Is the black thyroid really an innocuous pathological finding?

We report the case of a 24-year-old euthyroid woman in whom the discovery of a cold nodule in the left thyroid lobe led to a thyroidectomy. The surgical specimen was characterized by a diffuse black discoloration. Optical examination revealed brown granules within the apical portion of the follicular cells whereas ultrastructural studies showed intralysosomal lipofuscin-like deposits, all findings consistent with pathological descriptions reported in black thyroids associated with the intake of minocycline. Retrospectively, we were told that the patient had received this antibiotic for at least three years for the treatment of acne vulgaris. As experimental models have demonstrated potential antithyroid effects of the drug, it appears relevant to monitor thyroid tests in patients receiving long-term minocycline therapy.

Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine.

BACKGROUND: Cases of so-called autoimmune hepatitis (AH) have been reported after liver transplantation. Our aim was to evaluate the incidence in a series of 471 pediatric liver transplant recipients. METHODS: Between 1984 and 1998, 471 children had orthotopic liver transplantation (OLT). Children are followed up on a regular basis, with full clinical, biochemical, and histologic evaluation at 6 months, 1, 2, 5, 7, and 10 years after OLT. Children with unexplained abnormal liver tests were screened for autoimmune markers (total gamma-globulins, smooth muscle antibodies [SMA], liver kidney microsome antibodies [LKM], antinuclear factor [ANA]). From January of 1998 until December of 1998, autoimmune markers were prospectively searched in all children admitted for regular posttransplant follow-up (n = 118). RESULTS: Eleven of 471 children (2.35%) were found with autoimmune hepatitis, 9 retrospectively and 2 prospectively. None had previous autoimmune liver disease. Patients had a history of steroid-dependent hepatitis. Histology showed variable degree of portal and lobular inflammation, piecemeal necrosis, and bridging collapse. Mean (+/-SDS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities at diagnosis were 173+/-145 and 196+/-157 IU/L, respectively (nl<32). Median gamma-globulin levels reached 1365 mg/dl versus 931 mg/dl in controls (P<0.05). Nine had ANA (titer 1/80 up to 1/10,000), 1 SMA (1/320), and 2 LKM1 antibodies (1/1280). Patients did not respond to increasing charge of cyclosporine (n=10) or tacrolimus (n=1). Eleven received steroids (prednisolone: 2 mg/kg per day, then tapered) and azathioprine (1.5 to 2.5 mg/kg per day). All patients normalized within 3 months (mean AST/ALT levels of 26+/-8 and 30+/-9 IU/L). Three had mild to moderate relapse with increase of ALT thereafter. Gamma-globulins decreased to 1190 mg/dl (ns). Amongst the 116 remaining prospectively evaluated patients, 85 had normal evaluation, despite low titers of autoantibodies in 15 (SMA< or =1/40, ANA 1/80). Thirty-one patients had graft dysfunction, related to well-explained posttransplant causes, among which 7 had similar low levels of autoantibodies. CONCLUSIONS: A total of 2.35% of our transplant children present evidence of immune hepatitis after transplantation. Patients do not respond to increasing cyclosporine or tacrolimus levels and require steroid and azathioprine. In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.

[Preparation of a specific anti-cytomegalovirus immunoglobulin for intravenous injection]. / Préparation d'une immunoglobuline spécifique anti-cytomégalovirus injectable par voie intraveineuse.

In the industrialised countries of Europe about 60-70% of adults possess antibodies against cytomegalovirus. Primary infections or exacerbations of a latent infection are in most cases clinically asymptomatic in healthy patients. By way of contrast, attenuations in the immunological defence system: prematureness, pregnancy, the presence of malignant disease, immunosuppressive therapy, as well as massive transfusions of blood, are the commonest causes of a raised incidence of CMV infections often combined with severe clinical overt illness. Because a critical level of antibody is needed to prevent infection and disseminating, we have produced cytomegalovirus hyperimmune globulin for intravenous administration. They are prepared from plasmas of healthy blood donors on the basis of a high antibody level against cytomegalovirus. About 6% are selected by an ELISA procedure. Immunoglobulins, treated to ensure excellent intravenous acceptability, are lyophilized. The final product is found to have an anti-CMV antibody titer of 25 600, by the ELISA test, at a protein concentration of 5%. This CMV-immunoglobulin I.V. has 8 fold higher antibody content than do conventional immunoglobulin preparations. The first trials of prophylaxis and treatment of clinically apparent CMV infections are under study.

[Anti-HAV-specific immunoglobulins]. / Immunoglobulines spécifiques anti-HAV.

The prevalence of anti-HAV antibodies declines dramatically in some European countries because of increasing socio-economical level, leaving the adult population susceptible to HAV infection at a higher age. Therefore an increasing proportion of plasma used for preparation of ISG will not contain anti-HAV. So, it seems to us that preselection of donors is necessary for ISG preparation, in order to reach a satisfactory content of anti-HAV. Firstly, 800 donors above 40 years old were selected and it appeared that ISG prepared was not different from ISG coming out of unselected donors. Titer was 200 UI/ml by RIA method. Secondly, we selected plasmas with high titer of anti-HAV: C 10 greater than 87% by a competitive-inhibition RIA. 498 plasmas among 3 050 tested (16%) were chosen to prepare hyper-immune serum globulin (HISG). In this case, anti-HAV level was 800 UI/ml. In these conditions, it is possible to produce hyperimmune globulin that has a known specific potency against HAV and the future prescription would account anti-HAV level and not merely the volume.

[Comparative study of various methods for the determination of the IgM or IgG class of antibodies, applied to the diagnosis of hepatitis A]. / Etude comparative de différentes méthodes de détermination du type IgM ou IgG des anticorps, appliquées au diagnostic de l'hépatite A.

We report herein results of comparative study of different methods for determination of M or G classes of antibodies applied to serodiagnosis of type A hepatitis. We have examined retrospectively 259 sera with a technique employing protein A and 2 kits, HAVAB-M (RIA-M) and Hepanostika anti-HAV-IgM (ELISA-M). Some sera were studied after treatment by 2-mercapto-ethanol. We have obtained the same results with RIA-M and ELISA-M: 119 sera contain Ac anti-HAV of M class and 116 of G class, 24 sera non classified with protein A owing to their low level of Ac anti-HAV, are all but one of G class. We have observed 23 discrepancies between protein A or RIA-M and ELISA-M. A first group is constituted by 15 sera obtained during late convalescence and containing rates of Ac anti-HAV-M too low to be determined with protein A or 2-mercapto-ethanol so they are classified G, while RIA-M and ELISA-M, more sensitive, could detect such antibodies. Another group is constituted by 8 sera containing low rates of anti-HAV antibodies so we could not dilute them for reaction, and IgG were not adsorbed entirely on protein A while 2-mercapto-ethanol, RIA-M and ELISA-M led them being classified Ac anti-HAV-G. RIA-M and ELISA-M are useful tools particularly for sera obtained during late convalescence while protein A and 2-mercapto-ethanol are effective for diagnosis during 1 month after acute phase.

[Determination of specific anti-HBO immunoglobulin of IgM or IgG type. Relation to other virus HB markers]. / Détermination du type IgM ou IgG des immunoglobulines spécifiques anti-HBc. Relations avec les autres marqueurs du virus HB.

A procedure for determining anti-HBc of IgM class is described herein. After IgG anti-HBc antibodies have been preferentially absorbed with Staphylococcus aureus cells positive for protein A, we have tested for residual IgM anti-HBc in the supernatant (absorbed serum) by radioimmunoassay. The occurrence and time course of anti-HBc, studied in 3 patients with ongoing infection, show that IgM anti-HBc persist for about 2 months in cases of acute hepatitis. IgM anti-HBc --marker for a recent HBV infection-- was found to be a useful tool in diagnosis of an unapparent hepatitis with transient or undetectable HBs antigenemia (case no 5). The presence of IgM or IgG anti-HBc, HBeAg and anti-HBe was determined by radioimmunoassay in 68 patients HBsAg positive. The immunoglobulin classes (IgM or IgG) of anti-HBc are dependent on the phase of hepatitis B. Of the 29 IgM anti-HBc positive specimens, 28 were found to be HBeAg positive, 18 of these patients were hemodialysed. 62 among 63 HBsAg positive blood donors had IgG anti-HBc, 6 associated with HBeAg and 56 with anti-HBe. All anti-HBc of anti-HBs positive sera were of IgG class (patients or blood donors). In order to estimate the anti-HBc titer, we have determined the per cent inhibition of 134 HBsAg and 46 anti-HBs positive sera diluted to 1 : 100. We correlate the presence of HBsAg --regardless of the level of titer of it --with high titers of anti-HBc and the presence of anti-HBs with low titers (P less than less than 0,0001). These results are very instructive with regard to the problem of anti-HBc titer and possibility of persisting HBV and we support the hypothesis that HBsAg negative but strongly anti-HBc positive blood might be infectious. IgM anti-HBc are on the average of lower titer than IgG anti-HBc, but we did not observe difference in IgG anti-HBc titer between HBeAg positive sera and anti-HBe, HBsAg positive sera.

Action du dibutyryl 3',5'-AMP cyclique et de l'insuline sur la synthese des acides gras dans les differentes fractions cellulaires de foie in vivo.

3',5'-Cyclic AMP inhibits fatty acid synthesis in mitochondria, microsomes and supernatant but does not provoke an enrichment in 3H with regard to 14C as it occurs during fasting after glucose 6-(3)H or 6-(14)C administration. Insulin does not exert any action on "controls" but restores lipogenesis in fasted animals in the examinated fractions and normalises the 3H/(14)C ratio, even that of microsomes. Control of neoglucogenesis by this hormone is more likely than by 3',5'-cyclic AMP.