Saleem Haj-Yahia | An-Najah National University (original) (raw)
Papers by Saleem Haj-Yahia
PLOS ONE
Background The longitudinal association of posttraumatic stress disorder (PTSD) with health-relat... more Background The longitudinal association of posttraumatic stress disorder (PTSD) with health-related quality of life (HRQL) in cardiac patients’ remains poorly studied, particularly in conflict-affected settings. Materials and methods For this cohort study, we used baseline and one-year follow-up data collected from patients 30 to 80 years old consecutively admitted with a cardiac diagnosis to four major hospitals in Nablus, Palestine. All subjects were screened for PTSD and HRQL using the PTSD Checklist Specific and the HeartQoL questionnaire. We used a generalized structural equation model (GSEM) to examine the independent predictive association of PTSD at baseline with HRQL at follow-up. We also examined the mediating roles of depression, anxiety, and stress at baseline. Results The prevalence of moderate-to-high PTSD symptoms among 1022 patients at baseline was 27∙0%. Patients with PTSD symptoms reported an approximate 20∙0% lower HRQL at follow-up. The PTSD and HRQL relationship...
The Journal of Thoracic and Cardiovascular Surgery, Feb 1, 2008
Journal of Heart and Lung Transplantation, Feb 1, 2007
Infectious complications are a major cause for morbidity and mortality in children following lung... more Infectious complications are a major cause for morbidity and mortality in children following lung transplantation. Further, lung transplant candidates and recipients are at high risk of infections from vaccine preventable diseases. However, well established vaccination and monitoring guidelines do not exist. We explored the current vaccination and monitoring guidelines of pediatric lung transplant centers. Methods and Materials: In April 2006, a self-administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative (Canada/Europe/USA). One member of each lung transplant centre provided information regarding vaccination guidelines in children before and after lung transplantation. Descriptive statistic analysis was used to analyze data. Results: Sixteen of 18 centers (89%) surveyed responded to the questionnaire. Pre-transplant, national vaccination guidelines are followed. Eleven centers reported post-transplant vaccination guidelines. Vaccine was more commonly provided by the primary care physician pre-transplant (69%) than post-transplant (38%). 56% of transplant centers do not delay transplantation due to administration of live virus vaccination, but aim to wait for a minimum of 3-4 weeks between live virus vaccine administration and possible transplantation. Post-transplant, 50% of centers recommend live vaccines for household contacts. Pre-transplant monitoring of response to prior vaccination was performed rarely except for varicella (88%). Only 44% of transplant centers measure for response to vaccination post-transplant, mostly hepatitis B. Conclusions: Current vaccination guidelines of pediatric lung transplant centers are heterogeneous. There is little knowledge with regards to vaccine response in children following lung transplantation.
The Annals of Thoracic Surgery, Oct 1, 2006
@ rbh.nthames.nhs.uk. Fig 1. Showing sites of minimally invasive incision (dashed line) and the p... more @ rbh.nthames.nhs.uk. Fig 1. Showing sites of minimally invasive incision (dashed line) and the position of the right ventricular assist device and inflow and outflow cannulas.
Journal of Heart and Lung Transplantation, Feb 1, 2004
Conclusions: Donor management with invasive monitoring and hormonal substitution improves the hae... more Conclusions: Donor management with invasive monitoring and hormonal substitution improves the haemodynamics of brainstem dead potential donors. The time required to establish optimise haemodynamic parameters is approximately 2 hours, which can then be maintained for a further 4 hours.
Journal of Heart and Lung Transplantation, Feb 1, 2007
, we performed 5 tests in 4 patients (Table). Two patients (#1, #2) tolerated the UWWP and were e... more , we performed 5 tests in 4 patients (Table). Two patients (#1, #2) tolerated the UWWP and were explanted. Patient #3 failed the first test because of high wedge pressure (Ͼ25mmHg). Medical therapy was intensified and when tested at 167 days of support, he passed and had successful explant. There has been no recurrence of heart failure 437, 97 and 182 days after explant, respectively. Patient #4 did not pass after 151 days of support because of low cardiac index (Ͻ2.0 l/min/m2) and gradual ventricular dilation and remains on VAD support. Conclusions: We describe the UWWP, a useful tool to identify candidates for successful VAD explantation. Myocardial recovery is expected in some patients and the UWWP can assist with timing of explant.
Human Immunology, Aug 1, 2005
Background: Renal allografts transplanted in the presence of donor specific HLA alloantibodies ar... more Background: Renal allografts transplanted in the presence of donor specific HLA alloantibodies are at risk of hyperacute rejection. Artificial antibody removal can render a positive crossmatch negative to allow a successful transplant. In order to monitor the efeectiveness of the removal process and to identify reemergence of donor specific antibody following transplantation, a precise and rapid testing of antibody levels is required. Methods: Two patients undergoing antibody removal by plasma exchange (PE) were studied. Each had antibody specific for HLA class II mismatches in their potential live donor (DR15 and DR53 respectively). Antibody specificity and levels were characterised using a luminex based assay. Results: Using Luminex we were able to track quantitative and qualitative changes in donor specific antibodies during successive rounds of PE. Antibody specificity and level were reported within 3 hours of receiving a sample. Reductions in antibody level measured by Luminex correlated with both cytotoxic antibody titre and with strength of donor-specific crossmatch measured by FACS. We monitored one patient post-transplant and could clearly demonstrate the reemergence then modulation of donor-specific antibody despite the presence and sustained high level of third party specific antibody. Conclusion: Monitoring antibody removal by Luminex is rapid and reliable and is a quicker and more consistent alternative to traditional cell-based methods of determining antibody strength. Evaluating antibody specificity and level in real time allows monitoring of antibody removal and the ability to respond effectively to post-transplant reemergence of donor-specific antibody.
Journal of Heart and Lung Transplantation, Feb 1, 2009
Anti-human leukocyte antigen (HLA) antibodies in the recipient are considered a risk factor for a... more Anti-human leukocyte antigen (HLA) antibodies in the recipient are considered a risk factor for allograft rejection and poor graft survival.Techniques including flow cytometry and solid-phase assays allow predetermination of HLA antibody specificity. The Virtual Crossmatch (VXM) strategy utilizes the results of this antibody screening to predict acceptable HLA mismatches.We reviewed our clinical experience with the use of the VXM and its influence on lung transplant (LTx) outcomes. Methods and Materials: 478 LTx performed between January 2003 and June 2008 were analyzed retrospectively.119 patients patients(24.8%) had HLA-specific antibodies determined by ELISA and Luminex (sensitized group) and VXM was used to pair the donor HLA antigens to the precharacterized antibody specificity of the recipient. Results: Age at the time of LTX was 54 years.71 patients (60%) were female and double LTx was performed in 73 patients (61%) in the sensitized group. The LAS score and ELISA PRA previous to transplantation was 45.2 : 44.5 and 27 : 3 for the sensitized and non sensitized patients with an average waiting time on the list of 257 and 249 days (pϭ0.86). 5 patients died waiting transplantation in each group.No difference in postoperative mortality was noted (pϭ0.07).Acute celular rejection (ՆGrade 2) ocurred in 60 patients (2.8 episodes /pt) in the sensitized population and 302 patients in the control group (2.0 episodes /pt) (pϭ 0.06).The 1 and 5 year Kaplan Meier survival is presented. Conclusions: The use of the VXM strategy in patients with HLAspecific antibodies allow adequate and timely donor selection with comparable outcomes to the non-sensitized population .This technique could be safely used as an alternative to prospective crossmatch.
The Journal of Thoracic and Cardiovascular Surgery, May 1, 2007
Journal of Biological Chemistry, Nov 1, 2007
The liver X receptors (LXR␣/) are part of the nuclear receptor family and are believed to regula... more The liver X receptors (LXR␣/) are part of the nuclear receptor family and are believed to regulate cholesterol and lipid homeostasis. It has also been suggested that LXR agonists possess anti-inflammatory properties. The aim of this work was to determine the effect of LXR agonists on the innate immune response in human primary lung macrophages and a pre-clinical rodent model of lung inflammation. Before profiling the impact of the agonist, we established that both the human macrophages and the rodent lungs expressed LXR␣/. We then used two structurally distinct LXR agonists to demonstrate that activation of this transcription factor reduces cytokine production in THP-1 cells and lung macrophages. Then, using the expression profile of ATP binding cassettes A1 (ABCA-1; a gene directly linked to LXR activation) as a biomarker for lung exposure of the compound, we demonstrated an LXR-dependent reduction in lung neutrophilia rodents in vivo. This inhibition was not associated with a suppression of c-Fos/c-Jun mRNA expression or NF-B/AP-1 DNA binding, suggesting that any anti-inflammatory activity of LXR agonists is not via inhibition of NF-B/AP-1 transcriptional activity. These data do not completely rule out an impact of these agonists on these two prominent transcription factors. In summary, this study is the first to demonstrate anti-inflammatory actions of LXRs in the lung. Chronic innate inflammatory responses observed in some airway diseases is thought to be central to disease pathogenesis. Therefore, data suggest that LXR ligands have utility in the treatment of lung diseases that involves chronic inflammation mediated by macrophages and neutrophils.
Journal of Pharmacology and Experimental Therapeutics, Dec 20, 2005
The exact role of p38 mitogen-activated protein kinase (MAPK) in the expression of inflammatory c... more The exact role of p38 mitogen-activated protein kinase (MAPK) in the expression of inflammatory cytokines is not clear; it may regulate transcriptionally, post-transcriptionally, translationally, or post-translationally. The involvement of one or more of these mechanisms has been suggested to depend on the particular cytokine, the cell type studied, and the specific stimulus used. Interpretation of some of the published data is further complicated by the use of inhibitors such as 4-(4-fluorophenyl)-2-(4methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB 203580) used at single, high concentrations. The aim of this study was to determine the impact of two second-generation p38 MAPK inhibitors on the expression of a range of inflammatory cytokines at the gene and protein levels in human cultured cells. Similar assessment of the impact of these compounds on inflammatory cytokine expression in a preclinical in vivo model Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
American Journal of Respiratory and Critical Care Medicine, Oct 15, 2005
Rationale: Nuclear factor (NF)-B is a transcription factor known to regulate the expression of ma... more Rationale: Nuclear factor (NF)-B is a transcription factor known to regulate the expression of many inflammatory genes, including cytokines, chemokines, and adhesion molecules. NF-B is held inactive in the cytoplasm, bound to I-B. The removal of I-B, via the actions of inhibitor of B (I-B) kinase-2 (IKK-2), allows NF-B to enter the nucleus. Objectives: To determine the impact of inhibiting IKK-2 on in vitro and in vivo models of airway inflammation. Methods: The effect of inhibiting IKK-2 was assessed in stimulated, cultured, primary human airway smooth muscle cells and an antigendriven rat model of lung inflammation. Measurements: The release of cytokines from cultured cells and inflammatory cytokine expression and cellular burden in the lung were determined. Main Results: Two structurally distinct molecules and dominant negative technology demonstrated that inhibition of IKK-2 activity completely blocked cytokine release from cultured cells, whereas the two glucocorticoid comparators had limited impact on granulocyte colony-stimulating factor, interleukin 8, and eotaxin release. In addition, in an in vivo antigen-driven model of airway inflammation, the IKK-2 inhibitor blocked NF-B nuclear translocation, which was associated with a reduction in inflammatory cytokine gene and protein expression, airway eosinophilia, and late asthmatic reaction, similar in magnitude to that obtained with budesonide. Conclusion: This study demonstrates that inhibiting IKK-2 results in a general reduction of the inflammatory response in vitro and in vivo. Compounds of this class could have therapeutic utility in the treatment of asthma and may, in certain respects, possess a beneficial efficacy profile compared with that of a steroid.
The European respiratory journal, Aug 13, 2009
2-agonists are also antitussive is controversial. Identifying an antitussive role for b 2-agonist... more 2-agonists are also antitussive is controversial. Identifying an antitussive role for b 2-agonists and dissecting the possible mechanism of action may help to explain the inconsistencies in the clinical literature and lead to the development of novel therapeutic agents. The aim of the present study was to determine whether or not b 2-agonists attenuate the tussive response in guinea pig and human models, and, if so, to identify the mechanism(s) involved. Depolarisation of vagal sensory nerves (human and guinea pig) was assessed as an indicator of sensory nerve activity. Cough was measured in a conscious guinea pig model. A b 2-agonist, terbutaline, dose-dependently inhibited the cough response to tussive agents in conscious guinea pigs. Terbutaline and another b 2-agonist, fenoterol, blocked sensory nerve activation in vitro. Using these mechanistic models, it was established that b 2-agonists suppress the tussive response via a nonclassical cyclic adenosine monosphosphate-dependent pathway that involves the activation of protein kinase G and, subsequently, the opening of largeconductance calcium-activated potassium channels. In conclusion, b 2-adrenoceptor agonists are antitussive, and this property occurs due to a direct inhibition of sensory nerve activation. These findings may help to explain the confusion that exists in the clinical literature, and could be exploited to identify novel therapies for the treatment of cough, which is a significant unmet medical need.
Journal of Cardiothoracic Surgery, Jan 8, 2019
The original article [1] contained an error whereby the author, Ahmad Darwazah's name was spelt i... more The original article [1] contained an error whereby the author, Ahmad Darwazah's name was spelt incorrectly. This error has now been corrected.
Journal of Cardiothoracic Surgery, Oct 26, 2018
Background: Idiopathic pulmonary artery aneurysm is a rare anomaly with only a handful reports in... more Background: Idiopathic pulmonary artery aneurysm is a rare anomaly with only a handful reports in the literature. It is often asymptomatic, while the first presentation could be severe hemoptysis or death. Surgical intervention needs to be planned carefully with a multidisciplinary team approach to secure optimal outcome. We hope to spread our experience with such cases and to encourage other surgeons worldwide to deal surgically with these cases when its indicated. Case presentation: A 47 years old man presented to our institution after three episodes of hemoptysis, echo demonstrated good left ventricle (LV) systolic function, normal right ventricle (RV) size and function, Chest computed tomography (CT) revealed aneurysmal dilatation with pending rupture of the pulmonary artery trunk (4.5 cm), the left pulmonary artery (6 cm) and the right pulmonary artery (2.3 cm). The patient successfully underwent replacement of Pulmonary artery trunk, left pulmonary artery and right pulmonary artery by Wovex Prosthetic graft (28 mm). The patient discharged home on the eight postoperative day in good clinical condition. Conclusion: With this case report we wish to emphasize the need for a careful multidisciplinary approach given the complex and rare nature of the reported pathology.
Expert Review of Medical Devices, Sep 28, 2015
Sudden cardiac death related to polymorphic ventricular tachycardia/ventricular fibrillation has ... more Sudden cardiac death related to polymorphic ventricular tachycardia/ventricular fibrillation has been well reported post atrioventricular junction ablation. The practice of faster pacing rate immediately after atrioventricular junction ablation is well recognized to decrease the risk of sudden cardiac death. We propose that this practice (faster pacing rate) be implemented in patients who need permanent pacemakers secondary to transcatheter aortic valve implantation (or even surgical aortic valve interventions).
Journal of Cardiothoracic Surgery, Feb 27, 2020
Introduction: Complications following Cardiopulmonary resuscitation (CPR) are rare and usually fo... more Introduction: Complications following Cardiopulmonary resuscitation (CPR) are rare and usually follows a vigorous CPR or in special cases like pregnancy are due to lack of knowledge and clinical practice of how to preform CPR in pregnancy. One of this complication is diaphragmatic rupture with herniation of abdominal organs. Surgical intervention needs to be planned carefully in multidisciplinary team approach and requires fine surgical techniques for better outcome. There are few reported cases of diaphragmatic rupture after Cardiopulmonary resuscitation but none in pregnant woman. Case presentation: We report a rare case of diaphragmatic rupture in a 29-year-old pregnant patient who experienced a full-blown diaphragmatic defect and herniation of the abdominal organs into the thoracic cavity, as a complication of CPR. Following careful assessment and diagnosis, the patient underwent urgent laparotomy with reduction of the contents and primary closure of the defect. One year follow up was satisfactory. To the best of our knowledge, this is the first reported case of diaphragmatic rupture with herniation of the abdominal organs following CPR in a pregnant woman in the literature. Conclusion: The application of external cardiac massage through CPR is a life-saving procedure for the management of cardiac arrest. Common complications related to CPR include rib fractures, sternal fractures and haemothorax. Diaphragmatic rupture with herniation of the abdominal organs is a rare complication, having been reported only once in the literature (Sabzi F, Faraji R, Tanaffos 16:170-172, 2017); however, it represents a serious and life-threating event. Thus, careful evaluation of the patient by a multidisciplinary team and prompt intervention is recommended in order to improve outcomes.
Canadian Journal of Cardiology, 2016
PLOS ONE
Background The longitudinal association of posttraumatic stress disorder (PTSD) with health-relat... more Background The longitudinal association of posttraumatic stress disorder (PTSD) with health-related quality of life (HRQL) in cardiac patients’ remains poorly studied, particularly in conflict-affected settings. Materials and methods For this cohort study, we used baseline and one-year follow-up data collected from patients 30 to 80 years old consecutively admitted with a cardiac diagnosis to four major hospitals in Nablus, Palestine. All subjects were screened for PTSD and HRQL using the PTSD Checklist Specific and the HeartQoL questionnaire. We used a generalized structural equation model (GSEM) to examine the independent predictive association of PTSD at baseline with HRQL at follow-up. We also examined the mediating roles of depression, anxiety, and stress at baseline. Results The prevalence of moderate-to-high PTSD symptoms among 1022 patients at baseline was 27∙0%. Patients with PTSD symptoms reported an approximate 20∙0% lower HRQL at follow-up. The PTSD and HRQL relationship...
The Journal of Thoracic and Cardiovascular Surgery, Feb 1, 2008
Journal of Heart and Lung Transplantation, Feb 1, 2007
Infectious complications are a major cause for morbidity and mortality in children following lung... more Infectious complications are a major cause for morbidity and mortality in children following lung transplantation. Further, lung transplant candidates and recipients are at high risk of infections from vaccine preventable diseases. However, well established vaccination and monitoring guidelines do not exist. We explored the current vaccination and monitoring guidelines of pediatric lung transplant centers. Methods and Materials: In April 2006, a self-administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative (Canada/Europe/USA). One member of each lung transplant centre provided information regarding vaccination guidelines in children before and after lung transplantation. Descriptive statistic analysis was used to analyze data. Results: Sixteen of 18 centers (89%) surveyed responded to the questionnaire. Pre-transplant, national vaccination guidelines are followed. Eleven centers reported post-transplant vaccination guidelines. Vaccine was more commonly provided by the primary care physician pre-transplant (69%) than post-transplant (38%). 56% of transplant centers do not delay transplantation due to administration of live virus vaccination, but aim to wait for a minimum of 3-4 weeks between live virus vaccine administration and possible transplantation. Post-transplant, 50% of centers recommend live vaccines for household contacts. Pre-transplant monitoring of response to prior vaccination was performed rarely except for varicella (88%). Only 44% of transplant centers measure for response to vaccination post-transplant, mostly hepatitis B. Conclusions: Current vaccination guidelines of pediatric lung transplant centers are heterogeneous. There is little knowledge with regards to vaccine response in children following lung transplantation.
The Annals of Thoracic Surgery, Oct 1, 2006
@ rbh.nthames.nhs.uk. Fig 1. Showing sites of minimally invasive incision (dashed line) and the p... more @ rbh.nthames.nhs.uk. Fig 1. Showing sites of minimally invasive incision (dashed line) and the position of the right ventricular assist device and inflow and outflow cannulas.
Journal of Heart and Lung Transplantation, Feb 1, 2004
Conclusions: Donor management with invasive monitoring and hormonal substitution improves the hae... more Conclusions: Donor management with invasive monitoring and hormonal substitution improves the haemodynamics of brainstem dead potential donors. The time required to establish optimise haemodynamic parameters is approximately 2 hours, which can then be maintained for a further 4 hours.
Journal of Heart and Lung Transplantation, Feb 1, 2007
, we performed 5 tests in 4 patients (Table). Two patients (#1, #2) tolerated the UWWP and were e... more , we performed 5 tests in 4 patients (Table). Two patients (#1, #2) tolerated the UWWP and were explanted. Patient #3 failed the first test because of high wedge pressure (Ͼ25mmHg). Medical therapy was intensified and when tested at 167 days of support, he passed and had successful explant. There has been no recurrence of heart failure 437, 97 and 182 days after explant, respectively. Patient #4 did not pass after 151 days of support because of low cardiac index (Ͻ2.0 l/min/m2) and gradual ventricular dilation and remains on VAD support. Conclusions: We describe the UWWP, a useful tool to identify candidates for successful VAD explantation. Myocardial recovery is expected in some patients and the UWWP can assist with timing of explant.
Human Immunology, Aug 1, 2005
Background: Renal allografts transplanted in the presence of donor specific HLA alloantibodies ar... more Background: Renal allografts transplanted in the presence of donor specific HLA alloantibodies are at risk of hyperacute rejection. Artificial antibody removal can render a positive crossmatch negative to allow a successful transplant. In order to monitor the efeectiveness of the removal process and to identify reemergence of donor specific antibody following transplantation, a precise and rapid testing of antibody levels is required. Methods: Two patients undergoing antibody removal by plasma exchange (PE) were studied. Each had antibody specific for HLA class II mismatches in their potential live donor (DR15 and DR53 respectively). Antibody specificity and levels were characterised using a luminex based assay. Results: Using Luminex we were able to track quantitative and qualitative changes in donor specific antibodies during successive rounds of PE. Antibody specificity and level were reported within 3 hours of receiving a sample. Reductions in antibody level measured by Luminex correlated with both cytotoxic antibody titre and with strength of donor-specific crossmatch measured by FACS. We monitored one patient post-transplant and could clearly demonstrate the reemergence then modulation of donor-specific antibody despite the presence and sustained high level of third party specific antibody. Conclusion: Monitoring antibody removal by Luminex is rapid and reliable and is a quicker and more consistent alternative to traditional cell-based methods of determining antibody strength. Evaluating antibody specificity and level in real time allows monitoring of antibody removal and the ability to respond effectively to post-transplant reemergence of donor-specific antibody.
Journal of Heart and Lung Transplantation, Feb 1, 2009
Anti-human leukocyte antigen (HLA) antibodies in the recipient are considered a risk factor for a... more Anti-human leukocyte antigen (HLA) antibodies in the recipient are considered a risk factor for allograft rejection and poor graft survival.Techniques including flow cytometry and solid-phase assays allow predetermination of HLA antibody specificity. The Virtual Crossmatch (VXM) strategy utilizes the results of this antibody screening to predict acceptable HLA mismatches.We reviewed our clinical experience with the use of the VXM and its influence on lung transplant (LTx) outcomes. Methods and Materials: 478 LTx performed between January 2003 and June 2008 were analyzed retrospectively.119 patients patients(24.8%) had HLA-specific antibodies determined by ELISA and Luminex (sensitized group) and VXM was used to pair the donor HLA antigens to the precharacterized antibody specificity of the recipient. Results: Age at the time of LTX was 54 years.71 patients (60%) were female and double LTx was performed in 73 patients (61%) in the sensitized group. The LAS score and ELISA PRA previous to transplantation was 45.2 : 44.5 and 27 : 3 for the sensitized and non sensitized patients with an average waiting time on the list of 257 and 249 days (pϭ0.86). 5 patients died waiting transplantation in each group.No difference in postoperative mortality was noted (pϭ0.07).Acute celular rejection (ՆGrade 2) ocurred in 60 patients (2.8 episodes /pt) in the sensitized population and 302 patients in the control group (2.0 episodes /pt) (pϭ 0.06).The 1 and 5 year Kaplan Meier survival is presented. Conclusions: The use of the VXM strategy in patients with HLAspecific antibodies allow adequate and timely donor selection with comparable outcomes to the non-sensitized population .This technique could be safely used as an alternative to prospective crossmatch.
The Journal of Thoracic and Cardiovascular Surgery, May 1, 2007
Journal of Biological Chemistry, Nov 1, 2007
The liver X receptors (LXR␣/) are part of the nuclear receptor family and are believed to regula... more The liver X receptors (LXR␣/) are part of the nuclear receptor family and are believed to regulate cholesterol and lipid homeostasis. It has also been suggested that LXR agonists possess anti-inflammatory properties. The aim of this work was to determine the effect of LXR agonists on the innate immune response in human primary lung macrophages and a pre-clinical rodent model of lung inflammation. Before profiling the impact of the agonist, we established that both the human macrophages and the rodent lungs expressed LXR␣/. We then used two structurally distinct LXR agonists to demonstrate that activation of this transcription factor reduces cytokine production in THP-1 cells and lung macrophages. Then, using the expression profile of ATP binding cassettes A1 (ABCA-1; a gene directly linked to LXR activation) as a biomarker for lung exposure of the compound, we demonstrated an LXR-dependent reduction in lung neutrophilia rodents in vivo. This inhibition was not associated with a suppression of c-Fos/c-Jun mRNA expression or NF-B/AP-1 DNA binding, suggesting that any anti-inflammatory activity of LXR agonists is not via inhibition of NF-B/AP-1 transcriptional activity. These data do not completely rule out an impact of these agonists on these two prominent transcription factors. In summary, this study is the first to demonstrate anti-inflammatory actions of LXRs in the lung. Chronic innate inflammatory responses observed in some airway diseases is thought to be central to disease pathogenesis. Therefore, data suggest that LXR ligands have utility in the treatment of lung diseases that involves chronic inflammation mediated by macrophages and neutrophils.
Journal of Pharmacology and Experimental Therapeutics, Dec 20, 2005
The exact role of p38 mitogen-activated protein kinase (MAPK) in the expression of inflammatory c... more The exact role of p38 mitogen-activated protein kinase (MAPK) in the expression of inflammatory cytokines is not clear; it may regulate transcriptionally, post-transcriptionally, translationally, or post-translationally. The involvement of one or more of these mechanisms has been suggested to depend on the particular cytokine, the cell type studied, and the specific stimulus used. Interpretation of some of the published data is further complicated by the use of inhibitors such as 4-(4-fluorophenyl)-2-(4methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB 203580) used at single, high concentrations. The aim of this study was to determine the impact of two second-generation p38 MAPK inhibitors on the expression of a range of inflammatory cytokines at the gene and protein levels in human cultured cells. Similar assessment of the impact of these compounds on inflammatory cytokine expression in a preclinical in vivo model Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
American Journal of Respiratory and Critical Care Medicine, Oct 15, 2005
Rationale: Nuclear factor (NF)-B is a transcription factor known to regulate the expression of ma... more Rationale: Nuclear factor (NF)-B is a transcription factor known to regulate the expression of many inflammatory genes, including cytokines, chemokines, and adhesion molecules. NF-B is held inactive in the cytoplasm, bound to I-B. The removal of I-B, via the actions of inhibitor of B (I-B) kinase-2 (IKK-2), allows NF-B to enter the nucleus. Objectives: To determine the impact of inhibiting IKK-2 on in vitro and in vivo models of airway inflammation. Methods: The effect of inhibiting IKK-2 was assessed in stimulated, cultured, primary human airway smooth muscle cells and an antigendriven rat model of lung inflammation. Measurements: The release of cytokines from cultured cells and inflammatory cytokine expression and cellular burden in the lung were determined. Main Results: Two structurally distinct molecules and dominant negative technology demonstrated that inhibition of IKK-2 activity completely blocked cytokine release from cultured cells, whereas the two glucocorticoid comparators had limited impact on granulocyte colony-stimulating factor, interleukin 8, and eotaxin release. In addition, in an in vivo antigen-driven model of airway inflammation, the IKK-2 inhibitor blocked NF-B nuclear translocation, which was associated with a reduction in inflammatory cytokine gene and protein expression, airway eosinophilia, and late asthmatic reaction, similar in magnitude to that obtained with budesonide. Conclusion: This study demonstrates that inhibiting IKK-2 results in a general reduction of the inflammatory response in vitro and in vivo. Compounds of this class could have therapeutic utility in the treatment of asthma and may, in certain respects, possess a beneficial efficacy profile compared with that of a steroid.
The European respiratory journal, Aug 13, 2009
2-agonists are also antitussive is controversial. Identifying an antitussive role for b 2-agonist... more 2-agonists are also antitussive is controversial. Identifying an antitussive role for b 2-agonists and dissecting the possible mechanism of action may help to explain the inconsistencies in the clinical literature and lead to the development of novel therapeutic agents. The aim of the present study was to determine whether or not b 2-agonists attenuate the tussive response in guinea pig and human models, and, if so, to identify the mechanism(s) involved. Depolarisation of vagal sensory nerves (human and guinea pig) was assessed as an indicator of sensory nerve activity. Cough was measured in a conscious guinea pig model. A b 2-agonist, terbutaline, dose-dependently inhibited the cough response to tussive agents in conscious guinea pigs. Terbutaline and another b 2-agonist, fenoterol, blocked sensory nerve activation in vitro. Using these mechanistic models, it was established that b 2-agonists suppress the tussive response via a nonclassical cyclic adenosine monosphosphate-dependent pathway that involves the activation of protein kinase G and, subsequently, the opening of largeconductance calcium-activated potassium channels. In conclusion, b 2-adrenoceptor agonists are antitussive, and this property occurs due to a direct inhibition of sensory nerve activation. These findings may help to explain the confusion that exists in the clinical literature, and could be exploited to identify novel therapies for the treatment of cough, which is a significant unmet medical need.
Journal of Cardiothoracic Surgery, Jan 8, 2019
The original article [1] contained an error whereby the author, Ahmad Darwazah's name was spelt i... more The original article [1] contained an error whereby the author, Ahmad Darwazah's name was spelt incorrectly. This error has now been corrected.
Journal of Cardiothoracic Surgery, Oct 26, 2018
Background: Idiopathic pulmonary artery aneurysm is a rare anomaly with only a handful reports in... more Background: Idiopathic pulmonary artery aneurysm is a rare anomaly with only a handful reports in the literature. It is often asymptomatic, while the first presentation could be severe hemoptysis or death. Surgical intervention needs to be planned carefully with a multidisciplinary team approach to secure optimal outcome. We hope to spread our experience with such cases and to encourage other surgeons worldwide to deal surgically with these cases when its indicated. Case presentation: A 47 years old man presented to our institution after three episodes of hemoptysis, echo demonstrated good left ventricle (LV) systolic function, normal right ventricle (RV) size and function, Chest computed tomography (CT) revealed aneurysmal dilatation with pending rupture of the pulmonary artery trunk (4.5 cm), the left pulmonary artery (6 cm) and the right pulmonary artery (2.3 cm). The patient successfully underwent replacement of Pulmonary artery trunk, left pulmonary artery and right pulmonary artery by Wovex Prosthetic graft (28 mm). The patient discharged home on the eight postoperative day in good clinical condition. Conclusion: With this case report we wish to emphasize the need for a careful multidisciplinary approach given the complex and rare nature of the reported pathology.
Expert Review of Medical Devices, Sep 28, 2015
Sudden cardiac death related to polymorphic ventricular tachycardia/ventricular fibrillation has ... more Sudden cardiac death related to polymorphic ventricular tachycardia/ventricular fibrillation has been well reported post atrioventricular junction ablation. The practice of faster pacing rate immediately after atrioventricular junction ablation is well recognized to decrease the risk of sudden cardiac death. We propose that this practice (faster pacing rate) be implemented in patients who need permanent pacemakers secondary to transcatheter aortic valve implantation (or even surgical aortic valve interventions).
Journal of Cardiothoracic Surgery, Feb 27, 2020
Introduction: Complications following Cardiopulmonary resuscitation (CPR) are rare and usually fo... more Introduction: Complications following Cardiopulmonary resuscitation (CPR) are rare and usually follows a vigorous CPR or in special cases like pregnancy are due to lack of knowledge and clinical practice of how to preform CPR in pregnancy. One of this complication is diaphragmatic rupture with herniation of abdominal organs. Surgical intervention needs to be planned carefully in multidisciplinary team approach and requires fine surgical techniques for better outcome. There are few reported cases of diaphragmatic rupture after Cardiopulmonary resuscitation but none in pregnant woman. Case presentation: We report a rare case of diaphragmatic rupture in a 29-year-old pregnant patient who experienced a full-blown diaphragmatic defect and herniation of the abdominal organs into the thoracic cavity, as a complication of CPR. Following careful assessment and diagnosis, the patient underwent urgent laparotomy with reduction of the contents and primary closure of the defect. One year follow up was satisfactory. To the best of our knowledge, this is the first reported case of diaphragmatic rupture with herniation of the abdominal organs following CPR in a pregnant woman in the literature. Conclusion: The application of external cardiac massage through CPR is a life-saving procedure for the management of cardiac arrest. Common complications related to CPR include rib fractures, sternal fractures and haemothorax. Diaphragmatic rupture with herniation of the abdominal organs is a rare complication, having been reported only once in the literature (Sabzi F, Faraji R, Tanaffos 16:170-172, 2017); however, it represents a serious and life-threating event. Thus, careful evaluation of the patient by a multidisciplinary team and prompt intervention is recommended in order to improve outcomes.
Canadian Journal of Cardiology, 2016