Intestinal ischemia measured by intraluminal microdialysis.

OBJECTIVE: To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon. METHODS: The studies were performed on male Sprague-Dawley rats. In the first part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation. RESULTS: Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage. CONCLUSION: Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and may prove to be a valuable clinical tool for diagnosing intestinal ischemia.

Age-related changes of muscle and plasma amino acids in healthy children.

The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1-4 years, n = 13 and group 3: 5-15 years, n = 15). A reference group of healthy adults (21-38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.

Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin.

Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 µg/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze-thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze-thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 µg/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

T-cell inhibition does not aggravate bacterial translocation from rat small bowel.

BACKGROUND: T-cell mediated immunity has been proposed to have an important function in the defence against translocating microbes from the gastrointestinal tract. After small bowel transplantation massive T-cell immunosuppression is necessary to avoid rejection. As a consequence, infections with intestinal bacteria are the main contributors to mortality in this setting. This could further imply that T cells are important in limiting bacterial translocation. In a model for bacterial translocation from small bowel in the rat we examined the outcome of T-cell inactivation. METHODS: The studies were performed in a model of bacterial translocation from a Thiry-Vella loop of small bowel in the rat. The animals were treated with an anti-alpha/beta T-cell receptor monoclonal antibody (R73). Inhibition of T-cell activation was also made using the immunosuppressive drug cyclosporin A. All animals were sacrificed on day 3 postoperatively and translocation to the mesenteric lymph nodes, liver, spleen, lung and blood was evaluated. RESULTS: Treatment with R73 resulted in an almost complete labelling of T cells but did not result in any increased bacterial translocation compared to animals treated with saline. Neither did immunosuppression with cyclosporin A. CONCLUSIONS: In the model of bacterial translocation from a defunctionalised loop of small bowel the inhibition of T cells does not increase bacterial translocation to mesenteric lymph nodes or promote the systemic spread of the translocating bacteria. This indicates that T cells do not have any important protective function against translocating microbes from defunctionalised small bowel.

Outcome and management in infants with esophageal atresia - A single centre observational study.

BACKGROUND/PURPOSE: A successful outcome in the repair of esophageal atresia (EA) is associated with a high quality pediatric surgical centre, however there are several controversies regarding the optimal management. The aim of this study was to investigate the outcome and management EA in a single pediatric surgical centre. METHODS: Medical records of infants with repaired EA from 1994 to 2013 were reviewed. RESULTS: 129 infants were included. Median follow-up was 5.3 (range 0.1-21) years. Overall survival was 94.6%, incidences of anastomotic leakage 7.0%, recurrent fistula 4.6% and anastomotic stricture 53.5% (36.2% within first year). In long gap EA (n=13), delayed primary anastomosis was performed in 9 (69.2%), gastric tube in 3 (23.1%) and gastric transposition in one (7.7%) infants. The incidences of anastomotic leakage and stricture in long gap EA were, 23.1% and 69.2%, respectively. Peroperative tracheobronchoscopy and postoperative esophagography were implemented as a routine during the study-period, but chest drains were routinely abandoned. CONCLUSION: The outcome in this study is fully comparable with recent international reports showing a low mortality but a significant morbidity, especially considering anastomotic strictures and LGEA. Multicenter EA registry with long-term follow up may help to establish best management of EA.

Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids.

METHODS: Anesthetized pigs were studied with [(11)C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [(11)C]-FAs from blood was measured together with the relative distribution of [(11)C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. RESULTS: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. CONCLUSIONS: [(11)C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [(11)C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs.

Reference ranges for muscle carnitine concentration in children.

BACKGROUND: We investigated muscle and plasma carnitine concentrations in children to establish reference intervals for use following biopsy of skeletal muscle. METHODS: The study comprised 50 children from newborns up to 14 years of age, all undergoing elective surgery. They were divided into six age groups, the youngest 0-2 days and the oldest 11-14 years. The samples were taken at the beginning of surgery. RESULTS: Gestational age was a major determinant of the total muscle carnitine concentration in newborns (Spearman's r(s) = 0.692, P < 0.01). This concentration was low during the first year, but subsequently did not differ between age groups. In neonates the median value (range) for total carnitine concentration in skeletal muscle was 5.9 (2.2-15.9) micro mol/g dry weight and the free to total carnitine ratio was 62 (31-81)%. In children 1-12 months old the corresponding figures were 6.0 (3.5-7.9) micro mol/g dry weight and 51 (28-71)% and in those 1-14 years they were 12.1 (6.6-17.4) micro mol/g dry weight and 76 (42-92)%. CONCLUSION: This study shows that muscle carnitine concentrations in newborns are dependent on gestational age. The data suggest that there is an accretion of carnitine in skeletal muscle during the first year of life. Reference intervals are given.

[Intestinal transplantation--an experimental therapy which has become a realistic alternative]. / Tarmtransplantation--experimentell terapi som blivit realistiskt alternativ.

Outcome after intestinal transplantation has improved dramatically since the introduction of novel immunosuppressive agents and refined surgical techniques. Small bowel transplantation is now considered to be the best treatment modality for patients with life threatening complications of intestinal failure and parenteral nutrition. We hereby review the international experience as well as the first ten cases of intestinal transplantation performed in Sweden.

The instant blood-mediated inflammatory reaction characterized in hepatocyte transplantation.

BACKGROUND: Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells. METHODS: By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood. RESULTS: We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate. CONCLUSION: Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.

Endogenous ethanol fermentation in a child with short bowel syndrome.

UNLABELLED: The term "auto-brewery syndrome" has been frequently used to describe patients who show features of alcohol intoxication because of abnormal yeast proliferation after ingesting carbohydrate-rich meals. We present a case of a 3-y-old girl with short bowel syndrome (SBS) who demonstrated signs of alcohol intoxication on repeated occasions. A blood test indicated an ethanol concentration of 15 mmol/l, and cultures from gastric fluid and faeces showed the presence of Candida kefyr. An association was found between the introduction of a carbohydrate-rich fruit drink and the occurrence of symptoms. CONCLUSION: The possibility of endogenous ethanol fermentation should be considered in patients with SBS and the diagnosis of auto-brewery syndrome added to the differential diagnosis list for D-lactic acidosis. Management includes both antifungal treatment and special diet modification.

The effect of mesenteric lymphadenectomy and Kupffer cell depletion on bacterial translocation.

BACKGROUND: Infectious complications are associated with high morbidity in patients with short bowel syndrome and after small bowel transplantation. Bacterial translocation from the intestine is probably an essential factor in the genesis of these infections. In a model for bacterial translocation in the rat we examined the consequence of mesenteric lymphadenectomy and the depletion of Kupffer cells. MATERIALS AND METHODS: The effect of mesenteric lymphadenectomy was studied in two different models; in rats where a Thiry-Vella loop had been created from small bowel and in rats that had received a syngeneic small bowel transplant. To study the role of the Kupffer cells, rats with Thiry-Vella loops were treated intravenously with the Kupffer cell inhibitor gadolinium chloride. All animals were sacrificed on Day 3 postoperatively and the bacterial translocation to the mesenteric lymph nodes, liver, spleen, lung, and blood was evaluated. RESULTS: Removal of the mesenteric lymph nodes did not result in any increased bacterial translocation in animals with a Thiry-Vella loop. However, the inactivation of Kupffer cells with gadolinium chloride produced a more severe translocation to the liver, spleen, and lungs. After small bowel transplantation the bacterial translocation to the spleen was increased in animals without mesenteric lymph nodes. CONCLUSIONS: In the model of bacterial translocation from a defunctionalized loop of small bowel the inhibition of Kupffer cells will promote the systemic spread of the translocating bacteria. This indicates an important protective function of the Kupffer cells against translocating microbes.