ORCID Profile
0000-0002-0636-5639
Current Organisations
Hunter New England Local Health District
,
Hunter Cardiac Investigations
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Publisher: Elsevier BV
Date: 2021
Publisher: Oxford University Press (OUP)
Date: 28-06-2022
Abstract: Purulent bacterial pericarditis (PBP) is a highly lethal infection of the pericardial space that arises as a complication of infective illnesses. Purulent bacterial pericarditis remains a diagnostic challenge given its non-specific clinical and investigative features and carries exceedingly high mortality rates due to fulminant sepsis and morbidity including constrictive pericarditis in survivors. We present our management of cardiac t onade and subsequent constrictive pericarditis due to Actinomyces meyeri PBP. A 53-year-old Caucasian male presented with acute New York Heart Association Class IV dyspnoea and chest discomfort, in the context of multiple hospital presentations over the preceding 8 weeks due to presumed recurrent viral pericarditis. On this admission, initial transthoracic echocardiography (TTE) demonstrated a large asymmetric pericardial effusion for which he underwent urgent pericardiocentesis. Serial TTE post-pericardiocentesis, however, demonstrated effusion re-accumulation and effusive-constrictive pericarditis, confirmed on cardiac magnetic resonance imaging. Fluid culture was positive for A. meyeri. He was diagnosed with PBP, but his condition deteriorated despite appropriate intravenous antibiotic therapy, necessitating semi-urgent surgical pericardiectomy. He recovered well and was discharged on Day 10 post-operatively. Unlike uncomplicated acute viral or idiopathic pericarditis, PBP portends a very poor prognosis if unrecognized and untreated. Diagnostic challenges persist given its rarity in modern clinical practice however, PBP should be considered in cases of seemingly recurrent pericarditis. Multi-modal cardiac imaging and careful analysis of pericardial fluid including cultures and lactate dehydrogenase/serum ratios may assist in earlier recognition. In this case, source control and symptom relief were achieved only with combined intravenous antibiotics, surgical evacuation, and pericardiectomy.
Publisher: Elsevier BV
Date: 2013
Publisher: Elsevier BV
Date: 2015
Publisher: Wiley
Date: 2017
DOI: 10.1111/IMJ.13305
Abstract: Anthracyclines are commonly used chemotherapeutic medications. In the current analysis, we evaluated all-cause mortality and incidence, timing and response to medical therapy of anthracycline cardiotoxicity. Left ventricular ejection fraction (LVEF) was serially assessed using gated heart pool scan/echocardiography in patients receiving anthracycline-based chemotherapy from January 2009 to December 2014. A total of 1204 patients was administered anthracyclines during the study period. During a median follow up of 32 (interquartile range: 15-58) months, all-cause mortality was 38% (n = 463), with the incidence of cardiotoxicity 10.2% (n = 123). Only 15.4% (n = 19) patients required heart failure hospitalisation, with 48% (n = 59) of patients commenced on beta blockade therapy and/or angiotensin-converting enzyme inhibitors. The majority of patients (73.2%, n = 90) experienced cardiotoxicity within 1 year of anthracycline initiation. The proportion of patients with complete, partial and no LVEF recovery were 16.3% (n = 20), 29.3% (n = 36) and 54.4% (n = 67) respectively. Mortality was higher in the cardiotoxicity group (49% vs 37%, P < 0.01). History of coronary artery disease, leukaemia, idarubicin use and high cumulative anthracycline dose were predictors of cardiotoxicity. Cardiotoxicity after anthracycline use predictably occurs within the first year of therapy and is dose-related, with variable degrees of recovery. While the need for hospitalisation for heart failure was uncommon, medical therapy appears underutilised, suggesting there may be a role for improved surveillance and early initiation of treatment.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 2015
Publisher: Japanese Society for the Study of Xenobiotics
Date: 2008
DOI: 10.2133/DMPK.23.165
Abstract: The work described in this study aimed to express CYP2C8 wild-type and mutant proteins in bacterial expression system and to use the expressed proteins to investigate the structural and functional consequences of a reported allele CYP2C8(*)4 (carrying Ile264Met substitution) on protein activity. Ile264 was replaced by three different amino acids resulting in three mutant constructs, 2C8I264M, 2C8I264R and 2C8I264D. The presence of isoleucine at position 264 in CYP2C8 was found to be important for proper haem insertion and protein folding whereas bulkier or charged residues were highly disruptive resulting in inactive proteins with minimum spectral and catalytic activities. This was evidenced from the low levels of Soret peak at 450 nm and negligible levels of tolbutamide methylhydroxylase activity. Kinetic study using paclitaxel indicated that all three mutants exhibited only 9.7 to 35.4% of the activity level observed in the wild-type. In addition, the mutants were more sensitive to proteinase K digestion, indicating a possible alteration of conformation. The combined effects of protein instability and compromised catalytic activity resulted in defective CYP2C8 protein which may have clinical implications in carriers of CYP2C8*4, particularly in terms of their capacity to clear potent drugs and their susceptibility to adverse drug reactions.
Publisher: Elsevier BV
Date: 08-2016
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.IJCARD.2017.03.013
Abstract: Clozapine is the cornerstone of therapy for refractory schizophrenia however, the potential for cardiotoxicity is an important limitation in its use. In the current analysis we sought to evaluate the long term cardiac outcomes of clozapine therapy. All-cause mortality, incidence of sudden death and time to myocarditis were assessed in a cohort of patients maintained on clozapine between January 2009 and December 2015. All patients had regular electrocardiograms, complete blood count, clozapine levels and echocardiography as part of a formal protocol. A total of 503 patients with treatment-resistant schizophrenia were maintained on clozapine during the study period of which 93 patients (18%) discontinued therapy with 29 (6%) deaths. The incidence of sudden death and myocarditis were 2% (n=10) and 3% (n=14) respectively. Amongst patients with sudden death, 7 out of 10 (70%) were documented to have used illicit drugs prior to death, with a tendency to weight gain also noted. The mean time to myocarditis post clozapine commencement was 15±7days. The reduction in left ventricular ejection fraction in those with myocarditis was 11±2%. Myocarditis and sudden cardiac death are uncommon but clinically important complications in a cohort of patients followed while maintained on clozapine undergoing regular cardiac assessment. Further studies are required to document the role of preventive measures for left ventricular dysfunction and sudden cardiac death in this population.
No related grants have been discovered for Rajinder Singh Harjit Singh.