Christoph Beglinger

Endoscopist-Directed Administration of Propofol: A Worldwide Safety Experience

BACKGROUND & AIMS Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. METHODS We reviewed all published work using EDP. We contacted all endoscopists performing EDP for endoscopy that we were aware of to obtain their safety experience. These complications were available in all patients: endotracheal intubations, permanent neurologic injuries, and death. RESULTS A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was

Meta‐analysis: the treatment of irritable bowel syndrome

5.3 million. CONCLUSIONS EDP thus far has a lower mortality rate than that in published data on endoscopist-delivered benzodiazepines and opioids and a comparable rate to that in published data on general anesthesia by anesthesiologists. In the cases described here, use of anesthesia specialists to deliver propofol would have had high costs relative to any potential benefit.

Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells.

To evaluate therapies available for the treatment of irritable bowel syndrome, and provide consensus recommendations for their use, a total of 51 double‐blind clinical trials using bulking agents, prokinetics, antispasmodics, alosetron, tegaserod and antidepressants were selected. The quality of studies was assessed using 5‐point scale. Meta‐analyses were performed on all studies, and on ‘high‐quality studies’. The efficacy of fibre in the global irritable bowel syndrome symptoms relief (OR: 1.9; 95% CI:1.5–2.4) was lost after exclusion of low‐quality trials (OR: 1.4; 95% CI: 1.0–2.0, P = 0.06). When excluding the low‐quality trials, an improvement of global irritable bowel syndrome symptoms with all antispasmodics (OR: 2.1; 95% CI:1.8–2.9) was maintained only for octylonium bromide, but on the basis of only two studies. Antidepressants were effective (OR: 2.6, 95% CI: 1.9–3.5), even after exclusion of low‐quality studies (OR: 1.9, 95% CI: 1.3–2.7). Alosetron (OR: 2.2; 95% CI: 1.9–2.6) and tegaserod (OR: 1.4; 95% CI: 1.2–1.5) showed a significant effect in women. We recommend the use of tegaserod for women with irritable bowel syndrome with constipation and alosetron for women with severe irritable bowel syndrome with diarrhoea. Antidepressants can be beneficial for irritable bowel syndrome with diarrhoea patients with severe symptoms. Loperamide can be recommended in painless diarrhoea. Evidence is weak to recommend the use of bulking agents in the treatment of irritable bowel syndrome with constipation.

Gene expression of CYP3A4, ABC-transporters (MDR1 and MRP1-MRP5) and hPXR in three different human colon carcinoma cell lines.

BACKGROUND GLP-1 is secreted into the circulation after food intake. The main biological effects of GLP-1 include stimulation of glucose dependent insulin secretion and induction of satiety feelings. Recently, it was demonstrated in rats and humans that GLP-1 can stimulate renal excretion of sodium. Based on these data, the existence of a renal GLP-1 receptor (GLP-1R) was postulated. However, the exact localization of the GLP-1R and the mechanism of this GLP-1 action have not yet been investigated. METHODS Primary porcine proximal tubular cells were isolated from porcine kidneys. Expression of GLP-1R was measured at the mRNA level by quantitative RT-PCR. Protein expression of GLP-1R was verified with immunocytochemistry, immunohistochemistry and Western blot analysis. Functional studies included transport assessments of sodium and glucose using three different GLP-1 concentrations (200 pM, 2 nM and 20 nM), 200 pM exendin-4 (GLP-1 analogue) and an inhibitor of the dipeptidylpeptidase IV (DPPIV) enzyme (P32/98 at 10 microM). Finally, the expression of NHE3, the predominant Na(+)/H(+) exchanger in proximal tubular cells, was also investigated. RESULTS GLP-1R, NHE3 and DPPIV were expressed at the mRNA level in porcine proximal tubular kidney cells. GLP-1R expression was confirmed at the protein level. Staining of human and pig kidney cortex revealed that GLP-1R was predominantly expressed in proximal tubular cells. Functional assays demonstrated an inhibition of sodium re-absorption with GLP-1 after 3 h of incubation. Exendin-4 and GLP-1 in combination with P32/98 co-administration had no clear influence on glucose and sodium uptake and transport. CONCLUSION GLP-1R is functionally expressed in porcine proximal tubular kidney cells. Addition of GLP-1 to these cells resulted in a reduced sodium re-absorption. GLP-1 had no effect on glucose re-absorption. We conclude that GLP-1 modulates sodium homeostasis in the kidney most likely through a direct action via its GLP-1R in proximal tubular cells.

The effect of cholecystokinin in controlling appetite and food intake in humans

Colon carcinoma cell lines are used widely as screening models for intestinal absorption of drugs. However, the expression of important transport systems and of metabolic enzymes is not completely characterized yet. The expression and inducibility of multidrug resistance gene 1 (MDR1) and cytochrome P450 isoform 3A4 (CYP3A4) was investigated in Caco‐2 parental, Caco‐2 TC‐7 (TC‐7) and LS180 cell lines. In the same three cell lines, we investigated the expression of isoforms of the multidrug resistance associated protein family (MRP1–MRP5) and the human pregnane × receptor (hPXR), which may be important for MDR1 and CYP3A4 induction. Cells were treated with rifampicin or 1α, 25‐dihydroxycholecalciferol (1,25(OH)2D3) for 72 h and the total RNA was extracted. Afterwards reverse transcription real‐time polymerase chain reaction (TaqMan) assay was performed to determine the mRNA expression level. We have shown that in LS180 cells, MDR1 and CYP3A4 were inducible with both inducers. In Caco‐2 parental and TC‐7 cells, CYP3A4 was only inducible with 1,25(OH)2D3. Furthermore, differences were shown in gene expression of several transport proteins (MDR1 and MRP1–MRP5) and CYP3A4 in different human colon carcinoma derived cell lines. hPXR mRNA was expressed in all three cell lines but the amount of mRNA detected was significantly higher in LS180 cells than in Caco‐2 and TC‐7 cells. We concluded that LS180 cells were a suitable model to study MDR1 and CYP3A4 induction, but for drug transport studies Caco‐2 parental and TC‐7 cells would be preferred as the more physiological model.

Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study

The present review of the satiating effect of cholecystokinin in humans has revealed that cholecystokinin is a physiological satiety factor in humans. The results demonstrate the efficacy of the satiating actions of exogenous and endogenous CCK in humans. The therapeutic potential of CCK analogues cannot be estimated until further studies are performed that demonstrate the efficacy of CCK analogues for decreasing body weight, and the safety of CCK when administered repetitively for prolonged periods.

The role and utility of faecal markers in inflammatory bowel disease

BackgroundThe evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort.MethodsIn an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.ResultsMedian calprotectin levels were higher in patients with significant findings (N = 212, median 97 μg/g, IQR 43-185) than in patients without (N = 326, 10 μg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 μg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165).ConclusionIn patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.

Prevalence of anaemia in inflammatory bowel disease in Switzerland: A cross-sectional study in patients from private practices and university hospitals

Crohn’s disease and ulcerative colitis are characterized by periods of symptomatic relapse and remission. Diagnosis and assessment of inflammatory bowel disease has so far been based on clinical evaluation, serum parameters, radiology and endoscopy. Faecal markers such as calprotectin or lactoferrin have emerged as new diagnostic tools to detect and monitor intestinal inflammation. This review focuses on their potential clinical applications and limitations in the management of inflammatory bowel disease.

Progressive development of diffuse liver hemangiomatosis

BACKGROUND Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. METHODS Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤120g/L in women and ≤130g/L in men. RESULTS 125 patients from RC (66 with Crohns disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P<0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P=0.032). Supplementation therapy (iron, vitamin B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. CONCLUSIONS Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy.

Digestive physiology of the pig symposium: secretion of gastrointestinal hormones and eating control.

Diffuse liver hemangiomatosis is extremely rare. The etiology and natural history of the disease are unknown. It is also unclear whether tumor growth is induced or modulated by drug therapy. Tumor recurrence after ablative therapy has not been described in patients with diffuse liver hemangiomatosis. Diffuse hemangiomatosis of the left hepatic lobe was suspected in a 35-year-old woman by ultrasonography, CT and hepatic arteriography, and confirmed by laparotomy and biopsies. The patient denied any drug or estrogen use. The tumor was removed by left hepatectomy. Two and six years later, the patient was again hospitalized with progressive tumor growth into the right hepatic lobe. Although diffuse liver hemangiomatosis is a rare disease, its diagnosis should be considered in patients with progressive tumor growth in one or both hepatic lobes. The absence of drug intake or estrogen use does not exclude the diagnosis.