Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Duodenal lymphangitis carcinomatosa: Endoscopic characteristics and clinical significance

Background and Aim: Duodenal lymphangitis carcinomatosa has been sporadically described, but so far little attention has been paid to duodenal lymphangitis carcinomatosa. Methods: Four cases with duodenal lymphangitis carcinomatosa were endoscopically and histologically examined. Results: The four cases exhibited multiple polypoid lesions along the Kerckring's folds and/or were covered by characteristically granular, non‐ulcerated mucosa upon thickening. The granularity seems to been caused by dilated lymph vessels containing the carcinoma cells. The lesions were microscopically characterized by: (i) involvement of lymph vessels located in the upper portion of the lamina propria; (ii) no inflammatory changes; and (iii) no desmoplastic changes. Primary sites were thought to be the stomach in case 1, the pancreas in cases 2 and 4, and unknown in case 3. All patients died within 6 months after admission or endoscopic examination. Conclusions: As duodenal lymphangitis carcinomatosis shows characteristic endoscopic appearance, endoscopic diagnosis is not difficult. We should realize that the lesion represents extremely poor prognosis, and it should be distinguished from ordinary metastatic duodenal carcinoma.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

A Rare Case of Biliobiliary Fistula

Abstract: Biliobiliary fistula is a rare clinical entity. The case of a 72 year old female, who presented with epigastric pain and jaundice, is detailed herein. Endoscopic retrograde cholangiopancreatography (ERCP) revealed two stones, one each in the common bile duct and the gallbladder. Continuous endoscopic nasobiliary drainage (ENBD) was performed to relieve obstructive jaundice. Further study with contrast medium administered via the ENBD tube revealed a fistula between the neck of the gallbladder and the common bile duct. The cystic duct was intact. A stone was considered to have migrated into the common bile duct through the fistula. A diagnosis of biliobiliary fistula, Corlette type I was made. However, in this particular case, a biliobiliary fistula was noted at a site below the junction of the cystic duct and common bile duct. Removal of the gallbladder stones was followed by cholecystectomy. The common bile duct was then repaired by utilizing a T-tube. No evidence of malignancy was recognized in the resected gallbladder specimen. In the one year to date since surgery, the patient has been asymptomatic and without signs of biliary disease.     

Slow-wave photic stimulation relieves patient discomfort during esophagogastroduodenoscopy

Background and Aim: Although pretreatment with a sedative drug is effective in relieving pain during esophagogastroduodenoscopy (EGD), such drugs can cause significant side‐effects. The aim of this study was to examine the effect of slow‐wave photic stimulation on discomfort and/or pain felt during EGD. Methods: Forty consecutive patients (25 men and 15 women) who underwent diagnostic EGD in our hospital were included in the study. Twenty patients received photic stimulation for 25 min, and underwent electroencephalographic recording, in addition to the usual premedications. Twenty control patients received the same treatment but without photic stimulation. All patients evaluated the discomfort/pain felt during endoscopy against a five‐grade scale in comparison with what they had experienced in their previous examination. Results: Patients with an improved discomfort/pain score were 18/20 and 3/20 in the treated and control groups, respectively. Overall comparison of pain scores between both groups was significant (P < 0.0001). The proportion of slow‐wave activity recorded in patients’ electroencephalograms significantly increased in the treated group compared to control values (36.6 ± 6.8% vs 29.1 ± 3.4%, P < 0.001). There was a close correlation between the degree of discomfort/pain felt during endoscopy and the proportion of slow‐wave activity (P < 0.001). Conclusion: Slow‐wave photic stimulation shows promise as a treatment for relieving the discomfort and/or pain felt by patients undergoing EGD.     

Lignocaine–induced convulsion does not induce c–fos protein (c–Fos) in rat hippocampus

Recent studies have shown that proto–oncogene c–fos mRNA is induced in the central nervous system by a variety of stimuli including generalised convulsions. In this study, the expression of c–fos protein (c–Fos) following lignocaine–induced convulsions was examined and compared with that following convulsions induced by non–anesthetic convulsants, such as pentylenetetrazol, kainic acid and electroconvulsive shocks, in rat brain.
Administration of 120 mg kg^-1 lignocaine by the intraperitoneal route induced generalised convulsions in all rats examined within 10 min. C–Fos was markedly induced in the piriform cortex and amygdala, and slightly induced in the neocortex and thalamus, while no c–Fos expression was observed in the hippocampus. In contrast, c–Fos expression following generalised convulsions induced by non–anaesthetic convulsants was very marked in the hippocampal region, piriform cortex and amygdala, and extended to the thalamus and neocortex.
These results contradict those of previously reported local cerebral metabolic studies using 2–deoxyglucose as a metabolic marker, and suggest that lignocaine–induced convulsions, unlike those induced by non–anaesthetic convulsants, may not cause severe sequelae (plastic changes) in the hippocampus.     

Prevalence of and risk factors for nocturia: Analysis of a health screening program

BACKGROUND: We examined the prevalence of and risk factors for nocturia in Kurashiki city and the surrounding area, a rural area in Japan. MATERIALS AND METHODS: We collected data on 6517 individuals (4568 men and 1949 women) who participated in a multiphasic health screening. We analyzed the relationships between nocturia assessed by a questionnaire (voiding twice or more during night) and other variables including age, hypertension, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus (DM), chronic renal failure, benign prostatic hyperplasia (BPH), smoking habit and alcohol intake. RESULTS: Overall, 1856 individuals (28.5%) answered that they arose to urinate at least twice during the night. This rate increased with age from 16.5% in individuals younger than 50 to 60.0% in those older than 69. Logistic regression analysis revealed that cohorts of subjects 50-59, 60-69, and 70 years old or over had, respectively, 1.75, 3.35, and 6.21 times the prevalence of nocturia of the 49 years or younger cohort. Hypertension (odds ratio [OR] 1.64) and DM (OR 1.70) were other independent positive risk factors for nocturia. On the other hand, current smokers who smoked 20 or more cigarettes per day were less likely to have nocturia than non-smokers (OR 0.72). In male individuals, BPH was another independent positive risk factor (OR 1.35). Gender was not associated with nocturia. CONCLUSIONS: Although population bias is an important limitation to this study, nocturia is associated with various factors suggesting that multiple approaches are needed to the treatment of patients with nocturia.     

Interaction of glucagon with artificial lipid bilayer membranes

The enhancement of fluorescence emission from the tryptophan residue of glucagon, the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl stearic acid, circular dichroism spectra, the release of 6-carboxytluorescein, and polarized infrared attenuated total reflection (IR-ATR) spectra were used to study the interaction of glucagon with intact lipid vesicles and flat bilayers. Dimyristoylphosphatidylcholine bound the peptide only below the main transition temperature, thus confirming earlier results of Epand et al. (1977). However, the peptide is also bound by vesicles of unsaturated lipids above their transition temperature, suggesting an influence of lipid area on the binding process. Circular dichroism showed that binding to such vesicles also increases the helix content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(I-13)-tridecapeptide revealed profound differences in orientation of the two peptides. The dichroic ratios and the derived order parameters indicated an isotropic orientation of the helical segments of glucagon, but did not exclude a principal orientation of the molecules lying flat on the nienibrane surface. In contrast, the axis of the dynorphin helix is clearly oriented normal to the interface. The two peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a deeper penetration of the primary amphiphilic helix of dynorphin A-(I-13) than of the secondary amphiphilic helix of glucagon.     

A Case of Postsurgical Pancreatic Pseudocyst Treated by Endoscopic Cystogastrostomy

Pancreatic pseudocyst after pancreatic surgery is a relatively rare condition and conservative therapy is the common treatment of choice. When symptoms persist or complications follow, however, surgical treatment is considered. There have been reports on endoscopic cystoenterostomy since the early 1980s. We herein describe a case of postsurgical pancreatic pseudocyst treated successfully by endoscopic cystogastrostomy. A nineteen-year-old female showing left hypochondralgia and back pain with elevation of her serum amylase level, who had undergone enucleation of a solid cystic tumor in the body of the pancreas, was referred to our department. She was diagnosed as having a pseudocyst of the pancreas 5.8×4.5 cm in size at the site of enucleation by US and CT. Endoscopic retrograde pancreatography and endoscopic ultrasonography performed simultaneously revealed obstruction of the main pancreatic duct and a cystic change in the body-tail of the pancreas just behind the gastric wall of the upper body. An extrinsic compression was seen in the posterior wall of the upper body of the stomach endoscopically. An incision was made using a sphincterotome. A pigtail stent, 7.2 Fr in size, was placed to keep the patency of the fistula, which was removed one and a half months later. Her symptoms showed great improvement immediately after the procedure. Follow-up CT demonstrated no recurrence of the pseudocyst.