ORCID Profile
0000-0001-7734-0087
Current Organisations
Australian National University
,
University of Sydney
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Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JOCN.2019.06.029
Abstract: Isolated traumatic medial rectus palsies associated with closed head injury is rarely reported in literature. We report the case of a 48 year-old male with an isolated right medial rectus palsy following a mechanical fall with occipital headstrike. Bifrontal and bitemporal haemorrhagic contusions were seen on computed tomography (CT). Magnetic resonance imaging (MRI) revealed a T2 hyperintense lesion at the right paramedian dorsal midbrain, with changes on diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC), suggestive of ischaemic changes in the oculomotor nucleus. He was followed up at two- and six-weeks.
Publisher: The Company of Biologists
Date: 2017
DOI: 10.1242/JCS.204461
Abstract: Ryanodine receptor (RyR) calcium channels are central to striated muscle function and influence signalling in neurones and other cell types. Beneficially low RyR activity and maximum conductance opening may be stabilised when RyRs bind to FK506 binding proteins (FKBPs) and destabilised by FKBP dissociation, with submaximal opening during RyR hyperactivity associated with myopathies and neurological disorders. However this is debated and quantitative evidence is lacking. Here we have measured altered FKBP binding to RyRs and submaximal activity with addition of wild-type (WT) CLIC2, an inhibitory RyR ligand, or its H101Q mutant that hyperactivates RyRs, likely causing cardiac and intellectual abnormalities. The proportion of sub-conductance opening increases with WT and H101Q CLIC2 and is correlated with reduced FKBP/RyR association. The sub-conductance opening reduces RyR currents in the presence of WT CLIC2. In contrast, sub-conductance openings contribute to excess RyR “leak” with H101Q CLIC2. There are significant FKBP and RyR isoform-specific actions of CLIC2, rapamycin and FK506 on FKBP/RyR association. The results show that FKBPs do influence RyR gating and that this would contribute to excess Ca2+ release in one RyR channelopathy.
Publisher: American Physiological Society
Date: 15-11-2012
DOI: 10.1152/AJPREGU.00263.2012
Abstract: Orexin neurons form a restricted group in the dorsal hypothalamus. The group is centered on the perifornical area within the classic hypothalamic defense area, an area which when activated produces marked cardiovascular and respiratory effects. Central administration of orexin can produce cardiorespiratory effects, but the extent to which orexin contributes to such responses evoked from the perifornical hypothalamus is not clear. To determine this, we used the dual orexin receptor antagonist Almorexant to challenge the cardiorespiratory effects evoked by disinhibition of the perifornical hypothalamus. Bicuculline (10 and 20 pmol) was microinjected in the perifornical area before and after administration of Almorexant (15 mg/kg iv) or vehicle in urethane-anesthetized rats. Almorexant significantly reduced the pressor, tachycardic, renal sympathoexcitatory, and tachypneic responses to bicuculline (10 pmol, by 55%, 53%, 28%, 77% 20 pmol, by 54%, 27%, 51%, 72%, respectively). Reductions of similar magnitude were observed with bicuculline microinjections centered on more caudal sites just peripheral to the orexin neuron group, which would likely have activated fewer orexin neurons. In contrast, Almorexant had no effect on the cardiorespiratory response of the chemoreflex (sodium cyanide injection) or the sympathetic component of the baroreflex. Thus orexin makes a major contribution to the cardiorespiratory response evoked from the perifornical area even though orexin neurons represent only a fraction of the output of this area. Orexin neurons may also mediate cardiorespiratory responses from non-orexin neurons in the caudal hypothalamus. However, under resting conditions, blockade of orexin receptors does not affect the chemo- and baroreflexes.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 08-08-2014
Publisher: Scientific Scholar
Date: 12-05-2023
Abstract: Middle meningeal artery (MMA) embolization has recently emerged as a potential treatment for chronic subdural hematoma (cSDH). Numerous retrospective studies have suggested that it can potentially reduce the risk of hematoma recurrence following surgical evacuation. We have conducted a randomized controlled trial to investigate the effectiveness of postoperative MMA embolization in reducing recurrence rate, residual hematoma thickness as well as improving functional outcome. Patients aged 18 or above were recruited. Following evacuation through burr hole or craniotomy, patients were randomly allocated to undergo either MMA embolization or standard care (monitoring). The primary outcome was symptomatic recurrence requiring redo evacuation. Secondary outcomes include residual hematoma thickness and modified Rankin Scale (mRS) at 6 weeks and 3 months. Thirty-six patients (41 cSDHs) were recruited between April 2021 and September 2022. Seventeen patients (19 cSDHs) were allocated to the embolization group and 19 patients (22 cSDHs) were in the control group. No symptomatic recurrence was observed in the treatment group while 3 control patients (15.8%) underwent repeat surgery for symptomatic recurrence, however, it was not statistically significant ( P = 0.234). Furthermore, there was no significant difference in residual hematoma thickness at 6 weeks or 3 months between the two groups. All patients in the embolization group had a good functional outcome (mRS 0–1) at 3 months, which was significantly higher than the 53% observed in the control group. No complications related to MMA embolization were reported. Further study with larger s le size is required to evaluate the efficacy of MMA embolization.
Publisher: Georg Thieme Verlag KG
Date: 2017
Abstract: Cerebral metastasis secondary to prostatic adenocarcinoma is rare and it is usually a late complication in patients with widespread distant metastases. Here, we report two unusual cases of such a rare condition. Our first case presented with a large frontal contrast-enhancing lesion-associated calcification and a large tumor cyst as shown on computed tomography and magnetic resonance imaging. This is the fifth reported case of prostatic metastasis manifesting as a cystic intraparenchymal tumor in the literature. The second case presented with a large soft tissue mass in the scalp and this lesion appeared to invade through the skull and into the middle cranial fossa. He was not known to have prostate cancer before his initial presentation and it was only diagnosed following histology results of the scalp lesion.
Publisher: The Company of Biologists
Date: 2014
DOI: 10.1242/JCS.156760
Abstract: We report the impact of redox potential on isolated cardiac ryanodine receptor (RyR2) channel activity and its response to physiological changes in luminal [Ca2+]. Basal leak from the sarcoplasmic reticulum (SR) is required for normal Ca2+ handling, but excess diastolic Ca2+ leak attributed to oxidative stress is thought to lower RyR2 threshold for spontaneous SR Ca2+ release to induce arrhythmia in pathological situations. Therefore we examined RyR2 response to luminal [Ca2+] under reducing or oxidising cytoplasmic redox conditions. Unexpectedly as luminal [Ca2+] increased from 0.1–1.5 mM RyR2 activity declined when pretreated with cytoplasmic 1 mM DTT, or GSH∶GSSG buffered to a “healthy” reduced cytoplasmic redox potential (−220 mV). Conversely, with 20 µM cytoplasmic 4,4′-DTDP, or redox buffered to an oxidising −180 mV, RyR2 activity increased with increasing luminal [Ca2+]. The luminal redox potential was constant at −180 mV in each case. These responses to luminal Ca2+ were maintained with 2 mM Na2ATP or 5 mM MgATP (1 mM free Mg2+). Overall the results suggest that the redox potential in the RyR2 junctional microdomain is normally more oxidised than the bulk cytoplasm.
Publisher: Proceedings of the National Academy of Sciences
Date: 13-05-2013
Abstract: We recently reported the isolation of a scorpion toxin named U 1 -liotoxin-Lw1a (U 1 -LITX-Lw1a) that adopts an unusual 3D fold termed the disulfide-directed hairpin (DDH) motif, which is the proposed evolutionary structural precursor of the three-disulfide-containing inhibitor cystine knot (ICK) motif found widely in animals and plants. Here we reveal that U 1 -LITX-Lw1a targets and activates the mammalian ryanodine receptor intracellular calcium release channel (RyR) with high (fM) potency and provides a functional link between DDH and ICK scorpion toxins. Moreover, U 1 -LITX-Lw1a, now described as φ-liotoxin-Lw1a (φ-LITX-Lw1a), has a similar mode of action on RyRs as scorpion calcines, although with significantly greater potency, inducing full channel openings at lower (fM) toxin concentrations whereas at higher pM concentrations increasing the frequency and duration of channel openings to a submaximal state. In addition, we show that the C-terminal residue of φ-LITX-Lw1a is crucial for the increase in full receptor openings but not for the increase in receptor subconductance opening, thereby supporting the two-binding-site hypothesis of scorpion toxins on RyRs. φ-LITX-Lw1a has potential both as a pharmacological tool and as a lead molecule for the treatment of human diseases that involve RyRs, such as malignant hyperthermia and polymorphic ventricular tachycardia.
Publisher: Cureus, Inc.
Date: 15-06-2017
DOI: 10.7759/CUREUS.1358
Publisher: Oxford University Press (OUP)
Date: 19-07-2012
DOI: 10.1093/HMG/DDS292
Publisher: Elsevier BV
Date: 2023
No related grants have been discovered for Alexander Lam.