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Biomedical subjects

Roy Freeman

Publications and source records attributed to Roy Freeman.

At least 19 recordsLinked to original sources
PubMed2006

Delayed orthostatic hypotension: a frequent cause of orthostatic intolerance.

OBJECTIVE: To investigate the prevalence, symptoms, and neurophysiologic features of delayed orthostatic hypotension (OH). METHODS: Blood pressures (BP) were measured at 1-minute intervals on 230 patients during 60 degrees head-up tilt for 45 minutes and standing for 5 minutes. OH was defined as a sustained fall in BP (>or=20 mm Hg systolic or >or=10 mm Hg diastolic) and delayed OH as a sustained BP fall occurring beyond 3 minutes of standing or upright tilt table testing. Beat-to-beat BP, tests of cardiovagal function, and sympathetic-adrenergic function were performed. RESULTS: Of patients with OH, only 46% had OH within 3 minutes of head up tilt; 15% had OH between 3 and 10 minutes; and 39% had OH only after 10 minutes of tilt table testing. The magnitude and the temporal distribution of the BP fall did not differ between those with and without symptoms of orthostatic intolerance. Patients with OH beyond 10 minutes tended to be younger (p < 0.05), have smaller BP falls during phase II of the Valsalva maneuver (p < 0.01), and have greater phase IV overshoot (p < 0.01). CONCLUSIONS: Delayed orthostatic hypotension occurred in 54% of our tested population and was associated with milder abnormalities of sympathetic adrenergic function, suggesting this disorder may be a mild or early form of sympathetic adrenergic failure.

Adult↗
PubMed2006

Assessment of cardiovascular autonomic function.

Autonomic assessment has played an important role in elucidating the role of the autonomic nervous system in diverse clinical and research settings. The techniques most widely used in the clinical setting entail the measurement of an end-organ response to a physiological provocation. The non-invasive measures of cardiovascular parasympathetic function involve the analysis of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Prolonged tilt-table testing, with or without pharmacological provocation, has become an important tool in the investigation of a predisposition to neurally mediated (vasovagal) syncope. Frequency domain analyses of heart rate and blood pressure variability, microneurography, occlusion plethysmography, laser Doppler imaging and flowmetry, and cardiac sympathetic imaging are currently research tools but may find a place in the clinical assessment of autonomic function in the future.

Animals↗
PubMed2006

Differential impairment of the sudomotor and nociceptor axon-reflex in diabetic peripheral neuropathy.

It is not known whether C-fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C-fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C-fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C-fiber-mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C-fiber-mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon-reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C-fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus.

Acetylcholine↗
PubMed2006

Cardiovascular manifestations of autonomic epilepsy.

Cardiovascular autonomic manifestations of seizures occur frequently in the epileptic population. Common manifestations include alterations in heart rate and rhythm, blood pressure, ECG changes and chest pain. The neuroanatomical and neurophysiological underpinnings of these autonomic manifestations are not been fully elucidated. Diagnostic confusion may arise when ictal symptoms are confined to the autonomic nervous system; conversely, such symptoms in association with convulsions or altered consciousness are more readily recognized as concomitant ictal features. Awareness of the diverse autonomic manifestations of epilepsy will enhance diagnosis and lead to more effective therapy of these patients.

Animals↗
PubMed2006

Treatment options for autonomic neuropathies.

Autonomic disorders may present in a varied fashion. Symptoms that may require treatment include orthostatic intolerance, gastrointestinal distress, sudomotor abnormalities, and urologic and sexual dysfunction. Realistic treatment goals should be outlined for patients, with the expectations that symptoms can be improved, but that the disease is unlikely to be cured and long-term therapy may be required. Orthostatic intolerance is usually treated by a combination of pharmacologic and nonpharmacologic therapies. Nonpharmacologic therapies include compression stockings, adequate fluid and salt intake, and lifestyle modifications. Polypharmacologic therapy is often the standard and can include a volume-expanding agent (such as fludrocortisone) and a sympathomimetic agent. This combination will improve symptoms dramatically in most patients. Treatment of gastrointestinal disorders should address the particular symptom involved: gastroparesis, constipation, or diarrhea. Treatment of sexual and urogenital dysfunction often requires a combination of pharmacologic intervention and lifestyle modifications for peak effectiveness. Patient education is the cornerstone of treatment in any of the autonomic disorders. Given enough education and motivation, many patients will be able to participate in their treatment, which will provide a feeling of empowerment and control over a disease that is often frustratingly resistant to treatment.

Journal Article↗
PubMed2005

L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy.

The authors report a 46-year-old woman with antibodies to the nicotinic acetylcholine receptor (NiAchR) of the autonomic ganglia. She presented with severe orthostatic intolerance refractory to treatment with midodrine, fludrocortisone, erythropoietin, vasopressin, salt, and fluid loading. Addition of L-threo-3,4-dihidroxyphenylserine (L-DOPS) substantially improved blood pressure and orthostatic tolerance. L-DOPS may benefit patients with severe orthostatic intolerance and be particularly effective in patients with ganglionic NiAchR antibodies.

Adrenergic Agonists↗
PubMed2005

Orthostatic dyspnea: a neglected symptom of orthostatic hypotension.

Dyspnea is a common symptom in patients with pulmonary and cardiac disease. Orthostatic hypotension is rarely considered a cause of dyspnea. We reviewed the medical records of 651 consecutive patients referred for the evaluation of dysautonomia to investigate the prevalence of dyspnea and its association with OH and other autonomic abnormalities. Dyspnea was reported by questionnaire in 30% of patients with OH, compared to 10% of age and sex matched patients without OH (P<0.05, chi(2)). There was a trend toward earlier blood pressure falls in patients with dyspnea. During autonomic testing, 25% of patients (10 of 40) with OH who reported dyspnea on the questionnaire had shortness of breath coincident with blood pressure falls during tilt table and active standing. The time to maximal blood pressure fall was shorter in patients with OH who experienced shortness of breath during testing compared to those without dyspnea (11 minutes vs. 21 minutes, P<0.05). In this study, dyspnea was frequently associated with OH. Ventilation perfusion mismatch, due to inadequate perfusion of ventilated lung apices may be the most likely underlying cause of orthostatic dyspnea in patients with OH.

Aged↗
PubMed2005

Newer agents for the treatment of painful diabetic peripheral neuropathy.

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies in diabetes. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-d-aspartate receptor antagonists, and the opioid analgesics. The availability of several newer agents, used alone or in combination, has resulted in the successful alleviation of neuropathic pain in many patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities with less prominent side effects.

Analgesics↗
PubMed2005

The treatment of neuropathic pain.

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. These manifestations of neuronal plasticity occur in the peripheral nerve, spinal cord, and brain. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-D-aspartate receptor antagonists, and opioid analgesics. The use of these adjuvant analgesics, either alone or in combination, should result in the alleviation of neuropathic pain in most patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities.

Anti-Arrhythmia Agents↗
PubMed2004

Sympathetic nerve activity in response to hypotensive stress in the postural tachycardia syndrome.

BACKGROUND: Increased central sympathetic activity and/or deficient peripheral sympathetic nerve function are among the proposed pathophysiological changes in patients with the postural tachycardia syndrome (POTS). Little is known about sympathetic nerve outflow and its role in hemodynamic control in this disorder. METHODS AND RESULTS: We recorded peroneal muscle sympathetic nerve activity in 9 POTS patients and 9 control subjects at rest and during a nitroprusside-induced hypotensive stimulus. Baseline blood pressure (BP) and heart rate were significantly higher in POTS patients than in controls. At rest, the burst frequency was similar in POTS patients and controls (18.1+/-6.2 and 20.1+/-7.9 bursts/min, respectively; P=NS), whereas the burst incidence was significantly lower (23.1+/-6.8 versus 32.2+/-11.4 bursts/100 heartbeats, P<0.05). Nitroprusside increased sympathetic outflow significantly more in POTS patients than in controls despite a similar BP decrease (burst frequency 20.4+/-7.5 versus 12.1+/-4.1 bursts/min, P=0.008, and burst incidence 21.8+/-8.4 versus 14.4+/-5.2 bursts/100 heartbeats, P=0.03). The change in mean burst area, a measure of the number of actively firing sympathetic neurons, was similar in patients and controls (117+/-15% versus 114+/-21%, P=NS). CONCLUSIONS: At rest, the tachycardia and normal burst frequency result in normal or even elevated BP in POTS patients. During a hypotensive stimulus, cardiovascular homeostasis is maintained by the increased sympathetic outflow and normal heart rate response despite the lack of concomitant increase in mean burst area that is most likely due to sympathetic denervation.

Adult↗
PubMed2004

Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure.

BACKGROUND: Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA). METHODS: In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS. RESULTS: Plasma L-DOPS peaked at 1.9 microg/ml (9 micromol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2-3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS. CONCLUSIONS: The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from LDOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves.

Aged↗
PubMed2004

Nonpharmacological treatment of reflex syncope.

Reflex syncope is a common medical problem. Vasovagal reflex syncope is the most frequent form. Although the prognosis of the disorder is excellent, it may impose substantial changes in life style and cause profound psychological distress. Thus, management of this disorder is an important issue. This chapter, based on a review of the literature and the authors' clinical experience, encompasses the non-pharmacological measures used in the management of reflex syncope. The cornerstone of the non-pharmacological management of patients with reflex syncope is education and reassurance regarding the benign nature of the condition. Patients should be instructed to avoid potential triggers. A tilt table test can be employed to teach the patient to recognize early premonitory symptoms. There are several physical maneuvers (e. g., leg crossing, muscle tensing and squatting) that are effective in combating orthostatic intolerance. For the majority of patients this approach is adequate. Patients with frequent attacks of reflex syncope are advised to increase their dietary salt intake. Exercise training also increases orthostatic tolerance. In highly motivated patients with recurrent syncope, raising the head of the bed to permit gravitational exposure during sleep and prolonged periods of enforced maintenance of the upright posture (tilt-training) can be considered. Preliminary data suggest that water drinking may improve orthostatic tolerance. Abdominal belts may also be effective in highly symptomatic subjects with reflex syncope.

Abdomen↗
PubMed2004

Pharmacological treatment of reflex syncope.

Patient education, identification of possible triggers of syncope and reassurance are a central feature of the management of patients with reflex syncope. Patients should be advised as to the importance of adequate hydration and taught physical countermaneuvers to enhance cardiac venous return. These maneuvers are sufficient for most patients, however, for a small number of patients who continue to have recurrent syncopal events, pharmacological intervention may be considered. Volume expansion can be enhanced with salt and fludrocortisone. Agents from diverse pharmacological classes have been used to attenuate the reflex response, enhance vasoconstriction and attenuate vagal outflow. Alpha adrenoreceptor agonists, anticholinergic agents, theophylline, beta adrenoreceptor antagonists, serotonin reuptake inhibitors and disopyramide are the most widely studied. None of these agents has shown a consistent therapeutic benefit in clinical trials.

Adrenergic Agents↗
PubMed2004

The evaluation of small fiber function-autonomic and quantitative sensory testing.

Disorders of the autonomic and small nerve fibers comprise a wide spectrum of disease states that cross a multitude of clinical specialties.The evaluation of these disorders allows the investigator to determine the presence or absence of abnormalities in the lightly myelinated and unmyelinated nerve fibers with minimal discomfort to the patient. The severity of dysfunction also can be determined to guide therapy and aid in prognostication for individual patients.

Autonomic Nervous System↗