Comparison of anti-Xa activity after a single intravenous bolus of low-dose enoxaparin in patients with and without end-stage renal disease.

This study was designed to evaluate anti-Xa activity hourly during the first 3 h after a single intravenous bolus of 0.5 mg/kg enoxaparin in 30 patients with end-stage renal disease (ESRD) who underwent haemodialysis, and in 30 patients with normal or mildly reduced renal function who underwent coronary angiography for chest pain (non-ESRD group). Mean +/- SD haemodialysis time was 3.9 +/- 0.3 h in the ESRD group. Of 24 patients diagnosed with coronary artery disease in the non-ESRD group, 20 underwent percutaneous coronary intervention (PCI). A peak anti-Xa activity > 0.5 IU/ml 10 min after enoxaparin injection was obtained in 90% and 93% of the non-ESRD and ESRD patients, respectively. The percentages of patients with peak anti-Xa activity in the target range (0.5 - 1.5 IU/ml) were similar in the two groups (non-ESRD 80%, ESRD 93%). Adequate anti-Xa activity (> 0.5 IU/ml) lasted about 2 h in both groups. It is concluded that a single intravenous low-dose enoxaparin (0.5 mg/kg) bolus provides anti-Xa activity adequate for elective PCI within 2 h irrespective of whether or not the patient had ESRD.

Efficacy and safety of valsartan/hydrochlorothiazide fixed-dose combination compared with amlodipine monotherapy as first-line therapy for mild to moderate hypertension.

This double-blind, active- and randomized-controlled study compared the efficacy and safety of a fixed-dose combination of valsartan/hydrochlorothiazide 80 mg/12.5 mg once daily (n = 32) with amlodipine monotherapy 5 mg once daily (n = 33) for 8 weeks in patients with mild to moderate hypertension. Non-inferiority of valsartan/hydrochlorothiazide to amlodipine was demonstrated by comparable reductions in sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP), and daytime, night-time and 24-h SBP and DBP on ambulatory blood pressure monitoring. Between-group comparisons of adverse events and changes in laboratory parameters did not reach statistical significance, except for uric acid which showed a significant increase in the valsartan/hydrochlorothiazide group compared with the amlodipine group, but was still below the laboratory's upper limit of normal. In conclusion, the use of the fixed-dose combination of valsartan/hydrochlorothiazide 80 mg/12.5 mg once daily as a starting regimen in patients with mild to moderate hypertension was shown to have non-inferior efficacy and comparable safety for daily practice compared with amlodipine 5 mg once daily monotherapy.

Time-dependent benefit of initial thrombosuction on myocardial reperfusion in primary percutaneous coronary intervention.

BACKGROUND: In ST-segment elevation acute myocardial infarction (STEMI), dislodgement of thrombus within the culprit artery during primary percutaneous coronary intervention (PCI) may cause distal embolisation and impaired myocardial reperfusion. Clinical results of thromboembolic protection strategies have been controversial. We conducted this study to investigate whether the benefit of thrombus removal is time dependent. METHODS: Seventy-four STEMI patients within 12 h from onset were randomised to receive either primary PCI with initial thrombosuction (IT) or standard strategy. Results were analysed in subgroups according to the onset-to-lab time intervals (subgroup 1: 0-240 min, subgroup 2: 241-480 min and subgroup 3: 481-720 min). RESULTS: The primary end-points were improvements in thrombolysis in myocardial infarction flow (DeltaTIMI) and myocardial blush grade (DeltaMBG) postprocedure. Better DeltaTIMI (2.2 +/- 1.1 vs. 1.5 +/- 1.3, p = 0.014) and DeltaMBG (2.3 +/- 1.1 vs. 1.0 +/- 1.5, p < 0.001) were observed in IT patients, compared with standard PCI patients. In onset-to-lab time subgroup analysis, the difference between IT and standard PCI is significant only in subgroup 2 (DeltaTIMI 2.6 +/- 1.0 vs. 1.3 +/- 1.2, p = 0.007; DeltaMBG 2.6 +/- 0.9 vs. 1.0 +/- 1.1, p = 0.010), but not in the other two subgroups. CONCLUSIONS: This prospective randomised study shows that primary PCI with IT may improve epicardial flow and myocardial reperfusion in patients with STEMI, and this benefit is the most significant in patients treated within 4-8 h after symptom onset.

The Angio-Seal arterial closure device for early ambulation after elective percutaneous coronary intervention in patients receiving low-dose enoxaparin.

This study evaluated the efficacy and safety of use of the Angio-Seal vascular closure device deployment for early ambulation (2 h) after elective percutaneous coronary intervention in 143 consecutive patients receiving either intravenous low-dose enoxaparin (0.5 mg/kg) or unfractionated heparin (UFH). The initial success rate of Angio-Seal(trade mark) deployment was 98.6%, with no significant difference between the UFH group (98.9%) and the enoxaparin group (98.0%). In-hospital and clinic outcomes were evaluated in the 141 patients with successful Angio-Seal deployment. During hospitalization, there were no deaths, myocardial infarction, urgent target vessel revascularization or bleeding events in either group; three patients in the UFH group and none in the enoxaparin group had minor vascular complications (differences not significant). In clinic follow-up, two patients in the UFH group and none in the enoxaparin group had major vascular complications (differences not significant). Routine use of the Angio-Seal(trade mark) for early ambulation in patients receiving intravenous low-dose enoxaparin compared with UFH provides promising efficacy and safety for daily practice.

Shock resuscitation with acupuncture: case report.

A 77 year old aboriginal woman in an isolated village became drowsy and shocked. Poor weather conditions delayed the arrival of the medical and support team--the roads had been seriously destroyed by torrential rains and helicopter was the only means for delivering critical medical care and support. While waiting for the arrival of the helicopter, and in the absence of the necessary emergency medical equipment, the patient's condition deteriorated. Administration of persistent emergency acupuncture stimulation for 80 minutes helped maintain the patient's vital signs until successful transfer of the patient to hospital. She recovered without any complications of shock and was discharged six days later.

Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults.

BACKGROUND: Homocysteine-mediated endothelial dysfunction has been proposed to occur via oxidative stress mechanisms in humans. However, there is controversy regarding the effects of homocysteine on endothelial function and oxidative status, which may in part result from age discrepancy across the studies. The present study was designed to investigate the aging effect on the relationship between endothelium-dependent vasodilation and oxidative status in methionine-induced hyperhomocysteinemia. METHODS AND RESULTS: Plasma homocysteine, phosphatidylcholine hydroperoxide (PCOOH), P-selectin levels, and brachial artery flow-mediated vasodilation were measured at baseline and 4 hours after an oral methionine load (0.1 g/kg) in 15 younger (21 to 40 years) and 15 older (55 to 70 years) healthy adults. Homocysteine increased from 7.3+/-1.3 micromol/L at baseline to 22.7+/-5.2 micromol/L at 4 hours in younger (P<0.001) and from 7. 4+/-1.4 to 24.3+/-4.5 micromol/L in older adults (P<0.001). PCOOH levels were not significantly different between baseline and 4 hours in both groups (P=0.10 in young; P=0.14 in old). P-selectin, which is expected to increase during oxidative stress, was not changed in older (P=0.08) but decreased in younger adults (P=0.037) at 4 hours. Flow-mediated vasodilation was preserved from 13.1+/-2.1% at baseline to 13.5+/-2.8% at 4 hours in younger (P=0.49) and decreased from 12.8+/-2.4% to 8.5+/-2.8% in older adults (P<0.001). CONCLUSIONS: The present study demonstrates that endothelial dysfunction caused by methionine-induced hyperhomocysteinemia is age-related and is mediated through impaired nitric oxide activity without change of oxidative status. Our data do not support previous hypotheses that endothelial damage by homocysteine is via oxidative stress mechanism in humans.

Impairment of cerebrovascular reactivity by methionine-induced hyperhomocysteinemia and amelioration by quinapril treatment.

BACKGROUND AND PURPOSE: Human studies have shown that methionine-induced hyperhomocysteinemia impairs brachial artery endothelial function via decreasing nitric oxide activity. However, the effect of homocysteine on cerebrovascular reactivity (CVR), which has been reported to be nitric oxide related in experimental and animal studies, remains unclear in humans. Inhibition of angiotensin-converting enzyme may improve nitric oxide-mediated cerebral as well as peripheral endothelial function. The aim of the present study was to investigate the effect of methionine-induced hyperhomocysteinemia on CVR before and after treatment with quinapril, an angiotensin-converting enzyme inhibitor, in healthy adults. METHODS: Plasma homocysteine and CVR were measured at baseline and 4 hours after methionine load (0.1 g/kg body wt) before and after quinapril treatment (10 mg/d for 1 week) in both younger and older groups. CVR was assessed by transcranial Doppler ultrasonography, measuring the percent increase of flow velocity in the middle cerebral artery after brief carotid compression (expressed as transient hyperemic response ratio [THRR]). RESULTS: Homocysteine levels were significantly increased after methionine load either before or after quinapril treatment in both groups. Before quinapril treatment, postmethionine THRR was preserved in younger adults (24.2+/-5.3% versus 23.8+/-6.3% at baseline, P:=0.73) and decreased in older adults (12.9+/-2.2% versus 21.8+/-4.0% at baseline, P:<0.001). After quinapril treatment, postmethionine THRR was preserved in both groups (24.5+/-5.9% versus 24.0+/-5.0% at baseline, P:=0.42 in younger adults; 20.4+/-3.9% versus 21.3+/-3.3% at baseline, P:=0.35 in older adults). CONCLUSIONS: Our study suggests that methionine-induced hyperhomocysteinemia may be causally associated with impairment of CVR in older normal subjects.

Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin.

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = -0.5, P = 0.01), waist (r = -0.4, P = 0.04) and hip (r = -0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = -0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (beta = -0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (beta = -0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.

The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis.

It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P=0.33; 95% CI, 0. 2-1.6). The geometric mean of HCY values was higher in CAD patients (11.10+/-1.51 micromol/l) than in non-CAD subjects (9.21+/-1.55 micromol/l) (P=0.003). HCY levels were higher in patients with multi-vessel disease (P<0.05) or in patients with > or = 90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles (> or = 14.0 and 10.1-13.9 micromol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (< or = 7.9 micromol/l) (P=0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.

Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia.

This study showed that short-term vitamin administration effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.

Torsade de pointes and T-wave alternans in a patient with brainstem hemorrhage.

Torsade de pointes, a form of life-threatening ventricular arrhythmia associated with QT prolongation, is rarely reported in intracranial hemorrhage. T-wave alternans is recently considered a risk marker for ventricular arrhythmias. To our knowledge, we report the first case of brainstem hemorrhage in which the patient presented with torsade de pointes and T-wave alternans. The implication of this association is discussed.

Excessive myocardial contraction in vasovagal syncope demonstrated by echocardiography during head-up tilt test.

The purpose of this study was to gain insight into the mechanism of vasovagal syncope and to test the efficacy of theophylline to prevent syncope. Twenty-six patients with vasovagal syncope underwent two-dimensional echocardiography and theophylline test during head-up tilt test. A standard parasternal short-axis view of echocardiography at the level of the papillary muscle was recorded to measure fraction shorting of the left ventricle, and left ventricular end-diastolic and end-systolic dimensions. Heart rate, blood pressure, and symptoms were recorded. There were three groups; Group 1: no syncope with and without isoproterenol (n = 5); Group 2: syncope only after the infusion of isoproterenol (n = 16); Group 3: syncope without isoproterenol (n = 5). Groups 2 and 3 proceeded to theophylline injection (250 mg). The study showed that the 80 degrees tilt induced an increase in heart rate of 6.6 +/- 4.0, 12.4 +/- 6.6, and 25.4 +/- 4.5 beats/min in Groups 1, 2, and 3, respectively (p < 0.05 in Groups 1 and 2, p < 0.05 in Groups 1 and 3). The addition of isoproterenol during posture change from supine to an 80 degrees tilt made the significant change of fractional shortening from 0.4 +/- 5% to 6 +/- 13% in Group 2 (p = 0.05), compared with no significant change in Group 1. There were no significant differences in left ventricular end-diastolic dimension and end-systolic dimension in each group between baseline and isoproterenol infusion during posture change. Vasovagal syncope was associated with vigorous myocardial contraction, rather than with contraction against an empty left ventricle. The acute loading of theophylline was not effective in preventing vasovagal syncope.

Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients.

The efficacy and safety profiles of barnidipine in the treatment of hypertension were evaluated in an open parallel-group study. Fifty-nine Chinese patients with mild-to-moderate essential hypertension were randomized to receive either barnidipine or felodipine (5 mg once daily, titrated to 10 mg or 15 mg once daily, as indicated) for 12 weeks. Both drugs reduced blood pressures significantly with > or = 68% of cases obtaining marked or moderate blood pressure reduction. Mean reductions in systolic and diastolic blood pressure for barnidipine treatment were 23.7 +/- 13.5 mmHg and 12.7 +/- 7.9 mmHg, and for felodipine, 24.3 +/- 18.4 mmHg and 14.5 +/- 10.0 mmHg, respectively. There was no significant difference between these two drugs in anti-hypertensive effect, heart rate, laboratory measurements or incidence of adverse events. The only difference was that more patients taking felodipine experienced palpitations. We conclude that barnidipine has similar efficacy and a similar safety profile to felodipine in the treatment of mild-to-moderate essential hypertension in Chinese patients.

Diagnosis of coronary artery disease using dipyridamole thallium-201 imaging.

Dipyridamole thallium-201 imaging, using single-photon emission computed tomography, was evaluated for its safety and diagnostic efficacy in 109 patients with angiographically documented coronary artery disease and 35 normal subjects. The most common side effects after the intravenous administration of dipyridamole thallium-201 (0.56 mg/kg) included chest pain in 41 patients, dizziness in 20 patients, headache in 16 patients, and ST segment depression > or = 1 mm in 15 patients. Aminophylline was required to reverse the side-effects in 46 patients, and 45 of the 46 patients experienced complete relief of symptoms. Of the 109 patients with coronary artery disease, 104 had abnormal dipyridamole thallium images. The per patient sensitivity was 95%. Of the 35 normal subjects, 27 had normal thallium images. The per patient specificity was 77%. The sensitivity and specificity for the individual vessels were 84% and 87% for the left anterior descending artery, 67% and 97% for the left circumflex artery, and 89% and 85% for the right coronary artery, respectively. Dipyridamole thallium-201 imaging is a relatively safe noninvasive method and is an effective alternative to exercise thallium-201 scintigraphy for the diagnosis of coronary artery disease.

Gender differences in the patterns of coronary angiography and PTCA use in a university hospital in Taiwan.

BACKGROUND AND PURPOSE: Coronary artery angiography (CAG) and percutaneous transluminal coronary angioplasty (PTCA) are important procedures for the diagnosis and treatment of patients with coronary artery disease. However, long-term trends in the frequency of CAG and PTCA use and their relation to gender have not been clearly determined in the Asian population. The purpose of this study was to investigate gender differences in the patterns of CAG and PTCA use in a university hospital in Taiwan during the period of 1983 through 1996. METHODS: We studied the monthly data of all patients who underwent CAG or PTCA in a university hospital in Taipei from 1983 through 1996. A time series analysis was used to estimate gender differences in the patterns of CAG and PTCA use. RESULTS: The frequency of CAG and PTCA increased significantly during this period. Before 1990, only a small number of patients underwent PTCA. However, this number increased steadily after 1990. Men were more likely to undergo CAG and PTCA than women. A time series analysis with fitted models was used to create an integrated moving average model. For CAG, the value of the estimated intercept for men was 2.5 times greater than that for women. In the PTCA series, the value of the intercept in men was 4.4 times greater than that in women. The patterns of trend change showed greater increases in men than in women, and a greater increase in the PTCA than in the CAG series. By transfer function modeling and intervention analysis, we found that the effect of CAG on the frequency of PTCA in men was 1.8 times greater than its effect in women. The estimated influence of the use of a new catheterization room (added in 1993) was 2.8 times greater in men than in women. The fitted model correlated well with the observed values in the next 12 months for both genders. CONCLUSIONS: We concluded that women had fewer CAG and PTCA procedures than men, and the influence of CAG on the PTCA series was significantly higher in men than in women.

Correlation between quantitative severity of stress thallium-201 myocardial perfusion defect and severity of coronary stenosis.

The correlation between the quantitative myocardial perfusion defect severity of stress 201Tl single-photon emission computed tomography and the severity of coronary stenosis was investigated in 28 patients with angina pectoris. Among the 28 patients, four had normal or nearly normal coronary angiograms, seven had one-vessel disease, six had two-vessel disease and 11 had three-vessel disease. Seven patients had prior myocardial infarctions and two had collateral flows to the diseased vessels. The quantitative 201Tl defect severity score was obtained by summing the standard deviations of each pixel in which the counts fell > 2.5 SD below the mean normal counts. The severity of coronary stenosis was expressed as the Gensini score. The quantitative 201Tl defect severity score correlated significantly with the Gensini score. In patients without prior myocardial infarction or collateral flow, a more significant correlation between the quantitative 201Tl defect severity score and the Gensini score was found. Quantitative analysis of stress 201Tl defect severity provides a useful, noninvasive assessment of the functional severity of coronary stenosis compared with coronary angiography.

Arsenic burden survey among refuse incinerator workers.

BACKGROUND: Incinerator workers are not considered to have arsenic overexposure although they have the risk of overexposure to other heavy metals. AIM: To examine the relationship between arsenic burden and risk of occupational exposure in employees working at a municipal refuse incinerator by determining the concentrations of arsenic in the blood and urine. SETTINGS AND DESIGN: The workers were divided into three groups based on their probability of contact with combustion-generated residues, namely Group 1: indirect contact, Group 2: direct contact and Group 3: no contact. Healthy age- and sex-matched residents living in the vicinity were enrolled as the control group. MATERIALS AND METHODS: Heavy metal concentrations were measured by atomic absorption spectrophotometer. Downstream rivers and drinking water of the residents were examined for environmental arsenic pollution. A questionnaire survey concerning the contact history of arsenic was simultaneously conducted. STATISTICAL ANALYSIS: Non-parametric tests, cross-tabulation and multinomial logistic regression. RESULTS: This study recruited 122 incinerator workers. The urine and blood arsenic concentrations as well as incidences of overexposure were significantly higher in the workers than in control subjects. The workers who had indirect or no contact with combustion-generated residues had significantly higher blood arsenic level. Arsenic contact history could not explain the difference. Airborne and waterborne arsenic pollution were not detected. CONCLUSION: Incinerator workers run the risk of being exposed to arsenic pollution, especially those who have incomplete protection in the workplace even though they only have indirect or no contact with combustion-generated pollutants.