Characterization of the cytotoxic effects of the combination of cisplatin and flavanol (-)-epicatechin on human lung cancer cell line A549. An isobolographic approach.

BACKGROUND: Among malignancies, lung cancer is a leading cause of death. Platinum-based therapeutic compounds used to treat lung cancer have not been able to increase the survival of patients and such compounds have a high incidence of adverse and toxic effects. It has been proposed that flavonoids such as catechins may significantly reduce the risk of developing cancer, alongside with other health benefits. The aim of this work was to determine the effect of (-)-epicatechin, the main flavanol found in cocoa, on the proliferation of the lung non-small cell adenocarcinoma cancer cell line A549, and to determine its effects when added simultaneously with cisplatin. MATERIALS AND METHODS: Concentration-response curves for cisplatin and epicatechin were obtained, inhibitory concentrations calculated and an isobolographic analysis was then performed. RESULTS: We found that epicatechin has a concentration-dependent inhibitory effect on proliferation of tumor cells and the isobolographic analysis reveals that the effect of its combination with cisplatin is synergistic. It was also observed that epicatechin promotes cell death by apoptosis. CONCLUSIONS: Epicatechin might be considered for future studies to explore its possible use as coadjuvant in cisplatin-based treatments.

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study.

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of

Cardiac amyloidosis, contrictive pericarditis and restrictive cardiomyopathy.

Cardiac amyloidosis is not characterized by a single hemodynamic pattern. Some of the cases present the clinical findings of restrictive cardiomyopathy and in these differentiation from constrictive pericarditis remains difficult in spite of the introduction of techniques designed to assess myocardial contractility and ventricular diastolic compliance. The clinical features and the demonstration of left ventricular diastolic pressure greater than right remain the most useful means of distinguishing restrictive cardiomyopathy from constrictive pericarditis. In other cases of cardiac amyloidosis the diastolic pressure is elevated throughout diastole and ventricular ejectile ability is lost. These cases do not simulate constrictive pericarditis and should not be classified as restrictive cardiomyopathy.

Echocardiographic changes after successful renal transplantation in young nondiabetic patients.

Eighteen young nondiabetic patients with chronic renal failure were studied by M-mode echocardiography before and three to 67 weeks after a successful renal transplant. Left ventricular mass (LVM), cardiac output (CO), and stroke work, which were increased before the operation, decreased afterward, in some cases to normal values. Both regression of the LVM and normalization of CO were detected as early as three weeks postoperatively and probably resulted from changes in the end-diastolic volume, mean systemic blood pressure, and hematocrit as a consequence of normal renal function. Because all the patients had normal left ventricular function and only moderate dilatation of the left ventricle, it is not known whether these striking beneficial changes after SRT also will occur in patients with significant dilatation or dysfunction of the left ventricle.

Structural and dynamic changes in the elastic arteries due to arterial hypertension and hypercholesterolemia.

Five groups of 20 patients each were studied to analyze the vascular dynamics and structure of the elastic arteries. Group I consisted of healthy young individuals (27 +/- 4 years); Group II of healthy adults (46 +/- 9 years); Group III of normotensive hypercholesterolemic adults (45 +/- 12 years and serum cholesterol > 239 mg/dl); Group IV of hypertensive normocholesterolemic adults (56 +/- 13 years); and Group V of hypertensive hypercholesterolemic adults (56 +/- 9 years). The differential arterial pressure was estimated and divided by the volume change (delta P/delta V) of the aorta and the carotid and brachial arteries. The volume change was calculated using the "cylinder formula", measuring the radius from the ultrasonographic vessel image and assigning the cylinder a height of 1 cm. The A/E index of the Doppler transmitral spectrum and the maximum velocity flow using Doppler in the above arteries were calculated. The presence of carotid atherosclerosis was observed and given an arbitrary scoring grade of 0, 1, or 2. A higher arterial and ventricular stiffness was found in the hypertensive patients regardless of the presence of hypercholesterolemia. A higher fall in Doppler velocity and an increase in atherosclerosis lesions were found in Group V. Based on the results of this study, it was concluded that vascular and left ventricular stiffness have a close relationship with arterial hypertension but not with hypercholesterolemia. The hypercholesterolemic patients had a higher prevalence of carotid atherosclerosis and a higher scoring grade of severity.

Vascular dynamics in isolated systolic arterial hypertension.

With a growing elderly population, the incidence of isolated systolic hypertension (ISH) has increased. This study characterizes dynamic vascular changes that occur with advanced age and with ISH. Fifty-five healthy individuals and seven with ISH were distributed in seven age groups from the second to the seventh decade. An index of aortic stiffness (delta P/delta V) was derived using a mercury sphygmomanometer to obtain pulse pressure, and ultrasonographic measurements were used to estimate aortic volumes applying the "cylinder formula." The mathematic derivation of this formula is explained in detail. Pulse pressure showed no significant change with age, but showed a significant increase with ISH. A decrease in volume change from systole to diastole was found with advanced age. Normotensive subjects aged 65 +/- 2 years had a 2.6-fold increase in aortic stiffness compared with young individuals. Elderly patients with ISH had a 7-fold increase in aortic stiffness compared with Group 1 (15 +/- 2 years) (p < 0.001) and a 2.7-fold increase compared with Group 6 (normotensive subjects aged 65 +/- 2 years). A strong correlation between systolic pressure and arterial stiffness was observed (r = 0.953) (p < 0.001). The proposed stiffness index was compared with the one described by Hirai, obtaining a high correlation, that is, r = 0.989 (p < 0.001). When compared with Stefanadis' index of distensibility, our index showed a correlation of r = 0.932 (p < 0.003). It is concluded that while systolic pressure is a main determinant of arterial stiffness, the delta P/delta V is a more sensitive method to estimate dynamic changes in elastic arteries such as the aorta.

Efficacy and tolerability of amlodipine in patients with mild-to-moderate hypertension.

Twenty-one subjects with mild or moderate systemic hypertension were treated for 12 weeks with amlodipine, a new calcium antagonist of the dihydropyridine group. Initial amlodipine dose was 5 mg once daily, but the dose could be increased after four or eight weeks to 10 mg once daily if diastolic blood pressure was not less than or equal to 90 mmHg (12.0 kPa). At the end of the study, a substantial reduction of systolic blood pressure (20 mmHg-2.7 kPa-from baseline) and diastolic blood pressure (14 mmHg-1.9 kPa-from baseline) was observed. Statistically significant changes in systolic and diastolic blood pressure were produced after four weeks of treatment. There were no statistically significant changes in heart rate throughout the study. Six patients with mild and five patients with moderate hypertension became normotensive after amlodipine treatment (64%). Two with mild hypertension finished the trial without change in hypertensive status, and four with initially moderate hypertension changed to mild at the end of the study. Only one patient dropped out due to an adverse reaction, two adverse events were rated severe, but did not require discontinuation. Overall impressions of efficacy were excellent or good in two-thirds of cases and poor in 10%; overall impressions of toleration were excellent or good in 71% of cases and poor in 10%. It is concluded that amlodipine is useful and well tolerated in patients with mild or moderate hypertension.

Cardiovascular risk factors in the urban Mexican population: the FRIMEX study.

BACKGROUND: Atherosclerotic ischaemic heart disease is the second leading cause of general mortality in Mexico due to the growing prevalence of atherosclerotic risk factors in our society. The data of the FRIMEX study (Factores de Riesgo en México, Risk Factors in Mexico), considered together with those of other contemporary epidemiological surveys, will aid in our comprehension of the current state of cardiovascular epidemics in Mexico. METHODS: Frequencies of obesity, hypertension and smoking, and total cholesterol and glucose in capillary blood were estimated in a non-probabilistic sample comprised of 140017 individuals (aged 44+/-13 years; 42% men and 58% women), from six Mexican cities (Mexico City, Guadalajara, Monterrey, Puebla, Leon and Tijuana). RESULTS: Obesity or overweight status was found in 71.9% of participants. Hypertension was found in 26.5%, and the proportions of awareness, treatment and control for this disease were 49.3, 73 and 36%, respectively. Prevalence of hypertension increased with age; while it was higher in men under 60 years of age, in the more aged individuals it was higher in women. Hypercholesterolaemia was found in 40% of the individuals and cholesterolaemia > or =240 mg/dl was significantly higher in women. Thirty-five and a half percent of men and 18.1% of women were smokers. Type 2 diabetes mellitus was found in 10.4% of participants. There was significant Pearson's correlation between body mass index and blood pressure, between hypertension and glucose levels, and between hypertension and total cholesterol concentrations. CONCLUSIONS: We conclude that this population has a high cardiovascular risk profile and a high probability of the occurrence of metabolic syndrome.

[Pulmonary complications of acute myocardial infarct. Therapeutic orientation]. / Las complicaciones pulmonares del infarto agudo del miocardio. Orientaciones terapéuticas

The heart and the lung make up an inseparable anatomic and functional unit. The changes in one affect the other and vice versa. In acute myocardial infarction a heart failure syndrome develops. This syndrome is characterized by passive pulmonary congestion, which leads to hypoxemia. This hypoxemia indicate the functional disturbance of the lung, and the hemodinamic evolution of the disease. Arterial gases determination is the best way to assess the sickness progression. A certain paralelism exists among the central venous saturation, cardiac insufficiency and the degree of pulmonary disfunction. Such a procedure is not very appreciable and does not substitute the direct analysis of the arterial PO2. The pulmonary complications in the myocardial infarction shock are directly responsable of death in 50% of the patients. To heart failure and shock, hipperfusion and hypoxia are added. Many vessels close due to the decrease in the pulmonary flow. This brings about the release of substances that are toxic to the vessel causing an inflammatory vascular reaction. The decrease in the flow harms the lung cell and for this reason atelectasia or alveolar colapse occur; besides inducing the formation of shunts. Under these conditions the lung compliance decreases. The areas that are badly ventilated and hypoperfused can easily become infected and pneumonitis and abscesses cause even more harm to the tissue. The decrease in the speed of circulation and hematologic changes of shock, induce a diseminated intravascular coagulation. What was stated before leads to an important reduction of the lung as a depurating organ and makes the shock irreversible. As far as therapy is concerned in the prevention of vascular colaps and the improvement of the oxemia, oxygen is very useful when there is a venous congestion (clinically, X rays, and oxemia). When the concentration of O2 is lower than 50% in the cases with slight cardiac failure; do not use oxygen in higher concentrations unless the hypoxia is associated to acute pulmonary edema and shock. Mechanic ventilators, and intermitent possitive pressure are recommended even though they have a posenous effect on the cardiac output. Always keep the air ways permeable: changing position, breathing exercises, humidifications, aspiration of secretions, intubation, or traqueostomy depending upon the various cases.

[The diastolic function of the left ventricle. I. The ventricular suction]. / La función diastólica del ventrículo izquierdo. I. El llenado ventricular.

The paper describes the normal and pathological characteristics of left ventricular filling. There are described some of the most sophisticated methods of assessing left ventricular function: The volume-time curve, the rate of change of left ventricular volume (dV/dt) and the pressure-volume loop. It is discussed the phenomenon of ventricular diastolic suction as an accessory mechanism of filling in some restrictive disorders.

[Electrocardiography changes in newborn infants during the 1st 6 weeks of life in Mexico City. Physiological implications]. / Los cambios electrocardiográficos en las primeras seis semanas de vida en los nacidos en la ciudad de Mexico. Implicaciones fisiológicas

The electrocardiograms of 150 newborns who were born in Mexico City (2,240 m. above sea level) were obtained in the first 24 hours of life and six weeks later. The electrocardiographic changes were similar to those observed at sea level; AQRS shifted to the left, the T waves became negative in the right precordial leads and the R/S relation increased in the left precordial leads. Mid-altitude does not affect the pulmonary vascular maturation of the normal newborn.

[Hemodynamic changes caused by prazocin in patients with uncomplicated arterial hypertension]. / Cambios hemodinámicos producidos por prazocin en pacientes con hipertensión arterial no complicada.

Hemodynamic changes produced by prazosin were evaluated in 19 patients with mild non complicated essential hypertension using M mode echocardiography. Patients received an initial dose of the drug of 0.5 mg tid, which was augmented gradually. As a whole, arterial pressure was reduced significantly. Heart rate did not show changes. Telediastolic and stroke volumes augmented significantly (p less than 0.05) and consequently cardiac output was increased. Systemic vascular resistance decreased notably (p less than 0.01). Left ventricular function indexes (EF, % shortening, Vcf) were not modified at all. These findings suggest that prazosin is a good antihypertensive drug and its actions upon the different hemodynamic parameters in normal and non complicated hypertensive patients are complex. Generally, it decreases systemic vascular resistance, without modification of contractility. Decreases in afterload were evident and something interesting, in contrast with other papers, is the demonstration of an augmented telediastolic volume, which indicates that the venodilatator effect with the consecutive decrease in blood return to the heart is masked by other effects. Nevertheless, it is necessary to perform a more detailed study with more sensitive methods in order to elucidate the complex hemodynamic interactions produced by prazosin in patients with mild non complicated essential hypertension.

[Comparison between echocardiographic and hemodynamic indices in the evaluation of mitral stenosis]. / Comparación entre los índices ecocardiográficos y hemodinámicos en la valoración de la estenosis mitral.

The echocardiographic data (the amplitude of the mitral echogram, the velocity of the E to F slope and the dimension of the left atrium) of 12 patients with mitral stenosis were compared with hemodynamic data obtained during a cardiac catheterization (the mitral valve area and the peak left ventricular filling rate, expressed in millimeters/second [dv/dtD] and normalized by the end-diastolic volume [dv/dtD/VTD seg-1]). None of the echocardiographic variables showed a good correlation with the hemodynamic indices. It is concluded that echocardiography is a useful total in the diagnosis of mitral stenosis, but at the same time there is not a single echocardiographic sign which by itself evaluate correctly the severity of mitral stenosis.

[Thrombolysis and beta-block in acute myocardial infarct. Their effects on left ventricular function]. / Trombolisis y betabloqueo en el infarto agudo del miocardio. Efectos sobre la función ventricular izquierda.

The effects of metoprolol or streptokinase or the combination of both drugs on left ventricular function and the rescue of the jeopardized myocardium in patients with acute myocardial infarction (AMI) were compared. Thirty-seven patients with AMI were allocated in 3 different groups: 19 received 15 mg of metoprolol i.v. in 15 minutes, 7 were treated with 1.5 million IU i.v. of streptokinase and 11 more received both drugs. The following variables were studied at control and one and twenty-four hours after treatment; blood pressure, heart rate, "double product", systolic time intervals, diastolic time and the sum of ST-segment elevation and the sum of the R wave in the EKG. Blood pressure, heart rate and "double product" decreased in the groups treated with metoprolol. The pre-ejection time/ejection time index did not change in any group. The diastolic time increased with metoprolol and the sum of ST-segment elevation was more reduced with the combined treatment. Also in this group, the sum of R wave did not decrease as it happened in the other 2 groups. It is concluded that the combination of streptokinase and metoprolol was more effective in the rescue of jeopardized myocardium than metoprolol or streptokinase administered alone.

[Differentiation of ejection systolic and regurgitant murmurs with inhaled isoproterenol]. / Diferenciación de los soplos sistólicos expulsivos y regurgitantes con isoproterenol inhalado.

A common clinical problem is the differentiation among ejection and regurgitant murmurs. Inhalation of amyl nitrite is useful for this purpose because it increases the intensity of ejection murmurs while decreases that of regurgitant ones. Because amyl nitrite is not easily available, inhaled isoproterenol was tested in seventeen patients with ejection murmurs and eighteen with regurgitant ones. Isoproterenol was administered at doses of 480-640 mcg, according to age and corpulence. The changes in murmur amplitude and heart rate were phonocardiographically registered immediately and then every 15'' up to a minute and a half after the inhalation, and were expressed as percent of change with respect to basal values. Heart rate increased in both groups. The intensity of ejection murmurs increased immediately and maximally 45'' after inhalation; on the contrary, the intensity of regurgitant murmurs decreased immediately and maximally 15'' after inhalation. It is concluded that isoproterenol, whose effects are similar to those of amyl nitrite, can substitute the latter in the clinical and phonocardiographically differentiation of systolic murmurs.

[Systolic stress in mitral stenosis]. / Estrés sistólico en la estenosis mitral.

Left ventricular systolic stress was studied in nineteen patients with mitral stenosis, twelve in sinus rhythm and seven in atrial fibrillation. Left ventricular dimensions and volumes and septal and posterior wall thickness were measured by means of M and two bidimensional echocardiography at rest and during isometric exercise. Expulsive indices: fractional shortening, ejection fraction and mean circumferential shortening rate were calculated. Ventricular mass, meridional stress and several end-systolic stress or pressure/volume relationships were estimated. Patients with atrial fibrillation were older and had systolic dysfunction: greater end-systolic volumes and depression of both expulsive fractions and some of the end-systolic indices. Preload and wall thickness were normal. Patients with atrial fibrillation showed higher ventricular stress as a consequence of greater ventricular dimensions. Ejection fraction correlates directly with mitral valve area and inversely with inotropic state and heart rate. It is concluded that systolic dysfunction in mitral stenosis is multifactorial. The most important determinants of the abnormality are heart rate and inotropic state. The study did not show any primary abnormality of afterload or hypotrophy of the left ventricle.

[Diagnostic and interventional heart catheterization through the radial artery]. / Cateterismo cardiaco diagnóstico e intervencionista a través de la arteria radial.

Diagnostic and interventional cardiac catheterization using the femoral approach demands hospitalization for more than 24 hours, and occasionally it is complicated by vascular events. This paper informs about out first 95 catheterizations using the radial percutaneous approach. We describe the technique, duration, length of hospitalization and complications. Eighty three male and 12 female patients, aged 54 +/- 12 years were included, 87 of them with coronary heart disease. There were 71 diagnostic procedures, 11 PTCA and 13 elective stenting. The initial success rate was 63% that reached 97% after three months. The mean duration was 46' for diagnostic procedures, 51' for PTCAs and 87' for stenting. Hospitalization length was 5, 31 and 39 hours respectively. Three patients lost the radial pulse, without distal ischemia. Pain was noticed in 16% of the cases. There were not other vascular complications. It is concluded that the percutaneous radial artery approach allows diagnostic and therapeutic procedures, with lesser hospitalization lengths and few vascular complications.

Complex angioplasty and stenting of a saphenous bypass graft using the percutaneous radial approach. Report of a case.

A severely diseased aortocoronary venous by-pass graft is reported. A successful angioplasty plus stenting was performed, via right radial artery, without using a guiding-catheter.

[The hostility complex and myocardial infarct]. / Complejo hostil e infarto del miocardio.

Several studies have associated the hostility complex (part of type A personality) to the development of coronary atherosclerosis. The complex is composed by aggressive behavior, frequent rage outbursts, intolerance to waiting lines and sense of urgency. To investigate the occurrence of this behavioral trait, 50 post-myocardial infarction men were compared against 50 normal male subjects of the same age. In all of them sphygmomanometric blood pressure was obtained, total blood cholesterol was measured and hostility was quantified by means of the Cook and Medley's questionnaire and an arbitrary ad hoc scale. Diastolic blood pressure was significatively higher in post-infarction patients (82 +/- 10 vs 77 +/- 9, p < 0.001), as well as the cholesterol level (231 +/- 55 vs 197 +/- 43, p < 0.001). Also, hostility score was higher in the post-infarcted men (16 +/- 4 vs 13 +/- 5, p < 0.001). The hostility score showed correlation with the occurrence of myocardial infarction (p < 0.02). These results establish that post-myocardial infarction patients express more hostility than control subjects. It was not possible to establish the true nature of the relationship among hostility and diastolic blood pressure, total cholesterol and the occurrence of coronary events. Nevertheless, this study confirms that the hostility complex is frequently present in atherosclerotic patients.