The association of the dietary approach to stop hypertension (DASH) diet with blood pressure, glucose and lipid profiles in Malaysian and Philippines populations.

BACKGROUND AND AIM: Despite a growing body of evidence from Western populations on the health benefits of Dietary Approaches to Stop Hypertension (DASH) diets, their applicability in South East Asian settings is not clear. We examined cross-sectional associations between DASH diet and cardio-metabolic risk factors among 1837 Malaysian and 2898 Philippines participants in a multi-national cohort. METHODS AND RESULTS: Blood pressures, fasting lipid profile and fasting glucose were measured, and DASH score was computed based on a 22-item food frequency questionnaire. Older individuals, women, those not consuming alcohol and those undertaking regular physical activity were more likely to have higher DASH scores. In the Malaysian cohort, while total DASH score was not significantly associated with cardio-metabolic risk factors after adjusting for confounders, significant associations were observed for intake of green vegetable [0.011, standard error (SE): 0.004], and red and processed meat (-0.009, SE: 0.004) with total cholesterol. In the Philippines cohort, a 5-unit increase in total DASH score was significantly and inversely associated with systolic blood pressure (-1.41, SE: 0.40), diastolic blood pressure (-1.09, SE: 0.28), total cholesterol (-0.015, SE: 0.005), low-density lipoprotein cholesterol (-0.025, SE: 0.008), and triglyceride (-0.034, SE: 0.012) after adjusting for socio-demographic and lifestyle groups. Intake of milk and dairy products, red and processed meat, and sugared drinks were found to significantly associated with most risk factors. CONCLUSIONS: Differential associations of DASH diet and dietary components with cardio-metabolic risk factors by country suggest the need for country-specific tailoring of dietary interventions to improve cardio-metabolic risk profiles.

Point of Care Tuberculosis Sero-Diagnosis Kit for Wild Animals: Combination of Proteins for Improving the Diagnostic Sensitivity and Specificity.

Tuberculosis is a significant problem globally for domestic animals as well as captive and free ranging wild life. Rapid point of care (POC) serology kits are well suited for the diagnosis of TB in wild animals. However, wild animals are invariably exposed to environmental non-pathogenic mycobacterium species with the development of cross reacting antibodies. In the present study, POC TB diagnosis kit was developed using a combination of pathogenic Mycobacteria specific recombinant antigens and purified protein derivatives of pathogenic and non-pathogenic Mycobacteria. To benchmark the TB antibody detection kit, particularly in respect to specificity which could not be determined in wildlife due to the lack of samples from confirmed uninfected animals, we first tested well-characterized sera from 100 M. bovis infected and 100 uninfected cattle. Then we investigated the kit's performance using sera samples from wildlife, namely Sloth Bears (n = 74), Elephants (n = 9), Cervidae (n = 14), Felidae (n = 21), Cape buffalo (n = 2), Wild bear (n = 1) and Wild dog (n = 1).In cattle, a sensitivity of 81% and a specificity of 90% were obtained. The diagnostic sensitivity of the kit was 94% when the kit was tested using known TB positive sloth bear sera samples. 47.4% of the in-contact sloth bears turned seropositive using the rapid POC TB diagnostic kit. Seropositivity in other wild animals was 25% when the sera samples were tested using the kit. A point of care TB sero-diagnostic kit with the combination of proteins was developed and the kit was validated using the sera samples of wild animals.

Smaller size of high metabolic rate organs explains lower resting energy expenditure in Asian-Indian Than Chinese men.

BACKGROUND: In Singapore, the obesity prevalence is disproportionately higher in the Asian-Indians and Malays than the Chinese. Lower resting energy expenditure (REE) may be a contributory factor. OBJECTIVE: We explored the association between ethnicity and REE in Chinese, Asian-Indian and Malay men living in Singapore and determined the influence of body composition, mass/volume of high metabolic rate organs, represented by brain volume and trunk fat-free mass (FFM), and physical activity on ethnic differences. DESIGN: Two hundred and forty-four men from Singapore (n=100 Chinese, 70 Asian-Indians and 74 Malays), aged 21-40 years and body mass index of 18.5-30.0 kg m(-2), were recruited in this cross-sectional study. REE was assessed by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Brain volume was measured by magnetic resonance imaging. Physical activity was assessed by the Singapore Prospective Study Program Physical Activity Questionnaire. RESULTS: REE was significantly lower in Asian-Indians compared with that in Chinese after adjusting for body weight. FFM (total, trunk and limb) and total fat mass were important predictors of REE across all ethnic groups. Brain volume was positively associated with REE only in Malays. Moderate and vigorous physical activity was positively associated with REE only in Asian-Indians and Malays. The difference in REE between Asian-Indians and Chinese was attenuated but remained statistically significant after adjustment for total FFM (59±20 kcal per day), fat mass (67±20 kcal per day) and brain volume (54±22 kcal per day). The association between REE and ethnicity was no longer statistically significant after total FFM was replaced by trunk FFM (which includes heart, liver, kidney and spleen) but not when it was replaced by limb FFM (skeletal muscle). CONCLUSIONS: We have demonstrated a lower REE in Asian-Indians compared with Chinese who may contribute to the higher rates of obesity in the former. This difference could be accounted for by differences in metabolically active organs.

Associations between complications and health-related quality of life in individuals with diabetes.

OBJECTIVE: Type 2 diabetes and associated complications adversely affect health-related quality of life (HRQoL). However, it is unclear whether different complications have the same or different associations with HRQoL. We examined associations between retinopathy, nephropathy, peripheral neuropathy (microvascular), coronary heart disease, stroke and peripheral arterial disease (macrovascular) in diabetes and HRQoL. DESIGN: This study was a follow-up examination between 2004 and 2007 of participants from four previous cross-sectional population-based studies in Singapore. METHODS: Health-related quality of life was assessed through self-administered SF-36 health survey version 2. Diabetes and complications status were assessed through self-report, clinical and laboratory examinations. About 2601 individuals, 2205 healthy and 396 with diabetes, were studied. RESULTS: Lower physical component scores (PCS) were associated with microvascular (2.96 points, P < 0.001) and both macro- and microvascular complications (4.67 points, P < 0.001), but not diabetes alone. Coronary heart disease (3.86 points, P = 0.007), peripheral neuropathy (11.46 points, P < 0.001) and severe retinopathy (4.46 points, P < 0.001) were associated with lower PCS. The greatest reduction in scores was seen in peripheral neuropathy. CONCLUSIONS: Quality of life in patients with diabetes is affected mainly by presence of complications, and not diabetes per se. Peripheral neuropathy was associated with the greatest reduction in quality of life. Improved management to prevent or delay onset of complications may reduce the effect on quality of life in patients with diabetes.

Multi-Body 3D-2D Registration for Robot-Assisted Joint Reduction: Preclinical Evaluation in the Ankle Syndesmosis.

Purpose: Existing methods to improve the accuracy of tibiofibular joint reduction present workflow challenges, high radiation exposure, and a lack of accuracy and precision, leading to poor surgical outcomes. To address these limitations, we propose a method to perform robot-assisted joint reduction using intraoperative imaging to align the dislocated fibula to a target pose relative to the tibia. Methods: The approach (1) localizes the robot via 3D-2D registration of a custom plate adapter attached to its end effector, (2) localizes the tibia and fibula using multi-body 3D-2D registration, and (3) drives the robot to reduce the dislocated fibula according to the target plan. The custom robot adapter was designed to interface directly with the fibular plate while presenting radiographic features to aid registration. Registration accuracy was evaluated on a cadaveric ankle specimen, and the feasibility of robotic guidance was assessed by manipulating a dislocated fibula in a cadaver ankle. Results: Using standard AP and mortise radiographic views registration errors were measured to be less than 1 mm and 1° for the robot adapter and the ankle bones. Experiments in a cadaveric specimen revealed up to 4 mm deviations from the intended path, which was reduced to <2 mm using corrective actions guided by intraoperative imaging and 3D-2D registration. Conclusions: Preclinical studies suggest that significant robot flex and tibial motion occur during fibula manipulation, motivating the use of the proposed method to dynamically correct the robot trajectory. Accurate robot registration was achieved via the use of fiducials embedded within the custom design. Future work will evaluate the approach on a custom radiolucent robot design currently under construction and verify the solution on additional cadaveric specimens.

Ethnicity modifies the relation between fasting plasma glucose and HbA1c in Indians, Malays and Chinese.

AIMS: To study whether HbA(1c) , and its relationship with fasting plasma glucose, was significantly different among Chinese, Malays and Indians in Singapore. METHODS: A sample of 3895 individuals without known diabetes underwent detailed interview and health examination, including anthropometric and biochemical evaluation, between 2004 and 2007. Pearson's correlation, analysis of variance and multiple linear regression analyses were used to examine the influence of ethnicity on HbA(1c) . RESULTS: As fasting plasma glucose increased, HbA(1c) increased more in Malays and Indians compared with Chinese after adjustment for age, gender, waist circumference, serum cholesterol, serum triglyceride and homeostasis model assessment of insulin resistance (P-interaction < 0.001). This translates to an HbA(1c) difference of 1.1 mmol/mol (0.1%, Indians vs. Chinese), and 0.9 mmol/mol (0.08%, Malays vs. Chinese) at fasting plasma glucose 5.6 mmol/l (the American Diabetes Association criterion for impaired fasting glycaemia); and 2.1 mmol/mol (0.19%, Indians vs. Chinese) and 2.6 mmol/mol (0.24%, Malays vs. Chinese) at fasting plasma glucose 7.0 mmol/l, the diagnostic criterion for diabetes mellitus. CONCLUSIONS: Using HbA(1c) in place of fasting plasma glucose will reclassify different proportions of the population in different ethnic groups. This may have implications in interpretation of HbA(1c) results across ethnic groups and the use of HbA(1c) for diagnosing diabetes mellitus.

Pulmonary hypertension is associated with increased nonrelapse mortality after allogeneic hematopoietic cell transplantation for myelofibrosis.

Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for primary myelofibrosis (MF) as well as myelofibrosis secondary to other myeloproliferative neoplasms (MPN). Pulmonary hypertension (PH) is a known complication of MF and may occur in up to 50% of such patients. PH (defined as a mean pulmonary artery pressure ≥25 mmHg at rest) can eventually lead to right heart failure and may be associated with complications after alloHCT. We examined the association of PH with alloHCT outcome in patients with MF associated with MPN. Pre- and post-HCT echocardiograms were reviewed to estimate the peak pulmonary artery systolic pressure (PASP). Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 of 65 patients (57%) studied. With median follow-up of 35.0 months (range: 3.3-119.4) PH was significantly associated with inferior OS (58.9% vs. 88.8%, P = 0.025), primarily due to increased NRM (21.6% vs. 7.1%, P = 0.007). The majority of the deaths (8 of 14) in patients with PH occurred within 100 days after HCT. In patients with an available post-HCT echocardiogram (n = 33), the median PASP was 30 mmHg (range: 5.0-56.2); eight patients (24%) had persistent PH. Compared with pre-HCT values, PASP was significantly reduced after HCT (p < 0.001). We conclude that PH is associated with inferior survival due to the increased NRM in patients with MF undergoing alloHCT. PH appears at least partially reversible after successful alloHCT. PH should be considered a risk factor for early mortality after alloHCT and surveillance of pulmonary artery pressure in MF patients being considered for alloHCT may be useful.

Ceramide as a second messenger: sticky solutions to sticky problems.

Much discussion has recently centred around the biochemical mechanisms by which ceramide is produced in signalling pathways. Since ceramide is virtually insoluble in aqueous solutions, the biological effects of ceramide should be considered in the context of its generation within the membrane lipid bilayer. To this end, we now summarize recent data describing some biophysical properties of ceramide that are of relevance for understanding the mode of ceramide action as a second messenger, and, as a consequence, how the site(s) of ceramide generation might impact upon its role in signalling.

Comparison of the metabolism of L-erythro- and L-threo-sphinganines and ceramides in cultured cells and in subcellular fractions.

Ceramide (Cer) is a key intermediate in the synthetic and degradative pathways of sphingolipid metabolism, and is also an important second messenger. Natural Cer exists in the D-erythro configuration. Three additional, non-natural stereoisomers exist, but conflicting reports have appeared concerning their metabolism. We now compare the stereospecificity of three enzymes in the sphingolipid biosynthetic pathway, namely dihydroceramide (dihydroCer), sphingomyelin (SM) and glucosylceramide synthases, in subcellular fractions and in cultured cells. The L-erythro enantiomers of sphinganine, dihydroCer and Cer do not act as substrates for any of the three enzymes. In contrast, the diastereoisomer, L-threo-sphinganine, is acylated by dihydroCer synthase, and L-threo-dihydroCer and L-threo-Cer are both metabolized to dihydroSM and SM, respectively, but not to dihydroglucosylceramide and glucosylceramide. No significant difference was detected in the ability of SM synthase to metabolize Cer containing a short (hexanoyl) versus long acyl chain (palmitoyl), demonstrating that short-acyl chain Cers mimic their natural counterparts, at least in the sphingolipid biosynthetic pathway.

High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support.

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels

Ethnic differences in insulin sensitivity and beta-cell function among Asian men.

BACKGROUND AND OBJECTIVES: Lean Asian Indians are less insulin sensitive compared with Chinese and Malays, but the pancreatic beta-cell function among these ethnic groups has yet to be studied in depth. We aimed to study beta-cell function in relation to insulin sensitivity among individuals of Chinese, Malay and Asian-Indian ethnicity living in Singapore. SUBJECTS AND METHODS: This is a sub-group analysis of 59 normoglycemic lean (body mass index (BMI) <23 kg m(-)(2)) adult males (14 Chinese, 21 Malays and 24 Asian Indians) from the Singapore Adults Metabolism Study. Insulin sensitivity was determined using fasting state indices (homeostatic model assessment-insulin resistance), the euglycemic-hyperinsulinemic clamp (ISI-clamp) and a liquid mixed-meal tolerance test (LMMTT) (Matsuda insulin sensitivity index (ISI-Mat)). Beta-cell function was assessed using fasting state indices (homeostatic model assessment-beta-cell function) and from the LMMTT (insulinogenic index and insulin secretion index). The oral disposition index (DI), a measure of beta-cell function relative to insulin sensitivity during the LMMTT, was calculated as a product of ISI-Mat and insulin secretion index. RESULTS: Asian Indians had higher waist circumference and percent body fat than Chinese and Malays despite similar BMI. Overall, Asian Indians were the least insulin sensitive whereas the Chinese were most insulin sensitive. Asian Indians had higher beta-cell function compared with Chinese or Malays but these were not statistically different. Malays had the highest incremental area under the curve for glucose during LMMTT compared with Asian Indians and Chinese. However, there were no significant ethnic differences in the incremental insulin area under the curve. The oral DI was the lowest in Malays, followed by Asian Indians and Chinese. CONCLUSION: Among lean Asians, Chinese are the most insulin sensitive whereas Asian Indians are the least insulin sensitive. However, Malays demonstrate higher postprandial glucose excursion with lower beta-cell response compare with Chinese or Asian Indians. The paths leading to type 2 diabetes mellitus might differ between these Asian ethnic groups.

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na+,K+-adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 +/- 8.9; drug-treated, 86.9 +/- 4.9 mm Hg; p less than 0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 +/- 1.8; drug-treated, 5.2 +/- 0.4 mmol/L cells; p less than 0.002) and calcium (placebo, 13.5 +/- 1.6; drug-treated 10.8 +/- 3.3 mumol/L cells; p less than 0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+,K+-ATPase of erythrocyte membranes (placebo, 7.1 +/- 1.1 X 10(-2); drug-treated, 9.0 +/- 0.6 X 10(-2) microM inorganic phosphate/hr/mg; p less than 0.001) at the end of the study. However, no significant change in the ouabain-insensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Isosorbide dinitrate in acute and chronic heart failure.

The hemodynamic effects of sublingual isosorbide dinitrate (ISD) were studied in 12 patients with congestive heart failure (CHF) of many causes. The duration of CHF in the chronic group varied from 3 to 62 months (mean, 29.5). Hemodynamic parameters were obtained serially before and 10, 20, 30, 45, 60, and 120 min after a 5 to 15 mg dose of ISD sublingually. The hemodynamic effects were pronounced at 45 min and returned to control levels in 120 min. Heart rate did not change. Hemodynamic parameters that changed after ISD were mean arterial pressure (-7%, p less than 0.05), mean pulmonary artery pressure (-17%, p less than 0.05), and mean pulmonary capillary wedge pressure (-29%, p less than 0.005). Mean cardiac index (+3%, p = NS) and mean stroke work index rose (+9.4%, P X NS); mean total systemic resistance fell (-10%, p = NS). Thus the duration of hemodynamic effects of ISD is less than 2 hr and sublingual ISD induces beneficial reduction of pulmonary capillary wedge pressure in patients with acute and chronic CHF without increasing cardiac index and stroke work index.

Synthesis and biological evaluation of ceramide analogues with substituted aromatic rings or an allylic fluoride in the sphingoid moiety.

The biological activity of synthetic ceramide analogues, having modified sphingoid and N-acyl chains, as well as fluorine substituents in the allylic position, was investigated in hippocampal neurons. Their influence on axonal growth was compared to that of C(6)-N-acyl analogues of natural ceramides. D-erythro-Ceramides with a phenyl group in the sphingoid moiety and a short N-acyl chain were able to reverse the inhibitory effect of fumonisin B(1) (FB(1)), but not of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), on accelerated axonal growth in hippocampal neurons. Moreover, we demonstrated that a ceramide analogue with an aromatic ring in the sphingoid moiety is recognized as a substrate by glucosylceramide synthase, which suggests that the observed biological effects are mediated by activation of the ceramide analogue via glucosylation. Introduction of a methyl, pentyl, fluoro, or methoxy substituent in the para position of the phenyl ring in the sphingoid moiety yielded partly active compounds. Likewise, substitution of the benzene ring for a thienyl group did not abolish the ability to reverse the inhibition of accelerated axonal growth by FB(1). Both D-erythro- and L-threo-ceramide analogues, having an allylic fluorine substituent, partly reversed the FB(1) inhibition.

Intracardiac electrocardiography during permanent pacemaker implantation: predictors of cardiac perforation.

Intracardiac electrograms from 50 successive patients undergoing permanent pacemaker implantation have been analyzed. There were 29 male and 21 female patients aged 14 to 93 years (mean age 68.4 years). The electrograms were obtained using methods that simulated the wave form that would be detected by unipolar cardiac pacemakers. Three types of electrographic patterns were identified: qR pattern with a q/R ratio of less than 1 (type I): QR pattern with a Q/R ratio between 1 and 4.4 (type II); and Qr pattern with a Q/r ratio between 12 and 15 (type III). A type I pattern was seen in 29 patients (58 percent), type II in 18 (36 percent) and type III in 3 patients (6 percent). The duration of the follow-up period ranged from 3 weeks to 20 months (mean 9.7 months); three patients were lost to follow-up study. There were four deaths apparently unrelated to the pacemaker. Recognizable problems (either pacing or sensing failure) occurred in one patient (6 percent) with a type II pattern, in two patients (66.7 percent) with a type III pattern and in no patient with a type I pattern. On the basis of these data it is suggested that at the time of pacemaker implantation, intracardiac electrograms with a type I pattern indicating good pacing thresholds and sensing should be sought. If type II wave forms occur with good pacing thresholds and sensing then the electrode could probably be left in position. The incidence of a type III pattern is rare; when it does occur it is greatly suggestive of myocardial perforation. When this pattern is seen, the pacemaker catheter must be repositioned.

Musical murmurs: an echo-phonocardiographic study.

Five patients with muscial murmurs were studied noninvasively with simultaneous echocardiography and phonocardiograpy and phonocardiography. Three patients had aortic regurgitation, one mitral regurgitation and one tricuspid regurgitation. The frequency of the muscial murmurs ranged from 40 to 158 cycles/sec. The patient with tricuspid regurgitation manifested an inspiratory honk. Simultaneous echo-phonocardiography revealed regular valve leaflet flutter (aortic, mitral or tricuspid) at a frequency identical to that of the simultaneously recorded muscial murmur. This study demonstrates that echocardiography is a useful noninvasive tool in identifying the site of origin of musical murmurs.

Problems in ultrasonic estimates of septal thickness.

Problems related to cardiac anatomy and ultrasonic instrumentation affect the accuracy of echographic identification of endocardial echoes. A cadaver model and 13 patients were studied, with direct identification or with the aid of echographic contrast techniques, to identify accurately the endocardial echo. The study showed that (1) echographic contrast agents delineate an endocardial echo in the central portion of the ultransonic beam; (2) a specular reflector exists within the right ventricular cavity; (3) specular reflectors within the septum may give the false appearance of border-forming echoes; (4) septal thickness varies by 1 to 5 mm after the endocardial echo has been identified by the contrast agent; and (5) spurious echoes, related to a wide beam angle, can be confused with the endocardial echo. In light of these problems, three criteria were utilized for endocardial echo identification: the prominent notch in the left septal echo, the specular quality of the right septal echo, and the association of multiple myocardial echoes moving in parallel. With these criteria, the endocardial echoes in 11 of the 13 patients could be accurately identified without the use of a contrast agent. The identification of these problems should provide helpful guidelines in developing more accurate and reproducible criteria for septal thickness measurements.

Efficacy and safety of nicardipine for chronic, stable angina pectoris: a multicenter randomized trial.

Nicardipine, a new calcium channel blocking drug of the dihydropyridine family, was administered to 63 patients at a dose of 30 or 40 mg 3 times daily in a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Nicardipine midly increased heart rate (HR) at rest and midly decreased the blood pressure (BP) at rest. When generally similar responses to the 30- and 40-mg doses were averaged, nicardipine produced a 7% increase in peak exercise HR, which was balanced by a 6% decrease in peak exercise BP. Thus, no change occurred in the exercise HR-BP product. With nicardipine, treadmill exercise duration increased 9%, time to angina increased 15%, time to 1-mm ST-segment depression increased 16%, and oxygen consumption at peak exercise increased 13%. Mean anginal frequency declined, as did mean weekly sublingual nitroglycerin consumption, but not significantly. There were more cardiovascular side effects with nicardipine than with placebo, with at least 3 patients having increased angina judged by investigators as probably related to the drug. Vasodilatory side effects were also more frequent with nicardipine, but were generally mild and well tolerated; the drug had to be discontinued in only 1 patient, because of vasodilatory effects. Nicardipine is effective and generally well tolerated in patients with chronic stable angina.

Circadian and power spectral changes of RR and QT intervals during treatment of patients with angina pectoris with nadolol providing evidence for differential autonomic modulation of heart rate and ventricular repolarization.

This study evaluates the effects of autonomic manipulation by chronic beta blockade with nadolol on the circadian and power spectral changes of heart rate and QT interval. It was hypothesized that differential innervation of the atria and ventricles by sympathetic and parasympathetic fibers may produce differential effects on heart rate and QT interval variabilities. Holter recordings of 12 male patients (age 63 +/- 7 years) with stable angina were analyzed before and after 3 weeks of nadolol therapy. The QT intervals were individually normalized by an exponential formula to study the circadian variation of QTc. Power spectra of RR and uncorrected QT intervals were obtained by fast-Fourier analysis from 256 consecutive sinus beats during the day at maximal heart rate and during the night at minimal heart rate. Frequency-specific variability was determined from areas under the spectral plots. Both heart rate and QTc exhibited significant circadian patterns (p < 0.01) in opposite phase with each other. Mean heart rate was significantly reduced with nadolol (81 +/- 12 vs 67 +/- 12 beats/min, p < 0.001), with greater reduction during daytime. The mean QTc was unexpectedly reduced after nadolol treatment, with borderline significance (p = 0.06). The RR variability in the frequency range of 0.05 to 0.25 Hz was significantly increased with nadolol at 3:00 A.M. (p < 0.01) but not at 1:00 P.M. The QT variability in the same frequency range of was not significantly increased with nadolol. The power spectra of RR and QT intervals were dissimilar except at the lower frequencies around 0.05 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)