Left ventricular geometry and function preceding neurally mediated syncope.

BACKGROUND: Neurally mediated syncope has been associated with increased left ventricular (LV) fractional shortening (FS) during tilt testing, which is consistent with the hypothesis that the stimulation of LV mechanoreceptors leads to reflex hypotension and/or bradycardia. However, FS does not represent true LV contractility because of its dependence on afterload and preload. METHODS AND RESULTS: To elucidate the role of increased contractility in the mediation of neurally mediated syncope, we compared echocardiographic measures of LV performance corrected for end-systolic stress (ESS) in 21 patients (13 women and 8 men) with unexplained syncope who had either positive (n=10) or negative (n=11) responses to a tilt-table test. Two-dimensional echocardiographic LV imaging was performed at baseline and during the initial 5 minutes of upright tilt. In the supine position, both groups had similar LV end-diastolic volume indexes, stroke volumes, FS, circumferential ESS, and afterload-independent measures of LV performance (stress-corrected midwall and FS). However, after 5 minutes of upright tilt, patients who subsequently had a positive test had a lower stroke volume, lower stress-corrected midwall shortening, and endocardial FS. The tilt-positive group also had a greater fall in ESS and FS early during upright tilt. CONCLUSIONS: Reduced ESS, LV volume, and chamber function during initial upright tilt are associated with a subsequent positive tilt response in patients with unexplained syncope. These data suggest that if paradoxic activation of LV mechanoreceptors has a role in mediating neurally mediated syncope, it is not triggered by LV hypercontractility or increased systolic wall stress during the initial period of upright tilt.

Effect of type 2 diabetes mellitus on left ventricular geometry and systolic function in hypertensive subjects: Hypertension Genetic Epidemiology Network (HyperGEN) study.

BACKGROUND: Type 2 diabetes is a cardiovascular risk factor. It remains to be elucidated in a large, population-based sample whether diabetes is associated with changes in left ventricular (LV) structure and systolic function independent of obesity and systolic blood pressure (BP). METHODS AND RESULTS: Among 1950 hypertensive participants in the HyperGEN Study without overt coronary heart disease or significant valve disease, 20% (n=386) had diabetes. Diabetics were more likely to be women, black, older, and have higher BMI and waist/hip ratio than were nondiabetics. After adjustment for age and sex, diabetics had higher systolic BP, pulse pressure, and heart rate; lower diastolic BP; and longer duration of hypertension than nondiabetics. LV mass and relative wall thickness were higher in diabetic than nondiabetic subjects independent of covariates. Compared with nondiabetic hypertensives, diabetics had lower stress-corrected midwall shortening, independent of covariates, without difference in LV EF. Insulin levels and insulin resistance were higher in non-insulin-treated diabetics (n=195) than nondiabetic (n=1439) subjects (both P:<0.01). Insulin resistance positively but weakly related to LV mass and relative wall thickness. CONCLUSIONS: In a relatively healthy, population-based sample of hypertensive adults, type 2 diabetes was associated with higher LV mass, more concentric LV geometry, and lower myocardial function, independent of age, sex, body size, and arterial BP. structural and functional abnormalities in addition to, and independent of, atherosclerosis.(13) (14) In the Framingham cohort, diabetes was associated with higher LV mass in women but not men.(15) High blood pressure (BP), obesity, and abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities(16) and may contribute to the association of diabetes with cardiovascular events. Cardiac features of diabetic and nondiabetic hypertensive subjects remain incompletely described in population-based samples. Therefore, we compared clinical and metabolic characteristics, LV geometry, and systolic function between diabetic and nondiabetic hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study.

OBJECTIVES: We sought to determine the effect of diabetes mellitus (DM) on left ventricular (LV) filling pattern in normotensive (NT) and hypertensive (HTN) individuals. BACKGROUND: Diastolic abnormalities have been extensively described in HTN but are less well characterized in DM, which frequently coexists with HTN. METHODS: We analyzed the transmitral inflow velocity profile at the mitral annulus in four groups from the Strong Heart Study: NT-non-DM (n = 730), HTN-non-DM (n = 394), NT-DM (n = 616) and HTN-DM (n = 671). The DM subjects were further divided into those with normal filling pattern (n = 107) and those with abnormal relaxation (AbnREL) (n = 447). RESULTS: The peak E velocity was lowest in HTN-DM, intermediate in NT-DM and HT-non-DM and highest in the NT-non-DM group (p < 0.001), with a reverse trend seen for peak A velocity (p < 0.001). In multivariate analysis, E/A ratio was lowest in HTN-DM and highest in NT-non-DM, with no difference between NT-DM and HTN-non DM (p < 0.001). Likewise, mean atrial filling fraction and deceleration time were highest in HTN-DM, followed by HTN-non-DM or NT-DM and lowest in NT-non-DM (both p < 0.05). Among DM subjects, those with AbnREL had higher fasting glucose (p = 0.03) and hemoglobin A1C (p = 0.04). CONCLUSIONS: Diabetes mellitus, especially with worse glycemic control, is independently associated with abnormal LV relaxation. The severity of abnormal LV relaxation is similar to the well-known impaired relaxation associated with HTN. The combination of DM and HTN has more severe abnormal LV relaxation than groups with either condition alone. In addition, AbnREL in DM is associated with worse glycemic control.

Relation of hemodynamic volume load to arterial and cardiac size.

OBJECTIVES: This study sought to assess the relation of Doppler stroke volume (SV) to cardiac and carotid artery size and to determine whether volume load accounts for the parallelism between the two. BACKGROUND: It has been suggested that altered hemodynamic volume load can modify the degree and pattern of left ventricular (LV) hypertrophy from that predicted from blood pressure (BP) alone. METHODS: We related Doppler echocardiographic SV in 342 normotensive or unmedicated asymptomatic hypertensive adults to echocardiographic LV mass, LV internal dimension (LVID), wall thickness, carotid ultrasound arterial lumen diameter, intimal-medial thickness (IMT) and cross-sectional area (CSA). RESULTS: SV was positively related to LV mass (r = 0.42), LVID (r = 0.45), ventricular wall thickness (r = 0.20 to 0.29) and carotid diameter (r = 0.23, all p < 0.0001); CSA (r = 0.17, p < 0.002); and IMT (r = 0.12, p = 0.03). In multivariate analyses controlling for awake ambulatory BP and the circumferential end-systolic stress/end-systolic volume index ratio, SV remained an independent predictor of LV mass and chamber size (both p < 0.0001) but not LV wall thickness. SV also predicted carotid diameter (p < 0.0002), CSA (p = 0.001) and, to a lesser degree, IMT (p = 0.02) after controlling for mean awake BP and age. In additional analyses, LV and carotid dimensions were significantly interrelated independent of SV. CONCLUSIONS: SV measured by invasively validated Doppler echocardiography is associated with LV and carotid artery enlargement and eccentric hypertrophy, independent of arterial pressure, LV contractility, age and body size; however, SV and other variables do not account for the previously documented parallelism between cardiac and arterial structure.

Prevalence and correlates of aortic regurgitation in American Indians: the Strong Heart Study.

OBJECTIVES: We sought to determine the prevalence and correlates of aortic regurgitation (AR) in a population-based sample group. BACKGROUND: Concern over induction of AR by weight loss medication highlights the importance of assessing the prevalence and correlates of AR in unselected patient groups. METHODS: Aortic regurgitation was assessed by color flow Doppler echocardiography in 3,501 American Indian participants age 47 to 81 years during the second Strong Heart Study. RESULTS: Mild (1+) AR was present in 7.3%, 2+ AR in 2.4% and 3+ to 4+ AR in 0.3% of participants, more frequently in those > or =60 years old than in those <60 years old (14.4% vs. 5.8%, p<0.001); AR was unrelated to gender. Compared with participants without AR, those with mild AR had a lower body mass index (p<0.004) and higher systolic pressure (p<0.003). Participants with AR had larger aortic root diameters (3.6+/-0.4 vs. 3.4+/-0.4 cm, p<0.001), higher creatinine levels (1.3+/-1.3 vs. 1.0+/-1.0 mg/dl, p<0.001) and higher urine albumin/creatinine levels (3.6+/-2.3 vs. 3.3+/-2.0 log, p<0.001), as well as higher prevalences of aortic stenosis (AS) or mitral stenosis (MS) (p<0.001). Regression analysis showed that AR was independently related to older age and larger aortic roots (p<0.0001), AS and absence of diabetes (p = 0.002), MS (p = 0.003) and higher log urine albumin/creatinine (p = 0.005). CONCLUSIONS: Aortic regurgitation occurred in 10% of a sample group of middle-aged to older adults and was related to older age, larger aortic root diameter, aortic and mitral stenosis and albuminuria. There was no association of AR with being overweight and a negative association of AR with diabetes.

Prevalence and correlates of mitral valve prolapse in a population-based sample of American Indians: the Strong Heart Study.

PURPOSE: Mitral valve prolapse is heritable and occurs frequently in the general population despite associations with mitral regurgitation and infective endocarditis, suggesting that selective advantages might be associated with mitral valve prolapse. SUBJECTS AND METHODS: Clinical examination and 2-dimensional and color Doppler echocardiography were performed in 3340 American Indian participants in the Strong Heart Study. RESULTS: Mitral valve prolapse (clear-cut billowing of one or both mitral leaflets across the mitral anular plane in 2-dimensional parasternal long-axis recordings or >2-mm late systolic posterior displacement of mitral leaflets by M mode) occurred in 37 (1.8%) of 2077 women and 20 (1.6%) of 1263 men (P = 0.88); 32 (3.5%) of 907 patients with normal glucose tolerance, 11 (2.3%) of 486 patients with impaired glucose tolerance, and 13 (0.7%) of 1735 patients with diabetes (P <0.0001). Participants with mitral valve prolapse had lower mean (+/- SD) body mass index (28 +/- 5 kg/m(2) vs. 31 +/- 6 kg/m(2), P = 0.001) and blood pressure (124/71 +/- 19/10 mm Hg vs. 130/75 +/- 21/10 mm Hg, P <0.05), as well as lower levels of fasting glucose, triglycerides, serum creatinine, and log urine albumin/creatinine ratio (all P <0.001), than did those without mitral valve prolapse, although all subjects were similar in age (60 +/- 8 years). Participants with mitral valve prolapse had lower ventricular septal (0.87 +/- 0.08 cm vs. 0.93 +/- 0.13 cm) and posterior wall thicknesses (0.82 +/- 0.08 cm vs. 0.87 +/- 0.10 cm), mass (38 +/- 7 g/m(2.7) vs. 42 +/- 11 g/m(2.7)), and relative wall thickness (0.33 +/- 0.04 vs. 0.35 +/- 0.05), and increased stress-corrected midwall shortening (all P <0.01). Mitral valve prolapse was associated with a higher prevalence of mild (16 of 57 [28%] vs. 614 of 3283 [19%]) and more severe mitral regurgitation (5 of 57 [9%] vs. 48 of 3283 [1%], P <0.0001). Regression analyses showed prolapse was associated with low ventricular relative wall thickness, high midwall function, and low urine albumin/creatinine ratio, independent of age, sex, body mass index, and diabetes. CONCLUSIONS: Mitral valve prolapse is fairly common and is strongly associated with mitral regurgitation in the general population. However, it is also associated with lower body weight, blood pressure, and prevalence of diabetes; a more favorable metabolic profile and ventricular geometry; and better myocardial and renal function.

Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the Strong Heart Study.

In selected clinical series, > or = 50% of adults with congestive heart failure (CHF) do not have left ventricular (LV) systolic dysfunction. Little is known of the prevalence of this phenomenon in population samples. Therefore, clinical examination and echocardiography were used in the second examination of the Strong Heart Study (3,184 men and women, 47 to 81 years old) to identify 95 participants with CHF, 50 of whom had normal LV ejection fraction (EF) (> 54%), 19 of whom had mildly reduced EF (40% to 54%), and 26 of whom had EF < or = 40%. Compared with those with no CHF, participants with CHF and no, mild, or severe decrease in EF had higher creatinine levels (2.34 to 2.85 vs 1.01 mg/dl, p < 0.001) and higher prevalences of diabetes (60% to 70% vs 50%) and hypertension (75% to 96% vs 46%, p < 0.05). Compared with those with no CHF, participants with CHF and normal EF had prolonged deceleration time (233 vs 204 ms, p < 0.05) and a reduced E/A, whereas those with CHF and EF < or = 40% had short deceleration time (158 ms, p < 0.05) and high E/A (1.70, p < 0.001); patients with CHF and normal EF had higher LV mass (98 vs 84 g/m2, p < 0.001) and relative wall thickness (0.37 vs 0.35, p < 0.05) than those without CHF. Patients with CHF with normal EF were, compared with those without CHF or with CHF and EF < or = 40%, disproportionately women (mean 84% vs 63% and 42%, p < 0.001), older (mean 64 vs 60 years and 63 years, respectively, p < 0.01), had higher body mass index (mean 33.1 vs 31.0 and 27.7 kg/m2, p < 0.05), and higher systolic blood pressure (mean 137 vs 130 and 128 mm Hg, both p < 0.05). Thus, in a population-based sample, patients with CHF and normal LV EF were older and overweight, more often women, had renal dysfunction, impaired early diastolic LV relaxation, and concentric LV geometry, whereas patients with CHF and severe LV dysfunction were more often men, had lower body mass index, a restrictive pattern of LV filling, and eccentric LV hypertrophy.

Prevalence and correlates of mitral regurgitation in a population-based sample (the Strong Heart Study).

Evidence suggesting that mitral regurgitation (MR) may be induced by appetite suppressant medications heightens the importance of understanding the prevalence and correlates of MR, especially its relation to obesity, in population-based samples. MR was assessed by color Doppler echocardiography in 3,486 American Indian participants in the Strong Heart Study. Mild (1+) MR was present in 19.2%, moderate (2+) MR in 1.6%, moderately severe (3+) in 0.3%, and severe (4+) in 0.2% of participants. In univariate analyses, MR was unrelated to gender, diabetes, or lipid levels, but was more frequent in North/South Dakota (28.3%) than in Oklahoma (21.6%) or Arizona (14.3%) (p <0.001). MR was related to lower body mass index (BMI) (p <0.001), older age (p <0.001), higher systolic blood pressure (p = 0.003), higher serum creatinine (p <0.001), and higher urine albumin/creatinine ratio (p <0.001). In multivariate analyses, the presence and severity of MR were independently associated with higher serum creatinine, lower BMI, mitral stenosis, prior myocardial infarction, female gender, mitral valve prolapse and, variably, older age. In conclusion, MR, mostly mild, is detected by color Doppler echocardiography in >20% of middle-aged and older adults. MR is independently associated with female gender, lower BMI, older age, and renal dysfunction, as well as with prior myocardial infarction, mitral stenosis, and mitral valve prolapse. It is not related to dyslipidemia or diabetes.

Separate and joint effects of systemic hypertension and diabetes mellitus on left ventricular structure and function in American Indians (the Strong Heart Study).

Although the association of systemic hypertension (SH) with diabetes mellitus (DM) is well established, the cardiac features and hemodynamic profile of patients with SH and DM diagnosed by American Diabetes Association criteria have not been elucidated. To address this issue, echocardiograms were analyzed in 1,025 American Indian participants of the Strong Heart Study with neither DM nor SH, 642 with DM alone, 614 with SH alone, and 874 with SH and DM. In analyses that adjusted for age, gender, body mass index, and heart rate, DM and SH were associated with increased left ventricular (LV) wall thicknesses, with the greatest impact of DM on LV relative wall thickness and of the combination of DM and SH on LV mass (both p <0.001). LV fractional shortening was reduced with SH and SH + DM, midwall shortening was reduced with DM, SH, and their combination, and was reduced in both diabetic groups compared with their nondiabetic counterparts (p <0.001). DM alone was associated with lower measures of LV pump performance (stroke volume, cardiac output, and their indexes) than SH alone. Pulse pressure/stroke index, an indirect measure of arterial stiffness, was elevated in participants with DM or SH alone and most in those with both conditions. There were progressive increases from the reference group to DM alone, SH alone, and DM + SH with regard to prevalences of LV hypertrophy (12% to 19%, 29% and 38%) and subnormal LV myocardial function (7% to 10%, 11% and 18%, both p <0.001). In conclusion, DM and SH each have adverse effects on LV geometry and function, and the combination of SH and DM results in the greatest degree of LV hypertrophy, myocardial dysfunction, and arterial stiffness.

The spectrum of epilepsy in sickle cell anemia.

In a study population of 152 patients seen at Thomas Jefferson University Hospital's sickle cell center between 1981 and 1992, 21 patients with seizures were identified. Clinical charts, electroencephalograms and neuroradiological studies were reviewed retrospectively. Seventeen patients with epilepsy were identified. Eleven had generalized tonic-clonic, 2 had partial, and 4 had poorly characterized seizures. CT/MRI evaluation was focally abnormal in 6 patients, 4 of whom had cortical lesions. Atrophy was noted in 3 patients, while imaging studies were normal in 6 patients. The EEGs demonstrated focal epileptiform discharges in 9 patients, generalized slowing in 5 patients, and was normal in 3 patients. Four patients had generalized seizures only with meperidine administration, all of whom had nonfocal EEG and radiological studies. We concluded that (1) epilepsy is more common in sickle cell patients than in the general population; (2) the majority of our epileptic sickle cell patients have nonfocal CT or MRI studies but demonstrate focal EEG abnormalities; and (3) meperidine administration is associated with generalized seizures in sickle cell patients.

Long-term outcome following sympathectomy for complex regional pain syndrome type 1 (RSD).

We performed a retrospective study of 29 patients with CRPS1 (RSD) who were initially examined between 1983 and 1993, and had either transthoracic (lower third of stellate ganglia to T3) or lumbar (L2-L4) sympathectomy. The patients were followed from 24 to 108 months after surgery. Patients with unsuccessful surgical outcomes had significantly longer duration of symptoms before surgery (median, 36 months) than those with successful outcomes (median, 16 months) by Wilcoxon rank sum test (chi2=8.69, df=1, P<0.01). All seven patients (100%) who had sympathectomy within 12 months of injury, nine of 13 patients (69.2%) who had sympathectomy within 24 months of injury, and only four of nine patients (44.4%) who had sympathectomy after 24 months of injury obtained permanent (greater than 24 months) symptom relief. Patient age, sex, occupation, site of injury, type of injury, presence of trophic changes, and duration of follow-up were not significantly related (P>0.05) to surgical outcome.

Shoulder-arm pain from cervical bands and scalene muscle anomalies.

Fourteen patients were identified with (1) pain and sensory changes in a brachial plexus distribution, (2) aggravation of pain with use of the affected extremity, and (3) pain on palpation over the brachial plexus. All patients had minimal or no intrinsic hand muscle atrophy. Only one patient had cervical ribs. Nerve conduction studies were normal, and electromyography (EMG) showed mild chronic neuropathic changes in 2 patients. None of the patients responded to conservative therapy over a prolonged period (7-12 months). A compressive brachial plexopathy from abnormally attached or enlarged scalene muscles that affected both upper and lower trunks of the brachial plexus was found at surgery in all patients. In 13 patients, at least one fibrous band compressed the lower trunk of the brachial plexus. Therefore, neurogenic thoracic outlet syndrome can occur from cervical bands and scalene muscle anomalies without intrinsic hand muscle atrophy, cervical ribs, enlarged C7 transverse processes, or EMG abnormalities.

Association of left bundle branch block with left ventricular structure and function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Electrocardiographic (ECG) left bundle branch block (LBBB) is associated with left ventricular hypertrophy (LVH), but its relation to left ventricular (LV) geometry and function in hypertensive patients with ECG LVH is unknown. Echocardiograms were performed in 933 patients (548 women, mean age 66+/-7 years) with essential hypertension and LVH by baseline ECG in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. LBBB, defined by Minnesota code 7.1, was present in 47 patients and absent in 886 patients. Patients with and without LBBB were similar in age, gender, body mass index, blood pressure, prevalence of diabetes, and history of myocardial infarction. Despite similarly elevated mean LV mass (126+/-25 vs 124+/-26 g/m(2)) and relative wall thickness (0.41+/-0.07 vs 0.41+/-0.07, P=NS), patients with LBBB had lower LV fractional shortening (30+/-6 vs 34+/-6%), ejection fraction (56+/-10 vs 61+/-8%), midwall shortening (14+/-2 vs 16+/-2%), stress-corrected midwall shortening (90+/-13 vs 97+/-13%) (all P<0.001), and lower LV stroke index (38+/-7 vs 42+/-9 ml/m(2)) (P<0.05). Patients with LBBB also had reduced LV inferior wall and lower mitral E/A ratio (0.75+/-0.18 vs 0.87+/-0.38) (all P<0.05). The above univariate results were confirmed by multivariate analyses adjusted for gender, age, blood pressures, height, weight, body mass index, heart rate, and LV mass index. Among hypertensive patients at high risk because of ECG LVH, the presence of LBBB identifies individuals with worse global and regional LV systolic function and impaired LV relaxation without more severe LVH by echocardiography.

Regression of electrocardiographic left ventricular hypertrophy predicts regression of echocardiographic left ventricular mass: the LIFE study.

The electrocardiogram (ECG) is widely used for detection of left ventricular hypertrophy (LVH). However, whether changes in ECG LVH during antihypertensive therapy predict changes in LV mass remains unclear. Baseline and year-1 ECGs and echocardiograms were assessed in 584 hypertensive patients with ECG LVH by Sokolow-Lyon or Cornell voltage-duration product criteria at entry into the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. A >/=25% decrease in Cornell product defined regression of ECG LVH; a <25% decrease defined no significant regression; and an increase defined progression of ECG LVH. Regression of echocardiographic LVH was defined by a >/=20% reduction in LV mass. After 1 year of therapy, 155 patients (27%) had regression of ECG LVH, 286 (49%) had no significant change, and 143 (25%) had progression of ECG LVH. Compared with patients with progression of ECG LVH, patients with no significant decrease and patients with regression of ECG LVH had stepwise greater absolute decreases in LV mass (-16+/-33 vs -29+/-37 vs -32+/-41 g, P<0.001), greater percent reductions in LV mass (-5.7+/-14.6 vs -11.3+/-13.6 vs -12.3+/-15.6%, P<0.001), and were more likely to decrease LV mass by >/=20% (11.2 vs 24.8 vs 36.1%, P<0.001), even after adjusting for possible effects of baseline and change in systolic and diastolic pressures. Compared with progression of ECG LVH, regression of the Cornell product ECG LVH is associated with greater reduction in LV mass and a greater likelihood of regression of anatomic LVH.

Impact of valvular regurgitation on left ventricular geometry and function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Mild-to-moderate aortic and mitral regurgitation are frequently detected by echocardiogram in asymptomatic hypertensive patients. Our goal was to assess the prevalence and impact of mild-to-moderate mitral and/or aortic regurgitation on left ventricular (LV) structure and function in patients with hypertension and LV hypertrophy (LVH). Hypertensive patients with ECG LVH enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy were evaluated. Among 939 patients with needed LV measurements and Doppler data, 242 had mild (1+) valvular regurgitation, and 51 patients had moderate (2+ or 3+) regurgitation of one or both valves. In analyses adjusting for gender, patients with mild mitral and/or aortic regurgitation had larger LV internal dimensions (5.25 vs 5.33 cm, P<0.05), higher LV mass indexed for body surface area (122 vs 125 g/m(2), P<0.05) or height(2.7) (55.4 vs 57.3, P<0.05), and larger left atrial diameter. Patients with moderate regurgitation of one or both valves had larger LV chambers (5.25 vs 5.9 cm, P<0.001), greater mean LV mass (232 vs 248 g, P<0.001) and LV mass indexed for body surface area or height(2.7), and higher Doppler stroke volume. Patients with moderate valvular regurgitation also had a higher prevalence of LVH due to an increased prevalence of eccentric LVH. There were no differences among groups defined by the presence and severity of valvular regurgitation in cardiac output, total peripheral resistance, or pulse pressure/stroke volume, indicating that the observed inter-group differences in LV geometry were not due to differences in the haemodynamic severity of hypertension. Hypertensive patients with mild-to-moderate mitral or aortic valvular insufficiency have additional LV structural and functional changes that may affect prognosis.

Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study.

While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrollment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97 mmHg) and men (149/85 from 173/99 mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1 l/min and both -0.20 mmHg/ml/m(2), respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24 g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23 g, P=0.001). LV mass regression was greater in women, by 8.0+/-2.8 g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.

New esterase enzymes involved in organophosphate resistance in Culex pipiens (Diptera: Culicidae) from Guang Zhou, China.

Organophosphate (OP) insecticides have been used widely to control Culex pipiens L. populations and this has led to the emergence of OP-resistance. Predominantly, resistance in Cx. pipiens is caused by over-production of nonspecific esterases, such as Est beta 1(1) and Est alpha 2(1)/beta 2(1). These esterases confer multiple resistance to organophosphorus and carbamate insecticides. To define the esterases in Chinese Cx. pipiens, restriction fragment-length polymorphism analysis was performed at the esterase beta locus. A new esterase haplotype (Est beta 8) was found. Starch gel electrophoresis indicated that Est beta 8 was coelevated with a novel Est alpha 8. This article reports Est alpha 8/beta 8 esterase-mediated resistance in Cx. pipiens complex.

Polynitroxylated starch/TPL attenuates cachexia and increased epithelial permeability associated with TNBS colitis.

Free radicals play an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, the reduction or elimination of adverse oxidant effects can provide novel therapy for IBD. Here, the antioxidant capacity and protective effects of a new class of chemically modified hetastarch (polynitroxyl starch, or PNS) plus 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol or TPL) (PNS/TPL) were assessed in a model of colitis. The superoxide scavenging capacity of PNS/TPL-that is, the inhibition of the reduction of cytochrome c in the presence of xanthine/xanthine oxidase (X/XO)-was evaluated in vitro. The effects of PNS/TPL on X/XO-induced neutrophil endothelial adhesion in vitro were investigated. Also, this study tested the protection produced by PNS/TPL in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. PNS/TPL was given intravenously immediately before (< 30 min) and intraperitoneally at 24 and 72 hr after TNBS induction. The body weight and survival rate of the mice were checked daily. Colonic mucosal damage was assessed on the 7th day by measuring intestinal permeability to Evans blue (EB) in vivo. The ability of PNS to reoxidize bioreduced TPL was documented by whole-body electron paramagnetic resonance (EPR) detection. We found that PNS or TPL exhibits superoxide dismutase (SOD)-like activity, with approximately 2% of SOD activity occurring on a molar basis. The endothelial-neutrophil adherence induced by X/XO was significantly inhibited by PNS/TPL but not by TPL alone. PNS/TPL protected against cachexia and mortality, both usually induced by TNBS. Epithelial permeability was increased significantly in TNBS mice but was ameliorated by the administration of PNS/TPL. In conclusion, PNS/TPL may be beneficial in the treatment or prevention of IBD through its antioxidant effects, which inhibit oxidant-mediated leukocyte adhesion and injury to endothelial cells.

Amplified esterases B1 and A2-B2 in field populations of Culex pipiens from China.

The main organophosphate (OP) resistance mechanism in the Culex pipiens complex is increased activity of esterases A and B. Fourth-stage larvae from 2 field populations of C. pipiens from Gaomi and Kunming, China, were compared for tolerance to parathion, dichlorovos (OP), and bassa (carbamate) insecticides. Both populations were resistant to OPs but not to bassa. Starch gel electrophoresis indicated that elevated esterase activity was correlated with OP resistance. High frequencies of amplified esterase genes B1 and A2-B2 (0.85 and 0.50) were discovered in Gaomi and Kunming, respectively. However, only low levels of gene amplification were detected.

A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation.

It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53 in vitro and in vivo. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G(1)/S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.