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Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiologic characteristics.

BACKGROUND: Isolated rest tremor, which is observed in some patients with essential tremor (ET), poses a diagnostic challenge. The phenomenon has been examined in few studies and is poorly understood. OBJECTIVES: To determine the prevalence and study the clinical correlates of rest tremor in ET and to examine the electrophysiologic features in a subgroup of patients. METHODS: Sixty-four patients with ET cared for at a tertiary referral center underwent neurologic examination. Five of 12 patients with rest tremor also underwent quantitative computerized tremor analysis using accelerometry and handwritten spiral analysis. RESULTS: Twelve of 64 patients with ET had rest tremor (prevalence, 18.8%; 95% confidence interval, 9.2%-28.4%). Compared with the 52 patients with ET without rest tremor, these 12 had disease of longer duration and greater severity. Also, their ET was more widely disseminated, as evidenced by a larger proportion with head tremor. None had clinical signs of bradykinesia or rigidity. The 5 patients with rest tremor who underwent electrophysiologic study had electrophysiologic features consistent with parkinsonism (eg, slow spiral speed and increased decrement of spiral speed with radius). CONCLUSIONS: In our sample, 1 in 5 patients with ET had rest tremor. The tremor was associated with disease that was more severe, more disseminated, and of longer duration. Some of these patients had electrophysiologic features consistent with parkinsonism. The basis for the rest tremor could be basal ganglia involvement, raising the possibility that the pathologic process responsible for ET may extend to these structures.

Aged↗

Intraarticular corticosteroid injections: should we rest the joints?

To prevent damage in injected joints, it has been our policy to rest them for 48 hours. To test this assertion we randomized 30 rheumatoid arthritis (RA) patients (rest, no-rest). Results in 28 patients (63 joints: 27 rest and 36 no-rest) are presented. Joint evaluation was performed at baseline and at 48 hours (pain/tenderness, swelling and range of motion). Two analyses were conducted, the first included all joints, and the second only joint pairs. In both cases measurements at 48 hours were comparable for the rest and no rest group for both upper and lower extremity joints (pain/tenderness/swelling and range of motion). At a later follow up (average 10 months) there were no differences in any of the parameters examined. Our study suggests that rest is not essential for intraarticular corticosteroids to be beneficial, at least in an inpatient setting. The applicability of our data to an outpatient population remains to be determined.

Adrenal Cortex Hormones↗

Advance toward S phase and retreat toward deeper "G0" states in resting 3Y1 cells with environmental changes.

To elucidate conditions which affect the lag time for resting cells to enter S phase after serum stimulation, we used a wild-type 3Y1 rat fibroblast line and four temperature-sensitive mutants of 3Y1 (3Y1tsD123, 3Y1tsF121, 3Y1tsG125, and 3Y1tsH203). Among these five lines, in only tsG125 cells was there an obviously prolonged lag time with increase in time in resting state at 33.8 degrees C. The resting wild-type 3Y1 cells, preexposed to 39.8 degrees C, also showed a prolongation of lag time. The prolongation in tsG125 had a certain limit. Preexposure to 39.8 degrees C before serum stimulation accelerated such prolongation in tsG125 to its limit, but did not change the limit, per se. Resting tsG125 cells stimulated by serum at 39.8 degrees C, did not enter S phase, yet they did advance toward S phase. When they were kept at 39.8 degrees C, they retreated toward a deeper resting state ("G0") with time. These retreats correlated with the decrease in stimulating activity in the culture media. About 20% of the resting tsG125 cells stimulated by serum at 39.8 degrees C were committed to enter S phase, when the extent of commitment was examined at 33.8 degrees C. Most of the tsG125 cells committed at 33.8 degrees C did not enter S phase, when the extent of commitment was examined at 39.8 degrees C. More cells were committed after stimulation at 33.8 degrees C than at 39.8 degrees C, when the test was done at 33.8 degrees C. We suggest that resting cells may be reversibly changed within range of resting states, in either direction, that is, advance toward S phase or retreat toward deeper "G0." These changes may be determined by alterations in the balance between synthesis and decay of the preparedness for the initiation of DNA synthesis caused by cellular response to environmental changes (e.g., medium activity, temperature, etc.). The ts defect in tsG125 may affect the cell cycle progression, both before and after commitment by serum.

Animals↗

Rest-dependence of twitch amplitude and sarcoplasmic reticulum calcium content in the developing rat myocardium.

Post-rest contractile response was studied in isolated ventricular muscle from rats aged 1 to 90 days. Amplitude of rapid cooling contractures (RCC) was taken as an index of the sarcoplasmic reticulum (SR) Ca2+ content. We observed that: (a) developed tension (per cross-section area) increased with age; (b) time to peak twitch force and relaxation half-time decreased from 87+/-6 to 56+/-2 ms and from 68+/-6 to 36+/-1 ms, respectively, from the neonatal period to adulthood; (c) post-rest twitch potentiation was observed at all ages, with greater relative potentiation in younger preparations, although relative potentiation of [Ca2+]i transient amplitude was similar in young and adult isolated ventricular myocytes; (d) rest did not significantly affect the amplitude of RCC in muscle or caffeine-evoked [Ca2+]i transients in myocytes at any studied age; (e) favoring Ca2+ efflux via Na+-Ca2+ exchange (NCX) during rest reversed twitch potentiation and caused a similar decrease in RCC amplitude ( approximately 40%) at all ages; (f) stimulation of Ca2+ influx via NCX during rest increased RCC amplitude ( approximately 40%) only in immature preparations. However, when this procedure was repeated after partial SR Ca2+ depletion, increase in RCC amplitude was not significantly age-dependent. We conclude that post-rest twitch potentiation is already present early after birth and does not require rest-dependent changes in SR Ca2+ content at any studied age. Our results suggest that NCX is close to equilibrium during rest in both adult and developing rat myocardium, and does not seem to mediate diastolic net Ca2+ fluxes which may affect the SR Ca2+ content.

Animals↗

Diabetic state-induced modification of resting membrane potential and conductance in diaphragm muscle of alloxan and diabetic KK-CAy mice.

The electrical properties of skeletal muscle membranes were investigated in genetically diabetic KK-CAy mice and alloxan-induced diabetic ddY mice. Using isolated phrenic nerve-diaphragm muscle or sciatic nerve-gastrocnemius muscle in situ preparations, nerve-stimulated twitch tensions (the maximal value) were obtained at lower voltage pulse in diabetic KK-CAy mice than in normal ddY mice. The diabetic state reduced resting membrane potentials (1.7-4.0 mV) and resting membrane conductance (0.37-0.44 mu siemen), decreased the amplitude (3.8-3.9 mV) and overshoot (4.5 mV) of directly induced-action potential, and prolonged action potential duration. In the diabetic state, resting membrane conductance was multiply-correlated with blood glucose level and resting membrane potential. In alloxan-induced diabetic mice, resting membrane potentials were significantly multiply-correlated with the weeks elapsed after alloxan injection and blood glucose level (p less than 0.01). Since the reduction of resting membrane potential correlated with the weeks, changes in resting membrane potential may be involved in the decrease in insulin-like growth factor action. The reduction of resting membrane conductance was correlated with the increase in blood glucose.

Action Potentials↗

The effects of the cardiotonic dihydropyridine derivatives Bay k 8644 and H160/51 on post-rest adaptation of guinea-pig papillary muscles.

In isolated guinea-pig papillary muscle, the effect of the two dihydropyridine derivatives Bay k 8644 (0.03-10 mumol/l) and H160/51 (0.1-3 mumol/l) on transmembrane action potentials and force of contraction were investigated at regular stimulation (1 Hz) and after a period of rest (10 min). The following results were obtained: At regular stimulation of the preparations, Bay k 8644 and H160/51 enhanced force of contraction without affecting time-to-peak tension. The time required for relaxation and the action potential duration were prolonged. These effects were transient with exposure to high concentrations of Bay k 8644 (greater than 3 mumol/l). The amplitude of the post-rest contraction thought to depend entirely on transmembrane calcium influx was small under control conditions and increased because of prolongation in time-to-peak tension in the presence of either dihydropyridine derivative. Isoprenaline (30 nmol/l) - as opposed to Bay k 8644 and H160/51 - increased the rate of force development of post-rest contractions. Bay k 8644 and H160/51 prolonged the duration of the first action potential after 10 min of rest. In the course of adaptation to steady state stimulation this prolongation transiently increased further resulting in a biphasic pattern which was attenuated by addition of nifedipine. With isoprenaline the biphasic pattern changed into a monotonous adaptation to pre-rest control. Our results show that the small enhancement of the post-rest contraction in the presence of Bay k 8644 or H160/51 is due to prolonged action potential duration after rest, whereas isoprenaline enhances the intensity of post-rest activation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Assessment of myocardial perfusion and viability with technetium-99m methoxyisobutylisonitrile and thallium-201 rest redistribution in chronic coronary artery disease.

We compare thallium-201 rest redistribution and fluorine-18 fluorodeoxyglucose ([18F]FDG) for the assessment of myocardial viability within technetium-99m methoxyisobutylisonitrile (MIBI) perfusion defects in 27 patients with chronic stable coronary artery disease. The following studies were performed: (1) stress 99mTc-MIBI, (2) rest 99mTc-MIBI, (3) 201Tl rest-redistribution single-photon emission tomography, (4) [18F]FDG positron emission tomography. The left ventricle was devided into 11 segments on matched tomographic images. The segment with the highest activity at stress was taken as the reference (activity=100%). Perfusion defects at 99mTc-MIBI rest were classified as severe (activity<50%), moderate (activity 50%-60%) or mild (activity 60%-85%). Uptakes of [18F]FDG and rest-redistributed 201Tl were recognized as significant if they exceeded 50% of that in the reference segment. Among the 33 segments with severe 99mTc-MIBI rest perfusion defects, 21 had significant [18F]FDG and 10 significant rest-redistributed 201Tl uptake. As regards the 37 segments with moderate defects, [18F]FDG was present in 29 and 201Tl in 31, while of the 134 segments with mild defects, 128 showed [18F]FDG uptake, and 131, 201Tl uptake. In conclusion, there is an inverse relationship between the severity of 99mTc-MIBI perfusion defects and the uptake of rest-redistributed 201Tl and [18F]FDG. Both tracers are adequate markers of viability in mild and moderate defects; in severe defects 201Tl might underestimate the presence of viability as assessed by [18F]FDG.

Adult↗

Influence of resting sympathetic activity on reflex sympathetic responses in normal man.

Reflex sympathetic responses to physiologic stress are known to be modulated by afferent sensory mechanisms. However, the potential influence of baseline sympathetic tone on these reflex-mediated responses is unclear. To test the hypothesis that the resting level of muscle sympathetic nerve activity (MSNA) influences reflex-mediated changes in MSNA in normal man, MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR) was measured in 38 normal subjects at rest and during deactivation of cardiopulmonary baroreceptors (CPBR) with lower body negative pressure (LBNP; 0 to -15 mmHg). A cold pressor test (CPT) also was performed in 25 subjects. Incremental LBNP decreased CVP (from 5.8 +/- 0.4 to 2.1 +/- 0.4 mmHg) without altering BP or HR, and increased in MSNA burst frequency (from 22.5 +/- 1.4 to 30.2 +/- 1.4 bursts/min). There was no significant correlation between levels of MSNA and any haemodynamic parameter at rest. There was a significant inverse correlation between CPBR sympathetic gain (CPBRSG, slope of the regression line correlating percentage change in MSNA (bursts/min) per mmHg decrease in CVP during non-hypotensive LBNP) and resting MSNA (r = -0.72, p < 0.0001). A significant inverse correlation was also observed between MSNA responses to the CPT (expressed as percentage change in burst frequency from control) and the resting MSNA (r = -0.63, p = 0.008). Sixteen subjects were restudied 3 weeks to 14 months later to determine reproducibility of measurements; resting BP and CVP, HR, and MSNA levels were not different between the two sessions, as was CPBRSG. In ten of these 16 subjects, in whom the CPT was repeated the MSNA response also was not significantly different. These studies demonstrate an inverse relationship between resting MSNA and both cardiopulmonary baroreflex sensitivity and sympathetic neural responses to the non-baroreflex mediated cold pressor stimulus. These findings suggest that resting levels of sympathetic neural activity influence reflex-mediated changes in muscle sympathetic nerve activity.

Adult↗

Low-dose dobutamine stress gated SPET for identification of viable myocardium: comparison with stress-rest perfusion SPET and PET.

The detection of viable myocardium is important for the prediction of functional recovery after revascularisation. However, a fixed perfusion defect often includes viable myocardium, and perfusion imaging then underestimates myocardial viability. We previously reported that low-dose dobutamine stress gated single-photon emission tomography (SPET) provides similar findings to dobutamine stress echocardiography in the assessment of myocardial viability. The present study investigated whether low-dose dobutamine stress gated SPET is of additional value as compared with stress-rest technetium-99m tetrofosmin SPET for the detection of myocardial viability. Standard stress-rest perfusion SPET, low-dose dobutamine stress gated SPET and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) were studied in 23 patients (mean age 67+/-7.6 years) with previous myocardial infarction. Twenty-one of them were successfully studied with each technique. FDG PET viability (FDG uptake >/=50%) was employed as the gold standard. One-day stress-rest (99m)Tc-tetrofosmin myocardial SPET was performed. After the resting study, gated SPET was acquired following infusion of 7.5 microg kg(-1) min(-1) of dobutamine. Left ventricular wall motion in 16 segments was assessed by cine mode display using a four-point scale. Myocardial viability was considered present when there was improvement by one point. Of a total of 336 segments analysed, 53 had persistent defects on stress-rest perfusion SPET. FDG viability was seen in 16 of 17 dobutamine-responsive segments, but in only 11 of 36 dobutamine non-responsive segments ( P<0.01). Thus, in the segments with persistent defects, viability findings on low-dose dobutamine stress gated SPET were concordant with those on FDG PET in 77% of segments (kappa value =0.55). For the detection of FDG-viable myocardium, the combination of stress-rest perfusion SPET and low-dose dobutamine stress gated SPET achieved a better sensitivity than stress-rest perfusion SPET alone (35/46, 76% vs 19/46, 41.3%, P<0.001), with a similar specificity (25/29, 86% vs 26/29, 90%, P=NS). We conclude that in the identification of viable myocardium, low-dose dobutamine stress gated SPET may provide additional information missed on a routine stress-rest perfusion scan. Dobutamine stress gated SPET may provide new insights into myocardial viability on the basis of ischaemia and contractile reserve.

Aged↗

Influence of verapamil therapy on left ventricular performance at rest and during exercise in hypertrophic cardiomyopathy.

To determine the hemodynamic effect of verapamil at rest and during exercise, 18 patients with hypertrophic cardiomyopathy were studied before and after 7 weeks of treatment with oral verapamil (maximal dose, 720 mg/day). At rest and at peak exercise, verapamil produced a significant increase in left ventricular (LV) systolic performance in terms of stroke volume index (rest, from 43 +/- 11 to 53 +/- 11 ml/m2, p less than 0.001; exercise, from 46 +/- 11 to 51 +/- 10 ml/m2, p less than 0.01), whereas heart rate decreased (rest, from 81 +/- 14 to 70 +/- 11 min-1, p less than 0.001; exercise, from 150 +/- 21 to 141 +/- 18 min-1, p less than 0.01). Cardiac index at rest and during exercise remained unchanged. Systolic vascular resistance did not change at rest, but decreased significantly during exercise (974 +/- 243 to 874 +/- 174 dynes s cm-5; p less than 0.05). After verapamil administration, pulmonary artery pressures did not change at rest, but decreased significantly during exercise. This was probably due to a shift in the LV pressure-volume relation. The improvement in LV hemodynamics was associated with a significant increase in exercise capacity. The findings of this study indicate that in patients with hypertrophic cardiomyopathy, hemodynamic improvement at rest and during exercise can be achieved by chronic administration of verapamil.

Adult↗

Effectiveness of percutaneous transluminal coronary angioplasty for patients with medically refractory rest angina pectoris and high risk of adverse outcomes with coronary artery bypass grafting.

This study was undertaken to test the hypothesis that percutaneous transluminal coronary angioplasty (PTCA) is a reasonable alternative to coronary artery bypass grafting (CABG) for some high-risk patients with medically refractory rest angina. Over a 5-year period, 1 operator at a tertiary Veterans Affairs Medical Center performed angioplasty on 624 patients, of whom 441 had unstable angina. Of these 441 patients, 288 had rest angina and 225 had medically refractory rest angina. Medically refractory unstable angina was defined as reversible myocardial ischemia occurring at rest in an intensive care unit setting with low flow oxygen despite the following medications: (1) oral aspirin, intravenous heparin, or both; (2) some combination of beta blocker, calcium blocker, and/or nitrate so that resting heart rate is < 70 beats/min or resting blood pressure < 140 mm Hg, or both. There were 207 patients with medically refractory rest angina who had > or = 1 of the following characteristics predictive of a more than twofold increased risk of operative death at CABG: age > 70 years, prior CABG, recent myocardial infarct, need for intravenous nitroglycerin, need for intraaortic balloon pump, and left ventricular ejection fraction < 0.35. Of these 207 patients, 11 died (5%) during index hospitalization, 196 (95%) were discharged, and 186 (90%) went home angina free. There were 2 emergency CABGs and 9 acute myocardial infarctions. At follow-up (3 to 60 months, average 24), there were 27 late deaths (for a total of 38 [18%]), 8 (4%) late CABGs, and 44 (21%) late PTCAs (with 17 [8%] late myocardial infarctions). The 2-year mortality of 18% for this cohort is comparable to a 21% 2-year mortality observed in a group of 1,073 "high-risk" patients who underwent CABG in the Veterans Affairs Medical Center from 1987 to 1988. These data support the hypothesis that PTCA provides an alternative to CABG in some high-risk patients with medically refractory rest angina.

Age Factors↗

Resting membrane potential in 41A3 mouse neuroblastoma cells. Effect of increased glucose and galactose concentrations.

Neuroblastoma cells were used to examine the effect of high concentrations of glucose or galactose and accumulation of polyols on the resting membrane potential. Polyol levels are increased and myo-inositol content decreased when neuroblastoma cells are chronically exposed to media containing 30 mM glucose or 30 mM galactose compared to cells grown in media containing 30 mM fructose. Furthermore, the 6 h accumulation and incorporation into phospholipid of extracellular myo-inositol is decreased in cells exposed to media containing 30 mM glucose or 30 mM galactose compared to cells grown in media containing 30 mM fructose. The resting membrane potential was determined by examining the steady-state accumulation of the lipophilic cation tetra[3H]phenylphosphonium bromide (TPP+). The resting membrane potential of cells grown in media containing 30 mM fructose is about -70 mV which is very similar to the resting membrane potential of cells grown in unsupplemented media. The resting membrane potential is significantly decreased in cells grown in media containing 30 mM glucose or 30 mM galactose. myo-Inositol metabolism and content and polyol levels are maintained at near normal values and the resting membrane potential is improved when media containing 30 mM glucose or 30 mM galactose are supplemented with 0.4 mM sorbinil. Acute exposure of neuroblastoma cells to 2 mM ouabain had no significant effect on [3H]TPP+ accumulation. This suggests that acute inhibition of Na+/K+ pump activity does not decrease the resting membrane potential of neuroblastoma cells. The decrease in resting membrane potential may be induced by the metabolic abnormalities and/or chronic decrease in Na+/K+ pump activity which occur when neuroblastoma cells are chronically exposed to increased glucose or galactose concentrations.

Animals↗

Clinical evaluation of removable partial denture rest seat adaptation.

The clinical relationship between the removable partial denture cast occlusal rest and the corresponding rest seat was examined. Under the conditions of the study, it was found that rests of mandibular Class I and II removable partial dentures fit significantly better than those of mandibular Class III and IV prostheses. No significant difference was noted between similar types of maxillary removable partial dentures in this regard. In evaluating the fit of specific portions of the occlusal rest, it was found that the marginal ridge zone was more closely adapted to the rest seat than other zones for all types of removable partial dentures. However, contact, as defined in this analysis, was found to exist on a random basis in all four quadrants of the occlusal rests evaluated. In spite of this fact, one fifth of the occlusal rests did not contact the opposing rest seat at any point. Improved fit with length of service was not substantiated by a cross-sectional analysis. Suggestions were made to assist the clinician in achieving a better fit between the framework and dentition in removable partial dentures.

Dental Abutments↗

Gated technetium-99m sestamibi for simultaneous assessment of stress myocardial perfusion, postexercise regional ventricular function and myocardial viability. Correlation with echocardiography and rest thallium-201 scintigraphy.

OBJECTIVES: This study compares technetium-99m sestamibi (sestamibi) electrocardiographic (ECG) gated single-photon emission computed tomography (gated SPECT) and echocardiography for the evaluation of myocardial function and assesses the feasibility of single-injection, single-acquisition stress perfusion/rest function technetium-99m sestamibi-gated SPECT as an alternative to conventional stress/rest imaging for assessment of myocardial perfusion and viability. BACKGROUND: Simultaneous assessment of stress perfusion and rest function is possible with gated SPECT acquisition of stress-injected technetium-99m sestamibi. METHODS: Rest thallium-201 SPECT followed by stress sestamibi-gated SPECT (acquired 0.5 to 1 h after sestamibi injection) was performed in 58 patients. Echocardiography was performed immediately after or before gated SPECT in 43 of the patients. All studies were analyzed by semiquantitative visual scoring. Sestamibi-gated SPECT studies were read for stress perfusion and rest wall motion and thickening. Reversibility on sestamibi-gated SPECT was defined as the presence of a definite stress defect with normal or mildly impaired wall motion or thickening on gated SPECT: RESULTS: There was high segmental score agreement between gated SPECT and echocardiography for wall motion (91%, kappa = 0.68, p < 0.001) and thickening (90%, kappa = 0.62, p < 0.001). Correlation for global wall motion (r = 0.98, p < 0.001) and thickening (r = 0.96, p < 0.001) scores between the two modalities was excellent. In 32 patients without previous myocardial infarction, there was excellent agreement for reversibility between stress sestamibi-gated SPECT and rest thallium-201/stress sestamibi (98%, kappa = 0.93, p < 0.01). However, in 26 patients with previous infarction, discordance between the two approaches was frequent, with 26% (20 of 78) of nonreversible defects by stress sestamibi-gated SPECT being reversible by rest thallium-201/stress sestamibi and 21% (23 of 112) of reversible defects by stress sestamibi-gated SPECT being nonreversible by rest thallium-201/stress sestamibi. CONCLUSIONS: Gated SPECT of stress-injected sestamibi correlates well with echocardiographic assessment of regional function and thus adds information to perfusion SPECT: In patients without previous myocardial infarction, a single-injection stress perfusion/rest function approach using sestamibi-gated SPECT can substitute for conventional stress/rest myocardial perfusion imaging, adding a rest perfusion study only if there are nonreversible defects or consideration of attenuation artifacts. In patients with previous myocardial infarction, the gated SPECT approach does not replace the need for a rest perfusion study.

Aged↗

Prognostic value of plasma catecholamines, plasma renin activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure: comparison with clinical evaluation, ejection fraction, and exercise capacity.

Survival in congestive heart failure is related to plasma catecholamines and atrial natriuretic peptide at rest, but the prognostic importance of changes during exercise is unknown. The aim of this study was to evaluate the prognostic value of catecholamines and atrial natriuretic peptide at rest and during maximal exercise in congestive heart failure, and to compare it to clinical and exercise test variables and left ventricular ejection fraction. One hundred ninety consecutive patients (136 men and 54 women; median age, 66 years; range, 42-75 years) with clinically stable congestive heart failure were included. Sixteen patients were in New York Heart Association class I, 87 in class II, 83 in class III, and 4 in class IV. Left ventricular ejection fraction was 0.30 (range, 0.06-0.74). Total survival after 1 year was 79%, after 2 years, it was 68%. Prognostic variables at univariate analysis were: plasma noradrenaline at rest (P < .0001), plasma adrenaline at rest (P = .049), and atrial natriuretic peptide at rest (P = .016). During exercise, plasma catecholamines and plasma atrial natriuretic peptide increased significantly; the change, however, was not related to survival. Six variables carried significant, independent prognostic information in a multivariate analysis: left ventricular ejection fraction (P = .03), plasma noradrenaline at rest (P = .009), New York Heart Association class III + IV (P = .005), increase in heart rate during exercise < or = 35 min-1 (P < .0001), serum creatinine > 121 mumol/L (P = .004), and serum urea > 7.6 mmol/L (P = .007). Patients with congestive heart failure have a poor survival despite intensive medical treatment. Plasma catecholamines and plasma atrial natriuretic peptide are elevated at rest and rises further during exercise; the increase, however, is not related to mortality. Plasma noradrenaline at rest contributes with further prognostic information despite knowledge of clinical and exercise variables and was the only neurohormonal variable with independent, significant prognostic information on survival.

Adult↗

Amlodipine therapy in congestive heart failure: hemodynamic and neurohormonal effects at rest and after treadmill exercise.

This study examined the acute effects of amlodipine treatment on left ventricular pump function, systemic hemodynamics, neurohormonal status, and regional blood flow distribution in an animal model of congestive heart failure (CHF), both at rest and with treadmill exercise. A total of 14 pigs were studied under control conditions and after the development of pacing-induced CHF (240 beats per minute, 3 weeks, n = 7) or with CHF and acute amlodipine treatment for the last 3 days of pacing (1.5 mg/kg per day, n = 7). Under resting conditions, left ventricular stroke volume (mL) was reduced with CHF compared with the normal state (15+/-2 vs. 31+/-1, p<0.05) and increased with amlodipine treatment (23+/-4, p<0.05). At rest, systemic vascular resistance increased with CHF compared with the normal state (3,078+/-295 vs. 2,131+/-120 dyne x s cm(-5), p<0.05) and was reduced after amlodipine treatment (2,472+/-355 dyne x s cm(-5), p<0.05). With exercise, left ventricular stroke volume remained lower and systemic vascular resistance higher in the CHF group, but was normalized with amlodipine treatment. With exercise, left ventricular myocardial blood flow increased from resting values, but was reduced from the normal state with CHF (normal: 1.69+/-0.12 to 7.62+/-0.74 mL/min per gram vs. CHF: 1.26+/-0.12 to 4.77+/-0.45 mL/min per gram, both p<0.05) and was normalized with acute amlodipine treatment (1.99+/-0.35 to 6.29+/-1.23 mL/min per gram). Resting plasma norepinephrine was increased by >5-fold in the CHF group at rest and was not affected by amlodipine treatment. However, with exercise, amlodipine treatment blunted the increase in plasma norepinephrine by >50% when compared with untreated CHF values. Resting plasma endothelin levels increased with CHF compared with the normal state (10.9+/-0.9 vs. 2.8+/-0.4 fmol/mL, p<0.05) and was reduced with amlodipine treatment (7.5+/-1.5 fmol/mL, p<0.5). In other vascular beds, acute amlodipine treatment with CHF improved pulmonary and renal blood flow both at rest and with exercise; however, there were no effects observed on skeletal muscle blood flow. With the development of CHF, acute amlodipine treatment does not negatively influence left ventricular pump function, but rather may provide favorable hemodynamic and neurohormonal effects.

Amlodipine↗

Factors affecting the resting pH of in vitro human microcosm dental plaque and Streptococcus mutans biofilms.

The aim was to examine factors that potentially control the resting pH, defined as the pH unaffected by meals, of microcosm dental plaques and Streptococcus mutans biofilms under standard conditions, and to examine the effect of supplying urea at concentrations found intraorally. Microcosm plaques were cultured from plaque bacteria-enriched saliva in an 'artificial mouth' with a continuous supply of a medium including 0.25% mucin [Basal Medium Mucin, (BMM), 3.6 ml/hr per plaque] and a periodic supply of sucrose. The steady-state resting pH was 6.4 (range +/- 0.1) in BMM containing no urea and supplied at the standard flowrate. This is a robust property of the ecosystem. In one experiment with a replicated (n = 9) set of measurements, the resting pH was approx. pH 6.3, 6.4, 6.7 and 7.3 with 0, 1, 5 and 20 mmol/l urea in the BMM. The magnitude of sucrose- and urea-induced pH responses was unaffected by elevating the resting pH to produce parallel pH curves. The sucrose-induced pH curves were analogous to those classically reported by Stephan that showed an association between caries activity and increasingly acidic plaque pH responses to glucose. Stopping the BMM flow caused a pH rise, indicating continuing net alkali generation from BMM components in the absence of a fluid flow. Step. mutans monoculture biofilms had an acidic resting pH of 5.0 to 5.3, which increased to 6.8 following an adventitious superinfection by Bacillus cereus. It was concluded that the resting pH in plaque results from a delicate balance between alkali and acid generation, which is in turn dependent both on the bacterial composition of the plaque and on the supply of substrates and buffers from, and metabolite clearance into, flowing oral fluid. In vivo the resting pH will vary with site-specific changing saliva flows. Urea continuously supplied at concentrations normal for saliva and gingival crevicular fluid can raise the resting pH of microcosm plaque by an amount tat in vivo would probably be significant in reducing dental caries.

Acids↗

Abdominal aortic hemodynamic conditions in healthy subjects aged 50-70 at rest and during lower limb exercise: in vivo quantification using MRI.

The prevalence of atherosclerosis in the abdominal aorta increases with age and is hypothesized to be related to adverse hemodynamic conditions including flow recirculation and low wall shear stress. Exercise has been shown to modulate these adverse conditions observed in the infrarenal aorta of healthy young subjects at rest. A custom magnetic resonance (MR)-compatible stationary cycle, an open MRI, and custom image processing software were used to quantify hemodynamic conditions in the abdominal aorta at rest and during cycling exercise in healthy subjects aged 50-70 years. The subjects increased their heart rate from 63+/-8 bpm at rest to 95+/-12 bpm during cycling exercise. Supraceliac blood flow increased from 2.3+/-0.4 to 6.0+/-1.4 l/min (P<0.001) and infrarenal flow increased from 0.9+/-0.3 to 4.9+/-1.7 l/min (P<0.001) from rest to exercise. Wall shear stress increased from 2.0+/-0.7 to 7.3+/-2.4 dynes/cm(2) at the supraceliac level (P<0.001) and 1.4+/-0.8 to 16.5+/-5.1 dynes/cm(2) at the infrarenal level (P<0.001) from rest to exercise. Flow and shear oscillations present at rest were eliminated during exercise. At rest, these older subjects experienced lower mean wall shear stress at the supraceliac level of the aorta and greater oscillations in wall shear stress as compared to a group of younger subjects (23.6+/-2.2 years). Compared to the younger subjects, the older subjects also experienced greater increases in mean wall shear stress and greater decreases in wall shear stress oscillations from rest to exercise.

Adult↗