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Biomedical subjects

E Orsini

Publications and source records attributed to E Orsini.

At least 37 records · Page 2Linked to original sources

Probability of long-term disease-free survival for acute myeloid leukemia patients after first relapse: A single-centre experience.

BACKGROUND: Various polichemotherapy regimens, including either high- or intermediate-dose Ara-C, are generally utilized to reinduce remission in relapsed AML patients. After achieving second CR, bone marrow transplantation (either allogeneic or autologous) represents the treatment of choice for eligible patients, with the aim of prolonging remission duration and improving disease-free survival. PATIENTS AND METHODS: Fifty AML patients in first hematological relapse were treated with MEC regimen, consisting of a 6-day induction cycle [mitoxantrone 6 mg/m2/day, cytarabine (Ara-C) 1 g/m2/day and VP-16 80 mg/m2/day] followed by a 4-day cycle with the same drugs for patients achieving complete remission (CR); allogeneic or autologous bone marrow transplantation (BMT) were planned as post-consolidation treatment. RESULTS: Thirty-four patients (68%) achieved second CR, 3 (6%) died during induction and 13 were refractory. CR rate was significantly higher in patients with a first CR lasting > 6 months (82% vs. 41%, P < 0.001). Out of the 34 patients in CR after the 4-day cycle, 18 (53%) were not eligible to transplant and did not receive any further therapy and 16 (47%) received autologous (15 cases) or allogeneic (1 case) BMT at a median time of 2 months from second CR. Twenty-two patients relapsed after a median time of 6 months (range 1-31), 1 patient died from transplant-related toxicity and 11 are in continuous CR [7 out of 16 (44%) in the transplanted and 4 out of 11 (36%) in the non-transplanted group]. Overall survival and event-free survival for the 50 patients were 29% and 19% at 70 months, respectively. The disease-free survival for the 34 patients who obtained second CR is 29% projected at 69 months [41% at 69 months for 16 transplanted patients versus 18% at 49 months for the remaining 18 patients (P = 0.007)]. CONCLUSIONS: These results show that MEC followed by high-dose post-consolidation treatment is a promising approach in relapsed AML; however, alternative strategies are to be investigated for the relevant fraction of patients that, even achieving second CR, are not eligible for BMT.

Adolescent↗

Autologous bone marrow transplantation in 44 patients with aggressive non-Hodgkin's lymphoma at University "La Sapienza" of Rome.

High dose therapy followed by infusion of autologous bone marrow has become a major treatment option for an increasing number of poor prognosis non-Hodgkin's lymphoma (NHL) patients. In our study we analyzed the outcome of autologous bone marrow transplantation (ABMT) in 44 high grade NHL patients transplanted at our institution between 1985 and 1992. Median age was 31 years (range 12-61); nineteen were in partial remission (PR) after first line chemotherapy and 25 in sensitive relapse (SR). Of the 25 patients transplanted in SR, 14 relapsed after a median time of 5.5 months (range 1-26), 8 are in complete remission after a median follow up of 41.5 months and three died from toxicity. Of the 19 patients grafted in PR, 11 are alive and progression free after a median follow up of 52 months, while 8 relapsed at a median time of 5 months. The overall progression free survival (PFS) projected at 6 years is 35% with a 47% PFS for patients transplanted in PR and 28% for patients in SR. In conclusion, high dose therapy and ABMT has achieved widespread use as salvage therapy for patients with relapsed/refractory high grade NHL. In particular, our experience confirms that myeloablative treatment is a safe and well tolerated procedure for patients in PR, that may be easily applied as early salvage therapy without major toxicities.

Adolescent↗

Adenosine-induced renal vasoconstriction in man.

OBJECTIVE: The aim of the study was to evaluate the effects of adenosine on renal blood flow in humans. METHODS: Eleven normotensive patients (mean age 53 +/- 11 years) with normal renal angiograms were enrolled in the study. Arterial blood pressure, one ECG lead and arterial renal blood flow velocity, by intravascular Doppler catheter, were monitored throughout the procedure. Incremental doses (10(-5), 10(-4), 10(-3), 2 x 10(-3), 5 x 10(-3), 10(-2), 10(-1), 1 mg) were selectively injected, at 5-min intervals, in a renal artery. RESULTS: Adenosine administration had no significant effects on blood pressure, heart rate and atrio-ventricular conduction. A progressive reduction in renal blood flow velocity (from 16.36 +/- 1.9 to 3.9 +/- 0.8 cm/s, P < 0.0001) was observed. Following adenosine the decrease of flow velocity was immediate and its duration was proportional to dosage (from 0.5 +/- 0.4 s at 10(-5) mg to 31 +/- 6.5 s at 1 mg). Renal angiography, repeated in four patients during flow velocity decrement, showed no changes in vessel diameter. CONCLUSIONS: Exogenous adenosine-induced a marked and transient reduction in renal blood flow in man. This effect suggests that adenosine or its metabolites may be directly implicated in rapid and powerful mechanisms of cardiac output redistribution. Thus endogenous adenosine could have a role in regulating renal blood flow in physiological and pathological situations like strenuous exercise, hemorrhage shock and cardiac failure.

Adenosine↗

CD3-induced T-cell activation in the bone marrow of myeloma patients: major role of CD4+ cells.

A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T-cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.

Bone Marrow↗

[Infections in intensive care units].

Hospital acquired infections are one of the most serious problems of public health. The problem of hospital infections assumes greatest relevance especially for patients in intensive care units (ICU). In these patients both the incidence (about 40%) and the mortality rate (non infected patients 13%; infected patients 47%) of infections is particularly high. Low respiratory tract represents the most frequent localization of ICU infections (30-50%). The causal pathogens are represented in more than 50% of cases by Gram-negative bacilli provided with low virulence and normally present in patients and in the hospital environment. The pathogenesis of infections in ICU is multiform, deriving from the interplay of many factors: the impairment of organic defenses; the age of the patients, often at the upper or lower limits; the multi-pathology and severity of underlying disease; the side effects of medical therapy (immunodepression); the closeness of many patients in narrow wards, that allows the diffusion of infections; the presence in the hospital environment of many pathogens with poly-antibiotic resistance. The control and prophylaxis programs should include: interventions on ICU structure in order to optimize the building projects and maintain high standard quality; training programs for medical and nursing personnel; interventions on patient-related factors; surveillance protocols (events documentation and monitoring of intervention results).

Cross Infection↗

An unusual pattern of growth disturbance of the hip in juvenile rheumatoid arthritis.

OBJECTIVE: An unusual deformity in the hip in juvenile rheumatoid arthritis (JRA) consisting of a small femoral head in a capacious acetabulum has been described as an isolated finding, but no explanation as to the cause of the deformity has been proposed. We have also observed this deformity and the objective of this investigation was to determine the cause. METHODS: In 1987, a review of hip disease in JRA was carried out at the Wellesley Hospital. Nine hips in 5 patients were identified as having a mismatch in size between the femoral head and acetabulum. Six of these hips came to surgery during the growth phase. RESULTS: The 6 hips undergoing surgery between the ages of 16-19 showed an identical picture at the time of surgery. The pattern of pathology consisted of a femoral head devoid of articular cartilage and an acetabulum that showed an intact triradiate cartilage. Each of the 6 hips was treated with a resurfacing arthroplasty. CONCLUSION: The femoral head grows in circumference by endochondral ossification of the articular cartilage. If the rheumatoid process destroys that articular cartilage, growth of the femoral head ceases. The intact triradiate cartilage permits continuing acetabular growth and the deformity of a small femoral head in a large capacious acetabulum results.

Adolescent↗

Usefulness of pirenzepine, an M1 antimuscarinic agent, for effort myocardial ischemia.

This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gallopamil and diltiazem: a double-blind, randomized, cross-over trial in effort ischaemia.

The aim of this study was to evaluate the efficacy and possibly the mechanism of action of gallopamil and diltiazem in a double-blind crossover trial in patients with effort ischaemia. Twenty male patients (mean age 57 +/- 6 years) with documented coronary atherosclerosis and exercise-induced ischaemia (ST depression greater than or equal to 0.15 mV) completed the study, which consisted of four 7 day periods. At the end of each period a multistage bicycle exercise stress test was performed under placebo (first and third periods) and randomly under gallopamil (50 mg t.i.d.) or diltiazem (90 mg t.i.d.) in the second and fourth periods. Both drugs significantly increased time to ischaemia (0.15 mV ST depression) as compared to placebo, from 7.9 +/- 1.7 min to 8.9 +/- 1.1 min (diltiazem) and 9.1 +/- 1.6 min (gallopamil) with no significant difference between the two drugs, and reduced the maximal extent of ST shift from 0.18 +/- 0.08 mV to 0.13 +/- 0.04 mV (diltiazem) and 0.12 +/- 0.05 mV (gallopamil). Analysis of the results from the whole population showed that the beneficial effect did not appear to be related to any specific parameter. Individual analysis showed that 13/20 patients under gallopamil and 13/20 under diltiazem increased time to ischaemia, while this was unchanged or reduced in the remainder. A positive correlation between changes in time to ischaemia and changes in rate x pressure product at ischaemia was found in both those administered gallopamil (R 0.80, P less than 0.01) and diltiazem (R 0.65, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Autologous transfusions for orthopaedic procedures at a children's hospital.

We conducted a critical review of the use of autologous transfusions in orthopaedics at a tertiary-care children's hospital. The cases of 198 children who deposited blood before an orthopaedic operation were analyzed. There were 175 children who were enrolled in the program of preoperative deposit of autologous blood who later needed transfusion of blood; 73 per cent of them received only autologous blood. Seventy patients also had intraoperative salvage. We were unable to document a proved benefit of intraoperative salvage of blood in this group of patients. Forty patients had some difficulty donating autologous blood preoperatively, but these problems were rarely serious. Major human errors occurred in thirteen patients and resulted in some patients receiving homologous transfusions while autologous blood components were still available. Fifty-five (40 per cent) of all of the transfusions were administered in clinical circumstances that failed to meet generally accepted criteria for transfusion, and fifty-four (38 per cent) of the postoperative transfusions also failed to meet these criteria. This was true of the homologous transfusions in the study as well. Although an autologous blood transfusion is a generally safe procedure, it is not without risk, and human errors can occur. In light of the potential complications, surgeons should adhere to the standard indications for transfusion when administering autologous blood.

Adolescent↗

Long-term prognosis of transient acute myocardial ischemia at rest.

A medical approach to treatment was adopted in 652 patients with documented myocardial ischemia at rest during both the acute and follow-up phases. No patient underwent coronary revascularization during hospitalization and only 86 patients (13%) underwent coronary bypass surgery within 8 months from discharge. During hospitalization 13 patients died. In the remaining group (639 patients), the likelihood of death in the 10-year period after discharge was 28% for all patients and 20% for cardiac causes only. A series of factors studied during the acute stage were assessed in an effort to predict long-term outcome. The following noninvasive characteristics, listed in decreasing order of statistical significance, were found to be significant univariate predictors of survival: abnormal basal electrocardiogram, duration of coronary artery disease, previous myocardial infarction, pattern of ST-T changes during episodes of ischemia at rest, age and systemic hypertension. The average annual mortality rate for patients with T-wave changes, ST-segment elevation and ST-segment depression was 0.9, 1.8 and 3%, respectively. The Cox survival analysis identified abnormal basal electrocardiogram, duration of coronary artery disease and pattern of ST-T changes as significant, independent predictors of death. When invasive characteristics were entered in the model, number of greater than or equal to 50% narrowed coronary arteries, left ventricular ejection fraction, abnormal basal electrocardiogram and smoking habit were found to be independent and additive prognostic variables. Thus, long-term prognosis of patients with ischemia at rest is related to the severity of anatomic impairment, independent of the pattern of ST-T changes observed during the acute phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

Actuarial Analysis↗

Electrocardiographic manifestations and in-hospital prognosis of transient acute myocardial ischemia at rest.

From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.

Adult↗

The basal electrocardiogram and the exercise stress test in assessing prognosis in patients with unstable angina.

The purpose of this study was to evaluate the prognostic usefulness of basal electrocardiogram and exercise stress test in 374 patients with unstable angina submitted to coronary angiography during the same hospitalization period. After stabilization of symptoms by medical therapy, patients were subdivided into four groups according to the ECG and stress test: Group 1 (54 patients with normal ECG and exercise stress test negative for ischaemia); Group 2 (86 patients with normal ECG and exercise stress test positive for ischaemia); Group 3 (59 patients with abnormal ECG and exercise stress test negative for ischaemia); Group 4 (175 patients with abnormal ECG and exercise stress test positive for ischaemia). The severity of coronary atherosclerosis and impairment of left ventricular function increased progressively from Group 1 to 4, although differences in ventricular function were not significant between Groups 2 and 3. When discharged, patients were treated with verapamil and nitrates and followed for a period ranging from 1 to 8 years; during follow-up, only one patient of Group 1 underwent coronary bypass surgery, compared to 22, 7 and 46 patients in Groups 2, 3 and 4, respectively. The eight-year survival rate in the four groups (1-4) was 100%, 97%, 88% and 70%, respectively. Statistically significant differences were observed between Groups 1 and 3, 1 and 4, 2 and 4, and 3 and 4. Thus, the ECG and exercise stress test allow a population of patients with unstable angina to be selected (Group 1), having excellent long-term prognosis. These patients could avoid angiography, thereby reducing hospital costs, without compromising their health.

Adult↗

Acute immune complex disease associated with hepatitis. Etiopathogenic and immunopathologic studies of the renal lesion.

Immune deposit glomerulonephritis has been associated with hepatitis B antigenemia. Immune complexes of this antigen and its antibody have been implicated in the pathogenesis of the renal disease. A boy had acute immune complex disease with glomerulitis in which cryoprecipitable complexes of HbsAg and its antibody were isolated from serum. HbsAg was concentrated in the cryoprecipitate and localized in a granular pattern along the glomerular basement membrane in association with immunoglobulins. Glomerular fixed antibody was eluted and shown to be directed against HbsAg. The level of antibody activity to HbsAg was higher in the eluate than the serum, suggesting immunopathogenic specificity of the antibody. The study demonstrates that the nephritis was mediated by immune complexes of HbsAg and its antibody, and the presence of immunoglobulin on the kidney did not represent trapping from the circulation.

Child↗