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Biomedical subjects

F Fantini

Publications and source records attributed to F Fantini.

At least 19 recordsLinked to original sources

Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin A.

OBJECTIVE: To evaluate the ability of low-dose cyclosporin A (CsA) to control radiologic disease progression, and to assess the clinical efficacy and tolerability of CsA, compared with conventional disease-modifying antirheumatic drugs (DMARDs), in patients with early active rheumatoid arthritis (RA). METHODS: In this long-term, multicenter, prospective, open, blinded end point, randomized trial, 361 consenting patients with early (<4 years since diagnosis) active RA were enrolled. Of the eligible patients, 167 were treated with CsA at 3 mg/kg/day, and 173 with DMARDs. The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used. The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study. RESULTS: Blinded evaluation of hand and foot radiographs after 12 months of treatment showed that CsA led to a significant (P < 0.001) delay in the mean +/- SD progression in the eroded joint count (1.3 +/- 3.1 versus 2.4 +/- 3.0 for the control group) and in the joint damage score (3.6 +/- 8.9 versus 6.9 +/- 9.1 for the control group), both measured by the Larsen-Dale method. When only the patients without erosion at baseline were considered (37 in the CsA-treated group and 54 in the control group), erosion appeared in only 10.8% of the CsA-treated patients, but in 51.8% of the controls (P = 0.00005). Low-dose CsA was as effective as traditional DMARDs in controlling clinical symptoms. Maintenance on the initially prescribed treatment regimen ("survival on treatment") was also better at 12 months with CsA than with DMARDs (89.2% versus 77.5%; P = 0.002). The tolerability of CsA was acceptable. CONCLUSION: These 12-month results suggest that low-dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints, in patients with early RA.

Adult

Left-ventricular diastolic dysfunction during pneumonectomy--a transesophageal echocardiographic study.

Left-ventricular dysfunction, with acute increase in capillary pulmonary pressure, can unexpectedly develop in patients submitted to pneumonectomy. In order to study the morphofunctional modifications induced by pneumonectomy on the left cardiac chambers, we performed intraoperative transesophageal echocardiography (TEE) in 8 patients (7 males, mean age 66 years) undergoing pneumonectomy for lung cancer. No patient had any cardiac involvement before surgery. The opening of the pericardium was associated with a slight paradoxical movement of the basal interventricular septum. After ligature of the pulmonary artery, the interventricular septum changed its geometry, losing the normal curvature and becoming rectilinear. These changes were related to an increase in right-ventricular (RV) dimensions. In all patients the pulmonary vein flow-profile (pulsed Doppler) showed an increased turbulence, associated with a reduced amplitude (5 patients) or an inversion (3 patients) of the second systolic component and with the development of mild mitral regurgitation (color Doppler). These changes disappeared at the end of intervention, before chest closure. No alteration in left-ventricular systolic function was found. These results suggest that the altered geometry of the interventricular septum, mainly due to acute RV overload, induces a transient left-ventricular diastolic dysfunction, associated with mild mitral regurgitation.

Aged

Is the control of disease progression within our grasp? Review of the GRISAR study. (Gruppo Reumatologi Italiani Studio Artrite Reumatoide).

A prospective, open, multicentre, randomized study with a blinded radiological end-point was started in 1991. The aim of the study was to assess whether cyclosporin A (CyA) controls ongoing anatomical damage in active early rheumatoid arthritis (RA) better than conventional disease-modifying anti-rheumatic drugs (DMARDs) as used in everyday clinical practice. A total of 340 consenting patients with early RA (mean duration 1.4 yr) were recruited; 167 were randomized to CyA 3mg/kg per day and 173 to DMARDs. Hand, wrist and foot X-rays were blindly scored by a central committee of three radiologists using the Larsen-Dale method. Any side-effects were carefully recorded. The control of clinical symptoms was similar in both groups. Radiological evaluation of 284 patients (141 on CyA; 143 on DMARDs) after 12 months showed a significant decrease in the mean progression in the eroded joint count (1.3 +/- 3.1 vs 2.4 +/- 3.0, P < 0.001). There was also better maintenance on treatment with CyA than in the group treated with DMARDs (89.2 vs 77.5%, respectively; P = 0.002). CyA seems to offer greater control of ongoing anatomical joint damage in early RA than conventional DMARDs after 12 months.

Adult

Outcome of left ventricular aneurysmectomy with patch repair in patients with severely depressed pump function.

To determine the efficacy of left ventricular (LV) aneurysm resection and endoventricular patch repair with septal exclusion in patients with severely depressed pump function, we retrospectively selected 62 patients (mean age 59 +/- 7 years) with preoperative LV ejection fraction < or = 20%, from a series of 322 patients with postinfarction LV aneurysm who underwent this type of surgery at our center during a 5-year period. Mean ejection fraction was 17 +/- 3%; all patients were in New York Heart Association (NYHA) class III/IV, and all had hemodynamic and electrophysiologic studies before and after surgery. We analyzed both operative and long-term survival, and hemodynamic, electrophysiologic, and angiographic variables, as well as the symptomatic state after surgery. Follow-up was available in all patients (mean 23 +/- 14 months). Subtotal endocardiectomy and cryotherapy were associated in patients presenting with spontaneous or inducible ventricular arrhythmias (VA). Hospital mortality rate was 19.3%. Ejection fraction improved from 17 +/- 3% to 37 +/- 10% (p < 0.001); ventricular arrhythmias decreased significantly after surgery. Factors influencing early mortality at multivariate analysis were the presence of critical lesions on the circumflex artery and the duration of cardiopulmonary bypass. At 1-year control, a significant reduction in NYHA class was observed and no patient was in NYHA class IV. The improvement in ejection fraction was maintained (39 +/- 11%), as well as the reduction in inducible and spontaneous ventricular arrhythmias. There were 5 late deaths at follow-up, accounting for a late mortality of 10% at 5 years.

Aged

Replacement of the ascending aorta and aortic arch with bovine pericardial grafts. A preliminary report.

Bovine pericardial (BP) grafts have been clinical use at Biocor Hospital since 1989 for replacement or repair of the ascending aorta (AsAo) and initial segment of the aortic arch (AoAr). The main advantages of BP grafts that have justified their clinical application are much easier surgical technique, perfect hemostasis and low cost. From Feb/89 to Feb/94, 88 BP grafts were implanted in the AsAo or the AoAr. There were 33 valved conduits, 47 non-valved conduits and 8 patches. The main indication for the procedure was acute dissection of the aorta, accounting for 50% of the cases. The total hospital mortality was 20.4%. Follow-up was obtained in all but two patients. Patients who survived 2 or more years postoperatively (n = 31) underwent either an echocardiographic or an angiographic study in order to access the behavior of the graft, which was perfect in all of them. The current follow-up is short and complications such as calcification may still develop. However the present study has clearly shown the superior handling and better hemostasis of BP grafts compared to the classical Dacron prosthesis.

Adult

Regional myocardial performance of non-ischaemic zones remote from anterior wall left ventricular aneurysm. Effects of aneurysmectomy.

The aim of this work was to investigate the effects of resecting a post-infarction left ventricular anterior aneurysm on the kinetics of the non-ischaemic inferior wall, remote from the healed lesion. Thirteen patients, with an anterior post-infarction aneurysm and a normal right coronary artery who underwent aneurysmectomy with endoventricular circular patch plasty reconstruction, had a complete haemodynamic study before and shortly after surgery. The shape of the left ventricle was quantitatively analysed by calculating the regional curvature at 90 points of the angiographic outlines (30 degrees right anterior oblique projection). Segmental wall motion was studied by means of the centreline method and by constructing pressure-length loops from the endocardial movement of 18 chords intersecting the left ventricular inferior contour and by simultaneously tracing the high-fidelity left ventricular pressure. Analysis of pressure-length regional loops showed a complex pattern of abnormal contraction and relaxation in the non-ischaemic inferior regions at baseline; after surgery such abnormalities decreased significantly and tended to revert to normal in many cases. Left ventricular shape in the inferior region was abnormal in 10/13 patients in that there was negative curvature at the interface between the aneurysm and the inferior wall that was corrected to positive after surgery. Regional inferior wall motion and global ejection fraction significantly improved after surgery in these 10 patients. The three patients whose global ejection fraction did not improve showed no inferior negative curvature pre-operatively, nor did they show an increase in inferior wall motion. The results indicate that regional function and shape in inferior, non-ischaemic regions, remote from an anterior aneurysm, are abnormal but potentially correctible if the abnormal mechanical burden imposed on the wall is relieved.

Aged

Neurochemical markers in human cutaneous Merkel cells. An immunohistochemical investigation.

Merkel cells (MCs) are specialized sensory cells widely distributed in the epithelia of vertebrates. A variable immunohistochemical pattern of neuronal and neurotransmitter markers has been demonstrated in MCs of several species including man. In the present study, we investigated the expression of neurochemical markers in a selected population of human cutaneous MCs by immunofluorescence. The structural neural proteins protein gene product 9.5 and neuron-specific enolase were found to be the most reliable markers for MC identification. Moreover, neurofilament immunoreactivity was shown in a small subset of epidermal MCs. Among the neurotransmitter markers, evidence for expression of calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine isoleucine amide, neuropeptide Y, neurokinin A, galanin, substance P, somatostatin and phenylethanolamine N-methyltransferase was found. These immunoreactivities were highly variable as far as number of positive cells and staining intensity were concerned. The results indicate that a complex and heterogeneous immunophenotype can be expressed even within a homogeneous population of human MCs.

Adult

Nerve growth factor receptor and neurochemical markers in human oral mucosa: an immunohistochemical study.

BACKGROUND: The innervation of the oral mucosa has so far been studied mainly by histochemical and ultrastructural techniques. Only few studies have investigated the presence of neural proteins and neurotransmitters in human gingival mucosa. OBJECTIVE: The purpose of the present study was to evaluate the presence and distribution of neural structural and transmitter proteins in different areas of normal human oral mucosa. METHOD: Indirect immunofluorescence was employed on specimens taken from different mucosal regions (gingiva, lips, gums, palate). Both structural (low-affinity nerve growth factor receptor, NGFr; protein gene product 9.5, PGP 9.5) and neuropeptide markers (substance P; calcitonin gene-related peptide; vasoactive intestinal peptide, neuropeptide Y) were used. RESULTS: NGFr and PGP 9.5 intensely labelled both nerve fibres and selected epithelial cells, while neuropeptide immunoreactivity was scarcely expressed and exclusively localized in nerve fibres. CONCLUSIONS: Similarly in the distribution pattern and neurochemistry between oral and cutaneous innervation is apparent. Expression of NGFr could be relevant to the trophism of both the oral innervation and epithelium.

Adolescent

Effects of peptide T derivatives on the proliferation of cultured human keratinocytes.

[D-Ala1]peptideT-amide, the linear hexapeptide H-Thr-Hse-Asn-Tyr-Thr-Asp-OH (LPT) and its cyclic analog, cyclo(-Thr-Hse-Asn-Tyr-Thr-Asp-) (CPT), were tested for their effects on the proliferation of cultured normal human keratinocytes (KTs) in comparison with vasoactive intestinal peptide (VIP). [D-Ala1]PT-NH2, LPT and VIP (all 0.1 mumol/l) increased the cell number in KT cultures, whereas CPT was ineffective. The VIP antagonist [N-Ac-Tyr1,D-Phe2]GRF (1-29)-NH2 significantly inhibited the VIP effects on KTs. On the other hand this antagonist did not affect the peptide T (PT) compounds-induced stimulation of KTs, providing indirect evidence that the mitogenic effects of VIP and PT peptides are probably mediated via different receptors.

Adenosine

Clonal expansions of V delta 1+ and V delta 2+ cells increase with age and limit the repertoire of human gamma delta T cells.

We have investigated the complexity of the human gamma delta T cell repertoire by means of a VJ heteroduplex analysis method. cDNA obtained from peripheral blood mononuclear cells was amplified with V delta 1-C delta or V delta 2-C delta primers. The product was denatured and renatured to allow random reannealing of the strands and the heteroduplexes carrying mismatched junctional sequences were separated from the homoduplexes on polyacrylamide gels. Whenever one or more T cell clones were expanded to over 10% of the polyclonal background, discrete bands of homo- and heteroduplex appeared. This method was applied to the analysis of the peripheral gamma delta compartment from healthy donors and rheumatoid arthritis patients of different ages. While samples from young individuals showed a polyclonal pattern, a clear tendency towards oligoclonality appeared with increasing age, both in normal individuals and rheumatoid arthritis patients. We also show that the VJ junctional sequence derived from the heteroduplex fragments can be successfully used to isolate and characterize the corresponding T cell clones in vitro, even after a period of 1 year. In conclusion, our findings indicate that the complexity of the gamma delta T cell repertoire decreases with age as a consequence of the expansion of a few T cell clones.

Adolescent

Surgical repair of transposition of great arteries and total anomalous pulmonary venous return to the coronary sinus (TGA with TAPVR).

The association of transposition of the great arteries (TGA) and total anomalous pulmonary venous return (TAPVR) is very rare; we report one case of this malformation with an intracardiac type of TAPVR draining into the coronary sinus. The surgical repair was performed directing the coronary sinus blood flow to the tricuspid valve. The proximity of the anatomical structures allowed an intra-atrial patch repair similar to a modified Mustard procedure. In the postoperative period the child developed low cardiac output for 2 days, requiring inotropic support and mechanical ventilation. Her recovery was otherwise uneventful. The postoperative echocardiogram showed an intact repair with perfect flow through the patch from the pulmonary veins to the right ventricle. Almost 2 years after surgery, the patient underwent cardiac catheterization that showed integrity of the surgical repair with normal pressures in all heart chambers. To our knowledge this is the first report in the medical literature of surgical treatment of this association.

Coronary Circulation

Left ventricular shape changes induced by aneurysmectomy with endoventricular circular patch plasty reconstruction.

Aneurysmectomy with left ventricular (LV) patch plasty reconstruction for anterior post-infarction LV aneurysm is usually followed by favourable haemodynamic results. The aim of this work was to describe the changes in LV shape induced by the intervention and to correlate them to the pre-operative data and to the surgical results. Twenty-two patients submitted to aneurysmectomy with this technique underwent a haemodynamic study before and 10-15 days after the intervention. Segmental wall motion was studied by the centreline method. LV shape was analysed by calculating the regional curvature of angiographic outlines (RAO 30 degrees projection). Results showed an improvement in LV pump function in 17 patients, which appeared mainly due to increased systolic shortening of the inferior wall. The intervention-induced modifications of LV geometry were characterized by: (1) marked reduction in end-diastolic volume, (2) shift of the angiographic apex counterclockwise, towards the aortic corner, (3) disappearance of the rim with negative curvature corresponding to the infero-apical border of the aneurysm, where the inferior wall resumed a normal outward convexity. No significant difference was found between the pre-operative haemodynamic data of patients who improved after surgery and those who did not. The presence of a rim of negative curvature at the infero-apical border of the aneurysm was the only pre-operative sign with a predictive value for the surgical outcome.

Aged

Expression and function of nerve growth factor and nerve growth factor receptor on cultured keratinocytes.

Keratinocytes, a key cellular component both for homeostasis and pathophysiologic processes of the skin, secrete a number of cytokines and are stimulated by several growth factors. Nerve growth factor (NGF) is synthesized in the skin and basal keratinocytes express the low-affinity nerve growth factor receptor (NGF-R). We present evidence that normal human keratinocytes in culture express the low- and the high-affinity NGF-R both at the mRNA level, as determined by reverse-transcription polymerase chain reaction and at the protein level, as shown by cytofluorimetric analysis. NGF significantly stimulates the proliferation of normal human keratinocytes in culture in a dose-dependent manner. This effect can be prevented by the addition of both an anti-NGF neutralizing antibody and a high-affinity NGF-R (trk) specific inhibitor, the natural alkaloid K252a. By contrast, keratinocyte proliferation is not inhibited by an anti-low-affinity NGF-R monoclonal antibody, thus suggesting that NGF effect on human keratinocytes is mediated by the high-affinity NGF-R. Moreover, NGF mRNA is expressed in normal human keratinocytes and NGF is secreted by keratinocytes in increasing amounts during growth, as detected by enzyme-linked immunosorbent assay. These results suggest that NGF could act as a cytokine in human skin and take part in disorders of keratinocyte proliferation.

Antibodies, Monoclonal

Alterations in left ventricular shape in patients with angina and single-vessel coronary disease.

BACKGROUND: Left ventricular shape alterations, apparently independent of acute ischaemia or previous myocardial infarction, have been described in patients with stable angina. Our previous observations had been made in a group of patients with multivessel coronary disease; it was therefore not possible to establish a clear-cut anatomical relationship between the location of ischaemia and the changes in left ventricular contour. The aim of this work was to extend the previous observations by analysing left ventricular shape in patients with angina and single-vessel coronary disease, in whom the potentially ischaemic region can be easily localized. METHODS: Fifty-eight patients with stable or unstable angina were retrospectively selected if they had single-vessel disease, normal regional and global function and no previous myocardial infarction: 37 had a critical stenosis (more than 75% diameter reduction) of the left anterior descending artery and 21 had a critical stenosis of the right coronary artery. Patients with left ventricular hypertrophy or any other obvious cause of myocardial dysfunction were excluded. All patients underwent haemodynamic study. Left ventricular global shape was evaluated by calculating eccentricity and circular indices; regional curvature was measured at 90 points along the angiographic contours (right anterior oblique projection) by applying a windowed Fourier analysis. Results were compared with those obtained in 16 normal subjects. RESULTS: Patients had significant diastolic alterations in left ventricular shape, which assumed a more rounded aspect than normal. Regional curvature was significantly altered at several points pertaining to the anterior, apical and inferior segments. The pattern of changes in regional curvature was about the same in the left anterior descending and right coronary artery groups, with the involvement of regions supplied by angiographically normal arteries, although the extent of alteration was greater in patients with stable, chronic angina (more than 6 months) and in patients with stenosis of the left anterior descending artery. CONCLUSIONS: Patients with angina, no previous myocardial infarction and normal systolic function had left ventricular shape abnormalities either in the potentially ischaemic or in the remote zones. The mechanism leading to these changes is still speculative.

Adult

Dipyridamole angina: a specific symptom of severe multivessel disease.

BACKGROUND: Several studies have indicated that ischemia induced by dipyridamole is frequently associated with angina or ischemic ST-segment depression and that it occurs mainly in patients with three-vessel disease, those with collateral vessels, or those with both. METHODS: In order to analyze the diagnostic relationships among them, we studied 227 consecutive patients who underwent coronary angiography and dipyridamole-thallium scintigraphy. RESULTS: A perfusion defect was found in 134 patients. Of these, 88 patients (66%) showed no significant ECG modifications or angina; 46 (34%) had a transient ST-segment depression, which was associated with typical angina ('dipyridamole angina') in 12. These 12 patients had three-vessel disease with intercoronary collateral circulation. Among the 134 patients with coronary critical stenoses and a positive thallium-dipyridamole test, collateral vessels were detected in 91 (68%). CONCLUSION: Dipyridamole angina, occurring during a positive dipyridamole-thallium test, is usually a manifestation of severe coronary stenoses with collateral circulation. However, as a diagnostic symptom it is characterized by high specificity but low sensitivity.

Aged