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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 73 records · Page 4Linked to original sources

Saguenay Lac Saint Jean cytochrome oxidase deficiency: sequence analysis of nuclear encoded COX subunits, chromosomal localization and a sequence anomaly in subunit VIc.

A biochemically distinct form of cytochrome oxidase (COX) deficiency found in the Saguenay region of Quebec is an autosomal recessive trait. The cDNA sequences of all 10 nuclear-encoded subunits from a patient's fibroblasts showed normal coding sequence. Sequences for subunit VIc in two atypical patients showed a heterozygous base substitution. Subunit VIc was localized to chromosome 18.

Animals↗

Histological studies of the dorsal nasal, angularis oculi, and facial veins of sheep (Ovis aries).

Selective brain cooling (SBC) requires vasoactivity in the superficial veins of the face of the animal. This vasoactivity is possible because of an adequate amount of smooth muscle in the tunica media of each of these superficial vessels, enabling it to act as a "muscle sphincter". In this study, the angularis oculi, dorsal nasal, distal, and proximal parts of the facial veins in sheep were examined histologically to describe an anatomical basis for SBC. Measurements of the tunica media thickness, the lumen diameter, and the ratio of these measurements showed that the relative tunica media thicknesses in the angularis oculi vein and the dorsal nasal vein are statistically smaller (P < 0.001) than in the distal or the proximal parts of the facial vein. In the angularis oculi, dorsal nasal, and distal part of the facial vein, the tunicae mediae were composed of five to seven circularly arranged smooth muscle layers, suggesting their ability to vasoconstrict. The proximal part of the facial vein possesses both circularly and longitudinally arranged smooth muscle layers. The circular smooth muscle layers suggest a vasoconstrictory function, whereas the longitudinal smooth muscle layers suggest a vasoconstrictory function in this part of the facial vein. Both the dorsal nasal and the proximal part of the facial vein, but not the angularis oculi or the distal part of the facial vein, possess endothelial valves near their confluences with other veins. It was concluded from this study that the angularis oculi and the distal part of the facial vein vasoconstrict, whereas the proximal part of the facial vein vasodilates, enabling the necessary changes in blood flow in SBC.

Animals↗

A model of bridging angiogenesis in the rat.

A model of angiogenesis has been developed in the rat. The epigastric vascular pedicle was exposed in the groin, a 7 mm segment of epigastric artery was excised leaving the vein intact and, after a variable period of time for angiogenesis to occur between the ends of the artery, a skin flap was elevated on the epigastric vascular pedicle so that it depended completely for its blood supply on bridging angiogenesis across the created gap. Skin flap survival and vessel counts were measured as indices of the angiogenic response. In this model we observed a spontaneous increase in vessel counts between the ends of the artery, and a corresponding increase in skin flap tissue survival until day 10 after which time vessel counts plateaued whilst tissue survival continued to increase until day 14. In the angiogenic pedicle, a time-dependent development of granulation tissue containing numerous macrophages and mast cells, and capillary sprouting were documented. When flap elevation was performed 7 days after arterial excision skin flap survival was 42%. Thus, in this model, 7 days is a suitable interval for the future evaluation of the effects of either pro- or anti-angiogenic agents.

Animals↗

Excision and low-dose radiotherapy for refractory laryngeal granuloma.

Laryngeal granulomas are uncommon lesions of an inflammatory origin. They are conventionally managed by simple excision with the occasional use of adjuvant treatment depending on the aetiological factors. Unfortunately, recurrences can occur, requiring repeated excision. Some lesions are refractory to this approach and alternative management approaches include excision and immediate adjuvant radiotherapy. The use of radiotherapy in the management of benign disease can be limited by the risk of induction of late malignancy and informed consent of a patient must include an assessment of this risk. We describe a case of refractory laryngeal granuloma successfully treated by excision and immediate radiotherapy in a patient occupationally dependent upon his voice.

Combined Modality Therapy↗

High dose behind inhomogeneities during medium-energy x-ray irradiation.

Medium-energy x-rays from orthovoltage treatment units are used for a variety of radiotherapy treatments ranging from cutaneous malignancies in the head and neck region to bone metastases. It was the aim of the present study to investigate the dose distribution due to secondary electrons close behind inhomogeneities in these radiation qualities. The dose was assessed in a solid water phantom using three plane-parallel ionization chambers (NE 2532/2, 'Markus' and 'Attix' chamber) and sheets of aluminium, copper, zinc, platinum, lead and bone equivalent material. The depth dose distribution directly behind the inhomogeneity was assessed using sheets of 15 microm thick polyethylene foil. A dose increase was found directly behind inhomogeneities of high atomic number with a rapid dose fall-off over the first 100 microm. The dose downstream of the inhomogeneity was found to increase with increasing beam quality from 120 kVp (HVL 2.8 mm Al) to 250 kVp (HVL 2 mm Cu). In the latter the dose was increased directly behind lead and platinum sheets by up to a factor of eight compared with a solid water depth of similar attenuation. The results of the study demonstrate the importance of using appropriate materials if shielding is in contact with the patient.

Bone Neoplasms↗

Assessment of GP management of symptoms of dying patients in an Australian community hospice by chart audit.

BACKGROUND: With specialist palliative care services becoming widespread, and the place of the GP in palliative care being examined, audit of patient care delivered by GPs is required in order to ensure adequate standards of care. OBJECTIVE: We aimed to evaluate symptomatic care delivered to palliative care patients by GPs in an Australian community hospice with a developed quality assurance programme. METHODS: The study was set in a newly established community-based, GP-run hospice in a provincial city in Queensland, Australia. A chart audit was carried out of the first 20 patients admitted to a community-based hospice, in order to establish (i) whether attempts were made by the treating doctor to find the direct cause of symptoms before initiating management; and (ii) whether management accorded with developed consensus-based guidelines. RESULTS: Twenty patients were treated by 14 GPs; 135 new symptoms were identified in the records of these patients. Of the 125 symptoms for which guidelines could be identified in the literature, in 87 (70%) an attempt by the treating GP to find a direct cause could be demonstrated. Of the 114 symptoms with treatments defined in the guidelines, 107 (90%) treatments conformed to the guidelines. Constipation, nausea/vomiting, anorexia and back pain were the conditions for which there were the fewest attempts at establishing a direct cause before treatment. In most cases these conditions were treated in accordance with the guidelines. CONCLUSION: Quality assurance mechanisms present in an in-patient palliative care setting appear to be associated with high-quality care by GPs.

Aged↗

Learning disability care staff's emotional reactions to aggressive challenging behaviours: development of a measurement tool.

OBJECTIVES: To describe the development of a rating scale measure of caregivers' emotional reactions to aggressive challenging behaviour, and to report preliminary psychometric data for the scale. DESIGN: Using previous research on staff working with people with learning disabilities, a range of likely emotional reactions to challenging behaviours were selected for possible inclusion in a rating scale measure. METHODS: A total of 83 care staff from 23 community residences for people with learning disabilities rated their recent emotional reactions to aggressive challenging behaviour using 18 emotion items. A further sample of 18 care staff participated in a test-retest study after the initial stages of scale development. RESULTS: A rating scale was developed on the basis of a factor analysis and further item analysis. The measure has two subscales: feelings of depression/anger (10 items), and feelings of fear/anxiety (5 items). The subscales have a high internal consistency, good test-retest reliability and are relatively unaffected by social desirability biases. CONCLUSIONS: The emotional reactions to aggressive challenging behaviour scale has excellent face and construct validity, and other preliminary psychometric data are promising. The scale has a number of potential research and clinical applications.

Activities of Daily Living↗

An electrophysiological method for measuring the potassium permeability of the nerve perineurium.

An electrophysiological method is described for measuring the potassium permeability (PK) of the perineurium of the sciatic nerve of the frog. The method is based on the principle of grease-gap recording, in which an insulating compartment separates two surface recording electrodes. The sciatic nerves of frogs Rana temporaria and R. pipiens were isolated and mounted across a five compartment chamber, with Vaseline grease seals on the partitions between compartments. Compartments #1, #2 and #5 contained frog Ringer solution, #4 was filled with Vaseline and formed the grease gap, and #3 was the test compartment in which solutions could be changed. The nerve was stimulated via platinum electrodes in compartments #1 and #2, and DC potentials and compound action potentials (CAP) were recorded between Ag/AgCl electrodes connected through Ringer-agar bridges to compartments #3 and #5. In nerves with undamaged perineurium, changing from normal Ringer to high [K+] Ringer (100 mM, KCl replacing NaCl) for 2 min caused negligible change in DC potential or CAP, indicating that raised [K+] was not reaching the axon surface, and hence that the perineurium was exerting a diffusional restriction on K+ entry. In nerves damaged by stretching or drying, K+ pulses caused a depolarising change in DC potential (delta DC), and corresponding decline in CAP amplitude, consistent with a leaky perineurium allowing K+ entry and axonal depolarisation. Ringer made hypertonic by the addition of 2.5 M sucrose or 5 M NaCl caused increased perineurial permeability to K+. The method was calibrated by measuring the delta DC in response to raised [K+] in the range 5-100 mM [K+] in desheathed nerves; from this calibration curve relating delta DC to endoneurial [K+] it was possible to calculate the change in endoneurial [K+] occurring in intact preparations. The calculations showed that the undamaged perineurium had a PK of < 6.3 x 10(-7) cm.s-1, similar to the value calculated for in situ nerves using radioisotopic techniques, but less than the value reported for isolated perineurial cylinders. The method gives real-time information on the K+ permeability of the nerve perineurium and its modulation by experimental treatments.

Animals↗

Chromosomal localization of the human liver form cytochrome c oxidase subunit VIIa gene.

The chromosomal loci corresponding to human cytochrome c oxidase (COX) subunit VIIa Liver (VIIa-L) isoform genes were determined utilizing a combined approach of genomic cloning, in situ hybridization, and somatic hybrid genetics. In contrast to the proposal of E. Arnaudo et al. (Gene (Amst.), 119: 299-305, 1992) that COX VIIa-L sequences are located on chromosomes 4 and 14, we found that COX VIIa-L related sequences reside on chromosome 6, while an additional COX VIIa-L cross-reacting sequence psi-gene) was located on chromosome 4.

Animals↗

Selective brain cooling: role of angularis oculi vein and nasal thermoreception.

We have measured blood flows in the angularis oculi (AOV), facial, and jugular veins and temperatures in the carotid artery and near the hypothalamus in three lightly anesthetized sheep while body and nasal mucosal (Tnm) temperatures were varied independently. Above a threshold hypothalamic temperature (Thyp) of 39 degrees C both selective brain cooling (SBC) and AOV blood flow increased. For a given Thyp, the increase in AOV flow and SBC was inversely proportional to Tnm: low Tnm resulted in high AOV flow and SBC, whereas increasing Tnm attenuated both AOV flow and SBC. This decrease in AOV flow results in submaximal SBC, which does not concur with the hypothesis that SBC functions to protect a thermally vulnerable brain. The trigger for these changes in AOV blood flow was Tnm. Occlusion of the AOV during SBC showed that AOV flow accounted for over 80% of SBC. We conclude that SBC is not only a mechanism for reducing brain temperature but may also be a means of adjusting Thyp to facilitate the appropriate thermoregulatory responses.

Animals↗

Do actions reported by physicians in training conflict with consensus guidelines on ethics?

OBJECTIVE: To assess the extent to which actions reported by internal medicine trainees conflict with published guidelines on ethics. METHODS: A confidential survey was sent to a random sample (N = 1000) of associate members of the American College of Physicians (ACP). Questions were asked about ethical decision making in areas addressed by the guidelines in the ACP Ethics Manual. Quoted manual guidelines were provided, followed by 55 yes or no questions, such that a yes answer represented an action that conflicted with a guideline. There were two follow-up mailings to nonresponders. RESULTS: Forty percent (n = 397) completed the questionnaire; 17% indicated they were aware of the guidelines on ethics. On average, associates responded yes to 16% of questions where a yes response indicated they have acted outside guidelines on ethics one or more times. The mean number of responses (n = 55) that conflicted with a guideline was 7.6 per person (SD, 4.7 responses; range, 0 to 33 responses). Ninety-eight percent of respondents reported actions falling outside a guideline one or more times and 80% did so four or more times. The most frequently reported reason (965/3219 [30%]) from a list of four choices for acting outside a guideline was "I was aware of the guideline, but this did not represent an ethical dilemma to me." CONCLUSIONS: Few responding ACP associates indicated awareness of the ACP guidelines on ethics. Physicians in training nevertheless reported acting according to the presented guidelines most of the time, although nearly all respondents acted outside a guideline at least once, and some did so many times. Reported behaviors were sometimes inconsistent with consensus ethical standards that apply to internists. Physicians in training need to know more about ethical standards that apply to their own practice and should be aware when their actions deviate from ethical norms. Before acting outside guidelines on ethics, trainees should discuss their conflicts with others, such as attending physicians, clinical ethicists, or hospital ethics committees.

Codes of Ethics↗

Evaluation of multiple sclerosis by 1H spectroscopic imaging at 4.1 T.

The authors report on high-field (4.1 T) magnetic resonance 1H spectroscopic imaging studies on eight patients with relapsing remitting multiple sclerosis (mean expanded disability status scale (EDSS) 1.0) and eight normal controls. Using T1-weighted imaging to determine lesion position, the authors found the ratios of choline/N-acetyl (NA) compounds and creatine/NA were increased significantly in the multiple sclerosis (MS) patients relative to controls in lesioned tissue, adjacent to lesion, far removed from lesions as well as in periventricular tissue. The gray matter creatine/NA was mildly increased (P < 0.01) in the MS patients, whereas the elevated gray-matter ratio of choline/NA was of borderline significance (P = 0.13). A more detailed comparison of white-matter and mean gray-matter metabolite values indicates that creatine is increased greatest in areas far from lesions. This is in contrast to choline, which was greatest in lesions, and NA, which was smallest in lesions. It is postulated that the creatine increase may reflect an astrocytic (gliotic) or oligodendrocytic remyelinating process. The increased choline most likely reflects varying levels of inflammation and membrane turnover, whereas the NA decrease is representative of axonal dysfunction or loss.

Adult↗

Chronic sodium benzoate therapy in children with inborn errors of urea synthesis: effect on carnitine metabolism and ammonia nitrogen removal.

Sodium benzoate (SB) therapy is known to increase ammonia (NH3) nitrogen elimination via conjugation with glycine and excretion as urinary hippurate. In 16 children with inborn errors of urea synthesis we studied two issues: (1) the effect of chronic SB administration upon carnitine metabolism and (2) the efficacy of chronic SB therapy as measured by the molar ratio of hippurate excretion to SB intake. Measurements were performed during elective hospitalizations when the patients were in stable metabolic condition. We found that chronic SB therapy is not associated with a constant level of hippurate elimination and that interindividual and intraindividual variability may result in irregular removal of NH3 nitrogen. This variability may be due to various factors including the formation of small quantities of benzoylcarnitine, which was detected in the plasma of three of four patients receiving SB and carnitine therapy and in one of two patients on SB therapy without carnitine supplementation. The ratios of acyl to free carnitine were elevated in both plasma and urine in patients not receiving carnitine supplementation, but were normal in patients receiving supplementation.

Adolescent↗