Convergence of Genetic, Nutritional and Inflammatory Factors in Gastrointestinal Cancers

Gastrointestinal cancers account for 20% of all cancer incidences worldwide. Colorectal cancer is the second most common cause of all cancer-related mortality and is increasing in Western societies. Infection and inflammation contribute to 15–20% of all malignancies, and are predisposing risk factors for gastrointestinal cancers. Helicobacter pylori infection is commonly associated with gastric cancers, and chronic inflammation increases the risk of colorectal cancer by 1% per year. Micronutrient status and common genetic variations in human populations modify risk for gastrointestinal cancer. Chronic inflammation promotes carcinogenesis by inducing gene mutations, inhibiting apoptosis, and stimulating an-giogenesis and cell proliferation. Inflammation also induces epigenetic alterations that are associated with cancer development. Two key genes in the inflammatory process, cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-kB), provide a mechanistic link between inflammation and cancer and are targets for chemoprevention. Dietary components, and human genetic variation that affects nutrient utilization, can directly modify inflammatory processes and/or suppress genomic alterations that are the molecular antecedents of cancers. The present report focuses on the convergence of genetic, nutritional, and inflammatory factors in the initiation and progression of gastrointestinal cancers, and the emerging dietary strategies for cancer prevention.     

Central tumour necrosis factor-α mediates the early gastrointestinal motor disturbances induced by lipopolysaccharide in sheep

Cytokines are involved in fever and other symptoms of the acute phase response induced by endotoxins. The aim of this work was to study the involvement of central tumour necrosis factor-alpha (TNF-alpha) in the changes induced by lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body temperature and myoelectric activity of the antrum, duodenum and jejunum was recorded continuously. Intravenous (i.v.) administration of LPS (0.1 micro g kg-1)-induced hyperthermia, decreased gastrointestinal myoelectric activity and increased the frequency of the migrating motor complex (MMC). These effects started 40-50 min after LPS and lasted for 6-7 h. TNF-alpha (50 and 100 ng kg-1) mimicked these effects when injected intracerebroventricularly (i.c.v.) but not i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 micro g kg-1, i.c.v.) abolished the TNF-induced actions and reduced those evoked by LPS. Furthermore, the effects induced by either LPS or TNF were suppressed by prior i.c.v. injection of indomethacin (100 micro g kg-1). In contrast, the i.v. injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS disturbs GI motility in sheep through a central pathway that involves TNF-alpha and prostaglandins sequentially.     

Prostate Development in Prune Belly Syndrome (PBS) and Posterior Urethral Valves (PUV): Etiology of PBS-Lower Urinary Tract Obstruction or Primary Mesenchymal Defect?

Prune belly syndrome (PBS) has been recognized since 1950 as the triad of absent abdominal wall musculature, undescended testes, and urinary tract anomalies. The etiology, however, remains uncertain. Theories of mesenchymal maldevelopment, obstruction, and genetic origin have been proposed. To evaluate the role of lower urinary tract obstruction as it relates to prostatic development and PBS, we studied the lower urinary tract of 15 cases of PBS, 8 cases of posterior urethral values (PUV), and 34 age-matched controls. It is generally accepted that prostatic growth and development are dependent on mesenchymal-epithelial interactions. We evaluated the mesenchymal and epithelial differentiation and relationships, and found distinctly different and consistent abnormalities between PBS and PUV as compared with one another and controls. The findings suggest that in PBS, prostatic growth and development are hindered because of destruction or absence of the appropriate primitive mesenchyme. Our studies could not definitely exclude very early obstruction as a cause of the findings because of lack of appropriate fetal material.     

Perioperative respiratory events in smokers and nonsmokers undergoing general anaesthesia

Background: The prevalence of respiratory diseases in smokers and nonsmokers and the incidence of perioperative respiratory events (PREs) were investigated for patients undergoing general anaesthesia. The aim was to quantify well-known problems and to identify possible new associations between smoking and PREs.
Methods: From July 1992 to December 1994, risk factors, demographic data, and PREs were documented by an automatically readable anaesthetic record (ARAR). PREs were used as defined by the German Society of Anaesthesiology and Intensive Care.
Results: Of 26 961 subsequent anaesthesias in adults, 7122 (26.4%) were performed in smokers with a prevalence of chronic bronchitis of 23.3% (4.8% in nonsmokers). 1573 PREs occurred in 1397 (5.2%) of all anaesthetics. 459 events concerned intubation problems and problems in technical airway management. 1114 specific respiratory events (SPREs) like re-intubation, laryngospasm, bronchospasm, aspiration, hy-poventilation/hypoxaemia and others had a total incidence of 5.5% in smokers and 3.1% in nonsmokers. The relative risk (RR) of SPREs was 1.8 in all smokers, 2.3 in young (16–39 years) smokers, and 6.3 in obese young smokers. The RR of perioperative bronchospasm was 25.7 in young smokers with chronic bronchitis.
Conclusion: The impact of smoking on perioperative respiratory problems should make anaesthetists take this widespread preoperative condition seriously, particularly in young adults. The presented method of incident reporting (based on a national classification) could contribute to future research in anaesthetic epidemiology.     

Splanchnic ischaemia and its role in multiple organ failure

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor α, and other biologic mediators by endotoxin–stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure.
Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identifed and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.     

大鼠孤束核含酪氨酸羟化酶、神经降压素和胆囊收缩素样神经元向伏核的投射—HRP和免疫细胞化学双重标记法的研究

本文应用HRP顺、逆行追踪法结合免疫细胞化学双重标记法,对大鼠孤束核向伏核的投射进行了研究。主要结果如下:1.WGA-HRP注入孤束核尾侧段,在伏核后部的腹、内侧区,出现较密集的标记纤维、终末和标记细胞;将HRP注入伏核后部的腹、内侧区,在孤束核尾侧段(主要在连合核和内侧亚核)出现大量的顺、逆行标记,以同侧为主。2.HRP注射到伏核并结合免疫细胞化学反应,在孤束核尾侧段发现HRP-TH,HRP-NT、HRP-CCK双重标记细胞。HRP-TH的数目最多,其次是HRP-NT双标细胞,HRP-CCK双标细胞最少。     

The impact of lower urinary tract symptoms on general health status and on the use of prostatectomy

Our objective was to determine the extent to which lower urinary tract symptoms affect the general health status of men and contribute to the decision to undergo surgery. A cross-sectional population survey using postal questionnaires was conducted in the North West Thames health region, followed by a prospective cohort study of men undergoing prostatectomy (North West Thames and Oxford regions). The subjects in the first survey were 221 men aged 55 and over with previously reported mild, moderate or severe urinary symptoms; subjects in the second study were 388 men undergoing prostatectomy. Main outcome measures were selfreported symptom severity, bothersomeness and general health status (Nottingham Health Profilie, Part 1). The response rate among eligible responders in the population survey was 85.7%. Increasing symptom severity was associated with worsening NHP scores for energy, emotional reactions, sleep and physical mobility (p<0.01). Increasing bother-someness of symptoms was associated with emotional reactions, sleep and pain (p<0.05). Men undergoing surgery reported worse health status than men in the population with the same severity of symptoms as regards emotional reactions, energy and pain. For a given level of symptom severity, the impact of those symptoms on aspects of a man's general health status may be the determinant of seeking and undergoing surgery. Greater understanding of the factors that affect a man's response to his symptoms is needed in interpreting the decision to seek and accept treatment.     

A comparison of the effects of omeprazole and ranitidine on gastric secretion in women undergoing elective Caesarean section

This study compares the efficacy of omeprazole and ranitidine at reducing gastric secretion in obstetric patients. Sixty-five women scheduled to undergo elective Caesarean section under general anaesthesia were randomly allocated to receive either omeprazole 40 mg or ranitidine 150 mg orally at 2200 hours the night before and at 0600 hours on the morning of surgery. Intragastric pH and volume were measured immediately after induction of anaesthesia and on completion of surgery. All patients had gastric aspirates less than 25 ml. None of the omeprazole group had an aspirate of pH less than 3.5. Six patients (19%) in the ranitidine group had aspirates of pH less than 3.5, a significant difference from the omeprazole group (p less than 0.05). Of these six, two (6%) had aspirates of pH less than 2.5. Hence this study showed that omeprazole was more effective and consistent than ranitidine at maintaining gastric pH greater than 3.5.     

Retrograde endoscopic laser therapy for transitional cell carcinoma of the upper urinary tract

AIM: The aim of the present study was to investigate the safety and efficacy of endoscopic laser therapy for transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: Tumors of the renal pelvis and ureteropelvic junction were detected by ureteroscopy. The tumors were subjected to biopsy, and after TCC was diagnosed, endoscopic laser therapy (Neodymium-YAG and Holmium-YAG) was conducted using a 6.9 Fr. flexible ureterorenoscope. RESULTS: From January 1997 to April 2002, six patients underwent ureteroscopic treatment. Tumor grade was 1 in four patients and 2 in two patients. Average tumor size was 1.45 cm. Endoscopic treatment was chosen for two patients because of the high medical risk associated with open surgery. Another patient underwent diagnostic ureteroscopy, followed immediately by endoscopic treatment. A further three patients elected to undergo ureteroscopic treatment. One patient with large (3 cm), multifocal and incompletely treated tumors died of metastatic disease 22 months after the initial operation. One patient requested nephroureterectomy one month after endoscopic treatment, and pathological examination of the resected specimen revealed no tumor. The other four patients have been followed up for a mean period of 14 months after initial treatment. Recurrence occurred in one patient, and was successfully treated by repeat endoscopic resection. None of the patients required blood transfusion or emergency open surgery. CONCLUSION: Ureteroscopic treatment of small, localized, low-grade TCC of the upper urinary tract is now a safe and feasible alternative to nephroureterectomy in selected patients.