Tandon Rk

Stress and the gastrointestinal tract.

Abstract  Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short‐ and long‐term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain–gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus–pituitary–adrenal axis and pain modulatory systems. Severe or long‐term stress can induce long‐term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4+ lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.

The Probiotic Preparation, VSL#3 Induces Remission in Patients With Mild-to-Moderately Active Ulcerative Colitis

BACKGROUND & AIMS Probiotics can maintain ulcerative colitis (UC) in remission effectively, but little is known of their ability to induce remission. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of a high-potency probiotic, VSL#3, for the treatment of mild-to-moderately active UC. METHODS Adult patients with mild-to-moderate UC were assigned randomly to groups that were given 3.6 x 10(12) CFU VSL#3 (n = 77) or placebo (n = 70), twice daily for 12 weeks. The primary end point was a 50% decrease in the Ulcerative Colitis Disease Activity Index (UCDAI) at 6 weeks. The secondary end points included remission by 12 weeks and reduction in total individual UCDAI parameters from baseline at 12 weeks. Intention-to-treat analysis was performed. RESULTS At week 6, the percentage of patients with an improvement in UCDAI score that was greater than 50% was significantly higher in the group given VSL#3 (25; 32.5%) than the group given placebo (7; 10%) (P = .001). At week 12, there were 33 patients given VSL#3 (42.9%) who achieved remission, compared with 11 patients given placebo (15.7%) (P < .001). Furthermore, significantly more patients given VSL#3 (40; 51.9%) achieved a decrease in their UCDAI that was greater than 3 points, compared with those given placebo (13; 18.6%) (P < .001). The VSL#3 group had significantly greater decreases in UCDAI scores and individual symptoms at weeks 6 and 12, compared with the placebo group. CONCLUSIONS VSL#3 is safe and effective in achieving clinical responses and remissions in patients with mild-to-moderately active UC.

An epidemic of veno-occlusive disease of liver in central India.

An outbreak of veno-occlusive disease which was probably caused by consumption of cereals mixed with seeds of a plant (Crotalaria sp.) containing pyrrolizidine alkaloids occurred in the Sarguja district of India in November-December 1975. 42% of the 67 recorded cases died.

A randomized controlled trial of antioxidant supplementation for pain relief in patients with chronic pancreatitis.

BACKGROUND & AIMS Oxidative stress has been implicated in the pathophysiology of chronic pancreatitis (CP). We evaluated the effects of antioxidant supplementation on pain relief, oxidative stress, and antioxidant status in patients with CP. METHODS In a placebo-controlled double blind trial, consecutive patients with CP were randomized to groups that were given placebo or antioxidants for 6 months. The primary outcome measure was pain relief, and secondary outcome measures were analgesic requirements, hospitalization, and markers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant status (ferric-reducing ability of plasma [FRAP]). RESULTS Patients (age 30.5+/-10.5 years, 86 male, 35 alcoholic, and 92 with idiopathic CP) were assigned to the placebo (n=56) or antioxidant groups (n=71). After 6 months, the reduction in the number of painful days per month was significantly higher in the antioxidant group compared with the placebo group (7.4+/-6.8 vs 3.2+/-4, respectively; P< .001; 95% CI, 2.07, 6.23). The reduction in the number of analgesic tablets per month was also higher in the antioxidant group (10.5+/-11.8 vs 4.4+/-5.8 respectively; P= .001; 95% CI, 2.65, 9.65). Furthermore, 32% and 13% of patients became pain free in the antioxidant and placebo groups, respectively (P= .009). The reduction in the level of TBARS and increase in FRAP were significantly higher in the antioxidant group compared with the placebo group (TBARS: placebo 1.2+/-2.7 vs antioxidant 3.5+/-3.4 nmol/mL; P= .001; 95% CI 0.96, 3.55; FRAP: placebo -5.6+/-154.9 vs antioxidant 97.8+/-134.9 microMFe(+2) liberated, P= .001, 95% CI 44.98, 161.7). CONCLUSIONS Antioxidant supplementation was effective in relieving pain and reducing levels of oxidative stress in patients with CP.

Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder

OBJECTIVE:The aim of this study was to identify risk factors for carcinoma of the gallbladder (CaGB) among patients with gallstones (GS) with special reference to role of chronic Salmonella typhi carrier state.METHODS:A prospective case-control study was conducted in a tertiary care center in India. Cases were defined as consecutive patients with CaGB and GS, whereas controls were patients with GS alone. All were assessed clinically and their demographic data, diet, and smoking history recorded. Patients were detected to be typhoid carriers on the basis of Vi serology by enzyme linked immunosorbent assay. Cases (n = 37) and controls (n = 80) were compared by univariate and logistic regression analysis.RESULTS:The mean age of the cases and the controls were 53.4 ± 11 yr and 43.5 ± 14 yr, respectively. Among the cases, six (16%) patients were detected to be typhoid carriers, in contrast to two (2.5%) among controls (p = 0.01). Compared to controls, cases were more often older (p = 0.0002), of a lower socioeconomic status (p = 0.0005), and smokers (p = 0.0002). Stepwise logistic regression analysis identified typhoid carrier state (OR = 14; CI 2–92), age ≥47 yr (OR = 5; CI 2–14) and smoking (OR = 11; CI 2–71) as the three independent risk factors for development of CaGB among patients with GS.CONCLUSION:Chronic typhoid carrier state was the most important risk factor among patients with CaGB and gallstones.

Association of extent and infection of pancreatic necrosis with organ failure and death in acute necrotizing pancreatitis

BACKGROUND & AIMS Organ failure is the usual cause of death in acute necrotizing pancreatitis. Our objective was to study whether the extent and infection of pancreatic necrosis correlate with organ failure and mortality. METHODS All consecutive patients with acute pancreatitis were prospectively studied. They underwent a detailed clinical and investigative evaluation. Pancreatic necrosis, diagnosed on a computed tomography scan, was graded as <30%, 30%-50%, and >50% necrosis and characterized as either sterile or infected. Logistic regression analysis was done to find out the association of the extent and infection of pancreatic necrosis with organ failure and mortality. RESULTS Of 276 patients (mean age, 41.25 years; 172 men), 104 had pancreatic necrosis: 30 had <30% necrosis, 37 had 30%-50% necrosis, and 37 had >50% necrosis; 74 had sterile necrosis, and 30 had infected necrosis. Of them, 37 (35%) patients developed organ failure. Two significant factors were associated with the development of organ failure, the extent of necrosis (<30% necrosis vs 30%-50% necrosis: P = .03; odds ratio [OR], 5.82; 95% confidence interval [CI], 1.15-29.45; <30% necrosis vs >50% necrosis: P = .0004; OR, 18.86; 95% CI, 3.75-94.92) and infected pancreatic necrosis (P = .02; OR, 3.29; 95% CI, 1.17-9.24). The overall mortality was 22%. Infected pancreatic necrosis (P = .006; OR, 4.99; 95% CI, 1.56-16.02) and Acute Physiology, Age, and Chronic Healthy Evaluation II score (P = .004; OR, 1.28; 95% CI, 1.08-1.52) were 2 independent predictors of mortality. CONCLUSIONS Extent of necrosis and infected pancreatic necrosis were associated with the development of organ failure in patients with acute necrotizing pancreatitis. Infected pancreatic necrosis was the most significant predictor of mortality.

Inflammatory bowel disease in the Asia-Pacific area: a comparison with developed countries and regional differences.

The Asia–Pacific region has been marked as an area with a low incidence of inflammatory bowel disease (IBD), although confusion always existed as to whether this low incidence was a result of low diagnostic awareness, a high incidence of infective diarrhoea and its diagnostic overlap or a true low incidence. As epidemiological studies from this region are being made available it is clear that the incidence and prevalence rates of IBD in Asia–Pacific region are low compared with Europe and North America. They are however, increasing rapidly. There are substantial variations in the incidence and prevalence rates of IBD in various ethnic groups in Asia. The highest incidence rates are recorded from India, Japan and the Middle East and there exists a genetic predisposition of South Asians (Indians, Pakistanis and Bangladeshis) to ulcerative colitis (UC). It appears that certain racial groups are more prone than others to develop IBD. For instance, Indians in South‐East Asia have higher rates than Chinese and Malays. While there is a host genetic predisposition, environmental factor(s) may be responsible for this difference. The clinical phenotypes and complication rates of Asian IBD resemble those of the Caucasian population in general, but some heterogeneity is observed in different regions of Asia. There is no evidence of a north‐south or an east‐west divide in the Asia–Pacific region. The available studies suggest an increasing incidence of UC in the Asia–Pacific region and hence it is an appropriate time to launch well‐designed epidemiological studies so that etiopathogenetic factors can be identified. There is a male predominance in Crohns disease in the Asian population. The NOD2/CARD15 gene is not associated with CD in the Japanese, Korean, Chinese and Indian population.

Survey on chronic pancreatitis in the Asia–Pacific region

Background and Aims:  A survey was conducted of chronic pancreatitis (CP) in different countries in the Asia–Pacific region. The main objective of the survey was to generate a database containing information regarding the prevalence, etiology, clinical presentation, diagnostic work‐up, and management of CP in the Asia–Pacific region.

Predictors of unsuccessful mechanical lithotripsy and endoscopic clearance of large bile duct stones.

BACKGROUND Mechanical lithotripsy is used to break large bile duct stones. This study investigated the predictors of unsuccessful mechanical lithotripsy. METHODS Consecutive patients with bile duct stones underwent endoscopic retrograde cholangiography, sphincterotomy, and basket removal of stones. Mechanical lithotripsy was performed for stones of large size (>15 mm diameter) that precluded extraction intact. Success was defined as complete clearance of the duct. Various predictive factors, including size and number of stones, stone impaction, serum bilirubin, presence of cholangitis, and bile duct diameter were analyzed in relation to the success or failure of lithotripsy. RESULTS A total of 669 patients underwent endoscopic retrograde cholangiography for suspected choledocholithiasis, which was found in 401 patients. Of the latter patients, 87 had large stones that required mechanical lithotripsy. Lithotripsy was successful in 69 (79%) patients. Impaction of the stone(s) in the bile duct was the only significant factor that predicted failure of lithotripsy and consequent failure of bile duct clearance. Other factors, including stone size, were not significant. CONCLUSIONS Mechanical lithotripsy is successful in about 79% of patients with large bile duct stones. The only significant factor that predicts failure of mechanical lithotripsy is stone impaction in the bile duct.

Management consensus of inflammatory bowel disease for the Asia-Pacific region.

At the present there are no large‐scale epidemiologic data on inflammatory bowel disease (IBD) in the Asia–Pacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohns disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the Asia–Pacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non‐IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some special problems in the Asia–Pacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination of Western guidelines and regional experiences, similar principles can be used for induction and maintenance of remission. A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the Asia–Pacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region.