Search PubMed⌕ Search

Biomedical subjects

M Wright

Publications and source records attributed to M Wright.

At least 91 records · Page 5Linked to original sources
PubMed1999

Prevalence of emotional and physical health concerns amongst young people in Victoria.

OBJECTIVE: To describe the emotional and physical health concerns of young people, and identify the concerns for which young people are more likely to seek help. METHODS: We surveyed a representative cross-sectional samples of students from 11 to 18 years of age from 24 Victorian secondary schools in late 1997 within the Health of Young Victorians Study. Included in this survey were items describing worries or concerns of physical and emotional health. Prevalence rates, Chi-square, and logistic regression analyses were used to describe relationships. RESULTS: 2361 questionnaires were completed (53% male, response rate 70%). Overall, most frequent reports concerned feelings of depression (40%), worries about weight (37%), worries about self confidence (34%), and trouble falling or staying asleep (30%). Females tended to report a greater range of health concerns. The most frequent reports, by gender, were worries about their weight (52% females), and feelings of depression (30% males). Feelings of being bullied (20%), and concerns about sex, drugs and alcohol (7-11%) were reported equally frequently by males and females. In contrast to the high levels of health concerns reported, few students also reported seeing someone about them other than parents or friends. This finding appeared consistent across ages and for both sexes; with higher rates of seeking help for their physical rather than emotional health concerns. DISCUSSION: These results show that adolescents across Victoria are reporting high levels of concerns or worries about their health which differ across age and gender. They are more likely to report concerns about emotional health, but less likely to seek professional help than for physical concerns.

Adolescent↗
PubMed1999

Results of small incision extracapsular cataract surgery using the anterior chamber maintainer without viscoelastic.

AIMS: To assess the efficacy of extracapsular cataract surgery using the anterior chamber maintainer (ACM) without the use of viscoelastic. To compare the effects of this surgical technique on non-diabetic and diabetic patients. METHODS: A prospective single armed clinical trial of 46 eyes in 46 patients undergoing cataract surgery using the ACM without viscoelastic. Patients were assessed preoperatively and at 3 weeks, 3 months, and 12 months postoperatively. The main outcome variables included visual acuity, surgically induced astigmatic change (SIAC), changes in endothelial cell density (ECD), and morphology affecting the central and superior regions of the cornea. RESULTS: Postoperatively, 56% and 70% of patients had unaided visual acuities of 6/12 or better at 3 weeks and 3 months respectively. Even after excluding those patients with pre-existing maculopathy (including diabetic maculopathy), there remains a significant difference between the non-diabetic and diabetic groups in terms of the proportion of patients attaining an unaided visual acuity of 6/12 or better at both 3 weeks (p = 0.003) and 3 months (p = 0.001). Three months postoperatively, the SIAC based upon the keratometric and refractive data was 1.1 dioptres (D) and 1.3 D respectively. There was no statistically significant difference in the SIAC when the non-diabetic and diabetic groups were compared. The mean central and superior endothelial cell losses at 3 months postoperatively were 16% and 22% respectively and at 12 months postoperatively were 20% and 25% respectively. The diabetic group demonstrated greater endothelial cell losses and a more marked and protracted deviation of endothelial cell morphology from normality when compared with the non-diabetic group; however, the differences did not reach statistical significance. CONCLUSIONS: The efficacy of small incision cataract surgery using the ACM in terms of visual outcome and induced astigmatism is comparable with the results obtained using other techniques that utilise a similar size of incision. However, in view of the magnitude and range of the endothelial cell losses associated with this technique the concurrent use of viscoelastic is suggested. There does not appear to be a statistically or clinically significant difference between non-diabetic and diabetic patients in terms of the magnitude of the endothelial cell losses or in the wound healing response in the 12 months after cataract surgery using the ACM.

Aged↗
PubMed1999

Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome.

BACKGROUND/AIMS: Hyaluronan (sodium hyaluronate) has been shown to confer objective and subjective improvement in patients with dry eye syndrome. This study compared the efficacy and safety of a 0.1% solution of hyaluronan with 0.9% saline, when administered topically to the eye, in the treatment of symptoms of severe dry eye syndrome. METHODS: A randomised, double blind, crossover clinical trial in which subjects were randomised to receive either hyaluronan or saline, applied as one or two drops to the eye, three or four times a day or as required. After 28 days' treatment, subjects crossed over to the other study medication for a further 28 days' treatment. RESULTS: 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer's score (p=0.0006) and rose bengal staining score (p=0.0001) were observed during treatment with hyaluronan. In a subjective assessment of the effectiveness of two treatments, a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness (p<0.001). No adverse events attributable to hyaluronan treatment were reported. CONCLUSION: The study demonstrates a clear benefit of hyaluronan over saline, in both subjective and objective assessments of dry eye syndrome. Hyaluronan was shown to be well tolerated.

Adult↗
PubMed1999

Everting suture correction of lower lid involutional entropion.

AIMS: To assess the long term efficacy of everting sutures in the correction of lower lid involutional entropion and to quantify the effect upon lower lid retractor function. METHODS: A prospective single armed clinical trial of 62 eyelids in 57 patients undergoing everting suture correction of involutional entropion. Patients were assessed preoperatively and at 6, 12, 24, and 48 months postoperatively. The main outcome variables were lower lid position and the change in lower lid retractor function. RESULTS: When compared with the non-entropic side, the entropic lid had a greater degree of horizontal laxity and poorer lower lid retractor function. These differences however, were not significant. At the conclusion of the study and after a mean follow up period of 31 months, the entropion had recurred in 15% of the patients. There were no treatment failures in the group of five patients with recurrent entropion. The improvement in lower lid retractor function after the insertion of lower lid everting sutures did not reach statistical significance. There was no significant difference between the treatment failure group and the group with a successful outcome with regard to: the degree of horizontal lid laxity or lower lid retractor function present preoperatively; patient age or sex; an earlier history of surgery for entropion. There was neither a demonstrable learning effect nor a significant intersurgeon difference in outcome. The overall 4 year mortality rate was 30%. CONCLUSIONS: The use of everting sutures in the correction of primary or recurrent lower lid involutional entropion is a simple, successful, long lasting, and cost effective procedure.

Aged↗
PubMed1999

Vinflunine, a new vinca alkaloid: cytotoxicity, cellular accumulation and action on the interphasic and mitotic microtubule cytoskeleton of PtK2 cells.

Vinflunine, a newly synthesized derivative, possesses marked in vivo antitumor properties and, like other alkaloids, inhibits in vitro tubulin assembly at microM concentrations. However, in contrast to other vinca alkaloids, vinflunine exhibits relatively low in vitro cytotoxic potency. The aim of this report was to investigate whether the action(s) of vinflunine on the microtubule cytoskeleton could account for its cytotoxicity or if its cellular action requires another molecular target. Four vinca alkaloids used in cancer therapy and vinflunine were studied using PtK2 cells. Their activities on the most dynamic microtubules were investigated in mitosis and in interphase by evaluating the disturbance of the metaphase plate and the splitting of the diplosome, respectively. No correlation was observed between the cellular accumulation of these compounds and either their cytotoxicity or their action(s) on the microtubule cytoskeleton. In contrast, cytotoxicity, mitotic disturbance and diplosome splitting were observed in the nM range for vinblastine, vincristine, vindesine and vinorelbine, although these events occurred at 10 times higher concentrations in the case of vinflunine. Hence, dynamic modifications of both the mitotic and interphasic microtubule cytoskeleton are compatible with in vitro cytotoxicity of vinflunine, raising questions about the conventional biochemical screening of these vinca alkaloids.

Animals↗
PubMed1998

A matrix metalloproteinase proenzyme activator produced by articular cartilage.

Matrix metalloproteinases (MMPs) are involved in connective tissue turnover under physiological and pathological conditions. MMP activity is regulated by the requirement for zymogen activation. This report describes a proMMP-3 activator produced by articular cartilage. The activator initiates a step-wise processing of proMMP-3 to generate an array of active species. Sequencing of activation intermediates demonstrated cleavage on the NH2-terminal side of certain basic residues in the MMP-3 propeptide. Metal ion chelators inhibited activator-dependent proteolysis, and activity was restored by low levels of ZnCl2. These catalytic properties suggest similarity to members of the insulinase superfamily of metalloendopeptidases with in vitro specificity for single arginine or paired basic processing sites in a variety of prohormones. Dibasic sites also exist in the propeptides of several MMPs including proMMP-3. This is the first report that cartilage produces a potent MMP proenzyme activator, opening the possibility of a novel intrinsic activation pathway for catabolic processes in this avascular tissue.

Amino Acid Sequence↗
PubMed1998

Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.

Mst1 is a ubiquitously expressed serine-threonine kinase, homologous to the budding yeast Ste20, whose physiological regulation and cellular function are unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3-like activity during apoptosis induced by either cross-linking CD95/Fas or by staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD-CHO and by the viral serpin CrmA. Caspase-mediated cleavage of Mst1 removes the C-terminal regulatory domain and correlates with an increase in Mst1 activity in vivo, consistent with caspase-mediated cleavage activating Mst1. Overexpression of either wild-type Mst1 or a truncated mutant induces morphological changes characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved, indicating that Mst1 can activate caspases that result in its cleavage. Kinase-dead Mst1 did not induce morphological alterations and was not cleaved upon overexpression, indicating that Mst1 must be catalytically active in order to mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co-transfection assays, suggesting that Mst1 may activate these pathways. Our findings suggest the existence of a positive feedback loop involving Mst1, and possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic response.

Amino Acid Chloromethyl Ketones↗
PubMed1998

ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand.

Adipose differentiation is an important part of the energy homeostasis system of higher organisms. Recent data have suggested that this process is controlled by an interplay of transcription factors including PPARgamma, the C/EBPs, and ADD1/SREBP1. Although these factors interact functionally to initiate the program of differentiation, there are no data concerning specific mechanisms of interaction. We show here that the expression of ADD1/SREBP1 specifically increases the activity of PPARgamma but not other isoforms, PPARalpha, or PPARdelta. This activation occurs through the ligand-binding domain of PPARgamma when it is fused to the DNA-binding domain of Gal4. The stimulation of PPARgamma by ADD1/SREBP1 does not require coexpression in the same cells; supernatants from cultures that express ADD1/SREBP1 augment the transcriptional activity of PPARgamma. Finally, we demonstrate directly that cells expressing ADD1/SREBP1 produce and secrete lipid molecule(s) that bind directly to PPARgamma, displacing the binding of radioactive thiazolidinedione ligands. These data establish that ADD1/SREBP1 can control the production of endogenous ligand(s) for PPARgamma and suggest a mechanism for coordinating the actions of these adipogenic factors.

3T3 Cells↗
PubMed1998

A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.

Adaptive thermogenesis is an important component of energy homeostasis and a metabolic defense against obesity. We have cloned a novel transcriptional coactivator of nuclear receptors, termed PGC-1, from a brown fat cDNA library. PGC-1 mRNA expression is dramatically elevated upon cold exposure of mice in both brown fat and skeletal muscle, key thermogenic tissues. PGC-1 greatly increases the transcriptional activity of PPARgamma and the thyroid hormone receptor on the uncoupling protein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose cells activates expression of UCP-1 and key mitochondrial enzymes of the respiratory chain, and increases the cellular content of mitochondrial DNA. These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis.

Adaptation, Physiological↗
PubMed1998

[Collaborative learning through the Internet--an empirical study in nursing education].

The increasing use of e-mail and other electronic means of communication with their associated informality, interactivity and speed provide an ideal vehicle for students from different Schools of Nursing to work together. The Internet services can provide an open education environment. This paper will document the processes that took place in one collaborative exercise where two student groups worked together to improve care planning skills with the added bonus of improving their confidence and abilities as communicators. From Finland thirteen psychiatric nurse students were involved in the exercise and from Wales there was a group of six students all of whom were Registered General Nurses following the Mental Health Branch Program. All the interaction between students and teachers was arranged by e-mail. There are a range of educational objectives that were achieved these include use of e-mail, improvement in care planning technique, developing abilities to constructively criticise the work of others, to learn from and share in the experience of others.

Communication↗
PubMed1998

Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.

The ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state. We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1. A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene. These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism.

3T3 Cells↗
PubMed1998

Terfenadine-antidepressant interactions: an in vitro inhibition study using human liver microsomes.

AIMS: Inhibition of the metabolism of terfenadine has been associated with torsades de pointes ventricular arrhythmias. The aim of this study was to assess in vitro the potency of the antidepressants nefazodone, sertraline and fluoxetine in inhibiting terfenadine biotransformation. METHODS: Human liver microsomes were incubated with terfenadine and the antidepressants at various concentrations. Formation of the two major metabolites of terfenadine was determined by h.p.l.c. RESULTS: The apparent Km for microsomes from four human livers was 11+/-5 and 18+/-3 microM (mean +/-s.e.mean) for the N-dealkylation and C-hydroxylation pathways, respectively. Nefazodone, sertraline and fluoxetine inhibited terfenadine N-dealkylation with K(i) values of 10+/-4, 10+/-3 and 68+/-15 microM respectively. Inhibition of the C-hydroxylation pathway yielded noncompetitive K(i) values of 41+/-4, 67+/-13 and 310+/-40 microM respectively. CONCLUSIONS: Nefazodone and sertraline were moderately weak in vitro inhibitors of terfenadine metabolism while fluoxetine was a very weak inhibitor. Clinically significant interaction of terfenadine is more likely with nefazodone than sertraline or fluoxetine since therapeutic plasma levels of nefazodone are comparatively higher.

Alkylation↗
PubMed1998

Incident monitoring in psychiatry.

Critical Incident Monitoring (CIM) as an instrument of quality assurance (QA) has received increasing attention in recent years. The present study was developed to explore a potential role for CIM in QA for clinical psychiatry. A questionnaire was sent to psychiatrists and requested retrospective reporting of clinical incidents, and a pilot study of an inpatient-based incident reporting system was performed. All Fellows of the Royal Australian and New Zealand College of Psychiatry (RANZCP) were sent a questionnaire. Eight psychiatric inpatient services were invited to participate in the pilot study. The returns of the questionnaires were aggregated and analysed to reveal a relatively small number of separate incident types, with little difference between the 'adverse outcome' and 'near-miss' categories. Similar results were found with the pilot study. It was concluded that the development of a unified incident reporting system for use by psychiatric clinicians and psychiatric services may add usefully to existing quality improvement processes.

Antidepressive Agents↗
PubMed1998

Nucleation and capture of large cell surface-associated microtubule arrays that are not located near centrosomes in certain cochlear epithelial cells.

This report deals with the as yet undetermined issue of whether cell-surface associated microtubules in certain cochlear epithelial cells are centrosomally nucleated and subsequently migrate to microtubule-capturing sites located at the surface regions in question. Alternatively, the cells may possess additional nucleating sites which are noncentrosomal and surface-associated. These alternative possibilities have been investigated for highly polarised epithelial cells called supporting cells in the mouse and guinea pig organ of Corti using antibodies to pericentrin and gamma-tubulin. There is substantial evidence that both proteins are essential components of microtubule-nucleating sites in cells generally. Each mature supporting cell possesses a large microtubule array that is remotely located with respect to its centrosome (more than 10 microns away). The antibodies bind to a cell's centrosome. No binding has been detected at 2 other microtubule-organising centres that are associated with the ends of the centrosomally-remote microtubule array while it is being constructed. Such arrays include thousands of microtubules in some of the cell types that have been examined. If all a cell's microtubules are nucleated by its centrosome then the findings reported above imply that microtubules escape from the centrosomal nucleating site and migrate to a new location. Furthermore capture of the plus and minus ends of the errant microtubules is taking place because both ends of a centrosomally-remote microtubule array are attached to sites that are precisely positioned at certain cell surface locations. Minus ends are locating targets with an exactitude comparable to that which has been demonstrated for plus ends in certain cell types. These cells apparently operate a single control centre strategy for microtubule nucleation that is complemented by precise positioning of plus and minus end-capturing sites at the cell surface.

Animals↗
PubMed1998

Papilloedema, a complication of progressive diaphyseal dysplasia: a series of three case reports.

BACKGROUND/AIMS: Progressive diaphyseal dysplasia (PDD) is a rare, autosomal dominant, osteosclerotic dysplasia affecting both endochondrally and intramembranously derived bones. Severely affected patients can develop progressive stenosis of the optic canals and compressive optic neuropathy. Although raised intracranial pressure (ICP) has been described in patients with PDD in whom visual loss has occurred, the elevation of ICP in those patients has been thought to be either non-contributory or only partially responsible for the accompanying visual loss. METHODS: Three cases were reviewed and the clinical and radiological characteristics are described here. RESULTS: All three patients had bilateral optic disc swelling with no radiological evidence of either compressive optic neuropathy or thrombosis of the intracranial venous sinuses. The aetiology of the disc swelling was proved to be papilloedema in the first two cases and was probably the dominant cause in the third case. CONCLUSION: The visual loss documented in at least two of the three patients reported appears to be solely attributable to raised ICP. Normalisation of the ICP has led to an improvement and stabilisation of the visual function in all three patients. Patients with PDD probably require periodic ophthalmic assessments.

Adult↗
PubMed1998

Modification of paclitaxel metabolism in a cancer patient by induction of cytochrome P450 3A4.

Biliary, plasma, and urinary disposition of paclitaxel and paclitaxel metabolites were determined simultaneously in a patient with percutaneous biliary drain. The complete chemical structures of the major metabolites were established by mass spectrometry and NMR spectroscopy. A nonlinear elimination model was indicated by the fact that the rate of biliary excretion of paclitaxel rose as plasma concentrations fell. Dihydroxypaclitaxel was the predominant biliary metabolite, in contrast to the barely detectable levels in two previous patients. This derivative results from hydroxylation at the C6 position of the taxane ring and at the phenyl C3'-position on the C13 side chain mediated by cytochrome P450 2C8 and 3A4, respectively. In line with this mechanism, the two other main metabolites corresponded to 6alpha-hydroxypaclitaxel and to the paclitaxel derivative hydroxylated in the para-position on the phenyl ring at the C3'-position of the C13. A high CYP3A4 activity in the patient is consistent with the repeated administration of methylprednisolone for 14 days before paclitaxel treatment, a compound known to induce the CYP3A isoform, and with the increased ratio of 6beta-hydroxycortisol/cortisol in urine, an index of CYP3A activity. These findings emphasize the influence of pretreatment with corticoids on the disposition of paclitaxel.

Antineoplastic Agents, Phytogenic↗