Lupus - the cold, hard facts.

Systemic lupus erythematosus (SLE) is a multisystem chronic disease with a multitude of clinical presentations. We review and synthesize how an environmental insult (exposure to extreme cold for a short duration) and endogenous (antiphospholipid antibody syndrome, SLE vasculitis) insults in a susceptible young female with lupus (peripheral arterial disease, smoking, SLE) led to a perfect storm resulting in catastrophic injuries (frostbite).

Differences in the control of breathing between Himalayan and sea-level residents.

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 CO(2) 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 CO(2) induced by hypoxia in lowlanders was absent in highlanders (P = 0.361). Furthermore, the ventilatory recruitment threshold (VRT) CO(2) 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 CO(2). Their response to hypoxia was heterogeneous, with the majority decreasing their VRT indicating either a CO(2)-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 CO(2), while in others VRT remained unchanged and their sub-threshold ventilations increased, although these were not statistically significant.

BOLD signal responses to controlled hypercapnia in human spinal cord.

Functional MRI of the spinal cord is challenging due to the small cross section of the cord and high level of physiological noise. Though blood oxygenation level-dependent (BOLD) contrast has been used to study specific responses of the spinal cord to various stimuli, it has not been demonstrated using a controlled stimulus. In this paper, we use hypercapnic manipulation to study the sensitivity and specificity of functional MRI in the human cervical spinal cord. Simultaneous MR imaging in the brain and spinal cord was performed for direct comparison with the brain, in which responses to hypercapnia have been more extensively characterized. Original contributions include: (i) prospectively controlled hypercapnic changes in end-tidal PCO(2), (ii) simultaneous recording of BOLD responses in the brain and spinal cord, and (iii) generation of statistical maps of BOLD responses throughout the brain and spinal cord, taking into account physiological noise sources. Results showed significant responses in all subjects both in the brain and the spinal cord. In anatomically-defined regions of interest, mean percent changes were 0.6% in the spinal cord and 1% in the brain. Analysis of residual variance demonstrated significantly larger contribution of physiological noise in the spinal cord (P<0.005). To obtain more reliable results from fMRI in the spinal cord, it will be necessary to improve sensitivity through the use of highly parallelized coil arrays and better modeling of physiological noise. Finely, we believe that the use of controlled global stimuli, such as hypercapnia, will help assess the effectiveness of new acquisition techniques.