Endosonography during endoscopic mucosal resection to enhance its safety

BACKGROUND: We have performed endoscopic mucosal resection of the esophagus (172 cases), stomach (102 cases), and colon (28 cases) using a transparent plastic cap. Because the lesion-bearing mucosa is suctioned up inside the cap under endoscopic suction, the mucosa should be dissected sufficiently from the proper muscle layer to prevent perforation. METHODS: To avert the risk of perforation, we introduced endosonographic assessment of submucosal dissection (47 cases). In all cases, just keeping the ultrasonic probe on the surface of the mucosa allowed us to evaluate whether the mucosal lesion was lifted up sufficiently from the proper muscle layer after local saline injection. RESULTS: It was possible to confirm that the muscle layer was kept outside the strangulating snare by the same procedure (32 of 37 cases, 86.5%). CONCLUSIONS: We experienced five muscular resections in cases without the ultrasonic probe and no muscular resection with the ultrasonic probe. Thus we recommend endosonographic assessment during endoscopic mucosal resection to enhance its safety.     

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: Report of a case

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.     

The role of perceived job stress in the relationship between smoking and the development of peptic ulcers

Although smoking has been considered a risk factor in causing pepticulcers, no study has examined the effects of job stress on the relationship between peptic ulcers and smoking. To establish a link between gastric or duodenal ulcers over two years and a state of perceived job stress, a questionnaire, including questions on demographics, smoking, history of peptic ulcer and perceived job stress was conducted. Follow-up surveys were carried out every six months to accumulate the data for this analysis and the time span of this follow up study was two years. To examine the role of perceived job stress on the relationship between smoking and peptic ulcers, stratified analyses were performed. Some specific causes of perceived job stress such as "Too much competition," "Schedule is too tight or pressed to work too hard" had high estimated relative risks: 2.13 with 95% confidence interval (CI) of 1.09-4.16 and 2.50 with 95% CI of 0.98-6.40, respectively. Stratified analyses suggested an effect-measure modification of perceived job stress in the relationship between peptic ulcers and smoking. Multiplicative and additive models suggest positive interaction between perceived job stress and smoking. These results suggest that specific perceived job stress is an effect modifier in the relationship between the history of the peptic ulcer and smoking.     

In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system.

1. The aim of the present study is to characterize the role of the P2X receptor in spinal nociceptive processing in vivo. We investigated the mechanisms of the P2X receptor agonist alpha,beta-methylene ATP (alpha,betameATP)-induced modulation of acute nociceptive signalling in mouse spinal cord. 2. Intrathecal administration of alpha,betameATP produced a significant and dose-dependent thermal hyperalgesic response. This response was completely blocked by intrathecal pretreatment with the non-selective P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and the selective P2X1, P2X3 and P2X2-3 receptor antagonist, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). Pretreatment with alpha,betameATP 15, 30 and 60 min prior to administration of a second dose of alpha,betameATP diminished the alpha,betameATP-induced thermal hyperalgesia. 3. A potent agonist for the P2X1 receptor, beta,gamma-methylene-L-ATP, did not show the hyperalgesic response, indicating that the P2X1 receptor is not involved in the spinal nociceptive pathway. 4. In fura-2 experiments using mouse dorsal root ganglion (DRG) neurons, alpha,betameATP (100 microM) increased intracellular Ca2+ ([Ca2+]i). This was not produced by a second application of alpha,betameATP. The same DRG neurons also showed a marked [Ca2+]i increase in response to capsaicin (3 microM). 5. Intrathecal pretreatment with the Ca2+-dependent exocytosis inhibitor, botulinum neurotoxin B, abolished the thermal hyperalgesia by alpha,betameATP. Furthermore, thermal hyperalgesia was significantly inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-5-phosphonopentanoate (APV), dizocilpine and ifenprodil. 6. These findings suggest that alpha,betameATP-induced thermal hyperalgesia may be mediated by the spinal P2X3 receptor subtype that causes unresponsiveness by repetitive agonist applications, and that alpha,betameATP (perhaps through P2X3 receptors) may evoke spinal glutamate release which, in turn, leads to the generation of thermal hyperalgesia via activation of NMDA receptors.     

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO₄ caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO₄ for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression. Received: 29 January 1999 / Accepted: 19 April 1999 / Published online: 22 June 1999     

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.     

Physical dependence liability test of ifenprodil in rats (author's transl)

A single administration of ifenprodil at the doses of 100, 200 and 400 mg/kg (p.o.), and 50 and 100 mg/kg (i.m.) produced a moderate CNS depression in rats, such as, sedation, ptosis, systemic muscle relaxation and decrease in motor activity. These symptoms appeared dose-dependently and persisted for about 4 hours following administration. In a direct physical dependence test, 5 groups of rats were fed the ifenprodil-admixed food together with drinking water ad libitum for 24 hours daily for 53 approximately 103 days (mean ifenprodil intake, 43--240 mg/kg/day), on the gradedly increased dosage schedule with a dosage level of 0.5 vs. 1 mg/g food to 4 mg/g food. In the natural withdrawal following administration, no significant withdrawal signs were observed in any group. In a substitution test either for phenobarbital or morphine, no suppression of withdrawal signs during the period of cross-administration of ifenprodil and no maintenance of dependence were observed. In a physical dependence-producing test, the rats fed ifenprodil never manifested withdrawal signs such as diarrhea, "wet shakes", sudden loss of body weight as in the levallorphan precipitation test. Ifenprodil apparently has no physical dependence liability.     

High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy.

Using the polymerase chain reaction and single-strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common "epithelial" ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G-->A and G-->C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow-cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P < 0.01 and P < 0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common "epithelial" type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy.