Evaluation of the cytogenetic effects of I-131 preceded by recombinant human thyrotropin (rhTSH) in peripheral lymphocytes of Wistar rats

The present study was carried out to investigate the cytogenetic effects of therapeutic exposure to radioiodine preceded by rhTSH in an animal model. Three groups of Wistar rats (n = 6) were used: one group was treated only with I-131 (11.1 MBq/animal); the other two groups received rhTSH (1.2 mu g/rat of either Thyrogen or rhTSH-IPEN, respectively) 24 h before administration of radioiodine. The percentage of lymphocytes with chromosome aberrations and the average number of aberrations and of dicentrics per cell were determined on blood samples collected 24 h, 7 and 30 days after administration of I-131. The data show that the treatment with radioiodine alone or associated with rhTSH resulted in a greater quantity of chromosome alterations in relation to basal values after 24 h, with a gradual decline after 7 and 30 days of treatment. An increase in chromosome alterations was also seen after rhTSH treatment alone. Neither of the treatments, i.e., with I-131 alone or associated with hormone, resulted in an aneugenic effect or influenced the kinetics of cellular proliferation in rat blood lymphocytes. There was no significant difference between the cytogenetic effects of Thyrogen and rhTSH-IPEN treatment. These data suggest that the treatment with radioiodine, associated or not with rhTSH, affects to a limited extent a relatively small number of cells although the occurrence of late stochastic effects could not be discarded.

Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high prevalence and complex pathogenesis. The skin of AD patients is usually colonized by Staphylococcus aureus (S. aureus); its exotoxins may trigger or enhance the cutaneous inflammation. Several mediators are related to the AD immune imbalance and interleukin-18 (IL-18), an inflammatory cytokine, may play a role in the atopic skin inflammation. To evaluate peripheral blood mononuclear cells (PBMC) proliferation response to staphylococcal enterotoxins A (SEA) and B (SEB) and the levels of IL-18 in adults with AD. Thirty-eight adult patients with AD and 33 healthy controls were analysed. PBMC were stimulated with SEA and SEB, phytohemaglutinin (PHA), pokeweed (PWM), tetanus toxoid (TT) and Candida albicans (CMA). IL-18 secretion from PBMC culture supernatants and sera were measured by ELISA. A significant inhibition of the PBMC proliferation response to SEA, PHA, TT and CMA of AD patients was detected (P <= 0.05). Furthermore, increased levels of IL-18 were detected both in sera and non-stimulated PBMC culture supernatants from AD patients (P <= 0.05). A decreased PBMC proliferation response to distinct antigens and mitogens (TT, CMA, SEA and PHA) in adults with AD suggest a compromised immune profile. IL-18 secretion from AD upon stimulation was similar from controls, which may indicate a diverse mechanism of skin inflammation maintained by Staphylococcus aureus. On the other hand, augmented IL-18 secretion from AD sera and non-stimulated cell culture may enhance the immune dysfunction observed in AD, leading to constant skin inflammation.

The effects of plantar fasciitis and pain on plantar pressure distribution of recreational runners

Background: Plantar fasciitis is the third most frequent injury in runners. Despite its high prevalence, its pathogenesis remains inconclusive. The literature reports overload as the basic mechanism for its development. However, the way that these plantar loads are distributed on the foot surface of runners with plantar fasciitis and the effects of pain on this mechanical factor has not yet been investigated. Therefore, the aim of this study was to evaluate and compare the plantar pressure distributions during running in runners with symptom or history of plantar fasciitis and runners without the disease. Methods: Forty-five recreational runners with plantar fasciitis (30 symptomatic and 15 with previous history of the disease) and 60 runners without plantar fasciitis (control group) were evaluated. Pain was assessed by a visual analogue scale. All runners were evaluated by means of the Pedar system insoles during running forty meters at a speed of 12(5%) km/h, using standard sport footwear. Two-way ANOVAS were employed to investigate the main and interaction effects between groups and plantar areas. Findings: No interaction effects were found for any of the investigated variables: peak pressure (P=0.61), contact area (P=0.38), contact time (P=0.91), and the pressure-time integral (P=0.50). Interpretation: These findings indicated that the patterns of plantar pressure distribution were not affected in recreational runners with plantar fasciitis when compared to control runners. Pain also did not interfere with the dynamic patterns of the plantar pressure distributions. (C) 2010 Elsevier Ltd. All rights reserved.

Physical function interfering with pain and symptoms in fibromyalgia patients

Objectives. The aim of this study was to assess the relationship between variables of physical assessment - muscular strength, flexibility and dynamic balance - with pain, pain threshold, and fibromyalgia symptoms (FM). Methods. Our sample consists of 55 women, with age ranging from 30 to 55 years (mean of 46.5, (standard deviation, SD=6.6)), mean body mass index (BMI) of 28.7(3.8) and diagnosed for FM according to the American College of Rheumatology criteria. Pain intensity was measured using a visual analogue scale (VAS) and pain threshold (PT) using Fisher`s dolorimeter. FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ); flexibility by the third finger to floor test (3FF); the muscular strength index (MSI) by the maximum volunteer isometric contraction at flexion and extension of right knee and elbow using a force transducer, dynamic balance by the time to get up and go (TUG) test and the functional reach test (FRT). Data were analysed using Pearson`s correlation, as well as simple and multivariate regression tests, with significance level of 5%. Results. PT and FIQ were weakly but significantly correlated with the TUG, MSI and 3FF as well as VAS with the TUG and MSI (p<0.05). VAS, PT and FIQ was not correlated with FRT. Simple regression suggests that, alone, TUG, FR, MSI and 3FF are low predictors of VAS, PT and FIQ. For the VAS, the best predictive model includes TUG and MSI, explaining 12.6% of pain. variability. For TP and total symptoms, as obtained by the FIQ, most predictive model includes 3FF and MSI, which respectively respond by 30% and 21% of the variability. Conclusion. Muscular strength, flexibility and balance are associated with pain, pain threshold, and symptoms in FM patients.

Prevalence of fibromyalgia and chronic widespread pain in community-dwelling elderly subjects living in Sao Paulo, Brazil

Objectives: To estimate the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in community-dwelling elderly individuals living in Sao Paulo, to assess the spectrum of problems related to these diseases using the Fibromyalgia Impact Questionnaire (FIQ) and to correlate the FIQ with the number of tender points and with pain threshold. Methods: Our sample consisted of 361 individuals (64% women, 36% men, mean age of 73.3 +/- 5.7 years). Individuals were classified into four groups: FM (according to American College of Rheumatology criteria), CWP, regional pain (RP) and no pain (NP). Pain characteristics and dolorimetry for 18 tender points and the FIQ were assessed. Results: The prevalence of FM was 5.5% [95% confidence interval (CI) = 5.4-5.7], and the prevalence of CWP was 14.1% (95% Cl: 10.5-17.7%). The frequency of RP was 52.6% and the prevalence of NP was 27.7%. FIQ scores were higher in people with FM (44.5), followed by CWP (31.4), RP (18.1) and NP (5.5) (p < 0.001). There was a positive correlation between the domains of the FIQ and the number of tender Points (p < 0.05), and a negative correlation between FIQ score and pain threshold (p < 0.05). Conclusion: In our elderly subjects, the prevalence of FM was slightly higher compared to previously reported studies, and CWP was around 14%. The spectrum of problems related to chronic pain was more severe in FM followed by CWP, strongly suggesting that these conditions should be diagnosed and adequately treated in older individuals. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

MEDIAL LONGITUDINAL ARCH CHANGE IN DIABETIC PERIPHERAL NEUROPATHY

Objective: To describe and compare foot anthropometry in healthy and diabetic subjects using Medial Longitudinal Arch (MLA) classificatory indexes: Arch Index (AI), Chippaux-Smirak Index (CSI) and (A) over cap Angle ((A) over cap), as well as to compare the classification of these methods in each group. Materials and Methods: Control Group (CG) composed by 21 healthy subjects and Diabetic Group (DG), with 46 diabetic neuropathy subjects. The indexes were calculated from footprints. Results: A larger proportion of flat feet was seen in DG for the three indexes (At: 32,2%, CSI: 59,7%, A: 17,5%), while highly arched feet acted oppositely. The groups were statistically different for the proportion of flat feet in (A) over cap (p=0,0080) and CSI (p=0,0000) and high feet in A (p=0,0036). There were significant differences when compared GC and GD in the three indexes: IA (p 0,0027), CSI (p=0,0064), (A) over cap (p=0,0296). Conclusion: Data showed motor and orthopedic changes originated by peripheral neuropathy, which is responsible for foot changes, causing longitudinal arch crumbling. It was seen that A Angle strongly disagreed when compared with the arch classification made by the other two indexes and therefore, its application needs care.

The effect of diabetic neuropathy and previous foot ulceration in EMG and ground reaction forces during gait

Background. We aimed at investigating the influence of diabetic neuropathy and previous history of plantar ulcers on electromyography (EMG) of the thigh and calf and on vertical ground reaction forces during gait. Methods. This study involved 45 adults divided into three groups: a control group (n = 16), diabetic neuropathic group (n = 19) and diabetic neuropathic group with previous history of plantar ulceration (it = 10). EMG of the right vastus lateralis, lateral gastrocnemius and tibialis anterior were studied during the stance phase. The peaks and time of peak occurrence were determined and a co-activation index between tibialis anterior and lateral gastrocnemius. In order to represent the effect of the changes in EMG, the first and second peaks and the minimum value of the vertical ground reaction force were also determined. Inter-group comparisons of the electromyographical and ground reaction forces variables were made using three MANCOVA (peaks and times of EMG and peaks of force) and one ANCOVA (co-activation index). Findings. The ulcerated group presented a delayed in the time of the lateral gastrocnemius and vastus lateralis peak occurrence in comparison to control`s. The lateral gastrocnemius delay may be related to the lower second vertical peak in diabetic subjects. However, the delay of the vastus lateralis did not cause any significant change on the first vertical peak. Interpretations. The vastus lateralis and lateral gastrocnemius delay demonstrate that ulcerated diabetic neuropathic patients have a motor deficit that could compromise their ability to walk, which was partially confirmed by changes on ground reaction forces during the push-off phase. (c) 2007 Elsevier Ltd. All rights reserved.

Musculoskeletal Dysfunction and Pain in Adults with Asthma

Background. The mechanical alterations related to the overload of respiratory muscles observed in adults with persistent asthma might lead to the development of chronic alterations in posture, musculoskeletal dysfunction and pain; however, these changes remain poorly understood. Objective. This study aimed to assess postural alignment, muscle shortening and chronic pain in adults with persistent asthma. Methods. This cross-sectional and controlled study enrolled 30 patients with mild (n = 17) and severe ( n = 13) persistent asthma. Fifteen non-asthmatic volunteers were also assessed. Asthma was classified by the Global Initiative for Asthma (GINA) guidelines. Postural alignment and muscle shortening were evaluated by head and shoulder positions, chest wall mobility, and posterior ( trunk and lower limb) muscle flexibility. In addition, the measures used were previously tested for their reproducibility. Pain complaints were also assessed. Results. In comparison with non-asthmatic subjects, patients with mild or severe persistent asthma held their head and shoulders more forward and had lower chest wall expansion, decreased shoulder internal rotation, and decreased thoracic spine flexibility. Chronic lower thoracic, cervical, and shoulder pain was significantly increased in patients with mild or severe asthma compared with non-asthmatic subjects (p < 0.05). Conclusion. Adults with persistent asthma have musculoskeletal dysfunction and chronic pain that is independent of the severity of their disease but that might be related to their age at the onset of disease symptoms.

Validation of brief pain inventory to Brazilian patients with pain

To validate the Brazilian version of the Brief Pain Inventory (BPI-B) scale and to determine the optimal cutpoints for mild, moderate, and severe pain based on patients` rating of their worst pain. One hundred forty-three outpatients with cancer were recruited in Hospital das Clinicas-University of Sao Paulo, Brazil. Confirmatory factor analysis confirmed two underlying dimensions, pain severity, and pain interference, with Cronbach`s alpha of 0.91 and 0.87, respectively. Convergent validity was shown by the correlation observed between the BPI dimensions with the EORTC-QLQ-C30 pain scale and the McGill Pain Questionnaire. The BPI-B detected significant differences in the two dimensions by disease and performance status, supporting known-group validity. For the worst pain, the optimal cutpoints were 4 and 7 (1-4 = mild pain, 5-7 = moderate, and 8-10 = severe). Our data show that BPI-B is a brief, useful, and valid tool for assessing pain and its impact on patient`s life.

Influence of Suture on Peripheral Nerve Regeneration and Collagen Production at the Site of Neurorrhaphy: An Experimental Study

BACKGROUND: Restoration of nerve continuity and effective maintenance of coaptation are considered fundamental principles of end-to-end peripheral nerve repair. OBJECTIVE: To evaluate the influence of the number of stitches on axonal regeneration and collagen production after neurorrhaphy. METHODS: Thirty male Wistar rats were equally divided into 3 groups and were all operated on with the right sciatic nerve exposed. In 2 groups, the nerve was sectioned and repaired by means of 3 (group B) or 6 (group C) epineurium sutures with 100 monofilament nylon. One group (group A) was used as a control. Each animal from groups B and C underwent electrophysiological evaluation with motor action potential recordings before nerve section and again at an 8-week interval after neurorrhaphy. Nerve biopsy specimens were used for histomorphometric assessment of axonal regeneration and quantification of collagen at the repair site. RESULTS: Animals from group C had significantly lower motor action potential conduction velocities compared with control animals (P = .02), and no significant difference was seen between groups B and C. Parameters obtained from morphometric evaluation were not significantly different between these 2 groups. Type I collagen and III collagen in the epineurium were significantly higher in group C than in either the control group (P = .001 and P = .003) or group B (P = .01 and P = .02). No differences were identified for collagen I and III in the endoneurium. CONCLUSION: Using 6 sutures for nerve repair is associated with worse electrophysiological outcomes and higher amounts of type I and III collagen in the epineurium compared with control. Neurorraphy with 6 stitches is also related to a significant increase in epineurium collagen I and III compared with 3-stitch neurorraphy.

Interleukin-12 but not interieukin-18 is associated with severe endometriosis

Objective: To evaluate interleukin (IL)-12 and IL-18 levels in the serum and peritoneal fluid of women with and without endometriosis. Design: Cross-sectional survey. Setting: University hospital. Patients: Interleukin-12 and IL-18 levels were compared in 105 patients submitted to laparoscopy because of symptoms suggestive of endometriosis (pain and/or infertility). The disease was confirmed in 72 patients (study group), while in 33 patients findings were not compatible with endometriosis (control group). Intevention(s): Blood sample and peritoneal fluid were obtained from patients during videolaparoscopy. Main Outcome Measure(s): The levels of IL-12 and IL-18 in peripheral blood and peritoneal fluid were determined and compared with the stage and site of the disease and histologic classification. Result(s): IL-12 levels measured in peritoneal fluid were higher inpatients with endometriosis compared with the control group. A significant increase in IL-12 levels was found when the more advanced stages of the disease were compared with the initial stages. No statistically significant differences were found in IL-18 levels, either in serum or in peritoneal fluid samples. Conclusion(s): Patients with severe endometriosis have higher IL-12 levels irrespective of IL-18 levels, suggesting that in this disease an alternative pathway is involved in induction of the Th1 immune response. (Fertil Steril (R) 2009;91:320-4. (C)2009 by American Society for Reproductive Medicine.)

Cross-cultural adaptation and validation of a Brazilian Portuguese version of the chronic pain grade

To verify the reliability and validity of a Brazilian Portuguese version of the chronic pain grade (CPG-Br). Cultural adaptation was made in accordance with established guidelines, with modifications aiming at improving this process. Adaptations were made based on interviews with 45 chronic pain patients from So Paulo city. Validation was studied by concurrent application of the short-form-36 health survey (SF-36) and other questionnaires to 283 participants with chronic pain from the general population. Temporal stability was verified by a second application to 131 individuals. Factor analysis resulted in a two-factor solution with factors named characteristic pain intensity and activity limitation due to pain. Alpha coefficients of 0.78 and 0.70 and intraclass correlation coefficients of 0.76 and 0.72 for each factor indicated good internal consistency and temporal stability. Significant correlations between CPG-Br and SF-36, Roland-Morris disability questionnaire and neck disability index scores were noted. A consistent linear trend was also observed between pain grades and SF-36 scores. Frequency of use of pain medications and of pain-related medical visits increased with pain grade. This Brazilian Portuguese version of the chronic pain grade, tested on a sample of the Brazilian population, demonstrated good reliability and validity.

Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and continuous immune cell infiltration in the synovium. These changes are linked to inflammatory cytokine release, leading to eventual destruction of cartilage and bone. During the last decade new therapeutic modalities have improved the prognosis, with the introduction of novel biological response modifiers including anti-TNF alpha CTLA4Ig and, more recently, anti-IL6. In the present study we looked at the immunological effects of these three forms of therapy. Serum, obtained from patients with RA was analyzed for TNF alpha, IL6, IL10, IFN gamma, and VEGF, and in parallel, circulating plasmacytoid and myeloid dendritic cells (DC) were enumerated before and after three infusions of the respective biological treatments. After treatment with anti-IL6, we found a significant reduction of IL6 and TNF alpha levels and the percentage of both DC subsets decreased. Although the results did not reach statistical significance for anti-TNF alpha treatment, similar trends were observed. Meanwhile, CTLA4Ig therapy led to the reduction IFN gamma levels only. None of the treatments modified significantly VEGF or IL10 levels. These findings may explain why patients with RA improve more rapidly on IL-6 therapy than with the other two modalities.

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

Background: Up to 60% of chronic obstructive pulmonary disease ( COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of alpha-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p <= 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test. Copyright (C) 2011 S. Karger AG, Basel

Irreversible blindness in juvenile systemic lupus erythematosus

Blindness caused by severe vasculitis or uveitis is rare in juvenile systemic lupus erythematosus (JSLE) patients. In a 27-year period, 5367 patients were followed at our Paediatric Rheumatology Division and 263 (4.9%) patients had JSLE (American College of Rheumatology criteria). Of note, two (0.8%) of them had irreversible blindness. One of them presented with cutaneous vasculitis and malar rash, associated with pain and redness in both eyes, impairment of visual acuity due to iridocyclitis and severe retinal vasculitis with haemorrhage. Another patient had peripheral polyneuropathy of the four limbs and received immunosuppressive drugs. Three weeks later, she developed diffuse herpes zoster associated with acute blindness due to bilateral retinal necrotizing vasculitis compatible with varicella zoster virus ocular infection. Despite prompt treatment, both patients suffered rapid irreversible blindness. In conclusion, irreversible blindness due to retinal vasculitis and/or uveitis is a rare and severe lupus manifestation, particularly associated with disease activity and viral infection. Lupus (2011) 20, 95-97.