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Biomedical subjects

M Hadchouel

Publications and source records attributed to M Hadchouel.

At least 91 records · Page 5Linked to original sources
PubMed1987

Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia).

Alagille syndrome is characterized by the association of chronic cholestasis with a paucity of interlobular bile ducts and a distinctive facies together with cardiovascular, skeletal and eye abnormalities. We examined the kidneys of 26 patients with this syndrome; 22 were under 3 years of age and 4 were 4, 6, 12 and 17 years old, respectively. Eighteen showed glomerular lesions of variable severity characterized by a mesangiolipidosis. In the 8 lesser affected patients light microscopy (LM) disclosed a fibrillar appearance of the mesangium, and electron microscopy (EM) showed lipid vacuoles widespread in the mesangial matrix. In the 10 patients who were affected to a greater degree LM and EM showed, in addition to the mesangial matrix changes, the presence of mesangial foam cells. Clinical signs of renal involvement were mild in all patients except for one who died from chronic renal failure at 8 months of age. The extent of mesangiolipidosis was not related to age but to the degree of cholestasis, the most severe lesions being observed in patients aged 3, 6, 8, and 14 months. The glomerular lesions observed in Alagille syndrome are strikingly similar to those observed in adults with lecithin-cholesterol acyl transferase deficiency and other conditions characterized by an increase in plasma lipoproteins rich in free cholesterol and in phospholipids. We conclude that glomerular involvement should be added to the characteristic features of Alagille syndrome. Also we found that the lipid deposition in the glomeruli of patients with Alagille syndrome is related to an abnormal lipid metabolism, which is the consequence of severe cholestasis. The most striking feature of our study is the early detection of the glomerular lesions, contrasting with the lack of overt clinical renal disease. Renal failure may be a major complication for patients with this syndrome in adulthood.

Adolescent↗
PubMed1987

Sclerosing cholangitis with neonatal onset.

Sclerosing cholangitis is characterized by irregular narrowing of extrahepatic or intrahepatic bile ducts, and in adults is defined mainly by radiologic findings. We describe eight children with cholestasis from the first week of life, followed by early cirrhosis and portal hypertension. Histologic examination of the liver showed absence of interlobular bile ducts in the early cholestatic phase in two patients and biliary cirrhosis later in all patients. Radiologic examination by percutaneous cholecystography under ultrasound guidance, carried out at age 8 months to 9 years, disclosed abnormal intrahepatic bile ducts with rarefaction of segmental branches, stenosis, and focal dilation. The extrahepatic ducts were involved in six patients. No intestinal disease has been found in these patients.

Bile Ducts↗
PubMed1987

Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases.

We have observed two types of paucity of interlobular bile ducts (PILBD) in children with chronic cholestasis: the syndromic type, which is more frequent (80 cases), and the nonsyndromic type (31 cases). Study of patients with syndromic PILBD has enabled us to recognize five major features: peculiar facies (95%), chronic cholestasis (91%), posterior embryotoxon (88%), butterfly-like vertebral arch defects (87%), and peripheral pulmonary artery hypoplasia or stenosis, either isolated or associated with complex cardiovascular abnormalities (85%). By observing these major features, it is possible to differentiate the "complete" syndrome, in which all five features are present (26 cases), from the "partial" syndrome, in which only four (42 cases) or three (12 cases) major features are present. Other less frequent features were observed in patients with complete or partial syndrome: growth retardation (50%), mental retardation (16%), renal disturbances, other vascular malformations, bone abnormalities, high-pitched voice, and delayed puberty. Death occurred in 21 (26%) patients with syndromic PILBD. Therapy consisted of supplementation of medium-chain triglycerides and fat-soluble vitamins and administration of cholestyramine or phenobarbital. An autosomal dominant mode of transmission, with variable penetrance, seems likely.

Bile Ducts, Intrahepatic↗
PubMed1987

Bacterial cholangitis after surgery for biliary atresia.

We retrospectively studied the incidence of bacterial cholangitis in 129 infants operated on because of biliary atresia over 5 years. Forty-six of the 101 children who underwent hepatic portoenterostomy had a total of 105 episodes of cholangitis (range one to eight episodes per child). Most episodes occurred within 3 months of the operation. Factors associated with cholangitis included good or partial restoration of bile flow, abnormal intrahepatic bile ducts or cavities at the porta hepatis, and routine postoperative use of antibiotics. External jejunostomy was not effective in preventing cholangitis. In addition to fever and decreased bile flow, increased erythrocyte sedimentation rate and signs of shock were frequently observed. The responsible organisms, most often gram-negative bacteria, were identified in 79 (75%) episodes by blood or liver cultures. Most were susceptible to trimethoprim-sulfamethoxazole and third-generation cephalosporins during the first episode, but only to cephalosporins during later episodes. The incidence of signs of portal hypertension in children with normal serum bilirubin values at age 5 years was not higher in those who had previously experienced one or more episodes of cholangitis.

Biliary Atresia↗
PubMed1987

Hepatitis B surface antigen gene expression is regulated by sex steroids and glucocorticoids in transgenic mice.

We have investigated the basis for liver-specific and sex-linked expression of hepatitis B surface antigen (HBsAg) gene in transgenic mice by monitoring the level of liver HBsAg mRNA and serum HBsAg at different stages of development and in response to sex-hormone regulation. Transcription of the HBsAg gene starts at day 15 of development, together with that of the albumin gene, and reaches a comparable level at birth. HBsAg mRNA level and HBsAg production are parallel in males and females during prenatal development and until the first month of life, but HBsAg gene expression increases 5-10 times in males at puberty. After castration, the level of expression decreases dramatically in both males and females and is subsequently increased by injection of testosterone or estradiol. Glucocorticoids also regulated positively expression of the HBsAg gene. Our results suggest that sex hormones play a role in hepatitis B virus gene expression during natural infection and could explain the difference in incidence of chronic carriers between men and women.

Animals↗
PubMed1986

Liver disease associated with anti-liver-kidney microsome antibody in children.

In the past 10 years we have examined 20 children with inflammatory liver disease associated with high serum titers of anti-liver-kidney microsome antibody (anti-LKM). The first hepatic symptoms were progressive fatigue and jaundice, the fortuitous finding of hepatomegaly or splenomegaly with raised transaminase activity, or an acute hepatitis-like illness. At the time of diagnosis, hepatomegaly was present in 18 children, splenomegaly in 16, jaundice in nine, and ascites in two. Serum alanine transferase activities were elevated in all but two, who had already received steroids. Serum total gammaglobulin values were greater than 2.0 gm/dl in 16 children, prothrombin activity less than or equal to 60% in six, and serum titer of anti-LKM between 1:100 and 1:100,000. All children but one had cirrhosis, and histologic signs of aggressivity were present in 14. In 11 children one or more extrahepatic diseases were present, including type 1 diabetes, vitiligo, glomerulonephritis, autoimmune hemolytic anemia, hypoglycemia with hyperinsulinism, autoimmune thyroiditis, chronic mucocutaneous candidiasis with hypoparathyroidism, and multiple cutaneous and visceral telangiectasias. Treatment with prednisone and azathioprine improved the liver condition in 16 of the 18 patients given treatment. In eight of them discontinuation of treatment resulted in rapid relapse; 14 are still receiving treatment and have stable hepatic function with follow-up from 8 months to 6 1/2 years. Only two are free of treatment. Four children died, two in spite of immunosuppressive therapy, one during a relapse, and one of extrahepatic disease. These results indicate that this autoimmune inflammatory liver disease may have onset early in life, with several clinical patterns; is frequently associated with certain types of extrahepatic manifestations of autoimmune origin; and is a potentially fatal disease for which immunosuppressive treatment must be started early.

Adolescent↗
PubMed1986

Semen abnormalities in patients with viral hepatitis B.

Semen parameters of 10 acute hepatitis and 5 chronic carriers were studies. The most common alterations were necrospermia (62% of the patients), teratospermia with irregular shape of the heads (46%), asthenospermia (36%), small volume (33%), and oligospermia (27%). The possible mechanisms of such anomalies are discussed.

Adult↗
PubMed1986

[Serum DNA of hepatitis B virus in children with chronic infection].

Viral replication has been studied in 44 children with chronic infection induced by hepatitis B virus (HBV) investigating HBV-DNA by molecular hydridization technique, correlating its presence with immunological markers and activity of liver disease. HBV-DNA presence is correlated to HBe Ag detection, but this antigen was also found in absence of viral DNA (7 cases of 31). That can mean viral replication diminishes or disappears before the seroconversion. No differences were found in viral replication phases as for clinical manifestations in children. In presence of viral DNA, serum aminotransferases were higher (p less than 0,005) and active hepatic lesions more frequent. Therefore, more cytolysis an inflammation are found in presence of circulating virus. On the other, more developed lesions (inactive cirrhosis and hepatocellular carcinoma) have been found in viral replication absence.

Adolescent↗
PubMed1985

Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice.

Two transgenic mice were obtained that contain in their chromosomes the complete hepatitis B virus (HBV) genome except for the core gene. These mice secrete particles of HBV surface antigen (HBsAg) in the serum. In one mouse, HBV DNA sequences that had integrated at two different sites were shown to segregate independently in the first filial generation (F1) and only one of the sequences allowed expression of the surface antigen. Among these animals the males produced five to ten times more HBsAg than the females. A 2.1-kilobase messenger RNA species comigrating with the major surface gene messenger RNA is expressed specifically in the liver in the two original mice. The results suggest that the HBV sequences introduced into the mice are able to confer a tissue-specific expression to the S gene. In addition, the HBV transgenic mice represent a new model for the chronic carrier state of hepatitis B virus infection.

Animals↗
PubMed1985

Presence of HBV DNA in spermatozoa: a possible vertical transmission of HBV via the germ line.

Using molecular hybridization we studied the presence and state of HBV DNA in sperm samples obtained from 17 patients with HBV infection (eight HBsAg chronic carrier, nine acute hepatitis B). Presence of HBV DNA was detected in three samples of seminal fluid from three patients with acute hepatitis. Restriction enzyme patterns of cellular DNA were consistent with presence of integrated HBV DNA sequences in spermatozoa from two of these three patients. The results indicate that HBV DNA may be present in the semen, at least during the acute phase of HBV infection. The presence of HBV DNA in seminal fluid confirms the possibility of venereal transmission. The presence of integrated sequences in spermatozoa suggests the possibility of true vertical transmission of HBV via the germ line.

DNA, Viral↗
PubMed1985

Acute hemorrhagic, hepatic, and neurologic manifestations in juvenile rheumatoid arthritis: possible relationship to drugs or infection.

Seven children with juvenile rheumatoid arthritis had a syndrome characterized by hemorrhage and neurologic, hepatic, hematologic, and metabolic manifestations. The disease did not seem to conform clearly to the characteristics of Reye syndrome or any other well-known entity. This severe complication may be induced by macrophage activation secondary to a drug or intercurrent infection. Our data suggest that a sudden fall in erythrocyte sedimentation rate or in platelet and fibrinogen levels may mark the start of this complication and may be an indication for rapid steroid therapy.

Acute Disease↗
PubMed1985

Medium-chain acyl-CoA dehydrogenase deficiency in two siblings with a Reye-like syndrome.

An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye syndrome. We describe two siblings who developed a Reye-like syndrome at ages 16 and 18 months, respectively, after a viral illness and salicylate therapy. Both had fasting hypoglycemia and hypoketonemia. At the time of the acute episode and after ingestion of a medium-chain triglyceride load, one of them excreted large amounts of abnormal metabolites derived from the omega- and (omega-1)-oxidation of medium-chain fatty acids. Medium-chain acyl-CoA dehydrogenase activity was lower than 20% of control values in fibroblasts from both patients. This enzyme defect should be considered in children with a Reye-like syndrome with these distinctive manifestations.

Acyl-CoA Dehydrogenase↗
PubMed1985

Hepatitis B virus DNA in Dane particles: evidence for the presence of replicative intermediates.

Half the Dane particle concentrates isolated from 84 serum samples of patients infected with hepatitis B virus (HBV) contained more than one HBV DNA species. At most, six HBV DNA molecules migrated on hybridization blots. The fastest migrating species was single minus-strand DNA, and the five slower species all were double-stranded relaxed circular DNA. One of the latter forms corresponded to the full-length HBV genome; the four others contained shorter plus strands of different lengths and might represent replicative intermediates. These results indicate that the replicative forms of HBV previously found in infected liver cells might be coated and exported as early as the step of single minus-strand synthesis.

Centrifugation, Density Gradient↗
PubMed1985

[Alpha-1-antitrypsin deficiency and renal involvement].

In a young girl with alpha 1-antitrypsin deficiency (Pi Z), cirrhosis, hypocomplementemia and proteinuria, renal biopsy showed features of type I membranoproliferative glomerulonephritis. Deposits contained IgA, IgG, IgM, Clq, C4 and C3 but not alpha 1-antitrypsin. A review of the literature found 10 similar cases. Type I membranoproliferative glomerulonephritis was present in all. The respective roles of alpha 1-antitrypsin deficiency and hepatic disease in the pathogenesis are discussed; membranoproliferative glomerulonephritis is probably the consequence of the chronic liver disease.

Child↗