LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Species differences in the hydrolysis of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile

The carcinogenic effects of acrylonitrile in rats are believedto be mediated by its DNA-reactive epoxide metabolite, 2-cyanoethyleneoxide (CEO). Previous studies have shown that conjugation withglutathione is the major detoxication pathway for both acrylonitrileand CEO. This study investigated the role of epoxide hydrolasein the hydrolysis of CEO by HPLC analysis of the products from[2,3-¹⁴C]CEO. CEO is a relatively stable epoxide with a half-lifeof 99 min at 37°C in sodium phosphate buffer (0.1 M), pH7.3. Incubation with hepatic microsomes or cytosols from maleF-344 rats or B6C3F1 mice did not enhance the rate of hydrolysisof CEO (0.69 nmol/min). Human hepatic microsomes significantlyincreased the rate of hydrolysis of CEO, whereas human hepaticcytosols did not. Human hepatic microsomal hydrolysis activitywas heat-sensitive and potently inhibited by 1,1,1-trichloropropeneoxide (IC₅₀ of 23 µM), indicating that epoxide hydrolasewas the catalyst. The hydrolysis of CEO catalyzed by hepaticmicrosomes from six individuals exhibited normal saturationkinetics with K_M ranging from 0.6 to 3.2 mM and V _max from 8.3to 18.8 nmol hydrolysis products/min/mg protein. Pretreatmentof rodents with phenobarbital or acetone induced hepatic microsomalhydrolysis activity toward CEO, whereas treatment with ß-naphthoflavone,dexamethasone or acrylonitrile itself was without effect. Thesedata show that humans possess an additional detoxication pathwayfor CEO that is not active in rodents (but is inducible). Thepresence of an active epoxide hydrolase hydrolysis activitytoward CEO in humans should be considered in assessments ofcancer risk from acrylonitrile exposure.     

Domiciliary mechanical ventilation in a patient with severe chronic obstructive lung disease and respiratory failure.

A patient of chronic obstructive pulmonary disease (COPD) with cor-pulmonale and chronic respiratory failure, who was given intermittent positive pressure ventilation at home, is reported. The patient did remarkably well on home mechanical ventilatory support. We believe this to be the first case report of domiciliary mechanical ventilation in a patient of COPD from India.     

Possible roles of vitamin E in immune response of calves.

The effect of vitamin E injections on immune responses of calves was investigated. Treatments were: 0, 900, 1800 and 2700 IU of D-alpha-tocopherol given by injection starting at birth and then a 3 wk interval until the age of 12 wk. Plasma vitamin E levels were significantly higher for supplemented calves than control calves at any of the sampling times. There were no significant differences in the concentrations of immunoglobulin IgG1, IgG2 and titre to Keyhole Limpet Haemocyanin among treatments. However, the general trend was to have higher concentrations of IgG1 and IgG2 with an increase in the levels of vitamin E. Immunoglobulin IgM was significantly higher for calves supplemented with 2700 IU of vitamin E than control calves.     

Antioxidant enzymes in Acanthocheilonema viteae and effect of antifilarial agents

Adult worms of Acanthocheilonema viteae were found to be susceptible to the reactive oxygen intermediates (ROI) generated by the xanthine-xanthine oxidase (X-XO) system. The damage caused by this system was completely abolished by superoxide dismutase (SOD) and catalase but not by mannitol. The results, therefore, suggest that superoxide anions (O2-) and hydrogen peroxide (H2O2) alone or in combination might be toxic to the filariid. A. viteae exhibited the presence of an active enzyme system to protect itself against the oxidants. SOD and catalase were present in high levels of activities and appeared to constitute the major defence system. The role of glutathione peroxidase (GPx), on the other hand, seemed less important due to the weak activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH). A. viteae also released SOD, catalase and GPx in the ambient medium, which appear useful in protecting the filariid against ROI generated by the host in the immediate surroundings of the parasite. Antifilarial agents, diethylcarbamazine (DEC) and 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (82/437) appreciably inhibited catalase and GPx of A. viteae. Inhibition of these enzymes appears to render the parasite prone to H2O2 toxicity leading to death. No adverse effect on antioxidant enzymes of liver, lungs and subcutaneous tissue of Mastomys natalensis recorded as a result of exposure to 82/437 suggests a non-toxic nature to the compound.