Management of patent foramen ovale in embolic stroke of undetermined source patients: Malaysian experts' consensus.

INTRODUCTION: About 20 to 40% of ischaemic stroke causes are cryptogenic. Embolic stroke of undetermined source (ESUS) is a subtype of cryptogenic stroke which is diagnosed based on specific criteria. Even though patent foramen ovale (PFO) is linked with the risk of stroke, it is found in about 25% of the general population, so it might be an innocent bystander. The best way to treat ESUS patients with PFO is still up for discussion. MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities. RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.

Substrate effects on surface morphologies and magnetic properties of nanostructured FePt thin films.

The substrate effects on surface morphologies, crystal structures, and magnetic properties of the sputter-deposited FePt thin films on Corning 1737, normal glass, and Si wafer substrates, respectively, were investigated. High in-plane coercivities of 10 kOe were obtained for the air-annealed films on Corning 1737 and Si wafer, where both films similarly have granular-like morphologies. Besides, increasing grain size and surface roughness of all the FePt films with the post-anneal temperature were observed. Moreover, partially separated grains were seen in the film on Si wafer, where the formation of Fe silicides during post-anneal is suspected, in which has enhanced the magnetic ordering.

Resection of a giant malignant mediastinal peripheral nerve sheath tumour under cardiopulmonary bypass.

Malignant peripheral nerve sheath tumour (MPNST) is a rare occurrence in the mediastinum. It is biologically aggressive and is generally resistant to chemoradiation therapy. The mainstay of treatment is complete surgical resection. We report a large MPNST which invaded into the adjacent aortic wall in a 50-year-old man. Extensive resection, which included aortic reconstruction under cardiopulmonary bypass and deep hypothermic arrest, was necessary for a good long-term outcome.

Identification of human metapneumovirus and Chlamydophila pneumoniae in children with asthma and wheeze in Singapore.

INTRODUCTION: The aim of our study was to determine if human metapneumovirus (hMPV) and Chlamydophila pneumoniae (CP) could be detected in Singaporean asthmatic children and wheezing infants during an acute asthma attack. METHODS: The study was performed on 30 older children (mean age 9.8 years) and 30 young children (mean age 1.3 years), who were admitted with an acute exacerbation of wheezing. Nasopharyngeal aspirates were collected and tested by polymerase chain reaction for CP, and for a panel of viruses (hMPV, respiratory syncytial virus, adenovirus, influenza virus types A and B, parainfluenza virus types 1 and 3, and rhinovirus). RESULTS: hMPV was isolated in eight out of 60 children (13.3 percent), while CP was isolated in two cases. Overall, 48/60 (80 percent) samples were positive for the presence of viruses. CONCLUSION: In most of the children admitted because of acute wheezing, a virus could be detected. hMPV was isolated for the first time in Singapore in children who were admitted with an acute asthma attack.

Improved silica-zirconia sol synthesis for fabrication of a single-mode embedded dielectric channel waveguide with low transmission losses.

A novel inorganic-organic hybrid silica-zirconia solgel material, which can generate 10 microm thick film in a single spin-coating process, has been developed and employed in the fabrication of an embedded dielectric channel waveguide on a silica buffer layer of a silicon substrate. The fabricated channel waveguide core had steep ridge walls, good smoothness, and high robustness, and the novel sol synthesis enabled a precise control of the geometrical and optical parameters of the embedded dielectric channel waveguide. In the 1.55 microm telecommunication window, the fundamental modes TE(00) and TM(00) in the embedded channel waveguide had low transmission losses of 0.40 +/- 0.03 dB/cm and 0.59 +/- 0.03 dB/cm, respectively.

Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems.

BACKGROUND: Cutaneous lymphomas other than mycosis fungoides (MF) are a heterogeneous group with wide variations in clinical presentation, biological behaviour and prognosis. New classification systems have been designed or proposed in recent years, with well-defined disease entities and emphasis on the importance of site. OBJECTIVES: This study aims to analyse a series of non-MF lymphomas in an institution-based dermatological setting in Singapore, based on the European Organization for Research and Treatment of Cancer (EORTC) classification and the World Health Organization (WHO) classification. A secondary objective is to highlight the clinical utility of both classification systems. PATIENTS AND METHODS: Forty cases diagnosed over a 12-year period were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD5, CD8, CD20, CD30, CD43, CD45RO, CD56 and CD68 in paraffin-embedded specimens. The immunohistological diagnosis was correlated with the clinical presentation and staging investigations for the final diagnosis and the course of disease recorded. RESULTS: Non-MF T-cell lymphomas presenting in the skin comprised 31 cases (78%) and were 3(1/2) times more common than B-cell lymphomas, which comprised nine cases (22%). The common subtypes were lymphomatoid papulosis, CD30+ large cell cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma. The commonly ascribed B-cell pattern with infiltrates in the mid and deep dermis and perivascular spaces was seen in 60% of T-cell lymphomas. Overall, there were equal numbers of primary cutaneous T-cell lymphomas and those due to concurrent or secondary cutaneous lymphoma. Five of six cases of subcutaneous panniculitis-like T-cell lymphoma had concurrent cutaneous and systemic involvement and their median survival was 7 months. CONCLUSIONS: The predominance of cutaneous T-cell lymphomas in this case series closely matched that reported from east Asia; cutaneous B-cell lymphomas are much less common than in Europe. The EORTC classification, which is designed only for primary cutaneous lymphomas, should be used in conjunction with the WHO classification because of the high prevalence of cutaneous lymphomas as the secondary site of disease from systemic lymphoma. In addition, subcutaneous panniculitis-like T-cell lymphoma is a primary cutaneous lymphoma where systemic involvement is common at initial presentation. We propose full immunophenotyping and complete clinical evaluation with staging investigations for all patients presenting with cutaneous lymphomas other than MF.

Resolution of vulvitis circumscripta plasmacellularis with topical imiquimod: two case reports.

Vulvitis circumscripta plasmacellularis (VCP) is a rare but well-described entity. It is notorious for its recalcitrant nature to various modalities of treatment. Intralesional interferon-alpha showed some promise, with complete resolution, but is coupled with the side-effect of myelosuppression. Topical imiquimod is a novel immune response modifier with the ability to induce the production of interferon-alpha. In this paper, we report two cases of VCP whose lesions were resistant to antibiotics, topical and oral corticosteroids, but resolved after a treatment trial with imiquimod.

Spindle cell variant of epithelioid sarcoma: an easily misdiagnosed tumour.

Epithelioid sarcoma is a histologically distinct soft tissue sarcoma of high grade malignancy. We report a case of epithelioid sarcoma in a young man who presented with multiple nodules over the left forearm, with bony invasion and pulmonary metastases. The histological features of the dermal tumour were those of a malignant spindle cell tumour with positive cytokeratin and vimentin staining and differed from the classical epithelioid sarcoma in its absence of typical necrobiotic nodular epithelioid pattern. It was the clinical presentation and the histology of the subcutaneous nodules that led to the final diagnosis of epithelioid sarcoma. This case illustrates a predominance of spindle cell pattern in the dermal tumour of epithelioid sarcoma, which has previously been reported as fibroma-like variant of epithelioid sarcoma.

G protein modulation of voltage-sensitive muscarinic receptor signalling in mouse pancreatic acinar cells.

Submaximal stimulation of mouse pancreatic acinar cells by acetylcholine (ACh) generates periodic Ca2+ responses sensitive to the membrane potential. Monitoring the muscarinic Ca2+ responses using patch-clamp whole-cell current recordings, we examined the mechanism of guanine nucleotide-binding protein (G protein)-receptor interaction in terms of the membrane potential. The lowest ACh concentration able to elicit consistent repetitive spikes was 50 nM, in the presence of which hyperpolarization increased and depolarization decreased the spike frequency. The saturating concentration was 10 microM, this induced a sustained response insensitive to voltage. Internal guanosine 5'-tri- and diphosphates (GTP, GDP) depressed and potentiated the voltage sensitivity, respectively, but not for the response to a saturating ACh concentration (10 microM). Internal guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) abolished the voltage sensitivity. The results indicate that the ACh-induced Ca2+ response is sensitive to the membrane potential and that a close linkage exists between voltage sensitivity and the G protein association/dissociation cycle in the muscarinic receptor.

Identification of cyclic ADP-ribose-dependent mechanisms in pancreatic muscarinic Ca(2+) signaling using CD38 knockout mice.

We showed that muscarinic acetylcholine (ACh)-stimulation increased the cellular content of cADPR in the pancreatic acinar cells from normal mice but not in those from CD38 knockout mice. By monitoring ACh-evoked increases in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) using fura-2 microfluorimetry, we distinguished and characterized the Ca(2+) release mechanisms responsive to cADPR. The Ca(2+) response from the cells of the knockout mice (KO cells) lacked two components of the muscarinic Ca(2+) release present in wild mice. The first component inducible by the low concentration of ACh contributed to regenerative Ca(2+) spikes. This component was abolished by ryanodine treatment in the normal cells and was severely impaired in KO cells, indicating that the low ACh-induced regenerative spike responses were caused by cADPR-dependent Ca(2+) release from a pool regulated by a class of ryanodine receptors. The second component inducible by the high concentration of ACh was involved in the phasic Ca(2+) response, and it was not abolished by ryanodine treatment. Overall, we conclude that muscarinic Ca(2+) signaling in pancreatic acinar cells involves a CD38-dependent pathway responsible for two cADPR-dependent Ca(2+) release mechanisms in which the one sensitive to ryanodine plays a crucial role for the generation of repetitive Ca(2+) spikes.

Effect of diadenosine tetraphosphate (AP4A) on coronary arterial microvessels in the beating canine heart.

Diadenosine tetraphosphate (AP4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was also investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP4A (1, 10, 100 and 1,000 micromol/L) was superfused onto the heart surface before and during the superfusion of 10 micromol/L of 8-phenyltheophylline (8-PT), a P1 purinoceptor blocker. In Protocol 2, AP4A (0.1, 1, 10, and 100 nmol x kg(-1) x min(-1)) was infused into the left anterior descending coronary artery before and during the superfusion of 10 micromol/L of 8-PT. In addition to 8-PT, 30 micromol/L of pyridoxalphosphate-6-azophenyl 2',4'-disulphonic acid (PPADS), a P2X purinoceptor blocker in Protocol 3, or 300 micromol/L of N(omega)-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10 micromol/L of alpha,beta-methylene ATP, an agonist of P2X purinoceptors, was superfused for 60 min. Superfused AP4A dilated arterioles in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel < or = 150 microm: 24.5+/-2.2% vs large vessel > 150 microm: 10.6+/-1.5% at a dose of 1,000 micromol/L, p<0.001). On the other hand, intraluminally applied AP4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP4A were attenuated and the lower doses of AP4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP4A was almost abolished in the presence of LNNA. Alpha,beta-methylene ATP had no effect on coronary microvascular diameters. AP4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects mediated by P1 purinoceptors and NO, which might be mediated by P2Y purinoceptors, and a vasoconstrictor effect, which is not mediated by P2X purinoceptors.

Cutaneous leishmaniasis: a report of two cases seen at a tertiary dermatological centre in Singapore.

Cutaneous leishmaniasis (CL) is not common in South-East Asia and often presents as a granulomatous plaque on the exposed areas, with a high index of suspicion required for diagnosis. Two such cases were seen at the National Skin Centre recently, and both were Gurkha men with a history of travel to Belize. They were treated with intravenous sodium stibogluconate with success. A discussion on CL and its management follows.

Cutaneous Rosai-Dorfman disease--a pathologic review of 2 cases.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare but distinct clinicopathologic entity characterised histologically by a benign s histiocytic proliferation. Isolated involvement of extranodal sites without concomitant nodal disease is rare. We describe the pathological features of 2 cases of Rosai-Dorfman disease that were clinically confined to the skin. In both male adult Chinese patients, proliferation of histiocytes was accompanied by S-100 protein expression demonstrated immunohistochemically within the histiocytes. The pathology of Rosai-Dorfman disease and its microscopic differential diagnoses are discussed.

A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence.

Voltage-gated sodium (Na(+)) channels are a fundamental target for modulating excitability in neuronal and muscle cells. When depolarized, Na(+) channels may gradually enter long-lived, slow-inactivated conformational states, causing a cumulative loss of function. Although the structural motifs that underlie transient, depolarization-induced Na(+) channel conformational states are increasingly recognized, the conformational changes responsible for more sustained forms of inactivation are unresolved. Recent studies have shown that slow inactivation components exhibiting a range of kinetic behavior (from tens of milliseconds to seconds) are modified by mutations in the outer pore P-segments. We examined the state-dependent accessibility of an engineered cysteine in the domain III, P-segment (F1236C; rat skeletal muscle) to methanethiosulfonate-ethylammonium (MTSEA) using whole-cell current recordings in HEK 293 cells. F1236C was reactive with MTSEA applied from outside, but not inside the cell, and modification was markedly increased by depolarization. Depolarized F1236C channels exhibited both intermediate (I(M); tau approximately 30 ms) and slower (I(S); tau approximately 2 s) kinetic components of slow inactivation. Trains of brief, 5-ms depolarizations, which did not induce slow inactivation, produced more rapid modification than did longer (100 ms or 6 s) pulse widths, suggesting both the I(M) and I(S) kinetic components inhibit depolarization-induced MTSEA accessibility of the cysteine side chain. Lidocaine inhibited the depolarization-dependent sulfhydryl modification induced by sustained (100 ms) depolarizations, but not by brief (5 ms) depolarizations. We conclude that competing forces influence the depolarization-dependent modification of the cysteine side chain: conformational changes associated with brief periods of depolarization enhance accessibility, whereas slow inactivation tends to inhibit the side chain accessibility. The findings suggest that slow Na(+) channel inactivation and use-dependent lidocaine action are linked to a structural rearrangement in the outer pore.

Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels.

1. Local anaesthetics such as lidocaine (lignocaine) interact with sodium channels in a manner that is exquisitely sensitive to the voltage-dependent conformational state of the ion channel. When depolarized in the presence of lidocaine, sodium channels assume a long-lived quiescent state. Although studies over the last decade have localized the lidocaine receptor to the inner aspect of the aqueous pore, the mechanistic basis of depolarization-induced 'use-dependent' lidocaine block remains uncertain. 2. Recent studies have shown that lowering the extracellular Na+ concentration ([Na+]o) and mutations in the sodium channel outer P-loop modulate occupancy of a quiescent 'slow' inactivated state with intermediate kinetics (termed IM) that involves structural rearrangements in the outer pore. 3. Site-directed mutagenesis and ion-replacement experiments were performed using voltage-clamped Xenopus oocytes and cultured (HEK-293) cells expressing wild-type and mutant rat skeletal muscle (mu1) sodium channels. 4. Our results show that lowering [Na+]o potentiates use-dependent lidocaine block. The effect of [Na+]o is maintained despite a III-IV linker mutation that partially disrupts fast inactivation (F1304Q). In contrast, the effect of lowering [Na+]o on lidocaine block is reduced by a P-loop mutation (W402A) that limits occupancy of IM. 5. Our findings are consistent with a simple allosteric model where lidocaine binding induces channels to occupy a native slow inactivated state that is inhibited by [Na+]o.

Squamous cell carcinoma arising in a cutaneous epidermal cyst--a case report.

INTRODUCTION: Cutaneous epidermal cysts are common lesions, but fortunately, malignant transformation of their epithelium is rare. There are only a few cases mentioned in recent literature, mostly occurring in epidermal cysts in the head and neck region. CLINICAL PICTURE: We present a case of malignant transformation in a long-standing buttock epidermal cyst, presenting a month after trauma to the cyst. TREATMENT: An excision biopsy and rotation flap was done. When the pathology was confirmed, a second resection was carried out and the defect covered with a free latissimus dorsi flap, a buttock rotation flap and a posterior thigh rotation flap. CONCLUSION: Although malignant transformation is rare, this case illustrates the importance of routine histology in excision of epidermal cysts.

Cutaneous Rosai-Dorfman disease presenting as pustular and acneiform lesions.

We report 2 cases of cutaneous Rosai-Dorfman disease (CRD) presenting with pustular and acneiform lesions. To our knowledge, these are the first reports of CRD presenting in this pattern. One patient had spontaneous resolution of the lesions, whereas the other was treated with cryotherapy with clinical improvement. We present a review of the literature regarding CRD and highlight the benign nature of this condition.