Is it useful to perform carbon monoxide diffusion capacity and respiratory muscle function tests in patients with multiple sclerosis without disability?

Background and objective: Impairment of respiratory function has been described in end‐stage multiple sclerosis (MS), as well as in patients with mild to severe disability. No data are available regarding the respiratory function of MS patients without disability. The objective of this study was to assess the pulmonary function, respiratory muscle strength and carbon monoxide diffusion capacity of the lungs (DL_CO) in patients with relapsing‐remitting multiple sclerosis (RRMS) without disability. Methods: Twenty‐seven RRMS patients and 25 healthy control subjects were recruited. All subjects underwent clinical and neurological examination, and spirometry; lung volumes, DL_CO and maximal respiratory pressures were measured. All subjects were rated on the Modified Fatigue Impact Scale and Fatigue Severity Scale scales. Results: There were no significant differences in age, gender, height, weight or body mass index between the groups. The mean duration of illness in the MS group was 5.44 ± 3.74 years, and the mean Expanded Disability Status Scale was 0.62 ± 0.65. The mean values for total lung capacity, forced expiratory volume in 1 s (FEV₁) and FEV₁/FVC were normal in both groups. Fifteen RRMS patients exhibited a reduction in maximal expiratory pressure (MEP), but only one patient exhibited a reduction in maximal inspiratory pressure. The mean values for DL_CO were lower in RRMS patients (P = 0.0004) than in the control group. DL_CO was decreased in 15 (55.55%), out of 27 RRMS patients. The fatigue scale results were not correlated with pulmonary function test results Conclusions: DL_CO and MEP may be impaired in RRMS patients without disability.     

Serological status: a predictor of response to intensive therapy in rheumatoid arthritis

BackgroundRheumatoid arthritis is the most common chronic inflammatory disease in the UK. Serological status such as rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity predict poor outcomes. Early intensive treatment regimens targeting remission reduce disease activity, structural damage, and long-term disability. However, we do not know whether all patients with active disease should have such intensive treatment regimens. Can serological status be used to predict the need for intensive therapy?MethodsWe analysed samples from a published randomised controlled trial which compared four treatment regimens in patients with early active rheumatoid arthritis (disease duration <2 years): methotrexate monotherapy, double therapy (methotrexate plus either ciclosporin or prednisolone), and triple therapy (methotrexate plus ciclosporin plus prednisolone). The trial randomised 467 patients (68% female, median age 54 years [IQR 46–63]). Disease activity was assessed with the disease activity score of 28 joints (DAS28). Remission was defined as DAS28 less than 2·6 at 24 months. RF isotypes (IgM and IgA) and ACPA levels were measured with commercial ELISA kits. Statistical analysis used Pearson's chi-squared test.Findings402 (86%) patients were positive for IgM RF, 346 (74%) for IgA RF, and 346 (74%) for ACPA. 98 (21%) patients achieved remission at 24 months. In RF IgM negative cases (n=65) the proportion of patients achieving remission at 24 months was similar in all treatment groups (25%, 22%, and 30% for monotherapy, double therapy, and triple therapy, respectively). In RF IgM positive cases, significantly fewer patients achieved remission with monotherapy (13/65, 17%) and double therapy (24/157, 15%) than with triple therapy (27/80, 34%) (p=0·001). There were similar, consistent findings with IgA RF and ACPA, with significantly more seropositive patients achieving remission with triple therapy than with monotherapy.InterpretationContemporary treatment of rheumatoid arthritis emphasises the use of intensive therapy to achieve remission. However, we have shown that not all patients require such an aggressive approach to therapy. Given the heterogeneity of the diease, treatment should be personalised to the individual, which would minimise costs of treatment as well as potentially toxic side-effects. Our study shows that only seropositive patients with rheumatoid arthritis should be given more intensive therapies.FundingNational Institute for Health Research.     

Use of a different buffer system in the phenolic glycolipid-I ELISA.

By changing the buffer system in the phenolic glycolipid-I (PGL-I) enzyme-linked immunosorbent assay (ELISA) the sensitivity of the test was increased without altering its specificity. Using a Tris-HCl buffer, significant titers of > or = 1:300 were found in 53.1% of the sera in paucibacillary (PB) and 98.0% of the sera in multibacillary (MB) groups of patients. Titer levels were also significantly increased. In the PB group of patients with Tris-HCl, the highest titer detected was 1:1200; in the MB group of patients, 1:76,800. Through this modification of the buffer system a more sensitive test was obtained thereby increasing the detectable level of PGL-I antibodies in both the PB and MB groups of patients.     

Translation and cross-cultural adaptation of the Multiple Sclerosis Walking Scale (MSWS-12) into Brazilian Portuguese

Poor walking performance is predictive of heart disease and osteoporosis and increases the risk of death in the elderly. Gait and vision have been identified as the most valuable physical functions according to multiple sclerosis patients' perceptions. The objective of this study was to perform a translation and cross-cultural adaptation of the Multiple Sclerosis Walking Scale (MSWS-12) into Brazilian Portuguese. A study of cross-cultural adaptation was conducted in ten steps. Participation in the study included four translators, two back-translators, twelve medical experts, twelve patients, twelve healthy subjects, and a Portuguese language expert. Only the question "Did standing make it more difficult to do things?" posed difficulty in the translation process. Maximum time for completion was less than three minutes (171 seconds). Internal consistency analyses showed high reliability (Cronbach's alpha = 0.94). The content validation and internal consistency stages were completed satisfactorily.     

Triterpene trimers from Maytenus scutioides: cycloaddition compounds?

Two novel trimers, triscutins A and B (1 and 2), based on pristimerin triterpene units, were isolated and characterized from Maytenus scutioides. Their structures were determined on the basis of spectroscopic evidence, including 1H-13C heteronuclear correlation (HMQC), long-range correlation with inverse detection (HMBC), and ROESY NMR experiments; and their absolute configurations, by means of CD studies. Compounds 1 and 2 were assayed for antimicrobial and cytotoxic activities, and their possible biosynthetic route is proposed.