Original Article

Lim PL, Ling ML, Lee HY, Koh TH, Tan AL, Kuijper EJ, Goh SS, Low BS, Ang LP, Harmanus C, Lin RTP, Krishnan P, James L, Lee CE
Correspondence: Dr Lim Poh Lian, pllim@post.harvard.edu

ABSTRACT
Introduction The incidence of Clostridium (C.) difficile infection (CDI) was on the rise from 2001 to 2006 in Singapore. Recent unpublished data suggests that its incidence had remained stable or decreased in most local public hospitals between 2006 and 2010. It is, however, not known if the polymerase chain reaction(PCR) ribotype 027 strains have been circulating, although reports suggest that this strain is emerging in Asia, with the first cases reported from Japan in 2007, as well as in Hong Kong and Australia in 2009. We initiated a culture based surveillance to detect this epidemic strain in Singapore.
Methods From September 2008 to December 2009, all non-duplicate toxin-positive stool samples from the three largest public hospitals in Singapore were collected for culture and further analysis.
Results Out of the 366 samples collected, 272 viable isolates were cultured. Of these, 240 tested toxin-positive and ten tested positive for the binary toxin gene; 35 different PCR ribotypes were found. Three isolates that tested positive for binary toxin contained the same PCR ribotyping pattern as the C. difficile 027 control strain. All three had the 18-bp deletion and single nucleotide tcdC deletion at position 117. Susceptibility testing was performed, demonstrating susceptibility to erythromycin and moxifloxacin.
Conclusion We report the first three isolates of C. difficile 027 from Singapore. However, their susceptibility patterns are more consistent with the historical 027 strains. Rising CDI incidence may not be associated with the emergence of the epidemic 027 strain at this time.

Keywords: Clostridium difficile, epidemiology, ribotype 027, Singapore, surveillance
Singapore Med J 2011; 52(5): 361-364

Mohamad Ikram I, Quah BS, Noraida R, Djokomuljanto S, Faris Irfan CY, Van Rostenberghe H
Correspondence: Dr Mohamad Ikram Ilias, drikram@kk.usm.my

ABSTRACT
Introduction The addition of glutamine to parenteral nutrition (PN) in neonates has not shown significant benefits as compared to adults thus far. This study aimed to determine the potential benefits of the addition of glutamine to neonatal PN in a tertiary hospital in a middle-income country.
Methods This was a double-blinded randomised controlled trial. Babies who were admitted to the neonatal intensive care unit (NICU) and who required PN were eligible for inclusion in the study. The subjects were randomised to receive either glutamine-added PN (intervention) or standard PN (control). The most important outcomes included time to full enteral nutrition, incidence of sepsis and necrotising enterocolitis (NEC), clinical or culture-proven sepsis.
Results Out of 270 subjects, 132 were randomised to the intervention group and 138, to the control group. Baseline data were comparable in both groups. The median time taken to reach full enteral nutrition was similar for both intervention and control groups (six days in each group, p-value is 0.52). The incidences of NEC, clinical sepsis and culture-proven sepsis did not differ significantly in the intervention and control groups (5.8 vs. 7.1 percent, p-value is 0.68; 15.7 percent vs. 10.2 percent, p-value is 0.21 and 16.5 percent vs. 15.7 percent, p-value is 0.38, respectively). Other outcomes such as duration of ventilation, duration of NICU stay and a subgroup analysis for preterm and term babies also showed no statistically significant differences.
Conclusion Addition of glutamine to neonatal PN was not shown to improve outcome.

Keywords: glutamine, neonate, parenteral nutrition, randomised controlled trial, sepsis
Singapore Med J 2011; 52(5): 356-360

Lee YQ, Kanagalingam J
Correspondence: Dr Jeevendra Kanagalingam, jeevendra_kanagalingam@ttsh.com.sg

ABSTRACT
Introduction This study aimed to review the microbiology of deep neck abscesses and identify the factors that influence their occurrence.
Methods A retrospective chart review was done of patients diagnosed with deep neck abscesses at the Department of Otorhinolaryngology, Tan Tock Seng Hospital, Singapore between 2004 and 2009. The data of 131 deep neck abscess patients were reviewed, and those with positive pus culture were included in the study. Logistic regression was applied to analyse and compare the incidence of common organisms in various conditions (age, gender, aetiology and effects of diabetes mellitus).
Results Of the 96 patients recruited, 18 had polymicrobial cultures. The leading pathogens cultured were Klebsiella (K.) pneumoniae (27.1 percent), Streptococcus milleri group (SMG) bacteria (21.9 percent) and anaerobic bacteria–not otherwise specified (NOS) (20.8 percent). K. pneumoniae (50.0 percent) was over-represented in the diabetic group. SMG bacteria (68.8 percent) and anaerobic bacteria–NOS (43.8 percent) were most commonly isolated in patients with odontogenic infections. K. pneumoniae was found more commonly among female patients (39.3 percent). The distribution of the three leading pathogens between patients aged below 50 years and those 50 years and above was comparable. K. pneumoniae was the commonest organism cultured in parapharyngeal space abscesses, while the submandibular space and parotid space most commonly isolated SMG bacteria and Staphylococcus aureus, respectively.
Conclusion Broad-spectrum antibiotics are recommended for treating deep neck abscesses. Empirical antibiotic coverage against K. pneumoniae infection in diabetic patients, and SMG and anaerobic bacteria in patients with an odontogenic infection, is advocated. Routine antibiotic coverage against Gram-negative bacteria is not paramount.

Keywords: diabetes mellitus, Klebsiella pneumoniae, neck abscesses, odontogenic infections, upper respiratory tract infections
Singapore Med J 2011; 52(5): 351-355

Pande KC, Hj Abdul Kadir KA
Correspondence: Dr Ketan C Pande, ketanpande@yahoo.com

ABSTRACT
Introduction Melioidosis caused by Burkholderia pseudomallei is an infectious disease endemic to Southeast Asia and northern Australia. It has a broad spectrum of clinical manifestations and high mortality, and can mimic other infectious diseases. The aim of this study was to review cases of melioidosis of the extremities in Brunei Darussalam.
Methods Culture-positive cases for Burkholderia pseudomallei in Raja Isteri Pengiran Anak Saleha Hospital were identified from records in the Microbiology Department. The case notes were reviewed to identify patients who were treated for problems affecting the extremities. 14 (13males and one female) out of 48 patients were identified.
Results The median age of the patients was 45 (range 14–55) years. Septicaemia was the most common presenting feature in 11 patients. Multisystem involvement was noted in eight patients, diabetes mellitus in nine patients and other risk factors in two patients. Blood culture was positive in ten patients and pus culture in 11 patients. The presentations noted were cellulitis of the limbs, abscess, osteomyelitis (three patients each) and septic arthritis (five patients). Orthopaedic intervention (joint washout/incision and drainage/curettage) was required in 11 patients. The median hospital stay was 27.5 (range 13–63) days; two patients required admission to intensive care. No mortality was reported.
Conclusion Melioidosis of the extremities is not uncommon in Brunei Darussalam. It is associated with significant morbidity, and a large number of patients require surgical intervention. Thus, a high index of suspicion is required for early diagnosis and institution of appropriate antibiotic therapy.

Keywords: Burkholderia pseudomallei, complications, diabetes mellitus, melioidosis, surgery
Singapore Med J 2011; 52(5): 346-350

Chong CF, Thien A, Mackie AJA, Tin AS, Tripathi S, Ahmad MA, Tan LT, Ang SH, Telisinghe PU
Correspondence: Dr Chong Chee Fui, chong_chee_fui@hotmail.com

ABSTRACT
Introduction The accuracy of the Alvarado score in diagnosing acute appendicitis in an Asian population has been disappointingly low. We prospectively compared the RIPASA score with the Alvarado score for the diagnosis of acute appendicitis.
Methods 200 consecutive patients who presented to the Accident and Emergency Department with right iliac fossa pain were recruited in the study. Both the RIPASA and Alvarado scores were derived, but decisions for appendicectomy were based on clinical judgement. Receiver operating curve (ROC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for both scoring systems were calculated.
Results Only 192 out of the 200 patients who satisfied the inclusion and exclusion criteria were included in the analysis. At the optimal cut-off threshold score of 7.5 derived from the ROC, the sensitivity, specificity, PPV, NPV and diagnostic accuracy of the RIPASA score were 98.0 percent, 81.3 percent, 85.3 percent, 97.4 percent and 91.8 percent, respectively. At the cut-off threshold score of 7.0 for the Alvarado score, the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 68.3 percent, 87.9 percent, 86.3 percent, 71.4 percent and 86.5 percent, respectively. The RIPASA score correctly classified 98 percent of all patients confirmed with histological acute appendicitis to the high-probability group (RIPASA score greater than 7.5) compared with 68.3 percent with the Alvarado score (Alvarado score greater than 7.0; p-value less than 0.0001).
Conclusion The RIPASA score at a cut-off threshold total score of 7.5 is a better diagnostic scoring system than the Alvarado score for the diagnosis of acute appendicitis in our local setting.

Keywords: acute appendicitis, appendicectomy, diagnostic technique, surgical, symptoms
Singapore Med J 2011; 52(5): 340-345

Poh BK, Mancer K, Goh D, Lim T, Ng V, Ng KK, Ng FC
Correspondence: Dr Poh Beow Kiong, beowkiong@hotmail.com

ABSTRACT
Introduction The aims of the study were to compare the degree of cautery artefacts in prostatic chips between monopolar and PlasmaKineticTM transurethral resection of prostate (TURP), and to determine if there is any difference in the intraoperative and post surgical parameters between them.
Methods After institutional review board approval, patients were prospectively enrolled to undergo PlasmaKineticTM TURP. Their parameters were compared with those of the historical monopolar TURP controls. All histological specimens were reviewed by a single senior pathologist.
Results 46 patients were recruited to undergo PlasmaKineticTM TURP. The resection time was significantly longer for the bipolar group compared to the monopolar group (50.2 versus 36.7 min, p-value is 0.001). The speed of resection (resection weight/time) was lower for the bipolar group (0.45 versus 0.56 g/min, p-value is 0.017). More irrigant was used for the bipolar group (21.2 versus 15.6 litres, p-value is 0.001) intraoperatively. There was no statistically significant difference in terms of intraoperative drop in haemoglobin and serum sodium change between the two groups. There seems to be a lesser degree of cautery artefacts in the PlasmaKineticTM group than the monopolar group (42.17 versus 45.07 microns); however, this was not statistically significant (p-value is 0.452).
Conclusion Bipolar TURP seems to result in a lesser degree of cautery artefacts when compared to conventional monopolar TURP, albeit statistically insignificant, compared to monopolar TURP. TURP also resulted in a longer resection time and increased irrigant use, but no difference in blood loss and serum sodium levels.

Keywords: bipolar, cautery artefacts, monopolar, PlasmaKineticTM, transurethral resection of prostate
Singapore Med J 2011; 52(5): 336-339

Kuru B
Correspondence: Dr Bekir Kuru, bekirkuru@yahoo.com

ABSTRACT
Introduction The aims of the present study were to define the prognostic factors for locoregional recurrence (LRR) and survival in stage IIIC breast carcinoma as well as to examine the impact of adjuvant radiotherapy on the outcome of the disease.
Methods The records of 586 consecutive patients with stage IIIC breast carcinoma who underwent modified radical mastectomy were evaluated, and the prognostic factors for LRR and survival were analysed. Survival curves were generated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard model.
Results Five-year LRR and survival of stage IIIC breast carcinoma were 15 percent and 41.3 percent, respectively. Five-year LRR was significantly lower and five-year survival was significantly higher for all patients as well as for T1–2 patients with one to three apical node involvements who were treated with adjuvant radiotherapy. In multivariate analysis, apical node involvement, age below 35 years, T4 tumour, grade 3, extracapsular extension and lymphovascular invasion decreased survival, whereas adjuvant tamoxifen and adjuvant radiotherapy risk ratio [RR] 0.51, 95 percent confidence interval [CI] 0.39–0.67) increased survival. Adjuvant radiotherapy was the sole independent factor that was found to be significantly associated with decreased LRR (RR 0.25, 95 percent CI 0.16–0.38).
Conclusion Radiotherapy decreased LRR and increased survival significantly in all stage IIIC patients and in the subgroup of T1–2 patients with one to three apical node involvements. Thus, it should be considered in the treatment of stage IIIC breast carcinoma.

Keywords: adjuvant radiotherapy, apex axillary invasion, one to three positive axillary nodes, stage IIIC breast carcinoma
Singapore Med J 2011; 52(4): 289-298

Rajesh KG, Surekha RH, Mrudula SK, Prasad Y, Sanjib KS, Prahthiba N
Correspondence: Dr Surekha Rani H, surekharanih@gmail.com

ABSTRACT
Introduction Oxidative and nitrosative stress caused by a disturbance in the homeostasis of pro-oxidants and antioxidants play a vital role in the pathogenesis of coronary heart disease (CHD). Enhanced formation of reactive oxygen species/reactive nitrogen species may also affect the oxidation/nitration of biomolecules such as lipids, proteins and DNA. The present study was undertaken to estimate oxidative and nitrosative stress, and to evaluate oxidative DNA damage.
Methods The study population consisted of 120 patients with angiographically documented CHD and an equal number of age- and gender-matched healthy controls. Lipid profiles were estimated using Glaxo kits. Estimation of plasma malondialdehyde (MDA), nitrite/nitrate and comet assay were carried out using previously published methods.
Results Lipid profiles were significantly different in patients with coronary artery disease compared to the controls (p-value less than 0.01). The levels of MDA, nitrite/nitrate and DNA damage in the patients were significantly higher compared to the controls, and a strong correlation was found between the comet tail length and the MDA and nitrite/nitrate levels. Further analysis revealed that the influence of nitrite/nitrate was greater than that of MDA.
Conclusion Our results indicate that abnormal levels of lipid profiles, along with increased oxidative and nitrosative stress as well as somatic DNA damage, could be important pathogenic factors that act as additional prognostic predictors. They may also serve as potential targets for therapeutic strategies in CHD for early management and prevention of the disease.

Keywords: coronary heart disease, DNA damage, nitrosative stress, oxidative stress
Singapore Med J 2011; 52(4): 283-288

Kaundal M, Sharma S
Correspondence: Dr Manju Kaundal, kaundalm@gmail.com

ABSTRACT
Introduction Beta-adrenergic agonists are highly abused by sportspeople for their muscle anabolic and lipolytic effects. Muscle growth effects are thought to result from beta-2 adrenoceptor activation. This study attempted to characterise muscle (gastrocnemius) tissue damage following the administration of isoproterenol.
Methods Adult male Balb-C mice were treated with a single oral dose of isoproterenol (100 mg/kg body weight) for 4, 8, 20, 48 and 72 hours. Control mice received equal doses of saline. The animals were killed at the respective stages, followed by the collection of gastrocnemius and blood. Serum was then separated from blood. Histopathology and lactate dehydrogenase (LDH) assays were performed.
Results Beta-adrenoceptor activation-induced histological changes began with structural aberrations, and ultimately resulted in myonecrosis and extensive degeneration within hours of the administration of isoproterenol. The effects of beta-agonist administration on muscle myofibre organisation were visible within four hours and became most prominent at 20 and 48 hours. Augmentation of more than 20 percent in muscle LDH activity was observed at 4, 8 and 72 hour stages, and was accompanied by a significant decline of 19 and 27 percent at 20 and 48 hour time points, respectively. Serum corroborated the above results.
Conclusion Isoproterenol treatment produced considerable histopathological changes, including myonecrosis in mice gastrocnemius, resulting in a leaky sarcolemma and the release of marker enzyme, LDH into the serum (more evident after 20 and 48 hours). This suggests that isoproterenol promotes the process of necrosis in mice gastrocnemius at the concentration employed, which raises a significant question regarding the use and abuse of beta-agonists.

Keywords: electrophoresis, gastrocnemius muscle, isoproterenol, lactate dehydrogenase, tissue damage
Singapore Med J 2011; 52(4): 274-282

Kavakli HS, Koktener A, Yilmaz A
Correspondence: Dr Havva Sahin Kavakli, havvasahin1973@yahoo.com

ABSTRACT
Introduction The aim of this study was to investigate the value of renal resistive index (RI) for the assessment of renal colic and to determine whether it is predictive of renal stone disease.
Methods A total of 70 participants were included in the research study. Group 1 comprised 43 patients with acute unilateral ureteral obstruction due to a stone disease (G1), while Group 2 consisted of seven patients with flank pain without stone disease (G2) and the control group comprised 20 healthy individuals with two normal kidneys (G3). Urinalysis, abdominal plain film radiography, conventional ultrasonography (US) and colour Doppler US were performed in all three groups. RI was calculated for all patients using Doppler US. The RI values in G1 were then compared with those in G2 and the control group.
Results There were statistically significant differences in the RI between the stone-positive group and stone-free groups (0.71 +/- 0.07 for G1; 0.69 +/- 0.06 for G2; 0.62 +/- 0.03 for G3, p-value < 0.05).
Conclusion RI measurement using Doppler US can be effectively used for the assessment of renal colic patients by non-invasive means.

Keywords: Doppler ultrasound, emergency department, renal colic, resistive index, stone disease
Singapore Med J 2011; 52(4): 271-273