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Biomedical subjects

J Rahier

Publications and source records attributed to J Rahier.

At least 91 records · Page 5Linked to original sources
PubMed1993

Monoclonal antibodies in prophylactic immunosuppression after liver transplantation. A randomized controlled trial comparing OKT3 and anti-IL-2 receptor monoclonal antibody LO-Tact-1.

A prospective trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were randomly divided into three groups according to immunosuppression during the first 10 days post-OLT: triple drug therapy only (TDIS: cyclosporine, steroids, azathioprine) (group I: n = 42); TDIS with a 10-day course of OKT3 (group II: n = 44); and LO-Tact-1 (anti-IL-2 receptor mAb) (group III: n = 43). Biopsy-proved acute rejection (AR) was treated using the same biopsy-guided protocol in the 3 groups. One-year patient survival rates were 67%, 84%, and 93% in groups I, II, and III, respectively (I vs. II, NS; I vs. III, P = 0.001; II vs. III, P = 0.044). Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection, with an overall rate of 89% during the first 3 months post-OLT, similar in the 3 groups. However, incidences of steroid-resistant rejection diagnosed during the 10 first days post-OLT were 54%, 24%, and 34% in groups I, II, and III and 46%, 26%, and 11%, respectively, during the 10-90 days interval. Sixteen patients with CMV had received OKT3, whereas the 5 remaining CMV cases had not (P = 0.019). In summary: (1) mAbs did not modify crude incidence of AR; (2) in the early period (< 10 days), TDIS immunoprophylaxis combined with OKT3 was more efficient than TDIS alone; (3) when compared with groups I and II, LO-Tact-1 apparently better prevented steroid-resistant rejection during the 10-90 days post-OLT; (4) OKT3 significantly increased incidence of CMV infection. In conclusion, TDIS with LO-Tact-1 seemed to achieve the better risk-benefit ratio in induction immunosuppression after OLT.

Acute Disease↗
PubMed1993

[Total thyroidectomy in a young girl presenting C cell hyperplasia at the time of a family screening for medullary carcinoma of the thyroid gland].

The authors report on the case of a 5,8 year-old girl whose father died of medullary thyroid carcinoma. When she was 4,5 year-old, her physical examination was normal but plasma calcitonin and katacalcin (PDN-21) levels were abnormally high in response to pentagastrin infusion. Total thyroidectomy was performed and immunohistochemical staining showed confluent C-cell hyperplasia. No recurrence occurred in this patient over four years on follow-up.

Carcinoma, Medullary↗
PubMed1993

[Localizing of Langerhans islets adenoma by transhepatic portal catheterization].

BACKGROUND: The procedures used to locate pancreatic endocrine tumors have only limited success in infants and children in whom the nodules may be small. Portal catheterization may therefore be useful. CASE REPORT: A child aged 6 yrs 4 months was admitted because of several recent episodes of pallor and sweating associated with hypoglycemia. Further investigation showed moderate hyperinsulinemia and low blood levels of ketone bodies and branched amino-acids after a 15 hr fast. Celiac angiography was normal. The hypoglycemic episodes recurred despite treatment with diazoxide for 6 months. A transparietal portal catheterization was therefore performed. Selective pancreatic venous sampling showed high concentrations of insulin in two small veins draining one part of the head of the pancreas (117 and 89 microU/ml). The head of pancreas was removed 16 months later. Extemporaneous examination revealed an adenoma 0.8 cm in diameter. This patient has completely recovered, 8 months after surgery. CONCLUSION: Transparietal portal catheterization can detect pancreatic areas with high insulin secretion. It may also help the interpretation of celiac angiographs in children, as diagnosis may be obscured by the normal rich vascularity of the pancreas in these patients.

Adenoma, Islet Cell↗
PubMed1992

Influence of the decrease of intracellular antigenic content on morphometric analysis: effect of the type and dilution of the first antibody.

The aim of the study is to determine the effect degranulation of B cells on their immunohistochemical detection and to evaluate whether this effect depends on the technique of immunological detection. The biological model is the pancreatic insulin-containing B cell. To decrease the insulin content of the pancreas, insulin release was stimulated by five intraperitoneal injections of glibenclamide (2 mg/kg). Specimens of the pancreas were taken for insulin extraction and quantitation by radioimmunoassay (RIA), ultrastructural analyses and immunocytochemistry. The sections were treated either by polyclonal or monoclonal anti-insulin serum at various concentrations and peroxidase-antiperoxidase (PAP) technique eventually followed by silver amplification. The B-cell insular fraction or relative B-cell area (RBA) was measured with an automatic image analyser. The reference value for the relative B-cell area was established in control rats and corresponds to the ratio of the insular area occupied by immunostained B cells to the islet area. Its value was confirmed by calculation of the area occupied by non-B cells. RIA indicates a decrease of 83% of the insulin content in treated rats while the number of B granules decreases by 72% at the ultrastructural level. In usual conditions (polyclonal serum, 1/1500) the degranulation leads to a 16% underestimation of the B-cell insular fraction. This underestimation increases when monoclonal antibodies are used and further increases when higher dilutions are tested. The silver amplification does not prevent this underestimation and, in this particular model, exclusively acts by increasing the contrast. The only means of restoring the correct level of detection is to use the serum at a higher concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Acute adenovirus hepatitis in liver transplant recipients.

An acute or fulminant adenovirus hepatitis developed in 5 of 224 pediatric patients who were recipients of orthotopic liver transplants. All had received prednisolone, azathioprine, and cyclosporine as basal immunosuppression, and four received monoclonal (OKT3) or polyclonal (antithymocyte globulin) antibodies for steroid-resistant rejection episodes. These patients initially had high fever and a worsening condition for a mean of 73 days after transplantation (range 44 to 140 days). Results of biochemical tests showed very high serum levels of lactate dehydrogenase. Aspartate aminotransferase values were always markedly more elevated than those of alanine aminotransferase. Two patients had severe leukopenia. Results of histologic studies of the liver showed extensive areas of confluent necrosis and targetlike hepatocyte nuclei. Typical intranuclear viral inclusions were observed on electron microscopy. Adenovirus was cultured in all patients and in two relatives. Two patients died of liver failure; others recovered after cessation of immunosuppression. We conclude that adenovirus hepatitis can be fatal in liver transplant recipients. There is no specific treatment, and immunosuppression must be discontinued.

Adenovirus Infections, Human↗
PubMed1992

Immunoquantification of cytochrome P-450 3A on rat paraffin-embedded liver tissue.

The cytochrome P-450 3A family is involved in the metabolism of several drugs, including nifedipine, cyclosporine, quinidine and erythromycin. The purpose of this study was to develop a reliable method to obtain a relative quantification of cytochrome P-450 3A apoproteins in rat liver specimens by immunocytochemistry and to correlate such quantification to erythromycin N-demethylase activity, a biochemical pathway sustained by that enzymatic system. Thirty-six male Wistar rats were treated with an injection of either saline or dexamethasone phosphate (10, 30 or 50 mg/kg), a potent inducer of cytochrome P-450 3A. Specimens taken from the same lobe were processed for immunocytochemistry and determination of erythromycin N-demethylase activity. Paraffin sections were treated with a polyclonal antiserum directed against cytochrome P-450 3A. The density of cytochrome P-450 3A immunostaining measured by an automatic image analyzer increased with the dose of dexamethasone pretreatment, and with the erythromycin N-demethylase activity, both parameters being closely correlated. Our data indicate that in rats, when cytochrome P-450 3A is concerned, there is a close correlation between the results of immunoquantitation and biochemical activity. This suggests that such a method of investigation might be used on small paraffin-embedded liver specimens obtained by needle biopsy.

Animals↗
PubMed1992

Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up.

We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.

Adult↗
PubMed1992

Fever, hepatitis and acute interstitial nephritis in a patient with rheumatoid arthritis. Concurrent manifestations of azathioprine hypersensitivity.

We describe a patient with rheumatoid arthritis (RA) who developed hypersensitivity after 3 weeks of therapy with azathioprine with fever, jaundice and renal insufficiency. A percutaneous liver biopsy was compatible with hypersensitivity hepatitis. During azathioprine rechallenge, the symptoms recurred within a few days, consistent with the diagnosis of an acute hypersensitivity reaction. This report is the first to describe the association of an azathioprine induced hypersensitivity simultaneously involving the liver and the kidneys, in the same patient with RA, with resurgence after rechallenge.

Acute Disease↗
PubMed1991

Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases.

Clinical presentation, changes in liver function test results, and liver morphology were examined in 41 consecutive patients with vitamin A hepatoxicity. The cause of liver disease was suspected at initial interview in only 13 instances, whereas histological evidence of fat-storing cell hyperplasia with fluorescent vacuoles led to the diagnosis in the remaining cases. Cirrhosis was found in 17, mild chronic hepatitis in 10, noncirrhotic portal hypertension in 5, and "increased storage" alone in 9 cases. During a mean follow-up period of 4.6 years, 6 patients died of causes related to the liver disease. A precise appraisal of drug consumption was obtained in 29 cases. Among them the total cumulative intake was the highest in patients with cirrhosis (423 +/- 103 x 10(6) IU) and significantly lower in those with noncirrhotic liver disease (88.5 +/- 41; P less than 0.02). The smallest continuous daily consumption leading to cirrhosis was 25,000 IU during 6 years, whereas higher daily doses (greater than or equal to 100,000 IU) taken during 21/2 years resulted in similar histological lesions. It was concluded that at least in some western countries chronic vitamin A consumption might represent an appreciable cause of chronic liver disease, the recognition of which mainly relies on expert liver biopsy interpretation. The data also indicate that prolonged and continuous consumption of doses in the low "therapeutic" range can result in life-threatening liver damage.

Chemical and Drug Induced Liver Injury↗
PubMed1991

Reversible cholestasis with bile duct injury following azathioprine therapy. A case report.

A 67-year-old patient, with primary polymyositis and without previous evidence of liver disease, developed clinical and biochemical features of severe cholestasis 3 months after initiation of azathioprine therapy. Liver biopsy showed cholestasis with both cytological and architectural alterations of interlobular bile ducts. Azathioprine withdrawal resulted after 7 weeks in the resolution of clinical and biochemical abnormalities. It is believed that this is the first reported case of reversible azathioprine-induced cholestasis associated with histological evidence of bile duct injury.

Azathioprine↗
PubMed1990

Liver transplantation in children less than 1 year of age.

Of 139 children who received an orthotopic liver transplant in our center between March 1984 and July 1989, a total of 17 patients (12%) had transplants before their first birthday (mean age 10.3 months; range 8 to 11). The mean weight was 7.3 kg (range 5.2 to 13). Nine retransplantations were performed in five children because of primary nonfunction (three children), hepatic artery thrombosis (four), or rejection (two). A reduced donor liver was used for 11 of 26 transplants. Baseline immunosuppression included cyclosporine, prednisone, and azathioprine with OKT3 or anti-thymocyte globulin for steroid-resistant rejection episodes. Survivors were discharged after a mean hospital stay of 47 days (range 22 to 87), and nonsurvivors died within a mean of 40 days (range 0 to 120). The 1 year actuarial survival rate was 64.7%, in comparison with 75.8% in the whole series. One patient died perioperatively, two died from primary nonfunction, one from adenovirus infection, two from rejection, and one from bone marrow aplasia. Eighteen rejection episodes, of which 11 were steroid resistant, occurred in 11 patients. Our series shows that liver transplantation can be successful in this age group.

Biliary Atresia↗
PubMed1990

Changes of relaxin concentrations determined by immunodensitometry in ovaries of NMRI mice during pregnancy.

Relaxin has been localized in corpora lutea (CL) of pregnant NMRI mice using the avidin-biotin complex immunocytochemical procedure and an antiserum against highly purified porcine relaxin. The immunostaining was measured by immunodensitometry. Relaxin immunostaining was first observed in luteal cells of type I gestational CL on day 11.5 (D11.5). For each investigated day, all CL were identically stained, and immunostaining was evenly dispersed all over the CL. Seventy-five percent of cells were stained at D11.5, and nearly all cells were stained between D13.5 and D18.5. The staining intensity increased throughout the last half of pregnancy, reaching a maximum at D18. A few hours before parturition, at D18.5, relaxin immunostaining decreased dramatically and reached the background level shortly after delivery. From our results we may conclude that, in murine CL, the number of relaxin-secreting cells and the intracellular storage of the peptide increase during pregnancy. The disappearance of relaxin with the cells occurs rapidly +/- 12 h before parturition.

Animals↗
PubMed1989

Lipid peroxidation in acrylonitrile-treated rats, evidenced by elevated ethane production.

The intraperitoneal administration of acrylonitrile (greater than 25 mg kg-1) to rats is associated with an increased production of ethane and a rise of the serum activity of the cytosolic enzyme, sorbitol dehydrogenase. These effects are prevented by pretreatment with vitamin E and the microsomal enzyme inhibitor SKF 525A, but are exacerbated by pretreatment with the microsomal enzyme inducer, phenobarbital. Repeated intraperitoneal administration of acrylonitrile (40 mg kg-1) for four weeks also increases ethane production and serum SDH activity, and produces various morphological changes in liver parenchymal cells (necrosis, increased mitotic activity, increased nucleolar size and myelinic figures in mitochondria) and inhibits the growth of the animals. All these effects are prevented by the administration of vitamin E (190 mg kg-1 i.p., daily) during the last two weeks of treatment. A dose of sodium cyanide (2.5 mg kg-1 i.p.) which leads to a urinary excretion of thiocyanate similar to that found after the intraperitoneal administration of 25 mg kg-1 acrylonitrile, does not stimulate ethane production. This study suggests that the hepatoxicity of acrylonitrile may, at least partly, result from a lipoperoxidation process and is linked with its microsomal oxidative biotransformation.

Acrylonitrile↗
PubMed1989

Primary sclerosing cholangitis and idiopathic pulmonary fibrosis: a case report.

Primary sclerosing cholangitis (PSC) and idiopathic pulmonary fibrosis (IPF) were each separately described in association with a variety of chronic idiopathic inflammatory diseases such as retroperitoneal fibrosis, Sicca complex or Riedel's thyroiditis. We report a case which may be the first description of the association between PSC and IPF. The physiopathogenic implications of such an association are discussed.

Biopsy↗