Involvement of the nervous system by the human T-lymphotropic virus type I (HTLV-I) was demonstrated in the tropics and Japan in two chronic neurological disorders, tropical spastic paraparesis (TSP) {l] and HTLV-I-associated myelopathy (HAM) {2]. HAM and HTLV-I-positive TSP are recognized as clinically and pathologically identical diseases [3], and the name HAWTSP is now used for this disorder {3a].In previous reports, treponemal infections have been suggested as a suspected cause of TSP by serological and pathological studies {4]. In subsequent investigations to evaluate this hypothesis, Rodgers-Johnson and colleagues { 57 noted that Treponemu pertenue and Treponemu pallidum were unlikely to be etiological candidates for TSP. Samples were also tested for the presence of antibody to Bowelia burgdorferi, a causative agent of Lyme disease, which was recognized as a multisystem disease involving neurological complication [67. Rodgers-Johnson and colleagues [5] were able to demonstrate that 25% of Jamaican patients with TSP had antibodies to B. burgdofleri. In Japan, some cases of Lyme disease have been reported since 1987 [7].We recently examined 2 patients who had facial diplegia and elevated serum antibodies to B. burgdorferi in the Kagoshima prefecture, one of the areas in Japan in which HAWTSP is most prevalent {8]. Neuroborreliosis apparently exists in this area, and consequently, it would be important to know whether B. burgdorferi might play a role in the development of HAWTSP in Japan.Serum samples were obtained from 20 patients with HAWTSP (15 women and 5 men) from the Kagoshima prefecture. Their ages ranged from 23 to 76 years (mean, 52). The two groups of control subjects consisted of 20 healthy carriers of HTLV-I (15 women and 5 men; age range, 21 to 75, mean, 52) and 20 seronegative healthy individuals (1 5 women and 5 men; age range, 2 1 to 76, mean, 52). The serum samples from these groups were tested by immunofluorescence assay using B. burgdorferi (IFA-Bb) from Ixodes ricinus as the antigen. Positive samples in IFA-Bb were examined by the Treponema pallidum hemagglutination test (TPHA) to exclude syphilis or other treponemal infections.Only one of the HAWTSP patients was positive by IFABb. However, this patient was also positive by TPHA, indicating a previous syphilis infection. All samples from the control groups consisting of healthy carriers and healthy individuals were negative when tested by IFA-Bb and TPHA.The present results clearly demonstrate that there is not a causal relationship between B. burgdorferi and HAWTSP in Japan. However, since some differences of clinical features are known to exist between HAWTSP in Japan and in the Caribbean basin 131, the possibility remains that these differences may be influenced by infection with B. burgdofleri, which may act as a cofactor.
Background and Aims High-dose methotrexate (MTX) chemotherapy is used to treat a variety of malignancies, including lymphoma, lymphoid leukemia, and sarcomas. Since MTX binds to proteins at a binding ratio of 50%, and nearly 90% of MTX in the blood is excreted via the kidneys, impaired kidney function would cause accumulation of MTX and result in complications. We encountered 4 patients who developed acute renal failure following high-dose MTX administration, but recovered after several modalities of blood purification therapies at our hospital. To clarify which blood purification method might be the most effective to remove accumulated MTX, we retrospectively investigated the removal rate of MTX by different modalities of blood purification therapy. Four patients (3 males and 1 female) who developed acute renal failure immediately after the start of administration of high-dose MTX therapy received blood purification therapies, including hemodialysis (HD), hemodiafiltration (HDF), plasma exchange (HD + PE), direct hemoperfusion (DHP), or any combination of the above, from January 2010 to December 2015. Methods Case 1: Patient (female, 57 years old, weight 54 kg) received HD (9times) followed by HDF (5 times) for 4 h each using a cellulose triacetate (CTA) membrane. Case 2: Patient (male, 56 years old, weight 90.7 kg) received HD (8 times) with 2different membranes (polyethersulfone and polyarylate blended polymer (PEPA); CTA; polymethyl methacrylate (PMMA)) for 4 h each. Case 3: Patient (male, 79 years old, weight 56 kg) received HD (3 times) followed by HDF (6times), HD + PE (once) for 4 h each. Case 4: Patient (male, 23 years old, weight 104.6kg) received HDF using CTA (3 times) membranes, followed by HD + PE, HD + DHP (3 times) and DHP (once) for 4 h each. We retrospectively investigated the blood level of MTX before and after each of the blood purification therapies and compared the removal rate of MTX by the different modalities. Results and discussion The average dose of MTX prescribed was 1.1 g/m2 (0.9-3.8). The blood levels of MTX reduced from 29.4 μM (9.8-57.8) to 0.06 μM (0.02-0.09) after several treatment sessions, and improvement of the renal function was observed in all cases. The highest removal rate was observed with HD + DHP (61.7%, n = 3), followed by DHP (50.0%, n = 1), HDF (44.1%, n = 19), HD (34.6%, n = 23) and HD + PE (30.3%, n = 2). As for the most effective membrane used for HD, the highest removal ratio was observed with PEPA (69.6%, n = 3), followed by PMMA (36.5%, n = 3) and CTA (28.2% %, n = 17). In regard to the most effective modality for removing accumulated MTX from the blood, high removal efficiencies were observed for HD + DHP and DHP. Therefore, it appears that use of these modalities would be the most desirable, as these appear to be highly capable of effectively removing accumulated MTX. Higher removal rates were observed with the use of the PEPA membranes than with that of the CTA and PMMA membrane, probably due to the better adsorption capacities of PEPA membrane. From these results, we conclude that HD or HDF with a high-adsorption characteristics (PEPA) combined with DHP might be the most effective method for removing accumulated MTX from the blood, as well as controlling water removal and correcting electrolyte concentrations. Conclusion Improvement of the renal function was observed after several sessions of blood purification therapy in all patients who developed acute renal failure after high-dose MTX therapy. The removal efficiency of MTX was sufficiently high when HD + DHP, HDF or HD was performed, especially with the use of a membrane with high adsorption characteristics.
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