Biomedical subjects

Max J Hilz

Publications and source records attributed to Max J Hilz.

27 records · Page 2Linked to original sources

PubMed2003

Terminal vessel hyperperfusion despite organ hypoperfusion in familial dysautonomia.

Patients with familial dysautonomia (FD) exhibit orthostatic hypotension as well as recumbent hypertension. In addition, during dysautonomic crises, patients have hypertensive blood pressure that is presumed to be secondary to episodic vasoconstriction, as well as swollen hands that are presumed to be secondary to vasodilatation. This discrepancy in vascular control is poorly understood, yet may provide insight into the pathophysiology of autonomic crises. To evaluate the pathological mechanisms of overall blood flow and end-organ perfusion, we assessed resting and post-ischaemic limb and skin blood flow in FD patients. In groups of 15 FD patients and 15 controls, we measured resting and post-ischaemic forearm blood flow using venous occlusion plethysmography, and superficial skin blood flow using laser Doppler flowmetry. At rest, arterial inflow was averaged from eight venous occlusion measurements and expressed as percentage volume change/min. Post-ischaemic plethysmographic inflow was determined from the peak influx during the first venous occlusion following 3 min of ischaemia. Transcutaneous forearm partial pressures of oxygen and carbon dioxide were monitored continuously. At rest, plethysmographic limb perfusion was lower in FD patients than in controls, while skin blood flow did not differ between the two groups. After ischaemia, hyperperfusion of the forearm and hand was less pronounced in FD patients than in controls, while skin blood flow was significantly higher in patients than in controls. Partial pressures of O(2) and CO(2) did not differ between the two groups. We conclude that the reduced overall limb perfusion in patients with FD is due to hypertension-induced structural changes to vessel walls, with an increase in resistance vessel rigidity. The exaggerated post-ischaemic skin perfusion in FD patients seems to be due to deficient sympathetic innervation of precapillary vessels and arteriovenous shunts and to denervation hypersensitivity of intradermal small nerve fibres. Both the reduced limb perfusion and the dysfunctional end-organ blood supply in FD patients are likely to be major contributors to the vasomotor instability observed in these subjects, particularly during periods of stress.

Adult↗

PubMed2003

Inherited autonomic neuropathies.

Inherited autonomic neuropathies are a rare group of disorders associated with sensory dysfunction. As a group they are termed the "hereditary sensory and autonomic neuropathies" (HSAN). Classification of the various autonomic and sensory disorders is ongoing. In addition to the numerical classification of four distinct forms proposed by Dyck and Ohta (1975), additional entities have been described. The best known and most intensively studied of the HSANs are familial dysautonomia (Riley-Day syndrome or HSAN type III) and congenital insensitivity to pain with anhidrosis (HSAN type IV). Diagnosis of the HSANs depends primarily on clinical examinations and specific sensory and autonomic assessments. Pathologic examinations are helpful in confirming the diagnosis and in differentiating between the different disorders. In recent years identification of specific genetic mutations for some disorders has aided diagnosis. Replacement or definitive therapies are not available for any of the disorders so that treatment remains supportive and directed toward specific symptoms.

Animals↗

PubMed2003

Dynamic cerebral autoregulation remains stable during physical challenge in healthy persons.

The effects of physical activity on cerebral blood flow (CBF) and cerebral autoregulation (CA) have not yet been fully evaluated. There is controversy as to whether increasing heart rate (HR), blood pressure (BP), and sympathetic and metabolic activity with altered levels of CO2 might compromise CBF and CA. To evaluate these effects, we studied middle cerebral artery blood flow velocity (CBFV) and CA in 40 healthy young adults at rest and during increasing levels of physical exercise. We continuously monitored HR, BP, end-expiratory CO2, and CBFV with transcranial Doppler sonography at rest and during stepwise ergometric challenge at 50, 100, and 150 W. The modulation of BP and CBFV in the low-frequency (LF) range (0.04-0.14 Hz) was calculated with an autoregression algorithm. CA was evaluated by calculating the phase shift angle and gain between BP and CBFV oscillations in the LF range. The LF BP-CBFV gain was then normalized by conductance. Cerebrovascular resistance (CVR) was calculated as mean BP adjusted to brain level divided by mean CBFV. HR, BP, CO2, and CBFV increased significantly with exercise. Phase shift angle, absolute and normalized LF BP-CBFV gain, and CVR, however, remained stable. Stable phase shift, LF BP-CBFV gain, and CVR demonstrate that progressive physical exercise does not alter CA despite increasing HR, BP, and CO2. CA seems to compensate for the hemodynamic effects and increasing CO2 levels during exercise.

Adult↗

PubMed2003

Delayed cerebrovascular autoregulatory response to ergometer exercise in normotensive elderly humans.

BACKGROUND: Relatively little is known about physiological cerebrovascular haemodynamics during physical stress in elderly healthy individuals. The aim of this study was to determine the effect of ergometer stress on cerebrovascular haemodynamics in elderly healthy individuals in comparison with young healthy individuals, using non-invasive methods. METHODS: Continuous middle cerebral artery blood flow velocity (CBFV; transcranial Doppler ultrasound), beat-to-beat blood pressure, heart rate and transcutaneous pCO(2) were measured in response to 3 min ergometer exercise stress in 18 elderly healthy subjects (mean age +/- SD 66.5 +/- 5.8 years) and 18 healthy young subjects (mean age +/- SD 29.4 +/- 4.7 years). Pulsatility index (PI) was used as a parameter for cerebrovascular resistance. The subjects were in a supine position with an elevated trunk and performed exercise by pedalling on an ergometer, generating 75-100 W. Statistical analysis was carried out using MANOVA, a general linear model with repeated measures. RESULTS: In both groups, blood pressure increased significantly (p < 0.001) with time during exercise, with no significant differences between the groups or regarding interaction (time sequence/group factor). Heart rate increased significantly with time during exercise (p < 0.001) and was significantly more prominent (p = 0.002) and prolonged (p < 0.001) in the young group. pCO(2) did not differ with time or between the groups and with regard to interaction. Mean CBFV (MFV) increased significantly during time (p < 0.001). Between the groups, there was no significant difference (p = 0.836), but with regard to interaction (time sequence/group factor), there was a significant delay in MFV increase in the group of young subjects (p = 0.002). The PI, a measure of cerebrovascular resistance, increased significantly with time without significant differences between the groups (p = 0.061), but was significantly delayed in the elderly regarding the interaction time sequence/group factor (p < 0.001). CONCLUSION: The cerebrovascular changes during ergometer exercise may reflect the combined activation of the cerebrovascular autoregulative mechanisms (predominantly neurogenic and myogenic). In healthy normotensive elderly subjects, cerebral autoregulatory capacity is retained but delayed in response to ergometer stress compared with young healthy subjects. We speculate that these findings may contribute to a higher risk of cerebral hypoperfusion in the elderly.

Adult↗

PubMed2002

Assessment and evaluation of hereditary sensory and autonomic neuropathies with autonomic and neurophysiological examinations.

The five different types of the rare hereditary sensory and autonomic neuropathies (HSAN) are classified by their mode of inheritance, pathology, natural history, biochemical, neurophysiologic and autonomic abnormalities. Clinically, the different types of HSANs can be identified by a detailed history and examination and 'bedside' tests of sympathetic or parasympathetic function such as active standing, metronomic breathing or the Valsalva maneuver, sensory and motor nerve conduction studies, quantitative sensory testing of thermal and vibratory perception, and the analysis of sudomotor function by recordings of the sympathetic skin response (SSR) or the sweat output during quantitative sudomotor axon reflex testing (QSART). The slowly progressive, symmetrical HSAN type I manifests between the second and fourth decade with ulcers or mutilations of the lower extremities, low normal sensory and motor nerve conduction velocities, but abnormal warm, cold and heat pain perception and distal anhidrosis. In HSAN type II, symptoms occur already in infancy, trophic alterations affect fingers and toes. There are acral anhidrosis and various autonomic dysfunctions such as tonic pupils, eating and swallowing difficulties, constipation, episodic fever, profound hypotonia and episodes of apnea. Sensory perception is severely impaired and accounts for elevated vibratory but also thermal perception thresholds. Sensory nerve conduction is highly abnormal while motor nerve conduction studies are almost normal. Type III, the autosomal recessive familial dysautonomia (FD), is the most common of the HSANs. FD is characterized by pronounced autonomic, primarily sympathetic dysregulation with severe orthostatic hypotension, repeated episodes of autonomic crises with excessive arterial hypertension, profuse sweating, skin blotching, puffy hands and behavioral abnormalities. FD manifests only in children of Ashkenazi Jewish ancestry. Cardinal findings are diminished deep tendon reflexes, absence of overflow tears, absence of fungi-form papillae of the tongue and of axon flare response following intradermal histamine injection. Thermal and vibratory testing show pronounced impairment of temperature and pain but also of vibratory perception. Children with HSAN IV, 'congenital insensitivity to pain with anhidrosis' experience repeated episodes of high fevers during high environmental temperature due to anhidrosis. The anhidrosis of the hyperkeratotic skin accounts for absence of the SSR or lack of sweat output during QSART. The patients' insensitivity to superficial as well as deep, visceral pain can be demonstrated e. g. by quantitative heat pain testing. Patients develop severe mutilations e. g. of the tip of their tongue, they might have severe burn injuries and multiple, unnoticed fractures with neuropathic joints. Children with the very rare HSAN type V respond normally to tactile, vibratory or thermal stimuli, but have a selective loss of pain perception with otherwise normal neurological examination. Painful stimuli reveal no signs of discomfort.

Hereditary Sensory and Autonomic Neuropathies↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2002

Baroreflex stimulation shows impaired cardiovagal and preserved vasomotor function in early-stage amyotrophic lateral sclerosis.

OBJECT: In ALS patients, autonomic nervous system dysfunction might account for an additional reduction of the quality and expectancy of life of individual patients and contribute to unexpected early fatalities. This study was undertaken to assess baroreflex-mediated vagal and sympathetic cardiovascular control of the heart and blood vessels in ALS patients. METHODS: In 12 early-stage ALS patients (age 54 +/- 4 years) and 12 controls (age 55 +/- 3 years) we assessed resting baroreflex sensitivity (BRS) by spectral analysis, then stimulated the carotid baroreflex by oscillating neck suction at 0.1 Hz to assess the autonomic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. RESULTS: Resting heart rate was significantly higher in the ALS patients than in the controls (P < 0.05), but resting baroreflex sensitivity did not differ significantly between the groups. Stimulation at 0.2 Hz induced an oscillation in R-R interval that was significantly smaller (P < 0.05) in ALS patients than in controls. R-R interval responses to 0.1 Hz stimulation were significantly (P < 0.01) reduced in ALS patients compared to controls. Responses of blood vessels to 0.1 Hz stimulation did not differ significantly between the groups. CONCLUSION: In early-stage ALS patients, BRS might be normal at rest. Only baroreflex activation reveals impaired cardiovagal responses while sympathetic vasomotor control is preserved. Treatment to restore sympathetic-parasympathetic balance to the heart could prevent early cardiovascular fatalities in some ALS patients.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation.

The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex.

Acetylcholine↗

PubMed2002

Evidence of an intrinsic sinus node abnormality in patients with postural tachycardia syndrome.

OBJECTIVE: To determine whether an intrinsic sinus node abnormality is involved in the pathophysiology of the postural tachycardia syndrome (POTS). SUBJECTS, PATIENTS, AND METHODS: In this prospective study, we compared the relationship between P-wave axis (PWA) and heart rate (HR) in 11 healthy controls and 14 patients with POTS by obtaining 12-lead electrocardiographic recordings during supine rest and during gradual head-up tilt. The HR of controls was titrated with isoproterenol infusion to match the HR of patients. The PWA was compared at different HR levels, and the relationship between HR and PWA was assessed for patients and controls. Primary end points were the PWA-HR relationship in healthy controls, comparison of these data with data from patients with POTS as a group, and identification of a possible subgroup of patients with POTS with irregular PWA-HR relationship. RESULTS: The PWA increased with increasing HR following a similar logarithmic trendline in both groups. The PWA of patients was significantly lower at the lowest comparable HR level but not different at faster HR levels. Three patients (21%) had a clearly abnormal HR-PWA relationship with substantial shift toward lower PWA. CONCLUSIONS: Our data support the hypothesis of a primary sinus node abnormality in a subset of patients with POTS. The ability to identify patients with primary sinus node abnormality may have important therapeutic implications.

Adult↗