Gut microbiota of the European Brown Hare (Lepus europaeus).

Diseases of the gastrointestinal tract due to changes in the bacterial flora have been described with increasing incidence in the European brown hare. Despite extensive demographic and phylogeographic research, little is known about the composition of its gut microbiota and how it might vary based on potential environmental or host factors. We analysed the intestinal and faecal microbiota of 3 hare populations by Illumina MiSeq 16S rRNA gene amplicon sequencing. The phyla and OTU abundance composition differed significantly between intestinal and faecal samples (PERMANOVA: P = 0.002 and P = 0.031, respectively), but in both sample types Firmicutes and Bacteroidetes dominated the microbial community composition (45.51% and 19.30% relative abundance). Intestinal samples contained an enrichment of Proteobacteria compared with faecal samples (15.71-fold change, P < 0.001). At OTU level, a significant enrichment with best BLAST hits to the Escherichia-Shigella group, Eubacterium limosum, Sphingomonas kyeonggiensis, Flintibacter butyricus and Blautia faecis were detected in intestinal samples (P < 0.05). In our statistical model, geographic location and possibly associated environmental factors had a greater impact on the microbiota composition than host factors. Population had a significant effect on the composition of abundant intestinal and faecal OTUs, and on the abundance of potential pathogenic bacteria of the family Enterobacteriaceae, regularly associated with intestinal dysbiosis in hares, in faecal samples. Our study is the first to describe the microbiota in brown hares and provides a foundation to generate hypothesis aiming to test the role of gut health in population fluctuations of the species.

[Myelodysplastic syndromes and autoimmunity]. / Syndromes myélodysplasiques et auto-immunité.

Myelodysplastic syndromes (MDS) are characterized by inefficient hematopoiesis and result in peripheral cytopenia. This heterogenous disease group arises from clonal disorders of hematopoietic stem cells. Several cohort studies and numerous case reports have highlighted a link between MDS and autoimmune disorders. Patients with MDS are more prone to develop particular systemic inflammatory diseases. On the other hand, patients suffering from autoimmune diseases are at higher risk to develop MDS. The scope of this article is to review the association between myelodysplasia and autoimmunity. It gives practical clues when to look for MDS in a patient suffering from autoimmunity and lists the main autoimmune diseases which may complicate the course of a MDS.

Multiple strain infections and high genotypic diversity among Mycobacterium avium subsp. paratuberculosis field isolates from diseased wild and domestic ruminant species in the eastern Alpine region of Austria.

Johne's disease, or paratuberculosis, is a chronic fatal ruminant gastroenteritis caused by Mycobacterium avium subspecies paratuberculosis (MAP) whose foodborne zoonotic potential and association with Crohn's disease are still under debate. The disease is widespread but its epidemiology and epizootiology remains elusive. Wildlife is suspected to play a major role. After a surge in MAP seroprevalence in Austrian cattle, paratuberculosis was declared a notifiable disease in Austria in 2006. At the same time a rise in MAP cases in wild ruminant populations in the Austrian province of Styria was reported. All five autochthonous ruminants were affected. Genetic analysis of isolates, yielded numerous genotypes (>15) and several multiple strain infections (15%) across host species. Identical MIRU-VNTR profiles were identified in different species and sampling locations. On the other hand varying MIRU-VNTR profiles were revealed at the same location and in conspecifics. Our data, taken together with earlier epidemiological studies on MAP and other mycobacteria, raised concerns about the organisms' ecology. Constraints regarding in vitro culture of this highly fastidious organism potentially bias our current understanding of its epidemiology. We suggest that MAP infections could be polyclonal and question the informative value of genotyping a single MAP colony derived from a single specimen for epidemiological analysis of MAP.

Cooling and freezing of epididymal sperm in the common hippopotamus (Hippopotamus amphibius).

Knowledge concerning reproduction in common hippopotamus is scarce and in particular very little is known about male reproductive physiology and sperm cryopreservation. Testes were obtained from nine castrated bulls and sperm extracted from the epididymides of eight of these individuals. Mean ± SEM values of reproductive parameters were: testicular weight (including epididymis and tunicas)--275.9 ± 54.1 g, total sperm motility--88.1 ± 4.2%, total cells extracted--11.0 ± 3.6 × 10(9), intact acrosome--87.7 ± 1.8%, intact sperm morphology--51.6 ± 4.1%, and, for 3 individuals, hypoosmotic swelling test for membrane integrity-83.3 ± 1.8%. Chilled storage extenders tested were Berliner Cryomedium (BC), Biladyl(®), modification of Kenney modified Tyrode's medium (KMT), and Human Sperm Refrigeration Medium (HSRM). Extender had significant effect on post-dilution motility and motility and intact morphology after 4h and 24h at 4°C (P ≤ 0.007 for all). Berliner Cryomedium and HSRM were superior to Biladyl(®) and KMT. Freezing extenders tested were BC with either 6% dimethyl sulfoxide (Me(2)SO), or 5%, 7%, or 10% glycerol. Post-thaw motility was < 5% in 3/7 bulls in all extenders. When frozen in BC with 6% Me(2)SO, one bull had 15% post-thaw motility and 3/7 had 20 to 60%. In glycerol, 3/7 had 15-30% post-thaw motility in 5%, 2/7 in 7%, and 1/7 in 10%. The extender had significant effect on post-chilling motility (P = 0.008), post-thaw morphology (P = 0.016), and motility 30 min after thawing (P = 0.015). Berliner Cryomedium with 6% Me(2)SO or 7% glycerol were the freezing extenders of choice. Information obtained in this study allows initiation of cryobanking of sperm from the common hippopotamus which is of particular importance for genetically valuable individuals.

Non-invasive glucose monitoring in patients with diabetes: a novel system based on impedance spectroscopy.

The aim of this work was to evaluate the performance of a novel non-invasive continuous glucose-monitoring system based on impedance spectroscopy (IS) in patients with diabetes. Ten patients with type 1 diabetes (mean+/-S.D., age 28+/-8 years, BMI 24.2+/-3.2 kg/m(2) and HbA(1C) 7.3+/-1.6%) and five with type 2 diabetes (age 61+/-8 years, BMI 27.5+/-3.2 kg/m(2) and HbA(1C) 8.3+/-1.8%) took part in this study, which comprised a glucose clamp experiment followed by a 7-day outpatient evaluation. The measurements obtained by the NI-CGMD and the reference blood glucose-measuring techniques were evaluated using retrospective data evaluation procedures. Under less controlled outpatient conditions a correlation coefficient of r=0.640 and a standard error of prediction (SEP) of 45 mg dl(-1) with a total of 590 paired glucose measurements was found (versus r=0.926 and a SEP of 26 mg dl(-1) under controlled conditions). Clark error grid analyses (EGA) showed 56% of all values in zone A, 37% in B and 7% in C-E. In conclusion, these results indicate that IS in the used technical setting allows retrospective, continuous and truly non-invasive glucose monitoring under defined conditions for patients with diabetes. Technical advances and developments are needed to expand on this concept to bring the results from the outpatient study closer to those in the experimental section of the study. Further studies will not only help to evaluate the performance and limitations of using such a technique for non non-invasive glucose monitoring but also help to verify technical extensions towards a IS-based concept that offers improved performance under real life operating conditions.

Hypotheses on the role of cytokines in peptic ulcer disease.

Helicobacter pylori is the cause of chronic type B gastritis and occurs in almost all patients with duodenal ulcers. Infection with H. pylori is characterized by an increased production of several inflammatory cytokines. Increasing evidence suggests a central role of these cytokines in the pathogenesis of H. pylori-associated gastritis and peptic ulcer disease. Cytokines may be crucial in the recruitment and activation of inflammatory cells and in stimulation of gastrin release. In addition to their proinflammatory properties, cytokines may also inhibit the ulcer occurrence by stimulation of prostaglandins and somatostatin release and by direct impairment of acid secretion. The balance of these factors may determine the clinical outcome of H. pylori infection.

Performance of panel-based criteria to evaluate the appropriateness of colonoscopy: a prospective study.

BACKGROUND: Prospective data describing the appropriateness of use of colonoscopy based on detailed panel-based clinical criteria are not available. METHODS: In a cohort of 553 consecutive patients referred for colonoscopy to two university-based Swiss outpatient clinics, the percentage of patients who underwent colonoscopy for appropriate, equivocal, and inappropriate indications and the relationship between appropriateness of use and the presence of relevant endoscopic lesions was prospectively assessed. This assessment was based on criteria of the American Society for Gastrointestinal Endoscopy and explicit American and Swiss criteria developed in 1994 by a formal panel process using the RAND/UCLA appropriateness method. RESULTS: The procedures were rated appropriate or equivocal in 72.2% by criteria of the American Society for Gastrointestinal Endoscopy, in 68.5% by explicit American criteria, and in 74.4% by explicit Swiss criteria (not statistically significant, NS). Inappropriate use (overuse) of colonoscopy was found in 27.8%, 31.5%, and 25.6%, respectively (NS). The proportion of appropriate procedures was higher with increasing age. Almost all reasons for using colonoscopy could be assessed by the two explicit criteria sets, whereas 28.4% of reasons for using colonoscopy could not be evaluated by the criteria of the American Society for Gastrointestinal Endoscopy (p < 0.0001). The probability of finding a relevant endoscopic lesion was distinctly higher in the procedures rated appropriate or equivocal than in procedures judged inappropriate. CONCLUSIONS: The rate of inappropriate use of colonoscopy is substantial in Switzerland. Explicit criteria allow assessment of almost all indications encountered in clinical practice. In this study, all sets of appropriateness criteria significantly enhanced the probability of finding a relevant endoscopic lesion during colonoscopy.

Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.

Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition

Early glycogenolysis and late glycogenesis in human liver after intravenous administration of galactose.

Galactose is incorporated by a different metabolic pathway than glucose. Its contribution to glycogen synthesis has not been studied in humans. We administered galactose (0.5 g/kg iv) to overnight-fasted normal human volunteers and examined its effects on hepatic glycogen synthesis and hepatic glucose output (HGO). Hepatic glycogenesis was assessed noninvasively, determining glycogen concentration by 13C magnetic resonance spectroscopy (MRS) and liver volume by magnetic resonance imaging. HGO was determined by [6,6-2H2]glucose and gluconeogenesis calculated by adding the amount of hepatic glycogenesis to the HGO. After galactose administration, liver glycogen concentration (baseline 254 +/- 11 mmol/l) decreased in the first 45 min to 207 +/- 15 mmol/l (P < 0.05) and increased thereafter to 313 +/- 7 mmol/l (P < 0.01). Net hepatic glycogenesis was 101 +/- 12 mmol over 150 min. HGO (baseline 14.3 +/- 1.9 mumol.kg-1.min-1) increased threefold in the first 15 min and then returned to baseline. The average rate of gluconeogenesis was 12.3 mumol.kg-1.min-1. Intravenous galactose leads to an increase in hepatic glycogen and hepatic glucose output in normal humans. Competitive inhibition of UDP-glucose pyrophosphorylase by UDP-galactose could explain the apparent glycogenolysis observed early after galactose administration. 13C MRS in combination with a stable isotope tracer is a noninvasive and safe method to study hepatic carbohydrate metabolism in humans.

[Sphincter-conserving surgery in tumors of the middle and distal rectum: methods, indications and limitations]. / Sphinktererhaltende Chirurgie bei Tumoren des mittleren und distalen Rektums: Methoden, Indikation und Grenzen.

The purpose of this review is to summarize new developments in the surgical treatment of benign and malignant tumors of the rectum, focusing on oncological requirements and postoperative functional aspects which affect the quality of life. One of the developments is the transanal endoscopic microsurgical (TEM) approach to resection of adenomas and low risk early cancers in the rectum. Another focus is total rectum resection with colo-anal reconstruction with a colon pouch. This procedure reconstructs anorectal anatomy and provides nearly normal function. The reconstruction exists in two forms, (a) the colon-J-pouch and (b) the ileocecal interposition pouch (cecum pouch), which was developed at our institution. The review includes 33 consecutive patients with a rectum tumor. Standardized tumor-specific and functional staging determines which technique is used. 12 patients were operated on using the transanal endoscopic approach, 3 patients had a posterior proctotomy, another patient a transanal local excision and 17 patients total rectum resection with colon pouch reconstruction as described above.

[Helicobacter pylori resistance against metronidazole in Switzerland: implications for eradication therapy?]. / Resistenz von Helicobacter pylori gegen Metronidazol in der Schweiz: Implikationen für die Eradikationstherapie?

Gastroduodenal ulcers are strongly associated with Helicobacter pylori (HP) infection. Successful eradication drastically diminishes ulcer recurrence. Most of the eradication schemes include metronidazole (Flagyl). The present study was designed to establish the metronidazole resistance rate in Switzerland. Antral biopsies were taken in 153 patients with suspected ulcers (115 men, 38 women, mean age 46 +/- 16 [SD] years) during upper endoscopy for bacteriological testing. Metronidazole resistance (> 8 micrograms/ml) was found in 47/153 (31%) of the isolates. Resistance was found in no case to amoxicillin (Clamoxyl) (0/104 = 0%) and only in 3% (2/66) to clarithromycin (Klazid). Metronidazole resistance of HP in a third of the isolates studied is comparable to numbers found in other European countries. These findings raise the question whether eradication schemes including metronidazole without prior sensitivity testing are justified. Amoxicillin and clarithromycin appear to be valid alternatives.

[Which way ahead? Carcinoma of the exocrine pancreas, the gallbladder and the bile ducts--nonsurgical therapy in the locally advanced and in the metastasized stage]. / Wo bleibt der Fortschritt? Karzinome des exokrinen Pankreas, der Gallenblase und der Gallengänge--nicht-chirurgische Therapie im lokal fortgeschrittenen und metastasierten Stadium.

Carcinomas of the pancreas, gallbladder and bile ducts in inoperable stages can be treated with chemotherapy, radiotherapy and a combination of both modalities. Therapy is always palliative. In the past 20 years treatment results have not improved. Patients treated should be entered in controlled clinical studies with new substances randomized versus less toxic 5-FU or optimum supportive care. Pain and jaundice can be relieved by radiotherapy, bypass surgery and stent insertion. The choice of an option should be made according to patient characteristics and risk factors, as well as the possibilities and experience of the treating center.

Noninvasive observation of hepatic glycogen formation in man by 13C MRS after oral and intravenous glucose administration.

The formation of glycogen in the liver of normal volunteers was followed noninvasively with 13C magnetic resonance spectroscopy (MRS) under two different conditions: a) intravenous infusion of [1-13C]glucose under hyperglycemic and hyperinsulinemic clamp conditions, and b) oral intake of glucose in the form of a bolus. For the intravenous infusion, [1-13C]glucose with an enrichment level of 99% was employed. The C1 signals of alpha- and beta-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by 13C-MRS using nonlabeled glucose or [1-13C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance 13C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 +/- 34 mM (minimum = 160 mM; maximum = 274 mM).

[Pathophysiological and pharmacotherapeutic aspects of portal hypertension]. / Pathophysiologische und pharmakotherapeutische Aspekte der portalen Hypertonie.

Pharmacological prophylaxis and the therapy of complications of portal hypertension have recently been attracting more attention. This especially holds true for gastroesophageal variceal bleeding. Vasoconstrictors such as vasopressin, somatostatin, and beta-blockers, as well as vasodilators such as organic nitrates, alpha 2-adrenergic agonists and serotonin-antagonists, are currently used in clinical settings. The aim of this article is to delineate the present pathophysiological concepts accounting for the hemodynamic changes in animal models and patients with portal hypertension, and to summarize the mechanisms of action of the most frequently used pharmacological agents.

[Is flexible sigmoidoscopy as preventive measure for colorectal carcinoma in asymptomatic patients over 45 practicable?]. / Ist die flexible Sigmoidoskopie bei über 45jährigen asymptomatischen Patienten als Vorsorgeuntersuchung für kolorektale Karzinome praktikabel?

The efficacy of flexible sigmoidoscopy as a screening method for colorectal cancer is still undetermined, and a reduction in mortality due to this cancer by mass screening has not been demonstrated so far. An important precondition for the practicability of screening sigmoidoscopy is its acceptability by the persons to be screened. Acceptability was tested in 294 volunteers without abdominal symptoms from a general medical outpatients clinic. Mean age of participants was 58 years (45-86), 65% were men and 35% women. Sigmoidoscopy was judged harmless by 221 persons (75.1%), painful by 62 (21.1%), very painful by 11 (3.7%), and unacceptable by none. Every participant would have agreed to repeat the examination. In 36 patients 52 polyps were detected, comprising one carcinoma, 18 adenomas (in 15 patients), 32 hyperplastic polyps and one lipoma. We conclude that sigmoidoscopy was well accepted in this study and should be evaluated further as a mass screening method for colorectal cancer.

Intestinal phase of superior mesenteric artery blood flow in man.

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to study the contribution of the small intestine to the postprandial splanchnic hyperaemia, and to determine the relative potencies of the major food components in the postprandial mesenteric flow response. Duplex parameters of vessel diameter, mean velocity, and volume flow were determined serially in the basal state and after stimulation. Flow parameters were significantly (p less than 0.05) increased after liquid and solid oral meals. Modified sham feeding did not alter mesenteric blood flow. Intestinal perfusion of an isocaloric liquid test meal induced flow increases comparable with oral intake. Superior mesenteric artery blood flow also significantly (p less than 0.05) increased after isocaloric and iso-osmolar loads of intraduodenal carbohydrate, fat, and protein meals. Responses were similar after the test meal, fat, and protein, but were significantly (p less than 0.05) less for carbohydrates. Different osmolar loads of saline did not affect flow responses. We conclude that the intestinal phase is the major regulator of the postprandial mesenteric blood flow response in healthy humans and that the chemical nature of food determines the mesenteric response pattern.

[Needlestick injuries in hospital personnel and the risk of hepatitis-B infection]. / Nadelstichverletzungen beim Spitalpersonal und Risiko der Hepatitis-B-Infektion.

The risk of employees of the University Hospital of Basel acquiring virus hepatitis B following needle stick injuries (NSI) was evaluated prospectively. Over four years, 555 NSI were reported, resulting in a mean incidence of 48 NSI/1000 persons working/year. Of the injured, 455 (82%) had previously been vaccinated against hepatitis B, 32 (6%) were HBsAg and/or anti-HBc positive, and only 65 (12%) were at risk for HBV infection. The origin of 365 (66%) of the needles implicated in the NSI was identified, and of these 15 (4%) had been contaminated with HBsAg-positive blood. None of the 555 persons with NSI developed hepatitis. We conclude that the risk of HBV infection following NSI is low at our institution, but general measures need to be enforced to reduce the incidence of NSI in view of the potential risk that other infectious diseases may be transmitted by NSI.

[Multicystic chylous lymphangioma in the mesentery of the small intestine]. / Multizystisches chylöses Lymphangiom im Dünndarm-Mesenterium.

In the search for metastases computed tomography and ultrasonography of the abdomen were performed in a 47-year-old man with a known malignant melanoma in the left lower leg. Numerous fluid-filled cavities, about 8 cm in diameter, were an incidental finding. He died two years after diagnosis of the melanoma, which had extensively metastasized. At autopsy a large multicystic tumour (21 x 15 x 8 cm) was found in the mesentery of the small intestine. The cysts were filled with chyle. Histologically they proved to be multicystic lymphangiomas. Mesenteric lymphangiomas are very rare, multicystic ones and manifestation in adults even more so.