Active orthostatic stress and respiratory sinus arrhythmia in patients with Chagas' disease with preserved left ventricular global systolic function.
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OBJECTIVE: To assess the use of the active orthostatic stress test for detecting vagal dysfunction in patients with Chagas' disease with preserved overall systolic function, and to compare it with the respiratory sinus arrhythmia test. METHODS: Sixty-one chagasic patients (Ch) and 38 nonchagasic (NCh) patients with no significant evidence of heart disease or systemic diseases underwent Doppler echocardiography and autonomic function tests. The respiratory sinus arrhythmia test was performed through electrocardiographic recording during deep breathing, at 6 ripm, calculating the E:I ratio (mean ratio between the longest expiratory RR interval and the shortest inspiratory RR interval at each cycle). The electrocardiogram was recorded during the act of standing and during the following 30 seconds (active orthostatic stress test), and the max RR/min RR ratio (the longest and shortest RR intervals right after change in posture) was calculated. The indices were adjusted for significant covariables. RESULTS: The max RR/min RR ratio (NCh: 1.52 [1.44-1.74] x Ch: 1.43 [1.33-1.51], P < 0.001) and the E:I ratio (NCh: 1.38 +/- 0.02 x Ch: 1.25 +/- 0.02, P<0.001) were lower among chagasic patients. A high correlation was observed between the adjusted max RR/min RR ratio and E:I ratio (r = 0.628, P < 0.001), but neither significantly correlated with left ventricular ejection fraction. CONCLUSION: Chagasic patients with preserved left ventricular overall systolic function showed a significant reduction in the vagal indices obtained on short-lasting tests, as compared with normal controls. The active orthostatic stress test that, showed a good correlation with the respiratory sinus arrhythmia maneuver, constituted a valid option for the outpatient care assessment of vagal control. (+info)
Cardiovascular responses to orthostatic stress in healthy altitude dwellers, and altitude residents with chronic mountain sickness.
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High altitude (HA) dwellers have an exceptionally high tolerance to orthostatic stress, and this may partly be related to their high packed cell and blood volumes. However, it is not known whether their orthostatic tolerance would be changed after relief of the altitude-related hypoxia. Furthermore, orthostatic tolerance is known also to be influenced by the efficiency of the control of peripheral vascular resistance and by the effectiveness of cerebral autoregulation and these have not been reported in HA dwellers. In this study we examined plasma volume, orthostatic tolerance and peripheral vascular and cerebrovascular responses to orthostatic stress in HA dwellers, including some with chronic mountain sickness (CMS) in whom packed cell and blood volumes are particularly large. Eleven HA control subjects and 11 CMS patients underwent orthostatic stress testing, comprising head-up tilting with lower body suction, at their resident altitude (4338 m) and at sea level. Blood pressure (Portapres), heart rate (ECG), brachial and middle cerebral artery blood velocities (Doppler) were recorded during the test. Plasma volumes were found to be similar in both groups and at both locations. Packed cell and blood volumes were higher in CMS patients than controls. All subjects had very good orthostatic tolerances at both locations, compared to previously published data in lowland dwellers. In CMS patients responses of forearm vascular resistance to the orthostatic stress, at sea level, were smaller than controls (P < 0.05). Cerebral blood velocity was less in CMS than in controls (P < 0.01) and, at sea level, it decreased more than the controls in response to head-up tilting (P < 0.02). Cerebral autoregulation, assessed from the relationship between cerebral pressure and velocity, was also impaired in CMS patients compared to HA controls, when examined at sea level (P < 0.02). These results have shown that the good orthostatic tolerance seen in high altitude dwellers at altitude is also seen at sea level. There was no difference in orthostatic tolerance between CMS patients, with their exceptionally large blood volumes, and the HA controls. This may be because peripheral vascular and cerebrovascular responses (at least at sea level) are impaired in the CMS patients relative to HA controls. Thus, the advantage of the large blood volume may be offset by the smaller vascular responses. (+info)
A phase II study of etanercept (Enbrel), a tumor necrosis factor alpha inhibitor in patients with metastatic breast cancer.
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PURPOSE: Tumor necrosis factor (TNF) alpha is a key player in the tumor microenvironment and is involved in the pathogenesis of breast cancer. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-alpha and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biological activity, and therapeutic efficacy of Etanercept in metastatic breast cancer. EXPERIMENTAL DESIGN: We initiated a Phase II, nonrandomized, open-labeled study in patients with progressive metastatic breast cancer refractory to conventional therapy (Phase I toxicity data were available in patients with rheumatoid arthritis). Etanercept was administered subcutaneously at a dose of 25 mg twice weekly until disease progression. RESULTS: Sixteen patients were recruited [median age 53 years (range, 34 to 74)]. A total of 141.6 weeks of therapy was administered (median of 8.1 weeks). Seven patients received > or =12 weeks of therapy. The most common side effects were injection site reactions (6), fatigue (5), loss of appetite (2), nausea (1), headache (1), and dizziness (1). Brief period of disease stabilization was seen in 1 patient lasting for 16.4 weeks. Immunoreactive TNF-alpha was elevated within 24 hours of therapy and persisted until the end of treatment (days 7, 28, 56, and 84). Phytohemagglutinin stimulates the production of interleukin-6 and CCL2 in peripheral blood cells, and the ability of Etanercept to modulate this response was assessed in a cytokine release assay. A consistent decrease in interleukin-6 and CCL2 level was seen compared with pretreatment values in serial blood samples (days 1, 7, 28, 56, and 84). CONCLUSIONS: Our study shows the safety and biological activity of Etanercept in breast cancer and provides data to assess pharmacodynamic endpoints of different schedules of Etanercept and combinations with chemotherapy or other biological therapies. (+info)
Effects of bilateral vestibular nucleus lesions on cardiovascular regulation in conscious cats.
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The vestibular system participates in cardiovascular regulation during postural changes. In prior studies (Holmes MJ, Cotter LA, Arendt HE, Cas SP, and Yates BJ. Brain Res 938: 62-72, 2002, and Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999), transection of the vestibular nerves resulted in instability in blood pressure during nose-up body tilts, particularly when no visual information reflecting body position in space was available. However, recovery of orthostatic tolerance occurred within 1 wk, presumably because the vestibular nuclei integrate a variety of sensory inputs reflecting body location. The present study tested the hypothesis that lesions of the vestibular nuclei result in persistent cardiovascular deficits during orthostatic challenges. Blood pressure and heart rate were monitored in five conscious cats during nose-up tilts of varying amplitude, both before and after chemical lesions of the vestibular nuclei. Before lesions, blood pressure remained relatively stable during tilts. In all animals, the blood pressure responses to nose-up tilts were altered by damage to the medial and inferior vestibular nuclei; these effects were noted both when animals were tested in the presence and absence of visual feedback. In four of the five animals, the lesions also resulted in augmented heart rate increases from baseline values during 60 degrees nose-up tilts. These effects persisted for longer than 1 wk, but they gradually resolved over time, except in the animal with the worst deficits. These observations suggest that recovery of compensatory cardiovascular responses after loss of vestibular inputs is accomplished at least in part through plastic changes in the vestibular nuclei and the enhancement of the ability of vestibular nucleus neurons to discriminate body position in space by employing nonlabyrinthine signals. (+info)
Clinical characteristics of hypervagotonic sinus node dysfunction.
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BACKGROUND: Sinus node dysfunction (SND) is caused not only by intrinsic sinus node disease, but also by the extrinsic factors. Among the extrinsic factors, autonomic imbalance is most common. Symptomatic SND usually requires permanent pacemaker therapy. However, the clinical characteristics and patient response to medical therapy for hypervagotonic SND have not been properly clarified. MATERIALS AND METHODS: Thirty two patients (14 men, 18 women, 51 +/- 14 years) with hypervagotonic SND were included in this study, but those patients who had taken calcium antagonists, beta-blockers or other antiarrhythmic drugs were excluded. Hypervagotonic SND was diagnosed if the abnormal electrophysiologic properties of the sinus node were normalized after the administration of atropine (0.04 mg/kg). RESULTS: The presenting arrhythmias were 16 cases of sinus bradycardia (50.0%), 12 of sinus pause (37.5%), 3 of sinoatrial block (9.4%) and 1 of tachy-bradycardia (3.1%). Nine (28.1%) patients had hypertension, 7 (21.9%) smoked, 2 (6.3%) had diabetes mellitus, and 1 (3.1%) had hypercholesterolemia. Among the patients, 3 had no remarkable symptoms, 13 had dizziness, 7 had syncope, 3 had weakness and 6 had shortness of breath. Twenty five (78.1%) patients were treated with theophylline, 1 patient with tachy-bradycardia syndrome was treated with digoxin and propafenone, and 6 (18.8%) were treated with no medication. During the 43 +/- 28 month follow-up, 25 patients remained asymptomatic, but 6 who took no medication developed mild dizziness. One patient needed permanent pacemaker implantation owing to recurrent syncope despite of theophylline treatment. CONCLUSION: These results show that hypervagotonic SND has a benign course and most of the patients can be managed safely without implanting a pacemaker. (Ed note: I like the abstract. It is short and direct, as it should be.) (+info)
Relation of postural vasovagal syncope to splanchnic hypervolemia in adolescents.
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BACKGROUND: The mechanisms of simple faint remain elusive. We propose that postural fainting is related to excessive thoracic hypovolemia and splanchnic hypervolemia during orthostasis compared with healthy subjects. METHODS AND RESULTS: We studied 34 patients 12 to 22 years old referred for multiple episodes of postural faint and 11 healthy subjects. Subjects were studied in the supine position and during upright tilt to 70 degrees for 30 minutes and subgrouped into S+, historical fainters who fainted during testing (n=24); S-, historical fainters who did not faint during testing (n=10); and control subjects. Supine venous occlusion plethysmography showed no differences between blood flows of the forearm and calf in S+, S-, or control. Cardiac index, total peripheral resistance, and blood volume were not different. Using impedance plethysmography, we assessed blood redistribution during upright tilt. This demonstrated decreased thoracic blood volume and increased splanchnic, pelvic, and leg blood volumes for all subjects. However, thoracic blood volume was decreased in S+ compared with control volume, correlating well with the maximum upright heart rate. Splanchnic volume was decreased in the S+ and S- groups, correlating with the change in thoracic blood volume. Pelvic and leg volume changes were similar for all groups and uncorrelated to thoracic blood volume. CONCLUSIONS: Enhanced postural thoracic hypovolemia and splanchnic hypervolemia are associated with postural simple faint. (+info)
Clinical findings of intracranial vertebral artery disease using magnetic resonance angiography.
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The vertebral artery lesion has a variety of clinical characteristics. We sought to clarify the clinical patterns and the location of the intracranial vertebral artery (ICVA) diseases according to analyses of images obtained using magnetic resonance angiography (MRA). We studied vascular lesions, risk factors, symptoms, signs, and outcomes in 35 patients with ICVA disease (3 had bilateral occlusion; 9, unilateral occlusion; 6, bilateral stenosis; and 17, unilateral stenosis). The most common site of unilateral and bilateral lesions was the distal ICVA after the origin of posterior inferior cerebellar artery (PICA). We found accompanying basilar artery disease in 28.6% of patients with unilateral and bilateral ICVA disease. The majority of the ICVA lesions were associated with internal carotid arteries disease (48.8%). The common vascular risk factors were hypertension (71%), diabetes mellitus (34%), hyperlipidemia (31%), smoking (29%), and coronary artery disease (23%). Eighteen patients (51.4%) had transient ischemic attacks (TIAs) only, 10 patients (28.6%) had TIAs before stroke, and 5 patients (14.3%) had strokes without TIAs. Most patients (80%) with TIAs, with or without stroke, had multiple episodes. Vertigo or dizziness, ataxia, limbs weakness and abnormal gait were the common symptoms and signs. At 6 months follow-up, 66.7% patients had no symptoms or only slight symptoms that caused no disability. Our data showed (1) the usual location of ICVA disease (occlusion or severe stenosis) was distal to PICA, especially near the vertebrobasilar junction; (2) the risk factors were hypertension, diabetes mellitus, hyperlipidemia, smoking, and coronary artery disease; (3) patients with ICVA disease had a high frequency of accompanying internal carotid, middle cerebral, or basilar artery disease; (4) vertigo or dizziness, and ataxia were the common symptoms and signs; (5) TIA was the most common clinical pattern; (6) the outcome was favorable, except in cases with bilateral ICVA occlusion. (+info)
Electrocardiographical case. Asymptomatic patient with ST-segment elevation.
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A 46-year-old man complained of recurrent episodes of giddiness which was not associated with chest pain or breathlessness. There was no family history of sudden death. Clinical examination was unremarkable.12-lead electrocardiogram (ECG) showed ST segment elevation in the right precordial leads, with coved ST segment elevation at its J point followed by a negative T wave with no isoelectric separation, specifically in V2. These ECG features are characteristic of the Brugada syndrome. He underwent a flecanide challenge which produced further elevation of ST segment at its J point and spontaneous ventricular ectopy. Electrophysiological studies induced ventricular fibrillation with 3 extra stimuli. An implantable cardioverter-defibrillator was implanted for prevention of sudden cardiac death. The Brugada syndrome is discussed. (+info)