Position and Mobilisation Post-Angiography Study (PAMPAS): a comparison of 4.5 hours and 2.5 hours bed rest.
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Bed Rest↗
Biomedical subjects
J Gunn
Publications and source records attributed to J Gunn.
Revascularisation for acute coronary syndromes: PCI or CABG?
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Angioplasty, Balloon, Coronary↗
Paget's disease in New Zealand: evidence for declining prevalence.
The prevalence rate of Paget's disease in New Zealand is believed to be among the highest in the world, but recent data suggest that it may have decreased in recent decades. We estimated the current prevalence of Paget's disease in subjects of European origin (>55 years of age) in two New Zealand cities (Dunedin and Auckland) based on review of nearly 2000 pelvic radiographs. Prevalence rate increased with age (p = 0.022) and was higher in men (p = 0.014), but there was no significant difference between the two cities. The Dunedin data were compared with a 1983 survey from the same city, and prevalence was approximately half its previous level (p = 0.012). In Auckland, the prevalence of an isolated raised plasma alkaline phosphatase level (>150 U/L, normal range <120 U/L) was estimated in over 80,000 blood samples processed at a community laboratory. The prevalence of "biochemical Paget's disease," as assessed by this surrogate marker, was very similar to that observed in the radiographic survey in Auckland for subjects <80 years of age, but not for older subjects. We conclude that the prevalence of Paget's disease in New Zealand has declined over the past two decades, indicating that there are important environmental determinants in its development. Biochemical estimates of the prevalence of Paget's disease agree well with radiographic estimates, except in the elderly. The method used herein offers an alternative way of determining the prevalence of Paget's disease.
Aged↗
Coronary artery stretch versus deep injury in the development of in-stent neointima.
OBJECTIVE: To investigate the relative importance of stent induced arterial stretch and deep injury to the development of in-stent neointima. SETTING: Normal porcine coronary arteries METHODS: 30 BiodivYsio stents (Biocompatibles) were deployed at a stent to artery ratio of 1.25:1 (a moderate injury) and harvested at 28 days. Multiple serial cross sections were analysed morphometrically and the neointimal areas were correlated with the type and degree of injury. RESULTS: Arterial stretch occurred in 78% of struts (77% of sections) and produced moderate neointimal growth (neointimal area 1.93 (0.13) mm2). Deep injury (rupture of the internal elastic lamina) occurred in 20% of struts (23% of sections) and produced a 1.7-fold increase in neointimal area (3.33 (0.41) mm2) compared with stretch only (p = 0.0002). With even deeper injury (rupture of the external elastic lamina), there was a 2.6-fold increase in neointimal area (5.01 (0.48) mm2) compared with stretch only (p = 0.02). A new injury score, incorporating both stretch and deep injury, correlated with neointimal area (r = 0.60, p < 0.001). CONCLUSIONS: Stretch of the coronary artery in a stent is common, and a major contributor to neointima formation, even in the absence of deep injury. Deep injury is, however, a more potent stimulus to neointima formation than stretch. Greater degrees of stretch are associated with thicker neointima. Where neither deep injury nor stretch are seen, the stent has no effect upon the development of neointima.
Animals↗
Effect of selective or combined inhibition of integrins alpha(IIb)beta(3) and alpha(v)beta(3) on thrombosis and neointima after oversized porcine coronary angioplasty.
BACKGROUND: Thrombosis and neointima formation limit the efficacy of coronary angioplasty (PTCA). Clinical trials have implicated the adhesion molecules integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) in these processes. The roles of these molecules in vascular smooth muscle cell adhesion, platelet aggregation, and the thrombotic and neointimal response to oversize porcine PTCA was investigated by use of a selective alpha(IIb)beta(3) antagonist (lamifiban), a selective alpha(v)beta(3) antagonist (VO514), and a combined alpha(IIb)beta(3)/alpha(v)beta(3) antagonist (G3580). METHODS AND RESULTS: In vitro, both alpha(v)beta(3) inhibitors caused dose-dependent inhibition of porcine vascular smooth muscle cell adhesion to vitronectin but not to collagen type IV, fibronectin, or laminin, whereas selective alpha(IIb)beta(3) inhibition had no effect. Intravenous infusions of either alpha(IIb)beta(3) inhibitor in swine profoundly inhibited ex vivo platelet aggregation to ADP, whereas selective alpha(v)beta(3) inhibition had no effect. In a porcine PTCA model, intravenous infusions of the integrin antagonists were administered for 14 days after oversized balloon angioplasty injury. After PTCA, there was regional upregulation of integrin alpha(v)beta(3) in the developing neointima, as assessed by immunohistochemistry. Six hours after PTCA, obstruction of lumen by thrombus was reduced significantly by alpha(IIb)beta(3) inhibition compared with either control or alpha(v)beta(3) inhibition (mean control, 18.7%; VO514, 18.5%; lamifiban, 6.4%; G3580, 7.9%). Twenty-eight days after PTCA, there was a significant reduction of neointima with inhibitors of either integrin (mean intima/media ratio: control, 3.08; VO514, 1.33; lamifiban, 0.97; G3580, 1.32). CONCLUSIONS: We conclude that both integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) participate in neointima development after experimental angioplasty.
Acetates↗
TGFbeta is active, and correlates with activators of TGFbeta, following porcine coronary angioplasty.
OBJECTIVE: Restenosis following angioplasty involves processes that may be influenced by local production of cytokines. We investigated the expression of active and total transforming growth factor beta (TGFbeta) following porcine coronary angioplasty (PTCA), and have correlated this with the expression of potential in vivo activators of TGFbeta: mannose-6-phosphate/insulin-like growth factor-II (M6P/IGF-II) receptor and thrombospondin-1. METHODS: Oversized porcine PTCA was performed and the arteries excised after selected intervals. Levels of in situ active and total (active plus latent) TGFbeta were determined using a modified plasminogen activator-inhibitor/luciferase bioassay. RESULTS: Levels of active TGFbeta significantly increased 2 h to 7 days after angioplasty, compared to non-injured controls. Levels returned to baseline by 28 days. Active TGFbeta in tissues adjacent to the injured artery did not change. Total TGFbeta was significantly higher than controls 2-6 h after injury. M6P/IGF-II receptor mRNA was upregulated between 6 h and 3 days after injury, with protein detectable at 3-28 days. Thrombospondin-1 was detected between 1 h and 14 days. CONCLUSIONS: We conclude that balloon injury causes an early rapid increase in levels of active TGFbeta, that correlates with the expression of TGFbeta activators. Thus, TGFbeta is a good potential target for anti-restenotic therapies.
Angioplasty, Balloon, Coronary↗
The dose response of the internal anal sphincter to topical application of glyceryl trinitrate ointment.
INTRODUCTION: Glyceryl trinitrate (GTN) ointment has been used for the treatment of chronic anal fissure based on the assumed pathophysiology that the fissure is due to internal anal sphincter hypertonia and that GTN causes relaxation. METHOD: 48 patients, with a diagnosis of haemorrhoids, underwent 24 h anal manometry following application of different concentrations (placebo, 0.1%, 0.2%, 0.4%) of GTN ointment. RESULTS: We have found that there was a progressive relaxation with increasing doses (placebo -8.8%, 0.1% GTN -21.9%, 0.2% GTN -27.2%, 0.4% GTN -33.1%). One way ANOVA showed this progression was significant (P=0.020), with the difference lying between placebo and 0.4% GTN (Tukey multiple comparisons, P=0.017). Only 3 patients experienced headaches and these were split evenly between the treatment arms. CONCLUSION: The internal anal sphincter has a dose related response to GTN and when dose application is strictly applied higher doses may be used without an increase in side-effects.
Clinical Trial↗
Ultrasound as treatment for coronary artery disease.
Therapeutic ultrasound is already established in the treatment of diverse surgical conditions, such as cataract, liver cancer, and stones, without danger to healthy tissue. Clinical trials of catheter-delivered, high energy, low frequency (kHz) ultrasound undertaken over the last decade have demonstrated the safety of ultrasound in the treatment of peripheral and coronary artery disease, and have identified a number of indications in which it may be particularly advantageous. The dispersal of thrombus, the recanalization of chronic total occlusions, and the favorable modification of the distensibility of small, atherosclerotic vessels are three promising areas. The authors review developments in these fields.
Angioplasty, Balloon, Coronary↗
Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty.
BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is limited by the recurrence of luminal stenosis, which occurs in up to 50% of procedures. It has been shown that patient specific factors, perhaps genes, contribute to this process. OBJECTIVE: To determine whether completion of healing after PTCA is part of an acute self limiting inflammatory process and whether polymorphism at important inflammatory gene loci might determine susceptibility to restenosis after PTCA. DESIGN: DNA samples were collected from 171 patients attending for elective PTCA in Sheffield (S) and Leicester (L), who were scheduled to undergo follow up angiography (at four months (L) or six months (S)) as part of other restenosis studies. At follow up angiography, the patients were separated into restenosers (> 50% luminal narrowing) and non-restenosers (< 50% luminal narrowing). Four DNA polymorphisms within interleukin 1 (IL-1) related loci (IL-1A (-889), IL-1B (-511), IL-1B (+3954), and IL-1RN intron 2 VNTR (variable number tandem repeat)) were genotyped using methods based on polymerase chain reaction. Significance was assessed by chi(2) analysis of the relevant contingency table, and the magnitude of effect was estimated by calculating odds ratios. The Mantel-Haenszel (MH) test was applied to summarise data across the two populations. RESULTS: Allele 2 at IL-1RN (IL-1RN*2) was significantly over represented in the non-restenoser group (L+S, 34% v 23% in restenosers). Furthermore, IL-1RN*2 homozygosity was increased in the non-restenoser population compared with the restenosers (MH test: p = 0.0196 (L+S); p = 0.031 (L+S, single vessel disease only), and the effect seemed to be restricted to the single vessel disease subpopulation. For other polymorphism within IL-1 related loci no significant associations were found with either restenosis or non-restenosis. CONCLUSIONS: IL-1RN*2 may be associated with protection from restenosis after PTCA for individuals with single vessel disease. As this polymorphism has functional significance, this finding suggests that alteration in an individual's inflammatory predisposition may modulate the blood vessel response to injury.
Alleles↗
Localization of c-Myb and induction of apoptosis by antisense oligonucleotide c-Myb after angioplasty of porcine coronary arteries.
Previous studies have shown that inhibition of the proto-oncogene c-myb inhibits neointimal formation in various animal models. However, the temporal and spatial expression of c-Myb in the vessel wall after injury is not known, and the mechanism of action of antisense oligonucleotide (AS-ODN-c-myb) inhibition remains unclear. One potential effect of cell cycle dysregulation by inhibition of c-myb is an increase in the rates of apoptosis. In this study, c-Myb expression after percutaneous transluminal coronary angioplasty (PTCA) injury and induction of apoptosis after AS-ODN-c-myb treatment were determined. Immunohistochemistry and cellular phenotyping were used to localize c-Myb expression in porcine coronary arteries at various time intervals after PTCA. In vitro, the effects of AS-ODN-c-myb on the apoptosis of porcine vascular smooth muscle cells (PVSMCs) and endothelial cells were determined by using a cell-death ELISA and time-lapse video microscopy. In vivo, local delivery of AS-ODN-c-myb was performed after PTCA of pig coronary arteries, and apoptosis was quantified at 6 hours. c-Myb is induced in pig coronary arteries after angioplasty, with maximal expression in inflammatory cells at 18 hours and in vascular smooth muscle cells at 3 to 7 days. In vitro, AS-ODN-c-myb enhanced PVSMCs (6.8+/-0.8% [P=<0.001] versus 0.5% serum) but not endothelial cell apoptosis (1.4+/-0.5% [P=NS] versus 0.5% serum). In vivo, 6 hours after porcine coronary angioplasty and delivery of AS-ODN-c-myb, the proportion of apoptotic cells within the media was 4.2+/-0.8% (PTCA alone), 2.3+/-0.2% (PTCA+vehicle), and 9.0+/-1.1% (PTCA+AS-ODN-c-myb; P<0.05 versus PTCA alone and P<0.01 versus PTCA+saline). c-Myb is expressed after PTCA of pig coronary arteries, and AS-ODN-c-myb induces apoptosis of PVSMCs in vitro and medial cells in vivo.
Angioplasty, Balloon, Coronary↗
Phosphorylcholine-coated stents in porcine coronary arteries: in vivo assessment of biocompatibility.
AIMS: To examine the angiographic (quantitative coronary angiography), morphometric, light microscopic (LM) (i.e., histology and immunohistochemical staining) and electron microscopic (EM) findings after implantation of phosphorylcholine (PC)-coated compared to uncoated stents in porcine coronary arteries. METHODS: Forty (25 PC-coated, 15 uncoated) divYsio stents were implanted into the coronary arteries of 20 pigs. Quantitative coronary angiography (QCA) was performed pre-stent and post-implantation in fifteen pigs, at 28 days. Two pigs were killed at 5 days (LM and scanning EM), one pig at 14 days (scanning EM) and 17 pigs at 28 days (LM, scanning EM, transmission EM). At 28 days, thirty-two of 34 stented segments excised were formalin-fixed, of which 30 were embedded in resin and sectioned for morphometry and LM. Remaining stents were examined by TEM and SEM. RESULTS: No angiographically occlusive thrombosis occurred in any of the stents. LM at 5 days showed endothelialization of PC-coated and uncoated stents, which was also confirmed by scanning EM at 14 days. At 28 days, QCA and morphometry showed no significant differences between PC-coated and uncoated stents. A few inflammatory cells were seen in both stent types at 5 days but there was no inflammatory or additional tissue reaction to PC-coated compared to uncoated stents at 28 days. CONCLUSIONS: The divYsio stents, with or without PC coating, performed equally well in terms of acute patency, 28-day QCA and morphometry. The PC coating allows a stent to endothelialize normally and is not associated with specific histological changes. The PC coating on the divYsio stent appears biocompatible.
Animals↗
Keratin 20 is a specific marker of submicroscopic lymph node metastases in colorectal cancer: validation by K-RAS mutations.
Lymph node status has major prognostic importance in colorectal cancer and greater precision in the diagnosis of lymph node metastases should provide better prognostic and therapeutic guidance. Keratin 20 (K20) gene expression has been used as a marker of lymph node metastases, but the evidence for this remains circumstantial. This study has therefore sought to determine K20 specificity and to correlate K20 expression with mutant K-RAS expression, in order to provide direct evidence that K20 expression in lymph nodes of colorectal cancer patients genuinely reflects metastatic disease. Specificity of K20 expression was established against a range of tissue types and 289 lymph nodes from 41 non-cancer control patients. K20 expression was restricted to gastrointestinal epithelia and was only present in one of the 289 control lymph nodes, giving a calculated specificity of 97.6% (95% confidence limits: 87.1-99.9%). Forty-two tumour samples were analysed for the presence of K-RAS codon 12 gene mutations using a RT-PCR mutant allele-specific amplification (MASA) technique. Thirteen tumours (31%) had codon 12 mutations detected by MASA and these were further analysed to determine the exact nature of the mutation. MASA was then used to screen the lymph nodes from these patients for the presence of the tumour-specific K-RAS transcript and the results were compared with K20 RT-PCR and histopathology from the same samples. Whilst K-RAS MASA was not as sensitive as K20 RT-PCR, there was substantial agreement between the assays. There were no K20-negative lymph nodes which were found to be K-RAS MASA-positive, whereas seven nodes in four patients were K20-positive and K-RAS-negative, in keeping with the differences in assay sensitivity. These results further validate K20 as a marker by providing greater certainty that what is being detected represents occult metastatic disease.
Biomarkers, Tumor↗
[Interventional therapy of aortic isthmus stenosis with concomitant thoracic aortic aneurysm with a stent graft].
A 23 year old male presented with hypertension and a systolic murmur. ECG and echo revealed signs of left ventricular hypertrophy. Aortography showed aortic coarctation (delta p max. 40 mmHg) in combination with an aneurysm originating from the coarcted segment distal from the origin of the left subclavian artery. Coarctation and aneurysm were treated using direct placement of a stent graft and subsequent balloon dilatation. On final aortography, the outline of the stented segment was smooth with good stent apposition and the aneurysm entry was closed. The residual gradient was 10 mmHg (max). Six months later, the patient has no symptoms and a blood pressure of 120/80 mmHg on both arms.
Adult↗
General practitioners: their contact with maternal and child health nurses in postnatal care.
OBJECTIVE: To assess the level of contact of general practitioners (GP) with maternal and child health nurses (MCHN) in postnatal care. METHODOLOGY: A postal survey of 1104 Victorian GP was used, with a response rate of 70%. To account for the clustered sampling frame, hierarchical data analysis techniques were used. RESULTS: Half of the GP (351/710) had no contact with their local MCHN in the previous month; and one in 10 had four or more contacts. Eighty-eight per cent of GP described the contact as helpful. In 56% of cases the MCHN was reported as the usual initiator of the contact. The most common reason for contact concerned the baby's physical problems (42%). After adjusting for the number of women seen for the routine 6-week postnatal review and other GP characteristics, male GP were as likely as female GP to report MCHN contact (odds ratio (OR) = 1.00; 95% confidence interval (CI) = 0.67-1.62). General practitioners aged 31-40 years were more likely to report contact with MCHN than GP aged 51-60 (OR = 0.45; 95% CI = 0.22-0.86) as were GP with the FRACGP qualification (OR = 1.64; 95% CI = 1.21-2.45). CONCLUSIONS: This study provides baseline information on the level of GP contact with MCHN as they provide postnatal care. Although there were GP in Victoria who maintained a level of contact with MCHN, almost half reported no contact in the previous month. Most GP who reported contact with MCHN found it useful. This finding should encourage GP and MCHN coordination to improve continuity and postnatal care outcomes.
Attitude of Health Personnel↗
Sharing obstetric care: barriers to integrated systems of care.
OBJECTIVES: To map the provision of shared obstetric care in Victoria, and investigate the views of care providers about the ways in which current practice could be improved. METHOD: All Victorian public hospitals with > or = 300 births per annum and a purposive sample of hospitals with < 300 births per annum were mailed a questionnaire seeking information about current practice. Interviews with key informants (n = 32) were conducted at four case study sites. RESULTS: The response rate to the hospital survey was 98% (42/43). Fourteen different models of shared care were identified. Two-thirds of hospitals with > or = 300 births per annum (16/28) had three or more different models of shared care. Six hospitals (15%) had written guidelines for all models of shared care offered; 13 (32%) had written guidelines covering some models. Practice varied considerably in relation to: exclusion criteria, recommended schedule of visits and use of patient-held records. There was little consensus about the content of visits and responsibility for covering particular aspects of care. Few hospitals (6/42) had written information for women about shared care. Care providers expressed divergent views regarding the question of where ultimate responsibility lies for individual patient care and for the overall management of shared care. CONCLUSIONS: Current funding arrangements provide strong incentives to expand enrollment in shared obstetric care. Expansion of shared care has occurred without the development of formal, consultative and agreed arrangements between providers, or adequate provision for monitoring, evaluation and review. The variety, complexity and fluidity of models of shared care and lack of agreed procedures contribute to difficulties experienced by both providers and women participating in shared care. IMPLICATIONS: Detailed evidence-based agreed guidelines developed in consultation with hospital and community providers, and provision of improved information to women about what to expect in shared care arrangements are urgently required.
Attitude of Health Personnel↗
Future directions for treatment in forensic psychiatry.
BACKGROUND: As the availability of mental hospital beds has fallen, so the number of people in prison has risen. AIMS: To review current policy trends in British forensic psychiatry and put them in an international context. METHOD: Literature on the prevalence rates of psychiatric disorder in prisons and jails has been examined for the USA, England & Wales and New Zealand. RESULTS: All studies show a high prevalence of mental disorder in prisons and jails. Authors in the USA suggest that prisons are replacing mental hospitals. In England & Wales rates of psychosis are reported as 4-10% for remanded prisoners and 2-7% for sentenced prisoners. Substance misuse among prisoners is a major problem. Prison is the preferred place of disposal for large numbers of mentally disordered people. Does this matter? Why should this be the case? Is this the cheapest option? Politicians are considering new powers to direct more people into institutions (presumably prisons) on the grounds of public protection. CONCLUSIONS: We need more information about attitudes and their formation. We need more interprofessional dialogue about the best arrangements for people with mental disorders, and inter-disciplinary education.
Attitude to Health↗
Substance misuse as a marker of vulnerability among male prisoners on remand.
BACKGROUND: More treatment for substance misuse should be provided within prisons. AIMS: To examine differences between prisoners on remand with substance misuse problems and other prisoners on remand. METHOD: Random selection and interview of unconvicted male prisoners (n = 750, a 9.4% sample), plus examination of the prison medical record. RESULTS: Of the sample of 750, 253 subjects (33.7%) reported either drug- or alcohol-related health problems or dependency. Compared with other prisoners on remand, they reported more childhood adversity, conduct disorder, self-harm, past psychiatric treatment and current mood disorder, and had fewer qualifications, were more likely to be unemployed and have more housing difficulties. CONCLUSIONS: One-third of unconvicted men in prison report substance-related problems, and these are a marker for vulnerability within a disadvantaged population. Health care providers should involve this group in treatment and rehabilitation, both inside prison and following release.
Adolescent↗
How I treat ... a woman with a hatred of children.
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Communication↗