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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed2000

Managing ADHD in general practice. N of 1 trials can help!

OBJECTIVE: To pilot single patient trials designed to improve decision making about stimulant use for attention deficit hyperactivity disorder (ADHD) in general practice. METHOD: Patients previously stabilised on dexamphetamine were enrolled from a general practice. Each undertook a six week same patient randomised, double blind, placebo controlled crossover comparison of dexamphetamine with placebo for ADHD. Rating scales were completed weekly by self, parent and teacher. RESULTS: Three of the four patients were clear responders to dexamphetamine (including a noncompleter, as his results still demonstrated a clear response). The results were clinically useful in each case. Management was confirmed for three patients and changed for one (who ceased dexamphetamine). DISCUSSION: Prescribing stimulant medications only to children with diagnosed ADHD and who are found to respond, limits use of these worrisome drugs to those who will respond, and minimises their use in those who will not benefit.

Adolescent↗
PubMed1999

Children's weights: guess or measure by tape?

Children's doses of drugs are prescribed according to bodyweight but in resource-poor countries weighing scales may be unavailable, inaccurate, or broken. We designed a length/weight tape for use in our community and found it reasonably accurate for weights of 4-16 kg and better than a clinician's guess.

Body Height↗
PubMed1999

Metalloproteinases are involved in lipopolysaccharide- and tumor necrosis factor-alpha-mediated regulation of CXCR1 and CXCR2 chemokine receptor expression.

The neutrophil-specific G-protein-coupled chemokine receptors, CXCR1 and CXCR2, bind with high affinity to the potent chemoattractant interleukin-8 (IL-8). The mechanisms of IL-8 receptor regulation are not well defined, although previous studies have suggested a process of ligand-promoted internalization as a putative regulatory pathway. Herein, we provide evidence for two distinct processes of CXCR1 and CXCR2 regulation. Confocal microscopy data showed a redistribution of CXCR1 expression from the cell surface of neutrophils to internal compartments after stimulation with IL-8, whereas stimulation with bacterial lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) did not induce CXCR1 internalization but instead mediated a significant loss of membrane-proximal CXCR1 staining intensity. To investigate whether proteolytic cleavage was the mechanism responsible for LPS- and TNF-alpha-induced downmodulation of IL-8 receptors, we tested a panel of proteinase inhibitors. The downmodulation of CXCR1 and CXCR2 by LPS and TNF-alpha was most dramatically inhibited by metalloproteinase inhibitors; 1, 10-phenanthroline and EDTA significantly attenuated LPS- and TNF-alpha-induced loss of CXCR1 and CXCR2 cell surface expression. Metalloproteinase inhibitors also blocked the release of CXCR1 cleavage fragments into the cell supernatants of LPS- and TNF-alpha-stimulated neutrophils. In addition, while treatment of neutrophils with LPS and TNF-alpha inhibited IL-8 receptor-mediated calcium mobilization and IL-8-directed neutrophil chemotaxis, both 1, 10-phenanthroline and EDTA blocked these inhibitory processes. In contrast, metalloproteinase inhibitors did not affect IL-8-mediated downmodulation of CXCR1 and CXCR2 cell surface expression or receptor signaling. Thus, these findings may provide further insight into the mechanisms of leukocyte regulation during immunologic and inflammatory responses.

Antigens, CD↗
PubMed1999

Bacterial superantigens induce down-modulation of CC chemokine responsiveness in human monocytes via an alternative chemokine ligand-independent mechanism.

Staphylococcal superantigens (SAgs) are very potent T cell mitogens, but they can also activate monocytes by binding directly to MHC class II molecules in a manner independent of TCR coengagement. Induction of proinflammatory cytokines and chemokine expression in monocytes by superantigens has recently been reported. Here we report that superantigen stimulation of human peripheral blood monocytes results in a rapid, dose-dependent, and specific down-regulation of chemokine (macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemotactic protein-1 and MIP-1beta) binding sites (e.g., CCR1, CCR2, and CCR5), which correlates with a concomitant hyporesponsiveness of human monocytes to these CC chemokine ligands. This down-regulation occurs 15-30 min following superantigen stimulation and is specific to chemokine receptors, in that binding and responsiveness of monocytes to the chemoattractant formyl-tripeptide FMLP are not affected. We further demonstrate that SAg-induced down-modulation of chemokine binding and monocyte hyporesponsiveness to the chemokines MIP-1alpha, monocyte chemotactic protein-1, and MIP-1beta is mediated through cellular protein tyrosine kinases, and the down-modulation can be mimicked by an MHC class II-specific mAb. Additionally, our observations indicate that SAg-induced loss of chemokine binding and monocyte responsiveness is probably mediated by secreted serine proteinases. Bacterial SAg-induced down-modulation of chemokine responsiveness represents a previously unrecognized strategy by some bacteria to subvert immune responses by affecting the intricate balance between chemokine and chemokine receptor expression and function.

Antigens, Bacterial↗
PubMed1999

Non-thermal signals govern selective brain cooling in pigs.

We used implanted miniature data loggers and fine thermistors to measure arterial blood and brain temperatures in four female pigs, to a resolution of 0.04 degree C, every 5 min, for 4 weeks. Within that period, pigs were exposed on different days, and in random order, to a cold (5 degrees C) or hot (38 degrees C) environment. In the thermoneutral environment of the pigs' home pens, brain temperature was usually lower than blood temperature. Such selective brain cooling was absent for 2 days after surgery, during handling and transport stress, and on waking. The magnitude of selective brain cooling was greatest when pigs were sleeping and body temperatures were low, and was smallest, or even absent, during hyperthermia and natural fever. Our results showed that selective brain cooling was present in pigs, but there was no clear relationship between blood temperature and the magnitude of selective brain cooling. Instead, the degree of selective brain cooling in pigs was governed by non-thermal factors, especially those associated with high sympathetic nervous system activity. Our results further support the concept that selective brain cooling does not serve to protect the brain from thermal damage during heat stress.

Animals↗
PubMed1999

Brain, abdominal and arterial blood temperatures of free-ranging eland in their natural habitat.

Using implanted miniature data loggers we measured brain, arterial blood and abdominal temperatures at 5-min intervals in two free-ranging eland (Tragelaphus oryx) in their natural habitat. The animals were subjected to a nychthemeral range of globe temperature which exceeded 40 degrees C. Arterial blood exhibited a moderate amplitude (2.3 degrees C) nychthemeral rhythm, with a temperature peak at 1600-1800 hours, and a trough in the early morning at 0600-0800 hours. Mean abdominal temperature was 0.2-0.3 degrees C lower than the corresponding blood temperature, and had a peak-to-trough amplitude of 2.6 degrees C. Brain temperature closely paralleled changes in blood temperature but usually exceeded blood temperature by about 0.5 degrees C. Sporadic episodes of selective brain cooling occurred in one animal, but the duration and magnitude of such cooling was small (less than 0.4 degrees C), and took place only well above the mode of blood temperature. Our results do not support the concept that eland routinely employ adaptive heterothermy and selective brain cooling to survive in their natural environment.

Abdomen↗
PubMed1999

Funding options for research: facing the market as well as government.

Parasitology is a challenge. At one level, the structural and genetic complexities of parasites provide ample technical challenges in regard to an understanding of parasite variability and adaptability, epidemiological diversity, drug resistance, etc. The intricacies of host parasite relationships including the immunology of parasitism will continually surprise yet frustrate the vaccine developer and keep the bravest immunoparasitologist busy and creative for decades. As if the technical considerations were not challenging enough, we see difficulties arising in sustaining a research endeavour and preserving a critical mass of researchers through the generation of high-level, long-term funding support. Contributing to this situation is the fact that most parasitic diseases of major impact in humans are largely centred around the rural poor in tropical, less industrially-developed countries and therefore of little or of fickle interest to the strictly commercially oriented. Moreover, the focus in the rural industries has moved away from aspects of on-farm production with lower priority given to studies on even the 'economically-important' parasites of livestock. It is contended that this may change again with pressures and clear marketing advantages to preserving a 'clean and green' image for Australia's primary industries. Overall, the extraordinary technical and conceptual advances in recent times have been tempered by uncertainties in research funding and severe cuts from some traditional sources for both fundamental and strategic/applied research in Parasitology. Several have highlighted the fact that deliverables in terms of new methods of disease control have been sparse and some claims made in the past have certainly been exaggerated. Yet the prospects and achievements at the front end of the long R&D pathway have never been brighter. In this article we examine the merits of a 'portfolio approach' to generating research funds in Parasitology and Science and Technology in Australia more generally, with an emphasis on strategies that, through welding good science with clear, medium-term product objectives, increase research funding opportunities.

Biotechnology↗
PubMed1999

Phase II evaluation of high dose accelerated radiotherapy for anaplastic thyroid carcinoma.

BACKGROUND AND PURPOSE: Anaplastic thyroid cancer responds poorly to conventional radiotherapy and prognosis in the absence of effective chemotherapy is dismal. The median survival following diagnosis is only 4 months and the majority of patients die with uncontrolled local disease. This study describes the use of accelerated radiotherapy aiming to improve local response in patients with anaplastic thyroid carcinoma. Toxicity was assessed prospectively. PATIENTS AND METHODS: Seventeen patients with anaplastic thyroid carcinoma were treated and assessed for both outcome and treatment toxicity. Eight further patients with primary carcinomas arising in the neck were also treated with this protocol but were assessed for treatment toxicity only. Patients were treated twice daily, 5 days a week, to a total dose of 60.8 Gy in 32 fractions over 20-24 days in two or three phases. RESULTS: Three patients with anaplastic carcinoma demonstrated a complete clinical response and seven patients achieved a partial response. Five patients had stable disease and two patients died before radiotherapy was completed. Toxicity from oesophagitis and dysphagia was high with 10 patients requiring intravenous fluids or nasogastric tube feeding. CONCLUSION: This approach improved the response rate to radiotherapy but toxicity was unacceptable. A modified accelerated radiotherapy protocol is being explored.

Adult↗
PubMed1999

A comparison of AIUM/NEMA thermal indices with calculated temperature rises for a simple third-trimester pregnancy tissue model. American Institute of Ultrasound in Medicine/National Electrical Manufacturers Association.

Temperature rises due to diagnostic ultrasound exposures have been calculated for a simple third-trimester pregnancy tissue model. This consisted of a layer of soft tissue representing the abdominal/uterine wall, a layer of liquid and a layer of fetal bone. The ultrasound field parameter used in the calculations was the temporal average of the square of the acoustic pressure (p2TA), measured in water but corrected for attenuation in the tissue model. The three-dimensional (3-D) distribution of p2TA was measured for five probes operating in B-mode, and four probes operating in pulsed Doppler and color flow imaging modes. The calculated temperature rises were compared to the AIUM/NEMA-defined thermal indices appropriate to third-trimester scanning. In B-mode, the ratio of calculated temperature rise to thermal index varied between 0.62 and 1.25, with calculated temperature rises as high as 1.4 degrees C. In color-flow imaging mode, this ratio varied between 1.26 and 2.45 and, in pulsed Doppler mode, between 1.46 and 2.92, with calculated temperature rises as high as 1.8 degrees C and 5.8 degrees C, respectively. These results indicate that, for scanning situations where bone is insonated through an overlying low attenuation liquid layer, the thermal index may substantially underestimate the maximum temperature rise that could occur.

Abdominal Muscles↗
PubMed1999

Ejection fraction by radionuclide ventriculography and contrast left ventriculogram. A tale of two techniques. SAVE Investigators. Survival and Ventricular Enlargement.

OBJECTIVES: We assessed the abilities of two methods to measure ejection fraction (EF)-radionuclide ventriculography (RVG) and contrast left ventriculography (Cath-EFa) to predict cardiovascular events. BACKGROUND: Both RVG and Cath-EFa are commonly used methods to measure left ventricular performance and assess prognosis. Their comparative abilities to predict clinical events have not been reported. METHODS: Both RVG EF and Cath-EFa were measured within 16 days of myocardial infarction (MI) in 688 patients. The results were divided into terciles. Prognosis by terciles was assessed for each technique. A multivariate analysis was performed to determine which EF measurement was a better predictor of prognosis. RESULTS: Average RVG-EF was 32%+/-7, while Cath-EFa was 42%+/-10. Both RVG and Cath-EFa were poorly correlated (R=0.42). Event rate declined across terciles with increasing EF for both techniques (events in lowest to highest tercile of Cath-EFa 40.7%, 25.9%, 11.6%, p < 0.001; and RVG-EF 39.9%, 26.1%, 15.6%, p < 0.001). There was concordance of terciles in 303 of 688 patients (44%). When patients in the highest RVG terciles were in the highest Cath-EFa tercile, the event rate was 7%. However, when patients in the highest RVG terciles were in the lowest Cath-EFa tercile, the event rate was 19%. Both Cath-EFa (p < 0.001) and RVG-EF (p < 0.001) were independent predictors of cardiovascular events. CONCLUSIONS: Ejection fraction measured by RVG or during catheterization is a valuable tool in the risk stratification of postinfarct patients. When disagreement is present between clinical impression and measurement by either method, the use of an alternative measurement is warranted and complementary.

Adult↗
PubMed1999

The plastid in Plasmodium falciparum asexual blood stages: a three-dimensional ultrastructural analysis.

The plastid in Plasmodium falciparum asexual stages is a tubular structure measuring about 0.5 micron x 0.15 micron in the merozoite, and 1.6 x 0.35 microns in trophozoites. Each parasite contains a single plastid until this organelle replicates in late schizonts. The plastid always adheres to the (single) mitochondrion, along its whole length in merozoites and early rings, but only at one end in later stages. Regions of the plastid are also closely related to the pigment vacuole, nuclear membrane and endoplasmic reticulum. In merozoites the plastid is anchored to a band of 2-3 subpellicular microtubules. Reconstructions show the plastid wall is characteristically three membranes thick, with regions of additional, complex membranes. These include inner and outer membrane complexes. The inner complex in the interior lumen is probably a rolled invagination of the plastid's inner membrane. The outer complex lies between the outer and middle wall membranes. The interior matrix contains ribosome-like granules and a network of fine branched filaments. Merozoites of P. berghei and P. knowlesi possess plastids similar in structure to those of P. falciparum. A model is proposed for the transfer of membrane lipid from the plastid to other organelles in the parasite.

Animals↗
PubMed1999

Employer-provided vision benefits: have they gone mainstream?

As managed care inches closer to becoming the standard mechanism for delivering health benefits to American workers, we looked to see if the status of vision/eye health benefits have changed in the 1990s. Has vision care become a "mainstream" benefit?

Delivery of Health Care↗
PubMed1999

Working with school nurses: improving children's vision and building relationships.

The 45,000-plus school nurses in the U.S. have an astonishing array of responsibilities, and serve as important gatekeepers to the health care of millions of children. By building relationships with local school nurses, doctors of optometry can play an important part in improving children's vision care, and build their practices as well. We take a look at the challenges school nurses face, and an AOA program designed to reach out to them and improve the quality of vision screenings.

Child↗
PubMed1999

Carrying hope.

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Attitude of Health Personnel↗
PubMed1998

CXCR1 and CXCR2 are rapidly down-modulated by bacterial endotoxin through a unique agonist-independent, tyrosine kinase-dependent mechanism.

The expression of the seven-transmembrane domain chemokine receptors CXCR1 and CXCR2 modulates neutrophil responsiveness to the chemoattractant IL-8 and a number of closely related CXC chemokines. In the present study, we investigated the mechanism by which bacterial LPS induces the down-modulation of IL-8 responsiveness and CXCR1 and CXCR2 expression on human neutrophils. Treating neutrophils with LPS reduced IL-8R expression to 55 +/- 5% of the control within 30 min and to 23 +/- 2% within 1 h of stimulation. Furthermore, this down-modulation could not be attributed to increased concentrations of IL-8, TNF-alpha, or IL-1beta, since ELISA studies indicated that LPS-stimulated neutrophils did not release detectable amounts of these proteins before 2 h poststimulation. The tyrosine kinase (TK) inhibitors genistein and herbimycin A attenuated the LPS-mediated down-modulation of CXCR1 and CXCR2, indicating that the activation of a TK is required for LPS to mediate its effect. The effect of LPS on receptor expression paralleled the hyperphosphorylation of the protein TK p72syk. Although IL-8 induced a comparable down-modulation of CXCR1 and CXCR2, TK inhibitors did not attenuate this effect. These studies provide the first evidence of an agonist-independent, TK-dependent pathway of chemokine receptor regulation by endotoxin.

Antigens, CD↗
PubMed1998

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↗
PubMed1998

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↗