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Therapeutic challenges in the era of antibiotic resistance

Lee C

Int J Antimicrob Agents, 2008 Dec;32 Suppl 4:S197-9.
PMID: 19134519 DOI: 10.1016/S0924-8579(09)70002-0

Multidrug microbial resistance poses major challenges to the management of infection, particularly with the paucity of new drugs with activity against these bacteria. Since the turn of this century a few new antibiotics have been licensed, including linezolid, daptomycin and tigecycline. This supplement reports data presented at the 13th International Congress of Infectious Diseases held in Kuala Lumpur in June 2008. Dr R. Isturiz reviews the data on global resistance trends and the potential impact on empirical therapy; Dr J.-H. Song reviews new agents on the antimicrobial horizon; and the final paper in the supplement, by Dr L.R. Peterson, reviews the role of tigecycline in the management of complicated intra-abdominal and skin and soft tissue infections.
Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters

Lee CY

J Anim Physiol Anim Nutr (Berl), 2015 Apr;99(2):317-25.
PMID: 25196093 DOI: 10.1111/jpn.12247

This study investigated the effect of repeated acute restraint stress and high-fat diet (HFD) on intestinal expression of nutrient transporters, concomitant to intestinal inflammation. The ability of adenosine to reverse any change was examined. Six-week-old male Sprague Dawley rats were divided into eight groups: control or non-stressed (C), rats exposed to restraint stress for 6 h per day for 14 days (S), control rats fed with HFD (CHF) and restraint-stressed rats fed with HFD (SHF); four additional groups received the same treatments and were also given 50 mg/l adenosine dissolved in drinking water. Fasting blood glucose, plasma insulin, adiponectin and corticosterone were measured. Intestinal expression of SLC5A1, SLC2A2, NPC1L1 and TNF-α was analysed. Histological evaluation was conducted to observe for morphological and anatomical changes in the intestinal tissues. Results showed that HFD feeding increased glucose and insulin levels, and repeated acute restraint stress raised the corticosterone level by 22%. Exposure to both stress and HFD caused a further increase in corticosterone to 41%, while decreasing plasma adiponectin level. Restraint stress altered intestinal expression of SLC5A1, SLC2A2 and NPC1L1. These changes were enhanced in SHF rats. Adenosine was found to alleviate HFD-induced increase in glucose and insulin levels, suppress elevation of corticosterone in S rats and improve the altered nutrient transporters expression profiles. It also prevented upregulation of TNF-α in the intestine of SHF rats. In summary, a combination of stress and HFD exaggerated stress- and HFD-induced pathophysiological changes in the intestine, and biochemical parameters related to obesity. Adenosine attenuated the elevation of corticosterone and altered expression of SLC5A1, NPC1L1 and TNF-α.
Fulltext The Effect of High-Fat Diet-Induced Pathophysiological Changes in the Gut on Obesity: What Should be the Ideal Treatment?

Y Lee C

Clin Transl Gastroenterol, 2013;4:e39.
PMID: 23842483 DOI: 10.1038/ctg.2013.11

Obesity is a metabolic disorder and fundamental cause of other fatal diseases including atherosclerosis and cancer. One of the main factor that contributes to the development of obesity is high-fat (HF) consumption. Lipid ingestion will initiate from the gut feedback mechanisms to regulate glucose and lipid metabolisms. But these lipid-sensing pathways are impaired in HF-induced insulin resistance, resulting in hyperglycemia. Besides that, duodenal lipid activates mucosal mast cells, leading to the disruption of the intestinal tight junction. Lipopolysaccharide that is co-transited with dietary fat postprandially, promotes the release of cytokines and the development of metabolic syndrome. HF-diet also alters microbiota composition and enhances fat storage. Although gut is protected by immune system and contains high level of antioxidants, obesity developed presumably when this protective mechanism is compromised by the presence of excessive fat. Several therapeutic approaches targeting different pathways have been proposed. There may be no one single most effective treatment, but all aimed to prevent obesity. This review will elaborate on the physiological and molecular changes in the gut that lead to obesity, and will provide a summary of potential treatments to manage these pathophysiological changes.
Fasting and sampling time affect liver gene expression of high-fat diet-fed mice

Lee CY

Animal, 2010 May;4(5):709-13.
PMID: 22444123 DOI: 10.1017/S1751731109991583

Several physiological and biological variables are known to affect peroxisome proliferator-activated receptor (PPAR)-α-dependent signaling pathway and plasma biochemical profiles. However, less is known about the effect of these variables on high-fat diet-fed mice. In a 5-week study, C57BL/6 mice were divided into control (C) and high-fat diet-fed (H) groups, whereby before dissection, each group was subdivided into non-fasted (nC and nH) and a 15-h fasted mice (fC and fH) killed in the early light cycle, and a 15-h fasted mice (eC and eH) killed in the late phase of the light cycle. Liver and blood from the vena cava were collected. Non-fasted nC and nH mice have a marginal difference in their body weight gain, whereas significant differences were found for fasted mice. In nH mice, PPAR-α, acyl-CoA oxidase and insulin-like growth factor-binding protein expressions were significantly elevated, in contrast to fatty acid synthase (Fasn), stearoyl CoA-desaturase (SCD)-1, and elongase (ELOVL)-6 expressions. Fasn was profoundly induced in fH mice, while decreased sterol regulatory-binding protein-1 and SCD-1 were found only in eH mice. Different from the gene expression profiles, plasma total cholesterol level of the eH mice was higher than controls, whereas nH mice have increased plasma non-esterified fatty acids. Only glucose level of the fH mice was higher than that observed for controls. Results showed that fasting and sampling time have significantly affected liver gene expression and plasma biochemical indices of the high-fat diet-treated mice. An overlook in these aspects can cause serious discrepancies in the experimental data and their interpretations.
Fulltext HIV Associated Opportunistic Pneumonias

Ismail T, Lee C

Med J Malaysia, 2011 Mar;66(1):76-82.
PMID: 23765154 MyJurnal

Opportunistic pneumonias are major causes of morbidity and mortality in HIV infected individuals. The majority of new HIV infections in Malaysia are adults aged 20 to 39 years old and many are unaware of their HIV status until they present with an opportunistic infection. HIV associated opportunistic pneumonias can progress rapidly without appropriate therapy. Therefore a proper diagnostic evaluation is vital and prompt empiric treatment of the suspected diagnosis should be commenced while waiting for the results of the diagnostic studies. Tuberculosis, Pneumocystis pneumonia (PCP) and recurrent bacterial pneumonias are common causes of AIDS-defining diseases and are discussed in this article.
Sharpening the Sharpened Romberg

Lee CT

SPUMS J, 1998 Sep;28(3):125-32.
PMID: 11542272

The Sharpened Romberg Test (SRT) is a test of balance commonly used in Diving Medicine. Interpretation of an abnormal test can be confounded by several factors. This study was conducted to further evaluate the usefulness of the SRT. In the first part of the study, naval and civilian volunteers in a Naval Base were recruited as subjects. The SRT scores were recorded in two separate trials; once in the morning (4 attempts) and once in the evening (4 attempts) to evaluate the effect of practice on the SRT. In the second part of the study immediate pre- and post-dive scores in a group of divers were measured to evaluate: (1) the effect of decompression; (2) the effect of the normal post-dive fatigue; and (3) the vestibular effect of swaying after a boat ride. Comparisons were also made between the distributions of the SRTs of the normal subjects and those of a retrospective group of DCI patients treated at the Slark Hyperbaric Unit, Royal New Zealand Navy Hospital (RNZNH), Auckland. The SRT was found to have an early learning effect. Second attempts were significantly better than the first (p<0.001) within the same trial. However this learning effect plateaued by the third and fourth attempts. No difference was found between trials (morning and evening). There was a post-dive decline in the scores of the first attempts only (p<0.05). Subsequent second to fourth attempts were not affected by diving. The practice effect is only evident between the first and second attempts within the same trial but not between trials. The pre- and post-dive data showed that the SRT was not affected by decompression, post-dive fatigue or the vestibular sensation of swaying that is commonly experienced after a boat ride. Comparison of the distributions between controls and DCI patients showed a bimodal pattern. Fifty-four percent (54%) of the DCI patients had 'normal' scores (60 seconds), while 14% had scores between 16-35 seconds and 32% scored less than 15 seconds. In contrast, 95% of the control groups had 'normal' scores while 5% scored between 16-35 seconds. Therefore, accepting a score of less than 40 seconds as being "abnormal" will give the SRT a sensitivity of 46%, specificity of 95% and predictive value of 82%.
Cerebral arterial gas embolism in air force ground maintenance crew--a report of two cases

Lee CT

Aviat Space Environ Med, 1999 Jul;70(7):698-700.
PMID: 10417007

Two cases of cerebral arterial gas embolism (CAGE) occurred after a decompression incident involving five maintenance crew during a cabin leakage system test of a Hercules C-130 aircraft. During the incident, the cabin pressure increased to 8 in Hg (203.2 mm Hg, 27 kPa) above atmospheric pressure causing intense pain in the ears of all the crew inside. The system was rapidly depressurized to ground level. After the incident, one of the crew reported chest discomfort and fatigue. The next morning, he developed a sensation of numbness in the left hand, with persistence of the earlier symptoms. A second crewmember, who only experienced earache and heaviness in the head after the incident, developed retrosternal chest discomfort, restlessness, fatigue and numbness in his left hand the next morning. Both were subsequently referred to a recompression facility 4 d after the incident. Examination by the Diving Medical Officer on duty recorded left-sided hemianesthesia and Grade II middle ear barotrauma as the only abnormalities in both cases. Chest X-rays did not reveal any extra-alveolar gas. Diagnoses of Static Neurological Decompression Illness were made and both patients recompressed on a RN 62 table. The first case recovered fully after two treatments, and the second case after one treatment. Magnetic resonance imaging (MRI) of the brain and bubble contrast echocardiography performed on the first case 6 mo after the incident were reported to be normal. The second case was lost to follow-up. Decompression illness (DCI) generally occurs in occupational groups such as compressed air workers, divers, aviators, and astronauts. This is believed to be the first report of DCI occurring among aircraft's ground maintenance crew.
Quaternized wood as sorbent for hexavalent chromium

Low KS, Lee CK, Lee CY

Appl Biochem Biotechnol, 2001 Jan;90(1):75-87.
PMID: 11257809

The potential of quaternized wood (QW) chips in removing hexavalent chromium from synthetic solution and chrome waste under both batch and continuous-flow conditions was investigated. Sorption was found to be dependent on pH, metal concentration, and temperature. QW chips provide higher sorption capacity and wider pH range compared with untreated wood chips. The equilibrium data could be fitted into the Langmuir isotherm model, and maximum sorption capacities were calculated to be 27.03 and 25.77 mg/g in synthetic chromate solution and chrome waste, respectively. The presence of sulfate in high concentration appeared to suppress the uptake of chromium by QW chips. Column studies showed that bed depth influenced the breakthrough time greatly whereas flow rate of influent had little effect on its sorption on the column.
Fulltext A case of prolonged fever and a diagnosis obscured by an opaque sinus

Velayudhan M, Lee CW

Med J Malaysia, 2014 Jun;69(3):140-1.
PMID: 25326357 MyJurnal

Prolonged fever in patients can be a diagnostic challenge. Clinicians generally consider infectious diseases, malignant diseases and collagen vascular diseases as possible causes of pyrexia of unknown origin (PUO). Even after extensive evaluation as many as 15 percent of patients with prolonged fever may remain undiagnosed. This case report describes subacute thyroiditis as a cause of prolonged fever and documents how that diagnosis was finally made after 40 days of fever.
Fulltext Pain during venous cannulation: Double-blind, randomized clinical trial of analgesic effect between topical amethocaine and eutectic mixture of local anesthetic

Yeoh C, Lee C

J Anaesthesiol Clin Pharmacol, 2012 Apr;28(2):205-9.
PMID: 22557744 DOI: 10.4103/0970-9185.94869

BACKGROUND: Venous cannulation is often a painful procedure for the patient. Eutectic mixture of local anesthetic (EMLA) is the commonest topical analgesic used but suffers from disadvantages such as slow onset and skin blanching, which may interfere with venous cannulation. Amethocaine is a newer topical analgesic which seems to be devoid of such problems.
MATERIALS AND METHODS: This prospective randomized double-blind study compared the analgesic efficacy of EMLA with amethocaine during venous cannulation in adults. Eighty ASA I-II patients, aged 18-65 years, were recruited. The test drug was applied on the designated site of venous cannulation and covered with an occlusive dressing for at least 60 min prior to the procedure. Data collected included visual analogue score (VAS) during first attempt at venous cannulation, the ease and success rate at cannulation, and cutaneous changes at the application site.
RESULTS: Mean and median VAS for the EMLA group were 27.9 ± 9.8 and 30 mm, respectively; while for the Amethocaine group were 19.1 ± 14.1 and 20 mm, respectively. Differences in VAS did not reach statistical significance. No statistically significant differences were observed in the ease and success rate at cannulation. Cutaneous changes in the form of local induration and erythema (three patients in the Amethocaine group) and blanching (eight patients in the EMLA group) were mild, localized, and required no further treatment. No patient developed severe allergic reactions.
CONCLUSION: Topical EMLA and amethocaine were comparable in terms of analgesic efficacy and ease of venous cannulation in adult patients.
Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer

Lee CC, Houghton P

J Ethnopharmacol, 2005 Sep 14;100(3):237-43.
PMID: 15888378

The SRB cytotoxicity assay was used to screen extracts and isolated constituents of some traditional medicinal plants from Malaysia and Thailand against two human cancer cell lines, COR L23 lung cancer cell line and MCF7 breast cancer cell line and the non-cancer MCF5 cell line. Five out of the seven species tested, i.e. Thai Alpinia galanga, Alpinia officinarum, Cayratia japonica, Physalis minima, Tabernaemontana divaricata, exhibited interesting cytotoxicity activity and this is the first report of cytotoxicity from any Cayratia species. Following bioassay-guided fractionation, 1'-acetoxychavicol acetate (48h exposure against COR L23 cells, IC(50) 7.8 microM against MCF7 cells, IC(50) 23.9 microM) was isolated as the major cytotoxic component of the Alpinia species, physalin F as the major cytotoxic component of Physalis minima (48 h exposure against COR L23 cells IC(50) 0.4 microM against MCF7 cells, IC(50) 0.59 microM). The Malaysian Alpinia galanga showed weak activity compared with the Thai sample and this was shown to be due to the relatively high amounts of 1'-acetoxychavicol acetate present in the Thai sample.
A study of chest infections in HIV seropositive patients in Kuala Lumpur

Wood E, Cheong I, Lee C

Int J Clin Pract, 1998 Jan-Feb;52(1):23-6.
PMID: 9536563

A retrospective study of 144 adults with HIV infection was conducted to investigate the prevalence of upper and lower respiratory tract infections (URTIs and LRTIs). The patients were divided into two groups: those with acquired HIV through intravenous drug abuse (IVDA), and those who had acquired HIV through 'other' risk behaviours. LRTIs were more prevalent than URTIs overall, and LRTIs were significantly more common (p < 0.001) in IVDAs than in the other-risk group. Tuberculosis (40%) and bacterial pneumonias (33%) comprised the majority of LRTIs among IVDAs, while Pneumocystis carinii pneumonia (40%) was the commonest LRTI in the other-risk group. Analysis of CD4 T-lymphocyte counts indicated that HIV-seropositive IVDAs are at greater risk of developing chest infections at higher CD4 counts than other-risk patients. The IVDAs were also found to have a much higher rate of co-infection with hepatitis C and B, which may be a factor accelerating the progression from HIV infection to AIDS. The mean time averaged for the two groups from known seroconversion to development of respiratory tract infection is only 1.37 years, which suggests HIV-infected patients are presenting late for treatment in Malaysia.
Infantile spasms in a Malaysian population. Clinical and EEG studies at initial presentation

Vignaendra V, Raju L, Lee C, Ghee T

J Trop Pediatr Environ Child Health, 1976 Oct;22(5):220-4.
PMID: 1051827
Combinational system of a truncated ball lens and a hyperbolic lens for collimating a highly divergent source

Chen LC, Low AL, Chien SF

Appl Opt, 2004 Dec 10;43(35):6380-3.
PMID: 15617273

We propose the use of a truncated ball lens in a collimating system to transform a spherical wave from a highly divergent source into a plane wave. The proposed scheme, which incorporates a hyperbolic lens, is discussed, and the overall system is found to have a large acceptance angle and to be free of spherical aberration. Diffraction and polarization effects are neglected, as well as skew rays.
Compound parabolic tapered fiber for fiber coupling with a highly divergent source

Chen LC, Low AL, Chien SF

Appl Opt, 2004 Nov 10;43(32):5923-5.
PMID: 15587718

A novel fiber tapering shape, which is based on compound parabolic geometry, is proposed to increase the acceptance angle of a compound parabolic concentrator. The proposed design is described by use of ray optics on a step-index multimode fiber.
Fulltext Human Plasmodium knowlesi infections in Klang Valley, Peninsula Malaysia: a case series

Lee CE, Adeeba K, Freigang G

Med J Malaysia, 2010 Mar;65(1):63-5.
PMID: 21265252

We report seven cases of naturally acquired human Plasmodium knowlesi infections which were admitted to our centre from July 2007 till June 2008. Diagnosis was confirmed by nested PCR. Cases of P. knowlesi infections, dubbed the fifth type of human malaria, have been reported in East Malaysia (Sabah and Sarawak) as well as in the state of Pahang in Peninsula Malaysia. These seven patients appear to be the first few reported cases of P. knowlesi infection in the Klang valley, Peninsula Malaysia. We then discuss the characteristics of human P. knowlesi infections, which include its natural hosts, responsible vectors, clinical presentation, and the treatment of such infections.
Comparison between the effects of propofol and etomidate on motor and electroencephalogram seizure duration during electroconvulsive therapy

Tan HL, Lee CY

Anaesth Intensive Care, 2009 Sep;37(5):807-14.
PMID: 19775046

An ideal anaesthetic for electroconvulsive therapy (ECT) should have rapid onset and offset with no effect on seizure duration, and provide cardiovascular stability during the procedure. Propofol is commonly used, even though it has been shown to shorten seizure duration which might affect the efficacy of ECT Etomidate has been advocated as an alternative. This prospective, randomised, single-blind, crossover study was conducted to compare the effects of etomidate (Etomidate-Lipuro, B. Braun Ltd, Melsungen, Germany) and propofol (Diprivan, AstraZeneca, UK) on seizure duration as well as haemodynamic parameters in patients undergoing ECT Twenty patients aged between 18 and 70 years were recruited. Group I received etomidate 0.3 mg/kg for the first course of ECT (Group IA) and propofol 1.5 mg/kg for the second ECT (Group IB), while Group II received propofol for the first ECT (Group IIA) and etomidate for the second ECT (Group IIB). There was a washout period of two to three days in between procedures. Parameters recorded included motor seizure duration, electroencephalogram seizure duration, blood pressure and heart rate. Analysis demonstrated neither period effect nor treatment period interaction. Etomidate was associated with a significantly longer motor and electroencephalogram seizure duration compared with propofol (P < 0.01). Neither drug demonstrated consistent effects in suppressing the rise in heart rate or blood pressure during ECT Myoclonus and pain on injection were the most common adverse effects in etomidate group and propofol group respectively. Etomidate is a useful anaesthetic agent for ECT and should be considered in patients with inadequate seizure duration with propofol.
Fulltext Imaging of Osteo-odontokeratoprosthesis(OOKP) Using Multidetector Computed Tomography: A UKMMC Experience

Abu Bakar N, Lee CL

Med J Malaysia, 2013;68(1):73-5.
PMID: 23466774

Osteo-odontokeratoprosthesis (OOKP) surgery is a technique used to replace damaged cornea in blind patients for whom cadaveric transplantation is not feasible. OOKP surgery is a complex procedure requiring lifetime follow-up. The preservation of the osteo-odontolamina is the vital feature in maintaining the stability of the OOKP. Early detection of lamina resorption enables early prophylactic measures to be taken and prevent resorption-related complications. This case illustrates the radiological findings of the first OOKP surgery in Malaysia and the role of multidetector computed tomography (MDCT) in postoperative management of OOKP surgery.
Fulltext Epidemiology and clinical characteristics of HIV-infected patients in Kuala Lumpur

Cheong I, Lim A, Lee C, Ibrahim Z, Sarvanathan K

Med J Malaysia, 1997 Dec;52(4):313-7.
PMID: 10968106

Between 1987 to 1995, a total of 334 patients infected with HIV were treated at the Hospital Kuala Lumpur. There were 159 Malays, 108 Chinese, 64 Indians, and 3 from other ethnic groups. Three hundred and twenty-one (96.1%) of these individuals were males and 262 (65.9%) were between the ages of 26-45 years. Intravenous drug users made up 77% (256) of the attributable risk behaviour from the group although many of them also had added risk behaviours like heterosexual activity with multiple partners (50 patients), tattoos (7 patients), homosexual practice (4 patients) and previous transfusions (3 patients). The others acquired their infection through heterosexual promiscuity (59 patients), homo/bisexual activity (7 patients), previous transfusion (5 patients) and tattoos (1 patient). Sixty-six patients (all males) had since progressed to full blown AIDS and 10 have died. The two commonest AIDS-defining events were tuberculosis infection and Pneumocystic carinii pneumonia occurring in 37 (56%) and 15 (22.7%) of patients respectively. Forty-one patients with AIDS presented for the first time with their AIDS-defining infections. The mean CD4 count of the patients when they progressed to AIDS was 130/mm3. The mean time for progression from "known" seropositivity to AIDS was 2.42 years. These results suggest that Malaysians infected with HIV are not coming forward for treatment until they are in the advanced stage of the disease.
Properties of a cyclic 3'5'-nucleotide phosphodiesterase from Vigna mungo

Lee CH, Abidin UZ

Biochem. Int., 1989 Oct;19(4):745-53.
PMID: 2559728

Cyclic AMP phosphodiesterase (PDE) partially purified from roots of Vigna mungo exhibited optimum activity at pH 5.5 to 6.0 and maximum enzyme activity at 50 degrees C. Levels of PDE activity in roots remained relatively constant from the first to the eleventh day after germination; on the twelfth day there was a 400% increase in PDE activity. The enzyme was stable for at least 48 hours at 28 degrees C, retaining 92% of its original activity. Plant growth hormones including gibberellic acid, indoleacetic acid and kinetin at 1.0 and 10.0 microM concentrations did not have any significant effect on enzyme activity. Nucleotides tested including cyclic 2'3' AMP, cyclic 2'3' GMP completely abolished enzyme activity at 1.0mM while cyclic 3'5' GMP, cyclic 3'5' GMP, 2'deoxy 5' ATP, 2'deoxy 5'GTP and 5'ADP were also inhibitory to the enzyme. The enzyme was stimulated by Mg2+, Fe2+ and NH4+ while Cu2+ and Fe3+ were inhibitory. Theophylline, caffeine, phosphate, pyrophosphate and EDTA were inhibitory to the enzyme.

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