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Biomedical subjects

S H Lim

Publications and source records attributed to S H Lim.

At least 73 records · Page 4Linked to original sources

Comparative effects of diltiazem with enflurane or desflurane on myocardial contractility and heart rate in the isolated rat hearts.

BACKGROUND: The volatile anesthetics may reduce cardiac contractility by limiting both membrane Ca2+ entry and altering intracellular Ca2+ release. Additional pharmacological effects of calcium channel blockers could potentially enhance anesthetic-induced depression. The aim of this study was to compare the direct cardiac effects of enflurane and a new volatile anesthetic, desflurane, in combination with diltiazem on the isolated Sprague-Dawley rat heart. METHODS: After stabilization period isolated rat hearts (n = 40) were perfused with an oxygenated modified Krebs' solution at 55 mmHg equilibrated with 1, 2 and 3 MAC of enflurane (1.7, 3.4 and 5.1 vol% respectively) or desflurane (6, 12 and 18 vol% respectively) in combination with 100 ng/mL diltiazem at 36 degrees C. Isovolumetric left ventricular pressure (LVP), rate of change of ventricular pressure (dp/dt), spontaneous heart rate and coronary flow were measured. To examine the indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction (POE) were also monitored. RESULTS: Diltiazem plus enflurane or desflurane depressed LVP and dp/dt dose-dependently. Enflurane plus diltiazem significantly decreased heart rate more than desflurane plus diltiazem in a dose-dependent manner. Desflurane plus diltiazem significantly increased coronary flow more than enflurane plus diltiazem and oxygen delivery increased proportionally with coronary flow. But there were statistically insignificant dose-dependent increases in both groups. Myocardial oxygen consumption and percentage of oxygen extraction were also decreased dose-dependently in both groups. Bradydysrhythmia that accompanied atrioventricular dissociation occurred with diltiazem plus high enflurane or desflurane concentration at an incidence of 46% and 40% respectively. CONCLUSIONS: These in vitro results demonstrate that diltiazem plus enflurane or desflurane depresses left ventricular contractile function and diltiazem plus enflurane causes higher incidence of bradydysrhythmia more than equivalent levels of diltiazem plus desflurane.

Anesthetics, Inhalation↗

Cymbidium mosaic virus coat protein gene in antisense confers resistance to transgenic Nicotiana occidentalis.

The nucleotide sequence of the 3'-terminal region of the Korean isolate of cymbidium mosaic virus (CyMV-Ca) from a naturally infected cattleya was determined. The sequence contains an open reading frame (ORF) coding for the viral coat protein (CP) at the 3'-end and three other ORFs (triple gene block or movement protein) of CyMV. The CP gene encodes a polypeptide chain of 220 amino acids with a molecular mass of 23,760 Da. The deduced CP sequence showed a strong homology with those of two CyMVs reported. A construct of the CyMV-Ca CP gene in the antisense orientation in the plant expression vector pMBP1 was transferred via Agrobacterium tumefaciens-mediated transformation into Nicotiana occidentalis which is a propagation host of CyMV. The T1 progeny of the transgenic plants were inoculated with CyMV and found to be highly resistant to CyMV infection.

Agrobacterium tumefaciens↗

Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma.

Idiotypic protein (Id) produced by myeloma cells is clone-specific and may be a suitable tumor-specific antigen for immune targeting. Advances in dendritic cell (DC) technology suggest the opportunity for using this potent antigen presentation system to deliver myeloma Id to the autologous host to elicit anti-tumor immune responses. We have generated DCs from adherent PBMCs from 6 patients with IgG myeloma. These cells were pulsed with the autologous Id and a control vaccine, KLH, and re-infused i.v. back to the patients on 3 separate occasions. Immune responses to KLH and autologous Id were measured and clinical responses monitored. We found that all treatments were well tolerated without any side effects. All patients developed both B- and T-cell responses to KLH, suggesting the integrity of the host immune system to mount immune responses to an antigen delivered using our vaccination strategy. Id-specific responses were also observed. PBMC proliferative responses to Id were observed in 5 of the 6 patients following treatment. In 2 patients, the responses were associated with the production of IFN-gamma. There were also increases in cytotoxic T-cell precursor frequencies for Id-pulsed autologous targets in 3 patients. B-cell responses characterized by the production of anti-Id IgM occurred in 3 and anti-Id IgG in 4 of the 5 evaluated patients. In 1 patient, a modest (25%) but consistent drop in the serum Id level was observed. Id-pulsed DC vaccination can therefore elicit potentially useful anti-myeloma immune responses in patients with multiple myeloma.

Aged↗

Customisation of AFLP analysis for cassava varietal identification.

Amplified fragment length polymorphism (AFLP) markers were used in the characterization of eight cassava varieties. This nonradioactive AFLP system was customized in terms of the choice of restriction enzymes used and the selection of nucleotides added to the 3' end of primers. EcoRI/MseI and HindIII/MseI fragments generally gave monomorphic profiles while ApaI/TaqI fragments produced polymorphic profiles suggesting a genome with high G + C content. It was possible to identify the eight cassava varieties used in this study using CTG as selective bases at the TaqI primer. For cassava, the AFLP system provided a higher number of loci detected per run when compared to RAPD. The reliability accompanying AFLP analysis would thus make it suitable for the characterization of cassava varieties.

DNA Fingerprinting↗

Emergency medicine in Singapore: past, present, and future.

What began in 1948 as a "Casualty and Outpatient Service" at the Singapore General Hospital grew into the first 24-hour emergency unit in 1964 and has since expanded to the current emergency departments of the 6 public hospitals providing acute 24-hour accident and emergency services with an annual patient load of up to 540,000. In 1984, emergency medicine was recognized as a distinct medical specialty by the Ministry of Health. Five years later, structured academic postgraduate training programs were introduced. In 1990, a specialist training committee for emergency medicine was appointed to oversee the development of advanced training in emergency medicine locally. Seven areas of subspecialization have since been identified and are in various stages of development: emergency cardiac care, emergency trauma care, emergency toxicology, prehospital emergency care, pediatric emergency medicine, disaster medicine, and observation medicine. The achievements in emergency medicine in Singapore can help to provide a model for the future development of emergency medicine in other similar environments.

Emergency Medical Services↗

X-linked adrenoleukodystrophy: spinocerebellar variant.

The phenotypic variability in X-linked adrenoleukodystrophy (X-ALD) can be wide and varied. Rarely, it can present with clinical signs of spinocerebellar degeneration. There are very few reported cases of selective predominant white matter disease of the cerebellum in these patients. We report a patient with a rare variant of adult onset ALD who was previously diagnosed as spinocerebellar ataxia. He was a 24-year-old male who had delayed developmental milestones, developed signs of spinocerebellar degeneration (SCD) after 10 years of Addison's disease. Serial Magnetic Resonance Imaging (MRI), revealed cerebellar and pontine white matter disease but sparing the cerebral cortex and supratentorial white matter. His diagnosis of X-ALD was subsequently confirmed by the elevated serum very long chain fatty acids. This patient illustrates the unusual clinical presentation and imaging features of X-ALD and the importance of considering X-ALD in the clinical context of spinocerebellar degeneration. Early recognition of this rare variant would allow proper genetic counselling and institution of dietary therapy and/or bone marrow transplantation.

Addison Disease↗

Sensitization to local dust-mite fauna in Singapore.

BACKGROUND: Recent studies showed the presence of a unique dust-mite fauna in the indoor environment of Singapore. Immediate hypersensitivity to these dust mites, along with other known indoor allergens, may play a role in the pathogenesis of allergic respiratory diseases. This study evaluated the sensitization rates of the local atopic population to these allergens. METHODS: The skin prick test was performed on a total of 391 individuals (289 patients with asthma and/or allergic rhinitis and 102 healthy controls) using extracts of six species of local dust mites (Austroglycyphagus malaysiensis, Blomia tropicalis, Dermatophagoides pteronyssinus, D. farinae, Sturnophagoides brasiliensis, and Tyrophagus putrescentiae) and 10 other common indoor allergens. Total serum IgE and specific IgE to these dust mites were also quantified with the fluorescence allergosorbent test (FAST). RESULTS: The sensitization rates among patients with asthma and/or allergic rhinitis to dust mites and other inhalant allergens tested (via skin prick tests) were as follow: B. tropicalis (96.2%), D. pteronyssinus (93.4%), D. farinae (92.3%), A. malaysiensis (78.2%), S. brasiliensis (71.6%), T. putrescentiae (71.3%), canary feathers (69.9%), Periplaneta americana (cockroach) (59.5%), Blattella germanica (cockroach) (56.4%), mosquito (Aedes sp.) (46.4%), dog epithelia (mixed breed) (34.3%), kapok seed (31.8%), cat hair (29.1%), Aspergillus fumigatus (20.8%), Penicillium notatum (18.0%), and Candida (Monilia) albicans (9.3%). All patients were observed to react to at least three of the six dust-mite extracts, with 254/289 (87.9%) reacting to at least five or to all six. Skin prick responses to the dust mites were found to correlate with the corresponding specific IgE levels quantified by FAST (P<0.001). In addition, specific IgE levels to D. pteronyssinus and D. farinae were highly correlated (Spearman's rank coefficient = 0.76, P<0.001), as were those to B. tropicalis and A. malaysiensis (r = 0.60, P<0.001). CONCLUSIONS: Asthma and/or allergic rhinitis patients were highly sensitized to the local dust-mite fauna. Thus, these dust mites should be considered important allergenic sources of this region.

Adolescent↗

Expression of testicular genes in haematological malignancies.

The gene expression of a new group of tumour antigens known as cancer/testis (CT) antigens is now well-recognized in some solid tumours. However, their expression in haematological malignancies remained unclear. In this study, we have used reverse transcription polymerase chain reaction and Southern blot analysis to examine the presence of transcripts for the three CT antigens, NY-ESO-1, SSX2 and SCP1 in haematological malignant cells. We found that transcripts for SCP1 could be detected in 10% of myeloma, 5.7% of acute myeloid leukaemia and 23% of chronic myeloid leukaemia. In contrast, NY-ESO-1 and SSX2 were not detected in any of the 107 tumour samples.

Antigens, Neoplasm↗

Different properties of T-cell epitopes within complementarity-determining regions 1 and 2 of idiotypic VH in B-lymphoma.

The idiotypic protein expressed by B-lymphoma cells can evoke an autologous idiotype-specific T-cell response in both animal studies and lymphoma patients. However, the locations within the idiotypic protein of the immune epitopes remains unclear. In this study, we determined the nature of any immune responses generated by peptides corresponding to the complementarity-determining region 1 (CDR1) and complementarity-determining region 2 (CDR2) sequences of idiotypic heavy chain variable region (VH) to identify the clinical potential of the peptides for immunotherapy of lymphoma. We found that a synthetic peptide corresponding to CDR1 sequence contains a functional T-cell epitope able to evoke a major histocompatibility complex (MHC) class II-dependent T-cell proliferative response and cytokine release without direct cytotoxicity for peptide-pulsed target or fresh autologous lymphoma cells. Although a peptide corresponding to CDR2 was able to generate MHC class I and class II dependent T-cell proliferative responses and cytokine release, T-cell epitopes within the peptide were cryptic in the context of intact idiotypic protein. Our results therefore suggest that the CDR1 sequence could be used for the immune targeting of B-lymphoma.

Amino Acid Sequence↗

A hemorrhagic factor (Apicidin) produced by toxic Fusarium isolates from soybean seeds.

Fifty-two isolates of Fusarium species were obtained from soybean seeds from various parts of Korea and identified as Fusarium oxysporum, F. moniliforme, F. semitectum, F. solani, F. graminearum, or F. lateritium. These isolates were grown on autoclaved wheat grains and examined for toxicity in a rat-feeding test. Nine cultures were toxic to rats. One of these, a culture of Fusarium sp. strain KCTC 16677, produced apicidin, an antiprotozoal agent that caused toxic effects in rats (including body weight loss; hemorrhage in the stomach, intestines, and bladder; and finally death) when rats were fed diets supplemented with 0.05 and 0.1% apicidin. The toxin was toxic to brine shrimp (the 50% lethal concentration was 40 microg/ml) and was weakly cytotoxic to human and mouse tumor cell lines.

Animals↗

Effect of eradication of Helicobacter pylori on the benign gastric ulcer recurrence--a 24 month follow-up study.

OBJECTIVES: To evaluate the effect of eradication of Helicobacter pylori (H. pylori) on the recurrence of benign gastric ulcer (BGU) in the patients with BGU. METHODS: This study was performed for 40 H. pylori-positive BGU patients cured of BGU and H. pylori eradicated, and for 25 H. pylori-positive patients (non-eradicated group) who were not treated with H. pylori eradication regimen or H. pylori was not eradicated. Four different methods--CLOtest, microscopy of Gram stained mucosal smear, culture and histology of modified Giemsa staining--were taken for identifying colonization of H. pylori before treatment, and 4 weeks after completion of triple therapy. For the control group in which triple therapy was not tried, follow-up gastroscopy was done to confirm the healing of the ulcer. To detect BGU recurrence, the gastroscopy was performed at 6, 12, 18, and 24 months after therapy. RESULTS: In the non-eradicated group, the BGU recurrence rate was 16% within 6 months, 40% within 1 year, 56% within 18 months and 60% within 2 years. The respective recurrence rates in the 40 patients in whom the bacteria had been eradicated were 0%, 7.5%, 10% and 10% (4 patients), respectively. Among the four BGU-recurred patients in whom H. pylori had been eradicated, one patient was found to have BGU recurring with H. pylori positive again in one year, and another two patients had NSAIDs ingestion history. CONCLUSION: The eradication of H. pylori in patients with BGU reduces the recurrence of BGU. In addition, the major causes of BGU recurrence look like NSAIDs ingestion and reinfection of H. pylori.

Adult↗

Acupuncture treatment at Ang Mo Kio Community Hospital--a report on our initial experience.

BACKGROUND: We report our initial experience with acupuncture treatment at the Ang Mo Kio Community Hospital's Acupuncture Research Clinic. PATIENTS: One thousand one hundred and twenty-eight patients received a total of 12,172 acupuncture treatment sessions during the period between September 1995 and December 1996. The majority were Chinese (94%), between 40-70 years (70%) with either dialect or Mandarin (68%) as the main spoken language. However, one third of the patients were English speaking, and educational level did not seem to be a factor among our patients accepting acupuncture treatment. Most had either painful conditions (58%) or stroke-related dysfunction (23%). Amongst the painful conditions, arthritis (25%), low back pain (22%) and other musculo-skeletal pain (12%) were the most common. RESULTS: Prior to treatment, about three-quarter of patients believed acupuncture would benefit them while 40% had tried acupuncture before. After completion of treatment, 70% of all patients considered acupuncture safe, 54% were satisfied with the overall result, 51% felt acupuncture was beneficial, while 54% would recommend acupuncture to others with similar conditions. In a subgroup of patients treated for painful conditions, > 90% reported improvement. Near-syncope occurred in 2 patients (0.18%) or during 2 treatment sessions (0.02%). There was no other acupuncture-related complication. CONCLUSION: Our preliminary experience showed that acupuncture is safe, and appears to be beneficial to patients with painful conditions. An overview of acupuncture treatment is presented, and the issues of safety, efficacy and a need to conduct randomised controlled clinical trials are discussed.

Acupuncture Therapy↗

Role of magnetic resonance imaging and magnetic resonance angiography in patients with hemifacial spasm.

Vascular compression of the facial nerve is a well recognized cause of hemifacial spasm (HFS). In this study, we described the magnetic resonance imaging (MRI) and three-dimensional magnetic resonance angiography (MRA) techniques used and findings in 34 patients with hemifacial spasm. A vascular abnormality, defined as a vessel seen in close proximity, touching or compressing the facial nerve, was identified in 22 of the 25 patients (88%) who had both MRI and MRA studies. Vessels identified were anterior inferior cerebellar artery (59.2%), posterior inferior cerebellar artery (13.6%), vertebral artery (18.2%) and basilar artery (4.5%). All vascular abnormalities were ipsilateral to the side of the HFS. Only 3 of the 12 controls (25%) had a vascular abnormality in both MRI and MRA studies. One of the 9 HFS patients (11.1%) who had MRI only had an ipsilateral vascular abnormality. There is a role for combined MRI and MRA studies in the non-invasive evaluation of patients with HFS.

Adult↗

The use of magnesium sulphate in the intensive care management of an Asian patient with tetanus.

Tetanus, a potentially fatal but largely preventable disease through immunisation, is rare in Singapore. Timely diagnosis and appropriate intensive care management is essential to ensure survival. We aim to report the management of such a patient with magnesium sulphate. This has not been reported locally. By maintaining serum magnesium at 3 to 4 mmol/l we were able to control sympathetic overactivity by day 6, stop neuromuscular blockade by day 7 and wean off ventilator by day 11. Aminoglycoside-induced hypomagnesemia was also demonstrated, necessitating an increase in magnesium sulphate infusion rate to maintain serum magnesium at therapeutic level.

Adult↗

Prevalence of antibodies against proteins derived from leukemia cells in patients with chronic myeloid leukemia.

Although various studies supported the notion that leukemia cells in chronic myeloid leukemia (CML) may be recognized by the immune system, direct evidence showing the immunogenicity in vivo of proteins derived from the leukemia cells is lacking. In this study, we have constructed an expression cDNA library from the leukemia cells of a patient with CML and used the autologous serum to screen for high-titer IgG antibodies directed at the leukemia-derived proteins. We isolated eight distinct clones from the library, suggesting that multiple immune responses were elicited in the autologous host. Sequence analysis showed high degrees of homology to known gene sequences in six of the eight clones. Neither bcr-abl nor proteinase 3 sequences were isolated. Using Northern blot analysis, seven of the eight clones showed ubiquitous expression in normal bone marrow, leukemia cell lines, fresh leukemia cells, and normal tissues. However, clone no. 4 showed restricted mRNA expression, being only detected in some fresh leukemia cells, K562 cells, and normal testicular RNA. Using bacterial lysates in dot blot analysis, a panel of sera from normal individuals and patients with CML and other hematological malignancies were screened for high-titer antibodies against these eight clones. There were, among the CML patients, signficantly higher prevalence of antibodies against seven of the eight clones. They were observed even after omitting from the analysis patients with multiple myeloma whose associated immune paresis may impair immune responses to these proteins. Interestingly, antibodies against these proteins were also detected in a small number of normal individuals. Although the precise clinical significance of our findings remains to be determined, this study provides evidence in support of the potential immunogenicity of leukemia-derived proteins in the autologous host. It also provides basis for further investigations to characterize these proteins, especially clone no. 4, and determine their potential for immune targeting in CML.

Adolescent↗

Molecular characterisation of tumour infiltrating lymphocytes in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is often associated with a lymphocytic infiltrate that is believed to represent an in vivo immune reaction to the tumour cells. In this study, the tumour-infiltrating lymphocytes (TIL) associated with primary OSCC were characterised molecularly in six newly-diagnosed patients to determine the nature of the immune response to the primary tumour. The primary tumours in three of the six patients were associated with a moderate to dense CD8+ T cell infiltrate whilst the cellular infiltrate in the other primary tumours was sparse. The CD3+ T cells were also HLA-DR+. In all cases, there were few CD56+ cells, suggesting that TIL were predominantly T cells bearing the alpha/beta T cell receptors (TCR). The TCR Vbeta repertoire of TIL in these six cases was analysed. TCR Vbeta gene usage by TIL was heterogeneous. A restricted usage of TCR Vbeta genes by TIL was evident in two tumours associated with a dense CD3+ T cell infiltrate. In one of these, there was histological evidence of tumour cell destruction by TIL. Further analysis of the predominant TCR Vbeta gene family used by TIL in this individual showed a unique in-frame nucleotide sequence in 100% of the transcripts. This recurrent transcript was not detected in the peripheral blood of this patient, indicating a local T cell clonal expansion in the vicinity of the tumour. Overall, these results suggest that activation and clonal expansion of T cells occurs and may play a role in local tumour destruction in OSCC.

Adult↗

Acetazolamide-induced severe pancytopenia mimicking myelodysplasia relapse following allogeneic bone marrow transplantation.

Pancytopenia with severe bone marrow dysplasia following allogeneic bone marrow transplantation for acute myeloid leukemia (M6) may pose a diagnostic problem. We report a case of M6 acute myeloid leukemia in which progressive macrocytosis, pancytopenia and severe bone marrow dysplasia induced by acetazolamide therapy developed after successful engraftment of a donor marrow. We discuss the diagnostic problems and the usefulness of conventional cytogenetics and interphase fluorescence in situ hybridisation in excluding recipient myelodysplasia relapse. We also suggest that acetazolamide should be used with caution, especially following bone marrow transplantation.

Acetazolamide↗