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Biomedical subjects

M Di Franco

Publications and source records attributed to M Di Franco.

At least 19 recordsLinked to original sources

[Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis].

OBJECTIVE: P-selectin is an adhesion molecule expressed by activated endothelial cells and platelets favouring the leukocyte adherence to microvascular endothelium. A soluble form of this molecule has been described, whose serum levels were found to be elevated and correlate with disease activity in rheumatoid arthritis (RA) patients. Aim of this study was to determine soluble P-selectin levels in synovial fluid (SF) and serum from patients with psoriatic arthritis (PsA), where it has never been investigated, to define its involvement in PsA synovial damage. METHODS: we analysed, by ELISA, soluble P-selectin serum and SF levels in 100 patients presenting a knee joint effusion: 38 of them presented PsA, 40 RA and 22 osteoarthritis (OA). We examined the main clinical and laboratory parameters of these patients. Soluble P-selectin serum levels were also detected in 15 healthy subjects. RESULTS: soluble P-selectin SF levels were significantly higher in PsA and RA patients respect to OA subjects. Soluble P-selectin SF levels were lower than those found in serum and the SF/serum ratio was higher in PsA and RA patients respect to OA. Soluble P-selectin serum levels were not significantly different among patients and controls. No correlation was found between SF and serum levels of soluble P-selectin and the main clinical parameters. CONCLUSIONS: our study of soluble P-selectin in PsA reveals a prominent local role of this molecule, with no differences respect to RA. Histological findings may be of help in understanding the role of this adhesion molecule in PsA.

Adolescent↗

Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities.

The aim of this study was to investigate whether interleukin-13 (IL-13) serum levels correlate to different nailfold capillaroscopy (NC) findings in patients with systemic sclerosis (SSc). IL-13 serum levels were measured using an ELISA method. The following NC abnormalities were considered: the presence of giant loops, haemorrhages, loss of capillaries, disorganisation of the vascular array, ramified/bushy capillaries and sludging of blood. A semiquantitative rating scale was adopted to score these changes, as well as a rating system for avascular areas and three morphological NC patterns ('early', 'active' and 'late'). Mean capillary density was determined by counting the total number of capillaries in a 1 mm length, and the arterial and venous diameters of the capillary as well as the total loop diameter were measured. In SSc patients IL-13 serum levels were significantly higher than in controls ( P < 00.1), whereas in patients with ( n=8) and without ( n=24) abnormal IL-13 serum levels (>17 pg/ml) the comparison of the NC features showed significantly relevant differences concerning a more frequent 'active' NC pattern ( P < 0.02), the presence of haemorrhages ( P < 0.0037) and sludging of blood ( P < 0.038), as well as larger total loop ( P < 0.036) and arterial ( P < 0.03) diameters, in those patients with elevated IL-13 serum levels. The study confirmed that IL-13 serum levels are higher in the sera of patients with SSc, and shows for the first time the significant correlations between this serological finding and some of the main relevant SSc capillaroscopic features, leading us to believe that this cytokine not only seems to sustain the immunological and fibrotic process of SSc, but might have a role in determining the more severe microvascular lesions in this disease.

Adult↗

Prevalence and clinical features of skin diseases in chronic HCV infection. A prospective study in 96 patients.

BACKGROUND: Between extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis, etc. The aim of this study was to determine the prevalence of some dermatoses in our population of patients with HCV infection and describe the more characteristics clinical pictures. METHODS: Ninety-six patients (36 men and 60 women) aged from 35 to 74 years with HCV documented by 3rd generation ELISA and RIBA tests were prospectively examined for 3 years to determine the prevalence of some skin disorders, reported as associated with HCV infection. All patients were also studied for presence and quantification of HCV-RNA by polymerase chain reaction and genotyping when possible. Eighty-one underwent a liver biopsy. Routine laboratory tests and some immunological investigations (ANA, AMA, SMA, LKM, ANCA, ICC, crioglobulins) were performed using standard procedures and indirect immunofluorescence, nephelometric, RIA methods. RESULTS: Twelve of 96 patients (12.5%) presented skin disorders in progress of chronic virus C hepatitis: 5 cases of leukocytoclastic vasculitis (LCV) by mixed cryoglobulinemia, 1 case of pruritus, 2 cases of oral lichen planus (OLP), 2 cases of alopecia areata, 1 case of urticaria, 1 case of psoriasis. CONCLUSIONS: Our findings show a calculated prevalence of clinical dermatoses in HCV infected patients around 12.5%. These findings confirm however the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

Aged↗

Evaluation of myocardial involvement in systemic lupus erythematosus by signal-averaged electrocardiography and echocardiography.

OBJECTIVE: The myocardial involvement in systemic lupus erythematosus (SLE) patients, frequently found at autopsy or at endomyocardial biopsy, is less easily detected clinically. The myocardial lesions are characterized by an increase in interstitial connective tissue and myocardial scarring. Signal-averaged electrocardiography (ECG-SA) is currently used for recording ventricular late potentials which are the expression of slowed and disorganized conduction through zones of myocardial scarring. M-mode, two-dimensional and Doppler echocardiography (ECHO) represent relatively simple methods for evaluating the left ventricular function. This study was aimed to evaluate by ECG-SA and ECHO the myocardial involvement of SLE patients without clinical and electrocardiographic evidence of cardiac disease. METHODS AND RESULTS: Twenty outpatients with SLE were studied and compared with 18 normal controls. Late potentials were recorded in 20% of SLE patients and in 5.5% of controls. A significant increase of abnormal left ventricular diastolic filling was found in the SLE patients, characterized by reduced E/A (p = 0.018), a lower deceleration rate of early diastolic flow velocity (p = 0.048) and a prolonged isovolumic relaxation time (p = 0.001). SLE patients had diastolic dysfunction of various degrees although the depolarization abnormalities detected by ECG-SA were found only in a few subjects. CONCLUSIONS: The depolarization abnormalities, revealed by ECG-SA, probably reflect a longer extent of myocardial fibrosis in SLE patients with ECHO evidence of abnormal left ventricular filling. The simultaneous occurrence of ECHO and ECG-SA alterations could be a marker of subclinical myocardial involvement.

Adult↗

A morphological study of bone and articular cartilage in ochronosis.

An ochronotic femoral head has been studied morphologically under the light and the electron microscope. Its articular cartilage showed the alterations already reported in the literature, mainly consisting of erosions of the surface, pigment accumulation in chondrocytes and intercellular matrix, chondrocyte degeneration, the formation of pigmented, calcified and uncalcified microshards, and the presence of granulation tissue with macrophagic cells. The changes in bone were less severe than those in cartilage. Pigment was present in the calcified matrix. This did not seem to disturb the organization of the bone tissue, although it was diffusely osteoporotic, perhaps because of limb disuse. The preservation of calcified matrix might depend on the fact that its collagen fibrils are encrusted by mineral substance, which avoids the dangerous effects that the deposition of ochronotic pigment induces in the fibrils of soft connective tissues. On the other hand, the newly formed osteoid matrix remains uncalcified for too short a time to be modified by the pigment. Diffuse or granular pigmentation was found in a few osteocytes, while several of them were condensed or reduced to cellular fragments. Bone resorption often occurred near these osteocytes. However, this did not seem to alter the degree of bone remodelling, possibly because of the relatively low numbers of degenerated or dead osteocytes. Pigment was also contained in the cytoplasmic vacuoles of otherwise active osteoclasts, whereas it was not found in osteoblasts. On the whole, ochronosis in bone seems to induce the same changes as in other connective tissues. However, their severity appears to be limited by calcification, which prevents modifications in collagen fibrils, and by bone remodelling, which to some extent eliminates the oldest, pigment-richest parts of the tissue.

Bone Resorption↗

Study of peripheral bone mineral density in patients with diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is an ossifying systemic enthesopathy which involves not only the spine but which may also appear in other sites. Degenerative, inflammatory and metabolic factors have been reported for a possible pathogenic role in the new bone growth that characterises DISH. In the present study peripheral bone mineral density (BMD) has been measured in patients affected by DISH and the results compared to those of a control group. Forty-two patients (33 females and 9 males) affected by DISH and 84 controls (66 females and 18 males) were examined. All subjects underwent radiological study of the lumbar and dorsal spine and the pelvis. BMD was evaluated using dual-energy X-ray absorptiometry and the examination was performed in the distal radius. In DISH patients the mean value of BMD was significantly higher than in controls (P<0.002), even when it was referred to sex subgroups. Statistical analysis showed significant differences between both the two male groups (P<0.002) and the two female groups (P<0.01). In the two female subgroups (DISH patients and controls) BMD was significantly inversely related to age and to the duration of the postmenopausal period. The present study showed higher BMD in DISH patients than in the control group.

Absorptiometry, Photon↗

Diastolic function abnormalities in rheumatoid arthritis. Evaluation By echo Doppler transmitral flow and pulmonary venous flow: relation with duration of disease.

OBJECTIVE: The aim of this study was to evaluate left ventricular filling in patients with rheumatoid arthritis (RA), analysing transmitral flow and pulmonary venous flow, with special regard to age and disease duration. METHODS: 32 patients affected by RA according to ARA criteria were selected, without evidence of cardiac disease, and compared with matched control subjects. All patients and the control group were submitted to M-mode, two dimensional, Doppler and colour Doppler (continuous and pulsed wave) echocardiography. The following diastolic parameters were evaluated: transmitralic flow (E/A ratio), pulmonary venous flow (S/D ratio), a-Pw, IVRT and DT. RESULTS: In RA patients left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean (SD) 1.16 (0.31) v. controls 1.37 (0.32); p = 0.02) and an increased S/D ratio (1.43 (0.40) v. controls 1.22 (0.29); p = 0.017). In the group of patients a relation was found between E/A ratio and disease duration (r= 0.40, p = 0.01 Spearman rank correlation). CONCLUSIONS: At present, it is concluded that RA patients, in absence of clinical evidence of heart disease, show diastolic dysfunction characterised by impaired E/A and S/D ratio. The relation between transmitral flow alteration and disease duration suggests a sub-clinical myocardial involvement.

Adult↗

Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the rate of thromboxane biosynthesis in patients with systemic lupus erythematosus (SLE), exploring the interplay between antiphospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thrombin generation and platelet activation. METHODS: A comparison of 11-dehydrothromboxane B2 (TXB2) excretion, which is a marker of in vivo platelet activation, aPL, von Willebrand factor (vWF) and tissue plasminogen activator (tPA), which are 2 circulating markers of endothelial perturbation, and plasma levels of the prothrombin fragment F1+2, which is a marker of thrombin generation, was performed in 40 SLE patients and 40 healthy subjects. Thromboxane metabolite excretion was also measured in 8 SLE patients before and after treatment with low-dose aspirin. RESULTS: SLE patients had significantly higher 11-dehydro-TXB2 excretion, plasma F1+2, vWF, and tPA levels than controls. A statistically significant correlation was found between plasma levels of vWF and tPA and excretion of thromboxane metabolite. Moreover, significantly higher 11-dehydro-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB2 by 80%, suggesting a predominant platelet source of enhanced thromboxane biosynthesis. After a median followup of 48 months, all SLE patients who experienced major cardiovascular events had thromboxane metabolite excretion, aPL positivity, and signs of endothelial perturbation. CONCLUSION: We have characterized a sensitive marker of platelet activation, which is abnormal in SLE patients who were positive for aPL and endothelial perturbation. This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet therapy.

Adult↗

Relationship of rheumatoid factor isotype levels with joint lesions detected by magnetic resonance imaging in early rheumatoid arthritis.

OBJECTIVE: To evaluate the relationship between rheumatoid factor isotypes and articular damage detected by magnetic resonance imaging and plain radiography in early rheumatoid arthritis. METHODS: 20 consecutive patients with early active rheumatoid arthritis underwent determinations of serum IgM, IgA, and IgG rheumatoid factors by enzyme-linked immunosorbent assay (ELISA). Plain radiographs of the hands and wrists were obtained, and the wrist, metacarpophalangeal joints, and proximal interphalangeal (PIP) joints on the more severely affected side were investigated by magnetic resonance imaging before and after gadolinium-DTPA injection. RESULTS: IgM, IgA, and IgG rheumatoid factors were found in 13 (65%), 13 (65%), and 15 (75%) of patients, respectively. Sera from five patients (25%) contained no detectable rheumatoid factor isotypes. Correlations were found among the levels of the three rheumatoid factor isotypes. Levels of IgA, IgG, and IgM rheumatoid factor were significantly higher in patients with than without erosions on magnetic resonance imaging scans. No such difference was found when patients with and without erosions on plain radiographs were compared. Magnetic resonance imaging detected soft tissue lesions more frequently than plain radiography. Magnetic resonance imaging was also more likely than plain radiography to show bone erosions and bone cysts, but this difference was not statistically significant. CONCLUSIONS: Quantitative rheumatoid factor isotype assays and magnetic resonance imaging evaluation of erosions of the hand and wrist may be useful for investigating patients with early rheumatoid arthritis.

Adolescent↗

Circulating levels of soluble CD30 are increased in patients with systemic sclerosis (SSc) and correlate with serological and clinical features of the disease.

Activated Th2 lymphocytes express the surface molecule CD30 and release a soluble form of the same molecule which can be detected both in vivo and in vitro. In the present study, high levels of soluble CD30 were found in the peripheral blood of patients with SSc, and a significant correlation with skin score and erythrocyte sedimentation rate (ESR) was detected. Furthermore, we observed a higher spontaneous release of soluble CD30 in the supernatants of unstimulated cultures of peripheral blood mononuclear cells from our patients compared with healthy controls. Taken together, these data suggest a possible involvement of Th2 cells in the immunopathogenesis of SSc, and the dosage of CD30 soluble in the peripheral blood may be helpful in following the outcome of the disease.

Adult↗

Intra-articular somatostatin 14 reduces synovial thickness in rheumatoid arthritis: an ultrasonographic study.

Sixteen patients with RA (3 males, 13 females), diagnosed according to RA revised criteria, were selected and entered the study. They underwent six intra-articular injections of 750 mcg of SST14 at 15-day intervals. The thickness of the synovial membrane (SM) was measured with a 5-MHz linear sound with longitudinal and transversal scanning carried out on the upper patellar cavity. The contralateral knee was also assessed together with the injected knee in order to ascertain any systemic effect of the drug. A significant reduction of SM thickness was observed already at the first control (T3) in 14 out of 16 patients. At the 5th and 6th injections (T5 and T6) the reduction was still significant but to a lower extent. In 8 out of 16 cases a reduction of SM thickness was observed in the contralateral knee. Analysis of these data clearly shows that the intra-articular injection of SST14 is able to reduce the thickness of SM in patients with RA, and indicates that SST14 may directly reduce synovitis. This particularity has been detected in our work with a non-invasive technique such as the joint ultra-sound (US). In conclusion, our work confirms the efficacy of SST14 in the control of RA synovial hypertrophy and the reliability of US technique in the measurement of SM thickness.

Arthritis, Rheumatoid↗

[Intra-articular treatment with somatostatin 14 in rheumatoid arthritis].

19 patients with RA underwent six intraarticular injections of 750 micrograms of Somatostatin 14 in one knee at 15-day intervals. In all patients some clinical parameters were evaluated: articular function, pain on pressure, spontaneous pain, pain on movement, duration of morning stiffness. Also some laboratory parameters were examined: complete blood cell count, ESR and CRP. An overall and significant improvement of the symptomatology of the treated knee was seen in all patients especially after the 3rd infiltration and still more after the 5th. At follow up 3 months after the end of treatment 12 patients were controlled, 11 of these showed a persistence of the improvement. No side-effects were seen.

Arthritis, Rheumatoid↗

Characterization of differences in insulin receptors from young and old red blood cells.

It has been demonstrated that young RBCs (reticulocytes and early mature erythrocytes) possess more insulin receptors than old RBCs (late mature erythrocytes) but it is not yet known whether insulin receptors on young and old RBCs are regulated similarly. In the present investigation insulin receptors on young and old RBCs have, therefore, been studied in five normal male subjects before and after 2 days dexamethasone ingestion (0.5 mg tablet every 6 h) and, in the same subjects, before and 5 h after ingestion of 75 g glucose. The results obtained clearly demonstrate that dexamethasone increases insulin receptor concentration while glucose ingestion increases both insulin receptor affinity and concentration on young RBCs. By contrast, neither stimuli modify insulin receptors on old RBCs. Studies on RBCs are usually performed on the whole RBC population not taking into account this differential responsiveness of receptors on young versus old RBCs; consequently, this phenomenon might be responsible of the fact that some data reported on RBCs are not in agreement with those reported on monocytes or adipocytes and it should be taken into consideration when using RBCs to evaluate insulin receptor regulation.

Adult↗

Morphologic left ventricular patterns and prevalence of high-grade ventricular arrhythmias in the normotensive and hypertensive elderly.

In the elderly, systemic hypertension is the main risk factor for cardiovascular diseases. Left ventricular hypertrophy, the most common adaptation to chronic pressure overload, has been recognized as an independent risk factor for an increased incidence of sudden death and arrhythmic disturbances. This study compared the prevalence of serious ventricular arrhythmias in elderly individuals with uncomplicated hypertension and in normotensive age-matched controls, using left ventricular mass index (LVMI) to differentiate patterns of anatomic adaptation to systolic, diastolic, or systolic-diastolic hypertension. The study enrolled 378 consecutive untreated elderly subjects (> or = 65 years of age), without clinical evidence of heart failure; 203 were hypertensive and 175 were normotensive. Each participant underwent standard 12-lead electrocardiography, M-mode and B-mode echocardiography, and 24-hour ambulatory electrocardiographic monitoring. Serious, statistically significant arrhythmias (Lown classes > or = 3) were present in 6.8% of normal subjects versus 17.1% of individuals with systolic, 31.5% of those with diastolic, and 20.4% of participants with systolic-diastolic hypertension. Arrhythmias did not differ in terms of left ventricular morphologic patterns or LVMI or between subgroups of hypertensive patients. Our data support the hypothesis that the pathogenesis of arrhythmias is related not to the electrophysiologic derangement of hypertrophied muscle but, rather, to the effects of hypertension on the cardiac structure. Cardiac fibrosis, one of the deleterious events accompanying hypertension, may be the main substrate for ventricular arrhythmias.

Aged↗

Natural history of cardiac involvement in myotonic dystrophy (Steinert's disease): a 13-year follow-up study.

Myotonic dystrophy (MD) is associated with a wide spectrum of cardiac abnormalities, but only a few longitudinal studies have investigated the natural course of heart disease in MD. To assess whether neuromuscular involvement significantly predicts cardiac disorders in MD, 83 patients with various grades of disease severity were enrolled in a 13-year follow-up study (mean, 60.6 +/- 37.8 months) that included periodic physical and instrumental cardiac examinations (standard and Holter electrocardiography, echocardiography). During follow-up, muscular disease worsened clinically in 9 patients (11%) whose baseline severity grade changed accordingly; only 3 of them demonstrated parallel worsening of cardiac disturbance, however, compared with a large number of patients who showed additional cardiac abnormalities. These included further worsening of pre-existing pathologic features (19/83) and the appearance de novo of serious arrhythmias and/or conduction defects (23/83). Pacemaker implantation was necessary in 11 of 83 patients (13.2%) who had symptomatic bradyarrhythmias, bifascicular block, and P-R prolongation with a His-to-ventricle interval exceeding 55 ms, as documented by electrophysiologic study. Eight (9.6%) patients died: 2 from noncardiac and 1 from unknown causes, 1 from heart failure, and 4 from sudden death closely related to documented ventricular tachycardia. The incidence and seriousness of arrhythmic and conduction disturbances correlated with the severity of the muscular involvement. Nevertheless, cardiac and muscular disease did not show a linear progression. Cardiac involvement generally worsened more rapidly than did skeletal muscle disease.

Adolescent↗

[Occupational therapy in rheumatoid arthritis: short term prospective study in patients treated with anti-TNF-alpha drugs].

OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). RESULTS: At baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. CONCLUSION: Our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment.

Activities of Daily Living↗

[Rationale for the use of renin-angiotensin inhibitors in the treatment of arterial hypertension and correlated organ damage].

The treatment of hypertension has evolved in recent years. Blood pressure lowering per se is no longer a sufficient parameter to evaluate its beneficial effects on end-organ damage. Drugs must be considered on the basis of their effects on cellular level and structural alterations that occur in the vasculature, heart and kidney. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, two classes of drugs that inhibit angiotensin II effects, may protect target organs from damage and thereby improve outcomes. The mechanisms of action are different even if both counteract all noxious effects of angiotensin II. Angiotensin II receptor blockers selectively inhibit AT1 receptors whose stimulation mediates the hypertensive and proliferative effects of angiotensin II while do not interfere with AT2 receptors. These last ones have a role not well established but it has been postulated that they have antihypertensive and antiproliferative effects. A review will be made on the cellular mechanisms of angiotensin II activity and the effects of AT receptor antagonists.

Angiotensin-Converting Enzyme Inhibitors↗