Biomedical subjects

M Ferrario

Publications and source records attributed to M Ferrario.

At least 19 recordsLinked to original sources

PubMed2001

Thrombogenic potential of human coronary atherosclerotic plaques.

Higher levels of tissue factor (the initiator of blood coagulation) have been found in coronary atherosclerotic plaques of patients with unstable coronary artery disease, but it is not established whether they are associated with a different thrombotic response to in vivo plaque rupture. In 40 patients undergoing directional coronary atherectomy, prothrombin fragment 1 + 2, a marker of thrombin generation, was measured in intracoronary blood samples obtained proximally and distally to the coronary atherosclerotic plaque before and after the procedure. Before the procedure, plasma prothrombin fragment 1 + 2 levels were significantly increased across the lesion in patients with unstable, but not in those with stable, coronary disease (unstable, median increase, 0.37 nM; range, -0.35-1.16 nM) (stable, median increase, -0.065 nM; range, -0.58-1.06 nM) (P =.0021). After plaque removal, an increase in prothrombin fragment 1 + 2 across the lesion was observed only in patients with unstable coronary disease (unstable, median increase, 0.25 nM; range, -1.04-4.9 nM) (stable, 0.01 nM; range, -0.48-3.59 nM) (P =.036)]. There was a correlation between the tissue factor content of the plaque and the increase in thrombin generation across the lesion (rho = 0.33; P =.038). The higher tissue factor content found in plaques obtained from patients with unstable coronary disease was associated with a local increase in thrombin generation, thus suggesting a link with the in vivo thrombogenicity of the plaque.

Aged↗

PubMed2001

Non-Hamiltonian equations of motion with a conserved energy.

In 1980 Andersen introduced the use of "extended system" as a means of exploring by molecular dynamics simulation the phase space of a physical model according to a desired ensemble distribution different from the standard microcanonical function. Following his original work on constant pressure-constant enthalpy a large number of different equations of motion, not directly derivable from a Hamiltonian, have been proposed in recent years, the most notable of which is the so-called Nosé-Hoover formulation for "canonical" molecular dynamics simulation. Using a generalization of the symplectic form of the Hamilton equations of motion we show here that there is a unique general structure that underlies most, if not all the equations of motion for "extended systems." We establish a unifying formalism that allows one to identify and separately control the conserved quantity, usually known as the "total energy" of the system, and the phase-space compressibility. Moreover, we define a standard procedure to construct conservative non-Hamiltonian flows that sample the phase space according to a chosen distribution function [Tuckerman et al., Europhys. Lett. 45, 149 (1999)]. To illustrate the formalism we derive new equations of motion for two example cases. First we modify the equations of motion of the Nosé-Hoover thermostat applied to a one-dimensional harmonic oscillator, and we show how to overcome the ergodicity problem and obtain a canonical sampling of phase space without making recourse to additional degrees of freedom. Finally we recast an idea recently put forward by Marchi and Ballone [J. Chem. Phys. 110, 3697 (1999)] and derive a dynamical scheme for sampling phase space with arbitrary statistical biases, showing as an explicit application a demixing transition in a simple Lennard-Jones binary mixture.

Journal Article↗

PubMed2001

Alternative splicing of mGlu6 gene generates a truncated glutamate receptor in rat retina.

A novel splice variant of metabotropic glutamate receptor type 6 (mGlu6 receptor) was identified by reverse transcription-polymerase chain reaction amplification and sequence analysis of rat retina cDNA. The new rat receptor isoform (mGlu6b receptor) is characterized by an additional exon of 88 nucleotides containing an inframe stop codon, thus predicting the expression of a truncated protein of 508 amino acids. In situ hybridization reveals mGlu6b receptor mRNA to be predominantly expressed in the outer part of the inner nuclear layer of rat retina, containing ON-bipolar cells. The mGlu6b protein would comprise the extracellular domain of the receptor containing the ligand-binding site, but would lack the transmembrane and intracellular portions, thus possibly acting as a retinal soluble receptor for glutamate.

Alternative Splicing↗

PubMed2001

Dynamics-function correlation in Cu, Zn superoxide dismutase: a spectroscopic and molecular dynamics simulation study.

A single mutation (Val29-->Gly) at the subunit interface of a Cu, Zn superoxide dismutase dimer leads to a twofold increase in the second order catalytic rate, when compared to the native enzyme, without causing any modification of the structure or the electric field distribution. To check the role of dynamic processes in this catalytic enhancement, the flexibility of the dimeric protein at the subunit interface region has been probed by the phosphorescence and fluorescence properties of the unique tryptophan residue. Multiple spectroscopic data indicate that Trp83 experiences a very similar, and relatively hydrophobic, environment in both wild-type and mutant protein, whereas its mobility is distinctly more restrained in the latter. Molecular dynamics simulation confirms this result, and provides, at the molecular level, details of the dynamic change felt by tryptophan. Moreover, the simulation shows that the loops surrounding the active site are more flexible in the mutant than in the native enzyme, making the copper more accessible to the incoming substrate, and being thus responsible for the catalytic rate enhancement. Evidence for increased, dynamic copper accessibility also comes from faster copper removal in the mutant by a metal chelator. These results indicate that differences in dynamic, rather than structural, features of the two enzymes are responsible for the observed functional change.

Amino Acid Sequence↗

PubMed2001

Living donor liver transplantation for children with liver failure and concurrent multiple organ system failure.

Liver transplantation for pediatric patients in liver failure and multiple organ system failure (MOSF) often results in poor patient survival. Progression of organ failure occurs while awaiting a cadaveric allograft. Therefore, we considered living donor liver transplantation (LDLT) in this critically ill group of children and report our initial results with comparison to a similar group who received cadaveric donation (CAD). A retrospective chart review was performed on all pediatric liver transplant recipients who met criteria for MOSF at the time of transplantation. Data collection involved pretransplantation patient profiles, as well as postoperative complications and patient survival. Eight patients in MOSF received living donor transplants and 11 patients received a cadaveric allograft. Mean wait time was 3.5 days in the LDLT group and 6.5 days in the CAD group. Pretransplantation patient profiles and postoperative complications were similar between groups. Mean cold ischemia times were 3.8 hours in the LDLT group and 7.9 hours in the CAD group (P = .0002). Thirty-day and 6-month survival rates of the LDLT group were 88% and 63% compared with 45% and 27% in the CAD group, respectively. Living donor transplant recipients in MOSF had decreased wait times to transplantation, as well as decreased cold ischemia times, compared with cadaveric transplant recipients. Patients in the LDLT group had markedly improved survival compared with the CAD group. Timely transplantation before worsening organ failure may account for these findings.

Cadaver↗

PubMed2001

Failed primary management of iatrogenic biliary injury: incidence and significance of concomitant hepatic arterial disruption.

BACKGROUND: Vasculobiliary injury (VBI) is a well-recognized complication of laparoscopic cholecystectomy (LC). In patients with failed primary management of bile duct injury (BDI), an assessment of the hepatic arterial system may be important to determine the presence of VBI. This study was conducted to determine the incidence of VBI in patients with failed primary management of LC-related BDI and to establish a potential correlation between the level of BDI and the incidence of VBI. METHODS: A retrospective review was conducted on 18 patients referred for failed primary management of LC-related BDI who underwent prospective arteriography as part of the preoperative work-up. RESULTS: Of the 18 patients who sustained BDI, Bismuth level 4 lesions were found in 7 patients (39%), level 3 in 8 patients (44%), and level 2 in 3 patients (17%). VBI was identified on arteriography in 11 patients (61%). VBI was present in 71% of patients with level 4 lesions, 63% of patients with level 3 lesions, and 33% of patients with level 2 lesions. The time interval from primary management to its failure was longer in VBI than in BDI alone. CONCLUSIONS: We have observed a high incidence of VBI in patients with failed primary management of LC-related BDI. Arterial disruption may affect the outcome of primary management of BDI.

Adult↗

PubMed2001

Time trends of major coronary risk factors in a northern Italian population (1986-1994). How remarkable are socioeconomic differences in an industrialized low CHD incidence country?

BACKGROUND: The goals are to estimate time trends (1986-1994) of major coronary risk factors in an industrialized low CHD incidence population and to assess education class (EC) differences in risk factor prevalence and in time trends. METHODS: Three population surveys were conducted in 1986-1987, 1989-1990 and 1993- 1994 on independent and two-stage age- and gender-stratified random samples (1906 men and 1941 women) of 35-64 year old residents of Brianza, an affluent region of northern Italy. The protocol for data collection, clinical measurements and biochemical determinations adhered to the WHO MONICA manual and underwent repeated quality control assessments. EC were identified according to gender- and 5-year birth-cohort specific tertiles. RESULTS: In the initial, middle and final surveys 1258, 1259 and 1330 subjects were enrolled, corresponding to participation rates of 70.1%, 70.3% and 74.3%, respectively. Over the 8-year period, in men systolic blood pressure and smoking habits declined, body mass index and serum total cholesterol increased. In women systolic blood pressure showed a constant reduction, total cholesterol and BMI increased and the prevalence of smokers remained stable. Overall inverse associations with EC were found for body mass index, for prevalence of cigarette smokers in men and for systolic blood pressure in women. Decreases in blood pressure were more evident in the lowest EC. Cigarette smoking was on the decline in the higher EC in men. BMI and total cholesterol increased in all EC with the notable exception of the 'low' EC in women. CONCLUSIONS: Favourable changes of the risk factor profile in the low socio-economic classes may have contributed to reduce CHD rates in this population. Specific policies oriented to lowest socio-economic classes are needed to continue to combat the smoking epidemic.

Adult↗

PubMed2001

Surveillance of ischaemic heart disease: results from the Italian MONICA populations.

BACKGROUND: The major objectives are to report on coronary event mortality, incidence and attack rates and changes over time observed in the Italian MONICA populations and to assess if trends are consistent when different disease definitions are considered. An analysis of diagnostic agreement between clinical and MONICA categories is presented in the context of developing a model for estimating disease incidence in a population, based on currently available data. METHODS: Data were provided by the three Italian MONICA (MONItoring trends and determinants of CArdiovascular diseases) registers. The areas of Brianza and Friuli, both located in northern Italy, completed the 10-year period of registration. Data from the MONICA Latina area, located close to Rome, were limited to the first 3 years of registration. These data are used for assessing geographical differences in rates in the mid- 1980s and estimating the diagnostic agreement between International Classification of Diseases (ICD) codes and MONICA categories. Two diagnostic aggregates have been used: the standard MONICA diagnostic definition for myocardial infarction (MI), which includes non-fatal definite myocardial infarction and fatal coronary events, and the coronary event definition which includes, in addition, non-fatal possible myocardial infarctions. RESULTS: From the mid-1980s to the mid-1990s, a considerable reduction in all-cause, cardiovascular and coronary mortality rates occurred in the monitored populations. Data from the MONICA registers confirm the accuracy of official reports of death rates and changes in Italy. Comparisons of time differences in attack and incidence rates of myocardial infarction and all coronary events indicate that the impact of the more severe manifestations of coronary heart diseases (fatal coronary event and acute MI) reduced during the period of observation, but when less severe events (minor myocardial infarction and angina pectoris) are considered, the overall impact of the disease on the population remained stable. CONCLUSION: Epidemiological surveillance of coronary syndromes is relevant over this time period of impressive changes in prevention and treatment. Continuing restrictions in available resources necessitate the development of simplified registration systems.

Adult↗

PubMed2001

Trends in coronary risk factors in the WHO MONICA project.

BACKGROUND: The World Health Organization (WHO) MONICA Project was established to determine how trends in event rates for coronary heart disease (CHD) and, optionally, stroke were related to trends in classic coronary risk factors. Risk factors were therefore monitored over ten years across 38 populations from 21 countries in four continents (overall period covered: 1979-1996). METHODS: A standard protocol was applied across participating centres, in at least two, and usually three, independent surveys conducted on random samples of the study populations, well separated within the 10-year study period. RESULTS: Smoking rates decreased in most male populations (35-64 years) but in females the majority showed increases. Systolic blood pressure showed decreasing trends in the majority of centres in both sexes. Mean levels of cholesterol generally showed downward trends, which, although the changes were small, had large effects on risk. There was a trend of increasing body mass index (BMI) with half the female populations and two-thirds of the male populations showing a significant increase. CONCLUSIONS: It is feasible to monitor the classic CHD risk factors in diverse populations through repeated surveys over a decade. In general, the risk factor trends are downwards in most populations but in particular, an increase in smoking in women in many populations and increasing BMI, especially in men, are worrying findings with significant public health implications.

Adult↗

PubMed2001

Socio-occupational differences in acute myocardial infarction case-fatality and coronary care in a northern Italian population.

AIMS: To appraise 28-day case-fatality of myocardial infarction (MI) among socio-occupational classes; to assess the consistency of the results for different degrees of MI severity; to explore if such differences are related to differences in management and treatment of the acute attack. METHODS: All coronary events (n = 1077), registered in 1993-1994 among the 35-64 year old male residents in MONICA Area Brianza were investigated and classified into diagnostic categories according to MONICA criteria. For all cases standardized information on acute coronary care and interventions before and during hospitalization was collected. Classification of social classes was derived from the Erikson-Goldthorpe-Portocarero social class scheme, based on information on occupational characteristics widely available in European countries. RESULTS: An increasing rate of case-fatality for decreasing levels of socio-occupational class was found. The social gradient resulted mainly from the higher incidence of out-of-hospital cardiac arrests. Treatment before and during the acute attack cannot explain the observed differences. CONCLUSION: Combining these results with those obtained in other MONICA centres, it appears that further decreases in coronary mortality might be achieved through specific programmes addressed in particular to the reduction of out-of-hospital case-fatality in lower social classes.

Adult↗

PubMed2001

[Identification of individuals with high coronary risk in the Italian population: indications of the Epidemiologic Cardiovascular Observatory].

BACKGROUND: The absolute global coronary risk has recently been introduced as an indicator of the incidence predicted by the main risk factors. It offers numerous options for the treatment of individuals at high risk. The identification of the absolute global coronary risk is produced through the application of functions obtained by longitudinal studies; their adequacy depends on the characteristics of the population from which they were estimated. The aim of this work was to evaluate the impact of the application of the absolute global coronary risk evaluation using the chart of risk proposed to the Italian physicians and to compare it with the results obtained from the application of other risk functions. METHODS: The database of the Osservatorio Epidemiologico Cardiovascolare (OEC), consisting of men and women aged 35-74 years, has been considered as being representative of the Italian population. The individual risk has been computed using the functions and coefficients from the Framingham study, the PROCAM study and the Seven Countries Study-Italy. The prevalence of high risk factors has been estimated on the basis of the recommendations on coronary prevention of the Task Force of the European Societies. RESULTS: The prevalence of high risk factors estimated by the Framingham function is 23.7% among men and 3.8% among women aged 35-74 years. In men aged 35-64 years, this estimated prevalence decreases from 14.2 to 8.7% when the Framingham function is adjusted using the mean value of the risk factors of the OEC, to 5.2% when the PROCAM function is applied, and to 1.1% when the function of the Seven Countries Study-Italy is employed. CONCLUSIONS: The application of the risk function suggested to the Italian physicians implies that more than 2,700,000 men and more than 500,000 women aged 35-74 years are potential candidates for treatment with lipid-lowering drugs. The comparison between the use of different functions in the OEC sample produces high numerical differences. The over-evaluation of the individual at high risk implies significant human and social costs. It is therefore essential to determine risk functions and coefficients derived from recent Italian studies including all age groups, both sexes and taking into account the different geographic characteristics of our country.

Adult↗

PubMed2000

Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations.

BACKGROUND: From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates across the populations. METHODS: In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. FINDINGS: Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, bodymass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. INTERPRETATION: Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

Adult↗

PubMed2000

Models to assess nitrogen losses in pediatric patients on chronic peritoneal dialysis.

To develop models to estimate nitrogen (N) losses of children on chronic peritoneal dialysis (CPD) from easily measurable indexes and laboratory tests, we measured the N content and all nitrogenous compounds in dialysate (D), urine (U), and feces over 3 days in 19 pediatric patients on CPD. Total measured N losses (TNm) were 5.56+/-2.26 g/day (69.9+/-11.1% in dialysate, 16.3+/-10.6% in urine, and 13.6+/-4.6% in feces). Correlation coefficients between measured dialysate and urinary N losses and the single nitrogenous compounds indicated values of over 0.9 only for urea in dialysate and urine; fecal N losses correlated well with body surface area (BSA). Taking into account these correlations, we developed a univariate additive model and three multivariate models to predict total estimated N losses (TNe). The best prediction of TNm was obtained with model 3, which considered not only urea output in dialysate and urine but also dialysate protein loss and BSA: TNe (g/day)=0.03+/-1.138 UN urea+0.99 DN urea+1.18 BSA+0.965 DN protein. A confirmatory analysis performed on a second group of 23 pediatric patients on CPD, using all four models, showed a higher percentage of studies with a relative difference between TNm and TNe less than 10% for model 3 than for the other models. Thus, N losses of pediatric patients on CPD can be estimated from measured urea and protein losses in dialysate and urea loss in urine, together with BSA.

Adolescent↗

PubMed2000

How to program rate responsive pacemakers.

Because oxygen uptake (VO2) increases linearly with heart rate during exercise, the oxygen pulse reserve (OPR) method (VO2 reserve divided by heart rate reserve) may provide a valid guide for rate responsive parameter tailoring. Using custom-made software (Pacing Rate Profile Software [PRPS]) it is possible to predict the exercise pacing rate profile with significant accuracy, according to the patient's functional class when ergospirometry apparatus is not available for a cardiopulmonary stress test (CPX). PRPS for Windows is based on the OPR method and some known workload/metabolic cost of exercise relationships during effort. The present study had two aims; first, to evaluate the reliability of PRPS in accurately predicting pacing rate profiles; and second, the suitability of activity and metabolic rate responsive sensors in supplying pacing rates sufficiently near to those predicted using CPX or PRPS. To test the reliability of PRPS we studied 244 patients, NYHA Class I-II, under two different stress test protocols. In one, the bicycle protocol (25 W, 2-minute steps), we tested 137 normal patients (94 men and 43 women, mean age 67 +/- 15 years). Sixty-eight of these were simultaneously CPX tested. PRPS predicted pacing rates were matched against the patients' sinus rhythms or their theoretical CPX measured VO2 heart rates (OPR method). Linear regression analysis was highly significant (r = 0.93 and r = 0.97, respectively). The other, the treadmill protocol, consisted of three different protocols. (1) Speed Incremental Treadmill Stress Test (SITST): 57 patients underwent CPX (33 men and 24 women, mean age 67 +/- 15 years, NYHA Class I-II). All had been pacemaker implanted for SSS and/or advanced atrioventricular block (AVB). PRPS pacing rates were matched against CPX VO2 OPR calculated heart rates (r = 0.93), (linear regression analysis). (2) CAEP: 30 patients underwent CPX (26 men and 4 women, mean age 61 +/- 11 years, NYHA Class I-II). Thirteen of them had been pacemaker implanted for SSS and/or advanced AVB. In all 30 patients the PRPS rates were matched against CPX VO2 calculated rates (r = 0.90). In the 17 normal nonimplanted patients, the PRPS rates were also matched against sinus rhythms, (r = 0.80). (3) Weber: 20 patients underwent CPX (16 men and 4 women, mean age 68 +/- 8 years, NYHA Class I-II). As above, in six normal nonimplanted patients, statistical analysis between PRPS rates and sinus rhythms was performed (r = 0.89). The comparison between PRPS theoretical pacing rates and VO2 predicted rates in all 20 patients was also statistically significant (r = 0.93). Finally, to test the reliability of PRPS also in NYHA Class III-IV patients, we tested 22 implanted patients (15 men and 7 women, mean age 70 +/- 9 years) and compared PRPS predicted rates against VO2 CPX measured rates (r = 0.92). To determine if the wide variety of RR pacers were able to supply pacing rates near to those predicted, whether by means of CPX or PRPS, we studied a total of 89 patients: 49 of these (26 men and 23 women, mean age 66 +/- 12 years) had been implanted with activity sensors; 12 patients (11 men and one woman, mean age 70 +/- 7 years) had been implanted with metabolic sensors, and finally 28 patients (19 men and 9 women, mean age 70 +/- 12 years) had been implanted with dual sensors (activity + QT or minute ventilation). Linear regression analysis showed r = 0.93 for activity sensors, r = 0.94 for metabolic sensors, and r = 0.92 for dual sensor. In conclusion, when rate responsive pacing causes symptoms or functional impairment, physicians must provide a personalized rate response tailoring derived from precise, simple physiological testing. OPR is an easy physiological method for tailoring rate response settings, suitable for activity and metabolic sensors. When ergospirometry apparatus is not available, PRPS can successfully replace CPX testing for tailoring.

Aged↗

PubMed2000

[The assessment of the coronary risk in a work setting. The results of the SEMM study and the outlook for prevention in Italy. Surveillance of Employees Municipality of Milan].

BACKGROUND: The goals of the present report are to assess the differences in distribution of traditional coronary risk factors in a work setting, aimed at identifying specific groups at risk and to compare mean values of such risk factors and of an overall risk score of the entire working sample with the results observed in the third WHO-MONICA population survey carried out in northern Italy (Area Brianza). METHODS: In the SEMM study 7872 employees (2601 men and 5271 women) were enrolled between 1992 and 1996. The third MONICA survey in Brianza was carried out on an age- and gender-stratified random sample of 831 men and 884 women in 1993-1994, selected from the 25-64-year-old residents of five municipalities, representative of the study population. In both studies coronary risk factors were measured according to the MONICA protocol, adopting standardized methods. RESULTS: In comparison with the MONICA population sample, the entire working group showed lower mean levels of blood pressure and total cholesterol, higher prevalence of current cigarette smokers and lower mean levels of HDL cholesterol, in both gender groups. Prevalence of overweight subjects was higher among men in the working group, but the opposite pattern was detected in women. The overall risk score, calculated using the coefficients of a proportional hazard survival equation estimated in a large collaborative Italian follow-up study, resulted lower in the working sample, in both gender groups. This result may be attributed to a selection bias known in occupational epidemiology as "healthy worker effect". In contrast to this finding, the prevalence of smokers, in particular among women, was higher in the employed sample, indicating that working stress conditions may play some role. CONCLUSIONS: In order to extend the assessment of cardiovascular risk factors as well as prevention activities in work settings, some advantages are highlighted: the high participation rates, the feasibility to adopt standardized protocols, and easier and cheap procedures for censoring in follow-up studies. Moreover, due to the recently adopted legislation in Italy which increases the number of working categories to be included in periodic clinical examinations, prevention activities in work settings to contrast the epidemic of widespread chronic diseases, like cardiovascular diseases, are encouraged. This will also allow for the investigation of individual variations over time of coronary risk factors.

Adult↗

PubMed2000

Pancreas transplantation at Northwestern University.

The collective advances made by many groups have significantly improved the results of pancreas transplantation. We have focused on the development of safe and effective immunotherapy, including a new protocol of rapid withdrawal of corticosteroids, the analysis of surgical technique of pancreas exocrine drainage on outcome and the role of SPK transplantation in patients with significant cardiovascular disease. We have found that multimodal immunotherapy including induction with tacrolimus-based maintenance combined with either MMF or sirolimus, with or without corticosteroids, resulted in excellent patient and graft survival rates with low rates of rejection. In this setting, enteric drainage was preferable to bladder drainage because of a lower rate of complications leading to hospital readmissions. Careful pretransplant screening for cardiovascular disease should be routinely performed for all SPK candidates. If successful coronary revascularization can be achieved, these patients can safely undergo SPK transplantation, with 5-year outcomes similar to those for recipients without coronary disease. Finally, we have observed that pancreas transplantation has an important ameliorating effect on hypertension that is independent of the method of pancreas exocrine drainage.

Adrenal Cortex Hormones↗

PubMed1999

Prothrombotic genetic risk factors in young survivors of myocardial infarction.

It has long been thought that an individual thrombotic tendency increases the risk of myocardial infarction, especially in young adults. Several "prothrombotic" genetic factors that may influence the individual thrombotic risk have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be associated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of the methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, and G20210A of the prothrombin gene), we performed a case-control study evaluating 200 survivors (185 men, 15 women) of myocardial infarction who had experienced the event before the age of 45 years and 200 healthy subjects with a negative exercise test, individually matched for sex, age, and geographic origin with the cases. The presence of the PIA2 polymorphic allele was the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals (CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, carrying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the only genetic prothrombotic factor associated with the risk of developing myocardial infarction at a young age. The clinical expression of this genetic predisposition seems to be enhanced by smoking.

Adult↗

PubMed1999

Antithrombotic therapy of unstable angina and non-Q-wave myocardial infarction.

Unstable angina and non-Q-wave myocardial infarction still represent an unsolved problem for clinicians, owing to their unpredictable evolution and high incidence of coronary events in the follow-up. Traditional antithrombotic agents, unfractionated heparin and aspirin, have been proved to be highly effective, but show some important limitations. New potent antithrombotic therapy have been studied to improve their efficacy, with encouraging results. Among these drugs, low molecular weight heparins (for subcutaneous administration) and inhibitors of platelet glycoprotein receptor IIb/IIIa (for intravenous, and possibly oral, administration) are the most promising and are now under extensive investigation.

Abciximab↗