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A tiered testing strategy has been employed to evaluate the potential of tobacco processes, ingredients, or technological developments to change the biological activity resulting from burning cigarette tobacco. The strategy is based on comparative chemical and biological testing. The introduction of banded cigarette papers in cigarettes to meet New York state "Fire Safety Standards for Cigarettes" constitutes an example of a technological development evaluated utilizing this tiered testing strategy that included a comparison of the chemical and biological effects of cigarettes with and without the banded cigarette paper technologies (BCPT) (representative of current marketed technologies). Specific testing included mainstream cigarette smoke chemistry studies; in vitro studies included genotoxicity (Ames and sister chromatid exchange) and cytotoxicity studies (neutral red); in vivo studies included a 13-week inhalation study in Sprague-Dawley rats and a 30-week dermal tumor promotion study in SENCAR mice. Collectively, data indicated that cigarettes with and without BCPT had a similar toxicological profile in this test battery.

Contains fulltext : 58515.pdf (Publisher’s version ) (Closed access) BACKGROUND: Identification of mononuclear cellular infiltrates in skeletal muscle tissue is the histological cornerstone of the diagnosis of idiopathic inflammatory myopathy (IIM). However, these infiltrates are not always present. OBJECTIVE: To determine whether MHC class I antigen expression on the sarcolemma, which is absent in normal muscle tissue, is upregulated in IIM and could serve as an additional diagnostic test. METHODS: Expression of MHC class I antigens was studied in 224 muscle samples of 61 adult patients with IIM (9 dermatomyositis, 23 polymyositis, 29 inclusion body myositis) and 163 controls (normal subjects and patients with various neuromuscular disorders) in a prospective blinded manner. RESULTS: The sensitivity of the test for diagnosing IIM was 78% (95% confidence interval (CI), 66% to 88%), with a specificity of 95% (91% to 98%). The sensitivity before the start of immunosuppressive treatment was 89% (76% to 96%). The sensitivity was not changed by including all patients who had been on immunosuppressive treatment for less than four weeks before muscle biopsy (sensitivity 90% (79% to 97%)). False positive results were found in only seven controls (4%), six of whom had a muscular dystrophy. CONCLUSIONS: Detection of sarcolemmal MHC class I is a valid test for IIM. It is not affected by the short term use of immunosuppressive agents (less than four weeks) and it should be incorporated in the histological evaluation when the diagnosis of IIM is under consideration or needs to be excluded.

Objectives: This paper reports for the first time three cases of infection by HTLV-I via organ transplantation; all the organs coming from the same asymptomatic infected donor. The need is considered for the implementation of compulsory screenings for HTLV antibodies on organ donors and on blood banks. Methods: The determination of antibodies for HTLV-I/II on samples of serum and cerebral spinal fluid from the patients and the donor was performed by enzyme immunoassay and western blot. Analysis of proviral DNA was performed by polymerase chain reaction. To detect changes in the sequence of aminoacids, the tax gene was sequentiated, amplified, and compared with ATK prototype stocks. Spinal cord magnetic resonance imaging, cerebral spinal fluid, and somatosensory evoked potential studies were carried out in all patients. Results: All three transplanted patients developed a myelopathy within a very short period of time. In all three patients and donor the virus belonged to the Cosmopolitan A subtype. The homology of HTLV-I sequences recovered from the patients and donor was 100% in all four cases. Proviral load was high in all three patients. The factors that certainly contributed to the infection in the first place, and the development of the disease later, were on the one hand the high proviral load and their immunosupressed condition, and on the other the virus genotype, which proved to be an aggresive variant. However, the analysis of the histocompatibility antigen showed that two of the patients carried an haplotype that has been associated with a lower risk of developing this disease. Conclusions: It is argued that, although in Spain and other European countries there is not compulsory screening for HTLV antibodies because of the studies that show a low seroprevalence, in view of the cases here reported, and to avoid the serious consequences that such infection has on transplanted patients, compulsory screenings, both on organ donors and on blood banks, should be implemented.

Background: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS). Aims: To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression. Methods: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen-cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source. Results: Median follow up was 36 months (range, 7-36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases. Conclusions: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.