[Chronic motility disorders of the upper gastrointestinal tract in the elderly. Pharmaceutical, endoscopic and operative therapy]. / Chronische Motilitätsstörungen des oberen Gastrointestinaltrakts im Alter. Medikamentöse, endoskopische und operative Therapien.

Primary motility disorders of the upper gastrointestinal (GI) tract result from an impairment of the motor function of the esophagus, stomach, and duodenum by malfunction of the enteric nervous system or degeneration of the gastrointestinal muscle layer. Other forms of upper GI motility disorders occur secondary to underlying systemic diseases. The exact pathophysiology of the disturbances within the enteric nervous system of the upper GI tract is not yet clearly understood. For motility disorders resulting from systemic diseases the lack of knowledge with respect to the underlying pathomechanism is even greater. The term functional dyspepsia summarizes some symptoms of the upper abdomen, suggesting a disorder of upper GI motility or perception; however, this link to disturbed physiology has never been convincingly demonstrated. This overview describes therapeutic options for motility disorders of the upper GI tract regarding medicinal, endoscopic and surgical targets. The efficacy of medicinal therapy of upper GI motility disorders is low due to the lack of understanding of the pathophysiology. Therefore, endoscopic and other interventional therapies have to be applied also in the elderly patient group. The restrictions for metoclopramide published by the European Medicines Agency (EMA) in July 2013 have limited the armentarium of medicinal therapy of chronic motility disorders of the upper GI tract.

[How safe is sedation in gastrointestinal endoscopy? A multicentre analysis of 388,404 endoscopies and analysis of data from prospective registries of complications managed by members of the Working Group of Leading Hospital Gastroenterologists (ALGK)]. / Wie sicher ist die Sedierung in der gastrointestinalen Endoskopie? Eine multizentrische Auswertung von 388 404 Endoskopien und Auswertung der Daten aus prospektiv geführten Komplikationsregistern von Mitgliedern der Arbeitsgemeinschaft leitender Gastroenterologen im Krankenhaus (ALGK).

BACKGROUND: Gastrointestinal endoscopies are increasingly being carried out with sedation. All of the drugs used for sedation are associated with a certain risk of complications. Data currently available on sedation-associated morbidity and mortality rates are limited and in most cases have substantial methodological limitations. The aim of this study was to record severe sedation-associated complications in a large number of gastrointestinal endoscopies. METHODS: Data on severe sedation-associated complications were collected on a multicentre basis from prospectively recorded registries of complications in the participating hospitals (median documentation period 27 months, range 9 - 129 months). RESULTS: Data for 388,404 endoscopies from 15 departments were included in the study. Severe sedation-associated complications occurred in 57 patients (0.01 %). Forty-one percent of the complications and 50 % of all complications with a fatal outcome (10/20 patients) occurred during emergency endoscopies. In addition, it was found that 95 % of the complications and 100 % of all fatal complications affected patients in ASA class ≥ 3. CONCLUSIONS: Including nearly 400,000 endoscopies, this study represents the largest prospective, multicenter record of the complications of sedation worldwide. The analysis shows that sedation is carried out safely in gastrointestinal endoscopy. The morbidity and mortality rates are much lower than previously reported in the literature in similar groups of patients. Risk factors for the occurrence of serious complications include emergency examinations and patients in ASA class ≥ 3.

OTC laxative use of sodium picosulfate â results of a pharmacy-based patient survey (cohort study).

OBJECTIVES: Constipation is one of the most frequent gastrointestinal symptoms. Traditionally, drug therapy for constipation is not prescribed and controlled by physicians. Instead, laxatives are sold by pharmacists as over-the-counter (OTC) medication. The aim of this study was to explore the safety and usage pattern of the OTC laxative sodium picosulfate use by collecting data from patients at their pharmacies. The study describes how self-treatment of constipation is practiced. In addition, the characteristics of patients buying the contact laxative, sodium picosulfate, for self-treatment of constipation were analyzed. METHODS: The survey was a pharmacy-based observational study (PHOBS) in community pharmacies in Germany. Participating pharmacists asked customers requesting a specific contact laxative to participate in the study. Customers gave verbal informed consent to study participation before receiving a structured questionnaire to be completed at home and then returned to the pharmacy. RESULTS: Data from 1,845 patients recruited by 243 pharmacies were collected. Compliance with the recommended dosage of 5 â 10 mg/day was 96%, compliance with the indication of constipation was 99%. More than 90% rated the efficacy as "very good" to "good". There was no weakening of the efficacy rating with increasing duration of use. 8% of patients reported mild-to-moderate adverse events. Nearly 60% of respondents reported to be satisfied with less than 1 bowel movement per day. Therefore, users appear to have a rational way of using OTC laxatives. CONCLUSIONS: Self-medication of constipation with sodium picosulfate is efficacious and considered to be safe.

Cardiotoxicity of the antiproliferative compound fluorouracil.

The antimetabolite fluorouracil (5-FU) is frequently administered for chemotherapy of various malignant neoplasms. The drug is well known for its adverse effects involving bone marrow, skin, mucous membranes, intestinal tract and central nervous system, whereas its cardiotoxicity is less familiar to clinicians. The pathophysiology of fluorouracil-associated cardiac adverse events is controversial and conclusions are based on clinical studies and case reports more than on solid experimental evidence. While clinical and electrocardiographic features suggest myocardial ischaemia as a main aetiological factor, possibly induced by coronary vasospasm, histomorphological and biochemical studies indicate a more direct drug-mediated cytotoxic action. Estimates of the overall incidence of fluorouracil cardiotoxicity have varied widely from 1.2 to 18% of patients. Patients may present with angina-like chest pain, cardiac arrhythmias or myocardial infarction. There is no unequivocally effective prophylaxis or treatment in this syndrome. Once fluorouracil administration is discontinued symptoms are usually reversible, although fatal events have been described. The overall mortality rate has been estimated to be between 2.2 and 13.3%. There is a high risk of relapse when patients are re-exposed to this drug following previous cardiac incidents. From the present data it is concluded that cardiotoxicity is a relevant but underestimated problem in fluorouracil treatment. Since the mechanisms of fluorouracil-associated cardiotoxicity are not yet fully understood, all patients undergoing this chemotherapy have to be carefully evaluated and monitored for cardiac risk factors and complaints. After cardiotoxic events, fluorouracil should definitely be withdrawn and replaced by an alternative antiproliferative regimen.

Effects of cisapride on ano-rectal sphincter function.

To investigate the effects of cisapride, a motility-inducing agent, on ano-rectal sphincter functions, standard manometry was performed in 10 healthy male volunteers after 5 days on a 20-mg dose of cisapride in a placebo-controlled double-blind randomized crossover fashion. All subjects kept stool diaries during the experiment. Cisapride significantly increased stool frequency by adding soft and liquid stools; in addition, anal resting pressure was reduced with cisapride in seven of the 10 subjects; mean resting pressure decreased by 16%, while all other measurements were not altered. This suggests that cisapride may act directly on the smooth muscle of the internal anal sphincter. It also supports the view that enhanced defaecation in chronic constipation induced by cisapride may not be achieved by propulsive motor activity in the colon but also by a decreased anal sphincter tone.

Breath hydrogen as a test for gastrointestinal transit.

Intestinal transit is an important indicator of small-bowel function. This study served to investigate oro-cecal and duodeno-cecal transit times of different carbohydrate test meals and to evaluate intra- and interindividual variability of the breath hydrogen test. Breath hydrogen was analysed by an electrochemical cell in 25 healthy volunteers. Oro-cecal transit time of lactulose was much shorter than that of a standardized normal test meal. Duodeno-cecal transit was approximately one hour shorter than oro-cecal transit. Considerable intra- and interindividual differences were observed. It is concluded that results of lactulose test meals do not permit conclusions as to the physiological situation. Large intra- and interindividual variability of transit times must be taken into account in any study using the breath hydrogen test.

[Spectrum and results of operative interventions in HIV infection patients]. / Spektrum und Ergebnisse operativer Eingriffe bei HIV-infizierten Patienten.

Owing to their number, multimorbidity, and prolonged survival following improved antiretroviral therapy, HIV-infected subjects represent an important subgroup of the patients requiring surgical treatment. The spectrum of operative interventions performed in these people comprises both characteristic diagnostic, palliative, and therapeutic measures and all the same surgical indications as in an age-matched non-HIV-infected patient population. Published data concerning the results of operative interventions in these patients are rather scarce. The surgical success rate is 68-90% for elective therapeutic measures. In 21-94% of HIV-infected patients intraoperative findings of a HIV-associated opportunistic disease are reported. Depending on patient selection and the kind of operation performed, the perioperative morbidity of these subjects was 9-87% (median 33.5%), while postoperative mortality ranged from 0 to 71% (median 8%). Particular determining factors of perioperative morbidity and mortality are the degree of individual immunosuppression and the urgency of surgical intervention. In summary, operation-associated morbidity and mortality of HIV-infected patients appear not to be significantly increased compared to non-HIV-infected patients in similar preoperative health condition. The present analysis reflects a marked improvement of operative results in HIV-infected patients during the past 20 years.

[Preoperative risk assessment and perioperative management of HIV-infected patients]. / Präoperative Risikoabschätzung und perioperatives Management HIV-infizierter Patienten.

PROBLEM: Due to their impaired immune function, unusual multimorbidity, and extensive concomitant medication HIV-infected patients impose special and specific demands on those who deal with their perioperative care. PREOPERATIVE ASSESSMENT: Beside standardized diagnostic and therapeutic preparations the preoperative knowledge, quantification, and treatment of HIV-associated opportunistic disorders and chronic organ damage are of particular importance. This requires an extended problem-orientated work-up. Furthermore, antiretroviral medication may interact with perioperatively administered pharmaceutics and lead to hardly foreseeable synergistic and antagonistic adverse effects. In contrast, "drug holidays" favor the development of HIV drug resistance. OPERATIVE MANAGEMENT: Anesthetic and surgical procedures basically depend on the underlying indication and consequently follow common principles. Laparoscopic techniques do not have any specific advantage in HIV-infected subjects. PERIOPERATIVE MORBIDITY: During their postoperative course, HIV-infected patients have to be more often admitted to intensive care unit and kept on artificial respiration unplannedly. Perioperative morbidity of HIV-infected patients increases with the stage of their disease. It is, however, not significantly elevated compared to that of HIV-negative subjects in similar preoperative health condition.

[Intestinal pseudo-obstruction]. / Die intestinale Pseudoobstruktion.

Intestinal pseudo-obstruction is a rare and heterogeneous syndrome caused by severe disorders of gastrointestinal motility. It affects the entire gastrointestinal tract or only segments, giving rise to symptoms and physical signs of a mechanical obstruction of the gut despite negative results of all imaging procedures. The disease may occur in an acute or chronic form. The acute and some of the chronic forms develop as complication of other gastrointestinal or extragastrointestinal diseases, e.g. pancreatitis or systemic sclerosis. The primary forms of chronic intestinal pseudo-obstruction are most often caused by genetic neuromuscular disorders of the gastrointestinal tract, e.g. familial visceral neuropathies. The diagnosis of intestinal pseudo-obstruction is based on the exclusion of a mechanical obstruction of the gut by fluoroscopy and endoscopy. Manometric studies may disclose the underlying disorder of gastrointestinal motility. In a few patients, results of all imaging procedures as well as motility studies are inconclusive, and laparatomy (with full thickness biopsy of the gut wall) has to be performed to exclude mechanical obstruction of the gut. Acute intestinal pseudo-obstruction is treated by elimination of the underlying intestinal or extraintestinal disease. In case of extensive colonic dilatation with imminent colonic perforation endoscopic decompression should be evaluated. Treatment of chronic pseudo-obstruction aims to correct the underlying motility disorder. Usually, restoration of normal gastrointestinal motility is attempted by prokinetic drugs, but often their effect is limited. Surgery may be helpful in the few patients in whom the disease is confined to small segments of the gut, leaving all other parts unaffected. Some patients with otherwise intractable disease may need long-term parenteral nutrition.

The effect of mental stress induced by noise on gastric acid secretion and mucosal blood flow.

Mental stress is thought to promote the development of peptic ulcer. In the present study the effect of mental stress induced by noise on gastric acid secretion and mucosal blood flow was studied. A 90 dBA broad frequency noise applied by headphones increased diastolic and systolic blood pressure by 4 and 8 mmHg, but left acid secretion and mucosal blood flow unchanged.

[Scanning electron microscopy of the zonula apparatus of higher primates. A further approach to a new theory of accommodation (author's transl)]. / Rasterelektronenmikroskopische Untersuchungen über den Zonulaapparat höherer Primaten als weiterer Beitrag zu einer neuen Akkommodationstheorie

The architecture of the zonula apparatus of two species of monkeys is studied by scanning electron microscopy. Some specimens were treated with pilocarpine respectively atropine immediately before enucleation. The zonula consists of two functionally different groups of fiber strands, i.e. span and holding bundles (after Rohen and Rentsch), the course and structure of which is described in detail. After application of atropine the "holding bundles" appear to be stretched in the area between the ciliary processes and the lens, whereas after pilocarpine application they appear loose and irregularly arranged. Screw-like, spiral fiber strands were often seen in the scanning electron microscope. It is assumed that the spiral fibers develop in the stage of relaxation of the zonula apparatus.

[Anal sphincter function and recto-anal continence]. / Analsphinkterfunktion und rekto-anale Kontinenz.

Recto-anal continence results from a complex interplay of motor, sensory and anatomical continence mechanisms. Accordingly, fecal incontinence may be due to motor defects, sensory defects, neurological defects, or defects of the reservoir function of the ano-rectum. In a study in 16 patients with fecal incontinence and 16 continent controls the question was examined, to which extent disturbances of the motor function of the internal and external anal sphincter contribute to the pathogenesis of fecal incontinence. Basal and squeeze anal sphincter pressures were not different in incontinent and continent patients. However, 8/16 incontinent patients showed no or only an insufficient increase of external anal sphincter function while squeezing. It is concluded that disturbances of the motor function of the anal sphincters contribute to fecal incontinence in only about one half of the patients. In addition, the pressure increase of the sphincters during squeezing is of more importance for recto-anal continence than the absolute height of the muscular force of the anal sphincters.

Spontaneous variation of anal "resting" pressure in healthy humans.

To investigate anal sphincter performance during sleep and after a meal, a two-channel micro-transducer probe was used for 12-h stationary recording of basal anal pressure overnight in eight healthy male volunteers. It was shown that the basal anal pressure ("resting" pressure) exhibits three distinct patterns of cyclic activity changes in all subjects: a long-term rhythm with a prominent decrease of pressure during which sleep was approximately circadian, an ultradian rhythm of approximately 20 to 40 min in length that was more prominent at night, and spontaneous relaxations of the sphincter tone occurring between 3 and 20 times per hour with the maximum frequency after breakfast. These data indicate that the anal sphincter is a dynamic structure not often at rest. Long-term anorectal manometry may be supplementary to short-term clinical evaluation of anal sphincter performance in healthy subjects as well as in patients with defecation disorders.

Sensory and motor function in the maintenance of anal continence.

Anorectal function was prospectively evaluated in 43 consecutive patients with fecal incontinence and in 19 healthy volunteers using manometry and electrical stimulation of the anoderm. Both anorectal motor and sensory function was impaired in incontinent patients as compared with healthy controls. Further statistical analysis identified four subgroups of patients showing different pathomechanisms of fecal incontinence: severe combined anorectal motor and sensory dysfunction, isolated anal sphincter dysfunction, isolated anorectal sensory dysfunction, and combined dysfunction of the internal anal sphincter and impaired anorectal sensitivity. These data support the hypothesis that sensory function of both the rectum and the anal canal is an important and independent factor in the preservation of continence.

Effect of balloon compliance on symptomatic success of pneumatic dilation in achalasia patients.

BACKGROUND: Pneumatic dilation is the standard non-surgical treatment of achalasia. The dilation devices in use differ in their physical properties, particularly with regard to balloon compliance. PATIENTS AND METHODS: 35 achalasia patients (18male, 20-82 years, median 45 years) diagnosed by accepted criteria were prospectively and randomly assigned to 39 dilation procedures by either a low compliance dilation device (LCDD, polyethylene balloon, Rigiflex(trade mark), Microvasive Boston Scientific, USA, n = 18) or a high compliance dilation device (HCDD, latex balloon, Rüsch Inc., Germany, n = 17). Individual complaints were graded by a standardized questionnaire before treatment and prospectively after a median of 3 and 13 months. Furthermore, the patients' readiness to retrospectively re-consent (treatment satisfaction) and treatment complications were recorded. RESULTS: Patient groups did not differ with regard to age, sex, number of previous dilations, and duration of follow-up (Mann-Whitney U-test, p > 0.05). 2 patients were excluded from follow-up, with one individual (HCDD) having suffered a dilation-related perforation (2.6 %) and another subject (LCDD) having not been able to re-contact. Initial and post-treatment symptom scores as well as treatment complications were similar in both treatment groups (p > 0.05). Treatment satisfaction was 90 % for the LCDD and 82 % for the HCDD group at first control, and 89 % and 87 % at second control, respectively (p > 0.05). In both patient groups, dilation therapy best improved the symptom "dysphagia" (Wilcoxon rank sum test, p < 0.05). CONCLUSIONS: Achalasia patients' satisfaction of dilation treatment is high, with their dysphagia benefiting most from therapy. Low and high compliance balloon devices did not differ from each other with regard to symptomatic efficacy and safety in forceful dilation of these individuals.

[Rectal stenosis due to long-term therapy with ergotamine]. / Rektumstenosen bei Langzeittherapie mit Ergotamin.

Two patients (a woman aged 39, a man aged 46 years) had developed severe distal rectal stenoses after 20 years of anti-migraine treatment with ergotamine-containing suppositories. The woman required several bougie and laser treatments. In the man a megacolon had developed due to increasing, finally complete, rectal stenosis and this required a double colostomy (transverse colon) as an emergency. Ergotamine-containing suppositories are widely used in the treatment of migraine, but they should not be administered for prolonged periods.

Motility changes in primary achalasia following pneumatic dilatation.

The changes in esophageal motility after pneumatic dilatation were evaluated prospectively in 51 patients with achalasia. The patients were evaluated for a median of 14 months. Pneumatic dilatation led to a clinical improvement in 41 patients. On manometric evaluation, a significant decrease in lower esophageal sphincter pressure was observed (28.4 +/- 14.9 mmHg vs. 13.5 +/- 7.2 mmHg; p = 0.001); the resting pressure of the esophageal body dropped from 4.8 +/- 4.2 mmHg above gastric baseline to 0.1 +/- 3.9 mmHg below gastric baseline. After therapy, peristaltic activity was present in 10/51 (20%) patients; in 1 case, complete relaxation of the lower esophageal sphincter was recorded. Treatment-induced motility changes could not be predicted by clinical history or the lower esophageal sphincter pressure before or after therapy. However, the resting pressure of the esophageal body before and after therapy was significantly lower in these patients in whom peristalsis recurred after therapy than in patients with an unchanged motility pattern. The reappearance of peristaltic activity after pneumatic dilatation was unrelated to lower esophageal sphincter pressure. In conclusion, motility disturbances of the esophageal body in patients with achalasia do not simply reflect the functional obstruction of the lower esophageal sphincter. These findings support the hypothesis that achalasia is not a distinct motility disturbance but should be regarded as part of a broad spectrum of different interrelated esophageal motility disorders.

Stress effects on gastrointestinal transit in the rat.

Previous investigations of stress effects on gastric emptying, orocaecal, and colonic transit in rats have produced conflicting results. Here one type of stressor, a 'passive avoidance' situation, was used to investigate its effects on gastric emptying, orocaecal and colonic transit. After the rats had been trained to eat a standard amount of semisolid food, gastric emptying was determined (n = 12) by the food remaining in the stomach after various periods of rest, or stress exposure. Orocaecal transit (n = 14) was determined by breath hydrogen measurements after the food had been labelled with 1 g lactose. Colonic transit (n = 18) was measured as the arrival time of coloured faeces after infusion of a carmine red solution into the caecum through a chronically implanted catheter. The stressor had differential effects on transit through the stomach, small bowel and colon: gastric emptying was delayed (p less than 0.05) after stress (t1/2 = 2.66 h after stress, 1.97 h at rest). Orocaecal transit was accelerated (p less than 0.05) after stress; transit time decreased from 124.3 min at rest to 86.2 min after stress. Colonic transit was accelerated (p less than 0.01) under stress, from 15.5 h to 1.29 h. It is concluded that gastrointestinal transit in different parts of the gastrointestinal tract is differently affected by central nervous stimuli.