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Biomedical subjects

I Morgan

Publications and source records attributed to I Morgan.

At least 19 recordsLinked to original sources
PubMed2004

Using natural STOP growth signals to prevent excessive axial elongation and the development of myopia.

Myopia is emerging as a major public health issue due to its increasing prevalence and long-term pathological outcomes. Prevention must focus on limiting excessive axial elongation which is the cause of both myopic refractive error and its pathological outcomes. The increasing prevalence appears to be due to environmental changes involving near work, rather than to a genetic failure of emmetropisation. Attempts to control the progression of myopia optically have been unsuccessful; the only available preventive regime involves the use of atropine eye drops. This regime has short-term side effects, and since the site and mechanism of action of muscarinic antagonists are unclear, there are concerns about its long-term safety. Recent studies on natural STOP growth signals suggest that they are evoked by relatively brief periods of imposed myopic defocus, and can overcome strong pressures towards increased axial elongation. While STOP signals have only been successfully used in chickens to prevent excessive axial elongation, similar signals are generated in mammals and non-human primates. Further studies may define the conditions under which this approach could be used to prevent the development of myopia in humans.

Accommodation, Ocular↗
PubMed2003

Creep behavior of bone cement: a method for time extrapolation using time-temperature equivalence.

The clinical lifetime of poly(methyl methacrylate) (PMMA) bone cement is considerably longer than the time over which it is convenient to perform creep testing. Consequently, it is desirable to be able to predict the long term creep behavior of bone cement from the results of short term testing. A simple method is described for prediction of long term creep using the principle of time-temperature equivalence in polymers. The use of the method is illustrated using a commercial acrylic bone cement. A creep strain of approximately 0.6% is predicted after 400 days under a constant flexural stress of 2 MPa. The temperature range and stress levels over which it is appropriate to perform testing are described. Finally, the effects of physical aging on the accuracy of the method are discussed and creep data from aged cement are reported.

Journal Article↗
PubMed2002

Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter thyroid axis or uncoupling protein-1 in brown adipose tissue.

Orexin A, synthesised in the posterolateral hypothalamus, has widespread distribution including the paraventricular nucleus (PVN), which is rich in thyrotropin-releasing hormone (TRH) neurones. Nerve fibres in the PVN synapse on neurones that send polysynaptic projections to brown adipose tissue (BAT), which is important in thermogenesis. A number of observations suggests orexin A may be involved in regulation of metabolism and thermogenesis. We investigated the effect of orexin A injected intracerebroventricularly (ICV) on thyroid-stimulating hormone (TSH) and thyroid hormones in male rats. We then examined the effect of chronic iPVN injections of orexin A on plasma TSH and uncoupling protein-1 (UCP-1) protein in BAT. Orexin A (3 nmol) administered ICV significantly suppressed plasma TSH at 10 and 90 min. Orexin A (0.3 nmol) administered into the PVN twice daily for 3 days significantly increased day-time 2-h food intake, but did not significantly alter nocturnal food intake. Though chronic iPVN orexin A altered diurnal food intake, there was no effect on 24-h food intake or body weight. Furthermore, orexin A administered chronically into the PVN did not alter UCP-1 level in BAT, or plasma hormones relative to saline injected animals. Chronic iPVN orexin A does not appear to influence thermogenesis through activation of UCP-1 or the thyroid axis.

Adipose Tissue, Brown↗
PubMed2001

Orexins: effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem.

The orexins are neuropeptides originally reported to be involved in the stimulation of food intake. However, analysis of orexin immunoreactive fibres have revealed the densest innervation in brain sites involved in arousal and sleep-wake control, notably the noradrenergic locus coeruleus, an area that also expresses orexin receptor 1 (OX1R) messenger RNA (mRNA). We report here that, in the rat, a single intracerebroventricular injection of orexin A (1 and 3 nmol) or orexin B (3 nmol), during the early light phase, did not increase food intake over the first 4 h postinjection. However, the frequency of active behaviors such as grooming, rearing, burrowing and locomotion increased. Feeding behavior and food intake subsequently decreased over the following 20 h (4-24 h postinjection period) in the orexin A 3 nmol injected group whilst the frequency of inactive behavior (still or asleep) in this group increased. Using riboprobes, we performed in situ hybridization histochemistry to map the distribution of orexin receptor 2 (OX2R) mRNA within the rat brainstem. We report here, for the first time, the presence of OX2R mRNA in the nucleus of the solitary tract and the lateral reticular field (LRt). The LRt is a brainstem site that, amongst other functions, is implicated in attention and wakefulness. This distribution of OX2R and the effects on behavior support recent reports that the orexins might modulate central nervous system arousal and sleep-wake mechanisms rather than exclusively being involved in the control of food intake.

Animals↗
PubMed2001

The use of ADCON-T/N after repair of zone II flexor tendons.

This double-blinded randomised clinical trial investigated whether application of ADCON-T/N to zone II tendon repairs improved their outcome. Fifty-nine patients were randomised into control or ADCON-T/N treated groups and all followed an early mobilisation regime following tendon repair. Tendon rupture rates were comparable between the control and ADCON-T/N treated patients. At six months follow-up, the ADCON-T/N treated group had better proximal interphalangeal motion.

Adult↗
PubMed2001

The increasing prevalence of myopia: implications for Australia.

Myopia is often regarded as a minor priority in public health research, yet the public health costs of myopia are considerable, both due to the costs of optical correction and from the costs imposed by the morbidity resulting from myopia in terms of associated eye disease (glaucoma, posterior subcapsular cataract), and the visual impairment and blindness that can result from myopia due to myopic retinal degeneration and retinal detachment. There is clear evidence for a high and increasing prevalence of myopia in East Asia, apparently driven by increasing educational pressures and urbanization. Data from the USA, Europe and Australia are consistent with the data from Asia in terms of the role of these risk factors. However, the evidence for an increasing prevalence of myopia is more problematic, due to the lack of adequate longitudinal studies, and the confounding effects of age-related hypermetropization. It is concluded that the prevalence of myopia is probably increasing in Australia, although the changes are of much lower magnitude than n East Asia. Longitudinal studies are, therefore, clearly required to quantify changes in the prevalence of myopia in Australia, for accurate assessment of the public health impacts and to assist with the development of preventive approaches.

Adult↗
PubMed2001

Vitreal dihydroxyphenylacetic acid (DOPAC) as an index of retinal dopamine release.

Dopamine is generally accepted as a major neurotransmitter associated with light-adaptive processes in the retina. However, little is known about its precise release pattern in vivo, largely due to the lack of an unambiguous method for the determination of dopamine release. We have found that vitreal levels of dihydroxyphenylacetic acid (DOPAC) reflect the rate of dopamine release in chickens. Blocking re-uptake with nomifensine significantly lowered vitreal DOPAC and retinal dopamine, confirming the retinal origin and reliance of vitreal DOPAC on intact re-uptake mechanisms. Further, inhibition of monoamine oxidase with pargyline reduced vitreal as well as retinal DOPAC levels, confirming that the DOPAC detected is generated by monoamine oxidase. Finally, we found that DOPAC diffused freely into and out of isolated vitreous bodies and we found the vitreous to be metabolically inert with respect to DOPAC, supporting the idea that vitreal levels of DOPAC are consequential to the retinal metabolism of dopamine. Exposure to light, which is known to increase retinal dopamine release, readily increased vitreal DOPAC levels. The accumulation of DOPAC in the vitreous over 6 h light fitted a mathematical model of DOPAC accumulation based on zero-order influx (proportional to dopamine release rates) and diffusion driven, first-order efflux.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Evidence of an orexigenic role for cocaine- and amphetamine-regulated transcript after administration into discrete hypothalamic nuclei.

Cocaine- and amphetamine-regulated transcript is expressed in hypothalamic regions involved in the central control of food intake. Previous data have implicated cocaine- and amphetamine-regulated transcript as an anorectic peptide. We studied the effect of the active fragment of cocaine- and amphetamine-regulated transcript, cocaine- and amphetamine-regulated transcript-(55-102), on feeding when injected into discrete nuclei of the hypothalamus. Cocaine- and amphetamine-regulated transcript-(55-102) (0.04 nmol) elicited a delayed, but significant, increase in feeding in 24-h fasted rats after injection into the ventromedial nucleus (1-2 h, 261 +/- 60% of control; P < 0.05) and arcuate nucleus (1-2 h, 225 +/- 38% of control; P < 0.05) of the hypothalamus. Administration of a higher dose of cocaine- and amphetamine-regulated transcript-(55-102) (0.2 nmol) elicited a significant increase in feeding after injection into the ventromedial nucleus (1-2 h, 1253 +/- 179% of control; P < 0.001), arcuate nucleus (1-2 h, 265 +/- 43% of control; P < 0.05), paraventricular nucleus (2-4 h food intake, 186 +/- 29% of control; P < 0.05), lateral hypothalamic area (2-4 h, 280 +/- 34% of control; P < 0.001), anterior hypothalamic area (2-4 h, 252 +/- 42% of control; P < 0.01), dorsomedial nucleus (2-4 h, 368 +/- 29% of control;P < 0.001) and supraoptic nucleus (2-4 h, 212 +/- 34% of control; P < 0.05) of the hypothalamus. Administration of cocaine- and amphetamine-regulated transcript-(55-102) into the third ventricle of the hypothalamus resulted in an inhibition in feeding [0-4 h (0.4 nmol), 33 +/- 13% control; P < 0.001], but was associated with marked abnormalities in behavior, which may have interfered with feeding. These behavioral abnormalities were not observed after the administration of cocaine- and amphetamine-regulated transcript-(55-102) directly into the arcuate nucleus. These data suggest that cocaine- and amphetamine-regulated transcript may play an orexigenic role in the hypothalamic feeding circuitry.

Animals↗
PubMed2000

Effect of leptin on hypothalamic GLP-1 peptide and brain-stem pre-proglucagon mRNA.

Leptin, the adipocyte-derived plasma hormone, and CNS GLP-1 neurons reduce food intake and body weight. GLP-1 is produced in the CNS by post-translational processing of pre-proglucagon. ICV leptin administration prevented the reduction in hypothalamic GLP-1 peptide content seen in pair-fed food-restricted rats (P < 0.05). There was a significant overall positive correlation between pre-proglucagon mRNA expression in the NTS and hypothalamic GLP-1 peptide content (r = +0.34, P < 0.05). Intraperitoneal leptin administration also increased hypothalamic GLP-1 peptide in food-restricted mice (P < 0. 05). This supports the hypothesis that the anorectic actions of leptin are in part due to stimulation of GLP-1 neurons. Reduced CNS GLP-1 neuronal activity during food deprivation may act to stimulate feeding behaviour, and perhaps also inhibit hypothalamic LHRH neurons, as part of the neuroendocrine response to starvation.

Animals↗
PubMed1999

The 4 year outcome following the demonstration of bilateral renal pelvic dilatation on pre-natal renal ultrasound.

There is little in the literature regarding long-term prognosis in cases of fetal pyelectasis and calyceal dilatation. The aim of this study was to correlate antenatal ultrasound findings with outcome in a large group of children, most of whom had routine antenatal mid-trimester scans. 75 babies with bilateral pyelectasis and calyceal dilatation in the pre-natal period and complete radiological and clinical data were identified over a 3 year period. Pre-natal ultrasound was correlated with results of post-natal investigation and the frequency of post-natal surgery was established. Follow-up was documented to discharge or to at least 4 years of age. Prognosis was related to the degree of pelvic dilatation, but neonatal morbidity was much more likely to be associated with pre-natal calyceal dilatation and/or hydroureter. 68% (51 of 75) of babies had insignificant abnormalities on post-natal investigation, defined as either transient fetal pyelectasis and calyceal dilatation, extrarenal pelves, or transient neonatal pyelectasis and calyceal dilatation. Five babies died in the neonatal period, all classified as either moderate or severe disease. Of the surviving 70 cases (93.3%), 27% had renal anomalies that required treatment by prophylactic antibiotics or surgery. The remaining babies were conservatively managed and followed as outpatients. One child required transplantation and a further two had a severe degree of chronic renal failure by the age of 4 years. These data will be of value in prospective counselling.

Dilatation, Pathologic↗
PubMed1998

Transmyocardial laser revascularisation in Edinburgh.

UNLABELLED: This paper describes a feasibility study to evaluate the Xenon-Chloride Excimer laser in patients requiring myocardial revascularisation. METHODS: Between November 1995 and September 1997, 30 patients (aged 48 to 80 years) underwent Transmyocardial Laser Revascularisation (TMR), either combined with coronary artery bypass grafting (CABG) or as a sole procedure. These patients were considered unsuitable for conventional coronary revascularisation on the basis of angiographic findings. Evaluation included NYHA status, exercise tolerance test, dobutamine stress echocardiography, Thallium myocardial perfusion scan, with follow-up scan at 3 months and clinical review at 3, 6, 12 and 18 months. Operative technique initially was standardised comprising median sternotomy, full cardiopulmonary bypass, moderate systemic hypothermia and induced ventricular fibrillation. This was later modified to mini-left anterior thoracotomy, femoral cannulation with venous centrifugal assist. RESULTS: Patients undergoing TMR also had conventional grafts whenever possible (18/30 (60%), 1 graft 12/30, 2 grafts 6/30). 14 patients were redo cases, and 12 were unsuitable for further grafts, and therefore had TMR as a sole procedure. The number of channels created was between 6 and 100 (mean 45.6 +/- 20.7). The majority of the cases had severe angina (NYHA classes III or IV) at presentation, with an improvement of at least 2 points postoperatively (p < 0.001) which was sustained throughout the period of follow-up. Objective evidence of improved myocardial perfusion and function (dobutamine stress echocardiography and Thallium myocardial perfusion scan) was obtained in a few patients. Complications following TMR were uncommon-one patient developed complete AV dissociation requiring permanent pacemaker insertion. No other specific TMR-related complications were identified. CONCLUSION: Despite initial difficulties in recruiting adequate numbers of patients, TMR has proved to be a useful adjunct in relieving angina in patients who are either poor candidates for surgery or unsuitable for full revascularisation. Modification in the technique has allowed a less invasive approach and improved recovery period.

Adult↗
PubMed1997

Retinal control of scleral precursor synthesis.

There is a light-dependent diurnal rhythm in scleral precursor synthesis (SPS). In form-deprivation myopia (FDM) there is an increase in SPS. Daily periods of normal vision prevent FDM, but light intensities that maintain the retinal dark-light switch in its dark state do not, implicating melatonin, dopamine, enkephalin, neurotensin and somatostatin in the control of SPS. FDM is also prevented by pirenzepine, a cholinergic muscarinic antagonist To test if these compounds control the rate of SPS, agonists and antagonists were applied directly to the sclera, but the only effects detected were at very high concentrations, making them physiologically insignificant.

Adaptation, Ocular↗
PubMed1997

Deprivation of form vision suppresses diurnal cycling of retinal levels of leu-enkephalin.

Deprivation of form vision by the fitting of translucent occluders suppressed the diurnal cycling of enkephalinergic amacrine cells (the ENSLI amacrine cells), in the chicken. Daily periods of normal vision or enforcing temporal contrast using strobe lighting appeared to restore normal functioning of the ENSLI cells. These results suggest that the ENSLI cells are involved in retinal circuits that assess the quality of the visual image and control eye growth.

Adaptation, Ocular↗
PubMed1996

Differential and antagonistic effects of v-Jun and c-Jun.

We compared the ability of cellular and viral Jun (c-Jun and v-Jun) to transactivate target genes. c-Jun and v-Jun bind specifically to 12-O-tetradecanoylphorbol-13-acetate responsive elements [TREs, also called activator protein 1 (AP-1) motifs]. However, whereas c-Jun activates TRE-controlled promoters, v-Jun represses them. Cotransfection of the two Jun proteins reduces c-Jun-dependent transactivation. The expression of the endogenous c-jun gene, regulated through a promoter-proximal AP-1-binding site, is repressed in v-Jun-transformed chicken embryo fibroblasts. It is suggested that an M(r) 18,000 v-Jun peptide prominent in v-Jun-transformed cells acts as a transdominant-negative regulator of AP-1 activity and of c-jun expression. In contrast to the results with TRE sites, both v-Jun and c-Jun activate transcription through the human T-cell leukemia virus type I 21-bp repeat which contains a sequence homologous to the cyclic AMP responsive element. However, full-length Jun proteins bind to this site only with low affinity, and binding of the truncated v-Jun was barely detectable. These observations show that the oncogenic viral form of Jun differs from the cellular version in promoter preference and on certain promoters acts as an antagonist to c-Jun.

Animals↗
PubMed1996

Light controls scleral precursor synthesis.

Both axial clongation and scleral precursor synthesis are increased during form deprivation myopia (FDM). Since axial clongation is greater during the day than at night during normal development, it seemed likely that the rate of scleral precursor synthesis would be high in the day and low at night. Instead we found that the rate of scleral precursor synthesis is greater in the middle of the night than at the middle of the day. The rise and fall do not begin until about 4 h after lights off or lights on, respectively. These variations in precursor synthesis are light-driven, not circadian.

Animals↗
PubMed1995

The effects of thiocyanate on the intracellular ion concentrations of branchial epithelial cells of brown trout

Exposure of brown trout (Salmo trutta) in fresh water to 0.15 mmol l-1 external thiocyanate for 1 h resulted in a significant decrease in chlorine concentration in the branchial mitochondria-rich (MR) cells from 37 mmol l-1 to 22 mmol l-1. The intracellular sodium concentration in these cells decreased by a similar amount, whilst the intracellular phosphorus concentration increased significantly. In contrast to the MR cells, 0.15 mmol l-1 external thiocyanate had no effect on the intracellular ion concentrations in the pavement epithelial cells. Thiocyanate is known to inhibit chloride uptake in a number of freshwater animals and therefore these data suggest that it is only the MR cells that are involved in the uptake of Cl- in brown trout.

Journal Article↗