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Reported here are the results of a study carried out in order to assess the possible influence of the major circulating active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, on some aspects of polymorphonuclear leukocytes activation. The action of 6-methoxy-2-naphthylacetic acid was tested on the following features of polymorphonuclear leukocytes activation: reactive oxygen species production in polymorphonuclear leukocytes stimulated with different agonists, reactive oxygen species production in polymorphonuclear leukocytes treated with pertussis toxin, NADPH-oxidase activity. The findings showed that 6-methoxy-2-naphthylacetic acid decreased reactive oxygen species production in polymorphonuclear leukocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, and opsonized zymosan, but failed to provoke a decrease of reactive oxygen species production when the cells were stimulated with calcium ionophore A23187. Moreover, 6-methoxy-2-naphthylacetic acid did not influence the transduction of the signal following the binding of stimuli to membrane receptors, and NADPH-oxidase activity. Finally, our findings showed that 6-methoxy-2-naphthyl acetic acid had no scavenger effect on reactive oxygen species production.

The aim of this pictorial essay is to show a representative example of sonographic-guided injection in carpal tunnel syndrome associated with tenosynovitis of the finger flexor tendons.Images were obtained using a real-time ultrasound system (AU4-idea; Esaote Biomedica, Genoa, Italy) equipped with a 13-MHz linear transducer. The best injection site was detected using a fine metal clip placed between the skin and the transducer. The images here were obtained in a patient with rheumatoid arthritis and carpal tunnel syndrome secondary to tenosynovitis of the finger flexor tendons.Steroid injection within the carpal tunnel under sonographic control was easily performed. All steps of the needle placement within the widened tendon sheath were carefully evaluated on the monitor screen. Marked clinical improvement occurred shortly thereafter (3 days) and increased over the next 6 weeks.A detailed assessment of the carpal tunnel and a correct, safe placement of the needle for steroid injection can be quickly performed under sonographic guidance.

Sulphasalazine (SSZ) is now recognised to be a useful agent in the management of rheumatoid arthritis (RA). We studied SSZ toxicity (2 g/die) and duration of therapy in 102 patients with RA. Adverse events occurred in 25.4% of all patients. In all patients the reactions subsided on either discontinuation of the drug or decrease of the dose. Gastrointestinal was the most common. At 5 years of follow-up the percentage of patients treated with SSZ still on drug was 29%, the inefficacy was 40% of the total drop-out.

Non-steroidal anti-inflammatory drugs (NSAIDs) give rise to a wide range of gastrointestinal side-effects. These are reviewed and it is stressed that some safety measures are possible only if the risk factors are considered. The relations between dyspeptic symptoms and gastrointestinal lesions are also debated. It is suggested that the ulcerogenic potential of various molecules must be carefully evaluated, especially in elderly patients.

The effect of recombinant interferon alpha-2 (IFN alpha 2) therapy in Sjögren's syndrome (SS) was studied.An open study was performed in which 20 SS patients were given IFN alpha 2 3.10(6) MU/3 times/week or OH-chloroquine (OH-C) 6 mg/kg/daily, for a mean period of 11 months.Gland assessment showed that lacrimal and salivary function improved by 67% and 61% versus 15% and 18% respectively (p0.01) in the patients treated with IFN alpha 2 compared to those treated with OH-C. Immunological parameters did not change over time in either group. In 3 patients a decrease in the tissue score was observed in the IFN alpha 2 group, while no changes were seen in the control group. Tolerability was acceptable.This study shows that IFN can improve tear function and dry mouth in SS, without causing significant side effects.

To characterize finger tendon involvement in patients with rheumatoid arthritis (RA).The finger tendons of 20 RA patients were studied by ultrasonography using a high-frequency (13-MHz) transducer.Eighteen patients (90%) showed finger tendon abnormalities: widening of the flexor tendon sheath (80%), loss of the normal fibrillar echotexture (60%), irregularity of the extensor (30%) and flexor (50%) tendon margins, tendon tear (10%), synovial cyst (20%).High-frequency sonography is helpful in assessing even minimal finger tendon lesions in RA patients.

To determine the long-term efficacy and safety of weekly low-dose methotrexate (MTX) in rheumatoid arthritis (RA).Fifty-one patients receiving MTX for RA were prospectively studied over a mean treatment period of 36 months. Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, and at 3, 6, 12, 24 and 36 months.The overall probability of continuing to take MTX was 80.3% at 12 months, 74.5% at 24 months, and 70.5% at 36 months. Of the 36 patients who completed 36 months of therapy, a significant improvement was noted compared to baseline in all of the clinical disease variables and acute phase reactants, with a steroid-sparing effect. There were no significant differences in these parameters between the 36-month visit and the 24- or 12-month visit. Adverse events occurred frequently (80.3%), but only 15.6% of the patients discontinued MTX permanently. Four patients (7.9%) withdrew due to a lack of efficacy.Our findings indicate that MTX remains effective over 36 months of therapy, with an acceptable toxicity profile.

Obesity is often associated with knee osteoarthritis (OA) and with chronic hyperinsulinemia. The aim of our study was to investigate the relationship between overweight patients and OA of the knee.Forty-eight overweight outpatients (40 women and 8 men) were recruited into the study. They were separated into 2 groups: Group 1 patients with OA of the knee and Group 2 subjects without OA of the knee. Serum insulin levels were determined in all patients.Insulin levels were statistically higher in patients with OA (p0.01) compared to subjects without OA.Our data suggest that insulin may play a role in the pathogenesis of OA of the knee in overweight patients.

To examine capillary permeability in fibromyalgia (FMS) we studied the nailfold capillaries of 13 unselected patients with FMS and 9 healthy controls using dynamic fluorescence videomicroscopy.The transcapillary permeability of a 20% solution of sodium fluorescein injected into an antecubital vein was assessed by videodensitometric analysis. The pericapillary and interstitial fluorescent light intensities (FLI) were calculated at different sites on a transverse axis crossing the selected capillary.Fluorescence videomicroscopy revealed no abnormalities in the pattern of dye distribution around the nailfold capillaries in the patient group. Videodensitometric analysis showed a trend to an increased early transcapillary diffusion in patients with FMS, but the difference was only significant at 3 s from the first appearance of the dye (p0.05). From 10 s to 1 min after the dye's appearance, the mean FLI in the patients equalled that of the controls. The patients with FMS showed an earlier but lower FLI peak. Moreover, the FLI were significantly lower in the patients than in the controls from 5 to 30 min after the dye appearance in all of the sites of the densitometric analysis (p0.05). Thirty min after the first appearance of the dye, the FLI was reduced by more than 50% in the patient group compared to the controls.Our results indicate that transcapillary permeability and the interstitial persistence of the tracer in FMS are significantly reduced compared to controls. This difference may be caused by the abnormal microvascular dynamics induced by low capillary flow and/or capillary bed hypotension.

Chondrocalcinosis is an important, common, age-related joint disease. Its characteristic is the deposit of calcium pyrophosphate dihydrate crystals in hyaline and fibrous cartilages. Occasionally, it is a familial disorder; more often, it is a sporadic disease of adults sometimes in association with hormonal and metabolic disorders. The relationship between CC and diabetes mellitus (DM) is disputed. In this study the prevalence of radiographic CC (knee and/or wrist) in 184 DM patients was evaluated. For comparison two matched groups without DM were studied: i) 184 consecutive unselected out-patients seem in Rheumatology Department of Ancona University with X-rays of knee and/or wrist; ii) 184 consecutive unselected outpatients observed in a Radiology Department with X-rays of knee and/or wrist. No statistical difference was found between the prevalence of CC in DM patients vs controls. Moreover 113 CC patients were studied. No statistical difference was observed between the prevalence of DM and impaired glucose tolerance in CC patients vs controls. These results may suggest that there is no relationship between CC and diabetes mellitus, as other studies have recently shown.

Recently somatostatin (SST) intra-articular administration has been used in the treatment of some rheumatoid diseases such as rheumatoid arthritis, psoriatic arthritis and osteoarthritis with encouraging results. The aim of this study was to evaluate the efficacy and tolerability of SST intra-articularly injected, involving 20 patients with knee osteoarthritis. Treatment consisted of 4 injections, administered weekly, each of 750 mcg SST. Additionally, in six of them we evaluated the circulating levels of the insulin-like growth factor (IGF)-1 at the base-line time and then every 7 days (immediately before each dose of SST). The results revealed an improvement in pain and in joint function after intra-articular SST, confirmed by statistical analysis. The circulating levels of IGF-1 did not show significant variations following intra-articular administration of SST. The excellent tolerability and the absence of unwanted side-effects with SST allow us to foresee that intra-articular SST could be used in cases of painful knee osteoarthritis, especially in those patients in which other drugs are not appropriate. Moreover, in the absence of modifications of serum levels of IGF-1, SST could be used in athletes.

This study reports psychological symptoms assessed in 327 patients with fibromyalgia (FS) in a multicenter investigation. Two self-report scales, in their validated Italian translations, were used for screening: the CES-D (the Center of Epidemiologic Studies-Depression) developed at the NIMH for measuring depression and the Illness Behavior Questionnaire (IBQ) developed by Pilowsky and Spence. The cutoff point of 23 in the CES-D scores revealed about 49% of the fibromyalgic patients as depressed. In analyzing patterns of illness behavior patients with FS showed a high score on IBQ scales of disease conviction, psychological versus somatic focusing and denial. CES-D scores showed significant correlations with illness behavior scales. These results and their implications for the treatment of fibromyalgic patients are discussed.

The destructive process seen on the cartilage and on the sub-chondral bone of patients with rheumatoid arthritis, which is a chronic inflammatory disease of unknown aetiology, is in part unavoidable. The aim of the treatment is not only to reduce articular inflammation and/or to relieve pain, but also to prevent or delay articular damage and to improve quality of life of rheumatoid patients. The use of new available drugs, with a modern therapeutic approach, seems to be apt to improve considerably the outcome in rheumatoid patients.

Fifty rheumatoid patients were given the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales (AIMS) in order to determine the contribution of clinical and demographic variables to the overall disability. Among the clinical variables, pain intensity and depression were carefully assessed along with the classic morning stiffness and the joint count and tenderness/Ritchie's index. Two main findings arose: age contributed on its own to the overall disability, while disease duration had no significant effects; joint count and tenderness (Ritchie's index) correlated in a highly significant manner with depression as derived from the AIMS subscale and the Zung Depression Inventory (ZDI). ZDI items were separated into a "somatic factor" and a "dysphoric factor", showing a clear-cut influence of the somatic factor on the disability score. Our results suggest that age of the patient, pain intensity and a depressive mood related to physical impairment are chief predictive factor of the overall disability in rheumatoid arthritis.

Various pathogenetic theories of hypertrophic osteoarthropathy (HOA) have been proposed (neurogenic, hormonal, artero-venous shunts, genetic theory), but none of them is able to satisfactorily explain the genesis of HOA. The hypothesis of a central role of the "endothelium/platelet unit" was recently discussed. Above all, the release of the platelet derived growth-factor (PDGF) contained in platelet granules is particularly interesting. In order to assess the microvascular involvement in HOA we set up a research project whose aims were to evaluate the morphology of the capillary network at the nailfold, the dynamic aspects of microcirculation and in vivo platelet function. Since this study is still in progress, for the time being we present only a few preliminary results.

The validity and the reliability of the Italian version of AIMS (Arthritis Impact Measurement Scales) was tested in Rheumatoid Arthritis (RA). The factorial analysis performed on tests obtained from 274 patients showed a strict similarity with the original version. The five extracted factors (upper-limb function, lower-limb function, psycho-affective dimension, social dimension and pain) explain 80% of the common variance. The internal consistency (Cronbach's alfa coefficient = 0.78) and the test-retest performance (r = 0.86) support the reliability of the Italian AIMS. The analysis of the correlations with clinical parameters (the Ritchie's and Thompson's articular indexes, the systemic Lansbury's index, the joint count, the grip strength and morning stiffness), with pain measures (VAS, MPQ, PPI) and psychometric measures (ZDI, ZAI) assessed in 143 out of 274 patients, demonstrates the concurrent validity. The results show that the Italian version of AIMS is a practical value in the management of RA patients. The construct certainly allows its application even in other common chronic diseases.

The aim of this research was to evaluate in vitro interactions between platelets and polymorphonuclear leukocytes. The effects of supernatant from thrombin-activated platelets and two platelet release products (adenosine triphosphate and beta-thromboglobulin) were tested on the following features of polymorphonuclear leukocytes activation: opsonized zymosan and phorbol myristate acetate stimulated chemiluminescence, release of membrane bound calcium, NADPH-oxidase activity, and membrane fluidity (fluorescent polarization). The results showed that the addition of platelet supernatant to polymorphonuclear leukocytes induces a significant activation of cells. On the other hand, after three hours of preincubation of polymorphonuclear leukocytes with platelet supernatant, a decreased response of polymorphonuclear leukocytes to stimulation with phorbol myristate acetate, a significant decrease in NADPH-oxidase activity, and a lowered membrane fluidity were observed. Adenosine triphosphate modulated only opsonized zymosan stimulated chemiluminescence, with and without preincubation with polymorphonuclear leukocytes. Beta-thromboglobulin caused a decrease of the chemiluminescent response of polymorphonuclear leukocytes, using both agonists, with and without preincubation with polymorphonuclear leukocytes. Moreover beta-thromboglobulin only caused a decrease of the polymorphonuclear leukocytes membrane fluidity without preincubation with the cells. These results support the thesis that platelets have a “time-related” modulating activity on polymorphonuclear leukocytes.

The aim of this paper was to evaluate the "in vitro" interaction between beta-thromboglobulin, one specific platelet release product and polymorphonuclear leukocytes. The effects of beta-thromboglobulin were tested on the following features of polymorphonuclear leukocytes activation: opsonized zymosan and phorbol myristate acetate stimulated chemiluminescence, release of membrane bound calcium, NADPH-oxidase activity, and membrane fluidity. Beta-thromboglobulin caused a decrease of the chemiluminescent response of polymorphonuclear leukocytes, using both agonists, with and without preincubation with polymorphonuclear leukocytes. We observed that beta-thromboglobulin caused a decrease also in the activity of NADPH-oxidase but not in the release of membrane bound calcium. Moreover beta-thromboglobulin caused a decrease of the polymorphonuclear leukocytes membrane fluidity. Our results suggest that the beta-thromboglobulin could play a role in the reciprocal interactions between platelets and polymorphonuclear leukocytes.

The aim of the study was to investigate the interaction of opsonized zymosan with polymorphonuclear leukocytes (PMNLs) from 26 rheumatoid arthritis patients (six males and 20 females; mean age, 51.88 +/- 11.15 years; range, 33-72 years) and 11 control subjects (two males and nine females; mean age, 56.54 +/- 12.1 years; range, 33-75 years) using a luminol-amplified chemiluminescence (CL). The data obtained suggest that the opsonized zymosan stimulated CL is decreased in untreated rheumatoid patients compared with control subjects. The decreased stimulated CL may be the result of a physico-chemical alteration of the membrane (including decreased membrane fluidity and translocation of receptor sites) induced by free radicals of oxygen and/or by multiple exposures to chemotaxins. Auranofin enhances stimulated CL although the mechanism is not clear. Auranofin could interact with membrane lipids, induce changes in membrane surface charges and increase membrane fluidity. Our results are difficult to compare with those of previous studies, since different assays, and chemoattractants were applied. In addition, the disease activity and medication were also different.

Until now, little or no attention has been paid to the monitoring of therapy with nonsteroidal antiinflammatory drugs (NSAIDs). The authors discuss reasons for that situation. They emphasize that lack of monitoring of unwanted side-effects of the widely used NSAIDs is no doubt due to the overuse of these drugs. The expedience and a protocol concerning the efficacy and toxicity monitoring of such drugs are critically discussed. The authors stress that toxicity monitoring should be performed in selected patient groups that to only in those patients at risk.

The aim of this study was to investigate the prevalence of nail bed capillary abnormalities in rheumatoid arthritis and psoriatic arthritis. In 10 per cent of rheumatoid patients the morphological pattern of the nail bed capillaries of the ten fingers was remarkably variable. Long capillaries and a clearly visible subpapillary plexus were the most prominent findings in these patients. The only significant finding observed in patients with psoriatic arthritis was a high subpapillary plexus visibility. Avascular areas and giant loops (typical of scleroderma) were not found in either disorder.

30 probands affected by psoriasis, with or without arthropathy, and their relatives were typed for HLA-A, -B and -C antigens. Association of HLA-B16 and HLA-B17 with psoriasis was confirmed. One third of probands was without any known HLA-A, -B, -C marker. Considering probands with at least one HLA-B marker, we found that 50% of their sibs carrying marker is affected and the remaining 50% is healthy. To explain the weak association observed, an attempt to propose a model is made: such a model postulate a gene interaction between the HLA marker gene and an hypothetic "Ps (Psoriasis susceptibility) gene". The model, described in detail in this work, tries to explain why a large part (1/3) of probands is affected even if they do not carry any HLA marker and why 50% of marker positive sibs of marker positive probands are healthy.

Interactive measurements of 22 quantitative parameters concerning the status and inflammation of the mucosa were taken in the rectal biopsies of patients suffering from Rheumatoid Arthritis, or with mild nonspecific morphological abnormalities (M.N.M.A.) and inflammation of the lamina propria or with Infective Colitis. The results showed that mean and standard deviation values of the rheumatoid patients are generally intermediate between those of control cases and those of M.N.M.A. and Infective Colitis. The variance analysis revealed that significant differences in some of the features exist between the four groups. Stepwise discriminant analysis helped in identifying three parameters that contributed significantly to discriminating 96.30% of the cases: Mucin area/Mucosal area; Number of inflammatory cells in the lower half/Number of inflammatory cells in the upper half of the mucosal thickness; Number of Granulocytes/mm2 of the lamina propria. Of the 27 cases included in the study, only one belonging to the control group was allocated incorrectly by the computer to the Rheumatoid Arthritis category. High correlation coefficients were observed between some of the morphometric, serological and clinical data in the rheumatoid patients. The highest values were between Number of Mononuclear cells/mm2 of lamina propria and C-Reactive Protein (+0.920) as well as between Mucin area/Mucosal area and serum IgM level (-0.950).

In ankylosing spondylarthritis (AS), there is sometimes an anterior uveitis (AUV) or a previous history of AUV. The authors have reviewed the medical files of 338 hospitalised AS and 30 AS seen in consultation. They found an AUV in 28 hospitalised AS, or 8.3 p. cent of all cases (7.7 p. cent in men and 14.8 p. cent in women). In 3 cases (0.9 p. cent), the AUV was the first manifestation of the disease, preceding joint involvement. AUV was never found in patients seen in consultation. The findings of this investigation agree, but only partially, with those from the literature which, usually, acknowledge a greater frequency of AUV. Comparison with other previous investigations conducted in Italy enables to confirm that among Italian AS, AUV is less frequent than in other European and out of Europe series. It is possible that in a certain number of cases the AUV is not diagnosed clinically. However, it seems that the reduced incidence of the AUV discovered by a few Italian authors is not fortuitous (genetic factors?).

This study reports the psychological symptomatology assessed in 50 rheumatoid arthritis patients (RA) and 50 with primary fibromyalgic syndrome (PFS). Depression and illness behavior were investigated by two self-report scales in their validated Italian translations: the Center for Epidemiologic Studies Depression (CES-D) and Illness Behavior Questionnaire developed by Pilowsky and Spence (IBQ). Our results suggest that the average RA patients were not depressed to a clinically significant level at the time of the investigation. The mean scores of CES-D by RA patients do not differ from those found in Italian patients affected by other organic diseases. On the contrary, mean score in the CES-D depression scale obtained from PFS patients was significantly higher than the cut-off point. In analyzing the pattern of illness behavior the significant difference between RA and PFS patients in scale of denial of problems is relevant. This means the RA patients have a tendency to deny life stresses and to attribute all problems to the effects of their illness. Such a result is in line with a classic psychosomatic point of view, that defines RA patients as alexitimic ones, that is, with poor capacity to recognize and express emotions. Our data support both the hypothesis that depressive symptoms are more common among PFS patients than RA patients, and that psychological factors may play a significant role in most patients with PFS.

The authors suggest a method for "measuring" the morpho-functional damage of hands and wrists. This method analyzes three postural tests: - "Praying hands" (cf. Fig. 1,2) - "Back of the hands opposed" (cf. Fig. 3) - "Phalanges opposed (by their dorsum)" (cf. Fig 4). These tests define for each hand three angles a1, a2, a3. The corresponding indices I1, I2, I3 are obtained by the following formula: Ii = (1 - ai/90 degrees) . 100. One then defines a general index ITOT by the following expression: ITOT = (I1 + I2 + I3)/3 The index ITOT looks very effective in assessing the patient's condition in an objective way and is simple enough to be used in everyday practice. Hence it is also helpful in therapy-monitoring.

The authors suggest a suitable method for "measuring" morpho-functional involvement of hands (and wrists). This method analyzes four tests: three postural tests and a photogrammetric test. The three positions are: - "Praying hands" (fig. 1) - "Dorsum of the hands opposed" (fig. 2) - "Phalanges opposed (by their dorsum)" (fig. 3) These positions (1-2-3) define three angles alpha 1, alpha 2, alpha 3. The corresponding indices I1, I2, I3 are synthetized by the following mathematical formula: Ii = 1 - alpha i/90 Patients, in the photogrammetric (or surface) test, lean their hands on a Chigot's plantiscope. The illuminated area provides the fourth index expressed by this formula: I4 = 2,5 Sc/St - 0,25 It is possible to calculate a general index It with the following formula: (formula; see text) Angles and surfaces are documented photographically. The method may be very helpful in evaluating the clinical course and therapy of rheumatoid arthritis.

Although an incredible amount of time, work and money has been spent in the evaluation of the relative efficacy of anti-rheumatic drugs, no specific resolutive therapy is currently available for rheumatoid arthritis. In these authors' experience early rheumatoid arthritis should be treated with the most powerful non-steroidal anti-inflammatory drug (indomethacin) and the most tolerated disease modifying anti-rheumatic drug (hydroxychloroquine) available. With respect to hydroxychloroquine, auranofin has a comparable efficacy, but the incidence of side effects is significantly higher than with hydroxychloroquine. Sulphasalazine provides very good results. The enthusiasm for this drug is moderated only by the high frequency of patient drop outs. Corticosteroids should be only used in patients with active disease who do not respond to conventional therapy, and/or those with life-threatening complications (i.e., vasculitis).