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ABSTRACT: The aim of the present study was to describe the characteristics and the postoperative results of children diagnosed as having Hirschsprung disease (HD) after the age of 3 years.
All patients with HD diagnosed after the age of 3 years in our hospital from 1998 to 2011 were included. Patient characteristics and postoperative results were prospectively registered.
Eleven children were included. Age at diagnosis was 3.0 to 9.6 years. Ten patients had rectosigmoid disease, whereas 1 had total colonic aganglionosis. Three children were given a diverting ileostomy before the pull-through procedure, and all 3 had ileostomy-related complications. Early postoperative complications were seen in 5 children, of whom 2 had anastomotic leakage. At final follow-up, with a median of 3 years postoperatively, 7 had normal bowel function, 1 had frequent loose stools, and 3 were soiling.
Early postoperative complications, especially anastomotic leakage, occurred frequently in children with late-diagnosed HD. Therefore, a diverting stoma should be considered in these patients. The long-term functional results were comparable with those seen in children operated on as neonates.
Journal of Pediatric Surgery 10/2012; 47(10):1874-9. · 1.45 Impact Factor
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ABSTRACT: OBJECTIVES:: The aim of the study was to evaluate stress in mothers of children with feeding problems before and after gastrostomy placement and to identify changes in child health and variables affecting maternal stress. METHODS:: Psychological distress and parenting stress in thirty-four mothers of children referred for gastrostomy were assessed using General Health Questionnaire (GHQ) (overall psychological distress), Impact of Event Scale (IES) (intrusive stress related to child's feeding problems) and Parenting Stress Index (PSI) (stress related to parenting) before, 6 and 18 months after placement of a gastrostomy. Information of child health and long-term gastrostomy complications were recorded. A semistructured interview constructed for this study explored maternal preoperative expectations and child's quality of life. RESULTS:: Insertion of a gastrostomy did not significantly influence vomiting or the number of children with a low weight-for-height percentile. All children experienced peristomal complications. Despite this, mothers' overall psychological distress was significantly reduced after 6 and 18 months and the majority of mothers (85%) reported that their preoperative expectations were fulfilled and that the child's quality of life was improved after gastrostomy placement. Maternal concerns for the child's feeding problems, measured as intrusive stress, had impact on maternal overall psychological distress. CONCLUSIONS:: Despite frequent stomal complications the gastrostomy significantly reduced the mothers' psychological distress and improved the child's quality of life as reported by the mother.
Journal of pediatric gastroenterology and nutrition 05/2012; · 2.18 Impact Factor
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ABSTRACT: To describe the endosonographic anatomy of anal sphincters in healthy children and to evaluate the reproducibility of sphincter thickness measurements.
Forty-five healthy children with median age of 3.6 years (range, 1.0-14.5 years) were studied while under general anesthesia for minor surgery. Anal endosonography was performed with a 7- to 10-MHz rotating transducer with a diameter of 19 mm. The internal anal sphincter (IAS) and the external anal sphincter (EAS) were assessed by 2 independent observers.
IAS and EAS were identified in all children. The mean thickness of IAS and EAS were 1.3 mm and 5.3 mm, respectively. Identification of the inner and outer border of IAS was difficult, especially in children younger than 3 years. The thickness of EAS was easier to assess, and the interrater reliability for EAS thickness measurements was excellent. EAS thickness was positively correlated with the children's age. Reflectivity varied within the EAS with frequent hyporeflective areas.
Anal endosonography provided visualization of the IAS and EAS in children. Assessment of exact IAS thickness was difficult, especially in the youngest children. Mean EAS thickness was 5.3 mm, increasing with age. Hyporeflective areas of the intact EAS should not be misinterpreted as sphincter defects.
Journal of Pediatric Surgery 08/2011; 46(8):1587-92. · 1.45 Impact Factor
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ABSTRACT: 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.
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.
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%).
The functional outcome and in particular the rate of soiling did not differ between patients operated with LEPT or TEPT.
Journal of Pediatric Surgery 08/2010; 45(8):1640-4. · 1.45 Impact Factor
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ABSTRACT: We examined mental health and psychosocial functioning in adolescents with esophageal atresia (EA) and searched for predictors of impaired outcome.
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.
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.
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.
Journal of Pediatric Surgery 05/2009; 44(4):729-37. · 1.45 Impact Factor
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ABSTRACT: Chronic somatic illness in infancy may challenge the development of mental health and impinge the infant's capability to form close interpersonal relationships. Esophageal atresia (EA) is a congenital anomaly requiring neonatal surgery, medical aftertreatment, and extended hospitalization. The aim of the study was to assess mental health and to find prognostic factors for mental health among infants with EA. Thirty-nine infants treated consecutively during 2000 to 2003 and their mothers were included. Infant mental health was assessed by Diagnostic Classification: 0–3 (Zero to Three, 1994). Medical and environmental data were collected from medical records and semistructured interview with the mothers. Child development was assessed with the Bayley scales, second edition (N. Bayley, 1993). Maternal psychological distress, anxiety, and child temperament were assessed by self-report questionnaires: the General Health Questionnaire, 30-item version (D. Goldberg & P. Williams, 1988); the State Trait Anxiety Inventory (C.D. Spielberger, R. Gorsuch, & R. Lushene, 1970); and the Infant Behaviour Questionnaire (M.K. Rothbart, 1981). Thirty-one percent of the infants with EA showed mental health disorders by 1 year of age. Prognostic factors predicting mental health were posttraumatic symptoms reported by mother, more than one operation, mechanical ventilation beyond 1 day, and moderate/severe chronic family strain. Relational trauma, vulnerable attachment, and impaired self-development are highlighted as possible pathways for psychopathology. Children with EA are vulnerable to mental health disorders, and this study may help clinicians to identify children at risk.
Infant Mental Health Journal 12/2008; 30(1):40 - 56. · 0.61 Impact Factor
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ABSTRACT: Hirschsprung's disease (HD) may be associated with inflammation in the colon. Further, the etiology of Hirschsprung-associated enterocolitis (HEC) is unclear. To learn more about these features, we examined our cohort of HD patients during a period of 6 years for inflammation in their colonic mucosa as well as for signs of HEC.
Rectal suction biopsies and operative full thickness aganglionic and ganglionic colonic specimens from 36 patients were examined. Signs of inflammation were recorded in hematoxylin/eosin/saffron (HES)-stained sections and with fluorescence conjugated polyclonal antibodies to IgA and IgG applied on serial sections. The suction biopsies were also evaluated for the presence of mucus inspissation and crypt dilatation. Clinical signs of HEC were recorded from medical files of the same 36 patients.
HES-staining revealed that seven patients had inflammation in the suction biopsies; these patients were significantly older than the patients without inflammation. Slight mucus inspissation was identified in suction biopsies of five out of 33 patients, but crypt abscesses or ulcerations were not found in any specimens. Virtually all very young patients (<3 months) had slight crypt dilatation. We identified inflammation in resected colonic segments from 17 out of 36 patients. Thirteen of these 17 had a diverting colostomy, and only one out of 14 patients with colostomy had no inflammation. Inflammatory changes were similar in ganglionic and aganglionic bowel. By immunofluorescence (IF) staining, inflammation was found in resected colonic segments from five patients. Four of these had a colostomy. HEC was diagnosed in three patients, and inflammation detected in resected specimens from only one of these three.
We have not been able to identify particular characteristics in the colonic or rectal mucosa that are linked to development of HEC. Inflammation in the resected specimen was mainly found in patients with a diverting colostomy, and then in both ganglionic and aganglionic colon.
Pediatric Surgery International 12/2008; 25(2):133-8. · 1.25 Impact Factor
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ABSTRACT: Chronic illness in infancy may influence parent-infant interaction. We assessed quality of mother-infant interaction in children with esophageal atresia (EA) and searched for predictors for impaired interaction.
The study group comprised 37 one-year-old infants with EA born in 1999 to 2002 and their mothers. A comparison group comprised 10 infants with urologic problems without feeding difficulties and their mothers. Parent Child Early Relational Assessment was used to assess mother-child interaction in feeding and play situation. General Health Questionnaire and State Trait Anxiety Inventory were used to assess maternal psychological distress and anxiety.
Many aspects of mother-EA infant interaction showed strength. However, mothers of EA children were compared to control-mothers significantly influenced in their ability to interact and the EA-mothers' "positive affective involvement, sensitivity, and responsiveness" during feeding was in range of concern. Small but significant effect of the mother's feeling of incompetence on their interaction was found.
Mothers' attitude during feeding was negatively influenced in interaction between mother and infant with EA. The results suggest possibility for improvement in mother infant interaction by enhancing mothers' welfare when caring for infants with EA in medical services.
Journal of Pediatric Surgery 11/2008; 43(10):1796-801. · 1.45 Impact Factor
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ABSTRACT: This study aimed to develop and evaluate a scoring system for anal endosonography to assess anal canal structures after repair of anorectal malformations (ARM).
Forty patients with ARM aged 16 years (range, 1-22 years) and 20 controls aged 17 years (range, 0.5-20 years) were examined. Anal function was assessed clinically and by anal canal manometry. The anal canal structures were imaged by anal endosonography using a 7.5-MHz transducer. A scoring system was developed to assess the anal sphincters as visualized on the endosonographic images.
Continence was significantly correlated to anal canal pressures. The estimated extent of muscle defect (measured in quadrants) and the number of disruptions in the internal and external anal sphincters correlated significantly to the rest and squeeze pressures, respectively. Thus, patients (>4 years) with squeeze pressure of less than 80 cm H2O were characterized by more than 1 disruption in the external anal sphincter ring and 2 or more quadrants with scar tissue.
The extent of scar tissue and the number of disruptions in the anal sphincters correlate with anal canal pressures and continence after ARM repair. Anal endosonography may be used to study the results after different surgical techniques and for prognosis on continence in patients with ARM.
Journal of Pediatric Surgery 09/2007; 42(9):1549-54. · 1.45 Impact Factor
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ABSTRACT: Dysmotility of the upper gastrointestinal tract has been reported in children with Hirschsprung's disease. In the present study, gastric emptying was studied in adult patients with Hirschsprung's disease to elucidate whether there is a persisting involvement of the upper gastrointestinal tract in this group of patients.
Gastric emptying of caloric liquids and solids was studied in 16 adult patients with surgically treated Hirschsprung's disease during early childhood and in age-matched controls. To examine liquid emptying, the paracetamol absorption test was applied using a meal containing glucose, lactose, maize oil, water (2020 kJ) and paracetamol. To examine solid emptying, the 13C gastric emptying breath test was applied using a meal containing white bread, margarine, a one-egg omelette (1050 kJ) and [13C]-octanoic acid. Gastrointestinal symptoms were recorded according to a standardized questionnaire.
For liquid meal emptying, the time until emptying commenced was 8.1+/-1.9 and 2.9+/-0.9 min (mean+/-SE) in patients and controls, respectively (p=0.02). Thereafter, the first 25% of the meal emptied in 6.8+/-0.8 and 12.1+/-1.1 min in patients and controls, respectively (p=0.0005). The overall emptying rate tended to be delayed in patients compared with controls (p=0.06). For the solid meal, a delay in emptying was evident (p=0.02). The patients reported more symptoms from the upper gastrointestinal tract than the controls, but the symptoms were not significantly related to the emptying pathology demonstrated.
The present study demonstrates that adult patients with Hirschsprung's disease have an abnormal pattern of gastric emptying, indicating persisting involvement of the upper gastrointestinal tract.
Scandinavian Journal of Gastroenterology 02/2007; 42(1):34-40. · 2.02 Impact Factor
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ABSTRACT: 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.
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.
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 child's 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.
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.
Journal of pediatric gastroenterology and nutrition 12/2006; 43(5):624-8. · 2.18 Impact Factor
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ABSTRACT: Radiofrequency (RF) ablation of hepatic metastases from colorectal cancer (CRC) is associated with a high rate of local and intrahepatic tumor recurrence. Matrix metalloproteinases (MMPs) play an important role in inflammation, tissue repair and tumor cell invasion and metastasis. MMP-2 and MMP-9 are associated with increased risk of recurrence and decreased survival in patients with colorectal cancer. The primary aim of the study was to determine if hepatic RF ablation increased MMP-2 and MMP-9 activity in the transition zone surrounding the coagulated hepatic tissue.
Twelve pigs were randomized to hepatic RF ablation with (n = 6) or without (n = 6) hepatic vascular occlusion (Pringle maneuver). Four days after ablation tissue specimens were collected from the transition zone surrounding coagulated hepatic tissue, and from normal hepatic parenchyma. MMP activity was quantified by gelatin zymography. Cellular localization of MMPs was determined by immunohistochemistry using antibodies against MMP-2, MMP-9, and the macrophage marker CD68.
MMP-2 and MMP-9 activity was increased in the transition zone compared to normal hepatic parenchyma, with ratios of 3.0 (P = 0.005) and 2.6 (P = 0.001), respectively. Pringle maneuver did not influence MMP activity. MMP-2 and MMP-9 expression was localized to macrophages in the transition zone.
Hepatic RF ablation is associated with increased expression of MMP-2 and MMP-9 in macrophages in the transition zone surrounding the coagulated hepatic parenchyma. These findings may contribute to the understanding of possible mechanisms for the high recurrence rates observed in patients after RF ablation of CRC hepatic metastases.
Journal of Surgical Research 11/2006; 135(2):297-304. · 2.25 Impact Factor
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ABSTRACT: Traditional surgical management of Hirschsprung's disease consists of a three-stage approach including proximal colostomy, definitive pull-through resection at one year of age and closure of the stoma shortly after the pull-through. At our institution, patients with this disorder have been operated with a one-stage transanal technique without laparotomy and colostomy since 2001. The early results of this procedure are presented in the article.
Complications and postoperative bowel function have been recorded after the introduction of the one-stage transanal technique.
Transanal pull-through was intended in 20 children. Laparotomy (5 patients) and laparoscopy (1 patient) were done in 6 of the children due to technical reasons. Median weight at operation was five kg (3.5-25 kg), and a median of 25 cm of bowel (9-36 cm) were resected transanally. There were no perioperative complications. Postoperative complications included stricture (3 patients), perianal excoriations (2 patients) and severe constipation (1 patient). Short term follow up shows similar bowel habits as after laparotomy procedures.
Early results show that primary transanal pull-through in Hirschsprung's disease patients with aganglionosis to descending colon is safe. It is beneficial to avoid a colostomy and probably laparotomy.
Tidsskrift for den Norske laegeforening 10/2005; 125(17):2358-9.
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ABSTRACT: 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 < or = 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 < or = 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 microM) and ERK1/2 (PD98059, 25 microM) and inhibitors of Src Tyrosine kinase (PP2, 5 microM) and PI3-K (LY294002, 25 microM).
Shock 10/2005; 24(3):214-8. · 2.85 Impact Factor
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ABSTRACT: 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.
Pediatric Research 10/2005; 58(3):542-8. · 2.70 Impact Factor
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ABSTRACT: Osteosarcoma (OS) is a highly malignant bone tumor and is the most frequent malignant bone tumor in children and adolescents. Metastases are the major cause of death, and patients with relapse have poor prognosis. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently MMP-inhibitors have entered clinical trials. A disturbance of the MMP system in favor of enhanced proteolytic activity may be suspected in OS because OS growth is accompanied by both enhanced local bone destruction and bone formation, two processes that are dependant on proteolytic enzymes. Thus, the aim of the present study was to evaluate the involvement of MMPs in a panel of human OS cell lines, xenografts and biopsies.
Expression of MMPs and their endogenous inhibitors were studied by zymography and Northern blot analyses. In vitro invasion of OS cell lines and effects of MMP-inhibitors (Marimastat and doxycycline) were assessed in the transwell chamber assay.
In vitro invasiveness was compared with gelatinase activity, and the most invasive cell line secreted the highest amounts of MMP-2 and MMP-9. Two different MMP-inhibitors significantly reduced OS cell invasion. The majority of the OS xenografts expressed both the inactive and active form of MMP-2 and in some cases also MMP-9. The biopsies from primary and metastatic OS also expressed MMP-2 mRNA. However, MMP-9 levels were higher in the biopsies than in the xenografts.
The obtained results support the hypothesis that MMPs and their endogenous inhibitors participate in the invasive process of human OS.
Journal of Surgical Research 09/2005; 127(2):151-6. · 2.25 Impact Factor
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ABSTRACT: Fifteen one-year old infants with oesophageal atresia and their parents were used to demonstrate how the Parent-Child Early Relational Assessment (PCERA) can be used to explore the mother-child interaction in a clinical sample of children. The infants and their mothers were videotaped for 5-min episodes during feeding and free play, and the quality of the mother-infant interactions was assessed by PCERA. The results showed areas of strength regarding most of the maternal, infant and dyadic components. There was concern about maternal positive physical contact, maternal quality of verbalizations to or about the child, maternal social initiative, infant's communicative competence and infant's visual contact with mother. This concern of social proximity between infants and their mothers was most prominent in the feeding situation. The present study indicates that oesophageal atresia in infants may constitute stressors impinging on the parent-infant relationship. PCERA was found to be an adequate assessment tool with acceptable reliability to evaluate the mother-infant interaction.
Nordic Journal of Psychiatry 02/2005; 59(6):498-503. · 0.98 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) have been suggested to contribute to the organ injury in septic patients. We recently demonstrated that peptidoglycan (PepG) of S. aureus causes organ injury in the rat. A possible role for MMPs in the septic response to PepG is unknown. In the present study, we have examined whether the release of MMP-9 (gelatinase B) and MMP-2 (gelatinase A) is induced by PepG in the anesthetized rat. Male Wistar rats were injected intravenously with PepG (10 mg/kg), LPS (1 mg/kg), or a combination of LPS and PepG (1 mg/kg of each). After 1 or 3 h, liver, lung, and plasma were harvested. MMP-9 and MMP-2 levels were analyzed in organ homogenates and in plasma samples by zymography. MMP-9 levels were significantly increased in the lung within 1 h after injection of PepG, LPS, or combined treatment, compared with sham animals (P < or = 0.05). In the liver and plasma, MMP-9 was clearly increased by PepG or LPS at both 1 and 3 h compared with sham animals (P < or = 0.05). Considerable basal amounts of MMP-2 protein were seen in the liver and in plasma. In the lung, MMP-2 levels were elevated by combined LPS/PepG at 1 h and by LPS at 3 h (P < or = 0.05). In contrast, MMP-2 activity in the liver was significantly reduced by bacterial products. In the plasma, no major alterations of MMP-2 levels were observed. Our data show that PepG of S. aureus causes a rapid elevation of MMP-9 protein in the liver, lung, and blood of the rat. Based on these and previous data, we hypothesize that the release of MMP-9 in lung, liver, and blood is part of the septic host response to systemic PepG.
Shock 11/2004; 22(4):376-9. · 2.85 Impact Factor
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ABSTRACT: 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% O(2) (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.
Pediatric Research 11/2004; 56(5):783-90. · 2.70 Impact Factor
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ABSTRACT: 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.
The Journal of Pathology 09/2003; 200(5):589-95. · 6.32 Impact Factor
