Bernard Genin

A silicone-coated nylon dressing reduces healing time in burned paediatric patients in comparison with standard sulfadiazine treatment: a prospective randomized trial

Mepitel is a new grid like silicone coated nylon dressing containing no additional biological compounds. We describe a prospective randomized pilot study comparing Mepitel to the standard silver sulfadiazine cream (Flamazine) dressing for the topical treatment of paediatric burns. Seventy-six children presenting within 24 h of injury with a non previously treated burn were randomly assigned to Mepitel treatment (group M) or Flamazine treatment (group F). Age, sex, surface area of burn and causal agent were noted at admission. The depth of the burn, cumulative number of dressings, presence or absence of a complete epithelial cover, infection, bleeding and allergy were noted at each dressing change. There were 41 children in group M and 35 children in group F. Five children were subsequently withdrawn from each group because they required skin grafting. Analysis of the above mentioned criteria showed no statistical difference between the two groups except for the healing time (group M: 7.58+/-3.12, group F: 11.26+/-6.02, p < 0.01) and the number of dressings (group M: 3.64+/-1.5, group F: 5.13+/-2.9, p < 0.05). Mepitel has proved to be an easy-to-remove dressing, adhering only to intact skin. The faster healing time found in the Mepitel group may be related to a direct effect of silicone on epithelial growth or to a decrease in surface-cell damage compared to the silver sulfadiazine group. This attractive product will be further assessed on a larger scale trial to confirm our observations.

IL-1 receptor antagonist (IL-1Ra) does not inhibit the production of C-reactive protein or serum amyloid A protein by human primary hepatocytes. Differential regulation in normal and tumour cells.

The synthesis of some class 1 acute‐phase proteins (APP), including C‐reactive protein (CRP) and serum amyloid A (SAA) protein is completely blocked by the IL‐1 receptor antagonist (IL‐1Ra), whereas the production of fibrinogen, a class 2 APP, is increased by IL‐1Ra in hepatoma cells, but this has never been tested in human hepatocytes in primary culture. Since previous studies on the contributions of cylokine inhibitors in connective tissues diseases suggested that IL‐1 and tumour necrosis factor‐alpha (TNF‐α) might play an important role in the regulation of CRP, we decided to examine in more detail the respective roles of IL‐1β, IL‐6, and TNF‐α and their inhibitors in the production of APP by human primary hepatocytes versus the hepatoma cell line PLC/PRF/5. In the hepatoma cell line, IL‐1β and/or TNF‐α had synergistic effects with IL‐6 on the production of CRP and SAA. In contrast, these cytokines were devoid of effect in normal hepatocytes. The production of fibrinogen was increased by IL‐6 and decreased by IL‐1 (and TNF‐α) in both cell types. The secretion of CRP and SAA by primary hepatocytes incubated with a cytokine‐rich mononuclear cell‐conditioned medium was totally unaffected by IL‐1Ra or anti‐TNF‐α antibodies. In contrast, the addition of IL‐1Ra increased the production of fibrinogen by both hepatoma cells and primary hepatocytes incubated with the mononuclear cell‐conditioned medium. We therefore conclude that IL‐1β and TNF‐α do not exert any significant effect on the synthesis of CRP and SAA by human primary hepatocytes.

Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver

To investigate the contribution of IL‐11 and LIF to acute‐phase protein (APP) production, we first analysed the effects of IL‐11 and LIF on production of C‐reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL‐11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL‐11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL‐6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL‐11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL‐11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.

Long-term outcome of children with patent processus vaginalis incidentally diagnosed by laparoscopy.

INTRODUCTION Patent processus vaginalis (PPV) might be incidentally diagnosed during laparoscopy. The aims of this study were to determine the prevalence and the natural history of PPV, i.e. its possible development into symptomatic inguinal hernia. PATIENTS AND METHODS INCLUSION CRITERIA children <16years undergoing laparoscopy for pathologies other than processus vaginalis (PV) related, from 10/2000-10/2005. EXCLUSION CRITERIA past or present history of PV-related pathologies. The internal inguinal rings were documented during laparoscopy. Follow-up was provided by phone inquiry and clinical examination if needed. Median follow-up was 10.5years (range 7.1-12.8). RESULTS 416 patients were included. Median age at laparoscopy was 12.4years (range 3days-18.1years). Forty-three PPV (33 unilateral, 5 bilateral) were found in 38 patients (9.1%). Four children with PPV presented later with an ipsilateral inguinal hernia (10.5%, 95%CI [3%; 25%]), at a median age of 16.0years (range 11.8-17.3), at a median of 22.5months (range 12-50) after initial laparoscopy, as compared to no patient in the population with obliterated PV (0%, 95%CI [0%; 1%]). CONCLUSION 9.1% of the observed pediatric population showed an asymptomatic PPV, and 10.5% of these children later developed an inguinal hernia. None of the children with obliterated PV developed a hernia.

Improvement of the effect of hepatocyte isograft in the Gunn rat by cotransplantation of islets of Langerhans

PURPOSE Hepatocyte transplantation (HcTX) has been investigated for many years as an alternative therapy to orthotopic liver transplantation to treat hepatic congenital enzymatic deficiency disease. The animal model most used is the Gunn rat, which presents a hyperbilirubinemia caused by the lack of uridine-diphosphate-glucuronyl-transferase. Some investigators have clearly described a hepatotrophic effect mediated by islets of Langerhans (IL) when transplanted with hepatocytes (Hc). In this study, the functional effect of cotransplanted IL on hepatocytes (co-HcTX) in Gunn rats in an isograft model is assessed. METHODS Two groups are compared: group 1 (n = 6), HcTX to group 2 (n = 6), co-HcTX. Cells isolated by enzymatic digestion are transplanted directly into the splenic parenchyma. Blood samples are taken regularly until day 100 to measure the unconjugated bilirubin (UB). Histological examination of the spleen is performed at the end of the experiment. RESULTS Both groups show a significant decrease of the UB: group 1, 47%; group 2, 65%. The decrease is statistically more pronounced with co-HcTX. The histological analysis shows a trophic effect of the IL on the grafted hepatocytes in the co-HcTX group. CONCLUSIONS The HcTX and the co-HcTX correct partially the hyperbilirubinemia of the Gunn rat. A functional assessment has been performed to evaluate the effect of cotransplanted IL on HcTX.

Biliary Atresia and Orthotopic Liver Transplantation - 11 Years of Experience in Geneva

Biliary atresia (BA) is a congenital malformation or an evolutive inflammatory process which, without treatment, leads to cirrhosis, hepatic failure and death within two years of birth. The literature gives a survival rate of 60% at five years and 25% to adulthood after an initial operation performed for BA. 30% of children do not survive beyond two years of age. BA has become the most frequent indication for liver transplantation (LT) in children. With LT, survival expectancy is 90%. Results of the operation designed for BA remain unsatisfactory, and seem to depend on the age of the infants, as well as on other factors such as liver histology, and centre experience. Since 1989, onset of the paediatric hepatic transplantation program in Geneva, to July 2000, 20 children have been referred for initial treatment of BA, and 26 for possible hepatic transplantation after initial treatment done in another centre. The aim of the current study is to analyse our own results of the initial operation and to present the results of liver transplantation in this particular group of patients. All the patients with a BA are included in this study. The initial operation for BA yielded 43% favourable outcome at five years and the survival in this group following LT reached 91.3% survival. The importance of the age of the patient at time of initial operation is underlined.