Search PubMed⌕ Search

Biomedical subjects

A Cameron

Publications and source records attributed to A Cameron.

At least 19 recordsLinked to original sources
PubMed2002

Teaching paediatric dentistry by multimedia: a three-year report.

Clinical cases can now be simulated utilising multimedia and used to teach case management to dental students. The modules developed should provide intellectual stimulation, user-interaction and immediate feedback, in addition to being intuitively navigated and user-helpful. Five paediatric dental case modules (early childhood caries, anterior trauma, anterior coronal fragment, anterior crossbite and dentigerous cyst) were created, installed in a multimedia presentation tool, PathFinder (from Westmead Hospital Dental Clinical School, New South Wales, Australia), and used to teach three classes of fourth year dental students at The University of Melbourne. Questionnaires, focus groups and a review were conducted by an external educational expert. Students responded anonymously to general learning questions and case specific questions using a five-point Likert scale (strongly agree to strongly disagree). Student responses indicated they were very enthusiastic about learning via multimedia, although a few students disliked this educational approach. Focus groups and external review indicated that the modules were navigated readily and were suitably interactive.

Case Management↗
PubMed2002

Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder.

Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder.

Adolescent↗
PubMed2002

Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson's disease: a case series.

Parkinson's disease patients may suffer from cognitive impairment and behavioural problems such as apathy, personality changes, speech disturbances and visual hallucinations (Parkinson's disease dementia). However, there is currently no recommended treatment for Parkinson's disease dementia and antipsychotic agents can worsen extrapyramidal symptoms, making them unsuitable for patients with this condition. The observation that patients with Parkinson's disease dementia have extensive cholinergic deficits led to the hypothesis that cholinesterase inhibitors may provide benefits for patients with this condition. Here, we present a case series of patients with Parkinson's disease and dementia who we treated with rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) that shows brain region-selectivity. The introduction of rivastigmine led to improvements in cognitive and functional abilities, as well as the resolution of behavioural problems and visual hallucinations. Rivastigmine was well tolerated by our patients when the dose was escalated slowly, including one patient who had previously experienced severe side-effects with the AChE-selective inhibitor donepezil. Despite the large number and range of concomitant medications being received by the patients, no side-effects thought to be related to drug-drug interactions were reported. A large, placebo-controlled study is warranted to ascertain the full clinical profile of rivastigmine in Parkinson's disease dementia.

Aged↗
PubMed2001

Structural studies of a neuropeptide precursor protein with an RGD proteolytic site.

The snail Lymnaea stagnalis produces a neuropeptide precursor protein that contains seven Arg-Gly-Asp (RGD) sites. These sites are recognized and cleaved by one or more prohormone convertases in the first processing step to yield mature neuropeptides in the secretory pathway. Conformations of two synthetic RGD-containing peptides derived from the L. stagnalis precursor protein were determined by NMR spectroscopy. The peptides were tested in a platelet aggregation assay for RGD activity and were processed in vitro by PC2 and furin. The native peptide with a proline following the RGD site has minimal structure around the RGD region, does not inhibit platelet aggregation, and is properly processed by the enzymes PC2 and furin. A variant of the native fragment with a serine following the RGD sequence has a significant amount of a reverse turn around the RGD region, is a potent inhibitor of platelet aggregation, and is processed with the same specificity as the native fragment. The large conformational differences between the two peptides provide a molecular mechanism for effects of proline residues following the RGD site and suggest that precursor processing is influenced more by flexibility than by the conformation of the processing site.

Amino Acid Sequence↗
PubMed2001

A logit model for the effect of telecardiology on acute newborn transfers.

UNLABELLED: The deregionalization of neonatal intensive care in the United States has shifted the site of care for many newborn infants away from academic medical centers where subspecialty support is available. OBJECTIVE: To investigate the effect of immediate echocardiogram interpretation via telemedicine on rates of neonatal transfer to academic medical centers. METHODS: A logit model was developed to predict the probability of transfer from two regional level 3 neonatal intensive care units to academic medical centers. One of these units implemented a telecardiology program and the other acted as a comparison institution with on-site cardiology expertise. The telecardiology intervention began 18 months into the 36-month study period. SUBJECTS: Infants (n = 2,142) admitted to neonatal intensive care at either of the two institutions during calendar years 1994 through 1996. RESULTS: A statistically significant reduction in the rate of transfer to academic medical centers was observed. Telecardiology was associated with a 58% reduction of such transfers (p = .001, 95% CI = 30%, 75%). No such reduction was noted at the comparison institution. It is estimated that approximately 30 transfers were eliminated during the study period, resulting in the elimination of approximately $150,000 in hospital charges. In addition, the infants that were transferred after the adoption of telemedicine were more often transferred to their telemedicine partner institution (p < .02).

Academic Medical Centers↗
PubMed2001

Tissue distribution and processing of proSAAS by proprotein convertases.

The conversion of inactive precursor proteins into bioactive neuropeptides and peptide hormones involves regulated secretory proteins such as prohormone convertases PC1 and PC2. The neuroendocrine protein 7B2 represents a specific binding protein for PC2, and the protein proSAAS, which interacts with PC1, exhibits certain structural and functional homologies with 7B2. With the intention of better understanding the physiological role of proSAAS and its derived peptides, we investigated its tissue localization using a new radioimmunoassay (RIA) to a C-terminal proSAAS-derived peptide. Immunoreactivity corresponding to this SAAS-derived peptide is mostly localized to the brain and gut. Analysis of the brain distribution of the proSAAS-derived peptides indicates that the hypothalamus and pituitary are the two richest areas, consistent with the previously described high expression of PC1 in these two areas. In order to investigate the cleavage of proSAAS by prohormone convertases, we incubated recombinant His-tagged proSAAS with recombinant mouse proPC2 or furin, separated the cleavage products using high-pressure gel permeation chromatography and analyzed the products by RIA. Our results indicate that either PC2 or furin can accomplish in vitro rapid removal and efficient internal processing of the C-terminal peptide, exposing the inhibitory hexapeptide to possible further digestion by carboxypeptidases. Finally, we also studied proSAAS processing in the brains of wild-type and PC2 null mice and found that proSAAS is efficiently processed in vivo. Whereas the C-terminal peptide is mostly internally cleaved in wild-type mouse brain, it is not processed as efficiently in the brain of PC2 null mice, suggesting that PC2 is partially responsible for this cleavage in vivo.

Amino Acid Sequence↗
PubMed2001

Insulin-mediated vasorelaxation in pregnancy.

OBJECTIVE: To investigate insulin-mediated vasorelaxation in pregnancy, and the role of nitric oxide in this response. DESIGN: In vitro study of isolated subcutaneous resistance arteries from pregnant and non-pregnant women. METHODS: Small arteries (mean vessel diameter <300 microm) were isolated from biopsies of subcutaneous fat from 14 pregnant and seven non-pregnant women. Insulin-mediated attenuation of the vasoconstriction response to noradrenaline, before and after nitric oxide synthase inhibition, was studied in isolated arteries using wire myography. Vessel responses to noradrenaline following incubation with insulin were also tested after endothelial denudation. Maximum responses were compared using one-way ANOVA and Bonferroni's post hoc test for multiple comparisons. RESULTS: In pregnancy, the maximum vasoconstriction produced by noradrenaline was increased (P < 0.01). Insulin significantly reduced this response in pregnant women (P < 0.01), while inhibition of nitric oxide synthase with Nomega-nitro-L-arginine methyl ester (L-NAME) resulted in potentiation (P < 0.05). Following inhibition of nitric oxide synthase with L-NAME, addition of the insulin was still able to produce a significant attenuation in maximum vasoconstriction to noradrenaline in pregnant women (P < 0.01). Furthermore, the absence of functioning endothelium did not abolish the attenuating effect of the insulin on noradrenaline-induced vasoconstriction in pregnant women (P < 0.01). CONCLUSIONS: The vasodilatory effect of insulin is not diminished in pregnancy, despite the development of insulin resistance. Furthermore, the attenuation of vasoconstrictor tone is via an endothelium-independent mechanism. This suggests that the vascular dysfunction associated with diabetes mellitus does not occur with physiological insulin resistance.

Adult↗
PubMed2001

Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are independent of maternal responses.

Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein delta = 52.6 nmol/L, 95% CI (25.3-79.9), P = 0.001; mean beta-endorphin response delta =106 pg/mL, 95% CI (45.3-167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7-15.2)] for cortisol and 0.8 [95% CI (0.5-1.0)] for beta-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ss-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal beta-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16-10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

Blood Transfusion↗
PubMed2000

Processing and sorting of the prohormone convertase 2 propeptide.

The prohormone convertases (PCs) are synthesized as zymogens whose propeptides contain several multibasic sites. In this study, we investigated the processing of the PC2 propeptide and its function in the regulation of PC2 activity. By using purified pro-PC2 and directed mutagenesis, we found that the propeptide is first cleaved at the multibasic site separating it from the catalytic domain (primary cleavage site); the intact propeptide thus generated is then sequentially processed at two internal sites. Unlike the mechanism described for furin, our mutagenesis studies show that internal cleavage of the propeptide is not required for activation of pro-PC2. In addition, we identified a point mutation in the primary cleavage site that does not prevent the folding nor the processing of the zymogen but nevertheless results in the generation of an inactive PC2 species. These data suggest that the propeptide cleavage site is directly involved in the folding of the catalytic site. By using synthetic peptides, we found that a PC2 propeptide fragment inhibits PC2 activity, and we identified the inhibitory site as the peptide sequence containing basic residues at the extreme carboxyl terminus of the primary cleavage site. Finally, our study supplies information concerning the intracellular fate of a convertase propeptide by providing evidence that the PC2 propeptide is generated and is internally processed within the secretory granules. In agreement with this localization, an internally cleaved propeptide fragment could be released by stimulated secretion.

Amino Acid Sequence↗
PubMed2000

Polyarginines are potent furin inhibitors.

The ubiquitous serine endoprotease furin has been implicated in the activation of bacterial toxins and viral glycoproteins as well as in the metastatic progression of certain tumors. Although high molecular mass bioengineered serpin inhibitors have been well characterized, no small nontoxic nanomolar inhibitors have been reported to date. Here we describe the identification of such inhibitors using positional scanning amidated and acetylated synthetic l- and d-hexapeptide combinatorial libraries. The results indicated that l-Arg or l-Lys in all positions generated the most potent inhibitors. However, further investigation revealed that the peptide terminating groups hindered inhibition. Consequently, a series of non-amidated and acetylated polyarginines was synthesized. The most potent inhibitor identified, nona-l-arginine, had a K(i) for furin of 40 nm. The K(i) values for the related convertases PACE4 and prohormone convertase-1 (PC1) were 110 nm and 2.5 microm, respectively. Although nona-l-arginine was cleaved by furin, the major products after a 6-h incubation at 37 degrees C were hexa- and hepta-l-arginines, both of which retained the great majority of their potency and specificity against furin. Hexa-d-arginine was as potent and specific a furin inhibitor as hexa-l-arginine (K(i) values of hexa-d-arginine: 106 nm, 580 nm, and 13.2 microm for furin, PACE4, and PC1, respectively). PC2 was not inhibited by any polyarginine tested; indeed, PC2 showed an increase in activity of up to 140% of the control in the presence of l-polyarginines. Data are also presented that show extended subsite recognition by furin and PC2. Whereas N-terminal acetylation was found to reduce the inhibitory potency of the l-hexapeptide LLRVKR against furin 8-fold, C-terminal amidation reduced the potency < 2-fold. Conversely, N-terminal acetylation increased the potency against PC2 nearly 3-fold, whereas C-terminal amidation of the same peptide increased the potency by a factor of 1.6. Our data indicate that non-acetylated, poly-d-arginine-derived molecules may represent excellent lead compounds for the development of therapeutically useful furin inhibitors.

Animals↗
PubMed2000

The SAAS granin exhibits structural and functional homology to 7B2 and contains a highly potent hexapeptide inhibitor of PC1.

Prohormone convertases (PCs) 1 and 2 are thought to mediate the proteolytic cleavage of many peptide precursors. Endogenous inhibitors of both PC1 and PC2 have now been identified; the 7B2 protein is a nanomolar inhibitor of PC2, while the novel protein proSAAS was recently reported to be a micromolar inhibitor of PC1 [Fricker et al. (2000) J. Neurosci. 20, 639-648]. We here report evidence that 7B2 and proSAAS exhibit several elements of structural and functional homology. Firstly, 26 kDa human, mouse and rat proSAAS, like all vertebrate 7B2s, contain a proline-rich sequence within the first half of the molecule and also contain a C-terminal 40 residue peptide (SAAS CT peptide) separated from the remainder of the protein by a furin consensus sequence. The SAAS CT peptide contains the precise sequence of a hexapeptide previously identified by combinatorial peptide library screening as a potent inhibitor of PC1, and the vast majority of the inhibitory potency of proSAAS can be attributed to this hexapeptide. Further, like the 7B2 CT peptide, SAAS CT-derived peptides represent tight-binding competitive convertase inhibitors with nanomolar potencies. Lastly, recombinant PC1 is able to cleave the proSAAS CT peptide to a product with a mass consistent with cleavage following the inhibitory hexapeptide. Taken together, our results indicate that proSAAS and 7B2 may comprise two members of a functionally homologous family of convertase inhibitor proteins.

Amino Acid Sequence↗
PubMed2000

Managing the unmanageable? Nurse Executive Directors and new role developments in nursing.

This paper offers a unique insight into the factors affecting the functioning of the Nurse Executive Director(s) and their views on the realities of nursing management in the new National Health Service in England. It is based on the findings of the Exploring New Roles in Practice (ENRiP) project which was carried out for the Department of Health. As part of this project interviews were undertaken with Nurse Executive Directors from a 20% sample of acute hospital trusts in England. The interviews were designed to explore the Nurse Executive's perceptions of the process of new role development. The findings highlight a tension between the drive for professional development and the pragmatics of service delivery in a health care system which lacks dedicated funding for nursing development. It was evident that most Nurse Executives vacillated between responding either in an ad hoc way to internal and external pressures or leading and supporting managed development.

England↗
PubMed2000

The effect of mental practice on performance in a sequential reaction time task.

The effect of mental practice on performance in a dot-location RT task was investigated. Participants (N = 40) were required either to mentally practice, physically practice, or do no practice on an RT task in which the signals appeared in a repeating sequence. Correct mental practice, as opposed to incorrect mental practice and no practice, was predicted to have a positive (enhancing) effect on performance of the RT task. Despite previous evidence that mental rehearsal does enhance performance in many perceptual-motor tasks, neither correct nor incorrect mental rehearsal affected subsequent sequence learning; that is, no mental practice effect was observed. That surprising result is discussed in terms of motivational, psychoneuromuscular, separate memory systems, and transfer-appropriate processing explanations of mental practice.

Female↗
PubMed2000

Rapid disappearance of the medial epithelial seam during palatal fusion occurs by multifocal breakdown that is preceded by expression of alpha smooth muscle actin in the epithelium.

Breakdown of the medial epithelial seam (MES) is essential to allow bridging of the mesenchyme during palatal fusion. Evidence exists for three mechanisms for this breakdown that are incompatible at the level of individual cells in the seam. To determine if breakdown of the seam was regionally restricted, 3-dimensional reconstructions were generated using volume rendering software from 1 micron serial sections in the sagittal plane of rat palates fixed during the process of fusion. The earliest break detected in electron micrographs was cell separation and in reconstructions was a discrete defect, with a rounded outline, nearer to the nasal than to the oral margin of the seam. Further breakdown produced a pattern of rounded defects along the nasal margin of the seam resulting in interconnected columns of cells preferentially attached to the oral epithelium. Computer generated slicing of reconstructed seams showed that groups of cells evident in cross-sections as islands at this stage of breakdown of the MES could be artifacts. Unequivocal islands of epithelial cells formed later in fusion had a rounded outline, an incomplete basal lamina and a halo of cells containing phagocytosed apoptotic debris. The pattern of breakdown indicated that the MES breaks down under tension. Laser confocal microscopy of sections and whole-mounts of palates demonstrated alpha-smooth muscle actin preferentially localized in the epithelial cells of the palatal shelves immediately before and during formation of the seam. Expression in epithelial cells of the isoform of actin normally restricted to smooth muscle cells engaged in tonic contraction supported an interpretation that the epithelial cells of the seam may be capable of generating tension during the palatal fusion event.

Actins↗
PubMed2000

Do new roles contribute to job satisfaction and retention of staff in nursing and professions allied to medicine?

BACKGROUND: Studies have suggested that job dissatisfaction is a major factor influencing nurses' and occupational therapists' intention to leave their profession. It has also been related to turnover of qualified nurses. However, literature relating to these factors among nurses and professions allied to medicine in innovative roles is scarce. AIMS: This paper considers the views of 452 nurses and 162 professionals allied to medicine (PAMs) in innovative roles, on job satisfaction, career development, intention to leave the profession and factors seen as hindering and enhancing effective working. METHODS: A self-completion questionnaire was developed as part of a larger study exploring new roles in practice (The ENRiP Study). FINDINGS: Overall there was a high level of job satisfaction in both groups (nurses and PAMs). Job satisfaction was significantly related to feeling integrated within the post-holder's own professional group and with immediate colleagues, feeling that the role had improved their career prospects, feeling adequately prepared and trained for the role, and working to protocol. Sixty-eight percent (n = 415) of respondents felt the role had enhanced their career prospects but over a quarter of respondents (n = 163; 27%) said they would leave their profession if they could. Low job satisfaction was significantly related to intention to leave the profession. CONCLUSIONS: The vast majority of post-holders in innovative roles felt that the role provided them with a sense of job satisfaction. However, it is essential that the post-holders feel adequately prepared to carry out the role and that the boundaries of their practice are well defined. Career progression and professional integration both being associated with job satisfaction.

Adult↗
PubMed1999

Efficacy of an ovine caseous lymphadenitis vaccine formulated using a genetically inactive form of the Corynebacterium pseudotuberculosis phospholipase D.

Caseous lymphadenitis (CLA) is an economically significant disease of sheep caused by the gram-positive bacterium Corynebacterium pseudotuberculosis. CLA vaccines are currently formulated using formalin inactivated culture supernatants that are rich in the C. pseudotuberculosis phospholipase D (PLD) exotoxin. One alternative to chemical detoxification is to inactivate the PLD genetically. This procedure not only provides a means to remove an onerous chemical treatment step but also the opportunity to increase gene expression, therefore improve protein yields. Using site-specific mutagenesis the C. pseudotuberculosis PLD was inactivated by substituting a serine residue at histidine 20 within the enzyme active site. CLA vaccine formulated using genetically inactivated PLD protected 44% of sheep against C. pseudotuberculosis challenge compared with 95% protection offered by the formalin inactivated preparation. Since there was no apparent difference in immune response mounted by vaccinated sheep the reason for this variation in vaccine efficacy remains unclear. Although genetic inactivation can be a convenient means to produce toxoid vaccines its use to develop a new CLA vaccine provided no net benefit over the conventional formulation.

Animals↗