Improvement of blood gas levels after calcium-heparin treatment in patients with chronic obstructive pulmonary disease.
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Aged↗
Biomedical subjects
C Alessandri
Publications and source records attributed to C Alessandri.
Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis.
Sixty-one patients with different degrees of liver failure, 23 with Child-Pugh class B and 38 with Child-Pugh class C, were studied and observed for 3 yr. Coagulation index analysis showed significantly lower values of prothrombin activity, more prolonged activated partial thromboplastin time, higher bilirubin and fibrinogen degradation products values in class C patients. Among all patients, 28 had fibrinogen degradation products values greater than 10 micrograms/ml, and in these patients a hyperfibrinolytic state was confirmed by higher values of circulating plasminogen activator antigen (17.3 +/- 8.7 ng/ml vs. 5.41 +/- 1.9 ng/ml; p less than 0.0001) and activity (6.6 +/- 2.1 IU/ml vs. 1.92 +/- 1.12 IU/ml; p less than 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 +/- 3.5 ng/ml vs. 15.8 +/- 5.6 ng/ml; p less than 0.0001) and activity (3.6 +/- 2.2 IU/ml vs. 8.5 +/- 3.9 IU/ml; p less than 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 +/- 4 mg/dl vs. 2 +/- 2 mg/dl; p less than 0.0001) and lower fibrinogen (156 +/- 52 mg/dl vs. 194 +/- 62 mg/dl; p less than 0.02) than patients without hyperfibrinolysis. During the follow-up period, 41 patients died, 22 from fatal gastrointestinal hemorrhage and 19 from liver failure. Thirty patients experienced fatal (22 patients) and nonfatal (8 patients) gastrointestinal hemorrhage. Patients with positive fibrinogen degradation products or class C had a higher risk of gastrointestinal bleeding than patients with negative fibrinogen degradation products (odds ratio = 8) or class B (odds ratio = 3.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
1-year survey of patients with advanced liver cirrhosis. Prognostic value of clinical and laboratory indexes identified by the Cox regression model.
The relation between coagulation indexes and survival rate was studied and analyzed in 46 patients with advanced liver cirrhosis (grade B and C Child-Pugh Classification), during a follow-up of 1 year. Twenty-four patients (52%) died of liver failure or fatal haemorrhage within 12 months of follow-up. Prothrombin activity, fibrinogen, fibrin(ogen) degradation products, prekallikrein and factor VII, serum bilirubin, and the degree of liver insufficiency, scored by Child-Pugh classification, proved to be significantly correlated with survival by univariate analysis. A multivariate survival analysis (Cox regression model) disclosed two variables, prekallikrein and factor VII, that predicted survival. The rate ratios of death increased to 2.8 and 7.6 with values of prekallikrein < 26% and factor VII < 39%, respectively. This study shows that some simple laboratory tests exploring the clotting system may identify patients with poor prognosis in severe liver failure.
Adult↗
High density lipoprotein cholesterol low serum level as the only risk factor in male patients with coronary heart disease.
Forty-three male patients with myocardial infarction, severe angiographic coronary lesions, high or normal low density lipoprotein (LDL) cholesterol serum levels, and without other risk factors for coronary heart disease were selected. In all patients high density lipoprotein (HDL) cholesterol and HDL-cholesterol/total cholesterol ratio were significantly lower than in the control group; in particular, the ratio was below 0.240 which was the median value of normal subjects. Six patients with total cholesterol and LDL-cholesterol below 5.16 and 3.35 mmol/l respectively, had low serum levels of HDL-cholesterol; in 4 of them the value of this risk factor was below 0.9 mmol/l; 2 of 6 patients had a lipoprotein (a) serum concentration above 0.3 g/l but not a premature myocardial infarction or a clinical history of coronary heart disease. Our data confirm that HDL-cholesterol/total cholesterol ratio could be a better marker of coronary heart disease than HDL-cholesterol, total cholesterol or LDL-cholesterol and suggest the importance to check HDL-cholesterol serum levels also in subjects without risk factors for atherosclerotic disease.
Adult↗
[Clinical evaluation of a selective inhibitor of cholesterol synthesis: pravastatin].
The recent introduction in clinical practice of a new class of drugs able to reduce the endogenous synthesis of cholesterol has undoubtedly made a noteworthy contribution to the treatment of hypercholesterolaemia which, as is well known, is one of the greatest risk factors in the natural history of atherosclerotic disease and of its cardiovascular complications. A last generation drug belonging to this family is pravastatin which differs from the other substances inhibiting the activity of the key enzyme of cholesterol metabolism, HMGCaA reductase, because of certain features of the molecule, such as hydrophilia and the fact it is already pharmacologically active at the moment of oral administration. Pravastatin, which is probably a special category of HMGCoA reductase inhibitor, has shown, in numerous experimental studies and controlled clinical trials, a notable effectiveness in reducing in a highly selective fashion the synthesis of cholesterol in the liver cells and consequently the number of cholesterol-rich lipoproteins in the systemic circulation, without also determining significant biologically negative side-effects.
Adult↗
[Hypercholesterolemia: therapeutic approach].
Epidemiological observations, experimental and clinical researches have laid special stress on the importance of hypercholesterolemia in the natural development of the atherosclerotic disease and its cardiovascular complications. Primary and secondary trials have demonstrated the benefits of cholesterol-lowering therapy to modify the evolution of atherosclerotic disease. In particular, it was observed a significant reduction of incidence and mortality due to coronary heart disease, that is the most common complication of atherosclerosis. At the present time, we have a new class of cholesterol-lowering drugs which is able to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, the enzyme limiting the endogenous pathway of cholesterol synthesis. The HMGCoA reductase inhibitors, according to the chemical structure, can be divided into two groups. The first includes inactive lactone prodrugs, as Lovastatin and Simvastatin, that are enzymatically hydrolyzed to the corresponding ring-opened active forms in the liver, where the HMGCoA reductase inhibitors must chiefly reduce cholesterol synthesis. To the other group belongs the Pravastatin, a drug that is administered in its active open hydroxyacid form. Several clinical studies seem to demonstrate a greater cholesterol-lowering effect of the active form of Simvastatin, probably because of its more affinity for the HMGCoA reductase enzyme. Up to now, no inhibitor of HMGCoA reductase has showed serious toxic effects in man. The remarkable therapeutic efficacy showed by Simvastatin to reduce the serum concentrations of total and LDL-cholesterol, associated with moderate side-effects, ascribes to this molecule an important role in the therapeutic approach of familial and polygenic hypercholesterolemia.
Adult↗
Plasma thiobarbituric acid reactive substances a predictive marker of cerebral ischemia in patients at high risk?
The clinical meaning of high values of blood lipid peroxides, assessed as thiobarbituric acid reactive substances (TBA-RS), was investigated in 19 selected high risk patients with transient ischemic attacks (TIA). Patients were checked every 3-6 months and followed-up for 3 years. 8 patients experienced further vascular episodes, 4 having minor stroke and 4 TIA; one of the latter died from myocardial infarction. Unlike blood cholesterol and glucose. TBA-RS values discriminated patients with vascular episodes: they, indeed, showed significant higher values of TBA-RS. Discriminant analysis further indicated that TBA-RS levels differentiate patients with and without vascular accidents, suggesting that high blood values of lipid peroxides could represent a predictive sign of vascular ischemia.
Aged↗
Hydrogen peroxide as trigger of platelet aggregation.
In order to verify if H2O2 affects platelet function, platelet-rich plasma and human washed platelets were incubated with subthreshold concentrations (STC) of collagen or arachidonic acid or ADP and/or with 75-150 microM H2O2. While H2O2 alone did not affect platelet aggregation, it amplified platelet aggregation response in samples stimulated with STC of arachidonic acid and collagen but not in samples stimulated with STC of ADP. When platelets were preventively treated with aspirin, a cyclooxygenase inhibitor, the platelet activation by H2O2 was not observed. Thromboxane A2 (TxA2) was not produced by human washed platelets stimulated with STC of arachidonic acid, collagen or by H2O2 alone. On the contrary, when STC of agonists were tested on platelets supplemented with H2O2 an evident TxA2 production was seen. This effect was prevented by aspirin pretreatment or by the addition of catalase, an enzyme which destroys H2O2. This study suggests that H2O2 triggers the activation of platelets exposed to STC of collagen and arachidonic acid, via the cyclooxygenase pathway.
Adult↗
[Primary results of laser recanalization in the endovascular treatment of arterial stenosis and occlusion of the lower limbs. Apropos of 45 treated cases].
Forty-five lower limb arterial lesions were treated by Nd Yag laser angioplasty using 1.4 and 2 mm hybrid catheters in 31 patients. This population comprised 28 men and 3 women (average age 63.8 +/- 3 years) 20 were in Stage II, 5 in Stage III and 6 in Stage IV of Fontaine's classification. The arteriographic lesions were 22 occlusions with an average length of 12.3 cm and 23 stenoses averaging 87% luminal reduction a few millimeters long to a maximum of a string of stenoses. Seventeen of these lesions were very calcified. The stenoses were situated on the iliac artery (7 cases), superficial femoral artery (28 cases), popliteal artery (9 cases) and the tibio-peroneal artery (1 case). There were no fatalities or recourse to emergency surgery. All patients underwent complementary balloon dilatation. The immediate patency rate was 91% in stenotic and 72% in occlusive lesions. At one week, the patency rate for stenotic lesions was unchanged but it had fallen to 59% for occlusive lesions (arteriographic evaluation). Angioscopy was used 22 times: it was indissociable to laser angioplasty as it enabled diagnosis and controlled the result. The use of thermal laser with hybrid catheters (metallic window tip) in endovascular procedures is a safe and effective method of treating stenosis and occlusion of lower limb arteries.
Adult↗
[Effects of simvastatin on atherogenic blood lipid pattern].
The effect of a 6-month treatment with simvastatin, an HMG CoA-reductase inhibitor, on serum lipoprotein pattern was investigated in patients affected by primary hypercholesterolemia. After 4-6 weeks of lipid lowering diet, 46 patients showing serum cholesterol greater than 250 mg/dl and triglycerides less than 200 mg/dl were included in the study and treated with simvastatin (10-30 mg/day) plus diet. Serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides levels significantly decreased at the end of the follow-up (-27%, -33%, -22%, -26% respectively). Apolipoprotein A1 showed a significant increase as well as HDL-cholesterol, HDL3-cholesterol and apolipoprotein A1/B ratio. This study provides further findings on the simvastatin efficacy to normalize the lipoprotein pattern in primary hypercholesterolemia.
Adult↗
Dilute aPTT prolongation by antiphospholipid antibodies in patients with liver cirrhosis.
The behaviour of aPTT, as assessed by standard or diluted phospholipid mixture, was investigated in 20 patients suffering from liver cirrhosis. Standard aPTT was prolonged in 13 but it was corrected by 1:1 mixture with normal plasma. Dilute aPTT performed in samples mixed 1:1 with normal plasma and calculated by the difference in time between 1:80 and 1:5 phospholipid mixture was prolonged in 9 patients, who had also significantly higher titre of anticardiolipin antibodies (p less than 0.005). Unlike patients' plasma with normal dilute aPTT, the addition of 0.05 M PC/PS liposomes to patient's plasma with prolonged dilute aPTT significantly shortened dilute aPTT (p less than 0.001). This study shows the presence of antiphospholipid antibodies in some patients with liver cirrhosis; this seems to be responsible for the prolongation of dilute aPTT.
Aged↗
Inhibition of cyclooxygenase-independent platelet aggregation by low vitamin E concentration.
Platelet aggregation induced by threshold concentrations of agonists such as collagen, PAF or epinephrine was inhibited in vitro by 100 microM aspirin but was restored by stimulating platelets with high concentrations of collagen, PAF or by a combination of epinephrine and PAF. Incubating aspirin-treated platelets with 50-100 microM vitamin E or vitamin E acetate inhibited platelet aggregation by high concentrations of collagen and PAF and by the combination of epinephrine and PAF; platelet thromboxane A2 formation was less than 10% in samples incubated with 100 microM aspirin. Apyrase, added to aspirin-treated platelet, did not influence platelet aggregation induced by epinephrine and PAF. The present study suggests that concentrations of vitamin E as low as 50-100 microM inhibit cyclooxygenase-independent platelet aggregation when combined with an inhibitor of the arachidonate pathway.
Apyrase↗
Evaluation of D-dimer in patients with liver cirrhosis.
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Adult↗
Inhibition of cyclooxygenase-independent platelet aggregation by sodium salicylate.
The effect of acetylsalicylic acid (ASA) on platelet aggregation (PA) and thromboxane A2 (TxA2) formation was investigated in vitro and ex vivo after 1 g or 300 mg ASA administration to healthy subjects. 50-100 microM ASA inhibited PA by single aggregating agent such as platelet aggregating factor (PAF) or epinephrine and reduced to less than or equal to 5% of control platelet TxB2 formation, but did not influence PA by epinephrine plus PAF. The latter was inhibited by increasing ASA concentration. In samples incubated with 100 microM ASA and stimulated with epinephrine plus PAF, PA could be inhibited by the addition of 100-300 microM sodium salicylate. After 300 mg-1 g ASA administration to healthy subjects, the inhibition of PA by epinephrine plus PAF was more marked by highest doses of ASA. This study suggests that aspirin inhibits PA with a cyclooxygenase-independent mechanism; this effect is mediated, at least in vitro, by salicylic acid.
Adult↗
Superoxide anion scavenging property of dipyridamole.
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Antioxidants↗
Inhibition of tissue plasminogen activator inhibitor by defibrotide in atherosclerotic patients.
Defibrotide, an antithrombotic drug, was previously shown to activate fibrinolysis. In order to elucidate the relationship between defibrotide treatment and fibrinolysis, ten atherosclerotic patients were given 1200 mg/day defibrotide intravenously for 7 days and then 400 mg/day intramuscularly for another 20 days. t-PA antigen assessed before and after venous occlusion was not affected by the treatment. Tissue PAI activity significantly decreased and t-PA activity, measured after venous occlusion, increased after 8 and 28 days of treatment; both these changes disappeared after defibrotide was discontinued. No particular side effects were detected throughout the investigation. The study suggests that defibrotide increases t-PA activity by reducing PAI activity.
Adult↗
Blood lipid peroxides in TIA: relation to platelet function and metabolic profile.
Patients with transient ischemic attacks (TIA) were previously shown to have high plasma values of thiobarbituric acid-reactive substances (TBA-RS). To study whether these changes could be related to platelet activability, TBA-RS was investigated in 24 TIA patients before and 24 h after 1 g aspirin, an inhibitor of platelet cyclooxygenase pathway. Baseline TBA-RS values were significantly higher in TIA than in controls. Conversely, TIA patients had TBA-RS values after aspirin similar to controls, suggesting that the increase of plasma TBA-RS was not attributable to platelet hyperfunction. The evaluation of metabolic profile showed that patients with highest TBA-RS had hypercholesterolemia, hypertriglyceridemia, and/or diabetes mellitus. This study suggests that the increase of plasma TBA-RS in TIA could be an epiphenomenon of altered metabolic pathway.
Administration, Oral↗
Interrelation between factor VII, prekallikrein, and hyperfibrinolysis in advanced cirrhosis.
Factor VII and prekallikrein activities were studied in 37 patients with liver cirrhosis who were in a decompensated state. Sixteen of them died 30-70 days after admission; 21 survived and were discharged after 30-80 days. Seven who died and six survivors had signs of hyperfibrinolysis: factor VII activity differentiated the two groups independently of the presence of hyperfibrinolysis. The presence of hyperfibrinolysis significantly reduced prekallikrein activity, which did not differentiate clearly survivors from non-survivors. Long term follow up of survivors showed a good correlation between factor VII and prekallikrein activities with long term survival. Hyperfibrinolysis seemed to influence the clinical course of patients: 87% of patients with hyperfibrinolysis who died had fatal haemorrhagic episodes. Low factor VII activity may be a precursor of terminal liver insufficiency.
Adult↗