[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.

Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2- and toll-like receptor 4-dependent pathways.

Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 10(7) E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-kappaB activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways.

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.

[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.

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.

[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 loperamide on anorectal function in normal healthy men.

Loperamide improves anorectal functioning in patients with diarrhea and incontinence. Loperamide reduces sensitivity of the recto-anal inhibitory reflex and increases internal anal sphincter tone. Additionally, it has an effect on rectal compliance in incontinent patients with diarrhea. We studied the effect of loperamide versus placebo at different distances from the anal verge in 18 healthy male volunteers, using standard anorectal manometry was a double-blind, two-factorial design. We found that the recto-anal inhibitory reflex is most pronounced when stimulated in regions close to the anal canal and that distention stimuli are also perceived best in that region. Both effects are counteracted by loperamide. We found no effect on internal sphincter tone or rectal compliance. These results imply a gradient of sensitivity for rectal perception and the recto-anal inhibitory reflex in healthy volunteers. Loperamide action on both mechanisms suggests a common mediator for both effects.

[The prevention of Pneumocystis carinii pneumonia by pentamidine inhalation]. / Prophylaxe der Pneumocystis-carinii-Pneumonie durch Pentamidin-Inhalation.

167 HIV-positive patients (155 men, 12 women; mean age 31 [18-61] years) with CD4 lymphocyte counts below 250/microliter every 4 weeks received 300 mg pentamidine per aerosol inhalation during out-patient visits, as prophylaxis against Pneumocystis carinii. 89 patients were clinically in the AIDS stage and 33 in the AIDS-related complex (ARC) stage. 29 patients had a lymphadenopathy syndrome, while 16 were asymptomatic. 130 patients received primary prophylaxis, while 37 who had previously had an attack of Pneumocystis carinii pneumonia were given pentamidine as secondary prophylaxis. During a mean observation period of 8 months three patients developed Pneumocystis carinii pneumonia (1.7%): their CD4 lymphocyte count was under 20/microliters. Pentamidine inhalation reduced the incidence of a first attack of pneumonia to 0.18% per month and recurrence to 0.32% per month. These figures confirm the great effectiveness of primary and secondary prophylaxis with pentamidine inhalation.

Anorectal manometry and defecography in the diagnosis of fecal incontinence.

We carried out anorectal manometry and defecography prospectively in 43 consecutive patients with fecal incontinence. A subgroup of 17 patients with severe incontinence was identified radiologically by a short and incompletely closed anal canal. In these patients, the anal resting pressure was significantly lower than in the rest of the group (34.9 +/- 11.4 mm Hg versus 60.0 +/- 25.7 mm Hg, respectively; p less than 0.01). The anorectal angle did not change in 24 patients during squeezing, indicating a dysfunction of the puborectalis muscle. Manometric data did not differ between this subgroup and patients with a more acute anorectal angle during voluntary sphincter contraction. This indicates that the anal pressures recorded manometrically do not reflect the function of a muscular component that is important in the maintenance of fecal continence. We conclude that anorectal manometry and defecography are complementary diagnostic tools in the investigation of patients with fecal incontinence.

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.

[Prevalence of fecal incontinence and degree of information possessed by family physicians and health insurance]. / Häufigkeit der Stuhlinkontinenz und Informations-grad von Hausärzten und Krankenkassen.

Previous investigations have demonstrated that the prevalence of fecal incontinence ranges between 1.5 and 5% in the general population. It is, however, known that only a small portion of these patients consult a doctor for the complaints. To investigate the prevalence of fecal incontinence in Germany and to determine the reliability of epidemiological data from different sources, we distributed a questionnaire to healthy controls. In addition, two samples of patients were drawn from a local health insurance organization. Finally, the family physicians of incontinence patients from a specialized outpatient clinic which are covered by this health plan (AOK) were interviewed for whether they had noted the incontinence symptoms and had reported them to the health plan. It is shown that approximately 5% of people suffer from occasional incontinence, but that only 1.5% shown severe incontinence excluded fecal soiling. In patients with various disorders, the prevalence ranges between 0.2 and 0.35% according to health insurance data. However, in only about 75% of cases, the family physicians knew about the symptom, and in less than 50% of cases they had informed the health insurance. Epidemiological data, thus, contain a detection bias leading to an underestimation of the true prevalence of fecal incontinence.