Endobronchial aspergillosis in marrow transplant patients.
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Biomedical subjects
Publications and source records attributed to M Galimberti.
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Since 1983, 350 patients aged 1 to 19 years with beta-homozygous thalassemia were given infusions of HLA-identical marrow after high doses of busulphan and cyclophosphamide. Survival and event-free survival leveled off about 1 year after bone marrow transplantation at 82% and 75%, respectively. In 172 consecutive patients who were treated with our current regimen since June 1985, a multivariate analysis demonstrated that portal fibrosis, hepatomegaly, and a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly, portal fibrosis, and inadequate chelation therapy. Class 1 had none of the factors and class 3 had all three factors; class 2 had different associations of two out of the three factors. For class 1 patients, the 3-year probabilities of survival and event-free survival were 97% and 94%, respectively. For class 2 patients, the probabilities were 86% and 83%, and for class 3 patients, 58% and 52%. Bone marrow transplantation from HLA-identical donors is followed by a high probability of event-free survival in thalassemic patients, particularly if they belong to class 1.
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A controlled prospective study of 2165 outpatients undergoing skin surgery was performed to evaluate the utility and the effects of several antibiotic schedules for prophylaxis of wound infections. The patients were divided into four groups. Twenty-three of the 541 group A patients, given no antibiotics, had wound infections. Eight of the 542 group B patients, given systemic antibiotics from immediately after surgery until the third day, had wound infections. Four of the 540 group C patients, treated only with local sterile antibiotic powder sprinkled into the wound during surgery, had wound infections develop, and only one infection occurred in the 542 group D patients given systemic antibiotics from 2 days before surgery until the second day after surgery. This last schedule was the best for prophylaxis of wound infections in contamination-prone regions. Local antibiotic administration is a simple method for prevention of infections in routine skin surgery.
We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.
Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats. The study showed that ICRF-187, administered ip at a dose of 125 mg/kg, significantly prevented body weight loss. QT and ST prolongation, and the decreased contractile force induced by DXR. In addition, ICRF-187 caused a significant reduction in incidence and severity of myocardial lesions. The cardioprotective effect of ICRF-187 is not mediated by a modification in DXR pharmacokinetics in heart, since the drug was actually found to increase DXR uptake in myocardial cells.
High-resolution ultrasonography with small part probes was performed on 20 proliferative vascular lesions of the skin (3 lymphangiomas, 9 hemangiomas, 8 Kaposi sarcomas). All the lesions were submitted to histological examination. The histological cuts were made in the same planes as the ultrasound scans in order to obtain a direct comparison. The sonographic pattern of each histotype is characteristic and correlated with the corresponding histological picture. Lymphangiomas appear as large anechoic communicating cavities; hemangiomas have small hypoechoic areas separated by thin hyperechoic septa. Kaposi sarcomas possess a mixed sonographic structure with ill-defined margins. Ultrasound is proposed as a simple and harmless diagnostic aid to clinical examination of proliferative vascular lesions of the skin.
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The effects of two sulfhydryl compounds, glutathione (GSH) and N-acetylcysteine (NAC), on the cardiotoxicity of doxorubicin (DXR) were tested on in vitro and in vivo models. DXR was administered to rats as 4 weekly i.v. doses of 3 mg/kg. GSH (1.5 mmoles/kg), given i.v. 10 min before and 1 hr after DXR, was found to prevent the development of the delayed cardiotoxic effects of DXR, as assessed by electrocardiographic and mechanical parameters, as well as by histological examination of left ventricular preparations. In contrast, equimolar oral doses of NAC (1 hr before and 2 hrs after DXR) were found to be ineffective. Both GSH and NAC prevented the negative inotropic effect produced by DXR on isolated rat atria. A good correlation exists between the cardioprotective effects of the two agents and their ability to enhance the non-protein sulfhydryl group content of the myocardium. Differences observed in vivo between GSH and NAC might be accounted for by pharmacokinetic factors.
We report the incidence of cytomegalovirus (CMV) seroconversion, infections and mortality in 169 consecutive thalassemic patients transplanted in Pesaro. We observed a 44% incidence of early seroconversion and a 52% incidence of late seroconversion. No relationship was found between seroconversion and acute or chronic graft-versus-host disease (GVHD) or rejection. The donor status did not influence the incidence of seroconversion, GVHD and rejection. Only three patients died of CMV infection (1.7%); in each case CMV disease was the final cause of death in patients with severe acute GVHD.
The amino terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) is a degradation product comprising the entire growth factor-like and kringle domains. It has been previously shown that ATF is able to bind to the u-PA receptor through the growth factor-like domain and that the anti u-PA monoclonal antibody 5B4 (Mab 5B4) binds to ATF preventing u-PA receptor binding. To localize more precisely the epitope recognized by Mab 5B4, ATF was subfragmented by controlled enzymatic proteolysis with V8 protease. Three subfragments of 4,000 Mr (F-4k), 11,000 Mr (F-11k) and 12,000 Mr (F-12k) were purified from the reaction mixture and characterized. SDS-PAGE under reducing and non-reducing conditions, N-terminal aminoacid sequence analysis and C-terminal aminoacid analysis of each fragment indicate that F-4k and F-11k correspond to intact growth factor-like domain and kringle domain (residues 4-43 and 44-135 respectively) while F-12k corresponds to the kringle domain cleaved in the first loop at the glu52-gly53 bond. By Western blot and competitive binding experiments we show that Mab 5B4 recognizes an epitope located on the kringle domain of u-PA and that the binding is strongly reduced when the kringle contains an additional cleavage in its first loop. Since the receptor binding site of u-PA has been previously shown to be located on the growth factor-like domain, Mab 5B4 inhibits the binding of uPA to its cellular receptor likely by steric hindrance. Besides the proven utility in epitope localization of anti u-PA monoclonal antibodies, these u-PA fragments may represent powerful tools for studies of structure-function relationship of u-PA.
The incidence of the various types of ulcer is assessed in 180 subjects suffering from chronic ulcer of the legs and various syndrome. It emerges that about 10% of ulcers are not due to chronic venous insufficiency but to other pathologies.
Surgical treatment of subclavian artery atherosclerotic lesions has prophylactic significance in the evolution of cerebrovascular insufficiency. Local complications during interventions on subclavian artery are incidentally more significant than cerebral ischemic complications. Among local complications we reported 2 cases of phrenic nerve involvement and 1 case of thoracic duct lesion in a series of 86 operated patients. We never found cerebral ischemic complications in the surgery of subclavian artery atherosclerotic lesions.
The most frequent localisation of fibrous dysplasia of the arteries is at the renal arteries. Other localisations are rarer and those at the femoral as in the case described are exceptional. The case was observed in a 21-year-old woman who, in the absence of any previous traumatism and septic state, noticed the onset of a pulsating tumefaction at thigh level. Echography and arteriography showed the tumefaction to be an aneurysm of a collateral of the superficial femoral artery at the lower IIIrd of the thigh with the dimensions of a pigeon's egg. The aneurysm was successfully removed without the need for grafts and subsequent histological examination showed it was secondary to fibrous dysplasia. The rarity of such a clinical case is stressed.
Cardiac toxicity of idarubicin (4-demethoxydaunorubicin), a new daunorubicin derivative, was tested in 49 phase II patients with advanced malignancies. In 26 patients the drug was given intravenously at a dose of 13 mg/m2 and in 23 orally at a dose of 45 mg/m2. Cardiac toxicity was evaluated by means of electrocardiography, left ventricular systolic time intervals, echocardiography and radionuclide cineangiography. The type and incidence of ECG abnormalities were comparable to those observed with other anthracycline analogs. Other functional parameters, serially measured to evaluate delayed cardiotoxicity in patients who received more than 65 mg/m2 intravenously or 225 mg/m2 orally, were not significantly different from pretreatment values. No patient developed clinical congestive heart failure. Only one patient exhibited a drop in the left ventricular ejection fraction of more than 15% from pretreatment values. These data indicate that idarubicin given orally or intravenously at the tested doses has no significant cardiotoxic activity in the range of the cumulative doses attained.