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Biomedical subjects

C C Lim

Publications and source records attributed to C C Lim.

At least 19 recordsLinked to original sources

Endoscopic retrograde cholangiopancreatography in the elderly: outcomes, safety and complications.

INTRODUCTION: As the population ages, the incidence of biliary tract pathologies also increases, leading to an increase in the demand for endoscopic retrograde cholangiopancreatography (ERCP) interventions. Our aims are to assess the outcomes, safety and complications associated with ERCP performed in an elderly population. METHODS: Patients aged 80 years or over referred for ERCP from January 1999 to September 2002, were identified and retrospectively reviewed. RESULTS: 103 patients (68 females, mean age 84.6 +/- 3.9 years old) underwent 144 procedures (1-6 procedures/patient). The main indications were cholangitis (51.4 percent), choledocholithiasis (19.4 percent) and blocked stents (14.6 percent). Malignancies represented 5.6 percent of indications. The mean procedure time was 38 +/- 16 minutes. The overall success rate was 80.5 percent. Minor events occurred in 23 percent (tachycardia 13, desaturation six, transient hypotension six, self-limiting bleed four, extravasations three, and mild pancreatitis one). Major events were post sphincterotomy bleeding (five days post-procedure) one, duodenal perforation one (Billroth-II gastrectomy, survived after surgery), cholangitis two, and one death was probably procedure-related (acute myocardial event five days post-stenting in a patient with Klatskin tumour). Seven deaths occurred within one month of ERCP, due to advanced malignancies (four), sepsis (two) and acute myocardial infarction (one). Patients who died within one month had significantly higher serum urea (p-value equals 0.001), and creatinine (p-value equals 0.007) levels, and lower haemoglobin (p-value equals 0.014) level. More patients had an underlying malignancy (p-value less than 0.001). In addition, they were given significantly less conscious sedation (midazolam [p-value equals 0.002] and fentanyl [p-value equals 0.018]). CONCLUSION: Our study showed that ERCP is safe in an elderly Asian population. Minor complications are usually transient and related to sedation, and mortality is usually related to severity of illness and underlying malignancies.

Aged, 80 and over↗

Abnormal liver function tests in the symptomatic pregnant patient: the local experience in Singapore.

INTRODUCTION: The causes of abnormal liver function tests in pregnancy are varied and may or may not be pregnancy-related. Often, the diagnosis can be difficult. This study looked at the causes of deranged liver function tests in obstetric patients with significant symptoms and signs. MATERIALS AND METHODS: Data from 50 cases of abnormal liver function tests in pregnant patients, who presented from 1998 to 2001, were analysed. Their presenting symptoms included persistent vomiting (48%), pruritus (14%), jaundice (26%), upper abdominal discomfort (24%) and hypertension (46%). RESULTS: Pregnancy-related causes accounted for 84% of the abnormal liver function tests. Abnormal liver function tests occurred more frequently in the first (34%) and third (58%) trimesters than in the second trimester (8%). Hyperemesis gravidarum (94%) and partial haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (31%) were the commonest causes in the first and third trimesters respectively. Hepatitis B flare resulted in 2 maternal deaths. Seven patients with pre-eclampsia toxaemia, acute fatty liver of pregnancy or partial/complete HELLP syndrome had their liver function tests measured sequentially before and after delivery. All of them showed rapid improvement postpartum with their alanine aminotransferase (ALT) dropping 50% within 3 days. CONCLUSIONS: The majority of patients with abnormal liver function tests had a cause related to pregnancy, and pregnancy-related causes in the third trimester improved rapidly postpartum. Hepatitis B flare was a significant non-obstetric cause leading to maternal mortality. This diagnosis must therefore be considered in ethnic groups where the incidence of chronic hepatitis B infection is high, especially in chronic hepatitis B carriers with suspected pregnancy-related disease who deteriorate postpartum.

Adult↗

Clip-induced biliary stone.

Surgical clip migration is a well-known phenomenon ever since their first use in surgery. The mechanism of clip migration is poorly understood, and can occur from days to years after laparoscopic cholecystectomy. Migration of the surgical clips may be a complex process involving necrosis, pressure exerted from intra-abdominal movement, formation of stones over the exposed clip within the bile duct, and eventual migration into the common bile duct. We report two cases, a 58-year-old man and a 54-year-old woman, of clip- induced biliary stones resulting from surgical clip migration a few years after laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗

Diffusion-weighted MR imaging in intracranial infections.

INTRODUCTION: Diffusion-weighted magnetic resonance (MR) imaging (DWMRI) is valuable in the assessment of acute cerebral infarction and may be useful for other diseases of the central nervous system (CNS). In this study, we present the DWMRI appearance of intracranial infection. MATERIALS AND METHODS: Thirty patients with clinical diagnosis of CNS infection were reviewed. All patients underwent conventional contrast-enhanced MR examination and DWMRI using single-shot echo-planar imaging at b = 1000 s/mm2. RESULTS: Cerebral abscess, tuberculoma, subdural empyema and epidural abscess were hyperintense on DWMRI. Neurocysticercosis showed hypointense lesions on DWMRI. Four of 5 patients with encephalitis showed DWMRI hyperintensity; the appearance of toxoplasmosis lesions was variable. Patients suffering from meningitis without parenchymal involvement did not exhibit any abnormality of diffusion. One patient with tuberculous meningitis developed abnormality on DWMRI from acute cerebral infarction. CONCLUSION: DWMRI increased lesion conspicuity and may be useful in assessment of cerebral infection. There were striking differences in the DWMRI appearances caused by different organisms and diseases.

Brain Abscess↗

Intracerebral schwannoma--a rare cause of epilepsy.

INTRODUCTION: We report a case of schwannoma occurring in an intra-axial location causing seizures. CLINICAL PICTURE: A 13-year-old girl presented with a 4-month history of seizures. Preoperative computed tomography scan and magnetic resonance imaging revealed an enhancing right frontal lobe tumour with surrounding oedema. TREATMENT: The patient underwent craniotomy and a well-circumscribed tumour was completely resected. Histology with immunohistochemistry confirmed the diagnosis of an intracerebral schwannoma. OUTCOME: The patient made a complete recovery and was seizure-free at 1-year follow-up. CONCLUSION: Intracerebral schwannomas are rare, benign tumours. They may mimic astrocytomas or malignant tumours, and it is important to differentiate them from other neoplasms with less favourable outcomes. The neuroimaging features are, however, non-specific and definitive diagnosis can only be made on histology.

Adolescent↗

Advanced disseminated gastric carcinoma in pregnancy.

Gastric cancers associated with pregnancy are rare and often diagnosed at advanced stages where curative therapies are not possible. The outcomes have generally been very poor with death occurring within months of diagnosis. Suspicion and early endoscopy are necessary for early diagnosis. We herein report a case of advanced disseminated gastric cancer presenting in the third trimester with pre-eclampsia and death occurring less than a month after diagnosis.

Adenocarcinoma↗

MRI findings in osmotic myelinolysis.

OBJECTIVES: Osmotic myelinolysis is a distinctive clinical syndrome with characteristic CT and MR features. This study was undertaken to determine the MR appearance of these lesions on T1 and T2-weighted, and diffusion-weighted imaging (DWI) sequences with apparent diffusion coefficient (ADC) mapping. MATERIALS AND METHODS: We describe six patients who presented with deranged serum sodium levels and subsequently developed osmotic myelinolysis. CT and MRI scans were retrospectively reviewed, including the advanced functional MR sequence of DWI with ADC mapping. RESULTS: Both cerebral white matter and pontine lesions were typically hypo and hyper-intense on T1 and T2W sequences respectively. Lesions were mildly hyperintense on isotropic DWI images with elevation of the ADC. CONCLUSION: MRI is superior to CT in depicting lesions in osmotic myelinolysis. DWI with ADC mapping suggests that osmotic myelinolysis is not simply a demyelinating disorder but has similarities to multiple sclerosis.

Adult↗

Targeted inactivation of Galpha(i) does not alter cardiac function or beta-adrenergic sensitivity.

Inhibitory Galpha(i) protein increases in the myocardium during hypertrophy and has been associated with beta-adrenergic receptor (beta-AR) desensitization, contractile dysfunction, and progression of cardiac disease. The role of Galpha(i) proteins in mediating basal cardiac function and beta-AR response in nonpathological myocardium, however, is uncertain. Transgenic mice with targeted inactivation of Galpha(i2) or Galpha(i3) were examined for in vivo cardiac function with the use of conscious echocardiography and for ex vivo cardiac response to inotropic stimulation with the use of Langendorff blood-perfused isolated hearts and adult ventricular cardiomyocytes. Echocardiography revealed that percent fractional shortening and heart rate were similar among wild-type, Galpha(i2)-null, and Galpha(i3)-null mice. Comparable baseline diastolic and contractile performance was also observed in isolated hearts and isolated ventricular myocytes from wild-type mice and mice lacking Galpha(i) proteins. Isoproterenol infusion enhanced diastolic and contractile performance to a similar degree in wild-type, Galpha(i2)-null, and Galpha(i3)-null mice. These data demonstrate no observable role for inhibitory G proteins in mediating basal cardiac function or sensitivity to beta-AR stimulation in nonpathological myocardium.

Adrenergic beta-Agonists↗

High-throughput assessment of calcium sensitivity in skinned cardiac myocytes.

Isolated permeabilized cardiac myocytes have been used in the study of myofilament calcium sensitivity through measurement of the isometric force-pCa curve. Determining this force-pCa relationship in skinned myocytes is relatively expensive and carries a high degree of variability. We therefore attempted to establish an alternative high-throughput method to measure calcium sensitivity in cardiac myocytes. With the use of commercially available software that allows for precise measurement of sarcomere spacing, we measured sarcomere length changes in unloaded skinned cardiac myocytes over a range of calcium concentrations. With the use of this technique, we were able to accurately detect acute increases or decreases in myofilament calcium sensitivity after exposure to 10 mM caffeine or 5 mM 2,3-butanedione monoxime, respectively. This technique allows for the simple and rapid determination of myofilament calcium sensitivity in cardiac myocytes in a reproducible and inexpensive manner and could be used for high-throughput screening of pharmacological agents and/or transgenic mouse models for changes in myofilament calcium sensitivity.

Animals↗

The alpha1/2 helical backbone of the prodomains defines the intrinsic inhibitory specificity in the cathepsin L-like cysteine protease subfamily.

Proregions of papain-like cysteine proteases are potent and often highly selective inhibitors of their parental enzymes. The molecular basis of their selectivity is poorly understood. For two closely related members of the cathepsin L-like subfamily we established strong selectivity differences. The propeptide of cathepsin S was observed to inhibit cathepsin L with a K(i) of 0.08 nM, yet cathepsin L propeptide inhibited cathepsin S only poorly. To identify the respective structural correlates we engineered chimeric propeptides and compared their inhibitory specificity with the wild-types. Specificity resided in the N-terminal part, strongly suggesting that the backbone of the prodomain was the underlying structure.

Amino Acid Sequence↗

Impaired cell shortening and relengthening with increased pacing frequency are intrinsic to the senescent mouse cardiomyocyte.

Increased heart rate enhances cardiac contractility and accelerates relaxation. Both the force- and relaxation-frequency relationships are critical to myocardial function, especially during stress, and have been shown to be impaired in senescent myocardium. While senescent myocardium is characterized by decreased sarcoplasmic reticulum calcium ATPase activity, it is unclear if altered calcium regulation is directly responsible for the attenuated contractility and relaxation observed with increasing pacing frequency in aged myocardium. We examined this issue using freshly dissociated left ventricular myocytes, isolated from young adult and senescent mouse hearts. Myocytes were paced from 2 to 9 Hz at 37 degrees C, and cell shortening and [Ca(2+)](i)were simultaneously measured using video edge-detection and fura-2 fluorescence, respectively. In adult myocytes, increasing the pacing rate resulted in a progressive increase in percent cell shortening (CS) (P<0.01). This positive CS-frequency relationship was paralleled by an increase in [Ca(2+)](i)transient amplitude (P<0.05). In contrast, the CS-frequency relationship was blunted in senescent myocytes with no increase in percent CS or [Ca(2+)](i)transient amplitude with increasing pacing rate. With increased pacing, the decreases in time constants (tau) of cell relengthening and Ca(2+)transient decay were much steeper in adult compared to senescent myocytes (P<0.05). This study demonstrates that adult mouse myocytes exhibit augmented intracellular Ca(2+)transient amplitude and enhanced intracellular Ca(2+)removal with increasing pacing frequency, resulting in increased cell shortening and enhanced relengthening with frequency. In contrast, senescent mouse myocytes exhibit impaired calcium handling with increasing pacing frequency, which correlated with impairment of both cell shortening and relengthening.

Aging↗

Negative association between T102C polymorphism at the 5-HT2A receptor gene and bipolar affective disorders in Singaporean Chinese.

BACKGROUND: Serotonergic system abnormalities have been implicated in the pathogenesis of bipolar affective disorders. The 5-hydroxytryptamine type 2A (5HTR2A) receptor gene located on chromosome 13 (13q14-21) can be considered as a candidate gene for bipolar affective disorder (BPAD). METHODS: Seventy-two patients with BPAD and 74 normal population controls were genotyped with restriction fragment length polymorphism (RFLP) in the 5HTR2A receptor gene. RESULTS: We report a negative association between 5HTR2A receptor gene and BPAD. The association was examined using a case-control design. Allele and genotype frequencies as well as homozygote-heterozygote distribution at the 5HTR2A receptor gene polymorphism were compared between the two groups. There were no significant differences in the allelic or genotype frequencies and the homozygote-heterozygote distributions. LIMITATIONS: Patients were recruited from one hospital in Singapore. The case-control study design needs replication. CONCLUSION: Our finding indicates that the 5HTR2A receptor gene polymorphism is not a major factor in the genetic susceptibility to BPAD in Singaporean Chinese.

Adult↗

Altered beta-adrenergic signal transduction in nonfailing hypertrophied myocytes from Dahl salt-sensitive rats.

Desensitization of the beta-adrenergic receptor (beta-AR) response is well documented in hypertrophied hearts. We investigated whether beta-AR desensitization is also present at the cellular level in hypertrophied myocardium, as well as the physiological role of inhibitory G (G(i)) proteins and the L-type Ca(2+) channel in mediating beta-AR desensitization. Left ventricular (LV) myocytes were isolated from hypertrophied hearts of hypertensive Dahl salt-sensitive (DS) rats and nonhypertrophied hearts of normotensive salt-resistant (DR) rats. Cells were paced at a rate of 300 beats/min at 37 degrees C, and myocyte contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) were simultaneously measured. In response to increasing concentrations of isoproterenol, DR myocytes displayed a dose-dependent augmentation of cell shortening and the [Ca(2+)](i) transient amplitude, whereas hypertrophied DS myocytes had a blunted response of both cell shortening and the [Ca(2+)](i) transient amplitude. Interestingly, inhibition of G(i) proteins did not restore beta-AR desensitization in DS myocytes. The responses to increases in extracellular Ca(2+) and an L-type Ca(2+) channel agonist were also similar in both DS and DR myocytes. Isoproterenol-stimulated adenylyl cyclase activity, however, was blunted in hypertrophied myocytes. We concluded that compensated ventricular hypertrophy results in a blunted contractile response to beta-AR stimulation, which is present at the cellular level and independent of alterations in inhibitory G proteins and the L-type Ca(2+) channel.

Adenylate Cyclase Toxin↗

Comparison of hearts with 2 types of pressure-overload left ventricular hypertrophy.

Comparisons of myocardium remodeled by the 2 most common causes of left ventricular hypertrophy (LVH), hypertension and aortic constriction, are limited. We hypothesized that important differences may exist in the myocardium of hearts with these 2 origins of "pressure overload" LVH. Accordingly, we studied isolated hearts from 3 groups of Dahl salt-sensitive rats, controls, and hearts with matched amounts of LVH secondary to either hypertension or aortic constriction. Isovolumic LV function and myocardial energetics ((31)P nuclear magnetic resonance spectroscopy) were measured as coronary flow was lowered to 16% of baseline for 48 minutes. During this low-flow ischemia, isovolumic end-diastolic pressure, a measure of LV stiffness, increased to 52+/-4 mm Hg in controls and 51+/-6 mm Hg in aortic banded hearts but to only 35+/-5 mm Hg in hearts with hypertensive LVH. In all hearts, the P(i) resonance in the (31)P nuclear magnetic resonance spectrum, whose position indicates myocardial pH, split into 2 peaks during low-flow ischemia, which indicates distinct regions of pH 6.9 (moderate acidosis) and pH 6.2 (severe acidosis). Concentrations of ATP, PCr, P(i), and H(+) of the moderately acidotic region were not different among groups. However, the size of the severely acidotic region was smallest in the hypertensive LVH hearts, and in all 3 groups, the size of this region correlated (r(2)=0.65 to 0.80) with the degree of LV stiffening. We conclude that in Dahl rats, LVH secondary to hypertension protects against ischemia-induced diastolic dysfunction by minimizing the size of the region of severe acidosis.

Animals↗

Nipah viral encephalitis or Japanese encephalitis? MR findings in a new zoonotic disease.

BACKGROUND AND PURPOSE: An epidemic of suspected Japanese encephalitis occurred in Malaysia in 1998-1999 among pig farmers. In neighboring Singapore, an outbreak occurred among pig slaughterhouse workers. It was subsequently established that the causative agent in the outbreak was not the Japanese encephalitis virus but a previously unknown Hendra-like paramyxovirus named Nipah virus. METHODS: The brain MR images of eight patients with Nipah virus infection were reviewed. All patients tested negative for acute Japanese encephalitis virus. Seven patients had contrast-enhanced studies and six had diffusion-weighted examinations. RESULTS: All patients had multiple small bilateral foci of T2 prolongation within the subcortical and deep white matter. The periventricular region and corpus callosum were also involved. In addition to white matter disease, five patients had cortical lesions, three had brain stem involvement, and a single thalamic lesion was detected in one patient. All lesions were less than 1 cm in maximum diameter. In five patients, diffusion-weighted images showed increased signal. Four patients had leptomeningeal enhancement and four had enhancement of parenchymal lesions. CONCLUSION: The brain MR findings in patients infected with the newly discovered Nipah paramyxovirus are different from those of patients with Japanese encephalitis. In a zoonotic epidemic, this striking difference in the appearance and distribution of lesions is useful in differentiating these diseases. Diffusion-weighted imaging was advantageous in increasing lesion conspicuity.

Abattoirs↗

A randomised trial of amoxycillin versus clarithromycin in combination with omeprazole for eradication of Helicobacter pylori infection in Singapore.

Dual therapy has been reported to produce H.pylori eradication rate of 75-80%. This study is designed to determine the efficacy of omeprazole 20 mg bd in combination with amoxycillin 500 mg tid (Group A), amoxycillin 750 mg tds (Group B) and clarithromycin 500 mg tid (Group C) in Singapore. One hundred and forty-eight patients with H. pylori positive duodenal ulcers between ages of 22 and 69 were enrolled from two centres. There were 48 patients in Group A, 50 patients in Group B and 50 patients in Group C. The medication was given for 14 days. The patients were re-evaluated with an upper GI endoscope 4 weeks after cessation of treatment Successful eradication was defined as H.pylori negative on histology and culture. Based on intention to treat analysis, the eradication rate was 47.8% in Group A, 68% in Group B and 66% in Group C. The difference between GroupA and B were statistically significant (p = 0.04). Based on all patient treated analysis, the eradication rate was 57.5% in Group A, 70.7% in Group B and 75% in Group C. The difference in eradication rates was not statistically significant. Adverse events were reported in 21% of all patients with no difference in the adverse event rate between all groups. The eradication rate achieved with dual therapy in this study was similar to that attained in Western population. Higher dose amoxycillin regime gives a significantly higher eradication than a lower dose amoxycillin.

Adult↗

The influence of finishing time on the marginal seal of a resin-modified glass-ionomer and polyacid-modified resin composite.

The aim of this study was to compare the effect of immediate and delayed finishing on the microleakage of encapsulated resin-modified glass-ionomer, Fuji II LC and a polyacid-modified resin composite, Dyract compomer at both the enamel and dentine margins. Standardized Class V cavities were prepared along the cemento-enamel junction on buccal and palatal surfaces of 24 freshly extracted non-carious premolars. Equal numbers of buccal and palatal cavities in each group were restored with Fuji II LC and Dyract compomer following the manufacturer's instructions. The groups with delayed finishing were restored 1 week earlier, stored in saline at 37 degrees C and finished on the same day as the groups with immediate finishing. The specimens were then thermocycled 500 times and subjected to dye penetration testing. The results showed that both materials leaked more at the dentine than enamel margins for both regimes of finishing methods. There was no statistical difference in the microleakage of Dyract finished immediately or later at enamel and dentine margins and Fuji II LC finished immediately or later in dentine. However, a statistical difference existed between the microleakage in Fuji II LC finished immediately and later in enamel.

Bicuspid↗