Search

Objectives: The aim of the study was to describe the 5-year follow-up of children who received peginterferon and ribavirin in a global, open-label study. Methods: A 5-year follow-up study of 107 children and adolescents ages 3 to 17 years with chronic hepatitis C virus infection who received peginterferon and ribavirin for 24 or 48 weeks. No drugs were administered during follow-up. Results: Ninety-four patients were enrolled in the long-term follow-up portion of the study;the median duration of follow-up was 287 weeks (range, 73-339). Of 63 patients with sustained virologic response who were enrolled, 54 completed 5 years of follow-up;none had relapse in the 5-year follow-up period. Significant decreases in height z scores were observed during treatment. The effect of treatment on height z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 [P < 0.001] and -0.44 [P < 0.001] in the 247 and 48-week treatment groups, respectively). Among patients treated for 24 weeks, full recovery of height z scores to baseline was observed by 1 year of follow-up, whereas only partial recovery was observed during 5 years of follow-up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 (P=NS) and 0.32 (P < 0.05) in the 24- and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index z scores. Conclusions: Impairment of growth should be considered when assessing the risk-benefit profile of peginterferon/ribavirin therapy in children with hepatitis C virus infection. In deciding to treat children with chronic hepatitis C virus, considerations should include both deferring treatment in patients during optimal growth periods, and the possibility that interferon free regimens may be available to children in the next 5 to 10 years.

Chronic hepatitis B virus (HBV) infection leads to a risk of developing cirrhosis and hepatocellular carcinoma. In France, where the prevalence of HBV is low, mother-to-child transmission is the cause of chronic infection in more than one-third of cases. After exposure, the risk of chronic infection is the highest for newborns (90 %). The World Health Organization implemented a global immunization program in 1991, applied in France in 1994. A significant number of children are infected each year, however, and failure of postexposure prophylaxis is reported in 4-10 % of newborns. We report 11 children with chronic HBV infection due to failure of serovaccination, followed up in two centers between 1993 and 2015. We discuss maternal screening, serovaccination, and follow-up conditions, as well as the role of maternal viral load, amniocentesis, and mode of delivery as risk factors. These observations confirm that serovaccination failures are related to the nonobservance of recommendations for maternal screening or postexposure prophylaxis, and to a high maternal viral load (10

Pegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children.Children and adolescents ages 3-17 years were treated with PEG-IFN alfa-2b (60microg/m(2)/week) plus RBV (15mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (600,000IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (or=600,000IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy.SVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported.Therapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.

UNLABELLED Intestinal transplantation (IT) is the newest and most difficult of organ transplantations. The first ever (1987) and the longest surviving (1989) IT were performed in our institution. However, IT still has to demonstrate its benefit to children on long-term parenteral nutrition (PN). We tried to clarify this aspect by looking back at our 13 years' experience. PATIENTS From 1994 to December 2007, 74 IT were performed in 69 children, 39 with an isolated small bowel (IT), 35 combined with a liver transplant (LITx). The indications were: short bowel syndrome (n = 25), congenital mucosal diseases (n = 22), and motility disorders (n = 22). Median age at transplantation was 5 years (1 - 17 years). Follow-up was 1 to 12 years (median 5 years). RESULTS Thirty-one children have a functioning graft (42 %), 15/39 IT, 16/35 LITx. They are at home without PN, with a good quality of life. One child is PN-dependent 1.5 years post IT. Post IT, 16 children were detransplanted: 12 early on (1 for mechanical complications, 11 because of resistant rejection; 3 less than 3 years, one 9 years post SBT (chronic rejection). In 2 noncompliant teenagers, PN was reintroduced (one was detransplanted later on). Several years post LITx, 2 children underwent bowel detransplantation due to an acute viral infection complicated with rejection. Twenty-two children died (32 %, 8 IT, 14 LITx), 18 early on from infectious or surgical complications, 4 more than 1 year post IT, 3 after retransplantation (1 in another unit). Bad prognostic factors are multiple previous surgeries, an older age (> 7 y), and chronic intestinal pseudo-obstruction. DISCUSSION Complications post IT are frequent and life-threatening, especially early on: rejection (IT), infections (LITx). Later on, the rate of complications decreases but remains significant, especially in noncompliant patients. However we describe here a 13-year learning curve; the recent results are encouraging with regard to control of rejection and viral infections. CONCLUSION Intestinal transplantation is indicated only in selected patients in whom long-term PN cannot be performed safely any more. In every child with intestinal insufficiency, the therapeutic strategy must be discussed early on in order to perform IT at the right time under optimal conditions. IT should evolve from being a "rescue" procedure to becoming a true therapeutic option.

"Cholestasis" means abnormal synthesis or secretion of bile. The main symptom in a neonate or infant is jaundice. Urine is dark, staining diapers, and stools are variably pale or white. Vitamin K should be injected (to prevent coagulation disorders due to malabsorption). The two diagnoses requiring urgent treatment are urinary tract infection and biliary atresia. If stools are permanently white, biliary atresia is highly probable. A few genetic causes of intrahepatic cholestasis should be screened and corrective surgery organized. The diseases responsible for cholestasis in this age group are described as well as the investigations and treatments, including the management of non-specific complications of cholestasis. A delay in the diagnosis of biliary atresia can have such severe consequences that consultation with a hepatology unit or transfer should be easy and rapid.

BACKGROUND Successful small bowel transplantation remains a challenge due to the septic and immune content of the gut. The possible beneficial role of the liver was assessed in pediatric recipients of isolated intestinal and liver intestinal combined transplantation, receiving the same immunosuppressive therapy. METHODS Fifteen children who underwent small bowel transplantation (seven SbTx) or combined liver-small bowel transplantation (eight LSbTx) at a single center between 1994 and 1998 were retrospectively reviewed and compared with fifteen controls (eight normal and seven appendicitis as inflammatory control). Transplant and patient survival, acute rejection episodes were analyzed and compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and Bax intestinal immunostaining from days 0 to 20 after transplantation were assessed. RESULTS Graft and patient survivals at 5 years were respectively 75% and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter). Immunostaining of biopsies on day 0 after reperfusion showed different expression of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax), mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx. CONCLUSIONS Our results suggest a protective role of the liver toward intestinal transplantation even in absence of significative difference, probably due to the small number of children. Early changes in NF-kB immunostaining in the biopsies sampled on day 0, pointed to a possible beneficial effect of the liver in the very early phase following transplantation, perhaps through the differential control of ischemia-reperfusion.

Background Microvillous inclusion disease (MVID) is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. Despite long-term total parenteral nutrition, life expectancy is extremely reduced because of metabolic or septic complications or liver failure. Methods Twelve patients with early-onset MVID were evaluated between 1995 and 2002 for the possibility of small bowel transplantation (SbTx). Three patients died before they could be placed on the waiting list for SbTx, and one patient is still awaiting SbTx. SbTx was contraindicated in one patient. Results Seven of 12 patients (six boys and one girl) underwent transplantation (three SbTxs and four combined liver-SbTxs). Actuarial survival rates were 100% and 75% in the SbTx and combined liver-SbTx groups, respectively, with a mean follow-up of 3 years (1.1-8.5 years). In contrast, the survival rate was only 40% in the subgroup of five patients who did not undergo transplantation. After transplantation, all patients were weaned from parenteral nutrition: the five patients with an additional colon graft were weaned within 36 days as opposed to the others without colonic transplant who obtained full intestinal autonomy several months after transplantation. The only two surviving patients who did not undergo SbTx remain highly dependent on total parenteral nutrition, which is complicated by repeated episodes of metabolic decompensation. Conclusions SbTx alone or in combination with the liver is highly successful in children with MVID, offering them a long-term perspective for the first time. Associated colon grafting markedly improves the outcome and quality of life after SbTx in patients with MVID.

Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.

Background Familial defective apolipoprotein B-100, a dominantly inherited form of hypercholesterolemia caused by a single Arg3500Gln mutation, is silent in childhood but may confer a high risk of cardiovascular disease in adulthood. The objective was to determine the prevalence of familial defective apolipoprotein B-100 in hypercholesterolemic French children and to provide a basis for targeting screening efforts in this population. Methods One hundred ninety children attending 13 pediatric clinics distributed throughout France were included based on the presence of type IIa hypercholesterolemia with a plasma low-density lipoprotein-cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was detected in dried blood spots using a polymerase chain reaction assay combined with enzymatic restriction. Results Three hyperlipidemia phenotypes were found: monogenic dominant pure hypercholesterolemia (n = 117), polygenic hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three unrelated children were heterozygous for the Arg3500Gln mutation; all three had monogenic dominant pure hypercholesterolemia (3/94 families; 3.2%), yielding a prevalence of 1.83% (3/164) in hypercholesterolemic children, which is similar to prevalences reported in European adults. Conclusions The familial defective apolipoprotein B-100 mutation was common (1/31) in children with a phenotype of familial hypercholesterolemia, supporting screening in this population with the goal of preventing premature cardiovascular events.

The Registry has gathered information on intestine transplantation (IT) since 1985. During this time, individual centers have reported progress but small case volumes potentially limit the generalizability of this information. The present study was undertaken to examine recent global IT activity. Activity was assessed with descriptive statistics, Kaplan-Meier survival curves and a multiple variable analysis. Eighty-two programs reported 2887 transplants in 2699 patients. Regional practices and outcomes are now similar worldwide. Current actuarial patient survival rates are 76%, 56% and 43% at 1, 5 and 10 years, respectively. Rates of graft loss beyond 1 year have not improved. Grafts that included a colon segment had better function. Waiting at home for IT, the use of induction immune-suppression therapy, inclusion of a liver component and maintenance therapy with rapamycin were associated with better graft survival. Outcomes of IT have modestly improved over the past decade. Case volumes have recently declined. Identifying the root reasons for late graft loss is difficult due to the low case volumes at most centers. The high participation rate in the Registry provides unique opportunities to study these issues.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents in the United States, and most probably also in the rest of the industrialized world.As the prevalence of NAFLD in childhood increases with the worldwide obesity epidemic, there is an urgent need for diagnostic standards that can be commonly used by pediatricians and hepatologists. To this end, we performed a PubMed search of the adult and pediatric literature on NAFLD diagnosis through May 2011 using Topics and/or relevant Authors as search words. According to the present literature, NAFLD is suspected based on the association of fatty liver combined with risk factors (mainly obesity), after the exclusion of other causes of liver disease. The reference but imperfect standard for confirming NAFLD is liver histology. The following surrogate markers are presently used to estimate degree of steatosis and liver fibrosis and risk of progression to end-stage liver disease: imaging by ultrasonography or magnetic resonance imaging, liver function tests, and serum markers of liver fibrosis.NAFLD should be suspected in all of the overweight or obese children and adolescents older than 3 years with increased waist circumference especially if there is a NAFLD history in relatives. The typical presentation, however, is in children ages 10 years and older. The first diagnostic step in these children should be abdominal ultrasound and liver function tests, followed by exclusion of other liver diseases. Overweight/obese children with normal ultrasonographic imaging and normal liver function tests should still be monitored due to the poor sensitivity of these tests at a single assessment.Indications for liver biopsy include the following: to rule out other treatable diseases, in cases of clinically suspected advanced liver disease, before pharmacological/surgical treatment, and as part of a structured intervention protocol or clinical research trial.

Purpose: The aim of the authors was to report their experience with living related liver transplantation (LRLT) in children, particularly focusing on the safety of the two-center "Parisian' strategy. Methods: The records of donors and recipients of 26 pediatric living-related donor liver transplantations performed between November 1994 and March 1998 were reviewed retrospectively. Donors were assessed 1 year after transplantation for medical and overall status. Results: Indications for LRLT included biliary atresia (n = 18), Byler's disease (n = 5), alpha-1-antitrypsin deficiency (n = 1), Alagille syndrome (n = 1), and undefined cirrhosis (n = 1). Liver harvesting consisted of either a complete left hepatectomy (n = 14) or left lateral hepatectomy (n = 12) without vascular clamping. The recipient procedure essentially was the same as in split liver transplantation. Mean overall cold ischemia time averaged 140 minutes (range, 90 to 230 minutes). Twenty-four of 26 patients had end-to-end vascular anastomoses without interposition. Biliary reconstruction consisted of a Roux-en-Y choledochojejunostomy in all patients. All recipients except one received cyclosporine A (CSA). Mean donor hospitalization was 8 days (range, 6 to 13) with normalization of all liver function assays by the time of discharge. There were no donor deaths and two postoperative complications (perihepatic fluid collection and bleeding from the wound). One year after donation, the initial 19 donors had resumed their pretransplant status. Two of the children who underwent transplant died. Thirteen of the recipients required reoperation for hepatic artery thrombosis (n = 2), portal vein thrombosis (n = 2), biliary complications (n = 6), fluid collection (n = 3), small bowel perforation (n = 1), and plication for diaphragmatic eventration (n = 1). With mean follow-up of 2 years, 24 of 26 patients are alive and well (patients and graft survival rate, 92%). Conclusions: LRLY is still controversial, even with minimal and decreasing donor risk. The "Parisian" strategy consists of harvesting the liver in an adult unit by an adult hepatic surgery team. The transplantation is then performed in a pediatric hospital by the pediatric liver transplantation team. The two steps of the procedure allow units specialized in adult surgery, on one hand, and pediatric liver transplantation, on the other hand, to dedicate themselves completely to their respective procedures, improving the safety of the harvest, and alleviating stress for both the medical staff and the families.

We evaluated 131 patients (6 months–14 years) who experienced 21 deaths before listing, 11 continuing on the waiting list, 38 well on home parenteral nutrition, 6 off parenteral nutrition and 59 transplanted (20 girls) aged 2.5 to 15 years, (18 >7 years). They received cadaveric isolated intestine (ITx, n = 31) or liver-small bowel (LITx, n = 32), including right colon (n = 43; 23 LITx) for short bowel (n = 19), enteropathy (n = 20), Hirschsprung (n = 14), or pseudo-obstruction (n = 6). Treatment included tacrolimus, steroids, azathioprine, or interleukin-2 blockers. After 6 months to 10.5 years, the patient and graft survivals were 75% and 54%. Sixteen patients (10 LITx) died within 3 months from surgery (n = 3), bacterial (n = 5) or fungal (n = 6) sepsis, or posttransplant lymphoproliferative disorder (n = 2). Rejection occurred in 27 patients, including 10 steroid-resistant episodes requiring antilymphoglobulins. The grafts were removed due to uncontrolled rejection in seven ITx recipients. Surgical complications were observed in 38 recipients (25 LSBTx) within 2 months, including bacterial (n = 22) or fungal (n = 11) sepsis, cytomegalovirus disease (n = 12), adenovirus (n = 11), or posttransplant lymphoproliferative disorder (n = 12). Forty-two children (19 LSBTx) are alive. Weaning from parenteral nutrition was achieved after 42 days (median). Factors related to death or graft loss were pre-Tx surgery (P < .01), pseudo-obstruction (P < .01), age over 7 years (P < .03), fungal sepsis (P < .03), steroid resistant rejection (P < .05), hospitalized versus home patient (P < .01), and retransplantation (P < .05). Colon transplant did not affect the outcome. Interleukin-2 blockers improved isolated ITx (P < .05). Early referral and close monitoring of intestinal failure and related disorders are mandatory to achieve successful ITx.

Pruritus in the infant is predominantly related to common dermatosis. General causes remain exceptional. We report two cases of pruritus in infants revealing anicteric cholestasis.Case no 1. A thirteen month-old boy had exhibited pruritus since the age of 2 months. The clinical examination was non-specific. Biological explorations revealed an isolated and moderate rise in total bilary acids. The search for mutations in the genes of a familial fibrogenic cholestasis was negative. The diagnosis retained was hypercholanemia. Treatment combined ursodesoxycholic acid and rifampicine, which controlled the pruritus and normalized the bilary acid levels. Case no 2. A twenty-one month-old boy had exhibited pruritus since the age of 2 months and delayed growth. The clinical examination was unspecific. The biological explorations revealed cholestasis with normal delta GT, moderate cytolysis and liposoluble vitamin deficiency. The hepatic biopsy was normal. The diagnosis retained was familial fibrogenic cholestasis. Treatment combined ursodesoxycholic acid and rifampicine, which controlled the pruritus and normalized the hepatic parameters.Non-dermatological isolated pruritus is rare in infants. These two observations illustrate two abnormalities in bilary acid transport. Hypercholanemia is a faulty canalization of bilary acids by the hepatocyte. Familial fibrogenic cholestasis is a default in the elimination of these bilary acids. Such pathologies must be evoked because specific treatment will treat the symptoms and avoid the evolution of familial fibrogenic cholestasis towards cirrhosis.

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of < 1, 1 to 2, and > 2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is < 1 mmol/liter on admission.

Peripartum transmission is today the main cause of hepatitis C virus (HCV) infection in children. HCV infection rarely causes a clinical illness during childhood and adolescence, except when it is associated with additional risk factors such as hepatitis B or HIV infection, chemotherapy or immunodeficiency. Present data suggest that between 20 to 50 percent of contaminated infants will become spontaneously non viremic within 15 to 20 years. Studies on treatment with interferon-alpha are limited and show a mean recovery rate of 40%.

Elevated serum levels of transaminases must always be considered as an abnormal finding. Drugs and toxins must be eliminated first as possible hepatotoxic agents or co-factors. Antiviral hepatitis A IgM determination is the first test to perform. However, other viruses with spontaneous benign courses are the most frequent cause. Only if the initial presentation is severe, or if liver tests remain abnormal after several weeks, can other rare diseases be sought. Liver biopsy is rarely necessary to reach a diagnosis.

The term 'intestinal failure' is now often used to describe gastrointestinal function insufficient to satisfy body nutrient and fluid requirements. The first recognized condition of intestinal failure was short bowel syndrome. Severe motility disorders such as chronic intestinal pseudo-obstruction syndrome in children as well as congenital intractable intestinal mucosa disorders are also forms of intestinal failure, because no curative treatment for these diseases is yet available. Parenteral nutrition and home parenteral nutrition remain the mainstay of therapy for intestinal failure, whether it is partial or total, provisional or permanent. However, some patients develop complications while receiving standard therapy for intestinal failure and are considered for intestinal transplantation. Indeed, recent advances in immunosuppressive treatment and the better monitoring and control of acute rejection have brought intestinal transplantation into the realm of standard treatment for intestinal failure. Although it has been used in humans for the past two decades, this procedure has had a slow learning curve. According to the current results, this challenging procedure may be performed in children or adults, only under certain conditions.

The aim of this study was to assess the prevalence of de novo malignancy after solid organ transplantation in childhood. A retrospective questionnaire-based survey was sent to 9 referral centers for pediatric organ transplantation in France. Among 1326 children who underwent solid organ transplantation since 1996, 80 (6%) presented with de novo malignancy posttransplantation during childhood: posttransplant lymphoproliferative disease was the most common (5% of pediatric recipients) comprising 80% of all tumors, with a disproportionately high prevalence among combined liver and small bowel recipients (18%). Various solid tumors were observed mainly among kidney recipients. No skin cancer was reported.

Primary hyperoxaluria type I (PH I) is a congenital error of metabolism that can be manifested by an increased oxalate production, and ultimately result in kidney failure. After a combined liver/kidney transplantation, children with PH I have persistent excretion of oxalate that causes crystal formation in the urinary tract, and could result in systemic oxalosis and eventual graft failure. We speculated that crystalluria may be predictive of this nephrolithogenic tendency and thus investigated the effect of an intensive therapeutic strategy to prevent crystal formation in 13 children at our hospital. Oxalate crystal volume (OCV) measurements were performed at regular intervals for 36 months, and compared with urine supersaturation measurements. We found that crystalluria with the OCV measurement is non-invasive, easily performed, and gives feedback on the efficacy of PH I therapy within one hour. Further study is needed to determine whether this method is a better predictor of nephrocalcinosis than is supersaturation alone.

Bile acids are natural detergents and the end-products of cholesterol metabolism. Their functions are mostly digestive: induction of bile flow and solubilization of biliary and alimentary lipids. They circulate along the enterohepatic cycle, and probably also along a shorter route, the cholehepatic shunt. They are relatively hydrophobic and perpetuate or worsen the hepatic lesions when their excretion is impaired in cholestasis, because of their affinity for biological membranes. Their functions depend on their relative hydrophilicity and ionization, ie on their structure and state of conjugation. They have an immunosuppressive effect in vivo and in vitro. Ursodeoxycholic acid (UDC) is a hydrophilic bile acid used in chronic cholestatic diseases. Biological improvement has been proven in autoimmune cholangiopathies in adults, and cystic fibrosis-associated liver disease in children. Clinical studies are on the way for other indications. It is still too early to evaluate the long-term clinical benefits, eg the reduction in needs for liver transplantation. UDC acid may induce a bicarbonate-rich hypercholeresis through the cholehepatic shunt, that would explain its efficacy in cystic fibrosis. In disorders of bile acid synthesis or transport, it could shunt the enzymatic block, or reestablish the bile flow through its osmotic effect. Like other bile acids it interacts with membranes, and is thought to stabilize them. In chronic cholestasis it would protect the membranes against the adverse effect of non-excreted endogenous bile acids. This interaction can also explain its immunosuppressive effect, through non-specific inhibition of transmission at the cell surface. That would explain the preferential clinical efficacy of UDC in autoimmune cholestasis, and stimulate its evaluation in "immunological" indications, such as liver transplantation and hepatic graft versus host disease.

Ursodeoxycholic acid is an efficient treatment for putatively immune-mediated liver diseases, but its mechanism of action is unknown. We studied human mononuclear cell proliferation as an in vitro model for cell-mediated immunity in the presence of ursodeoxycholic acid, its glycoconjugate and tauroconjugate and chenodeoxycholic acid at concentrations of 5, 25 and 50 mumol/L. Proliferation was inhibited in a dose-dependent manner compared with control values (15% to 54% depending on the bile acid, concentration and mitogen used), except at 5 mumol/L where inhibition was significant with only one mitogenic stimulus of the three used. With one mitogen (phorbolester) the inhibition was additive with that of cyclosporine. The number of cell-surface receptors studied was not modified by bile acids. Interleukin-2 production was decreased 35% to 60% by ursodeoxycholic acid and its conjugates. The proliferation of the interleukin-2-dependent cell line CTLL-2 was also inhibited. The immunosuppression was reversible except at a chenodeoxycholic acid concentration of 50 mumol/L. Because bile acids are able to partition into membranes and change their properties, we speculate that this allows them to interact with cell-surface receptors or signaling systems within the membrane or on its inner face, thus impairing their function. This would inhibit the numerous extracellular messages that lymphocytes need to proliferate.

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone.

In 60 neonates (gestational age, 26.5-40 weeks; postnatal age, 1-14 days) and in 11 infants (gestational age, 26-33 weeks; postnatal age, 4.5-38 weeks), the accuracy of two wavelength pulse oximetry was examined. A total of 112 comparisons between transcutaneous pulse oximetry saturation (StcO2, NELLCOR N-100) and arterial oxygen saturation (SaO2, OSM2 RADIOMETER) were obtained. SaO2 ranged from 80 to 100%. Criteria for comparison between StcO2 and SaO2 were standardized: patients in behavioral state 1, StcO2 stable for 2 min, and arterial samples drawn from an indwelling arterial line. StcO2 was significantly related to SaO2 (P less than 0.01), but the difference, StcO2 - SaO2, significantly increased when SaO2 decreased [StcO2 - SaO2(%) = -0.39 SaO2(%) + 37.95; r = -0.64, P less than 0.01]. No significant relationship was found between StcO2 - SaO2 and either bilirubinemia (range, 5-222 mumol/L) or fetal hemoglobin (HbF) (range, 12-95%). We conclude that StcO2 overestimates SaO2 when SaO2 decreases, and this overestimation is not due to high levels of bilirubin or HbF.

Treatment of precocious puberty of central origin is aimed at controlling the development of sexual characteristics and improving final height. Increased growth rate is one of the major clinical symptoms, accompanied by an even more marked advance in bone age. Medroxyprogesterone acetate and cyproterone acetate have provided almost satisfactory control of pubertal characteristics, but with accompanying adrenal insufficiency. The data with regard to growth and bone maturation are contradictory. LHRH analogues have recently become available, and provide good control of gonadotrophin secretion. In a series of 21 cases (13 girls, 8 boys), a significant decrease in growth rate was achieved in both sexes with an LHRH analogue, with a significant increase in the height age/bone age ratio; control of gonadal secretions was also obtained. These results are only preliminary, but provide hope that the final height of these children will be improved.

In both adults and children RU 41740 exerts an immunomodulating effect and prevents recurrent respiratory infections. Patients with such infections frequently consult for acute episodes, and it was deemed necessary to evaluate the safety of the drug given concomitantly with antibiotic in acute infections. Three double-blind, drug versus placebo studies were conducted in fragile institutionalized or hospitalized patients. Antibiotics were administered simultaneously with RU 41740 in one group and with a placebo in another group. The studies performed by Albarede and Ollivier showed that in acute respiratory infections RU 41740 was well tolerated and resulted in a more rapid improvement of severity score. Grassi and al. studied chronic bronchitis patients admitted for acute on chronic episode. RU 41740 produced a more rapid improvement in the most severely ill patients, and it was well tolerated. It is concluded that RU 41740 can be initiated safely in acute episodes occurring in subjects with recurrent respiratory infections, and that it results in a faster improvement of clinical symptoms.

Anderson's disease is a rare autosomic recessive condition involving the transport of fat through the intestinal mucosa, which could be due to a defect in the intestinal form (B48) of apolipoprotein B. Isolated cases and one important series only have been reported. We wish here to complete the description of the disease. Seven children (age 6 months to 13 years at time of diagnosis) were followed for one month to 15 years. They presented with a malabsorption syndrome, malnutrition, fatty diarrhea (steatorrhea 4-18 g/24 h), failure to thrive (height -1 to -5.5 SD for age) and sometimes disappearance of deep tendon reflexes. Biologically they had signs of malabsorption, hypocalciuria, osteoporosis, low serum iron, decreased levels of vitamins A and E, and hypo-alpha- (50-127 mg/100 ml) and beta- (73-175 mg/100 ml) lipoproteinemia due to decreased levels of plasma cholesterol (40-70 mg/100 ml), and phospholipids (34-67 mg/100 ml); apolipoproteins A1 (26-69 mg/100 ml and B (21-44 mg/100 ml) were also low. After a fatty meal, triglycerides and apolipoproteins did not increase and chylomicrons did not appear. Jejunal biopsies showed the characteristic aspect of enterocytes loaded with lipid droplets. On electron microscopy, these fat droplets were seen in the cytoplasm but neither in the endoplasmic reticulum and the Golgi complex nor in the intercellular spaces. They did not appear to be enclosed in membranes and differed from chylomicrons by their size and density. The disease could thus be due to an abnormal apolipoprotein B48, which would prevent its binding to triglycerides and thus the formation of chylomicrons.