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Biomedical subjects

M C Roncaglioni

Publications and source records attributed to M C Roncaglioni.

At least 19 recordsLinked to original sources
PubMed2000

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95% confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95% CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

Administration, Oral↗
PubMed2000

Effects of vitamin E on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

A randomized controlled open trial studied the effect of vitamin E supplementation (300 mg/day) on clinic and 24-h ambulatory blood pressure (BP) in 142 treated hypertensive patients. After 12 weeks, clinic BP decreased whether or not patients were randomized to vitamin E. Ambulatory BP showed no change in systolic BP and a small decrease in diastolic BP (-1.6 mm Hg, 95% confidence intervals from -2.8 to -0.4 mm Hg), approaching statistical significance in comparison to the control group (P = .06). Vitamin E supplementation thus seems to have no clinically relevant effect on BP in hypertensive patients already under controlled treatment.

Antihypertensive Agents↗
PubMed1999

Clinical outcome and its predictors in 1560 patients with critical leg ischaemia. Chronic Critical Leg Ischaemia Group.

OBJECTIVE: to assess the predictivity of clinical variables in patients with chronic critical leg ischaemia (CLI). Design observational prospective cohort study. METHODS: the i.c.a.i. (ischemia critica degli arti inferiori) trial database was used to assess the impact of patients' history, cardiovascular risk, manifestations of the disease and specific invasive and pharmacological interventions on mortality, amputation rate and persistence of CLI. RESULTS: of 1560 patients, 298 died within one year; at six months 187 were amputees and 746 still suffered from CLI. Prior major vascular events doubled the risk of dying within one year. Previous revascularisation was associated with a lower mortality, but also with a higher probability of amputation. Among cardiovascular risk factors, only diabetes affected prognosis, in terms of increased mortality and lower probability of recovery from CLI. Patients with tissue loss had a higher amputation rate and less probability of recovery. Ankle pressure was predictive of mortality and amputation only when unmeasurable. Patients requiring revascularisation had better chances of recovering from CLI, but not of longer-term survival or limb salvage compared to those in whom surgery was deemed unnecessary. Antiplatelet drugs caused resolution of CLI and decreased the amputation rate by about 1/3, while the advantage of the test treatment (alprostadil-alpha-cyclodextrine) was confined to CLI resolution only. CONCLUSIONS: this study documents the high mortality and heterogeneity of patients with CLI. It provides stratification criteria for reliably estimating the achievable benefit in routine practice and for clinical trials.

Aged↗
PubMed1995

[Hemostatic factors and family history of thrombosis in patients with a myocardial infarct: a case-control study. The participants in GISSI-2-Efrim. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico].

We studied a series of hemostasis factors in a group of patients selected from a cohort of 916 patients affected by MI from the GISSI-2 study population. Following a case-control design, 73 patients with a family history of thrombosis (the presence of at least two first degree relatives affected by MI and/or stroke before 65 years) were matched with MI patients with no family history of thrombosis. Blood collection could be performed 6 +/- 1 months after the acute phase following MI in 53 pairs of such patients. The presence of mixed disulphides (MDS) was significantly higher in patients with family history than in controls; MDS were detected in 7 cases and only in 1 control. No difference was found in contrast in the distribution of fibrinogen, factor VII, factor VIII, vWF, protein C, protein S, AT III, HC II, PAI-1, lipoprotein (a). Nevertheless, independently from the family history, in the whole population of MI patients studied, 21 cases of suspected deficiency of protein C were found. Sixteen out of 53 patients with family history of MI and/or stroke had a family history of MI only. In patients with family history of MI the t-PA antigen levels were significantly lower than in the control group (7.5 +/- 4.4 vs 11.1 +/- 3.5 ng/ml, t = -2.6, p < 0.02). In the whole population of MI patients and in patients with a family history of thrombosis t-PA antigen was positively correlated with PAI-1 antigen and vWF. The correlation with PAI-1 was lost in patients with family history of MI.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Von Willebrand factor, plasminogen activator inhibitor-1 and C-reactive protein are markers of thrombolytic efficacy in acute myocardial infarction.

Plasma von Willebrand factor, plasminogen activator inhibitor activity and C-reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t-PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and > or = 50% resolution of maximal ST-deviation on the electrocardiogram. Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism.

Adult↗
PubMed1992

Role of family history in patients with myocardial infarction. An Italian case-control study. GISSI-EFRIM Investigators.

BACKGROUND: A family history of heart disease has been reported to increase the risk of coronary heart disease. We examined the relation between family history of myocardial infarction (MI) and risk of acute MI to establish the independency of this association, the degree of risk in relation to the number and age of relatives affected, and the possible interaction between family history and other major risk factors for MI. METHODS AND RESULTS: In a case-control study conducted in Italy within the framework of the GISSI-2 Trial, 916 cases of newly diagnosed MI and 1,106 hospital controls were identified. Using a structured questionnaire, data were collected on the history of MI in first-degree relatives and the age at which the event occurred. Compared with subjects without family history of MI in first-degree relatives, the relative risk (RR) of MI was 2.0 (95% confidence interval, CI, 1.6-2.5) in those with one and 3.0 (95% CI, 2.0-4.4) in those with two or more relatives affected (chi 2(1) test for trend, 54.1; p less than 0.001). Such an increase was not substantially affected by allowance for recognized risk factors. The risk related to family history involving at least two relatives was higher for early MI (less than 55 years) (RR, 20.0; 95% CI, 3.3-121.2) compared with later MI (less than or equal to 65 years) (RR, 3.5; 95% CI, 1.8-6.6). When known risk factors were considered for their interaction with family history, the effect on RR was approximately multiplicative for several variables, including smoking, serum cholesterol, hypertension, and hyperlipidemia but not for diabetes and body mass index. Thus, the presence of both family history and smoking and cholesterol levels greater than or equal to 226 mg/dl led to an RR of 14 (95% CI, 3.7-50.0) and 8.3 (95% CI, 1.8-38.7), respectively. CONCLUSIONS: This study indicates that a family history of MI is an independent risk factor for MI, and that the number of relatives and the age at which they were affected is related to the strength of the association. There is a multiplicative effect on RR between family history and several major risk factors for MI.

Case-Control Studies↗
PubMed1990

Early coronary reperfusion blunts the procoagulant response of plasminogen activator inhibitor-1 and von Willebrand factor in acute myocardial infarction.

The effects of early coronary recanalization on the plasma levels of two procoagulant acute phase proteins, the fastacting plasminogen activator inhibitor and von Willebrand factor, were investigated in 24 patients with myocardial infarction receiving intravenous recombinant tissue-type plasminogen activator (rt-PA) within 6 h of the onset of symptoms. Coronary angiography was performed before and 90 min after the start of rt-PA infusion. Continuous electrocardiographic recordings and 4 h plasma creatine kinase MB isoenzyme (CK MB) were performed over the first 24 h. Plasma plasminogen activator inhibitor activity, von Willebrand factor and C-reactive protein were measured before rt-PA infusion, daily for the first 3 days and after 90 days. In the entire group, plasminogen activator inhibitor activity peaked at 24 h (day 1), representing a significant increase over values at all other times (p = 0.03). von Willebrand factor was higher in the first 2 days of infarction compared with after 90 days (p = 0.001). C-reactive protein peaked on day 2, with an eightfold increase over values on admission (p = 0.001). In the 16 patients with a patent infarct-related artery at 90 min, infarct size estimated by integrated 24 h CK MB, time for ST segment elevation to decrease to half-maximum and peak C-reactive protein were reduced significantly by more than twofold compared with values in the 8 patients with an occluded artery at 90 min. The patients with early recanalization also had lower plasminogen activator inhibitor activity on day 2 (p = 0.05) and day 3 (p = 0.02) and lower 0 to 72 h averaged von Willebrand factor (p = 0.01). Thus, early coronary recanalization curtails the response of plasminogen activator inhibitor activity and von Willebrand factor to myocardial infarction, most likely by reducing the extent of ischemia and necrosis and the consequent acute phase reaction. By blunting the early postinfarction procoagulant state, prompt recanalization may reduce the risk of thromboembolic complications in the first days after myocardial infarction.

C-Reactive Protein↗
PubMed1988

Moderate anticoagulation by salicylate prevents thrombosis without bleeding complications. An experimental study in rats.

It has previously been shown that salicylate (S) acts as a vitamin K (vit K)-antagonist inducing a decrease in plasma levels of vit K-dependent clotting factors and inhibiting the vit K-dependent carboxylation reaction in the liver. In this study we evaluated whether this biochemical effect had a possible functional role. Indeed, we tested in rats the antithrombotic potency of S (175 mg/kg/i.p. twice a day for 3 days) on experimentally induced venous thrombosis. Its possible haemorrhagic effect was evaluated by measuring the bleeding time. Low-dose warfarin (W) (0.2, 0.1, 0.1 mg/kg/i.v. for 3 days) was utilized as control drug. To check for a possible potentiation between S and W, we tested the effects of their combination (S + W). Thrombotest was used to monitor the anticoagulant effect of each treatment. The incidence of thrombus formation, after venous stasis, was not significantly affected by any of the treatments used, but a significant reduction in thrombus weight was observed after either S or W treatment. Both drugs partially prolonged the Thrombotest without affecting either the bleeding time or the peri-operative mortality (mainly due to internal bleeding). When the combination S + W was used, no significant benefit was observed on the prevention of thrombus incidence or weight, although a marked Thrombotest prolongation was recorded. On the other hand this combination resulted in a pronounced bleeding tendency, as expressed in a significant prolongation of bleeding time and increased total mortality. Thus S, at doses inducing moderate anticoagulation may prevent venous thrombosis without relevant bleeding complications.

Animals↗
PubMed1987

Several murine metastasizing tumors possess a cysteine proteinase with cancer procoagulant characteristics.

Cancer Procoagulant (CP), a cysteine proteinase which triggers blood coagulation by directly activating Factor X (FX) in the absence of Factor VII (F VII), has recently been isolated from rabbit V2 carcinoma and biochemically characterized. We have studied the procoagulant activity of tissue extracts from 4 murine experimental tumors in order to define whether or not a F VII-independent activity with cysteine proteinase characteristics was present. The tumors studied were: Lewis lung carcinoma (3LL), B16 melanoma (B16), JW sarcoma (JWS) and the M4 variant of the mFS6 fibrosarcoma (M4). Extracts from 3LL, B16 and JWS tumor initiated coagulation in both the presence and absence of F VII, their procoagulant activity was sensitive to iodoacetamide (1 mM) and mercury chloride (0.1 mM). The procoagulant of M4 extract was dependent on the presence of F VII and was not significantly affected by the cysteine proteinase inhibitors. An Ouchterlony double immunodiffusion study showed immunological cross-reactivity of all but M4 extracts to a polyclonal antibody to purified CP. The present study suggests that the procoagulant(s) present in the murine tumors 3LL, B16 and JWS are enzymatically and immunologically indistinguishable from cancer procoagulant of the rabbit V2 carcinoma.

Animals↗
PubMed1986

Increased susceptibility to the anticoagulant effect of warfarin in mice bearing the Lewis lung carcinoma. Role of vitamin K deficiency.

This study reports an increased susceptibility to warfarin anticoagulation in mice bearing an experimental tumour, the Lewis lung carcinoma. In these animals, following a single i.v. injection of warfarin, the prothrombin complex activity decreased normally but recovered far slower than in controls, while the rate of degradation of the clotting factors was not modified. At the level of the vitamin K-dependent liver carboxylase, it was possible to demonstrate an increase in the endogenous substrate (reflecting an impairment of the carboxylase vitamin K dependent system). This abnormality was reversed by vitamin K administration and can be reasonably ascribed to a vitamin K deficiency in association with tumour growth.

Animals↗
PubMed1986

The vitamin K-antagonism of salicylate and warfarin.

When administered in high dosages, salicylate acts as a vitamin K-antagonist: it induces a decrease of the plasma concentration of the Gla-containing coagulation factors and an accumulation of microsomal substrates for vitamin K-dependent carboxylase in the liver and in the lung. In vitro the drugs inhibit the DTT-dependent reductases which mediate the reduction of vitamin K epoxide and vitamin K quinone. NADH-dependent reductase and vitamin K-dependent carboxylase are not inhibited.

Animals↗
PubMed1986

Vitamin K-dependent procoagulant in cancer cells: a potential target for the antimetastatic effect of warfarin?

Anticoagulants of the coumarin type have long been reported to inhibit metastasis growth in experimental animals; however, the mechanisms of such effects has not been clarified. Systemic anticoagulation per se does not appear to account completely for such metastasis growth depression. More recent information gathered on a cell procoagulant activity, which is vitamin K-dependent, could probably supply a fresh insight into this problem. Indeed, vitamin K deficiency induced either dietarily or pharmacologically by warfarin, does inhibit the activity of a cysteine protease with direct factor-X-activating properties. This protease is only present in warfarin-sensitive tumors. The correlation of this activity with cancer cell invasiveness is supported by experimental data in metastatic variants and, lately, also by the observation of markedly higher cancer procoagulant activity in extracts from metastases than from primary human melanomas.

Animals↗
PubMed1986

gamma-Glutamyl carboxylase activity in experimental tumor tissues: a biochemical basis for vitamin K dependence of cancer procoagulant.

Rabbit V2 carcinoma tissues have been described to possess a procoagulant activity with specific characteristics; this material has been purified and identified as a cysteine proteinase able to directly activate coagulation factor X. We have shown here that the procoagulant activity of V2 carcinoma extracts is depressed in warfarin-treated animals, thus suggesting that cancer procoagulant could represent a new vitamin K-dependent protein. The biochemical basis for this effect is offered by the identification of gamma-glutamyl carboxylase in the microsomal fraction of tumor tissues. The V2 carcinoma has a carboxylase activity which is increased in warfarin-treated animals. An endogenous substrate of tumor carboxylase, the nature of which has not been identified, has been found 5-fold increased in warfarin-treated animals. The presence of gamma-glutamyl carboxylase was also described in several murine tumors including both carcinomas and fibrosarcomas. It is worth mentioning that all the tumors tested produce a procoagulant with the peculiar characteristics of that described in V2 carcinoma. It is conceivable that cancer procoagulant could represent at least one of the substrates for gamma-glutamyl carboxylase in these experimental tumor tissues.

Animals↗
PubMed1983

Warfarin-induced accumulation of vitamin K-dependent proteins. Comparison between hepatic and non-hepatic tissues.

At high concentrations (7.5 mg/kg body weight), coumarin derivatives inhibit the vitamin K-dependent carboxylation reaction in hepatic as well as in non-hepatic tissues. Therapeutically this anti-vitamin K drug is frequently used in 100-fold lower dosages. Under these conditions the production of the vitamin K-dependent clotting factors in the liver is only partially inhibited. Using the rat as an experimental animal, we could demonstrate, that during a daily intake of these low amounts of warfarin, endogenous substrates for vitamin K-dependent carboxylase accumulate in the lung, spleen and testis in a similar way as they do in liver. Therefore it seems that in vivo the carboxylating enzyme systems in all these tissues are inhibited. It seems plausible, that this effect of warfarin is not restricted to rats, but that it will also occur in patients under anticoagulant therapy.

Animals↗
PubMed1983

Heparin counteracts the antiaggregating effect of prostacyclin by potentiating platelet aggregation.

It has recently been reported that heparin neutralizes the inhibitory effect of prostacyclin (PGI2) on human platelet aggregation. The mechanism of this interaction has not yet been unequivocally established. We present here evidence that heparin (Liquemin Roche) does not react directly with PGI2 but counteracts its inhibitory effect by potentiating platelet aggregation. In the absence of heparin, PGI2 was a less effective inhibitor of platelet aggregation induced by the combination of ADP and serotonin than by ADP alone. Moreover, the inhibitory effect of PGI2 was similarly reduced when increasing the concentrations of ADP (in the absence of heparin). The lack of a specific interaction between heparin and PGI2 is supported by the observation that, in the presence of heparin, other prostaglandins such as PGD2 and PGE1 and a non-prostanoid compound such as adenosine also appeared to lose their inhibitory potency. It is concluded that heparin opposes platelet aggregation inhibitory effect of PGI2 by enhancement of platelet aggregation.

Adenosine Diphosphate↗