Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.

This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K(ATP) channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

Computer-based testing of the modified essay question: the Singapore experience.

BACKGROUND: The modified essay question (MEQ), featuring an evolving case scenario, tests a candidate's problem-solving and reasoning ability, rather than mere factual recall. Although it is traditionally conducted as a pen-and-paper examination, our university has run the MEQ using computer-based testing (CBT) since 2003. AIMS: We describe our experience with running the MEQ examination using the IVLE, or integrated virtual learning environment (https://ivle.nus.edu.sg), provide a blueprint for universities intending to conduct computer-based testing of the MEQ, and detail how our MEQ examination has evolved since its inception. METHODS: An MEQ committee, comprising specialists in key disciplines from the departments of Medicine and Paediatrics, was formed. We utilized the IVLE, developed for our university in 1998, as the online platform on which we ran the MEQ. We calculated the number of man-hours (academic and support staff) required to run the MEQ examination, using either a computer-based or pen-and-paper format. RESULTS: With the support of our university's information technology (IT) specialists, we have successfully run the MEQ examination online, twice a year, since 2003. Initially, we conducted the examination with short-answer questions only, but have since expanded the MEQ examination to include multiple-choice and extended matching questions. A total of 1268 man-hours was spent in preparing for, and running, the MEQ examination using CBT, compared to 236.5 man-hours to run it using a pen-and-paper format. Despite being more labour-intensive, our students and staff prefer CBT to the pen-and-paper format. CONCLUSIONS: The MEQ can be conducted using a computer-based testing scenario, which offers several advantages over a pen-and-paper format. We hope to increase the number of questions and incorporate audio and video files, featuring clinical vignettes, to the MEQ examination in the near future.

Take a bao if you are not superstitious.

INTRODUCTION: Singaporeans are superstitious, and medical staff are no exception to the rule. We conducted a survey to determine the prevalence of superstitious beliefs and practices amongst doctors, nurses and medical students in Singapore. METHODS: Internet and face-to-face surveys of 68 respondents, all of whom completed the survey after being threatened with curses and hexes. RESULTS: Sixty-eight doctors, nurses and medical students responded to our survey. Only 11 admitted to being superstitious, yet 31 believed in the ill-fortune associated with eating bao or meat dumplings, 6 in the nefarious powers of black (5) or red (1) outfits on call, and 14 believed that bathing (6 insisting on the powers of the seven-flower bath) prior to the onset of a call portended good fortune, in terms of busy-ness of a call. Twenty-four believed in "black clouds", i.e. people who attracted bad luck whilst on call, and 32 refused to mouth the words "having a good call" until the day after the event. We discovered 2 hitherto undescribed and undiscovered superstitions, namely the benefits of eating bread and the need to avoid beef, for the good and ill fortune associated with their ingestion. DISCUSSION: Superstitious practices are alive and well in modern-day Singapore, the practice not necessarily being restricted to the poorly-educated or foolish.

Botulinum toxin: a novel therapeutic option for bronchial asthma?

Two components are essential for the development of an attack of bronchial asthma: inflammation and bronchoconstriction, the latter being mediated by smooth muscle contraction. Despite the efficacy of chronic therapy, many asthmatics relapse. Measures to inhibit contraction of the airway smooth muscle, such as vagotomy and thermoablation, may decrease the bronchoconstrictor component of the asthma attack and help to decrease morbidity and mortality from the disease. Botulinum toxin acts to weaken skeletal and smooth muscle by preventing the docking of the acetylcholine vesicle on the inner surface of the presynaptic membrane, thus causing chemical denervation and paresis of skeletal or smooth muscle. We explore the possibility that administration of botulinum toxin may achieve the same effect in bronchial asthma and examine the evidence to support this hypothesis.

Where has all the botox gone? (how) will we ever learn... using monoclonal antibodies to track botulinum toxin.

Botulinum toxin (BTX) is an important therapeutic tool in the treatment of overactive skeletal and smooth muscles, as well as hypersecretory and painful disorders. Despite advances in our understanding of how BTX works, much remains to be elucidated, such as how BTX ameliorates pain, how it produces weakness remote from the site of injection and the fate of the heavy and light chain components of the BTX molecule following endocytosis into the presynaptic membrane. BTX, conjugated to radionuclides, allows investigators to track the molecule both in vitro and in vivo. However, altering the BTX molecule may cause structural changes or pharmacokinetic and pharmacodynamic alterations, and disrupt its normal action. We propose instead to bind the biomarkers (appropriate dyes, radionuclides or MRI contrast agents) to monoclonal antibodies directed against either heavy or light chain components of BTX, thus allowing administration of native (i.e. unaltered) BTX.

Topical botulinum toxin to treat hyperhidrosis? No sweat!

Palmar, plantar and axillary hyperhidrosis, though benign, may be burdensome and occupationally restrictive, even hazardous. Treatment modalities range from topical antiperspirants, iontophoresis, systemic medications such as anticholinergics and benzodiazepines and injections of botulinum toxin, to thoracic sympathectomy. Intradermal injections of botulinum toxin (BTX), though effective, are painful especially when multiple injections are required. Iontophoretic administration of BTX has been described, the BTX entering the eccrine sweat glands via the sweat pores and through the sweat ducts. We postulate that BTX can be administered topically, either unassisted or assisted by application of an electrical gradient, low-frequency ultrasound or excipients such as dimethylsulfoxide. We examine the rationale and feasibility for such a treatment modality and route of administration.

Haplotypes of the beta2-adrenergic receptor gene are associated with essential hypertension in a Singaporean Chinese population.

OBJECTIVE: To investigate the relation between the gene encoding the beta2-adrenergic receptor (B2AR) and essential hypertension in a Singaporean Chinese cohort. METHODS: Three single nucleotide polymorphisms (SNPs) were genotyped in 190 cases and 323 controls, and eight haplotypes were determined and tested for association using the likelihood test statistic. RESULTS: We observed a significant difference in haplotype frequency distributions between the cases and the controls (P <0.00001). A logistic regression model fitted to the data supported this finding. CONCLUSION: The results suggest that variants at the B2AR locus may play a role in the pathophysiology of hypertension in this population.

Singapore's experience of SARS.

The coronavirus that causes severe acute respiratory syndrome (SARS) is transmitted mainly via respiratory droplets. Typical presenting symptoms are akin to those of ordinary pneumonia. Young patients start with fever, chills, malaise, headache, or myalgia; cough and dyspnoea follow. Older persons and those taking corticosteroids may have neither fever nor respiratory symptoms. Exceptional suspicion is needed to identify SARS early in the illness. During an outbreak, even patients with low suspicion of SARS should be promptly isolated, and all contacts quarantined. Health workers need training in the use of appropriate barriers against droplets and other body fluids. Any fever cluster in patients or carers requires immediate action: discharges, visits, and transfers between wards and hospitals should be stopped. Halting hospital admissions and ten-day quarantine of suspected cases create wide buffer zones. To counter a possible resurgence of SARS, a system of prepared isolation and quarantine facilities is important.

The challenges of "continuing medical education" in a pandemic era.

Closure of medical schools or the barring of "live patient" contact during an epidemic or pandemic is potentially disruptive to medical education. During the SARS epidemic, the use of web-based learning, role play, video vignettes and both live and mannequin-based simulated patients minimised disruptions to medical education. This article examines the pedagogical innovations that allow clinical teaching to continue without medical students examining actual patients, and proposes a contingency plan in the event of future outbreaks that may necessitate similar containment measures.

Harnessing the IT factor in medical education.

Escalating healthcare costs in Singapore have produced a significant movement of patients into ambulatory care, and the consequent dearth of clinical teaching materials. This deficiency has likewise prompted the creation of ambulatory teaching clinics and the use of standardised patients and simulators. In the last few decades, educators have utilised digital technology, for instance, digitally recorded heart and breath sounds, and digitised video vignettes, in medical education. We describe several pedagogical initiatives that we have undertaken at our university school of medicine.

Expression of neuronal nitric oxide synthase in the internal thoracic artery and saphenous vein.

OBJECTIVES: Endothelial nitric oxide synthase (type III) generates nitric oxide, which dilates blood vessels. Recently, it was discovered that arterial smooth muscle cells express neuronal nitric oxide synthase (type I). The purpose of this study was to determine the relative amounts of neuronal nitric oxide synthase in the human internal thoracic artery and saphenous vein. METHODS: Remainder segments of internal thoracic arteries and saphenous veins were obtained from 45 patients during coronary artery bypass grafting. Western blotting used specific antibodies against the 3 isoforms of human nitric oxide synthase and beta-actin (for normalization) to measure the relative amounts of the 3 isoforms of nitric oxide synthase proteins in vessel specimens. Immunohistochemistry was used to localize the 3 proteins in specific cells. RESULTS: Western blotting detected all 3 isoforms of nitric oxide synthase in the human internal thoracic artery. The band density (normalized to beta-actin) of neuronal nitric oxide synthase was not significantly different from the band density of endothelial nitric oxide synthase. The amounts of neuronal nitric oxide synthase in arteries and veins were equal. Immunohistochemistry showed that the highest expression of endothelial nitric oxide synthase was in endothelial cells, but some expression was also seen in smooth muscle cells. Most of the neuronal nitric oxide synthase was in smooth muscle cells. The location and relative amounts of inducible nitric oxide synthase were variable. CONCLUSIONS: Neuronal nitric oxide synthase is expressed in the vascular smooth muscle of patients undergoing bypass, and the amount in the internal thoracic artery is the same as in the saphenous vein.