Mast cell degranulation breaks peripheral tolerance.

Mast cells (MC) have been shown to mediate regulatory T-cell (T(reg))-dependent, peripheral allograft tolerance in both skin and cardiac transplants. Furthermore, T(reg) have been implicated in mitigating IgE-mediated MC degranulation, establishing a dynamic, reciprocal relationship between MC and T(reg) in controlling inflammation. In an allograft tolerance model, it is now shown that intragraft or systemic MC degranulation results in the transient loss of T(reg) suppressor activities with the acute, T-cell dependent rejection of established, tolerant allografts. Upon degranulation, MC mediators can be found in the skin, T(reg) rapidly leave the graft, MC accumulate in the regional lymph node and the T(reg) are impaired in the expression of suppressor molecules. Such a dramatic reversal of T(reg) function and tissue distribution by MC degranulation underscores how allergy may causes the transient breakdown of peripheral tolerance and episodes of acute T-cell inflammation.

Review article: bloating in functional bowel disorders.

Bloating is a frequently reported symptom in functional bowel disorders. It usually occurs in combination with other symptoms, but may also occur in isolation. The severity of bloating tends to worsen during the course of the day and improves overnight. Although frequently considered to be a subjective phenomenon, recent studies have shown that bloating is associated with a measurable increase in abdominal girth. The pathophysiology of bloating remains elusive, but the evidence supports a sensorimotor dysfunction of the bowel. The possible mechanisms include abnormal gas trapping, fluid retention, food intolerance and altered gut microbial flora. Further studies are needed to define the sensorimotor abnormalities associated with bloating, which might be segmental and transient rather than generalized and persistent. The lack of understanding of this symptom is paralleled by a limited availability of therapeutic options. Conventional medications used in functional bowel disorders are not helpful and may indeed worsen the symptoms. In future, new drugs with activity against serotonin and kappa receptors, or novel approaches such as the use of exclusion diets, probiotics and hypnotherapy, may prove to be useful.

Food hypersensitivity and irritable bowel syndrome.

Irritable bowel syndrome is a common condition but its pathophysiology remains poorly understood. Many irritable bowel syndrome patients give a history of food intolerance, but data from dietary elimination and re-challenge studies are inconclusive. Multiple aetio-pathological mechanisms have been postulated. The gut has an extensive immune system but current understanding of processing of food antigens in health and disease is limited. There is no clinically useful marker available to test for food hypersensitivity in irritable bowel syndrome. Researchers have employed both skin tests and serum immunoglobulins (IgG and IgE) as markers of food hypersensitivity in various disorders including irritable bowel syndrome, but published data are equivocal. In this article, the evidence for the role of food hypersensitivity in irritable bowel syndrome is reviewed and, based on the available data, a possible pathophysiological hypothesis has been formulated.

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147-325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61-140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64-206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.

Diverticular disease of the colon: ethnic differences in frequency.

BACKGROUND: Colonic diverticular disease is more common in Western populations than in developing countries. AIM: To determine whether the frequency of colonic diverticular disease is different in British patients of Indian-subcontinent Asian origin compared with other ethnic groups. METHODS: All colonoscopies performed over a 3-year period in a London hospital were studied. Patients of Indian-subcontinent Asian origin were identified by name. RESULTS: Five of 134 Indian-subcontinent Asian males (4%) had colonic diverticular disease, compared with 278 of 1268 patients of other ethnic groups (22%; P < 0.001). Five of 91 Indian-subcontinent Asian females (6%) had colonic diverticular disease, compared with 333 of 1486 patients of other ethnic groups (23%; P < 0.001). Although patients of Indian-subcontinent Asian origin (54.8 +/- 15.8 years) were younger than those of other ethnic groups (60.3 +/- 17.8 years; P < 0.0001), the ethnic difference in the frequency of diverticular disease persisted even when age was taken into account. CONCLUSION: There is a lower frequency of colonic diverticular disease in Indian-subcontinent Asians presenting for colonoscopy, compared with other ethnic groups. This cannot be explained by sex or age differences. Our findings require confirmation, but may provide opportunities for research into the aetiology of colonic diverticular disease.

Brain calcium in the rabbit: site of action for the alteration of body temperature.

Body temperature was recorded in the unanesthetized rabbit during push-pull perfusion of regions of the hypothalamus. Both the anterior and posterior hypothalamus were perfused with physiological solutions containing Ca++ in a concentration 2.0 or 5.0 times that of extracellular fluid. The animals were placed in an ambient temperature of 4.0 +/- 2.0degrees C for at least 1 hr before the perfusion and all experiments were carried out at this temperature. In the posterior hypothalamic area Ca++ produced a sharp fall in body temperature but did not cause body temperature to alter when it was perfused through the anterior hypothalamic area. These results indicate that the rabbit is similar to the cat and monkey since the effect of Ca++ on body temperature is localized to the posterior hypothalamic region.

Purification and Characterization of a Cation-stimulated Adenosine Triphosphatase from Corn Roots.

A membrane-bound, monovalent cation-stimulated ATPase from Zea mays roots has been purified to a single band on sodium dodecyl sulfate gel electrophoresis. Microsomal preparations with K(+) -stimulated ATPase activity were extracted with 1 m NaClO(4), and the solubilized enzyme was purified by chromatography on columns of n-hexyl-Sepharose, DEAE-cellulose, and Sephadex G-100 Superfine. A 500-fold purification over the activity present in the microsomes was obtained. The K(+) -stimulated activity shows positive cooperativity with increasing KCl concentrations. The purified enzyme shows K(+) -stimulated activity with ATP, GTP, UTP, CTP, ADP, alpha + beta-glycerophosphate, p-nitrophenyl phosphate, and pyrophosphate as substrates. Under most conditions ATP is the best substrate. Although dicyclohexyl carbodiimide and Ca(2+) inhibit and alkylguanidines stimulate the K(+) -ATPase while bound to microsomes, they have no effect on the purified enzyme.

Cost-benefit analysis of transesophageal echocardiography in cardiac surgery.

This article evaluates the costs and outcomes associated with TEE during and after cardiac surgery. The costs include the direct and indirect costs--the complications of TEE. The outcomes include the positive consequences or the benefits: money and lives saved. The article uses liberal (high) estimates of the direct and indirect costs of TEE and conservative (low) estimates of the benefits. The exact cost or benefit depends on the number of cases performed. The analysis shows that patients having surgery for congenital heart disease derive the greatest overall benefit: around $600 per case studied. Patients having valvular repair surgery derive the next greatest benefit: around $450 per case studied. In contrast patients having valve replacement have an overall cost of around $150 per case studied. Patients having surgery for coronary artery disease also derive an overall benefit: around $100-$300 per case studied, depending upon assumptions regarding TEE's role in prevention of intraoperative strokes. This analysis indicates that the financial benefits of TEE are substantial and frequently outweigh costs in patients requiring cardiac surgery.

Family of origin and current relationship influences on codependency.

This study investigated codependency in Caucasian individuals within the framework of Bowen's Family Systems Theory. The sample consisted of a group of couples, in which one member of the couple was a recovering alcoholic in an aftercare program, and a group of matched, comparison couples. Participants completed a demographic questionnaire, the Friel Codependency Assessment Inventory, and the Personal Authority in the Family System (PAFS) Questionnaire. The findings confirmed that codependency levels were higher in clinical than in comparison couples. Moreover, within the clinical group, there was little difference between alcoholics and their spouses with respect to dysfunction in their families of origin, current families, or their codependency levels. The findings further suggested that the etiology and function of codependency are different in clinical and nonclinical families. In the clinical sample, the family of origin and current relationship characteristics were related to codependency in patterns consistent with previous theory and research. For the nonclinical sample, however, the findings contradicted conventional codependency theory. The findings suggest that, in contrast to clinical populations, codependency in nonclinical populations has some links with favorable characteristics of family functioning.

Glutaraldehyde cross-linked collagen in the treatment of faecal incontinence.

BACKGROUND: The treatment of faecal incontinence secondary to internal anal sphincter dysfunction is unsatisfactory. The aim of the study was to evaluate the efficacy of anal glutaraldehyde cross-linked (GAX) collagen injections in patients with a surgically incorrectable disorder. METHODS: Seventeen patients were studied: nine had idiopathic faecal incontinence, three had incontinence following haemorrhoidectomy, two following internal sphincterotomy, two following an internal sphincter defect from obstetric injury and one following treatment for fistula in ano. All patients were refractory to conservative treatment and were unsuitable for surgical repair. All had anorectal physiology and endoanal ultrasonography before and after GAX collagen injections. RESULTS: All patients tolerated the injection without side-effects. All patients had an intact external anal sphincter. Following injection, 11 patients showed marked symptomatic improvement. One patient reported symptomatic improvement but remained in clinical grade 3, and two reported minimal improvement. There was no improvement in three patients, but one of these had a repeat injection and showed significant improvement subsequently. CONCLUSION: Injection of GAX collagen in the anal canal is a simple and well tolerated method of treating faecal incontinence due to internal sphincter dysfunction. Early results suggest it provides an easy and reliable alternative to the currently available methods that are often unsuccessful and at best unpredictable.

Assessment by prolonged ambulatory manometry of the effect of oral cisapride on proximal small bowel inter-digestive motility.

The effects of cisapride, given orally at standard therapeutic dosage (10 mg tds), on proximal small bowel interdigestive motility in ten healthy volunteers was assessed by prolonged ambulatory manometry. Cisapride did not alter the duration of the MMC cycle, duration of phase II or the propagation rate of phase III in either the daytime or nighttime periods. However, when compared to studies, in which subjects received no drug, both nighttime and daytime phase II mean contractile amplitude, but not contractile incidence, were significantly increased (P < or = 0.001) by cisapride. Cisapride significantly increased the incidence of distally propagated clustered activity. We conclude that the major effects of cisapride on healthy small bowel motor function is to increase the mean contractile amplitude and incidence of distally propagated clustered activity.

Characterization of distal colonic motility in early postoperative period and effect of colonic anastomosis.

Under standardized conditions, the manometric motility of the distal colon following rectosigmoid anastomosis (N = 11, median age 70 years, range 47-80), was compared to that following laparotomies not involving colonic anastomosis (N = 9, 56 years, 32-65). Microtransducer probes were inserted peroperatively and colonic activity recorded continuously (median 96 hr, range 48-109 anastomotic and 75 hr, range 46-107 control group) employing an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program. Total postoperative analgesic doses and duration of surgery were similar in both groups. The first return in the anastomotic group of isolated waveforms [median 1.8 hr, interquartile range (IQR) 1-3] and propagated waves (92 hr, 79-100), was comparable to the control group (4 hr, 1.8-7, and 73 hr, 72-101, respectively). Motor complexes, characterized by bursts of regular contractile activity at 3-5 cpm, returned faster in the control group (3 hr, 2-24 vs 24 hr, 19-30, P < 0.05). Motility index was significantly depressed during the first 72 hr following surgery in the anastomotic group compared to controls (P < 0.001). Flatus was passed at a median of 72 hr (IQR 45-79) in the control and 94 hr (81-105) in the anastomotic group (P = 0.05). The presence of a left-sided colonic anastomosis has a major inhibitory effect on distal colonic motility, compared to nonanastomotic surgery of similar severity, in the early postoperative period.

Urban-rural hospital affiliations: assessing control, fit, and stakeholder issues strategically.

Urban-rural hospital affiliations are an outgrowth of both the external pressures on rural hospitals to survive and the need for urban hospitals to maintain or increase their share of the tertiary referral market. This article discusses the significant role of stakeholders in these affiliations, develops a fourfold typology of urban-rural hospital affiliations based on the notions of organizational control and fit, suggests four generic strategies for forming affiliations, and analyzes four actual cases of affiliation.

The structure of family perceptions among adolescents and their parents: individual satisfaction factors and family system factors.

This study examined the underlying structure of self-reports of family functioning by adolescents, mothers, and fathers (N of individuals = 360) from intact families. Participants completed a multidimensional self-report measure of family functioning, and their responses were entered into a factor analysis with the family as the unit of analysis (N of cases = 120). The results indicate two types of factors: individual satisfaction factors and family system factors. The findings are consistent with the view that different types of characteristics assessed in self-report measures of the family may be stored as different kinds of memories. The findings also provide preliminary data toward understanding the linkages between family system factors and satisfaction with the family based on family roles as adolescents, mothers, and fathers.

Long-acting steroid injection after endoscopic dilation of anastomotic Crohn's strictures may improve the outcome: a retrospective case series.

BACKGROUND AND STUDY AIMS: Endoscopic balloon dilation of Crohn's strictures is widely practised, but may not result in long-term symptomatic benefit, leading to the need for repeat dilation or surgery. It is hypothesized that long-acting steroid injection into strictures after dilation may decrease the need for further stricture dilation and improve the outcome in symptomatic patients. PATIENTS AND METHODS: Patients with Crohn's disease who have had balloon dilation and triamcinolone injection performed for symptomatic anastomotic strictures were identified from endoscopy records. Case notes were reviewed to determine outcomes. RESULTS: Fourteen patients underwent a total of 26 dilations, with triamcinolone injected (median dose 20 mg, 10-40 mg) in 20 of the procedures. Seven patients (50%) had sustained remission after a single dilation and steroid injection, with a median follow-up period of 16.4 months (range 13.2-22.0 months). Four patients (28.5%) required more than one dilation (median three dilations, range two to four) to control their symptoms, with a median follow-up period of 27.8 months (range 14-32.8 months). Endoscopic management failed in three patients (21.4 %), who were referred for surgery. There were no complications due to dilation or triamcinolone injection. CONCLUSIONS: Triamcinolone injection into the stricture after dilation is safe, easy to perform, and may be a useful adjunct in the management of anastomotic Crohn's strictures. These data will require further support through a randomized and controlled trial.

The computer as referee in the analysis of human small bowel motility.

The aim of this study was to determine whether visual analysis of graphic records of small bowel motility is a reliable method of discriminating pressure events caused by bowel wall contraction from those of extraenteric origin and to compare this method with computerized analysis. Each of six independent observers was supplied with the same pair of records of 1 h of fasting diurnal duodenojejunal motility, acquired with a 3-channel ambulant data-logging system; one record included many artifacts due to body movement while the other did not. The observers were asked to identify and classify pressure events and to measure the duration and amplitude of "true" contractions. A computer program for on-line analysis is described; the algorithm was designed to overcome the problems of a variable baseline and sudden changes in pressure due to body movements that are unavoidable in prolonged recording from the small bowel of ambulant subjects. For regular contractions (phase III of migrating motor complex) there was good agreement between observers but not for irregular contractions, particularly when movement artifacts were abundant. When the observers were asked to repeat the analysis 6 mo later, there was poor agreement with their original identification of irregular contractions and artifacts. There was, however, good agreement between the computer analysis, which was totally reproducible, and the median decisions of the observer group; this agreement supports the validity of our computer algorithm. We conclude that computer analysis is not merely a valuable ergonomic aid for analysis of large quantity of data acquired in prolonged ambulatory monitoring, but also that, even for brief recordings, it provides a standard of reproducibility unmatched by "expert" inspection. Visual analysis is unreliable and thus susceptible to subjective bias; this may, in part, account for conflicting reports of small bowel motility under similar conditions reported by different workers in our own and other laboratories.

Effect of cisapride on distal colonic motility in the early postoperative period following left colonic anastomosis.

PURPOSE: This study was designed to investigate the modulatory effect of cisapride on colonic motility in the postoperative period. METHODS: A prospective, double-blind, randomized, placebo-controlled trial of 14 patients undergoing left colonic anastomosis was carried out. Manometric probes were positioned with transducers on either side of the anastomosis, and colonic activity was recorded continuously for a median of 98 (range, 72-144) hours using an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program. RESULTS: Isolated waveform activity returned at a median of 1.8 (interquartile range, 1-3) hours and motor complex activity at 24 (interquartile range, 19-30) hours in the placebo group and at similar times in the cisapride group. All motility variables except mean amplitude increased significantly with time in both groups. In the cisapride group the motility index was significantly increased compared with the placebo group (P = 0.03), resulting from an increase in percentage duration of activity (P = 0.002). Activity index, mean amplitude of waveforms, and number of waves greater than 50 cm H2O did not differ between groups. In contrast to placebo, cisapride significantly increased the median number of waves greater than 13 cm H2O and percentage duration of activity distal to the anastomosis compared with proximally. The return of bowel sounds (median, 43, interquartile range, 24-48 hours vs. 67, 29-69 hours; P = 0.2) or first passage of flatus (78, 54-94 hours vs. 94, 81-105 hours; P = 0.1) did not differ between groups. CONCLUSIONS: Although cisapride may have a differential effect on the colon proximal and distal to an anastomosis and significantly increases some indices of motility in the early postoperative period, these are unlikely to be of any clinical relevance.

Normal patterns of human upper small bowel motor activity recorded by prolonged radiotelemetry.

In order to characterise human interdigestive cyclical motor activity, and its interruption by food, jejunal pressure changes in healthy volunteers were recorded continuously for 24 hours, using an ingested pressure-sensitive radiotelemetry capsule tethered at the duodenojejunal flexure. In 20 studies, the subjects fasted throughout; in another 20 studies they received a single standard meal. Using this technique, fasting motor complexes were easily detected. There was considerable variation in interdigestive cycle duration and in the interruption caused by food. The data were not normally distributed. The study indicates that any descriptions of 'atypical' jejunal motility patterns must take into account the wide variations seen in health, before they can be regarded as representing dysfunction or disease.

Diagnostic and therapeutic push type enteroscopy in clinical use.

This study describes small bowel push enteroscopy in routine clinical practice, using a purpose designed instrument (Olympus SIF-10). Fifty six patients had a total of 60 procedures over a two and a half year period. The median (range) depth of small intestine intubated was 45 (15-90) cm. Procedure time varied from 10-45 minutes. Most enteroscopies were performed during routine gastroscopy lists. The technique was comparatively easy for experienced endoscopists to learn. Forty two procedures were for diagnostic purposes. Eleven patients had gastrointestinal bleeding where the source was obscure, or where early investigations had suggested a small bowel source: a specific diagnosis was made in 45% of these cases. Of seven iron deficient anaemic patients using non-steroidal anti-inflammatory drugs (NSAIDs), only one had a lesion detected in the upper small bowel. Nine patients had abnormal small bowel barium studies. Small bowel abnormalities were seen in six cases and were definitively diagnostic in three of these; in three patients the barium study appearances were confirmed as artefact. Fifteen patients were investigated for abdominal symptoms suggesting small bowel obstruction or malabsorption: a diagnosis was made in five cases. Fifteen patients underwent enteroscopy for therapeutic purposes, including successful treatment of difficult enteral feeding problems by nasojejunal tubes or by cutaneous endoscopic jejunostomies, polypectomy for Peutz-Jeghers syndrome, and dilatation of strictures. Additionally, bleeding lesions detected in patients during investigation of anaemia were successfully treated at the time by YAG laser or bipolar diathermy. In conclusion, push enteroscopy is a practical and valuable clinical service, which should probably become available on a subregional basis.

Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride.

BACKGROUND/AIMS: Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy. METHODS: Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours. RESULTS: Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11). CONCLUSIONS: This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit.