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Biomedical subjects

M Cagnoni

Publications and source records attributed to M Cagnoni.

At least 19 recordsLinked to original sources
PubMed2002

Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement.

OBJECTIVE: To evaluate the functional response of the kidney to an amino acid challenge (the so called renal functional reserve (RFR)) in patients with systemic sclerosis (SSc) with no clinical sign of renal involvement. METHODS: Before and after an intravenous amino acid load (Freamine III Baxter, 8.5% solution, 4.16 ml/min for two hours), glomerular filtration rate (GFR, as creatinine clearance), effective renal plasma flow (ERPF, as para-aminohyppurate clearance), and calculated total renal vascular resistance (TRVR) were measured in 21 patients with SSc with apparently normal renal function and 10 normal controls. RESULTS: In basal conditions, patients had lower ERPF (403.5 (SD 43.8) v 496.4 (SD 71.3) ml/min, p<0.0002) and higher TRVR (10 822 (SD 2044) v 8874 (SD 1639) dyne/sxcm(-5), p<0.014) than controls. The RFR, evaluated as the percentage increase of GFR after the amino acid load, was significantly reduced in patients with SSc (SSc +1.9 (SD18.6)%, controls +34.8 (SD 13.9)%; p<0.0002). However, the response of patients was not uniform. Multiple regression analysis showed that the RFR was inversely dependent on the patients' mean arterial pressure at admission and basal GFR (R(2)=65%, p<0.0001). CONCLUSIONS: Most patients with SSc cannot increase renal filtration under the challenge of a protein overload. This defective renal response to the amino acid load test sustains the concept of the prevalence of vasoconstrictor over vasodilating factors in the kidney of these patients.

Amino Acids↗
PubMed2001

Nerve growth factor and neuropeptides circulating levels in systemic sclerosis (scleroderma).

OBJECTIVE: To determine the circulating levels of nerve growth factor (NGF), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic sclerosis (SSc), and to correlate these levels with clinical and laboratory features. METHODS: Forty four patients with SSc were evaluated for circulating NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99mTc DTPA radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography), cutaneous involvement (skin score), joint involvement (evidence of tender or swollen joints, or both), peripheral nervous system (PNS) involvement (electromyography), rheumatoid factor, angiotensin converting enzyme (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte sedimentation rate (ESR) (Westergren). RESULTS: Circulating NGF levels in SSc were significantly increased compared with controls (p<0.00001) and significantly higher in the diffuse than in the limited subset of patients (p<0.01). Patients with articular disease had significantly higher levels of NGF. A significant indirect correlation between NGF levels and TLCO was detected (p<0.01), but no correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase or anticentromere antibodies, and ESR. NGF levels increased progressively as the disease worsened. Similarly, VIP circulating levels were significantly increased in patients with SSc (p<0.001), whereas the increase of NPY levels did not reach statistical significance. However, both neuropeptides, following the same trend as NGF, increased as the disease worsened (skin score and lung disease). CONCLUSIONS: The increase of NGF and VIP in patients with SSc, the former in the diffuse subset of the disease, and in patients with prominent articular disease, may suggest a link between neurotransmitters and the disease pathogenesis. Neuropeptide circulating levels seem to increase only in patients with the most severe disease.

Biomarkers↗
PubMed1999

Oxidative stress in Systemic Sclerosis.

In 63 patients affected by Systemic Sclerosis (SSc) (limited subset: 40; diffuse subset: 23; early: 30; advanced: 33) the peroxidation product diene-conjugates (DC) and antibodies against oxidised low density lipoproteins (Ab oxLDL) were tested in serum by a spectrophotometer (absorbance 234 mn) and by a standard ELISA respectively. The data were compared with those obtained by 21 healthy subjects. DC was significantly higher in patients (73.3 +/- 37.2 microM/l; p < 0.0001) than in controls (48.4 +/- 16.7) as well as in the limited (80 +/- 48.8; p < 0.05) than in the diffuse subset (64.5 +/- 36.4); and in early (84.1 +/- 31.4; p < 0.05) than in advanced stage of the disease (67.9 +/- 42.5). The levels of Ab oxLDL were significantly higher in SSc patients (309.5 +/- 367.2 mU/ml; p < 0.0001) in all its subsets (limited: 351.9 +/- 351.1, p < 0.0001; diffuse: 207.7 +/- 316.1, p < 0.05; early: 428.9 +/- 417.1, p < 0.001; advanced: 302.7 +/- 89.9, p < 0.0001) than in controls (89.3 +/- 29.1). These antibodies levels were higher in limited subset than in diffuse (p < 0.05) and in early SSc than in advanced SSc (p < 0.05). The highest values of parameters of oxidative stress are found in the early stages, when the episodes of reperfusion after ischemic episodes (Raynaud's phenomenon) are very frequent. Moreover, the damage is higher in the early stages of SSc, with intact microvessels, than in late stages, when microvessels are very reduced in number, destroyed by the worsening of the disease. These data show that the respiratory burst deduced by the lipoperoxidation is higher in SSc than in controls, and may be an important pathogenetic factors involved in tissue changes in SSc.

Antibodies↗
PubMed1999

Systemic sclerosis. A clinical overview.

Systemic Sclerosis (SSc) is a multisystem disease that affects the skin and internal organs (i.e., gastrointestinal tract, lung, heart, kidney and peripheral nervous system). In the early phase, lung involvement is characterized by interstitial inflammatory alterations that are detected by bronchoalveolar lavage analysis and high resolution computed tomography (ground glass). As the disease progresses, fibrotic changes become evident and the diffusing capacity for carbon monoxide (DLCO) is impaired. Cardiac involvement in SSc can be manifested as myocardial disease, pericardial disease, conduction system disease, or arrhythmias. Cardiac involvement is a poor prognostic factor, but the diagnosis may be late or missing because of the frequent discrepancy between clinical manifestations and the real cardiac involvement. For this reason, resort to all the available diagnostic procedures is recommended to achieve an early diagnosis. The motility disorders are a major feature of gastrointestinal involvement in SSc, striking any part of this system (especially esophagus and anorectal region). Kidney involvement and scleroderma renal crisis are now considered rare because of the introduction of ACE inhibitors. Some patients may develop myositis or erosive arthropathy that complicate enormously the joint retraction induced by skin fibrosis. The peripheral nervous system (PNS) is also targeted by SSc: a distal mononeuropathy of the median nerve is a frequent and early feature; autonomic nerve dysfunction (parasympathetic impairment and marked sympathetic overactivity) seems to be a fundamental etiologic factor linked to the development of microvascular, cardiac and gastrointestinal alterations. The whole approach to the SSc patient is very complex and must consider, at the same time, many organs and systems. Thus, a global vision of SSc patient is needed in order to assure an early diagnosis of specific organ involvement as well as early treatment. Systemic Sclerosis (SSc) is a multisystem disease, that affects the skin, the gastrointestinal tract, the lung, the heart and the kidney. The extent and severity of internal organ involvement are the more important factors influencing the disease outcome and prognosis in SSc. In recent years, it has become evident that early diagnosis and accurate staging of visceral involvement are fundamental for appropriate management and therapeutic approach to the disease. Diagnostic procedures for specific organ and system involvement are now more sensitive because of the continuous technological improvement and, mostly, because they take advantage of the studies carried out in other diseases by other medical branches. This review will consider briefly the most frequent and important organ involvement in SSc.

Gastrointestinal Diseases↗
PubMed1999

Discrepant expression of neprilysin on fibroblasts in diffuse systemic sclerosis.

OBJECTIVE: Neprilysin (NEP; EC3.4.24.11) is an ectopeptidase mainly produced by fibroblasts and cleaving a large number of neuropeptides. We previously found increased plasma circulating levels of NEP in patients with systemic sclerosis (SSc), but in SSc fibroblasts derived from the diffuse subset NEP was present in lower concentration. We evaluate in vitro fibroblasts of both subsets of the disease, diffuse and limited, the intracellular levels of NEP, and its expression as CD10 on the cellular surface. METHODS: Fibroblasts, derived from biopsies taken from affected skin of 8 patients with the limited subset and 5 with the diffuse subset, were grown in vitro and intracellular levels of NEP activity were measured with a fluorometric method, while CD10 surface expression was evaluated by FACS analysis. Cell proliferation was assessed by 3HThymidine incorporation. RESULTS: Intracellular NEP activity was significantly increased in diffuse (7.02+/-4.8 pg/ml/min 10(6) cells) compared to limited SSc (1.11+/-2.0) and control fibroblasts (1.41+/-0.9). CD10 expression was significantly impaired on diffuse SSc fibroblasts (47.3+/-15%) compared to controls (74.6+/-11%) and the limited subset (82.7+/-11%). Cell proliferation of diffuse SSc fibroblasts was strikingly higher than controls and limited SSc fibroblasts. CONCLUSION: These results confirm that NEP is produced by fibroblasts and indicate that in diffuse SSc fibroblasts NEP is produced in higher quantities, while the expression of the enzyme on the cell surface is significantly reduced. This condition may affect the proliferation rate of fibroblasts as well as the metabolism of various peptides.

Cell Division↗
PubMed1992

High resolution computed tomography in systemic sclerosis. Real diagnostic utilities in the assessment of pulmonary involvement and comparison with other modalities of lung investigation.

The real utility of high resolution computed tomography (HRCT) for early detection of lung involvement was investigated in eighteen patients affected with systemic sclerosis (SSc). The results obtained from HRCT have been compared with traditional (chest radiographs, pulmonary function tests (PFT)) and nontraditional (ventilation and perfusion scintiscan) modalities of lung investigation. A significant statistical correlation (p < 0.001) between HRCT scans and chest radiographs was observed. Moreover, HRCT was more sensitive in the detection of early pulmonary interstitial involvement and more accurate in the assessment of interstitial fibrosis in cases with severe lung involvement. A statistical correlation (P < 0.001) between HRCT and the modalities of investigation of alveolo-capillary membrane--as PFT and ventilation scintiscan--was also observed. These results indicate that in SSc HRCT may be a useful technique for assessing early pulmonary involvement and for complementing other methodologies of investigation of lung function.

Adult↗
PubMed1992

Suppression of autoantibodies to factor VIII and correction of factor VIII deficiency with a combined steroid-cyclophosphamide-porcine factor VIII treatment in a patient with rheumatoid arthritis.

The presence of autoantibodies against factor VIII is an unusual but serious complication in rheumatoid arthritis. We describe the case of a patient who developed this kind of complication, with spontaneous bleeding and marked changes in the haematological parameters, that was unsuccessfully treated with a high dose of intravenous gammaglobulin. Subsequently, combined therapy with porcine factor VIII concentrate, cyclophosphamide and steroids led to the disappearance of the anti-factor VIII autoantibodies.

Aged↗
PubMed1992

Clinical utility of non invasive methods in the evaluation of scleroderma lung in pediatric age.

Lung involvement in children affected with Systemic Sclerosis (SSc) has been studied. We used ventilation and perfusion scans and compared the results to those obtained with traditional pulmonary function tests. The vascular pulmonary area was examined with a gama-camera after infusion of 99mTc microspheres, while the alveolo-capillary membrane and the airways were investigated after administration of a radioaerosol, (99mTc DTPA). Pulmonary function tests revealed either alteration of the airways or a considerable involvement of the alveolo-capillary membrane in two patients. On the other hand ventilation scan showed airways alterations and a severe decrease of the alveolocapillary permeability in all patients. Our study indicates that ventilation scans may be useful in the diagnosis of early modifications of the lung function also in paediatric age and may complement the data obtained from traditional function tests.

Adolescent↗
PubMed1992

Gold salts and somatostatin: a new combined analgesic treatment for psoriatic arthritis.

In a group of patients affected with psoriatic arthritis the effects of the association between gold salts (GS) and somatostatin (SOM), in comparison with two groups treated with SOM and GS respectively, were investigated. Sixty patients with psoriatic arthritis were selected and randomly allocated in three groups of twenty patients each. Group 1 received SOM infusion (250 micrograms/h for 96 h) and was assessed at baseline and 1, 15, 30, 60, 90 and 120 days after; Group 2 received intramuscular GS and was assessed at baseline, four months later, and then every month for four months; Group 3 received GS for 8 months; at the fourth month SOM was infused (as in Group 1) and the patients assessed at baseline four months later and then as Group 1. Assessment was made with the Ritchie index, pain scale and morning stiffness evaluation. Growth hormone was assayed in Group 1 every 4 h for 24 h the day before and the day after SOM infusion. The association between GS and SOM demonstrated a particular analgesic activity, effective on joint pain and tenderness, that lasted for all four months of follow-up. SOM showed a good response only after 15 and 30 days, and GS proved to be effective at about the sixth month of treatment. Side effects were reported in Group 1 (abdominal cramps, mild erythrodermia and supraventricular arrhythmia). A growth hormone circadian rhythm was found in psoriatic patients both before and after SOM treatment. The beneficial effect of the SOM/GS combination is demonstrated in psoriatic arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Collagenase synthesis of rheumatoid arthritis synoviocytes: dose-dependent stimulation by substance P and capsaicin.

The synthesis and release of collagenase in the presence of the neuropeptide substance P (SP) and capsaicin, were investigated in vitro using identical synoviocyte cultures from patients with rheumatoid arthritis (RA). On average 10(-12) M SP augmented statistically significantly the collagenase production by approximately a factor of five. An increase in the concentrations up to 10(-6) M SP resulted in a decreased collagenase synthesis, which, however, was still above the level of that of the untreated synoviocytes. Capsaicin, a homovanillic acid derivative that acts as a releaser of SP from primary afferent neurons, caused a strong stimulation of collagenase production and release at 10(-8) and 10(-6) M (about 7 times the amount of the control). With increasing concentrations up to 10(-3) M capsaicin this effect diminished continuously. The experiments clearly show that in RA synoviocytes in vitro SP and capsaicin in low concentrations act as potent inducers of the synthesis and release of collagenase.

Arthritis, Rheumatoid↗
PubMed1990

Clinical correlations of plasma angiotensin converting enzyme (ACE) activity in systemic sclerosis: a longitudinal study of plasma ACE level, endothelial injury and lung involvement.

Lung involvement was studied by perfusion scan, ventilation scan, pulmonary clearance rate of 99mTc DTPA and pulmonary function tests in 20 patients with systemic sclerosis (SSc). Decreased plasma angiotensin converting enzyme (ACE) activity and increased levels of von Willebrand Factor Antigen (vWF:Ag) were found in all patients with SSc. The relationship between ACE levels and lung involvement was not statistically significant, however levels of vWF:Ag correlated with parameters of lung vascular alterations. An inverse relationship between the reduced ACE levels and ESR was found. It is likely that ACE levels reflect the inflammatory aspect of the disease. Further studies of ACE synthesis, release and inhibition are needed to determine the mechanism of the observed decreased activity in SSc.

Adolescent↗
PubMed1990

Fibrinolytic activity in the synovial membrane of osteoarthritis.

The fibrinolytic activity (FA) has been studied on the synovial membrane obtained from 16 patients with osteoarthritis (OA), 20 patients with rheumatoid arthritis (RA) and 11 control subjects. Todd's autohistographic method, modified by Lotti, was used to investigate the FA and the monoclonal antibodies against u-PA and t-PA were used to identify the main plasminogen activator. Our results show that the FA is increased in the synovial membrane of patients with OA in comparison with the synovial FA of control subjects. In the synovial membranes from patients with RA, the FA shows different results: in some specimens FA is increased, and in others it is diminished or similar, compared with FA of samples from healthy controls. Thus, our data on synovial FA in OA confirm the previous reports, performed in vitro, on the activation of the plasmin system in this degenerative disease. The activity of the fibrinolytic system seems to participate in the cartilage degeneration and, via the activation of collagenase, to perpetuate the cartilage damage.

Adult↗
PubMed1990

Effects of capsaicin on the metabolism of rheumatoid arthritis synoviocytes in vitro.

The effects of capsaicin, the ingredient of hot pepper, on rheumatoid arthritis synoviocytes have been studied. Capsaicin was shown to have a direct action on the metabolism of synovial cells. Thus at 10(-6) mol/l and at higher doses DNA synthesis was restored to the control level. Capsaicin at both doses induced an increase in the synthesis of collagenase and at the lower concentration (10(-8) mol/l) only of prostaglandins. These results indicate that the different effects of capsaicin on cellular proliferation and on metabolic activities are dependent on dose. The responses seen in rheumatoid arthritis synoviocytes in vitro might not be mediated by tachykinins if the synovial tissue is still able to produce neuropeptides in the absence of neuronal afferents. These results suggest that capsaicin, in addition to its direct action on the afferent nervous fibres and the consequent release of tachykinins, may also have a direct action on the cells. The mechanisms by which capsaicin stimulates DNA synthesis and production of collagenase and prostaglandin E2, in a manner dependent on dose, remain to be determined.

Arthritis, Rheumatoid↗
PubMed1990

Immunological abnormalities in a group of patients with limited cutaneous systemic sclerosis and prominent vascular disease.

Antinuclear antibodies, circulating immune complexes, rheumatoid factors and anticardiolipin antibodies were detected in the sera of 17 patients affected by the limited cutaneous subset of systemic sclerosis and marked clinical evidence of ischaemic cutaneous lesions (fingertip ulcerations). This study was designed to evaluate the possible role of anticardiolipin (aCL) antibodies and other immunological disorders in the endothelial damage characteristic of the disease. ACL antibodies were found in 41% of the patients. With the exception of a significant connection with positive rheumatoid factor tests (RIA), no notable associations between anticardiolipin antibodies and antinuclear antibodies, circulating immune complexes (CIC), and other serological abnormalities were found. ACL antibodies did not significantly correlate with the presence of vascular lesions in our patients. However, a role of these antibodies in endothelial damage cannot be excluded, possibly in association with other serum factors such as immune complexes and antinuclear antibodies. A positive connection between the incidence of CIC and the severity of lung perfusion impairment was observed, and the previously reported relationship between anticentromere antibodies and calcinosis was indirectly confirmed.

Adolescent↗