Triphenylboroxine stability under low-energy-electron interactions.

Triphenylboroxine (TPB) has chemical properties of great interest in organic synthesis, enabling the development of promising molecular architectures. Based on the possibility of the geometric arrangement of N-coordinated boron atoms, the dynamic interconversion ability of boroxine cages enables the optimization of relevant pharmacological properties in drug delivery, such as guest recognition and porosity. In addition, the synthesis of a novel 2D boroxine framework showed distinctive electronic and morphological properties that can be used in the design of new electronic devices. In the present study, the electron-driven fragmentation pathways from electron interactions with TPB using a gas-phase crossed-beam experiment have been investigated. The abundance of the molecular parent cation in the mass spectrum at 70 eV reflects the stability of TPB. The appearance energies of three fragment cations were reported, and the experimental first ionization potential was found at 9.12 ± 0.10 eV. Only the parent cation is formed in the energy range (∼9-16 eV) between the first ionization potential and the remaining thresholds. Regarding negative ion formation, four low-abundant anions in the electron energy range of 0-15 eV are discussed. These results indicate an interesting energy selectivity and stability of TPB upon electron interaction, which may justify the development of recent molecular architectures containing TPB used in a wide range of applications. These results are supported by quantum chemical calculations based on bound state techniques, electron ionization models and thermodynamic thresholds.

Perfluoro effect on the electronic excited states of para-benzoquinone revealed by experiment and theory.

We report a comprehensive study on the electronic excited states of tetrafluoro-1,4-benzoquinone, through high-resolution vacuum ultraviolet photoabsorption spectroscopy and time-dependent density functional theory calculations performed within the nuclear ensemble approach. Absolute cross section values were experimentally determined in the 3.8-10.8 eV energy range. The present experimental results represent the highest resolution data yet reported for this molecule and reveal previously unresolved spectral structures. The interpretation of the results was made in close comparison with the available data for para-benzoquinone [Jones et al., J. Chem. Phys., 2017, 146, 184303]. While the dominant absorption features for both molecules arise from analogous π* ← π transitions, some remarkable differences have been identified. The perfluoro effect manifests in different ways: shifts in band positions and cross sections, appearance of features associated with excitations to σCF* orbitals, and spectrum broadening by quenching of either vibrational or Rydberg progressions. The level of agreement between experiment and theory is very satisfactory, yet that required the inclusion of nuclear quantum effects in the calculations. We have also discussed the role of temperature on the absorption spectrum, as well as the involvement of core-excited resonances in promoting dissociative electron attachment reactions in the 3-5 eV range.

Formation of resonances and anionic fragments upon electron attachment to benzaldehyde.

Benzaldehyde is a simple aromatic aldehyde and has a wide range of applications in the food, pharmaceutical, and chemical industries. The positive electron affinity of this compound suggests that low-energy electrons can be easily trapped by neutral benzaldehyde. In the present study, we investigated the formation of negative ions following electron attachment to benzaldehyde in the gas-phase. Calculations on elastic electron scattering from benzaldehyde indicate a π* valence bound state of the anion at -0.48 eV and three π* shape resonances (0.78, 2.48 and 5.51 eV). The excited state spectrum of the neutral benzaldehyde is also reported to complement our findings. Using mass spectrometry, we observed the formation of the intact anionic benzaldehyde at ∼0 eV. We ascribe the detection of the benzaldehyde anion to stabilization of the π* valence bound state upon dissociative electron attachment to a benzaldehyde dimer. In addition, we report the cross sections for nine fragment anions formed through electron attachment to benzaldehyde. Investigations carried out with partially deuterated benzaldehyde show that the hydrogen loss is site-selective with respect to the incident electron energy. In addition, we propose several dissociation pathways, backed up by quantum chemical calculations on their thermodynamic thresholds. The threshold calculations also support that the resonances formed at higher energies lead to fragment anions observable by mass spectrometry, whereas the resonances at low electron energies decay only by electron autodetachment.

Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients.

OBJECTIVE: The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. METHODS: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ΔPGA ≥ 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. RESULTS: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho = 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ≥ 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. CONCLUSIONS: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research.

Overactive bladder symptom bother and health-related quality of life in patients with systemic lupus erythematosus and primary Sjögren syndrome.

OBJECTIVE: The objective of this paper is to assess overactive bladder (OAB) symptom bother (SB) and health-related quality of life (HRQL) among patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). METHODS: We recruited adult SLE and pSS patients and two groups of age- and sex-matched controls. We applied the OAB questionnaire-short form (OABq-SF) to all participants to assess SB and HRQL and collected clinical information relevant for OAB. We compared the OABq-SF scores for SB and HRQL between patients and controls using univariate and multivariate linear regression analysis. RESULTS: We recruited 95 rheumatic patients (68 SLE, 27 pSS) and 231 controls. Compared to controls SLE patients showed higher OABq-SF SB scores (22.6 ± 20.4 vs 14.7 ± 17.0, p = 0.004) and lower HRQL scores (89.8 ± 15.8 vs 93.8 ± 11.4, p = 0.044). On multivariate analysis SLE was significantly associated with a higher SB score (ß-coefficient 7.13, p = 0.008) and tended to be associated with worse HRQL values (ß-coefficient -3.53, p = 0.055). Patients with pSS had numerically higher mean SB scores (22.8 ± 22.5 vs 16.2 ± 18.0, respectively, p = 0.107) and lower HRQL scores (91.0 ± 10.7 vs 93.2 ± 11.6, respectively, p = 0.369), although these differences were not statistically significant. Diagnosis of pSS was not significantly associated with SB or HRQL scores on univariate or multivariate analysis. CONCLUSIONS: Patients with SLE have significantly worse OAB-SB and poorer HRQL compared to controls. A similar trend was seen for pSS patients, especially for SB. These findings suggest that clinically subtle OAB symptoms may be present in rheumatic patients for whom, later on, bladder pain syndrome may occur.

Psoriatic Arthritis Quality of Life questionnaire: translation, cultural adaptation and validation into Portuguese language.

Psoriatic arthritis (PsA) has a strong negative impact on the quality of life of patients. The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire is a disease-specific instrument developed to measure the quality of life in patients with PsA. The aims of this study were to culturally adapt the questionnaire for Portugal and evaluate its reliability and validity in patients with PsA. The original UK English version of the PsAQoL was translated into Portuguese by a bilingual and lay panel. Structured cognitive debriefing interviews were conducted with ten PsA patients. The Portuguese PsAQoL was subsequently applied to PsA patients followed at the Rheumatology Department of Centro Hospitalar do Baixo Vouga, E.P.E. To assess reproducibility, 30 patients with PsA completed the Portuguese PsAQoL on two occasions, 2 weeks apart. A larger sample was recruited to determine internal consistency and construct validity. The Nottingham Health Profile (NHP) was used as a comparator instrument. Translation and adaptation were successful. Cronbach´s alpha for the Portuguese version of the PsAQoL was 0.91 and the test-retest reliability was 0.93. The PsAQoL could distinguish between groups of patients defined by self-reported general health status, self-reported severity of PsA and flare of arthritis. There was a positive correlation between the total score of the PsAQoL and each of the sections of the NHP. The Portuguese version of the PsAQoL was found to be relevant, understandable and easy to complete, reliable and valid.

Encephalopathy with upper body hypertonia and myoclonus in patient with systemic lupus erythematosus and anti-CASPR2.

Systemic lupus erythematosus (SLE) may involve the nervous system but there are no specific biomarkers of neuroSLE. Limbic encephalitis has been rarely associated with SLE. We present a case of a 22-year-old black woman where typical SLE psychosis evolved to an encephalopathy with atypical features, normal MRI, electroencephalogram slowing and frontal and occipito-temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG PET).Memory deficits, bizarre behaviour, psychosis, neuromyotonia and movement disorders have been described in autoimmune central nervous system disorders and associated with specific antibodies. Brain MRI may be normal and cortical brain hypometabolism on FDG PET scans has been reported. We have not found any report of limbic encephalitis or other SLE neurological manifestation associated to positive titres of anti-CASPR2 antibodies and this may warrant systematic investigation. In the rare cases of limbic encephalitis associated with SLE no specific antibodies were documented. Anti-CASPR2 antibodies have been associated not only with limbic encephalitis but also with neuromyotonia and Morvan syndrome. Although our patient had a specific pattern of tone abnormalities with an impressive cervical and upper limb hypertonicity and flaccid lower limbs, no myotonic discharges were found. We did not find any association between myoclonus and anti-CASPR2 antibodies. We cannot exclude that a non determined autoantibody could have played a role; however, clinical and FDG PET improvement supports an antibody-mediated injury, in this case of neuroSLE.

Characterization of damage in Portuguese lupus patients: analysis of a national lupus registry.

BACKGROUND: Although the survival rate has considerably improved, many patients with systemic lupus erythematosus (SLE) develop irreversible organ damage. OBJECTIVES: The objectives of this paper are to characterize cumulative damage in SLE patients and identify variables associated with its presence and severity. METHODS: A cross-sectional analysis of SLE patients from the Portuguese Lupus register Reuma.pt/SLE in whom damage assessment using the SLICC/ACR-Disability Index (SDI) was available was performed. Predictor factors for damage, defined as SDI ≥ 1, were determined by logistic regression analyses. A sub-analysis of patients with severe damage (SDI ≥ 3) was also performed. RESULTS: In total, 976 patients were included. SDI was ≥1 in 365 patients, of whom 89 had severe damage. Musculoskeletal (24.4%), neuropsychiatric (24.1%) and ocular (17.2%) domains were the most commonly affected. Older age, longer disease duration, renal involvement, presence of antiphospholipid antibodies and current therapy with steroids were independently associated with SDI ≥ 1. The subpopulation with severe damage had, in addition, a greater interval between the first manifestation attributable to SLE and the clinical diagnosis as well as and more frequently early retirement due to SLE. CONCLUSIONS: This large lupus cohort confirmed that demographic and clinical characteristics as well as medication are independently associated with damage. Additionally, premature retirement occurs more often in patients with SDI ≥ 3. Diagnosis delay might contribute to damage accrual.

Septic arthritis: patients with or without isolated infectious agents have similar characteristics.

PURPOSE: Septic arthritis can be disabling and life-threatening, requiring prompt diagnosis and treatment. The infectious agent is not always identified in these patients. We revaluate septic arthritis cases discharged from our department, describing the affected population, causative microorganisms and antibiotic therapy used, and characterised differences between patients with and without isolated pathogenic agents. METHODS: Sixty-eight septic arthritis patients were included in this study. Diagnosis was based on clinical findings, and/or the presence of joint purulent material, and/or bacterial pathogen isolation from joint fluid/synovial membrane/blood cultures and response to antibiotics. Data analysis was performed using SPSS 20. RESULTS: Patients had a mean age of 61.1 ± 18.8 years, without sex predominance. 26.5 % had an infection ≤ 15 days before septic arthritis diagnosis. Besides previous infection, 57.4 % had ≥ 1 risk factors for septic arthritis, most commonly pharmacological immunosuppression (20.6 %), diabetes mellitus type 2 (19.1 %) and rheumatoid arthritis (17.6 %). The knee was the most often affected (54.3 %). Only 39.7 % presented fever from clinical onset until hospital admission (mean 13.4 ± 18.9 days). Leucocytosis was present in 45.6 % of patients, elevated erythrocyte sedimentation rate (ESR) in 75 % and elevated C-reactive protein (CRP) in 97.1 %. 5.9 % had articular damage attributable to septic arthritis. An infectious agent was isolated in 41.2 % of patients, with Staphylococcus aureus being the most frequent. 38.7 % of synovial fluid and 23.5 % of synovial membrane cultures were positive. Patients with an identified infectious agent have no significant differences other than more days of hospitalisation (p = 0.003) and in-hospital antibiotic treatment (p = 0.017). CONCLUSION: Synovial fluid and synovial membrane cultures more often identified pathogens compared to blood or urine cultures. Patients with and without an identified infectious agent have similar demographic, clinical, laboratory and radiographic characteristics.

Parent anion radical formation in coenzyme Q0: Breaking ubiquinone family rules.

We report electron attachment (EA) measurements for the parent anion radical formation from coenzyme Q0 (CoQ0) at low electron energies (<2 eV) along with quantum chemical calculations. CoQ0 may be considered a prototype for the electron withdrawing properties of the larger CoQ n molecules, in particular ubiquinone (CoQ10), an electron carrier in aerobic cell respiration. Herein, we show that the mechanisms for the parent anion radical formation of CoQ0 and CoQ n (n = 1,2,4) are remarkably distinct. Reported EA data for CoQ1, CoQ2, CoQ4 and para-benzoquinone indicated stabilization of the parent anion radicals around 1.2-1.4 eV. In contrast, we observe for the yield of the parent anion radical of CoQ0 a sharp peak at âˆ¼ 0 eV, a shoulder at 0.07 eV and a peak around 0.49 eV. Although the mechanisms for the latter feature remain unclear, our calculations suggest that a dipole bound state (DBS) would account for the lower energy signals. Additionally, the isoprenoid side chains in CoQ n (n = 1,2,4) molecules seem to influence the DBS formation for these compounds. In contrast, the side chains enhance the parent anion radical stabilization around 1.4 eV. The absence of parent anion radical formation around 1.4 eV for CoQ0 can be attributed to the short auto-ionization lifetimes. The present results shed light on the underappreciated role played by the side chains in the stabilization of the parent anion radical. The isoprenoid tails should be viewed as co-responsible for the electron-accepting properties of ubiquinone, not mere spectators of electron transfer reactions.

Bilateral MR imaging of the hand and wrist in early and very early inflammatory arthritis: tenosynovitis is associated with progression to rheumatoid arthritis.

PURPOSE: To identify bilateral hand and wrist findings of synovial inflammation associated with progression to rheumatoid arthritis (RA) in very-early-RA cohort (VERA) (duration, <3 months) and early-RA cohort (ERA) (duration, <12 but >3 months), to test tenosynovitis as a magnetic resonance (MR) imaging additional parameter for improving diagnostic accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, and to evaluate the symmetry of joint and tendon involvement. MATERIALS AND METHODS: With institutional review board approval and informed consent, 32 women and three men (mean age, 45 years) with untreated recent-onset inflammatory arthritis participated in this prospective study and underwent MR imaging of both wrists and hands. After 12-month follow-up, 25 patients fulfilled the criteria for RA (10 VERA and 15 ERA patients). Ten patients did not fulfill the criteria for RA (non-RA [control] group). Possible associations between synovitis for each joint and tendon and RA diagnosis at 12 months were tested (univariate logistic regression analysis). Diagnostic performance of the ACR/EULAR RA classification criteria was evaluated (receiver operating characteristic curve analysis). Asymmetry prevalence (all joints and tendons in the analysis) was calculated. RESULTS: Tenosynovitis of the extensor carpi ulnaris (odds ratio, 3.21) and flexor tendons of the second finger (odds ratio, 14.61) in VERA group and synovitis of the radioulnar joint (odds ratio, 8.79) and tenosynovitis of flexor tendons of the second finger (odds ratio, 9.60) in ERA group were significantly associated with progression to RA (P < .05). Consideration of tenosynovitis improved areas under the receiver operating characteristic curve of ACR/EULAR criteria performance for the diagnosis of RA from 0.942 (P < .0001; sensitivity, 52%; specificity, 100%) to 0.972 (P < .0001; sensitivity, 76%; specificity, 100%), with cutoff score of 6 or greater. Asymmetry was found in 80.0% (62 of 77) (VERA patients) and 69.3% (106 of 153) (ERA patients) of joint or tendon pairs (P < .05). CONCLUSION: Tenosynovitis is an imaging finding in early RA, and its inclusion as a scoring criterion might contribute for a better diagnostic performance of the 2010 ACR/EULAR classification; early RA is an asymmetric disease.

Genetic predisposition for medication-related osteonecrosis of the jaws: a systematic review.

The purpose of this study was to assess whether genetic variation is a predictor for the development of medication-related osteonecrosis of the jaws (MRONJ) in patients receiving bisphosphonate therapy for various conditions. A systematic review based on the PRISMA guidelines was performed. A search strategy was developed. Comprehensive searches of major databases were conducted for studies published January 2003 through July 2018. The PICOS strategy was used to develop the inclusion criteria. The analysis in each study was performed primarily using single nucleotide polymorphism (SNP) frequency mean values and odds ratios between cases and controls. A total of 3301 patients were enrolled in the 15 included studies (two genome-wide association studies, n = 1877; 10 candidate gene studies, n = 1195; three whole genome/whole exome studies, n = 229). Multiple myeloma was the most prevalent primary disease (54.8%). Zoledronate was prescribed in 68.8% of patients. No one SNP was definitively identified as a risk factor for the development of MRONJ. To date, studies have failed to show a single gene as a risk factor for MRONJ. Heterogeneity of case and control populations may be contributory. Next generation sequencing studies may help elucidate the role and interplay of genetic events in the development of MRONJ.

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

BACKGROUND: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. AIM: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. METHODS: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. CONCLUSIONS: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

[Dermatomyositis-like syndrome in x-linked agammaglobulinemia]. / SÍNDROMA DERMATOMIOSITE-LIKE EM DOENTE COM AGAMAGLOBULINÉMIA LIGADA AO CROMOSSOMA X.

Primary immunodeficiencies (PIDs) encompass more than 250 different pathological conditions. X-linked agammaglobulinemia (XLA) has been occasionally associated with cutaneous and muscular manifestations resembling dermatomyositis, often termed dermatomyositis-like syndrome (DLS). This syndrome has been associated with cutaneous, muscular and central nervous system manifestations, accompanying a persistent infection by an Echovirus. According to sixteen previously reported cases, this syndrome has a poor prognosis. We report the case of a 27-years old male, with XLA and DLS, successfully treated with 6 cycles of human immunoglobulin and methotrexate. Clinical symptoms improved dramatically with a complete resolution of the musculoskeletal manifestations. Despite this clinical response, prognosis should remain reserved. The evolution of this syndrome remains unpredictable and therapeutic options are limited. To the best of our knowledge, there are only a few reports of similar cases which have survived so many months after the diagnosis.

Psychometric properties of the Revised Fibromyalgia Impact Questionnaire (FIQR) - a contribution to the Portuguese validation of the scale.

BACKGROUND: Fibromyalgia (FM) remains a relatively misunderstood and clinically challenging condition that impact significantly in the individual´s life, impairing global functioning and diminishing quality of life. Management is complex and frequently unsatisfactory, requiring personal tailoring and adaptation of interventions according to the fluctuations of the disease manifestations and their response to therapy. The use of comprehensive and quantified assessment tools constitutes, therefore, an essential component of the management of patients with FM. The Revised Fibromyalgia Impact Questionnaire (FIQR) is currently one of the most used and well validated instruments to assess functional (in)capacity and global impact of FM and associated symptoms. OBJECTIVES: To translate to Portuguese the FIQR and to study its psychometric properties. MATERIAL AND METHODS: The total sample comprised 103 women with fibromyalgia, defined according to the established criteria for FM. A self-report battery composed by the Revised Fibromyalgia Impact Questionnaire (FIQR), the Portuguese version of Beck Depression Inventory-II (BDI-II) and the Profile of Mood States (PoMS) was administered. The FIQR was re-administered to twenty-four participants, six weeks after the first evaluation. Internal reliability was assessed through Cronbach's alpha, corrected item-total score correlations and alpha if item deleted. Spearman and Pearson correlations along with repeated measures tests were computed to assess the temporal stability of the scale. Convergent and divergent validity were assessed via Spearman and Pearson correlations. RESULTS: The FIQR demonstrated a good to very good internal consistency (from α = 0.87 to α = 0.94). All items correlated to a good degree (above 0.30) to the total score and contributed significantly to the overall reliability. Moreover, FIQR presented a good temporal stability (from r = .617 to r = .886, p ≤ .001) and favorable convergent and discriminant validity with depressive symptoms (r > .289, p ≤ .01) and positive (r > -.186, p > .05) and negative affect (r > .206, p ≤ .05). CONCLUSIONS: The Portuguese version of the FIQR demonstrated good psychometric properties, which renders it a proper and valuable tool to be used in different settings.

The use of the color Doppler ultrasonography in the diagnosis and monitoring of an atypical case of giant-cell arteritis.

Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically characterised by headache, scalp tenderness, jaw claudication and visual disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a sensitive and non-invasive image technique used in the diagnosis of this disease. This work highlights the importance of CDUS in the diagnostic workup of GCA and also demonstrates it´s usefullness in the evaluation and documentation of the response to corticosteroids therapy in an atypical case of ACG.

Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid arthritis.

Glucocorticoids have potent anti-inflammatory and immunomodulatory effects and are widely use in the management of rheumatoid arthritis in combination with other synthetic and with biological disease-modifying anti-rheumatic drugs. Concerns about the risk of adverse effects of glucocorticoids, especially if they are given at higher dosages and for a longer time, hamper their use despite the clear symptomatic and disease modifying benefits. However, the evidence base for these concerns for low dose glucocorticoid therapy is quite limited due to the scarcity of quality literature on its safety in rheumatoid arthritis. This review discusses the current understanding about their disease-modifying effects, toxicity data from recent trials and observational studies, recommendations for their management and the current efforts to improve the therapeutic ratio of glucocorticoid through the development of new formulations, such as modified-release prednisone.

Global functional status in rheumatoid arthritis: disease duration and patient age.

With the aim of clarifying whether patient age could be an additional explanation for the differences in the clinical expression of rheumatoid arthritis (RA) found in different populations, we evaluated the possibility of patient age being a significant factor associated with global functional status, independent from disease duration. Our present results suggest that both disease duration and patient age are major factors in the global functional status of patients with RA, and that patient age is particularly important when a subgroup of patients with more than 60 years of age and more than 20 years of disease duration is considered. These data are relevant when comparing two different RA groups: not only should we have a similar mean age and mean disease duration, but also the subgroups of patients more than 60 years of age and with more than 20 years of disease duration should correspond to equivalent proportions in the populations studied.

Effects of the neuropeptide, substance P, on lymphocyte proliferation in rheumatoid arthritis.

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10(-10) M to 10(-6) M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.