Biomedical subjects

Otto Appenzeller

Publications and source records attributed to Otto Appenzeller.

11 recordsLinked to original sources

PubMed2006

Autonomic regulation during orthostatic stress in highlanders: comparison with sea-level residents.

This report is a comparison of orthostatic tolerance and autonomic function in three groups of high-altitude dwellers: Andeans with and without chronic mountain sickness (CMS) and healthy Ethiopians. Results are compared with those from healthy sea-level residents. The aim was to determine whether different high-altitude populations adapted differently to the prevailing hypobaric hypoxia. Orthostatic tolerance was assessed using a test involving head-up tilt (HUT) and graded lower body suction. This was performed at the subjects' resident altitude. Blood pressure (Portapres) and R-R interval (ECG) were recorded during the test, and spectral and cross-spectral analyses of heart period and systolic blood pressure time series were performed using data obtained both while supine and during HUT. The transfer function gain in the low-frequency range (LF, approximately 0.1 Hz) at the point of maximal coherence was used as a measure of cardiac baroreflex sensitivity (BRS). As previously reported, Peruvians displayed an unusually good orthostatic tolerance, while Ethiopians showed an orthostatic tolerance comparable to that of healthy sea-level residents. There were no significant differences between groups in the supine values of the spectral analysis results. Head-up tilt induced the expected changes in Ethiopians (an increase in the LF components and a decrease in the respiratory components) but not in Andeans. Cross-spectral analysis showed abnormal results from all groups of high-altitude dwellers. These results indicate that Ethiopians, but not Peruvians, behave similarly to sea-level residents in terms of orthostatic tolerance and autonomic responses to orthostatic stress, as assessed from spectral analyses, and this indicates good adaptation to their environment. However, in all the high-altitude groups the results of cross-spectral analysis were atypical, suggesting some degree of impairment in baroreflex function.

Acclimatization↗

PubMed2006

Carotid baroreflex regulation of vascular resistance in high-altitude Andean natives with and without chronic mountain sickness.

We investigated carotid baroreflex control of vascular resistance in two groups of high-altitude natives: healthy subjects (HA) and a group with chronic mountain sickness (CMS), a maladaptation condition characterized by high haematocrit values and symptoms attributable to chronic hypoxia. Eleven HA controls and 11 CMS patients underwent baroreflex testing, using the neck collar method in which the pressure distending the carotid baroreceptors was changed by applying pressures of -40 to +60 mmHg to the chamber. Responses of forearm vascular resistance were assessed from changes in the quotient of blood pressure divided by brachial artery blood velocity. Stimulus-response curves were defined at high altitude (4338 m) and within 1 day of descent to sea level. We applied a sigmoid function or third-order polynomial to the curves and determined the maximal slope (equivalent to peak gain) and the corresponding carotid pressure (equivalent to 'set point'). The results showed that the peak gains of the reflex were similar in both groups and at both locations. The 'set point' of the reflex, however, was significantly higher in the CMS patients compared to HA controls, indicating that the reflex operates over higher pressures in the patients (94.4 +/- 3.0 versus 79.6 +/- 4.1 mmHg; P < 0.01). This, however, was seen only when subjects were studied at altitude; after descent to sea level the curve reset to a lower pressure with no significant difference between HA and CMS subjects. These results indicate that carotid baroreceptor control of vascular resistance may be abnormal in CMS patients but that descent to sea level rapidly normalizes it. We speculate that this may be explained by CMS patients having greater vasoconstrictor activity at altitude owing to greater hypoxic stimulation of chemoreceptors.

Adult↗

PubMed2006

Cerebral vasodilatation to exogenous NO is a measure of fitness for life at altitude.

BACKGROUND AND PURPOSE: Andean highlanders, unlike Ethiopians, develop chronic mountain sickness (CMS), a maladaptation to their native land. Ambient hypoxia induces NO-mediated vasodilatation. Fitness for life at altitude might be revealed by cerebrovascular responses to NO. METHODS: Nine altitude-native men were examined at 3622 and 794 m in Ethiopia and compared with 9 altitude-native Andean men tested at 4338 and 150 m in Peru. We assessed CMS scores, hematocrits, end-tidal pressure of carbon dioxide (P(ET)co2), oxygen saturations, and cerebral blood flow velocity (CBV). We evaluated fitness for life at altitude from the cerebrovascular response to an exogenous NO donor. RESULTS: At high altitude, CMS scores and hematocrits were higher in Andeans, and they had lower oxygen saturations. Ethiopians had higher P(ET)co2 at all study sites. At low altitude, saturations were similar in both groups. Responsiveness of the cerebral circulation to NO was minimal in Ethiopians at low altitude, whereas Andeans had a large response. In contrast, at high altitude, Ethiopians showed large responses, and Peruvians had minimal responses. CONCLUSIONS: By our measure, high altitude-native Peruvians were well-adapted lowlanders, whereas Ethiopian highlanders were well adapted to altitude life. Environmental pressures were sufficient for human adaptation to chronic hypoxia in Africa but not South America. The mechanisms underlying these differences are unknown, although studies of neurovascular diseases suggest that this may be related to a NO receptor polymorphism.

Acclimatization↗

PubMed2006

Chronic hypoxia in Andeans; are there lessons for neurology at sea level?

Hypoxia is implicated in aging and neurodegenerative diseases. We posited that changes in gene expression induced by ambient hypoxia at altitude may be neuroprotective to natives of these regions. We studied 30 men. Twenty natives of Cerro de Pasco (CP), altitude 4,338 m were examined in CP; then transported within 6 h to Lima (150 m-sea level) and examined 1 h after arrival. They were assessed by a Chronic Mountain Sickness-score (CMS-sc) in CP, 10 were normal Andeans and 10 had chronic mountain sickness (CMS), a sudden inexplicable loss of adaptation to their native environment. RNA was extracted from venous blood white cells. The Andeans were compared to 10 normal US men living at 1500 m using RT-PCR. We focused on the cyto-neuro-protective genes, Ataxia telangiectasia mutated (ATM), heme-oxygenase-1 (HMOX 1), heat shock protein-70 (HSP-70), heat shock protein-90 (HSP-90), and the neuroprotective enzyme, nicotinamide mononucleotide adenylyl transferase 1 (Nnmat 1). CMS patients had significantly higher levels of gene expression (HMOX-1, HSP-70, ATM) than Andean controls in CP. HSP-90 and Nmnat 1, however, were higher in Andean controls in all locations. Significant reductions of all gene products, within an hour of arriving in normoxia in Lima, were found. In Andean controls, the gene products in Lima fell to levels approaching US controls. Correlation and regression methods showed men with high expression of all gene products had an average CMS-sc=19.8; those with low expression a normal score (9.4, P=0.02). ATM expression was related to age (P<0.001). The natural experiment that unfolds in the mountainous regions of the world provides opportunities to study neuroprotection in intact humans.

Adaptation, Physiological↗

PubMed2006

Gene expression, autonomic function and chronic hypoxia:lessons from the Andes.

Autonomic function is altered by altitude in sojourners and natives. We hypothesized that these physiologic responses are modulated by changes in gene expression. We compared gene product levels in 20 natives of Cerro de Pasco (CP), (4338 m), 10 of which had chronic mountain sickness (CMS) established by a CMS-scoring system, with gene products in the same men after 1 h at sea level. We further compared the results with those obtained from 10 US men residing at 1500 m. We measured gene products in white cells by reverse transcription polymerase chain reaction (RT-PCR). We focused on genes important in vascular autonomic physiology, and/or activated by hypoxia; hypoxia inducible factor 1-alpha (HIF 1-alpha), 2 splicing variants of vascular endothelial growth factor (VEGF); VEGF-121, VEGF-165, and phosphoglycerate kinase 1 (PGK 1). Normal CP natives showed high expression of all genes in CP, compared to US controls. Within 1 h of arrival at sea level, they had comparable levels to US residents. In CMS, the gene products were higher in CP. Although gene products decreased in Lima in this group, they never reached US values. VEGF 121 and 165 were correlated (P<0.001). VEGF 165 was higher in CMS in CP (P=0.006), and was positively correlated with CMS-score (R=0.86, P<0.001), and negatively correlated with arterial saturation (R=-0.79, P<0.001). Our findings underscore the changes in gene expression levels in intact humans in response to environmental stress. These changes may support the physiologic alterations induced by the ambient hypoxia at altitude and impact organism survival. They also suggest therapeutic strategies for autonomic and neurodegenerative diseases at sea level.

Adaptation, Physiological↗

PubMed2006

Plasma catecholamines and blood volume in native Andeans during hypoxia and normoxia.

Plasma catechols and blood volume were measured in 20 male, native high-altitude residents of Cerro de Pasco, Peru (4338 m), while hypoxic and subsequently while normoxic at sea level. Ten subjects were healthy controls,with hematocrits lower than 61%, and ten had chronic mountain sickness (CMS), a syndrome of maladaptation to altitude, characterized by polycythemia (hematocrit > 61%), profound hypoxemia, and neurologic symptoms. The main aim of the study was to evaluate the chronic effects of hypoxia on plasma catechols and on blood volume, by studying these parameters during hypoxia at high altitude (HA) and shortly after exposure to normoxia at sea level (SL). Subjects were first studied at HA in their habitual hypoxic environment, and measurements were repeated within 4 hours of arrival at SL (Lima, Peru, 150 m). All subjects had higher plasma norepinephrine (NE), dopamine (DA), and dihydroxyphenylglycol (DHPG) levels in HA (NE in controls and CMS: 414+/-47 and 514+/-35 pg/mL; DA: 9+/-1 and 13+/-1 pg/mL, DHPG: 817+/-48 and 972+/-77 pg/mL) than at SL (NE: 164+/-9 and 243+/-28 pg/mL; DA: 4+/-0.5 and 5+/-1 pg/mL DHPG: 502+/-23 and 649+/-39 pg/mL). Group differences were statistically significant only for NE in the CMS group. Plasma volume was higher in HA in both groups (p<0.05); red cell volume was higher in HA only in the CMS group. The results indicate sympathetic nervous stimulation by chronic ambient hypoxia at altitude in Andean natives, independent of maladaptation to their native environment.

Adaptation, Physiological↗

PubMed2004

A brief exploration of neurological art history.

The invention of realistic portraiture to reveal "inner life" is attributed by some art historians to Jan van Eyck who worked in Flanders from 1420 onwards. We show, using clinical neurological examination of the gold mask of Agamemnon dating from 1550-1500 BC and of the portraits of Henry III and his son Edward I -- important English royals -- painted between 1216 and 1307, that realistic portraits were made well before the 15th Century. Thus artists unwittingly used neurology as part of their realistic approach to the presentation of the face. Because neurological diagnosis is often visual, neurology, in turn, has a rich potential to unveil examples of realism in art. We consider the art pieces examined here also pertinent to art historians, as they assess the role of art in documenting history.

Blepharoptosis↗

PubMed2003

Gene expression in the Andes; relevance to neurology at sea level.

Chronic mountain sickness (CMS), a maladaptation syndrome to chronic hypoxia, occurs in the Andes. Gene expression differences in Andeans could explain adaptation and maladaptation to hypoxia, both of which are relevant to neurology at sea level. Expression of genes responsive to cellular oxygen concentration, hypoxia-inducible factor-1alpha (HIF-1alpha), three splicing variants of vascular endothelial growth factor (VEGF) and von Hippel-Lindau protein (pVHL) was measured by reverse transcription polymerase chain reaction (RT-PCR) in 12 Cerro de Pasco (CP) (altitude 4338 m) natives and 15 CMS patients in CP. Thirteen high altitude natives living in Lima and five Lima natives were sea level controls. A CMS score (CMS-sc) was assigned clinically. Expression was related to the clinical assessment. High expression of HIF-1alpha and VEGF-121 was found in CMS (P<0.001). Samples from CP had higher expression than those from Lima (P<0.001). Expression of HIF-1alpha and VEGF-121 was related to age (P<0.001); adjusting for age did not abolish the group effect. Higher CMS-sc was related to expression independent of age (P<0.001). VEGF-165 and -189 were expressed only in CMS. Birth altitude had no effect on gene expression. pVHL was not quantifiable.HIF-1alpha and VEGF-121 participate in adaptation to hypoxia. The high levels may explain blood vessel proliferation in Andeans and hold lessons for patients at sea level. VEGF-165 expression suggests that it contributes to preservation of neuronal function in human chronic hypoxia. VHL mutations may mark those destined to develop neural crest tumors which are common in the Andes.

Adult↗

PubMed2002

An ancient eye.

Explore the source record for details and available documents.

Adolescent↗

PubMed2002

System times and time horizons for biospheric near-matches of primarily non-photic environmental cycles.

System time is defined as the duration (T) and sampling density (deltat) of a given study. A time horizon is obtained by combining analytical results on endpoints of time structures (chronomes), usually on control groups, from accumulating diverse studies carried out with drastically different values of T and deltat. These two design considerations depend upon and are limited by resources. The desideratum of a small At e.g., for studies of chaotic endpoints, limits T, e.g., has thus far precluded a continuous mapping of decadal cycles in endpoints such as the approximate entropy or the correlation dimension. Time horizons are being documented for an increasing number of variables that undergo cycles with infra-annual frequencies - with one cycle in about one, two and/or five decades - in the biosphere as in the environment. These infra-annuals, in and around us, modulate ultra-annuals, including circadians, as well as about 7-day (circaseptan) and about half-yearly (circasemiannual) cycles, all prominent, e.g., in geophysical and biospheric specta. Neglect of infra-annual chronomics can lead to blunders. A statistically highly significant decrease in the excretion of steroidal metabolites (or in heart rate variability) may be misinterpreted as premature aging if it lasts for several years, and may be unnecessarily acted upon, e.g., by drugs. The decrease, however, may only be transient, occurring only during a given stage of a circadecadal cycle, and it may be followed for the next several years by an also spurious "rejuvenation", possibly misinterpreted as a drug effect. When recognized as the alternating stages of decadal cycles and assessed with an affordable deltat, infra-annuals of variables involved in major problems of our day, including homicides and wars, may lead us to manipulable internal or external mechanisms, and thus, eventually, possibly to countermeasures to crime and terror as well as to the optimization of aims such as spirituality.

Circadian Rhythm↗

PubMed2002

Biological rhythms and behavior--then and now.

BACKGROUND: Living matter has its own 'biological time': a set of rhythmic oscillations, paced by genes whose expression varies over regular cycles. The resulting chronomes, or time structures, are usually studied in living matter. A human chronome is preserved long after death in the structure of tooth enamel. This fossil record can be compared with contemporary enamel thus providing insight into an ancient biological rhythm, and consequently into behavior in pre-historic civilizations. MATERIAL/METHODS: Eight adult 3rd molar teeth from human burials in Atacama oases of Northern Chile, dating from AD 400 to 900 and belonging to the pre-Hispanic San Pedro culture, were compared to 20 discarded contemporaneous teeth from Albuquerque, N. M. USA. Two adjacent, 100 mm thick ground sections from each tooth were examined using a stereoscopic dissecting microscope and polarized light. The intervals between consecutive brown striae of Retzius (TBS) and the width of the enamel were measured. We recorded the number of TBS and the number of Wilson's bands and calculated a ratio of enamel width/number of TBS for each section. We used ANOVA for statistical analysis and cosinor methodology for chronomics, time structure (chronome) mapping. RESULTS: The 'biological week' in the chronome (time structure) of ancient enamel, gauged by TBS, varied according to a multiseptan (multiple of seven) component faster than did the multiseptan of contemporaneous teeth (1/2.7 versus 1/4.6 biological weeks). CONCLUSIONS: Until now no human chronome has been isolated from fossilized structures. Our discovery indicates that behavior of ancient populations, such as rest and work spans, can be deduced to some extent after millennia.

Behavior↗