Gastroesophageal reflux disease is one of the most common conditions encountered by primary care ... more Gastroesophageal reflux disease is one of the most common conditions encountered by primary care physicians, gastroenterologists, foregut surgeons and otolaryngologists. While approximately 50% of patients experience nocturnal reflux symptoms, the relationship between gastroesophageal reflux disease and sleep is often overlooked. The aim of this review is to provide an update on the current understanding of this relationship and its clinical implications. Recent studies pertaining to the association between GERD and sleep with focus on sleep disturbances, obstructive sleep apnea, extraesophageal manifestations of GERD and treatment are discussed. There is a close relationship between GERD and sleep disturbances, but the nature of this relationship remains to be elucidated. Similarly, new data supports the association between GERD and obstructive sleep apnea, but whether this association is independent of confounding risk factors remains unresolved. Extraesophageal manifestations due...
Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to... more Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to compare the rates of febrile neutropenia (FN) between patients receiving no primary prophylaxis (PP) and those receiving PP with either granulocyte-colony stimulating factor (G-CSF) or antibiotics. We also analyzed cost-effectiveness of TC with and without either G-CSF or antibiotics. Charts were reviewed of all 340 patients who received adjuvant TC between January 2008 and December 2012 at two major cancer centers. Rates of FN in the three groups - no PP, PP with G-CSF and PP with antibiotics were compared. A Markov model was constructed comparing cost-effectiveness of PP with G-CSF, PP with antibiotics, and secondary prophylaxis (SP) with G-CSF after an episode of FN in a previous cycle. Costs were based on actual resource utilization and supplemented by the published literature, adjusted to 2012 Canadian dollars. Of the 73 (21%) patients who did not receive any PP, 23 (32%) of patients developed FN. Of the 192 (57%) patients receiving PP with G-CSF alone, only two (1%; p < 0.0001) developed FN; and of the 53 (16%) receiving PP with antibiotics alone, six (11%; p < 0.01) developed FN. From a cost-standpoint, PP with G-CSF was less cost-effective than PP with antibiotics. The rate of FN with TC chemotherapy exceeds 30%, and American Society of Clinical Oncology guidelines recommend PP with G-CSF in this situation. PP with antibiotics is more cost-effective, and is a reasonable option in resource-limited settings or for patients who decline or do not tolerate G-CSF.
Therapies for prostate cancer based on Fas (CD95) modulation have been under active development a... more Therapies for prostate cancer based on Fas (CD95) modulation have been under active development at the preclinical stage using immortalized cell lines. To address clinical applicability, the potential of 11 cultures of primary prostate cancer cells to be killed by Fas-mediated apoptosis was investigated. In addition, the effect of the chemotherapeutic agents mitoxantrone and docetaxel on this killing was determined. Apoptosis was induced in patient-derived, primary prostate cancer cells using effector cells engineered by recombinant lentivirus infection to express Fas ligand (FasL) and measured by 51Cr release assays. All cultured prostate cells were found to undergo Fas-mediated killing; cytotoxicity ranged from 12% to 87% after 6 h. These cells were significantly more sensitive to FasL-mediated killing than PC-3 cells. The basal expression of Fas or the expression of five inhibitors of apoptosis (c-FLIP, survivin, cellular inhibitors of apoptosis protein 1 and 2, and bcl-2) was not found to correlate with susceptibility to Fas-mediated killing. Both mitoxantrone and docetaxel were able to induce Fas receptor expression on primary prostate cancer cells, which translated into a 1.5- to 3-fold enhancement of apoptosis mediated by FasL. Whereas mitoxantrone increased the Fas-induced apoptotic response of all cultured prostate cells tested, docetaxel pretreatment was found to preferentially enhance the killing of bcl-2-expressing cells. These findings show that cultured primary prostate cancer cells are sensitive to Fas-mediated apoptosis. Furthermore, the incidence of apoptosis was found to be improved by combining Fas-mediated therapy with standard chemotherapeutic agents. These findings may have significant implications for prostate cancer therapy.
Yellow nail syndrome is a rare disorder involving characteristic nail changes, lymphedema and chr... more Yellow nail syndrome is a rare disorder involving characteristic nail changes, lymphedema and chronic respiratory symptoms. Currently there is no definitive treatment and there have been no prospective randomised controlled trials evaluating the available options. In order to strengthen the literature on this topic, we present the case of a 67-year-old man with YNS and a detailed review of current treatment options. We included 40 articles for the final review according to their relevance with the subject. Data for use of the commonly chosen therapies for YNS remains inconclusive, with small studies and case reports showing mixed results of efficacy. Although the date indicates that it is reasonable to recommend a trial of conservative therapy including vitamin E, antibiotics and compression stockings before pursuing more aggressive or invasive modalities, larger scale studies are required to determine the true efficacy of all treatment options.
Gastroesophageal reflux disease is one of the most common conditions encountered by primary care ... more Gastroesophageal reflux disease is one of the most common conditions encountered by primary care physicians, gastroenterologists, foregut surgeons and otolaryngologists. While approximately 50% of patients experience nocturnal reflux symptoms, the relationship between gastroesophageal reflux disease and sleep is often overlooked. The aim of this review is to provide an update on the current understanding of this relationship and its clinical implications. Recent studies pertaining to the association between GERD and sleep with focus on sleep disturbances, obstructive sleep apnea, extraesophageal manifestations of GERD and treatment are discussed. There is a close relationship between GERD and sleep disturbances, but the nature of this relationship remains to be elucidated. Similarly, new data supports the association between GERD and obstructive sleep apnea, but whether this association is independent of confounding risk factors remains unresolved. Extraesophageal manifestations due...
Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to... more Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to compare the rates of febrile neutropenia (FN) between patients receiving no primary prophylaxis (PP) and those receiving PP with either granulocyte-colony stimulating factor (G-CSF) or antibiotics. We also analyzed cost-effectiveness of TC with and without either G-CSF or antibiotics. Charts were reviewed of all 340 patients who received adjuvant TC between January 2008 and December 2012 at two major cancer centers. Rates of FN in the three groups - no PP, PP with G-CSF and PP with antibiotics were compared. A Markov model was constructed comparing cost-effectiveness of PP with G-CSF, PP with antibiotics, and secondary prophylaxis (SP) with G-CSF after an episode of FN in a previous cycle. Costs were based on actual resource utilization and supplemented by the published literature, adjusted to 2012 Canadian dollars. Of the 73 (21%) patients who did not receive any PP, 23 (32%) of patients developed FN. Of the 192 (57%) patients receiving PP with G-CSF alone, only two (1%; p < 0.0001) developed FN; and of the 53 (16%) receiving PP with antibiotics alone, six (11%; p < 0.01) developed FN. From a cost-standpoint, PP with G-CSF was less cost-effective than PP with antibiotics. The rate of FN with TC chemotherapy exceeds 30%, and American Society of Clinical Oncology guidelines recommend PP with G-CSF in this situation. PP with antibiotics is more cost-effective, and is a reasonable option in resource-limited settings or for patients who decline or do not tolerate G-CSF.
Therapies for prostate cancer based on Fas (CD95) modulation have been under active development a... more Therapies for prostate cancer based on Fas (CD95) modulation have been under active development at the preclinical stage using immortalized cell lines. To address clinical applicability, the potential of 11 cultures of primary prostate cancer cells to be killed by Fas-mediated apoptosis was investigated. In addition, the effect of the chemotherapeutic agents mitoxantrone and docetaxel on this killing was determined. Apoptosis was induced in patient-derived, primary prostate cancer cells using effector cells engineered by recombinant lentivirus infection to express Fas ligand (FasL) and measured by 51Cr release assays. All cultured prostate cells were found to undergo Fas-mediated killing; cytotoxicity ranged from 12% to 87% after 6 h. These cells were significantly more sensitive to FasL-mediated killing than PC-3 cells. The basal expression of Fas or the expression of five inhibitors of apoptosis (c-FLIP, survivin, cellular inhibitors of apoptosis protein 1 and 2, and bcl-2) was not found to correlate with susceptibility to Fas-mediated killing. Both mitoxantrone and docetaxel were able to induce Fas receptor expression on primary prostate cancer cells, which translated into a 1.5- to 3-fold enhancement of apoptosis mediated by FasL. Whereas mitoxantrone increased the Fas-induced apoptotic response of all cultured prostate cells tested, docetaxel pretreatment was found to preferentially enhance the killing of bcl-2-expressing cells. These findings show that cultured primary prostate cancer cells are sensitive to Fas-mediated apoptosis. Furthermore, the incidence of apoptosis was found to be improved by combining Fas-mediated therapy with standard chemotherapeutic agents. These findings may have significant implications for prostate cancer therapy.
Yellow nail syndrome is a rare disorder involving characteristic nail changes, lymphedema and chr... more Yellow nail syndrome is a rare disorder involving characteristic nail changes, lymphedema and chronic respiratory symptoms. Currently there is no definitive treatment and there have been no prospective randomised controlled trials evaluating the available options. In order to strengthen the literature on this topic, we present the case of a 67-year-old man with YNS and a detailed review of current treatment options. We included 40 articles for the final review according to their relevance with the subject. Data for use of the commonly chosen therapies for YNS remains inconclusive, with small studies and case reports showing mixed results of efficacy. Although the date indicates that it is reasonable to recommend a trial of conservative therapy including vitamin E, antibiotics and compression stockings before pursuing more aggressive or invasive modalities, larger scale studies are required to determine the true efficacy of all treatment options.
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Papers by Michael Kurin