Safety and efficacy of glucagon as a premedication for upper gastrointestinal endoscopy--a comparative study with butyl scopolamine bromide

BACKGROUND: Glucagon inhibits digestive motility and is used for endoscopic premedication; however, its effect on cardiopulmonary function during endoscopy has not yet been fully investigated. AIM: To clarify the efficacy and safety of glucagon compared with butyl scopolamine bromide as upper gastrointestinal endoscopy premedication. METHODS: Two hundred and forty consecutive patients over 40 years of age, referred for upper gastrointestinal endoscopy, without any complications, were studied. These patients were randomly premedicated with butyl scopolamine bromide (SC group) or glucagon (G group). Time course changes in blood pressure, arterial oxygen saturation, heart rate and the number of retching episodes during endoscopy were examined. The efficacy of glucose tablets after upper gastrointestinal endoscopy to prevent hypoglycaemia caused by glucagon was evaluated. Cardiopulmonary parameters were also examined in 77 complicated patients with glucagon premedication (GC group). RESULTS: A continuous increase in heart rate during upper gastrointestinal endoscopy was observed in the SC group, but not in the G and GC groups. Blood pressure, arterial oxygen saturation and number of retching episodes were not different between the groups. Hypoglycaemia-related symptoms were frequent in the G group without glucose tablets, but were prevented by the administration of glucose. CONCLUSIONS: Glucagon has a weaker effect on cardiopulmonary function during upper gastrointestinal endoscopy than butyl scopolamine bromide. Glucose administration prevents hypoglycaemia-related symptoms caused by glucagon.     

Effect of gentamicin on pharmacokinetics of lysozyme in rats: interaction between megalin substrates in the kidney

To investigate the pharmacokinetic interaction between substrates of megalin, a 600-kDa endocytic receptor abundantly expressed in the renal proximal tubules, we examined the effect of gentamicin infusion on the pharmacokinetics of fluorescein isothiocyanate (FITC)-lysozyme in rats. Infusion of gentamicin did not affect the plasma concentration-time profile of FITC-lysozyme. On the other hand, gentamicin significantly decreased the accumulation of FITC-lysozyme in the renal cortex and medulla, whereas the accumulation in the renal papilla, liver, brain and lung was not changed. Urinary excretion of FITC-lysozyme was increased by gentamicin, whereas there was no change in the biliary excretion of FITC-lysozyme or its degradation products. Gentamicin infusion had little influence on the ATP content in the renal cortex and urinary excretion of glucose, indicating that nephrotoxicity is not induced by short-term infusion of gentamicin. These findings suggest that lysozyme and gentamicin interact with each other in their reabsorption processes in the renal proximal tubules, probably by competing for their binding to megalin expressed in the apical membrane of the renal proximal tubules.     

Treatment of growth plate injury with autogenous chondrocytes: a study in rabbits

We designed this study to investigate transplantation of autogenous chondrocytes cultured in atelocollagen gel to treat the injured growth plate. An experimental model of growth arrest was made by resecting the medial two thirds of the left proximal tibial physis in 8-10-week-old Japanese white rabbits. Autogenous chondrocytes, which had been harvested from cartilage of the knee joints, embedded in atelocollagen gel, and cultured for a week, were transplanted into the defect in the growth plate. In two other experimental groups, we transplanted autogenous fat tissue into the same defects, or left them empty. Histological and radiographic examinations were done before and after transplantation at various times up to 52 weeks postoperatively. The histological study showed that grafted chondrocytes synthesized extracellular matrix and prevented early ossification and closure of the growth plate, which occurred in the Fat and Defect groups. Angular deformity and length discrepancy in the transplanted group were less than in the control group. Our findings suggest that transplantation of autogenous chondrocytes, cultured in atelocollagen gel, may improve treatment of the injured growth plate.     

Repair of articular cartilage defects with cultured chondrocytes in Atelocollagen gel

We attempted to repair full-thickness articular cartilage defects in rabbit knee joints with allogeneic cultured chondrocytes embedded in Atelocollagen gel. An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in the collagen gel and covered with periosteal flap (G group). In three other experimental groups, the same defects were transplanted with chondrocytes in monolayer culture with periosteal flap (M group), periosteal graft only (P group), or left empty (E group). At 4, 12, and 24 weeks after operation, the reparative tissue was analyzed macroscopically and histologically. At 4 weeks after operation, the surfaces of the reparative tissue were smooth, and the defects were filled with reparative tissues that resembled hyaline cartilage in all four groups. However, the reparative tissues degenerated gradually with time in the M, P, and E groups. In contrast, in the G group, the reparative tissue retained its thickness, and there was a steady integration of the grafted tissue into the adjacent normal cartilage at 24 weeks after operation. The results suggest that transplantation of allogeneic chondrocytes cultured in Atelocollagen gel is effective in repairing an articular cartilage defect.     

Prospective analysis of DNA ploidy, proliferative index and epidermal growth factor receptor as prognostic factors for pretreated uterine cancer

For the purpose of identifying prognostic factors for pretreated uterine cancer, DNA ploidy, proliferative index (P.I.) and epidermal growth factor receptor (EGFR) expression were analyzed in a large prospective series of 76 cervical cancer and 64 endometrial cancer patients observed for 5 years or more (median 76 months). The frequency of aneuploid cells was 62.0% (44/71) in cervical cancer and 16.7% (10/60) in endometrial cancer. There was no association between DNA ploidy and the clinicopathological findings without clinical stage, in which aneuploid cervical and endometrial cancers were significantly more common among advanced tumors (cervical: p<0. 05, endometrial: p<0.01). The P.I. was significantly higher in the patients with aneuploid tumors (cervical: p<0.05, endometrial p<0. 01). EGFR expression was detected in 56.6% (30/53) in cervical cancer and 59.6% (34/57) in endometrial cancer, and the mean EGFR level was 17.8+/-37.7 and 9.5+/-42.5 fmol/mg. protein, respectively. There was no correlation between EGFR expression and DNA ploidy, P.I. and clinicopathological findings analyzed. Five-year survival rate in patients with aneuploid tumors tended to have a worse outcome in cervical cancer cases (p=0.1003, log-rank test), and was significantly worse in endometrial cancer (p=0.0048, log-rank test). No significant relationship was noted between P.I., EGFR expression and 5-year survival. Cox multivariate analysis showed that DNA ploidy, P.I., and EGFR expression are not association with the risk of death. Our data showed neither DNA ploidy, P.I. nor EGFR expression were independent prognostic factors for pretreated uterine cancer.     

Effects of a selective inhibitor of inducible nitric oxide synthase, ONO-1714, on experimental hemodialysis-related hypotension in renal dysfunctional dogs

The effect of a selective inducible nitric oxide synthase inhibitor, ONO-1714 ((1S,5S,6R,7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride), on hemodialysis-related hypotension was investigated using a canine model of renal dysfunction. Renal dysfunction was induced in dogs by complete bilateral ligation of renal arteries. On performing hemodialysis with ultrafiltration, the blood pressure of the renal dysfunction dogs gradually decreased and persisted at reduced levels until completion. ONO-1714 ameliorated the hemodialysis-induced hypotension in the renal dysfunction dogs at a dose that did not influence blood pressure in non-hemodialysis dogs with normal renal function. The above findings indicated that ONO-1714 may elicit beneficial effects on hemodialysis-related hypotension.     

Case report: a young woman with advanced esophageal cancer showing pathological complete response to neoadjuvant chemotherapy (CDDP, 5-FU and ADM)

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.     

Overexpression of glyceraldehyde-3-phospahe dehydrogenase is not involved in 5-hydroxytryptamine (5-HT)-induced necrosis in cultured cerebrocortical neurons

Cerebrocortical cell cultures were prepared from 1-d-old rats. On post-culture day 6, 5-hydroxytryptamine (5-HT) was added to the medium and cells were exposed for another 3 d. 5-HT elicited cytotoxicity in a dose-dependent manner, and the survival rate of neuronal cells was decreased to 64.9+/-5.0% at 0.1 mM concentration. Chromatin staining with Hoechst 33258 and electron microscopy revealed that the 5-HT-induced neuronal death was entirely due to necrosis. Pretreatments with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antisense oligonucleotide and several classical apoptotic inhibitors did not exhibit neuroprotection in this paradigm. Northern blot analysis showed that the enhancement of GAPDH mRNA levels was undetected during cell death. The present results demonstrate that GAPDH overexpression is not involved in the 5-HT-induced necrotic death pathway.     

Model of neuropathic intermittent claudication in the rat: methodology and application

In the present study we characterize a rat neurogenic intermittent claudication model which was accomplished by placing two pieces of silicone rubber of various sizes into the lumbar (L4 and L6) epidural space. After induction of spinal stenosis walking function was measured using a treadmill apparatus and sensory functions were tested by measuring thermal and tactile withdrawal threshold (von Frey filaments) for the period of 28 days after stenosis. In addition, local spinal cord blood flow (SCBF) was measured, periodically, before and after induction of stenosis using laser Doppler. After implantation of two pieces of silicone rubber (width 1.25 mm, height 1.0 mm, length 4.0 mm) a significant running dysfunction, as evidenced by shortening of running distance, was measured as soon as 24 h after stenosis (178.5+/-59.1 m vs 681.3+/-70.2 m). This effect persisted for 28 days after surgery. Similarly, a significant tactile (but not thermal) hypersensitivity was measured for a period of 28 days (1.2+/-0.3 g vs 14.9+/-0.2 g). In this experimental group the measurement of local SCBF revealed a significant (30-50%) reduction in the territory of spinal stenosis measured at 3,7,14 or 28 days after surgery. Implantation of larger pieces of silicon rubber (1.5 mm width) caused a significant increase in the incidence of urinary retention and mortality rate. These data show that chronic partial spinal compression at L4 and L6 spinal level lead to the development of significant motor/sensory dysfunction which resemble those seen in patients with neurogenic intermittent claudication. The lack of motor dysfunction under resting conditions but its appearance during forced exercise also suggest that the development of local spinal ischemia can represent one of the mechanisms.     

Helicobacter pylori infection influences nocturnal gastric acid breakthrough

BACKGROUND: Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions. AIM: To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough. METHODS: Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody. RESULT: Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection. CONCLUSION: The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.