Hybrid cardiac imaging: insights in the dilemma of the appropriate clinical management of patients with suspected coronary artery disease.

AIM: To evaluate the potential of SPECT myocardial perfusion imaging (MPI)-computed tomography coronary angiography (CTCA) hybrid fusion imaging to improve the diagnostic performance of cardiac SPECT/MPI and CTCA alone in order to act as more accurate gate keeper to further investigation invasive or not. METHODS AND RESULTS: Twenty-five patients were subjected to SPECT/MPI and CTCA within a period of 1 month without any medical treatment modification. A fusion software package was used for cardiac SPECT-CTCA image fusion. Semiquantitative analysis was performed for cardiac SPECT, CTCA and SPECT/MPI-CTCA fusion images. Patients were classified in 2 groups according to the clinical decision for further investigation (group A), or not (group B). Statistically significant differences were observed when SPECT/MPI-CTCA fusion images were used instead of cardiac SPECT alone (p<0.05). No statistically significant differences were observed comparing CTCA alone to SPECT/MPI-CTCA fusion images (p=0.25). A mid-term follow-up (mean 3.58 ± 0.24 years) showed that all patients classified in group A based on the interpretation of SPECT MPI-CTCA fused images underwent conventional coronary angiography with further necessity for PTCA or CABG whereas absence of major or minor cardiac events was revealed for all patients of group B. CONCLUSION: In patients suspected for coronary artery disease, cardiac SPECT/MPI-CTCA fusion imaging was found to considerably alter the clinical decision for referral to further investigation derived from SPECT/MPI.

Increased levels of human placental growth hormone in the amniotic fluid of pregnancies affected by Down syndrome.

OBJECTIVE: To evaluate the concentrations of human placental growth hormone (hPGH) in amniotic fluid (AF) at gestational mid-trimester in normal pregnancies and in pregnancies complicated by Down's syndrome. DESIGN: AF samples from 21 women with Down's syndrome pregnancies were analyzed retrospectively. About 47 AF samples from women with singleton, uncomplicated pregnancies, who gave birth to healthy neonates with birth weight appropriate for gestational age were used as controls. All AF samples were obtained during amniocentesis for fetal karyotyping at 16-23 weeks' gestation. hPGH levels were measured by a solid phase immunoradiometric assay using two different epitopes. RESULTS: The mean hPGH values in the AF of the Down's syndrome-affected pregnancies were significantly higher (P<0.05) compared to those of normal pregnancies, at 16-23 weeks' gestation: mean-value+/-SD in the AF was 1.96+/-1.35 microg/l vs. 0.82+/-0.67 microg/l. CONCLUSIONS: Higher hPGH levels in AF were found in pregnancies affected by Down's syndrome as compared to normal pregnancies at gestational mid-trimester. hPGH was detected in all AF samples, and it provides evidence that this pregnancy-specific hormone enters the fetal compartment and is not limited to the maternal circulation. The physiological role and effect of hPGH on fetal growth in normal and pathological pregnancies needs further investigation.

Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) may cause an increase in the inflammatory status and oxidative stress as well as sympathetic nervous system overactivity, even in the absence of any other organic heart disease. We investigated the effect of perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of systemic inflammation and oxidative stress in normotensive patients with type 2 DM. We also examined the effect of the drug on the disturbances of left ventricular myocardial adrenergic innervation that may be seen in these patients. We studied 62 normotensive patients with type 2 DM, who were randomized to receive perindopril (n=32) or placebo (n=30). At the start of the study and after 6 months' therapy blood samples were taken to evaluate total peroxides (TP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy study. ACE-i caused a significant reduction in levels of cytokines and TP (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h was improved (P<0.001 for both). No significant alterations were observed in the placebo group. Our data indicate that the addition of ACE-i to the medication of normotensive diabetic type 2 patients may improve the disturbed myocardial adrenergic innervation, the systemic inflammatory status and oxidative stress. Our findings indicate the cardioprotective action of ACE-i and suggest that earlier treatment might be appropriate in those patients.

Increased human placental growth hormone at midtrimester pregnancies may be an index of intrauterine growth retardation related to preeclampsia.

OBJECTIVE: To evaluate the relationship between maternal serum and amniotic fluid levels of human Placental Growth Hormone (hPGH) with the fetal intrauterine growth retardation (IUGR) related to preeclampsia. DESIGN: We analyzed samples in pairs of serum and amniotic fluid retrospectively from 25 women, who manifested preeclampsia and IUGR in the late second or the third trimester of gestation. The samples were obtained at 16-22 weeks' gestation during amniocentesis for fetal karyotyping. At this time, there was no clinical or sonographic evidence of preeclampsia or IUGR, respectively. Sixty-two serum samples were used as controls which were obtained at 16-22 weeks' gestation from women with singleton, uncomplicated pregnancies, with normal outcome, and appropriate for gestational age neonatal birth weight. Forty-seven amniotic fluid samples were also used as controls which were obtained at 16-22 weeks' gestation from the women that were included in the control group who underwent an amniocentesis. hPGH levels were measured by a solid phase immunoradiometric assay. RESULTS: The mean hPGH values in the serum and the amniotic fluid of the IUGR related to preeclampsia affected pregnancies were significantly higher (P<0.05) than those of the normal pregnancies at 16-22 weeks' gestation: mean+/-SD in the serum was 13.16+/-10.52 ng/ml vs. 4.39+/-2.23 ng/ml; mean+/-SD in the amniotic fluid 2.49+/-1.6 ng/ml vs. 0.82+/-0.67 ng/ml. CONCLUSION: hPGH levels in maternal serum and amniotic fluid were found to be higher at 16-22 weeks' gestation in pregnancies that will be complicated subsequently by IUGR related to preeclampsia. Our findings suggest that the evaluation of the changes of hPGH levels at midtrimester should be further investigated for the possibility to provide a potential predictive index of IUGR and preeclampsia.

Clearance of technetium-99m-DTPA in pulmonary sarcoidosis.

BACKGROUND: The aim of this study was to explore the possible association of the lung clearance of 99mTc-DTPA scan with HRCT lung abnormalities and with the pulmonary function tests [PFTs] in patients with sarcoidosis. METHODS: We studied prospectively 15 patients [5 males, 10 females] of median age 46yr [range 27-67] with histologically proved sarcoidosis. HRCT scoring included the sum of the severity and extent of lymph node enlargement and parenchymal involvement. RESULTS: The mean DTPA clearance half-time [tau 1/ <40 min] was found [mean [SD]] 38.3+/-4.5min. The lymph node enlargement was found 34% and the parenchymal involvement 12%. DTPA clearance was negatively correlated with the parenchymal involvement [r= -0.651, p=0.0091]. The HRCT parenchymal abnormalities were found significantly correlated with PFTs [FVC [r= -0.65, p=0.008] and TLCO [r= -0.76, p=0.02]. CONCLUSIONS: Our data suggest a moderate association between 99mTc-DTPA scan and HRCT in pulmonary sarcoidosis. However, further studies in large scale of sarcoid patients are needed to clarify the role of this novel methodology in the evaluation and follow-up of this disorder.

Contribution of 99mTc-anti-carcinoembryonic antigen antibody and 99mTc-sestamibi scintimammography in the evaluation of high risk palpable breast lesions.

Mammography is the screening test of choice for breast cancer. Its low specificity leads to a large number of unnecessary biopsies. Scintimammography, with either Tc-sestamibi (MIBI) or Tc-anti-carcinoembryonic antigen (CEA) Fab', has been proposed as a non-invasive test to lower the high false positive rate of mammography in certain patients. The two agents have not been compared, nor has their combined application been evaluated. We performed a prospective, non-randomized, open-label, single-centre study of 32 women with clinically and mammographically suspected breast cancer [Breast Imaging Reporting and Data System (BI-RADS, American College of Radiology) 4 or 5]. All patients underwent Tc-MIBI and Tc-anti-CEA Fab' scintimammography, and the results were correlated with histopathology. Overall, the accuracies for MIBI and CEA scans were 90.3% (28/31) and 77.4% (24/31), respectively. The probability of disease after mammography was 0.939+/-0.081 (95% confidence interval, CI). The post-mammography probabilities after positive MIBI or CEA scan were 0.965 and 0.960, respectively, and after negative MIBI or CEA scan 0.750 and 0.875, respectively. None of the above differences is significant. The post-test probability when both scans were positive (irrespective of which was performed first) was 0.977. It can be concluded that there are indications that scintimammography with Tc-MIBI is superior to that with Tc-anti-CEA Fab' when these tests are used as screening tests for breast cancer. However, mammography remains the screening test of choice for highly suspicious clinically palpable breast lesions. In this group of patients, the application of scintimammography with either Tc-MIBI or Tc-anti-CEA Fab' (alone or in combination) offers no additional advantage.

Urinary N-telopeptide levels in multiple myeloma patients, correlation with Tc-99m-sestaMIBI scintigraphy and other biochemical markers of disease activity.

Urinary cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a sensitive and specific marker of bone resorption in multiple myeloma (MM). In this study, we measured the levels of NTx in 30 newly diagnosed MM patients and 25 controls. We examined its association with the overall score of skeletal involvement measured by Tc-99m-MIBI scintigraphy and other biochemical markers of bone disease (tumour necrosis factor a (TNF-a), serum calcium and creatinine). We further studied the correlation of NTx with the stage of disease (according to Durie-Salmon criteria) and bone marrow infiltration by plasma cells. High levels of NTx, bone marrow infiltration, TNF-alpha, calcium and creatinine were noted at advanced stages of disease (p < 0.05). NTx and TNF-a were found at significantly higher concentrations in patients with a high overall score (3 and 4) in Tc-99m-sestaMIBI in comparison to a low score (0, 1 and 2; p < 0.05). Positive correlations were found between NTx and TNF-a, as well as between bone infiltration and TNF-a or calcium. In conclusion, NTx is a useful marker for the monitoring of bone resorption in MM and correlates with imaging findings on Tc-99m-sestaMIBI and other biochemical markers of disease activity.

Association between increased levels of IL-2 and IL-15 and outcome in patients with early acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome remains a serious, often fatal, condition, despite progress in modern critical care treatment. Cytokines play an important role in the pathogenesis of the syndrome, although their role in the evolution and outcome has not been clearly elucidated. We explored whether the measurement of serum and bronchoalveolar lavage IL-2 and IL-15 at the time of hospital admission can predict the outcome of this syndrome. METHODS: Serum and bronchoalveolar lavage levels of IL-2 and IL-15 were measured in eight patients with ARDS (group A) and 26 patients on high risk for ARDS development who never developed ARDS (group B) from samples obtained at the time of admission. RESULTS: Serum IL-2 (P > 0.05) and IL-15 (P < 0.05) levels were higher in group A than in group B. Serum levels of both cytokines were higher in patients who did not survive in both of the groups A and B compared to those who survived (P < 0.05, and P < 0.0001, respectively). The only significant change in BALF was the higher level of IL-15 in surviving group A patients (P < 0.05) when compared with the non survivors of the same group. For a serum cut-off level of 173 pg mL(-1) for IL-2 and 250 pg mL(-1) for IL-15, they exhibited a very high positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for survival (100% in all). A positive correlation was found between serum levels of both cytokines and APACHE II score (IL-2, r = 0.61, and IL-15, r = 0.62, respectively, and P < 0.0001 for both). CONCLUSION: Determination of serum IL-2 and IL-15 levels may be a valuable and simple aid to improve identification of patients with ARDS or at risk for ARDS who are at high risk of subsequent mortality.

Octreotide enhances the accelerating effect of erythromycin on gastric emptying in healthy subjects.

BACKGROUND: Erythromycin exhibits gastrokinetic properties through cholinergic pathways. Reports regarding the action of octreotide on gastric emptying are conflicting. AIM: : To assess: (i) the hypothesis that serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying; and (ii) any modification of the gastrokinetic action of erythromycin induced by octreotide. SUBJECTS AND METHODS: Gastric emptying of a standard meal was estimated in 20 healthy subjects by scintigraphy on three different occasions in a double-blind, placebo-controlled manner and in random order: (i) after placebo; (ii) after 200 mg of intravenous erythromycin; and (iii) after 200 mg of intravenous erythromycin following pre-treatment with either 4 mg of intravenous ondansetron (10 subjects) or 50 micro g octreotide. RESULTS: Erythromycin significantly accelerated gastric emptying in all subjects by abolishing the lag phase. Pre-treatment with ondansetron abolished the accelerating effect of erythromycin by restoring the emptying times to placebo levels. Octreotide significantly enhanced the accelerating effect of erythromycin by reducing both the lag and post-lag phases of gastric emptying. CONCLUSIONS: Serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying. This effect seems to be enhanced by pre-treatment with octreotide, possibly as a result of the modification of the gastrointestinal hormonal environment.

Assessment of myocardial adrenergic innervation in patients with sick sinus syndrome: effect of asynchronous ventricular activation from ventricular apical stimulation.

OBJECTIVE: To investigate ventricular sympathetic innervation in patients with sick sinus syndrome and to detect regional deterioration of adrenergic innervation caused by asynchronous ventricular activation from right ventricular pacing. DESIGN: Prospective controlled study. SETTING: Tertiary cardiac referral centre. PATIENTS: 22 patients with sick sinus syndrome and indications for permanent dual chamber pacing; 20 healthy individuals as controls. INTERVENTIONS: All patients underwent myocardial imaging with planar and single photon emission computed tomography (SPECT) after an intravenous infusion of 5 mCi 123I-meta-iodobenzylguanidine (123I-MIBG) before and after pacemaker implantation. A SPECT thallium201 myocardial study was done during the same week as the 123I-MIBG study in all patients. MAIN OUTCOME MEASURES: The heart to mediastinum (H/M) ratio and washout rate were calculated during the 123I-MIBG study to assess the global cardiac sympathetic activity; the aim of the SPECT study was to investigate the regional distribution of adrenergic innervation. RESULTS: The H/M ratio was significantly smaller in the patients with sick sinus syndrome than in the controls (p < 0.001). In sick sinus syndrome there were regional adrenergic innervation defects, mostly in the inferior and apical walls. After a medium term pacing period, a redistribution of 123I-MIBG uptake was detected, with deterioration of adrenergic innervation in the inferior, apical, and posterior walls. The thallium201 myocardial perfusion study showed no change after three months of permanent pacing. CONCLUSIONS: Patients with sick sinus syndrome have global and regional disturbances of the adrenergic innervation of the left ventricular myocardium. These seem to deteriorate as a result of asynchronous electrical activation. The clinical significance of this finding requires further investigation.

Correlation between the uptake of Tc-99m-sestaMIBI and prognostic factors in patients with multiple myeloma.

Technetium 99m-2-methoxyisobutil-isonitrile (Tc-99m-MIBI), also called sestaMIBI, has been used successfully to detect malignant tumours at diagnosis. Recently, it has been proposed as a safe and effective tracer in patients with multiple myeloma (MM). The purpose of this study was to demonstrate the value of the Tc-99m-MIBI uptake in disease detection and to assess the correlation between the uptake of this scintigraphy agent and prognostic factors in newly diagnosed MM patients. Thirty-five untreated patients were enrolled in the study. Tc-99m-MIBI scanning was performed in 33 patients after intravenous injection of 7.4 MBq/kg. Whole-body anterior and posterior scans were obtained after 30 min, 60 min, 2 and 4 h. The correlation between known prognostic factors of MM and the intensity of Tc-99m-MIBI uptake was assessed. Our results showed seven patients with an intensity score of I0, 12 patients with I1, eight patients with I2 and six patients with a score of I3. There was a positive correlation between Tc-99m-MIBI intensity and C-reactive protein (CRP; r=0.506, P < 0.01), erythrocyte sedimentation rate (ESR; r=0.368, P < 0.05), beta2- microglobulin (beta2M; r=0.749, P < 0.001), interleukin-6 (IL-6; r=0.823, P < 0.001), soluble Interleukin-6 receptor (sIL-6r; r=0.806, P < 0.001), serum calcium (r=0.578, P < 0.001) and bone alkaline phosphatase (BAP; r=0.472, P < 0.01). An inverse correlation was found between Tc-99m-MIBI intensity and osteocalcin (OC) and type I procollagen carboxyterminal propeptide (PICP). In conclusion, the results of this study suggest that more extensive disease activity, as determined by high levels of CRP, beta2M, IL-6 and sIL-6r correlated with a higher uptake of the radiotracer.

Segmental pattern of myocardial sympathetic denervation in idiopathic dilated cardiomyopathy: relationship to regional wall motion and myocardial perfusion abnormalities.

BACKGROUND: Iodine 123-labeled metaiodobenzylguanidine (MIBG) has been used to study cardiac adrenergic nerve activity. Cardiac MIBG uptake is diminished in patients with heart failure. However, it is not known how this reduction is related to regional abnormalities of myocardial wall motion or perfusion. METHODS AND RESULTS: We studied 24 patients with idiopathic dilated cardiomyopathy (ejection fraction <45%) and 15 healthy control subjects using I-123 MIBG cardiac imaging, echocardiographic assessment of wall motion abnormalities, technetium 99m sestamibi perfusion scintigraphy, and hemodynamic assessment. Cardiac MIBG was significantly correlated with ejection fraction (r = 0.67), cardiac index (r = 0.57), left ventricular wall motion score index (r = -0.68), and systolic wall stress (r = -0.61). MIBG was lower in patients than in control subjects (1.43 +/- 0.19 vs 2.05 +/- 0.02; P <.01), whereas the washout rate was higher (P <.01). Moreover, a significant correlation was found between the reduction in MIBG uptake and the severity of echocardiographic wall motion abnormalities in the anterior wall (r = 0.543), apex (r = 0.530), and septum (r = 0.675), as well as with the severity of decrease in resting myocardial perfusion in the anterior wall (r = 0.480) and septum (r = 0.580). CONCLUSIONS: Patients with idiopathic dilated cardiomyopathy show not only global but also regional abnormalities of cardiac sympathetic innervation. The severity of these changes is partially correlated with abnormalities of regional wall motion and myocardial perfusion.

The role of 99m Tc-sestamibi scintimammography and colour Doppler ultrasonography in the evaluation of breast lesions.

In the present study we evaluated comparatively the diagnostic value of mammography, of 99mTc-sestamibi scintimammography (sestamibi-SC) and of colour Doppler ultrasonography (CD-US) in 116 breast lesions. Diagnosis was based on histopathological examination. Overall, out of 86 malignant tumours, 80 (93%) and 75 (87%) had a positive sestamibi-SC and positive CD-US, respectively. Out of 30 benign lesions, 25 (83%) and 26 (87%) had a negative sestamibi-SC and negative CD-US respectively. The true positive results were similar in palpable and in non-palpable lesions for both methods. Out of 19 non-palpable malignant tumours, mammography confirmed malignancy in only one case (5%), which was significantly lower than the results obtained by sestamibi-SC (89%; Px0.0001) and by CD-US (74%; P=0.0001). In palpable malignant tumours, by using mamography, true positive results were obtained in 54/67 (80.5%) patients, which was significantly lower than the results obtained by sestamibi-SC (94%; P=0.03) and marginally different to the results obtained by CD-US (91%; P=0.13). It is concluded that sestamibi-SC and CD-US are useful tools in clarifying the nature of breast lesions in cases with doubtful mammography. The clinical value of these diagnostic procedures in guiding subsequent therapeutic interventions requires further investigation.

Value of Tc-99m sestamibi scintigraphy in the detection of bone lesions in multiple myeloma: comparison with Tc-99m methylene diphosphonate.

Technetium 99m-2-methoxyisobutylisonitrile (Tc-99m MIBI) is a lipophilic agent that accumulates preferentially within living malignant cells due to the higher transmembrane electrical potential as a consequence of the higher metabolic rate than in the surrounding normal cells. It has been effectively used to detect malignant tumors at diagnosis and follow-up and has been reported to be useful in detecting disease lesions in multiple myeloma. We studied 28 consecutive patients with multiple myeloma at diagnosis to determine the value of Tc-99m MIBI in comparison with Tc-99m methylene diphosphonate (MDP), conventional X-rays, computed tomography (CT) scan, and magnetic resonance imaging (MRI). We found 26 patients with obvious osteolytic lesions in X-rays, 22 patients with positive Tc-99m MIBI scans, and 15 patients with positive Tc-99m MDP scans. There was no coincidence of the positive lesions in the two scans, while in two patients the osteolytic areas were positive in the Tc-99m MDP scans, and in one case the osteolytic area was positive in the Tc-99m MIBI scan. The intensity of Tc-99m MIBI scans correlated with disease activity as determined by lactate dehydrogenase (LDH) (p<0.05), C-reactive protein (CRP) (p<0.01), beta2-microglobulin (p<0.05), and serum ferritin (p<0.01). We believe that Tc-99m MIBI scintigraphy can detect bone marrow lesions in myeloma patients that cannot be detected by other imaging methods and that it can be useful especially in solitary myeloma to exclude other involved sites. In addition, it could be a prognostic factor related to disease activity and multidrug resistance. We believe that a multicenter study is needed to evaluate the usefulness of this agent.

Effects of asynchronous ventricular activation on myocardial adrenergic innervation in patients with permanent dual-chamber pacemakers; an I(123)-metaiodobenzylguanidine cardiac scintigraphic study.

AIMS: To evaluate myocardial sympathetic innervation abnormalities in patients with DDD pacemakers for complete heart block. METHODS: We studied 39 patients, chronically paced in DDD mode because of complete atrioventricular block. Twenty-three healthy individuals served as a control group. All patients underwent planar and single-photon emission computed tomography (SPECT) myocardial imaging 4 h after intravenous infusion of 185 MBq I(123)-MIBG. The heart to mediastinum ratio was calculated to quantify cardiac I(123)-MIBG accumulation, while the SPECT study was performed to investigate the regional distribution of adrenergic innervation. All patients underwent a SPECT thallium(201)myocardial study during the same week as the I(123)-MIBG study. RESULTS: The heart to mediastinum ratio was significantly smaller in paced patients than in the controls (P<0.001). 89.7% of paced patients had regional abnormalities of I(123)-MIBG uptake, mainly in the inferior (92.3%) and apical (38.5%) wall. 46.2% of paced patients had regional perfusion defects, also mainly in the inferior (46.2%) and apical (10.3%) wall. Neither the I(123)-MIBG abnormalities nor the perfusion defects were related to the duration of pacing. CONCLUSIONS: Stimulation from the apex of the right ventricle leads to regional disturbances of the adrenergic innervation of the left ventricular myocardium, as assessed by I(123)-MIBG activity.

Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries.

OBJECTIVES: The purposes of this study were to test the specificity of dipyridamole myocardial perfusion scintigraphy in patients with permanent ventricular pacing (PVP) and to evaluate coronary blood flow and reserve in these patients. BACKGROUND: Permanent ventricular pacing is associated with exercise perfusion defects on myocardial scintigraphy in the absence of coronary artery disease (CAD). On the basis of studies in patients with left bundle brunch block, coronary vasodilation with dipyridamole has been proposed as an alternative to exercise testing for detecting CAD in paced patients, but this approach has never been tested. METHODS: Fourteen patients with a PVP and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In these patients and in eight control subjects, coronary flow velocities were measured in the left anterior descending coronary artery (LAD) and in the dominant coronary artery before and after adenosine administration. RESULTS: In the paced patients, coronary flow velocities in the LAD and in the dominant coronary artery were significantly lower than those in the control subjects. In addition, seven patients showed perfusion defects on dipyridamole thallium-201 single-photon emission computed tomography, with a specificity of 50% for this test. The defect-related artery in these patients had lower coronary flow reserve (2.6 +/- 0.5) as compared with those without perfusion defects (3.9 +/- 1.0, p < 0.05) or the control group (3.5 +/- 0.5, p < 0.05). CONCLUSIONS: Permanent ventricular pacing is associated with alterations in regional myocardial perfusion. Furthermore, abnormalities of microvascular flow, as indicated by reduced coronary flow reserve in the defect-related artery, are at least partially responsible for the uncertain specificity of dipyridamole myocardial perfusion scintigraphy.

Evaluation of inflammatory cytokines in malignant and benign pleural effusions.

We measured the levels of inflammatory cytokines interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and serum in 65 consecutive patients: 32 with malignant pleural effusion (MPE) (group A), and 33 with inflammatory benign pleural effusion (BPE) (group B). Serum levels of 15 healthy individuals served as control. Concentrations of IL-1alpha were higher in serum compared to pleural fluid in both groups (47.1+/-33.9 vs. 25.9+/-1.7 fmol/ml, p<0.001, in group A; and 39.9+/-30.9 vs. 25.4+/-16.3 fmol/ml, p<0.02, in group B). Similarly, concentrations of IL-1beta and IL-2 were significantly higher in serum compared to pleural fluid in both groups. In contrast, IL-6, IL-8 and TNF-alpha were found at high concentration in MPE in comparison to serum IL-6: 171.8+/-60.4 vs. 7. 2+/-7 fmol/ml (p<0.001), IL-8: 1175.15+/-2385.6 vs. 285.2+/-187.2 pg/ml (p<0.05), TNF-alpha: 204.9+/-82.9 vs. 79.4+/-31.9 fmol/ml (p<0. 001). Similarly, pleural concentrations of IL-6, IL-8 and TNF-alpha were higher in BPE patients in comparison to serum IL-6: 124.3+/-56. 2 vs. 8.6+/-6.4 fmol/ml (p<0.001) IL-8: 2109.2+/-4121.5 vs. 291. 6+/-197.9 pg/ml (p<0.02), TNF-alpha: 183.8+/-28.2 vs. 86.2+/-23.9 fmol/ml (p<0.001). These data suggest that IL-6, IL-8 and TNF-alpha might be secreted locally at the site of active disease both in benign and malignant pleural effusions.

High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumours.

The blood-brain barrier is a major obstacle for the chemotherapeutic drugs to effectively reach primary or secondary brain tumours. Stealth liposomal drugs are highly accumulated in tumoural tissues. In the present study we investigated the relative accumulation of(99m)Tc-DTPA radiolabelled stealth liposomal doxorubicin (Caelyx) in 10 patients with metastatic brain tumours and five patients with brain glioblastoma undergoing radiotherapy. Patients with metastatic brain lesions were treated with 10 consecutive fractions of radiotherapy (whole brain, 3 Gy/fraction, day 1-12) followed by a booster dose of 9 Gy (3 Gy/fraction, day 21-23). Caelyx, at a dose of 25 mg mg(-2)was given on day 1 and on day 21. Radiolabelled Caelyx accumulation was 13-19 times higher in the glioblastomas and 7-13 times higher in the metastatic lesions, as compared to the normal brain. The drug accumulation in the tumoural areas was 40-60% of the accumulation in the bone marrow of the skull bones. The normal brain radioactivity was <4% of the bone marrow, confirming an important shielding effect of the blood-brain barrier in the normal but not in the tumoural tissue. Four of 10 patients with metastatic lesions showed a complete response in CT-scan performed 2 months following therapy. There was no severe toxicity related to radiotherapy or to chemotherapy noted. It is concluded that stealth liposomal drugs selectively overcome the blood-brain barrier in the tumoural areas. The clinical importance of this observation is now under investigation.

High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas--rationale for combination with radiotherapy.

Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth liposomal doxorubicin (Caelyx) is a novel drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy with Caelyx in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a total dose of 70 Gy. Caelyx was given as a 30-min infusion at a dose of 25 mg/m2 every 2 weeks. Scintigraphic imaging with Caelyx-99mTc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation compared to the surrounding healthy tissue. The regimen was well tolerated without any severe hematological or systemic toxicity. 'In field' radiation toxicity was not increased. Complete response was observed in 4/7 cases. It is concluded that combined chemo-radiotherapy with stealth liposomal doxorubicin for locally advanced sarcomas is feasible and promising, the benefit expected from the unique ability of the stealth liposomes to accumulate selectively in the tumoral tissue.