Kristin Bjørnland

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O2 compared with 21% O2. Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p = 0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O2 (p = 0.003) and 100% O2 (p = 0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O2 as compared with 21% O2 (p < 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O2 were considerably reduced compared with both baseline (p = 0.001) and piglets that were resuscitated with 21% O2 (p = 0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Our findings suggest that resuscitation of asphyxiated piglets with 100% O2 is detrimental to the piglet brain compared with resuscitation with 21% O2.

Percutaneous endoscopic gastrostomy in children : A safe technique with major symptom relief and high parental satisfaction

Background: Percutaneous endoscopic gastrostomy (PEG) is widely used for establishing enteral feeding. The aim of this study was to assess immediate and long-term results after PEG insertion. Patients and Methods: A total of 121 children were retrospectively reviewed. Median age was 2.4 years (range, 4 months–13.2 years) at the time of PEG insertion. Patient morbidity, indications for PEG, preoperative findings and perioperative complications were registered retrospectively. Parents/caregivers of 85 children were interviewed for long-term results. Results: Perioperative complications were seen in 12%. Twenty-four percent died at a median of 15 months (range, 1.5 months–8 years) after PEG. Eighty-five families were interviewed with a median follow-up time of 5.6 years (range, 1–10 years). A substantial majority (94%) of parents/caregivers reported that the PEG had a positive influence on their childs situation, and 98% would have chosen PEG insertion again. Vomiting/retching improved in 61% of the children, and oral intake enhanced in 43%. Stoma-related complications were frequent (73%). The gastrostomy tube was permanently removed at a median of 3 years (range, 7 months–7.3 years) after PEG placement in 25%. Delayed closure of the gastrocutaneous fistula after gastrostomy removal occurred in 48% of them. Time from insertion to removal was not predictive of delayed closure. Conclusion: PEG is a safe technique for establishing enteral feeding, even in very sick children. Major complications are rare, although most children experience minor stoma-related problems. Parents/caregivers report that the gastrostomy is of great help for themselves and their child.

Nuclear localization of the metastasis-related protein S100A4 correlates with tumour stage in colorectal cancer

A large number of experimental studies have linked the S100A4 gene product to the metastatic phenotype of cancer cells and clinical evidence indicates a correlation between S100A4 expression and poor prognosis in several cancer types. The aim of the present study was to analyse the expression of the S100A4 protein in colorectal cancer. Paraffin‐embedded samples from 277 colorectal cancer patients were immunostained with anti‐S100A4 antibody. Cytoplasmic staining was observed in 178 of 277 samples (64%), whereas, unexpectedly, nuclear expression of S100A4 was found in 88 of 277 of the samples (32%). This novel finding was confirmed by western blot analysis of nuclear fractions isolated from frozen tumour tissue. Statistical analysis revealed a significant correlation between nuclear expression of S100A4 and tumour stage at diagnosis, while there was no such correlation between cytoplasmic staining and tumour stage. The nuclear localization of S100A4 in colorectal cancer and its relationship to tumour stage suggest that this protein may be involved in gene regulatory pathways of relevance to the metastatic phenotype of cancer cells. Copyright

Bowel function, mental health, and psychosocial function in adolescents with Hirschsprung's disease.

Congenital intestinal malformations are uncommon and may pose lasting somatic difficulties. Patients with anorectal anomalies have a high frequency of persistent faecal dysfunction and psychosocial problems. This study examined whether adolescents with Hirschsprung’s disease have more psychosocial problems than their healthy peers. Nineteen adolescents (mean age 15.7 years) with Hirschsprung’s disease were assessed for bowel function, anorectal physiology, mental health, and psychosocial functioning by physical examinations, semistructured interview, and standardised questionnaires. The adolescents were compared with controls. The parents of 13 adolescents with Hirschsprung’s disease were interviewed and completed questionnaires. Thirty two per cent of the adolescents with Hirschsprung’s disease had significant impairment of continence, but no more psychopathology (16%) nor psychosocial dysfunction as a group than their healthy peers. Faecal incontinence was associated with poorer psychosocial functioning and parental criticism. The fact that a significant number of patients with Hirschsprung’s disease have incontinence into adulthood indicates the need for parental counselling, encouraging realistic expectations about continence.

Resuscitation of hypoxic piglets with 100% O2 increases pulmonary metalloproteinases and IL-8.

We hypothesized that resuscitation with 100% O2 compared with 21% O2 is detrimental to pulmonary tissue. The pulmonary injury was assessed by matrix metalloproteinase (MMP) activity, oxidative stress, IL-8, and histology 2.5 h after resuscitation from a hypoxic state. In pulmonary tissue extracts, MMP activity was analyzed by broad matrix–degrading capacity (total MMP) and zymography. MMP-2 mRNA expression was evaluated by quantitative real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay, and IL-8 was analyzed by ELISA technique. In bronchoalveolar lavage (BAL) fluid, MMPs were analyzed by zymography. In pulmonary tissue, pro- and active MMP-2 levels were increased in piglets that were resuscitated with 100% O2 compared with 21% O2. Pro–MMP-9, total MMP activity, and MMP-2 mRNA levels were significantly increased in resuscitated piglets compared with baseline. Net gelatinolytic activity increased in submucosa and blood vessels after 100% O2 and only in the blood vessels after 21% O2. Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O2 versus 21% O2 group. In BAL fluid, both pro–MMP-9 and pro–MMP-2 increased 2-fold in the 100% O2 group compared with 21% O2. Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O2 compared with 21% O2, suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O2 to the newborn infant.

Long-term functional, manometric, and endosonographic evaluation of patients operated upon with the Duhamel technique

Long-term functional results, anal endosonography (AES), and anal canal manometry were recorded in 48 patients aged 10 to 24 years (median 18) operated upon with the Duhamel technique for Hirschsprung’s disease; 60.4% had perfect fecal control, 31.3% occasional staining and/or gas incontinence, and 8.3% constant fecal soiling, and 10.4% complained of constipation. Compared to normals, the patients had significantly reduced anal canal resting and squeeze pressures. AES visualized scar tissue in both the internal and external anal sphincter.

Functional outcome after operation for Hirschsprung disease—transanal vs transabdominal approach

BACKGROUND It has been hypothesized that the extensive transanal dissection in transanal endorectal pull-through (TEPT) for Hirschsprung disease (HD) can impair the anal sphincters in neonates and thereby cause incontinence. Theoretically, transabdominal endorectal pull-through might have less impact on the sphincters. The aim of this study was to compare functional outcome in HD patients operated with either TEPT or laparotomy-assisted endorectal pull-through (LEPT) with particular focus on soiling and fecal incontinence. PATIENTS AND METHODS Anorectal function in 52 children older than 3 years is reported. The patients were operated for HD with either TEPT (n = 28) or LEPT (n = 24) and followed prospectively. Functional outcome was recorded by standardized interviews. The Krickenbeck criteria were used to classify voluntary bowel movements, soiling, and constipation. RESULTS The median age at follow-up was 5.7 years (3.1-13.2) for TEPT and 10.1 years (7.7-16.2) for LEPT. Twenty-nine patients reported soiling at final follow-up. There was no difference in the rate of soiling between children operated with TEPT (54%) or LEPT (58%). Constipation was reported in 11 children (TEPT, 25%; LEPT, 17%). CONCLUSIONS The functional outcome and in particular the rate of soiling did not differ between patients operated with LEPT or TEPT.

Peptidoglycan of staphyloccus aureus induces enhanced levels of matrix metalloproteinase-9 in human blood originating from neutrophils

Enhanced plasma levels of matrix metalloproteinase 9 (MMP-9) detected in patients with severe sepsis are thought to contribute to the development of organ dysfunction in endotoxemia. We have recently reported that peptidoglycan, the major wall component of gram-positive bacteria, increases MMP-9 levels in lung and liver and organ injury in the rat. Thus far, it is unclear whether MMP-9 is part of the septic response to peptidoglycan in human blood. The aim of the present study was to examine the regulation of MMP-9 by peptidoglycan in human leukocytes. The addition of peptidoglycan to whole human blood caused enhanced levels of MMP-9 after 1 h of incubation (306 vs. 75 ng/mL, P ≤ 0.05) and onward, as measured by enzyme-linked immunoabsorbant assay. In neutrophil cultures, MMP-9 values increased significantly after 30 min of incubation with peptidoglycan (242 vs. 121 ng/mL, P ≤ 0.05), whereas muramyl dipeptide had no effect. In contrast, adherent monocytes released insignificant amounts of MMP-9. To examine whether the released MMP-9 resulted from de novo synthesis, intracellular and secreted MMP-9 was measured during stimulation of neutrophils. The total MMP-9 values (the sum of intracellular and secreted MMP-9) before and after stimulation were mainly unaltered. The enhanced MMP-9 levels induced by peptidoglycan was attenuated by inhibitors of p38 mitogen-activated protein kinases (MAPK), (SB202190, 25 μM) and ERK1/2 (PD98059, 25 μM) and inhibitors of Src Tyrosine kinase (PP2, 5 μM) and PI3-K (LY294002, 25 μM).

Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide.

Background  Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia–reoxygenation injury.

Mental health and psychosocial functioning in adolescents with esophageal atresia

PURPOSE We examined mental health and psychosocial functioning in adolescents with esophageal atresia (EA) and searched for predictors of impaired outcome. METHODS The study group comprised 21 adolescents with EA and 1 or both parents. A comparison group comprised 36 adolescents from the general population. Mental health, self-esteem, psychosocial functioning, and parental/family functioning were assessed by standardized questionnaires and semistructured interviews. Physical health was assessed by growth and clinical symptoms. RESULTS Mental health and psychosocial functioning did not differ from the comparison group. Seven of 21 EA adolescents had special education. Dilatations of esophagus, birth weight, well-being, and maternal psychological distress were prognostic factors predicting mental health. Height, birth weight, well-being, dissociative symptoms, and family strain were prognostic factors predicting psychosocial functioning. CONCLUSION Adolescents with EA adjusted well, and mental health and psychosocial functioning did not differ from controls. Dilatations of esophagus and birth weight were significant predictors of mental health and psychosocial functioning.