Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

The Role of Donor Bone Marrow Infusions in Withdrawal of Immunosuppression in Adult Liver Allotransplantation

We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post-transplantation, with stable graft function. Forty-five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year. Patient and graft survival were similar between the two groups. Although rejection episodes were significantly less in G1 the first 2 years of the study (35% vs. 57%, p = 0.016), there was no significant difference overall (74% vs. 81%, p = 0.14). Until February 2004, 20 patients, 10 in each group, were immunosuppression free for 1-3 years. Approximately 20% of long-term survivors of liver transplantation can successfully discontinue their immunosuppression. DBMC infusions, do not increase this likelihood.     

Calorimetric study of blends of low density polyethylene (LDPE) and linear low density polyethylene (LLDPE) temperature rising elution fractionation (TREF) fractions

Preparative temperature rising elution fractionation (TREF) on commercial linear low density polyethylene (LLDPE) and low density polyethylene (LDPE) samples has been performed. The resulting fractions exhibited a bimodal and a unimodal distribution, respectively. Two LLDPE fractions of low (5 CH₃/1000 C) and high (21 CH₃/1000 C) short-chain branching content were solution-mixed with the LDPE central fraction (16 CH₃/1000 C). Indirect evidence based on differential scanning calorimetry results suggest that the fractions with similar branch contents are more miscible than those with dissimilar ones.     

Lymphocyte proliferation assays as potential biomarkers for toxicant exposures

Recently there has been interest in developing assays that can be used as indicators (biomarkers) of exposure to toxic agents. We have been exploring the potential utility of three lymphocyte proliferation assays [the responses of B lymphocytes to the mitogen lipopolysaccharide (LPS), the responses of T lymphocytes to the mitogen concanavalin A (ConA), and the responses of T lymphocytes to antigenic stimuli in a mixed lymphocyte culture (MLC) assay] as biomarkers of toxicant exposure. Studies were initiated to assess the applicability and specificity of these assays and to investigate the mechanisms by which toxicants alter lymphocyte proliferation. All studies were performed using cells isolated from Fischer 344 rats. To assess applicability, mitogen assays were performed using in vitro exposures to eight different toxicants: hydroquinone, benzoquinone, Aroclor 1254, styrene oxide, and the salts of mercury, cadmium, chromate, and nickel. In vitro concentrations spanned five orders of magnitude (100 to 0.01 mg/l). At the lowest concentration tested, all eight compounds induced changes in at least one mitogen assay, indicating that these assays may be applicable to a wide range of toxicants. Variations of the ConA and MLC assays were used to test for specificity. In both assays, splenocytes taken from rats exposed in vivo to either chromate or to cadmium responded differently when the cells were cocultured with exogenously added chromate or cadmium ions, indicating that it may be possible to detect exposure to a specific toxicant by performing modified lymphocyte proliferation assays. In the mechanistic studies, splenocytes from cadmium and chromate-treated rats altered the ConA-induced proliferation of cocultured syngeneic cells. In addition, the antigenicity of splenocytes isolated from cadmium-treated rats was enhanced when these cells were used as stimulators for allogeneic splenocytes. The results of these studies indicate that lymphocyte proliferation assays may be useful for detecting exposure to a wide range of toxicants and that variations of these assays may be useful for implementing immunologically based tests for detecting exposures to specific chemicals.     

Fast Three Dimensional Magnetic Resonance Imaging

To reduce the scan time in three-dimensional (3D) imaging, the authors consider alternative trajectories for traversing k-space. They differ from traditional 3D trajectories, such as 3DFT, in that they employ time-varying gradients allowing longer readouts and in turn a reduced scan time. Some of these trajectories reduce by an order of magnitude the number of excitations compared with 3DFT and provide flexibility for trading off signal-to-noise ratio for scan time. Other concerns are the minimum echo time and flow/motion properties. As examples, the authors show two applications: A 3D data set of the head (field of view of 30 x 30 x 7.5 cm and resolution of 1.5 x 1.5 x 1.5 mm) acquired in 56 s using a stack of spirals in 3D k-space; and a 3D movie of the heart (20 x 20 x 20 cm field of view, 2 x 2 x 2 mm resolution, and 16 time frames per cardiac cycle) acquired in 11 min using a cones trajectory.     

Analysis of genetic heterogeneity of hepatitis C viruses in Central America reveals a novel genetic lineage

Hepatitis C virus (HCV) has high genomic variability and at least six different types have been reported. The genotypes distribution is currently unknown among HCV strains circulating in Central America. In order to study the degree of genetic variability of strains isolated in Costa Rica, sequence data obtained from the 5' non coding region from 7 patients from Costa Rica were compared with published sequences from 57 strains of all types. The phylogenetic analysis revealed the existence of type 1 strains of a novel genetic lineage, recently described for some South American countries, and indicates an increasing diversification of HCV.