Colonic and anorectal function in constipated patients with anorexia nervosa

OBJECTIVES: Many patients with eating disorders complain of severe constipation. Previous studies have suggested that constipation in patients with anorexia nervosa may be associated with slow colonic transit. However, it is unclear whether a refeeding program will alter colonic transit in these patients. The aim of this study was to investigate colorectal function by measuring colonic transit and anorectal function in anorexic patients with constipation during treatment with a refeeding program. METHODS: We prospectively studied 13 female patients with anorexia nervosa who were admitted to an inpatient treatment unit and compared them to 20 previously studied, age-matched, healthy female control subjects. Patients underwent colonic transit studies using a radiopaque marker technique and anorectal manometry measuring anal sphincter function, rectal sensation, expulsion dynamics, and rectal compliance. Patients were studied both early (< 3 wk) and late (> 3 wk) in their admission. We restudied two patients who had slow colonic transit. All patients also underwent structured interviews. RESULTS: Four of six patients studied within the first 3 wk of their admission had slow colonic transit, defined as > 70 h (108.0 +/- 17.0 h, mean +/- SEM), on initial evaluation. In contrast, none of the seven patients studied later than 3 wk into their admission had slow colonic transit. Two of the four patients with slow transit were restudied later in their admission and were found to have normal transit times. Rectal sensation, internal anal sphincter relaxation threshold, rectal compliance, sphincter pressures, and expulsion pattern were normal in all subjects. CONCLUSIONS: Despite complaints of severe constipation, colonic transit is normal or returns to normal in the majority of patients with anorexia nervosa once they are consuming a balanced weight gain or weight maintenance diet for at least 3 wk.     

Pilot study of pathophysiology of constipation among community diabetics

We aimed to compare gastrointestinal transit and defecatory function in a random sample of people with or without diabetes mellitus in a US community who reported constipation or laxative use. In this pilot study we measured: gastric, small bowel, and colonic transit by scintigraphy; vector manometry of anal sphincters at rest and during squeeze; defecatory dynamics by balloon expulsion test; and scintigraphic measurement of anorectal angle at rest and during defecation. Autonomic function tests were performed in diabetics. Diabetics with constipation had a higher prevalence of abnormal evacuation or prolonged colonic transit during the first 24 hr than controls (P = 0.07): three had prolonged 24-hr colonic transit, and three abnormal evacuation. Among constipated controls, only one had anismus. Overall, diabetics had slower colonic transit during the first 24 hr than nondiabetics (P < 0.05). Community diabetics who experience constipation or use laxatives have a greater prevalence of delayed 24-hr colonic transit or evacuatory dysfunction than community controls.     

Evaluation of the pathogenesis of flatulence and abdominal cramps in patients with lactose malabsorption

Aim of this study was to assess whether the interindividual differences in the development of flatulence and cramps in patients with lactose malabsorption are due to the quantity of malabsorbed lactose or gas accumulation, or if accelerated intestinal transit or increased perception of gas might play a role. Hydrogen breath tests were performed in 43 patients with lactose malabsorption after ingestion of 50 g lactose and, on a separate day, 25 g lactulose. The unabsorbed amount of lactose, small bowel transit time and colonic hydrogen accumulation were assessed in patients who did and did not develop flatulence and cramps after ingestion of lactose. The unabsorbed amount of lactose, small bowel transit time and volume and rate of colonic hydrogen accumulation were the same in patients who did or did not have symptoms after lactose. Patients with flatulence and cramps had a significantly longer time interval between the onset of the increase and peak breath hydrogen concentration (p < 0.05) and a significant correlation between the time of occurrence of peak symptoms and the time of peak breath hydrogen concentration (r = 0.75, p < 0.001). Our data suggest that subjective symptoms of lactose intolerance are not due to the amount of malabsorbed lactose or to the volume or rate of gas accumulation per se, but are related to increased perception of gas.     

Colonic transit times and the effect of lactulose or lactitol in hospitalized patients

OBJECTIVE: To investigate whether a small dose (10 g per day) of a laxative (liquid lactulose, crystallized lactulose, or crystallized lactitol) can prevent the slow colonic transit associated with the physical inactivity of hospitalization. DESIGN: Patients were randomly allocated to one of four groups: control, liquid lactulose, crystallized lactulose or crystallized lactitol, and the average of mean colonic transit times in these groups was compared. SETTING: Gastroenterologic Unit, Hospital dos Covoes, Coimbra, Portugal. PATIENTS: Patients with normal bowel movements, admitted to hospital for the investigation of conditions not associated with constipation or diarrhoea, were allocated to one of the four treatment groups and had their mean colonic transit times studied after hospitalization using radiopaque markers and abdominal radiographs. Each study group had 18 patients. During the study, each patient was given a normal diet and no drugs except the relevant laxative. RESULTS: The average of the mean colonic transit times in each of the four groups were: 52.16 h [95% confidence interval (CI) 39.42-64.84] for controls; 22.45 h (95% CI 13.84-31.06) in the liquid lactulose group; 24.05 (95% CI 12.13-35.97) in the crystallized lactulose group; and 35.95 (95% CI 23.82-48.08) in the crystallized lactitol group. The differences were statistically significant for the two lactulose groups. The study of the mean colonic regional transit times showed that these differences related to transit in the right colon. CONCLUSIONS: A small dose of lactulose (either liquid or crystallized) was effective in preventing slow colonic transit and constipation in hospitalized patients without causing unwanted symptoms. The slow transit affected mainly the right colon, and it was in this region that the laxative had effect.     

Prehospital advanced life support for major trauma: critical need for clinical trials

BACKGROUND: By using a technique designated sham fecaloma, we were able to identify two types of segmentary motor phenomenon: displacement motor phenomena and nondisplacement motor phenomena. The aim of the study contained herein was to evaluate for identification of patients with different types of slow-transit constipation. METHODS: Studies were performed in healthy subjects (n = 5; colonic transit time <30 hours) and in constipated patients (n = 6; colonic transit time >125 hours; normal rectoanal manometry). A Foley-type recording probe with two perfused catheters (proximal and distal) was used. A rigid sigmoidoscope was used to place the probe at the sigmoid colon. Values recorded by the distal catheter were subtracted (point by point) from the values recorded by the proximal catheter. Subtraction curves were analyzed to quantify characteristics of displacement motor phenomena (an anally directed pressure gradient) and nondisplacement motor phenomena (an orally directed pressure gradient). RESULTS: All healthy subjects had contractions during the recording session. Displacement motor phenomena were predominant (displacement motor phenomena/30 minutes = 21.2 +/- 13.2; range, 3-39). Constipated patients yielded two different patterns: three patients had a very small number of contractions, and three patients had a prevalence of nondisplacement motor phenomena, with numbers similar to numbers of displacement motor phenomena in healthy subjects. A comparison of the patterns of constipated patients revealed a statistically significant difference (P = 0.039). CONCLUSION: Sham fecaloma is a simple and safe test. Constipated patients in this study had two different patterns of colonic motility: scarce activity without haustration and normal activity without displacement motor phenomena. This method might be useful as a diagnostic tool for clarification of the pathophysiology of severe colonic motor disorders.     

Gastrointestinal transit in patients with idiopathic megarectum

PURPOSE: In patients with idiopathic megarectum, it is unknown whether abnormality is limited to the dilated large bowel or whether the upper gut is abnormal, as in the various forms of chronic intestinal pseudo-obstruction. This has important implications for treatment, especially surgery. METHODS: Ten patients (4 females; median age, 18 (range, 17-26) years) with idiopathic megarectum had contrast studies of the upper and lower gut, radioisotope (technetium-99m liquid and indium-111 solid phase) measurement of gastric, small-bowel, and colonic regional transit, and radiopaque marker colonic studies. RESULTS: All patients had a dilated large bowel. No patient had radiographic evidence of upper gut dilation. Four patients had normal and six patients had abnormally slow gastric emptying. Both the radioisotope scans and radiopaque marker studies showed abnormal colonic transit. Regions of delay corresponded with the region of dilated bowel. Symptoms of abdominal distention and bloating did not correspond to abnormalities of gastric emptying but rather with effectiveness of rectal evacuation. CONCLUSION: Patients with idiopathic megarectum have abnormal colonic transit, delay occurring predominantly in the dilated gut. Marker studies are less sensitive than isotope studies but provide adequate information for clinical purposes. Although motility abnormalities of the upper gut are common, symptoms correlate with large-bowel abnormalities.     

Misoprostol in the treatment of chronic refractory constipation: results of a long-term open label trial

BACKGROUND: Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short-term trials. The aim of this study was to determine the utility of misoprostol in the long-term management of patients with chronic refractory constipation. METHODS: Eighteen patients were offered misoprostol (600-2400 microg/day) as adjunctive therapy in an open-ended, non-blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit. RESULTS: Six patients withdrew prior to 4 weeks because of side-effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P = 0.0004). Eight patients continued the long-term treatment, with sustained response seen in six. In a subset of patients (n = 4) the effect of single-dose misoprostol (400 microg) was evaluated compared to healthy controls (n = 5) on post-prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05). CONCLUSIONS: Misoprostol can be effective as part of the long-term medical treatment of patients with chronic refractory constipation, but side-effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.     

Simplified method for the measurement of segmental colonic transit time

Segmental colonic transit has been measured in 101 patients. Two MBq of 111Indium absorbed on resin pellets and encapsulated in an enteric coated capsule was given at 7 00 am. Hourly images during the first day, and three images during each subsequent day were acquired for up to three days. Using all scan and patient data the scans were categorised in one of the five patterns of colonic transit: normal, rapid, right delay, left delay, or generalised delay. The geometric centres and per cent activity at each time point was compared between the five groups of colonic transit patients to find the best time for imaging and so to distinguish the five groups. During the first day, early images did not help in diagnosis of patterns of transit, however, in the later images (six hours onwards after the ingestion of the activity) the rapid transit groups could be identified. Images at 27 and 51 hours were both required to distinguish all five groups of patients from each other. Only in the 'normal' transit patients was there some excretion of the activity during the course of the second day, otherwise there was no difference in the images taken in the course of a day (second or third day). A simplified protocol requires a minimum of three images to distinguish all five patterns of colonic transit. The activity should be ingested in the morning (7 00 am) and the first image taken at the end of the working day (8-10 hours after ingestion), the second image on the morning of the second day, and the third image during the course of the third day. This simple protocol would provide all the clinically relevant information necessary for correct classification of the colonic transit.     

Clinical pharmacodynamics of SDZ HTF 919, a new 5-HT4 receptor agonist, in a model of slow colonic transit

OBJECTIVES: To explore the pharmacodynamic effects of the new promotile agent SDZ HTF 919, a selective partial 5-HT4 receptor agonist, in healthy subjects. METHODS: A pharmacodynamic model was applied to prolong colonic transit by dietary means. Subsequently, the effects of twice-daily multiple doses of SDZ HTF 919 (1, 5, 25, and 100 mg) were investigated in a randomized, double-blind, placebo-controlled parallel-group study with 12 subjects per dose level. The sequential design with three study periods of 7 days each included intake of a self-selected diet, a liquid formula diet with soluble fiber supplementation, and a fiber-supplemented diet together with either SDZ HTF 919 or placebo administration. Stool characteristics (frequency and consistency) and total colonic transit times (with use of radiopaque markers) were recorded in each study period. RESULTS: SDZ HTF 919 was well tolerated at all dose levels. The frequency of loose stool and headache increased with higher doses. After a fiber-supplemented diet intake, the median stool frequency decreased from 8 1/2-9 to 5-7 defecations per study period. SDZ HTF 919 in doses of 25 and 100 mg twice a day increased the stool frequency (p < 0.05). Stool consistency was softened by all but the lowest SDZ HTF 919 dose. A fiber-supplemented diet prolonged total colonic transit time in all groups by 45 hours on average. Twice-a-day administration of SDZ HTF 919 for 6 days in addition to a fiber-supplemented diet significantly shortened the total colonic transit time only at the 5 mg dose. The lack of effect at lower and higher SDZ HTF 919 doses suggests a biphasic dose-response relationship for total colonic transit time. CONCLUSIONS: The suitability of total colonic transit time measurements in healthy subjects as a surrogate marker should be confirmed by patient studies.     

The distal colon provides reserve storage capacity during colonic fluid overload

BACKGROUND: In addition to its absorptive function the capacity of the colon to retain fluid might be relevant in compensating for increased fluid loads and prevention of diarrhoea. The distal colon is considered to be mainly a conduit without extensive storage function. AIMS: To evaluate colonic volume capacity in a model of pure osmotic diarrhoea. METHODS: A non-absorbable, iso-osmotic solution (OS) containing polyethylene glycol (500 ml) was infused into the caecum of nine healthy volunteers; the control group (n = 5) received an equal amount of an easily absorbable electrolyte solution (ES). Fluids were radiolabelled with technetium-99m and gamma camera images were obtained for 48 hours. Counts in the proximal and distal colon were measured and regional and overall colonic transit and stool output were quantified. RESULTS: After OS, in contrast to ES, faecal output was increased significantly (p < 0.05), but colonic transit after OS was not different from transit after ES (p > 0.05). This indicates storage of OS in the colon: after OS infusion, counts in the proximal colon decreased linearly while the distal colon stored approximately 30% of radioactivity for the whole 48 hour study period. After OS, stool output correlated with distal (p < 0.01), but not with proximal (p > 0.05), colonic transit. In contrast, after ES, stool output was determined by proximal colonic transit (p < 0.05) but not by transit through the distal colon (p > 0.05). CONCLUSION: The distal colon retains non-absorbable fluid volumes extensively. In our model transit through the distal colon--but not the proximal colon--determined the time at which diarrhoea occurred.     

Cisapride in neurologically impaired children with chronic constipation

The efficacy of cisapride as a treatment for chronic constipation in children with severe brain damage was studied in 20 children. Each subject was randomly assigned to double-blind treatment with either cisapride (N = 10) or placebo (N = 10) for 12 weeks. Stool habits, total gastrointestinal transit time, colonic segmental transit times, and anorectal motility were evaluated in all children before and at the end of the treatment period. Although cisapride significantly (P < 0.05) increased stool frequency from baseline to week 12 and no significant change was documented in the placebo group, the mean change in stool frequency per week from baseline to 12 week was not significantly different between the two treatment groups. The use of laxatives or suppositories was significantly (P < 0.05) decreased by cisapride, but remained unchanged in the placebo group. Furthermore, cisapride significantly (P < 0.05) reduced rectal compliance but had no effect on total gastrointestinal transit time and colonic segmental transit times. In summary, in neurologically impaired children with chronic constipation, cisapride increased bowel frequency but did not alter the delay in total and segmental gastrointestinal transit times.     

Constipation assessed on the basis of colorectal physiology

BACKGROUND: Constipation is a collective term for symptoms of different aetiologies and pathophysiologies. Our aim was to determine the prevalence of colorectal pathophysiology findings in a prospective series of patients with chronic constipation. METHODS: A total of 155 consecutive patients with chronic constipation underwent anorectal manometry, electromyography (EMG), the balloon expulsion test, colonic transit-time study, and defecography. RESULTS: All investigations were completed by 134 patients (112 females) with a median age 52 (range, 17-79) years. Patients were categorized on the basis of transit time and pelvic-floor function as belonging to 1 of 4 groups: slow-transit constipation (STC) (delayed transit time but normal pelvic-floor function, n = 28), pelvic-floor dysfunction (PFD) (pelvic-floor dysfunction and normal transit time, n = 32), combined slow transit and pelvic-floor dysfunction (STC + PFD) (n = 27), and normal-transit constipation (NTC) (normal transit time and normal pelvic-floor function, n = 47). There was no difference between diagnostic groups in anal sphincter pressures. However, rectal sensitivity to balloon distension was lower (P < 0.05) in patients with delayed transit. Paradoxical puborectalis contraction (PPC) was found on EMG in 42 patients (31%). The prevalence of PPC was higher (P < 0.001) in patients with pelvic-floor dysfunction. Inability to evacuate the rectal balloon was reported by 37% of patients with pelvic-floor dysfunction and 12% of patients with normal pelvic-floor function (P < 0.001). Rectocele was the only anatomic abnormality at defecography which was associated with poor rectal emptying. CONCLUSIONS: About two-thirds of our patients with constipation had objective evidence of delayed transit or pelvic-floor dysfunction. No single test could reliably identify any of the pathophysiologic subgroups of constipation.     

Long-term results of subtotal colectomy and evidence of noncolonic involvement in patients with idiopathic slow-transit constipation

BACKGROUND: Patients with chronic idiopathic constipation can be difficult to manage either medically or surgically. We report our experience of long-term follow-up of 21 patients who had undergone colectomy with ileorectal anastomosis for difficult chronic idiopathic constipation. METHODS: The patients (19 female, 2 male) were aged 26-68 (median = 46) years and had undergone subtotal colectomy 5-12 (median = 8) years before their assessment. They answered a questionnaire about severity of abdominal pain, bloating, urgency, and straining. They also completed the hospital anxiety and depression questionnaire. Fifteen ulcerative colitis patients with panproctocolectomy and 13 colon cancer patients with colonic resection who had a similar follow-up period served as control groups. The following assessments were performed in chronic idiopathic constipation patients with subtotal colectomy: a) oesophageal manometry; b) scintigraphic gastric emptying test; c) review of barium follow-through; d) glucose H2 breath test; e) urodynamic studies; and f) autonomic function tests. RESULTS: Twenty-four per cent of patients with chronic idiopathic constipation had a family history of difficult constipation requiring hospital investigations and treatment. At the time of assessment abdominal pain, bloating, urgency, and straining at defecation were all significantly more frequent in patients with chronic idiopathic constipation with colectomy than in the control groups with colectomy. Seventy-one per cent of chronic idiopathic constipation patients had at least one episode of intestinal obstruction after subtotal colectomy, which is significantly higher (P < 0.01) than in the control groups (ulcerative colitis, 13%; colonic carcinoma, 8%). In patients with chronic idiopathic constipation, among those studied, 68% had some oesophageal motor dysfunction: 19% delayed gastric emptying; 10%, prolonged small-bowel transit on barium follow-through; 54%, abnormal urodynamic variables; and 14%, abnormal autonomic function tests. CONCLUSIONS: This study shows considerable morbidity in a selected cohort of patients with chronic idiopathic constipation who were sufficiently disabled by their symptoms to undergo subtotal colectomy. They had more abdominal and rectal symptoms and more frequent intestinal obstructive episodes than control groups with colonic resection. Evidence of generalized smooth-muscle dysfunction and familial occurrence of constipation suggests a primary chronic intestinal pseudo-obstruction-like disorder in some of these patients.     

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.     

Validation of a new transit time ultrasound flowmeter for measuring blood flow in colonic mesenteric arteries

OBJECTIVE: To validate a transit time ultrasound flowmeter (CardioMed CM 4000) for measuring blood flow in isolated colonic mesenteric arteries. DESIGN: Experimental and clinical study. SETTING: Teaching hospital, Denmark. ANIMALS AND SUBJECTS: One female pig, and 6 patients being operated on for carcinoma of the sigmoid colon and rectum. INTERVENTIONS: Volume blood flow measured by Cardiomed CM 4000 and pump withdrawal flow recordings. MAIN OUTCOME MEASURES: Correlation between the two methods. RESULTS: There was good agreement between transit time flow recordings and pump withdrawal flow recordings (correlation coefficient of 1.0). Of the differences between the two methods, 95% were between -0.16 ml min(-1) and 1.29 ml min(-1), mean 0.57 ml min(-1), or (in percentages) 105, 95% lying between 97-115. There was also good reproducibility in transit time flow recordings, the mean difference between repeated measurements being 0.06 ml min(-1), 95% lying between -0.66 ml min(-1) and 0.78 ml min(-1). CONCLUSION: Ultrasound transit time flow recordings gave precise measurements of blood flow in isolated colonic mesenteric arteries.     

Total and segmental colonic transit time in non ulcer dyspepsia

BACKGROUND: Patients with non ulcer dyspepsia (NUD) often have associated lower alimentary tract symptoms which are labelled as due to the irritable bowel syndrome. AIMS: To asymptomatic colonic dysmotility is present in patients with NUD. METHODS: We studied total and segmental colonic transit times in 25 patients with NUD (14 men age range 20-70 yr), and 25 matched normal controls (13 men; 18-50 yr), using the multiple-marker, single-film technique. Twenty markers each were administered at 0, 9 and 18 h and an abdominal film taken at 27 h. RESULTS: Total colonic transit time was shorter (median 9 h) in patients with NUD as compared to controls (median 15.8 h) p = 0.0018, with similar segmental motility pattern as in controls. There was no significant difference between the symptom subgroups of NUD. CONCLUSIONS: Patients with NUD often have altered colonic transit even in the absence of symptoms. NUD may therefore be only a subset of diffuse gastrointestinal dysmotility with predominant proximal alimentary tract symptoms, whereas the term irritable bowel syndrome is used when lower tract symptoms predominate.     

Prosthetic replacement of the ureters

STUDY AIM: The aim of this study is to demonstrate the reliability of silicone prosthesis for the replacement of ureters. This prosthesis derives from the biliary prosthesis developed after a personal experimental study continued by Triboulet. PATIENTS AND METHODS: In 38 patients suffering from a malignant disease, a right silicone prosthesis was used for the replacement of an ureter during a 20-year period. There were 30 female and eight male patients. The mean age was 71 (range: 51-88 years). Forty one prostheses were used; one patient underwent two successive operations on the same side with a change of prosthesis, and two patients required a bilateral prosthesis. There were 12 gynaecological carcinomas (three with ureteral fistula), three prostatic carcinomas, 16 cancers of the rectum and recto-sigmoid junction, four cancers of the right colon with retroperitoneal carcinomatosis, and three ureteral fistulas after extended colonic resection. RESULTS: Early complications were limited to ureteral fistulas (n = 6, 16%) in patients who had already a preoperative fistula (n = 3) and in patients with peritoneal metastases on the superior wall of the bladder. The secondary destruction of the kidney (four secondary nephrectomies) occurred when the function of the kidney was already impaired at the time of the procedure. There were no secondary fistulas, no secondary obstruction of the prosthesis. The longest follow-up was 69 months. CONCLUSION: The silicone prostheses used for the replacement of ureters are reliable and still permeable beyond 5 years. The protection of the renal function in patients often submitted to chemotherapy improves the duration and quality of survival. These prostheses must be reserved to advanced malignant diseases with a rather long life expectancy.     

The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson's disease

Disorders of autonomic regulation are common in patients with Parkinson's disease (PD). Patients most frequently complain of dysphagia and therapy resistant constipation, as far as the gastrointestinal tract is concerned. These symptoms have to be attributed to a neuronal degeneration. In a pilot study we therefore investigated the effect of stimulation of the myenteric plexus by cisapride. 11 women and 13 men were examined, the average age was 67.3 years, the Webster rating 17 points. In 2 out of 24 patients, colonic transit was prolonged up to the limit, both with and without therapy. The other 22 patients showed an acceleration in transit on response to cisapride. On average the colonic transit of 130 hours was reduced to 79 hours. This objective improvement was associated with a subjective improvement. Central side effects or a worsening of Parkinsonian symptoms were not found. We conclude that cisapride is effective in the treatment of constipation in idiopathic PD.     

Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFbeta1-induced apoptosis in colorectal adenoma cells

Bcl-2 expression is confined to the base of the colonic crypt, whereas transforming growth factor beta (TGFbeta) is expressed in the upper crypt, as are the apoptotic death promoters, Bak and Bax. In colonic adenoma cells, TGFbeta induces a growth arrest. In some adenoma cell lines, this is accompanied by apoptosis and in others it is not. In this study, we used two human colonic adenoma cell lines: RG/C2, in which TGFbeta induces a G1 arrest without apoptosis, and BH/C1, in which TGFbeta induces both a G1 arrest and apoptosis. TGFbeta does not induce apoptosis in RG/C2 cells even if hydrocortisone and insulin are removed from the culture medium. In BH/C1 cells, TGFbeta induces apoptosis in the presence of insulin and hydrocortisone. Apoptosis induced by TGFbeta is preceded by a reduction in p26-Bcl-2 protein levels. There was no change in the levels of the p30 phosphorylated form of Bcl-2 or in levels of the proapoptotic proteins Bax or Bak. RG/C2 cells did not show decreased Bcl-2 levels in response to TGFbeta-induced growth inhibition. Therefore, TGFbeta regulates Bcl-2 expression in colonic adenoma cells which undergo apoptosis in response to TGFbeta, but not in those which are growth inhibited, but resistant to TGFbeta-induced apoptosis. TGFbeta may play an important role in the colonic epithelium, not only in the inhibition of cell proliferation, but also in the regulation of apoptosis.     

A radiopaque marker technique for measuring gastrointestinal transit in subjects with an ileostomy

We aimed to develop a simple, clinically useful technique for measuring gut transit time in patients with an ileostomy, in order to distinguish easily when patients have fast or slow transit. Seventeen healthy subjects (mean age, 55 years; range, 43-71 years; nine males) who had had a proctocolectomy for ulcerative colitis more than 1 year previously and without small intestinal resection were studied. Subjects were studied on 4 days after an overnight fast, two studies with and two without breakfast. A standard diet was used on all days. Twenty radiopaque markers were given at the start of each study day. Ileostomy effluent was collected over 24 hr and x-rayed to determine the number of retained markers. Studies with breakfast demonstrated greater intrasubject reproducibility. The mean transit time for passage of 50% of markers was 16.6 hr with, and 14.8 hr without, breakfast (p < 0.02). From the data obtained we suggest that the optimum time for taking a single abdominal radiograph in a patient with suspected fast transit is 6 hr after ingestion of markers, while the optimum time for a patient with suspected slow transit is 24 hr.