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2.
Pharmacol Ther ; 211: 107529, 2020 07.
Article in English | MEDLINE | ID: mdl-32197794

ABSTRACT

The Third International Consensus Definitions (Sepsis-3) define sepsis as life-threatening multi-organ dysfunction caused by a dysregulated host response to infection. Sepsis can progress to septic shock-an even more lethal condition associated with profound circulatory, cellular and metabolic abnormalities. Septic shock remains a leading cause of death in intensive care units and carries a mortality of almost 25%. Despite significant advances in our understanding of the pathobiology of sepsis, therapeutic interventions have not translated into tangible differences in the overall outcome for patients. Clinical trials of antagonists of various pro-inflammatory mediators in sepsis have been largely unsuccessful in the past. Given the diverse physiologic roles played by G-protein coupled receptors (GPCR), modulation of GPCR signaling for the treatment of sepsis has also been explored. Traditional pharmacologic approaches have mainly focused on ligands targeting the extracellular domains of GPCR. However, novel techniques aimed at modulating GPCR intracellularly through aptamers, pepducins and intrabodies have opened a fresh avenue of therapeutic possibilities. In this review, we summarize the diverse roles played by various subfamilies of GPCR in the pathogenesis of sepsis and identify potential targets for pharmacotherapy through these novel approaches.


Subject(s)
Receptors, G-Protein-Coupled/metabolism , Sepsis/drug therapy , Shock, Septic/drug therapy , Animals , Drug Development , Humans , Ligands , Molecular Targeted Therapy , Sepsis/physiopathology , Shock, Septic/physiopathology , Signal Transduction/drug effects
4.
J Pak Med Assoc ; 69(6): 864-868, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31201393

ABSTRACT

OBJECTIVE: To assess knowledge, attitudes, practices and perceptions of healthcare professionals regarding use of portable gadgets in daily clinical practice and for academic purposes. METHODS: The questionnaire-based, cross-sectional study was performed at Aga Khan University Hospital, Karachi, from February to March, 2015, and comprised healthcare professionals recruited using convenience-based sampling. A self-administered questionnaire was used for data collection. Items in the instrument pertained to use of portable gadgets, knowledge of radiology applications and perceptions regarding benefits/drawbacks of such gadgets. 'Portable gadgets' referred to any handheld electronic device, such as mobile phones, tablet or personal digital assistants. SPSS 20 was used for data analysis. RESULTS: Of the 100 subjects, 38(38%) were radiology residents, 34(34%) consultant radiologists 28(28%) were radiographers. The overall mean age was 32.7}8.66 years. Overall, 80 (80%) subjects possessed a portable gadget. Although 64(64%) participants commonly used the gadgets for clinical and academic activities, only 46(46%) had heard of radiology smartphone applications. Majority 80(80%) preferred hardcopies for studying books as opposed to digital formats. However, 78(78%) believed that portable gadgets had a positive impact on their clinical practice. CONCLUSIONS: Portable gadgets were being used by a substantial proportion of healthcare professionals for clinical and academic activities.


Subject(s)
Allied Health Personnel , Attitude of Health Personnel , Computers, Handheld , Internship and Residency , Radiologists , Smartphone , Adult , Cross-Sectional Studies , Humans , Mobile Applications , Pakistan , Periodicals as Topic , Radiology/education , Reading , Surveys and Questionnaires , Young Adult
6.
Eur J Trauma Emerg Surg ; 45(3): 517-525, 2019 Jun.
Article in English | MEDLINE | ID: mdl-29484462

ABSTRACT

PURPOSE: Esophageal perforation has a high mortality rate. Fluoroscopic esophagography (FE) is the procedure of choice for diagnosing esophageal perforation. However, FE can be difficult to perform in seriously ill patients. METHODS: We retrospectively reviewed charts and scans of all patients who had undergone thoracic CT (TCT) without oral contrast and FE for suspicion of esophageal perforation at our hospital between October, 2010 and December, 2015. Scans were interpreted by a single consultant radiologist having > 5 years of relevant experience. Statistical analysis was performed using SPSS version 20. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TCT were computed using FE as reference standard. RESULTS: Of 122 subjects, 106 (83%) were male and their median age was 42 [inter-quartile range (IQR) 29-53] years. Esophageal perforation was evident on FE in 15 (8%) cases. Sensitivity, specificity, PPV and NPV of TCT for detecting esophageal perforation were 100, 54.6, 23.4 and 100%, respectively. When TCT was negative (n = 107), an alternative diagnosis was evident in 65 cases. CONCLUSION: Thoracic computed tomography (TCT) had 100% sensitivity and negative predictive value for excluding esophageal perforation. FE may be omitted in patients who have no evidence of mediastinal collection, pneumomediastinum or esophageal wall defect on TCT. However, in the presence of any of these features, FE is still necessary to confirm or exclude the presence of an esophageal perforation.


Subject(s)
Esophageal Perforation/diagnostic imaging , Esophagus/diagnostic imaging , Extravasation of Diagnostic and Therapeutic Materials/diagnostic imaging , Postoperative Complications/diagnostic imaging , Thoracic Injuries/diagnostic imaging , Wounds, Gunshot/diagnostic imaging , Accidents, Traffic , Adult , Contrast Media , Esophageal Perforation/complications , Esophagus/injuries , Extravasation of Diagnostic and Therapeutic Materials/etiology , Female , Fluoroscopy , Humans , Male , Mediastinal Emphysema/diagnostic imaging , Mediastinal Emphysema/etiology , Middle Aged , Postoperative Complications/etiology , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Thoracic Injuries/complications , Tomography, X-Ray Computed , Wounds, Gunshot/complications
7.
J Pak Med Assoc ; 68(11): 1699-1704, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30410153

ABSTRACT

Causes and outcomes of children diagnosed with hydronephrosis in resource-limited countries with a low utilization of antenatal ultrasonography remain unexplored. We performed a retrospective, crosssectional study of all paediatric patients diagnosed with hydronephrosis and managed at a tertiary care center in Karachi, Pakistan between 2005 and 2010. Data relating to demographics, clinical features, etiologies and treatment modalities were systematically collected. Of a total of 234 cases (74.4% male), 83 (35.5%) and 42 (17.9%) were neonates and infants respectively. Congenital urinary tract pathologies were noted in 192(72.2%) patients, of which only 96(50%) had undergone foetal ultrasonography and 77(40.1%) first presented after the age of 1 year. At a median follow-up of 4 years, 24(12.5%) of these patients had evidence of renal dysfunction. Worse urologic outcomes in this study were most likely attributable to delayed diagnosis of congenital urinary tract abnormalities.


Subject(s)
Disease Management , Hydronephrosis/diagnosis , Tertiary Care Centers/statistics & numerical data , Urodynamics/physiology , Urogenital Abnormalities/diagnosis , Child, Preschool , Cross-Sectional Studies , Female , Humans , Hydronephrosis/epidemiology , Hydronephrosis/etiology , Incidence , Infant , Infant, Newborn , Male , Pakistan/epidemiology , Retrospective Studies , Ultrasonography , Urogenital Abnormalities/complications , Urogenital Abnormalities/epidemiology
9.
Neuroradiol J ; 31(5): 496-503, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29890915

ABSTRACT

Introduction In patients with cranial venous sinus thrombosis, the occurrence of subarachnoid haemorrhage in association with haemorrhagic venous infarcts is a well described phenomenon. However, the presence of subarachnoid haemorrhage in patients with cranial venous sinus thrombosis in the absence of a haemorrhagic venous infarct is exceedingly rare. Methods We retrospectively reviewed charts and scans of all patients who had cranial venous sinus thrombosis confirmed by magnetic resonance venography at our hospital between September 2004 and May 2015. The presence of subarachnoid haemorrhage was ascertained on fluid-attenuated inversion recovery, susceptibility-weighted imaging and/or unenhanced computed tomography scans by a single experienced neuroradiologist. Statistical analysis was performed using the Statistical Package for Social Sciences version 20. Differences in the proportion of haemorrhagic venous infarcts among patients with subarachnoid haemorrhage versus those without subarachnoid haemorrhage were compared using the chi-square test. A P value of less than 0.05 was considered significant. Results A total of 138 patients who had cranial venous sinus thrombosis were included in the study. Seventy-three (52.9%) were women and the median age of subjects was 35 (interquartile range 22-47) years. Venous infarcts and haemorrhagic venous infarcts were noted in 20/138 (14.5%) and 62/138 (44.9%) cases, respectively. Subarachnoid haemorrhage was present in 15/138 (10.9%) cases and, in three cases, subarachnoid haemorrhage occurred in the absence of a venous infarct. Haemorrhagic venous infarcts were more prevalent ( P = 0.021) among patients with subarachnoid haemorrhage (11/15) than in those without subarachnoid haemorrhage (51/123). Conclusion In patients with cranial venous sinus thrombosis, subarachnoid haemorrhage can occur even in the absence of a haemorrhagic venous infarct. The recognition of cranial venous sinus thrombosis as the underlying cause of subarachnoid haemorrhage is important to avoid misdiagnosis and inappropriate management.


Subject(s)
Brain Infarction/complications , Brain Infarction/epidemiology , Sinus Thrombosis, Intracranial/complications , Sinus Thrombosis, Intracranial/epidemiology , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/epidemiology , Adult , Brain/diagnostic imaging , Brain Infarction/diagnostic imaging , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Phlebography , Prevalence , Retrospective Studies , Sinus Thrombosis, Intracranial/diagnostic imaging , Subarachnoid Hemorrhage/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
10.
Expert Rev Cardiovasc Ther ; 16(5): 331-340, 2018 May.
Article in English | MEDLINE | ID: mdl-29564922

ABSTRACT

INTRODUCTION: Idiopathic systemic capillary leak syndrome (SCLS) is a unique disorder characterized by episodes of massive systemic leak of intravascular fluid leading to volume depletion and shock. A typical attack of SCLS consists of prodromal, leak and post-leak phases. Complications, such as compartment syndrome and pulmonary edema, usually develop during the leak and post-leak phases respectively. Judicious intravenous hydration and early use of vasopressors is the cornerstone of management in such cases. Areas covered: The purpose of the present review is to provide an up-to-date, evidence-based review of our understanding of SCLS and its management in the light of currently available evidence. COMMENTARY: Idiopathic SCLS was first described in 1960 and, since then, more than 250 cases have been reported. A large number of cases have been reported over the past one decade, most likely due to improved recognition. In the acute care setting, most patients with SCLS are managed as per the Surviving Sepsis guidelines and receive aggressive volume resuscitation - which is not the optimal management strategy for such patients. There is a need to raise awareness amongst physicians and clinicians in order to improve recognition of this disorder and ensure its appropriate management.


Subject(s)
Capillary Leak Syndrome/therapy , Shock/etiology , Capillary Leak Syndrome/diagnosis , Humans
11.
Abdom Radiol (NY) ; 43(5): 1254-1261, 2018 05.
Article in English | MEDLINE | ID: mdl-28828512

ABSTRACT

PURPOSE: To ascertain the accuracy and reliability of tablet as an imaging console for detection of radiological signs of acute appendicitis [on focused appendiceal computed tomography (FACT)] using Picture Archiving and Communication System (PACS) workstation as reference standard. METHODS: From January, 2014 to June, 2015, 225 patients underwent FACT at our institution. These scans were blindly re-interpreted by an independent consultant radiologist, first on PACS workstation and, two weeks later, on tablet. Scans were interpreted for the presence of radiological signs of acute appendicitis. Accuracy of tablet was calculated using PACS as reference standard. Kappa (κ) statistics were calculated as a measure of reliability. RESULTS: Of 225 patients, 99 had radiological evidence of acute appendicitis on PACS workstation. Tablet was 100% accurate in detecting radiological signs of acute appendicitis. Appendicoliths, free fluid, lymphadenopathy, phlegmon/abscess, and perforation were identified on PACS in 90, 43, 39, 10, and 12 scans, respectively. There was excellent agreement between tablet and PACS for detection of appendicolith (к = 0.924), phlegmon/abscess (к = 0.904), free fluid (к = 0.863), lymphadenopathy (к = 0.879), and perforation (к = 0.904). CONCLUSIONS: Tablet computer, as an imaging console, was highly reliable and was as accurate as PACS workstation for the radiological diagnosis of acute appendicitis.


Subject(s)
Appendicitis/diagnostic imaging , Computers, Handheld/standards , Radiology Information Systems , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Appendix/diagnostic imaging , Child , Female , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Young Adult
15.
J Clin Gastroenterol ; 50(9): 754-60, 2016 10.
Article in English | MEDLINE | ID: mdl-26646804

ABSTRACT

BACKGROUND: Acute lower gastrointestinal bleeding (LGIB) is a major cause of morbidity and mortality. Multidetector row computed tomography (CT) with gastrointestinal (GI) bleed protocol is a novel diagnostic technique for detecting and localizing LGIB. Being rapid and noninvasive, it may be useful as a first-line modality to investigate cases of acute LGIB. GOALS: To assess and compare diagnostic accuracy of (99M)Technetium (Tc)-labeled red blood cell (RBC) scintigraphy and multidetector row CT with GI bleed protocol for detection and localization of source of acute LGIB. STUDY: Requirement of informed consent was waived for this retrospective study. Seventy-six patients had undergone either RBC scintigraphy, CT with GI bleed protocol, or both, followed by conventional angiography for evaluation of acute persistent LGIB between January 2010 and February 2014 at our institution. Accuracy of both modalities was assessed using conventional angiography as reference standard and compared using the 2-tailed, Fisher exact test. A P-value of <0.05 was considered statistically significant. RESULTS: Fifty-one, 20, and 5 patients had undergone RBC scintigraphy only, CT with GI bleed protocol only, and both modalities, respectively. Fourteen of 25 patients in the CT group had angiographic evidence of active bleeding as compared with 32 of 56 patients in the scintigraphy group. CT with GI bleed protocol had higher accuracy (96%) than (99M)Tc-labeled RBC scintigraphy (55.4%, P<0.001). CONCLUSIONS: CT with GI bleed protocol was more accurate in detecting and localizing the source of acute LGIB as compared with (99M)Tc-labeled RBC scintigraphy.


Subject(s)
Gastrointestinal Hemorrhage/diagnostic imaging , Aged, 80 and over , Clinical Protocols , Erythrocytes , Female , Humans , Male , Predictive Value of Tests , Radionuclide Imaging , Radiopharmaceuticals , Technetium Tc 99m Pentetate , Tomography, X-Ray Computed
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