An examination chair to measure internal rotation of the hip in routine settings: a validation study

OBJECTIVE: To determine the performance of a newly developed examination chair as compared with the clinical standard of assessing internal rotation (IR) of the flexed hip with a goniometer. METHODS: The examination chair allowed measurement of IR in a sitting position simultaneously in both hips, with hips and knees flexed 90 degrees, lower legs hanging unsupported and a standardized load of 5 kg applied to both ankles using a bilateral pulley system. Clinical assessment of IR was performed in supine position with hips and knees flexed 90 degrees using a goniometer. Within the framework of a population-based inception cohort study, we calculated inter-observer agreement in two samples of 84 and 64 consecutive, unselected young asymptomatic males using intra-class correlation coefficients (ICC) and determined the correlation between IR assessed with examination chair and clinical assessment. RESULTS: Inter-observer agreement was excellent for the examination chair (ICC right hip, 0.92, 95% confidence interval [CI] 0.89-0.95; ICC left hip, 0.90, 95% CI 0.86-0.94), and considerably higher than that seen with clinical assessment (ICC right hip, 0.65, 95% CI 0.49-0.77; ICC left hip, 0.69, 95% CI 0.54-0.80, P for difference in ICC between examination chair and clinical assessment

Measurement of ventilation and cardiac related impedance changes with electrical impedance tomography

Introduction Electrical impedance tomography (EIT) has been shown to be able to distinguish both ventilation and perfusion. With adequate filtering the regional distributions of both ventilation and perfusion and their relationships could be analysed. Several methods of separation have been suggested previously, including breath holding, electrocardiograph (ECG) gating and frequency filtering. Many of these methods require interventions inappropriate in a clinical setting. This study therefore aims to extend a previously reported frequency filtering technique to a spontaneously breathing cohort and assess the regional distributions of ventilation and perfusion and their relationship. Methods Ten healthy adults were measured during a breath hold and while spontaneously breathing in supine, prone, left and right lateral positions. EIT data were analysed with and without filtering at the respiratory and heart rate. Profiles of ventilation, perfusion and ventilation/perfusion related impedance change were generated and regions of ventilation and pulmonary perfusion were identified and compared. Results Analysis of the filtration technique demonstrated its ability to separate the ventilation and cardiac related impedance signals without negative impact. It was, therefore, deemed suitable for use in this spontaneously breathing cohort. Regional distributions of ventilation, perfusion and the combined ΔZV/ΔZQ were calculated along the gravity axis and anatomically in each position. Along the gravity axis, gravity dependence was seen only in the lateral positions in ventilation distribution, with the dependent lung being better ventilated regardless of position. This gravity dependence was not seen in perfusion. When looking anatomically, differences were only apparent in the lateral positions. The lateral position ventilation distributions showed a difference in the left lung, with the right lung maintaining a similar distribution in both lateral positions. This is likely caused by more pronounced anatomical changes in the left lung when changing positions. Conclusions The modified filtration technique was demonstrated to be effective in separating the ventilation and perfusion signals in spontaneously breathing subjects. Gravity dependence was seen only in ventilation distribution in the left lung in lateral positions, suggesting gravity based shifts in anatomical structures. Gravity dependence was not seen in any perfusion distributions.

Postural effects on interstitial fluid pressure in humans

BACKGROUND: Direct assessment of the effect of postural changes on interstitial fluid pressure (IFP) in the human skin under physiological conditions is important for the understanding of mechanisms involved in diseases resulting in lower limb edema. Previous techniques to measure IFP had limitations of being invasive, and acute measurements were not possible. Here we describe the effect of postural changes on IFP in the skin of the foot using the minimally invasive servonulling technique. RESULTS: Measurements were performed in 12 healthy subjects. IFP (means +/- SD) was significantly higher in the sitting (5.1 +/- 2.9 mm Hg) than in the supine position (-0.3 +/- 3.6 mm Hg, p = 0.04) when measured in the sitting position first. The difference between the sitting and the supine position was not significant when measurements were taken in the supine position first [from 1.0 +/- 4.3 (supine) to 3.6 +/- 6.7 mm Hg (sitting), p = 0.46]. Spontaneous low-frequency pressure fluctuations occurred in 58% of the recordings during sitting, which was almost twice as frequent as in the supine position (33%; p = 0.001), while no effects on lymphatic capillary network extension were observed (p = 0.12). CONCLUSION: Using the servonulling micropressure system, postural effects on IFP can be directly assessed. IFP is higher in the sitting position, but differences are influenced by the time in the upright position.

Unexplained syncope--is screening for carotid sinus hypersensitivity indicated in all patients aged >40 years?

OBJECTIVE: To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15-92 years) referred to two autonomic referral centres during a 10-year period. METHODS: Carotid sinus massage (CSM) was performed both supine and during 60 degree head-up tilt. Beat-to-beat blood pressure, heart rate and a three-lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole > or = 3 s), vasodepressor (systolic blood pressure fall > or = 50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure. RESULTS: CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged < 50 years (n = 65), 2.4% in those aged 50-59 years (n = 82), 9.1% in those aged 60-69 years (n = 77), 20.7% in those aged 70-79 years (n = 92) and reached 40.4% in those > 80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none. CONCLUSIONS: CSH was confirmed in patients > 50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients > 40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them.

Prospective study on bright lumen magnetic resonance colonography in comparison with conventional colonoscopy

The aim of this prospective trial was to evaluate sensitivity and specificity of bright lumen magnetic resonance colonography (MRC) in comparison with conventional colonoscopy (CC). A total of 120 consecutive patients with clinical indications for CC were prospectively examined using MRC (1.5 Tesla) which was then followed by CC. Prior to MRC, the cleansed colon was filled with a gadolinium-water solution. A 3D GRE sequence was performed with the patient in the prone and supine position, each acquired during one breathhold period. After division of the colon into five segments, interactive data analysis was carried out using three-dimensional post-processing, including a virtual intraluminal view. The results of CC served as a reference standard. In all patients MRC was performed successfully and no complications occurred. Image quality was diagnostic in 92% (574/620 colonic segments). On a per-patient basis, the results of MRC were as follows: sensitivity 84% (95% CI 71.7-92.3%), specificity 97% (95% CI 89.0-99.6%). Five flat adenomas and 6/16 small polyps (< or =5 mm) were not identified by MRC. MRC offers high sensitivity and excellent specificity rates in patients with clinical indications for CC. Improved MRC techniques are needed to detect small polyps and flat adenomas.

Local vascular dysfunction after coronary paclitaxel-eluting stent implantation

BACKGROUND: Paclitaxel-eluting stents (PES) have been shown to reduce the rate of restenosis and the need for repeated revascularization procedures compared with bare metal stents. However, long-term effects of paclitaxel on vascular function are unknown. The purpose of the present study was to assess coronary vasomotor response to exercise after paclitaxel-eluting stent implantation. METHODS: Coronary vasomotion was evaluated by biplane quantitative coronary angiography at rest and during supine bicycle exercise in 27 patients with coronary artery disease. Twelve patients were treated with a bare metal stent (controls), and fifteen patients with a paclitaxel-eluting stent. All patients were restudied 6+/-2 (range 2-12) months after stent implantation. Minimal luminal diameter, stent diameter, proximal, distal and a reference vessel diameter were determined. RESULTS: Reference vessels showed exercise-induced vasodilation in both groups (+20+/-5% controls; +26+/-3% PES group). Vasomotion within the stented vessel segments was abolished. In the controls, the adjacent segments proximal and distal to the stent showed exercise-induced vasodilation (+17+/-3% and +24+/-4%). In contrast, there was exercise-induced vasoconstriction of the proximal and distal vessel segments adjacent to the paclitaxel-eluting stent (-13+/-6% and -18+/-4%; p<0.005). After sublingual nitroglycerin, the proximal and distal vessel segments dilated in both groups. Exercise-induced vasoconstriction adjacent to paclitaxel-eluting stent correlated inversely with the time interval after stent implantation. CONCLUSIONS: Paclitaxel-eluting stent implantation is associated with exercise-induced vasoconstriction in the persistent region suggesting endothelial dysfunction as the underlying mechanism. Improvement of vascular function occurs over time, indicating delayed vascular healing.

Cerebral correlates of muscle tone fluctuations in restless legs syndrome: A pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography

BACKGROUND: The pathology of restless legs syndrome (RLS) is still not understood. To investigate the pathomechanism of the disorder further we recorded a surface electromyogram (EMG) of the anterior tibial muscle during functional magnetic resonance imaging (fMRI) in patients with idiopathic RLS. METHODS: Seven subjects with moderate to severe RLS were investigated in the present pilot study. Patients were lying supine in the scanner for over 50min and were instructed not to move voluntarily. Sensory leg discomfort (SLD) was evaluated on a 10-point Likert scale. For brain image analysis, an algorithm for the calculation of tonic EMG values was developed. RESULTS: We found a negative correlation of tonic EMG and SLD (p <0.01). This finding provides evidence for the clinical experience that RLS-related subjective leg discomfort increases during muscle relaxation at rest. In the fMRI analysis, the tonic EMG was associated with activation in motor and somatosensory pathways and also in some regions that are not primarily related to motor or somatosensory functions. CONCLUSIONS: By using a newly developed algorithm for the investigation of muscle tone-related changes in cerebral activity, we identified structures that are potentially involved in RLS pathology. Our method, with some modification, may also be suitable for the investigation of phasic muscle activity that occurs during periodic leg movements.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure

OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after patients are switched from a nonfixed combination of latanoprost and timolol. DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two hundred patients with glaucoma or ocular hypertension. METHODS: Included were patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of latanoprost and timolol for at least 3 months before the baseline visit or patients on monotherapy with either latanoprost or timolol who were eligible for dual therapy not being fully controlled on monotherapy. The latter group of patients underwent a 6-week wash-in phase with the nonfixed combination of latanoprost and timolol before baseline IOP determination and study inclusion. Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am, noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An analysis of covariance model was used for a noninferiority test of the primary efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of treatment as response variable and treatment, center, and baseline IOP as factors. A secondary analysis was performed on the within-treatment change from baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/-2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no significant difference between the 2 treatment groups could be found. As compared with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively. CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a controlled level during a 24-hour period in patients switched from the nonfixed combination of latanoprost and timolol.

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma

AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage.

Aquatic therapies in patients with compromised left ventricular function and heart failure

With water immersion, gravity is partly eliminated, and the water exerts a pressure on the body surface. Consequently there is a blood volume shift from the periphery to the central circulation, resulting in marked volume loading of the thorax and heart. This paper presents a selection of published literature on water immersion, balneotherapy, aqua exercises, and swimming, in patients with left ventricular dysfunction (LVD) and/or stable chronic heart failure (CHF). Based on exploratory studies, central hemodynamic and neurohumoral responses of aquatic therapies will be illustrated. Major findings are: 1. In LVD and CHF, a positive effect of therapeutic warm-water tub bathing has been observed, which is assumed to be from afterload reduction due to peripheral vasodilatation caused by the warm water. 2. In coronary patients with LVD, at low-level water cycling the heart is working more efficiently than at lowlevel cycling outside of water. 3. In patients with previous extensive myocardial infarction, upright immersion to the neck resulted in temporary pathological increases in mean pulmonary artery pressure (mPAP) and mean pulmonary capillary pressures (mPCP). 4. Additionally, during slow swimming (20-25m/min) the mPAP and/or PCP were higher than during supine cycling outside water at a 100W load. 5. In CHF patients, neck- deep immersion resulted in a decrease or no change in stroke volume. 6. Although patients are hemodynamically compromised, they usually maintain a feeling of well-being during aquatic therapy. Based on these findings, clinical indications for aquatic therapies are proposed and ideas are presented to provoke further research.

Hypovolemia contributes to the pathogenesis of orthostatic hypotension in patients with diabetes mellitus

PURPOSE: To investigate whether body sodium content and blood volume contribute to the pathogenesis of orthostatic hypotension in patients with diabetes mellitus. SUBJECTS AND METHODS: Exchangeable sodium, plasma and blood volumes, and catecholamine, renin, and aldosterone levels were assessed in 10 patients with Type II diabetes mellitus who had orthostatic hypotension and control groups of 40 diabetic patients without orthostatic hypotension and 40 normal subjects of similar age and sex. In subgroups, clinical tests of autonomic function and cardiovascular reactivity to norepinephrine and angiotensin II infusions were performed. RESULTS: In diabetic patients with orthostatic hypotension, mean (+/- SD) supine blood pressure was 165/98 +/- 27/12 mm Hg (P <0.05 compared with other groups) and mean upright blood pressure was 90/60 +/- 38/18 mm Hg. Compared with controls, diabetic patients with orthostatic hypotension had a 10% lower blood volume. They also had less exchangeable sodium than patients with diabetes who did not have orthostatic hypotension (P <0.01). Compared with both groups of controls, diabetic patients with orthostatic hypotension had decreased 24-hour urinary norepinephrine excretion and a reduced diastolic blood pressure response to handgrip (P <0.05). Moreover, they displayed reduced products of exchangeable sodium or blood volume and sympathetic function indexes. Cardiovascular pressor reactivity to norepinephrine was enhanced (P <0.01) and beat-to-beat variation decreased (P <0.01) in both groups of diabetic patients. Microvascular complications were more prevalent in the diabetic patients with orthostatic hypotension (90% vs 35%). CONCLUSIONS: Patients who have Type II diabetes mellitus and orthostatic hypotension are hypovolemic and have sympathoadrenal insufficiency; both factors contribute to the pathogenesis of orthostatic hypotension.

Cardiovascular regulation during administration of co-dergocrine to normal subjects

Whether and to what extent activation of peripheral presynaptic dopamine2-receptors may modulate the release of norepinephrine (NE) and so affect blood pressure (BP) in normal or hypertensive man is not clear. The hydrogenated ergotoxine derivative, co-dergocrine, given in effective antihypertensive rather than excessive experimental doses, has recently been shown to act predominantly as a peripheral dopamine2-receptor agonist in several species. Accordingly, BP regulation assessed has been in 8 normal men on placebo and after 3 weeks on codergocrine 4 mg/day. Co-dergocrine significantly reduced urinary NE excretion from 43 to 33 micrograms/24 h, supine and upright plasma NE 21 to 16 and 49 to 36 ng/dl, respectively, heart rate (-8 and -5%, respectively) and upright systolic BP, 115 to 102 mm Hg; upright diastolic BP also tended to be lower. A standard pressor dose of infused NE was lowered from 131 to 102 ng/kg/min, and the relationship between NE-induced changes in BP and concomitant NE infusion rate or plasma NE concentration was displaced to the left. Exchangeable sodium and plasma volume tended to be slightly decreased. Plasma and urinary electrolytes and epinephrine, plasma renin activity and aldosterone levels, pressor responsiveness to angiotensin II, the chronotropic responses to isoproterenol, and the NE-induced rise in BP, plasma clearance of NE, glomerular filtration rate and effective renal plasma flow were not consistently modified. The findings are consistent with effective peripheral dopamine2-receptor agonism by co-dergocrine in humans. Peripheral presynaptic dopaminergic activation may modulate sympathetic activity and BP in normal man.

Serum lipoproteins during treatment with the antihypertensive agent indapamide

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.

Omega-3 fatty acids and the neurovascular responses to mental stress in humans

Hypertension is the most prevalent form of cardiovascular disease (CVD) in the world, and is known to increase the risk for developing other diseases. Recently, the American Heart Association introduced a new classification of blood pressure, prehypertension (PHT). The criteria for PHT include a systolic of 120-139 mmHg and/or a diastolic blood pressure of 80-89 mmHg. It has been observed that individuals with PHT have a higher risk of developing hypertension later in life. Therefore, it is important to understand the mechanisms contributing to PHT in order to possibly prevent hypertension. Omega-3 fatty acids found in fish oils have been suggested as a means of lowering blood pressure. However, little is known on the effects of fish oil in PHT humans. Therefore we conducted two studies. In Study 1 we investigated PHT and normotensive (NT) individuals during a mental stress task. Mental stress is known to contribute to the development of hypertension. In Study 2 PHT and NT subjects were placed in an eight week double-blind placebo controlled study in which subjects consumed 9g/day of either fish oil or placebo (olive oil) in addition to their regular diets. Subjects were tested during a resting baseline (seated and supine), 5 minutes of a mental stress task, and 5 minutes of recovery both pre and post supplementation. We measured arterial pressure (AP), heart rate (HR), muscle sympathetic nerve activity (MSNA), and forearm and calf vascular responses. In Study 1 PHT demonstrated augmented AP and blunted vasodilation during mental stress, but MSNA did not change. In Study 2, fish oil did not directly influence blood pressure, MSNA or vascular responses to mental stress. However, it became clear that fish oil had an effect on some but not all subjects (both PHT and NT). Specifically, subjects who experienced a reduced blood pressure response to fish oil also demonstrated a decrease in MSNA and HR during mental stress. Collectively, the investigations in this dissertation had several novel findings. First, PHT individuals demonstrate an augmented pressor and blunted vascular response to mental stress, a response that may be contributing to the development of hypertension. Second, fish oil does not consistently lower resting blood pressure, but the interindividual responses may be related to MSNA. Third, fish oil attenuated the heart rate and MSNA responses and to mental stress in both PHT and NT. In conclusion, we found that there are both similarities and differences in the way PHT and NT individuals respond to mental stress and fish oil.

INFLUENCE OF 24-HOUR SLEEP DEPRIVATION ON CARDIOVASCULAR AND NEURAL CONTROL AT REST AND DURING ACUTE STRESS IN HUMANS

Recent epidemiological studies report a consistent association between short sleep and incidence of hypertension, as well as short sleep and cardiovascular disease-related mortality. While the association between short sleep and hypertension appears to be stronger in women than men, the mechanisms underlying the relations between sleep deprivation, stress, risks of cardiovascular diseases, and sex remain unclear. We conducted two studies to investigate the underlying neural mechanisms of these relations. In study 1, we examined sympathetic neural and blood pressure responses to experimentally-induced sleep deprivation in men and women. We further investigated the influence of sleep deprivation on cardiovascular reactivity to acute stress. In study 2, we examined the neural and cardiovascular function throughout the ovarian cycle in sleep deprived women. Twenty-eight young healthy subjects (14men and 14 women) were tested twice in study 1, once after normal sleep (NS) and once after 24-h total sleep deprivation (TSD). We measured the blood pressure, heart rate (HR), muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) during 10min baseline, 5min of mental stress (MS) and 2 min cold pressor test (CPT). We demonstrated that TSD increased resting arterial blood pressure to a similar extent in both men and women, but MSNA decreased only in men following TSD. This MSNA response was associated with altered baroreflex function in women and divergent testosterone responses to TSD between men and women. Regarding TSD and cardiovascular reactivity, TSD elicited augmented HR reactivity and delayed recovery during both MS and CPT in men and women, and responses between sexes were not statistically different. Fourteen young healthy women participated in study 2. Subjects were tested twice, once during their early follicular (EF) phase after TSD, once during their mid-luteal (ML) phase after TSD. Blood pressure, HR, MSNA, and FBF were recorded during 10min baseline, 5 min MS, and 2 min CPT. We observed an augmented resting supine blood pressure during EF compared to ML in sleep deprived women. In contrast, resting MSNA, as well as cardiovascular responses to stressors, were similar between EF and ML after TSD. In conclusion, we observed sex differences in MSNA responses to TSD that demonstrate reductions of MSNA in men, but not women. TSD elicited augmented HR reactivity and delayed HR recovery to acute stressors similarly in men and women. We also reported an augmented supine blood pressure during EF compared to ML in sleep deprived women. These novel findings provide new and valuable mechanistic insight regarding the complex and poorly understood relations among sleep deprivation, sex, stress, and risk of cardiovascular disease.