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Biomedical subjects

A Del Rosso

Publications and source records attributed to A Del Rosso.

At least 19 recordsLinked to original sources
PubMed2006

Circulating levels of Nepsilon-(carboxymethyl)lysine are increased in systemic sclerosis.

OBJECTIVE: Advanced glycation endproducts (AGEs), including Nepsilon-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage. METHODS: In 66 SSc patients (limited SSc, n = 55; diffuse SSc, n = 11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement. RESULTS: CML levels were significantly higher in SSc (79.2 +/- 39 mg/ml vs 49.6 +/- 26.1 mg/ml, mean +/- s.d.; P<0.01), without significant differences between SSc subsets. CML levels were significantly higher in all capillaroscopic patterns: the 'early' pattern showed higher levels than 'active' and 'late' patterns. IMT was significantly higher in SSc (P<0.01) than in controls, whilst ABI was no different from controls. CONCLUSIONS: These data indicate that although both CML formation and macrovascular involvement are increased in SSc, there is no correlation between these two parameters. However, the characteristic early nailfold capillaroscopy changes of SSc are associated with proportionally greater CML formation, suggesting that AGEs are involved in SSc microangiopathy.

Adult↗
PubMed2006

Systemic sclerosis fibroblasts inhibit in vitro angiogenesis by MMP-12-dependent cleavage of the endothelial cell urokinase receptor.

Failure of endothelial cells to develop new vessels in response to hypoxia is a distinctive feature of systemic sclerosis (SSc) in the avascular phase. We have previously shown that SSc endothelial cells over-express matrix metalloproteinase-12 (MMP-12), which blocks angiogenesis by cleavage of the endothelial urokinase-type plasminogen activator receptor (uPAR). In the present study, we have investigated whether over-expression of MMP-12 and of angiostatic factors, or hypo-expression of angiogenic factors by SSc fibroblasts, contributes to impaired angiogenesis in SSc. Dermal fibroblasts were isolated from healthy subjects (N-Fb) and patients with diffuse SSc (SSc-Fb). Angiogenesis of target normal human microvascular endothelial cells (H-MVECs) was assayed by Matrigel invasion, cell proliferation, and capillary morphogenesis. uPAR cleavage and MMP-12 activity were evaluated by western blotting. We show that the over-expression of MMP-12 by SSc-Fb determines uPAR cleavage in H-MVECs. Conditioned medium from SSc-Fb impaired H-MVEC proliferation, invasion, and capillary morphogenesis. Anti-MMP-12 antibodies restored such impairment. Altered expression of angiostatic/angiogenic factors, including transforming growth factor beta1, did not account for SSc-Fb-dependent impairment of angiogenesis. The over-expression of MMP-12 by both SSc-Fb and SSc endothelial cells indicates that MMP-12 over-production may have a critical pathogenic role in SSc-associated vascular alterations.

Blotting, Western↗
PubMed2005

Raloxifene reduces urokinase-type plasminogen activator-dependent proliferation of synoviocytes from patients with rheumatoid arthritis.

Extracellular fibrinolysis, controlled by the membrane-bound fibrinolytic system, is involved in cartilage damage and rheumatoid arthritis (RA) synovitis. Estrogen status and metabolism seem to be impaired in RA, and synoviocytes show receptors for estrogens. Our aims in this study were to evaluate in healthy and RA synoviocytes the effects of Raloxifene (RAL), a selective estrogen receptor modulator (SERM), on: proliferation; the components of the fibrinolytic system; and chemoinvasion. The effects of RAL were studied in vitro on synoviocytes from four RA patients and four controls. Proliferation was evaluated as cell number increase, and synoviocytes were treated with 0.5 microM and 1 microM RAL with and without urokinase-plasminogen activator (u-PA) and anti-u-PA/anti-u-PA receptor (u-PAR) antibodies. Fibrinolytic system components (u-PA, u-PAR and plasminogen activator inhibitor (PAI)-1) were assayed by ELISA with cells treated with 0.5 microM and 1 microM RAL for 48 h. u-PA activity was evaluated by zymography and a direct fibrinolytic assay. U-PAR/cell and its saturation were studied by radioiodination of u-PA and a u-PA binding assay. Chemoinvasion was measured using the Boyden chamber invasion assay. u-PA induced proliferation of RA synoviocytes was blocked by RAL (p < 0.05) and antagonized by antibodies alone. The inhibitory effect of RAL was not additive with u-PA/u-PAR antagonism. RA synoviocytes treated with RAL showed, compared to basal, higher levels of PAI-1 (10.75 +/- 0.26 versus 5.5 +/- 0.1 microg/10(6) cells, respectively; p < 0.01), lower levels of u-PA (1.04 +/- 0.05 versus 3.1 +/- 0.4 ng/10(6) cells, respectively; p < 0.001), and lower levels of u-PAR (11.28 +/- 0.22 versus 23.6 +/- 0.1 ng/10(6) cells, respectively; p < 0.001). RAL also significantly inhibited u-PA-induced migration. Similar effects were also shown, at least partially, in controls. RAL exerts anti-proliferative and anti-invasive effects on synoviocytes, mainly modulating u-PAR and, to a lesser extent, u-PA and PAI-1 levels, and inhibiting cell migration and proliferation.

Arthritis, Rheumatoid↗
PubMed2005

Deflazacort modulates the fibrinolytic pattern and reduces uPA-dependent chemioinvasion and proliferation in rheumatoid arthritis synoviocytes.

OBJECTIVE: Extracellular fibrinolysis, controlled by the cell-associated fibrinolytic system (urokinase plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor type-1, PAI-1), is involved in cartilage damage generation and in rheumatoid arthritis (RA) synovitis. Since steroids reduce the rate of radiological progression of RA, we planned to evaluate in healthy and RA synoviocytes the effects of the steroid deflazacort on uPA, uPAR and PAI-1 expression, and subsequent phenotypic modifications in terms of uPA/uPAR-dependent invasion and proliferation. METHODS: uPA, uPAR and PAI-1 levels were studied by ELISA, RT-PCR (uPAR) and zymography (uPA) in synoviocytes from four RA patients and four healthy controls. Chemoinvasion was assessed by the Boyden chamber invasion assay, using Matrigel as the invasion substrate. Proliferation was evaluated by cell counting. Both invasion and proliferation were measured upon treatment with deflazacort 5 muM with or without parallel stimulation with uPA 500 ng/ml or in the presence of monoclonal anti-uPA and anti-uPAR antibodies. RESULTS: Invasion and proliferation of RA synoviocytes require a proper functional balance of the fibrinolytic system. Both deflazacort and monoclonal antibodies against uPA and uPAR reduced expression and activity of the system, thus inhibiting invasion and proliferation. In RA synoviocytes, deflazacort induced higher PAI-1 and lower uPA and uPAR levels, as well as a decrease in uPA enzymatic activity. The levels of uPAR mRNA were concomitantly reduced, as was uPA-induced chemoinvasion. All these effects were also shown in controls, though to a lesser extent. CONCLUSIONS: Deflazacort might control RA synovial proliferation and invasion by differential modulation of single members of the fibrinolytic system.

Adult↗
PubMed2005

Damage of cutaneous peripheral nervous system evolves differently according to the disease phase and subset of systemic sclerosis.

OBJECTIVE: Evidence shows that peripheral nervous system (PNS) is involved in systemic sclerosis (SSc), but few morphological studies have assessed the ultrastructural pathological modifications. The aim was to study ultrastructural modifications of skin PNS fibres in SSc according to subsets [limited SSc (lSSc) and diffuse SSc (dSSc)] and phases (early and advanced) of the disease. METHODS: Skin biopsies were taken from the forearms of 23 SSc patients (11 lSSc and 12 dSSc) and 10 controls. Each biopsy was processed for transmission electron microscopy (TEM). RESULTS: At TEM, observation in skin from early lSSc, signs of inflammation were evident, while PNS fibres were not damaged. The microvascular wall showed hypertrophic endothelial cells bulging into the lumen. In advanced lSSc, fibrosis prevailed on inflammation and slight ultrastructural alterations of PNS fibres were evident in the papillary derma. In early dSSc, ultrastructural alterations of PNS fibres, similar to those observed in the advanced phase of lSSc, were found together with signs of inflammation and fibrosis. In advanced dSSc, in the papillary and reticular dermis PNS fibres were reduced and showed relevant ultrastructural alterations. CONCLUSIONS: In SSc, PNS ultrastructure damage is linked to the progression and severity of skin involvement. The alterations evolve from the early to the advanced phase mainly in the diffuse subset. In particular, the severe PNS lesions found in advanced lSSc are already present and widely diffuse in early dSSc and the microvascular involvement in early lSSc seems to precede the modification of the PNS in the skin. Thus, an early therapeutic approach can be useful to reduce the progression of PNS and skin damage in SSc patients.

Adult↗
PubMed2005

Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement.

BACKGROUND: In systemic sclerosis (SSc) the lack of an angiogenic response to hypoxia may be due to inappropriate synthesis of angiogenic and angiostatic factors. Tissue kallikrein (t-kallikrein), regulating the kallikrein-kinin system and acting on the microcirculation, is a potent angiogenic agent, and kallistatin is its natural inhibitor. OBJECTIVE: To evaluate, in patients with SSc, t-kallikrein and kallistatin levels and their correlation with clinical features and measures of microvascular involvement. PATIENTS AND METHODS: Serum levels of t-kallikrein and kallistatin (ELISA) and t-kallikrein skin expression (immunohistochemistry) were studied in patients with SSc, and evaluated for subset (dSSc or lSSc), clinical and immunological features, and microvascular involvement (ulcers, telangiectasias, nailfold videocapillaroscopy). RESULTS: Circulating levels of t-kallikrein were higher in SSc than in controls (p<0.001). T-kallikrein did not differ between lSSc and dSSc, although it was higher in lSSc than in controls (p<0.001).T-kallikrein levels were higher in patients with early and active capillaroscopic pattern than in those with late pattern (p = 0.019 and 0.023). Patients with giant capillaries and capillary microhaemorrhages had higher t-kallikrein concentrations than patients with architectural derangement (p = 0.04). No differences in kallistatin levels were detected between patients with SSc and controls, or between lSSc and dSSc. In early SSc skin, the presence of t-kallikrein was found in endothelial and in perivascular inflammatory cells, while no staining in skin of advanced SSc was detected. CONCLUSION: T-kallikrein levels are increased in patients with SSc, particularly in lSSc, and are associated with early and active capillaroscopic patterns. T-kallikrein may play a part in SSc microvascular changes.

Adult↗
PubMed2005

Differential expression of tissue kallikrein in the skin of systemic sclerosis.

Systemic sclerosis (SSc) is characterised by ischemic damage, impaired angiogenesis and skin fibrosis. Tissue kallikrein (t-kallikrein) is involved through kinins in inflammation, vasorelaxation and angiogenesis. T-kallikrein is synthetised by endothelial, smooth muscle, and inflammatory cells and, in skin, also by dark cells of the sweat glands, where it is involved in sweat formation. Our aim was to analyse, by immunohistochemistry and RT-PCR, the expression of t-kallikrein in the skin of patients with different SSc subsets, limited (lSSc) and diffuse (dSSc), and phases, early and advanced. Skin biopsies were taken from 18 SSc patients and 10 controls. Immunohistochemistry was performed on paraffin sections with an antibody against human urinary t-kallikrein. For RT-PCR, cDNA from skin biopsies was amplified using primers specific for human t-kallikrein. In the control skin, dark cells of the secretory units of sweat glands showed immunopositivity for t-kallikrein as well as blood vessels. In the lSSc skin, immunoreactivity was observed only in some glands, with weak staining in the advanced phase. In early lSSc skin, immunoreactivity was observed in microvessel walls and in the inflammatory infiltrate. In dSSc skin, dark cells of the glandular fundus units, and the few remaining vessels showed scarcity (early phase) or lack (advanced phase) of immunoreactivity for t-kallikrein. RT-PCR confirmed a decrease of t-kallikrein mRNA levels from early to advanced phase in SSc subsets, reaching its lowest level in advanced dSSc. In conclusion, immunohistochemical and biomolecular results indicate that t-kallikrein is decreased in the skin of SSc patients and decreases progressively from the early to advanced phase of lSSc and dSSc. The decreased expression of t-kallikrein may be involved in the impairment of the sweating process, vessel functionality and angiogenesis.

Adult↗
PubMed2004

Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations.

OBJECTIVE: To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha (TNFalpha) monoclonal antibody (infliximab) in the treatment of spondyloarthropathy (SpA) associated with active and inactive Crohn's disease (CD). METHODS: Twenty four patients with SpA associated with active or inactive CD (16 active, 8 quiescent) were treated with anti-TNFalpha monoclonal antibody (infliximab) with repeated infusions for a period of 12-18 months. The treatment aimed at ameliorating the general musculoskeletal and spinal pain, controlling peripheral arthritis and enthesitis, decreasing the BASDAI score, modifying acute phase reactants, and reducing CD activity. RESULTS: Infliximab improved both gastrointestinal (p<0.01) and overall articular symptoms (BASDAI, p<0.01; general musculoskeletal and spinal pain, p<0.01; peripheral arthritis, p<0.01) in patients with active CD. Additionally, infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis (p<0.01) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers. Amelioration of gut and musculoskeletal involvement persisted for up to 12 months. CONCLUSION: Infliximab may act on the inflammation of entheses and of periarticular structures, which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA, suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD.

Adult↗
PubMed2003

Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis.

OBJECTIVE: To evaluate the coagulative/fibrinolytic cascade and the circulating markers of the endothelial injury in systemic sclerosis (SSc). METHOD: Plasma was obtained from 29 patients with SSc and tested for thrombin-antithrombin (TAT), fragments 1+2 (F1+2), dermatansulphate (DS), thrombomodulin (TM), lipoprotein (a) [Lp(a)], von Willebrand factor (vWF), tissue type plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimers, intercellular adhesion molecole-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin. The data were correlated with lung (forced vital capacity, diffusing lung capacity for carbon monoxide, vital capacity) and skin (skin score) involvement. RESULTS: Coagulation was significantly activated (increase in F1+2, P <.001; TAT, P <.01; and Lp(a), P <.05). TM was not significantly different from controls. vWF was significantly increased (P <.01), and its supranormal multimers increased in more than 50% of patients. DS was significantly increased in diffuse cutaneous SSc (P <.01). Fibrinolysis was impaired as shown by reduced D-dimers (P <.01) and decreased levels of PAI (P < 0.01). The markers of endothelial injury were also significantly elevated. DS correlated significantly with forced vital capacity (P <.01) and forced vital capacity ratio (P <.01). CONCLUSION: Injury to the endothelium reduces endothelial function, as suggested by impairment of fibrinolysis and activation of the coagulative pathway. The loss of the balance between fibrinolysis and coagulation contributes to vessel engulfment with fibrin and breakdown of vessel patency. The increase of circulating DS suggests that this factor may be a new marker of endothelial injury.

Adult↗
PubMed2002

A standardized conventional evaluation of the mechanism of syncope in patients with bundle branch block.

BACKGROUND: The finding of bundle branch block in patients with syncope suggests that paroxysmal AV block may be the cause of syncope, even though its prevalence is unknown. METHODS: We evaluated 55 consecutive patients with syncope and bundle branch block (mean age 75 +/- 8 years; median of two syncopal episodes per patient) referred to three Syncope Units. The hierarchy and appropriateness of diagnostic tests and the definitions of the final diagnoses followed standardized predefined criteria. RESULTS: Cardiac syncope was diagnosed in 25 patients (45%): AV block in 20, sick sinus syndrome in 2, sustained ventricular tachycardia in 1, aortic stenosis in 2. Neurally mediated syncope was diagnosed in 22 (40%): carotid sinus syndrome in 5, tilt-induced syncope in 15, adenosine-sensitive syncope in 2. Syncope remained unexplained in 8 (15%). CONCLUSIONS: Less than half of the patients with bundle branch block have a final diagnosis of cardiac syncope; in these patients, paroxysmal AV block is the most frequent but not the only mechanism supposed.

Aged↗
PubMed2002

The application of a standardized strategy of evaluation in patients with syncope referred to three syncope units.

BACKGROUND: The appropriate diagnostic work-up of patients with syncope is not well defined. We applied the guidelines of Italian 'Associazione Nazionale Medici Cardiologi Ospedalieri' to a group of consecutive patients with syncope referred to three Syncope Units. The aim of the study was to evaluate the applicability of those guidelines in the 'real world' and their impact on the use of the tests. METHODS: We evaluated 308 consecutive patients with syncope (mean age 61 +/- 20 years; median of three syncopal episodes per patient). The hierarchy and appropriateness of diagnostic tests and the definitions of the final diagnosis followed standardized predefined criteria. In brief, all patients underwent initial evaluation consisting of history, physical examination, supine and upright blood pressure measurement and standard electrocardiogram (ECG) (only in patients > 45 years or with history of heart disease). Any subsequent investigations were based on the findings of the initial evaluation. Priority was given to cardiological tests (prolonged ECG monitoring, exercise test, electrophysiological study), or to neurally mediated tests (carotid sinus massage, tilt test, ATP test), or to neuro-psychiatric tests, as appropriate. FINDINGS: The initial evaluation alone was diagnostic in 72 patients (23%). One further test was necessary for diagnosis in 65 patients (21%), > or = 2 tests in 64 (21%) and > or = 3 tests in 50 (16%). The diagnostic yield was 10% for ECG, 3% for echocardiogram, 16% for Holter, 5% for exercise test, 27% for electrophysiological study, 57% for carotid sinus massage, 52% for tilt testing and 15% for ATP test. At the end of the work-up the mechanism of syncope remained unexplained in 57 patients (18%). CONCLUSIONS: When standardized criteria based on the appropriateness of indications are used, few simple tests are usually needed for diagnosis of syncope.

Adult↗
PubMed2001

Diagnostic value of history in patients with syncope with or without heart disease.

OBJECTIVES: We sought to establish what historical findings are predictive of the cause of syncope. BACKGROUND: The clinical features of the various types of syncope have not been systematically investigated. METHODS: Three hundred forty-one patients with syncope were prospectively evaluated. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. RESULTS: A cardiac cause of syncope was established in 23% of the patients, a neurally mediated cause in 58% and a neurologic or psychiatric cause in 1%, and in the remaining 18%, the cause of syncope remained unexplained. In a preliminary analysis including age, gender and the presence of suspected or certain heart disease after the initial evaluation, only heart disease was an independent predictor of a cardiac cause of syncope (odds ratio 16, p = 0.00001), with a sensitivity of 95% and a specificity of 45%. In contrast, the absence of heart disease allowed us to exclude a cardiac cause of syncope in 97% of the patients. In patients with certain or suspected heart disease, the most specific predictors of a cardiac cause were syncope in the supine position or during effort, blurred vision and convulsive syncope. Significant and specific predictors of a neurally mediated cause were time between the first and last syncopal episode >4 years, abdominal discomfort before the loss of consciousness and nausea and diaphoresis during the recovery phase. In the patients without heart disease, palpitation was the only significant predictor of a cardiac cause. CONCLUSIONS: The presence of suspected or certain heart disease after the initial evaluation is a strong predictor of a cardiac cause of syncope. A few historical findings are useful to predict cardiac and neurally mediated syncope in patients with and without heart disease.

Algorithms↗
PubMed2001

Cell invasion is affected by differential expression of the urokinase plasminogen activator/urokinase plasminogen activator receptor system in muscle satellite cells from normal and dystrophic patients.

The aim of this study was to evaluate the differential expression and the function in cell movement and proliferation of the urokinase plasminogen activator (u-PA) system in muscle satellite cells (MSC) of normal individuals and patients with Duchenne muscular dystrophy (DMD). By immunoenzymatic, zymographic, and radioligand binding methods and by quantitative polymerase chain reaction of the specific mRNA we have shown that both normal and DMD MSC produce u-PA and the plasminogen activator inhibitor-1 and express u-PA receptors (u-PAR). During the proliferation phase of their growth-differentiation program, MSC from DMD patients show more u-PAR than their normal counterpart, produce more plasminogen activator inhibitor-1, and release low amounts of u-PA into the culture medium. By Boyden chamber Matrigel invasion assays we have shown that normal MSC are more prone than DMD cells to spontaneous invasion but, when subjected to a chemotactic gradient of u-PA, DMD MSC sense the ligand much better and to a greater extent than normal MSC. u-PA also stimulates proliferation of MSC, but no difference is observable between normal and DMD patients. Antagonization of u-PA/u-PAR interaction with specific anti-u-PA and anti-u-PAR monoclonal antibodies and with antisense oligonucleotides inhibiting u-PAR expression indicates that u-PA/u-PAR interaction is required in spontaneous and u-PA-induced invasion, as well as in u-PA-induced proliferation.

Base Sequence↗
PubMed2001

The vasovagal Syncope and pacing (Synpace) trial: rationale and study design.

BACKGROUND: Though vasovagal syncope probably does not directly cause death, it is often associated with severe trauma and, when recurrent, significantly impairs the patient's quality of life. While drug therapy for vasovagal syncope is still controversial, recently two randomized studies revealed the efficacy of dual-chamber pacemaker implantation in decreasing recurrences in very symptomatic patients. However, since both studies were not placebo-controlled, the benefits observed might have been due to the placebo effect of the pacemaker. AIM OF THE STUDY: The aim of the vasovagal Syncope and pacing (Synpace) trial, a multicentre, prospective, randomized, double-blind, placebo-controlled trial, is to ascertain whether, in patients suffering from recurrent vasovagal syncope, the implantation of a dual-chamber pacemaker with rate drop response algorithm programmed to ON, will reduce syncope relapses compared with the implantation of a pacemaker programmed to OFF. Moreover, in order to evaluate the role of the haemodynamic response during tilt-induced syncope in identifying those patients who will benefit most from pacemaker implantation, enrolled patients will be divided into two groups on the basis of their haemodynamic behaviour during tilt-induced syncope: group 1, asystolic response (development of asystole >3 s), and group 2, mixed response (development of bradycardia <60 bpm, without asystole >3 s). The head-up tilt testing protocol will consist of 20 min at 60 degrees without drug potentiation, followed by 15 min at the same inclination after 400 microg of sublingual nitroglycerin. Results from the two groups will be analysed both separately and globally. The primary clinical endpoint of the study will be syncope. INCLUSION AND EXCLUSION CRITERIA: To be enrolled, patients will have to meet the following criteria: at least six syncopal episodes in the patient's lifetime; positive head-up tilt testing with asystolic or mixed response; at least one syncope recurrence following a positive head-up tilt test. The following constitute exclusion criteria: non-vasovagal syncope; other indications for pacing. SAMPLE SIZE: We hypothesize a risk of syncope recurrence of 70% after one year, and we estimate that--owing to the placebo effect alone--pacemaker will produce a 20% decrease in risk, which corresponds to a 50% risk of recurrence after one year, in those patients randomized to 'pacemaker OFF'. We calculate conservatively a risk decrease of 60% in patients with 'pacemaker ON'. This implies a 10% incidence of syncope recurrence after one year, vs 50% in patients with 'pacemaker OFF'. Fifty patients will need to be enrolled in the study: 25 patients for each group.

Databases as Topic↗
PubMed2001

Prospective evaluation of adenosine-induced proarrhythmia in the emergency room.

The arrhythmogenic hazard of adenosine treatment in an emergency room (ER) has not been established. Thus, in this study, we set out to prospectively determine the prevalence and clinical consequences of the arrhythmogenic effects associated with urgent adenosine treatment in the ER. One hundred and sixty consecutive patients treated with adenosine for regular wide or narrow complex tachyarrhythmias at our ER were included in the study. An initial bolus of 3 mg of adenosine was used, up to a maximum dose of 18 mg (mode 6 mg). Proarrhythmia was defined as the new appearance of any brady- or tachyarrhythmia within 1 minute from the bolus administration of adenosine. Of the 160 study patients, 84% had narrow complex tachycardia and 16% had wide complex tachycardia. Adenosine was effective in the diagnosis and/or treatment of the underlying arrhythmia in 92%. The overall prevalence of adenosine-induced proarrhythmia was 13%, including prolonged AV block inducing asystole > 4 seconds (7%), paroxysmal atrial fibrillation (1%) and non-sustained ventricular tachycardia (5%). All adenosine-induced arrhythmias were transient and subsided spontaneously. It is concluded, firstly, that adenosine-induced proarrhythmia proved to be frequent in a consecutive ER series, and included potentially dangerous arrhythmias. Secondly, nevertheless, all adenosine-induced arrhythmias subsided spontaneously and did not require treatment. Therefore, urgent adenosine treatment is safe and can be recommended in an emergency setting, provided a strict protocol of administration under close monitoring by highly trained personnel.

Adenosine↗
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↗