Compromised duodenal mucosal integrity in children with short bowel syndrome after adaptation to enteral autonomy

BackgroundIntestinal adaptation has been extensively studied experimentally, but very limited data is available on human subjects. In this study we assessed intestinal adaption in humans with short bowel syndrome (SBS).MethodsWe comparatively evaluated mucosal hyperplasia, inflammation, barrier function and nutrient transport using histology, immunohistochemistry and qPCR for selected 52 key genes in duodenal biopsies obtained from children with SBS after weaning off parenteral nutrition (n = 33), and matched controls without intestinal pathology (n = 12). Small bowel dilatation was assessed from contrast small bowel series.ResultsDuodenal mucosa of SBS children showed increased histologic inflammation of lamina propria (p = 0.033) and mucosal mRNA expression of tumor necrosis factor (p = 0.027), transforming growth factor (TGF)-β2 (p = 0.006) and caveolin-1 (CAV1; p = 0.001). Villus height, crypt depth, enterocyte proliferation, apoptosis and expression of proliferation and nutrient transport genes remained unchanged. Pathologic small bowel dilatation reduced crypt depth (p = 0.045) and downregulated mRNA expression of interleukin (IL)-6 by three-fold (p = 0.008), while correlating negatively with IL6 (r = -0.609, p = 0.004). Loss of ileocecal valve (ICV) upregulated mRNA expression of toll-like receptor 4 (TLR4), TGF-β1, CAV1, several apoptosis regulating genes, and mRNA expression of zonulin (p < 0.05 for all).ConclusionsDespite successful adaptation to enteral autonomy, duodenal mucosa of SBS children displayed histologic and molecular signs of abnormal inflammation and regulation of epithelial permeability, whereas no structural or molecular signs of adaptive hyperplasia or enhanced nutrient transport were observed. Excessive dilatation of the remaining small bowel paralleled impaired duodenal crypt homeostasis, while absence of ICV modified regulation of mucosal inflammation, regeneration and permeability.Level of evidenceII     

Colonic methanogenesis in vivo and in vitro and fecal pH after resection of colorectal cancer and in healthy intact colon

Purpose  

We compared colonic methanogenesis in vivo and in vitro as well as fecal pH in healthy subjects and in patients with resected colorectal cancer thus without the possible confounding effects of the tumor.     

High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

AIM: To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism.METHODS: Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF).RESULTS: Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P < 0.001). The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P < 0.01) and correlated inversely with intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon.CONCLUSION: High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.     

Comprehensive characterization of HNPCC-related colorectal cancers reveals striking molecular features in families with no germline mismatch repair gene mutations

A considerable fraction of families with HNPCC shows no germline mismatch repair (MMR) gene mutations. We previously detected 'hidden' MMR gene defects in 42% of such families, leaving the remaining 58% 'truly' mutation negative. Here, we characterized 50 colorectal carcinomas and five adenomas arising in HNPCC families; 24 truly MMR gene mutation negative and 31 MMR gene mutation positive. Among 31 tumors from MMR gene mutation positive families, 25 (81%) had active Wnt signaling as indicated by aberrant beta-catenin localization with or without CTNNB1 mutations, compared to only 7/18 tumors from MMR gene mutation negative families (39%; P=0.005). CGH studies revealed stable profiles in 9/16 (56%) of MMR gene mutation negative tumors, which was significantly associated with membranous beta-catenin (P=0.005). Tumors with membranous beta-catenin from the MMR gene mutation negative group also showed low frequency of TP53 mutations compared to those with nuclear beta-catenin. Thus, a majority of the MMR gene mutation negative cases exhibited a novel molecular pattern characterized by the paucity of changes in common pathways to colorectal carcinogenesis. This feature distinguishes the MMR gene mutation negative families from both HNPCC families linked to MMR defects and sporadic cases, suggesting the involvement of novel predisposition genes and pathways in such families.     

Do individuals with former amphetamine dependence have cognitive deficits?

The association between former amphetamine dependence and cognitive performance was studied in a sample of 12 individuals with former amphetamine dependence who had been abstinent for at least 1 year and in 12 age-, gender- and verbal IQ-matched controls. The groups were compared by cognitive tests on attention, memory, executive function and fluid intelligence. Individuals with former amphetamine dependence performed significantly poorer than controls in memory domain. Follow-up analysis of variance showed minor deficits in tests of delayed verbal memory. The results remained essentially the same when participants with current DSM-IV axis I diagnosis were excluded from the analysis. It is concluded that individuals with former amphetamine dependence have normal cognitive function with the possible exception of verbal memory. Thus, if widespread cognitive deficits are found in individuals with former amphetamine dependence, etiologies other than amphetamine abuse as such should be carefully investigated.     

Color vision and contrast sensitivity in epilepsy patients treated with initial tiagabine monotherapy

The purpose of the study was to determine whether the use of a GABAergic antiepileptic drug (AED), tiagabine, affects color vision and contrast sensitivity. Twenty newly diagnosed patients with partial epilepsy (aged 19-72 years), receiving tiagabine as their initial monotherapy for 5-41 months were examined. Color vision was examined with the Standard Pseudoisochromatic Plates 2 (SPP2), with the Farnsworth-Munsell 100 Hue Test (FM100) and with the Color Vision Meter 712 (CVM) anomaloscope. Contrast sensitivity was measured with the Pelli-Robson letter chart. Three patients excluded from the color vision evaluation for congenital red-green color vision defects. Seven out of 17 patients (41%) had acquired color vision deficit examined with the FM100. The CVM anomaloscope revealed minor defects in two patients. Contrast sensitivity function was within normal ranges. The present study suggests that AED therapy with tiagabine, like with other established and newer AEDs may interfere with color perception.     

The use of physical restraint in institutional care of older people in Finland: nurses’ individual,communal and alternative modes of action

Aims and objectives. The aim of the study was to map nursing staff’s individual, communal and alternative modes of action in situations where they used physical restraint of older people in Finland. Background. The use of physical restraint in institutional care of older people involves modes of action that are linked to the personalities and modes of operation of individual nurses or to communal modes of operation mutually agreed on in the workplace. Nurse’s individual modes of operation are linked to consideration towards older people when using physical restraint. Communal modes of operation include joint discussion among nurses, decision‐making and written guidelines concerning the use of physical restraint. Design. A quantitative survey. Methods. The data were collected from nurses (n = 1148) working in healthcare centre wards, municipal and private nursing homes in Finland using a structured questionnaire (response rate 78%). Results. Older nurses and those with the longest working experience were most active in using individual modes of operation in situations where physical restraint was applied. Nurses’ participation in continuing education in care of older people increased the use of both individual and alternative modes of action. The alternative modes of action were one that understands the older person and one that focuses on negotiation. The use of physical restraint was often discussed in the workplace during information sessions or during work, but only 33% had written guidelines on the use of physical restraint. Conclusions. Education can be used to increase nurses’ ability to use alternative modes of action and thus decrease the use of physical restraint in institutional care of older people. Nursing management has a key role in making sure that units caring for older people receive written guidelines on the use of physical restraint. Relevance to clinical practice. Locums especially need more education to avoid the use of physical restraint.     

Propofol and barbiturates for the anesthesia of refractory convulsive status epilepticus: pros and cons

OBJECTIVE: To discuss mainly the use of propofol and barbiturates in the anesthesia of refractory status epilepticus (RSE). METHODS: Review of literature. RESULTS: There are no prospective, randomized works comparing the effects of anesthetics in the treatment of RSE. Recently, the use of propofol has increased in the treatment of RSE. Propofol terminates both clinical and electric seizures quickly, but the maintenance of burst-suppression EEG pattern requires repetitive titration of doses. Relapses of seizures have occurred in 19-33% of patients, especially when tapering of dose. The advantages of barbiturates are lower frequency of short-term treatment failures, breakthrough seizures and changes to a different anesthetic agent. On the other hand, prolonged recovery leads to prolonged duration of mechanical ventilation, intensive care and hospital stay. DISCUSSION: The use of propofol, barbiturates or midazolam in the anesthesia of RSE can be justified. When using propofol, the duration of high doses should be limited to 48 hours and the risk of propofol infusion syndrome should be kept in mind. High doses of barbiturates terminate effectively seizures but recovery from anesthesia prolongs ventilator treatment and intensive care.