Identification of patients with gout: elaboration of a questionnaire for epidemiological studies.

OBJECTIVES: In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. METHODS: We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. RESULTS: We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. CONCLUSIONS: We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France.

Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells.

UNLABELLED: In order to understand mechanisms involved in osteoporosis observed during iron overload diseases, we analyzed the impact of iron on a human osteoblast-like cell line. Iron exposure decreases osteoblast phenotype. HHIPL-2 is an iron-modulated gene which could contribute to these alterations. Our results suggest osteoblast impairment in iron-related osteoporosis. INTRODUCTION: Iron overload may cause osteoporosis. An iron-related decrease in osteoblast activity has been suggested. METHODS: We investigated the effect of iron exposure on human osteoblast cells (MG-63) by analyzing the impact of ferric ammonium citrate (FAC) and iron citrate (FeCi) on the expression of genes involved in iron metabolism or associated with osteoblast phenotype. A transcriptomic analysis was performed to identify iron-modulated genes. RESULTS: FAC and FeCi exposure modulated cellular iron status with a decrease in TFRC mRNA level and an increase in intracellular ferritin level. FAC increased ROS level and caspase 3 activity. Ferroportin, HFE and TFR2 mRNAs were expressed in MG-63 cells under basal conditions. The level of ferroportin mRNA was increased by iron, whereas HFE mRNA level was decreased. The level of mRNA alpha 1 collagen type I chain, osteocalcin and the transcriptional factor RUNX2 were decreased by iron. Transcriptomic analysis revealed that the mRNA level of HedgeHog Interacting Protein Like-2 (HHIPL-2) gene, encoding an inhibitor of the hedgehog signaling pathway, was decreased in the presence of FAC. Specific inhibition of HHIPL-2 expression decreased osteoblast marker mRNA levels. Purmorphamine, hedgehog pathway activator, increased the mRNA level of GLI1, a target gene for the hedgehog pathway, and decreased osteoblast marker levels. GLI1 mRNA level was increased under iron exposure. CONCLUSION: We showed that in human MG-63 cells, iron exposure impacts iron metabolism and osteoblast gene expression. HHIPL-2 gene expression modulation may contribute to these alterations. Our results support a role of osteoblast impairment in iron-related osteoporosis.

Bone mineral density assessed by dual-energy X-ray absorptiometry in patients with viral or alcoholic compensated cirrhosis. A prospective study.

BACKGROUND/AIM: Cirrhosis is considered as a risk factor for osteoporosis whose prevalence is poorly known. The aim was to assess prospectively bone mineral density (BMD) in patients with alcoholic or viral compensated cirrhosis. METHODS: From 2006 to 2008, patients with viral or alcoholic compensated cirrhosis had BMD assessment by dual-energy X-ray absorptiometry. The prevalence of osteopenia (-2.5SD

Bone status in a mouse model of genetic hemochromatosis.

UNLABELLED: Genetic hemochromatosis is a cause of osteoporosis; mechanisms leading to iron-related bone loss are not fully characterized. We assessed the bone phenotype of HFE (-/-) male mice, a mouse model of hemochromatosis. They had a phenotype of osteoporosis with low bone mass and alteration of the bone microarchitecture. INTRODUCTION: Genetic hemochromatosis is a cause of osteoporosis. However, the mechanisms leading to iron-related bone loss are not fully characterized. Recent human data have not supported the hypothesis of hypogonadism involvement. The direct role of iron on bone metabolism has been suggested. METHODS: Our aim was to assess the bone phenotype of HFE (-/-) male mice, a mouse model of human hemochromatosis, by using microcomputed tomography and histomorphometry. HFE (-/-) animals were sacrificed at 6 and 12 months and compared to controls. RESULTS: There was a significant increase in hepatic iron concentration and bone iron content in HFE (-/-) mice. No detectable Perls' staining was found in the controls' trabeculae. Trabecular bone volume (BV/TV) was significantly lower in HFE (-/-) mice at 6 and 12 months compared to the corresponding wild-type mice: 9.88 ± 0.82% vs 12.82 ± 0.61% (p = 0.009) and 7.18 ± 0.68% vs 10.4 ± 0.86% (p = 0.015), respectively. In addition, there was an impairment of the bone microarchitecture in HFE (-/-) mice. Finally, we found a significant increase in the osteoclast number in HFE (-/-) mice: 382.5 ± 36.75 vs 273.4 ± 20.95 ¢/mm(2) (p = 0.004) at 6 months and 363.6 ± 22.35 vs 230.8 ± 18.7 ¢/mm(2) (p = 0.001) at 12 months in HFE (-/-) mice vs controls. CONCLUSION: Our data show that HFE (-/-) male mice develop a phenotype of osteoporosis with low bone mass and alteration of the microarchitecture. They suggest that there is a relationship between bone iron overload and the increase of the osteoclast number in these mice. These findings are in accordance with clinical observations in humans exhibiting genetic hemochromatosis and support a role of excess iron in relation to genetic hemochromatosis in the development of osteoporosis in humans.

[Cutaneous lupus induced by etanercept in rheumatoid arthritis]. / Lupus érythémateux cutané induit par étanercept au cours de la polyarthrite rhumatoïde.

Therapy with anti-TNFalpha in rheumatoid arthritis may induce autoimmune disorders. Induction of autoantibodies is frequently observed, but lupus-like syndrome is rare and few cases only have been reported. We report a 41-year-old female, treated with etanercept for a rheumatoid arthritis, who developed a cutaneous lupus induced without any other organ involvement, associated with high ANA and DNA antibody titres. The skin biopsy and the histological analysis with immunofluorescence confirmed the diagnosis. The anti-TNFalpha treatment was stopped. Corticosteroids were increased and hydroxychloroquine administered because skin lesions persist after three months.

[Evaluation of CT guided cervical epidural injections in patients with mechanical cervicobrachial neuralgia]. / Evaluation des infiltrations épidurales cervicales sous contrôle tomodensitométrique dans le traitement des névralgies cervico-brachiales mécaniques.

PURPOSE: Prospective study evaluating the efficacy and tolerability of CT guided cervical epidural injections for mechanical cervicobrachial neuralgia. MATERIALS AND METHODS: Between July 2003 and August 2004, 34 patients (16 females, 18 males) with mean age of 44.5 years were enrolled. Enrollment criteria included mechanical cervicobrachial neuralgia of more than 1 month's duration, refractory to medical management, with good correlation between clinical and imaging findings. An evaluation using the Neck Pain Disability Score (NPDS) and associated Secondary criteria was performed by a single observer at day 0, day 30 and day 90. The injections were performed under CT guidance. RESULTS: The symptomatic efficacy of CT guided injections at 3 months was 45% using the NPDS, 47.1% using an analog pain scale, and 58.8% as graded by patients (effective/very effective). Tolerability was excellent (55.9%), moderate (41.2%) and poor (2.9%). CONCLUSION: CT guided cervical epidural injections appear effective and well-tolerated. A blinded randomized study could validate its value. However, a study comparing steroids and placebo raises ethical concerns.

[Sciatica with motor loss revealing meningoradiculitis due to varicella-zoster virus]. / Sciatique déficitaire révélant une méningoradiculite attachée au virus zona-varicelle.

Herpes zoster is a disease which occurs secondary to the reactivation of varicella-zoster virus. Motor involvement in acute herpes zoster is rare. We report a case of sciatica L5 due to herpes zoster infection with motor loss. Typical skin lesions occurred one week before the sciatica. Radiological finding did not explain the paresis. The diagnosis of zoster sciatica with motor involvement was suspected. Serological tests and cerebrospinal fluid examination established the diagnosis. The antiviral and physical treatment was conducted in order to improve functional outcome.

High-energy extracorporeal shock-wave therapy for calcifying tendinitis of the rotator cuff: a randomised trial.

In a prospective randomised trial of calcifying tendinitis of the rotator cuff, we compared the efficacy of dual treatment sessions delivering 2500 extracorporeal shock waves at either high- or low-energy, via an electromagnetic generator under fluoroscopic guidance. Patients were eligible for the study if they had more than a three-month history of calcifying tendinitis of the rotator cuff, with calcification measuring 10 mm or more in maximum dimension. The primary outcome measure was the change in the Constant and Murley Score. A total of 80 patients were enrolled (40 in each group), and were re-evaluated at a mean of 110 (41 to 255) days after treatment when the increase in Constant and Murley score was significantly greater (t-test, p = 0.026) in the high-energy treatment group than in the low-energy group. The improvement from the baseline level was significant in the high-energy group, with a mean gain of 12.5 (-20.7 to 47.5) points (p < 0.0001). The improvement was not significant in the low-energy group. Total or subtotal resorption of the calcification occurred in six patients (15%) in the high-energy group and in two patients (5%) in the low-energy group. High-energy shock-wave therapy significantly improves symptoms in refractory calcifying tendinitis of the shoulder after three months of follow-up, but the calcific deposit remains unchanged in size in the majority of patients.

Bone mineral density in men with genetic hemochromatosis and HFE gene mutation.

Genetic hemochromatosis (GH) is an iron overload disorder mainly due to the C282Y mutation of the HFE gene. The possibility of bone involvement was only recently recognized. The aims of this study were to assess bone mineral density (BMD) and bone remodeling in men with GH, and to examine the influence of iron overload. Thirty-eight men (mean age 47.2+/-9.4 years) with well-defined HFE-related GH were studied. They had an important iron overload with liver iron concentration to age ratio >2.5, no previous venesection therapy and were C282Y homozygotes (n=37) or compound C282Y/H63D heterozygote (n=1). BMD measured by DXA was 0.925+/-0.15 g/cm2 at the lumbar spine (LS) and 0.778+/-0.13 g/cm2 at the femoral neck (FN). Osteopenia (T-score<-1 SD) was observed in 78.9% of patients and osteoporosis (T-score<-2.5 SD) in 34.2%. Vitamin D levels were normal, and no 1-84 parathyroid hormone dysfunction was found. Hypogonadism was found in only 13.2% of patients. Patients with hypogonadism had lower LS BMD than eugonadal patients (0.788+/-0.16 and 0.954+/-0.14 g/cm2). Bone remodeling and parathyroid hormone levels were lower in patients with cirrhosis, but BMD values were similar to those in patients without cirrhosis. FN BMD appeared to fall with rising hepatic iron concentrations (r=-0.399). We conclude that there is significant bone loss in HFE-related hemochromatosis that cannot solely be explained by hypogonadism or cirrhosis. Further investigations are needed to determine the role of iron overload itself.

Confidence in the diagnosis of early spondylarthropathy: a prospective follow-up of 270 early arthritis patients.

OBJECTIVE: To study the confidence of office-based rheumatologists (OBR) and a college of 5 experts in their diagnosis of spondylarthropathy (SpA) for early arthritis after more than 2 years of follow-up; to determine whether at that time the degree of confidence was improved by the fulfilment of the ESSG criteria. METHODS: 270 patients with early-onset (< 1 year) arthritis were prospectively followed-up for 29+/-11 months. At the final examination, OBR and the college of 5 experts rated their confidence in the diagnosis of SpA on a 0-10 analogue scale and on a 1-4 Likert scale, respectively. RESULTS: After 29+/-11 months OBR had classified 56 patients (21%) as SpA, while a collegial diagnosis of probable (N = 32) or certain SpA (N = 14) was made for 46 patients (17%). At the final examination OBR confidence in their diagnosis (gold standard) was only 6.7+/-2.4 for all 56 cases of SpA. The cumulative fulfilment of ESSG criteria for SpA after 29+/-11 months correlated with the confidence of OBR and the experts in SpA, but improved only slightly the final confidence of OBR (7.1+/-2.3 versus 6.7+/-2.4 for all 56 SpA). Similarly, OBR confidence for the 18/56 SpA patients positive for HLA-B27 was only 7.1+/-2.0. Only 21 of these 56 patients were considered as SpA at baseline, although 37/56 (66%) had fulfilled ESSG criteria since thefirst examination. CONCLUSION: This study indicates a probable lack of consensus on the nosology of early SpA and the limited help provided by the ESSG criteria to differentiate early SpA from otherforms of arthritis at baseline.

Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two-dimensional complexity.

Trabecular bone has been reported as having two-dimensional (2-D) fractal characteristics at the histological level, a finding correlated with biomechanical properties. However, several fractal dimensions (D) are known and computational ways to obtain them vary considerably. This study compared three algorithms on the same series of bone biopsies, to obtain the Kolmogorov, Minkowski-Bouligand, and mass-radius fractal dimensions. The relationships with histomorphometric descriptors of the 2-D trabecular architecture were investigated. Bone biopsies were obtained from 148 osteoporotic male patients. Bone volume (BV/TV), trabecular characteristics (Tb.N, Tb.Sp, Tb.Th), strut analysis, star volumes (marrow spaces and trabeculae), inter-connectivity index, and Euler-Poincaré number were computed. The box-counting method was used to obtain the Kolmogorov dimension (D(k)), the dilatation method for the Minkowski-Bouligand dimension (D(MB)), and the sandbox for the mass-radius dimension (D(MR)) and lacunarity (L). Logarithmic relationships were observed between BV/TV and the fractal dimensions. The best correlation was obtained with D(MR) and the lowest with D(MB). Lacunarity was correlated with descriptors of the marrow cavities (ICI, star volume, Tb.Sp). Linear relationships were observed among the three fractal techniques which appeared highly correlated. A cluster analysis of all histomorphometric parameters provided a tree with three groups of descriptors: for trabeculae (Tb.Th, strut); for marrow cavities (Euler, ICI, Tb.Sp, star volume, L); and for the complexity of the network (Tb.N and the three D's). A sole fractal dimension cannot be used instead of the classic 2-D descriptors of architecture; D rather reflects the complexity of branching trabeculae. Computation time is also an important determinant when choosing one of these methods.

Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later.

OBJECTIVE: To determine how well the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 classification criteria for rheumatoid arthritis (RA), when used at study inclusion in a cohort of 270 patients with early (<1 year) arthritis, predicted a diagnosis of RA 2 years later and how well they classified these patients at the end of the 2 years. METHODS: Patients were evaluated during 1995-1997 at 7 hospitals in the Brittany region of France. Patients were evaluated at 6-month intervals until November 1999. The diagnosis made by a panel of 5 rheumatologists (P5R) after the last visit was used as the "gold standard." The ACR 1987 criteria for RA were applied prospectively, without taking into account the initial diagnosis. RESULTS: At the last visit (mean +/- SD followup 29.1 +/- 11.8 months; median 30 months), the P5R diagnosed RA in 98 patients. At the last visit, classification by the ACR criteria was satisfactory, and the combination of an office-based rheumatologist's (OBR's) diagnosis of RA and fulfillment of the ACR criteria was sensitive (87%; 85 of 98 RA patients had both) and highly specific (99%; 170 of 172 non-RA patients did not have both). Application of the criteria at the first visit was of limited value for predicting a diagnosis of RA 2 years later. CONCLUSION: After a 2-year followup, the ACR 1987 classification criteria used in combination with an OBR's diagnosis were effective in distinguishing patients with and without RA. The criteria were not useful for predicting RA in patients with arthritis onset within the previous year. Some patients who met the criteria at baseline and after 2 years did not have RA, suggesting that incorporating exclusion criteria may improve the performance of the ACR criteria when used without taking into account the diagnosis by a rheumatologist, particularly in early arthritis.

Forceful sacrococcygeal injections in the treatment of postdiscectomy sciatica. A controlled study versus glucocorticoid injections.

UNLABELLED: The role of epidural fibrosis in postoperative sciatica is unclear. Few therapeutic trials have been published. We evaluated the mechanical effects of forceful saline injections through the sacrococcygeal hiatus comparatively with glucocorticoid injections. PATIENTS AND METHODS: Forty-seven patients with postdiscectomy sciatica but no evidence of compression by computed tomography or magnetic resonance imaging were included in a multicenter, randomized, controlled, parallel-group study comparing forceful injections of saline (20 ml) with or without prednisolone acetate (125 mg) to epidural prednisolone acetate (125 mg) alone. Each of the three treatments was given once a month for three consecutive months. Outcome measures were pain severity on a visual analog scale (VAS) and the scores on the Dallas algofunctional self-questionnaire on day 0, day 60, and day 120. Analysis of variance for repeated measures and Student's t test for paired series were used to evaluate the data. RESULTS: Forty-seven patients were evaluated. The VAS score improved significantly between day 0 and day 30 in the glucocorticoid group as compared to the forceful injection group (P = 0.01). No other significant differences were found across the groups. The VAS score improved steadily in the forceful injection group, producing a nearly significant difference on day 120 as compared to baseline (P = 0.08). CONCLUSION: Forceful epidural injections produced a non-significant improvement in postdiscectomy sciatica four months after surgery. Epidural glucocorticoids used alone induced short-lived pain relief.

Ability of hand radiographs to predict a further diagnosis of rheumatoid arthritis in patients with early arthritis.

OBJECTIVE: To evaluate the ability of hand radiographs collected at study inclusion to predict a diagnosis of rheumatoid arthritis (RA) 2 years later, in a cohort of patients with early arthritis. METHODS: We evaluated 270 patients with arthritis of less than one year duration. At the first visit, all patients underwent a standardized evaluation including laboratory tests and radiographs. Followup was 30+/-11.3 mo. The hand radiographs were read by observers blinded to patient data who looked for item 7 of the 1987 ACR criteria for RA and used Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for ACR item 7 was < 0.65 for bony decalcification and > 0.8 for erosions. Intra and interobserver correlation coefficients for Sharp score ranged from 0.90 to 0.95. The "erosion" component of ACR item 7 was more specific than the full item 7 (96% versus 87.5%; p = 0.02). Sharp erosion score was not better than the erosion component of item 7 (sensitivity 17%; specificity 96%). CONCLUSION: Regardless of the criterion used, hand radiographs were of limited value to predict which patients would be considered as having RA 2 years later. Diagnostic performance was similar for the "erosions" component of the 1987 ACR item 7 and for Sharp erosion score. The full 1987 ACR item 7 (erosions or bony decalcification) performed less well.

Analysis of TNFalpha microsatellites in 35 patients with primary Sjögren's syndrome.

OBJECTIVES: Although the cause of Sjögren's syndrome remains unknown, many arguments suggest a role for both environmental and genetic factors. An association with HLA molecules has been established. Other genes on the short arm of chromosome 6 may be involved, most notably the TNF gene, which may be pivotal in the development of the epithelial lesions. METHODS: We investigated TNFalpha microsatellites in 35 patients with primary Sjogren's syndrome and in 146 healthy controls. RESULTS: The frequency of the TNFalpha10 allele showed a non-significant increase in the Sjögren's disease group (28.6% vs 15.8%; P = NS). We found significant increases when we considered only those Sjögren's disease patients with joint manifestations (N = 24; 37.5% vs 15.7%; P < 0.05) or only those with anti-Ro(SSA) antibodies (N = 10; 50% vs 15.7%; P < 0.05). CONCLUSION: Our data support a role for the TNFalpha10 allele in primary Sjögren's syndrome, particularly those forms with joint symptoms and anti-Ro(SS-A) antibodies.

Prompt regression of paravertebral and epidural abscesses in patients with pyogenic discitis. Sixteen cases evaluated using magnetic resonance imaging.

OBJECTIVE: To determine whether spinal magnetic resonance imaging performed one month into anti-microbial therapy for pyogenic discitis demonstrated changes of value for predicting outcomes and making therapeutic decisions. METHODS: Prospective study of 16 patients with discitis. A physical evaluation, laboratory tests for inflammation, plain radiographs centered on the affected vertebral level, and magnetic resonance imaging with gadolinium injection were performed at baseline and on day 30. All 16 patients were reevaluated after three months and 15 after six months. RESULTS: The 12 men and four women had a mean age of 59 years. Fourteen patients had a paravertebral abscess (n=12) and/or an epidural abscess (n=6). On day 30, 14 of the 16 patients were clinically improved and ten were radiologically improved. The C-reactive protein level was still elevated in five cases. All reevaluated patients were improved after three months (16/16) and six months (15/15). Only two magnetic resonance imaging features improved during the first month: the size of paravertebral abscesses decreased in 11 of 12 patients, and the size of epidural abscesses decreased in four of six patients. CONCLUSION: Paravertebral and epidural abscesses improve promptly under antimicrobial therapy. However, the presence of these lesions have no prognostic significance. Magnetic resonance imaging does not add significantly to the follow-up of patients who respond clinically to antimicrobial therapy. However, in patients with an unsatisfactory clinical response, follow-up magnetic resonance imaging can provide useful therapeutic orientation by showing whether the paravertebral and/or epidural abscesses have decreased in size.

Positive association of the HLA DMB1*0101-0101 genotype with rheumatoid arthritis.

OBJECTIVE: HLA DM is a non-classical major histocompatibility complex (MHC) class II molecule that has been shown to facilitate peptide loading with classical class II molecules. METHODS: In this study, we analysed the polymorphism in exon 3 of HLA DMA and DMB genes by a polymerase chain reaction-sequence-specific oligonucleotide probe method in 163 rheumatoid arthritis (RA) patients and 146 ethnically matched controls. The HLA-DRB1 genotype was also analysed by a reverse-dot blot method. RESULTS: Our results show in RA patients a significant increase in the HLA DMB*0101 allele frequency (83% vs 72.3% of the controls, P < 1.6 x 10(-3), significance at P < 0.0125) and in the HLA DMB*0101-0101 homozygote genotype frequency [70.8% vs 50% of the controls, P < 4.2 x 10(-4), significance at P < 0.00625, odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.43-4]. The increase in DMB*0101 allele and homozygote genotype frequencies was independent of a linkage disequilibrium between DMB and DRB1 alleles. The analysis of non-random associations between the HLA-DM and DRB1 alleles only revealed a significant association in controls between DMB*0104 and DRB1*07 alleles (delta = 0.01, P < 7 x 10(-4), significance at P < 9.6 x 10(-4)). On the other hand, the DMB*0101-0102 genotype frequency was increased in DRB1*0401-negative RA patients as compared to controls (11% vs 2%, P < 0.011, significance at P < 0.015, OR = 6.2, 95% CI: 1.2-30). CONCLUSION: Our data suggest that HLA-DM alleles could play a role in the genetic susceptibility to RA.

Elevated parathyroid hormone 44-68 and osteoarticular changes in patients with genetic hemochromatosis.

OBJECTIVE: To determine whether the osteoarticular changes associated with genetic hemochromatosis could be explained by metabolic parathyroid hormone (PTH) disorders. METHODS: The study involved 210 patients with liver iron overload syndromes. Osteoarticular changes were numerically scored as the number of damaged joints. PTH 1-84 and 44-68 were assayed. RESULTS: An increase in serum PTH 44-68 levels was found in one-third of untreated patients who had no calcium or PTH 1-84 abnormalities. Serum PTH 44-68 levels correlated positively with serum ferritin levels. In multivariate analyses, the number of affected joints correlated positively with age, serum PTH 44-68 levels, and serum ferritin levels. CONCLUSION: Liver iron overload syndromes, especially genetic hemochromatosis, are associated with elevated circulating levels of PTH fragments containing the 44-68 region, which appears to play a role in osteoarticular changes. This increase seems to be a consequence of iron overload.

Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo.

This multicenter randomized, double-blind, controlled study was performed to compare the efficacy and tolerability of chondroitin sulfate (CS, Condrosulf, IBSA, Lugano, CH) 1200 mg/day oral gel vs CS 3 x 400 mg/day capsules vs placebo, in patients with mono or bilateral knee osteoarthritis (Kellgren and Lawrence radiographic score grade I to III). A total of 127 patients, 40 of whom were treated with CS 1200 mg/day, 43 with CS 3 x 400 mg/day and 44 with placebo, were included in the statistical analysis of this 3-month treatment study. In the CS groups, Lequesne's Index and spontaneous joint pain (VAS) showed a significant reduction of clinical symptoms (P < 0.01 for both parameters), while only a slight reduction was observed in the placebo group (P = ns for Lequesne's Index and P < 0.05 for VAS). The physician's and patient's overall efficacy assessments were significantly in favour of the CS groups (P < 0.01). The treatment carried out with the three formulations was very well tolerated. In conclusion, these results indicate that CS favours the improvement of the subjective symptoms, improving the joint mobility. An additional consideration is that the efficacy of 1200 mg CS as a single daily dose does not differ from that of 3 x 400 mg daily doses of CS for all the clinical parameters taken into consideration.

Primary Sjögren's syndrome: role of the HLA-DRB1*0301-*1501 heterozygotes.

OBJECTIVE: To examine the respective role of the DRB1*, DQB1*, and DPB1* HLA alleles in primary Sjögren's syndrome (SS) and in the clinical and autoantibody profile of primary SS. METHODS: HLA-DRB1*, DQB1*, and DPB1* alleles were analyzed in 42 patients with primary SS and 200 controls by reverse dot blot hybridization for DRB1* and DPB1* and by polymerase chain reaction-restriction fragment length polymorphism for DQB1*. RESULTS: We found a significant increase of the HLA-DRB1*15-*03 heterozygote genotype frequency (19% primary SS vs 3.5% controls; p<0.0006, OR=6.49) and especially for the HLA-DRBI*1501-*0301 genotype (16.7% primary SS vs 3% controls; p<0.002, OR=6.47). The DQB1*0201-*0602 genotype was also significantly increased in primary SS (17.1% primary SS vs 4% controls; p<0.006, OR=4.86). However, the higher risk to primary SS development was associated with the DRB1*1501-*0301 genotype (OR=6.47 vs 4.86). There were no differences between patients and controls in DPB1* allele frequencies. The HLA-DRB1*15-*03 heterozygote genotype was also associated with systemic features such as hematologic manifestations and Raynaud's phenomenon (RP) and with autoantibody production such as antinuclear, anti-Ro(SSA) or La(SSB) autoantibodies and rheumatoid factor. CONCLUSION: Our data suggest a role of the HLA-DRB1*1501-*0301 heterozygote genotype in susceptibility to primary SS. Moreover, the HLA-DRB1*1501-*0301 genotype was also found to be associated with a particular form of the disease characterized by RP, hematologic manifestations, and autoantibody production.