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Palmerston North, New Zealand

Roesl C.,University of Edinburgh | Sato K.,University of Florida | Schiemann A.,Massey University | Pollock N.,Palmerston North Hospital | Stowell K.M.,Massey University
Cell Calcium

Malignant hyperthermia (MH) is a pharmacogenetic disorder that manifests in susceptible individuals exposed to volatile anaesthetics. Over 400 variants in the ryanodine receptor 1 (RYR1) have been reported but relatively few have been definitively associated with susceptibility to MH. This is largely due to the technical challenges of demonstrating abnormal Ca2+ release from the sarcoplasmic reticulum. This study focuses on the R2452W variant and its functional characterisation with the aim of classifying this variant as MH causative. HEK293 cells were transiently transfected with full-length human wildtype or R2452W mutant RYR1 cDNA. In addition, B-lymphoblastoid cells from blood and myoblasts propagated from in vitro contracture tests were extracted from patients positive for the R2452W variant. All cell lines generated were loaded with the ratiometric dye Fura-2 AM, stimulated with the RYR1-specific agonist 4-chloro-m-cresol and Ca2+ release from the sarcoplasmic/endoplasmic reticulum was monitored by fluorescence emission. All cells expressing the RYR1 R2452W variant show a significantly higher Ca2+ release in response to the agonist, 4-chloro-m-cresol, compared to cells expressing RYR1 WT. These results indicate that the R2452W variant results in a hypersensitive ryanodine receptor 1 and suggest that the R2452W variant in the ryanodine receptor 1 is likely to be causative of MH. © 2014 Elsevier Ltd. Source

Machin S.E.,Palmerston North Hospital | Mukhopadhyay S.,Norwich University
Menopause International

Pelvic organ prolapse is a common condition affecting a large number of women. Incidence increases after the menopause. Age, parity and obesity are the most consistently reported risk factors. Many women can be asymptomatic of prolapse but common symptoms include a sensation of a bulge or fullness in the vagina or urinary, bowel or sexual dysfunction. Management depends upon symptoms and the type and grade of the prolapse as well as any associated medical co-morbidities. Management options include expectant, conservative or surgical approaches. Up to 10% of women having a surgical procedure for prolapse will require a second procedure. It is, therefore, important to consider lifestyle modifications such as weight loss and conservative measures including pelvic floor muscle training, topical estrogens and pessaries as initial management options. Source

Murdoch B.,Broadway Surgical Clinic | Buchanan J.,Middlemore Hospital | Cliff J.,Palmerston North Hospital
International Journal of Oral and Maxillofacial Surgery

Alloplastic total temporomandibular joint replacement (TMJ TJR) has been performed in New Zealand utilizing the TMJ Concepts patient-fitted system since 2000. The data analysed in this study were collected retrospectively from questionnaires sent to all maxillofacial surgeons in New Zealand who had implanted TMJ Concepts devices between 2000 and 2011. A total of 63 devices were implanted in 42 patients (13 males, 29 females) during this 12-year period. The primary indication for TMJ TJR was end-stage joint disease resulting from ankylosis and arthritis. The mean age of the patients was 47 years (range 7-80 years). The most common complication reported was transient facial nerve impairment in 4.8% of the patients. Objective results, measured as the maximal incisional opening, improved by a mean of 17.3 mm (P < 0.01); 90% of patients reported improved quality of life. New Zealand oral and maxillofacial surgeons have concluded that TMJ TJR using the TMJ Concepts prosthesis is a reliable treatment option for the management of end-stage TMJ disease. © 2013 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons. All rights reserved. Source

McHugh G.,Palmerston North Hospital | Freebairn R.,Intensive Care Services
Current Respiratory Medicine Reviews

Whatever the aetiology and whatever the severity, the active management of respiratory failure habitually results in the administration of supplemental oxygen therapy. This review re-examines aspects of the optimization of such therapy. The oft-cited and well described risks of oxygen toxicity are revisited. Although no universal absolutes can be stipulated, the safe use of oxygen therapy is explored with particular reference to optimal oxygen targets. Specific attention is directed to the balance between the tolerable lower limits of systemic oxygenation and the putatively safe limits for titration of supplemental inspired oxygen fraction. Additional consideration is given to the emerging concept of permissive hypoxaemia. The attractiveness of this notion, and its potential role when the adverse effects of pursuing increased oxygenation combine to outweigh any benefit, has been enhanced by recent experiences with severe hypoxic respiratory failure arising from pandemic influenza viruses. Significant shortcomings remain in the existing definitions and descriptors of dysoxia, as well as the available technology for monitoring oxygenation. In clinical practice, oxygen displays a relatively narrow therapeutic index, and requires a careful balance of its benefits and risks. A detailed understanding of this ubiquitous therapy is obligatory in the optimal care of the critically ill. © 2010 Bentham Science Publishers Ltd. Source

Sato K.,University of Florida | Roesl C.,Massey University | Pollock N.,Palmerston North Hospital | Stowell K.M.,Massey University

Background: Mutations within the gene encoding the skeletal muscle calcium channel ryanodine receptor can result in malignant hyperthermia. Although it is important to characterize the functional effects of candidate mutations to establish a genetic test for diagnosis, ex vivo methods are limited because of the low incidence of the disorder and sample unavailability. More than 250 candidate mutations have been identified, but only a few mutations have been functionally characterized. Methods: The human skeletal muscle ryanodine receptor complementary DNA was cloned with or without a diseaserelated variant. Wild-type and mutant calcium channel proteins were transiently expressed in human embryonic kidney-293 cells expressing the large T-antigen of simian virus 40, and functional analysis was carried out using calcium imaging with fura-2 AM. Six human malignant hyperthermia-related mutants such as R44C, R163C, R401C, R533C, R533H, and H4833Y were analyzed. Cells were stimulated with a specific ryanodine receptor agonist 4-chloro-m-cresol, and intracellular calcium mobility was analyzed to determine the functional aspects of mutant channels. Results: Mutant proteins that contained a variant linked to malignant hyperthermia showed higher sensitivity to the agonist. Compared with the wild type (EC50 = 453.2 μm, n = 18), all six mutants showed a lower EC50 (21.2-170.4 μm, n = 12-23), indicating susceptibility against triggering agents. Conclusions: These six mutations cause functional abnormality of the calcium channel, leading to higher sensitivity to a specific agonist, and therefore could be considered potentially causative of malignant hyperthermia reactions. Copyright © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Source

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