Impaired expression of erythrocyte glycosyl-phosphatidylinositol-anchored membrane CD59 in patients with psoriatic arthritis. Relation to terminal complement pathway activation.

OBJECTIVE: Complement-mediated injury is regulated by many factors; among these CD59 has been identified as a widely distributed glycoprotein that inhibits membrane C5b-9 (terminal complement component) formation. The aim of the study was to assess erythrocyte CD59 expression in patients with psoriatic arthritis in order to understand the role of CD59 in the pathogenesis. METHODS: Washed erythrocytes from 50 patients with psoriatic arthritis, 8 with cutaneous psoriasis and 24 healthy subjects were incubated with monoclonal anti-CD59 antibody followed by a second FITC conjugated antibody and fluorescence intensity analysed by FAC-Scan flow cytometer to assess their CD59 membrane expression. SC5b-9 levels were measured in the plasma by ELISA and results compared with CD59 values. Immune complexes, complement C3 and C4 and rheumatoid factor were also determined. RESULTS: Impaired expression of erythrocyte membrane-anchored CD59 was found in patients with psoriatic arthritis; the lowest levels were seen in active patients (p < 0.01). Increased SC5b-9 was seen in the plasma of patients with active disease. An inverse correlation was also found between plasma C5b-9 and the CD59 expression levels (r = -0.81, p < 0.001). CONCLUSION: The low CD59 expression on erythrocytes from patients with psoriatic arthritis may be an index of a low tissue CD59 expression. This impairment could facilitate the activation of complement pathway and increase the risk for arthritis. Membrane attack complex formation in deficient membrane bound CD59 may also exacerbate synovial cell injury and inflammation.

[Periungual capillaroscopy in psoriatic arthritis]. / La capillaroscopia periungueale nell'artrite psoriasica.

PURPOSE: The aim of the study is the evaluation of the microcirculation trough periungueal capillaroscopy in patients suffering from psoriatic arthritis. MATERIALS AND METHODS: Eighteen patients (mean age 44 years, nine males and nine females) were examined according to the different clinical forms (spondylitic, mutilans, simil-rheumatoid, onyco-arthritis, oligo-articular) of the disease. RESULTS: In most of the patients, the exam showed a reduction in ansas' density and in capillary length and calibre as well as interstitial edema and expansion of the ansa venular portion with coiling and kinking, demonstrating the re-organization of the veins and the neo-angiogenesis. Avascular areas and microaneurysm have been found only in the "mutilans" form. In the "simil-rheumatoid" form, ansa reduced in length and calibre have been observed at capillaroscopy, a pattern different from that reported by others, in rheumatoid arthritis (characterized by thin but lengthened ansa). In the "spondylitic" form, the video-microscopical pattern was negative. CONCLUSIONS: This study is still ongoing in order to evaluate the results in a more representative sample.

[Magnetic resonance imaging of seronegative sacroiliitis]. / Studio delle sacro-ileiti sieronegative con Risonanza Magnetica.

INTRODUCTION: The inflammatory involvement of the sacroiliac joint is frequent during seronegative spondylarthritis. The clinical diagnosis of sacroiliitis may be very difficult, especially in the early stage, because joint motion cannot be assessed directly and the clinical picture is very similar to that of lumbar pain. Conventional radiography is negative as long as the structural change in the joint is limited to the synovial membrane and the cartilage (early stage). Computed Tomography (CT) also has many drawbacks, and thus the changes can be shown only when chondritis and enthesitis have already damaged the bone. The disease onset is usually preceded by a long latency; early diagnosis is needed for a proper and timely treatment, which can be made only with a highly sensitive and specific technique. We investigated the diagnostic accuracy of MRI in the early detection of sacroiliitis during seronegative spondylarthritis. MATERIAL AND METHODS: Forty patients with suspected sacroiliitis and negative radiographic findings were submitted to MRI; thirty-seven of them were HLA B27 positive. MRI was performed with a .5 T superconducting unit; T1-weighted SE, T2-weighted FSE, T2* GE, and STIR images were acquired on the oblique coronal plane parallel to the anterior sacrum. Ten asymptomatic volunteers were also examined as a control group. RESULTS: An irregular sacral border and marrow changes at the insertion of the sacroiliac ligaments were seen in 3/10 asymptomatic volunteers. MRI was negative in 7/40 patients, while the synovial compartment was replaced by some tissue with low signal intensity of T1 and high signal on T2 in the other 33 patients; this finding was referred to synovial pannus. Persisting low-signal foci were seen in the synovial compartment in 16/33 patients, which were referred to spared cartilage. High-signal regions were depicted at the bone periphery in 9/33 patients, which areas were consistent with bone erosion; the subchondral bone was markedly hypointense in 5 of these patients, indicating sclerosis. Finally, diffuse high signal intensity was found in the bone marrow in 3/33 patients and referred to infectious sacroiliitis. CONCLUSIONS: MRI appears the method of choice for the early detection of seronegative sacroiliitis because it can show the early changes in cartilage and subchondral bone, filling the gap between the onset of symptoms and radiographic evidence. Moreover, MRI uses no ionizing radiations and makes therefore a precious tool for the diagnosis and follow-up of young patients, hopefully decreasing the use of CT which however provides better detailing of bone and bone degeneration.

[Efficacy and tolerability of methotrexate in the treatment of rheumatoid arthritis]. / Efficacia e tollerabilità del methotrexate nel trattamento dell'artrite reumatoide.

OBJECTIVE: To verify, in an open study, the efficacy and safety of long-term administration of low weekly doses (5 mg) of methotrexate (MTX) i.m. in different stage rheumatoid arthritis patients. PATIENTS AND METHODS: The study has been performed for 24 months in 42 patients (37 females and 5 males), fulfilling the ARA criteria for rheumatoid arthritis. Main functional parameters, main serological data and some immunology indexes were periodically monitored (after 1, 3, 6, 12 and 24 months of therapy); moreover, some instrumental exams (X-ray of involved joints, liver ultrasound, respiratory function tests) have been performed. RESULTS: Thirty of 42 enrolled patients completed the whole 24 month therapy, and 22 are still using methotrexate. Results were as follows: therapeutic remission in one patient, marked improvement in 12 cases, moderate improvement in 16 and worsening in 1. Among the 12 remaining patients, 2 refused further treatment; 6 and 4 patients were withdrawn from the study because of inefficacy and toxicity, respectively. A significant improvement was observed in all of the main efficacy parameters taken into consideration. Moderate and reversible side effects were registered in 23 patients. CONCLUSIONS: Our results confirm the value of MTX in the treatment of rheumatoid arthritis. In our opinion this drug is very effective even in a relatively early stage of the disease, mainly in patients whose genetic and clinical markers may predict a more aggressive and severe outcome.

[Exfoliative conjunctival cytology in Sjögren's syndrome]. / La citologia esfoliativa congiuntivale nella sindrome di Sjögren.

The study has been performed in order to give a contribution to the knowledge of the conjunctival cytology in Sjögren's syndrome. Exfoliated cells were obtained by a tampon from the inferior conjunctival sac of 11 patients affected by primary or secondary Sjögren's syndrome; the material was placed onto a microscope slide and it was stained with May-Grumwald-Giemsa, after the ferning test had been performed. Tear production had been previously assessed in all patients by Schirmer's I test and basic secretion test that showed an evident tear fluid hyposecretion. Cytoanalysis of tear fluid showed, in all patients, a marked lymphocytosis, presence of epithelial cells (sometimes cell-adhesion) and a number of "snake-cells", with a nucleus-cytoplasm ratio in favour of cytoplasm. Some of those cells have a thicker cytoplasmic membrane and/or a spindle-shaped peripheral nucleus, characteristic finding of keratoconjunctivitis sicca. In all cases we found mucus and fibrin (sometimes with included cells), organic debris and big crystals, some of which aggregated.

Echo-Doppler left ventricular filling abnormalities in patients with rheumatoid arthritis without clinically evident cardiovascular disease.

Our investigation aimed at verifying diastolic abnormalities in rheumatoid patients, without clinically evident cardiovascular disease and other confounding complaints, by using pulsed Doppler examination of transmitral blood flow. We selected 40 patients fulfilling revised American Rheumatism Association (ARA) criteria for the diagnosis of rheumatoid arthritis having no symptoms of cardiac disease or clinical findings of other extracardiac diseases. We also studied 40 rheumatoid-matched healthy volunteers as a control group. An echocardiographic examination was carried out on each subject. Left ventricular structural and functional measurements were obtained. Interventricular, septal thickness and left ventricular mass index were significantly higher in rheumatoid patients than in the control group. We also found in rheumatoid patients higher mean values of peak A velocity and A/E ratio. When multiple linear regression analysis was performed on the data of rheumatoid patients we found an independent relationship only between A/E ratio and left ventricular mass. In conclusion, our results confirm diastolic abnormalities in rheumatoid patients and point out that these abnormalities also affect echo-Doppler parameters of left ventricular filling. Moreover, further analysis of our data may suggest the possibility that structural left ventricle changes could be responsible for left ventricular filling impairment.

[Reflexions on the Tietze syndrome. Clinical contribution]. / Considerazioni sulla sindrome di Tietze. Contributo clinico.

The authors report 4 cases of Tietze's syndrome. In 3 of them the syndrome onset during a rheumatic disease (psoriatic arthritis, sternoclavicular hyperostosis). It is thus necessary to distinguish between the idiopathic of unknown ethiology and the secondary form due to, a well defined disease, in 3 cases observed.

Cardiac involvement in rheumatoid arthritis: evidence of silent heart disease.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic disease involving many organ systems and is frequently accompanied by cardiac alterations. However, there is considerable disagreement concerning the cardiac abnormalities found in patients with RA. The purpose of our investigation was to determine, by a non-invasive method such as echocardiography, the nature and extent of cardiac involvement in RA patients with no symptoms of cardiac disease, in comparison with a control sample. METHODS: We selected 35 patients affected by rheumatoid arthritis (five men, 30 women), aged 51 +/- 11 years. No patient had either symptoms of cardiac disease or extra cardiac complaint. As a control group we studied 52 volunteers, aged 51 +/- 12 years, randomly selected among a larger group of subjects with no symptoms, signs and/or clinical findings of extra cardiac diseases. All were in sinus rhythm and without any cardiac symptom. Standard two-dimensional, M-mode and Doppler echocardiographic examination was carried out on each subject. RESULTS: In RA patients we found a higher prevalence of several abnormalities. We found no statistically significant differences between the groups of RA patients based on the stage and duration of disease. We found no correlation between cardiac abnormalities and inflammatory indices or drug therapy. DISCUSSION: At least three alterations seem to be typical of RA patients in the absence of any symptom of cardiac disease: (1) posterior pericardial effusion, (2) aortic root alterations and (3) valvular thickening. The prevalence of MVP is controversial and needs further investigation. These alterations are variously combined in each patient, and for this reason we think that it is possible to represent such a heart involvement as 'silent rheumatoid heart disease'. Moreover the knowledge of the presence of unrecognised cardiac abnormalities can be very important for the correct assessment and management of the RA patient.

[Prevalence of pericardial effusion in subjects with rheumatoid arthritis: an echocardiographic study]. / Prevalenza del versamento pericardico in soggetti con artrite reumatoide: studio ecocardiografico.

We used echocardiography to determine the prevalence of pericardial effusion in rheumatoid arthritis (RA) patients without cardiac systems and compared our results to those obtained in a control group of age-matched subjects. Thirty-six patients with RA (6 men, 30 women; mean age 51 +/- 11 years) were selected from a patient population in treatment at our outpatient Rheumatology Clinic. None of the patients had any symptoms of cardiac disease, and all patients with signs and/or systems of extracardiac disease were excluded from the study. The control group consisted of 60 volunteers (mean age 51 +/- 12 years) randomly selected from a larger group of subjects with neither symptoms, signs and/or clinical findings of extracardiac disease nor symptoms of cardiac disease. Standard two-dimensional and M-mode echocardiography was carried out on all subjects. In the RA patients, we found a high prevalence of pericardial involvement, especially minimal pericardial effusion. There was no statistically significant difference among subgroups of RA patients based on stage and duration of disease respectively. There was no correlation between pericardial involvement and inflammatory indexes or drug therapy. The minimal pericardial effusion found in our patients could be caused by the extra-articular inflammatory process and might be one aspect of a more complex picture characterized by silent cardiac involvement. The potential for symptomless pericardial alterations documented in our patients indicates that careful cardiac evaluation should be given high priority in the assessment and management of subjects with RA.

Two-site ELISA for quantification of the terminal C5b-9 complement complex in plasma. Use of monoclonal and polyclonal antibodies against a neoantigen of the complex.

A quantitative ELISA procedure using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex has been developed. The ELISA was demonstrated to be both sensitive and reproducible. The normal range for C5b-9 determinations, defined as 2.5-97.5% interval of the values obtained in 76 healthy blood donors, was 3.12-10.3 AU/ml. The presence of rheumatoid factor did not affect the determination of C5b-9 as demonstrated by immunoabsorption studies.

[Efficacy and tolerability of ketoprofene administered through iontophoresis in rheumatoid arthritis. Results from a multicentric study]. / Attività e tollerabilità del ketoprofene somministrato per jonoforesi nella patologia artroreumatica. Risultati di uno studio policentrico.

Three-hundred and twelve patients with osteoarthritic diseases were admitted to a multicenter clinical trial. The patients were given 100 mg Ketoprofen twice-a-day by iontophoresis for 10 consecutive days. Pain relief was almost complete in 94.6% of the patients, improvement of active motility in 83.6%, disappearance of swelling in more than half of the patients and functional improvement in about all the cases. Two allergic skin reactions of a mild degree (0.6%) were registered. Therefore, Ketoprofen administered by iontophoresis showed to be efficacious and safe in the treatment of acute osteoarthritic diseases also in high risk patients.

[Cardiovascular response to sympathetic stimulation in normal subjects with or without familial hypertension]. / Risposta cardiovascolare ai test di stimolazione simpatica in soggetti normotesi con o senza familiarità ipertensiva.

UNLABELLED: The aim of our study was to seek out a possible different reactiveness to cardiovascular stimulation tests among normotensives with and without positive family history of essential hypertension. We have studied about 200 inhabitants of Ustica and 49 medicine students, all normotensives according to the World Health Organization and the Joint National Committee criteria. In an isolated room and in a supine position, blood pressure (BP) and heart rate were measured every 30 s for 15 min with an automatic sphygmomanometer. Averages of last 4 measurements were considered baseline values. Then we have carried out mental stress (MS), handgrip and active orthostatism test (AO) in the inhabitants of Ustica; cold pressor test and AO in students. Patients were divided in 2 groups, genetics and controls, on the basis of a positive family history of essential hypertension. The 2 groups, in every sample, were similar for sex, age, body mass index and alimentary and life habits. RESULTS: a preliminary estimation of Ustica sample showed a different prevalence of positive history between hypertensives and normotensives (63.9% vs 46.61%; p less than 0.05) and no difference between hypertensive and borderline patients (63.9% vs 64.2%); BP and heart rate were slightly higher in controls; there was no statistical difference between genetics and controls. CONCLUSIONS: our results can be explained in various ways: pressor dysregulation in candidates for hypertension may be masked in a large group of normotensives; exaggerated pressor response do not exist in genetics or this pressor dysregulation is impossible to find out with the cardiovascular stimulation tests we have used; other mechanisms are responsible for genetic hypertension.

[Relapsing polychondritis. A case report]. / Policondrite ricorrente. Presentazione di un caso.

The authors describe a case of "relapsing polychondritis" showing that the characteristic manifestation of the disease on nasal and ear cartilage took place at a later stage than in the eye vessels, the inner ear and the trunk and valves of the aorta. The authors therefore consider the term "relapsing polychondritis" to be somewhat restrictive and claim that owing to the systemic diffusion of the disease in all vessels, R.P. should be included among systemic vasculitis diseases.

Microproteinuria as an index of initial renal lesion in patients with rheumatoid arthritis.

Our investigation included 20 patients with rheumatoid arthritis and a negative routine (albustix) proteinuria test, and 20 healthy controls. The albustix test was compared with a method based on multifractional Cellogel RS electrophoresis of urinary proteins. The albustix test was found to be not reliable in patients with RA. Microproteinuria was in fact detected by the electrophoresis method in 12 out of 20 RA patients. Eleven patients showed glomerular type proteinuria (which was "selective" in 5 patients and "non-selective" in 6 patients), and 1 patient showed mixed type proteinuria. Electrophoresis failed to show microproteinuria in the controls. The high sensitivity, easy handling and low cost of multifractioned electrophoresis (which does not involve disturbing the patients) suggest its introduction as a routine test for all RA patients, thus achieving both accurate clinical assessment of proteinuria and a rational therapeutic approach.

[Cytoprotective effect of rosaprostol during treatment with non-steroidal anti-inflammatory agents in arthrorheumatic pathologies]. / L'azione citoprotetiva del rosaprostol in corso di trattamento con FANS in patologie artroreumatiche.

A clinico-endoscopic study has been carried out in a group of 22 patients treated with 1 g of naproxene + 2 g of rosaprostol compared in a blind situation with another group of 19 patients treated with a similar dose of naproxene + placebo in order to evaluate the cytoprotective action of rosaprostol. Analysis of the results showed a high correlation between intake of rosaprostol and low onset of algico-dyspeptic disturbances and mucosal lesions of some gravity, although the problem of the monitoring of patients undergoing long-term treatment with NSAID remains unsolved.

[Different prevalence of some indices of cardiac and vascular impairment in normal weight and obese patients with essential arterial hypertension]. / Differente prevalenza di alcuni indici di compromissione cardiaca e vascolare in pazienti normopeso e obesi affetti da ipertensione arteriosa essenziale.

Certain physiopathological features that differentiate essential arterial hypertension in normal weight and obese patients are recalled. The results of a retrospective study carried out in 293 hypertensive patients admitted to the Clinic in recent years are reported with a view to evaluating the prevalence of certain parameters (ischaemic cardiopathy, left ventricular hypertrophy, renal, vasculo-cerebral and retinal impairment) in patients subdivided into two groups: normal weight and obese. The study showed in the first group a higher prevalence of signs of ischaemic cardiopathy; in the second a higher prevalence of left ventricular hypertrophy. This difference is accentuated in the subgroup of smokers as regards ischaemic cardiopathy and in non-smokers as regards left ventricular hypertrophy. The possible explanations for this different behaviour are discussed.

[Telethermographic evaluation of the intra-articular administration of thymopentin in rheumatoid arthritis of the knee]. / Valutazione teletermografica dell'impiego della timopentina per via intraarticolare nell'artrite reumatoide del ginocchio.

Fifteen subjects with rheumatoid arthritis defined as "classical" or "definite" according to A.R.A. criteria and classified according to Steinbrocker as stages I to III were submitted to knee joint infiltration (bilateral where both knees were involved) with 50 mg thymopentin in 1 ml, once a week for five weeks. Telethermographic examination was performed in all cases in order to evaluate the thermal inflammatory component before the first and 48 hours after the last infiltration. In none of the patients with the exception of only one case, did the drug lead to a significant change of the thermal index. This evaluation does not take into account any other objective and subjective parameters the study of which was beyond the scope of the above research.

[Audio-vestibular changes in patients with rheumatoid arthritis]. / Alterazioni audio-vestibolari in soggetti con artrite reumatoide.

A functional audio-vestibular investigation based on impedance metric techniques and electronystagmography was carried out in a group of patients with "classical" rheumatoid arthritis (RA) and with treated or untreated "definite" RA in various stages. Data obtained from these patients were compared with those obtained from a control group. Significant hypoacusis of the transmissive type was found in initial stages of RA while sensorineural or mixed type hypoacusis was found in later stages of RA. Significant vestibular alterations of the central type suggesting supratentorial involvement were found in several cases independently of the stage of RA and of the age of the patients.

[Monoclonal antibody assessment of lymphocyte subpopulations in rheumatoid arthritis in adult patients in relation to stage and treatment]. / Valutazione con anticorpi monoclonali delle sub-popolazioni linfocitarie nell'artrite reumatoide dell'adulto, in rapporto allo stadio ed al trattamento.

Twenty patients with various stages of RA were examined. They included: 1) 7 cases in Steinbroker stage 1 (onset); 2) 13 cases in Steinbroker stage 2-3 (chronic). The group was divided into 16 treated and 4 untreated cases. Monoclonal antibodies were used to assay T3, T4, T8 and T4/T8 ratio and the results were compared with those in a control group. The results showed a T8 deficit and a consequent change in the T4/T8 ratio in untreated subjects with "onset" RA. The immune situation of the chronic and treated cases was very similar to that in the control group probably as a result of treatment.