The Experts below are selected from a list of 16062 Experts worldwide ranked by ideXlab platform
Pia Österlund - One of the best experts on this subject based on the ideXlab platform.
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chemotherapy induced Gastrointestinal Toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male sprague dawley rats
Cancer Chemotherapy and Pharmacology, 2017Co-Authors: Richard A. Forsgård, Riitta Korpela, Rafael Frias, Thomas Spillmann, Vannina G Marrachelli, Katri Korpela, Maria Carmen Collado, Daniel Monleon, Pia ÖsterlundAbstract:PURPOSE: Chemotherapy-induced Gastrointestinal Toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. METHODS: A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance (1H-NMR). RESULTS: Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. CONCLUSIONS: Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.
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Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced Gastrointestinal Toxicity in Sprague–Dawley rats
Cancer Chemotherapy and Pharmacology, 2016Co-Authors: Richard A. Forsgård, Riitta Korpela, Reetta Holma, Jere Lindén, Rafael Frias, Thomas Spillmann, Pia ÖsterlundAbstract:Purpose Gastrointestinal Toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of Gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced Gastrointestinal Toxicity.
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colonic methane production modifies Gastrointestinal Toxicity associated with adjuvant 5 fluorouracil chemotherapy for colorectal cancer
Journal of Clinical Gastroenterology, 2013Co-Authors: Reetta Holma, Riitta Korpela, Ulla Sairanen, Mikko Blom, Merja Rautio, Tuija Poussa, Maija Saxelin, Pia ÖsterlundAbstract:Goals:To investigate the association of colonic methane, formed by methanogenic achaea, and pH with Gastrointestinal symptoms during colorectal cancer chemotherapy.Background:Adjuvant 5-fluorouracil chemotherapy reduces recurrences in colorectal cancer, but causes severe Gastrointestinal Toxicity, p
Audrius Dulskas - One of the best experts on this subject based on the ideXlab platform.
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Late Gastrointestinal Toxicity after radiotherapy for rectal cancer: a systematic review
International Journal of Colorectal Disease, 2020Co-Authors: Agne Sipaviciute, Ernestas Sileika, Arvydas Burneckis, Audrius DulskasAbstract:Purpose Although the multimodal cancer treatment techniques have greatly improved over the years, irradiation-induced late Gastrointestinal Toxicity remains a great concern as it may highly affect the quality of life of a patient. The aim of this study was to define the prevalence of late Gastrointestinal toxicities. Methods Electronic databases of Cochrane Library, Embase, Web of Science, CENTRAL and PubMed were searched until September 2019. We used the following keywords: radiotherapy, radiation therapy, irradiation, rectal cancer, Gastrointestinal Toxicity, adverse effects, late effects, pelvic radiation and pelvic radiation disease. Results Nine studies were included into this review out of 4785 that were preidentified as potentially relevant. Overall prevalence of severe (Grade 3 or higher) late irradiation-induced Gastrointestinal toxicities was up to 19%. Most frequent toxicities of any grade were reported to be diarrhoea (up to 35%), faecal incontinence (22%), incontinence to gas (71%), rectal bleeding (9%), rectal pain (13%) and obstruction (7.4%). Preoperative treatment approaches and more advance radiotherapy techniques such as intensity-modulated and image-guided radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) turn out to result in lower late Gastrointestinal Toxicity rates. Conclusion After great improvements in rectal cancer treatment, late Gastrointestinal Toxicity after radiotherapy is experienced less frequent and less severe; however, it remains a great concern associated with worse quality of life.
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Late Gastrointestinal Toxicity after radiotherapy for rectal cancer: a systematic review.
International Journal of Colorectal Disease, 2020Co-Authors: Agne Sipaviciute, Ernestas Sileika, Arvydas Burneckis, Audrius DulskasAbstract:PURPOSE: Although the multimodal cancer treatment techniques have greatly improved over the years, irradiation-induced late Gastrointestinal Toxicity remains a great concern as it may highly affect the quality of life of a patient. The aim of this study was to define the prevalence of late Gastrointestinal toxicities. METHODS: Electronic databases of Cochrane Library, Embase, Web of Science, CENTRAL and PubMed were searched until September 2019. We used the following keywords: radiotherapy, radiation therapy, irradiation, rectal cancer, Gastrointestinal Toxicity, adverse effects, late effects, pelvic radiation and pelvic radiation disease. RESULTS: Nine studies were included into this review out of 4785 that were preidentified as potentially relevant. Overall prevalence of severe (Grade 3 or higher) late irradiation-induced Gastrointestinal toxicities was up to 19%. Most frequent toxicities of any grade were reported to be diarrhoea (up to 35%), faecal incontinence (22%), incontinence to gas (71%), rectal bleeding (9%), rectal pain (13%) and obstruction (7.4%). Preoperative treatment approaches and more advance radiotherapy techniques such as intensity-modulated and image-guided radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) turn out to result in lower late Gastrointestinal Toxicity rates. CONCLUSION: After great improvements in rectal cancer treatment, late Gastrointestinal Toxicity after radiotherapy is experienced less frequent and less severe; however, it remains a great concern associated with worse quality of life.
Brian L Strom - One of the best experts on this subject based on the ideXlab platform.
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moderate and high affinity serotonin reuptake inhibitors increase the risk of upper Gastrointestinal Toxicity
Pharmacoepidemiology and Drug Safety, 2008Co-Authors: James D Lewis, Brian L Strom, Russell A Localio, David C Metz, John T Farrar, Robert M Weinrieb, Lisa Nessel, Colleen M Brensinger, Stephen E KimmelAbstract:Objective Serotonin release from platelets is important for regulating hemostasis. Some prior studies suggest an association between use of selective serotonin reuptake inhibitors and Gastrointestinal bleeding and a possible synergistic effect of these medications with non-steroidal anti-inflammatory drugs (NSAIDs). This study examined the effect of medications that inhibit serotonin uptake on upper Gastrointestinal Toxicity. Methods 359 case subjects hospitalized for upper Gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. 1889 control subjects were recruited by random digit dialing from the same region. Data were collected during structured telephone interviews. Antidepressant medications were characterized according to their affinity for serotonin receptors. Exposure to medications required use on at least 1 day during the week prior to the index date. Results Any moderate or high affinity serotonin reuptake inhibitor (MHA-SRI) use was reported by 61 cases (17.1%) and 197 controls (10.4%). After adjusting for potential confounders, MHA-SRI use was associated with a significantly increased odds of hospitalization for upper Gastrointestinal Toxicity (adjusted OR = 2.0, 95%CI 1.4–3.0). A dose–response relationship in terms of affinity for serotonin uptake receptors was not observed (p = 0.17). No statistical interaction was observed for use of high dose NSAIDs or aspirin concomitantly with MHA-SRIs (p = 0.5). When MHA-SRIs were used concomitantly with high dose NSAIDs, the adjusted odds ratio for the association with upper Gastrointestinal Toxicity was 3.5 (95%CI 1.9–6.6). Conclusions Use of MHA-SRIs is associated with an increased risk of hospitalization for upper Gastrointestinal Toxicity. Copyright © 2008 John Wiley & Sons, Ltd.
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risk of serious upper Gastrointestinal Toxicity with over the counter nonaspirin nonsteroidal anti inflammatory drugs
Gastroenterology, 2005Co-Authors: James D Lewis, Russell A Localio, David C Metz, John T Farrar, Lisa Nessel, Colleen M Brensinger, Stephen E Kimmel, Karen Mcgibney, Brian L StromAbstract:Background & Aims: Use of prescription nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) increases the risk of serious upper Gastrointestinal Toxicity. Less is known about over-the-counter (OTC) NANSAIDs, which are typically used at lower doses and for shorter durations. This study assessed the risk of Toxicity with OTC NANSAIDs. Methods: A total of 359 case subjects hospitalized for upper Gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. A total of 1889 control subjects were recruited by random digit dialing from the same region. Data on medication use were collected via structured telephone interview. Results: Use of OTC NANSAIDs on ≥4 days during the most recent week had an adjusted odds ratio (OR) of 1.83 (95% confidence interval [CI], 1.14–2.95). Use of high-dose OTC NANSAIDs during the index week had an adjusted OR of 5.21 (95% CI, 2.32–11.69). In contrast, use of OTC NANSAIDs Conclusions: Use of OTC NANSAIDs at recommended doses has a relatively good safety profile compared with prescription NANSAIDs. However, use of high-dose OTC NANSAIDs (comparable to a prescription dose) is associated with serious Gastrointestinal Toxicity.
Rafael Frias - One of the best experts on this subject based on the ideXlab platform.
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chemotherapy induced Gastrointestinal Toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male sprague dawley rats
Cancer Chemotherapy and Pharmacology, 2017Co-Authors: Richard A. Forsgård, Riitta Korpela, Rafael Frias, Thomas Spillmann, Vannina G Marrachelli, Katri Korpela, Maria Carmen Collado, Daniel Monleon, Pia ÖsterlundAbstract:PURPOSE: Chemotherapy-induced Gastrointestinal Toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. METHODS: A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance (1H-NMR). RESULTS: Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. CONCLUSIONS: Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.
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Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced Gastrointestinal Toxicity in Sprague–Dawley rats
Cancer Chemotherapy and Pharmacology, 2016Co-Authors: Richard A. Forsgård, Riitta Korpela, Reetta Holma, Jere Lindén, Rafael Frias, Thomas Spillmann, Pia ÖsterlundAbstract:Purpose Gastrointestinal Toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of Gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced Gastrointestinal Toxicity.
Stephen E Kimmel - One of the best experts on this subject based on the ideXlab platform.
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moderate and high affinity serotonin reuptake inhibitors increase the risk of upper Gastrointestinal Toxicity
Pharmacoepidemiology and Drug Safety, 2008Co-Authors: James D Lewis, Brian L Strom, Russell A Localio, David C Metz, John T Farrar, Robert M Weinrieb, Lisa Nessel, Colleen M Brensinger, Stephen E KimmelAbstract:Objective Serotonin release from platelets is important for regulating hemostasis. Some prior studies suggest an association between use of selective serotonin reuptake inhibitors and Gastrointestinal bleeding and a possible synergistic effect of these medications with non-steroidal anti-inflammatory drugs (NSAIDs). This study examined the effect of medications that inhibit serotonin uptake on upper Gastrointestinal Toxicity. Methods 359 case subjects hospitalized for upper Gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. 1889 control subjects were recruited by random digit dialing from the same region. Data were collected during structured telephone interviews. Antidepressant medications were characterized according to their affinity for serotonin receptors. Exposure to medications required use on at least 1 day during the week prior to the index date. Results Any moderate or high affinity serotonin reuptake inhibitor (MHA-SRI) use was reported by 61 cases (17.1%) and 197 controls (10.4%). After adjusting for potential confounders, MHA-SRI use was associated with a significantly increased odds of hospitalization for upper Gastrointestinal Toxicity (adjusted OR = 2.0, 95%CI 1.4–3.0). A dose–response relationship in terms of affinity for serotonin uptake receptors was not observed (p = 0.17). No statistical interaction was observed for use of high dose NSAIDs or aspirin concomitantly with MHA-SRIs (p = 0.5). When MHA-SRIs were used concomitantly with high dose NSAIDs, the adjusted odds ratio for the association with upper Gastrointestinal Toxicity was 3.5 (95%CI 1.9–6.6). Conclusions Use of MHA-SRIs is associated with an increased risk of hospitalization for upper Gastrointestinal Toxicity. Copyright © 2008 John Wiley & Sons, Ltd.
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risk of serious upper Gastrointestinal Toxicity with over the counter nonaspirin nonsteroidal anti inflammatory drugs
Gastroenterology, 2005Co-Authors: James D Lewis, Russell A Localio, David C Metz, John T Farrar, Lisa Nessel, Colleen M Brensinger, Stephen E Kimmel, Karen Mcgibney, Brian L StromAbstract:Background & Aims: Use of prescription nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) increases the risk of serious upper Gastrointestinal Toxicity. Less is known about over-the-counter (OTC) NANSAIDs, which are typically used at lower doses and for shorter durations. This study assessed the risk of Toxicity with OTC NANSAIDs. Methods: A total of 359 case subjects hospitalized for upper Gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. A total of 1889 control subjects were recruited by random digit dialing from the same region. Data on medication use were collected via structured telephone interview. Results: Use of OTC NANSAIDs on ≥4 days during the most recent week had an adjusted odds ratio (OR) of 1.83 (95% confidence interval [CI], 1.14–2.95). Use of high-dose OTC NANSAIDs during the index week had an adjusted OR of 5.21 (95% CI, 2.32–11.69). In contrast, use of OTC NANSAIDs Conclusions: Use of OTC NANSAIDs at recommended doses has a relatively good safety profile compared with prescription NANSAIDs. However, use of high-dose OTC NANSAIDs (comparable to a prescription dose) is associated with serious Gastrointestinal Toxicity.
