Clustering of traditional risk factors and precocity of coronary disease in women.

BACKGROUND: Women usually develop coronary artery disease (CAD) 10 years later than men do. CAD in women is associated with menopausal status and the number and intensity of risk factors. But, when the age gap between men and women narrows, less is known about the influence of risk factors on CAD. METHODS: We assessed the prevalence of traditional risk factors in 850 men and 468 women with stable CAD who had mean age, 58.3+/-8.6 and 58.8+/-10.3 years (P=NS), respectively. RESULTS: Univariate analysis of risk factors showed that body mass index (BMI), hypertension (all three stages), diabetes, triglycerides (> or =2.8 mmol/l), cholesterol (> or =6.2 mmol/l) and family history were more prevalent in women. Smoking and previous myocardial infarction (MI) were more prevalent in men. Multivariable analysis disclosed hypertension, diabetes, dyslipidemia and family history as independent risk factors for women with stable CAD and smoking and previous MI as independent risk factors for men. CONCLUSION: Clustering of traditional risk factors may explain the precocity of CAD in women who are near in age to men.

SPECT dipyridamole scintigraphy for detecting coronary artery disease in patients with isolated severe aortic stenosis.

BACKGROUND: The sensitivity and specificity of non-invasive methods--specifically single-photon emission computed tomography (SPECT) dipyridamole-thallium myocardial perfusion--for detecting coronary artery disease (CAD) in patients with severe aortic stenosis remains unclear. Occasionally, these patients present with atypical angina. Therefore, a CAD diagnosis must be excluded to prevent unnecessary cardiac catheterization. METHODS: To determine the diagnostic value of SPECT dipyridamole-thallium imaging in this population, we compared the effectiveness of the imaging procedure with that of coronary angiography by prospectively analyzing patients who underwent both procedures. Group 1 included 59 patients who were asymptomatic or had atypical angina; group 2; 51 preoperative aged-matched patients with typical angina. SPECT acquisition was performed 15 min after 0.142 mg/kg/min of dipyridamole infusion completion, and redistribution images were performed 4 h after thallium injection. Two cut-off values of luminal diameter narrowing, >50 and >70%, defined significant CAD. RESULTS: Coronary angiography with significant CAD (>50%) was present in 15 (25%) group 1 patients and in 16 (32%) group 2 patients (P=NS). The sensitivity was greater in group 2 than in group 1 (56 versus 26%; P=0.001). The specificity, positive and negative predictive value, and accuracy in the groups were similar. CAD of >70% luminal stenosis was present in 11 (19%) group 1 patients and in 12 (23%) group 2 patients (P=NS). The positive predictive value was greater in group 2 than in group 1 (75 versus 43%; P=0.001) but similar sensitivity, specificity, negative predictive value, and accuracy. The likelihood ratio for abnormal test increased in patients with CAD of >70%. CONCLUSIONS: symptoms of typical angina had significant impact on test sensitivity, positive predictive value and likelihood ratio for abnormal test. Furthermore, SPECT dipyridamole-thallium imaging was a useful non-invasive method to exclude the diagnosis of significant CAD (high specificity) in asymptomatic and symptomatic patients with isolated severe aortic stenosis.

[The role of quantitative determination of the volume fraction of interstitial collagen and fibronectin in the pathogenesis of myocardial remodeling in dilated cardiomyopathy]. / Rol' kolichestvennogo opredeliniia ob''emnoi fraktsii interstitsial'nogo kollagena i fibronektina v patogeneze remodelirovaniia miokarda pri dilatatsionnoi kardiomiopatii.

The role of myocardial fibrosis in the pathogenesis of left-ventriclar remodeling was studied in patients with idiopathic and ischemic dilatation cardiomyopathy. The percentage of volumic collagen fraction in the left-ventricular myocardium was significantly increased, this increase correlating with the degree of dilatation of left-ventricular cavity. A sufficient increase of plasma fibromectin level was observed in patients with idiopathic dilatation cardiomyopathy at all stages of circulatory insufficiency.

Trends in death from circulatory diseases in Brazil between 1979 and 1996.

OBJECTIVE: To analyze the trends in mortality due to circulatory diseases in men and women aged > or =30 years in Brazil from 1979 to 1996. METHODS: We analyzed population count data obtained from the IBGE Foundation and mortality data obtained from the System of Information on Mortality of the DATASUS of the Ministry of Health. RESULTS: Circulatory diseases, ischemic heart disease, and cerebrovascular disease were the major causes of death in men and women in Brazil. The standardized age coefficient for circulatory disease in men aged > or =30 years ranged from 620 to 506 deaths/100,000 inhabitants and in women from 483 to 383 deaths/100,000 inhabitants for the years 1979 and 1996, respectively. In men, the mean coefficient for the period was 586.25 deaths with a significant trend towards a decrease (P<0.001) and a decline of 8.25 deaths/year. In women, the mean coefficient for the period was 439.58 deaths, a significant trend towards a decrease (P<0.001) and a rate of decline of 7.53 deaths/year. The same significant trend towards a decrease in death (P<0.001) was observed for ischemic heart disease and cerebrovascular disease. Risk of death from these causes was always higher for men of any age group (P<0.001). Cerebrovascular disease was the primary cause of death in women. CONCLUSION: Although circulatory diseases have been the major cause of mortality in men and women in the Brazilian population, with a greater participation by cerebrovascular diseases, a trend towards a decrease in the risk of death from these causes is being observed.

Apolipoproteins AI, B, and E polymorphisms in severe aortic valve stenosis.

Hypercholesterolemia has been related to aortic valve stenosis (AS). Polymorphisms of apolipoproteins (apo) AI, B, and E are associated with variable levels of plasma lipids, but the association between these polymorphisms and AS is unknown. In a case-control study of groups matched by age, sex, comparable body mass index, hypertension, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, we analyzed the distribution of apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length. and apo E polymorphisms in 62 non-diabetic patients with severe aortic valve stenosis and 62 control subjects. All patients underwent echocardiographic analysis. Univariate analysis showed a higher prevalence of the XbaI X + /X + genotype (p = 0.007) of apo B and the apo E2 allele (p = 0.034) in patients with severe AS. Apo polymorphisms were not associated with lipid levels, left ventricular mass, or the aortic gradient.

Angiotensin-converting enzyme and apolipoproteins genes polymorphism in coronary artery disease.

BACKGROUND: Association between angiotensin-converting enzyme (ACE) as well as apolipoprotein (apo) AI, B, and E polymorphisms and dyslipidemia and coronary artery disease (CAD) is controversial. HYPOTHESIS: This study assessed the distribution of ACE insertion/deletion, apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length, and apo E polymorphisms in 388 nondiabetic patients. METHODS: The study population included 112 patients with stable CAD, 139 patients with acute myocardial infarction (AMI), and 137 age-matched control subjects. RESULTS: Univariate analysis showed higher prevalence of XbaI X+/X+ genotype in patients with CAD (p = 0.02). Angiotensin-converting enzyme and apo polymorphisms were not associated with lipid levels or severity of CAD. When all genotypes known to be related to CAD; such as ACE DD, apo AI GG, apo B del/del, and XbaI X+X+, and E4 allele of apo E, were pooled, again no significant differences among groups were seen. Multivariate regression analysis disclosed traditional risk factors and elevated levels of apo B for men and reduced levels of apo AI for women as independent variables for CAD. CONCLUSIONS: In addition to traditional coronary risk factors, apo B and AI could be considered predictors of CAD. No association between either form of CAD and polymorphisms was noted.

Angiotensin-converting enzyme and apolipoprotein B polymorphisms in coronary artery disease.

The association between angiotensin-converting enzyme (ACE) as well as apolipoprotein B polymorphisms and dyslipidemia and coronary artery disease (CAD) is controversial. We assessed the distribution of ACE insertion and/or deletion, apolipoprotein B signal peptide insertion and/or deletion, and apolipoprotein B XbaI restriction fragment length polymorphisms in 388 nondiabetic patients. We studied 112 patients with angiographically defined asymptomatic CAD or with stable functional classes I and II angina and 139 patients with acute myocardial infarction who were age matched to 137 control subjects. Univariate analysis showed higher prevalence of Xba50% reduction of lumen diameter. Overall, multivariable regression disclosed traditional risk factors and elevated levels of apolipoprotein B for men and reduced levels of apolipoprotein AI for women as independent variables for CAD. After adjustment for the most important subset of risk factors (age, hypertension, hypercholesterolemia, and smoking), apolipoprotein B XbaI polymorphism was disclosed as an independent variable for CAD. Apolipoprotein B XbaI was also selected as an independent variable for acute myocardial infarction after adjusting for age, hypertension, hypercholesterolemia, and smoking. Thus, in addition to traditional coronary risk factors, apolipoproteins B and AI, and apolipoprotein B XbaI polymorphism could be considered predictors of CAD.

Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability.

The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) > or = 115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10, 20, 30, 60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18%, P = NS), DBP (14 vs 8%, P = NS) and HR (22 vs 28%, P = NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 +/- 72 vs 41 +/- 12 ng/ml, P < 0.05; time to reach CMAX (TMAX): 34 +/- 18 vs 52 +/- 11 min, P < 0.05; biological half-life (t1/2b): 0.91 +/- 0.54 vs 2.41 +/- 1.16 h, P < 0.05; area under the curve (AUCT): 245 +/- 134 vs 79 +/- 54 ng h-1 ml-1, P < 0.05; total body clearance (CLT/F): 44 +/- 23 vs 26 +/- 12 ml min-1 kg-1, P = NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.

Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability

The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) =115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10,20,30,60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18 percent, P=NS), DBP (14 vs 8 percent, P=NS) and HR (22 vs 28 percent, P=NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 + 72 vs 41 + 12 nl/ml, P<0.05; time to reach CMAX (TMAX): 34 + 18 vs 52 + 11 min, P<0.05; biological hall-life (t1/2b): 0.91 + 0.54 vs 2.41 + 1.16 h, P<0.05; area under the curve (AUCT): 245 + 134 vs 79 + 54 ng h(-1) ml(-1), P<0.05; total body clearance (CLT/F):44 + 23 vs 26 + 12 ml min(-1) kg(-1), P=NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.

[Prostaglandin D2-synthase from cattle brain: purification and physico-chemical properties]. / Prostaglandin D2-sintaza iz mozga byka: ochistka i fiziko-khimicheskie svoistva.

Prostaglandin D2-synthase has been purified from bovine brain for the first time and characterized. The enzyme has a molecular mass of 21 kDa and a pH optimum at 9.0 and is activated by dithiothreitol. The presence in the enzyme molecule of carbohydrates and lipids has been established and a preliminary conclusion made about the qualitative composition of the lipids. The ability of the enzyme to form aggregates under the influence of the detergent has been demonstrated. The role of the lipid component in the preservation of the enzyme monomeric structure as well as the possible mechanisms of action of the above inhibitors and activators are discussed.

Evaluation of a comprehensive algorithm for blunt and penetrating thoracic and abdominal trauma.

The objective was to develop a single branched-chain decision tree for both blunt and penetrating thoracic and abdominal trauma and to test its feasibility to track clinical decisions. The algorithm consisted of 14 specific patient management loops and 31 decision nodes. During a 4-month period, the management decisions and clinical course of 434 trauma patients were prospectively observed. Thirty-four patients had no signs of life on arrival to the emergency department (ED) and were excluded from the statistical evaluation; the remaining 400 patients constituted the study group. The mean Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Trauma Score (TS) scores in the series were 21 +/- 10, 34 +/- 12, and 13 +/- 3. The overall patient mortality of the study group was 17 per cent; it was 61 per cent in those patients with major deviations from the algorithm and 6 per cent in patients who complied with the algorithm. The ISS, PATI, and TS scores were 29 +/- 9, 32 +/- 12, and 13 +/- 2 in patients with deviations and 20 +/- 10, 37 +/- 12, and 14 +/- 2 in patients who complied with the algorithm. Of the 37 patients who died with major deviations from the algorithm, the deviation was directly contributory to death in 21 cases (57%) and probably contributory in another 14 cases (38%). There were 108 patients with ISS scores between 20 and 50. In this group, mortality was 55 per cent when a major deviation occurred and 5 per cent without major deviations from the algorithm. The authors conclude that the survival of trauma patients may be improved by following the specific management criteria outlined by the algorithm.

[Comparison of the effects of diazepam, nifedipine, propranolol and a combination of nifedipine and propranolol, by sublingual administration, in patients with hypertensive crisis]. / Efeito comparativo do diazepam, nifedipina, propranolol e da associação nifedipina e propranolol, por via sublingual, em pacientes com crise hipertensiva.

PURPOSE: To evaluate the effects of sublingual administration of diazepam, nifedipine, propranolol and the association of nifedipine with propranolol patients with hypertensive crisis. METHODS: Eighty patients with hypertensive crisis, DAP greater than 120 mmHg, and mean age of 54 +/- 7.4 years, 33 women and 47 men, were evaluated. The AP was measured with an aneroid sphygmomanometer, in mmHg, in orthostatic position, before and after 10, 20, 30 and 60 minutes of treatment. The heart rate in one minute was also measured at the same intervals. The patients were divided randomly into four groups and treated, respectively, with 10 mg of diazepam, 10 mg of nifedipine, 40 mg of propranolol and 10 mg of nifedipine associated with 40 mg of propranolol. RESULTS: A significant and gradual reduction of SAP and DAP were observed in all groups of patients. The percentage of reduction, after 60 minutes, for SAP was, respectively, 10.1%, 12.9%, 15.4% and 16%, and for DAP 7.7%, 11.3%, 13.6% and 13% in groups I to IV. The heart rate did not change in groups I and II, but significative reduction was observed in groups III (p = 0.002) and IV (p = 0.009). CONCLUSION: The drugs used were effective for the treatment of hypertensive crisis, and the sublingual administration is an important and easy way for their administration.

Changes in the activity of enzymes, participating in glycogen metabolism of alloxan diabetic rats.

Alloxan diabetes induced in white rats by intraperitoneal injection of alloxan-monohydrate (15 mg/100 g body weight) was used to study changes in the glycogen phosphorylase a and b, phosphoprotein phosphatases and hexokinase activities under insulin deficiency conditions. Among the enzymes studied, an increase in muscle phosphorylase a activity as well as the a/b ratio have been obtained. In diabetic muscle phosphoprotein phosphatases and hexokinase activities were diminished. AMP increased the liver glycogen phosphorylase activity twice in diabetic rats whereas in normal animals the enzyme was less sensitive to this effector. The changes in liver hexokinase activity at diabetes were not connected and correlated with the altered phosphorylase and protein phosphatase activities. The logical chain of probable molecular events taking place in muscle glycogen metabolism under the conditions of insulin deficiency is offered.

[Status of the microcirculatory bed in healthy newborn infants in the postnatal period]. / Sostoianie mikrotsirkuliatornogo rusla v postnatal'nom periode u zdorovykh novorozhdennykh.

Noncontact biomicroscopy of the vessels of the bulbar conjunctiva was employed to examine the microcirculatory bed in 91 normal full-term infants, who received 8-9 points according to Apgar's scale, in the course of the postnatal period. Immaturity and fragility of the vessels, the spastic status of the arterioles and enlargement of the respective venules accompanied by the outflow embarrassment were discovered along with the rheological properties and great compensatory possibilities of the microcirculatory bed, favouring the children's normal adaptation following birth.

[Use of lithium carbonate and vitamin E in the complex treatment of epileptics]. / Primenenie karbonata litiia i vitamina E pri kompleksnoi terapii bol'nykh épilepsiei.

Using clinico-biochemical and EEG examinations, the authors have studied over time 30 epileptic patients who along with anticonvulsants received lithium carbonate orally and vitamin E in injections. Before the administration of the above drugs epileptic patients with a progressive course of the disease showed intensified lipid peroxidation, low levels of total and free cholesterol of erythrocyte membranes, elevated concentrations of vitamin E and a decreased activity of superoxide dismutase (SOD) in the blood. The use of lithium carbonate and vitamin E leads to a considerable decrease in lipid peroxidation, an elevation in the content of total and free cholesterol of red cell membranes and an increased SOD activity in the blood. There was also a considerable improvement in EEG parameters. The above positive changes in paraclinical indices were accompanied by a reduction in the frequency of epileptic attacks and affective calming of patients. The authors believe that the obtained results can be explained by the normalization of the cell membrane permeability and recommend that lithium carbonate and vitamin E be included into the array of anticonvulsive drugs.