Gamma scintigraphic study of the hydrodynamically balanced matrix tablets of Metformin HCl in rabbits.

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.

Production and first use of 153SmCl3-ion exchange resin capsule formulation for assessing gastrointestinal motility.

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.

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 ¹5³Sm³âº and ¹¹¹In³âº 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.

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

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.

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.

Relapsed and late-onset Nipah encephalitis.

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.