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Quantitative ultrasound measurement of the calcaneus in Southeast Asian children with thalassemia: comparison with dual-energy X-ray absorptiometry

Sani FM, Sarji SA, Bilgen M

J Ultrasound Med, 2011 Jul;30(7):883-94.
PMID: 21705720

OBJECTIVES: The purpose of this study was to test the hypothesis that quantitative ultrasound properties of the calcaneus in Southeast Asian children treated for thalassemia have different characteristics than those of their healthy counterparts and thereby can be used for assessing the risk of osteoporosis.
METHODS: Broadband ultrasound attenuation and the speed of sound were measured from groups of thalassemic and healthy children and compared with bone mineral density (BMD) estimated from dual-energy X-ray absorptiometry to determine intergroup and intragroup dependencies of the measurements and variations with differences in sex and anthropometric characteristics.
RESULTS: Broadband ultrasound attenuation and speed of sound measurements were found to be independent of sex but dependent on age in the thalassemic children. Consistently, broadband ultrasound attenuation had lower values and the speed of sound had higher values compared with those of the healthy children in each age group. Broadband ultrasound attenuation correlated well with the speed of sound and also with age, weight, and height, but the speed of sound did not show an association with these parameters. Broadband ultrasound attenuation correlated moderately with BMD in the lumbar spine and whole body, but the corresponding association was much weaker for the speed of sound. In the thalassemic children, both broadband ultrasound attenuation and BMD increased with age as they grew older but not fast enough compared with the healthy children, and the risk of osteoporosis was greater at older ages.
CONCLUSIONS: Calcaneal quantitative ultrasound may be used as a diagnostic screening tool for assessing the bone status in thalassemic Southeast Asian children and for deciding whether further dual-energy X-ray absorptiometry is needed, particularly in those who are at a greater risk for osteoporosis as identified by low body weight and height.
Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a child: diagnostic usefulness of magnetic resonance cholangiopancreatography

Lee WS, Saw CB, Sarji SA

J Paediatr Child Health, 2005 Apr;41(4):225-7.
PMID: 15813880

A 5-year-old Chinese girl with 1-year history of progressive jaundice, steatorrhoea and pruritus was referred. Physical examination showed failure to thrive, marked jaundice, finger clubbing and hepatomegaly. There was laboratory evidence of cholestatic jaundice and autoimmunity, with marked elevation of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gammaGT). Histology of percutaneous liver biopsy revealed hepatitis around the portal triad, as well as features of liver cirrhosis. Primary sclerosing cholangitis (PSC) overlapping with autoimmune hepatitis (AIH) was suspected. Endoscopic retrograde cholangiopancreatography (ERCP) was not feasible as there was no weight-appropriate ERCP scope available. Magnetic resonance cholangiopancreatography (MRCP) was performed and revealed areas of irregularity and slight attenuation of the right and left hepatic ducts, representing stricturing, in keeping with PSC. PSC/AIH overlap syndrome was diagnosed in this child in which MRCP has contributed to its diagnosis.
Failed magnetic resonance imaging examinations due to claustrophobia

Sarji SA, Abdullah BJ, Kumar G, Tan AH, Narayanan P

Australas Radiol, 1998 Nov;42(4):293-5.
PMID: 9833363

A recognized cause of incomplete or cancelled MRI examinations is anxiety and claustrophobic symptoms in patients undergoing MR scanning. This appears to be a problem in many MRI centres in Western Europe and North America, where it is said to be costly in terms of loss of valuable scan time, and has led to researchers suggesting several anxiety-reducing approaches for MRI. To determine the incidence of failed MRI examination among our patients and if there are any associations with a patient's sex, age and education level, we studied claustrophobia that led to premature termination of the MRI examination in the University Malaya Medical Centre (UMMC) in 3324 patients over 28 months. The incidence of failed MRI examinations due to claustrophobia in the UMMC was found to be only 0.54%. There are associations between claustrophobia in MRI with the patients' sex, age and level of education. The majority of those affected were male patients and young patients in the 25-45-years age group. The patients' education level appears to be the strongest association with failed MRI examinations due to claustrophobia, where the majority of the affected were highly educated individuals. Claustrophobia in MRI is more of a problem among the educated individuals or patients from a higher socio-economic group, which may explain the higher incidence in Western European and North American patients.
Increased fracture risk and osteoporosis not associated with vitamin D levels in Malaysian patients with inflammatory bowel disease

Hilmi I, Sunderesvaran K, Ananda V, Sarji SA, Arumugam K, Goh KL

J Clin Endocrinol Metab, 2013 Jun;98(6):2415-21.
PMID: 23553858 DOI: 10.1210/jc.2013-1147

INTRODUCTION: Osteoporosis and osteopenia are well-recognized complications of inflammatory bowel disease. Previous studies have suggested that vitamin D deficiency is an important risk factor for the development of osteoporosis. We hypothesized that low vitamin D levels is the main reason for reduced bone mineral density in patients with inflammatory bowel disease. We aimed to study its potential role in Malaysia, which is a tropical country with 3 large ethnic groups. We also sought to examine the relationship between fracture risk and bone mineral density in this group.
METHODOLOGY: Relevant history as well as 25-hydroxycholecalciferol (vitamin D) levels and bone mineral density were obtained. Normal, inadequate, and low vitamin D levels were defined as 61-160 nmol/L (24-64 ng/mL), 30-60 nmol/L (12-24 ng/mL), and less than 30 nmol/L (<12 ng/mL), respectively.
RESULTS: Seventy-two patients were recruited. The prevalence of osteopenia and osteoporosis, respectively, were 58% and 17% in the spine and 51% and 14% in the hip. Mean vitamin D level in the group was low at 45.12 ± 17.4 nmol/L (18.05 ± 6.96 ng/mL), but there was no significant association between bone mineral density and vitamin D level. Twelve patients (16.7%) had a fragility fracture after the diagnosis of inflammatory bowel disease. The cumulative fracture incidence was 10% at 5 years and 35% at 10 years. There was a statistically significant association between osteoporosis of hip and a history of fracture (odds ratio 5.889; 95% confidence interval 1.41-24.53, P = .009).
CONCLUSION: Osteoporosis is prevalent among Malaysian patients with inflammatory bowel disease and is associated with a 6-fold increased risk of fractures. Most inflammatory bowel disease patients had inadequate or low vitamin D levels, but there was no association between vitamin D levels and BMD.
Fulltext Gamma scintigraphic study of the hydrodynamically balanced matrix tablets of Metformin HCl in rabbits

Razavi M, Karimian H, Yeong CH, Sarji SA, Chung LY, Nyamathulla S, et al.

Drug Des Devel Ther, 2015;9:3125-39.
PMID: 26124637 DOI: 10.2147/DDDT.S82935

The purpose of this study is to evaluate the in vitro and in vivo performance of gastro-retentive matrix tablets having Metformin HCl as model drug and combination of natural polymers. A total of 16 formulations were prepared by a wet granulation method using xanthan, tamarind seed powder, tamarind kernel powder and salep as the gel-forming agents and sodium bicarbonate as a gas-forming agent. All the formulations were evaluated for compendial and non-compendial tests and in vitro study was carried out on a USP-II dissolution apparatus at a paddle speed of 50 rpm. MOX2 formulation, composed of salep and xanthan in the ratio of 4:1 with 96.9% release, was considered as the optimum formulation with more than 90% release in 12 hours and short floating lag time. In vivo study was carried out using gamma scintigraphy in New Zealand White rabbits, optimized formulation was incorporated with 10 mg of (153)Sm for labeling MOX2 formulation. The radioactive samarium oxide was used as the marker to trace transit of the tablets in the gastrointestinal tract. The in vivo data also supported retention of MOX2 formulation in the gastric region for 12 hours and were different from the control formulation without a gas and gel forming agent. It was concluded that the prepared floating gastro-retentive matrix tablets had a sustained-release effect in vitro and in vivo, gamma scintigraphy played an important role in locating the oral transit and the drug-release pattern.
MR imaging features of Nipah encephalitis

Sarji SA, Abdullah BJ, Goh KJ, Tan CT, Wong KT

AJR Am J Roentgenol, 2000 Aug;175(2):437-42.
PMID: 10915690

The newly discovered Nipah virus causes an acute febrile encephalitic illness in humans that is associated with a high mortality. The purpose of this study is to describe the MR imaging findings of Nipah encephalitis.
Production and first use of 153SmCl3-ion exchange resin capsule formulation for assessing gastrointestinal motility

Yeong CH, Abdullah BJ, Ng KH, Chung LY, Goh KL, Sarji SA, et al.

Appl Radiat Isot, 2012 Mar;70(3):450-5.
PMID: 22178699 DOI: 10.1016/j.apradiso.2011.11.056

We produced an enteric-coated gelatine capsule containing neutron-activated (153)Sm-labelled resin beads for use in gastrointestinal motility studies. In vitro test in simulated gastrointestinal environment and in vivo study on volunteers were performed. Scintigraphic images were acquired from ten volunteers over 24h while blood and urine samples were collected to monitor the presence of (153)Sm. All the capsules remained intact in stomach. This proved to be a safe and practical oral capsule formulation for whole gut transit scintigraphy.
Neutron-activated ¹⁵³Sm-ion-exchange resin as a tracer for gastrointestinal scintigraphy

Yeong CH, Abdullah BJ, Ng KH, Chung LY, Goh KL, Sarji SA, et al.

Nucl Med Commun, 2011 Dec;32(12):1256-60.
PMID: 21934547 DOI: 10.1097/MNM.0b013e32834b3ac8

Nuclear medicine techniques are well established for the investigation of gastrointestinal (GI) motility and transit. Ion-exchange resins radiolabelled with ⁹⁹mTc and ¹¹¹In are widely used as nonabsorbable radiopharmaceutical markers, with ¹¹¹In being preferred for whole-gut transit studies. This radionuclide, however, is not produced in many countries and may be expensive when obtained through international shipment. This study describes the use of neutron-activated ¹⁵³Sm-resin as an alternative tracer for use in GI scintigraphic investigation. A measure of 50 mg of stable samarium-152 chloride (¹⁵²SmCl₃) was incorporated into 100 mg of cation-exchange resin and irradiated in a neutron flux of 1 × 10¹³ cm⁻² s⁻¹ for 100 s to achieve an activity of 5 MBq after 66 h. Aliquots of ¹¹¹In-radiolabelled resin (5 MBq) were prepared for comparison of labelling and stability. Radiolabelling efficiencies were obtained by washing resin with distilled water, and the activity lost was measured. The radiolabelled resins were immersed in simulated gastric and intestinal fluid environments, and the retention of ¹⁵³Sm³⁺ and ¹¹¹In³⁺ was measured over a 24 h period. At 66 h after production, 91.15 ± 12.42% of ¹⁵³Sm was bound to the resin after washing in distilled water, whereas radiolabelling with ¹¹¹In achieved 99.96 ± 0.02% efficiency. Both radiolabelled resins demonstrated almost 100% stability in simulated intestinal fluid and >90% stability in artificial gastric juice over 24 h. The performance of neutron-activated ¹⁵³Sm-resin is similar to that of ¹¹¹In-resin and can be used as an alternative tracer for GI transit studies when In is not available.
Echovirus 7 associated encephalomyelitis

Lum LC, Chua KB, McMinn PC, Goh AY, Muridan R, Sarji SA, et al.

J Clin Virol, 2002 Jan;23(3):153-60.
PMID: 11595594

Hand, foot, and mouth disease (HFMD) is endemic in Malaysia. In 1997, a large outbreak of enterovirus 71 (EV-71) associated HFMD resulted in 41 deaths due to severe left ventricular dysfunction and central nervous system infection with extensive damage to the medulla and pons. The clinical presentation in all these patients were rapid cardio-respiratory decompensation leading to cardiac arrest. Another large outbreak of HFMD with 55 fatal cases and a similar clinical picture was reported in Taiwan in 1998. In 2000, an outbreak of HFMD resulted in the deaths of three children who had rapid cardio-respiratory decompensation and one child who survived a central nervous system infection.
Relapsed and late-onset Nipah encephalitis

Tan CT, Goh KJ, Wong KT, Sarji SA, Chua KB, Chew NK, et al.

Ann Neurol, 2002 Jun;51(6):703-8.
PMID: 12112075

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.
Fulltext Clinical features of Nipah virus encephalitis among pig farmers in Malaysia

Goh KJ, Tan CT, Chew NK, Tan PS, Kamarulzaman A, Sarji SA, et al.

N Engl J Med, 2000 Apr 27;342(17):1229-35.
PMID: 10781618 DOI: 10.1056/NEJM200004273421701

BACKGROUND: Between September 1998 and June 1999, there was an outbreak of severe viral encephalitis due to Nipah virus, a newly discovered paramyxovirus, in Malaysia.
METHODS: We studied the clinical features of the patients with Nipah virus encephalitis who were admitted to a medical center in Kuala Lumpur. The case definition was based on epidemiologic, clinical, cerebrospinal fluid, and neuroimaging findings.
RESULTS: Ninety-four patients with Nipah virus infection were seen from February to June 1999 (mean age, 37 years; ratio of male patients to female patients, 4.5 to 1). Ninety-three percent had had direct contact with pigs, usually in the two weeks before the onset of illness, suggesting that there was direct viral transmission from pigs to humans and a short incubation period. The main presenting features were fever, headache, dizziness, and vomiting. Fifty-two patients (55 percent) had a reduced level of consciousness and prominent brain-stem dysfunction. Distinctive clinical signs included segmental myoclonus, areflexia and hypotonia, hypertension, and tachycardia and thus suggest the involvement of the brain stem and the upper cervical spinal cord. The initial cerebrospinal fluid findings were abnormal in 75 percent of patients. Antibodies against Hendra virus were detected in serum or cerebrospinal fluid in 76 percent of 83 patients tested. Thirty patients (32 percent) died after rapid deterioration in their condition. An abnormal doll's-eye reflex and tachycardia were factors associated with a poor prognosis. Death was probably due to severe brain-stem involvement. Neurologic relapse occurred after initially mild disease in three patients. Fifty patients (53 percent) recovered fully, and 14 (15 percent) had persistent neurologic deficits.
CONCLUSIONS: Nipah virus causes a severe, rapidly progressive encephalitis with a high mortality rate and features that suggest involvement of the brain stem. The infection is associated with recent contact with pigs.

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