Original Article

Kaleem M, Medha P, Ahmed QU, Asif M, Bano B
Correspondence: Prof Bilqees Bano, bilqeesbano@gmail.com

ABSTRACT
Introduction The present study investigated the possible therapeutic effects of Annona squamosa (A. squamosa) extract on certain biochemical markers in streptozotocin (STZ)-induced diabetes mellitus in rats.
Methods The effects of an aqueous extract of A. squamosa leaves on blood glucose, insulin, C-peptide, albumin, albumin/globulin ratio, urea, uric acid and creatinine and the activities of diagnostic marker enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase were examined in the plasma, liver and kidney tissues of control and experimental groups.
Results Oral administration of A. squamosa (300 mg/kg) aqueous extract to diabetic rats for 30 days significantly reduced blood glucose, urea, uric acid and creatinine, but increased the activities of insulin, C-peptide, albumin, albumin/globulin ratio and restored all marker enzymes to near control levels.
Conclusion The present results shown that A. squamosa extract has an antihyperglycaemic effect and consequently may alleviate liver and renal damage associated with STZ-induced diabetes mellitus in rats.

Keywords: Annona squamosa, blood glucose, diabetes mellitus, insulin
Singapore Med J 2008; 49(10): 800-804

Sonkar GK, Usha, Singh S
Correspondence: Mr Gyanendra Kumar Sonkar, gettwinklestar@rediffmail.com

ABSTRACT
Introduction Seronegative spondyloarthritis (SSA) is a type of arthritis that involves joints in the spine, as well as the hips, shoulders, knees and ankles. The diagnosis of juvenile spondyloarthritis is rarely entertained in young children who present with back and leg pain. The aim of the present study was to assess the role of HLA-B27 as a diagnostic marker in children with spondyloarthropathy, and correlation of HLA-B27 with radiological features and tuberculosis.
Methods Routine haematological and immunological tests were done by standard method and HLA-B27 typing was done by the lymphocytotoxicity method. A total of 70 cases of juvenile spondyloarthropathy were studied from May 2006 to September 2007. It included both males and females.
Results Positivity of HLA-B27 in childhood SSA was only 71.4 percent (50/70). Gender-wise analysis showed that 76.7 percent (46/60) males and 20.0 percent (2/10) of the female patients were HLA-B27 positive. In HLA-B27-positive cases, the sacroiliac, hip, ankle, lower spine and knee joints were more involved. Urinary tract infection, diarrhoea and constipation were more common in HLA-B27-positive cases. None of the HLA-B27 cases were positive for rheumatoid factor; however, C-reactive protein was raised in 60.5 percent. In bilateral/unilateral sacroiliitis diagnosed by radiographs, only 81.5 percent patients were HLA-B27 positive. Tuberculosis was diagnosed in 14.3 percent (10/70) of total cases in which HLA-B27 positivity was seen in 60 percent of cases (6/10).
Conclusion Our study concludes that both HLA-B27 and radiological tests should be done in male children suspected to have SSA, because it can indicate early cases of juvenile spondyloarthropathy when radiological changes are not present, and it produces a more severe disease. HLA-B27 positivity probably also predisposes to tuberculosis.

Keywords: ankylosing spondylitis, HLA-B27, juvenile spondyloarthropathies, seronegative spondyloarthritis
Singapore Med J 2008; 49(10): 795-799

Matalka I, Bani-Hani K, Shotar A, Bani Hani O, Bani-Hani I
Correspondence: Dr Ismail I Matalka, imatalka@hotmail.com

ABSTRACT
Introduction The aim of the paper was to highlight the clinicopathological features of urinary bladder cancer in Jordan as a model for the Middle East. Only scattered reports from this region are currently available.
Methods A total of 115 patients with bladder cancer were managed at our hospital, between the years 1994 and 2000. Transitional cell carcinoma (TCC) comprised 110 patients. The medical records of these patients were reviewed and included in the present study.
Results There were 99 male and 11 female patients. The mean age of the patients was 60.6 (range 19-91) years. 66 of the cases had low-grade and 44 had high-grade tumours. Pathological staging showed that 60 (54.5 percent) of the cases were stage PTa, 19 (17.3 percent) PT1, 22 (20 percent) PT2, eight (7.3 percent) PT3 and one (0.9 percent) PT4. Transurethral resection, segmental resection, radical cystectomy, and partial cystectomy with intestinocystoplasty, was performed in 81, 12, eight, and four patients, respectively. Palliative urinary diversion and radiotherapy were done in two patients. Three patients were unsuitable for surgery. Recurrence was found in 22 patients (31.4 percent). Of the 105 patients who received definitive surgical treatment, 97 patients were followed-up for a mean period of 23.1 months. By the end of the study, five patients died from cancer.
Conclusion The age of presentation of TCC in Jordan is similar to that in the west, but a higher male-to-female ratio was observed. The stage at presentation is also very close to that in the west but inadequate follow-up may be the cause of a lower rate of recurrence observed in this study.

Keywords: bladder cancer, transitional cell carcinoma, urinary bladder
Singapore Med J 2008; 49(10): 790-794

Sonkar GK, Usha, Singh RG
Correspondence: Prof Usha, usha_ugcitrc@rediffmail.com

ABSTRACT
Introduction Beta-2-microglobulin (beta2M) is a light chain of HLA class I molecule, which is filtered by glomerulus, reabsorbed and catabolised by proximal tubule. It is one of the markers of transplant rejection. The aim of the present study was to find out the level of beta2M in acute renal failure (ARF), chronic renal failure (CRF), renal transplant rejection (TR) and renal transplantation stable (TS) cases, and correlation of beta2M with serum creatinine (SCr) in assessing renal failure.
Methods 23 patients with ARF, 22 patients with CRF, six cases of TR, seven patients with TS, and 28 normal healthy controls were studied within a one-year period.
Results Highest mean value of beta2M was noted (12.97 +/- 3.83 microg/ml) in CRF, and all cases had elevated beta2M of which 81.8 percent of cases had beta2M above 10 microg/ml. In ARF, all cases had elevated beta2M and 78.3 percent patients had a value more than 10 microg/ml with a mean value of 11.75 +/- 2.09 microg/ml. TR cases also had elevated beta2M but 50 percent had mild elevation (less than 10 microg/ml) and 50 percent had marked elevation (more than 10 microg/ml). 42.8 percent of TS patients also had mild elevation of beta2M in the range 2.10-3.70 microg/ml. Interestingly, in normal healthy controls, 21.4 percent of patients had mild elevation of beta2M of 2.1-2.75 microg/ml, while 78.6 percent of cases had a normal range of beta2M (less than 2 microg/ml). All normal healthy controls and 71.4 percent of TS cases had normal SCr (less than 1.4 mg/dL). All cases of CRF and TR cases, and 28.6 percent of TS cases had elevated SCr. 81.8 percent of cases with CRF and 60.9 percent of cases with ARF had a marked rise of serum creatinine above 5 mg/dL.
Conclusion Our study showed that beta2M is not superior over SCr for renal failure and TR cases, because it is also elevated in 21.4 percent of normal controls and 42.8 percent of TS cases. SCr is a cheaper, simpler and comparatively good test to assess renal failure and TR.

Keywords: acute renal failure, beta-2-microglobulin, chronic renal failure, renal transplant rejection, serum creatinine
Singapore Med J 2008; 49(10): 786-789

Tan CHR, Loh PT, Yang WS, Chan CM
Correspondence: Dr Roger Tan Choon Hian, rogertanch@hotmail.com

ABSTRACT
Introduction The aim of this study was to determine the effectiveness of mycophenolate mofetil (MMF) in IgA nephropathy (IgAN).
Methods A search through Cochrane Library, EMBASE and PubMed was carried out. Randomised controlled trials (RCTs), which compared MMF with conventional treatments, were identified. Patients' baseline, treatment strategies and study end-points were compared.
Results Four RCTs (168 patients) were selected. All patients had histologically-confirmed IgAN and proteinuria greater than 1 g/day. The follow-up duration ranged from 1.5 to 3.0 years. MMF was used at a titrated dose of 1-2 g/day. In the two trials with subjects having moderate to high risk for progressive disease, MMF did not demonstrate any significant difference in retarding the decline in renal function and proteinuria reduction. One trial concluded that there was a trend towards worse outcomes when MMF was used in moderately-advanced disease. Only one trial involving subjects with less advanced disease (reflected by a favourable histological grade) showed a significant decrease in proteinuria in the MMF-treated group. No serious adverse events occurred in all the four trials using MMF.
Conclusion No benefit was seen in moderately-advanced IgAN treated with MMF. In a selected group of patients with less advanced disease, MMF was effective in proteinuria reduction. Larger randomised studies are needed to confirm or reject these results.

Keywords: glomerulonephritis, IgA nephropathy, mycophenolate mofetil, nephropathy, proteinuria
Singapore Med J 2008; 49(10): 780-785

Khu JV, Siow HC, Ho KH
Correspondence: Mr Khu Jia Vui, jiavui@hotmail.com

ABSTRACT
Introduction We sought to determine the epidemiological features and the headache burden of headache patients in the Singapore primary care setting. Particular attention was given to the adequacy of migraine diagnosis and management as well as the utilisation of prophylactic medication by primary care doctors.
Methods Consenting patients who consulted participating general practice clinics with the chief complaint of headache, were administered a questionnaire incorporating demographical data, headache characteristics and burden as well as treatment patterns. For each patient, the attending doctor independently completed a second questionnaire covering diagnosis and treatment of the patient.
Results A disproportionate number of non-Chinese and females presented for headache management in the primary care setting as compared to the Singapore population at large. Migraineurs had more headache-related disability (67.3 percent) than non-migraineurs (45.7 percent). In our study setting, the IHS diagnostic criteria (38.2 percent of respondents), ID migraine (61.1 percent) and physician's diagnosis (62.0 percent) correlated poorly with each other when employed for case definition of migraine. In the study population, 22.6 percent used acute pain medication excessively (more than four days a week), 39.3 percent were dissatisfied with their current treatment and 58.3 percent had frequent headaches (more than four attacks a month). Only a minority of those in whom prophylaxis was indicated were treated appropriately.
Conclusion Diagnosis of migraine is inconsistent in the primary care setting despite the condition being responsible for considerable disability. Prophylactic treatment is underutilised as a management strategy, and the risk of medication-overuse headaches is underestimated. Our results emphasise the continuing need for education of primary care physicians and the public about strategies for effective headache diagnosis and treatment.

Keywords: headache, headache-related disability, migraine, migraine prophylaxis, primary healthcare
Singapore Med J 2008; 49(10): 774-779

Phua DH, Ng TW, Seow E
Correspondence: Dr Phua Dong Haur, dong_haur_phua@ttsh.com.sg

ABSTRACT
Introduction In our Asian society, respect for our elderly is deeply entrenched and highly valued. However, a previous study had shown that physical mistreatment of the elderly exists in the local population. This present descriptive study aims to evaluate the other types of elderly mistreatment and epidemiology of suspected victims in the local population.
Methods Over a period of 12 months, from June 2005 to May 2006, doctors of the Emergency Department (ED) were trained to look for clinical features of mistreatment in patients aged 65 years and above. A specially-developed evaluation form was used to help the staff in assessing suspected cases; these were then referred to medical social workers for further evaluation.
Results 42 cases of suspected mistreatment were detected, with almost three times more female than male patients. The average age of suspected victims was 78.8 years. There were 27 cases of possible physical mistreatment, 25 of possible neglect, six of possible psychological mistreatment, two of possible financial mistreatment, one of possible abandonment and one of possible self-neglect. Most suspected perpetrators were family members, and more than half were the victims' sons. 37 suspected victims had to be warded after ED consultation and eight died within six months of presentation.
Conclusion Mistreatment of the elderly in the local population is more prevalent than expected and victims can suffer adverse outcomes. Understanding of this problem is still incomplete and more research is required. Increased awareness of this problem in the community and the medical fraternity can better identify such patients.

Keywords: domestic violence, elder abuse, elderly mistreatment, geriatric problems, neglect
Singapore Med J 2008; 49(10): 765-773

Ranade AV, Rai R, Pai MM, Nayak SR, Prakash, Krisnamurthy A, Narayana S
Correspondence: Dr Anu V Ranade, anuranade@yahoo.co.in

ABSTRACT
Introduction The organogenesis of the thyroid gland in humans is often disturbed, leading to a variety of morphological variations of the gland, such as hypoplasia, ectopy, hemiagenesis and agenesis. As the morphological variations are usually diagnosed incidentally during examination for other thyroid gland diseases, the true incidence is therefore uncertain.
Methods This study was structured to investigate the gross anatomical features of the thyroid gland in 105 (88 male and 17 female) cadavers from the coastal belt of southern India, an endemic goitre region.
Results The pyramidal lobe was present in 61 (58 percent) male cadavers, and 52 (49.5 percent) cadavers showed the presence of the levator glandulae thyroideae. 33 percent of the specimens studied showed agenesis of the isthmus. However, the accessory thyroid tissue was found in only one cadaver.
Conclusion This study highlights the various developmental anomalies of the thyroid gland, which forms a cornerstone to safe and effective surgery.

Keywords: accessory thyroid tissue, anatomical variations, ectopic thyroid tissue, levator glandulae thyroideae, pyramidal lobe
Singapore Med J 2008; 49(9): 831-834

Medhi B, Prakash O, Jose VM, Pradhan B, Chakrabarty S, Pandhi P
Correspondence: Dr Bikash Medhi, drbikashus@yahoo.com

ABSTRACT
Introduction Lithium still remains an important choice in the therapy of manic-depressive psychosis (MDP), and though there are reports of seasonal variation in lithium levels from a few countries, such studies have not been conducted in India. Variability in the lithium level can lead to lack of efficacy or toxicity, making seasonal variation clinically relevant.
Methods A retrospective case sheet audit was performed for 101 MDP patients for recording plasma lithium level, oral lithium dose, age and gender for one year. The overall average oral lithium dose and level were recorded; the monthly average to which it most closely matched was noted as the control month, and values of other months were compared with this control month by Friedman's test followed by Dunn's test.
Results The mean age of patients was 38.22 (standard deviation 12.07) years, and 72 out of 101 patients were male. The mean lithium dose in November (938.61 +/- 243.40 mg/day), which was the closest to the overall mean dose (938.24 +/- 241.78 mg/day) was taken as the control month, which when compared with other monthly values, did not show any significant difference. The June (0.54 +/- 0.23 meq/L), July (0.55 +/- 0.24 meq/L) and August (0.55 +/- 0.24 meq/L) mean plasma lithium values were significantly high when compared to the October value (0.45 +/- 0.22 meq/L) as control. High-low variability between the plasma lithium values of different months was found to be 25 percent.
Conclusion The present study showed a significant high variability of lithium levels in different months of the year, therefore frequent plasma level monitoring and oral lithium dose adjustment to prevent situations of toxicity and lack of efficacy in MDP.

Keywords: lithium, manic-depressive psychosis, oral lithium, seasonal variation in plasma lithium, therapeutic drug level monitoring
Singapore Med J. 2008; 49(9): 724-7

Lateef F, Ong MEH, Alfred T, Leong BSH, Ong VYK, Tiah L, Tham LP, Anantharaman V
Correspondence: Dr Fatimah Abdul Lateef, fatimah.abd.lateef@sgh.com.sg

ABSTRACT
Introduction There appears to be a circadian rhythm in the timing of cardiovascular and neurovascular events. The majority of studies have been conducted in western populations. This is the first study to look at the peaks and distribution of out-of-hospital cardiac arrest (OHCA) patients in Singapore.
Methods The Cardiac Arrest and Resuscitation Epidemiology Studies I and II were prospective observation studies on OHCA in Singapore from October 1, 2001 to October 14, 2004. This study analysed data for patients older than 16 years. All data was collected and recorded as per the Utstein style template. Analysis was done for each of the quadrants of the 24-hour clock: 0001-0600, 0601-1200, 1201-1800 and 1801-2400 hours.
Results Of the 2,428 cases, 2,167 OHCA patients qualified for the final analysis. Their mean ages were in the 60s for all the four quadrants, with a male predominance. The two peaks noted were at 0800 and 1900 hours for cardiac causes of death (n = 1,591), and at 0900 and 2000 hours for non-cardiac causes of death (n = 576). At all times of the day, the majority of OHCA occurred in residences and the bystander cardiopulmonary resuscitation rate ranged from 14.6 to 24.3 percent in the different quadrants of the day.
Conclusion OHCA has a bimodal distribution in our local cohort of patients. The information obtained will be utilised for fine-tuning emergency medical services strategies, as we strive to improve our current survival rates for OHCA.

Keywords: cardiac arrest, circadian rhythm, out-of-hospital cardiac arrest, ventricular fibrillation, emergency medical services
Singapore Med J. 2008; 49(9): 719-23