Peter T. Kirchner

Recombinant Human Erythropoietin Treatment in Pre-Dialysis Patients: A Double-Blind Placebo-Controlled Trial

STUDY OBJECTIVE To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients. DESIGN Randomized, double-blind, placebo-controlled trial for 8 weeks. SETTING Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital. PATIENTS Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01). INTERVENTIONS Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week. MEASUREMENTS AND MAIN RESULTS Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9. CONCLUSIONS Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients.

Regional Cerebral Blood Flow in Normal Pressure Hydrocephalus

Regional cerebral blood flow (rcbf) was studied preoperatively and at 2 and 6 months postoperatively in 22 normal pressure hydrocephalus patients using xenon-133 inhalation and single photon emission computed tomography. Sixteen of the 22 patients improved (improved group) and six did not (unimproved group). The following comparisons were made: (1) preoperative rcbf in the improved group, to 14 normal elderly volunteers and to that in 59 SDAT (senile dementia of the Alzheimer type) patients; (2) preoperative rcbf in the improved and unimproved groups to determine if rcbf could predict surgical outcome; (3) pre- to postoperative rcbf in the improved group to see if increased cbf accounted for clinical improvement. The findings were: (1) preoperative rcbf in the improved group was lower than that in normal controls but was the same as that in SDAT; however, the ratios of rcbf values in anterior and posterior brain regions were significantly different between improved group and SDAT (p = 0.02); (2) an anterior/posterior ratio of 1.05 correctly classified surgical outcome in 19/22 patients; five of six in the unimproved group were above this cut off while 14/16 in the improved group were below; (3) in the improved group rcbf increased at 2 but not at 6 months after surgery without a corresponding reduction of clinical signs, supporting the notion that increase in cbf probably does not account for clinical improvement in normal pressure hydrocephalus.

NeuroSPECT correlates of disabling mild head injury: Preliminary findings

Objective: To study mild head injury patients with poor psychosocial and vocational outcomes using neurological single photon emission computed tomography (neuroSPECT) imaging. Design: Case‐comparison study. Setting: VA Medical Center, outpatient clinics. Patients: Fourteen mild head injury patients with normal computed tomography (CT) and/or magnetic resonance imaging (MRI) scans and five normal controls. Head‐injured patients were selected because they had obtained and maintained highly responsible employment prior to injury, but were unable to sustain any occupation despite multiple attempts over a number of years after injury. Intervention: NeuroSPECT with technetium Tc 99m hexamethylpropyleneamine oxime. Main Outcome Measure: Regional abnormalities in cerebral perfusion as indicated by neuroSPECT. Results: This carefully preselected population consistently showed anterior mesial temporal hypoperfusion. By contrast, posterior temporal abnormalities were very infrequent. NeuroSPECT findings with regard to orbitofrontal damage were not as striking, but were statistically significant on the left and were sufficient to raise the question of dysfunction in this area as well. Conclusions: Findings indicate that some “mild” head injuries with unusually catastrophic psychosocial consequences can produce regional abnormalities in cerebral perfusion that are apparent with neuroSPECT, even in the absence of abnormalities seen on CT or MRI.

Influence of baseline ejection fraction and success of thrombolysis on mortality and ventricular function after acute myocardial infarction

The efficacy of streptokinase (STK) thrombolytic therapy was prospectively evaluated in 77 consecutive patients presenting within 9 hours of onset of acute myocardial infarction. Serial left ventricular (LV) ejection fraction (EF) was assessed by radionuclide ventriculography, initially (acute) and at 1 month (late). The role of initial LVEF was examined by comparing patients with an acute LVEF greater than or equal to 50% (type I) with those with LVEF less than 50% (type II). Sixty-five patients (84%) had total coronary occlusion and received STK. Initial successful reperfusion was achieved in 34 patients (52%), but repeat angiograms at 10 to 14 days revealed persistent patency in only 27 patients. Within the type I and type II classification, 2 patient subgroups were compared: Group A had successful and persistent thrombolysis and group B had initial failure of thrombolysis or in-hospital reocclusion. There was no significant change in global LVEF in any group from acute to 1 month follow-up: group IA--acute EF = 56 +/- 2% (mean +/- standard error of the mean), late EF = 55 +/- 2% (p = not significant [NS]); group IB--acute EF = 58 +/- 1%, late EF = 55 +/- 2% (NS); group IIA--acute EF = 35 +/- 2%, late EF = 4 +/- 4%, (NS); group II B--acute EF = 36 +/- 2%, late EF = 41 +/- 3% (NS). No patient with an acute EF greater than or equal to 50% died, i.e., group IA patients (n = 7) or group IB patients (n = 13).(ABSTRACT TRUNCATED AT 250 WORDS)

The Safety and the Efficacy of Maintenance Therapy of Recombinant Human Erythropoietin in Patients With Renal Insufficiency

Ten anemic predialysis renal patients participated in a study to examine the long-term effects of recombinant human erythropoietin (r-HuEPO) treatment. The drug was initially given intravenously three times a week for 1 to 5 months, then by subcutaneous injections three times each week for 4 to 8 months, and finally by subcutaneous injection once weekly for 3 to 18 months. The duration of follow-up ranged from 11 to 29 months. Anemia was ameliorated in all participants. Mean hematocrit increased from a basal value of 26.8% to 35.1% during the intravenous phase and to 36.7% and 34.6% during the two subcutaneous periods. Mean weekly doses of erythropoietin (EPO) were 276 units/kg during intravenous therapy and 134 and 108 units/kg in the two subcutaneous periods. The differences in the doses were significant only between the intravenous and the two subcutaneous periods. Mean erythrocyte mass increased from a baseline value of 13.6 mL/kg to 20.4 mL/kg 8 months after initiation of treatment. Mean erythrocyte survival half-time was increased from 23 days before to 26 days, 8 months after r-HuEPO treatment, P less than 0.002. Mean blood pressure (mm Hg) was 105 before and 95 after treatment. Mean serum creatinine was 513 mumol/L (5.8 mg/dL) at the beginning of the study. At the time of this writing (11 to 29 months after treatment), seven patients have required dialysis treatment. There were three episodes of transient refractoriness to r-HuEPO documented during periods of infection and surgical procedures. All subjects tolerated the medication well, and no serious side effects attributable to the medication were noted. Furthermore, circulating antibodies against r-HuEPO were consistently negative.

An emission-based technique for obtaining attenuation correction data for myocardial SPECT studies.

In this paper, a technique is described for obtaining the information needed to perform attenuation correction in the thorax entirely from an emission study. This technique is based on the observation that the variation in soft tissue and lung attenuation coefficients is small among individuals. Thus only the outer contours of the body and lungs need be determined for obtaining the attenuation map. The contours are determined by using 99Tcm-macroaggregated albumin (MAA) to locate the lungs and an external source wrapped about the chest to locate the body boundary. Simulation studies were performed to investigate how errors in the presumed tissue attenuation coefficients affect the accuracy of the correction. Body and lung attenuation coefficients were varied from 20% less to 20% more than the coefficients used in the corrections. Over this range, there was less than a 15% alteration in the relative distribution of counts in the left ventricle. To test clinical feasibility, seven patients referred for clinical myocardial perfusion studies were scanned before and after the placement of the body source and the administration of 99Tcm-MAA. Reconstructed images from these studies showed clear demarcation of all body and lung boundaries. The presence of 99Tcm-MAA in the lungs had no significant effect on the clinical interpretation of the single photon emission computed tomographic (SPECT) studies. It is concluded that this technique is feasible for clinical application and that it offers important advantages over other current methods.

Dual isotope brain SPECT imaging for monitoring cognitive activation: initial studies in humans

A dual isotope, single photon emission tomography (SPECT) technique using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 123I-iodoamphetamine (IMP) was investigated to determine its suitability for assessing regional cerebral blood flow (rCBF) changes resulting from cognitive activation. The similarity of the 123I-IMP and 99Tcm-HMPAO distributions under the same physiological conditions was first investigated by administering the two agents to human subjects (n = 8) either simultaneously or at different times but during the performance of the same task. Normalized ratio images generated from the 99Tcm and 123I data showed that the two tracers distributed similarly in the left and right cerebral hemispheres when administered under similar physiological conditions. There was, however, a significant anterior/posterior gradient that appears to be the result of partial volume effects due to small differences in spatial resolution of the two agents. In two subjects, 99Tcm-HMPAO was administered during a resting period with eyes-closed and 123I-IMP was injected later during visual checkerboard stimulation. Ratio images showed a localized increase in the occipital lobes during the visual stimulation consistent with the expected increase in rCBF. The dual isotope strategy appears promising for study of changes in rCBF due to cognitive activation.

Crossed cerebellar diaschisis associated with balloon test occlusion of the carotid artery

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomographic (SPECT) brain imaging performed in conjunction with balloon test occlusion of the carotid artery has been used to assess risk of neurologic sequelae that might follow permanent surgical ligation of the artery. The predictive value of cortical hypoperfusion during temporary carotid occlusion for adverse neurologic events has been debated in previous publications. We believe that the risk of an adverse event is greater when a reduction in cortical perfusion during balloon test occlusion is associated with crossed cerebellar diaschisis (CCD). To test our hypothesis we evaluated the results of 27 99Tcm-HMPAO SPECT brain studies obtained in association with balloon test occlusions of the carotid artery. In each case we correlated clinical outcome with the presence or absence of regional decreases in cerebral perfusion and CCD. All of the 27 patients were free of neurologic symptoms during the balloon test occlusion. Seventeen of the 27 scintigraphic studies were felt to be abnormal, showing cortical perfusion defects all on the side of the occlusion. Among these 17 patients, five demonstrated CCD. Four of these five CCD patients showed evidence for cerebral cortical ischaemia on the side of the temporary carotid occlusion either shortly after the procedure or following carotid artery sacrifice. Of the remaining 12 patients with regionally reduced cerebral perfusion and no CCD, none showed evidence for cortical ischaemia in association with balloon test occlusion, and five of these 12 patients had carotid ligation without subsequent neurologic sequelae. Our results provide evidence to support our hypothesis that when CCD accompanies regional hypoperfusion on a brain SPECT study obtained after injection of 99Tcm-HMPAO during balloon test occlusion of the carotid artery, the patient is likely to be at increased risk of adverse neurologic sequelae following carotid sacrifice.

Design And Investigation Of A Modular Focused Collimator Based Multiple Detector Ring System For SPECT Imaging Of The Brain

The ability of focused collimators to achieve both high sensitivity and high resolution at depth makes them highly desirable for SPECT imaging. Tomographic systems with stationary detector rings are known to have the advantages of simplicity, stability and tolerance to variations in detector response. We have combined these two desirable features in the design of a multidetector ring SPECT system with a unique modular focused collimator for brain imaging. In a manner similar to that employed by 4th generation CT scanners, each detector unit acquires a set of fan beam projection data while the collimator assembly makes a complete rotation. Our investigation shows that the new tomograph can be expected to achieve a spatial resolution of 8 mm and a system sensitivity of 2,500 cps/pCi/cc for a 13 mm thick image slice. The high performance characteristics of the new SPECT system should make it a useful tool in functional imaging of the brain, especially in perfusion studies using the current 1-123 or Tc-99m labeled agents.

Emission-based attenuation correction of myocardial perfusion studies

BackgroundNonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement.Methods and ResultsThe attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201TI study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients.ConclusionsThe results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.