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.

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.

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

Increased arterial stiffness in children with a parental history of hypertension.

The vascular dynamics of children with a parental history of hypertension has not been defined. The purpose of the current study was to determine whether or not these children have different arterial stiffness compared to the offspring of normotensive parents. One hundred healthy, nonobese subjects (ages 10-21 years) were divided into two groups of 50. Group A included the offspring of hypertensive patients and group B the offspring of normotensive parents. The variables studied were body surface area, blood pressure, and systolic and diastolic diameters of the aortic and carotid arteries as well as maximum velocity flow of these vessels. Carotid and aortic stiffness were calculated. Children and adolescents with a parental history of hypertension had higher carotid stiffness and smaller carotid diameters. These differences continued to be significant when correcting for body surface area. A higher blood pressure and a greater body surface area were also found.

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.

[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.

[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.

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.

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.

[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.

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.

[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.

[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.

Antihypertensive treatment with metoprolol or hydrochlorothiazide in patients aged 60 to 75 years. Report from a double-blind international multicenter study.

In a randomized double-blind study (N = 562), a traditional treatment schedule, starting antihypertensive treatment in elderly hypertensive patients (60 to 75 years old) with 25 mg of hydrochlorothiazide once daily and doubling the dose if a satisfactory response was not achieved, was compared with antihypertensive treatment of 100 mg of metoprolol once daily, adding 12.5 mg of hydrochlorothiazide for patients whose response was not satisfactorialy achieved with metoprolol alone. Systolic and diastolic blood pressure was significantly reduced with both regimens. The frequency rates of responders (diastolic blood pressure, less than or equal to 95 mm Hg) in the metoprolol group and the hydrochlorothiazide group were 50% and 47% after four weeks and 65% and 61% after eight weeks, respectively. There were no significant differences in total symptom score or single symptoms between the regimens, but significantly more patients had hypokalemia and hyperuricemia with the hydrochlorothiazide regimen. Thus, we conclude that beginning antihypertensive treatment with 100 mg of metoprolol once daily and adding a small dose of hydrochlorothiazide (12.5 mg) in patients whose response is not satisfactory with metoprolol alone appears to be effective and safe in elderly hypertensive patients.

[Simplified method of obtaining the correction factor for calculating ventricular volumes]. / Obtención simplificada del factor de corrección para el cálculo de los volúmenes ventriculares.

For the accurate measurement of ventricular volume it is required the obtainment of a correction factor for the magnification caused by the non-parallel X-rays and the "pincushion" distortion, which causes more magnification in the periphery than in the center of the fluoroscopic field. The Kasser and Kennedy method is based in the attainment of the relation between the actual and projected dimensions of a micrometrically calibrated grid filmed at the distance measured between the intensifier tube and the mid-thoracic line during the ventriculography. This technique is very accurate but expensive and troublesome. With the simpler catheter method it is obtained the relation between the projected and actual linear dimensions of the ventriculographic catheter inmediately before ventriculography. This study was aimed to compare the accuracy of the catheter method and two other proposed methods, in which the relation between the projected and actual dimensions were obtained by filming one central coin or five arranged through the fluoroscopic field at the distance measured between the tube and the patients during the ventriculography. These four correction factors were obtained in 15 patients undergoing a diagnostic cardiac catheterization. The catheter method showed a poor correlation with the grid method (r = 0.34), while both coin methods showed a high correlation with the grid method (r = 0.93 and 0.92, respectively). It is concluded that the catheter method is inaccurate and therefore is unwise to use it for the estimation of ventricular volumes. Because the peripheric distortion is clinically unimportant, the central coin methods is proposed as a simplified method for obtaining the magnification correction factor.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

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.