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Biomedical subjects

R Latini

Publications and source records attributed to R Latini.

At least 55 records · Page 3Linked to original sources
PubMed1997

Synthesis and pharmacokinetic behaviour of ester derivatives of 4-isobutylphenyl-2-propionic acid (Ibuprofen) with end-hydroxylated poly(N-vinyl pyrrolidinone) and poly(N-acryloyl morpholine) oligomers.

Four derivatives of 4-isobutylphenyl-2-propionic acid (Ibuprofen), in which the drug was bound by ester linkages to poly(ethylene glycols) (PEG 2000-I), monomethoxy poly(ethylene glycols) (PEG 1900-I), poly(N-vinyl pyrrolidinone) (PVP-I) and poly(N-acryloyl morpholine) (PACM-I), all having approximatively the same number average molecular weight (Mn congruent equal to 2000), were prepared and tested for their pharmacokinetic properties after oral administration. It was found that the two end-hydroxylated amphiphilic oligomers of polyvinylic structure, PACM and PVP, whose physico-chemical properties are comparable to those of PEGs especially as regards solvent affinity, have in principle a similar potential as promoieties for preparing oligomeric prodrugs.

Acrylic Resins↗
PubMed1997

Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study.

BACKGROUND: The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF). OBJECTIVES: Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s). DESIGN: Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II). SETTING: Sixty out-patient clinics in five countries. PATIENTS: Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less. INTERVENTIONS: In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.

Adrenergic beta-Antagonists↗
PubMed1996

Mechanism of inhibition of tumor necrosis factor production by chlorpromazine and its derivatives in mice.

In previous work, we reported that chlorpromazine inhibits tumor necrosis factor (TNF) production in endotoxin lipopolysaccharide-treated mice, and protects against lipopolysaccharide toxicity. Chlorpromazine is used as an antipsychotic and has several effects on the central nervous system. It acts on different neurotransmitter receptors and has other biochemical activities some of which, like inhibition of phospholipase A2, might be responsible for the inhibitory effect on TNF production. To investigate the role of these actions in the inhibition of TNF production by chlorpromazine, we have synthesized some chlorpromazine derivatives that do not have central activities. Some of these analogs have lost their affinity for various receptors and their phospholipase A2 inhibitory activity, but still inhibit TNF production. No correlation was found between TNF inhibition and the ability to inhibit nitric oxide (NO) synthase, whereas a good correlation was evident between TNF inhibition and antioxidant activity.

Animals↗
PubMed1996

Prognostic significance of heart rate variability in post-myocardial infarction patients in the fibrinolytic era. The GISSI-2 results. Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico.

BACKGROUND: Studies performed before the introduction of fibrinolysis showed that a low heart rate variability (HRV) is associated with higher mortality in post-myocardial infarction (MI) patients. We evaluated whether HRV adds information relevant to risk stratification in patients treated with fibrinolysis as well. METHODS AND RESULTS: From 24-hour ECG recordings obtained at discharge in patients treated with recombinant tissue-type plasminogen activator or streptokinase, we measured several time-domain indexes of HRV: standard deviation (SDNN), root-mean-square of successive differences (RMSSD), and number of RR interval increases > 50 ms ("NN50+"). The prognostic value of HRV for total and cardiovascular mortality was assessed. Of 567 patients with valid recordings, 52 (9.1%) died during the 1000 days of follow-up, 44 (7.8%) of cardiovascular causes. All indexes of low HRV were able to identify patients (16% to 18% of total population) with a higher total mortality (20.8% to 24.2% versus 6.0% to 6.8%, depending on index used). The independent predictive value of low HRV was confirmed by the adjusted analysis with the following relative risks: NN50+, 3.5 (95% CI, 1.9 to 6.7); SDNN, 3.0 (95% CI, 1.55 to 5.9); and RMSSD, 2.8 (95% CI, 1.5 to 5.3). Advanced age, previous MI, Killip class at entry, and use of digitalis were also independent predictors. Similar data were obtained for cardiovascular mortality. CONCLUSIONS: Time-domain indexes of HRV retain their independent prognostic significance even in post-MI patients of all ages treated with fibrinolysis.

Aged↗
PubMed1996

Trends and determinants of calcium antagonist usage after acute myocardial infarction (the GISSI experience).

In the last decade, several clinical trials in patients with, or recovering from, acute myocardial infarction (AMI) have evaluated the role of calcium antagonists in affecting patients' prognosis. Results have been disparate, with evidence of possible harm, no effect, or some benefit, depending on the agent used. We evaluated how the evidence from these trials has influenced the pattern of prescription of calcium antagonists and assessed the important determinants of use of these agents in patients after AMI. We analyzed retrospectively the prescription of calcium antagonists at discharge in all patients recovering from AMI enrolled in 3 large randomized clinical trials (Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto-1 [GISSI-1], GISSI-2, and GISSI-3) during the last 10 years. A progressive decrease in prescriptions for calcium antagonists was evident, from 47.2% in GISSI-1 to 35.1% in GISSI-2 to 19.0% in GISSI-3 (p<0.001). The presence of post AMI angina, history of hypertension, and occurrence of reinfarction were associated with a higher usage of calcium antagonists, whereas the use of beta blockers at discharge was a major independent negative determinant. Use of calcium antagonists for secondary prevention after AMI (i.e., without specific clinical indications for their use) decreased by approximately 60% (from 26.1% to 10.3%). The data indicate that the usage of calcium antagonists in GISSI studies has been strongly affected by the results of other large multicenter trials evaluating calcium antagonists. These agents are now prescribed in patients after AMI almost exclusively in the presence of specific indications such as systemic hypertension or angina.

Aged↗
PubMed1996

The prognostic value of predischarge quantitative two-dimensional echocardiographic measurements and the effects of early lisinopril treatment on left ventricular structure and function after acute myocardial infarction in the GISSI-3 Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.

BACKGROUND: Left ventricular dilatation and a low ejection fraction after acute myocardial infarction are independent indicators of a poor prognosis. ACE inhibitors have been shown to decrease left ventricular dilatation after myocardial infarction. In the GISSI-3 trial, patients were randomly assigned, within 24 h of onset of myocardial infarction symptoms, to 6 weeks of treatment with lisinopril, nitroglycerin, both or neither, in an open, 2 x 2 factorial design. The study showed that early treatment in relatively unselected patients with lisinopril decreases mortality at 6 weeks and severe left ventricular dysfunction. We assessed (1) the prognostic value of pre-discharge 2-D echocardiographic variables, and (2) the effects of lisinopril on the progression of left ventricular dilatation. METHODS AND RESULTS: 2-D echocardiograms were available pre-discharge in 8619 GISSI-3 trial patients discharged alive. In 6405 of these patients, a 2-D echocardiographic study was also available at 6 weeks, and at 6 months. Pre-discharge end-diastolic and end-systolic volumes, and ejection fraction predicted 6-month mortality and non-fatal clinical congestive heart failure (P < 0.01). The increase in left ventricular volumes over time was significantly reduced by 6 weeks' lisinopril treatment in patients with wall motion asynergy pre-discharge of > or = 27%. Patients with wall motion asynergy < 27% showed no dilatation and lisinopril did not affect volumes at 6 months. Patients randomized to lisinopril also had smaller volumes after withdrawal of treatment at 6 weeks. Lisinopril did not affect left ventricular ejection fraction. CONCLUSIONS: 2-D echocardiography independently contributes to pre-discharge risk stratification in terms of 6-month mortality and clinical heart failure after myocardial infarction, and early, short-term treatment with lisinopril in unselected myocardial infarction patients attenuates left ventricular dilatation; an effect evident in patients with larger infarcts. These results probably only partly explain the effect of lisinopril on total mortality concentrated in the first week after infarction.

Aged↗
PubMed1996

Effects of a new angiotensin-converting enzyme inhibitor (idrapril) in rats with left ventricular dysfunction after myocardial infarction.

We evaluated the effects of a new angiotensin-converting enzyme (ACE) inhibitor (idrapril) in terms of hemodynamics and ventricular remodeling after myocardial infarction in rats. The animals were randomly assigned to four experimental groups. Myocardial infarction was induced by left coronary artery ligation in the first two groups treated with either idrapril (300 mg kg-1 day-1) or vehicle for 4 weeks after myocardial infarction. Two groups of sham-operated rats were treated accordingly. Hemodynamics were measured, and the diastole-arrested hearts were analyzed morphometrically to quantify left ventricular (LV) remodeling and infarct size. In infarcted rats, idrapril reduced the arterial systolic blood pressure (SBP) from 128 +/- 10 to 97 +/- 6 mm Hg (p < 0.05) and LV end-diastolic pressure (LVEDP) from 19 +/- 3 to 13 +/- 3 mm Hg (p < 0.01). The decrease in diastolic wall stress conferred by idrapril to infarcted rats (from 499 +/- 99 to 269 +/- 68 dynes mm-2, p < 0.05) was mainly due to a reduction in LVEDP and, to a lesser extent, in LV volume. Idrapril also reduced body and heart weights as compared with those of vehicle-treated animals. Four-week treatment with idrapril initiated immediately after myocardial infarction reduced LVEDP and limited LV wall stress, a major prognostic factor for the progression toward chronic ventricular failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Myocardial infarction: when and how should we initiate treatment with ACE inhibitors? GISSI-3 Investigators.

Recent trials have shown that angiotensin-converting enzyme (ACE) inhibitors can reduce mortality and the occurrence of severe left ventricular dysfunction (LVD) when started within the first day after acute myocardial infarction and continued for 4-6 weeks thereafter. When started within this time window, ACE inhibitors are safe in relatively unselected myocardial infarction (MI) patients provided they are clinically and hemodynamically stable. GISSI-3, ISIS-4 and CCS-1 studies show that more than half of the lives are saved by ACE inhibitor treatment within the first week of therapy. Although the benefit from ACE inhibitors is larger in patients presenting with congestive heart failure (Killip class > 1), the number of lives saved in patients at low risk, who represent the majority of the population, is relevant. This supports the approach of treating all hemodynamically stable MI patients. Treatment could be stopped after about 1 month in patients without evidence of LVD while those with LVD should follow a long-term therapy with ACE inhibitors.

Adult↗
PubMed1995

A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group.

BACKGROUND: Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. METHODS: A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). RESULTS: The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P < 0.001). Mortality was 48.4, 48.6, and 52.1 percent, respectively (P = 0.638), up to the time of discharge from the intensive care unit and 62.3, 61.7, and 63.8 percent (P = 0.875) at six months. Among patients who survived, the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups. No differences in mortality among the three groups were found for any diagnostic category. A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates: 44.8, 40.4, and 39.0 percent, respectively (P = 0.478). CONCLUSIONS: Hemodynamic therapy aimed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients.

Adult↗
PubMed1995

Antiarrhythmic drug prescription in patients after myocardial infarction in the last decade. Experience of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI).

BACKGROUND: Recent clinical trials have shown increased, rather than decreased, mortality in patients treated with antiarrhythmic drugs after acute myocardial infarction. OBJECTIVE: To determine whether these findings had an impact on prescription of antiarrhythmic drugs after acute myocardial infarction. METHODS: We retrospectively analyzed the class I and III antiarrhythmic prescription data of 38,072 patients with acute myocardial infarction enrolled in three large randomized clinical trials endorsed by a highly representative sample (about 75%) of Italian coronary care units during the last 10 years. The first study was conducted in 1984 to 1985; the second, in 1988 to 1989; the pilot for the third, in 1991; and the third, in 1991 to 1994. RESULTS: Total class I and III antiarrhythmic prescriptions after acute myocardial infarction was halved during the last decade, from 11.9% at discharge and 14.4% at follow-up in 1984 to 1985 to 5.8% and 5.8%, respectively, in 1991 to 1994. The trend was independent of the different distributions in the three studies of the patients' characteristics associated with antiarrhythmic use (ie, age > or = 70 years, anterior acute myocardial infarction, ventricular fibrillation during hospitalization, and Killip class > or = 2 at randomization). The same decreasing trend was observed for each antiarrhythmic drug. The drug most widely used was amiodarone, accounting for about half of the antiarrhythmic prescriptions, followed by mexiletine hydrochloride and propafenone hydrochloride; flecainide acetate was dropped from the prescription list after the publication of the Cardiac Arrhythmia Suppression Trial results. CONCLUSION: The negative results of the recent clinical trials on class I antiarrhythmic drug use after acute myocardial infarction have been rapidly transferred into routine clinical practice in Italy, since the proportion of patients who received class I and III antiarrhythmic drugs after acute myocardial infarction was halved from the early 1980s to the early 1990s.

Aged↗
PubMed1995

A simple, automatic method for morphometric analysis of the left ventricle in rats with myocardial infarction.

Induction of acute myocardial infarction in the rat is an established model for studying effects of therapeutic interventions. Images of sections of the rat left ventricle, stained with nitroblue tetrazolium, were digitized and several parameters estimated by dedicated software on an image analyzer (IBAS 2.0). The method was tested on 7 rats with 48-hr-old myocardial infarction and 4 sham-operated controls. Infarct size can be evaluated by two largely used methods, based on area or on angular extension of the lesion. Results of the two methods are linearly correlated, but area calculations give values half of those obtained from angular extension. Five minutes were needed for a complete evaluation of a section of the left ventricle. Estimates of the parameters showed a relatively low between- and within-operator variability and a good correlation with a classic, but time-consuming, planimetric method. The method simultaneously measures infarct size and left ventricular geometry in the rat. The advantages over previous nonautomatic methods are simplicity, good reproducibility, and speed of execution, which make it particularly useful in the evaluation of drug effects.

Analysis of Variance↗
PubMed1995

Effects of an early treatment with lisinopril and isosorbide-5-mononitrate on hemodynamics and late ventricular remodelling in rats with 9-week myocardial infarction.

This study was undertaken to assess whether the converting enzyme inhibitor lisinopril, and the long-acting nitrate, isosorbide-5-mononitrate, affect left ventricle dysfunction and anatomical remodelling in rats with myocardial infarction. Lisinopril, isosorbide-5-mononitrate or vehicle were given to rats (n = 10-14 per group) immediately after coronary artery occlusion (by an intravenous bolus) and then for nine weeks (in drinking water). At the end of the study, left ventricular pressures were measured, the heart arrested in diastole, and infarct size, left ventricular chamber volume and wall thicknesses measured. Lisinopril significantly lowered systemic blood pressure and left ventricular systolic pressure in rats with small (< 15% scarred tissue of the left ventricle) and large (> 15%) infarcts; the weight of the left ventricle (including the septum) was reduced by 24% and 28% in animals with small and large infarcts, respectively. Lisinopril lowered left ventricular end-diastolic pressure (by 33% and 39%) and chamber volume (by 4% and 34%) in rats with small and large infarcts, respectively, compared with controls (NS). The combined anatomical and hemodynamic changes led to a reduction of the circumferential wall stress by 20% and 44% in lisinopril-treated rats with small and large infarcts, respectively (NS). No significant changes were seen in the nitrate-treated hearts compared with controls. Lisinopril, given early after myocardial infarction and continued for nine weeks, significantly affected cardiac hemodynamics and ventricular weights in rats with infarcts of different sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Effects of lisinopril and nitroglycerin on blood pressure early after myocardial infarction: the GISSI-3 pilot study.

OBJECTIVES: To evaluate the safety in terms of hypotensive action of nitroglycerin and lisinopril started early after myocardial infarction. PATIENTS AND METHODS: One thousand five hundred twenty-six patients with suspected myocardial infarction were randomized by 174 centers within 24 hours from the onset of symptoms to receive oral lisinopril (5 then 10 mg/day), nitroglycerin (intravenous infusion during the first 24 hours, then 10 mg/day transdermal), or neither. RESULTS: Systolic blood pressure, intensively monitored during the first 72 hours, decreased sharply by 11 mm Hg during the first 2 hours, then more slowly to an average value of 120 mm Hg. Nitroglycerin lowered systolic blood pressure during the first 24 hours by 2.7 mm Hg versus control subjects, and it was similar to control subjects from 24 hours. Lisinopril reduced systolic blood pressure by 4.2 mm Hg over 72 hours compared with control subjects. Persistent hypotension was significantly more frequent in the lisinopril group (21.4%) than in the nitroglycerin group (10.9%) or control group (9.8%), but absolute numbers of deaths in patients with persistent hypotension were almost identical. CONCLUSIONS: Lisinopril and nitroglycerin are both safe and effective in reducing blood pressure in the first day after myocardial infarction. However, the effect is lost thereafter with transdermal nitroglycerin, but persists with lisinopril.

Aged↗