The impact of longitudinal intestinal lengthening and tailoring on liver function in short bowel syndrome.

INTRODUCTION: Short bowel syndrome is a functional or anatomic loss of major parts of the small bowel leading to severe malnutrition. The limiting factor for the survival of these patients remains parenteral nutrition-related liver damage leading to end-stage liver failure. Longitudinal intestinal lengthening and tailoring (LILT) has been proven to enhance peristalsis, to decrease bacterial overgrowth and to extend the mucosal contact time for the absorption of nutrients. The aim of this study was to show the impact of LILT on the development of parenteral nutrition-related liver damage. PATIENTS AND METHODS: A cohort of 55 patients with short bowel syndrome managed with LILT in our institution between 1987 and 2007 was retrospectively reviewed. LILT was performed at a mean age of 24 months (range 4 - 150 months). Mean follow-up time was 83.76 months (range 5 - 240 months). We obtained reliable data from 31 patients with regard to liver enzymes and function parameters in blood samples before LILT and at the present time. Liver biopsy was performed in 14 patients prior to LILT. RESULTS: Liver enzymes ALAT (mean 121 U/l), ASAT (mean 166 U/l) and bilirubin (mean 2.49 mg/dl) were elevated preoperatively in 27/31 children. After the lengthening procedure, ALAT (mean 50 U/l), ASAT (mean 63 U/l) and bilirubin (mean 1.059 mg/dl) normalized except in 5 of 8 patients who could not be weaned from parenteral nutrition after LILT. Liver function parameters such as the international normal ratio (INR) were slightly elevated in 5/31 patients. Albumin was generally low, probably due to parenteral nutrition. Liver biopsy was performed in 14 patients preoperatively, showing 4 patients with low-grade, 6 patients with intermediate and 4 patients with high-grade fibrosis. End-stage liver disease with cirrhosis was an exclusion criterion for LILT. All patients with liver fibrosis showed a normalization of liver enzymes when they were weaned from parenteral nutrition. But patients with higher grade liver fibrosis tend to develop more complications perioperatively. CONCLUSION: After LILT, all patients with liver fibrosis who could be weaned from parenteral nutrition showed a normalization of liver enzymes. Preoperative liver biopsy is mandatory in order to differentiate reversible liver fibrosis from end-stage liver disease. A higher grade of liver fibrosis and elevated INR has been shown to be a sensitive parameter for peri- and postoperative complications.

Association between students' personality traits and hand hygiene compliance during objective standardized clinical examinations.

BACKGROUND: Although the need for hand hygiene (HH) is generally accepted, studies continue to document inadequate compliance. Medical students are taught about the importance of HH to prevent nosocomial infections, and receive training in the correct procedures for HH. However, personality traits (social orientation and achievement orientation) may influence HH compliance. People with high social orientation feel socially responsible and act cooperatively, and people with high achievement orientation are ambitious and competitive. AIM: To evaluate the relationship between HH compliance and personality traits of medical students. METHODS: The HH compliance of 155 students was observed during objective standardized clinical examinations (OSCEs). Social orientation and achievement orientation were measured using the corresponding scales of the Freiburg Personality Inventory - Revised. FINDINGS: Social orientation did not differ between students with high HH compliance and students with low HH compliance [F(1) = 3.87, P = 0.052, η(2) = 0.045]. For achievement orientation, a moderate effect was found between low and high HH compliance [F(1) = 11.242, P = 0.001, η(2) = 0.119], and students with high HH compliance were found to be more achievement orientated than students with low HH compliance. CONCLUSION: Achievement orientation plays a major role during OSCEs, while social orientation is less emphasized. To the authors' knowledge, this is the first study to show that HH compliance is associated with achievement orientation in achievement situations.

What do knockout models teach us about the enteric nervous system?

Since the first histological studies, enormous strides have been made in understanding the genetics and cell biology of enteric nervous system (ENS) formation. Several mitogenic and trophic factors have been implicated in the process of neural cell proliferation and differentiation. A number of natural (piebald-lethal mice [s l], lethal spotting mice [ls], spotting lethal rats [sl]) or target (Gfralpha1-deficient mice, ret.k - mice, and NT-4 knockout mice) mutations have been reported to produce developmental defects in neural crest cell migration, differentiation or survival. Study of these mutations continues to provide new insights into this complex system. In the present investigation, we showed that a lack of basic fibroblast growth factor (FGF) or growth hormone (GH) leads to morphological abnormalities of the enteric nervous system. Because knockouts, neither of FGF nor of GH, produce enteric nervous system defects substantial enough to compromise the ability of the gut to support life, we postulate that FGF and GH affect only a relatively small subset of neurons and/or that compensatory effects of other growth factors might occur.

How to approach the ENS: various ways to analyse motility disorders in situ and in vitro.

Motility disorders of the human intestine are so variable that they cannot be diagnosed by just one technique. Their aetiology is obviously so varied that they have to be approached with a broad range of technical methods. These reach from the simple haematoxylin-stained section to the isolation of stem or precursor cells. In this study, various methods to investigate the enteric nervous system and its surrounding tissue are demonstrated. While sections from paraffin-embedded material or cryostat sections provide only a two-dimensional perspective of the ENS, the whole-mount method yields three-dimensional perspectives of large areas of the gut wall. The three-dimensional impression can even be enhanced by electron microscopy of the isolated ENS. Dynamical aspects of ENS development can be tackled by in vitro studies. The myenteric plexus can be isolated and cultivated under the influence of the microenvironment (protein extracts). Although the postnatal myenteric plexus is not fully developed, the choice of embryological neuronal cells seems to be more effective for certain approaches. They can be isolated from the embryonic mouse gut and cultivated under the influence of various factors. This method seems to us a valuable tool for the investigation of the aetiology of motility disorders, although only a "complete" approach which considers all available methods will yield at the end a clear understanding which might lead to new therapeutical concepts.

Enteric neurons from postnatal Fgf2 knockout mice differ in neurite outgrowth responses.

The enteric nervous system (ENS) consists of several neuronal subclasses with distinct functional properties. The formation and maintenance of these distinct populations during development and aging is dependent on the support of appropriate neurotrophic factors. During early postnatal development, the ENS has to adept continuously to changing alimentation situations, which might also affect neuronal maturation and differentiation. There is evidence that basic-fibroblast-growth-factor (Fgf2) exerts neurotrophic effects in the ENS. In this study primary myenteric plexus cultures from both wild type and Fgf2-knockout mice were investigated under the influence of Fgf2 and glial-cell-line-derived-factor (GDNF). It could be demonstrated, that the influence of neurotrophic support is decreased in the Fgf2-knockouts, while the neuronal cultures of wild type revealed a more pronounced receptiveness for trophic support. These data show that Fgf2 plays a role in the development of the ENS.

Temporal and regional morphological differences as a consequence of FGF-2 deficiency are mirrored in the myenteric proteome.

The enteric nervous system with its intricate network of neurons and glia shows a high plasticity, which not only changes during pre- and postnatal development, but also with disease or changing dietary habits. FGF as a potent neurotrophic factor in the central nervous system might also play a specific role for the ENS development, FGF-2 knockout and corresponding wild-type mice were histologically and functionally analyzed. FGF-2 knockout mice are viable and thrive normally and do apparently not display any obvious neurological deficit. Morphological differences were studied on whole mount preparations of muscle and submucous layer using either cuprolinic blue or immunohistochemical stainings for the neuronal marker PGP 9.5. Ussing-chamber and isometric muscle contraction experiments were performed on isolated gut wall, respectively muscle preparations. Intravital microscopy with GFP-transfected E. coli bacteria was used to investigate influences upon bacterial translocation. In additional experiments the protein pattern of the isolated myenteric plexus of knockout and wild-type mice were compared using 2D-DIGE technology. The morphometric analysis of the myenteric plexus revealed significant differences between FGF-2 knockout and wild-type animals, resulting in larger neurons in the knock out animals, embedded in less densely packed enteric ganglia. While muscle contractility appeared not to be affected, there was a significant difference in bacterial translocation as well as differences in basal chloride secretion to be seen. The observed morphological differences were reflected in the varying protein patterns, which were revealed by 2D-DIGE. A large number of differentially expressed proteins were found in both colonic and duodenal samples. FGF obviously influences the development of well established gastrointestinal functions by various means, thus leading to minor but significant deficiencies. Whether the revealed deficits in the mucous barrier are indebted to the morphological alterations in the ENS cannot yet be proved, but is very likely.