Original Article

Chong VH, Wang CL
Correspondence: Dr Chong Vui Heng, chongvuih@yahoo.co.uk

ABSTRACT
Introduction Chronic disorders, such as rheumatic disorders, are associated with increased gastrointestinal (GI) complaints. Medications may be a contributory factor. This study assessed the prevalence of GI symptoms among patients followed-up in a rheumatology clinic.
Methods Enquiries about GI, psychological and psychosomatic symptoms (headache, insomnia, anxiety, backache and depression) were made from patients. Non-related visitors served as the control group. The underlying disorders were rheumatoid arthritis (RA, 37 percent), systemic lupus erythromatosus (SLE, 23 percent) and others (40 percent).
Results The symptom prevalence of the following complaints were: reduced appetite (10.2 percent), nausea (20.2 percent), vomiting (10.7 percent), dysphagia (7.3 percent), odynophagia (5.1 percent), early satiety (27.5 percent), heartburn (15.2 percent), dyspepsia (44.6 percent), abdominal bloating (20.8 percent) and irregular bowel habit (6.7 percent). There were no differences between the various rheumatic disorders (RA/SLE and RA/others) except for more heartburn in SLE compared to others (p-value is less than 0.05). There was no significant difference between nonsteroidal anti-inflammatory drug (NSAID) users and non-users. Patients on medications with GI (disease modifying/steroid/NSAIDs) adverse effects, experienced a higher rate of early satiety (odds-ratio [OR] 3.5, 95 percent confidence interval [CI] 1.4-8.9) and dyspepsia (OR 2.1, 95 percent CI 1.2-4.3). Compared to the control group, patients had more GI symptoms (all p-values are less than 0.05) except for irregular bowel habits. Patients also experienced more anxiety (OR 2.1, 95 percent CI 1.1-2.4) and backache (OR 2.6, 95 percent CI 1.6-4.2), and had significantly higher symptom clustering (more than two symptoms) compared to the controls (p-value is less than 0.001).
Conclusion GI symptoms are common among patients with rheumatic disorders. Medications alone do not account for the high prevalence, suggesting that the underlying conditions predispose to GI symptoms.

Keywords: dyspepsia, endoscopy, heartburn, rheumatoid arthritis, systemic lupus erythromatosus
Singapore Med J 2008; 49(5): 419-424

Fatnoon NNA, Azarisman SMS, Zainal D
Correspondence: Dr Azarisman Shah Mohd Shah, risman1973@hotmail.com

ABSTRACT
Introduction This study aims to determine the prevalence and the types of menstrual disorders among patients with systemic lupus erythematosus (SLE) and to identify factors that influence their development.
Methods 61 patients with SLE were enrolled into a cross-sectional, observational study at the medical outpatient clinic, Hospital Universiti Sains Malaysia. A total of 120 healthy women were selected randomly to act as the control group. A questionnaire was administered, vital signs were recorded, and blood was evaluated for routine investigations. A review of past medical records was also undertaken.
Results The mean age and standard deviation for the study group was 33.23 +/- 10.96 years, the majority being ethnic Malays. 75 percent had a severe SLE disease activity index score on initial presentation, and 59 percent were on cyclophosphamide. 49 percent of the study population had menstrual irregularities, of which 60 percent had sustained amenorrhoea. Nine patients with sustained amenorrhoea had hormonal assays, which confirmed the diagnosis of premature menopause.
Conclusion This study showed that SLE patients had a higher risk of developing menstrual irregularities compared to the normal/healthy population. The risk was higher in the older age group (greater than 30 years old) and those on cyclophosphamide therapy, especially those with a cumulative dose of more than 10 g. Sustained amenorrhoea was the commonest irregularity and a majority of them had confirmed premature menopause.

Keywords: amenorrhoea, menstrual disorders, premature menopause, systemic lupus erythematosus
Singapore Med J 2008; 49(5): 413-418

Sadeghi-Bojd S, Hashemi M, Karimi M
Correspondence: Dr Mohammad Hashemi, hashemim@zdmu.ac.ir

ABSTRACT
Introduction In patients with beta-thalassaemia major, impaired biosynthesis of the beta-globin leads to accumulation of unpaired alpha-globin chain. Shortened red cell lifespan and iron overload cause functional and physiological abnormalities in various organ systems. Thus, in patients with beta-thalassaemia major, the most important cause of mortality and morbidity is organ failure due to deposits of iron. The aim of this study is to investigate renal tubular and glomerular functions in patients with beta-thalassaemia major.
Methods 166 subjects with beta-thalassaemia major (96 male, 70 female) were enrolled in the study. Fasting blood and 24-hour urine samples were obtained for haematological and biochemical analyses.
Results Patients with beta-thalassaemia major showed significant signs of renal tubulopathy, such as hypercalciuria (12.9 percent), proteinuria (8.6 percent), phosphaturia (9.2 percent), magnesiumuria (8.6 percent), hyperuricosuria (38 percent) and excretion of beta-2 microglobin (13.5 percent). We found that 95.1 percent of patients had iron overload (ferritin more than 1,000 ng/ml).
Conclusion The determination of biochemical indices of renal function might help prevention of serious kidney damage before any clinical symptom is observed. Beta-thalassaemia patients present multiple renal abnormalities which may be due to iron overload. We suggest the appropriate chelation therapy and regular monitoring of the status of iron overload.

Keywords: β-thalassaemia, iron overload, renal function, renal tubular function, thalassaemia major
Singapore Med J 2008; 49(5): 410-412

Isman F, Kucur M, Tanriverdi T, Kacira T, Sanus GZ, Kemerdere R,  Hanimoglu H, Kaynar M
Correspondence: Dr Taner Tanriverdi, tanerato2000@yahoo.com

ABSTRACT
Introduction The purpose of this study was to investigate the time course(s) of the serum hyaluronidase levels in patients with aneurysmal subarachnoid haemorrhage and to show whether there is a correlation between symptomatic vasospasm and serum levels of hyaluronidase.
Methods This prospective, open, non-randomised clinical study consisted of 20 patients with aneurysmal subarachnoid haemorrhage, and eight patients with normotensive hydrocephalus who served as the control group. Serum hyaluronidase levels were detected within the first three days, days five and seven after aneurysmal subarachnoid haemorrhage, and the results were compared with those from the control group. The results were also compared with those of the clinical parameters, including the patient’s outcome at six months and symptomatic vasospasm.
Results Mean serum hyaluronidase levels were higher on days five and seven, and comparisons with either day five (p-value is 0.001) and/or day seven (p-value is 0.00001) showed a statistical difference between subarachnoid haemorrhage and controls. However, no relationship was found between elevated serum hyaluronidase levels and the clinical parameters including symptomatic vasospasm (p-value is greater than 0.05) and outcome at sixth months (p-value is greater than 0.05).
Conclusion Our results indicate that serum hyaluronidase is elevated in the acute stage(s) of subarachnoid haemorrhage; however, no difference was found between serum hyaluronidase levels and subarachnoid haemorrhage severity. Clinical studies with larger population of patients with aneurysmal subarachnoid haemorrhage are required.

Keywords: aneurysm, extracellular matrix, hyaluronidase, subarachnoid haemorrhage, vasospasm
Singapore Med J 2008; 49(5): 405-409

Kannan TP, Azman BZ, Ahmad Tarmizi AB, Suhaida MA, Siti Mariam I, Ravindran A, Zilfalil BA
Correspondence: Dr Kannan Thirumulu P, tpkannan@kb.usm.my

ABSTRACT
Introduction Turner syndrome affects about one in 2,000 live-born females, and the wide range of somatic features indicates that a number of different X-located genes are responsible for the complete phenotype. This retrospective study highlights the Turner syndrome cases confirmed through cytogenetic analysis at the Human Genome Centre of Universiti Sains Malaysia, from 2001 to 2006.
Methods Lymphocyte cultures were set up using peripheral blood samples, chromosomes were prepared, G-banded, karyotyped and analysed in accordance to guidelines from the International System for Human Cytogenetic Nomenclature.
Results The various karyotype patterns observed were 45,X; 46,X,i, (Xq); 45,X/45,X,+mar; 45,X/46,X,i,(Xq) and 45,X/46,XY. The mean age of our patients with Turner syndrome was 21 years, and the most common clinical features encountered in all these patients were short stature (100 percent), primary amenorrhoea (85.7 percent), absence of secondary sexual characteristics (57.1 percent), scanty pubic and axillary hair (50 percent), webbed neck (42.9 percent), wide carrying angle (42.9 percent), rudimentary uterus with bilateral streak ovaries (42.9 percent), underdeveloped breasts (35.7 percent) and wide-spaced nipples (21.4 percent).
Conclusion Even though there is no causal therapy for Turner syndrome, management and treatment are possible for malformations and conditions associated with it. In addition, counselling of the parents and of the patients themselves are necessary. Hence, establishing an early diagnosis, educating and increasing awareness among doctors, and if possible, a prenatal diagnosis, will help in early intervention, genetic counselling and in improving the quality of life in these patients.

Keywords: cytogenetic analysis, genetic counselling, gonadal dysgenesis, short stature, Turner syndrome
Singapore Med J 2008; 49(5):400-404

Chang SKY, Tan WB
Correspondence: Dr Stephen Kin Yong Chang, surv7@nus.edu.sg

ABSTRACT
Introduction Laparoscopic cholecystectomy is currently the treatment of choice for symptomatic gallstone disease. In recent years, there has been a trend towards outpatient cholecystectomy. The aim of our study was to report on our experience with day surgery laparoscopic cholecystectomy and to assess its feasibility and safety.
Methods Data on all the patients who underwent day surgery laparoscopic cholecystectomy between February 2006 and December 2006 were collected. They all had symptomatic cholelithiasis proven on imaging or had previous history of biliary pancreatitis or cholangitis with normalisation of liver function test and imagery clearance of the common duct. The patients' biographical data (age, gender, American Society of Anaesthesiology [ASA] status, medical comorbidities) and surgical outcomes were then obtained. The success rate of day surgery laparoscopic cholecystectomy, reasons for overnight admission and re-admission rate were evaluated.
Results A total of 50 patients were included in our study. The success rate for day surgery laparoscopic cholecystectomy was 92 percent. The patients who failed day surgery procedure are mostly of an older age group with high ASA grading. Reasons for admission for these patients included persistent abdominal pain and postoperative emesis. Our re-admission rate was four percent.
Conclusion Day surgery laparoscopic cholecystectomy is both safe and feasible in local settings. Careful patient selection is essential in ensuring a high success rate.

Keywords: ambulatory surgery, day surgery, discharge planning, laparoscopic cholecystectomy,  patient safety
Singapore Med J 2008; 49(5): 397-399

Pojchamarnwiputh S, Na Chiangmai W, Chotirosniramit A, Lertprasertsuke N
Correspondence: Dr Suwalee Pojchamarnwiputh, spojcham@med.cmu.ac.th; spojcham@gmail.com

ABSTRACT
Introduction Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare biliary ductal neoplasms of the liver. This study aims to describe the computed tomography (CT) findings of these neoplasms and to distinguish between both entities.
Methods We retrospectively reviewed the CT findings of five patients with proven BCA and seven patients with proven BCAC at our institution from July 2000 to August 2006. The CT parameters were analysed, including number, size, location, and characteristics of the cystic lesion: presence and number of internal septation, calcifications and enhanced mural nodule.
Results All 12 patients had a solitary, large well-defined intrahepatic cystic lesion. Lesions in all five patients with proven BCA (100 percent) and six patients with proven BCAC (86 percent) had a multilocular appearance. The remaining patient with proven BCAC had a unilocular lesion. Smooth, thin septa and walls were found in five patients with BCA (100 percent). The enhanced mural nodule at the septum or wall was identified in seven patients with BCAC (100 percent) but was not found in the BCA patients (p-value is less than 0.001). The other parameters including size, location and number of septa had no statistically significant differences between BCA and BCAC.
Conclusion BCA and BCAC should be considered in the differential diagnosis, when a solitary large well-defined multilocular intrahepatic cystic lesion is detected in a middle-aged woman. The presence of an enhanced mural nodule is the most important finding to suggest BCAC.

Keywords: biliary cystadenocarcinoma, biliary cystadenoma, biliary ductal tumour, computed tomography, liver neoplasm
Singapore Med J 2008; 49(5): 392-396

Jahanshahi M, Sadeghi U, Hosseini A, Naghdi N, Marjani A
Correspondence: Dr Mehrdad Jahanshahi, mejahanshahi@yahoo.com

ABSTRACT
Introduction Astrocytes play an important role in the hippocampus, probably in memory and learning. The aim of this study was to evaluate the number of astrocytes in the CA3 subfield of the rat hippocampus after spatial learning using the Morris water maze with reference and working memory methods.
Methods 45 male albino wistar rats were divided into three groups, with 15 rats in the control group and 15 rats in each of the other two groups. The two study groups of rats underwent spatial learning using the Morris water maze, with one group trained using the reference memory and the other, the working memory technique, respectively. After histological processing, the slides of the brains were stained with the phosphotanguestic acid haematoxylin staining method for detection of the astrocytes.
Results There was a significant difference in the number of astrocytes in the CA3 area between the control and reference memory groups. The difference between control and working memory groups was significant as well. Additionally, when comparing the two learning groups, we also found significant differences between them.
Conclusion The number of astrocytes increased due to spatial learning.

Keywords: astrocytes, CA3 subfield, hippocampus, Morris water maze technique, spatial learning
Singapore Med J 2008; 49(5): 388-391

Lee HY, Ariyasinghe JTN, Thirumoorthy T
Correspondence: Dr Lee Haur Yueh, hauryueh@starhub.net.sg

ABSTRACT
Introduction Allopurinol is a widely-prescribed urate-lowering agent. Allopurinol hypersensitivity syndrome, a severe form of cutaneous adverse reaction, is associated with significant mortality and morbidity. The aim of this study was to document the clinical presentation of allopurinol hypersensitivity in a local population, examine the indications for urate-lowering therapy and to identify potential associations with such a syndrome.
Methods Retrospective review was done for all patients who were referred to the dermatology unit of a tertiary hospital for allopurinol hypersensitivity syndrome over a four-year period.
Results Over four years, there were 28 patients with allopurinol hypersensitivity syndrome, of which there were 27 (96 percent) Chinese and one (four percent) Malay. The average age was 69 years. At baseline, 24 patients (86 percent) had renal impairment, and 21 patients (75 percent) had higher dosages of allopurinol. The cutaneous manifestation included generalised maculopapular exanthem (22 patients, 79 percent), Stevens Johnson/toxic epidermal necrolysis overlap (two patients, seven percent) and Stevens-Johnson syndrome (two patients, seven percent) and generalised exfoliative dermatitis (one patient, four percent). Mortality rate was 18 percent. Indications for allopurinol therapy were clear in ten patients (36 percent).
Conclusion Allopurinol hypersensitivity syndrome is a life-threatening cutaneous adverse reaction. Allopurinol should be initiated under clear indications with appropriate dosages. Potential associations with this syndrome include the Chinese race, the elderly, and patients with underlying renal impairment.

Keywords: allopurinol, cutaneous adverse reaction, drug hypersensitivity, drug-induced hypersensitivity syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis
Singapore Med J 2008; 49(5): 384-387

Peh ALH, Tay LK
Correspondence: Dr Andrew LH Peh, lai_huat_peh@cgh.com.sg

ABSTRACT
Introduction Bipolar disorder, or manic depressive psychosis, is a psychiatric disorder characterised by extreme changes in mood, thinking, energy and behaviour. Western studies on this condition show a delay in diagnosis and treatment. The aim of this study is to examine the demographical profile and clinical features of this group of patients in Singapore to see if there is a similar delay.
Methods Data of patients diagnosed with this condition and treated in two separate outpatient practices in the private sector from January 1999 to October 2003 were retrieved from case files and analysed.
Results Of the 121 patients with bipolar disorder treated, there were 45 percent male and 55 percent female patients, and most of them were in the 20-39 year age group. Chinese formed the largest ethnic group while Malays were underrepresented. 58 percent were employed, and 48 percent were married. While the age of onset of illness ranged mainly from age 10 to 29 years, the age when they first sought treatment was from 20 to 39 years. A duration of illness of more than two years was found in 79 percent of these patients. In terms of diagnostic categories, 17 percent were bipolar I, 76 percent were bipolar II and 7 percent of the bipolar disorders, not otherwise specified. The first episode presented was depression in 75 percent and bipolar disorder was the initial diagnosis in only 34 percent of the cases. A delay in the correct diagnosis for more than two years accounted for 34 percent of the cases. Only 17 percent had a family history of bipolar disorder. 28 percent had a history of antidepressant-induced manic episodes and 17 percent had a previous episode of mixed state. Psychotic symptoms were absent in 75 percent, and 65 percent had never been hospitalised for their condition. Nine percent had made a past suicide attempt and 39 percent had a comorbid diagnosis. 46 percent were treated with a combination of mood stabilizers, neuroleptics and antidepressants and 16 percent had electroconvulsive therapy. Only 34 percent were in full remission of their illness.
Conclusion There was a preponderance towards the younger age groups for the age of onset, and the type of first episode was typically depression. There was a significant delay in diagnosis and treatment of patients with bipolar disorder. These features were strikingly similar to Western studies. Bipolar II was the diagnostic category seen more than bipolar I in the outpatient setting. Polypharmacy was the norm and a large group of patients did not achieve full remission.

Keywords: bipolar depression, bipolar disorder, depression, manic depressive psychosis, psychosis
Singapore Med J 2008; 49(5): 380-383