Original Article

Chong CF, Khoo KL, Lim TK, Chang AY, Lim HL, Lee CN, Wong PS
Correspondence: Mr Chee Fui Chong, chong_chee_fui@hotmail.com

ABSTRACT
Introduction We compared the accuracy of clinical nodal (cN) status N0-1 with that of pathological nodal (pN) status obtained from systematic mediastinal lymph node dissection (SMLD) in primary non-small cell lung cancer.
Methods Data from 22 consecutive patients, who underwent lung cancer resection and SMLD of at least three mediastinal lymph node stations, from November 2001 to May 2003, were ana1ysed retrospectively. Only patients with cN0-1 status on computed tomography (CT) referred for surgery, were included in this study.
Results Mean age of patients was 66.6 +/- 8.1 years with a male to female ratio of 17:5. Mean number of lymph node stations dissected was 5.8 +/- 1.8. 41 percent had squamous cell carcinoma, 45.5 percent had adenocarcinoma, and 4.5 percent each had large cell carcinoma, bronchioalveolar carcinoma or a lymphoepithelial carcinoma. pN2 metastases were found in 27.3 percent of patients. The sensitivity of cN0-1 was only 12.5 percent, with a specificity of 92.9 percent and an area under the receiver operating characteristics curve of 0.53. The positive and negative predictive values of cN0-1 status were 50 percent and 65 percent, respectively, with an accuracy of 59 percent. 41 percent of patients were understaged with 27.3 percent in pathological stage III. Curative resections were achieved in 59 percent of patients.
Conclusion The sensitivity of cN0-1 status based on CT alone is extremely poor when compared with pN status from SMLD. Based on cN0-1 status alone without SMLD, 27.3 percent of patients in pN2 would have been understaged. We recommend that all patients with cN0-1 status should undergo SMLD of at least three appropriate mediastinal node stations, for more accurate staging.

Keywords: lung carcinoma, lymph node excision, neoplasm staging, non-small cell lung cancer
Singapore Med J 2007; 48(7): 620–624

Hamidah A, Lim YS, Zulkifli SZ, Zarina AL, Nordiah AJ, Jamal R
Correspondence: Dr Hamidah Alias, midalias@mail.hukm.ukm.my

ABSTRACT
Introduction We evaluated the efficacy of cefepime in association with amikacin in the initial empirical therapy of febrile neutropenic children.
Methods The study was an open-labelled, non-randomised prospective trial to assess the efficacy and safety of this association, from January 2003 to December 2003. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received cefepime (50 mg per kg per dose every 8 hours for children weighing less than or equal to 40 kg; and 2 g every 8 hours for those weighing more than 40 kg) plus a single daily dose of amikacin at 15 mg per kg per day, up to a maximum 250 mg. If fever persisted, a second-line therapy with carbapenem was administered. Amphotericin B was added at 96 hours if fever and neutropenia persisted.
Results 103 episodes of fever and neutropenia were evaluated in 54 patients. 18.4 percent of the episodes were microbiologically-documented infections, 24.3 percent were clinically documented, and 57.3 percent were episodes with unexplained fever. 54.4 percent of the episodes responded to cefepime plus amikacin without a need for treatment modification. A higher success rate (74.6 percent) was observed in episodes with unexplained fever. In all cases of persistent fever, the antibiotics were changed to carbapenem within 72 hours and all patients survived. One patient died because of culture-negative septic shock within 24 hours of admission. A mild gastrointestinal intolerance occurred in three patients.
Conclusion This study suggests that cefepime plus amikacin presents a satisfactory efficacy and a good tolerance as an initial empirical therapy for febrile neutropenic children.

Keywords: amikacin, cefepime, childhood cancer, febrile neutropenia
Singapore Med J 2007; 48(7): 615–619

Al-Joudi FS, Iskandar AZ, Hasnan J, Rusli J, Kamal Y, Imran AK, Ahmed M, Zakaria J
Correspondence: Dr Fawwaz Shakir Al-Joudi, fajoudi@yahoo.com

ABSTRACT
Introduction Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
Methods In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
Results Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
Conclusion This is the first known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.

Keywords: breast cancer, invasive ductal breast carcinoma, survivin expression
Singapore Med J 2007; 48(7): 607–614

Anu VR, Pai MM, Rajalakshmi R, Latha VP, Rajanigandha V, D' Costa S
Correspondence: Dr Anu V Ranade, anuranade@gmail.com

ABSTRACT
Introduction Developmental anomalies in the origin and branching pattern of the external carotid artery are not common. The level of the bifurcation of the common carotid artery and also the variations in the origin/branching pattern of the external carotid artery are well known and documented.
Methods The variations in the level of bifurcation of the common carotid artery and the branching pattern of the external carotid artery were studied on 95 cadavers (52 male and 43 female). The common, external and internal carotid arteries were dissected on both sides. The level of carotid bifurcation was determined by comparison with the cervical vertebrae. Branching patterns of the carotid arteries were examined.
Results Apart from the textbook description of the arteries, we came across several interesting variations. The bifurcation level of the common carotid artery was determined to be 50 percent at the C3 level, 40 percent at the C4 level and ten percent at the C2 level on the right side, and 55 percent at the C3 level, 35 percent at the C4 level, one percent at the C5 level and nine percent at the C2 level on the left side.
Conclusion Anatomical knowledge of the origin, course, and branching pattern of the external carotid artery, as well as the level of bifurcation of the common carotid artery, will be useful to surgeons when ligating the vessels in the head and neck regions during surgery and to avoid unnecessary complications during carotid endarterectomy.

Keywords: carotid artery variants, carotid endarterectomy, common carotid artery, external carotid artery
Singapore Med J 2007; 48(6): 566–569

Yousuf RM, Fauzi ARM, How SH, Rasool AG, Rehana K
Correspondence: Dr RM Yousuf, drmyrathor@yahoo.com

ABSTRACT
Introduction Informed consent is now accepted as the cornerstone of medical practice, with reasonable patient standards typically considered to be appropriate in the developed countries; however it is still challenged in many developing countries. The objective of this descriptive study was to evaluate the perceptions and practices among attending medical professionals in matters relating to informed consent in selected hospitals.
Methods A questionnaire-based cross sectional survey among doctors in the two tertiary care hospitals, one in Malaysia and the other in Kashmir, was performed.
Results Awareness on informed consent was universal with "reasonable physician standard" as the most popular choice. As compared to doctors in Malaysia, doctors from Kashmir showed a tendency to reservedly disclose medical information (p-value equals 0.051) and withhold it, if it was deemed potentially harmful (p-value is less than 0.001) or requested so by relatives (p-value is less than 0.023). They also withheld some information from female patients (p-value is less than 0.001). When consent was refused despite needing lifesaving intervention, the majority of both respondents (73 percent versus 80 percent) considered intervention without consent to be justified. Respondents from Malaysia felt that parents could refuse treatment on their children's behalf on the basis of their beliefs (p-value is less than 0.001).
Conclusion Despite a very high awareness of informed consent, the model chosen reflected age-old medical paternalism. Doctors' opinions are accorded a larger role in clinical decision-making in Kashmir. The results emphasise the need for doctors to change their attitude and acknowledge the patient's autonomy, which is the basis of modern medical ethics, and yet still be aware of the cultural and religious views of the local population.

Keywords: clinical decision-making, informed consent, medical ethics, patient autonomy
Singapore Med J 2007; 48(6): 559–565

Venkatesan T, Thomas N, Ponniah M, Khan D, Chacko AG, Rajshekhar V
Correspondence: Dr Nihal Thomas, nihal_thomas@yahoo.com

ABSTRACT
Oral triiodothyronine (T3) has never been described in literature as a major form of perioperative therapy. This series highlights the role of oral triiodothyronine in the perioperative management of patients with overt hypothyroidism for semi-urgent surgeries. We describe 12 patients with central hypothyroidism occurring secondary to pituitary tumours manifesting with severe neurological symptoms that required early surgical intervention. These patients were managed without any significant complications by administering perioperative oral triiodothyronine.

Keywords: central hypothyroidism, hypothyroidism, oral triiodothyronine, peri-operative management, pituitary surgery
Singapore Med J 2007; 48(6): 555–558

Azman BZ, Ankathil R, Siti Mariam I, Suhaida MA, Norhashimah M, Tarmizi AB, Nor Atifah MA, Kannan TP, Zilfalil BA
Correspondence: Dr Zilfalil BA, zilfalil@kb.usm.my

ABSTRACT
Introduction This study was designed to evaluate the karyotype pattern, clinical features and other systemic anomalies of patients with Down syndrome in Malaysia.
Methods Retrospective analysis was performed on the case records of 149 patients confirmed as Down syndrome by cytogenetic analysis at Human Genome Centre and Genetic Clinic at the Universiti Sains Malaysia.
Results Among the 149 cases of Down syndrome presenting over a period of 4.2 years, free trisomy (non-disjunction) was present in 141 cases (94.6 percent). One case (0.7 percent) had translocation, and seven cases (4.7 percent) were mosaics. Average age at presentation was 10.6 months. Average maternal age at birth of the affected child was 32.3 years. The prominent craniofacial features noted were upslanting palpebral fissures (89.3 percent), flat facial profile (64.9 percent), low set ears (56.1 percent), epicanthic folds (17.5 percent) and protruding tongue (19.2 percent). A total of 52.6 percent of the cases had documented hypotonia. Characteristic limb and dermatoglyphic anomalies included short stubby fingers (24.5 percent), sandal gap (33.3 percent), unilateral or bilateral simian crease (36.8 percent) and clinodactyly (19.2 percent). Ophthalmological abnormalities, such as hypertelorism, were presented in 33.3 percent of the cases. Congenital heart disease was diagnosed in 35 out of 71 cases (49.3 percent) and gastrointestinal anomalies were noted in 18 out of 79 cases (22.7 percent) analysed.
Conclusion Efforts to establish early diagnosis and a proper screening for high association with systemic anomalies should be undertaken among the Down syndrome patients in this population.

Keywords: cytogenetic analysis, Down syndrome, karyotype pattern, non-disjunction, trisomy 21
Singapore Med J 2007; 48(6): 550–554

Ahmed KS, Khan AA, Ahmed I, Tiwari SK, Habeed A, Ahi JD, Abid Z, Ahmed N, Habibullah CM
Correspondence: Prof CM Habibullah, cmhabib@gmail.com

ABSTRACT
Introduction In developing countries, the Helicobacter pylori (H. pylori) infection rate is high, especially in lower socioeconomic groups. The populace in developing countries lives in conditions that are highly conducive to the acquisition of microorganisms. Poor hygiene, crowded household conditions and deficient sanitation mark their day-to-day life. We aimed to find out the roles of household hygiene and water source in the prevalence and transmission of H. pylori infection among the South Indian population using polymerase chain reaction (PCR) assay.
Methods The selected population consisted of 500 adults of varying ages ranging from 30 to 79 years, with upper gastrointestinal tract symptoms. Each participant in the study was given a questionnaire to complete. Samples to assess H. pylori infection included three gastric biopsies (two from the antrum and one from the corpus region). Infection was detected by PCR amplification of the 16S rRNA gene of H. pylori. The data was then examined statistically by univariate and multivariate analyses.
Results The overall prevalence of H. pylori was detected to be 80 percent. Prevalence increased with an increase in age and it was found to be 90 percent in the 70-79 year age group (p-value is less than 0.01). The prevalence of infection among people who drank water from wells was 92 percent compared with 74.8 percent of those who drank tap water (p-value is less than 0.001). H. pylori infection prevalence was found to be higher in people with low clean water index (CWI) (88.2 percent) than in those with higher CWI (33.3 percent) (p-value is less than 0.001). While the prevalence of H. pylori in the subjects with lower socioeconomic status was 86.1 percent, in higher groups, it was 70 percent (p-value is less than 0.001). The prevalence of H. pylori was also found to be higher in subjects who lived in overcrowded houses. It was 83.7 percent with high crowding index, 76.6 percent with medium crowding index, and 71.3 percent with low crowding index (p-value is less than 0.05).
Conclusion The results of the present study suggest that the risk of acquisition and transmission of H. pylori can be prevented to a large extent by following improved household hygienic practices, proper waste disposal measures as well as the regular use of boiling water for drinking purposes.

Keywords: Helicobacter pylori, household hygiene, hygiene, polymerase chain reaction assay, water source, 16S rRNA gene
Singapore Med J 2007; 48(6): 543–549

Udayakumar N, Venkatesan S, Rajendiran C
Correspondence: Dr N Udayakumar, udhaykumar81@yahoo.co.in

ABSTRACT
Introduction There are limited studies on the prevalence of diastolic dysfunction in rheumatoid arthritis (RA) from the Indian subcontinent. The aim of this study was to evaluate left ventricular filling abnormalities in patients with RA without clinically-evident cardiovascular manifestations, and to correlate it with disease duration.
Methods 45 patients affected with RA according to the American Rheumatism Association criteria, were selected without evidence of cardiac disease, and compared with age- and sex-matched control subjects. All patients and the control group were submitted to M-mode, two-dimensional and Doppler echocardiography. The following diastolic parameters were evaluated: peak of early diastolic (E) and late diastolic (A) mitral flow velocity, E/A ratio, isovolumic relaxation time (IVRT), ejection fraction and fractional shortening.
Results In RA patients, left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean [SD] 0.98 [0.22] versus controls 1.09 [0.11]; p-value equals 0.004), prolonged IVRT (75.77 [8.12] ms versus 70.43 [2.94] ms; p-value equals 0.001) and increased late diastole flow velocity (76.91 [11.61] cm/s versus 70.11 [5.32] cm/s; p-value equals 0.001). In the group of patients, a negative correlation was found between E/A ratio and disease duration (Pearson correlation, r equals -0.56, p-value equals 0.001), indicating diastolic dysfunction with increasing disease duration. A strong correlation was also found between IVRT and disease duration (r equals 0.66, p-value equals 0.01) and also between late diastolic flow velocity and disease duration (r equals 0.61, p-value equals 0.001).
Conclusion The present study confirms a high frequency of left ventricular diastolic dysfunction characterised by impaired E/A ratio, prolonged IVRT and increased late diastole flow velocity in patients with RA without evident cardiovascular disease. The correlation between transmitral flow alteration and disease duration suggests a subclinical myocardial involvement with disease progression. This may be relevant to the high incidence of cardiovascular deaths observed in patients with RA.

Keywords: cardiovascular disease, congestive heart failure, diastolic dysfunction, rheumatoid arthritis
Singapore Med J 2007; 48(6): 537–542

Ruiz-Ruiz FJ, Ruiz-Laiglesia F, Lasierra-Diaz P, Samperiz-Legarre P, Morales-Rull JL, Sánchez-Marteles M, Amores M, Perez-Calvo JI
Correspondence: Dr Francisco J Ruiz-Ruiz, fruiz@comz.org

ABSTRACT
Introduction Interleukin-6 (IL-6) has been identified as a predictor of death, new heart failure (HF) episodes and need for heart transplantation in patients with advanced HF. The aim of this study was to examine the relationship between plasma IL-6 levels in patients with decompensated HF and either survival or new admissions due to HF.
Methods We studied 111 patients admitted due to decompensated HF. Long-term survival was assessed from the day of admission to the hospital to the day of death or new admissions due to HF.
Results The mean IL-6 concentration was 90 +/- 115 pg/ml (range 1.5-743 pg/ml). There were no differences in IL-6 concentration with regard to age, gender and cause of HF. At the end of follow-up period, 22 patients (20 percent) had died due to causes related to HF and 54 patients (48 percent) had been readmitted to the hospital due to new HF episodes. Using regression analyses, serum IL-6 levels were not identified as a prognostic factor. Systolic dysfunction, previous diagnosis of HF and diabetes mellitus were independent predictors of death.
Conclusion These findings suggest that a single measurement of serum IL-6 in patients with decompensated HF lacks clinical usefulness in long-term follow-up.

Keywords: cytokines, decompensated heart failure, heart failure prognosis, interleukin-6
Singapore Med J 2007; 48(6): 532–536