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Biomedical subjects

F Santini

Publications and source records attributed to F Santini.

At least 55 records · Page 3Linked to original sources

Primary cardiac leiomyosarcoma: seven-year survival with combined surgical and adjuvant therapy.

Primary cardiac sarcomas constitute a rare entity that have been uniformly associated with poor long-term survival. A case of left atrial leiomyosarcoma involving the interatrial septum and the right atrial free wall and presenting with syncope and atrial fibrillation, is described. Two extensive surgical excisions followed by adjuvant radiation and chemotherapy improved survival with a good quality of life. This approach of combined surgical, medical and radiation therapy may offer better longterm outcome, since our patient is the longest survivor thus far reported.

Adult↗

Pulmonary autograft versus homograft replacement of the aortic valve: a prospective randomized trial.

BACKGROUND: Pulmonary autografts offer many theoretical advantages. However, the operation is complex, may interfere with right ventricular and pulmonary outflow function, and requires a longer operative time than does the homograft operation. The effects of these potential disadvantages are unknown. METHODS: To clarify these issues we randomized 70 patients undergoing aortic valve replacement to an aortic homograft group (group A = 37 patients; 53%; 34 male, 3 female) or a pulmonary autograft group (group B = 33 patients; 47%; 28 male, 5 female). Ages varied from 12 to 65 years (mean 39 +/- 15 years) for group A and from 3 to 54 years (mean 29 +/- 15 years) for group B (p = not significant). Eleven patients in group A (30%) and eight in group B (24%) had previous aortic valve surgery. All patients were operated on by the same surgeon. The mean cardiopulmonary bypass time was 113 +/- 29 minutes (range 66 to 175 minutes) for group A and 151 +/- 31 minutes (range 115 to 226 minutes) for group B (p < 0.002). Mean aortic crossclamp time was 85 +/- 19 minutes (range 45 to 140 minutes) for group A and 109 +/- 20 minutes (range 74 to 164 minutes) for group B (p = 0.02). In 32 patients (86.5%) the aortic homograft was implanted as a root with coronary reimplantation. All pulmonary autografts were implanted as a root. RESULTS: No early or late deaths had occurred in this series at a mean follow-up time of 16 months (range 3 to 21 months). Two patients (one in each group) required reexploration for bleeding. No statistically significant differences were observed between the two groups with regard to ventilatory support (group A, mean 10 +/- 8.5 hours; group B, mean 29 +/- 85 hours), total blood loss (group A, mean 471 +/- 347 ml; group B, mean 543 +/- 404 ml), intensive care unit stay (group A, mean 1.2 +/- 0.6 days; group B, mean 2 +/- 3.7 days), and hospital stay (group A, mean 9.5 = 3.2 days; group B, mean 12 +/- 6 days). Postoperatively, all patients are in New York Heart Association class I (93%) or II (7%) (p = not significant). Ejection fraction for the two groups did not change significantly over the follow-up period. Left ventricular mass and diastolic diameter showed progressive regression, with no apparent difference between the two treatment groups to date. Echocardiographic evaluation of aortic valve function at 6 months showed good valve function in all patients with no evidence of aortic regurgitation in 80% of both groups. In group B the right ventricular outflow gradient was below 15 mm Hg over the follow-up period. Holter monitoring, available only in 44 patients (63%), showed most of the arrhythmias to be grade 0 to 1 of the modified Lown grading system. CONCLUSION: Although the pulmonary autograft requires a significantly longer operating time, this does not seem to affect early and medium-term outcome when compared with results obtained with aortic homografts. Continued patient evaluation is warranted, particularly with regard to evidence of valve degeneration and right ventricular function and arrhythmias in the long term.

Adolescent↗

Heterotopic cardiac transplantation in infants and children.

BACKGROUND: Children with advanced heart failure, particularly those with elevated pulmonary vascular resistance, pose a difficult management problem because the normal donor right ventricle cannot cope with the high pulmonary resistance and because of the relative shortage of donor organs of an appropriate size for this age group. METHODS: In an attempt to address these issues and evaluate the role of heterotopic transplantation in this context, we operated on 12 children, six boys and six girls, in the period between January 1, 1991, and March 31, 1996. Their ages ranged from 11 months to 15.2 years (mean 81.6 +/- 62.8 months) and their mean weight was 23.3 kg (range 7.6 to 56.8 kg). Eight patients (66.6%) had significant elevation of pulmonary artery pressure (pulmonary artery systolic pressure = 66 +/- 9.4 mm Hg, mean transpulmonary gradient = 22.3 +/- 3.4 mm Hg). In all patients the donor pulmonary artery was anastomosed to the recipient right atrium without the use of any prosthetic material. Ischemic times varied between 135 and 255 minutes (mean 182.1 +/- 30.7 minutes). The immunosuppression regimen included cyclosporine and azathioprine. Steroids were not routinely used. RESULTS: One patient died in the hospital of acute rejection on postoperative day 16. Three patients had lobe collapse within 1 week and all were treated successfully. Two late deaths (18.2%) occurred as a result of cardiac rejection 3 months and 2 years after the operations. Nine survivors (75%) are alive, active, and growing normally at a mean follow-up of 2.2 years (range 11 months to 4.75 years). Repeated cardiac catheterization performed in seven patients with preoperative pulmonary hypertension showed a slow progressive drop in mean pulmonary artery pressure. No significant change was observed in the function of the recipient hearts. CONCLUSION: We conclude that heterotopic heart transplantation is feasible for a selected group of children with good medium-term results, notably regression of pulmonary artery pressure, normal growth, and lack of long-term chest complications.

Adolescent↗

Single aortic cross-clamp technique in coronary surgery: a prospective randomized study.

OBJECTIVE: To test the hypothesis of an improved myocardial and cerebral protection by combining blood cardioplegia and the single aortic cross-clamp technique, 100 patients were enrolled in a prospectively randomized study and stratified for preoperative conditions. METHODS: In Group I, 55 patients underwent myocardial revascularization using crystalloid cardioplegia and the conventional partial occluding clamp technique to perform proximal anastomoses, whereas in Group II, 45 patients were operated on combining blood cardioplegia and the single aortic cross-clamp technique. Unstable angina, emergency procedures, reoperations and preoperative counterpulsation accounted for an higher risk score in group II patients (P < 0.03). Operations were performed by the same surgical team. Aortic cross-clamp time was significantly longer in group II patients (59 +/- 22 vs. 47 +/- 18 min.) (P < 0.001). Other intraoperative variables were not significant. RESULTS: A 70-year-old male in group I died on post-operative day 5 as a consequence of a major neurological event. Length of ventilatory dependency, post-operative bleeding, need for blood transfusions, ICU stay, and hospital stay were similar between the two groups (P = NS). Patients in group I showed a strict correlation between the duration of surgical ischemia and post-operative myocardial necrosis. Analysis of combined mortality and morbidity events (adverse events) between the two groups, led to a significant prevalence in group I patients (P < 0.03) in spite of an higher pre-operative risk score and longer ischemic times in group II patients. Neurological lesions remained confined to group I patients. CONCLUSIONS: The combined use of blood cardioplegia, delivered via the antegrade and retrograde routes, and the single-clamp technique to perform myocardial revascularization, might enhance myocardial and cerebral protection when compared to conventional methods. Larger groups of patients are needed to support this trend.

Adult↗

Clinical features of patients with Graves' disease undergoing remission after antithyroid drug treatment.

The clinical course of 306 Graves' patients treated with methimazole (MMI) was reviewed with the aim of establishing criteria able to predict remission of hyperthyroidism after medical treatment. One hundred and ninety-four (149 females, 45 males) of 306 (63.4%) patients had relapse of hyperthyroidism after antithyroid drug (ATD) withdrawal. Relapse was more frequent during the first months of the follow-up, but still it was observed 3 years after MMI withdrawal. The relapse rate was dependent on the age of the patient, the size of goiter, and the level of TSH-receptor antibody (TRAb) at diagnosis, being observed in 40 of 47 (85%) patients with high (> 30 U/L) TRAb level and in 54 of 101 (53%) patients with low TRAb level (< or = 30 U/L; p <.0002). Remission was more frequent (43.3%) in patients having the combination goiter size < or = 40 mL, TRAb level < or = 30 U/L, than in patients with goiter size > 40 mL and high TRAb levels (9%). In the subgroup of patients with the combination: goiter < or = 40 mL- TRAb < or = 30 U/L - age at onset > 40 years, the remission rate was 80%, and all relapses occurred within the first 9 months after MMI withdrawal. In conclusion, our study confirms that hyperthyroidism relapses in the majority of patients with Graves' disease treated with ATD. Among different clinical and laboratory features, age at onset of hyperthyroidism, goiter size and TRAb level are particularly helpful in identifying those patients who are more prone to undergo a remission of hyperthyroidism after medical treatment and may be useful to select the minority of Graves' patients who will benefit from antithyroid drug treatment as a first choice.

Adult↗

[Replacement of the aortic valve with a pulmonary autograft: experience at the University of Verona].

BACKGROUND: Early and long term results after surgical replacement of the aortic valve depend to a large degree on the type of valve substitute used. Pulmonary autograft offers many theoretical advantages, particularly in young patients. METHODS: Between July 1994 and August 1996, 15 patients (12 male) with a mean age of 28 +/- 6 years (range 14 to 36 years) were selected for aortic valve replacement with a pulmonary autograft. The aortic valve disease was isolated insufficiency in 7 cases (47%), stenosis in 3 (20%) and mixed lesion in 5 (33%). One patient in the last group had bacterial endocarditis (Streptococcus mitis). Seven patients (47%) had a bicuspid aortic valve. In 3 cases (20%) the autograft was inserted as a scalloped subcoronary implant. Twelve patients (80%) had total aortic root replacement with re-implantation of the coronary ostia. The right ventricular outflow tract was reconstructed with a cryopreserved homograft (13 pulmonary; 2 aortic). The aortic cross-clamp time was 156 +/- 18 minutes with a total bypass time of 221 +/- 26 minutes. RESULTS: All patients survived the operation. Three postoperative bleeding (20%) necessitated re-exploration. Mean post-operative hospital stay was 10 +/- 2 days. All patients were discharged on aspirin for the period of three months. One patient (7%) with moderate neo-aortic valve insufficiency died suddenly 11 months post-operatively. All survivors are asymptomatic, in NYHA FC 1 at a mean follow-up time of 15.7 months. Freedom from reoperation, valve related complication and endocarditis is 100%. Two-dimensional (2-D) echocardiography six months postoperatively showed a mean left ventricular outflow gradient of 13 +/- 4 mmHg with no evidence of aortic regurgitation in 11 cases (78.5%) and trivial in 3 (21.5%). CONCLUSIONS: Although the Ross operation is technically more challenging and requires a longer operating time than standard procedures, this does not seem to affect early mortality and morbidity. Clinical and haemodynamic results appear to be gratifying. Continued patients evaluation particularly with regard to evidence of valve degeneration and arrhythmias in the long term is warranted.

Adolescent↗

Current techniques to reduce blood loss after the Ross procedure.

BACKGROUND AND AIMS OF THE STUDY: Although pulmonary autograft (PA) offers many theoretical advantages, the operation is more complex and the need for extensive reconstruction carries an increased risk for postoperative bleeding. The study aim was to evaluate the impact of different pharmacological and surgical strategies on total blood loss and blood product requirements after PA use. METHODS: Between July 1994 and March 1997, 26 patients (22 males) with a mean age of 26 +/- 8 years (range: 11 to 36 years) underwent aortic valve replacement with PA (22 root; four subcoronary implant). A relatively high incidence of re-exploration for bleeding (n = 3) and significant total blood loss during our early experience (Group I, n = 8), prompted the subsequent introduction of different strategies (Group II, n = 18). These included perioperative use of aprotinin, reinforcement of suture lines of the neo-aortic root with autologous pericardium and accurate hemostasis of the raw surface on the back of the right ventricular outflow tract (RVOT) during a brief period of circulatory arrest, also with application of fibrin glue, RESULTS: There were no hospital deaths. No patients in group II required re-exploration or transfusion, and mean total postoperative blood loss was reduced (group I, 720 +/- 465 ml/m2 body surface area (BSA), versus group II, 323 +/- 84 ml/m2 BSA). By-pass and aortic cross-clamp times were not significantly longer in group II patients. At a mean follow up of 15 months, all 25 survivors are asymptomatic, in NYHA functional class I, and with normal social interactions. CONCLUSIONS: Early survival after aortic valve replacement with the PA appears comparable with the use of more conventional valve substitutes. Blood loss containment by routine application of medical and surgical strategies appears feasible. In view of the common concern about blood transfusion, particularly in young patients, these findings may help to widen the range of indications for the Ross procedure.

Adolescent↗

Coronary translocation during aortic root replacement with the pulmonary autograft: complications and their management.

BACKGROUND AND AIMS OF THE STUDY: Aortic root replacement with the pulmonary autograft has become an alternative to replacement of the diseased aortic valve with mechanical or biological prostheses. Due to greater technical complexity of the operation, complications with autograft root replacement (ARR) may be more common. In particular, a higher prevalence of coronary complications has been suggested. METHODS: In order to assess the prevalence, cause and management of coronary complications after ARR, results with 26 consecutive operations were reviewed and compared with previously published series. Between July 1994 and Apri 1997, 22 males and four females (mean age 26 +/- 8 years; range: 11 to 36 years) underwent aortic root (n = 22) or valve replacement (n = 4) with a pulmonary autograft for regurgitation (n = 14), stenosis (n = 4) or both (n = 8). Associated lesions were present in 10 (38%) patients, including three cases of major coronary artery anomalies such as origin of the circumflex from the right coronary sinus, high origin of the right coronary, aneurysmal and calcified right and left main coronaries, both in one patient. RESULTS: There were no early deaths. Major complications occurred in six patients; re-exploration for bleeding was required in three (11%) and partial take down of repair for coronary complications in three (11%), all with preoperative coronary anomalies. Two of the latter patients presented with intraoperative right ventricular ischemia due to kinking of the right coronary (corrected by re-implantation at a higher level), and one had intraoperative hemorrhage due to rupture of a calcified left main coronary, which required transection of the pulmonary homograft above the valve to expose the tear. Recovery was prompt in all patients (mean ICU stay 35 +/- 28 h) with no metabolic or electrocardiographic evidence of ischemia. Echocardiography at discharge showed satisfactory biventricular kinetics in all; mild regurgitation of the autograft was found in two (8%) who had undergone subcoronary implant, and absent or trivial in 22 (92%). One patient died suddenly 13 months after ARR; hence actuarial survival rate was 100% and 96% at 12 and 24 months, respectively. At mean follow up of 15 +/- 11 months (range 1 to 32 months), all patients are in NYHA class I and have returned to school or prior employment. CONCLUSIONS: Complications with coronary artery translocation during ARR may be a definite risk, particularly in the presence of coronary anomalies. Prompt recognition and an aggressive intraoperative approach, including partial take down of the repair, may limit the morbidity of this complex surgical procedure.

Adolescent↗

Influences of thyroid diseases in diabetic pregnant women.

Thyroid disorders are particularly frequent in women and, second to diabetes mellitus, are the most common endocrine diseases during pregnancy. An association between insulin-dependent diabetes mellitus and thyroid autoimmunity has long been recognized. Management of thyroid diseases in pregnancy is different than in non pregnant women, due to physiological changes of thyroid hormone economy in the childbearing period. Thyroid dysfunction may affect carbohydrate metabolism and worsen glucose control in diabetic patients. On the other hand, poorly compensated diabetes mellitus may cause alteration in the production and metabolism of thyroid hormones. Pregnant women with insulin-dependent diabetes mellitus have an increased risk of developing post partum thyroiditis. These observations have lead to the recommendation that thyroid function should be checked in diabetic women during pregnancy and in the post partum.

Adult↗

1H and 13C NMR spectral assignments of the major sequences of twelve systematically modified heparin derivatives.

The complete 1H and 13C NMR spectral assignments are described for the most prevalent patterns of sulfation and acetylation which can be found in polymeric heparin or can be obtained by standard chemical modifications. These include a number of novel structures containing unsubstituted or acetylated amino groups and the first complete NMR assignments of many of the other derivatives. Beef lung heparin was chosen as a model system and studies were carried out using conditions to control the influences on the chemical shift positions in heparin samples of divalent cations and variations in pH and temperature.

Acetylation↗

Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor.

The ability of a system to regulate its responsiveness in the presence of a continuous stimulus, often termed desensitization, has been extensively characterized for the beta2-adrenergic receptor (beta2AR). beta2AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein beta-arrestin. Ultimately the receptor undergoes internalization, and although the molecular mechanism is unclear, receptor phosphorylation and beta-arrestin binding have been implicated in this processs. Here we report that beta-arrestin and arrestin-3, but not visual arrestin, promote beta2AR internalization and bind with high affinity directly and stoichiometrically to clathrin, the major structural protein of coated pits. Moreover, beta-arrestin/arrestin chimaeras that are defective in either beta2AR or clathrin binding show a reduced ability to promote beta2AR endocytosis. Immunofluorescence microscopy of intact cells indicates an agonist-dependent colocalization of the beta2AR and beta-arrestin with clathrin. These results show that beta-arrestin functions as an adaptor in the receptor-mediated endocytosis pathway, and suggest a general mechanism for regulating the trafficking of G-protein-coupled receptors.

Animals↗

Activation of the mitogen-activated protein kinase cascade is suppressed by low concentrations of dexamethasone in mast cells.

Antigen stimulation of mast cells via the IgE receptor, Fc epsilon RI, results in recruitment of the cytosolic tyrosine kinases, Lyn and Syk, and the phosphorylation of proteins. We examined the effects of the glucocorticoid dexamethasone on these events in a cultured (RBL-2H3) mast cell line. Nanomolar concentrations of dexamethasone suppressed phosphorylation of proteins that were associated with the activation of the mitogen-activated protein (MAP) kinase/phospholipase A2 pathway without inhibiting initial events. For example, tyrosine phosphorylation of the subunits of Fc epsilon RI, Lyn, or Syk or of the Ras-guanine nucleotide exchange factor, Vav, was not suppressed in cells treated with up to 1 microM dexamethasone. In contrast, phosphorylation of Raf1, MEK1, p42mapk, and cytosolic phospholipase A2, as well as the associated increase in MAP kinase activity and release of arachidonic acid, were markedly inhibited in cells treated with as little as 10 nM dexamethasone--a concentration that only partially inhibited hydrolysis of inositol phospholipids or release of secretory granules. Prolonged exposure to dexamethasone also resulted in a partial decrease in expression of MEK1, p42mapk, and cytosolic phospholipase A2, which may contribute further to the effects of dexamethasone on this pathway. Activation of the MAP kinase/phospholipase A2 pathway by the calcium-mobilizing agent thapsigargin was similarly suppressed in dexamethasone-treated cells. These findings suggested that an early step in the pathway, possibly a step immediately before the activation of Raf1, was suppressed by low concentrations of dexamethasone.

Animals↗

Transfection with the cDNA of the human thyrotropin receptor of a poorly differentiated rat thyroid cell line (FRT).

A cell line derived from the Fisher rat thyroid (FRT), that does not have functional TSH receptor, was stably transfected with the cDNA of the human TSH receptor (h TSH-R). In wild FRT cells TSH (1-1000 mU/l) was unable to increase cAMP production, while 10-10000 nmol/l forskolin elicited a 10-30 fold cAMP stimulation. Two of the transfected clones were responsive to TSH in terms of cAMP production. In particular, the FRT-R3 transfected clone showed the highest sensitivity to the hormone with a 10 fold cAMP increase over the basal at 100 mU/l TSH. The Northern blot analysis using a 2.4 kbp cDNA probe for the hTSH-R showed a band corresponding to the mRNA of TSH receptor in FRT-R3 cells, but not in wild FRT cells. In both cell types TSH was ineffective in stimulating growth assayed by 3H-thymidine incorporation into DNA. Hybridization with a probe for thyroperoxidase on polymerase chain reaction products after reverse transcription of mRNA showed that FRT-R3, as well as FRT cells, do not have a transcript for thyroperoxidase. In conclusion, the data reported in this paper show that the insertion of the hTSH-R cDNA in the genome of poorly differentiated rat thyroid cells results in the recovery of TSH-dependent adenylate cyclase, but not other differentiated thyroid cell functions.

Adenylyl Cyclases↗