Glucagon and GLP-1 inhibit food intake and increase c-fos expression in similar appetite regulating centres in the brainstem and amygdala.

BACKGROUND: Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. The combination of glucagon and GLP-1 could cause weight loss through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucagon and GLP-1 on food intake and neuronal activation has not previously been studied. Furthermore, the effect of glucagon on neuronal activation in appetite regulating centres has not been assessed. Characterisation of the effects of glucagon when administered singly and in combination with GLP-1 on neuronal activation will be important for determining the mechanism of action of related potential antiobesity therapies. OBJECTIVES: To investigate the effects of peripherally administered GLP-1 and glucagon on food intake, neuronal activation and blood glucose in mice when administered individually and in combination. METHODOLOGY: Food intake, blood glucose and c-fos expression in the hypothalamus, amygdala and brainstem were measured in response to GLP-1 and glucagon, alone and in combination. RESULTS: Peripherally administered GLP-1 and glucagon decreased food intake and increased c-fos expression in the brainstem and amygdala. Doses of GLP-1 and glucagon that individually did not significantly affect feeding, in combination were anorectic and stimulated neuronal activation in the area postrema (AP) and central nucleus of the amygdala. Combined administration of GLP-1 and glucagon prevented the acute hyperglycemic effect of glucagon alone. CONCLUSION: Anorectic doses of glucagon and GLP-1 induced similar patterns of c-fos expression. Combined administration of low dose GLP-1 and glucagon inhibited food intake and induced c-fos expression in the AP and amygdala. The combination of both hormones may offer the opportunity to utilise the beneficial effects of reduced food intake and increased energy expenditure, and may therefore be a potential treatment for obesity.

Testing clinical surveillance of acute flaccid paralysis in Egypt post-eradication of poliomyelitis.

OBJECTIVE: To assess the knowledge of polio detection and notification by front-line clinicians in Egypt. METHODS: This study examines clinicians' knowledge and awareness of polio detection and notification using a multiple-choice questionnaire (maximum score=43) in three large health care centres in central Cairo (n=52). RESULTS: The results reveal a significant variation of knowledge amongst doctors, with junior and senior house officers scoring an average of 30.6 (95% CI: 29.5-31.7), specialist registrars and consultant paediatricians 30.3 (CI 28.9-31.7), and public health doctors 35.4 (CI 32.9-36.8). Mean total scores of public health doctors were significantly higher than those of other clinicians. Senior paediatricians performed no better than newly qualified doctors. CONCLUSIONS: The results suggest that there is a need for more clinical teaching and training amongst junior doctors as well as senior clinicians and consultants. Appropriate knowledge of diagnosing AFP and of the correct protocol amongst clinicians is essential to maintain the high quality of the WHO programme in Egypt.

Multiple sclerosis: correlation between immunoglobulin-G in cerebrospinal fluid and brain.

There is a positive correlation between the concentration of immunoglobulin-G in plaques of demyelination due to multiple sclerosis (as well as in white matter of normal appearance) and the concentration of this globulin in the cerebrospinal fluid. The tentative conclusion drawn from these results was that, in patients with multiple sclerosis, the increase in immuno-globulin-G in the cerebrospinal fluid is a reflection of an excess of this globulin in the brain.

Sperm donation: implications of Canada's Assisted Human Reproduction Act 2004 for recipients, donors, health professionals, and institutions.

BACKGROUND: On April 22, 2004, the Assisted Human Reproduction Act came into force, prohibiting the purchase of sperm or eggs from donors in Canada. In response to the concerns of medical professionals and some consumers that prohibiting payment would lead to a decline in the number of gamete donors, Health Canada commissioned research on altruistic donor recruitment and recruitment strategies. METHODS: Twenty-two studies of sperm donors were located and their findings reviewed. The studies spanned 23 years (1980-2003), were undertaken in a range of countries, and were chosen on the merit of their relevance to the development of recruitment strategies within a policy of altruistic sperm donation. Observations were derived from assessing and comparing the purposes, findings, and implications of the 22 studies. RESULTS: Payment for providing sperm was made in all but three studies, although participants in 15 studies indicated clearly that their motivations were primarily altruistic. Observations indicate that men who are more willing to be identified to offspring in the future share demographic characteristics, such as age and parental status, with those who are prepared to donate altruistically. These characteristics appear to be a factor in motivation to donate altruistically. CONCLUSION: The studies show that there are men who are prepared to donate sperm without financial payment. The findings suggest that a change is required in the culture of sperm donation, specifically the adoption of a new approach to donor recruitment.

Early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator.

To assess abnormalities of right heart function and their reversal with thrombolysis in pulmonary embolism, serial imaging and Doppler echocardiographic studies were performed before and after a 6 hour intravenous infusion of 80 to 90 mg of recombinant tissue-type plasminogen activator (rt-PA) in seven patients with segmental or lobar acute pulmonary embolism. None of the five men and two women had known prior pulmonary hypertension. Substantial clot lysis and improvement in pulmonary blood flow, as determined by serial pulmonary angiography and perfusion lung scanning, were achieved in all. Coincident with clot lysis, pulmonary artery systolic pressure decreased (from 42 +/- 11 to 26 +/- 7 mm Hg, p less than 0.005), right ventricular diameter decreased (from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm, p less than 0.005) and left ventricular diameter increased (from 3.7 +/- 0.9 to 4.4 +/- 0.6 cm, p less than 0.01). Right ventricular wall movement, initially mildly, moderately or severely hypokinetic in one, two and four patients, respectively, normalized in five and improved to mild hypokinesia in two. Tricuspid regurgitation was present before lytic therapy in six patients. In five, flow velocity in the tricuspid regurgitant jets indicated a peak systolic right ventricular minus right atrial pressure gradient of 25 to 52 mm Hg. Tricuspid regurgitation was detected early after lytic therapy in only two patients. Systolic septal flattening was noted before but not after lysis. These findings confirm that pulmonary emboli may result in appreciable right ventricular dysfunction and dilation, resultant tricuspid regurgitation, abnormal septal position and decreased left ventricular size.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia.

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The pacing stress test reexamined: correlation of pacing-induced hemodynamic changes with the amount of myocardium at risk.

To assess the relation between extent of ischemia and the magnitude of hemodynamic changes, 25 patients (5 with normal coronary arteries and 20 with significant coronary obstructive disease) were studied with rapid atrial pacing and thallium scintigraphy at the time of cardiac catheterization. Hemodynamic variables were measured before, during and after maximal pacing. Thallium was injected intravenously during maximal pacing and scans in three standard views were obtained immediately in the catheterization laboratory, with delayed scans obtained 4 hours after the cessation of pacing. The three thallium scans were each subdivided into five segments, and a thallium score was obtained on the basis of the total number of segments that were hypoperfused. Each patient was assigned a total thallium score corresponding to thallium defects at maximal pacing, as well as a redistributed thallium score corresponding to the difference between thallium score at maximal pacing and that 4 hours later. With pacing, patients with normal coronary arteries demonstrated no significant change in baseline hemodynamic variables, whereas patients with coronary artery disease exhibited a decrease in cardiac index, an increase in systemic vascular resistance, a widening of arteriovenous oxygen difference, an increase in pulmonary capillary wedge pressure and mean pulmonary artery pressure during maximal pacing and an increase in left ventricular end-diastolic pressure immediately after pacing. There was a significant correlation (Spearman rank r = 0.64, p less than 0.01) between redistributed thallium score and an increase in left ventricular end-diastolic pressure in the postpacing period. Moreover, there was an even higher correlation (Spearman rank r = 0.90, p less than 0.001) between total thallium score and the postpacing increase in end-diastolic pressure. It is concluded that in patients with coronary artery disease the magnitude of pacing-induced hemodynamic changes reflects both the amount of myocardial tissue at ischemic jeopardy and the total mass of hypoperfused myocardium during maximal pacing stress.

The pacing stress test: thallium-201 myocardial imaging after atrial pacing. Diagnostic value in detecting coronary artery disease compared with exercise testing.

Many patients suspected of having coronary artery disease are unable to undergo adequate exercise testing. An alternate stress, pacing tachycardia, has been shown to produce electrocardiographic changes that are as sensitive and specific as those observed during exercise testing. To compare thallium-201 imaging after atrial pacing stress with thallium imaging after exercise stress, 22 patients undergoing cardiac catheterization were studied with both standard exercise thallium imaging and pacing thallium imaging. Positive ischemic electrocardiographic changes (greater than 1 mm ST segment depression) were noted in 11 of 16 patients with coronary artery disease during exercise, and in 15 of the 16 patients during atrial pacing. One of six patients with normal or trivial coronary artery disease had a positive electrocardiogram with each test. Exercise thallium imaging was positive in 13 of 16 patients with coronary artery disease compared with 15 of 16 patients during atrial pacing. Three of six patients without coronary artery disease had a positive scan with exercise testing, and two of these same patients developed a positive scan with atrial pacing. Of those patients with coronary artery disease and an abnormal scan, 85% showed redistribution with exercise testing compared with 87% during atrial pacing. Segment by segment comparison of thallium imaging after either atrial pacing or exercise showed that there was a good correlation of the location and severity of the thallium defects (r = 0.83, p = 0.0001, Spearman rank correlation). It is concluded that the location and presence of both fixed and transient thallium defects after atrial pacing are closely correlated with the findings after exercise testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular pressure-volume diagrams and end-systolic pressure-volume relations in human beings.

Assessment of left ventricular pressure-volume relations serially in response to altered loading conditions and heart rate has been difficult to achieve with contrast ventriculography. Accordingly, to study changing pressure-volume relations during altered loading and heart rate, left ventricular pressure and radionuclide absolute volume curves (obtained using a counts-based method with attenuation factor corrections) were recorded in 20 patients. Ventricular pressure and radionuclide volume curves were digitized and synchronized to end-diastole, and pressure-volume plots were subsequently constructed from 32 pressure-volume coordinates throughout the cardiac cycle. In all patients, the correlation between radionuclide absolute volumes and angiographic ventricular volumes was r = 0.92. In 10 patients in whom both radionuclide and angiographic pressure-volume diagrams were constructed, the agreement between the two methods was excellent. With this method, end-systolic pressure-volume relations were examined during altered left ventricular loading conditions, pacing-induced incremental increases in heart rate and pacing-induced ischemia. Using pharmacologically induced changes in left ventricular loading conditions, the slope and volume intercept of the end-systolic pressure-volume line could be calculated as a means of assessing basal contractility. During pacing-induced tachycardia, the slope and volume intercept of the end-systolic pressure-volume line could be calculated to quantify the Treppe effect and assess negative inotropic changes secondary to ischemia. This study supports the validity of using serial recordings of left ventricular pressure and radionuclide volumes to assess left ventricular pressure-volume relations, and indicates that this approach may be useful in the analysis of end-systolic pressure-volume relations in patients.

Intracoronary thallium-201 scintigraphy after thrombolytic therapy for acute myocardial infarction compared with 10 and 100 day intravenous thallium-201 scintigraphy.

Thallium-201 imaging has been utilized to estimate myocardial salvage after thrombolytic therapy for acute myocardial infarction. However, results from recent animal studies have suggested that as a result of reactive hyperemia and delayed necrosis, thallium-201 imaging may overestimate myocardial salvage. To determine whether early overestimation of salvage occurs in humans, intracoronary thallium-201 scans 1 hour after thrombolytic therapy were compared with intravenous thallium-201 scans obtained approximately 10 and 100 days after myocardial infarction in 29 patients. In 10 patients with angiographic evidence of coronary reperfusion, immediate improvement in thallium defects and no interim clinical events, there was no change in imaging in the follow-up studies. Of nine patients with coronary reperfusion but no initial improvement of perfusion defects, none showed worsening of defects in the follow-up images. Six of these patients demonstrated subsequent improvement at either 10 or 100 days after infarction. Seven of 10 patients with neither early evidence of reperfusion nor improvement in perfusion defects had improvement of infarct-related perfusion defects, and none showed worsening. In conclusion, serial scanning at 10 and 100 days after infarction in patients with no subsequent clinical events showed no worsening of the perfusion image compared with images obtained in acute studies. Therefore, there is no evidence that thallium-201 imaging performed early in patients with acute myocardial infarction overestimates improvement.

Mechanisms of pulsus paradoxus during resistive respiratory loading and asthma.

To determine the mechanisms of pulsus paradoxus during asthma, six subjects known to have cold air bronchial hyperreactivity were studied while in a quiescent phase of their disease. All were free of significant airway obstruction at the time of study. After placement of an esophageal balloon to estimate intrathoracic pressure, the subjects were assessed during quiet breathing, resistive airway loading and then during a stable period of airway obstruction induced by cold air. Steady state left ventricular volume and performance were measured using radionuclide ventriculography; right ventricular volume was calculated from the stroke volume ratio and right ventricular ejection fraction. Cardiac cycles were segregated according to their occurrence in inspiration or expiration using a flow signal from a pneumotachograph. Combined inspiratory and expiratory resistance produced pulsus paradoxus and changes in esophageal pressure that were similar to those during asthma and significantly greater than those during quiet breathing. These changes were accompanied by decreases in left ventricular diastolic volume and stroke volume during inspiration, and increases in these variables during expiration; right ventricular volume and stroke volume demonstrated changes reciprocal to those seen in the left ventricle. These data indicate that during periods of increase in airway resistance, abnormal pulsus paradoxus results from an exaggeration in the normal inspiratory-expiratory difference in stroke volume mediated primarily by the effects of intrathoracic pressure on ventricular preload.

Comparison of ultrashort-lived iridium-191m with technetium-99m for first pass radionuclide angiocardiographic evaluation of right and left ventricular function in adults.

Ultrashort-lived iridium-191m (Ir-191m, physical half-life = 5.0 seconds) has been used in angiocardiography, primarily in pediatric patients. A theoretical obstacle to more widespread use of Ir-191m is the belief that its physical half-life is too short to permit evaluation of left ventricular function in adult patients. To evaluate its usefulness in adults, first pass ejection fractions of the left and right ventricles determined with use of Ir-191m and technetium-99m (Tc-99m) were compared in 33 adult patients. An osmium-191m----iridium-191m (Os-191----Ir-191m) generator was employed to deliver doses of 150 to 250 mCi (5.5 to 9.2 GBq) of Ir-191m for intravenous injection. The whole body radiation absorbed dose with Ir-191m was 15 to 25 mrad. High quality angiocardiograms were obtained with both Tc-99m and Ir-191m. Total counts per image for the right ventricle were 51,000 +/- 8,000 (mean +/- SD) for Ir-191m and 30,000 +/- 8,000 for Tc-99m. The left ventricular counts were comparable for both radiotracers (25,000 +/- 7,000 for Ir-191m and 25,000 +/- 8,000 for Tc-99m). Right ventricular ejection fractions were similar: 44 +/- 8% for Ir-191m and 47 +/- 9% for Tc-99m. The correlation coefficient was 0.93 with a standard deviation of the regression of 3.1% ejection fraction units. The left ventricular ejection fractions were also similar: 45 +/- 14% for Ir-191m and 46 +/- 13% for Tc-99m. The left ventricular ejection fraction correlation coefficient was 0.96 with a standard deviation of the regression of 3.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion, function and exercise tolerance after the arterial switch operation.

OBJECTIVES: This study was conducted to determine the prevalence of myocardial perfusion abnormalities at rest and exercise and to assess exercise capacity in children after the arterial switch operation. BACKGROUND: There have been sporadic reports of myocardial ischemia or sudden death in children after the arterial switch operation for transposition of the great arteries, possibly related to inadequate coronary perfusion due to kinking or stenosis of the translocated coronary arteries. METHODS: Myocardial perfusion at rest and peak exercise was assessed using the scintigraphic agent technetium-99m methoxyisobutyl isonitrile (sestamibi). Exercise capacity was determined with a modified Bruce protocol. Ambulatory electrocardiographic (ECG) Holter monitoring was performed. Ventricular function, contractility and wall motion were assessed echocardiographically. RESULTS: Twenty-three children (aged 4.2 to 7.9 years) underwent evaluation. Abnormalities were found on the rest perfusion scans in 22 children (95.6%). The left ventricular myocardium was divided into 13 segments for analysis. Of 299 rest segments, 225 (75.3%) were normal, 11 (3.7%) showed mild defects, 45 (15%) moderate defects and 18 (6%) severe defects at rest. At peak exercise, 237 segments (79.3%) were normal, 24 (8%) showed mild defects, 33 (11%) moderate defects and 5 (1.7%) severe defects. Compared with rest studies, myocardial perfusion grade at exercise was unchanged in 246 segments (82.3%), improved in 42 (14%) and worsened in 11 (3.7%). All patients had normal exercise tolerance without symptoms or ischemic ECG changes. No ventricular tachycardia was seen on Holter monitoring. All patients had a shortening fraction > or = 27%. Left ventricular contractility was normal in 12 children in whom it was assessed. Regional wall motion was normal in 17 children with adequate echocardiographic images for this analysis. CONCLUSIONS: Myocardial perfusion scan abnormalities assessed by technetium-99m sestamibi are common after an arterial switch operation. These abnormalities are of uncertain clinical significance and generally lessen with exercise. The normal exercise tolerance without symptoms or ECG changes suggests that myocardial perfusion is adequate during the physiologic stress of exercise in children up to 8 years after an arterial switch operation.

Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial.

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.

Preoperative evaluation of thyroid nodules with 18FDG-PET/CT.

BACKGROUND: Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) has become an important tool in the postoperative management of de-differentiated thyroid cancer. The utility of this imaging modality in the preoperative assessment of thyroid nodules is unclear. This study was designed to determine whether (18)FDG-PET/CT improves the preoperative diagnosis of thyroid nodules. METHODS: A total of 31 patients with 48 lesions underwent fine-needle aspiration and (18)FDG-PET/CT before surgical resection of thyroid nodules. PET/CT images were obtained 1 hour after intravenous administration of (18)FDG. Standard uptake values were calculated for regions of increased (18)FDG uptake. CT scans were evaluated to identify thyroid pathology. Final pathologic diagnoses were compared with PET/CT findings. RESULTS: Fifteen of 48 lesions were malignant and 33 were benign. Nine of 15 malignant lesions were (18)FDG-avid (sensitivity 60%). Thirty of 33 benign lesions were (18)FDG-cold (specificity 91%). Positive and negative predictive values were 75% and 83%, respectively. CONCLUSIONS: (18)FDG-PET/CT provides a high negative predictive value for malignancy, making this a potentially useful tool in the evaluation of thyroid nodules with indeterminate fine-needle aspiration. However further studies with larger sample sizes are needed to determine the true efficacy of this test.

Postprandial hypotension in elderly patients with unexplained syncope.

BACKGROUND: Syncope in older patients may be caused by a variety of disorders, including hypotension, but frequently remains unexplained. Postprandial hypotension is a common disorder of blood pressure regulation in the elderly. OBJECTIVE: To determine the pathogenic mechanisms and potential role of postprandial hypotension in elderly patients with otherwise unexplained syncope. METHODS: We studied 16 elderly patients with unexplained syncope and nine elderly controls. Blood pressure, heart rate, forearm vascular resistance, plasma norepinephrine level, and cardiac and splanchnic blood volumes were measured before and after a 1680-kJ meal. RESULTS: Eight elderly patients with syncope had postprandial hypotension, with a decline in supine mean arterial blood pressure of 17 +/- 2 mm Hg after a meal (P < .001). The blood pressure remained unchanged after the meal in the other patients with syncope and the controls. In patients with postprandial hypotension, systemic vascular resistance fell after the meal, while it remained unchanged in the other groups. Heart rate and plasma norepinephrine level increased to a similar extent in all three groups. Forearm vascular resistance increased only in the control subjects. Splanchnic blood volume increased by 26% (P < .01) in patients with syncope who had postprandial hypotension and by 22% (P < .01) in control subjects. Splanchnic blood volume remained unchanged in the patients with syncope without postprandial hypotension. CONCLUSIONS: Postprandial hypotension may be an important causative factor in elderly patients with unexplained syncope. The evaluation of syncope in elderly patients should therefore include blood pressure measurements surrounding a meal. Elderly patients with syncope who have postprandial hypotension fail to maintain systemic vascular resistance, probably because of splanchnic blood pooling without a compensatory increase in peripheral vascular resistance.

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Accuracy of deconvolution algorithms assessed by simulation studies: concise communication.

Deconvolution has been used to correct first-pass radionuclide angiocardiography for the time course of the delivery of radiopharmaceutical into the cardiopulmonary system. The extreme sensitivity of deconvolution to random errors in the data may account for some of the problems encountered in practice. We implemented several deconvolution algorithms that were suitable for use with the unimodal and multimodal superior vena caval and pulmonary curves found in left-to-right shunt quantification. The sensitivity of the algorithms to random errors was assessed using mathematical test problems degraded with pseudorandom noise. An algorithm that constrained the deconvolved pulmonary curve to be expressable as the non-negative sum of a set of lagged normal curves was found to have the smallest maximum error on the curves tested. Comparison with results from a previously published test problem indicated an error reduction of greater than 50% over previously used algorithms. Use of this algorithm may permit more accurate deconvolution of pulmonary time-activity curves and thereby improve shunt quantification.

Scintigraphy of hepatic hemangiomas: the value of Tc-99m-labeled red blood cells: concise communication.

Fourteen patients with hepatic hemangiomas were evaluated by Tc-99m colloid scintigraphy and Tc-99m RBC angiography, including flow studies and early and delayed static studies. On colloid scintigraphy, the liver appeared enlarged, with single or multiple focal defects. During the flow and early static Tc-99m RBC studies, the lesions showed poor perfusion and were filled only partially or not at all. Delayed Tc-99m RBC studies demonstrated the whole extent of the lesion and all the lesions when multiple hemangiomas were present. A flow study showing decreased perfusion and a late blood-pool study showing increased local blood volume appear characteristic of hemangiomas. Liver biopsy should not be attempted in such cases.

Radionuclide angiocardiographic calculation of the ratio of left-to-right heart outputs in a patient with unusual cardiovascular anatomy: case report.

The subject of this case report is an unusual patient whose right lung receives blood from the right heart and whose left lung receives blood from the left heart. Due to this unusual anatomy, it was possible to calculate the ratio of the outputs of the left and right hearts using standard techniques.