Effects of beta-adrenergic blockade on the natural progression of myocardial infarct size and compensatory hypertrophy.

Using contrast-enhanced computed tomography, the effects of beta-adrenergic blockade were assessed on experimentally produced myocardial infarcts in dogs evaluated serially over the course of approximately 1 month. Infarct size, initial perfusion defect (jeopardized segment) and noninfarcted muscle mass were studied in two groups of conditioned mongrel dogs. Group 1 (n = 11) served as the control group and Group 2 (n = 10) was pretreated with propranolol (2 mg/kg). Each animal in the propranolol-treated group was given identical amounts of the agent twice daily for 7 days after coronary occlusion. Both groups developed increases in the noninfarcted muscle mass of the left ventricle (compensatory hypertrophy). The mean increase averaged 19.8% over 30 days when the two groups were included together. Infarct size was smaller in the propranolol-treated group, and averaged 28% less (p less than 0.05) than that of the control group 30 days after initial myocardial infarction. Thus, pharmacologic interventions were shown by computed tomography to alter the size of an acute experimental myocardial infarct, particularly when examined over the time course of infarct healing. Moreover, compensatory hypertrophy occurred in both the control and propranolol-treated groups.

Effects of transient coronary ischemia and reperfusion on myocardial edema formation and in vitro magnetic relaxation times.

The effects of transient ischemia and reperfusion on regional myocardial function, salvage and swelling have been systematically analyzed in experimental canine preparations. The results of these interventions on myocardial in vitro measurements of magnetic relaxation times (T1 = magnetization recovery, T2 = spin echo) are of significant importance with respect to future nuclear magnetic resonance tomographic imaging. Thus, using a pulsed magnetic resonance spectrometer (10.7 MHz), myocardial tissue samples from two groups of dogs were evaluated. In group 1 (n = six dogs), the left anterior descending artery was occluded for 3 hours before sacrifice; in group 2 (six dogs), 3 hours of occlusion was followed by 1 hour of reperfusion. Multiple tissue samples from normal and ischemic (or ischemic and reperfused) myocardium were obtained for measurement of T1, T2 and % water content (wet weight--dry weight/wet weight). Water content increased with ischemia (78 +/- 4%) and reperfusion (81 +/- 4%) (both p less than 0.01 versus control values). Values for T1 increased with ischemia (598 +/- 39 versus 487 +/- 23 ms in normal tissue from the same heart, p less than 0.01). Even greater T1 changes occurred in the animals with reperfusion (654 +/- 52 ms, p less than 0.01 versus the intra-animal control values). Changes in T2 were similar but less marked (ischemic zone 43.9 +/- 1.0 versus 41.2 +/- 1.0 ms in nonischemic tissue in the corresponding heart, p less than 0.05; reperfusion zone 48.3 +/- 3.5 versus 41.9 +/- 2.3 ms in the normal zone, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarct size determined by computed transmission tomography in canine infarcts of various ages and in the presence of coronary reperfusion.

Thirty-one dogs underwent in vivo scanning with computed transmission tomography; 15 dogs were studied within 7 days (mean 4) after coronary occlusion, 10 dogs 21 to 25 days (mean 28) after occlusion and 6 dogs 4 days after coronary reperfusion of a 2 to 3 hour coronary ligation. Ungated scans (1 cm in depth) of the left ventricle were obtained from apex to base to determine infarct size. In all animals with documented (postmortem) infarction (n = 26), contrast medium caused delayed enhancement of the entire infarct or the periphery of the infarct. Infarct size was calculated from scans showing contrast enhancement of the infarct. Infarct size was also determined from the postmortem heart using histochemical morphometry (nitroblue tetrazolium) and then compared with infarct size derived from tomography using the outer margin of the contrast-enhanced periphery of the infarct as the border of the infarct. Infarct size calculated by the tomographic technique (excluding the animals without an infarct) correlated well with infarct size determined at autopsy (r = 0.90, p less than 0.001). The tomographic estimate (18.2 +/- 11.3 g) of infarct size was similar to autopsy values (18.6 +/- 11.8 g, p = NS). Thus, ungated computed transmission tomographic imaging of the heart can reliably estimate infarct size in a variety of potential clinical circumstances, particularly when the area of rim enhancement of the infarct is included within the presumed infarct region.

Analysis of phase-angle histograms from equilibrium radionuclide studies: correlation with semiquantitative grading of wall motion.

Quantitative wall motion assessment from gated radionuclide left ventriculograms using phase analysis was studied in 14 subjects (6 normal volunteers and 8 patients with previous acute myocardial infarction). The standard deviation and skewness of the phase-angle histograms were determined from both global and segmental left ventricular (LV) regions of interest (septal, apical and posterolateral). Studies were performed at rest, after administration of atropine and after combined administration of phenylephrine and atropine. Both the standard deviation and skewness showed significant correlations with semiquantitative wall motion scoring. From the global analyses, the highest correlations were found after atropine administration (r = 0.86, p less than 0.001 for standard deviation and r = 0.72, p less than 0.001 for skewness). Nevertheless, deterioration in global wall motion scores correlated poorly with directional changes in standard deviation (r = 0.06, difference not significant) or skewness (r = 0.33, p less than 0.05). No significant correlation between skewness or change in skewness and wall motion scores were found with the segmental analyses. The maximal correlation between segmental standard deviation and segmental wall motion grading was again noted after atropine administration (r = 0.68, p less than 0.001), but deterioration in grading did not correlate with similar deterioration of the standard deviation (r = -0.05, difference not significant). Based on 90% confidence limits for normal standard deviation and skewness, an abnormal standard deviation (greater than 14.5) identified 13 of 28 wall motion disorders (sensitivity 46%), whereas an abnormal skewness (greater than 1.4) identified 1 of 28 wall motion disorders (sensitivity 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of computerized tomography to assess myocardial infarct size and ventricular function in dogs during acute coronary occlusion and reperfusion.

Prospectively ECG-gated and nongated computed tomography (CT) can be used to assess global and regional left ventricular (LV) function and to measure myocardial infarct (MI) size. In the current study, CT was used to assess the effects of coronary occlusion and reperfusion in 16 dogs. Ten dogs were subjected to permanent occlusion of the proximal left anterior descending coronary artery and 6 dogs were reperfused after a 2-hour period of total coronary occlusion. Gated scans were used to quantitate the extent of wall thickening in the ischemic zone and to assess changes in mid-LV cross-sectional chamber area at end-diastole and end-systole. Nongated scans were used to estimate the size of the initial perfusion defect during contrast injection shortly after coronary occlusion and the size of the MI as indicated by delayed enhancement of the infarct 10 to 30 minutes after cessation of contrast administration. Neither group showed significant changes in end-diastolic chamber area during acute occlusion or 3 days later. Both groups showed a significant deterioration in percent change in chamber area both early after coronary occlusion and 3 days later; however, in the permanent occlusion group, percent wall thickening in the ischemic zone decreased from 46.2 +/- 16.5% (mean +/- standard deviation) to 1.6 +/- 9.0% during acute occlusion (p less than 0.01) and thickening remained depressed 3 days later (2.4 +/- 10.1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo assessment by computed tomography of the natural progression of infarct size, left ventricular muscle mass and function after acute myocardial infarction in the dog.

Quantification of myocardial infarct (MI) size is of prognostic importance in patients with acute ischemic damage. Evaluation of the efficacy of interventions for salvage of ischemic myocardium depends on the accurate estimation of the ischemic area and a knowledge of the natural progression of the infarct. Computerized transmission tomography (CTT) is a reliable in vivo technique for estimating infarct size. We serially studied 8 dogs over approximately 1 month after occlusion of the left anterior descending coronary artery using both ungated and prospectively electrocardiogram-gated CTT. Scans were obtained 20 minutes after occlusion and then several more times until the dogs were killed. Using the ungated CTT scans, infarct size increased from 0 to 4 days (+ 65 +/- 20%, mean +/- standard error of the mean, p less than 0.05), then progressively decreased. The initial perfusion defect overestimated the eventual MI size at 1 month by 33 +/- 15% (p less than 0.05). The MI size at necropsy correlated well (r = 0.98, p less than 0.001) with CTT MI size determined just before sacrifice. Non-infarcted left ventricular (LV) muscle mass increased significantly (27 +/- 7% greater at 1 month compared with day 0, p less than 0.01) over time, presumably representing compensatory LV hypertrophy. The LV muscle mass at necropsy correlated well (r = 0.94, p less than 0.001) with CTT LV muscle mass just before sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of pulmonic and aortic constriction on regional left ventricular thickening dynamics, geometry and the radius of septal curvature. Analysis by gated computed transmission tomography.

We evaluated the effects of aortic and pulmonic constriction on cross-sectional cardiac dynamics using prospectively gated computed transmission tomography (CT) in six dogs in order to evaluate 1) the effect of altering the end-diastolic trans-septal pressure gradient on the radius of septal curvature, and 2) the effect of right ventricular overload on regional left ventricular geometry and wall thickening dynamics. Cross-sectional CT data were obtained in a control state, at two incrementally higher levels of right ventricular end-diastolic pressure produced by constriction of the pulmonary artery (PA1 and PA2) and then at one higher level of left ventricular end-diastolic pressure resulting from acute aortic constriction (Ao). Using fluid-filled polyethylene catheters, we measured right and left ventricular pressures simultaneous with the image acquisition. The measured radius of septal curvature was then normalized by the calculated average radius derived from the left ventricular area at end-diastole. The end-diastolic radius of septal curvature ratio increased as delta [LVEDP-RVEDP] declined (from 1.03 +/- 0.13 at control; 1.20 +/- 0.18 PA2; 1.27 +/- 0.14 PA2 and 0.87 +/- 0.11 Ao). As this LVEDP-RVEDP gradient declined (ie, RVEDP increased in proportion to LVEDP) septal wall thickening declined (P less than 0.005), with significantly less change in left ventricular anterior or lateral wall thickening. With PA hypertension, LV end-diastolic volume and percent delta volume significantly declined (P less than 0.005) while RV end-diastolic volume increased. With PA pressure overload, septum-free wall distance declined (P less than 0.01) as did percent shortening along this dimension (P less than 0.01). We conclude that predictable changes in LV and RV dynamics occur when trans-septal pressure gradients change.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary density distribution in experimental noncardiac canine pulmonary edema evaluated by computed transmission tomography.

We evaluated the density distribution (anterior-posterior) of the right lung in 19 acutely anesthetized supine dogs using computed transmission tomography (CTT). Eleven dogs served as controls, and eight received 0.12 cc/kg of intravenously administered oleic acid. The latter were sequentially imaged over 1 hour. Nine of these dogs (three control and six oleic acid dogs) had wet weight/dry weight ratios of the corresponding anterior and posterior lung sections evaluated immediately upon completion of the scans. In the control animals, the posterior (dependent) lung was 25 +/- 8% (+/- S.D.) denser than the anterior lung, and did not differ if a second section of the lung was evaluated (1 cm cranial or caudal), or if the animal was imaged on a second day (n = 6). In the oleic acid dogs, the posterior portion of the lung was significantly denser 10 minutes after injection of oleic acid (P less than 0.05), and almost twice as dense 1 hour after initial injection. The density changes determined by CTT in the anterior and posterior lung zones correlated well with the increasing regional wet weight/dry weight relationships determined from the lung on postmortem exam (r = 0.90). We conclude that early subtle density changes in the posterior lung can be found in oleic acid injury pulmonary edema. This can be easily quantitated using CTT, and may prove useful in following physiologic and therapeutic interventions during leaky membrane acute pulmonary injury.

Combined actions of verapamil and contrast media on atrioventricular conduction. Influence of osmolality of the media.

Since verapamil and contrast media both cause depression in the electrophysiologic function of the heart and both may exert these effects by actions on ionic calcium, the possible interaction of verapamil and intracoronary contrast media on atrioventricular conduction was studied in six dogs using surface electrocardiography and HIS bundle electrogram. The effects of intracoronary injection of standard ionic media (Renografin 76) and low osmolal contrast media (Hexabrix and Hexabrix with calcium [8 mEq/L]) were compared. Each contrast media was assessed in the normal state and at four increasing doses of verapamil (0.125, 0.25, 0.5, and 1.0 mg/kg). The PR and AH intervals were substantially prolonged by intracoronary injection of Renografin 76 in the presence of a 1.0 mg/kg dose of verapamil (172 +/- 41 msec to 724 +/- 48 msec, P less than 0.05 for PR interval, and 182 +/- 41 msec to 734 +/- 51 msec, P less than 0.05 for AH interval), with most animals developing second degree heart block (Mobitz, type I). There was no change in the HV interval. Hexabrix and Hexabrix with calcium did not cause significant changes in PR or AH intervals at similar doses of verapamil. Thus, standard ionic contrast causes severe inhibition of atrioventricular conduction in the presence of verapamil, whereas low osmolal contrast media cause no significant negative dromotropic effects either in the presence or absence of verapamil. The osmolality of contrast media is an important mechanism responsible for the depression in atrioventricular conduction attending intracoronary contrast media in the presence of verapamil.

Perfluoroctylbromide. Acute hemodynamic effects, in pigs, of intravenous administration compared with the standard ionic contrast media.

Perfluoroctylbromide (PFOB) is a relatively new noniodinated contrast media that, after intravenous administration, produces prolonged opacification of the blood pool and subsequently selectively enhances the liver and spleen on computed tomography. There has been concern regarding the hemodynamic effect of this agent but little actual knowledge exists in this regard. Accordingly, the acute transient hemodynamic effects of PFOB emulsion were evaluated in five pigs and compared with the standard ionic contrast agent meglumine sodium diatrizoate (Renografin-76). Left ventricular (LV) pressure, internal diameter, and wall thickness were monitored during the alternate intravenous administration of 930 mg/ml PFOB and 370 mg/ml R-76 at a rate of 20 mls/second for a total volume of 1 ml/kg body weight. Renografin-76 caused a significant decrease in LV pressure and dp/dt (rate of change of LV pressure), and an increase in LV end-systolic diameter and a decrease in LV end-diastolic wall thickness. PFOB caused no change in LV pressure and dimensions. Thus, rapid intravenous administration of PFOB does not induce significant acute alterations in left ventricular pressure, dp/dt, dimension, or wall thickness.

MR of Zellweger syndrome.

PURPOSE: To determine characteristic MR imaging features of Zellweger syndrome. METHODS: Clinical records, laboratory records, and MR studies of six patients with Zellweger syndrome were reviewed retrospectively. MR studies were examined for the state of myelination; the presence, extent, and morphologic appearance of cerebral cortical anomalies; the status of the cerebellar cortex, basal nuclei, and brain stem; and the presence or absence of any regions of abnormal signal intensity. RESULTS: The diagnosis of Zellweger syndrome was established in all patients by clinical findings combined with laboratory and MR results. All patients had impaired myelination and diffusely abnormal cortical gyral patterns that consisted of regions of microgyria (primarily in the frontal and perisylvian cortex) together with regions of thickened pachygyric cortex (primarily perirolandic and occipital). The pachygyric regions were in the form of deep cortical infoldings. Germinolytic cysts were visible in the caudothalamic groove in all patients, seen best on coronal or sagittal T1-weighted images. One patient had T1 shortening in the bilateral globus pallidus, presumably related to hepatic dysfunction and hyperbilirubinemia. CONCLUSION: The combination of hypomyelination, cortical malformations that are most severe in the perisylvian and perirolandic regions, and germinolytic cysts are highly suggestive of Zellweger syndrome in the proper clinical setting.

The wedge-shaped cord terminus: a radiographic sign of caudal regression.

Imaging studies from 13 patients with caudal regression were reviewed retrospectively to assess the spectrum and findings of this anomaly. Seven patients were evaluated with MR and six with myelography (supplemented with CT in three). The level of regression varied from T9 to the coccyx. Although osseous abnormalities were more readily identified and characterized by CT, MR effectively depicted the level of vertebral regression, presence of central spinal stenosis, and vertebral dysraphic anomalies. MR demonstrated a characteristic wedge-shaped (longer dorsally) cord terminus in seven of the patients. When this characteristic cord terminus is seen, imaging of the lower lumbar and sacral regions should be performed to verify the diagnosis of caudal regression. Tethered spinal cords have been described in patients with caudal regression and were seen in two of our patients. We present the first cases of individuals who have survived with absence of vertebrae above the T10 level and an unusual case of caudal regression with absent lumbar vertebrae and preserved lower sacral and coccygeal vertebrae. The syndrome of caudal regression encompasses a wide spectrum of pathology that is analyzed well by modern imaging techniques.

Posterior pituitary ectopia: an MR feature of pituitary dwarfism.

Using high-field-strength, 1.5-T, high-resolution MR, we identified the following complex of neurohypophyseal abnormalities in each of five pituitary dwarfs: (1) severe hypoplasia or total absence of the infundibulum; (2) absence of the posterior pituitary bright spot in its normal location; and (3) a 3-8-mm tissue nodule at the median eminence exhibiting lipidlike signal on T1-weighted images. On the basis of its signal features and the clinical absence of diabetes insipidus in these patients, the median eminence nodule appears to represent an ectopic and functional posterior pituitary gland. We propose that this anatomic derangement is the end result of a localized defect of developmental origin, possibly ischemic in nature, and involving principally the infundibular stem. Thus, human growth hormone deficiency could result from perinatal disruption of the peri-infundibular hypophyseal portal system, which in turn impairs anterior pituitary function through deprivation of direct delivery of crucial hypothalamic-releasing factors. Finally, we suggest that the trophic influence of continued axonal neurosecretion at the median eminence engages proliferation of rest cell pituicytes; a process that induces formation of an ectopic and functional posterior pituitary gland, complete with its characteristic bright spot.

Emerging impact of CTA/perfusion CT on acute stroke thrombolysis in a community hospital.

Our objective was to retrospectively review the emerging role of CT, CTA, and perfusion CT (pCT) in the hyperacute stroke population of a community hospital. We reviewed 50 consecutive patients' records and imaging studies, who were treated with thrombolytic therapy within 6 h of symptom onset. Multidetector CT, CTA, and pCT studies were evaluated. Subsequent CT, magnetic resonance, or angiographic studies when available were correlated. Patients' clinical data at admission and outcomes at discharge were evaluated. Complications were tabulated. Of the 50 patients treated with thrombolytics, 37 had CT/CTA/pCT, the others non-contrast CT only. CT blood volume defect was present in a total of 14 patients, presaging permanent infarct in all. Arterial clot was seen in 28/37 CTAs (carotid "T" 6, MCA 16, vertebrobasilar 6). Viable penumbra was shown in 20/37; rescued penumbra was depicted after treatment in 14. 39 patients were treated with intravenous, nine with intra-arterial, two with both forms of thrombolysis. Modified Rankin score showed clinical improvement in 58%, three patients had complete recovery. Subsequent bleed was shown in two (4%), symptomatic in one (2%). Two patients died. Our experience suggests advanced CT is more sensitive to ischemia than routine CT, that salvageable penumbra can be identified, and that triage of patients with acute stroke for thrombolysis with CT/CTA/pCT is more robust than routine CT alone, and may improve outcomes in the community hospital setting.

Brown-Séquard syndrome secondary to spontaneous bleed from postradiation cavernous angiomas.

SUMMARY: The spontaneous occurrence of acute Brown-Séquard syndrome is an extremely rare event, with most reported cases being secondary to spontaneous epidural hematomas and spinal cord ischemia. We report a rare case of Brown-Séquard syndrome from spontaneous intraspinal hemorrhage in a patient with multiple cavernous angiomas in the spinal cord secondary to craniospinal radiation in childhood. Postulated mechanisms leading to the condition include postradiation molecular changes and venous occlusion.

Sustained venous occlusion plethysmography: effects on protein osmotic pressure, intravascular volume, and capillary filtration.

In six acutely anesthetized, mechanically ventilated mongrel dogs, we evaluated sequential changes (over 30 minutes) of sustained forelimb venous occlusion (occlusion pressures 30 to 65 mm Hg) on strain gauge dimension, radionuclide blood pool emissions, and venous, subcutaneous, and intramuscular pressures (Wick technique). Forelimb intravascular volume (assessed by decay-corrected radionuclide counts/unit time) changed by a mean of only -1.2 +/- 2.8% (+/- SEM) and thus was ignored in the calculation of filtration rate. Forelimb (distal to the occlusion site) hematocrit changed insignificantly (45.3 +/- 1.4% at the control point to 48.2 +/- 1.1% at 30 minutes), colloid osmotic pressure rose slightly 19.4 +/- 1.4 mm Hg to 22.7 +/- 1.6 mm Hg, p less than 0.01), and serum osmolality remained unchanged. During sustained occlusion, venous pressure remained constant, subcutaneous pressure rose (-0.7 +/- 1.2 mm Hg control vs 0.5 +/- 1.4 mm Hg at 30 minutes, p less than 0.05), and intramuscular pressure also rose (-0.4 +/- 1.1 mm Hg to 2.6 +/- 1.6 mm Hg, p less than 0.01). Driving pressure, defined by venous pressure - oncotic pressure less the average of intramuscular and subcutaneous pressure declined slightly over the 30 minutes of the study (27.8 +/- 5.5 mm Hg to 23.3 +/- 1.3 mm Hg, p less than 0.05). The relationship between either the initial driving pressure or the initial difference between venous and protein osmotic pressure correlated (r = 0.83 for both) well with strain gauge estimates of capillary fluid flux (evaluated by the change in forelimb strain gauge dimension over time and given as cc/100 cc forelimb volume/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular mural thrombus caused by myocardial infarction diagnosed by computed tomography.

Thrombi of the left ventricle are common sequelae to acute anterior myocardial infarctions that involve the apex of the heart and produce akinetic or dyskinetic wall thickening patterns. While infarctions of the right ventricle are being increasingly recognized in the setting of inferior myocardial infarcts, little data on in vivo clot formation in the right ventricle of the heart are available in these patients. In the current study we were able to demonstrate a right ventricular mural thrombus using gated computed tomography of the heart. Although an abnormality in the right ventricle extending from the septal margin of the ventricle into the outflow tract could be identified with standard blood pool computed tomographic images and from cross sectional echocardiograms, only with cardiac gating could the relationship between the mass (thrombus) and the noncontractile section of the right ventricular myocardium be clearly identified. We conclude that cardiac gating may help in the evaluation of cardiac masses, and in particular cardiac thrombi. This will be particular valuable in the setting of recent or remote infarction, as the relationship between wall-motion abnormalities and thrombus formation has been well documented.

Pulmonary edema formation with myocardial infarction and left atrial hypertension: intravascular and extravascular pulmonary fluid volumes.

The response of pulmonary blood volume (PBV) and extravascular lung water (EVLW) was examined by indicator-dilution techniques in 14 "open chest" dogs, seven that underwent coronary occlusion (group 2) and seven that served as controls (group 1). Data were obtained in a control stage (control stage 1) 45 min after coronary ligation (control stage 2), and 90 min after the left atrial pressure had been increased to approximately 35 mm Hg with a left atrial balloon. In group 2 animals, EVLW increased after coronary ligation without a marked change in left atrial pressure (6.9 +/- 0.4 to 8.2 +/- 0.5 ml/kg mean +/- SD; p less than .05) and increased to 20.1 +/- 1.4 ml/kg after the production of left atrial hypertension (p less than .005 vs control and vs coronary ligation). In the control dogs, EVLW was unchanged 45 min after the initial data had been collected (7.1 +/- 0.7 to 7.0 +/- 0.8 ml/kg). After the production of left atrial hypertension in these dogs, EVLW rose (14.8 +/- 1.2 ml/kg; p less than .005 vs control stage 1 and control stage 2, p less than .01 vs group 2 dogs). PBV did not change significantly with ligation and increased similarly in both groups during left atrial hypertension. We conclude that coronary ligation can increase EVLW, independent of microvascular hydrostatic pressure. During the production of left atrial hypertension there was greater transcapillary fluid flux in group 2 dogs at matched levels of left atrial pressure elevation. This may be due to an alteration in the permeability of the pulmonary capillary membrane during myocardial infarction and provides a partial explanation for the occasional disparity between left heart dynamics and the chest radiograph in acute myocardial infarction.

MR of soft tissue chloroma in a patient presenting with left public and hip pain.

A patient with a history of chronic granulocytic leukemia presented with hip and pubic pain. Magnetic resonance study showed a mass infiltrating the obturator externus muscle, which was biopsied under CT guidance. Pathology of the mass was chloroma. Magnetic resonance can be extremely valuable in determining the etiology of hip and pubic pain in patients with a history of leukemia.