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Biomedical subjects

Horacio Kaufmann

Publications and source records attributed to Horacio Kaufmann.

17 recordsLinked to original sources
PubMed2005

Electrical activation of the human vestibulo-sympathetic reflex.

Muscle sympathetic nerve activity (MSNA) is modulated on a beat-to-beat basis by the baroreflex. Vestibular input from the otolith organs also modulates MSNA, but characteristics of the vestibulo-sympathetic reflex (VSR) are largely unknown. The purpose of this study was to elicit the VSR with electrical stimulation to estimate its latency in generating MSNA. The vestibular nerves of seven subjects were stimulated across the mastoids with short trains of high frequency, constant current pulses. Pulse trains were delivered every fourth heartbeat at delays of 300-700 ms after the R wave of the electrocardiogram. Vestibular nerve stimulation given 500 ms after the R wave significantly increased baroreflex-driven MSNA, as well as the diastolic blood pressure threshold at which bursts of MSNA occurred. These changes were specific to beats in which vestibular stimulation was applied. Electrical stimulation across the shoulders provided a control condition. When trans-shoulder trials were subtracted from trials with vestibular nerve stimulation, eliminating the background baroreflex-driven sympathetic activity, there was a sharp increase in MSNA beginning 660 ms after the vestibular nerve stimulus and lasting for about 60 ms. The increase in the MSNA produced by vestibular nerve stimulation, and the associated increase in the diastolic blood pressure threshold at which the baroreflex-driven bursts occurred, provide evidence for the presence of a short-latency VSR in humans that is likely to be important for the maintenance of blood pressure during rapid changes in head and body position with respect to gravity.

Adult↗
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

[Pure autonomic failure. Bradbury Eggleston Syndrome. Case report].

Pure Autonomic Failure is a progressive, adult onset, degenerative disorder of the autonomic nervous system characterized clinically by orthostatic hypotension, bladder, sexual and sudomotor dysfunction. Since there are no other associated somatic neurological deficits, this condition must be considered in the differential diagnosis of orthostatic hypotension. We report a 64 years old man with a history of seven years of autonomic dysfunction, with severe orthostatic hypotension, erectile and bladder dysfunction. Autonomic tests showed low circulating norepinephrine levels, sweating abnormalities with regional anhydrosis of the left side of the trunk and abnormal cardiovagal response, indicating generalized autonomic failure. Peripheral somatic neuropathies with autonomic involvement were excluded by normal electrophysiologic tests and the patient was diagnosed pure autonomic failure. Treatment with fludrocortisone and midodrine improved orthostatic tolerance.

Autonomic Nervous System Diseases↗
PubMed2004

Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies.

The authors report the clinical and postmortem neuropathologic findings of two patients, one with Parkinson disease (PD) and one with dementia with Lewy bodies (DLB), both of whom initially sought treatment for isolated autonomic failure. These cases suggest that neurodegeneration in PD and DLB may begin outside the CNS in autonomic postganglionic neurons, a finding with potential diagnostic and therapeutic implications.

Aged↗
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

Defining and classifying syncope.

There is no widely adopted definition or classification of syncope and related disorders. This lack of uniformity harms patient care, research, and medical education. In this article, syncope is defined as a form of transient loss of consciousness (TLOC) due to cerebral hypoperfusion. Differences between syncope and other causes of TLOC such as epilepsy, and disorders mimicking TLOC are described. A pathophysiological classification of syncope is proposed.

Diagnosis, Differential↗
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

Syncope: a clinically guided diagnostic algorithm.

The initial evaluation of a patient with syncope should include a thorough clinical history, physical examination and 12 lead electrocardiogram (ECG). The history is the best diagnostic tool. Clinical findings guide further testing. Patients with syncope and heart disease require echocardiography, Holter monitoring or exercise testing. The tilt test and carotid sinus massage are useful to reproduce reflex syncope. An insertable subcutaneous loop recorder can provide prolonged ECG monitoring.

Algorithms↗
PubMed2003

Norepinephrine precursor therapy in neurogenic orthostatic hypotension.

BACKGROUND: In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture. METHODS AND RESULTS: We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L-aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH (8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine (from 101+/-4 to 141+/-5 mm Hg) and standing (from 60+/-4 to 100+/-6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patients CONCLUSIONS: Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.

Administration, Oral↗
PubMed2003

Primary hyperhidrosis--evidence for autosomal dominant inheritance.

Primary hyperhidrosis is a neurogenic disorder of unknown cause characterized by excessive sweating in the palmar surface of the hands, armpits, groin and feet. In the course of a therapeutic trial for primary hyperhidrosis, 62 % of patients reported a positive family history. Examination of these pedigrees demonstrated a sibling recurrence risk of lambdas = 29-48 and an offspring recurrence risk of lambdao = 41-68 indicating that hyperhidrosis can be an inherited condition. The pattern of inheritance suggests an autosomal dominant mode of transmission with incomplete disease penetrance.

Female↗
PubMed2003

Autonomic failure in neurodegenerative disorders.

Autonomic failure with orthostatic and postprandial hypotension, bowel and bladder disturbances, and sexual dysfunction are frequent, disabling features in patients with the three most prevalent neurodegenerative movement disorders: Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA), and the related neurodegenerative Lewy-body disorder characterized by isolated severe autonomic failure (pure autonomic failure, PAF). All of these disorders have in common the presence of alpha-synuclein in the cytoplasmic precipitates found in neurons in Lewy body disorders or glia in MSA. Autonomic failure with disabling orthostatic hypotension is the clinical hallmark of PAF. It may also be the initial presentation of MSA, making diagnosis difficult. Within a few years, however, MSA patients develop movement disorders, which are differentiated from PD by the paucity of unilateral resting tremor, the lack of response to levodopa, and their rapidly progressive nature, resulting in disability and death in 7 to 8 years. Moderately effective treatment is available for autonomic symptoms, but management of movement disorders remains unsuccessful. Discoveries relevant to physiology and common pathological conditions were initially made in patients with autonomic failure. Meals induce profound hypotension in these patients. Conversely, commonly used nasal decongestants can produce substantial pressor effects. Even 500 mL of water can increase blood pressure by a previously unrecognized sympathetic reflex. Residual sympathetic tone is able to induce sustained supine hypertension in MSA, because it is resolved after ganglionic blockade. These phenomena were not previously recognized because of the buffering capacity of the baroreflex, but were unmasked in autonomic failure patients.

Animals↗
PubMed2002

Brain magnetic resonance imaging in multiple-system atrophy and Parkinson disease: a diagnostic algorithm.

BACKGROUND: Brain magnetic resonance (MR) imaging offers the potential for objective criteria in the differential diagnosis of multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson disease (PD), since it frequently shows characteristic abnormalities in patients with MSA-P and is believed to be normal in patients with PD. OBJECTIVE: To determine concordance between clinical and MR imaging-based diagnoses of MSA-P and PD. DESIGN: Two neuroradiologists identified and rated striatal and infratentorial abnormalities in 39 brain MR images and assigned a diagnosis of PD, MSA-P, or MSA with additional marked cerebellar ataxia (MSA-C). SETTING: Academic medical center. PATIENTS: Thirty-nine patients with parkinsonism, including 21 with a clinical diagnosis of PD, 14 with MSA-P, and 4 with MSA-C. RESULTS: All patients with MSA and 14 (67%) of 21 patients with PD had some abnormality on brain MR imaging. Brainstem atrophy was seen in patients with MSA-P and MSA-C. Putaminal atrophy was seen only in MSA-P. Putaminal hypointensity and lateral slitlike hyperintensity were seen in both PD and MSA-P but were always mild in PD. Cerebellar abnormalities, seen in all patients with MSA-C and 11 patients with MSA-P, were also identified in 6 patients with PD, albeit always rated as mild. Nonconcordance between clinical and radiological diagnosis occurred in 2 patients with PD, 5 with MSA-P, and 1 with MSA-C. CONCLUSION: Since several features on brain MR imaging are seen only in MSA-P, a simple diagnostic algorithm may improve the MR imaging diagnosis of MSA-P and PD.

Adult↗
PubMed2002

Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study.

Neurally mediated syncope is the most frequent cause of syncope in patients without structural heart disease. Its most common trigger is a reduction in venous return to the heart due to excessive venous pooling in the legs. We conducted a double-blind, randomized, crossover trial to investigate the efficacy of midodrine, a selective alpha-1 adrenergic agonist that decreases venous capacitance, in preventing neurally mediated syncope triggered by passive head-up tilt. Twelve patients with history of recurrent neurally mediated syncope, which was reproduced during head-up tilt, were randomized to receive a nonpressor dose of midodrine (5mg) or placebo on day 1 and the opposite on day 3. One hour after drug or placebo administration, patients underwent 60-degree head-up tilt lasting 40 minutes (unless hypotension or bradycardia developed first). In the supine position, midodrine produced no significant change in blood pressure or heart rate. The responses to head-up tilt were significantly different on the midodrine and the placebo day: on the placebo day, 67% (8/12) of the subjects suffered neurally mediated syncope, whereas only 17% (2/12) of the subjects developed neurally mediated syncope on the midodrine day (p < 0.02). These results indicate that midodrine significantly improves orthostatic tolerance during head-up tilt in patients with recurrent neurally mediated syncope.

Adult↗
PubMed2002

Autonomic cardiovascular reflexes in Wilson's disease.

We studied autonomic cardiovascular function in fourteen patients with Wilson's disease. Four had abnormalities on autonomic testing and, of these, three had evidence of severe central nervous system abnormalities. In contrast, of the remaining ten patients with normal cardiovascular reflexes, only two had severe deficits of the central nervous system. We suggest that autonomic impairment in Wilson's disease is due to involvement of central autonomic neurons.

Adult↗
PubMed2002

Diagnosis and treatment of neurally mediated syncope.

BACKGROUND: Syncope is caused by a severe but reversible reduction in blood flow to the brain stem neurons responsible for supporting consciousness (reticular activating system). Neurally mediated syncope, also referred to as vasovagal or reflex syncope, is the most frequent cause of loss of consciousness in apparently normal subjects. REVIEW SUMMARY: Neurally mediated syncope is believed to be a reflex response with afferent, central, and efferent pathways. Characteristic autonomic changes in neurally mediated syncope are an increase in parasympathetic efferent activity causing bradycardia and a reduction in sympathetic vasoconstrictor outflow causing vasodilatation. Premonitory symptoms, such as nausea, diaphoresis, abdominal discomfort, and blurred vision, are caused by autonomic activation and are distinguishing features of neurally mediated syncope. Neurally mediated syncope frequently has a characteristic trigger, although this may not be apparent. Testing orthostatic tolerance during passive head-up tilt is the best available diagnostic procedure to evaluate patients with syncope in whom a cardiac cause has been excluded. In many cases, once the diagnosis of neurally mediated syncope is confirmed, it may suffice to reassure the patient and teach him to avoid known triggers and to recognize and act upon early warning symptoms. Because subjects with neurally mediated syncope may potentially be sodium depleted, increasing salt intake can be beneficial in improving their orthostatic intolerance. CONCLUSIONS: Neurally mediated syncope is the most common form of syncope in healthy adults. The best diagnostic tools are the clinical history and passive head-up tilt. The best treatment strategies are the avoidance of triggering factors as well as intravascular volume expansion.

Journal Article↗
PubMedDate not supplied

Artificial gravity: a possible countermeasure for post-flight orthostatic intolerance.

Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith-ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith-ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith-sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.

Acceleration↗