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PubMedDate not supplied

Pathology of perbutylated-N-butyl-1-deoxynojiromycin (an alpha-glucosidase-1 inhibitor) in Sprague-Dawley rats.

Perbutylated-N-butyl-1-deoxynojiromycin (p-N-butyl-DNJ, SC-49483), an alpha-glucosidase-1 inhibitor, is a candidate anti-HIV agent targeted against viral glycoprotein processing in host cell endoplasmic reticulum. The potential toxicity of this compound was evaluated in Sprague-Dawley rats after 4, 13, or 26 wk of oral administration at doses ranging from 300 to 3,670 mg/kg/day. In these studies, the target organs of p-N-butyl-DNJ effects were thyroid gland, salivary gland, stomach, and pancreas. The most prominent histologic change in these organs was the presence of clear or lightly eosinophilic vacuoles in the cytoplasm of thyroid follicular cells, gastric chief cells, salivary gland acinar cells, and exocrine pancreatic acinar cells. Ultrastructurally, these vacuoles were consistent with dilated rough endoplasmic reticulum, which sometimes contained homogeneously stained, moderately electron-dense material. The vacuoles in thyroid follicular cells contained pale eosinophilic colloidlike material consistent with accumulated thyroglobulin, as shown by immunohistochemical staining methods. The biological functions of these organs were not adversely affected as evidenced by the absence of clinical signs and the results of selected hormonal analyses. The morphologic changes were completely reversed after a 4-wk recovery period. The incidence and severity of histologic changes were decreased after 13 and 26 wk of treatment compared to 4 wk of treatment, indicating an attenuation of the host response or adaptation to the prolonged p-N-butyl-DNJ administration. We believe that morphologic changes in thyroid follicular cells, salivary gland acinar cells, pancreatic acinar cells, and gastric chief cells were the result of nonspecific inhibition of host alpha-glucosidase(s) by p-N-butyl-DNJ, causing clinically silent perturbation in host cell glycoprotein processing and/or glycoprotein transport.

Animals↗
PubMed2006

Functional conduit disorders after esophagectomy.

Unfortunately normal gastrointestinal function after an esophagectomy is rare. Most patients will never eat the way they did before their illness. Most patients require smaller more frequent meals. It is common for patients to loose up to 15% of their body weight from the time of diagnosis through the first 6 months postoperatively, but fortunately this trend levels off after 6 months. Dumping syndrome, delayed gastric emptying, reflux, and dysphagia can all contribute to nutritional deficiency and poor quality of life. There is no one surgical modification to eliminate any one of these complications, but several guidelines can help reduce conduit dysfunction. Most patients seem to benefit from a 5-cm-wide greater-curvature gastric tube brought up through the posterior mediastinum. The gastric-esophageal anastomosis should be placed higher than the level of the azygous vein. Drainage procedures seem to be helpful, especially when using the whole stomach as a conduit. Early erythromycin therapy significantly aids in the function of the gastric conduit. Proton-pump inhibitors are important for improvement of postoperative reflux symptoms and to help prevent Barrett's metaplasia in the esophageal remnant. Single-layer hand-sewn or semi-mechanical anastomoses provide greater cross-sectional area and fewer problems with stricture. When benign strictures occur, early endoscopy and dilation with proton-pump inhibition greatly reduces the morbidity. Patients should be instructed to eat six small meals a day and to remain upright for as long as possible after eating. Simple sugars and fluid at mealtime should be avoided until the function of the conduit is established.

Deglutition Disorders↗
PubMed1994

Endoscopic examination of the operated stomach: a review and a systematic approach.

The endoscopist examining a patient with a history of gastric surgery is expected to know details of the history, the present physical condition, and relevant laboratory results. Familiarity with the appropriateness or limitations of different types of fiberscopes in relation to the individual case, and knowledge of how to overcome common difficulties, is important. The preparation must address the particular characteristics of the case, and the endoscopist must be aware of contraindications, complications, and recommendations to be observed in special circumstances. Based on situations confronted in daily practice, the authors suggest a systematic approach to the examination of patients with a history of gastric surgery, and point to the importance of observing the following steps: measurement of the length of the greater curvature in the gastric stump, verification of artifacts and anatomic modifications and their repercussions, removal of symptomatic suture line or staples, dilatation of strictures, fragmentation of bezoars, exeresis of polypoid lesions, collection of tissue samples, and regular follow up of the patients.

Follow-Up Studies↗
PubMed1999

Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos.

NKX2.1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. We demonstrate that septation of the anterior foregut along the dorsoventral axis, into distinct tracheal and esophageal structures, is blocked in mouse embryos carrying a homozygous targeted disruption of the Nkx2.1 locus. This is consistent with the loss of Nkx2.1 expression, which defines the dorsoventral boundary within the anterior foregut in wild-type E9 embryos. Failure in septation between the trachea and the esophagus in Nkx2.1(-/-) mice leads to the formation of a common lumen that connects the pharynx to the stomach, serving both as trachea and as esophagus, similar in phenotype to a human pathologic condition termed tracheoesophageal fistula. The main-stem bronchi bifurcate from this common structure and connect to profoundly hypoplastic lungs. The mutant lungs fail to undergo normal branching embryogenesis, consist of highly dilated sacs that are not capable of sustaining normal gas exchange functions, and lead to immediate postnatal death. In situ hybridization suggests reduced Bmp-4 expression in the mutant lung epithelium, providing a possible mechanistic clue for impaired branching. Functional deletion of Nkx2. 1 blocks pulmonary-specific epithelial cell differentiation marked by the absence of pulmonary surfactant protein gene expression. Altered expression of temporally regulated genes such as Vegf demonstrates that the lung in Nkx2.1(-/-) mutant embryos is arrested at early pseudoglandular (E11-E15) stage. These results demonstrate a critical role for Nkx2.1 in morphogenesis of the anterior foregut and the lung as well as in differentiation of pulmonary epithelial cells.

Animals↗
PubMed1984

Photodynamic effects of exposure to hematoporphyrin derivatives and dye-laser radiation on human gastric adenocarcinoma cells.

The phototoxicity of hematoporphyrin derivatives (HPD) and dye-laser radiation on adenocarcinoma cells of the human stomach was examined by light and electron microscopy. Adenocarcinoma cells were obtained from human stomach tissue by endoscopic biopsy. The cells were incubated for 5 minutes in the patient's own serum that contained 0.6 mg HPD/ml and then were exposed to dye-laser radiation at 630 nm at an irradiance of 15 mW/cm2. Electron microscopy showed that cytotoxicity was mediated by mitochondrial damage, dilatation of the rough endoplasmic reticulum, and alterations of the nuclear membrane. The degenerative changes were greater and more frequent in poorly differentiated adenocarcinoma cells than in well-differentiated ones. No marked temperature rise was detected during irradiation. Neither the dye alone nor light alone had any effect. A singlet oxygen-trapping agent, 1,3-diphenylisobenzofuran, prevented adenocarcinoma cell degeneration that otherwise would result from exposure to HPD and dye-laser radiation. Thus singlet oxygen may be the cytotoxic agent in this system.

Adenocarcinoma↗
PubMed1982

Significance of abnormal gastrointestinal gas in systemic amyloidosis.

Nine cases of amyloidosis involving the gastrointestinal tract were reviewed for the presence of abnormal gastrointestinal gas by taking plain roentgenograms of the abdomen (PRA) as a diagnostic adjunct. Findings were compared to data obtained by conventional barium study or endoscopic examination. PRA revealed marked gaseous dilatation of the gastrointestinal tract simulating intestinal obstruction in three cases and a moderate or mild increase of gas in two cases each. Abnormality was thus found in seven of the nine cases by PRA. Conventional barium study by means of upper gastrointestinal series, small bowel series and barium enema showed abnormal findings in five of seven cases. Endoscopic examination of the stomach and distal colon disclosed mucosal abnormality in three of seven cases. The rate of abnormal findings detected by the three methods cannot easily be compared to each other because of the differences in symptoms and treatment of individual patients. Nevertheless, PRA seem to be valuable in demonstrating a high rate of abnormalities in amyloidosis.

Adult↗
PubMed2006

[Laparoscopic devascularization of the stomach and the abdominal esophagus with the LigaSure instrument in a porcine model].

OBJECTIVES: In this study we proved the feasibility of a new minimally invasive procedure for the devascularisation of the proximal stomach and the abdominal esophagus to prevent recurrent variceal bleeding in portal hypertension in a new animal model. MATERIALS AND METHODS: Experiments were performed on 12 female pigs, in two animal groups. In the first step (I. group n=6) portal hypertension was created by controlled laparoscopic clip ligation of the portal vein. The increased portal pressure was established by the needle puncture of the portal vein and the spleen. Two weeks later, the dilated veins were sealed along the lesser and greater curvature and the transhiatal esophagus with the 10 mm LigaSure instrument. Successful of the experimental model had encouraged us to perform this method on other animals (II. group, n=6), using the 5 mm instrument. RESULTS: There was no intraoperative bleeding after using both LigaSure instruments. Autopsy (2 weeks later) showed correct placed clips with partial occlusion of the portal vein without portal vein thrombosis. There was no evidence of postoperative bleeding. Histological investigation of the gastric surface confirmed complete sealing of the extended varices. CONCLUSION: The laparoscopic LigaSure instrument was found to be safe and suitable equipment for the ligation of the dilated veins along the gastric surface and the abdominal esophagus, and this method could be an alternate choice for the patients with recurrent variceal bleeding.

Animals↗
PubMed1986

The innervation of the pyloric region of the crab, Cancer borealis: homologous muscles in decapod species are differently innervated.

The muscles of the pyloric region of the stomach of the crab, Cancer borealis, are innervated by motorneurons found in the stomatogastric ganglion (STG). Electrophysiological recording and stimulating techniques were used to study the detailed pattern of innervation of the pyloric region muscles. Although there are two Pyloric Dilator (PD) motorneurons in lobsters, previous work reported four PD motorneurons in the crab STG (Dando et al. 1974; Hermann 1979a, b). We now find that only two of the crab PD neurons innervate muscles homologous to those innervated by the PD neurons in the lobster, Panulirus interruptus. The remaining two PD neurons innervate muscles that are innervated by pyloric (PY) neurons in P. interruptus. The innervation patterns of the Lateral Pyloric (LP), Ventricular Dilator (VD), Inferior Cardiac (IC), and PY neurons were also determined and compared with those previously reported in lobsters. Responses of the muscles of the pyloric region to the neurotransmitters, acetylcholine (ACh) and glutamate, were determined by application of exogenous cholinergic agonists and glutamate. The effect of the cholinergic antagonist, curare, on the amplitude of the excitatory junctional potentials (EJPs) evoked by stimulation of the pyloric motor nerves was measured. These experiments suggest that the differences in innervation pattern of the pyloric muscles seen in crab and lobsters are also associated with a change in the neurotransmitter active on these muscles. Possible implications of these findings for phylogenetic relations of decapod crustaceans and for the evolution of neural circuits are discussed.

Acetylcholine↗
PubMed2004

Complete mechanical cervical anastomosis using a narrow gastric tube after esophagectomy for cancer.

OBJECTIVE: Fibrous stenosis of the esophagogastric cervical anastomosis remains a significant complication occurring in up to one-third of cases. Trying to reduce the incidence of this complication, we describe our technique of cervical esophagogastric anastomosis using endoscopic linear stapler which seems to reduce the incidence of fibrous stricture formation after resection of esophageal cancer. METHODS: Between March 2000 and June 2003, 26 patients (15 males and 11 females) underwent esophagectomy using tubulized stomach for reconstruction. Cervical esophagogastric anastomosis using linear endoscopic stapler was performed in all cases. The occurrence of post-operative anastomotic leak and development of anastomotic stricture were recorded and analyzed. RESULTS: All patients survived esophagectomy and were available for post-operative follow-up. Anastomotic leak developed in one case. No patient developed fibrous stenosis that required dilatation therapy. CONCLUSION: Complete mechanical esophagogastric anastomosis, using endoscopic linear stapler is effective and safe, even when a narrow gastric tube is used as esophageal substitute. This technique seems superior to other techniques to reduce the incidence of post-operative anastomotic complications.

Adult↗
PubMed1985

[Endotube as a palliative measure in stenosing cancer of the esophagus and cardia].

93 patients with advanced carcinoma of the esophagus or cardia were treated by positioning an endoprothesis under combined endoscopic and radiological control. Before this procedure the esophagus had been dilated - in 31 cases with our new multistage bougie. 14% of patients died in the hospital, 7,5% of these as a consequence of the procedure described. If no complications occur, the patients can be discharged from the hospital 24 hours later. Swallowing is improved definitely, mean survival time of our group was 10.9 weeks. Complications occurring later are mostly due to technical problems of the endoprothesis. Endoscopic positioning of the endoprothesis is a satisfactory palliative procedure. Positioning the endoprothesis by surgery to day is outdated.

Adenocarcinoma↗
PubMed1998

[Endoscopic palliation of dysphagia due to anastomotic recurrences after esophageal surgery and total gastrectomy due to carcinoma].

BACKGROUND: Dysphagia is the main symptom of locally recurrent esophageal and gastric carcinoma and generally suggests extensive disease. The safety and efficacy of endoscopic palliation in patients who developed locally recurrent disease after surgery is evaluated. METHODS: Twenty-six males and 12 females, with an average age of 63.5 years were included in the patients group. In 12 patients there was an esophago-gastric anastomosis, in 26 an esophago-jejunostomy, after total gastrectomy. Anastomotic recurrences were divided into predominantly polypoid (16 cases) and predominantly stenosing (22 cases). Three treatment modalities were employed: endoscopic dilation (6 cases), Nd-Yag laser therapy (16 cases) and prostheses (16 cases). RESULTS: Successful endoscopic treatment was obtained in 33 out of 38 patients (86.8%). Major complications occurred in 5 patients (15%) with a mortality rate of 6%. CONCLUSIONS: The endoscopic palliation is effective. Technically, endoscopic treatment is easier to perform, with better results, when dealing with polypoid rather than stenosing recurrences.

Adult↗
PubMed1996

Emptying of the intrathoracic stomach using three different pylorus drainage procedures--results of a comparative study.

Patterns of gastric emptying in the vagotomized intrathoracic stomach (used for esophageal replacement) were studied using radioisotope techniques. Following esophagectomy and gastric mobilization, the patients were randomized into three groups: group 1, pyloroplasty; group 2, pyloromyotomy; and group 3, pylorus stretching. A total of 30 patients surviving the operation and who were still alive at least 3 months afterwards were included in this study. Gastric emptying (GE) was evaluated 6-8 weeks after the operation. The mean GE time for liquids was 3.3 +/- 2.7, 4.1 +/- 3.1, and 5.5 +/- 4.3 min in the three groups, respectively. The corresponding GE time for solids in the three groups was 9.9 +/- 5.1, 10.31 +/- 6.6, and 7.7 +/- 3.4 min. No statistical difference was observed in the GE in the three groups even though liquids tend to empty faster than solids. Clinically there was also no significant difference in their ability to tolerate normal meals. When evaluated for clinical evidence of altered GE (effect of vagotomy) there did not appear to be any significant differences between the three groups. It is therefore concluded that all pylorus drainage procedures behave in much the same way. Patients may develop some problems, but these disappear in due course after proper adjustments have been made in both posture and diet.

Dilatation↗