Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists.

BACKGROUND AND STUDY AIMS: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. PATIENTS AND METHODS: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists' knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). RESULTS: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 ­â€Š5.5 minutes) without intervention and 6 minutes (IQR 4 ­â€Š9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 ­â€Š9 minutes) and 8 minutes (IQR 7 ­â€Š11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 ­â€Š8.705; P < 0.001). CONCLUSIONS: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR.

[Functional diarrhea - pathophysiology, investigation and treatment]. / Funktionelle Diarrhoe - Pathophysiologie, Abklärung und Therapie.

The most important reason for functional diarrhea in clinical practice is diarrhea-predominant irritable bowel syndrome (IBS) which is characterized by chronic intermittent diarrhea and abdominal pain. The pathophysiology underlying IBS is complex and includes visceral hypersensitivity, abnormal gut motility and autonomous nervous system dysfunction as well as genetic and psychosocial factors. Treatment should be tailored to the individual's symptoms and involves general measures, pharmacological treatments, dietary interventions, psychotherapy and complementary and alternative approaches. The following manuscript will give an overview over pathophysiology, reasonable investigations and treatment of IBS.

The Predominance of the Health-Promoting Patterns of Work Behavior and Experience in General Practice Teams-Results of the IMPROVEjob Study.

This study aims to identify the distribution of the "Work-related behavior and experience patterns" (Arbeitsbezogenes Verhaltens-und Erlebnismuster, AVEM) in general practitioners and their teams by using baseline data of the IMPROVEjob study. Members of 60 general practices with 84 physicians in a leadership position, 28 employed physicians, and 254 practice assistants participated in a survey in 2019 and 2020. In this analysis, we focused on AVEM variables. Age, practice years, work experience, and working time were used as control variables in the Spearman Rho correlations and analysis of variance. The majority of the participants (72.1%) revealed a health-promoting pattern (G or S). Three of eleven AVEM dimensions were above the norm for the professional group "employed physicians". The AVEM dimensions "striving for perfection" (p < 0.001), "experience of success at work" (p < 0.001), "satisfaction with life" (p = 0.003), and "experience of social support" (p = 0.019) differed significantly between the groups' practice owners and practice assistants, with the practice owners achieving the higher values, except for experience of social support. Practice affiliation had no effect on almost all AVEM dimensions. We found a high prevalence of AVEM health-promoting patterns in our sample. Nearly half of the participants in all professional groups showed an unambitious pattern (S). Adapted interventions for the represented AVEM patterns are possible and should be utilized for maintaining mental health among general practice teams.

Small Changes in Patient Arrival and Consultation Times Have Large Effects on Patients' Waiting Times: Simulation Analyses for Primary Care.

(1) Background: Workflows are a daily challenge in general practices. The desired smooth work processes and patient flows are not easy to achieve. This study uses an operational research approach to illustrate the general effects of patient arrival and consultation times on waiting times. (2) Methods: Stochastic simulations were used to model complex daily workflows of general practice. Following classical queuing models, patient arrivals, queuing discipline, and physician consultation times are three key factors influencing work processes. (3) Results: In the first scenario, with patients arriving every 7.6 min and random consultation times, the individual patients' maximum waiting time increased to more than 200 min. The second scenario with random patient arrivals and random consultation times increased the average waiting time by up to 30 min compared to patients arriving on schedule. A busy morning session based on the second scenario was investigated to compare two alternative intervention strategies to reduce subsequent waiting times. Both could reduce waiting times by a multiple for each minute of reduced consultation time. (4) Conclusions: Aiming to improve family physicians' awareness of strategies for improving workflows, this simulation study illustrates the effects of strategies that address consultation times and patient arrivals.

180° view on general practitioners' leadership skills: practice-level comparisons of leader and staff assessments using data from the cluster-randomised controlled IMPROVEjob study.

OBJECTIVES: Strong primary care leaders are needed to assure high quality services for patient populations. This study analysed general practitioners' (GP) leadership skills comparing practice-level self and staff assessments based on the full range of leadership model and the leader-member exchange (LMX). SETTING: The questionnaire survey was conducted among German general practice leaders and their staff participating in the IMPROVEjob trial. PARTICIPANTS: The study population comprised 60 German general practices with 366 participants: 84 GP practice leaders and 282 employees (28 physicians and 254 practice assistants). PRIMARY AND SECONDARY OUTCOME MEASURES: Leadership skills of the practice leaders were measured using the Integrative Leadership Questionnaire (German Fragebogen für integrative Führung) and the LMX-7 questionnaire. Leaders rated themselves and practice staff rated their leaders. The data was analysed by paired mean comparisons on the practice level. RESULTS: For most leadership dimensions, practice leaders rated themselves higher than their employees rated them. Differences were found for transformational leadership (p<0.001, d=0.41), especially for the dimensions 'innovation' (p<0.001, d=0.69) and 'individuality focus' (p<0.001, d=0.50). For transactional leadership, the dimension 'goal setting' differed significantly (p<0.01, d=0.30) but not the other dimensions. Scores for negative leadership were low and showed no differences between leaders and employees. Interestingly, employed physicians' rated their practice leaders higher on the two transformational ('performance development', 'providing a vision') and all transactional dimensions. The LMX-7 scale showed high quality relationships between leaders and employees. CONCLUSIONS: This 180° analysis of GPs' leadership skills with self and employee ratings indicated good relationships. There is a potential to improve leadership regarding goal-setting, innovation and focusing on individual team members. These results allow for the development of targeted interventions. TRIAL REGISTRATION NUMBER: German Clinical Trials Register, DRKS00012677. Registered 16 October 2019.

Gastrointestinal bleeding during anticoagulation with direct oral anticoagulants compared to vitamin K antagonists.

Aim: Patients receiving oral anticoagulants with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have an increased risk of gastrointestinal bleeding (GIB). We compared cases of GIB associated with VKAs and DOACs in terms of risk factors, scores, timing, location, severity, and outcome. Methods: Data from patients treated at a university hospital in Switzerland for GIB under VKA and DOACs between 2012 and 2018 were analyzed in this investigator-driven, retrospective, single-center study. Results: A total of 248 patients (110 males; median age, 80 years; 134 VKA, 114 DOAC) were included. No significant differences in age, weight or sex were observed. The propensity of the VKA group for risk factors such as comorbidities, interacting medications, or a high risk for bleeding (HAS-BLED score) was higher than that of the DOAC group. 56% of the VKA-treated patients had a supratherapeutic INR, and 25% in the DOAC group received an unlicensed dose. Significantly more patients in the DOAC group were not formally overdosed with OAC whilst receiving amiodarone compared to the VKA group (57% vs. 18%, respectively, p = 0.03). Latency between the documented start of oral anticoagulation and GIB was shorter in the DOAC group (median 3 months) than in the VKA group (median 23.5 months, p¡0.001). There were no differences in terms of location and severity of the GIB, length of hospitalization, or mortality. Conclusion: Patients taking VKAs displayed more risk factors for GIB than those taking DOACs. Treatment with DOACs was associated with early GIB and calls for increased vigilance during the first months after commencement. Co-medication with amiodarone appeared to be a risk factor for GIB in patients taking DOACs.

Higher Work-Privacy Conflict and Lower Job Satisfaction in GP Leaders and Practice Assistants Working Full-Time Compared to Part-Time: Results of the IMPROVEjob Study.

Background: Work-privacy conflict (WPC) has become an important issue for medical professionals. The cluster-randomized controlled IMPROVEjob study aimed at improving job satisfaction (primary outcome), with additional outcomes such as examining the work-privacy conflict in German general practice personnel. Using baseline data of this study, the relationship between work-privacy conflict and job satisfaction (JS) was analyzed. In addition, factors associated with higher WPC were identified. Methods: At baseline, 366 participants (general practitioners (GPs) in leadership positions, employed general practitioners, and practice assistants) from 60 German practices completed a questionnaire addressing socio-demographic data and job characteristics. Standardized scales from the German version of the COPSOQ III requested data concerning job satisfaction and work-privacy conflict. Both scores range from 0 (lowest) to 100 (highest). Multilevel analysis accounted for the clustered data. Statistical analyses were performed using IBM SPSS and RStudio software, with a significance level set at p < 0.05. Results: Job satisfaction was 77.16 (mean value; SD = 14.30) among GPs in leadership positions (n = 84), 79.61 (SD = 12.85) in employed GPs (n = 28), and 72.58 (SD = 14.42) in practice assistants (n = 254). Mean values for the WPC-scale were higher for professionals with more responsibilities: GPs in leadership positions scored highest with 64.03 (SD = 29.96), followed by employed physicians (M = 45.54, SD =30.28), and practice assistants (M = 32.67, SD = 27.41). General practitioners and practice assistants working full-time reported significantly higher work-privacy conflict than those working part-time (p < 0.05). In a multilevel analysis, work-privacy conflict was significantly associated with job satisfaction (p < 0.001). A multiple regression analysis identified working hours, as well as and being a practice owner or an employed physician as factors significantly influencing WPC. Discussion: WPC was high among general practice leaders and practice personnel working full-time. Future interventions to support practice personnel should focus on reducing WPC, as there is good evidence of its effects on job satisfaction.

Leadership program with skills training for general practitioners was highly accepted without improving job satisfaction: the cluster randomized IMPROVEjob study.

Leadership has become an increasingly important issue in medicine as leadership skills, job satisfaction and patient outcomes correlate positively. Various leadership training and physician psychological well-being programmes have been developed internationally, yet no standard is established in primary care. The IMPROVEjob leadership program was developed to improve job satisfaction among German general practitioners and practice personnel. Its acceptance and effectiveness were evaluated. The IMPROVEjob intervention is a participatory, interdisciplinary and multimodal leadership intervention that targets leadership, workflows and communication in general practices using three elements: (1) two leadership workshops with skills training; (2) a toolbox with printed and online material, and (3) a 9-month implementation phase supported by facilitators. A cluster-randomised trial with a waiting-list control evaluated the effectiveness on the primary outcome job satisfaction assessed by the Copenhagen Psychosocial Questionnaire (range 0-100). A mixed-methods approach with questionnaires and participant interviews evaluated the acceptance of the intervention and factors influencing the implementation of intervention content. Statistical analyses respected the clustered data structure. The COVID-19 pandemic necessitated intervention adjustments: online instead of on-site workshops, online material instead of facilitator practice visits. Overall, 52 of 60 practices completed the study, with altogether 70 practice leaders, 16 employed physicians, and 182 practice assistants. According to an intention-to-treat analysis, job satisfaction decreased between baseline and follow-up (not significantly) in the total study population and in both study arms, while the subgroup of practice leaders showed a non-significant increase. A mixed multilevel regression model showed no effect of the intervention on job satisfaction (b = - 0.36, p > 0.86), which was influenced significantly by a greater sense of community (b = 0.14, p < 0.05). The acceptance of the IMPROVEjob workshops was high, especially among practice leaders compared to assistants (1 = best to 5 = worst): skills training 1.78 vs. 2.46, discussions within the practice team 1.87 vs. 2.28, group discussions 1.96 vs. 2.21. The process evaluation revealed that the COVID-19 pandemic complicated change processes and delayed the implementation of intervention content in practice routines. The workshops within the participatory IMPROVEjob intervention were rated very positively but the multimodal intervention did not improve job satisfaction 9 months into the pandemic. Qualitative data showed an impairment of implementation processes by the unforeseeable COVID pandemic.Trial registration Registration number: DRKS00012677 on 16/10/2019.

Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by dense tissue eosinophilia; it is refractory to proton pump inhibitor therapy. EoE affects all age groups but most frequently individuals between 20 and 50 years of age. Topical corticosteroids are effective in pediatric patients with EoE, but no controlled studies of corticosteroids have been reported in adult patients. METHODS: We performed a randomized, double-blind, placebo-controlled trial to evaluate the effect of oral budesonide (1 mg twice daily for 15 days) in adolescent and adult patients with active EoE. Pretreatment and posttreatment disease activity was assessed clinically, endoscopically, and histologically. The primary end point was reduced mean numbers of eosinophils in the esophageal epithelium (number per high-power field [hpf] = esophageal eosinophil load). Esophageal biopsy and blood samples were analyzed using immunofluorescence and immunoassays, respectively, for biomarkers of inflammation and treatment response. RESULTS: A 15-day course of therapy significantly decreased the number of eosinophils in the esophageal epithelium in patients given budesonide (from 68.2 to 5.5 eosinophils/hpf; P < .0001) but not in the placebo group (from 62.3 to 56.5 eosinophils/hpf; P = .48). Dysphagia scores significantly improved among patients given budesonide compared with those given placebo (5.61 vs 2.22; P < .0001). White exudates and red furrows were reversed in patients given budesonide, based on endoscopy examination. Budesonide, but not placebo, also reduced apoptosis of epithelial cells and molecular remodeling events in the esophagus; no serious adverse events were observed. CONCLUSIONS: A 15-day course of treatment with budesonide is well tolerated and highly effective in inducing a histologic and clinical remission in adolescent and adult patients with active EoE.

Long-term budesonide maintenance treatment is partially effective for patients with eosinophilic esophagitis.

BACKGROUND & AIMS: Topical corticosteroids are effective in inducing clinical and histologic remission in patients with eosinophilic esophagitis (EoE). However, the best long-term management strategy for this chronic inflammatory disease has not been determined. METHODS: In a randomized, double-blind, placebo-controlled, 50-week trial, we evaluated in 28 patients the efficacy of twice-daily swallowed budesonide (0.25 mg each) to maintain quiescent EoE in remission. Pretreatment and posttreatment activity was assessed clinically, endoscopically, histologically, immunohistologically, and by endosonography. The primary end point was the therapy's ability to maintain EoE in histologic remission. Secondary end points were efficacy in symptom control, prevention of tissue remodeling, and safety. RESULTS: In patients given low-dose budesonide, the load of esophageal eosinophils increased from 0.4 to 31.8 eosinophils/high-power field (P = .017). In patients given placebo, the load increased from 0.7 to 65.0 eosinophils/high-power field (P = .0001); this increase was significantly greater than in patients given budesonide (P = .024). The symptom scores developed in a similar manner in the 2 groups. Budesonide, but not placebo, reduced noneosinophilic markers of inflammation, epithelial cell apoptosis, and remodeling events. Compared with control individuals, patients had significantly thickened esophageal walls, based on endosonography (3.05 vs 2.18 mm; P < .0001). Budesonide therapy was associated with a significant reduction in mucosal thickness (0.75-0.45 mm; P = .025), but epithelial thickness remained stable (261.22 vs 277.23 µm; P = .576). No serious adverse events occurred. CONCLUSIONS: Low-dose budesonide is more effective than placebo in maintaining EoE in histologic and clinical remission. Signs of esophageal remodeling showed a trend toward normalization. Long-term administration of topical corticosteroids was well tolerated without induction of epithelial atrophy.

Propofol sedation alone or in combination with pharyngeal lidocaine anesthesia for routine upper GI endoscopy: a randomized, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: In patients undergoing routine upper EGD, propofol is increasingly used without pharyngeal anesthesia because of its excellent sedative properties. It is unclear whether this practice is non-inferior in regard to ease of endoscopic intubation and patient comfort. OBJECTIVE: To assess the relevance of local pharyngeal anesthesia regarding the ease of EGD performance in patients sedated with propofol as monotherapy. DESIGN: Randomized, double-blind, placebo-controlled, non-inferiority trial. SETTING: One community hospital and one university hospital in Switzerland. PATIENTS: We enrolled 300 consecutive adult patients undergoing elective EGD. INTERVENTION: Pharyngeal anesthesia with 4 squirts of lidocaine spray versus placebo spray immediately before propofol sedation. MAIN OUTCOME MEASUREMENTS: Number of gag reflexes (primary endpoint), number of intubation attempts, and degree of salivation during intubation (secondary endpoints) assessed by the endoscopists and staff. RESULTS: In the lidocaine group, 122 patients (82%) had no gag events, and 25 patients had a total of 39 gag events, whereas in the placebo group 104 patients (71%) had no gag events, and 43 patients had a total of 111 gag events. The rate ratio of gagging with quasi-likelihood estimation of placebo compared with lidocaine was 2.85 (95% confidence interval [CI], 1.42-6.19; P = .005). In adjusted logistic regression analysis, the odds ratio for gagging for placebo pharyngeal anesthesia compared with lidocaine was 1.9 (95% CI, 1.03-3.54). The number of intubation attempts and the degree of salivation were similar in both groups. Two patients in the placebo group experienced oxygen desaturation and needed short-term mask ventilation. LIMITATIONS: The level of sedation and possible long-term side effects of pharyngeal anesthesia were not assessed. CONCLUSION: Topical pharyngeal anesthesia reduces the gag reflex in patients sedated with propofol even though it does not seem to have an influence on the ease of the procedure and on patient or endoscopist satisfaction in adequately sedated patients.

Job Satisfaction and Chronic Stress of General Practitioners and Their Teams: Baseline Data of a Cluster-Randomised Trial (IMPROVEjob).

Background: A high prevalence of poor job satisfaction and high chronic stress is documented for general practitioners (GPs) and non-physician practice staff from various countries. The reasons are multifactorial and include deficits in leadership, communication and workflows. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVEjob intervention on improving job satisfaction among GPs and practice personnel. Here, we report the baseline characteristics of the participating GPs and practice assistants, focusing on job satisfaction and perceived chronic stress. Methods: The IMPROVEjob study was performed as a cluster-randomised, controlled trial (cRCT) with German GP practices in the North Rhine Region. The IMPROVEjob intervention comprised two leadership workshops (one for practice leaders only; a second for leaders and practice assistants), a toolbox with supplemental printed and online material, and a nine-month implementation phase supported by IMPROVEjob facilitators. The intervention addressed issues of leadership, communication, and work processes. During study nurse visits, participants completed questionnaires at baseline and after nine months follow up. The primary outcome was the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (German COPSOQ, version 2018). Perceived chronic stress was measured using the Trier Inventory of Chronic Stress (TICS- SSCS). Results: Recruitment of 60 practices was successful: 21 were solo, 39 were group practices. At baseline, n = 84 practice owners, n = 28 employed physicians and n = 254 practice assistants were included. The mean age of all participants was 44.4 (SD = 12.8). At baseline, the job satisfaction score in the total sample was 74.19 of 100 (±14.45) and the perceived chronic stress score was 19.04 of 48 (±8.78). Practice assistants had a significantly lower job satisfaction than practice owners (p < 0.05) and employed physicians (p < 0.05). In the regression analysis, perceived chronic stress was negatively associated with job satisfaction (b= -0.606, SE b = 0.082, p < 0.001, ICC = 0.10). Discussion: The degree of job satisfaction was similar to those in other medical professionals published in studies, while perceived chronic stress was markedly higher compared to the general German population. These findings confirm the need for interventions to improve psychological wellbeing in GP practice personnel.

Colon Capsule Endoscopy compared to Conventional Colonoscopy under routine screening conditions.

BACKGROUND: Colonoscopy (CSPY) for colorectal cancer screening has several limitations. Colon Capsule Endoscopy (PillCam Colon, CCE) was compared to CSPY under routine screening conditions. METHODS: We performed a prospective, single-center pilot study at a University Hospital. Data were obtained from November 2007 until May 2008. Patients underwent CCE on Day 1 and CSPY on Day 2. Outcomes were evaluated regarding sensitivity and specificity of polyp detection rate, with a significance level set at >5 mm. RESULTS: 59 individuals were included in this study, the results were evaluable in 56 patients (males 34, females 22; median age 59). CCE was complete in 36 subjects. Polyp detection rate for significant polyps was 11% on CSPY and 27% on CCE.6/56 (11%) patients had polyps on CSPY not detected on CCE (miss rate).Overall sensitivity was 79% (95% confidence interval [CI], 61 to 90), specificity was 54% (95% CI, 35 to 70), positive predictive value (PPV) was 63% and negative predictive value (NPV) was 71%. Adjusted to significance of findings, sensitivity was 50% (95% CI, 19 to 81), specificity was 76% (95% CI, 63 to 86), PPV was 20% and NPV was 93%. CONCLUSION: In comparison to the gold standard, the sensitivity of CCE for detection of relevant polyps is low, however, the high NPV supports its role as a possible screening tool. TRIAL REGISTRATION: NCT00991003.

Serum protein electrophoresis: an underused but very useful test.

Serum protein electrophoresis is used in clinical practice to identify patients with multiple myeloma and other serum protein disorders. It is an inexpensive and easy-to-perform screening procedure. Electrophoresis separates serum proteins based on their physical properties and identifies morphologic patterns in response to acute and chronic inflammation, various malignancies, liver or renal failure, and hereditary protein disorders. For gastroenterologists, the use of serum protein electrophoresis may be helpful in the diagnosis of both common diseases with unusual presentations and rare disorders with typical presentations. Therefore, it represents an ideal screening tool.

Cystic and solid lesions of the pancreas.

More than 95% of malignant tumours of the pancreas are exocrine carcinomas. The exocrine carcinomas have to be distinguished from benign serous cystadenomas and tumours, the latter including mucinous cystic neoplasms, serous cysts, and solid pseudopapillary neoplasms. Cystic lesions have to be separated from pseudocysts, which are the most common cysts. Pseudocysts are due to extensive confluent autodigestive tissue necrosis caused by alcoholic, biliary, or traumatic acute pancreatitis. This review focuses on the classification of the different types of solid and cystic lesions based on histological criteria. The various imaging procedures are also discussed, along with their strengths and limitations.

Escherichia coli bloodstream infection preceding the diagnosis of rectal carcinoma.

BACKGROUND: Cancer is one of the major comorbidities in patients with sepsis, and conversely, bloodstream infections (BSI) may precede the diagnosis of colorectal malignancy, in particular when Streptococcus gallolyticus is isolated. We present the rare case of an Escherichia coli BSI preceding the diagnosis of rectal adenocarcinoma. CASE PRESENTATION: A 56-year-old man with a history of ocular myasthenia gravis presented with fever and shaking chills, and was diagnosed with E. coli BSI of unknown origin. After a thorough history and examination, diagnostic workup revealed a rectal adenocarcinoma as portal of entry for E. coli BSI. The choice of definitive antibiotic treatment was complicated by the risk of myasthenia gravis exacerbation by several classes of antibiotics. CONCLUSIONS: In patients with E. coli BSI of unknown origin, clinicians need a high index of suspicion regarding underlying colorectal malignancies. This may permit earlier diagnosis in a potentially curable stage.

Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects.

CONTEXT: An oral formulation of EP01572, a peptidomimetic growth hormone secretagogue, was studied. An oral delivery system would be preferable in many of the possible therapeutic indications of ghrelin agonists such as EP01572. OBJECTIVES: Our objective was to establish the pharmacological profile and the GH-releasing activity of increasing oral doses of EP01572 in healthy volunteers. In addition, the pharmacokinetics and pharmacological effects of EP01572 were investigated after intraduodenal (ID) administration. SETTING: This study was a single-center escalating dose study with oral and ID applications. SUBJECTS AND METHODS: In the first part, EP01572 was given orally to 36 male subjects; the treatment consisted of one oral dose of either EP01572 or placebo (0.005, 0.05, and 0.5 mg/kg body weight). Six subjects received two additional oral doses of EP01572: 0.125 and 0.25 mg/kg body weight. In the second part, the following treatments were performed in a randomized order: 1) administration of a bolus of saline (placebo) to the small intestine; 2) ID administration of a bolus of EP01572 at 0.2 mg/kg body weight; 3) ID perfusion of a bolus of EP01572 at 0.35 mg/kg body weight; and 4) ID perfusion of a bolus of EP01572 at 0.5 mg/kg body weight. RESULTS: The oral and ID administration of EP01572 induced a rapid and dose-dependent increase in plasma drug concentrations and a potent GH release in healthy male volunteers. CONCLUSIONS: This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration.

Primary intestinal lymphangiectasia in an elderly female patient: A case report on a rare cause of secondary immunodeficiency.

Protein loss via the gut can be caused by a number of gastrointestinal disorders, among which intestinal lymphangiectasia has been described to not only lead to a loss of proteins but also to a loss of lymphocytes, resembling secondary immunodeficiency. We are reporting on a 75-year-old female patient who came to our hospital because of a minor stroke. She had no history of serious infections. During the diagnostic work-up, we detected an apparent immunodeficiency syndrome associated with primary intestinal lymphangiectasia. Trying to characterize the alterations of the immune system, we not only found hypogammaglobulinemia and lymphopenia primarily affecting CD4+, and also CD8+ T cells, but also marked hypocomplementemia affecting levels of complement C4, C2, and C3. The loss of components of the immune system most likely was due to a chronic loss of immune cells and proteins via the intestinal lymphangiectasia, with levels of complement components following the pattern of protein electrophoresis. Thus, intestinal lymphangiectasia should not only be considered as a potential cause of secondary immune defects in an elderly patient, but can also be associated with additional hypocomplementemia.

Gastrointestinal satiety signals in humans--physiologic roles for GLP-1 and PYY?

The present review summarizes the appetite suppressing effects of PYY and GLP-1 in the regulation of food intake in humans. Current evidence supports a role for gastrointestinal peptides as regulators of satiety. The regulation of satiety is, however, complex and it is not surprising that multiple control systems exist. It is interesting to note that nutrients in the small intestine such as hydrolysis products of fat stimulate the release of satiety peptides such as GLP-1 or PYY that serve as satiety signals. Both peptides, released from L-cells from the gastrointestinal tract by the local action of digested food, exert various regulatory functions: stimulation of insulin secretion and inhibition of glucagon secretion as typical actions of GLP-1, inhibition of gastric emptying, and inhibition of appetite for both GLP-1 and PYY. The review focuses on the question, whether the two peptides are true endocrine factors that act as physiologic, hormonal regulators of appetite.