturbed.

Animals↗
PubMed2001

Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I).

Increased stiffness of the conduit arteries has been associated with increased risk of death and cardiovascular death in a number of populations. None of these populations, however, are fully representative of the US population. The cohort examined in the First National Health and Nutrition Examination Survey (NHANES I) that was free of overt cardiovascular disease was selected to be representative of the US population. We assessed and quantified the increased risk of death associated with elevated pulse pressure in this population. A cohort of 5771 subjects from NHANES I was used to determine the value of adding pulse pressure to standard cardiovascular disease risk factors for assessment of the risk of death during a mean follow-up period of 16.5 years. Analyses were performed by use of the SUDAAN statistical package for performing Cox proportional regression, logistic regression, and other standard methods in complex, weighted samples. Pulse pressure increased with increasing age, body mass index, cholesterol level, and mean arterial pressure. With increasing pulse pressure, the percentage of cigarette smokers decreased and the percentage of diabetics increased. Despite these associations with known risk factors, pulse pressure was independently predictive of an increased risk of death from cardiovascular disease, coronary heart disease, and all-cause mortality. It provides independent prognostic information beyond that provided by known risk factors that were evaluated in this study, including the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension classification. A 10 mm Hg increase in pulse pressure in persons 25 to 45 of age was associated with a 26% increase in risk of cardiovascular death (95% confidence interval [CI], 5 to 50) and with an 10% increase (95% CI, 2 to 19) in persons 46 to 77 years of age. In a cohort designed to be representative of the US population, elevated pulse pressure has been shown to provide independent prognostic information. This variable may be a marker for the extent of vascular disease and may contribute to the occurrence of clinical events.

Adult↗
PubMed2001

Infertility and testicular defects in hormone-sensitive lipase-deficient mice.

The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, where a specific 120-kDa testis-specific isoform is expressed, is unknown. To study this, we examined the fertility and testicular histology of gene-targeted hormone-sensitive lipase-deficient mice. Homozygous hormone-sensitive lipase-deficient male mice are infertile and have decreased testis weights; female homozygotes are fertile. Testicular abnormalities, detected at the light and electron microscopic levels, included the presence of multinucleated round and elongating spermatids, vacuolization of the seminiferous epithelium, asynchronization of the spermatogenic cycle, sloughing of postmeiotic germ cells from the seminiferous epithelium into the lumen, and a marked reduction in the numbers of late spermatids. Extensive nuclear head deformation was noted in late spermatids as well as the sharing of a common acrosome in multinucleated cells. In some multinucleated cells, nuclei were separated from their acrosomes, with the acrosomes remaining attached to areas of ectoplasmic specializations, suggesting defects in intercellular cytoplasmic bridge integrity. Although the lumen of the epididymis was essentially devoid of spermatozoa and filled instead with spherical degenerating cells, the epididymal epithelial cells appeared normal. The few late spermatids present in the epididymis were abnormal. There was no morphological evidence, as judged by the absence of lipid droplets of triacylglycerol or cholesteryl ester accumulation in the testis. Together, the data suggest that hormone-sensitive lipase deficiency results in abnormalities in spermiogenesis that are incompatible with normal fertility. We speculate that a metabolite downstream from the hormone-sensitive lipase reaction may be essential for membrane stabilization and integrity in the seminiferous epithelium and, in particular, may play an important role in the maintenance of intercellular cytoplasmic bridges between postmeiotic germ cells.

Animals↗
PubMed2001

Coping, burnout, and emotion in staff working in community services for people with challenging behaviors.

Staff in mental retardation services identify challenging behavior as a significant source of work-related stress. However, there has been little examination of the psychological processes that may explain an association between challenging behavior and staff stress. In the present study, direct-care staff (N = 83) from five community services completed a questionnaire on their emotional reactions to aggressive behavior, the coping strategies that they employ, and their experience of burnout. Staff more frequently reported using adaptive strategies than maladaptive ones to cope with aggressive behavior. Regression analyses showed that staff disengagement and adaptive coping strategies and their emotional reactions to aggressive behavior predicted burnout scores. Implications of these results for future research and for staff mental health are discussed.

Adaptation, Psychological↗
PubMed2001

Developing palliative care services in regional areas. The Ipswich Palliative Care Network model.

BACKGROUND: Although there are over 350 palliative care services present in Australia and New Zealand, the distribution of these is patchy. Patients in some regional and rural areas have little or no access to specialist services, and manage with the enthusiasm and general expertise of local practitioners. OBJECTIVE: This paper discusses the problems encountered in maintaining skills in palliative care in the face of small patient numbers and poor resources, and describes a solution that was developed in Ipswich, Queensland. DISCUSSION: The twin problem of GP skills maintenance and adequate community service provision in palliative care can be overcome by developing a general practice based service in conjunction with local health authorities and the community. Highlighting the benefits to the health authority and the community of maximal general practitioner involvement is the most important lever in securing cooperation.

Australia↗