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Biomedical subjects

D J Pearce

Publications and source records attributed to D J Pearce.

At least 19 recordsLinked to original sources

The prehospital electrocardiogram in acute myocardial infarction: is its full potential being realized? National Registry of Myocardial Infarction 2 Investigators.

OBJECTIVES: This study sought to examine the management and subsequent outcomes of patients with a prehospital electrocardiogram (ECG) in a large, voluntary registry of myocardial infarction. BACKGROUND: The prehospital ECG has been proposed as a means of rapidly identifying patients with acute myocardial infarction who might be eligible for reperfusion therapy. METHODS: The characteristics and outcomes of patients with a prehospital ECG were compared with those without a prehospital ECG in the National Registry of Myocardial Infarction 2 data base. Included in the analysis were those patients who presented to the hospital within 12 h of an acute myocardial infarction. Excluded were patients with an in-hospital infarction, transferred-in referrals and self-transported patients. RESULTS: Prehospital ECGs were obtained in 3,768 (5%) of 66,995 National Registry of Myocardial Infarction 2 patients meeting study criteria. Median time from myocardial infarction symptom onset until hospital arrival was longer among those having a prehospital ECG (152 vs. 91 min, p < 0.001). However, once in the hospital, the prehospital ECG group experienced a shorter median time to the initiation of either thrombolysis (30 vs. 40 min, p < 0.001) or primary angioplasty (92 vs. 115 min, p < 0.001). The prehospital ECG group was more likely to receive thrombolytic therapy (43% vs. 37%, p < 0.001) and to undergo primary angioplasty (11% vs. 7%, p < 0.001). Also, the prehospital ECG group was more likely to undergo coronary arteriography (55% vs. 40%, p < 0.001), angioplasty (24% vs. 16%, p < 0.001) or bypass surgery (10% vs. 6%, p < 0.001). The in-hospital mortality rate was 8% in patients with a prehospital ECG and 12% in those without a prehospital ECG (p < 0.001). After adjusting for baseline covariates utilizing multiple logistic regression analysis, this mortality difference remained statistically significant (odds ratio 0.83, 95% confidence interval 0.71 to 0.96, p = 0.01). CONCLUSIONS: The prehospital ECG is infrequently utilized for diagnosing myocardial infarction, and among patients with a prehospital ECG, is associated with a longer time from symptom onset to hospital arrival. Despite these shortcomings, the prehospital ECG is a test that may potentially influence the management of patients with acute myocardial infarction through wider, faster in-hospital utilization of reperfusion strategies and greater usage of invasive procedures, factors that may possibly reduce shortterm mortality. Efforts to implement the prehospital ECG more widely and more rapidly may be indicated.

Aged

The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia.

OBJECTIVES: We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI). BACKGROUND: Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy. METHODS: ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI. RESULTS: New ST segment deviation > or = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with > or = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either > or = 1 mm or > or = 0.5 mm remained independent predictors of death or MI by 1 year. CONCLUSIONS: The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not only > or = 1-mm ST segment deviation but also > or = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

Aged

Comparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links.

We have compared the use of new markers of bone turnover in the assessment and treatment of Paget disease and made observations on the mechanisms of bone resorption. Urine hydroxyproline (Hyp) as a bone resorption marker and serum alkaline phosphatase (ALP) as a bone formation marker have traditionally been used to biochemically assess and monitor treatment of Paget disease. Hyp and total ALP were compared with total urine pyridinoline (Pyd) and deoxypyridinoline (Dpd), free urine Pyd and Dpd, urine type I collagen N-terminal cross-linked telopeptide (NTX), type I collagen C-terminal propeptide (PICP), serum osteocalcin, and bone ALP in Paget patients treated with pamidronate. Patients were divided into three biochemical severity-based treatment groups by their fasting urine hydroxyprolline excretion (HypE) levels (Le., group 1, HypE < 5.0 mumol/l of glomerular filtrate [GF]; group 2, HypE of 5.0-9.9 mumol/l of GF; group 3, HypE > 10 mumol/l of GF). Group 1 received one 60 mg intravenous infusion of pamidronate, and groups 2 and 3 received four and six 60 mg infusions at weekly intervals, respectively. Fasting serum and morning urine specimens were taken before and at 2, 6, 13, and 26 weeks after starting treatment. Baseline Z scores were used to compare separation of patient results from normal, and the difference in Z scores from baseline to 13 weeks was used to compare response to treatment. Baseline discrimination and response to treatment at all disease activity levels was greatest for NTX and was poor for osteocalcin, PICP, and C-terminal cross-linked telopeptide of type I collagen (ICTP). The other markers showed good discrimination and response at medium and high levels of disease activity. NTX, total Pyd and Dpd, free Pyd and Dpd, and ICTP are all pyridinoline cross-link-based markers, but discrimination and response by NTX was generally much greater than for the others. Determination of the mechanism of the difference between NTX and other cross-link measures is necessary for appropriate use of the markers and may also lead to a better understanding of the bone resorption process. It has been proposed that the greater sensitivity and discrimination of NTX is because it is more bone-specific than the other cross-link markers with significant amounts of free Pyd and Dpd coming from nonbone sources. We propose another model where the proportion of peptide-bound cross-links such as NTX may be increased in high bone turnover states partly due to a rate-limiting step in their degradation to free cross-links. Conditions with high bone resorption rates would have high levels of NTX that would decline rapidly when resorption rates fall to a level where the capacity to degrade NTX matches the rate of production.

Aged

Right and left ventricular volumes and function after acute pulmonary hypertension in intact dogs.

A canine model was developed to record right (RV) and left ventricular (LV) volumes and high-fidelity pressures during acute pulmonary hypertension without the need for major surgery. In this study, new methodology was applied to record high-fidelity RV and LV pressures during cinemagnetic resonance imaging of the heart before and after acute pulmonary hypertension in six anesthetized intact dogs in which the pericardium and thorax were never disturbed by any surgical procedure. After pulmonary embolus, RV systolic pressure increased from 27 + 2 (SD) to 43 +/- 8 mmHg (P < 0.01) as LV systolic pressure decreased (97 +/- 17 to 76 +/- 3 mmHg; P < 0.05). Stroke volume (26 +/- 7 to 21 +/- 5 ml; P < 0.05) and RV ejection fraction (45 +/- 9 to 28 +/- 3%; P < 0.01) decreased as LV ejection fraction was unchanged (50 +/- 5 to 52 +/- 5%; P = NS). LV end-diastolic pressure decreased from 11 +/- 4 to 7 +/- 3 mmHg (P < 0.05), and RV end-diastolic pressure increased from 6 +/- 3 to 11 +/- 3 mmHg (P < 0.01). RV end-diastolic volume increased from 57 +/- 14 to 75 +/- 20 ml (P < 0.01) as LV end-diastolic volumes decreased from 53 +/- 11 to 42 +/- 10 ml (P < 0.01), resulting in no change in total ventricular volume at end diastole (111 +/- 24 to 116 +/- 28 ml). The observed mean decrease of 4.0 mmHg and 11 ml in LV end-diastolic pressure and volume, respectively, was associated with no change in total ventricular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Respiratory acidosis and subcutaneous emphysema during laparoscopic cholecystectomy.

A case is presented of a healthy 69-year-old woman who underwent elective laparoscopic cholecystectomy under general anaesthesia. As surgery proceeded she developed hypercapnia (arterial blood PaCO2 = 100 mmHg) and a related respiratory acidosis (arterial blood pH 7.07). The cause was attributed to subcutaneous insufflation and absorption of CO2, directly related to the surgical pneumoperitoneum.

Acidosis, Respiratory

Assessment of ventricular volumes using cine magnetic resonance in the intact dog. A comparison of measurement methods.

UNLABELLED: RATIONALE, OBJECTIVE AND METHODS: The authors recently combined magnetic resonance imaging with high-fidelity left ventricular (LV) pressure measurement in a closed-chested, intact animal model. However, LV volumes derived from summated serial short axis slices require long imaging times and make it difficult to record LV volumes in response to acute alterations in load. In this study, geometry-based LV end-systolic volume estimates calculated from a single long-axis image (Area-Length formula) and from a long-axis and short-axis image (Bullet formula) were compared to those derived from summated short-axis images of the left ventricle (Simpson's rule) during altered loading conditions in six anesthetized, intact dogs. RESULTS: Angiotensin infusion produced three different LV systolic pressures (89 +/- 8 vs. 123 +/- 12 vs. 151 +/- 10 mmHg, P < .001). Area-Length and Bullet formula end-systolic volumes correlated with Simpson's rule volumes (r = .95 and .97; respectively). However, Bullet formula end-systolic volumes provided a significantly better agreement with Simpson's rule end-systolic volumes. CONCLUSIONS: The Bullet formula can be substituted for Simpson's rule to record magnetic resonance LV volumes during steady-state alterations in load in our intact animal model.

Angiotensin II

A stable model of left ventricular dysfunction in an intact animal assessed with high fidelity pressure and cinemagnetic resonance imaging.

OBJECTIVE: Numerous models of acute and chronic left ventricular dysfunction have been used over the years. However, few can produce a rapid onset of global systolic and diastolic dysfunction that is stable and potentially reversible. The aim of this study was to develop such a model. METHODS: A model of left ventricular dysfunction was produced in six intact dogs using 1% halothane anaesthesia and pharmacological autonomic blockade with atropine (0.1 mg.kg-1) and propranolol (2 mg.kg-1). Left ventricular function was assessed by combined high fidelity pressure and cinemagnetic resonance imaging (cine-MR) during increases in afterload using infusions of angiotensin. RESULTS: Left ventricular systolic dysfunction was characterised by a diminished resting ejection fraction of 45(SD 4)% and a depressed +dP/dtmax of 1537(100) mm Hg.s-1. Diastolic dysfunction was manifested by an increased left ventricular end diastolic pressure of 16(2) mm Hg, a decreased -dP/dtmax of -1705(369) mm Hg.s-1, and a prolonged time constant of left ventricular relaxation of 42(9) ms. As left ventricular systolic pressure steadily rose with angiotensin infusion from 87(7) to 124(13) to 152(10) mm Hg (p < 0.001), left ventricular ejection fraction decreased markedly from 45(4) to 35(4) to 27(4)% (p < 0.001). Left ventricular +dP/dtmax did not change [1537(100) to 1500(110) to 1498(84) mm Hg.s-1] in spite of a significant increase in left ventricular end diastolic pressure from 16(2) to 21(5) to 29(7) mm Hg (p < 0.001) and left ventricular end diastolic volume from 59(12) to 71(14) to 78(17) ml (p < 0.001). Individual slopes of the end systolic pressure-volume relationship were also low, ranging between 2.1 and 4.4 mm Hg.s-1 (r = 0.99 to 1.00), typical of impaired contractility. CONCLUSIONS: Halothane anaesthesia in dogs pretreated with large amounts of propranolol and appropriate muscarinic cholinergic blockade produces a moderate decrease in baseline systolic and diastolic function in our intact dog model. However, left ventricular systolic function showed limited contractile reserve when challenged by physiological increases in systemic arterial pressure. Impaired systolic and diastolic function may, at least in part, be related to diminished activator calcium produced by halothane in addition to the well known negative inotropic action of beta adrenergic blockade.

Anesthesia

Relationship between shortening load, contractility, and myocardial energetics in intact dog.

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Time-varying wall stress: an index of ventricular vascular coupling.

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Postoperative analgesia: a comparison of intravenous on-demand fentanyl with epidural bupivacaine.

In a randomised trial postoperative pain relief was provided by either epidural injections of bupivacaine or an infusion of fentanyl adjusted by the patient to achieve adequate pain relief. Both techniques produced satisfactory analgesia without respiratory depression after peripheral arterial surgery. The technique of infusing intravenously a potent analgesic in a dose adjusted by the patient appears to offer several advantages in postoperative care.

Blood Gas Analysis

Clinical and biochemical evaluations of premedicants. A double-blind assessment of clobazam, a new 1,5 benzodiazepine.

Clobazam is a new 1,5 benzodiazepine which differs from the 1,4 benzodiazepines such as diazepam, in that it displays a wide separation of its tranquillising or anxiolytic effects from impairment of cortical arousal and psychomotor performance. Its potential advantages as a premedicant for day-case or outpatient surgery were evaluated in a placebo-controlled double-blind study in female patients undergoing minor day surgery. Anxiety reduction was evaluated clinically and by means of plasma cortisol estimations. The clinical evaluation, using an established portocol, did not differentiate either active drug from placebo or between the active drugs; the cortisol results permitted opposing conclusions depending on the statistical approach used. Potential fallacies inherent in the methodology current used for evaluating premedicant drugs are discussed.

Adult

Pre-induction priming of the uterine cervix with oral prostaglandin E2 and a placebo.

A double blind study was undertaken to determine the effectiveness or oral prostaglandin E2 as a means of improving the pelvic score prior to induction of labour. 48 patients who were greater than 37 weeks gestation and who had Bishop scores of less than 6 entered the study. Ten tablets were given on an hourly regime. Of 25 patients in the prostaglandin group, 17 were considered successes (68.0%), whereas of 23 patients who received a placebo, 9 were successes (39.1%). No adverse effects were recorded. Prostaglandin E2 is therefore considered a safe and effective method for priming the unfavourable cervix prior to induction of labour.

Administration, Oral