Interaction of six candidate genes in essential hypertension.

We explored the interaction of 6 candidate genetic mutations in essential hypertension (EH). The mutations AGT M235T, ACE I/D, eNOS Glu298Asp, ET-2 A985G, ANP T2238C, and NPRC A-55C were detected using a genechip microarray in 100 patients with EH and 97 controls from the Han population living in the Yunnan Province of China. Risks of EH were evaluated with respect to a combination of these genotypes. Interactions were analyzed using multifactor dimensionality reduction (MDR). P values were corrected using Bonferroni's adjustment. Results showed that CC genotype frequencies for NPRC A-55C (0.540) in EH were significantly higher than those in controls (0.237, Pc < 0.01; odds ratio (OR) = 3.777; 95% confidence interval (CI) = 2.050-6.960). The OR for NPRC A-55C CC combined with ET-2 A985G GG increased to 4.673 and to 5.529 when the MT genotype of AGT M235T, the EE genotype of eNOS Glu298Asp, the GG genotype of ET-2 A985G, and the CC genotype of NPRC A-55C were combined. MDR showed that ET-2/NPRC is the best model (OR = 4.002; 95%CI = 2.1597-7.4159). The CC genotype for NPRC A-55C and the G allele for ET-2 A985G were associated with susceptibility to EH. Although the contributions of the candidate genes differ, they may have cooperative effects on conferring risk for EH. Moreover, potential gene-gene interactions were found between ET-2 A985G and NPRC A-55C in EH.

Atrial natriuretic peptide elevation in congestive heart failure in the human.

A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.

Total correction of tetralogy of Fallot at age 40 years and older: long-term follow-up.

Whether total surgical correction of tetralogy of Fallot in adults aged 40 years old or older has acceptable operative risk and gratifying long-term results is unknown. The Mayo Clinic experience (June 1960 to May 1982) with 30 patients 40 to 60 years old (mean 47) who had total surgical correction of tetralogy of Fallot was reviewed. Preoperatively, 4 patients (13%) were in functional class I, 9 (30%) in class II and 17 (57%) in classes III and IV. Eight patients (27%) had had preoperative complications: five had a cerebrovascular accident and three had infective endocarditis. Only 11 patients (37%) had had palliative surgery 16 to 34 years (mean 22) before total surgical correction. Total surgical correction was successful in all patients. Right ventricular to left ventricular (RV/LV) pressure ratio of 0.65 or less was achieved in 28 (93%) of the 30 patients. One patient died of ventricular fibrillation (RV/LV ratio = 0.8) 2 days postoperatively, one had complete heart block and one had a cerebrovascular accident 7 days after operation. At follow-up of 5 to 266 months (mean 110), there were seven late deaths: two sudden at 5 and 21 years, respectively, after operation, one from myocardial infarction at 11 years, one from cerebrovascular accident at 11 years, one from congestive heart failure (RV/LV ratio = 1.0) at 8 years and two from noncardiac causes. Of the 22 patients who survived, 16 are in class I, 5 are in class II and 1 is in class III.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomic and functional significance of a hypotensive response during supine exercise radionuclide ventriculography.

The significance of a decline in systolic blood pressure (BP) during supine exercise was examined in 820 patients who underwent both supine exercise gated equilibrium radionuclide ventriculography and coronary angiography. Twenty-seven patients, 3% of the study population, had a decrease in systolic BP at peak exercise of more than 10 mm Hg from the systolic BP at rest. Other indicators of ischemia--angina, ST-segment depression, a decrease in ejection fraction and wall motion abnormality during exercise--were present frequently but not uniformly in these patients. Although most patients had a decline in ejection fraction and a new wall motion abnormality with exercise, 4 patients had an increase in ejection fraction with exercise without any regional wall motion abnormalities. Coronary angiography in the 27 patients with systolic hypotension demonstrated severe coronary artery disease (CAD). Twenty-two patients (81%) had 3-vessel or left main CAD. Twenty of these 22 patients with 3-vessel CAD had at least 2 arteries with 90% or more diameter stenoses. Systolic hypotension during supine exercise radionuclide angiography is infrequent, usually associated with evidence of global and regional left ventricular dysfunction, and a marker of very severe CAD.

Effects of dietary calcium on atrial natriuretic factor release from isolated rat atria.

Previous studies have shown that acute calcium load causes an increase in circulating plasma atrial natriuretic factor (ANF) levels. The present study was conducted to examine the effect of high dietary calcium on ANF release. Experiments were performed on two groups of male Wistar rats. Hypercalcemic (n = 12) and normocalcemic (n = 12) animals were placed on a high and normal calcium diet, respectively, for 14 days before study. A 24-hour renal clearance was conducted on all animals before superfusion studies. Clearance results showed that high dietary calcium induced a significant increase in plasma calcium (2.69 +/- 0.02 v 2.90 +/- 0.77 mmol/L; P less than .01). This elevation is plasma calcium was associated with a marked increase in calcium excretion (fractional excretion of calcium, 1.91% +/- 0.33% v 8.17% +/- 0.11%, and was correlated with a significant increase in plasma ANF levels (97 +/- 6 v 167 +/- 20 pg/mL). We also measured immunoreactive ANF in the atria of hypercalcemic and normocalcemic rats. ANF content and concentration in the atria were lower in hypercalcemic (465 +/- 36 ng/mg) than in normocalcemic rats (635 +/- 30 ng/mg). This implies that ANF secretion is stimulated by hypercalcemia. To examine this directly, the right atrium from hypercalcemic and normocalcemic rats was superfused in a modified Langendorff preparation. Spontaneous release of ANF from the isolated right atria of hypercalcemic animals (19 +/- 0.8 pg/min/mg) was significantly higher (P less than .01) than from the normocalcemic rats (8.6 +/- 0.3 pg/min/mg). These results suggest that elevation of plasma ANF levels in hypercalcemia is due to an increase in ANF secretion.

The differential response in atrial natriuretic peptide release during exercise in patients with and without ischemic heart disease.

The elevation of cardiac filling pressure induces the release of atrial natriuretic peptide into the circulation. Ischemia during exercise in patients with coronary artery disease may manifest itself with elevation of cardiac filling pressure before the onset of electrocardiographic changes or chest pain. Thus, patients with ischemic heart disease might have an elevated circulating atrial natriuretic peptide after exercise. The present study investigated the effect of exercise on circulating atrial natriuretic peptide in patients with and without ischemic heart diseases. Group 1 was composed of five patients who had ischemic heart disease by clinical history, previous myocardial infarction, angina or angiographically proven coronary artery disease and positive electrocardiogram during exercise. Group 2 was composed of five patients without ischemic heart disease and negative electrocardiogram response. Heart rate, blood pressure, and atrial natriuretic peptide were measured during routine treadmill exercise testing using the Bruce protocol. Our results indicate that the rate of rise of heart rate (12.3 +/- 1.8 vs. 8.5 +/- 0.7 beats/min/min), blood pressure (7.1 +/- 1 vs. 4.2 +/- 0.8 mm Hg/minute), and atrial natriuretic peptide (4.1 +/- 1 vs. 1.4 +/- 0.3 pg/ml/min) was significantly elevated in patients with ischemic heart disease compared to the group 2 patients. These findings suggest that the disproportionate elevation of atrial natriuretic peptide after exercise in ischemia may be caused by elevation of cardiac filling pressure, which may provide a noninvasive method for the diagnosis of ischemic heart disease.

Spontaneous closure of congenital ventricular septal defect in an adult.

Spontaneous closure of congenital ventricular septal defect occurs commonly in infants and young adults. Occurrence in adults--patients older than 21 years--however, is rare. For this reason, we report on spontaneous closure of a congenital ventricular septal defect in a patient older than 26 years. This case was documented by catheterization before and after spontaneous closure. They proposed mechanisms of spontaneous closure are briefly reviewed.

Long-term efficacy of recombinant interferon alpha 2a in the treatment of chronic hepatitis C: a randomized prospective study comparing two dose schedules in Chinese patients.

BACKGROUND/AIMS: This study is the first randomized prospective clinical trial of interferon in hepatitis to be conducted according to the guidelines of Good Clinical Practice (GCP) in China. The object of this study is to compare the long-term efficacy of a dose of 3MU of recombinant IFN alpha 2a (rIFN-alpha 2a) three times a week (t.i.w.) for 6 months with a starting dose of 6MU for 3 months and subsequent reduction to 3 MU t.i.w for a further 3 months. METHODOLOGY: Sixty-eight serological and histologically proven chronic hepatitis C patients with elevated serum ALT were randomized into two groups. A total of 63 patients were studied with full course of treatment. Five patients were withdrawn from the trial, 2 due to personal reasons and 3 due to adverse drug reactions during treatment. Thirty patients received 6MU IFN-alpha 2a t.i.w. for 3 months followed by 3MU t.i.w. for another 3 months (group A). Thirty-three patients received 3MU IFN-alpha 2a t.i.w. for 6 months (group B). RESULTS: The sex, age, baseline serum bilirubin, ALT and AST levels were matched in both groups. At the end of 6 months the complete and partial response rates in group A were 60.0% and 16.7%, respectively, and the clearance of serum HCV-RNA was 53.3%. In group B, the complete and partial response rates were 72.7% and 3.0%, respectively, and the clearance of HCV-RNA was 61.3%. These patients were followed up for 6, 12, and 18 months after stopping treatment. In group A, the rates of complete normalization of ALT and clearance of serum HCV-RNA at 24 months were 50.0% and 60.0%, respectively. In group B, the rates of normalization of ALT and clearance of HCV-RNA at 24 months were 54.4% and 41.9%, respectively. The efficacy between the two groups showed no statistically significant difference; the response rates of treatment were similar to the patients with HCV genotype 1b and 2a. Six patients (10.8% of the study population) developed neutralization antibodies to IFN-alpha 2a during treatment, 4 of them responded to the treatment. Adverse drug reactions (ADR) were common, but most of them were tolerable and the incidence of ADR was similar in both groups. CONCLUSIONS: IFN-alpha 2a is effective in the treatment of Chinese patients with chronic hepatitis C. The sustained response rates and ADR among two dose schedule groups are similar.

[A statistical wavelength selection method of infrared spectra used in exhaust gas detection].

In order to extract the quantitative features of the rare pollution components from noisy atmospheric infrared spectra and thus create calibration models, a wavelength selection method based on statistic theory is proposed in this paper. In this method, an objective function is defined based on the estimation of spectral noise level at every wavelength position. Because the size of the wavelength subset is also included in the function, the model size will not become too big during the minimization of the error of the calibration model. To test the performance of this method, the wavelength subsets of measured spectra with background noises were selected and the calibration models were then created using neural network technique for three pollution gases, respectively. The test showed that the sizes of the selected wavelength subsets accorded with the calculated results. The subset sizes were less than 2% of the total wavelength points. Meantime, the spectral noises were also restrained markedly in the calibration model because of the wavelength selection. The experimental results proved the validity of the wavelength selection method.

[Maximal entropy principle wavelet denoising].

In the filed of wavelet denoising, an essential problem is how to determine the cutting threshold of wavelet coefficients that divides the coefficients corresponding to signal and noise respectively. The wavelet denoising method discussed here determines this threshold by using the maximal entropy principle (MEP) of information theory. From the basic principle of probability theory, it can be deduced that the detailed wavelet coefficients sequence of an arbitrary distributed random noise sequence satisfies a normal distribution. Based on this conclusion, an optimal threshold is determined using MEP. Such that the coefficients whose absolute values are less than the threshold satisfies a normal probabilistic distribution. This threshold is an optimal value that distinguishes the wavelet coefficients of signal and noise in view of statistics. The simulation analysis using spectral data and the comparison with other methods showed that this method provides a best improvement of signal-to-noise ratio, and its performance is least sensitive to the change of signal-to-noise ratio.

[Input layer self-construction neural network and its use in multivariant calibration of infrared spectra].

In order to solve the problems of feature extraction and calibration modelling in the area of quantitatively infrared spectra analysis, an input layer self-constructive neural network (ILSC-NN) is proposed. Before the NN training process, the training data is firstly analyzed and some prior knowledge about the problem is obtained. During the training process, the number of the input neurons is determined adaptively based on the prior knowledge. Meantime, the network parameters are also determined. This algorithm of the NN model helps to increase the efficiency of calibration modelling. The test experiment of quantitative analysis using simulated spectral data showed that this modelling method could not only achieve efficient wavelength selection, but also remarkably reduce the random and non-linear noises.

Effect of dietary magnesium on atrial natriuretic peptide release.

Magnesium is the second most abundant divalent ion in the body, but the effects of this cation on atrial natriuretic peptide (ANP) release have not been examined. The present study was conducted to determine the effect of magnesium on ANP secretion. Experiments were conducted in six groups of male Wistar rats. Each group was assigned a diet containing a different amount of magnesium. Plasma magnesium was 0.42 +/- 0.01, 0.63 +/- 0.01, 0.75 +/- 0.02, 0.97 +/- 0.03, 1.03 +/- 0.01, and 1.19 +/- 0.01 mM in groups I, II, III, IV, V, and VI, respectively. Plasma ANP concentration was significantly higher in the hypermagnesemic animals and significantly lower in the hypomagnesemic rats. A significant positive correlation was found between plasma magnesium and plasma ANP levels (y = 88 + 23 chi; r = 0.46; P less than 0.01). ANP concentration in the atria was lower in hypomagnesemic rats and higher in hypermagnesemic rats. This suggests that the low concentrations of ANP found in the plasma of hypomagnesemic animals were due to the lack of ANP in the atria. The atria from the various groups were isolated and perfused in a modified Langendorff apparatus to measure the rate of ANP secretion. Our results showed that the hypomagnesemic rats have a lower release rate as opposed to that seen in hypermagnesemic animals. A significant correlation was also seen between ANP secretion and tissue ANP concentration. The higher rate of ANP release from the heart of hypermagnesemic animals was due to the presence of more ANP, which was reduced during hypomagnesemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic factor release in cardiomyopathic hamsters.

Studies were done in male cardiomyopathic and normal hamsters to examine the effect of heart failure on atrial natriuretic factor (ANF) secretion. Five groups of animals were studied. The hamsters were 70, 150, 200, 250 and 300 days old. The degree of heart failure became more severe with age. This was associated with a marked increase in left and right atrial weight. Plasma ANF rose in the cardiomyopathic hamsters with age, and no significant change was seen in the normal animals. ANF levels in the atrial tissue declined as the animals developed heart failure, suggesting that ANF release increased in heart failure. To examine these directly, the right and left atria of these animals were isolated and superfused in a modified Langendorff apparatus. The effluents from these experiments were collected and analyzed for ANF levels. Analysis showed that ANF secretion (expressed as pg/min/mg of tissue) declined in heart failure. Since there were significant atrial hypertrophy, the results were also expressed as picogram per minute per atrium. When the data were shown as picogram per minute per atrium, there was a marked increase in ANF secretion. The present data show that one of the factors causing an increase in circulating ANF in heart failure is augmented secretion.

Effect of alpha- and beta-adrenergic stimulation on atrial natriuretic peptide release in vitro.

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was studied using the isolated left and right atria from a rat. The atria were perfused with Tyrode's solution, equilibrated with 95% O2-5% CO2 at 37 degrees C with a constant flow of 0.5 ml/min. Addition of epinephrine (10(-6) M), an alpha- and beta-agonist, to the perfusate induced the biphasic release of ANP from the right atrium without effect on the left. The initial peak (19.2 +/- 2.6 pg.min-1.ml-1) occurs 2-4 min after the administration of epinephrine, which lasted 4-6 min and returned to base line (10.4 +/- 1.1 pg.min-1.mg-1). The second peak (16.5 +/- 2.0 pg.min-1.ml-1) appeared 30-35 min after epinephrine administration and was sustained for 100 min, at which time the experiment was terminated. The first peak was stimulated by isoproterenol (10(-6) M), a beta-agonist, and blunted by propranolol (10(-6) M), a beta-antagonist. The second peak appeared following methoxamine (10(-6) M), an alpha-agonist, and could be suppressed by phentolamine (10(-6) M), an alpha-antagonist. These studies indirectly suggest that the adenosine 3',5'-cyclic monophosphate system and the inositol triphosphate system are involved in ANP secretion, with the former responsible for the initial rapid release and the latter maintaining the secretion.

Effects of thyroid status on atrial natriuretic peptide release from isolated rat atria.

The effect of thyroid hormone on circulating levels of atrial natriuretic peptide (ANP) was studied in experimental hyperthyroid and hypothyroid rats. Plasma ANP was 102 +/- 5 pg/ml in euthyroid rats, 82 +/- 4 pg/ml in hypothyroid rats, and 138 +/- 11 pg/ml in hyperthyroid rats. We have also measured immunoreactive ANP in the atria of euthyroid, hypothyroid, and hyperthyroid rats. ANP content and concentration in the atria were lower (546 +/- 32 pg/mg tissue) in hyperthyroid rats than in hypothyroid rats (802 +/- 74 pg/mg tissue). Right atrium from euthyroid, hypothyroid, and hyperthyroid rats was superfused with a modified Langendorff preparation. Spontaneous release of ANP was significantly higher from the hyperthyroid rats (20 +/- 2 pg.min-1.mg-1) than from the hypothyroid rats (5.6 +/- 0.5 pg.min-1.mg-1). ANP release from the euthyroid rats was 9.3 +/- 1.2 pg.min-1.mg-1. These results indicate hyperthyroidism causes an increase in ANP secretion and a decreased release occurs during hypothyroidism.

Effect of sinus node on spontaneous release of natriuretic peptide in isolated atria.

Experiments were conducted to examine the release of atrial natriuretic peptide (ANP) in an isolated atrium in the presence and absence of sinus node tissue. The first series of experiments were conducted with the aid of a metabolic chamber to examine the spontaneous release of ANP by the right atrium with and without the sinus node region. The left atrium was also studied. The right atrium with the sinus node, quiescent right atrium without the sinus node, and the left atrium were incubated at 35 degrees C in 10 mL of oxygenated Tyrode's solution. After 40 min of equilibration, the incubation medium was removed at 10-min intervals for the determination of immunoreactive ANP concentration. The right atria with the sinus node released the highest amount of ANP into the incubation medium (32.2 +/- 2.7 pg.min-1.mg-1), compared with quiescent right atria (20.9 +/- 3.7 pg.min-1.mg-1). The left atria released the least amount of ANP into the incubation medium (9.9 +/- 1.5 pg.min-1.mg-1) when compared with the quiescent right atria and the right atria. In the second series of experiments, the right atrium was divided into the sinus node region and the quiescent right atrium, and these tissues were studied in paired fashion with a modified Langendorff preparation. The right atrium without the sinus node and sinus node region were perfused with Tyrode's solution, equilibrated with 95% O2 and 5% CO2 at 37 degrees C with a constant flow of 0.5 mL/min.(ABSTRACT TRUNCATED AT 250 WORDS)

A non-invasive method for evaluating cirrhotic portal hypertension by administration of 99mTc-MIBI per rectum.

A study was performed to evaluate radio-isotopic imaging using technetium-99m hexakis 2-methoxyisobutyl isonitrile administered per rectum to assess portal collateral circulation. The heart-liver ratios (H/L; mean +/- standard deviation) in 15 controls, 13 cases of histologically confirmed viral hepatitis and 57 cirrhosis patients were 0.27 +/- 0.11, 0.43 +/- 0.14 and 1.00 +/- 0.28, respectively (P < 0.001). Among the cirrhosis patients those with the Child-Pugh classification A, B and C had H/L of 0.56 +/- 0.14, 1.00 +/- 0.20 and 1.19 +/- 0.26, respectively (P < 0.001). A high value of H/L was associated with a high risk of hepatic encephalopathy (1.25 +/- 0.17, P < 0.01) and oesophageal varices (1.02 +/- 0.20, P < 0.01). There were associations between H/L and serum bilirubin (P < 0.01), albumin (P < 0.05) and prothrombin time (P < 0.05). The results also showed a good correlation between H/L and portal vein pressure measured during operation in 13 patients (P < 0.001, r = 0.87). The regression equation: y = 6.77 + 32.5 H/L, allowed portal vein pressure to be estimated. The prognostic value of the test was supported by the fact that good correlations were observed between the H/L ratio and widely accepted prognostic classification (Child-Pugh). It is suggested that this new method could be a reliable non-invasive way to give an indication of the degree of portasystemic shunting to evaluate the prognosis and to follow up the effects of medications for reducing portal hypertension in patients with cirrhotic portal hypertension.