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Biomedical subjects

G S Hillis

Publications and source records attributed to G S Hillis.

At least 19 recordsLinked to original sources
PubMed2005

B-type natriuretic peptide and the prediction of outcome in patients admitted to intensive care.

B-type natriuretic peptide is known to predict outcome in congestive cardiac failure and myocardial infarction. We aimed to determine whether measurement of B-type natriuretic peptide would predict hospital mortality in patients admitted to an intensive care unit. We conducted a prospective observational cohort study in 78 consecutive patients. Demographics, clinical details and clinical outcomes were recorded. Admission and 24 h B-type natriuretic peptide and cardiac troponin I levels were measured. B-type natriuretic peptide and cardiac troponin I levels taken on intensive care admission and 24 h after admission did not accurately predict hospital mortality for all patients, including patients with severe sepsis or septic shock (all p > 0.05). B-type natriuretic peptide levels were higher in patients with severe sepsis and septic shock (p = 0.02), in patients > or = 65 years (p = 0.04) and in patients with raised creatinine > or = 110 micromol.l(-1) (p = 0.02). We concluded that B-type natriuretic peptide, measured soon after admission to intensive care, does not usefully predict outcome after intensive care.

APACHE↗
PubMed2004

Reducing call-to-needle times: the critical role of pre-hospital thrombolysis.

BACKGROUND: Current guidelines recommend that patients with acute myocardial infarction should receive thrombolysis within 60 min of seeking professional help. AIM: To compare current rates of pre-hospital thrombolysis in Grampian with historical data, and assess the effect of pre-hospital thrombolysis on the proportion of patients achieving 'call-to-needle' times within national guidelines. DESIGN: Prospective audit. METHODS: Data were collected on all patients (n=535) admitted to the coronary care unit and thrombolysed, either in hospital or in the community from July 2000 to June 2002, using standardized forms. RESULTS: One hundred and thirty-three patients (25%) received pre-hospital thrombolysis and 402 (75%) received in-hospital thrombolysis. This compares with a 19% (195/1046) pre-hospital thrombolysis rate in the mid-1990s (p=0.005). Median 'call-to-needle' times were 45 min for pre-hospital thrombolysis and 105 min for patients who received in-hospital thrombolysis (p < 0.001). Only 24% (96/396) of patients receiving in-hospital thrombolysis were treated within the recommended guideline, vs. 79% (88/111) of pre-hospital thrombolysis patients (p <0.001). DISCUSSION: Pre-hospital thrombolysis rates in Grampian are increasing. Administration of thrombolysis in the community greatly increases the proportion of patients achieving a 'call-to-needle' time of 60 min, with a median time saving of approximately 1 h.

Acute Disease↗
PubMed2001

Coronary artery disease in patients with chest pain who have low-risk clinical characteristics and negative cardiac troponin I.

Patients who have low-risk clinical features and negative cardiac troponin levels may be suitable for early discharge after a brief period of observation in the emergency department (ED). Little is known about the prevalence and severity of coronary artery disease in such patients, although this has implications for follow-up. Subjects included 570 patients who were at < or =7% risk of acute myocardial infarction (AMI), remained clinically stable (defined as the absence of new ischemic changes on their electrocardiograph, signs or symptoms of heart failure, the development of a cardiac arrhythmia or hypotension requiring either inotropes or volume repletion) and had cardiac troponin I (cTnI) levels <0.2 microgl(-1) during the initial 12 hours of hospitalization. Clinical features were documented and those undergoing stress tests and/or coronary angiograms had these graded by 2 independent observers. Overall, 190 (33.3%) of this population, who might be considered suitable for early discharge, had objective evidence of coronary artery disease. Patients with chest pain who are at low risk of AMI, remain clinically stable and have negative cTnI over the initial 12 hours of observation are a heterogeneous population, some of who have threatening coronary disease. This does not preclude early discharge from the ED but emphasizes the need for careful assessment and follow-up.

Aged↗
PubMed2001

Soluble intercellular adhesion molecule-1 as a predictor of early adverse events in patients with chest pain compatible with myocardial ischemia.

STUDY OBJECTIVE: Inflammation plays an important role in acute coronary syndromes, and some evidence indicates that patients with a more pronounced vascular inflammatory response have a poorer outcome. Soluble intercellular adhesion molecule-1 (sICAM-1) is a specific marker for vascular endothelial cell activation. The aim of this study was to investigate the prognostic value of plasma sICAM-1 levels in patients with acute chest pain compatible with myocardial ischemia. METHODS: This prospective study was conducted at 2 urban university medical centers. The study cohort consisted of 119 consecutive patients with chest pain in whom myocardial ischemia was suspected clinically at presentation. Patients with conditions that affect sICAM-1 levels were ineligible. Cardiac troponin I (cTnI), C-reactive protein, and sICAM-1 levels were assayed at presentation to the emergency department. The primary end point was the occurrence of a serious cardiac event (death, nonfatal acute myocardial infarction, coronary revascularization) in the hospital. RESULTS: Although sICAM-1 levels tended to be higher in patients with a serious cardiac event, there was no significant association. In contrast, a cTnI level greater than 0.2 ng/mL was a powerful predictor of an in-hospital serious cardiac event (odds ratio 16.3, 95% confidence interval [CI] 4.7 to 55.9; P <.0001). Soluble ICAM-1 levels of more than 260 ng/mL at presentation had a sensitivity for predicting a serious cardiac event of 63% (95% CI 46% to 81%) but a specificity of only 47% (95% CI 38% to 57%). CONCLUSION: In a heterogeneous population of patients with chest pain compatible with myocardial ischemia, elevated sICAM-1 levels are poor predictors of an individual patient suffering a serious cardiac event in the hospital.

Adult↗
PubMed2000

Dobutamine magnetic resonance imaging as a predictor of myocardial functional recovery after revascularisation.

OBJECTIVE: To assess the use of dobutamine magnetic resonance imaging (MRI) as a preoperative predictor of myocardial functional recovery after revascularisation, comparing wall motion and radial wall thickening analyses by observer and semi-automated edge detection. PATIENTS: 25 men with multivessel coronary disease and resting wall motion abnormalities were studied with preoperative rest and stress MRI. MAIN OUTCOME MEASURES: Observer analysis for radial wall thickening was compared with a normal range, while wall motion analysis used a standard four point scale. Semi-automated analysis was performed using an edge detection algorithm. Segments displaying either improved or worsened thickening or motion with dobutamine were considered viable. Postoperative rest images were performed 3-6 months after coronary artery bypass grafting (CABG) for comparison. RESULTS: For observer analysis the values for sensitivity and specificity were 50% and 72% for wall motion, with respective values of 50% and 68% for thickening. With semi-automated edge detection the figures for motion were 60% and 73%, with corresponding values of 79% and 58% for thickening. Combining thickening and motion for the semi-automated method to describe any change in segmental function yielded a sensitivity of 71% and specificity of 70%. CONCLUSIONS: Dobutamine MRI is a reasonably good predictor of myocardial functional recovery after CABG. The use of semi-automated edge detection analysis improved results.

Aged↗
PubMed1999

Utility of cardiac troponin I, creatine kinase-MB(mass), myosin light chain 1, and myoglobin in the early in-hospital triage of "high risk" patients with chest pain.

OBJECTIVE: To evaluate the use of cardiac troponin I (cTnI), creatine kinase-MB(mass) (CK-MB(mass)), myosin light chain 1 (MLC 1), and myoglobin in identifying "high risk" patients with chest pain who will experience serious cardiac events (SCEs) in hospital. DESIGN: Prospective study. SETTING: University affiliated medical centre in Philadelphia, USA. PATIENTS: 208 patients with chest pain, at > 7% risk of acute myocardial infarction (MI), but without new ST segment elevation on their presenting ECG. INTERVENTIONS: cTnI, CK-MB(mass), MLC 1, and myoglobin concentrations were obtained on admission (0 hour) and at 4, 8, 16, and 24 hours. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive and negative predictive value, and pre- and post-test probabilities of patients suffering an SCE in hospital were determined. SCEs included cardiac death, acute MI, cardiac arrest, life threatening cardiac arrhythmia, cardiogenic shock, and urgent coronary revascularisation. RESULTS: Admission concentrations of all markers were poor predictors of SCEs in hospital but improved substantially at subsequent timepoints. cTnI and CK-MB(mass) were consistently the most useful prognostic indicators. If both were negative at 0, 4, and 8 hours, then 99% (95% confidence interval 96% to 100%) of patients remained free from SCEs. The only SCEs not thus predicted were revascularisation procedures and associated complications. Additional tests after 8 hours, or the inclusion of additional markers, did not improve predictive accuracy further. CONCLUSIONS: Patients with high risk clinical features on admission who have negative cTnI and CK-MB(mass) concentrations at 0, 4, and 8 hours later have a favourable in-hospital prognosis and could be considered for early triage out of coronary care units.

Biomarkers↗
PubMed1998

The expression of beta 1 integrins in human coronary artery.

The beta 1 integrin adhesion receptors mediate the binding of cells to extracellular matrices, facilitating their growth, migration, and capacity to deposit matrix proteins: important factors in arterial restenosis and atherosclerosis. The expression of integrins in human coronary artery is, however, unexplored. The aim of the current study was, therefore, to define the expression of beta 1 integrins by cultured human coronary artery vascular smooth muscle cells (hCAVSMC) and in normal human coronary artery; confirming whether or not this differs from the repertoire found in other species and human vessels. The expression of beta 1 integrins by hCAVSMC was assessed by immuno-precipitation and the alkaline phosphatase anti-alkaline phosphatase (APAAP) immunochemical technique. In addition, mRNA expression was defined by reverse transcription polymerase chain reaction (RT-PCR). Normal adult human coronary arteries (n = 4) were also stained by the APAAP method. In vitro hCAVSMC express alpha 2 beta 1 (a collagen and occasional laminin receptor) and alpha 5 beta 1 (a fibronectin receptor) with lesser expression of alpha 3 beta 1 (a multifunctional receptor). They do, however, possess mRNA for several other integrins. Cells within the media of human coronary artery wall express alpha 3 beta 1 and alpha 5 beta 1 but not alpha 2 beta 1: instead the alternative collagen/laminin receptor, alpha 1 beta 1, is expressed in vivo. This pattern of expression differs subtly from that described in rats through it closely parallels that found in other human arteries.

Aged↗
PubMed1998

Cell adhesion molecules in cardiovascular disease: a clinical perspective.

In summary, there is increasing evidence that cell adhesion molecules play an important role in cardiovascular pathology. They are involved in the main processes that underlie cardiac disease including thrombosis, leucocyte infiltration, smooth muscle proliferation, and cell migration. Anti-integrin treatment is already widely used to treat thrombotic complications, and it seems likely that manipulation of other cell adhesion molecules will be used clinically in the near future.

Cardiovascular Diseases↗
PubMed1998

Dipyridamole inhibits human mesangial cell proliferation.

BACKGROUND: Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin. METHODS: Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using 3H-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells. RESULTS: At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity. CONCLUSION: These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.

Cell Count↗
PubMed1998

Risk stratification after myocardial infarction in Scotland.

The objective was to determine how patients are selected for invasive investigation after myocardial infarction in Scotland. Cardiologists in Scotland were surveyed by postal questionnaire asking them to detail their approach to four sample clinical scenarios. Complete responses were obtained from 82% of those surveyed. Substantial differences in practice were observed in the management of subjects with non-Q wave myocardial infarction. Of the cardiologists surveyed 40% would undertake coronary angiography irrespective of the results of non-invasive testing in a 45 year old patient, but only one would adopt the same policy in an otherwise fit 77 year old. Only 44% would perform any investigations (beyond echocardiography) in the 77 year old. A minority of respondents felt that their practice was influenced by resource limitation. Considerable variation continues to exist in the approach to risk stratification after myocardial infarction for some groups of patients. This variation may occur principally as a consequence of physician preference.

Adult↗
PubMed1997

Upregulation and co-localization of connexin43 and cellular adhesion molecules in inflammatory renal disease.

Connexin43 (Cx43) is a major component of gap junctions. These are widely distributed in the human kidney and are thought to be involved in the inflammatory response and in the regulation of cell growth. Cellular adhesion molecules (CAMs) are also thought to be important in these processes, where they possibly facilitate gap junction formation. The aims of the current study were to define for the first time the expression of Cx43 in inflammatory glomerulonephritis and to compare the localization of this connexin with that of the intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Human renal biopsies and control sections of normal human kidney were stained using the alkaline phosphatase/anti-alkaline phosphatase immunohistochemical technique, demonstrating that Cx43 was strongly expressed on inflammatory cells, on damaged tubular cells, and on interstitial cells. This pattern of expression was paralleled closely by that of ICAM-1 and, to a lesser extent, by that of VCAM-1. Cx43 is therefore primarily implicated in tubulointerstitial inflammation.

Adult↗
PubMed1997

Scleroderma, D-penicillamine treatment, and progressive renal failure associated with positive antimyeloperoxidase antineutrophil cytoplasmic antibodies.

Progressive renal failure in patients with scleroderma is a sinister development that is usually attributed to impaired renal blood flow. In some exceptional cases, the underlying pathology is a crescentic glomerulonephritis, which has been associated with positive antineutrophil cytoplasmic antibodies, and in particular antimyeloperoxidase antibodies. The prognosis in such cases has been very poor. We report such a patient whose renal function has improved and stabilized on immunosuppressive therapy.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Expression of beta 1 integrins in IgA nephropathy.

AIM: To compare the expression of beta 1 integrins in renal biopsies from patients with IgA nephropathy with that found in normal human kidney. METHODS: Thirty renal biopsies from patients with IgA disease plus six control specimens were stained with monoclonal antibodies directed against the alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, and beta 1 integrin chains using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The intensity of integrin expression was graded semiquantitatively by a pathologist unaware of the antibody used. RESULTS: Glomerular crescents stained strongly for alpha 3, alpha v, and beta 1, but integrin expression was greatly reduced or absent in fibrotic glomeruli. There were no alterations in the intensity of mesangial cell staining for any of the integrins tested. There was accentuated staining for the alpha 2, alpha 5, alpha v, and beta 1 chains in areas of interstitial scarring plus alpha 2, alpha 3, alpha v, and beta 1 on damaged tubules. Inflammatory cells expressed alpha 4, alpha 5, and beta 1. CONCLUSIONS: In IgA nephropathy the interstitium is the main site of altered beta 1 integrin expression. Glomerular crescents also express several beta 1 integrins, but we found no differences in the intensity of integrin expression on mesangial cells. Altered beta 1 integrin expression may play a role in tubulointerstitial scarring in IgA disease. Thus modulation of integrin expression might attenuate this process.

Antibodies, Monoclonal↗
PubMed1997

Respiratory arrest during dipyridamole stress testing.

There is an increasing usage of radionuclide scanning to assess myocardial perfusion, with dipyridamole, the most commonly used stress agent. Although this is an effective, and usually very safe, means by which to assess myocardial blood supply, there have been several incidents of acute bronchospasm in asthmatic patients. There have, however, been no previous reports of respiratory arrest occurring in patients with emphysema. This case illustrates the dangers of administering intravenous dipyridamole, or even adenosine, to patients with chronic lung disease.

Cardiopulmonary Resuscitation↗