1.Are "Patellofemoral Symptoms" Truly Related to the Patellofemoral Joint?
Rafik YASSA ; Mahdi Yacine KHALFAOUI ; Andrew P DAVIES
The Journal of Korean Knee Society 2016;28(1):68-74
PURPOSE: The pattern of symptoms of knee osteoarthritis has been thought to be indicative of specific compartment involvement. This study investigated whether there was a true correlation between patellofemoral joint (PFJ) symptoms and unicompartmental patellofemoral arthritis. MATERIALS AND METHODS: A prospective analysis of 34 patients rendered to be suffering from PFJ osteoarthritis and subsequently undergoing unicompartmental patellofemoral arthroplasty (PFA) was performed. A control cohort of 32 patients suffering from medial tibiofemoral joint (MTFJ) osteoarthritis was included in the analysis. Four questions derived from the Oxford knee score questionnaire, traditionally deemed to be indicative of PFJ osteoarthritis, were combined to create a PFJ subscore and statistically analyzed for their potential relationship with PFJ osteoarthritis and outcomes following PFA. RESULTS: The PFJ subscore indicated slightly worse pathology in patients undergoing PFA compared to MTFJ replacement, but the difference was not significant (9.7 and 9.6, respectively; p=0.851). The improvement in PFJ symptoms was higher in those undergoing PFA compared to MTFJ surgery; however, the difference was not statistically significant (3.7 and 2.2 respectively, p=0.074). CONCLUSIONS: We were unable to prove that these symptoms were predictive of PFJ pathology in the preoperative setting, nor were they useful in interpreting which symptoms would likely improve following PFA.
Arthritis
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Arthroplasty
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Cohort Studies
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Humans
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Joints
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Knee
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Osteoarthritis
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Osteoarthritis, Knee
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Patellofemoral Joint
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Pathology
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Prospective Studies
2.Extended Wireless pH Monitoring Significantly Increases Gastroesophageal Reflux Disease Diagnoses in Patients With a Normal pH Impedance Study
Sebastian S ZEKI ; Ismail MIAH ; Pierfrancesco VISAGGI ; Anna WOLAK ; Minerva DESILVA ; Jason M DUNN ; Andrew DAVIES ; James GOSSAGE ; Abrie BOTHA ; Guiping SUI ; Jafar JAFARI ; Terry WONG
Journal of Neurogastroenterology and Motility 2023;29(3):335-342
Background/Aims:
Extended wireless pH monitoring (WPM) is used to investigate gastroesophageal reflux disease (GERD) as subsequent or alternative investigation to 24-hour catheter-based studies. However, false negative catheter studies may occur in patients with intermittent reflux or due to catheter-induced discomfort or altered behavior. We aim to investigate the diagnostic yield of WPM after a negative 24-hour multichannel intraluminal impedance pH (MII-pH) monitoring study and to determine predictors of GERD on WPM given a negative MII-pH.
Methods:
Consecutive adult patients (> 18 years) who underwent WPM for further investigation of suspected GERD following a negative 24-hour MII-pH and upper endoscopy between January 2010 and December 2019 were retrospectively included. Clinical data, endoscopy, MII-pH, and WPM results were retrieved. Fisher’s exact test, Wilcoxon rank sum test, or Student’s t test were used to compare data.Logistic regression analysis was used to investigate predictors of positive WMP.
Results:
One hundred and eighty-one consecutive patients underwent WPM following a negative MII-pH study. On average and worst day analysis, 33.7% (61/181) and 34.2% (62/181) of the patients negative for GERD on MII-pH were given a diagnosis of GERD following WPM, respectively. On a stepwise multiple logistic regression analysis, the basal respiratory minimum pressure of the lower esophageal sphincter was a significant predictor of GERD with OR = 0.95 (0.90-1.00, P = 0.041).
Conclusions
WPM increases GERD diagnostic yield in patients with a negative MII-pH selected for further testing based on clinical suspicion. Further studies are needed to assess the role of WPM as a first line investigation in patients with GERD symptoms.
3.Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars.
Isaac M WESTWOOD ; Sanjib BHAKTA ; Angela J RUSSELL ; Elizabeth FULLAM ; Matthew C ANDERTON ; Akane KAWAMURA ; Andrew W MULVANEY ; Richard J VICKERS ; Veemal BHOWRUTH ; Gurdyal S BESRA ; Ajit LALVANI ; Stephen G DAVIES ; Edith SIM
Protein & Cell 2010;1(1):82-95
New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting intracellularly. Mycobacteria have a unique cell wall. Deletion of the gene for arylamine N-acetyltransferase (NAT) decreases mycobacterial cell wall lipids, particularly the distinctive mycolates, and also increases antibiotic susceptibility and killing within macrophage of Mycobacterium bovis BCG. The nat gene and its associated gene cluster are almost identical in sequence in M. bovis BCG and M. tuberculosis. The gene cluster is essential for intracellular survival of mycobacteria. We have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT activity. Here, we characterize one class of such molecules-triazoles-in relation to its effects on the target enzyme and on both M. bovis BCG and M. tuberculosis. The most potent triazole mimics the effects of deletion of the nat gene on growth, lipid disruption and intracellular survival. We also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth, and use ligand-protein analysis to give further insight into the structure-activity relationships. We conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved.
Antitubercular Agents
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chemistry
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isolation & purification
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pharmacology
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Arylamine N-Acetyltransferase
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antagonists & inhibitors
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chemistry
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Enzyme Inhibitors
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chemistry
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isolation & purification
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pharmacology
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High-Throughput Screening Assays
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Humans
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Mycobacterium bovis
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drug effects
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enzymology
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genetics
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Mycobacterium tuberculosis
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drug effects
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enzymology
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genetics
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Protein Conformation
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Structure-Activity Relationship
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Triazoles
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chemistry
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isolation & purification
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pharmacology
4.Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action
Kosmas I. PARASKEVAS ; Dimitri P. MIKHAILIDIS ; Hediyeh BARADARAN ; Alun H. DAVIES ; Hans-Henning ECKSTEIN ; Gianluca FAGGIOLI ; Jose Fernandes e FERNANDES ; Ajay GUPTA ; Mateja K. JEZOVNIK ; Stavros K. KAKKOS ; Niki KATSIKI ; M. Eline KOOI ; Gaetano LANZA ; Christos D. LIAPIS ; Ian M. LOFTUS ; Antoine MILLON ; Andrew N. NICOLAIDES ; Pavel POREDOS ; Rodolfo PINI ; Jean-Baptiste RICCO ; Tatjana RUNDEK ; Luca SABA ; Francesco SPINELLI ; Francesco STILO ; Sherif SULTAN ; Clark J. ZEEBREGTS ; Seemant CHATURVEDI
Journal of Stroke 2021;23(2):202-212
The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient’s life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.
5.Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action
Kosmas I. PARASKEVAS ; Dimitri P. MIKHAILIDIS ; Hediyeh BARADARAN ; Alun H. DAVIES ; Hans-Henning ECKSTEIN ; Gianluca FAGGIOLI ; Jose Fernandes e FERNANDES ; Ajay GUPTA ; Mateja K. JEZOVNIK ; Stavros K. KAKKOS ; Niki KATSIKI ; M. Eline KOOI ; Gaetano LANZA ; Christos D. LIAPIS ; Ian M. LOFTUS ; Antoine MILLON ; Andrew N. NICOLAIDES ; Pavel POREDOS ; Rodolfo PINI ; Jean-Baptiste RICCO ; Tatjana RUNDEK ; Luca SABA ; Francesco SPINELLI ; Francesco STILO ; Sherif SULTAN ; Clark J. ZEEBREGTS ; Seemant CHATURVEDI
Journal of Stroke 2021;23(2):202-212
The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient’s life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.
6.Optimal Management of Asymptomatic Carotid Stenosis: Counterbalancing the Benefits with the Potential Risks
Kosmas I. PARASKEVAS ; Dimitri P. MIKHAILIDIS ; Hediyeh BARADARAN ; Alun H. DAVIES ; Hans-Henning ECKSTEIN ; Gianluca FAGGIOLI ; Jose Fernandes e FERNANDES ; Ajay GUPTA ; Mateja K. JEZOVNIK ; Stavros K. KAKKOS ; Niki KATSIKI ; M. Eline KOOI ; Gaetano LANZA ; Christos D. LIAPIS ; Ian M. LOFTUS ; Antoine MILLON ; Andrew N. NICOLAIDES ; Pavel POREDOS ; Rodolfo PINI ; Jean-Baptiste RICCO ; Tatjana RUNDEK ; Luca SABA ; Francesco SPINELLI ; Francesco STILO ; Sherif SULTAN ; Clark J. ZEEBREGTS ; Seemant CHATURVEDI
Journal of Stroke 2022;24(1):163-165