Multiple diaphyseal sclerosis (Ribbing disease): what about neridronate?

Sclerosing bone disorders are uncommon diseases and represent a diagnostic challenge. Osteocondensation is a bone alteration, involving both acquired and hereditary conditions. Multiple diaphyseal sclerosis (Ribbing disease) is an inherited condition. It is characterized by excessive proliferation of endosteal and periosteal osseous tissue at the diaphyses of long bones, especially of tibias and femurs. The conventional radiology depicts cortical thickening of diaphyses of long bones while bone scintigraphy shows characteristically an abnormal tracer concentration in the involved diaphyses. The magnetic resonance imaging (MRI) examination confirms the presence of sclerosis and reveals bone marrow edema in the diaphyses of the afflicted bones. Due to the lack of knowledge of the pathophysiology, the treatment is empirical with glucocorticoids or bisphosphonates. Concerning bisphosphonates, the literature reports are conflicting. We report the case of a patient that showed lack of response to intravenous neridronate within 1 year of treatment, both in terms of pain and persistence of bone marrow edema at MRI.

The sources of pain in osteoarthritis: a pathophysiological review.

The pain of osteoarthritis (OA) has multifaceted etiologies within and outside the joint. It is believed to be driven by both nociceptive and neuropathic mechanisms, as well as abnormal excitability in the pain pathways of the peripheral and central nervous system. Inflammation in the joint triggers a cascade of events that leads to peripheral sensitization, increased sensitivity of nociceptive primary afferent neurons, and hyperexcitability of the nociceptive neurons in the central nervous system. Pain receptors have been found in the synovium, ligaments, capsule, subchondral bone and surrounding tissues, with the exception of articular cartilage. The bone-related causes of pain in OA include subchondral microfractures, bone stretching with elevation of the periosteum due to osteophyte growth, bone remodeling and repair, bone marrow lesions, and bone angina caused by decreased blood flow and increased intra-osseous pressure. Central factors alter pain processing by setting the gain in such a way that, when a peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. As a complex phenomenon with a strong subjective component, pain can also be influenced by the nature of the underlying disease, personal predisposition (biological and psychological), and environmental and psychosocial factors. This review examines the current literature regarding the sources and mechanisms of pain in OA.

Pain assessment strategies in patients with musculoskeletal conditions.

Valid and reliable assessment of pain is fundamental for both clinical trials and effective pain management. The nature of pain makes objective measurement impossible. Chronic musculoskeletal pain assessment and its impact on physical, emotional and social functions require multidimensional qualitative tools and healthrelated quality of life instruments. The recommendations concerning outcome measurements for pain trials are useful for making routine assessments that should include an evaluation of pain, fatigue, disturbed sleep, physical functioning, emotional functioning, patient global ratings of satisfaction, and quality of life. Despite the growing availability of instruments and theoretical publications related to measuring the various aspects of chronic pain, there is still little agreement and no unified approach has been devised. There is, therefore, still a considerable need for the development of a core set of measurement tools and response criteria, as well as for the development and refinement of the related instruments, standardized assessor training, the cross-cultural adaptation of health status questionnaires, electronic data capture, and the introduction of valid, reliable and responsive standardized quantitative measurement procedures into routine clinical care. This article reviews a selection of the instruments used to assess chronic musculoskeletal pain, including validated newly developed and well-established screening instruments, and discusses their advantages and limitations.

Colour Doppler ultrasonography evaluation of vascularization in the wrist and finger joints in rheumatoid arthritis patients and healthy subjects.

OBJECTIVES: To evaluate the presence of blood flow by colour Doppler ultrasonography (CDUS) in the wrist and finger joints of rheumatoid arthritis (RA) patients and healthy subjects and to define a cut-off value of CDUS resistive index (RI). METHODS: Forty-three patients with RA and 43 healthy controls were examined by CDUS. The wrists, second and third metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were evaluated in each patient and healthy subject. Spectral Doppler analysis was performed in order to characterize the type of flow and a mean RI was measured to define a cut-off level. The area under receiver operating characteristic curve was used to evaluate the screening method's performance. RESULTS: Flow was detected in 219 of the 430 total joints (50.9%) of RA patients (111 in the wrists, 49 in the MCP and 30 in the PIP joints). Healthy subjects had a quantifiable flow in 45 of the 430 joints (10.5%) and, in particular, 39 (86.4%) in the wrist, 5 (11.14%) in the MCP and 1 (2.2%) in the PIP joints. The intra- and inter-reader agreements for the detection of Doppler signal were very good (kappa 0.82 and 0.89, respectively). Mean RI values were 0.72±0.06 in RA patients and 0.86±0.06 in healthy subjects (p<0.01). At cut-off point of RI<0.79 the sensitivity was 89.6% and the specificity was 78.8% (positive likelihood ratio 4.22). CONCLUSION: DUS is a useful tool for the detection of abnormal blood flow in inflammatory joints of RA patients.

A comparison of utility measurement using EQ-5D and SF-6D preference-based generic instruments in patients with rheumatoid arthritis.

OBJECTIVES: The purposes of this study were to analyse and compare aspects of validity (concurrent and discriminant) of the two widely used indirect utility instruments, the EuroQol-5D (EQ-5D) and the Short Form-6D (SF-6D) in a representative cohort of patients with rheumatoid arthritis (RA). METHODS: Five hundred and eighty-three consecutive adult patients (435 women, 148 men) with RA and referred to the outpatient Clinic were evaluated. Patients were asked to complete EQ-5D and SF-36. SF-6D utility scores were calculated using the eight mean SF-36 scores, according to published algorithms. Disease-related characteristics included disease duration, co-morbidities, a measure for disease activity [Disease Activity Score-28 joint (DAS28)] and for radiographical damage (Sharp van der Heijde scoring method, SHS). The agreement between the utility instruments was evaluated by Bland-Altman analysis. Construct validity was assessed using the Kruskal-Wallis test, Mann-Whitney U-test, Spearman's correlations, and receiver operating characteristic (ROC) curves. Multivariate analyses were used to assess the relationship among HRQoL and disease-related characteristics and socio-demographic data. RESULTS: A comparison of means showed that SF-6D values exceeded EQ-5D values (p<0.0001). Agreement between both measures was only moderate. Utility scores and domains and summary scores of the SF-36 were highly correlated. The EQ-5D and SF-6D both detected change in different health status (<0.0001). The discriminatory power of both indexes was good, without significant difference, with an AUC of 0.869 and 0.820, respectively for EQ-5D and SF-6D. The EQ-5D and SF-6D both detected change over different health status among RA patients (both al level of p<0.0001) although EQ-5D was more efficient in detecting differences between groups in almost all cases. Comparison of EQ-5D and SF-6D scores within VAS groups showed that, for less healthy individuals (VAS scores 0-50), the median EQ-5D score was significantly lower than the median SF-6D score. The multivariate regression models for EQ-5D and SF-6D included both SHS and DAS28 (p=0.0001). The relative contribution of these domains differed substantially between patients with short and long standing disease duration. The presence of multiple chronic conditions also appeared to contribute to reduce the levels of utility of both instruments. CONCLUSIONS: Although EQ-5D and SF-6D appeared to measure similar constructs, these instruments are quite different from each other in the assessment of RA. For worse health status the median EQ-5D scores were significantly lower than the median SF-6D scores. Moreover, EQ-5D and SF-6D appeared both significantly influenced by disease activity, radiological damage and co-morbidity. For that reason, we advise caution in the employment of these preference-based instruments, especially in RA patients with severe disease.

Imaging findings of sacroiliac joints in spondyloarthropathies and other rheumatic conditions.

PURPOSE: The authors sought to evaluate the role of the different imaging techniques in the study of sacroiliac joints in patients with spondyloarthropathies (SpA) and other rheumatic conditions and to assess potential pitfalls in the radiological diagnosis. MATERIALS AND METHODS: Forty-three consecutive patients with sacroiliitis as the predominant symptom of a rheumatic disorder were retrospectively studied. Radiography, computed tomography (CT) and magnetic resonance (MR) imaging were performed. The following imaging findings were evaluated: bone marrow oedema, intra-articular effusion, synovial reaction, joint-space widening, bone sclerosis or hyperostosis, subchondral erosions and, in final stages, joint-space narrowing and ankylosis. All images were independently reviewed by two musculoskeletal radiologists. RESULTS: Radiography demonstrated bone sclerosis in 10 patients (23%), subchondral erosions in 15 (34%), jointspace widening in 8 (18%), joint-space narrowing in 17 (39%) and ankylosis in 3 (6%). CT examination showed sclerosis of the sacroiliac joint in 17 patients (41%), subchondral erosions in 21 (53%), joint-space widening in 22 (53%), joint-space narrowing in 18 (43%) and ankylosis in 7 (17%). At MR, we found bone marrow oedema in 25 patients (92%), intra-articular effusion in 26 (96%), synovial reaction in 21 (77%) and joint-space widening in 5 (18%). CONCLUSIONS: Radiological study of the sacroiliac joints in patients with different rheumatic disorders represents a problem of difficult diagnostic evaluation due to the complexity of the anatomical region and the variability of radiographic findings. The integrated use of conventional radiography, CT and MR imaging is suggested to avoid misdiagnosis.

A clinical prediction rule combining routine assessment and power Doppler ultrasonography for predicting progression to rheumatoid arthritis from early-onset undifferentiated arthritis.

OBJECTIVES: The ability to predict the development of rheumatoid arthritis (RA) in patients with an early-onset undifferentiated arthritis (UA) is highly required if the remission or an adequate response to the treatment are the main goal. The aim of the study was to develop a predictive rule combining clinical variables, serological biomarkers and power Doppler ultrasonography (PDUS) for the progression from an early-onset UA to RA in daily rheumatological practice. METHODS: A prediction rule was developed after a 12 months study of 149 adult patients with a recent-onset UA. The combination of routine assessment variables and PDUS findings was investigated. Logistic regression analysis was performed to identify the independent factors for the development of RA and global predictive score was calculated. The score of the predictive rule ranged from 0 to 10. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance of the rule. The post-test probability (post-TP) was evaluated using the Bayes theorem. RESULTS: Sixty-two patients (41.6%) developed a RA. The rule demonstrated excellent discriminative ability, with an AUC of 0.919 (p=0.0001). With the optimal cut-off point of 5, sensitivity was 89.9%, specificity was 88.6% and positive likelihood ratio was 7.89. If a threshold of 6.5 was applied a higher value of specificity (97.7%) was obtained, but sensitivity (47.6%) decreased. The post-TP value of the two different cut-off points mentioned above were 62% and 80%, respectively. CONCLUSIONS: Our predictive rule, which includes PDUS assessment, revealed an excellent discriminative ability for assessing the likelihood of development of RA in patients with an early-onset UA. Further studies are required to confirm the results and to tailor a therapeutic approach in patients with an early-onset UA.

[Contrast-enhanced ultrasound in musculoskeletal diseases]. / Echographie de contraste et pathologie ostéo-articulaire.

Contrast-enhanced US (ultrasonography) can be used for the study of musculoskeletal diseases but this application still belongs to clinical research. Despite a theoretical value for the identification of microvascularity, the technical limitations of musculoskeletal US are challenging the use of contrast enhanced US. This can explain the slow development of this application and the reason why it remained limited to the assessment of Doppler signal intensity increase. However, the recent availability of real time contrast-enhanced US imaging and quantification data is very promising. The majority of published papers involves rheumatoid arthritis and demonstrates the value of this technique to improve diagnosis, stage the activity of the disease and follow the patients under therapy. These preliminary studies are extending to other disorders (inflammatory arthritides as well as degenerative disorders). Structures other than articular synovium are undergoing investigations (bone, enthesis). New applications are being developed such as contrast-enhanced US of muscular diseases. This new imaging technique appears to have great potentials for the assessment of musculoskeletal diseases.

[Sjögren's syndrome: comparison among the main imaging techniques in the study of major salivary glands]. / Sindrome di Sjögren: confronto fra le principali tecniche di imaging per lo studio delle ghiandole salivari maggiori.

Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune etiology, that affects exocrine glands, in particular salivary and lacrimal glands. Among the diagnostic criteria of SS, imaging techniques play an important role. The aim of our study is to compare three imaging techniques, such as sonography, scintigraphy and sialography in the evaluation of major salivary glands. The use of the these techniques is of great importance for the diagnosis of SS. Sonography is the most frequently used for its prompt execution, non invasivity, great acceptance by the patient and low cost. In the diagnostic patient management of SS, sonography results are eventually confirmed by the other imaging techniques, sialography and scintigraphy.

Ultrasonography of salivary glands in primary Sjögren's syndrome: a comparison with contrast sialography and scintigraphy.

OBJECTIVE: To compare ultrasonography (US) of salivary glands with contrast sialography and scintigraphy, in order to evaluate the diagnostic value of this method in primary SS (pSS). METHODS: The diagnostic value of parotid gland US was studied in 77 patients with pSS (male/female ratio 3/74; mean age 54 yrs) and in 79 with sicca symptoms but without SS. The two groups were matched for sex and age. Imaging findings of US were graded using an ultrasonographic score ranging from 0 to 16, which was obtained by the sum of the scores for each parotid and submandibular gland. The sialographic and scintigraphic patterns were classified in four different stages. The area under receiver operating characteristic curve (AUC-ROC) was employed to evaluate the screening method's performance. RESULTS: Of the 77 patients with pSS, 66 had abnormal US findings. Mean US score in pSS patients was 9.0 (range from 3 to 16). Subjects without confirmed pSS had the mean US score 3.9 (range from 0 to 9) (P < 0.0001). Results of sialography showed that 59 pSS patients had abnormal findings at Stage 1 (n = 4), Stage 2 (n = 8), Stage 3 (n = 33) or Stage 4 (n = 14), and 58 patients had abnormal scintigraphic findings at Stage 1 (n = 11), Stage 2 (n = 18), Stage 3 (n = 25) or Stage 4 (n = 4). Through ROC curves US arose as the best performer (AUC = 0.863 +/- 0.030), followed by sialography (AUC = 0.804 +/- 0.035) and by salivary gland scintigraphy (AUC = 0.783 +/- 0.037). The difference between AUC-ROC curve of salivary gland US and scintigraphy was significant (P = 0.034). Setting the cut-off score >6 US resulted in the best ratio of sensitivity (75.3%) to specificity (83.5%), with a likelihood ratio of 4.58. If a threshold >8.0 was applied the test gained specificity, at the cost of a serious loss of sensitivity (sensitivity 54.5%, specificity 97.5%, likelihood ratio 21.5). CONCLUSIONS: Salivary gland US is a useful method in visualizing glandular structural changes in patients suspected of having pSS and it may represent a good option as a first-line imaging tool in the diagnostics of the disease.

The crowned dens syndrome as a cause of neck pain: clinical and computed tomography study in patients with calcium pyrophosphate dihydrate deposition disease.

OBJECTIVE: To investigate the association between articular chondrocalcinosis and calcification of the atlantoaxial region on a cervical computed tomography (CT) scan and to explore the relation between such calcifications and neck pain. MATERIALS AND METHODS: CT slices of the cervico-occipital junction were performed routinely in 49 consecutive patients (male/female ratio 28/21; mean age 70.4 yrs), diagnosed with calcium pyrophosphate dihydrate crystal deposition disease (CPPD). Of these, 35 met criteria for definite CPPD and 14 met the criteria for probable. The cervical CT scans were analyzed for the presence of periodontoid calcifications by 2 independent musculoskeletal radiologists. Both assessors were blinded to the disease status of the patients. Furthermore, conventional radiographs of the upper cervical spine were performed. An ad hoc designed protocol was used to register information at diagnosis, including age, sex, location of pain and stiffness, fever, presence of synovitis and its location. RESULTS: CT scan of the cervico-occipital junction showed periodontoid calcified deposits in 25 out of 49 patients (51%) with CPPD. In 10 of the 25 cases (40%) with periodontoid calcified deposits, CT scanning showed osseous abnormalities of the odontoid process, such as subchondral cysts or erosions. Conventional radiographs showed calcification behind the odontoid process in 17 patients (34.7%). Nine of CPPD cases (18.4%) presented with neck symptoms. In three patients, articular chondrocalcinosis was revealed only by an acute attack of neck pain with segmentary stiffness, fever, and an increased erythrocyte sedimentation rate; in one of them initial clinical examination found cervical stiffness with Kernig's and/or Brudzinski's sign. For the other two patients, impairment of general condition, occipito-temporal and mandible pain and weakness with inflammatory pain of the shoulder girdle was suggestive of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR). In the six additional patients, questioning elicited a history of previous subacute or chronic neck pain, from one week to one year before their admission to our ambulatory or hospital. CONCLUSIONS: These results suggest that CPPD deposition disease frequently involves the cervical spine. Although such calcification often remains asymptomatic, it may be associated with attacks of acute neck pain with segmentary stiffness, fever, and an increased erythrocyte sedimentation rate, sometimes mimicking PMR and/or GCA or neurological symptoms.

Inter-observer agreement of standard joint counts in early rheumatoid arthritis: a comparison with grey scale ultrasonography--a preliminary study.

OBJECTIVES: The aims of the present study were to assess the inter-observer agreement of standard joint count and to compare clinical examination with grey scale ultrasonography (US) findings in patients with early rheumatoid arthritis (RA). METHODS: The study was conducted on 44 RA patients with a disease duration of <2 yrs. Clinical evaluation was performed independently by two rheumatologists for detection of tenderness in 44 joints and swelling in 42 joints. All patients underwent US assessment by a rheumatologist experienced in this method and blinded to the clinical findings. Joint inflammation was detected by US when synovial fluid and/or synovial hypertrophy was identified using OMERACT preliminary definitions. The inter-observer reliability was calculated by overall agreement (percentage of observed exact agreement) and kappa (kappa)-statistics. The reliability of US was calculated in 12 RA patients. RESULTS: There was fair to moderate inter-observer agreement on individual joint counts for either tenderness or joint swelling apart from the glenohumeral joint. US detected a higher number of inflamed joints than did clinical examination. The mean (+/-S.D.) US joint count for joint inflammation was 19.1 (+/-4.1), while the mean (+/-S.D.) number of swollen joints was 12.6 (+/-3.6), with a significant difference of P = 0.01. CONCLUSIONS: Our results provide evidence in favour of the hypothesis that clinical examination is far from optimal for assessing joint inflammation in patients with early RA. Furthermore, this study suggests that US can considerably improve the detection of signs of joint inflammation both in terms of sensitivity and reliability.

Validity and reliability of the Italian version of the ECOS-16 questionnaire in postmenopausal women with prevalent vertebral fractures due to osteoporosis.

OBJECTIVE: To investigate the reliability and validity of the Italian version of ECOS-16 (Assessment of health related quality of life in osteoporosis) in comparison to other questionnaires in postmenopausal women with osteoporosis. METHODS: A cross-sectional multicentre study was carried out among postmenopausal women with osteoporosis who were attending primary care centres and hospital outpatient clinics. The patient group included 234 females (mean age 69 years, range 48-89) who presented vertebral fractures due to osteoporosis. The control group consisted of 244 asymptomatic osteoporotic subjects matched for age with the patient group. The psychometric properties of the questionnaires were evaluated in terms of feasibility, validity (construct validity and discriminant validity) and internal consistency. Test-retest reliability was analysed for 196 outpatients who reported that their general health status due to osteoporosis had not changed after one week. In all patients the ECOS-16, the SF-36 (Medical Outcomes Study Short Form-36), EUROQoL (EQ-5D), mini-OQLQ (mini-Osteoporosis Quality of Life Questionnaire), and RMDQ (Roland-Morris Disability Questionnaire) were administered, and all clinical variables and sociodemographic variables were taken into account. Construct and discriminant validity were assessed by Spearman's correlations, the Wilcoxon rank sum test, the Kruskal Wallis test and by receiver operating characteristic (ROC) curves. Internal consistency was evaluated using Cronbach's alpha and the test-retest reliability was evaluated by intra-class correlation coefficients (ICCs). RESULTS: 96.9% of the patients answered all items of the ECOS-16 questionnaires. The mean administration time was 10 minutes. Factor analysis yielded two factors that accounted for 88.4% of the explained variance in the ECOS-16 questionnaire. The first factor was the ECOS-16 Physical Component Score (PCS) (45.9% of the explained variance) and the second factor was the ECOS-16 Mental Component Score (MCS) (42.4% of the explained variance). The inter-item correlation between the two factors was 0.48. Significant correlations were found between the scores of similar domains or subscales of the ECOS-16 and SF-36, EQ-5D and mini-OQLQ, supporting the concept of convergent construct validity. The total ECOS-16 score progressively increased with the number of prevelant vertebral fractures (p<0.001) and the effect of the first fracture was already statistically significant (p<0.01). On ROC curve analysis the total ECOS-16 score showed the highest performance among the different questionnaires in discriminating between patients with vertebral fractures and controls with no fractures. In the reliability study, internal consistency within the domain of ECOS-16 was generally good, with Chronbach's alpha values ranging from 0.81 to 0.89. Test-retest reliability was 0.87 for the total ECOS-16 score. CONCLUSION: The Italian version of the ECOS-16 questionnaire was demonstrated to have good psychometric properties and could offer a useful tool in research and routine clinical practice to evaluate HRQoL in post-menopausal women with osteoporosis. A full validation of the psychometric properties will require data on its sensitivity to change.

Radiological scoring methods for ankylosing spondylitis: a comparison between the Bath Ankylosing Spondylitis Radiology Index and the modified Stoke Ankylosing Spondylitis Spine Score.

OBJECTIVE: The main objective of the present study was to test the interobserver reliability, truth, discrimination and feasibility of two scoring methods available in ankylosing spondylitis (AS) over a follow-up period of 3 years. METHODS: Two blinded trained observers scored 95 AS radiographs from a cohort of AS patients. Each radiograph was scored by two scoring methods, the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), and the Bath Ankylosing Spondylitis Radiology Index--spine (BASRI-spine). Interobserver agreement was analyzed by intraclass correlation coefficients (ICC). The construct validity was assessed by examining the correlation of the scoring methods with measures of spinal mobility (Bath Ankylosing Spondylitis Metronomy Index--BASMI), functional limitation (Bath Ankylosing Spondylitis Functional Index--BASFI) and disease duration. Bland and Altman's 95% limits of agreement method and effect size (ES) analysis were used to estimate the smallest detectable difference (SDD) of radiological progression and responsiveness. RESULTS: The BASRI-spine reached intra- and interobserver ICC of 0.755 and 0.831, respectively. The mSASSS scores were more reliable, with ICC of 0.874 and 0.941, respectively. Both scoring systems correlated significantly with BASMI (p = 0.01), while only the mSASSS showed a significant correlation (p = 0.02) with BASFI. With regards to sensitivity to change, it was found that mSASSS classified the highest percentage of patients with more changes than the BASRI-spine (mSASSS: 35.8% vs. BASRI-spine: 15.8%). The ES analysis also suggested that the mSASSS was more responsive than BASRI-spine. Concerning feasibility, the BASRI-spine takes less time for scoring. CONCLUSION: We have shown that the mSASSS offers advantages in measurement properties and is the most appropriate method by which to assess progression of structural damage in AS.

[Atherosclerosis in rheumatoid arthritis: the role of high-resolution B mode ultrasound in the measurement of the arterial intima-media thickness]. / Aterosclerosi nell'artrite reumatoide: ruolo dell'ecografia ad alta risoluzione nella valutazione dello spessore arterioso medio-intimale.

BACKGROUND: Patients with rheumatoid arthritis (RA) have a reduced life expectancy and high cardiovascular morbidity and mortality as compared to the general population. A number of possible factors for the atherogenesis in this disease have been described, such as homocysteine, altered serum levels of selected lipoproteins and treatment. Recent findings indicate that the systemic inflammation may contribute to the development of atherosclerosis and confer an additional risk for cardiovascular death among patients with RA. The aim of our study was to evaluate the ability of high resolution Bmode ultrasound and color Doppler to assess the existence of subclinical atherosclerosis in RA patients, measuring the intima-media thickness (IMT) and resistance index of the common carotid arteries. METHODS: Carotid IMT and carotid plaque were measured using high-resolution B-mode ultrasound in 40 patients with RA and 40 age- and sex-matched healthy persons. We used color Doppler ultrasound to assess vascular damage of the common carotid arteries and the resistance index (RI) was determined by analysis of the spectral waveforms. Serum total cholesterol, triglycerides-density lipoprotein cholesterol, low-density lipoprotein cholesterol, rheumatoid factor, body mass index (BMI), visual analogue scale (VAS) were determined in patients and controls. C-reactive protein (CRP) and the DAS28 were used to measure systemic inflammation. RESULTS: Common carotid IMT were significantly higher (p=0.0009) in RA patients (0.83 +/- 0.23) compared with controls (0.66 +/- 0.22). In RA patients common carotid IMT was significantly correlated with serum total cholesterol (p=0.0008), low-density lipoprotein cholesterol (p=0.006), triglycerides (p=0.042), age (p=0.031) and disease duration (p=0.019). No significant correlation was found with clinical and laboratory parameters reflecting disease activity. The prevalence of plaques was higher in RA patients compared with controls (25% vs 12.5%). There was no significant difference in color Doppler findings, and in particular in RI, between patients and controls. CONCLUSIONS: Our results confirm an accelerated atherosclerosis, as shown by increased common carotid IMT, in patients with RA compared with controls and it is related mainly to lipid levels. High-resolution B-mode ultrasound may be considered a promising, sensitive and non invasive tool for assessing the existence of subclinical atherosclerosis in RA patients.

Role of gonadotropin-releasing hormone (GnRH) in the regulation of gonadal differentiation in the gilthead seabream (Sparus aurata).

It has been proposed that gonadotropin-releasing hormone (GnRH) plays an autocrine/paracrine regulatory role in mammalian and fish ovaries. The marine teleost gilthead seabream is an interesting model since, during the life span of the fish, gonadal tissues develop first as testes, which then regress allowing the development of ovarian follicles. Recent studies carried out in ovaries of the gilthead seabream have demonstrated that various GnRH transcripts as well as GnRH splicing variants are expressed. The mRNA level of several GnRH forms in the female and male areas of the switching gonad, and their possible role in this process, were further investigated. The results here reported show that sGnRH, cGnRH-II, and sbGnRH transcripts are locally expressed during gilthead seabream gonadal differentiation; the expression of the three GnRH forms was found to differ among the morphologically defined areas of the switching gonad, as demonstrated by applying reverse transcription-polymerase chain reaction (RT-PCR), together with in situ hybridization, and semiquantitative PCR analyses. Moreover, the hypothesis that GnRH forms may regulate testicular regression via an apoptotic mechanism was investigated by analyzing the different areas of switching gonads for caspase-3 activity as a measure of apoptosis. Our results showed a marked increase of caspase-3 activity in the area corresponding to the regressing testes in which a significant decrease of testosterone production was also found. The present findings demonstrate that the changes in the endogenous GnRH transcripts could be related with the gonadal differentiation in gilthead seabream, and that exogenous GnRH plays a role by stimulating apoptosis in the degenerating testis.

Respiratory system involvement in systemic vasculitides.

The respiratory system may be involved in all systemic vasculitides (SV), although with a variable frequency. Lung disease is a very common and important feature of the antineutrophil cytoplasmic antibodies (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules and masses are the most common findings on chest radiograph. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis, frequently complicated by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar hemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation of the respiratory involvement, clinically expressing with hemoptysis, respiratory distress and anemia. However, DAH may be subclinical and has to be suspected when chest radiograph demonstrates new unexplained bilateral alveolar infiltrates, in the face of falling hemoglobin levels. In giant cell arteritis, the most frequent respiratory symptom is cough, usually non-productive, persistent, and responsive to corticosteroids. In Takayasu arteritis, pulmonary involvement is frequently subclinical and detectable by non-invasive techniques. Pulmonary involvement is rare in polyarteritis nodosa, Kawasaki disease, Henoch-Schönlein purpura and cryoglobulinemic vasculitis. In conclusion, the involvement of the respiratory system is a very common and important feature of AASV, whereas is less frequent in other SV. It comprises a wide spectrum of clinical features and radiological findings, and may have a prognostic significance. The assessment of the respiratory system should be included in the work-up of all patients with SV, especially of those with AASV.

[Usefulness of ultrasonography and color Doppler sonography in the diagnosis of major salivary gland diseases]. / Utilità dell'ecografia e del color Doppler nella diagnosi delle malattie delle ghiandole salivari maggiori.

The algorithm for imaging of the salivary glands depends on the clinical scenario with which the patient presents to the clinician. Ultrasound has been increasingly used in recent years and thanks to high performance, easy to use apparatus, it can now be used for exploration of the salivary glands. This non invasive, painless and relatively inexpensive examination provides rapid visualisation of the salivary glands and is a useful adjunct to computed tomography and magnetic risonance imaging examination, particularly in tumour pathology. In recent years, publications have highlighted the potential uselfulness of salivary gland ultrasonography as a simple and non-invasive adjunctive test for the detection of gland involvement in Sjögren's syndrome (SS). SS is a chronic inflammatory disease of the salivary glands characterised by focal lymphocytic infiltrates that cause progressive destruction of the acinar structures. The findings of a previous study lead us to believe, in agreement with other examiners, that semiquantitative assessment of ultrasonographic images of the salivary glands is a sensitive and very useful means of evaluating salivary involvement in SS. Color Doppler sonography is a recently introduced method which makes it possible to evaluate intra- and perilesional vascularization and to perform a hemodynamic study of the area being explored. The color Doppler sonography can provide a useful adjunct to conventional ultrasound, increasing diagnostic accuracy in submandibular- parotid masses and to analyze physiologic changes that occur during salivary stimulation in normal subjects and the flow alterations that occur in diseased glands of SS patients. This article reviews the normal ultrasound anatomy of the salivary glands along with lithiasic, inflammatory, tumoral, and autoimmune disease such as SS.

[Validation of the Italian versions of the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) in patients with ankylosing spondylitis]. / Validazione delle versioni italiane del Bath Ankylosing Spondylitis Functional Index (BASFI) e del Dougados Functional Index (DFI) in pazienti con spondilite anchilosante.

OBJECTIVES: The Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) are the most commonly used instruments to measure functioning in ankylosing spondylitis (AS). The aim of this study was to translate, adapt and validate these instruments into the Italian language. METHODS: The BASFI and DFI questionnaires were translated into Italian by two independent bilingual physicians who were familiar with the medical aspects of AS and by one professional translator. Two rheumatologists familiar with instrument validation, and who were aware of the purpose of the study, examined semantic, idiomatic and conceptual issues and produced by consensus unified versions of each instrument. English back-translations from the Italian were done by a professional translator unaware of the original version. Both English versions were compared, and where needed, modifications to the Italian versions were made. RESULTS: A total of 95 patients were included: 77 males, age (mean+/-SD) 47.9+/-9.3years, and disease duration 12.4+/-6.6 years, and 18 females, age 45.9+/-8.7 years, and disease duration 11.3+/-8.2 years. Reliability, measured in 23 patients participating a physiotherapy program, showed an acceptable one-week test-retest intraclass correlation coefficient (ICC)--BASFI ICC: 0.91, 95% CI: 0,87-0.94 and DFI ICC: 0.86, 95% CI: 0.83-0.90. The internal consistency was 0.90 (Cronbach's alpha) for the BASFI and 0.87 for the DFI. For validity the functional indices were correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), modified Health Assesment Questionnaire (HAQ-S), SF-36 physical component summary (SF-36 PCS), stiffness, pain, physician's assessment of disease activity, Bath AS Radiology Index-total (BASRI-t), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The functional indices (BASFI and DFI) were correlated with each other (p<0.0001) and with activity variables. There was no significant relationship between functional indices and BASRI-t and acute phase reactants. The receiver operating characteristic (ROC) curve analysis indicated that the BASFI ranked superior compared to HAQ-S, (p = 0.019) and SF36 PCS (p = 0.002), but not respect to DFI (p = NS), in distinguishing between patients with high and low disease activity. CONCLUSIONS: The Italian versions of the BASFI and DFI showed adequate reliability and validity in patients with AS. Because of psychometric advantages, the BASFI may be preferred in clinical trial settings. However, sensitivity to changes due to drug therapy and/or rehabilitation remains to be determined.