CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) which are characterized by dysfunctional regulation of the immune system. A number of immune modifying drugs are used to treat CD and UC. Therapy is adjusted largely on the bases of subjective reports of disease activity and non-specific laboratory tests. Identification of a single or combination of immune markers of disease activity could be useful to select and monitor therapeutic responses. However, to date no reliable quantitative associations between IBD activity and laboratory measures of immune function have been identified. This study was designed to evaluate the usefulness of a commercially available laboratory measure of CD4(+) immune function, the Cylex® ImmuKnow®, as a surrogate marker of IBD activity. METHODS: Adult IBD patients with either CD (N=55, 27 males, mean, SD age=38.5, 11.5 years) or UC (N=45, 24 males, mean, SD age=41.7, 15.4 years) were enrolled. Patients both in clinical remission and with active disease provided responses to structured, validated questionnaires (CDAI and HBI for CD patients and SCCAI for UC patients) used to monitor IBD activity. Whole blood and plasma samples were collected to quantify various markers of disease status including routine cell counts and differentials (CBCs), CRP, and albumin (Alb), as well as CD4(+) immune response (Cylex® ImmuKnow®, N=98). Results were compared between all IBD patients as well as between CD and UC subgroups. RESULTS: There was a good correlation between the results of CDAI and HBI scores (r=0.811, p<0.01, Spearman-Rho) but HBI scores correlated slightly better (r=0.575, p<0.001) than the CDAI's (r=0.449, p=0.001) with CD patients' reported perception of their general condition. CDAI and HBI scores categorized 12/55 versus 36/55 of CD patients respectively as having active disease. SCCAI scores indicated that 25/45 of UC patients had active disease. Cylex® results (in ng/mL of ATP) were increased in 74/98 IBD subjects (≥525 ng/mL) but were influenced by the use of systemic corticosteroids (SCS) and infliximab. There were weak but statistically significant Spearman-Rho correlations between Alb concentrations and both CDAI (r=0.413, p=0.002) and HBI (r=0.325, p=0.017) scores as well as between CRP values and HBI scores (r=0.331, p=0.016). Correlations between CRP and both CDAI and SCCAI scores and between Alb and SCCAI scores were not significant and there were no significant positive associations between any of the three clinical scores and Cylex® results. CONCLUSIONS: CD4(+) immune responses were significantly elevated in IBD patients whether or not they were in clinical remission but were influenced by treatment. There were some significant correlations between the clinical scores and CRP or Alb but not with the CD4(+) results. Both other clinical scoring systems, other measures of immune function, and CD4(+) immune response changes over time should be examined to see if this or other laboratory measures of immune response are predictive of actual disease activity or symptoms in CD or UC patients.

[Anorectal manometry]. / Empfehlungen zur Anorektalen Manometrie im Erwachsenenalter.

This document contains the guidelines of the German Societies of Neurogastroenterology and Motility, Gastroenterology (committee for proctology), Abdominal Surgery (coloproctology working group), and Coloproctology for anorectal manometry in adults. Recommendations are given about technical notes, study preparation (equipment; patient), technique for performing manometry and data analysis, reproducibility, and indications. Minimum standards for anorectal manometry are measurement of resting and squeeze pressure, testing of rectoanal inhibitory reflex, determination of rectal sensation (first perception and urge), and calculation of rectal compliance. Anorectal manometry is indicated in patients with fecal incontinence and constipation in the context of a structured programme.

[Pharyngitis, massive ESR elevation and hyperthyroidism in a 71-year-old female patient]. / Pharyngitis, Sturzsenkung und Hyperthyreose bei einer 71-jährigen Patientin.

We present a 71-year-old female patient suffering from a sore throat with unilateral neck swelling, pain on swallowing, subfebrile temperatures and general fatigue persisting for several weeks without any clinical signs of hyperthyroidism, although laboratory findings show high concentrations of T(3) and T(4) and a low TSH. A massive ESR elevation is found as well. Ultrasound reveals an inhomogeneous pattern of the thyroid gland with low echogenicity. (99m)Tc pertechnetate uptake is suppressed. The diagnosis of acute/subacute thyroiditis de Quervain is concluded. Therapeutic application of prednisone leads to a swift improvement, yet two weeks later asymptomatic hypothyroidism is diagnosed, requiring substitution of thyroxine. We discuss de Quervain's thyroiditis and the differential diagnosis of inflammatory disorders of the thyroid gland.

Magnetic marker monitoring of disintegrating capsules.

Magnetic marker monitoring was studied for its applicability to investigate the in vivo fate and behavior of disintegrating magnetically marked dosage forms. As a model, hard gelatin capsules were filled with an effervescent mixture of lactose, ascorbic acid and sodium hydrogen carbonate containing 1.3 mg black iron oxide as a magnetic label. The accuracy of the localization procedure whilst calculating all parameters of the dipole in one fitting procedure was checked in phantom experiments where the capsules were moved in well-defined paths with respect to the measurement device. The calculated position coordinates of the capsules deviated between less than 2 mm up to 8 mm from the expected position values depending on the distance between the sensor area and the capsule's path. Further experiments on the in vitro disintegration of the capsules showed that the value of the magnetic moment of the capsules can serve as a measure for their disintegration behavior. In vivo monitoring of the capsules was performed in eight experiments where a healthy volunteer swallowed each time one of the capsules. It was found that the in vivo disintegration behavior of the capsules corresponds well to their disintegration observed in water of about 37 degrees C.

Diagnosis of enteroceles by dynamic anorectal endosonography.

PURPOSE: Enteroceles are herniations of the lining of the peritoneum and intestinal loops into the pouch of Douglas. They may accompany other pelvic and anorectal disorders or cause outlet obstruction. So far they are only diagnosed by defecography. We investigated the use of dynamic anorectal endosonography to detect this disorder. METHODS: Seventeen female patients with a defecation disorder were investigated by proctoscopy and endoluminal ultrasonography. In 14 patients defecography followed. Endosonography was performed using the curved array 7.5 MHz scanner directed to the ventral rectal wall. Dynamic studies were undertaken during rest and during maximal straining. The minimal distance between the inner verge of the anal canal and the peritoneal cavity was determined. RESULTS: Dynamic endosonography detected enteroceles in six patients in which the pouch of Douglas opened during straining and intestinal loops moved toward the anus. The diagnosis of enteroceles was confirmed in all patients by defecography giving a specificity of 100 percent. No enterocele was detected in the remaining eight patients with defecography, leading to a 100 percent sensitivity for endosonography. Comparing the 6 patients with enteroceles with the 11 patients without enterocele, the peritoneal-anal distances were at rest 3.9 +/- 0.5 and 3.3 +/- 0.5 cm (P < 0.05) and during straining 3.6 +/- 0.5 and 1.3 +/- 0.2 cm (P < 0.001), respectively. The change in peritoneal-anal distance was 2 +/- 0.5 cm in the enterocele group and 0.3 +/- 0.4 cm in the control group (P < 0.001). Two patients with enteroceles had complete rectal prolapse. Four patients with enteroceles underwent surgery. Postsurgical endoluminal endosonography showed closure of the pouch of Douglas. CONCLUSIONS: Enteroceles may be diagnosed by dynamic anorectal endosonography. Compared with defecography dynamic anorectal endosonography is easier to perform, less cumbersome for the patient, and bears no radiation exposure. Therefore, this new diagnostic means may be useful in first-line search for enteroceles, but further studies are needed to prove its sensitivity for screening of this disorder.

Pylorus preservation after complete gastrectomy and jejunal interposition: experimental study investigating motility and alkaline reflux.

BACKGROUND: Pylorus preservation has been proposed to reduce the disturbance in gastric emptying following gastrectomy but little is known about the role of the pylorus regarding motility patterns and alkaline reflux. AIMS: To assess the motility patterns and alkaline reflux following pylorus preservation after complete gastrectomy and jejunal interposition in the pig. METHODS: Motility patterns and alkaline reflux were studied in 12 conscious pigs before and after gastrectomy and jejunal interposition with preservation of the pylorus and a 1 cm antral ring (PYL+) or excised pylorus (PYL-) 6 and 14 weeks postoperatively. Gastroduodenal motility was investigated by manometry after fasting and fed, respectively and alkaline reflux by a fiberoptic system for detecting bilirubin. RESULTS: The number of propagated phase-III activities of the jejunal interponat to the duodenum and propagating velocity were lower in the PYL+ group after 6 weeks (p < 0.05) but higher after 14 weeks (p < 0.05) compared to the PYL- group. In the PYL+ the number of intrapyloric pressure waves (IPPWs) was lower after 6 weeks (p < 0.05) but higher after 14 weeks (p < 0.05) in comparison to preoperative controls. Alkaline reflux was significantly higher in the PYL- group than in the PYL+ group throughout the time observed. CONCLUSIONS: Pyloric function shows a delay after 6 weeks but restores within 14 weeks postoperatively. Pylorus preservation was associated with a significant decrease of alkaline reflux compared to PYL- in this setting.

Randomised double-blind comparison of simethicone with cisapride in functional dyspepsia.

AIM: To compare the efficacy of simethicone with cisapride in patients with functional (non-ulcer) dyspepsia. METHODS: After standardized diagnostic work-up and at least 6-days wash-out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19-71 years) were randomized and treated using a double-dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as 'very good', 'good', 'moderate' or 'no effect'. RESULTS: A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Delta30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Delta10.2%, P=0.11). CONCLUSIONS: In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.

Magnetic marker monitoring of esophageal, gastric and duodenal transit of non-disintegrating capsules.

The purpose of the study was to investigate in detail the esophageal, gastric and duodenal passage of non-disintegrating capsules in a fasted, healthy volunteer using Magnetic Marker Monitoring (MMM). Five independent experiments were performed. In each case the same healthy male volunteer ingested one magnetically marked capsule after fasting for at least 8 h. The magnetic dipole fields of the capsules were recorded by biomagnetic multichannel measuring equipment. The positions of the capsules were calculated from the recorded data by methods established in magnetic source imaging. The esophageal, gastric and duodenal passages of the capsules were successfully reconstructed from all recorded data sets. The spatial resolution of the capsules' three-dimensional positions in the organs of the gastrointestinal tract was within a range of several millimeters, with a chosen temporal resolution of up to four milliseconds. The esophageal transit times were between 3-13 s, the gastric residence times were between 14-133 min and the duodenal transit times were between 7-245 s. The data demonstrate that Magnetic Marker Monitoring permits the detailed investigation of the gastrointestinal transit of solids.

Solitary rectal ulcer induced by excessive use of analgesic suppositories containing paracetamol, caffeine, and codeine.

We report the case of a 53-yr-old woman who developed an ulcer of the distal rectum with mild stenosis after prolonged use of suppositories containing paracetamol, caffeine, and codeine. After undergoing extensive diagnostic tests with exclusion of other possible causes, she admitted to the abuse of the suppositories. She was treated with frequent endoscopic balloon dilations to prevent progression of the rectal stenosis. Because of severe pain on defecation, she needed a protective colostomy which could be closed after the healing of the ulcer 7 months later. There was no significant residual stenosis. This case is compared to cases described in the past 30 years.

Gastroesophageal reflux in patients with sleep apnea syndrome.

UNLABELLED: Gastroesophageal reflux (GER) may be associated with pulmonary diseases. The aim of this study was to investigate the role of GER in patients with sleep apnea syndrome (SAS). We evaluated, therefore, in patients with SAS the occurrence of GER during simultaneous apnea monitoring, and whether GER is related to the severity of SAS. METHODS: 17 consecutive patients with proven SAS were divided into two groups according to the severity of SAS: (A) apnea index > or = 5 and < 15, n = 8; (B) apnea index > or = 15, n = 9. All patients underwent 24 hours pH-metry in the proximal and distal esophagus and simultaneous apnea monitoring during the night. RESULTS: There was a high occurrence of GER in patients with SAS, but no significant difference was found between the two groups with respect to reflux times at the distal or at the proximal esophageal site. Reflux episodes and apnea periods were not timely correlated. Most of the patients of both groups were obese. CONCLUSIONS: Patients with SAS often have GER. However, there is neither a relation of GER with the severity of SAS nor a timely association between GER- and SAS-episodes. Thus, it is unlikely that there is a direct link between GER and SAS. However, there may be factors predisposing for both diseases.

Effects of absorption rate, flow rate and fluid load on colonic motor activity in dogs.

We investigated the relationship between absorption rate, flow rate, fluid load and colonic motor activity in an in vivo isolated colonic loop model. Motor activity was recorded by implanted strain gauge transducers. Two electrolyte solutions were perfused at 0.4 and 1.6 mL min-1 through the open colonic loop (distal end open) or infused into the closed loop (distal end closed). The first solution resembled ileostomy fluid (ES1) and the second solution was an iso-osmolar mannitol solution (ES2). The absorption rate for H2O measured by 14C PEG concentrations of ES2, 0.2 +/- 0.03 mL min-1, was significantly less than that of ES1, 0.6 +/- 0.06 mL min-1. Infusion of ES1 under open loop conditions served as control. Motor activity was analysed for area under contractions and expressed as motor index ratio in comparison to the control. None of the solutions altered motor activity when perfused at the two rates through the open loop. Under closed loop conditions, the infusion of either solution at 0.4 mL min-1 had no significant effect on colonic motor activity. Infusion of ES1 or ES2 at 1.6 mL min-1 into the closed loop, however, increased the motor index ratio 2.5-fold and 3.6-fold, respectively (P < 0.01). The proximal half of the colon was less affected than the distal half during infusion of ES1 but not during infusion of ES2. We conclude that flow rate and absorption rate do not influence colonic motor activity as long as the fluids can leave the colon. When the distal end is closed, inflow, resulting in fluid accumulation and distension, leads to stimulation of colonic motor activity.

Effects of CCK-receptor antagonist on colonic motor activity in dogs.

This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the colon. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by four strain gauge transducers implanted on the colon. The effects of the CCK-analogue caerulein and the CCK-antagonist loxiglumide (Rotta, Italy) were studied in fasted and fed states. The motor activity was computed for the area under contractions. Caerulein given as an intravenous bolus of 50 ng kg-1 during a quiescent state caused a burst of phasic and tonic contractions resembling a regular non-migrating motor complex. Physiological doses of 10 ng kg-1 caerulein, which increases plasma CCK-immunoreactivity to postprandial levels, had no effect. Continuous intravenous infusion of 10 mg kg-1 h-1 loxiglumide completely abolished the effects of 50 ng kg-1 caerulein. The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 micrograms kg-1) was not altered by loxiglumide. Loxiglumide given in the fasted state reduced the area under contractions in the proximal colon by 26.8 +/- 12.8% compared to the control without loxiglumide (P < 0.05). The postprandial increase in motor activity in the distal colon, the gastrocolonic response, was significantly inhibited by loxiglumide. Moreover, loxiglumide reduced the area under contractions in the fed state by 25.4 +/- 10.7% and 19 +/- 7.2% in the proximal and distal colon, respectively (P < 0.05). The present results show that loxiglumide acts as a specific antagonist of the actions of CCK on colonic motor activity in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)

[Occurrence of obstructive sleep related respiratory disorder in conjunction with gastroesophageal reflux]. / Untersuchungen über das Auftreten einer obstruktiven schlafbezogenen Atmungsstörung in Zusammenhang mit einer gastro-ösophagealen Refluxerkrankung.

In 30 patients with suspected or, respectively 27 patients with confirmed, sleep apnea syndrome, 24-h esophagus pH metering was carried out. The patients were divided into two groups (number of apnea per 6 h > or < 100). A pH value of < 4 was defined as a pathological reflux when it occurred in total in at least 4% of the measuring period. Pathological reflux was encountered in 76% of the light SAS group and in 68% of the patients with severe SAS. Positional variations through upright and supine positions were apparent but not significant. Further investigations are therefore necessary to evaluate the relationships between degree of severity, position, and accompanying diseases.

Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome.

Colonic motor activity and plasma concentrations of cholecystokinin (CCK) both increase after oral intake of a meal. Thus, CCK had been thought to mediate the postprandial increase in colonic motor activity, which is termed gastrocolonic response. The present study used the substance loxiglumide, which acts as a specific antagonist at the CCK-A receptor, to evaluate this hypothesis. In the first set of experiments, eight healthy subjects were studied four times on separate days. A multilumen catheter was endoscopically placed with its tip lying in the descending colon. Motor activity was recorded by a low-compliance perfusion manometry system at six locations 60-45 cm from the anus. Basal activity was recorded for at least 2 hours to achieve steady-state conditions. The order of the following four experiments was randomized: (a) intravenous infusion of the CCK analogue cerulein at increasing doses (7.5, 15, 30, and 60 ng/kg.h, each given for 30 minutes); (b) intravenous cerulein plus 5 mg/kg.h loxiglumide; (c) a 1000-kcal solid/liquid meal consisting of regular German food; and (d) a meal plus 5 mg/kg.h loxiglumide. In the second set of experiments, eight patients with irritable bowel syndrome were studied twice on two separate days, and two experiments were performed n randomized order: (a) a 1000-kcal solid/liquid meal consisting of regular German food; or (b) a meal plus 5 mg/kg.h loxiglumide. The motor index was calculated as the area under contractions by a computerized system. The 1000-kcal meal markedly increased colonic motor activity. This gastrocolonic response was significantly greater in patients with irritable bowel syndrome than in healthy volunteers. Cerulein stimulated motor activity only at pharmacological doses (30-60 ng/kg.h), which resulted in plasma CCK levels markedly exceeding postprandial values. Loxiglumide abolished the effects of cerulein even at pharmacological doses. However, loxiglumide did not inhibit the gastrocolonic response to a regular meal either in healthy volunteers or in patients with irritable bowel syndrome. Loxiglumide also failed to alter the interdigestive colonic motor activity. Therefore, effects mediated by the CCK-A receptor do not play a major physiological role in the regulation of the interdigestive and postprandial motility of the left colon.