Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

Autoinduction of Androgen Receptor mRNA in Primary Cultures of Hamster (Mesocricetus auratus) Harderian Gland Cells

The Harderian gland (hg) is a gland which occupies a large portion of the orbital cavity. In many species, a sexual dimorphism occurs, which suggests a gonadal steroid control of the hg. The present study examines, in primary cultures of hamster hg cells, the regulation of the androgen receptor mRNA (AR mRNA) expression. In dose–response experiments measuring the expression of AR mRNA, testosterone (T) (10⁻¹²M) induced a 1-fold increase of AR mRNA compared with unexposed cells, and this effect reached its zenith (6.2-fold) when cells were exposed to 10⁻⁸MT. In other experiments, cells were exposed or not to different drugs [T, T + flutamide (F), F, T + cycloheximide (Cy), Cy] for different times (up to 96 hr). These experiments showed a time-dependent increase of AR mRNA in the cells exposed to T, while in the cells exposed to F, T+F, T+Cy, Cy, and control (unexposed), a time-dependent decrease of AR mRNA was observed. The size of the hamster AR mRNA in thesein vitroexperiments was similar to that observed in other mammals (9.5 kb). It is concluded that primary cultures of hamster hg cells are a valuable model for studying hg cell activity and that in this system T autoinduces its own receptor.     

Hemagglutination and proteoglycan binding by the Lyme disease spirochete, Borrelia burgdorferi.

The ability of the Lyme disease spirochete to attach to host components may contribute to its ability to infect diverse tissues. We present evidence that the Lyme disease spirochete expresses a lectin activity that promotes agglutination of erythrocytes and bacterial attachment to glycosaminoglycans. Among a diverse collection of 21 strains of Lyme disease spirochete, hemagglutinating activity was easily detected in all but 3 strains, and these three strains were noninfectious. The ability to agglutinate erythrocytes was associated with the ability of the spirochete to bind to the sulfated polysaccharide dextran sulfate and to mammalian cells. Soluble dextran sulfate was a potent inhibitor of both hemagglutination and attachment to mammalian cells, while dextran had no effect on either activity, suggesting that dextran sulfate may inhibit attachment by mimicking host cell glycosaminoglycans. Consistent with this, the spirochete bound to immobilized heparin, and soluble heparin inhibited bacterial adhesion to mammalian cells. The bacterium did not bind efficiently to Vero cells treated with heparinase or heparitinase or to mutant CHO cell lines that are deficient in proteoglycan synthesis. Sulfation of glycosaminoglycans was critical for efficient bacterial recognition, as Vero cells treated with an inhibitor of sulfation, or a mutant CHO cell line that produces undersulfated heparan sulfate, did not mediate maximal spirochetal binding. Binding of the spirochete to extracellular matrix also appeared to be dependent upon this attachment pathway. These findings suggest that a glycosaminoglycan-binding activity which can be detected by hemagglutination contributes to the attachment of the Lyme disease spirochete to host cells and matrix.     

Conjunctival cytologic features of primary Sj?gren's syndrome.

To determine whether there are specific cytologic features associated with primary Sj?gren's syndrome (SS), the authors evaluated impression cytology specimens from three conjunctival sites (temporal bulbar [TB], inferior bulbar [IB], and inferior tarsal [IT]) from 38 SS eyes, 34 eyes of aqueous tear-deficient patients without SS, 35 eyes of seborrheic blepharitis patients, and 17 eyes of normal controls in a masked fashion. The following features were observed more frequently in SS eyes than in the eyes of the other groups: squamous metaplasia of the TB and IB (P less than 0.05), extensive (greater than 75%) goblet cell loss of the TB (P less than 0.05), mucous aggregates of the bulbar conjunctiva (P less than 0.05), and inflammatory cells intercalated with epithelial cells on the IT conjunctiva (P less than 0.06). The conjunctival inflammatory cell infiltrate correlated with the presence of extensive squamous metaplasia (P less than 0.01) in SS specimens. The inflammatory cells on the IT conjunctival epithelium were found to consist predominantly of T-lymphocytes by immunofluorescent staining of cytologic specimens from six eyes. Based on these findings, the authors speculated that conjunctival squamous metaplasia, in addition to aqueous tear deficiency, may be due to primary involvement of the dysfunctional immune system of SS.     

Ten cases of transitional cell carcinoma of bladder causing ureteric obstruction

A review was carried out on 10 patients with superficial transitional cell carcinoma of the bladder (Ta lesions) that were causing ureteric obstruction. Evidence of upper tract obstruction did not necessarily indicate deep invasion.     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Radiation doses deriving from patients undergoing 111In-DTPA-d-Phe-1-octreotide scintigraphy

The purpose of this study was to estimate the radiation doses to nursing staff, other patients, accompanying persons and family members deriving from patients undergoing ¹¹¹In-DTPA-d-Phe-1-octreotide (¹¹¹In-OCT) scintigraphy. Dose rates were measured from 16 patients who had received an intravenous injection of 140±40 MBq ¹¹¹In-OCT. The measurements were performed at three different distances (0.5, 1 and 2 m) at 10–20 min, 5–7 h and 24 h (and in some cases, up to 48 h) after administration of ¹¹¹In-OCT. The effective half-lives of the biexponential decrease of the dose rates were estimated to be 2.94±0.27 h (T ₁) and 65.17±0.58 h (T ₂). The calculated maximum dose to other persons in the waiting area was 27.2 μSv, to family members 61.5 μSv, to nursing staff in a ward 24.1 μSv and to neighbouring patients in the ward 69.5 μSv. Our results clearly demonstrate that the calculated maximum radiation exposure to accompanying persons, personnel, family members and other patients is well below the maximum annual dose limit for non-professionally exposed persons. Received 20 May and in revised form 9 July 1997