A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma.

PURPOSE: In patients with an osteosarcoma, the prognosis is still poor. The aim of the present study was to investigate whether routinely tested biochemical parameters or additional parameters on bone scintigraphy could be identified which can select prognostic subgroups at the time of diagnosis. METHODS: A retrospective study was performed in 115 consecutive patients (70 male, 45 female) (mean age: 25.6 years; range: 3.50-78.0 years) who were referred for bone scintigraphy prior to treatment from March 1986 to September 2000 because of a newly diagnosed osteosarcoma. All bone scans were reassessed for the intensity and pattern of uptake and a bone-scan index. All pre-treatment general, histological, biochemical, and scintigraphic data were correlated with clinical outcome during follow-up. RESULTS: During follow-up 54 patients died. Tumour volume and GGT showed significance as independent variables for metastases. Patients with metastases demonstrated a significantly lower survival rate (23% 5-year survival) than patients without metastases (98% 5-year survival). Tumours of the humerus and femur had a significantly lower survival rate. With respect to significant biochemical parameters (ALP, GGT, ASAT), it was not possible to determine a cut-off value that could be used to differentiate between high- and low-risk patients. Additional parameters assessed on bone scintigraphy were not important for prognostic stratification. CONCLUSION: The strongest predictor of survival in osteosarcoma is the presence or absence of metastasis. Some biochemical parameters have prognostic value, but they cannot be used for the unequivocal identification of subgroups. Additional scintigraphic parameters are irrelevant for prognostic stratification.

No gender bias in referral for coronary angiography after myocardial perfusion scintigraphy with technetium-99m tetrofosmin.

BACKGROUND: Several studies have shown that the application of diagnostic and invasive procedures varies between men and women. The purpose of this study was to assess if referral for coronary angiography after technetium-99m tetrofosmin myocardial perfusion scintigraphy in 616 patients with undiagnosed chest pain might demonstrate gender bias. METHODS AND RESULTS: The primary end point for this study was coronary angiography within 90 days of myocardial perfusion scintigraphy. Women had more normal perfusion images than men (207 [70.9%] vs 160 [50.5%], P < .05). Of 242 patients with abnormal images (157 men, 85 women), 28 men (17.7%) and 17 women (20.0%) were referred for further invasive testing (P = not significant). Referral for coronary angiography increased relative to the number of defects. Univariate analysis showed that reversible and persistent defects were the most predictive variables for referral to coronary angiography (odds ratio [OR] 5.45, 95% confidence interval [CI] 3.10-9.58, P < .001, and OR 2.67, 95% CI 1.52-4.67, P = .001, respectively). More importantly, multivariate analysis showed that reversible perfusion defects (OR 4.77, 95% CI 2.48-9.17, P < .001) and persistent perfusion defects (OR 2.14, 95% CI 1.11-4.14, P = .02) were predictive of subsequent coronary angiography. No significant association between gender and subsequent coronary angiography was found both in univariate and multivariate logistic regression analysis (OR 0.64, 95% CI 0.37-1.12, P = .12, and OR 0.70, 95% CI 0.36-1.36, P = .28, respectively). CONCLUSIONS: Our study reveals that after correction for the presence and the severity of myocardial perfusion abnormalities, men and women were referred to coronary angiography at a similar rate. Thus, based on the results of technetium-99m tetrofosmin myocardial perfusion imaging, no substantial evidence for a gender-related bias could be found in the referral for further invasive testing.

Disturbed enterogastric inhibitory reflex after esophageal resection and narrow gastric tube reconstruction.

BACKGROUND/AIMS: The gastric emptying pattern after esophageal resection and narrow gastric tube reconstruction is determined by multiple factors. One of the possible factors is a disruption in the neurohumoral enterogastric inhibitory reflex. The aim of the present study was to determine the possible alterations of this reflex after esophageal resection and narrow gastric tube reconstruction. METHODS: Nine patients each underwent two gastric tube emptying studies, one without and one with high caloric duodenal tube feeding. The dual isotope scintigraphic data were corrected for subject movement, radionuclide decay, downscatter and gamma-ray attenuation. RESULTS: The median gastric tube emptying rate of solid food was 57%/h (range 27-195). The median T(1/2) of liquid food was 67 (range 4->80) min. Both for solid and for liquid food, the gastric tube emptying patterns without and with duodenal tube feeding were not significantly different. CONCLUSION: The neurohumoral enterogastric inhibitory reflex is disrupted after esophageal resection and narrow gastric tube reconstruction, which may contribute to disturbed gastric emptying.

Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis.

It has been suggested that enteric-coated pancreatin microsphere (ECPM) preparations with sphere sizes larger than 1.7 mm pass through the stomach at a slower rate than a meal and therefore may be less efficacious in restoring pancreatic enzyme activity than preparations with smaller sphere sizes. The aim of this study was to investigate the gastric transit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneously measure enzyme activities in eight patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Gastric transit was assessed by double-isotope scintigraphy. A pancake was labeled with 99mTc. A 2-mm ECPM preparation was labeled with 171Er. Intraluminal pancreatic enzyme activities were assessed during a 6-hr period with the cholesteryl-[14C]octanoate breath test (for carboxyl ester lipase activity) and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test (for chymotrypsin activity). The ECPM preparation passed through the stomach more rapidly (median 24 min) than the pancake (median 52 min, P < 0.05). During ECPM therapy, mean cumulative 14CO2 outputs rose significantly from 30% to 70% (P < 0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasma PABA concentrations rose significantly from 46% to 87% (P < 0.05) and were not significantly different from outcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass through the stomach more slowly than a solid meal, but in fact faster. Digestion of ester lipids and proteins showed an improvement to subnormal and normal levels, respectively.

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy.

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.

Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy.

In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used to visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.

Cardiac 123I-MIBG uptake is affected by variable uptake in reference regions: implications for interpretation in clinical studies.

Cardiac 123I-meta-iodobenzyl guanidine (123I-MIBG) uptake, using the mediastinal region as a reference, is a predictor of outcome in heart failure. Constant uptake in a reference region is required when studying the pharmacotherapeutic effects on the integrity of the cardiac adrenergic system. The aim of this study was to verify the assumption of constant uptake in reference regions and their relation to established predictors of clinical outcome. Planar 123I-MIBG images were obtained in 28 patients with heart failure. The left ventricular ejection fraction correlated with the heart-to-mediastinum (H/M) ratio but not with myocardial 123I-MIBG uptake. Plasma noradrenaline correlated with the H/M ratio, the heart-to-lung (H/L) ratio, mediastinal uptake and age, but not with uptake in the myocardium and lung. Age correlated with the H/M ratio, H/L ratio, mediastinal uptake and lung uptake, but not with myocardial uptake. In a regression model, after the inclusion of age, the H/M ratio and mediastinal uptake were not related to noradrenaline. We conclude that changes in the H/M and H/L ratios are predominantly due to confounding changes in mediastinal uptake or lung uptake. In pharmacological intervention studies, myocardial 123I-MIBG uptake should be assessed using single photon emission tomography or positron emission tomography, which do not rely on reference regions in mediastinum or lung.

Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure.

OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake. DESIGN: Consecutive patients were treated with enalapril and served as their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference. RESULTS: Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference.

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([123I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [123I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [123I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [123I]MIBG planar and single-photon emission tomographic (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the 123I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31 +/- 0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4 +/- 2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [123I]MIBG uptake.

Prophylaxis of delayed nausea and vomiting after cancer chemotherapy.

OBJECTIVE: To compare ondansetron and domperidone for treatment of delayed nausea/vomiting (DN/V) following highly emetogenic chemotherapy, after attaining total suppression of emesis on the day of chemotherapy by mean of ondansetron (combined with dexamethasone in the case of cisplatin-treated patients). METHODS: Domperidone (3 x 20 mg daily) was compared with ondansetron (3 x 8 mg daily) in a randomized double-bind placebo-controlled study. Out of 65 consecutive patients who received a first course of either cyclophosphamide and cisplatin for advanced stage ovarian cancer or cyclophosphamide, doxorubicin and 5-fluoro-uracil for metastatic breast carcinoma, 60 patients were eligible for entering the study. According to data from the literature these chemotherapeutic regimens with induce DN/V to a comparable degree. The patients were questioned daily from day 2 through day 5 by the same investigator and the severity of nausea or vomiting was scored on a numerical scale. RESULTS: Emesis was totally suppressed in all patients on the day of chemotherapy. As to DN/V, 16 out of 20 patients receiving placebo required "rescue" medication versus none in the other two groups (p < 0.001). Only 2 (10%) patients were symptomatic with domperidone versus 9 (45%) symptomatic patients in the ondansetron-treated group (p < 0.05). CONCLUSIONS: Both drugs are effective, but domperidone (3 x 20 mg) is more effective than ondansetron (3 x 8 mg) for the prevention of the delayed nausea and/or vomiting which occur after highly emetogenic chemotherapy (p < 0.05).

Dosimetric optimization of postproduction neutron-activated erbium-170-oxide-enriched pancreatin.

UNLABELLED: The feasibility of postproduction neutron activation of an enteric-coated pancreatic enzyme preparation for in vivo gastric emptying studies has been investigated. METHODS: During production of this multicomponent preparation, small amounts of 170Er-enriched erbium oxide, suitable for neutron activation, were added. RESULTS: Postproduction neutron irradiation of the labeled preparation resulted in short-lived (7.5 hr) gamma-emitting 171Er. Various radiocontaminants, however, are produced also. Because of variations in activation yields, half-lives, decay schemes and radiotoxicities, both major and trace constituents were considered for optimization of both dosimetry and the diagnostic measurement. Conditions were optimized for the best ratio of the committed dose equivalent due to 171Er to the total committed dose equivalent. CONCLUSION: The results show that postproduction neutron activation of a 170Er-enriched multicomponent preparation can be performed safely within the guidelines set by the WHO for experiments in humans involving radioactive materials.

The value of radiographs and bone scintigraphy in suspected scaphoid fracture. A statistical analysis.

The role of radiography and bone scintigraphy in the diagnostic management of suspected scaphoid fracture is controversial. Two strategies were compared for patients with initial negative radiographs: repeated radiography versus selective bone scintigraphy. Using the known positive predictive value of scintigraphy, the sensitivity and specificity of both diagnostic strategies were evaluated in a series of 78 consecutive patients. The kappa value for initial radiographs was 0.76 but decreased to 0.5 for follow-up radiographs. Similarly, sensitivity decreased from 64% to 30% in follow-up radiographs. Specificity of the bone scan was 98%. The best diagnostic strategy in the management of clinically suspected scaphoid fractures consists of initial radiography followed by bone scintigraphy in patients with negative radiographs.

Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans.

To evaluate the role of tumor necrosis factor (TNF) in the initiation of the metabolic response to acute infection, we performed a crossover saline-controlled study in six healthy postabsorptive men, investigating the metabolic effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a transient stress hormone response, associated with an early and sustained rise in plasma glucose concentrations (percentage increase at 2 h 23 +/- 7; P less than 0.05). Glucose turnover, measured 7.5 h postinjection, was 10 +/- 3% higher after TNF administration (P less than 0.05). Plasma free fatty acids (FFA) and glycerol concentrations increased transiently after TNF injection, peaking after 4 h (percentage increase 363 +/- 83 and 67 +/- 14, respectively; both P less than 0.05). FFA turnover, determined 6.5 h postinjection, increased in five subjects to a variable extent (percentage increase 126 +/- 55; P less than 0.05). Finally, resting energy expenditure showed a transient rise after TNF injection (34 +/- 2% at 4 h; P less than 0.05). We conclude that intravenous TNF reproduces many of the metabolic changes observed in septicemia, suggesting that TNF may be an initiating factor in the development of the metabolic response to acute infection.

A new computerized impedance plethysmograph: accuracy in the detection of proximal deep-vein thrombosis in symptomatic outpatients.

Because of the lack of specificity of the clinical diagnosis it is appropriate in patients with clinically suspected deep-vein thrombosis to apply an objective test before starting anticoagulant treatment. Impedance plethysmography is a highly accurate technique for the detection of proximal-vein thrombosis with a reported sensitivity and specificity of 93 and 97%, respectively. In all previous reported evaluations of impedance plethysmography an apparatus which was developed in 1971 was used. A new computerized impedance plethysmography, using a novel device to measure impedance, was blindly compared against venography in 443 consecutive outpatients with clinically suspected deep-vein thrombosis. In the first phase of the study the computerized impedance plethysmography test results of 242 symptomatic patients were used to develop a discriminant line. Subsequently, this discriminant line was validated in the second phase of the study in another 201 symptomatic patients. The combined sensitivity and specificity of these two phases for proximal-vein thrombosis was 91% [95% confidence interval (CI), 86 to 94%] and 94% and (95% CI, 90 to 96%), respectively, which compares favourably with impedance plethysmography. It is concluded that computerized impedance plethysmography is a simple, portable, non-invasive technique with a high accuracy for the detection of proximal vein thrombosis. However, before computerized impedance plethysmography can be used as the only test in the diagnosis of deep-vein thrombosis, the safety of withholding anticoagulant treatment to patients with repeated normal computerized test results should be assessed during long-term follow-up studies.

Protein C activity and antigen levels in childhood.

Hereditary protein C deficiency is an important risk factor for thrombosis. To enable its diagnosis shortly after birth, we determined reference values of protein C antigen and activity levels for the first 3 months of life. To establish an age-related range of protein C levels we also determined median values for individuals up to 18 years of age. A good correlation between the two levels was seen from the 3rd/4th month of life onwards, whereas in the first 2 months the activity levels were significantly lower than the antigen levels. This was not due to interference by the increased plasma citrate concentration at high haematocrit values, and may suggest a dysfunctional protein C molecule in the neonatal period. We found a rapid rise in protein C activity and antigen levels until the age of 7-9 months, followed by a slower progression toward adolescence. In contrast to previous reports, our results indicate that adult values are probably not achieved until sometime during the 2nd decade of life.

Low antithrombin III: accurate predictor of idiopathic respiratory distress syndrome in premature neonates.

A prospective study was performed in premature neonates to determine the predictive values of antithrombin III (AT III) deficiency immediately after birth, for the subsequent development of idiopathic respiratory distress syndrome (IRDS), intraventricular haemorrhage (IVH) and death. Of the 81 premature infants studied, 24 developed IRDS (30%). Of these 24 premature infants, 8 also developed IVH and 9 infants died within the follow-up period of 7 days. The mean plasma AT III level was significantly lower in the infants developing IRDS (0.23 U/ml vs 0.35 U/ml, P less than 0.0005). Within this study group 33 neonates of less than 30 weeks' gestation showed a prevalence for IRDS of 48%. In this group, AT III activity levels below 0.30 U/ml were 8.5 times as likely to result from infants with IRDS than from infants without IRDS. The diagnostic accuracy indices of criteria for the development of IRDS were: a sensitivity of 100%, a specificity of 88%, a positive predictive value of 89% and a negative predictive value of 100%. The predictive values for the development of IVH and occurrence of death were insignificant. Therefore, in premature neonates the combination of less than 30 weeks' gestation and an AT III below 0.30 U/ml is highly suggestive of IRDS and may facilitate the evaluation of early treatment.