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Dante places the sinners who promoted scandals, schism, and discord in the ninth Ditch of the Inferno. Among those is also the Prophet Muhammad. Describing the Prophet's punishment, Dante resorts to technical terms and vulgar expressions. This poetic representation highlights Dante's medical and anatomical knowledge and reflects 14th c. Christian religious beliefs. At that time, autopsies were performed only on prisoners, prostitutes and people without identity. By comparing the Prophet to an autopsied corpse, Dante associates Muhammad with those bearing the badge of shame. Moreover, this description is a further confirmation that Dante had good medical knowledge. [ABSTRACT FROM AUTHOR]

Background: The upright posture imposes a significant challenge to blood pressure regulation that is compensated through baroreflex-mediated increases in heart rate and vascular resistance. Orthostatic cardiac responses are easily inferred from heart rate, but vascular resistance responses are harder to elucidate. One approach is to determine vascular resistance as arterial pressure/blood flow, where blood flow is inferred from ultrasound-based measurements of brachial blood velocity. This relies on the as yet unvalidated assumption that brachial artery diameter does not change during orthostatic stress, and so velocity is proportional to flow. It is also unknown whether the orthostatic vascular resistance response is related to initial blood vessel diameter. Methods: We determined beat-to-beat heart rate (ECG), blood pressure (Portapres) and vascular resistance (Doppler ultrasound) during a combined orthostatic stress test (head-upright tilting and lower body negative pressure) continued until presyncope. Participants were 16 men (aged 38.4±2.3 years) who lived permanently at high altitude (4450m). Results: The supine brachial diameter ranged from 2.9–5.6mm. Brachial diameter did not change during orthostatic stress (supine: 4.19±0.2mm; tilt: 4.20±0.2mm; -20mmHg lower body negative pressure: 4.19±0.2mm, p = 0.811). There was no significant correlation between supine brachial artery diameter and the maximum vascular resistance response (r = 0.323; p = 0.29). Forearm vascular resistance responses evaluated using brachial arterial flow and velocity were strongly correlated (r = 0.989, p<0.00001) and demonstrated high equivalency with minimal bias (-6.34±24.4%). Discussion: During severe orthostatic stress the diameter of the brachial artery remains constant, supporting use of brachial velocity for accurate continuous non-invasive orthostatic vascular resistance responses. The magnitude of the orthostatic forearm vascular resistance response was unrelated to the baseline brachial arterial diameter, suggesting that upstream vessel size does not matter in the ability to mount a vasoconstrictor response to orthostasis. [ABSTRACT FROM AUTHOR]

A1AT deficiency- a genetically inherited autosomal codominant disease with more than 120 identified alleles- was first identified by Laurell and Eriksson in 1963. The most common hereditary disorder in adults, A1AT causes an increased risk of developing pulmonary emphysema and liver disease. In A1AT patients, lung disease generally presents at a younger age than “usual” chronic obstructive pulmonary disease (COPD) and it may be misdiagnosed as asthma. Because A1AT deficiency patients can show the same clinical features as non-deficient COPD (including increased evidence of bronchiectasis, frequent exacerbations, impaired health status and a degree of reversibility of airflow obstruction), the World Health Organization recommend to test every patient with a diagnosis of COPD or adult-onset asthma for A1AT deficiency. Despite these recommendations, the epidemiology of A1AT deficiency remains uncertain. Although recently discovered A1AT deficiency has affected human populations since antiquity. By using scientific data and recently studied skeletons and historical cases, we show that it is now possible to reconstruct the natural history of pathological processes, whether due to genetic, infectious or environmental factors. We believe that the evolution of disease in patients and research to elucidate the relationship between social science and environmental are pertinent contemporaneous subjects. [ABSTRACT FROM AUTHOR]

We compared the control of breathing of 12 male Himalayan highlanders with that of 21 male sea-level Caucasian lowlanders using isoxic hyperoxic ( = 150 mmHg) and hypoxic ( = 50 mmHg) Duffin's rebreathing tests. Highlanders had lower mean ±s.e.m. ventilatory sensitivities to CO2 than lowlanders at both isoxic tensions (hyperoxic: 2.3 ± 0.3 vs. 4.2 ± 0.3 l min−1 mmHg−1, P= 0.021; hypoxic: 2.8 ± 0.3 vs. 7.1 ± 0.6 l min−1 mmHg−1, P < 0.001), and the usual increase in ventilatory sensitivity to CO2 induced by hypoxia in lowlanders was absent in highlanders ( P= 0.361). Furthermore, the ventilatory recruitment threshold (VRT) CO2 tensions in highlanders were lower than in lowlanders (hyperoxic: 33.8 ± 0.9 vs. 48.9 ± 0.7 mmHg, P < 0.001; hypoxic: 31.2 ± 1.1 vs. 44.7 ± 0.7 mmHg, P < 0.001). Both groups had reduced ventilatory recruitment thresholds with hypoxia ( P < 0.001) and there were no differences in the sub-threshold ventilations (non-chemoreflex drives to breathe) between lowlanders and highlanders at both isoxic tensions ( P= 0.982), with a trend for higher basal ventilation during hypoxia ( P= 0.052). We conclude that control of breathing in Himalayan highlanders is distinctly different from that of sea-level lowlanders. Specifically, Himalayan highlanders have decreased central and absent peripheral sensitivities to CO2. Their response to hypoxia was heterogeneous, with the majority decreasing their VRT indicating either a CO2-independent increase in activity of peripheral chemoreceptor or hypoxia-induced increase in [H+] at the central chemoreceptor. In some highlanders, the decrease in VRT was accompanied by an increase in sensitivity to CO2, while in others VRT remained unchanged and their sub-threshold ventilations increased, although these were not statistically significant. [ABSTRACT FROM AUTHOR]

Cerebral blood flow is known to increase in response to hypoxia and to decrease with hypocapnia. It is not known, however, whether these responses are altered in high-altitude dwellers who are not only chronically hypoxic and hypocapnic, but also polycythaemic. Here we examined cerebral blood flow responses to hypoxia and hypocapnia, separately and together, in Andean high-altitude dwellers, including some with chronic mountain sickness (CMS), which is characterized by excessive polycythaemia. Studies were carried out at high altitude (Cerro de Pasco (CP), Peru; barometric pressure ( PB) 450 mmHg) and repeated, following relief of the hypoxia, on the day following arrival at sea level (Lima, Peru; PB 755 mmHg). We compared these results with those from eight sea-level residents studied at sea level. In nine high-altitude normal subjects (HA) and nine CMS patients, we recorded middle cerebral artery mean blood flow velocity (MCAVm) using transcranial Doppler ultrasonography, and expressed responses as changes from baseline. MCAVm responses to hypoxia were determined by changing end-tidal partial pressure of oxygen ( PET,O2) from 100 to 50 mmHg, with end-tidal partial pressure of carbon dioxide clamped. MCAVm responses to hypocapnia were studied by voluntary hyperventilation with ( PET,O2) clamped at 100 and 50 mmHg. There were no significant differences between the cerebrovascular responses of the two groups to any of the interventions at either location. In both groups, the MCAVm responses to hypoxia were significantly greater at Lima than at CP (HA, 12.1 ± 1.3 and 6.1 ± 1.0%; CMS, 12.5 ± 0.8 and 5.6 ± 1.2%; P < 0.01 both groups). The responses at Lima were similar to those in the sea-level subjects (13.6 ± 2.3%). The responses to normoxic hypocapnia in the altitude subjects were also similar at both locations and greater than those in sea-level residents. During hypoxia, both high-altitude groups showed responses to hypocapnia that were significantly smaller at Lima than at CP (HA, 2.17 ± 0.23 and 3.29 ± 0.34% mmHg−1, P < 0.05; CMS, 1.87 ± 0.16 and 3.23 ± 0.24% mmHg−1; P < 0.01). The similarity of the results from the two groups of altitude dwellers suggests that haematocrit is unlikely to greatly affect cerebrovascular reactivity to hypoxia and hypocapnia. The smaller vasodilatation to hypoxia and larger vasoconstriction to hypoxic hypocapnia at high altitude suggest that cerebrovascular responses may be impaired at the high altitude, i.e. a maladaptation. The changes in the responses within less than 24 h at sea level indicate that this impairment is rapidly reversible. [ABSTRACT FROM AUTHOR]

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... [ABSTRACT FROM AUTHOR]

Orthostatic tolerance is a measure of the ability to prevent hypotension during gravitational stress. It is known to be dependent on the degree of vasoconstriction and the magnitude of plasma volume, but the possible influence of packed cell volume (PCV) is unknown. High altitude residents have high haematocrits and probably high packed cell volumes. However, it is not known whether plasma volume and blood volume are affected, or whether their orthostatic tolerance is different from low altitude residents. In this study we determined plasma volume, PCV and orthostatic tolerance in a group of high altitude dwellers (HA), including a subgroup of highland dwellers with chronic mountain sickness (CMS) and extreme polycythaemia. Plasma volume and PCV were determined using Evans Blue dye dilution and peripheral haematocrit. Orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilting and lower body suction. All studies were performed at 4338 m. Results showed that plasma volumes were not significantly different between CMS and HA, or in highland dwellers compared to those seen previously in lowlanders. PCV and haematocrit were greater in CMS than in HA. Orthostatic tolerance was high in both CMS and HA, although the heart rate responses to orthostasis were smaller in CMS than HA. Orthostatic tolerance was correlated with haematocrit (r = 0.57, P < 0.01) and PCV (r = 0.54, P < 0.01). This investigation has shown that although high altitude residents have large PCV, their plasma volumes were similar to lowland dwellers. The group with CMS have a particularly large PCV and also have a very high orthostatic tolerance, despite smaller heart rate responses. These results are compatible with the view that PCV is of importance in determining orthostatic tolerance. [ABSTRACT FROM AUTHOR]

Background: Clinical paleoneurology is almost non-existent, but recognition of neurological diseases in ancient people might be possible by scrutinising portraits apparently representing people as they appeared in life.Methods: About 200 mummy portraits painted in colour at the beginning of the first millennium were examined. Thirty two skulls excavated at Hawara in the Fayum (northern Egypt), where most of the portraits were found were measured, and nine caliper measures on each side of the skulls were taken. The right/left ratios were statistically analyzed by analysis of variance (ANOVA). One skull was subjected to 3D CT scanning and transilluminated.Results: Two patients were found with progressive facial hemiatrophy (Parry-Romberg syndrome), three with deviations of the visual axes (tropia) and one with oval pupils (corectopia).Conclusions: Clinical paleoneurology is possible in the absence of a living nervous system. The patients probably had focal epilepsy, hemiplegic migraine, and autonomic nervous system dysfunction. [ABSTRACT FROM AUTHOR]

Aim Interval hypoxic training was proposed as a technique for adapting hypoxia of various origins. Its effects on the hypoxic ventilatory response and on cardiovascular autonomic control are unknown.Methods and Results We recorded ventilation, end-tidal oxygen (PETO2) and carbon dioxide partial pressures, RR interval and blood pressure during progressive isocapnic hypoxia, before and after 14 days of: (a) interval hypoxic training (three to four periods of 7min progressive hypoxia in 1h, each day) in 12 healthy men (training group); (b) breathing into a spirometer by six age-matched male controls. The hypoxic ventilatory response was estimated by the hyperbolic relationship between PETO2and ventilation (shape factor A). Spectral analysis was used to characterize low- (mainly sympathetic) and high-frequency (vagal) cardiovascular fluctuations. Shape factor A was increased in the interval hypoxic training group from 268±59 to 984±196 l.mmHg−1(P<0·003), but not in the control group (from 525±180 to 808±245 l.mmHg−1,P =ns). Before interval hypoxic training, progressive hypoxia decreased, to a similar extent in both groups, mean RR, RR variability and high-frequency power. After interval hypoxic training, RR still decreased significantly, but the decrease in RR variability and high-frequency power was no longer significant in the training group. No significant changes were observed in blood pressure fluctuations. No changes were observed in the control group.Conclusions Two weeks of interval hypoxic training increased the hypoxic ventilatory response, in association with reduced vagal withdrawal during progressive hypoxia. [ABSTRACT FROM PUBLISHER]

Objective: To characterise the clinical features and nerve biopsy findings in patients with chronic mountain sickness (CMS) living in the Peruvian Andes, with particular attention to the occurrence of the "burning feet-burning hands" syndrome.Methods: Symptoms and signs were documented clinically in 10 patients with CMS and compared with those in five healthy subjects all living at 4338 metres altitude. Sural nerve biopsies were obtained from three patients with CMS. The nerve fibre population and endoneurial microvessels were analyzed morphometrically.Results: All patients with CMS experienced burning and tingling paraesthesiae in the distal parts of their limbs. Similar but milder symptoms confined to the feet occurred in four of five controls. Three patients with CMS had a mild sensory neuropathy on examination, controls were clinically normal. Nerve biopsies showed a mild demyelinating neuropathy in all three with a reduction in the unmyelinated axon population in one. The endoneurial blood vessels showed a reduced thickness in the basal laminal zone compared with control values but were otherwise normal.Conclusions: Apart from well recognised symptoms and signs of CMS, the study has shown that such patients may also exhibit a mild sensory neuropathy. Its relation to the burning feet-burning hands syndrome, which was not confined to the patients but was also found in controls at altitude, is uncertain. The time course and pattern of the centrifugal resolution of the burning paraesthesiae complex on low altitude sojourn of high altitude natives raises the possibility that a mechanism involving altered axonal transport may be involved. The reduced thickness of the basal laminal zone of microvessels implies that adaptive structural changes to hypobaric hypoxia may also occur in peripheral nerve and are similar to those reported in other tissues of high altitude natives. [ABSTRACT FROM AUTHOR]

We found sustained activation of the proto-oncogene c-fos in neurons of the medial and dorsal neostriatum and suppression of this activation in NO-synthase (NOS) -containing cells within the islands of Calleja after unilateral lesions of the dopaminergic mesostriatal system induced by 6-hydroxydopamine (6-OHDA). Systemic administration of nitroglycerin (NTG) resulted in a decreased expression of c-Fos protein in the dorsal part of the denervated neostriatum: respective numbers of Fos-positive neuronal nuclei were 420.71 ± 21.32 in control and 141.38 ± 11.48 after NTG injection (the mean numbers in 50-μm-thick slices). However, other brain structures, NTG evoked sustained expression of c-Fos protein in the groups of NOS-containing neurons and sources of catecholaminergic projections involved In the control of cardiovascular reactions. We hypothesize that systemic administration of an NO donor and a potent vasodilator, NTG, partially normalized an excessively Increased glutamate level in the denervated neostriatum manifested in c-Fos protein expression. [ABSTRACT FROM AUTHOR]

We studied rats with a hemi-Parkinsonian model created by lesions of mesostriatal dopaminergic neurons. Correlation between the extent of lesions and intensity of forced rotation movements (apomorphine (APO)-induced rotations, i.e., exercise) was investigated. The levels of endothelins (ET) in the circulation after rotation under normoxic and hypoxic conditions were measured. In normoxia, the rotation sessions were associated with significant decreases in circulating ET levels, from 21.32±4.06 to 9.32±1.08 pg/ml. Although hypoxia had no effect on the frequency of rotations induced by APO, it significantly attenuated a decrease in the ET levels in the circulation of rats with the most extensive lesions. We suggest that the mesostriatal dopaminergic system modulates endothelial function by an active process. This may have relevance for some clinical manifestations of disordered striatal function observed in humans. [ABSTRACT FROM AUTHOR]

White rami communicantes were studied quantitatively in patients with chronic alcoholism or diabetes mellitus. The fascicular area of interganglionic segments of the paravertebral sympathetic chain showed less variation than that previously reported for controls. Fibre densities were higher in the patients than in controls of similar age and the percentage of small fibres in alcoholics and diabetics is larger than in controls. Only 17% of fibres were larger than 5 μm in diameter in the patients, whereas, in controls, 33% of fibres were larger than 5 μm in diameter. No correlation between internodal lengths and fibre diameter was found in the patients who showed uniformly short internodes averaging only about half of internodal distances found in control subjects. The uniformly short internodes are attributed to complete degeneration followed by partial regeneration and are compatible with either Wallerian degeneration or a `dying back' phenomenon. The short internodal lengths should be reflected in slowed conduction velocities in white rami communicantes and could account for abnormalities in baroreflex activity, sweating, and in visceral dysfunction commonly seen in patients with chronic alcoholism or diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS--11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES--24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS--All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS--These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress. [ABSTRACT FROM PUBLISHER]

Myelinated fibres in the human sympathetic paravertebral chain were examined histologically and in single teased fibre preparations in various age groups in subjects dying from disorders not affecting primarily the autonomic nervous system. An increase in fibre density predominantly due to an increase in the number of small fibres was found in older subjects. A correlation between internodal length and fibre diameter was found but the internodes of sympathetic myelinated fibres are shorter for any given diameter than those found on fibres of comparable size in the sural nerve. A reduction in internodal lengths with advancing years was demonstrated. These observations are interpreted to show that Wallerian degeneration and segmental demyelination occur with increasing frequency in old age and that regeneration does not keep pace with successive degenerative events. The deterioration in function of the autonomic nervous system with advancing years may be attributed in part to the changes found in myelinated fibres in the paravertebral sympathetic chain. [ABSTRACT FROM AUTHOR]

Autonomic functions were studied in three patients with hydrencephalus and five with hydrocephalus. Autonomic failure of central origin was found in the patients with hydrencephalus; whereas, those suffering from hydrocephalus had essentially normal autonomic function. In two patients with hydrencephalus, the hypothalamus was markedly abnormal but the rest of the autonomic nervous system was histologically normal. From this it is concluded that in some patients with mental and motor retardation, autonomic failure may be of cerebral origin but that this is not a feature of patients with hydrocephalus. [ABSTRACT FROM AUTHOR]

Films are useful for medical education and introduce Science fiction movies or historic documentaries and pioneering scientists who developed the field of infectious disease research. Between the late nineteenth and early twentieth centuries, expert talents such as von Behring, Koch, and Ehrlich were present at the Charité Hospital. These individuals contributed significantly to the scientific study of infections, their prevention, treatment, and social impact. Here, we compare the relative impact of infectious disease research centers during the study period (late nineteenth and early twentieth centuries) by assuming that the number of publications listed on Wikipedia about the individual scientists working in London, Paris, and Berlin is Poisson distributed. We show that using reference counts that appear after individuals’ names on Wikipedia is a useful tool to assess the impact of centers of excellence in the study of infectious diseases. However, the accumulation of talent in Berlin during a relatively short period, even though historically the protagonists did not interact or support each other, lead to greater advances in the treatment and prevention of infections in humans than the work of individuals such as Pasteur in Paris or Lister in London. [ABSTRACT FROM AUTHOR]

Discusses the pattern of systemic lupus erythematosus, and its involvement of the central nervous system. Pathogenesis of the disease; Prevention; Significance of antineuronal antibody in lupus erythematosus.

In animal models and humans, chronic intermittent hypoxia increases subclinical atherosclerosis. High animal fat diets and hypertension are also risk factors for arterial disease. Noninvasive ultrasound permits measurements of intima-media thickness (IMT) in the human carotid artery. This measure is a surrogate for subclinical atherosclerosis. We measured common carotid artery IMT in 96 (20 female) geographically, perhaps genetically, isolated native highlanders from Korzok, India (4550 m). This population has a high animal fat consumption and a high prevalence of hypertension. They also have normal BMIs and high daily aerobic work loads. Data are mean (SD): The linear regression equation relating age to IMT was IMT = 0.006(Age) + 0.24 (r=0.74, p<0.05). Age matched mean IMT values of controls from industrialized countries in normobaria ranged from 0.60-1.10 mm with slopes of 0.009-0.016 and intercepts from 0.12-0.19. This field study suggests that compared to industrialized, normobaric populations, IMT is attenuated in Ladakh highlanders. This reduction occurs in spite of risk factors which increase IMT at sea level, and may be related to their aerobic load and genetics. Our findings are consistent with the low prevalence of cardiovascular diseases in this cohort. [ABSTRACT FROM AUTHOR]