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Biomedical subjects

A G Mitchell

Publications and source records attributed to A G Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1992

Paradoxical early lengthening and subsequent linear shortening of the QT interval in response to exercise.

The QT responses to exercise during ventricular pacing were evaluated in 12 patients in whom permanent pacemakers were implanted for complete heart block. The initial response of the QT to exercise was a paradoxical lengthening during the first minute of exercise (mean 4.8 ms P < 0.01). Thereafter, the QT was found to shorten in a linear fashion in response to increasing exercise, both in terms of exercise duration (r = 0.787; P < 0.001) and atrial rate (r = 0.712; P < 0.001). The total QT shortening with exercise was small (20 ms for a mean increase in atrial rate of 60 beats.min-1) and displayed substantial inter-individual variability (9-31 ms). These results explain some of the limitations of the QT pacemaker, and provide insights in to the dynamics of the QT response, which may help tailor the programming of these systems to the individual patient.

Adult↗
PubMed1992

Optimized hemodynamics by implantation of a dual chamber pacemaker after heterotopic cardiac transplantation.

A patient who underwent prior heterotopic cardiac transplantation had persistent complaints of dyspnea, palpitations, and fatigue in spite of normal pump function of the donor heart. Repeated Holter monitoring excluded paroxysmal arrhythmias. It was thought that synchronization of both heart rates might alleviate his symptoms. The intrinsic heart rate of the donor heart was 90 beats/min, the recipient heart was 60 beats/min with acceleration up to 130 beats/min on exercise. A DDD pacemaker was implanted, the atrial lead was positioned in the right ventricule of the donor heart and the ventricular lead in the atrium of the recipient heart. Search for an optimal AV interval was evaluated by echo-Doppler and intraarterial pressure recordings. By increasing the AV interval from 125 to 300 msec, the maximum aortic flow velocity of the recipient heart increased from 1.0 to 1.2 m/sec. Left ventricular end-diastolic diameter remained unchanged, left ventricular end-systolic diameter decreased from 52 to 48 mm. Wall motion of the recipient left ventricle improved. At an AV interval of 125 msec there was alternate systolic contraction of both hearts, resulting in arterial pressure waves at a rate of 180/min. This did not relieve his symptoms and he complained further of headaches. At an AV interval of 300 msec contraction of the recipient heart just preceded that of the donor heart, resulting in arterial pressure waves at a rate of 90/min, normalization of the wave form, relief of symptoms, and improvement of exercise tolerance.

Adult↗
PubMed1992

Estimation of elastic recovery, work of decompression and Young's modulus using a rotary tablet press.

Capping and lamination occur when the bonds within a tablet cannot withstand the elastic recovery during decompression. To estimate tablet recovery, it is necessary to subtract the machine recovery from the total recovery during decompression. A direct relationship between the force and machine deformation is applied in a novel fashion to calculate in-die tablet recovery on a Manesty Betapress and to estimate the Young's modulus, E, of various solids from the recovery data. The E values of about twenty-five pharmaceutical solids were found to be in reasonable agreement with literature values. This procedure allows in-process analysis of tablet recovery and gives E without the use of specialized equipment.

Algorithms↗
PubMed1992

Changes in myocardial echo amplitude during reversible ischaemia in humans.

OBJECTIVE: This study investigated the changes in regional myocardial ultrasonic backscatter, measured as myocardial echo amplitude, that occur during reversible myocardial ischaemia in humans. DESIGN: Left anterior descending coronary angioplasty was used to produce reversible myocardial ischaemia in human subjects. Regional myocardial echo amplitude was studied in the interventricular septum and left ventricular posterior free wall before, during, and after coronary occlusion with the angioplasty balloon. Wall motion analysis of the left ventricle was performed from simultaneous cross sectional echocardiographic imaging. Patients were studied prospectively. PATIENTS: Six patients (mean age 56 (SD 11), range 46 to 69 years) with single vessel, left anterior descending coronary artery stenoses, were investigated during elective coronary angioplasty. A total of 11 balloon inflations were studied. SETTING: All patient studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. INTERVENTIONS: Angioplasty was performed by the usual procedure at Harefield Hospital for elective coronary angioplasty. All routine medication including beta blockers and calcium antagonists were continued. Inflation pressures were up to 12 atm (1212 kPa) and mean inflation time ranged from 30 to 120 (86 (31)) s. In four studies the first inflation was examined, in three the second, in two the third, and in one each the fourth and fifth inflations. Echo amplitude and cross sectional echo-cardiographic studies were recorded with a 3.5 MHz Advanced Technology Laboratories (ATL) (720A/8736 series) mechanical sector scanner and an ATL Mark III (860-1 series) echocardiograph system with 45 dB logarithmic grey scale compression. MAIN OUTCOME MEASURES: Regional echo amplitude was examined in four regions of the left ventricle--namely, the basal and mid-septum, and basal and mid-posterior wall. Consecutive end diastolic and end systolic frames were analysed and cyclic variation was determined as the difference between the level of echo amplitude at end diastole and at end systole. Measurements were made before balloon inflation, at peak inflation, and after balloon deflation. Regional wall motion and systolic wall thickening were analysed qualitatively. RESULTS: Before balloon inflation, cyclic variation in echo amplitude was noted in all regions (basal septum, 2.4 (SD 1.1) dB; mid-septum, 2.5 (1.1) dB; basal posterior wall, 3.3 (2.1) dB; mid-posterior wall, 3.9 (1.6) dB). During balloon inflation there was a significant fall in cyclic variation to 0.4 (0.9) dB (p < 0.0002) in the mid-septum. This was predominantly owing to an increase in end systolic echo amplitude from 5.4 (2.0) dB to 9.3 (1.9) dB (p < or = 0.01). This was associated with the development of severe hypokinesis or akinesis in the mid-septum. No significant changes in echo amplitude occurred in the three other regions examined. Changes were completely reversed after balloon deflation. CONCLUSIONS: These results suggest a causal relation between occlusion of the supplying coronary artery and blunting of myocardial echo amplitude cyclic variation. It is suggested that balloon occlusion produced myocardial ischaemia. The resultant impairment of myocardial contraction then caused a blunting of cyclic variation in echo amplitude. The results of this study provide further data about the ability of quantitative studies of ultrasonic backscatter to identify alterations in the myocardium during injury.

Aged↗
PubMed1992

Early and long term results of re-operation for coronary artery disease.

OBJECTIVE: To define the incidence, possible causes, operative procedure, and early and medium term results of patients undergoing reoperation for coronary artery disease. DESIGN: A retrospective analysis of patients undergoing reoperation in one hospital during a 10 year period. SETTING: A regional cardiothoracic centre. PATIENTS: 115 patients had reoperation for recurrent angina, 1-17 years (mean (SD) 7.4 (3.9)) after primary revascularisation. MAIN OUTCOME MEASURES: They received 279 grafts (2.4 grafts per patient); 58% of the grafts were anasatomosed to previously grafted vessels. The internal mammary artery was used in 87% of patients who required grafts to the left anterior descending coronary artery. RESULTS: Reoperation accounted for 8.3% of the total number of patients who underwent coronary bypass grafting. Graft failure alone or in combination with other factors was judged to be the cause of recurrence of symptoms in 87%. 42% of patients had two or more coronary risk factors. The early mortality was 5.2% and the actuarial survival at five and 10 years was 90.4% and 88.4% respectively. 85% of the survivors had initial complete relief of angina and 14% had partial improvement. Freedom from recurrent symptoms at five and 10 years was 66.6% and 34.6% respectively. CONCLUSIONS: Vein graft failure either alone or in combination with progression of native coronary disease is the main cause for symptomatic deterioration after bypass grafting. Reoperation can be performed with slightly increased risk and can give good early and medium term results.

Adult↗
PubMed1992

Doppler examination of superior vena caval flow for the detection of acute cardiac rejection.

BACKGROUND: Doppler echocardiographic studies have previously documented abnormalities of mitral flow during acute rejection similar to those seen in patients with "restrictive" physiology. As central venous flow is known to be abnormal in such patients, it was proposed that examination of superior vena caval flow with Doppler echocardiography might be useful for the detection of acute cardiac rejection. METHODS AND RESULTS: Thirty orthotopic cardiac transplant patients, 15 of whom had acute cardiac rejection diagnosed by endomyocardial biopsy, were studied within 36 hours of biopsy. Superior vena caval Doppler flow velocities as well as mitral and tricuspid flow velocities were recorded using a Hewlett-Packard Sonos 500/1000 echocardiograph system. Examinations were performed blinded to the biopsy result. Mitral and tricuspid peak early flow velocities in the nonrejector group were similar to those seen in normal subjects (mitral, 70 +/- 5 cm/sec; tricuspid midexpiratory apnea, 50 +/- 11 cm/sec). Superior vena caval flow was abnormal with 13 of 15 patients demonstrating a biphasic pattern of forward flow with dominant diastolic flow. In the 15 patients with acute cardiac rejection, both mitral and tricuspid flow velocities developed a "restrictive"-type pattern with increased peak early flow velocities (mitral, 89 +/- 24 cm/sec; tricuspid midexpiratory apnea, 63 +/- 19 cm/sec; p < or = 0.05 versus nonrejectors) and decreased mitral early flow-velocity deceleration times (rejectors, 97 +/- 26 msec; nonrejectors, 144 +/- 41 msec; p < or = 0.05). The pattern of superior vena caval flow became markedly abnormal with a virtually complete loss of forward systolic flow (rejectors, 4.4 +/- 6.6 cm/sec; nonrejectors, 26.1 +/- 8.8 cm/sec at midexpiratory apnea; p < or = 0.0001). In 10 of 15 patients, systolic forward flow was absent. If acute rejection was defined as forward systolic flow < or = 17 cm/sec, then sensitivity was 100%, specificity was 80%, and predictive accuracy was 90%. CONCLUSIONS: During acute cardiac rejection, forward systolic superior vena caval flow is markedly diminished compared with nonrejectors. This is accompanied by other Doppler echocardiographic features consistent with the development of "restrictive" physiology. It is postulated that the loss of forward systolic flow in the superior vena cava is due to diminished long-axis shortening of the right ventricle associated with acute cardiac rejection.

Acute Disease↗
PubMed1991

Oral treatment with enoximone in patients referred for cardiac transplantation.

A prospective, uncontrolled, open ended study was performed to assess the effect of treatment with oral enoximone therapy in patients with end stage cardiac failure unresponsive to conventional treatment. The primary objective of treatment, hospital discharge, was achieved in 27 of 35 patients studied. Baseline haemodynamics were obtained in 21 patients. The mean cardiac index of patients who improved by one or more grades (New York Heart Association) was 2.1 litres/min while, in those who had less improvement, the mean cardiac index was 1.5 l/min (P less than 0.01). The average duration of treatment was 13 weeks, treatment being discontinued in 25 patients within twelve weeks. The main reasons for discontinuation were side effects (n = 11), and progressive cardiac failure (n = 7). The prognosis of patients in whom therapy was discontinued was very poor, only 5 of 28 being discharged from hospital without cardiac transplantation. Sudden death was uncommon (1/13), and Holter monitoring in 17 showed no aggravation of ventricular arrhythmias. Oral treatment with enoximone is a useful adjunct in the treatment of end stage cardiac failure.

Administration, Oral↗
PubMed1991

Substance P for evaluation of coronary endothelial function after cardiac transplantation.

The endothelium-dependent vasodilator substance P dilates normal and diseased coronary vessels in humans in vivo and produces a maximal response similar to that seen with intracoronary isosorbide dinitrate. Twelve cardiac transplant recipients underwent intracoronary infusion of substance P after routine annual investigations. All patients were well, with no evidence of rejection and with angiographically normal coronary arteries. Substance P was infused at 2 ml/min for 2 min into the coronary artery, starting at a dose of 1.4 pmol/min and increasing by doubling increments, and followed by isosorbide dinitrate (1 mg/min) infused over 2 min. Coronary artery diameter was measured in 23 vessel segments from 12 transplant recipients. The following doses were infused: saline solution (1 ml/min), substance P (0.7 [three patients], 1.4, 2.8, 5.6, 11.2, 22.4 pmol/min) and isosorbide dinitrate (1 mg/min). The mean percent increase in diameter (+/- SEM) in response to increasing doses of substance P was as follows: 0, 6.5 +/- 2.9%, 10.9 +/- 2.9%, 12.1 +/- 2.9%, 16.5 +/- 2.6%, 19.2 +/- 3.1% and 25.8 +/- 2.2%, respectively. Half maximal dilation was produced with 1.4 to 2.8 pmol/min of substance P; the maximal response (mean percent diameter change) was 22 +/- 2.5%. This was not significantly different from that achieved with isosorbide dinitrate. It is concluded that coronary endothelial function as assessed by response to substance P is preserved in cardiac transplant recipients with angiographically normal coronary arteries. Substance P may be a suitable agent for testing endothelial function in these patients.

Coronary Angiography↗
PubMed1991

Peak offset times as an indication of stress relaxation during tableting on a rotary tablet press.

During powder compaction on a Manesty Betapress, peak pressures, Pmax, are reached before the punches are vertically aligned with the centres of the upper and lower compression roll support pins. The interval between the time taken to reach this alignment and the time to reach Pmax is defined as the peak offset time, t(off). The duration of t(off) depends on the ability of the compacted powder to relieve stress and is an indication of the predominant mechanisms of particle deformation during consolidation. Thus, at a given Pmax, short t(off) values are characteristic of materials that consolidate mainly by brittle fracture while longer values indicate an increase in plastic flow. On the Betapress, the decrease in stress during t(off) occurs under conditions approaching constant strain and t(off) therefore, is an indirect measure of stress relaxation. Stress relaxation, and hence t(off), decreases with increase in Pmax due to the reduction in the porosity of the compact and consequent restriction of plastic flow into the void spaces. In addition to Pmax, the effects of variables such as punch head geometry, press speed and formulation on t(off) are reported.

Acetaminophen↗
PubMed1991

Detection of free radicals and cholesterol hydroperoxides in blood taken from the coronary sinus of man during percutaneous transluminal coronary angioplasty.

Patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were investigated for the production of free radicals and cholesterol hydroperoxides during reperfusion. Fifteen patients were studied. Ischaemia during balloon inflation was assessed by serial coronary sinus lactate analysis (mean maximal increase in anterior descending artery dilation was 130%), and by the demonstration of reperfusion hyperaemia (mean increase of coronary sinus oxygen saturation 74%). Free radicals were detected by electron spin resonance (ESR) spin trapping using the spin trap PBN (N-t-Butyl-alpha-phenylnitrone). Radical adducts were detected in up to 50% of samples taken during reperfusion after anterior descending lesion angioplasty. No radicals were detected in control samples or during the ischaemic phase. Radical detection was positively correlated with the change in coronary sinus lactate (p less than 0.025). Coronary sinus cholesterol hydroperoxide analysis did not show a significant increase over control during reperfusion, due in part to unexpectedly high pre angioplasty levels. This study provides clear evidence for the production of a burst of free radicals and evidence for lipid peroxidation in the minutes following myocardial reperfusion during angioplasty. A relationship between the severity of the ischaemic insult and the detection of radical adducts has also been found.

Angina Pectoris↗
PubMed1990

Comparison of calculated and experimentally determined punch displacement on a rotary tablet press using both Manesty and IPT punches.

An indirect method of calculating punch displacement on a rotary tablet press from measurements of the change in punch force with the turret position was in good agreement with direct measurements of punch displacement made using a linear variable displacement transducer (LVDT)-slip ring system. The direct measurements were made during the compaction of three direct compression agents using Manesty punches. However, the agreement between calculated and experimentally determined punch displacements was unsatisfactory when IPT punches were used. The IPT punches have a much flatter punch head profile than the Manesty punches. Due to this difference, the analytic equation does not accurately describe the dynamics of the press under normal operating conditions. Terms in the analytic equation, determined originally under static conditions, were re-evaluated under dynamic conditions for both sets of tooling using the LVDT-slip ring system. Excellent agreement for both IPT and Manesty punches was found between punch displacement calculated using the revised analytic equation and direct experimental measurements. Punch displacements determined from punch head profile and machine geometry only, without taking machine deformations into account, were shown to differ widely from the calculated and experimental values.

Drug Compounding↗
PubMed1989

Cardiac transplantation in the seventh decade of life.

Twenty-five patients older than 60 years of age underwent cardiac transplantation using an immunosuppression protocol with cyclosporin and azathioprine, but without routine use of oral steroids. There were 24 men and 1 woman (age range 60 to 69 years, mean 63). The etiology of heart disease was coronary artery disease in 21 and idiopathic dilated cardiomyopathy in 4. Six patients had previous coronary artery bypass operations, 1 had undergone repair of an abdominal aneurysm and 1 had pulmonary embolism. Sixteen patients were in New York Heart Association class IV and 9 in class III. Donor mean age was 30 (14 to 46) years. Hospital stay after transplantation was 10 to 90 days (median 11). Four died within 30 days and none from 5 to 59 months (mean 22). The 1-year actuarial survival was 84%. The incidence of rejection was 2.16 episodes per patient. Only 1 patient (4%) had serious infection. Six patients received antihypertensive treatment, 3 had reversible impairment of renal function, 2 had gout and 1 had drop foot. No patient had convulsions, transient ischemic attack or cerebrovascular accident. None had significant psychological problems. The 21 patients currently alive are in New York Heart Association class I. Quality of life, assessed by the Nottingham Health Profile, showed marked improvement. It is concluded that the initial results of cardiac transplantation in the seventh decade of life are encouraging.

Actuarial Analysis↗
PubMed1989

Cardiac involvement by lymphoma: diagnostic difficulties.

A patient presenting with recurrent tamponade was subsequently shown to have non-Hodgkin's lymphoma. Catheterization demonstrated obstruction of the tricuspid valve by tumour and shunting through a patent foramen ovale. The difficulties in making an ante-mortem diagnosis of cardiac lymphoma are discussed.

Aged↗
PubMed1989

Calculation of punch displacement and work of powder compaction on a rotary tablet press.

To calculate the work of compaction during tableting it is necessary to have accurate values of force and punch displacement. The direct measurement of punch displacement on a rotary press is both costly and complicated but calculated displacements will be in considerable error unless deflections in the press during compression, are taken into account. By analysing the physical restraints imposed on the punches during tablet compression, an expression for punch displacement was derived. From preliminary measurements made on the table press of machine deflections and punch displacement under static conditions, the terms of this expression were evaluated for dynamic conditions. This analytic solution was then used to determine the true punch displacement and work of compaction from direct measurements of vertical force and turret position.

Drug Compounding↗