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Biomedical subjects

W D Flatman

Publications and source records attributed to W D Flatman.

11 recordsLinked to original sources

A dual-isotope method for studying protein kinetics in pleural effusions in humans.

A method is described for studying protein kinetics in pleural effusions in humans. In 15 patients with pleural effusions from a variety of causes, protein inflow was monitored by measuring the rate of appearance in the effusion of the plasma protein transferrin, radiolabelled in vivo by intravenous injection of 113InmCl3. Protein outflow was measured from the rate of appearance in the blood of intrapleurally administered 125I-albumin. Compartmental analysis has been used to determine rate constants k(in) and kout for the movement of labelled proteins into and out of the effusion, respectively. The mean value of k(in) for 15 patients was 9.4 x 10(-4) h-1 (range 2.2-21.4). The mean value of kout in the same patients was 28 x 10(-4) h-1 (range 6-68). Using appropriate assumptions where necessary, the absolute transfer rates of albumin and transferrin were also estimated. For albumin, the mean rate of outflow was 66 mg h-1 (range 27-158), compared to mean estimated inflow of 133 mg h-1 (range 36-381). Protein inflow was highest in a case of metastatic ovarian carcinoma with pleural and peritoneal seedlings, indicating high vascular permeability. Protein outflow was very low in a case of mesothelioma, suggesting severely impaired lymphatic drainage. The technique may prove to be a useful tool for studying mechanisms resulting in the formation of malignant and nonmalignant pleural effusions, and may also be useful for studying the effects of putative therapeutic intervention.

Aged

Influence of respiratory variations on right ventricular function.

Respiratory effort during inspiration, expiration, and the Valsalva manoeuvre changes right ventricular preload and afterload. On inspiration these changes should improve systolic emptying of a larger end diastolic volume and so increase the ejection fraction, whereas on expiration the reverse should be true. The resting right ventricular ejection fraction was measured by first pass radionuclide angiography with gold-195m (half life 30.5 s) in 17 individuals at maximal inspiration and expiration and in eight at rest and during the strain phase (phase 2) of the Valsalva manoeuvre. The right ventricular ejection fraction was significantly lower during expiration than during inspiration. There were, however, no significant differences in bolus duration or right ventricular transit time. The Valsalva manoeuvre, in contrast, significantly increased the ejection fraction and also significantly prolonged both the bolus duration and right ventricular transit time. The conformation of the bolus curves during the Valsalva manoeuvre suggested the development of tricuspid regurgitation. These data suggest that relative influences of venous return, pulmonary arterial pressure, pulmonary vascular resistance, and possible functional tricuspid regurgitation vary during inspiration, expiration, and the Valsalva manoeuvre and can affect the right ventricular ejection fraction. Changes in right ventricular function on exercise assessed by first pass radionuclide angiography must be interpreted with caution because maximal respiratory effort may alter the right ventricular ejection fraction independently of ischaemia or other non-ischaemic factors.

Blood Pressure

Nonischemic changes in right ventricular function on exercise. Do normal volunteers differ from patients with normal coronary arteries?

Factors other than ischemia may alter right ventricular function both at rest and on exercise. Normal volunteers differ from cardiac patients with normal coronary arteries with regard to their left ventricular response to exercise. This study examined changes in right ventricular function on exercise in 21 normal volunteers and 13 patients with normal coronary arteries, using first-pass radionuclide angiography. There were large ranges of right ventricular ejection fraction in the two groups, both at rest and on exercise. Resting right ventricular ejection fraction was 40.2 +/- 10.6% (mean +/- SD) in the volunteers and 38.6 +/- 9.7% in the patients, p = not significant, and on exercise rose significantly in both groups to 46.1 +/- 9.9% and 45.8 +/- 9.7%, respectively. The difference between the groups was not significant. In both groups some subjects with high resting values showed large decreases in ejection fraction on exercise, and there were significant negative correlations between resting ejection fraction and the change on exercise, r = -0.59 (p less than 0.01) in volunteers, and r = -0.66 (p less than 0.05) in patients. Older volunteers tended to have lower rest and exercise ejection fractions, but there was no difference between normotensive and hypertensive patients in their rest or exercise values. In conclusion, changes in right ventricular function on exercise are similar in normal volunteers and in patients with normal coronary arteries. Some subjects show decreases in right ventricular ejection fraction on exercise which do not appear to be related to ischemia.

Adult

Observations on the function of normal adrenomedullary tissue in patients with phaeochromocytomas and other paragangliomas.

123I-MIBG is a norepinephrine analogue used for imaging phaeochromocytomas and other paragangliomas. In this study 7 normal volunteers and 31 subjects with high or borderline high plasma catecholamine and urinary metanephrine and VMA levels were investigated. In the normals the uptake by the adrenal medulla was in the range of 0.01%-0.21% of the injected dose at 22 h. In 22 subjects there was no evidence for any paraganglioma, with the uptake by the adrenal medulla in the range of 0.01%-0.22% of the injected dose at 22 h. In nine patients there was evidence of a paraganglioma on imaging which was confirmed on surgery. The uptake by the tumours was in the order of 0.001%-0.14% of the injected dose per gram of tumour tissue. In all nine cases the non-tumorous adrenal medulla could be visualized; the uptake in the adrenals was in the range of 0.01%-0.21% of the injected dose. This study shows that in the presence of elevated plasma catecholamines of tumour origin the unaffected adrenal medullary tissue retains the capacity for 123I-MIBG uptake. In the two cases also studied by adrenal venous sampling, catecholamine release was also within the normal range.

3-Iodobenzylguanidine

Global and regional right ventricular function after acute myocardial infarction: dependence upon site of left ventricular infarction.

The relation of global and regional right and left ventricular function during the acute phase after a first myocardial infarction was assessed by first pass radionuclide angiography in 20 patients (10 after anterior and 10 after inferior myocardial infarction). The right ventricular ejection fraction did not differ significantly between the groups, but left ventricular ejection fraction was significantly depressed after anterior myocardial infarction. There was evidence of right ventricular dilatation and impaired transit in the group with inferior infarction. Five patients with anterior infarction and six with inferior infarction had abnormal right ventricular ejection fractions. Right ventricular wall motion abnormalities affected the septal wall in the group with anterior infarction and the free wall in the group with inferior infarction. The relation between right and left ventricular ejection fractions was markedly different in the two groups. In the group with anterior infarction there was a significant linear relation between right and left ventricular ejection fraction, whereas in the group with inferior infarction there was not. Thus right ventricular dysfunction commonly occurs after both anterior and inferior myocardial infarction. Right and left ventricular impairment are related after anterior myocardial infarction, but are independent after inferior myocardial infarction. Finally, the different effects of anterior and inferior myocardial infarction on right ventricular function may be explained by differences in septal and free wall involvement.

Adult

Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison.

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.

3-Iodobenzylguanidine

Quantitation of iodine-123 MIBG uptake by normal adrenal medulla in hypertensive patients.

Eighteen hypertensive patients with a clinical suspicion of pheochromocytoma and raised or borderline raised plasma catecholamine and urinary vanillyl mandelic acid (VMA) levels were studied by scintigraphy using 123I-labeled metaiodobenzylguanidine (MIBG). None of these patients had any scintigraphic evidence of pheochromocytoma at the time of study or on subsequent clinical follow-up. A quantitative approach was taken to calculate the adrenal medullary uptake of [123I]MIBG in these patients. Three different methods of quantitation were evaluated using data acquired from an anthropomorphic phantom and analysed by three independent observers. In the patient studies 34 out of 35 adrenal medullas were visualized with uptake in the range of 0.01-0.22% of the administered dose 22 hr postinjection which was calculated using the preferred quantitation method. This is an appropriate control group range for comparison with patients who have proven norepinephrine and epinephrine secreting tumors. A quantitative approach to [123I]MIBG imaging provides an important tool for studying adrenomedullary pathophysiology.

3-Iodobenzylguanidine

The adequacy of radioisotope mixing from bolus injections in first-pass radionuclide angiographic assessment of right ventricular function: a study using gold-195m.

The adequacy of radioisotopic mixing in first-pass radionuclide studies of right ventricular function was assessed in 27 patients using multiple injections of gold-195m (half-life 30.5 sec). A theoretical disadvantage of the first-pass technique is inadequate mixing of the injected bolus with blood prior to entry into the right ventricle. Since the calculation of ejection fraction is based on the assumption of complete mixing, this would lead to errors. In order to assess the effects of bolus injection rates and bolus duration on the calculation of right ventricular ejection fraction, multiple, rapid, sequential studies were performed using gold-195m at four bolus injection rates (10, 5, 2 and 1 ml/sec). Slowing the injection rate caused a significant increase in bolus duration, and a significant increase in the number of cardiac cycles available for analysis. Mean ejection fraction, however, was not significantly changed. There was good correlation between right ventricular ejection fraction at all injection rates when compared to 10 ml/sec, and no injection rate led to a consistent over or underestimate of right ventricular ejection fraction. There was no significant relationship between change in bolus duration and variation in ejection fraction. These data indicate that mixing is adequate for first-pass studies of right ventricular function using a rapid bolus.

Cardiac Output

Relation between coronary anatomy and serial changes in left ventricular function on exercise: a study using first pass radionuclide angiography with gold-195m.

Serial changes in left ventricular function on exercise were assessed by first pass radionuclide angiography with gold-195m (half life 30.5 s) in 25 men with known coronary anatomy. In the seven patients with three vessel disease, abnormalities of global left ventricular function and regional wall motion occurred earlier during exercise, were of greater extent at peak exercise, and persisted longer after exercise than in the 11 patients with one and two vessel disease or the seven with normal coronary arteries. Although there were significant differences between the groups in absolute change in ejection fraction and the rate of change in ejection fraction related to exercise duration and heart rate, a considerable overlap of values between groups precluded the accurate prediction of coronary anatomy in individuals. These data suggest that the amount of myocardium at risk from ischaemia in some patients with one and two vessel disease may resemble that in patients with three vessel disease. This study shows that an anatomical classification based solely on the number of diseased vessels will not predict the extent of the impairment of left ventricular function on exercise.

Blood Pressure

Gated right ventricular studies using krypton-81m: comparison with first-pass studies using gold-195m.

Krypton-81m, given by continuous i.v. infusion, has been successfully used for the equilibrium ECG-gated assessment of right ventricular function. We compared gated studies with 81mKr (half-life 13 sec) with first-pass studies using 195mAu (half-life 30.5 sec). Krypton studies analyzed using variable regions of interest (ROIs) led to a significantly higher calculated right ventricular ejection fraction (RVEF) than with a fixed ROI, both with and without background correction. The differences between first-pass studies and gated studies without background correction were significant (p less than 0.01), whereas they were not with background correction. These data suggest that large systematic errors exist in the calculation of RVEF depending on the analysis method and that background correction is important when different techniques are compared.

Adult

Effects of projection and background correction method upon calculation of right ventricular ejection fraction using first-pass radionuclide angiography.

There is no consensus as to the best projection or correction method for first-pass radionuclide studies of the right ventricle. We assessed the effects of two commonly used projections, 30 degrees right anterior oblique and anterior-posterior, on the calculation of right ventricular ejection fraction. In addition two background correction methods, planar background correction to account for scatter, and right atrial correction to account for right atrio-ventricular overlap were assessed. Two first-pass radionuclide angiograms were performed in 19 subjects, one in each projection, using gold-195m (half-life 30.5 seconds), and each study was analysed using the two methods of correction. Right ventricular ejection fraction was highest using the right anterior oblique projection with right atrial correction 35.6 +/- 12.5% (mean +/- SD), and lowest when using the anterior posterior projection with planar background correction 26.2 +/- 11% (p less than 0.001). The study design allowed assessment of the effects of correction method and projection independently. Correction method appeared to have relatively little effect on right ventricular ejection fraction. Using right atrial correction correlation coefficient (r) between projections was 0.92, and for planar background correction r = 0.76, both p less than 0.001. However, right ventricular ejection fraction was far more dependent upon projection. When the anterior-posterior projection was used calculated right ventricular ejection fraction was much more dependent on correction method (r = 0.65, p = not significant), than using the right anterior oblique projection (r = 0.85, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult