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E Brad Thompson - One of the best experts on this subject based on the ideXlab platform.
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Gene expression profiling of leukemic cells and primary thymocytes predicts a signature for apoptotic sensitivity to glucocorticoids
Cancer Cell International, 2007Co-Authors: Aaron L Miller, M Scott Webb, Spogmai Komak, Edward H Leiter, E Brad ThompsonAbstract:Background Glucocorticoids (GC's) play an integral role in treatment strategies designed to combat various forms of hematological malignancies. GCs also are powerful inhibitors of the immune system, through regulation of appropriate cytokines and by causing apoptosis of immature thymocytes. By activating the glucocorticoid receptor (GR), GCs evoke apoptosis through transcriptional regulation of a complex, interactive gene network over a period of time preceding activation of the apoptotic enzymes. In this study we used microarray technology to determine whether several disparate types of hematologic cells, all sensitive to GC-evoked apoptosis, would identify a common set of regulated genes. We compared gene expression signatures after treatment with two potent synthetic GCs, dexamethasone (Dex) and Cortivazol (CVZ) using a panel of hematologic cells. Pediatric CD4+/CD8+ T-cell leukemia was represented by 3 CEM clones: two sensitive, CEM-C7–14 and CEM-C1–6, and one resistant, CEM-C1–15, to Dex. CEM-C1–15 was also tested when rendered GC-sensitive by several treatments. GC-sensitive pediatric B-cell leukemia was represented by the SUP-B15 line and adult B-cell leukemia by RS4;11 cells. Kasumi-1 cells gave an example of the rare Dex-sensitive acute myeloblastic leukemia (AML). To test the generality of the correlations in malignant cell gene sets, we compared with GC effects on mouse non-transformed thymocytes. Results We identified a set of genes regulated by GCs in all GC-sensitive malignant cells. A portion of these were also regulated in the thymocytes. Because we knew that the highly Dex-resistant CEM-C1–15 cells could be killed by CVZ, we tested these cells with the latter steroid and again found that many of the same genes were now regulated as in the inherently GC-sensitive cells. The same result was obtained when we converted the Dex-resistant clone to Dex-sensitive by treatment with forskolin (FSK), to activate the adenyl cyclase/protein kinase A pathway (PKA). Conclusion Our results have identified small sets of genes that correlate with GC-sensitivity in cells from several hematologic malignancies. Some of these are also regulated in normal mouse thymocytes.
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Comparison of two structurally diverse glucocorticoid receptor agonists: Cortivazol selectively regulates a distinct set of genes separate from dexamethasone in CEM cells.
Steroids, 2007Co-Authors: Aaron L Miller, M Scott Webb, E Brad ThompsonAbstract:One goal of steroid research is precise differential regulation of gene expression by steroid hormone receptors through use of distinct ligands which modulate defined sets of cellular effects. Such "selective modulator" ligands are known for several receptors. Potent pyrazolo-glucocorticoid (11beta,16alpha)-21-(Acetyloxy)-11,17-dihydroxy-6,16-dimethyl-2'-phenyl-2'H-pregna-2,4,6-trieno[3,2-c]pyrazol-20-one) Cortivazol activates the glucocorticoid receptor to regulate gene expression and can bring about apoptosis of leukemic CEM cells resistant to (9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one) dexamethasone. We therefore tested the hypothesis that Cortivazol and dexamethasone regulate non-identical sets of genes in CEM cells. We found that while Cortivazol and dexamethasone overlap in regulation of most genes, each steroid regulates an exclusive set of transcripts in clone CEM-C7-14 (sensitive to apoptosis by both dexamethasone and Cortivazol) and clone CEM-C1-15 (dexamethasone-resistant but Cortivazol-sensitive). Fifty-seven genes were regulated uniquely to a statistically significant extent by Cortivazol in both clones. Many of the Cortivazol specific genes are key components of various signal transduction pathways. Our data clearly show Cortivazol to be a selective modulator of GR action.
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Comparison of two structurally diverse glucocorticoid receptor agonists: Cortivazol selectively regulates a distinct set of genes separate from dexamethasone in CEM cells
Steroids, 2007Co-Authors: Aaron L Miller, M Scott Webb, E Brad ThompsonAbstract:Abstract One goal of steroid research is precise differential regulation of gene expression by steroid hormone receptors through use of distinct ligands which modulate defined sets of cellular effects. Such “selective modulator” ligands are known for several receptors. Potent pyrazolo-glucocorticoid (11β,16α)-21-(Acetyloxy)-11,17-dihydroxy-6,16-dimethyl-2′-phenyl-2′ H -pregna-2,4,6-trieno[3,2- c ]pyrazol-20-one) Cortivazol activates the glucocorticoid receptor to regulate gene expression and can bring about apoptosis of leukemic CEM cells resistant to (9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[ a ]phenanthren-3-one) dexamethasone. We therefore tested the hypothesis that Cortivazol and dexamethasone regulate non-identical sets of genes in CEM cells. We found that while Cortivazol and dexamethasone overlap in regulation of most genes, each steroid regulates an exclusive set of transcripts in clone CEM-C7-14 (sensitive to apoptosis by both dexamethasone and Cortivazol) and clone CEM-C1-15 (dexamethasone-resistant but Cortivazol-sensitive). Fifty-seven genes were regulated uniquely to a statistically significant extent by Cortivazol in both clones. Many of the Cortivazol specific genes are key components of various signal transduction pathways. Our data clearly show Cortivazol to be a selective modulator of GR action.
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Cortivazol mediated induction of glucocorticoid receptor messenger ribonucleic acid in wild-type and dexamethasone-resistant human leukemic (CEM) cells.
The Journal of steroid biochemistry and molecular biology, 1991Co-Authors: Javed Ashraf, Sarada Kunapuli, David Chilton, E Brad ThompsonAbstract:Cortivazol is a phenylpyrazolo glucocorticoid of high potency and unusual structure. In both wild-type and highly dexamethasone(dex)-resistant clones of the human leukemic cell line CEM, exposure to Cortivazol leads to cell death. It has been shown recently that in wild-type CEM cells but not in a dex-resistant, glucocorticoid receptor(GR)-defective clone ICR-27 TK-3, dex induces GR mRNA. To test the hypothesis that Cortivazol acts in dex-resistant cells by making use of the residual GR found there, wild-type and dex-resistant clones were treated with various concentrations of Cortivazol and induction of GR mRNA was studied. Cortivazol significantly induced GR mRNA in the normal CEM-C7 as well as in two classes of dex-resistant clones, although the dex-resistant clones needed at least 10 times more Cortivazol than the normal cells for significant GR mRNA induction. Increased levels of GR mRNA were noticed as early as 3 h after treatment. A general correlation between induction of GR mRNA and lysis of the normal and dex-resistant cells was found. Positive induction of GR mRNA might be one of the earliest crucial steps in the lysis of normal and dex-resistant CEM cells, or might serve as a marker for the process. However, the lysis pathway in the dex-resistant cells is defective in that dex-resistant clones needed significantly more Cortivazol than the normal cells for lysis of the cells.
Adrian Kastler - One of the best experts on this subject based on the ideXlab platform.
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ct guided infiltration of greater occipital nerve for refractory craniofacial pain syndromes other than occipital neuralgia
Diagnostic and interventional imaging, 2020Co-Authors: Ricquart A Wandaele, Adrian Kastler, Alexandre Comte, G Hadjidekov, R Kechidi, O Helenon, B KastlerAbstract:Abstract Purpose The purpose of this study was to evaluate the effectiveness of computed tomography (CT)-guided infiltration of greater occipital nerve (GON) for the treatment of refractory craniofacial pain syndromes other than occipital neuralgia. Materials and methods Fifty-six patients suffering from refractory craniofacial pain syndromes were included between 2011 and 2017. There were 33 women and 23 men with a mean age of 50.7 years ± 13.1 (SD) (range: 27–74 years). CT-guided infiltration was performed at the intermediate site of the GON with local anesthetics and Cortivazol. Twenty-six (26/56; 46%) patients suffered from chronic migraine, 14 (14/56; 25%) from trigeminal neuralgia and 16 (16/56; 29%) from cluster headaches. Clinical success at 1, 3, and 6 months was defined by a decrease of at least 50% of pain as assessed using visual analog scale (VAS). Results Mean overall VAS score before infiltration was 8.7 ± 1.3 (SD) (range: 6 - 10). Mean overall VAS scores after infiltration were 2.3 ± 3 (SD) (range: 0 - 10) (P Conclusion CT-guided infiltration at the intermediate site of the GON appears as an effective treatment of craniofacial pain syndromes especially in patients with chronic migraine and those with cluster headaches.
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Dual Site Pudendal Nerve Infiltration: More than Just a Diagnostic Test?
January 2018, 2018Co-Authors: Adrian KastlerAbstract:Background: Pudendal neuralgia (PN) is a very painful and often disabling condition in which pudendal nerve blocks play an important role in both the diagnosis and management of PN. Some previous reports have advocated the use of pudendal nerve infiltration (PNI) as a diagnostic test only. Objective: We aim to assess the outcomes of patients with typical refractory PN who underwent dual site computed tomography (CT)-guided pudendal nerve infiltration. Study Design: A bicentric, retrospective cohort analysis. Setting: An academic practice. Methods: Between 2002 and 2016, 385 PNIs were performed in 195 patients in the 2 units. Only patients suffering from typical clinical PN were included, and only the first infiltration in each patient was considered for analysis. Therefore, 95 patients who underwent 155 procedures were assessed. Pain was assessed using a visual analog scale (0–10) and self-reported estimated improvement (SRI), expressed as a percentage. Efficacy of the procedure was assessed at 1, 3, and 6 months after procedure follow-up, and clinical success was defined as a 50% decrease of the VAS score. All procedures were performed under CT guidance and on an outpatient basis. Dual site infiltration was performed in each case at both the ischial spine and intra-Alcock’s canal sites using a mixture of fast- and slow-acting anesthetic (1 mL lidocaine hydrochloride 1% and 2 mL ropivacaine chlorhydrate) along with a half dose of 1.5 mL of Cortivazol (3.75 mg). Results: Clinical success at one month post-procedure was present in 63.2% of patients (60/95) with a mean VAS score of 2.07 (P < 0.05) and a mean SRI of 71%. At 3 months follow-up, clinical success was still present in 50.5% of patients (48/95) with a mean VAS score of 2.90/10 (P < 0.05) and a mean SRI of 62.3%. At 6 months follow-up, the efficacy rate decreased to 25.2% with a mean VAS score of 3.2/10 and SRI of 60%. Limitations: The retrospective aspect of the study is a limitation, as well as the lack of a control group. Conclusion: Dual site PNI under CT guidance may offer significant mid-term pain relief to a majority of patients suffering from typical refractory PN. Key words: Pudendal nerve, neuralgia, block, Alcock, CT, guidance
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Dual Site Pudendal Nerve Infiltration: More than Just a Diagnostic Test?
Pain physician, 2018Co-Authors: Adrian Kastler, Julien Puget, Florence Tiberghien, Jean-michel Pellat, Alexandre Krainik, Bruno KastlerAbstract:BACKGROUND Pudendal neuralgia (PN) is a very painful and often disabling condition in which pudendal nerve blocks play an important role in both the diagnosis and management of PN. Some previous reports have advocated the use of pudendal nerve infiltration (PNI) as a diagnostic test only. OBJECTIVE We aim to assess the outcomes of patients with typical refractory PN who underwent dual site computed tomography (CT)-guided pudendal nerve infiltration. STUDY DESIGN A bicentric, retrospective cohort analysis. SETTING An academic practice. METHODS Between 2002 and 2016, 385 PNIs were performed in 195 patients in the 2 units. Only patients suffering from typical clinical PN were included, and only the first infiltration in each patient was considered for analysis. Therefore, 95 patients who underwent 155 procedures were assessed. Pain was assessed using a visual analog scale (0-10) and self-reported estimated improvement (SRI), expressed as a percentage. Efficacy of the procedure was assessed at 1, 3, and 6 months after procedure follow-up, and clinical success was defined as a 50% decrease of the VAS score. All procedures were performed under CT guidance and on an outpatient basis. Dual site infiltration was performed in each case at both the ischial spine and intra-Alcock's canal sites using a mixture of fast- and slow-acting anesthetic (1 mL lidocaine hydrochloride 1% and 2 mL ropivacaine chlorhydrate) along with a half dose of 1.5 mL of Cortivazol (3.75 mg). RESULTS Clinical success at one month post-procedure was present in 63.2% of patients (60/95) with a mean VAS score of 2.07 (P < 0.05) and a mean SRI of 71%. At 3 months follow-up, clinical success was still present in 50.5% of patients (48/95) with a mean VAS score of 2.90/10 (P < 0.05) and a mean SRI of 62.3%. At 6 months follow-up, the efficacy rate decreased to 25.2% with a mean VAS score of 3.2/10 and SRI of 60%. LIMITATIONS The retrospective aspect of the study is a limitation, as well as the lack of a control group. CONCLUSION Dual site PNI under CT guidance may offer significant mid-term pain relief to a majority of patients suffering from typical refractory PN. KEY WORDS Pudendal nerve, neuralgia, block, Alcock, CT, guidance.
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Ultrasound-Guided Intermediate Site Greater Occipital Nerve Infiltration: A Technical Feasibility Study.
Pain physician, 2016Co-Authors: Jonathan Zipfel, Adrian Kastler, Laurent Tatu, Julien Behr, Rachid Kechidi, Bruno KastlerAbstract:BACKGROUND Two studies recently reported that computed tomography (CT) guided infiltration of the greater occipital nerve at its intermediate site allows a high efficacy rate with long-lasting pain relief following procedure in occipital neuralgia and in various craniofacial pain syndromes. OBJECTIVE The purpose of our study was to evaluate the technical feasibility and safety of ultrasound-guided intermediate site greater occipital nerve infiltration. STUDY DESIGN Retrospective study. SETTING This study was conducted at the imaging department of a 1,409 bed university hospital. METHODS Local institutional review board approval was obtained and written consent was waived. In this retrospective study, 12 patients suffering from refractory occipital neuralgia or craniofacial pain syndromes were included between April and October 2014. They underwent a total of 21 ultrasound-guided infiltrations. Infiltration of the greater occipital nerve was performed at the intermediate site of the greater occipital nerve, at its first bend between obliqus capitis inferior and semispinalis capitis muscles with local anestetics and Cortivazol. Technical success was defined as satisfactory diffusion of added iodinated contrast media in the fatty space between these muscles depicted on control CT scan. We also reported first data of immediate block test efficacy and initial clinical efficacy at 7 days, one month, and 3 months, defined by a decrease of at least 50% of visual analog scale (VAS) scores. RESULTS Technical success rate was 95.24%. Patients suffered from right unilateral occipital neuralgia in 3 cases, left unilateral occipital neuralgia in 2 cases, bilateral occipital neuralgia in 2 cases, migraine in one case, cervicogenic headache in one case, tension-type headache in 2 cases, and cluster headache in one case. Block test efficacy was found in 93.3% (14/15) cases. Clinical efficacy was found in 80% of cases at 7 days, in 66.7% of cases at one month and in 60% of cases at 3 months. No major complications were noted. LIMITATIONS Some of the limitations of our study include that it represents a single institution. The low number of infiltrations included in this study, for this guidance procedure, is another bias. CONCLUSIONS This ultrasound-guided infiltration technique appears to be feasible, safe, non-ionizing, and fast when targeting the greater occipital nerve in its intermediate portion. This imaging guidance modality should be used in routine clinical practice. KEY WORDS Greater occipital nerve, infiltration, ultrasound guidance, corticosteroids, occipital neuralgia, craniofacial pain syndrome.
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A simplified CT-guided approach for greater occipital nerve infiltration in the management of occipital neuralgia
European Radiology, 2015Co-Authors: Adrian Kastler, Alexandre Comte, Yannick Onana, Arnaud Attyé, Jean-louis Lajoie, Bruno KastlerAbstract:Objectives To evaluate the efficacy of a simplified CT-guided greater occipital nerve (GON) infiltration approach in the management of occipital neuralgia (ON). Methods Local IRB approval was obtained and written informed consent was waived. Thirty three patients suffering from severe refractory ON who underwent a total of 37 CT-guided GON infiltrations were included between 2012 and 2014. GON infiltration was performed at the first bend of the GON, between the inferior obliqus capitis and semispinalis capitis muscles with local anaesthetics and Cortivazol. Pain was evaluated via VAS scores. Clinical success was defined by pain relief greater than or equal to 50 % lasting for at least 3 months. Results The pre-procedure mean pain score was 8/10. Patients suffered from left GON neuralgia in 13 cases, right GON neuralgia in 16 cases and bilateral GON neuralgia in 4 cases. The clinical success rate was 86 %. In case of clinical success, the mean pain relief duration following the procedure was 9.16 months. Conclusions Simplified CT-guided infiltration appears to be effective in managing refractory ON. With this technique, infiltration of the GON appears to be faster, technically easier and, therefore, safer compared with other previously described techniques. Key Points • Occipital neuralgia is a very painful and debilitating condition • GON infiltrations have been successful in the treatment of occipital neuralgia • This simplified technique presents a high efficacy rate with long-lasting pain relief • This infiltration technique does not require contrast media injection for pre-planning • GON infiltration at the first bend appears easier and safer
Bruno Kastler - One of the best experts on this subject based on the ideXlab platform.
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Dual Site Pudendal Nerve Infiltration: More than Just a Diagnostic Test?
Pain physician, 2018Co-Authors: Adrian Kastler, Julien Puget, Florence Tiberghien, Jean-michel Pellat, Alexandre Krainik, Bruno KastlerAbstract:BACKGROUND Pudendal neuralgia (PN) is a very painful and often disabling condition in which pudendal nerve blocks play an important role in both the diagnosis and management of PN. Some previous reports have advocated the use of pudendal nerve infiltration (PNI) as a diagnostic test only. OBJECTIVE We aim to assess the outcomes of patients with typical refractory PN who underwent dual site computed tomography (CT)-guided pudendal nerve infiltration. STUDY DESIGN A bicentric, retrospective cohort analysis. SETTING An academic practice. METHODS Between 2002 and 2016, 385 PNIs were performed in 195 patients in the 2 units. Only patients suffering from typical clinical PN were included, and only the first infiltration in each patient was considered for analysis. Therefore, 95 patients who underwent 155 procedures were assessed. Pain was assessed using a visual analog scale (0-10) and self-reported estimated improvement (SRI), expressed as a percentage. Efficacy of the procedure was assessed at 1, 3, and 6 months after procedure follow-up, and clinical success was defined as a 50% decrease of the VAS score. All procedures were performed under CT guidance and on an outpatient basis. Dual site infiltration was performed in each case at both the ischial spine and intra-Alcock's canal sites using a mixture of fast- and slow-acting anesthetic (1 mL lidocaine hydrochloride 1% and 2 mL ropivacaine chlorhydrate) along with a half dose of 1.5 mL of Cortivazol (3.75 mg). RESULTS Clinical success at one month post-procedure was present in 63.2% of patients (60/95) with a mean VAS score of 2.07 (P < 0.05) and a mean SRI of 71%. At 3 months follow-up, clinical success was still present in 50.5% of patients (48/95) with a mean VAS score of 2.90/10 (P < 0.05) and a mean SRI of 62.3%. At 6 months follow-up, the efficacy rate decreased to 25.2% with a mean VAS score of 3.2/10 and SRI of 60%. LIMITATIONS The retrospective aspect of the study is a limitation, as well as the lack of a control group. CONCLUSION Dual site PNI under CT guidance may offer significant mid-term pain relief to a majority of patients suffering from typical refractory PN. KEY WORDS Pudendal nerve, neuralgia, block, Alcock, CT, guidance.
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Ultrasound-Guided Intermediate Site Greater Occipital Nerve Infiltration: A Technical Feasibility Study.
Pain physician, 2016Co-Authors: Jonathan Zipfel, Adrian Kastler, Laurent Tatu, Julien Behr, Rachid Kechidi, Bruno KastlerAbstract:BACKGROUND Two studies recently reported that computed tomography (CT) guided infiltration of the greater occipital nerve at its intermediate site allows a high efficacy rate with long-lasting pain relief following procedure in occipital neuralgia and in various craniofacial pain syndromes. OBJECTIVE The purpose of our study was to evaluate the technical feasibility and safety of ultrasound-guided intermediate site greater occipital nerve infiltration. STUDY DESIGN Retrospective study. SETTING This study was conducted at the imaging department of a 1,409 bed university hospital. METHODS Local institutional review board approval was obtained and written consent was waived. In this retrospective study, 12 patients suffering from refractory occipital neuralgia or craniofacial pain syndromes were included between April and October 2014. They underwent a total of 21 ultrasound-guided infiltrations. Infiltration of the greater occipital nerve was performed at the intermediate site of the greater occipital nerve, at its first bend between obliqus capitis inferior and semispinalis capitis muscles with local anestetics and Cortivazol. Technical success was defined as satisfactory diffusion of added iodinated contrast media in the fatty space between these muscles depicted on control CT scan. We also reported first data of immediate block test efficacy and initial clinical efficacy at 7 days, one month, and 3 months, defined by a decrease of at least 50% of visual analog scale (VAS) scores. RESULTS Technical success rate was 95.24%. Patients suffered from right unilateral occipital neuralgia in 3 cases, left unilateral occipital neuralgia in 2 cases, bilateral occipital neuralgia in 2 cases, migraine in one case, cervicogenic headache in one case, tension-type headache in 2 cases, and cluster headache in one case. Block test efficacy was found in 93.3% (14/15) cases. Clinical efficacy was found in 80% of cases at 7 days, in 66.7% of cases at one month and in 60% of cases at 3 months. No major complications were noted. LIMITATIONS Some of the limitations of our study include that it represents a single institution. The low number of infiltrations included in this study, for this guidance procedure, is another bias. CONCLUSIONS This ultrasound-guided infiltration technique appears to be feasible, safe, non-ionizing, and fast when targeting the greater occipital nerve in its intermediate portion. This imaging guidance modality should be used in routine clinical practice. KEY WORDS Greater occipital nerve, infiltration, ultrasound guidance, corticosteroids, occipital neuralgia, craniofacial pain syndrome.
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A simplified CT-guided approach for greater occipital nerve infiltration in the management of occipital neuralgia
European Radiology, 2015Co-Authors: Adrian Kastler, Alexandre Comte, Yannick Onana, Arnaud Attyé, Jean-louis Lajoie, Bruno KastlerAbstract:Objectives To evaluate the efficacy of a simplified CT-guided greater occipital nerve (GON) infiltration approach in the management of occipital neuralgia (ON). Methods Local IRB approval was obtained and written informed consent was waived. Thirty three patients suffering from severe refractory ON who underwent a total of 37 CT-guided GON infiltrations were included between 2012 and 2014. GON infiltration was performed at the first bend of the GON, between the inferior obliqus capitis and semispinalis capitis muscles with local anaesthetics and Cortivazol. Pain was evaluated via VAS scores. Clinical success was defined by pain relief greater than or equal to 50 % lasting for at least 3 months. Results The pre-procedure mean pain score was 8/10. Patients suffered from left GON neuralgia in 13 cases, right GON neuralgia in 16 cases and bilateral GON neuralgia in 4 cases. The clinical success rate was 86 %. In case of clinical success, the mean pain relief duration following the procedure was 9.16 months. Conclusions Simplified CT-guided infiltration appears to be effective in managing refractory ON. With this technique, infiltration of the GON appears to be faster, technically easier and, therefore, safer compared with other previously described techniques. Key Points • Occipital neuralgia is a very painful and debilitating condition • GON infiltrations have been successful in the treatment of occipital neuralgia • This simplified technique presents a high efficacy rate with long-lasting pain relief • This infiltration technique does not require contrast media injection for pre-planning • GON infiltration at the first bend appears easier and safer
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Evaluation of the efficacy of CT-guided epidural and transforaminal steroid injections in patients with diskogenic radiculopathy
Journal de radiologie, 2008Co-Authors: C. Riboud, J.m. Lerais, N. Sailley, Bruno KastlerAbstract:PURPOSE To evaluate the efficacy of CT-guided epidural and transforaminal steroid injections in patients with diskogenic radiculopathy. MATERIALS AND METHODS Seventy patients underwent CT guided injections after failure of medical management. Only patients with minimal degenerative changes and diskogenic monoradicular symptoms were treated. Only two patients with fibrosis were included. RESULTS 78.6% of patients experienced persistent symptomatic improvement. No difference was noted between lumbar segments and there was no more failures with epidural injections compared to transforaminal injections. Cervical disk herniations responded better than lumbar disk herniations. Good results were obtained in younger patients (M=46.25 years), symptomatic for 3-4 months or less, and with clear radicular symptoms and clinical neurological deficits (hypoesthesia, absent DTR) without motor deficit. No patient with severe spinal stenosis (S-) was included and the disk herniations were small (b1, b2, c1, c2 or d1, d2). Only a single injection was needed. Cortivazol provided superior results compared to dexamethasone. CONCLUSION CT-guided injections should be included in the therapeutic armamentarium after standard medical management, with cure as the goal.
Aaron L Miller - One of the best experts on this subject based on the ideXlab platform.
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Gene expression profiling of leukemic cells and primary thymocytes predicts a signature for apoptotic sensitivity to glucocorticoids
Cancer Cell International, 2007Co-Authors: Aaron L Miller, M Scott Webb, Spogmai Komak, Edward H Leiter, E Brad ThompsonAbstract:Background Glucocorticoids (GC's) play an integral role in treatment strategies designed to combat various forms of hematological malignancies. GCs also are powerful inhibitors of the immune system, through regulation of appropriate cytokines and by causing apoptosis of immature thymocytes. By activating the glucocorticoid receptor (GR), GCs evoke apoptosis through transcriptional regulation of a complex, interactive gene network over a period of time preceding activation of the apoptotic enzymes. In this study we used microarray technology to determine whether several disparate types of hematologic cells, all sensitive to GC-evoked apoptosis, would identify a common set of regulated genes. We compared gene expression signatures after treatment with two potent synthetic GCs, dexamethasone (Dex) and Cortivazol (CVZ) using a panel of hematologic cells. Pediatric CD4+/CD8+ T-cell leukemia was represented by 3 CEM clones: two sensitive, CEM-C7–14 and CEM-C1–6, and one resistant, CEM-C1–15, to Dex. CEM-C1–15 was also tested when rendered GC-sensitive by several treatments. GC-sensitive pediatric B-cell leukemia was represented by the SUP-B15 line and adult B-cell leukemia by RS4;11 cells. Kasumi-1 cells gave an example of the rare Dex-sensitive acute myeloblastic leukemia (AML). To test the generality of the correlations in malignant cell gene sets, we compared with GC effects on mouse non-transformed thymocytes. Results We identified a set of genes regulated by GCs in all GC-sensitive malignant cells. A portion of these were also regulated in the thymocytes. Because we knew that the highly Dex-resistant CEM-C1–15 cells could be killed by CVZ, we tested these cells with the latter steroid and again found that many of the same genes were now regulated as in the inherently GC-sensitive cells. The same result was obtained when we converted the Dex-resistant clone to Dex-sensitive by treatment with forskolin (FSK), to activate the adenyl cyclase/protein kinase A pathway (PKA). Conclusion Our results have identified small sets of genes that correlate with GC-sensitivity in cells from several hematologic malignancies. Some of these are also regulated in normal mouse thymocytes.
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Comparison of two structurally diverse glucocorticoid receptor agonists: Cortivazol selectively regulates a distinct set of genes separate from dexamethasone in CEM cells.
Steroids, 2007Co-Authors: Aaron L Miller, M Scott Webb, E Brad ThompsonAbstract:One goal of steroid research is precise differential regulation of gene expression by steroid hormone receptors through use of distinct ligands which modulate defined sets of cellular effects. Such "selective modulator" ligands are known for several receptors. Potent pyrazolo-glucocorticoid (11beta,16alpha)-21-(Acetyloxy)-11,17-dihydroxy-6,16-dimethyl-2'-phenyl-2'H-pregna-2,4,6-trieno[3,2-c]pyrazol-20-one) Cortivazol activates the glucocorticoid receptor to regulate gene expression and can bring about apoptosis of leukemic CEM cells resistant to (9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one) dexamethasone. We therefore tested the hypothesis that Cortivazol and dexamethasone regulate non-identical sets of genes in CEM cells. We found that while Cortivazol and dexamethasone overlap in regulation of most genes, each steroid regulates an exclusive set of transcripts in clone CEM-C7-14 (sensitive to apoptosis by both dexamethasone and Cortivazol) and clone CEM-C1-15 (dexamethasone-resistant but Cortivazol-sensitive). Fifty-seven genes were regulated uniquely to a statistically significant extent by Cortivazol in both clones. Many of the Cortivazol specific genes are key components of various signal transduction pathways. Our data clearly show Cortivazol to be a selective modulator of GR action.
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Comparison of two structurally diverse glucocorticoid receptor agonists: Cortivazol selectively regulates a distinct set of genes separate from dexamethasone in CEM cells
Steroids, 2007Co-Authors: Aaron L Miller, M Scott Webb, E Brad ThompsonAbstract:Abstract One goal of steroid research is precise differential regulation of gene expression by steroid hormone receptors through use of distinct ligands which modulate defined sets of cellular effects. Such “selective modulator” ligands are known for several receptors. Potent pyrazolo-glucocorticoid (11β,16α)-21-(Acetyloxy)-11,17-dihydroxy-6,16-dimethyl-2′-phenyl-2′ H -pregna-2,4,6-trieno[3,2- c ]pyrazol-20-one) Cortivazol activates the glucocorticoid receptor to regulate gene expression and can bring about apoptosis of leukemic CEM cells resistant to (9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[ a ]phenanthren-3-one) dexamethasone. We therefore tested the hypothesis that Cortivazol and dexamethasone regulate non-identical sets of genes in CEM cells. We found that while Cortivazol and dexamethasone overlap in regulation of most genes, each steroid regulates an exclusive set of transcripts in clone CEM-C7-14 (sensitive to apoptosis by both dexamethasone and Cortivazol) and clone CEM-C1-15 (dexamethasone-resistant but Cortivazol-sensitive). Fifty-seven genes were regulated uniquely to a statistically significant extent by Cortivazol in both clones. Many of the Cortivazol specific genes are key components of various signal transduction pathways. Our data clearly show Cortivazol to be a selective modulator of GR action.
Yves Maugars - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of local glucocorticoid after local anesthetic in low back pain with lumbosacral transitional vertebra: A randomized placebo-controlled double-blind trial.
Joint bone spine, 2017Co-Authors: Joëlle Glémarec, Stéphane Varin, Céline Cozic, Gilles Tanguy, Christelle Volteau, Philippe Montigny, Benoit Le Goff, Christelle Darrieutort Laffite, Yves Maugars, Grégoire CormierAbstract:Abstract Objective The primary objective of this study was to compare the efficacy of local injection of a local anesthetic with a glucocorticoid versus a local anesthetic with saline to treat low back pain due to lumbosacral transitional vertebras (LSTV) with a pseudoarticulation. Methods A randomized placebo-controlled double-blind study was conducted in patients with unilateral low back pain ascribed clinically to LSTV. Patients were randomized to lidocaine plus saline (LS group) or lidocaine plus Cortivazol (LC group) injected locally under computed tomography guidance. The primary outcome measure was the 24-hour mean visual analog scale (VAS) score for low back pain 4 weeks after the injection. Results Of 16 randomized patients, 15 were included in the analysis, 8 in the LS group and 7 in the LC group. The mean VAS pain score at week 4 was not significantly different between the two groups. In the two groups pooled, the mean VAS pain score decreased significantly from baseline to week 4, from 5.52 ± 0.99 to 3.86 ± 2.55 (P ≤ 0.05). The difference remained significant at week 12. Significant improvements occurred in the EIFEL disability index and items of the Dallas Pain Questionnaire. No adverse events were recorded. Conclusion In patients with chronic low back pain consistent with a symptomatic LSTV type II or IV in the Castellvi classification, a local injection of lidocaine with or without Cortivazol may provide sustained improvements in pain and function. The underlying mechanism is unclear.
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SAT0509 Feasibility of Ultrasound-Guided Facet Joint Injections through A Longitudinal Approach
Annals of the Rheumatic Diseases, 2016Co-Authors: C. Darrieutort-laffite, Joëlle Glémarec, Yves Maugars, A. Colombey, B. Le GoffAbstract:Background Facet joint-mediated pain has been identified as a common cause of lumbar pain. Steroid injections are currently made to treat them, they are usually performed under fluoroscopy or computed tomography guidance. Ultrasound (US) is also appropriate to study facet joints and some studies showed feasibility and efficacy of facet joint injections performed under US-guidance through a transversal approach. On a longitudinal view, facet joints are easy-to-identify as a series of lumps with the joint capsule appearing as a thin hypoechoic line that envelops the joint. Objectives Considering the good visibility of these joints and their capsule on the longitudinal view, we studied the feasibility of US-guided facet joint injections using a longitudinal inline approach. Methods Patients referred to our rheumatology department to receive facet joint injections under fluoroscopy were included. To realize the injection, we first located the accurate lumbar level on a longitudinal median view going through the spinous processes. Facet joints were identified as previously described placing the probe 2–3 cm away from the median line. Then, the needle was inserted to reach the hypoechoic line corresponding to the capsule or, if not visible, the top of the lump formed by the inferior articular process of the superior vertebra overlying the superior articular process of the vertebra below it. When we obtained the bone contact, we injected iodinated contrast medium followed by Cortivazol. Finally, we made a lumbar X-ray to analyze the needle position and the quality of the arthrography. The first objective was to assess the number of injections realized in front of the joint. For secondary objectives, we assessed the number of accurate arthrography, the duration of the procedure and the occurrence of adverse events. During US examination, the visibility of the capsule and the presence of osteophytes were collected. Results Thirty-eight patients have been included by two operators. We excluded four patients because of a poor visibility of the spinal structures. Mean age was 58,4 years (range, 30–82) and mean BMI was 25,2 kg/m 2 (range, 18–34). US showed osteophytes in 42% and the joint capsule was inconstantly visible (25%). One-hundred and forty-four injections were performed (72 at the L4-L5 level and 72 at the L5-S1 level) and 141 X-ray were analyzed. One-hundred and twenty-three injections (87%) were accurately realized in front of the joint, i.e. in front of the inferior articular process of the superior vertebra. However, a proper arthrogram was obtained in only 35 cases (25%). Mean procedure duration was 8.5 minutes for four injections. Six patients (18%) reported transient pain exacerbation and no severe complication occurred during the first month after the procedure. Conclusions With a longitudinal inline approach, US-guided facet joint injections were feasible and 87% injections were realized right in front of the joint. However, we obtained a correct arthrogram in only 25%. The depth of the target-point, the inconstant visualization of the capsule and the obliquity of the needle probably explain this result. Additional studies will be necessary to improve the accuracy of the technique. Disclosure of Interest None declared
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Tachon's syndrome (suracute back and/or thoracic pain following local injections of corticosteroids). A report of 318 French cases.
Joint bone spine, 2005Co-Authors: Jean-marie Berthelot, Joëlle Glémarec, Alain Prost, Laetitia Tortellier, Pascale Guillot, Jean-pierre Caumon, Yves MaugarsAbstract:Abstract Objectives. – To assess the frequency, features, and outcome of excruciating lumbar, dorsal, and/or thoracic pain following injections of local corticosteroids in rare instances. Methods. – A questionnaire mailed to 500 French rheumatologists. Results. – Three hundred and eighteen cases were reported by 92 rheumatologists (one event per 8000 injections or 6.5 years of practice), following injections into lumbar epidural space (39%), an upper limb (30%), a lower limb (mostly the heel) (24%), or other locations (7%), of Cortivazol (67%), hydrocortisone (25%), betamethasone (7%), or paramethasone (1%). Symptoms occurred 1–5 min (78%) or less than 1 min (22%) after injection, and highly acute axial pain usually lasted for less than 5 min (34%) or 5–15 min (51%). In addition to pain in lumbar (84%) and/or dorsal regions (25%) [often preceded or associated with thoracic pain (36%)], other signs were: anxiety (87%), shortness of breath (64%), facial flushing (64%), diffuse sweating (41%), agitation (29%), transient cough (23%), abdominal pain (20%), transient hypertension (15%), paleness (10%), hypotension (8%), diarrhoea (3%) and headache (3%). None of these patients was known to be allergic, and urticaria developed in only 2%. Outcome was favourable in all cases (even though 4/318 patients were transiently hospitalised) with an overall duration of 25 ± 71 min. Another injection was performed later in 146/318 cases (46%), but Tachon’s syndrome recurred in only 20 of these 146 patients (14%). Conclusion. – The outcome of this impressive syndrome seems excellent. Tachon’s syndrome might be the venous counterpart of Nicolau’s syndrome (injection of corticosteroids in an artery).
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Efficacy of nerve root versus interspinous injections of glucocorticoids in the treatment of disk-related sciatica. A pilot, prospective, randomized, double-blind study.
Joint bone spine, 2000Co-Authors: Kolsi I, Delecrin J, Thomas L, Alain Prost, Yves MaugarsAbstract:STUDY OBJECTIVES Pilot study comparing the short-term efficacy on pain and functional impairment of nerve root sheath versus interspinous glucocorticoid injections in patients admitted to a French rheumatology department for disk-related sciatica or femoral neuralgia. PATIENTS AND METHODS Thirty patients with refractory nerve root pain (sciatica, n = 29; femoral neuralgia, n = 1) for a mean of four months were randomized to nerve root injection (n = 17) or interspinous injection (n = 13) of the same mixture of 0.10 g of lidocaine hydrochloride and 3.75 mg of Cortivazol. Both injection methods were performed under analgesia and benzodiazepine sedation to maintain double blinding. Each patient was evaluated daily during the first seven days of bed rest in the hospital, then after discharge on postinjection day 28. RESULTS Prompt pain relief was obtained in both groups. On day 1, the mean pain scale score (0-100) fell from 70 +/- 3.9 to 26 +/- 5.6 in the nerve root group and from 63 +/- 4 to 23 +/- 4.7 in the interspinous group. These results were sustained on D7 and D28. CONCLUSIONS The unusually high level of efficacy of glucocorticoid injection in our study may be ascribable in part to strong placebo and Hawthorne effects and in part to the intrinsic effects of the injections. Whether nerve root injection is superior over interspinous injection remains unproven.
