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Biomedical subjects

K Jolly

Publications and source records attributed to K Jolly.

16 recordsLinked to original sources

Plasma haemostatic markers, endothelial function and ambulatory blood pressure changes with home versus hospital cardiac rehabilitation: the Birmingham Rehabilitation Uptake Maximisation Study.

BACKGROUND: Cardiac rehabilitation is an accepted therapeutic intervention in patients after myocardial infarction or coronary revascularisation. The effects of cardiac rehabilitation programmes, whether home based or hospital based, on haemostatic indices (as reflected by fibrinogen, plasma viscosity, fibrin D-dimer (an index of thrombogenesis), von Willebrand factor (vWf, an index of endothelial damage/dysfunction), soluble P-selectin (an index of platelet activation)), vasomotor function (using flow-mediated dilatation (FMD)) and ambulatory blood pressure (ABP) in patients with coronary heart disease are unknown. METHODS: 81 patients (66 men, mean (SD) 59 (11) years) after myocardial infarction or coronary revascularisation were randomised to comprehensive hospital-based (n = 40) or home-based (n = 41) cardiac rehabilitation. Plasma levels of vWf, D-dimer, fibrinogen, soluble P-selectin and plasma viscosity, as well as FMD and 24-h ABP, were measured at baseline and after 3 months of cardiac rehabilitation. RESULTS: In patients who completed cardiac rehabilitation, levels of vWf, fibrinogen and D-dimer were significantly lower and FMD improved (all p<or=0.001), whereas levels were unchanged in controls. Significant reductions were also observed in 24-h mean systolic blood pressure, diastolic blood pressure and mean aortic pressure after completion of cardiac rehabilitation (all p<0.05). No significant differences were observed between the hospital-based and home-based cardiac rehabilitation programmes on these indices. CONCLUSIONS: Cardiac rehabilitation improves haemostasis, endothelial function and ABP in patients with coronary heart disease, with no significant differences between home-based and hospital-based cardiac rehabilitation programmes. These effects may contribute to the beneficial effects of cardiac rehabilitation programmes on CV outcomes.

Blood Pressure↗

Incremental shuttle walking is associated with activation of haemostatic and haemorheological markers in patients with coronary artery disease: the Birmingham rehabilitation uptake maximization study (BRUM).

OBJECTIVE: To test the hypothesis that an incremental shuttle walk test (ISWT) affects plasma indices of endothelial damage and dysfunction (von Willebrand factor (vWf)), platelet activation (soluble P-selectin), thrombogenesis (D-dimer), fibrinogen, and plasma viscosity more adversely in coronary artery disease (CAD) than in health. ISWT is a standardised walking test that provokes maximal performance and correlates strongly with maximum oxygen uptake. METHODS: Research indices were measured before a practice ISWT and immediately after the second ISWT in 53 patients with CAD (48 men, mean (SD) age 59 (10) years) and in 19 matched healthy controls (16 men, 61 (10) years). Data were analysed before and after ISWT. RESULTS: Despite no significant difference in total distance walked between patients and controls, vWf (162 (45) before v 170 (48) UI/dl after) and fibrinogen (2.9 (0.7) v 3.1 (0.7) g/l) concentrations, plasma viscosity (1.63 (0.12) v 1.71 (0.14) mPa.s), and D-dimer (0.20 (interquartile range 0.10-0.30) v 0.21 (0.12-0.31 mg/l; all p < 0.05), but not soluble P-selectin, were significantly increased after ISWT in patients with CAD, even after correction for plasma volume change. Only fibrinogen (2.5 (0.7) v 2.7 (0.7 g/l) and plasma viscosity (1.60 (0.08) v 1.64 (0.08) mPa.s; both p < 0.01) increased among controls. The increment of fibrinogen was significantly higher in patients than in controls (p = 0.035) and correlated with total walking distance (r = 0.46, p < 0.001) and peak heart rate (r = 0.28, p = 0.02). The increment of plasma viscosity rise also significantly correlated with total distance walked (r = 0.66, p < 0.001). CONCLUSIONS: ISWT in patients with CAD appears to increase fibrinogen, vWf, and D-dimer compared with healthy controls.

Biomarkers↗

Re-organizing services for the management of upper gastrointestinal cancers: patterns of care and problems with change.

The 'Calman-Hine' report (1995) recommended that cancer surgery should be limited to specialist high-volume units. National guidance from the National Health Service (NHS) Executive in 2001 stated that specialist oesophagogastric cancer centres should 'aim to draw patients from catchment areas with a population of 1-2 million.' For pancreatic cancers, the catchment areas should be between 2 and 4 million, reflecting the relatively lower incidence of disease. For the West Midlands region, these recommendations would suggest that four or five centres might be required to provide specialist surgical management for oesophagogastric cancer, and one or two centres for pancreatic disease. We used Hospital Episode Statistics to analyse trends in management patterns for these tumours within the West Midlands during the period 1992-2000. Over 20 different units were involved in the management of oesophagogastric and pancreatic disease, and we were unable to discern any clear and consistent move towards the centralisation of the upper gastrointestinal work in high-volume units since the publication of the Calman-Hine report in 1995. Although the drive for centralisation might be anticipated to increase following the publication of the NHS Executive's guidance, there is a substantial way to go before the provision of surgical services for upper gastrointestinal cancers is limited to a small number of high-volume specialist units.

Cancer Care Facilities↗

Volumes of cancer surgery for breast, colorectal and ovarian cancer 1992-97: Is there evidence of increasing sub-specialization by surgeons?

The 'Calman-Hine Report' (1995) recommended that cancer surgery should be limited to 'high-volume' consultants. Through an analysis of 5 years of Hospital Episode Statistics for the West Midlands region (1992-1997), we have investigated whether there is evidence of increasing numbers of patients with breast, colorectal or ovarian cancer being treated by high throughput, i.e. sub-specialist surgeons, who carry out more than a threshold level of primary cancer resections annually. The proportion of cases treated by the high-volume breast, colorectal and ovarian cancer surgeons increased annually during the 5 years. The absolute number of consultant firms who undertook breast cancer resections reduced during the 5 years; but the number doing colorectal and ovarian surgery increased. Throughout the 5 years, half of the ovarian cancer resections were carried out by consultant firms who did very few procedures - less than 5 of these procedures annually. The relatively high case-load, the elective nature of breast cancer surgery and an early policy change have undoubtedly facilitated the move towards sub-specialization. The weaker trends for colorectal and ovarian cancer surgery suggest continued monitoring is required to ensure that there is a reduction in the proportion of people treated by surgeons who undertake few cancer resections annually.

Breast Neoplasms↗

Galactofuranoic-oligomannose N-linked glycans of alpha-galactosidase A from Aspergillus niger.

Extracellular alpha-galactosidase A was purified from the culture filtrate of an over-producing strain of Aspergillus niger containing multiple copies of the encoding aglA gene under the control of the glucoamylase (glaA) promoter. Endoglycosidase digestion followed by SDS/PAGE, lectin and immunoblotting suggested that glycosylation accounted for approximately 25% of the molecular size of the purified protein. Monosaccharide analysis showed that this was composed of N-acetyl glucosamine, mannose and galactose. Mild acid hydrolysis, mild methanolysis, immunoblotting and exoglycosidase digestion indicated that the majority of the galactosyl component was in the furanoic conformation (beta-D-galactofuranose, Galf). At least 20 different N-linked oligosaccharides were fractionated by high-pH anion-exchange chromatography following release from the polypeptide by peptide-N-glycosidase F. The structures of these were subsequently determined by fast atom bombardment mass spectrometry to be a linear series of Hex(7-26)HexHA(c2). Indicating that oligosaccharides from GlcNA(c2)Man(7), increasing in molecular size up to GlcNA(c2)Man(24) were present. Each of these were additionally substituted with up to three beta-Galf residues. Linkage analysis confirmed the presence of mild acid labile terminal hexofuranose residues. These results show that filamentous fungi are capable of producing a heterogeneous mixture of high molecular-size N-linked glycans substituted with galactofuranoic residues, on a secreted glycoprotein.

Aspergillus niger↗

Has Calman-Hine succeeded? Analysis of breast cancer procedure loads per consultant firm before and after the Calman-Hine report.

The Calman-Hine report was published in the UK in April 1995. It recommended the reorganization of cancer services into high-volume specialist units. This study analyzes Health Episode Statistics from the West Midlands Region of the UK NHS in order to establish whether--for breast cancer--specialization is occurring. We believe it is. Each year since the start of our analysis (1992) the proportion of procedures performed by 'high-volume' firms increased. The number of firms undertaking breast cancer procedures fell.

Journal Article↗

Epidemiology and diagnosis of meningitis: results of a five-year prospective, population-based study.

Implementation of the advice to give penicillin prior to admission, a fall in the lumbar puncture rate and the introduction into routine use of the meningococcal polymerase chain reaction (PCR) test are factors that have led us to reassess the way meningitis is diagnosed. We examined data for the period 1994-98 from a health district of 800,000 population. Of the 355 cases of meningitis reported, 258 (73%) had either confirmed, probable or possible meningococcal disease. Only 28% of meningococcal cases had received pre-admission benzylpenicillin. The proportion of suspected meningitis cases undergoing lumbar puncture fell over the period. It was 79% in 1994 and 61% in 1998 (p < 0.001). After meningococcal PCR was introduced in 1996, 73 (68%) meningococcal cases were microbiologically confirmed, compared to 72 (48%) before 1996 (p = 0.001). In all cases, age was an independent predictor of meningitis mortality, and for meningococcal cases, age and serogroup were independent predictors. Advice to general practitioners (GPs) to give preadmission benzylpenicillin to any suspected case of meningitis or meningococcal septicaemia should be reinforced regardless of age or whether a rash is present.

Adolescent↗

Coronary artery stents in the treatment of ischaemic heart disease: a rapid and systematic review.

BACKGROUND: Coronary artery stents are prosthetic linings inserted into coronary arteries via a catheter to widen the artery and increase blood flow to ischaemic heart muscle. They are used in the treatment of ischaemic heart disease (IHD). IHD is a major cause of morbidity and mortality (123,000 deaths per annum) in the UK and a major cost to the NHS. Clinical effects of IHD include subacute manifestations (stable and unstable angina) and acute manifestations (particularly myocardial infarction [MI]). Treatment includes attention to risk factors, drug therapy, percutaneous invasive interventions (PCIs) (including percutaneous transluminal coronary angioplasty [PTCA] and stents) and coronary artery bypass graft surgery (CABG). In the last decade there has been a steady and significant increase in the rate of PCIs for IHD. In the UK, rates per million population increased from 174 in 1991 to 437 in 1998. Stents are now used in about 70% of PCIs. Data from the rest of Europe suggest there is potential for PCI and stent rates to increase considerably. In the UK there is evidence of under-provision and inequity of access to revascularisation procedures. OBJECTIVES: The following questions were addressed. 1. What are the effects and effectiveness of elective stent insertion versus PTCA in subacute IHD, particularly stable angina and unstable angina? 2. What are the effects and effectiveness of elective stent insertion versus CABG in subacute IHD, particularly stable angina and unstable angina? 3. What are the effects and effectiveness of elective stent insertion versus PTCA in acute MI (AMI)? 4. What are best estimates of UK cost for elective stent insertion, PTCA and CABG in the circumstances of review questions 1 to 3? 5. What are best estimates of cost-effectiveness and cost-utility for elective stent insertion relative to PTCA or CABG in the circumstances of review questions 1 to 3? METHODS: A systematic review addressing the objectives was undertaken. DATA SOURCES: A search was made for RCTs comparing stents (inserted during a PTCA procedure) with PTCA alone or with CABG in any manifestation of IHD. The search strategy covered the period from 1990 to November 1999 and included searches of electronic databases (MEDLINE, EMBASE, BIDS ISI, The Cochrane Library), Internet sites, and hand-searches of cardiology conference abstracts and 1999 issues of cardiology journals. Lead researchers and local clinical experts were contacted. Manufacturers' submissions to the National Institute for Clinical Excellence were searched. The search strategy was expanded to look for relevant economic analyses and information to inform the economic model (including searching MEDLINE, the NHS Economic Evaluation Database and the Database of Abstracts of Reviews of Effectiveness). Searches focused on research that reported costs and quality of life data associated with IHD and interventional cardiology. STUDY SELECTION: For the review of clinical effectiveness, inclusion criteria were: (i) RCT design; (ii) study population comprising adults with IHD in native or graft vessels (including patients with subacute IHD or AMI); (iii) procedure involving elective insertion of coronary artery stents; (iv) elective PTCA (including PTCA with provisional stenting) or CABG as comparator; (v) outcomes defined as one or more of: combined event rate (or event-free survival), death, MI, angina, target vessel revascularisation, CABG, repeat PTCA, angiographic outcomes; (vi) trials that had closed and reported results for all or almost all recruited patients. For the economic evaluation, studies of adults with IHD were included if they were of the following types: studies reporting UK costs; comparative economic evaluation combining both costs and outcomes; economic evaluations reporting costs and outcomes separately for the years 1998 and 1999 (to ensure current practice was included).(ABSTRACT TRUNCATED)

Adult↗

Randomised controlled trial of follow up care in general practice of patients with myocardial infarction and angina: final results of the Southampton heart integrated care project (SHIP). The SHIP Collaborative Group.

OBJECTIVE: To assess the effectiveness of a programme to coordinate and support follow up care in general practice after a hospital diagnosis of myocardial infarction or angina. DESIGN: Randomised controlled trial; stratified random allocation of practices to intervention and control groups. SETTING: All 67 practices in Southampton and south west Hampshire, England. SUBJECTS: 597 adult patients (422 with myocardial infarction and 175 with a new diagnosis of angina) who were recruited during hospital admission or attendance at a chest pain clinic between April 1995 and September 1996. INTERVENTION: Programme to coordinate preventive care led by specialist liaison nurses which sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow up. MAIN OUTCOME MEASURES: Serum total cholesterol concentration, blood pressure, distance walked in 6 minutes, confirmed smoking cessation, and body mass index measured at 1 year follow up. RESULTS: Of 559 surviving patients at 1 year, 502 (90%) were followed up. There was no significant difference between the intervention and control groups in smoking (cotinine validated quit rate 19% v 20%), lipid concentrations (serum total cholesterol 5.80 v 5.93 mmol/l), blood pressure (diastolic pressure 84 v 85 mm Hg), or fitness (distance walked in 6 minutes 443 v 433 m). Body mass index was slightly lower in the intervention group (27.4 v 28.2; P=0.08). CONCLUSIONS: Although the programme was effective in promoting follow up in general practice, it did not improve health outcome. Simply coordinating and supporting existing NHS care is insufficient. Ischaemic heart disease is a chronic condition which requires the same systematic approach to secondary prevention applied in other chronic conditions such as diabetes mellitus.

Angina Pectoris↗

The success of an integrated care programme for patients with ischaemic heart disease: the practice nurses' perspective of SHIP.

Follow-up care of patients with angina and myocardial infarction after hospital discharge is known to be suboptimal across the UK. The employment of cardiac liaison nurses ensured timely notification of hospital discharge and good communication of each patient's current and planned care. The direct ongoing support of the liaison nurse was valued by more practice nurses than educational support meetings and the initial counselling skills course. The most important factor which enabled practice nurses to expand their role to provide post-hospital follow-up care was the support of the doctors in the practice. After the conclusion of the Southampton Heart Integrated Care Project (SHIP) and the withdrawal of cardiac liaison nurses, the lack of hospital discharge notification was the most important reason for practice nurses discontinuing follow-up care.

Aftercare↗

Follow-up care in general practice of patients with myocardial infarction or angina pectoris: initial results of the SHIP trial. Southampton Heart Integrated Care Project.

OBJECTIVE: We aimed to assess the effectiveness of a nurse-led programme to ensure that follow-up care is provided in general practice after hospital diagnosis of myocardial infarction (MI) or angina pectoris. METHODS: We conducted a randomized controlled trial with stratified random allocation of practices to intervention and control groups within all 67 practices in Southampton and South-West Hampshire, England. The subjects were 422 adult patients with a MI and 175 patients with a new diagnosis of angina recruited during hospital admission or chest pain clinic attendance between April 1995 and September 1996. Intervention involved a programme of secondary preventive care led by specialist liaison nurses in which we sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow-up. The main outcome measures were: extent of general practice follow-up; attendance for cardiac rehabilitation; medication prescribed at hospital discharge; self-reported smoking, diet and exercise; and symptoms of chest pain and shortness of breath. Follow-ups of 90.1 % of subjects at 1 month and 80.6% at 4 months were carried out. RESULTS: Median attendance for nurse follow-up in the 4 months following diagnosis was 3 (IQR 2-5) in intervention practices and 0 (IQR 0-1) in control practices; the median number of visits to a doctor was the same in both groups. At hospital discharge, levels of prescribing of preventive medication were low in both intervention and control groups: aspirin 77 versus 74% (P = 0.32), cholesterol lowering agents 9 versus 10% (P = 0.8). Conversely, 1 month after diagnosis, the vast majority of patients in both groups reported healthy lifestyles: 90 versus 84% reported eating healthy food (P = 0.53); 73 versus 67% taking regular exercise (P = 0.13); 89 versus 92% not smoking (P = 0.77). Take up of cardiac rehabilitation was 37% in the intervention group and 22% in the control group (P = 0.001); the median number of sessions attended was also higher (5 versus 3 out of 6). CONCLUSIONS: The intervention of a liaison nurse is effective in ensuring that general practice nurses follow-up patients after hospital discharge. It does not alter the number of follow-up visits made by the patient to the doctor. Levels of prescribing and reported changes in behaviour at hospital discharge indicate that the main tasks facing practice nurses during follow-up are to help patients to sustain changes in behaviour, to encourage doctors to prescribe appropriate medication and to encourage patients to adhere to medication while returning to an active life. These are very different tasks to those traditionally undertaken by practice nurses in relation to primary prevention, where the emphasis has been on identifying risk and motivating change. Assessment of the effectiveness of practice nurses in undertaking these new tasks requires a longer follow-up.

Adult↗

The renal transport of taurine and the regulation of renal sodium-chloride-dependent transporter activity.

A model for the beta-amino acid taurine transport is presented to help define the ionic, pH, and voltage requirements for the movement of taurine into the rat proximal tubule brush border membrane vesicle (BBMV). Sodium-(Na+)-taurine symport across the apical surface of the proximal tubule has a highly specific requirement for Cl- and Br-. Active taurine transport operates with a 2 Na+:1 Cl-:1 taurine-carrier complex. Complexes like the one required for maximal taurine transport may be pertinent for many other amino acids whose uptake is Na(+)-dependent. Renal epithelial cell lines LLC-PK and MDCK were used to define the nature of taurine uptake; they express Na(+)-Cl(-)-taurine cotransport that is inhibited by beta-alanine. The cell lines up- or down-regulate taurine transport in response to changes in the taurine concentration of the medium in a manner similar to that seen in BBMV. The adaptation is present by 12 h and depends on new protein synthesis and protein import to the cell membrane. The role of trafficking in the adaptive response was also explored in brush border vesicles. During dietary surfeit, transporter could be down-regulated and transporters could be shifted back into the microtubule system, resulting in taurinuria. Use of continuous renal cell lines allowed a more mechanistic exploration of intracellular trafficking in the up- and down-expression of the Na(+)-Cl(-)-taurine cotransporter. Colchicine appeared to be a more potent inhibitor of the rapid (over hours) adaptive response to a reduction in media and, therefore, intracellular taurine content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased Na+-taurine symporter in rat renal brush border membranes: preformed or newly synthesized?

The renal adaptive response to a varied intake of sulfur amino acids is demonstrated by an increase in the initial rate of Na+-taurine symport (cotransport) by rat renal brush border membrane vesicles (BBMVs) after 8-14 days of a low methionine diet. A high (3%) taurine diet reduces Na+-taurine symport. Fasting for 3 days, which depletes renal tubule cell taurine content, also enhances Na+-taurine symport both initially (15 s) and throughout the overshoot. In this study we examine the possibility that a rapid-onset adaptive response is expressed in BBMV, with the increased Na+-taurine symport reflecting the incorporation of preformed symporter into membranes rather than new synthesis. Rats fed the low methionine diet for 14 days were placed on the high taurine diet for 12-18 h; Na+-taurine symport activity fell by 40%. Fasting for 4 h restored low methionine diet levels of Na+-taurine symport activity (92 pmol.mg protein-1.15 s-1), defining a rapidly induced rise in uptake. Colchicine (0.6 mg) was injected prior to fasting in a group of rats because it blocks the incorporation (import) of preformed symporter into the membrane. Animals injected with colchicine had a pattern of BBMV uptake similar to that found in animals switched to the high taurine diet for 18 h. This agent blocked the rapidly induced rise in uptake. Feeding with the high taurine diet for 4 h caused a fall in uptake of 16.5%; colchicine blocked this reduction in uptake. These results indicate that the nephron can respond rapidly to changes in the intake of amino acids, conserving taurine in periods of nutrient lack and excreting excess taurine within 4 h in periods of surfeit. This rapid response is expressed at the brush border surface. The use of cholchicine indicates that the increase or reduction in Na+-taurine symport activity is due to incorporation (import) of transporter into the BBMV rather than to de novo synthesis.

Amino Acids, Sulfur↗