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Biomedical subjects

F Nicolini

Publications and source records attributed to F Nicolini.

36 records · Page 2Linked to original sources

[Experimental results of the use of hyaluronic acid based materials (CV Seprafilm and CV Sepracoat) in postoperative pericardial adhesions].

Repeat cardiac surgical procedures are associated with increased technical difficulty and risk related to the presence of dense adhesions between the heart and the surrounding tissues. We examined the efficacy of a bioabsorbable membrane containing hyaluronic acid in the prevention of pericardial adhesions in 23 rabbits. After thoracotomy and pericardiotomy the animals were divided in three groups: Group 1 (9 animals) in which the epicardial surfaces were covered by Seprafilm membrane, Group 2 (9 animals) treated with both Seprafilm membrane and Sepracoat solution, and Group 3 (5 animals) as controls. The animals were reexplored at 10, 30 and 60 days: no intrapericardial adhesions were found in all the animals of Group 2. In 4 animals (44%) of Group 1 localized post-operative adhesions were detected, in absence of epicardial hyperplasia; in contrast, dense and diffuse adhesions were present in all the control animals. The use of the bioabsorbable membrane Seprafilm significantly reduces adhesion formation even if better results are possible with the previous intrapericardial administration of Sepracoat solution. Application of these biocompatible products could reduce the technical difficulty and risk of repeat surgical procedures.

Animals↗

Coronary artery spasm after coronary artery bypass grafting.

We report a case of a 62-year-old man with severe manifestations of postoperative coronary artery spasm following effective coronary artery bypass grafting. The coronary artery spasm was manifested by ST segment elevation, hypotension and wall motion abnormalities on echocardiography. Urgent angiography confirmed the diagnosis and intracoronary infusion of nitroglycerine and verapamil relieved the coronary spasm.

Cardiac Catheterization↗

Left ventricular hemangioma.

Cardiac hemangiomas are rare, primary benign cardiac tumors. The authors report their experience of diagnosis and treatment of an hemangioma localized into the left ventricle. The tumor could be successfully resected and there is no recurrence at 1 year follow-up.

Aged↗

Impact of cyclosporine and methylprednisolone dose used for prophylaxis and therapy of graft-versus-host disease on survival and relapse after allogeneic bone marrow transplantation.

In order to determine whether doses of cyclosporine and methylprednisolone used for prophylaxis and therapy of acute graft-versus-host disease (GVHD) have any influence on relapse and survival following allogeneic bone marrow transplantation (BMT), we studied 176 adult patients with hematologic malignancies, who underwent a first allogeneic transplant from an HLA-identical sibling donor. Two methods of management of acute GVHD used in two different centers were compared: group I included 62 patients who had 'standard' management of GVHD including prophylaxis with 1-3 mg/kg/day of cyclosporine and treatment with 2 mg/kg/day of methylprednisolone when acute GVHD developed; group II included 114 patients who received 'intensive' management of GVHD including prophylaxis with 5 mg/kg/day of cyclosporine and treatment with high-dose methylprednisolone (8-20 mg/kg/day for 3 days) at the onset of GVHD. The overall incidence of GVHD was the same in both groups. However, acute GVHD was more severe in group I than in group II (P < 0.0001), with consequently less resolution of GVHD after treatment in group I (61%) than in group II (80%) (P = 0.06). Overall survival and disease-free survival (DFS) did not differ between the two groups. However, actuarial risk of disease relapse was significantly higher in group II than in group I (36% vs 17%, P = 0.02). In a multivariate analysis taking into account known factors influencing GVHD and relapse, only type of GVHD management and age were significantly predictive for the occurrence of GVHD, while only type of GVHD management and pathology other than chronic myeloid leukemia (CML) were predictive for relapse. This study demonstrates that intensity of GVHD prophylaxis and therapy can influence the graft-versus-leukemia effect by decreasing severity of GVHD but at the price of increasing relapse rate post transplant.

Acute Disease↗

Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial).

The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12 mg/m2 day on days 1-3, etoposide, 200 mg/m2/day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m2/day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML. The goal of the EMA91 study was to determine whether administration of GM-CSF between the two sequences of EMA chemotherapy and during the second sequence could increase therapeutic efficacy by potentially increasing leukemic cell recruitment into the S phase of cell cycle before the second sequence. One hundred and ninety-two patients aged less than 65 years with previously treated AML received GM-CSF, 5 microg/kg/day or placebo from day 4 to day 8 of EMA chemotherapy. One hundred and twenty were refractory and 72 were in first relapse after a complete remission (CR) of more than 6 months duration. CR rates after one course of chemotherapy were 65% in the GM-CSF group (refractory: 51%; first relapse: 89%), not significantly different from the 59% CR rate (refractory: 46%; first relapse: 81%) in the placebo group. Median time to recovery of neutrophils was 38 and 37 days and median time to last platelet transfusion 32 and 32 days respectively in the GM-CSF and placebo groups. WHO grade > or = 3 non-hematologic toxicities were mainly sepsis (45% and 51%, respectively) and mucositis (34% and 31%) and did not differ between the two groups. Toxic death rate was 5% and 8%, respectively, in the GM-CSF and placebo groups. Patients achieving CR were scheduled to receive six courses of maintenance with reduced-dose EMA. Time to progression tended to be longer in the GM-CSF group (median 154 vs 115 days, progression-free rate at 18 months 33% vs 19%, P = 0.08), particularly in refractory patients (P = 0.06). However, at the current follow-up, this did not translate into a significantly longer disease-free survival and survival. Cell cycle studies showed increased recruitment of cells in the S phase between day 4 and day 8 in the GM-CSF group compared to placebo (P = 0.006). However, this did not significantly relate to prognosis in this cohort of patients. GM-CSF might marginally increase efficacy of sequential chemotherapy without increasing its toxicity in the absence of any detected relationship between this effect and observed leukemic cell recruitment into the cell cycle.

Acute Disease↗

[Myocardial revascularization in patients with severely depressed left ventricular function].

BACKGROUND: Improvements in anesthetic and surgical management of patients with left ventricular dysfunction have resulted in a decline in perioperative mortality and morbidity. Nevertheless, coronary artery bypass grafting (CABG) in patients with left ventricular ejection fraction < or = 0.30 remains a surgical challenge. METHODS: Fifty-one patients with end-stage coronary artery disease and left ventricular ejection fraction between 16 and 30% underwent CABG. Mean age at operation was 66.1 +/- 7.85 years. Selection criteria included the clinical diagnosis of ischemic heart disease with angiographic demonstration of critical coronary artery obstructive lesions. Mean number of grafts per patient was 2.94 (range 1-5). Average duration of cardiopulmonary bypass was 74.5 +/- 22.4 min and mean aortic cross clamp time was 47.6 +/- 17 min. RESULTS: No operative and in-hospital deaths occurred. Eight patients (15.7%) had postoperative low cardiac output syndrome, requiring intraaortic balloon counterpulsation. There were two major neurological complications (3.9%). There were four late deaths (7.8%), due to recurrence of untreatable congestive heart failure. Left ventricular ejection fraction increased from a mean of 25.51 +/- 4.75% preoperatively to 31.35 +/- 9.9% postoperatively (p < 0.001). Improvement in NYHA functional class (preoperatively 2.98 +/- 0.79 vs 2.35 +/- 0.6 postoperatively, p < 0.001) was found in this group at follow-up. CONCLUSIONS: CABG leads to an excellent prognosis in high risk patients with ischemic heart disease and low left ventricular ejection fraction, improving their functional and clinical outcome and consequently their life expectancy.

Aged↗

Spontaneous dissection of coronary artery in a patient with ascending aortic aneurysm and aortic valve regurgitation.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction associated with a significant high morbidity and mortality. It usually occurs in relatively young patients and it is frequently found at autopsy. We report a case of a 42-year-old woman, who underwent resection of subaortic diaphragm ten years earlier presenting with postero-lateral myocardial infarction. Coronary arteriography revealed a dissection of the left main stem extending distally to the left anterior descending artery (LAD) and circumflex artery (Cx); occlusion of the postero-lateral branch of the Cx; severe aortic valve regurgitation and ascending aortic aneurysm. She was successfully operated on in emergency and underwent myocardial revascularization and separate replacement of the aortic valve and the ascending aorta. In this specific case of coronary dissection and severe aortic regurgitation it is mandatory to perform surgery in emergency to limit infarction evolution and avert loss of life.

Adult↗

"Hybrid" and combined percutaneous and surgical intervention to treat selected cardiac patients: a new strategy.

The term "hybrid revascularization" describes the combined use of minimally-invasive surgery without cardiopulmonary bypass and percutaneous coronary revascularization in selected cases. The theoretical advantage of a less invasive surgical intervention must be weighted against the need for additional percutaneous procedures, with their own risks and limitations. We describe our initial experience with hybrid revascularization at the Istituto Clinico Humanitas in Milan. From 7/97 to 10/98, twelve patients underwent hybrid revascularization or a combined percutaneous and surgical intervention. A "classic" hybrid approach, consisting of minimally-invasive direct coronary artery bypass to the left anterior descending coronary artery and angioplasty or stenting of arteries in the right coronary artery or circumflex territories, was used in nine patients. In three patients, myocardial revascularization could be completed with percutaneous procedures after bypass surgery without cardiopulmonary bypass (in two patients because of severe aortic calcification) or valve surgery in a patient with two previous bypass operations. In-hospital complications were observed in three patients. Two required urgent median sternotomy (one for impending cardiac tamponade, one for conversion to bypass on extra-corporeal circulation). One patient developed atheroembolism after percutaneous intervention: after hospital discharge, there was a recurrence of symptoms, clinical deterioration with renal failure and eventually death. At a mean follow-up of 152 +/- 91 days (range 17 to 283) after minimally-invasive surgery and 166 +/- 122 days (range 13 to 397) after angioplasty, all surviving patients are well and free of anginal symptoms. Closer collaboration between surgical and interventional operators may offer a novel approach to effective treatment of difficult patient subsets. However, our initial experience suggests that a cautious evaluation of possible risks and benefits must carefully be entertained in each patient who may be considered a candidate for hybrid revascularization or combined percutaneous and surgical intervention.

Aged↗

Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group.

BACKGROUND: Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine. METHODS: Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months. RESULTS: The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P<0.001). CONCLUSIONS: The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.

Adolescent↗

[Myocardial localization of malignant non-Hodgkin lymphoma responsive to chemotherapy].

Cardiac malignant non-hodgkinian lymphoma, which is usually asymptomatic, is observed in 15 to 25% of autopsy cases of this condition. The authors report an unusual case of myocardial lymphoma diagnosed during pulmonary oedema. Echocardiography showed left ventricular hypertrophy with increased echogenicity of the myocardial walls and marked decrease in left ventricular ejection fraction. Myocardial biopsy confirmed the diagnosis of a high grade malignant lymphoma. The disease responded to chemotherapy. Early diagnosis of myocardial involvement of a lymphoma, presenting with non-specific electrocardiographic changes, requires investigation by histological study of a myocardial biopsy. This invasive technique is justified because of its therapeutic implications.

Adult↗

[Heart surgery with cardiopulmonary bypass in patients on chronic dialysis treatment: our experience].

METHODS: To determine the mortality and the morbidity of cardiac surgery in patients on chronic hemodialysis, we retrospectively reviewed eighteen adult patients (13 males and 5 females) with a mean age of 54.7 years (range: 30-67 years) who underwent cardiopulmonary bypass procedures between 1987 and 1995. The operations included: isolated coronary artery bypass grafting in 12 patients, coronary artery bypass grafting plus mitral ring annuloplasty in 1 patient, mitro aortic valve replacement in 2 patients, isolated aortic valve replacement in 1 patient, aortic valved conduit implantation in 1 patients and mitral valve replacement plus tricuspid annuloplasty in 1 patient. There were 10 and 3 patients in CCS functional classification III and IV respectively; 1 and 4 patients were in NYHA classification II and III respectively. All of them were hemodialyzed the day before surgery: the average time they had been on hemodialysis was 6.5 years. Anesthesia and the cardiopulmonary bypass (CPB) in these patients required attention in order to provide the optimal fluids and electrolytes balance: particularly intravenously administered fluids were kept to a minimum and drug dosages were reduced to recommended levels for anephric patients. An hemoconcentrator was used in all patients during the CPB and, in the last 4 cases, we used a dialysis filter and a sterilized perfusional solution to reduce the level of potassium and to put off postoperative dialysis. RESULTS: In three patients there were major bleeding problems resulting in reoperation; 5 perioperative deaths occurred: two of them due to myocardial infarction and three due to irreversible low cardiac output state. In our experience there were four late deaths: one patient died four months after surgery for chronic heart failure, another one died twelve months after surgery for dilated cardiomyopathy and two patients died respectively seventeen and seventy two months after discharge for myocardial infarction. Two of the remaining patients reported recurrence of angina while the others achieved symptomatic improvement. CONCLUSIONS: In conclusion, cardiac surgery is performed on chronic renal dialysis patients with high mortality and morbidity and it's indicated only if medical treatment is ineffective. The successful surgical results, obtained with an adequate management between surgeons, anesthesiologists and nephrologists, don't assure the long-term survival of the patients.

Adult↗

Verapamil and aspirin modulate platelet-mediated vasomotion in arterial segments with intact or disrupted endothelium.

OBJECTIVES: This study was designed to examine the effects of verapamil and aspirin, which decrease thromboxane A2 and serotonin release, on the modulation of vascular tone by platelets. BACKGROUND: Aggregating platelets cause constriction of de-endothelialized arterial segments through thromboxane A2 and serotonin release. These cells cause relaxation of arterial segments with intact endothelium through release of the endothelium-derived relaxing factor. METHODS: Healthy subjects were given either no drug, verapamil or aspirin for > or = 5 days before their platelets were obtained. The effects of platelets obtained from subjects before and after treatment with aspirin or verapamil on the tone of rat aortic rings were determined. RESULTS: As expected, control platelets (before verapamil or aspirin treatment) induced concentration-dependent relaxation of rat aortic rings with intact endothelium and a concentration-dependent contraction of de-endothelialized rings. Verapamil treatment enhanced (p < 0.02) the platelet-mediated relaxation in rings with intact endothelium and abolished platelet-mediated constriction (p < 0.01) in the de-endothelialized rings. Aspirin treatment also abolished (p < 0.05) platelet-mediated constriction of the de-endothelialized rings. The de-endothelialized rings contracted normally in response to the synthetic thromboxane A2 analogue U46,619, as well as to serotonin, indicating that the vascular smooth muscle response to thromboxane A2 and serotonin was intact. CONCLUSIONS: This study provides evidence for the modulation of platelet-mediated vasoconstriction of de-endothelialized arterial segments by prior treatment of subjects with verapamil or aspirin. In clinical syndromes characterized by endothelial dysfunction or disruption, treatment with verapamil or aspirin may modify platelet-vessel wall interactions.

Animals↗

[Evaluation of three types of empirical antibiotherapy in patients with febrile neutropenia: imipenem-cilastatin versus ceftazidime-vancomycin versus ticarcillin-amikacin-vancomycin].

A three-arm prospective randomized trial was designed to compare the effectiveness of single drug therapy with imipenemcilastatin (IC), two-drug therapy with ceftazidime-vancomycin (CV), and three-drug therapy with ticarcillin-vancomycin-amikacin (TVA) for the empirical antimicrobial treatment of febrile neutropenia events. The objectives of the study were to determine whether IC monotherapy was as effective as combination drug therapy (CV or TVA) and to assess the value of adding vancomycin at initiation of treatment. One hundred eighty-three febrile neutropenia events were randomized and 125 were evaluable. Success rates were 73% with IC, 67% with CV, and 72% with TVA. There were no statistically significant differences between the three treatment groups, regardless of the duration and severity of neutropenia. Fifty-four bacterial isolates were recovered from 43 patients. Among recovered bacterial strains, 55% were Gram-negative and 45% were Gram-positive. Rates of bacteriologically documented failures (14/33) and superinfections (3/33) were similar in the three groups. Adverse events were rare but two patients given CV and three given TVA developed severe skin toxicity requiring modification of the antimicrobial regimen. IC alone showed similar effectiveness and less toxicity, as compared with CV or TVA. Vancomycin given initially increased toxicity but failed to improve the success rate. Vancomycin may be appropriate only in patients at high risk for infection with methicillin-resistant staphylococci.

Adolescent↗

Effect of L-arginine and an arginine-containing pentapeptide on canine femoral arterial blood flow.

The amino acid L-arginine is a precursor of endothelium derived relaxing factor (EDRF). The pentapeptide 6A (Ala-Arg-Pro-Ala-Lys) released by plasmin degradation of fibrinogen also contains arginine and relaxes vascular smooth muscle by releasing EDRF (nitric oxide). To determine and compare the effects of L-arginine, peptide 6A and a combination of L-arginine and peptide 6A on femoral artery blood flow and vascular resistance, anesthetized mongrel dog were administered saline, L-arginine, D-arginine, peptide 6A and L-arginine + peptide 6A in a random order. L-arginine and peptide 6A both induced an immediate dose-dependent short-lasting increase in femoral blood flow and a decrease in vascular resistance. Peptide 6A exerted a much greater (P less than 0.01) vasodilatory effect than did L-arginine at the same molar concentration suggesting that properties besides the arginine content are important in the effect of the pentapeptide. D-arginine had much less effect than L-arginine, indicating that the effect of L-arginine may be related to its utilization for synthesis of EDRF. When the peptide 6A was given soon after L-arginine, its effect on blood flow was not greater than that of L-arginine alone suggesting that L-arginine in a large amount makes guanylate cyclase less available for the more active peptide.

Amino Acid Sequence↗

[Alloreactive donor lymphocytes (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT): study of toxicity and efficacy].

Adoptive immunotherapy represents a new therapeutic tool able to eradicate or to improve the course of various hematological malignancies and solid tumors. Alloreactive lymphocytes present within the hematopoietic transplant have been shown to be responsible for the occurrence of acute and chronic graft-versus-host-disease (GVHD). Retrospective analysis of survival curves after allogeneic bone marrow transplantation performed for leukemia have shown that GVHD was accompanied with lower relapse rates suggesting graft-versus leukemia (GVL) affect. T cell-depletion demonstrated the inverse balance existing between GVHD/GVL and relapse. Allogeneic bulk lymphocyte infusions were further used for successful treatment of relapse after transplantation in CML patients. However they were responsible for some cases of lethal acute GVHD and myelosuppressions in some patients. The concept of allogeneic transplantations after reduced intensity conditioning regimen (RICT) has recently emerged as a new strategy to treat cancer. This strategy exploited the immunological properties of the graft followed or not by donor lymphocyte infusions (DLI) while reducing the toxicity of the preparative regimen. Different means to perform RICT have been described, however the systematic use of DLI (bulk or escalating doses) after these transplantations remains controversial. Hereby, we report a summary of historical data that lead to the concept of adoptive immunotherapy and its applications.

Dose-Response Relationship, Immunologic↗