Multidisciplinary approach in the long-term management of intrahepatic stones: Indian experience.

BACKGROUND: Intrahepatic stones, though common in East Asia, are uncommon in India. There is paucity of data from India regarding the treatment and long-term outcome of patients with intrahepatic stones. METHODS: We retrospectively analyzed medical records of 35 patients with intrahepatic stones who had been treated surgically. Endoscopic biliary drainage had been used in patients who presented with acute cholangitis. Intraoperative stone clearance was confirmed by choledochoscopy and intraoperative cholangiography. Outcome of surgery, frequency and subsequent management of recurrent intrahepatic stones, and factors associated with stone recurrence and cholangitis were analyzed. RESULTS: Twenty-one (60%) patients had bilobar disease. Eight patients underwent hepatectomy and 16 hepatico-jejunostomy with access loop; 12 of these were jejuno-duodenal anastomoses. Postoperative morbidity was observed in 10 patients (29%). Recurrence of stones occurred in 12 patients (34%) and cholangitis in 9 patients (26%). Presence of bilobar disease and associated biliary strictures were associated with recurrent cholangitis (p< 0.05). Two patients (6%) required re-operation for recurrent cholangitis. Complete removal of recurrent stones using conventional endoscope was possible through jejuno-duodenostomy in all 5 cases who had this type of access loop construction. CONCLUSION: Surgical treatment for intrahepatic stones depends on the site of involvement. Construction of a jejuno-duodenal access loop in patients with bilobar disease and intrahepatic strictures is helpful in facilitating postoperative stone clearance. A multidisciplinary approach is beneficial especially when the disease is bilobar and recurrent in type.     

The Intestinal Absorption of a Prodrug of the mGlu2/3 Receptor Agonist LY354740 is Mediated by PEPT1: In Situ Rat Intestinal Perfusion Studies

LY354740 is a potent mGlu2/3 agonist with a limited oral bioavailability. Its alanyl prodrug, LY544344, showed high affinity to the intestinal peptide transporter PEPT1, and improved the oral bioavailability of LY354740 in various animal models. The aim of the present study was to investigate the mechanism of in vivo absorption of the dipeptidic prodrug LY544344. The permeabilities of LY544344 and LY354740 were examined in the rat in situ single‐pass intestinal perfusion model. The intestinal absorptive flux of LY354740 was shown to be very low in comparison with LY544344. The absorptive flux of LY544344 could best be described by a Michaelis–Menten process in parallel with a linear process. The estimated parameters were: J_max = 26.7 × 10^?5 µmol/(cm²‐s), K_m = 2.6 mM. The absorptive permeability of LY544344 was reduced to approximately 5% of control in the presence of excess Gly‐Sar, a known PEPT1 substrate. Intracellular accumulation of LY354740 and LY544344, estimated postperfusion, showed high levels of LY354740 over LY544344 at all perfusate concentrations studied. However, there was a decline in the intracellular ratio of LY354740 to LY544344 at higher concentrations, suggesting that the metabolic activation to release LY354740 is saturable. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1574–1581, 2010     

Prospective randomised comparison of current coagulation and injection sclerotherapy for the outpatient treatment of haemorrhoids

The feasibility and early results of a new technique of outpatient proctoscopic coagulation of haemorrhoids by means of an electronic probe (Ultroid^®, Microvasive Inc., USA) were evaluated in comparison to conventional injection sclerotherapy. Age, symptom and sex-matched groups were analysed before and 6 weeks after outpatient treatment, using scoring systems (n=51). A mean of 6.2±0.4 ml of phenol in oil were injected over 2.4±0.2 min compared to a mean current of 15.8 ±0.2 mA over a period of 11.9±0.8 min (p<0.001, treatment time). Sclerotherapy was found significantly less tedious than coagulation. More patients complained of discomfort during coagulation, but the difference in tolerance scores between the 2 groups was not significant. Three patients in the coagulation group but none in the injection group refused to be treated by the same method again due to discomfort. Significant benefits were achieved by both modes of treatment after 6 weeks. The early cure rates for bleeding were 84% for sclerotherapy and 64% for coagulation (p=0.2) and for prolapse 56% and 44% respectively (p=0.72). Injection sclerotherapy is preferable to Ultroid^® coagulation for the outpatient treatment of haemorrhoids because it is a quicker, less tedious and more comfortable procedure with equally effective early results.

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Résumé La réalisation et les premiers résultats d'une nouvelle technique de coagulation ambulatoire des hémorroïdes au moyen d'une sonde électronique (Ultroïd, Microvasive inc. USA) on été évalués par comparaison avec la sclérothérapie conventionnelle. Deux groupes appariés selon l'âge, les signes et le sexe ont été analysés avant et six semaines après un traitement ambulatoire en utilisant un score (n=51). Une moyenne de 6,2±0,4 ml d'huile phéniquée a été injectée en 2,4±0,2 mn comparée à une application de courant moyen de 15,8±0,2 mA dans une période de 11,9±0,8 mn (p<0,001, temps de traitement). La sclérothérapie a été trouvée moins pénible que la coagulation. Plus de malades se plaignaient d'inconfort durant la coagulation mais la différence de tolérance n'était pas significative entre les deux groupes. Trois malades dans le groupe de coagulation ont refusé de poursuivre le traitement en raison du disconfort contre aucun malade dans le groupe d'injection. Les résultats furent bons dans les deux groupes après six semaines. Les résultats immédiats pour les saignements étaient de 84% et de 64% pour la coagulation (p=0,2) et pour les procidences de 56% pour la scléro-thérapie contre 44% pour la coagulation (p=0,72). Les injections sclérosantes sont préférables à la coagulation Ultroid comme traitement ambulatoire des hémorroïdes car il s'agit d'un procédé plus rapide, moins pénible et plus confortable avec des résultats immédiats aussi bons.

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Paper presented at the Spring Meeting of the British Society of Gastroenterology, University of Warwick, UK, March 1990     

Cases of buprenorphine abuse in India.

Buprenorphine was introduced as a potent analgesic with low abuse potential. Reports of buprenorphine abuse by opiate abusers have accumulated over the years, highlighting its use as a cheap alternative to heroin. The lower potency compared with heroin is being compensated by using a cocktail of buprenorphine with benzodiazepines or cyclizine. This study of 18 cases seen over 3 years broadly confirms these findings. Four cases reported haematemesis during acute withdrawal, a symptom not reported in earlier studies.     

Diagnosing intramuscular myxoma by fine-needle aspiration: A multidisciplinary approach

The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (nonplexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma. Diagn Cytopathol 1994;11:255–261. © 1994 Wiley-Liss, Inc.     

Induction of ultraviolet cataracts in vitro: prevention by pyruvate.

Ultraviolet (UV) radiation is one of the important cataract risk factors. The present studies examined the hypothesis that this effect is due to the UV penetration through the cornea and subsequent induction of a photochemical generation of reactive species of oxygen (ROS) in the aqueous and lens. The hypothesis was ascertained by rat lens organ culture studies conducted under UV (365 nm), with media containing micromolar levels of riboflavin, with and without pyruvate, the latter acting as an ROS scavenger. The implication of ROS in the UV-induced damage was confirmed by measurements of peroxide generation. Damage to the lens was assessed physiologically by measuring the decrease in its active transport of rubidium ions. Biochemically, it was assessed by measuring the lowering of adenosine triphosphate and glutathione. The incorporation of pyruvate in the medium protected the lens against these deleterious effects. That the beneficial effect of pyruvate is attributable to its ROS-scavenging property was proven by the peroxide depletion in its presence, commensurate with its own utilization in parallel. A protective effect of this keto acid against UV-induced tissue damage has been shown for the first time, suggesting its clinical usefulness against UV irradiation-induced pathologies. Hence, further studies on the possible protective effects of such alpha-keto acids against UV damage are in progress.