Clinical and manometric evaluation of anorectal function following low anterior resection with low anastomotic line using an EEA™ stapler for rectal cancer

Anorectal function was evaluated in eight patients who had low anterior resection of the rectum with a low anastomotic line, using an EEA^™ stapler, with determination of function based on periodic manometric studies and clinical symptoms. Immediately following surgery all patients suffered from frequent bowel actions and soiling. These symptoms improved with time and most patients could enjoy almost normal daily life by the sixth postoperative month. One month after surgery, anal canal resting pressure and maximum squeeze pressure were significantly reduced and rectoanal inhibitory reflex was absent; neither showed a distinct tendency to improve thereafter. Rectal sensation and reservoir capacity, which also were seriously impaired, recovered satisfactorily by the time of the six-month examination. This suggests that an improvement of clinical symptoms following this operation is dependent upon the recovery of reservoir capacity and sensation of the neorectum, and that this operative procedure is a functionally acceptable option for low rectal cancer.     

Bleeding from gastric ulcer halted by laparoscopic suture ligation

In a 48-year-old Japanese man there was an uncontrollable and recurrent bleeding from a gastric ulcer and laparoscopic surgery was done. Two cannulae were placed in the gastric cavity through the abdominal wall and suture ligation of the bleeding vessel at the posterior wall of the stomach was done under videovisual control with endoscopic guidance. The bleeding ceased, complications were nil, and he remains well.This article reports on surgery done to repair uncontrollable, recurrent bleeding from a gastric ulcer. Two cannulae were placed in the gastric cavity through the abdominal wall and suture of the vessel at the posterior wall of the stomach was done with videovisual control and endoscopic guidance. This approach is concluded to have supplied minimal-access surgery, cost effectiveness, early discharge, less pain, and doctor-patient satisfaction.     

Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.     

Mucoadhesive Microspheres Containing Amoxicillin for Clearance of Helicobacter pylori

In an effort to augment the anti-Helicobacter pylori effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance of H. pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H. pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared H. pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H. pylori.     

Gender-specific response to isoflurane preconditioning in focal cerebral ischemia.

Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1(+/+) and Akt1(-/-) mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.     

Two case reports of childhood liver cell adenomas harboring beta-catenin abnormalities

The benign epithelial neoplasm liver cell adenoma is rare, especially in childhood. We report 2 such cases, 1 of which was associated with Prader-Willi syndrome. Differential diagnosis of the liver cell adenomas on the basis of histopathologic findings proved difficult and was based on the absence of cellular and nuclear atypia, mitotic activity, and invasive growth. In both cases, immunohistochemical staining demonstrated the nuclear accumulation of beta-catenin, and in 1 case, the tumor cells carried a mutation of the beta-catenin gene. Recently, disregulation of the Wnt/beta-catenin pathway, attributable to abnormalities of the beta-catenin gene, has been reported to be a major event in the development of hepatocellular carcinomas and hepatoblastomas. Our report may be the first to describe the beta-catenin abnormalities in childhood liver cell adenoma. These findings imply that abnormalities of beta-catenin can be an early initiating event in human liver tumorigenesis.