Toluene toxicity primarily affects central nervous system white matter, causing a characteristic ... more Toluene toxicity primarily affects central nervous system white matter, causing a characteristic brain MRI pattern.A toluene addicted man, after an abstinence period and a treatment with neuroleptics, presented with severe worsening of preexisting generalized tremor, opsoclonus, dysarthria, gait inability, jerky tendon reflexes and behaviour disorders. Magnetic resonance imaging showed mild leukoencephalopathy and hypointensities in deep gray matter nuclei. The DaT-scan revealed a decrease in presynaptic dopamine reuptake.Clinical and neuroradiological findings and the possible sensitivity to neuroleptics indicate dopaminergic impairment. Our case suggests that chronic toluene abuse causes presynaptic dopaminergic depletion.
Toluene toxicity primarily affects central nervous system white matter, causing a characteristic ... more Toluene toxicity primarily affects central nervous system white matter, causing a characteristic brain MRI pattern.A toluene addicted man, after an abstinence period and a treatment with neuroleptics, presented with severe worsening of preexisting generalized tremor, opsoclonus, dysarthria, gait inability, jerky tendon reflexes and behaviour disorders. Magnetic resonance imaging showed mild leukoencephalopathy and hypointensities in deep gray matter nuclei. The DaT-scan revealed a decrease in presynaptic dopamine reuptake.Clinical and neuroradiological findings and the possible sensitivity to neuroleptics indicate dopaminergic impairment. Our case suggests that chronic toluene abuse causes presynaptic dopaminergic depletion.
European Journal of Nuclear Medicine and Molecular Imaging, 2010
Purpose To prospectively evaluate the predictive value of various bone formation and resorption m... more Purpose To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP). Methods Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with 186Re-HEDP. None had received any treatment that would have interfered with bone metabolism before 186Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Results Pain response was correlated only with pretreatment ΝΤx/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p=0.0025–0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to 186Re-HEDP treatment were a posttreatment decrease in NTx of ≥20% (RR=3.44, p=0.0005) and a pretreatment NTx/PINP ratio of ≥1.2 (RR=3.04, p=0.036) Conclusion NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with 186Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.
European Journal of Nuclear Medicine and Molecular Imaging, 2008
Purpose The aim of this study is to evaluate the effectiveness of 111In-DTPA-Phe1-octreotide infu... more Purpose The aim of this study is to evaluate the effectiveness of 111In-DTPA-Phe1-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst2 receptor-positive neuroendocrine tumours due to the effect of 111In Auger electron emission, minimising in parallel the toxicity of non-target tissue. Methods The average dose per session administered monthly to each patient (17 cases in total) was 6.3 ± 2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. Results Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 ± 81 to 60 ± 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. Conclusion In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of 111In-DTPA-Phe1-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of 111In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.
Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with ... more Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with neuroendocrine identities but also malignancies without neuroendocrine expression. Recently, the somatostatin analog pentetreotide was labeled with In-111 (OctreoScan 111, Mallinckrodt Medical BV, Petten, Holland) and introduced for the in vivo visualization in man of SR-positive tissues. In the present report, SR-specific scintigraphy is evaluated as a clinical tool for tissue characterization in correlation with histological and radiological examinations. Scintigraphy was focused and performed in cancer types without neuroendocrine tissue expression such as brain (n = 6) and breast tumors (n = 9) and lymphomas (n = 5). Scintigraphy was performed for comparison at 6 and 22 h after i.v. application of 111 MBq (3 mCi) of In-111-Pentetreotide. In the breast cancer group, the primary tumor was visualized in all 9 women as well as in all 4 cases with palpable axillary lymph nodes. Three women with a negative axillary node scan and impalpable nodes had positive biopsy. In two cases, mediastinal lymph node involvement was observed. So far the role of SR-positive breast cancer (BC) scans remains unknown. It is tempting to speculate that in resected women who are histologically and scintigraphically SR positive, it might be of value in the early detection of symptom-free recurrences. High densities of SR were present within both meningiomas, the high-grade astrocytoma and the craniopharyngioma. Differentiation of low- and high-grade astrocytomas could not be successfully achieved because both grades showed intense radioactivity uptake, even though high-grade tumors lack SR. The latter might be due to the damaged blood-brain barrier and the poor radioactivity washout observed in high-grade astrocytomas. All five lymphomas could be detected due to the presence of activated lymphocytes and macrophages that express SR at a sufficient density. In conclusion, SR scintigraphy in non-neuroendocrine malignancies does not seem to be reliable for an initial tumor staging but rather more suitable for a tissue characterization and extremely useful for monitoring changes of SR expression after treatment.
European Journal of Nuclear Medicine and Molecular Imaging, 2006
By the beginning of the twentieth century, two of the fundamental laws in nature, those of gravit... more By the beginning of the twentieth century, two of the fundamental laws in nature, those of gravity and electromagnetism, had been elucidated. The development of classical mechanics, from Galileo Galilei and Isaac Newton through to Joseph Louis Lagrange and William R. Hamilton, had proved the dominion of the law of gravity on earth and in the universe, while studies by Michael Faraday, James Clerk Maxwell and Heinrich R. Hertz on electromagnetic forces had made parallel potent contributions to scientific knowledge. The evolution of the kinetic theory of gases and thermodynamics had led scientists to consider matter in terms of molecular or atomic constituents. However, many properties of the basic building blocks of matter remained undiscovered or poorly understood.The quest for detailed knowledge of the fundamental constituents of matter dates back to the ancient world. In the 6th century B.C.E. (Before the Common Era), Kanada and Pakhuda Katyayana in ancient India had propounded ideas
To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), ... more To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), in patients suffering from prostate cancer with bone only metastases. Thirty-six males with hormone-refractory prostate carcinoma, bone only metastases and no history of therapies, drugs, or diseases that affect bone metabolism were studied. Karnofsky performance status, pain scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of type I collagen were analysed. Twenty-four healthy controls of the same age were also established. With only the exception of OC, bone marker values of patients were significantly increased compared with the upper reference limits (P<0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal telopeptide of type I collagen). All bone markers and prostate-specific antigen also showed significant paired correlations (P < or = 0.019) and linear increases with advancing EOD (P < or = 0.032). Finally, none of the measured markers correlated significantly with pain levels. Bone markers are remarkably elevated in the serum of prostate cancer patients with metastatic bone disease and correlate with EOD. Paired correlations also suggest an accelerated but proportional (coupled) bone metabolism.
Toluene toxicity primarily affects central nervous system white matter, causing a characteristic ... more Toluene toxicity primarily affects central nervous system white matter, causing a characteristic brain MRI pattern.A toluene addicted man, after an abstinence period and a treatment with neuroleptics, presented with severe worsening of preexisting generalized tremor, opsoclonus, dysarthria, gait inability, jerky tendon reflexes and behaviour disorders. Magnetic resonance imaging showed mild leukoencephalopathy and hypointensities in deep gray matter nuclei. The DaT-scan revealed a decrease in presynaptic dopamine reuptake.Clinical and neuroradiological findings and the possible sensitivity to neuroleptics indicate dopaminergic impairment. Our case suggests that chronic toluene abuse causes presynaptic dopaminergic depletion.
Toluene toxicity primarily affects central nervous system white matter, causing a characteristic ... more Toluene toxicity primarily affects central nervous system white matter, causing a characteristic brain MRI pattern.A toluene addicted man, after an abstinence period and a treatment with neuroleptics, presented with severe worsening of preexisting generalized tremor, opsoclonus, dysarthria, gait inability, jerky tendon reflexes and behaviour disorders. Magnetic resonance imaging showed mild leukoencephalopathy and hypointensities in deep gray matter nuclei. The DaT-scan revealed a decrease in presynaptic dopamine reuptake.Clinical and neuroradiological findings and the possible sensitivity to neuroleptics indicate dopaminergic impairment. Our case suggests that chronic toluene abuse causes presynaptic dopaminergic depletion.
European Journal of Nuclear Medicine and Molecular Imaging, 2010
Purpose To prospectively evaluate the predictive value of various bone formation and resorption m... more Purpose To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP). Methods Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with 186Re-HEDP. None had received any treatment that would have interfered with bone metabolism before 186Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Results Pain response was correlated only with pretreatment ΝΤx/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p=0.0025–0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to 186Re-HEDP treatment were a posttreatment decrease in NTx of ≥20% (RR=3.44, p=0.0005) and a pretreatment NTx/PINP ratio of ≥1.2 (RR=3.04, p=0.036) Conclusion NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with 186Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.
European Journal of Nuclear Medicine and Molecular Imaging, 2008
Purpose The aim of this study is to evaluate the effectiveness of 111In-DTPA-Phe1-octreotide infu... more Purpose The aim of this study is to evaluate the effectiveness of 111In-DTPA-Phe1-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst2 receptor-positive neuroendocrine tumours due to the effect of 111In Auger electron emission, minimising in parallel the toxicity of non-target tissue. Methods The average dose per session administered monthly to each patient (17 cases in total) was 6.3 ± 2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. Results Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3 (17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12 (70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 ± 81 to 60 ± 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. Conclusion In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of 111In-DTPA-Phe1-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of 111In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed.
Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with ... more Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with neuroendocrine identities but also malignancies without neuroendocrine expression. Recently, the somatostatin analog pentetreotide was labeled with In-111 (OctreoScan 111, Mallinckrodt Medical BV, Petten, Holland) and introduced for the in vivo visualization in man of SR-positive tissues. In the present report, SR-specific scintigraphy is evaluated as a clinical tool for tissue characterization in correlation with histological and radiological examinations. Scintigraphy was focused and performed in cancer types without neuroendocrine tissue expression such as brain (n = 6) and breast tumors (n = 9) and lymphomas (n = 5). Scintigraphy was performed for comparison at 6 and 22 h after i.v. application of 111 MBq (3 mCi) of In-111-Pentetreotide. In the breast cancer group, the primary tumor was visualized in all 9 women as well as in all 4 cases with palpable axillary lymph nodes. Three women with a negative axillary node scan and impalpable nodes had positive biopsy. In two cases, mediastinal lymph node involvement was observed. So far the role of SR-positive breast cancer (BC) scans remains unknown. It is tempting to speculate that in resected women who are histologically and scintigraphically SR positive, it might be of value in the early detection of symptom-free recurrences. High densities of SR were present within both meningiomas, the high-grade astrocytoma and the craniopharyngioma. Differentiation of low- and high-grade astrocytomas could not be successfully achieved because both grades showed intense radioactivity uptake, even though high-grade tumors lack SR. The latter might be due to the damaged blood-brain barrier and the poor radioactivity washout observed in high-grade astrocytomas. All five lymphomas could be detected due to the presence of activated lymphocytes and macrophages that express SR at a sufficient density. In conclusion, SR scintigraphy in non-neuroendocrine malignancies does not seem to be reliable for an initial tumor staging but rather more suitable for a tissue characterization and extremely useful for monitoring changes of SR expression after treatment.
European Journal of Nuclear Medicine and Molecular Imaging, 2006
By the beginning of the twentieth century, two of the fundamental laws in nature, those of gravit... more By the beginning of the twentieth century, two of the fundamental laws in nature, those of gravity and electromagnetism, had been elucidated. The development of classical mechanics, from Galileo Galilei and Isaac Newton through to Joseph Louis Lagrange and William R. Hamilton, had proved the dominion of the law of gravity on earth and in the universe, while studies by Michael Faraday, James Clerk Maxwell and Heinrich R. Hertz on electromagnetic forces had made parallel potent contributions to scientific knowledge. The evolution of the kinetic theory of gases and thermodynamics had led scientists to consider matter in terms of molecular or atomic constituents. However, many properties of the basic building blocks of matter remained undiscovered or poorly understood.The quest for detailed knowledge of the fundamental constituents of matter dates back to the ancient world. In the 6th century B.C.E. (Before the Common Era), Kanada and Pakhuda Katyayana in ancient India had propounded ideas
To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), ... more To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), in patients suffering from prostate cancer with bone only metastases. Thirty-six males with hormone-refractory prostate carcinoma, bone only metastases and no history of therapies, drugs, or diseases that affect bone metabolism were studied. Karnofsky performance status, pain scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of type I collagen were analysed. Twenty-four healthy controls of the same age were also established. With only the exception of OC, bone marker values of patients were significantly increased compared with the upper reference limits (P<0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal telopeptide of type I collagen). All bone markers and prostate-specific antigen also showed significant paired correlations (P < or = 0.019) and linear increases with advancing EOD (P < or = 0.032). Finally, none of the measured markers correlated significantly with pain levels. Bone markers are remarkably elevated in the serum of prostate cancer patients with metastatic bone disease and correlate with EOD. Paired correlations also suggest an accelerated but proportional (coupled) bone metabolism.
Uploads
Papers by GEORGIOS LIMOURIS