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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 19 recordsLinked to original sources

Genetic predisposition to cancer: the consequences of a delayed diagnosis of Gorlin syndrome.

This report outlines a case of Gorlin syndrome, the diagnosis of which was delayed for many years, and raises a number of important issues. These are the spectrum of late radiotherapy effects, particularly after treatment for benign disease, and the importance of considering the possibility of the presence of a genetic syndrome predisposing to cancer in all individuals before starting any treatment. As our knowledge of genetic syndromes expands, this will become increasingly important. Finally, if a genetic predisposition to cancer is suspected, consideration should be given to obtaining a blood sample from the affected patient for DNA storage, particularly if their prognosis is limited. Currently, genetic testing can only be instituted in most families by first obtaining DNA from an individual affected by cancer, as most genetic mutations are unique to a family. If all relatives with cancer have died, then, at this time, genetic testing cannot usually be attempted, unless such samples have previously been stored.

Aged↗

Planning research in rural and remote areas.

INTRODUCTION: In order to set a regional research agenda, an interactive research workshop was planned by the joint University of Queensland and University of Southern Quennsland Centre for Rural and Remote Area Health (CRRAH), in which researchers and regional organisations would meet together to discuss and prioritise local research needs, then formulate constructive ideas and activities. METHODS: Selection of Participants: Organisations representing all key consumer, academic and health professionals within the Toowoomba, Queensland, Australia region were sent a letter inviting them to attend and to send at least one representative, resulting in a total of 75 workshop participants from 45 organisations representing 20 separate entities. The Design of the Workshop: The workshop was planned as an interactive research workshop, with a preliminary brainstorming to identify and prioritise topics, followed by facilitated small group discussions, and finally presentations to the reassembled total group. RESULTS: Forty three topics were put forward by participants during the plenary session, in which the following 12 major themes were evident: (1) health professional development and support; (2) mechanisms for identifying regional/local needs; (3) mental health; (4) health and interaction with the environment; (5) management of common conditions of which little is known; (6) post acute/aged care; (7) evidence based practice; (8) health workforce including volunteers; (9) indigenous health; (10) access to health service delivery; (11) economic impact of new programs; and (12) outcomes impact of research partnerships. Five subject areas from four of these themes were chosen for further small group discussion. A summary of the views, ideas and conclusions of each group, which were presented to a plenary session of reassembled participants over a 10-15 minute period by each group facilitators, are discussed below. Following each presentation, a 5-10 minute question session was provided after each topic. CONCLUSION: A workshop, enabling rural and remote organisations and regional researchers to meet and identify local research needs attracted strong local support. Although the final benefits of the workshop remain to be determined, a number of new collaborative research avenues are now being actively explored within the region, by a number of the participants.

Journal Article↗

Burnout in direct care staff in intellectual disability services: a factor analytic study of the Maslach Burnout Inventory.

BACKGROUND: There is gathering research interest in the well-being of staff working in services for people with intellectual disability (ID), including the assessment of burnout and its correlates. However, no previous studies have considered the applicability of the main three dimensions of burnout to staff in ID services. METHODS: Data were analysed from two samples of staff (total n=184) who participated in research studies that included completion of the Maslach Burnout Inventory (MBI). RESULTS: Nineteen of the MBI items loaded clearly onto factors closely resembling the three original subscales: emotional exhaustion, depersonalization and personal accomplishment. Internal consistency for the three MBI subscales was fair to good (range 0.68-0.87). CONCLUSIONS: The original three MBI dimensions were found to be highly relevant to the present sample of staff. The analyses support the construct validity and reliability of the MBI for staff in ID services.

Adult↗

Training and supporting GPs in providing palliative care to a Vietnamese-Australian community.

The mooted increasing role for general practitioners to provide palliative care for an aging Australian population has raised the need for improved training and support for GPs to provide 'healthcare for dying people that maximizes quality of life and assists families and carers during and after death'. In order to address this need, the Commonwealth Department of Health and Ageing commissioned a study into the education, training and support needs of GPs in palliative care. This article reports one element of this national study: the needs of GPs who provide palliative care to a Vietnamese-Australian community in Sydney, New South Wales.

Australia↗

Batch growth of Salmonella typhimurium LT2: stoichiometry and factors leading to cessation of growth.

Salmonella typhimurium LT2 was grown in batch culture (trypticase soy broth, with 0.3%(w/v) yeast extract, 1% (w/v) glucose and 0.5% (w/v/) NaCl, 20 degrees C) at a range of initial pH (4.4, 4.8, 5.0 and 7.0). The consumption of oxygen and glucose was found to be independent of initial pH, and stoichiometric with growth. Mean yield coefficients of 6.9 x 10(-15) and 15.5 x 10(-15) mol oxygen/cell were estimated. Calculation of the instantaneous state of carbon during the cultivation showed stoichiometric conversion of glucose into biomass, carbon dioxide and organic acids. The concentration of the undissociated form of the primary acidic product (acetic acid) was shown to be the factor limiting growth.

Acetic Acid↗

Pre-operative short-course radiotherapy is associated with faecal incontinence after anterior resection.

OBJECTIVE: To determine the contribution of total mesorectal excision (TME), short-course pre-operative radiotherapy (SCRT), the level of the anastomosis and other putative contributory factors to the incidence and degree of faecal incontinence after anterior resection of the rectum. PATIENTS AND METHODS: Survivors of anterior resection of the rectum performed between February 1996 and February 2001, with a functioning anastomosis, were asked to complete a telephone questionnaire regarding their current bowel habit. Faecal incontinence was scored using the St. Mark's Incontinence Score. RESULTS: The median age of 124 patients who completed the questionnaire was 76 years. Of these, 104 patients had neoplastic disease, 66 (53%) patients exhibited some degree of incontinence, median St. Marks' Score 6, interquartile range 3-10. There was a significant association between the anastomotic level, and the St. Mark's Score (P < 0.0001, linear regression). Male sex (P = 0.047), SCRT (P = 0.0014) and an anastomotic leak (P = 0.038) were associated with significantly higher incontinence scores. Age, splenic flexure mobilization, TME, anastomotic configuration or use of a temporary stoma had no detectable independent effect on incontinence scores. CONCLUSIONS: Poor functional outcome following anterior resection was associated with a low anastomosis, SCRT or an anastomotic leak. The finding that SCRT was a predictor of postoperative incontinence emphasizes the need for stringent patient selection for this treatment modality.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗