Dominique Hermans

Saccharomyces boulardii upgrades cellular adaptation after proximal enterectomy in rats.

BACKGROUND Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic effects on human and rat small intestinal mucosa. AIMS To examine the effects of S boulardii on ileal adaptation after proximal enterectomy in rats. METHODS Wistar rats, aged eight weeks, underwent 60% proximal resection or transection and received by orogastric intubation either 1 mg/g body wt per day lyophilised S boulardii or the vehicle for seven days. The effects on ileal mucosal adaptation were assessed eight days after surgery. RESULTS Compared with transection, resection resulted in mucosal hyperplasia with significant decreases in the specific and total activities of sucrase, lactase, and maltase. Treatment of resected animals with S boulardii had no effect on mucosal hyperplasia but did upgrade disaccharidase activities to the levels of the transected group. Enzyme stimulation by S boulardii was associated with significant increases in diamine oxidase activity and mucosal polyamine concentrations. Likewise, sodium dependentd-glucose uptake by brush border membrane vesicles, measured as a function of time and glucose concentration in the incubation medium, was significantly (p<0.05) increased by 81% and three times respectively in the resected group treated withS boulardii. In agreement with this, expression of the sodium/glucose cotransporter-1 in brush border membranes of resected rats treated with S boulardii was enhanced twofold compared with resected controls. CONCLUSION Oral administration of S boulardii soon after proximal enterectomy improves functional adaptation of the remnant ileum.

Early central catheter infections may contribute to hepatic fibrosis in children receiving long-term parenteral nutrition

Background: Bacterial infections in infants constitute a risk factor for parenteral nutrition (PN)–related cholestasis. The possible role of infections in the development of liver fibrosis, the most severe long-term complication, has yet to be documented. This study retrospectively compares the incidence of sepsis in children with and without severe liver fibrosis. Patients and Methods: Medical reports of 30 children in prolonged PN programs between March 1985 and March 2000 were reviewed. Starting at birth, the mean PN duration was 65 months (range, 8–150 months). According to the results of liver biopsy (LB), patients were split into 2 groups: group A (n = 16) with severe liver fibrosis (ie, septal fibrosis involving >50% of portal fields or cirrhosis) and group B (n = 14) with normal hepatic architecture or mild fibrosis (<50% of portal fields). Results: Duration of PN at the time of LB was shorter in group A (30.5 months; range, 8–96 months) than in group B (105 months; range, 37–150 months; P < 0.001). In group A the incidence of sepsis was significantly higher than in group B (3.2 ± 0.3/year vs 1.5 ± 0.2/year) and the first infection occurred earlier (group A, 1 month [range, 1–2 months]; group B, 4 months [range, 1–19 months]). By contrast, both groups were similar in terms of pregnancy duration, birth weight, age of PN onset, underlying diseases, mode of PN delivery, and number of cholestasis episodes. Conclusions: Incidence and early onset of infections may contribute to the development of liver fibrosis in cases of long-term PN. New strategies are required in prevention and treatment of infections in children receiving PN.

Mitochondrial respiratory chain defect: a new etiology for neonatal cholestasis and early liver insufficiency.

Two siblings presented with neonatal cholestasis and early liver insufficiency. The older was admitted for end-stage cirrhosis with severe hypoglycemia and had long-term successful liver transplant at the age of 15 months. The second child presented a similar neonatal history of cholestasis, hypoglycemia, hyperlactacidemia, liver insufficiency and progressive cirrhosis. Extensive work-up excluded all known causes of neonatal cholestasis. Gluconeogenesis was found normal following alanine and fructose infusion. Repeated hypoglycemia with early post-prandial hyperlactacidemia led us to investigate the mitochondrial respiratory chain enzyme activities. Selective defects of complexes I, III and IV, coded by mitochondrial DNA, were detected in liver tissue of this patient and on preserved frozen tissue from his sibling, whilst normal activities were found in liver tissue samples from control patients with end-stage liver diseases. No extrahepatic manifestations were found. We conclude that liver deficiency of mitochondrial respiratory chain enzymes may cause liver disease in neonates, associated with hypoglycemia and post-prandial hyperlactacidemia. The disease is cured by liver transplantation.

Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model

OBJECTIVES Autologous mesenchymal stem cell transplantation has been shown to improve myocardial function in ischaemic cardiomyopathy. We studied one hypothetical mechanism, neo-angiogenesis, using allogeneic mesenchymal stem cell transplantation in an ischaemic swine model. METHODS Allogeneic mesenchymal stem cells were injected in the peri-infarct area (1×10(6) cells kg(-1)) 2 weeks after myocardial infarction. Myocardial infarction alone (n=3) served as a control group. In the myocardial infarction-mesenchymal stem cells group (n=6), tacrolimus was given from day 0 to day 12. Capillary density and inflammatory/rejection processes (anti-factor VIII and anti-CD3/CD68 monoclonal antibodies, respectively) were compared between groups. RESULTS In scarred myocardium, capillary density was similar between both ischaemic groups: 15.4 (±15.3) and 14.7 (±15.2) vessel/field in myocardial infarction-mesenchymal stem cells and myocardial infarction-alone groups (non-significant). In viable myocardium adjacent to the infarction, capillary density was significantly increased in the myocardial infarction-mesenchymal stem cells group than in the myocardial infarction-alone group (p=0.002). The number of infiltrating CD3+ cells was equivalent in both myocardial infarction-alone and myocardial infarction-mesenchymal stem cells groups (CD3+: 8.6% vs 9.3%, non-significant). However, CD68+ cell infiltration was more prominent after mesenchymal stem cell transplantation (4.7% vs 2% in myocardial infarction alone, p<0.01). CONCLUSIONS Allogeneic mesenchymal stem cell transplantation enhances angiogenesis after myocardial infarction. This effect is limited to the viable myocardium. Using a concomitant 12-day course of tacrolimus, no mesenchymal stem cell-specific cellular immune response was demonstrated.

Intractable ulcerative colitis of infancy in a child with mitochondrial respiratory chain disorder.

Inflammatory bowel diseases are rare in young infants. Most cases of colitis are associated with necrotizing enterocolitis, bacterial infection, or intolerance to dietary proteins. Some cases are associated with immune disorders, Behçet disease, or vascular ischemic causes (systemic vasculitis, hemolytic uremic syndrome) (1). There is one report of five infants with intractable ulcerative enterocolitis of infancy (2). We report a 2-month-old child with a presentation suggesting this last diagnosis. However, elevated lactic acidosis and subsequent onset of a cardiomyopathy led to the discovery of a defect of mitochondrial respiratory chain complex I.

Differential effects of injections of anti-mu and anti-delta monoclonal antibodies on B-cell populations in adult mice: regulation of xenoreactive natural antibody-producing cells.

BACKGROUND The depletion of differential B cell and xenoreactive natural antibodies (XNA) by anti-delta and anti-mu injections was analyzed in adult mice. Sequential treatment with anti-delta and then anti-mu induces a complete depletion of B cells and XNA and represents a potential approach to induce xenograft tolerance. METHODS Adult mice were injected with anti-mu, anti-delta, anti-delta then anti-mu, or control isotype monoclonal antibodies from day 0 to day 14. The different B-cell populations were analyzed by FACS and immunohistology. Ig production was tested by ELISA. XNA were analyzed by FACS. RESULTS Anti-mu injections induced a depletion of IgMhigh, immature B cells, marginal zone B cells, and B1 cells and an increase of IgG-XNA production. Anti-delta injections induced mature conventional IgDhigh B-cell depletion and increased IgM-XNA production. Interestingly, sequential injections of anti-delta then anti-mu induced a depletion of immature B cells, mature B cells (MZ, B2, and B1), and XNA. CONCLUSIONS These results demonstrate that mature B-cell depletion in adult mice can be obtained by mAb injections and depends on the surface immunoglobulin cross-linking threshold. Indeed, anti-mu mAb depleted IgMhigh B cells (MZ and B1) and anti-delta, IgDhigh B cells (B2). The differential B-cell suppression shows that conventional B cells are responsible in the IgG-XNA production and MZ and B1 cells in the IgM-XNA production. Sequential repeated injections of anti-delta then anti-mu mAb depleted all B-cell populations and suppressed the whole XNA production.Background. The depletion of differential B cell and xenoreactive natural antibodies (XNA) by anti-d and anti-m injections was analyzed in adult mice. Sequential treatment with anti-d and then anti-m induces a complete depletion of B cells and XNA and represents a potential approach to induce xenograft tolerance. Methods. Adult mice were injected with anti-m, anti-d, anti-d then anti-m, or control isotype monoclonal antibodies from day 0 to day 14. The different B-cell populations were analyzed by FACS and immunohistology. Ig production was tested by ELISA. XNA were analyzed by FACS. Results. Anti-m injections induced a depletion of IgM high , immature B cells, marginal zone B cells, and B1 cells and an increase of IgG-XNA production. Anti-d injections induced mature conventional IgD high B-cell depletion and increased IgM-XNA production. Interestingly, sequential injections of anti-d then anti-m induced a depletion of immature B cells, mature B cells (MZ, B2, and B1), and XNA. Conclusions. These results demonstrate that mature B-cell depletion in adult mice can be obtained by mAb injections and depends on the surface immunoglobulin cross-linking threshold. Indeed, anti-m mAb depleted IgM high B cells (MZ and B1) and anti-d, IgD high B cells (B2). The differential B-cell suppression shows that conventional B cells are responsible in the IgGXNA production and MZ and B1 cells in the IgM-XNA production. Sequential repeated injections of anti-d then anti-m mAb depleted all B-cell populations and suppressed the whole XNA production.

Successful sublingual cobalamin treatment in a child with short-bowel syndrome.

Vitamin B12 (B12) is essential for deoxyribonucleic acid synthesis, to maintain normal hematologic and neurologic functions. Studies suggest that cobalamin deficiency in children is more common than previously recognized. Main causes are decreased intake, abnormal absorption, and inborn errors of metabolism. The classic treatment for cobalamin deficiency is intramuscular administration of B12. There are no data concerning the use of alternative routes of cobalamin administration in children. This report shares the experience of sublingual administration of B12 to a patient with short-bowel syndrome and B12 malabsorption. We report the case of successful treatment of cobalamin deficiency by sublingual administration in a 9-year-old patient who had undergone intestinal resection and jejunum-colon, with anastomosis of 32 cm of residual small intestine and absence of distal jejunum and ileocecal junction. We determined a B12 deficiency because low serum cobalamin levels (<200 pg/mL) were shown in 2 consecutive tests (130 pg/mL and 170 pg/mL). The patient presented with neither clinical nor hematological manifestations. He received sublingual cobalamin preparation, 1000-mcg sublingual nuggets per day for 1 month. Normalization of serum cobalamin was obtained (790 pg/mL) after 1 month of treatment. The sublingual route of administration not only improved the quality of life of this patient by avoiding monthly painful injections but also reduced the cost of treatment and the number of hospital visits.

Autologous gastrointestinal reconstructive surgery: complement or alternative to intestinal transplantation

Purpose of reviewAutologous intestinal reconstructive surgery has evolved over the past 3 decades from rescue to main surgical procedure in the multidisciplinary approach to short bowel syndrome (SBS) patients with intestinal failure. The purpose of this review is to clarify the actual place of intestinal reconstructive surgical techniques in the management of intestinal failure related to SBS and their relationship with intestinal transplantation. Recent findingsRecent reports from centers of excellence in intestinal rehabilitation underline the efficacy and safety of autologous intestinal reconstructive surgery in patients with SBS. Outcome parameters as survival, parenteral nutrition weaning, and clinical conditions were improved in SBS patients treated by gastrointestinal reconstructive surgery. SummaryAutologous intestinal reconstructive procedures are pivotal to achieve enteral autonomy in patients with intestinal failure related to SBS. They should be considered mutually supportive and not antagonistic to intestinal transplantation.

Anastomotic ulcers in short bowel syndrome: New suggestions from a multidisciplinary approach

BACKGROUND AND AIMS Anastomotic ulceration (AU) is a rare potential life-threatening complication that may occur after intestinal resection. The diagnosis is often delayed after a long-lasting history of refractory anemia. The pathogenesis remains unknown and there are no established therapies. The aim of the study was to analyze the medical history of children with short bowel syndrome (SBS) who were experiencing AU. METHODS Records of SBS children were retrospectively reviewed. Demographics, baseline characteristics, presentation, diagnosis and treatment of AU cases were analyzed. RESULTS Eight out of 114 children with SBS were identified as having AU. Mean gestational age was 32.5weeks. Underlying diseases were: 5 necrotising enterocolitis, 2 gastroschisis and 1 multiple intestinal atresia. The mean age at AU diagnosis was 6.5years (diagnosis delay of 35months). All but 2 patients had AU persistency after medical treatment. Endoscopic treatment (2 argon plasma coagulation; 1 platelet-rich fibrin instillation; 2 endoscopic hydrostatic dilations) was effective in 3 out of 5 children. Surgery was required in 3 patients. CONCLUSIONS Severe bowel ischemic injury, especially in preterm infant, could predispose to AU development. Medical treatment showed discouraging results. We firstly described that different endoscopic treatment could be attempted before resorting to further surgery. LEVEL OF EVIDENCE IV.

Saccharomyces boulardii Upgrades Cellular Adaptation Following Proximal Enterectomy in Rats

Saccharomyces boulardii Upgrades Cellular Adaptation Following Proximal Enterectomy in Rats