Serum klotho concentrations inversely correlate with the severity of nailfold capillaroscopic patterns in patients with systemic sclerosis.

Klotho is a transmembrane and soluble glycoprotein that governs vascular integrity. Previous studies have demonstrated reduced serum klotho concentrations in patients with systemic sclerosis (SSc), and it is known that klotho deficiency can impair the healing of digital ulcers related to microvessel damage. The aim of this study was to evaluate the association between serum klotho levels and nailfold capillaroscopic abnormalities in SSc patients. We retrospectively enrolled 54 consecutive patients with SSc diagnosed on the basis of the 2013 EULAR/ACR criteria [11 with diffuse SSc; 47 females; median age 68.0 years (IQ 18); median disease duration 11.0 years (IQ 7)]. Serum klotho concentrations were determined by means of an enzyme-linked immunosorbent assay. On the basis of the 2000 classification of Cutolo et al., 14 patients had normal nailfold capillaroscopic findings, 8 had an early scleroderma pattern, 21 an active scleroderma pattern, and 11 a late scleroderma pattern. The median serum klotho concentration was 0.29 ng/mL (IQ 1). Regression analysis of variation showed an inverse correlation between serum klotho concentrations and the severity of the capillaroscopic pattern (p=0.02; t -2.2284), which was not influenced by concomitant treatment. Logistic regression did not reveal any significant association between the risk of developing digital ulcers and nailfold capillaroscopic patterns, serum klotho levels, or concomitant medications. The presence of avascular areas significantly correlated with calcinosis (p=0.006). In line with previous studies, our findings confirm that klotho plays a role in preventing microvascular damage detected with nailfold capillaroscopy.

Transfer characteristics and contact resistance in Ni- and Ti-contacted graphene-based field-effect transistors.

We produced graphene-based field-effect transistors by contacting mono- and bi-layer graphene by sputtering Ni or Ti as metal electrodes. We performed electrical characterization of the devices by measuring their transfer and output characteristics. We clearly observed the presence of a double-dip feature in the conductance curve for Ni-contacted transistors, and we explain it in terms of charge transfer and graphene doping under the metal contacts. We also studied the contact resistance between the graphene and the metal electrodes with larger values of ~30 kΩµm(2) recorded for Ti contacts. Importantly, we prove that the contact resistance is modulated by the back-gate voltage.

The role of NSAIDs in psoriatic arthritis: evidence from a controlled study with nimesulide.

OBJECTIVE: To define the optimal dose of nimesulide (NIM) for treating psoriatic arthritis. METHODS: Eighty patients entered a 4-week, double-dummy, randomised, controlled study. Each patient was allocated to one of the following treatment groups: NIM 100 mg/day, NIM 200 mg/day, NIM 400 mg/day, or placebo. Primary end points for arthritis assessment were the scores for tender and swollen joints, and the physician's and patient's global assessment of efficacy. RESULTS: 76/80 patients completed the study. NIM decreased the score for tender and swollen joints from baseline to the end swollen joints from baseline to the end of therapy (p < 0.05). Pain severity on a visual analogue scale (VAS) was reduced by NIM 200 mg (p = 0.03) or NIM 400 mg (p = 0.019) compared to placebo, as was morning stiffness (p = 0.038 and p = 0.008, respectively), but the trends with 100 mg were not statistically significant. The investigators and patients assessed the global efficacy of the NIM 200 and 400 mg/day groups as better than placebo or NIM 100 mg. Side effects were observed in 12 patients (15%) during treatment. They were mostly mild, only one patient withdrew from the study as a result, and the trend for a higher incidence with NIM was not statistically significant. The Psoriasis Area Severity Index (PASI) and the ESR did not show any significant changes. Patients in the placebo group took more paracetamol per day compared with those in the NIM groups (p = 0.007). CONCLUSIONS: Nimesulide 200 and 400 mg/day are effective and safe in psoriatic arthritis.

Amtolmetin guacyl versus piroxicam in patients with osteoarthritis.

The efficacy and tolerability of amtolmetin guacyl (AMG), a new non-steroidal anti-inflammatory drug, were compared with piroxicam, in patients with osteoarthritis. In a randomized double-blind study patients with arthritis (n = 99) received either 600 mg AMG on an empty stomach or 20 mg of piroxicam on a full stomach, once daily for 30 days. All clinical parameters improved significantly with both drugs; there were no significant differences between the two treatments. Tolerability, assessed by the patients, was significantly better in the AMG group. In the piroxicam group nine of 50 patients withdrew because of side-effects (gastrointestinal) compared with two of 49 (nausea and headache) in the AMG group. There were three cases of perforation, ulcer and bleeding in the piroxicam group but no serious side-effects with AMG. Total numbers of side-effects were similar in the two groups, but epigastric and abdominal pain were more frequent and more intense with piroxicam. AMG was as effective as piroxicam in controlling the symptoms of osteoarthritis, but showed better gastrointestinal tolerability.

Rifamycin SV administered by intra-articular infiltrations shows disease modifying activity in patients with pauci- or polyarticular juvenile rheumatoid arthritis.

The therapeutic activity of rifamycin SV administered by the intra-articular route was evaluated in 52 children with juvenile rheumatoid arthritis (oligopolyarthritis). Each active joint was injected once a week for 10 weeks; thereafter patients were followed for 3-48 months. The number of active joints and joints with limitation of motion, the erythrocyte sedimentation rate (ESR) and C-reactive protein improved significantly at the end of the treatment cycle, with progressive improvement during the subsequent period of observation. At 48-month of follow-up, 78% of joints did not present signs of inflammation; and 66% of joints showed no functional limitations. Joints without radiological lesions at baseline and large joints responded best to the rifamycin treatment. Persistent knee effusions were reabsorbed completely in most cases during the treatment and within the first 6 months of follow-up. Recurrences of synovitis were observed in 7% of joints. De novo radiological lesions in initially undamaged joints occurred during the second year of follow-up in only 10% of patients. At 24 months, 62% of patients with oligoarthritis and 24% with polyarthritis showed complete remission in all affected joints and recovered movement in all those joints which had shown limitations at baseline. There was also a normalization of inflammatory indexes (ESR, C-reactive protein) and regression of general features of disease. Further long term studies are now required to confirm these promising preliminary results.

A double-blind crossover study of two cyclobenzaprine regimens in primary fibromyalgia syndrome.

In a double-blind crossover study, the efficacy and tolerability of oral cyclobenzaprine administered in two different regimens were compared in 40 patients affected by primary fibromyalgia syndrome. The patients were randomly divided into two groups. Each group of 20 patients was treated for 15 days with either a single dose of 10 mg/day cyclobenzaprine at bedtime or 30 mg/day cyclobenzaprine in three equal doses daily. Following treatment there was a 15-day washout period before the groups were crossed over to the other treatment. Both regimens resulted in a significant decline in the number of tender points; significant improvements were also reported in the quality of sleep, anxiety, fatigue, irritable bowel syndrome and stiffness. There was no significant difference in efficacy between the two therapeutic regimens at any stage during the trial. The frequency of reported side-effects was significantly greater (P < 0.001) when patients received 30 mg/day cyclobenzaprine (26 patients, 84%) than when they received 10 mg/day (10 patients, 27%). A dose of 10 mg cyclobenzaprine at bedtime significantly improved the symptomatology of patients affected by primary fibromyalgia syndrome. The higher dose did not further reduce these symptoms but did result in a higher incidence of side-effects.

Clinical improvement in ankylosing spondylitis with rifamycin SV infiltrations of peripheral joints.

In an open study, a new treatment modality was evaluated in 22 patients with active ankylosing spondylitis and compared with oral treatment. Patients were given a 10-week course of rifamycin SV infiltrations to all large peripheral joints, whether or not affected, and were followed for up to 12 months after the end of treatment. Clinical improvements observed at the end of the 10-week treatment cycle persisted for 12 months: morning stiffness (P less than 0.02); subjective pain (P less than 0.0001); Schober's test (P less than 0.006); hand-ground distance (P less than 0.001); erythrocyte sedimentation rate (P less than 0.001); and C-reactive protein (P less than 0.04). The number of painful joints became significantly lower at 6 (P less than 0.01) and 12 months (P less than 0.02) of the follow-up period. Oral administration of rifampin at three times the intra-articular dosage was devoid of any therapeutic activity. It is not known how treatment of peripheral joints influenced the inflammatory process at the level of the axial skeleton. These results must be considered preliminary due to the small number of patients and the short follow-up period, and because it was an open study.

Multiple intra-articular treatment of rheumatoid arthritis: a randomized prospective study comparing rifamycin SV with pefloxacin.

In a randomized, prospective study the efficacy and tolerability of extensive multiple intra-articular administrations of two antibiotics, rifamycin SV and pefloxacin, were evaluated in 40 patients with classical or definite rheumatoid arthritis. Total weekly doses of 525 mg rifamycin or 560 mg pefloxacin were given for 10 weeks, and 12 months after treatment all clinical indices, erythrocyte sedimentation rate and C-reactive protein improved significantly in the rifamycin group. Some of the treatment indices (morning stiffness, severity of pain by visual analogue scale, grip strength and Ritchie's index) were already improved when the treatment ended, whereas others (erythrocyte sedimentation rate, C-reactive protein, number of painful and swollen joints) improved progressively during the follow-up. In the pefloxacin treatment group all indices except C-reactive protein and severity of pain determined using a visual analogue scale were significantly improved 12 months after treatment. Comparison of the two treatments showed a significant difference in erythrocyte sedimentation rate (P less than 0.047), Ritchie's index (P less than 0.036) and C-reactive protein (P less than 0.028) in favour of rifamycin.

Prevention of appearance of radiological lesions in early rheumatoid arthritis: a randomized, single-blind study comparing intra-articular rifamycin with auranofin.

In a prospective, randomized, single-blind study of 116 patients with early rheumatoid arthritis (mean disease duration 7 months), therapeutic activity of intra-articular rifamycin SV (525 mg/week) infiltration into each peripheral joint over 10 weeks was compared with that of 3 mg auranofin given orally twice daily. The incidence of side-effects was lower in rifamycin-treated patients. At the end of follow-up, the clinical variables and erythrocyte sedimentation rate showed a significant and persistent improvement both in 16 patients who continued the auranofin treatment regularly and in 55 treated with rifamycin who had completed the therapeutic cycle 62.5 months before; the latex test decreased only in the rifamycin group. In patients treated with auranofin or who changed to other commonly used antirheumatic agents, 57% of those with an initially negative radiological picture developed new radiological lesions in at least one of the small joints compared with 9% in the rifamycin group. Although the number of patients treated with rifamycin was small and the follow-up relatively short, the results of the study indicated that treatment with intra-articular rifamycin SV may prevent the appearance of radiological lesions in patients with early rheumatoid arthritis and normal radiographs initially.

Clinical, laboratory and radiographic features in early rheumatoid arthritis.

We evaluated disease status in relation to age, sex and disease duration using some short term indices of disease activity, laboratory tests, and radiological features in 315 patients with rheumatoid arthritis of duration varying from 3 to 36 months (mean 12 months). No differences were observed among various age groups in disease duration, female/male ratio, incidence of radiologic lesions and other indices of disease process. Some clinical markers of the disease process such as involvement of the flexor tendons of the hands and Ritchie's index (score greater than 9) were significantly more frequent in the women (p less than 0.0013 and p less than 0.04, respectively). In the patients with disease of recent onset women were slightly more numerous (56%) than men; however, in those with disease duration of 36 months there were significantly more women (72%) (p less than 0.039), suggesting a greater tendency to chronic disease in this sex. Radiological lesions of the small joints of the hands, feet, and/or wrists were found in 37% of the cases with disease duration of up to 4 months and in 91% at 36 months (p less than 0.0001). The lesions were associated significantly more frequently with Ritchie index (p less than 0.02) and with laboratory indices of inflammatory activity (erythrocyte sedimentation rate greater than or equal to 25 mm/h) (p less than 0.001) and immune response (latex test greater than or equal to 80) (p less than 0.0001). Logistic regression analysis showed that the duration of illness is the most important factor correlating with radiologic lesions.

A comparison of dothiepin versus placebo in the treatment of pain in rheumatoid arthritis and the association of pain with depression.

The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either 'depressed' or 'not depressed'. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in 'depressed' patients was significantly improved in patients given dothiepin. The Cassano-Castrogiovanni self-evaluation rating scale in both 'depressed' and 'not depressed' patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy with tricyclic anti-depressants, such as dothiepin, therefore, may determine an improvement of pain indexes besides having an anti-depressant effect.

Double-blind study of dothiepin versus placebo in the treatment of primary fibromyalgia syndrome.

A double-blind study comparing the efficacy and tolerability of dothiepin with that of placebo in the treatment of primary fibromyalgia syndrome was carried out. Dothiepin was shown to improve significantly the condition of patients with primary fibromyalgia syndrome and there was a significant difference between dothiepin and placebo in all the clinical variables measured. Only mild and transient side-effects were reported. Further controlled studies are required to define the effects of dothiepin on fibromyalgia.

Absence of antinuclear antibodies in cryoprecipitates of patients with essential mixed or secondary non-lupoid cryoglobulinemia.

A panel of autoantibodies has been tested in serum samples and cryoprecipitates of 14 patients affected by essential mixed cryoglobulinemia (EMC) as well as in 12 subjects with secondary non-lupoid cryoglobulinemia (SC). Three out of 14 patients affected by EMC were ANA-positive (2 at 1:40 dilution and one at 1:80 dilution). Two out of 12 patients with SC were ANA-positive (both at 1:40 dilution). No autoantibodies were found in the cryoprecipitates. These data seem to confirm some previous observations and do not indicate a role of autoantibodies in the cryoprecipitate formation.

Effect of the chronic administration of oxprenolol on the aortic wall of the normotensive and hypertensive rats.

4 groups of male Wistar rats were studied: - normotensive control rats (4 animals) treated with s.c. water - normotensive rats (6 animals) treated with s.c. 5 mg/Kg Oxprenolol - hypertensive control rats (renal artery stenosis) (6 animals) treated with s.c. water - hypertensive rats (renal artery stenosis) (9 animals) treated with s.c. 5 mg/Kg Oxprenolol. The animals were treated and/or operated at six weeks of age and sacrificed at 12 weeks of age. Blood Pressure (BP), Heart Rate (HR), Ventricular Mass (VM) and Thickness of the Aortic Media (A Th) were determined. Oxprenolol did reduce HR but not BP in both normotensive and hypertensive rats: these animals showed a reduced A Th but not a reduced VM compared with untreated control rats. These results suggest a direct effect of Oxprenolol on A Th independently from BP values, but not on VM.

Rheumatoid knee synovitis successfully treated with intra-articular rifamycin SV.

Thirty rheumatoid patients with persistent knee effusion were treated intra-articularly with rifamycin SV, 500 mg weekly, or with saline solution, 10 ml, in a double-blind study. A complete disappearance of effusion and an impressive clinical improvement was observed in the patients on rifamycin. The synovial fluid and membrane underwent some changes. In 2 patients the rifamycin caused a painful local reaction. After a follow-up of 5 years only one patient has experienced effusion relapse, 5 months after the termination of rifamycin SV treatment. The patients on saline showed no significant change. On the basis of the results obtained from the monoarthritis experimental model and from clinical trials it is tempting to consider that rifamycin has an antimitotic effect, impeding the synthesis of RNA and DNA polymerases in immunocompetent cells.