Biomedical subjects
Publications and source records attributed to C Raimondi.
The intra-arterial administration of fibrinolytics in a massive embolism to the renal artery of a solitary functioning kidney determined quick normalization of the severe renal failure and hypertension.
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To what extent can damage to the central and peripheral nervous systems be ascribed to chronic aluminum (Al) intoxication taken as a chelating agent for phosphorus, to limit hyperphosphatemia in uremic patients? Since Al is normally eliminated by the renal route, its accumulation in uremia has to be ascribed to a reduced or abolished renal clearance of the metal, which results in preferential toxicity for certain tissues, especially nervous tissue, which shows difficulty in eliminating Al, even after intake has been stopped. This review discusses, on the basis of toxicologic, experimental and clinical data, the possible pathogenic steps of Al neurotoxicity in uremia, considering: the damage to axonal transport in which Al intoxication tends to affect the components of the cytoskeleton, the polymerization phase of the alpha and beta tubulin constituents of neurotubules, and the normal translocation of neurofilaments from the perikaryon to more distal positions of the axon; the abnormalities in the brain pool of adrenergic, cholinergic and GABA neurotransmitters; the increase in permeability and changes in perm-selectivity of the blood-brain-barrier, with further loss of neurotransmitters and with acquisition, from the systemic circulation, of neurotransmitter-like substances such as hormones, monoamines and peptides, which may adversely modulate synaptic and membrane functions; the cerebral energy metabolism and particularly the hexokinase reaction, by Al replacement of the Mg-ion in the Mg-ATP complex, so that phosphorylation of glucose to G6P is blocked; the interaction of Al with calmodulin by displacement of the Ca-ion and subsequent formation of a stable Al-calmodulin complex with a cytotoxic effect due to the increase in the intracellular calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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In transplanted patients graft rejection is the most frequent complication in the first year after surgery. Vascular lesions (necrosis, intimal proliferation, thrombosis) are signs of poor prognosis and lead to irreversible loss of renal function and graft removal in most cases. The problem of vascular rejection is still not solved and the results of therapy unsatisfactory, both because of inadequacy of diagnosis and/or inadequacy of available therapy. The role of prevention, very likely the best approach, is still sub judice. In an attempt to explore the validity of prevention, 22 transplanted patients (group A) were given a new antithrombotic agent (defibrotide) immediately after surgery, and the results were compared with those of a well-matched group of 30 patients on dipyridamole (group B). Follow-up lasted 6-19 months (mean 9.9) for group A; 5-21 months (mean 12) for group B. In group A, 8 patients (36%) had rejection episodes. Antirejection therapy was followed by recovery of renal function in all cases. In group B, 9 patients (29%) had rejection crises and graft removal was necessary in 7 instances due to severe vascular lesions. At the end of follow-up, all patients treated with defibrotide had normally functioning grafts: among the 30 patients on dipyridamole, 22 (73%) had satisfactory graft function.
Thrombotic microangiopathy (TMA) can occur whenever pathogenetic events lead to fibrin deposition in the microcirculation. It has been suggested that intravascular coagulation is important in the development of renal as well as cerebral lesions. The mortality rate in adults varies from 50 to 70%; chronic or progressive renal failure occurs in approximately two thirds of children over 2 years of age. Poor success may be due to therapy being initiated too late or to inappropriate use of antagonistic drugs, or both. In the last 2 years we have treated 8 patients with TMA (5 with thrombotic thrombocytopenic purpura; 3 with hemolytic uremic syndrome) with defibrotide, a new antithrombotic agent extracted from mammalian lungs. At admission all patients had severe renal involvement (serum creatinine 5.3-14.9 mg/dl) and coagulation abnormalities (low platelet count; high levels of circulating fibrin degradation products). There were neurological manifestations in 6 patients. Defibrotide administration was followed in 6 patients by recovery of renal function. In all patients, defibrotide therapy induced the disappearance of neurological manifestations and normalization of coagulation abnormalities. Defibrotide caused no side effects. All patients are alive after 7-22 months of follow-up.
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8 patients with thrombotic microangiopathy were treated with a new antithrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormalities. Neurological manifestations were present in 6. Defibrotide administration was followed by recovery of renal function in 6, disappearance of neurological symptoms and coagulation abnormalities in all patients. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.
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BACKGROUND: Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD). The aim of the study was to assess the efficacy of early warfarin administration, after TCC placement, in comparison to its administration after the first thrombosis or malfunction event of the TCC. PATIENTS AND METHODS: One hundred and forty-four chronic dialysis patients, who underwent TCC placement between June 2001 and June 2005, were randomized into two groups: 81 patients, group A, started oral anticoagulation 12 hr after the TCC placement (target international normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63 patients, group B, started warfarin after the first thrombosis/malfunction episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period, after TCC placement, in terms of: a) the number of patients with thrombotic-malfunction events; b) the number of thrombotic-malfunction events with urokinase infusion (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d) negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e) positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and f) bleeding complications. RESULTS: Ten patients (12%) in group A showed TCC thrombosis/malfunction vs. 33 patients (52%) in group B (p < 0.01). In group A, 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B (p < 0.001) were ob-served. BFR was respectively 305 +/- 34 vs. 246 +/- 42 ml/min (p < 0.001). AP was -124 +/- 13 in group A vs. -174 +/- 21 mmHg in group B (p < 0.05). VP was 112 +/- 28 in group A vs. 168 +/- 41 mmHg in group B (p < 0.05). No patient showed any bleeding events. CONCLUSIONS: Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event. This therapy did not induce any bleeding complications in the patients included in the study.
With the purpose of ascertaining the predictive value of residual myocardial ischemia, in stable clinical conditions at a distance after myocardial infarction, on the incidence of late cardiac events, we evaluated 55 patients 24.2 +/- 11.4 months after myocardial infarction with thallium-201 stress test imaging. All patients were either asymptomatic or with stable effort angina pectoris, well controlled with medical treatment. In the next follow-up period, whose duration has been 22.4 +/- 14.4 months, the incidence of unfavourable cardiac events, like unstable angina, reinfarction, coronary bypass surgery, sudden cardiac death has been monitored. Thirty-one patients (56.4%) presented a reversible perfusion defect (RPD) in one or more myocardial segments; 17 of these 31 showed cardiac events during follow-up. Only 2 patients of the remaining 24 without RPD had cardiac events, with a significant difference (p less than 0.01). The patients with RPD only in peri-infarct areas had a relatively smaller number of cardiac events, with respect to those patients with RPD also or only in distant areas. Fifteen of 21 patients with RPD in 2 or more segments manifested cardiac events, compared to 2 of 10 patients with RPD in only one segment (p less than 0.01). In 10/55 patients, increased lung uptake of thallium-201 activity was observed; 8 of them presented cardiac events (p less than 0.01). This analysis confirms the high predicting value of thallium-201 RPD imaging on the incidence of cardiac events in patients controlled at a distance after myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Eighty transplanted patients were randomized to receive either a new antithrombotic agent, defibrotide (group A), or dipyridamole (group B) in addition to immunosuppressive therapy, in order to evaluate the effectiveness of these drugs in preventing graft vascular damage. While the incidence of rejection and the occurrence of specific anti-HLA antibodies were similar in the two groups, the peak serum creatinine levels during rejection were significantly lower in patients treated with defibrotide (3.3 +/- 1.8 versus 5.6 +/- 2.4 mg/dl; P less than 0.01), 97.5 per cent of whom had a still-functioning graft after a mean follow-up period of 24 months, compared with 80.5 per cent of the patients treated with dipyridamole (P less than 0.05). Graft biopsy, carried out during rejection, showed less severe vascular lesions in patients from group A than in those from group B. Our results suggest that the prophylactic administration of defibrotide may play a role in improving the long-term results of renal transplantation.
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