Spreading of complex regional pain syndrome: not a random process

Complex regional pain syndrome (CRPS) generally remains restricted to one limb but occasionally may spread to other limbs. Knowledge of the spreading pattern of CRPS may lead to hypotheses about underlying mechanisms but to date little is known about this process. The objective is to study patterns of spread of CRPS from a first to a second limb and the factors associated with this process. One hundred and eighty-five CRPS patients were retrospectively evaluated. Cox’s proportional hazards model was used to evaluate factors that influenced spread of CRPS symptoms. Eighty-nine patients exhibited CRPS in multiple limbs. In 72 patients spread from a first to a second limb occurred showing a contralateral pattern in 49%, ipsilateral pattern in 30% and diagonal pattern in 14%. A trauma preceded the onset in the second limb in 37, 44 and 91%, respectively. The hazard of spread of CRPS increased with the number of limbs affected. Compared to patients with CRPS in one limb, patients with CRPS in multiple limbs were on average 7 years younger and more often had movement disorders. In patients with CRPS in multiple limbs, spontaneous spread of symptoms generally follows a contralateral or ipsilateral pattern whereas diagonal spread is rare and generally preceded by a new trauma. Spread is associated with a younger age at onset and a more severely affected phenotype. We argue that processes in the spinal cord as well as supraspinal changes are responsible for spontaneous spread in CRPS

Anhydrobiosis and Freezing-Tolerance:Adaptations That Facilitate the Establishment of Panagrolaimus Nematodes in Polar Habitats

<div><p>Anhydrobiotic animals can survive the loss of both free and bound water from their cells. While in this state they are also resistant to freezing. This physiology adapts anhydrobiotes to harsh environments and it aids their dispersal. <i>Panagrolaimus davidi</i>, a bacterial feeding anhydrobiotic nematode isolated from Ross Island Antarctica, can survive intracellular ice formation when fully hydrated. A capacity to survive freezing while fully hydrated has also been observed in some other Antarctic nematodes. We experimentally determined the anhydrobiotic and freezing-tolerance phenotypes of 24 <i>Panagrolaimus</i> strains from tropical, temperate, continental and polar habitats and we analysed their phylogenetic relationships. We found that several other <i>Panagrolaimus</i> isolates can also survive freezing when fully hydrated and that tissue extracts from these freezing-tolerant nematodes can inhibit the growth of ice crystals. We show that <i>P. davidi</i> belongs to a clade of anhydrobiotic and freezing-tolerant panagrolaimids containing strains from temperate and continental regions and that <i>P. superbus</i>, an early colonizer at Surtsey island, Iceland after its volcanic formation, is closely related to a species from Pennsylvania, USA. Ancestral state reconstructions show that anhydrobiosis evolved deep in the phylogeny of <i>Panagrolaimus</i>. The early-diverging <i>Panagrolaimus</i> lineages are strongly anhydrobiotic but weakly freezing-tolerant, suggesting that freezing tolerance is most likely a derived trait. The common ancestors of the <i>davidi</i> and the <i>superbus</i> clades were anhydrobiotic and also possessed robust freezing tolerance, along with a capacity to inhibit the growth and recrystallization of ice crystals. Unlike other endemic Antarctic nematodes, the life history traits of <i>P. davidi</i> do not show evidence of an evolved response to polar conditions. Thus we suggest that the colonization of Antarctica by <i>P. davidi</i> and of Surtsey by <i>P. superbus</i> may be examples of recent “ecological fitting” of freezing-tolerant anhydrobiotic propagules to the respective abiotic conditions in Ross Island and Surtsey.</p></div

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Endothelial and transendothelial delivery of pharmaceutically active agents; potential of liposomes

The architecture of the liver constitutes a favorable condition for cell-specific delivery of drugs by means of targeted delivery systems due to the presence of a fenestrated endothelium. This allows access of particulate drug carriers such as liposomes to not only the sinusoidally located Kupffer cells and the endothelial cells but also to the trans-endothelial hepatocytes and stellate cells.Relatively small liposomes are known to accumulate in hepatocytes to much larger extents than larger ones. However, we found that even substantial amounts of relatively large liposomes can be taken up by hepatocytes after i.v, administration, provided they have the proper lipid composition, i.e. containing the negatively charged phospholipid phosphatidylserine (PS) and consisting of fluid-phase lipids. Liposomes containing phosphatidylglycerol (PG) as a negatively charged constituent or PS-containing liposomes consisting of rigid bilayer lipids were shown not to gain access to the hepatocytes. We propose that the mechanism responsible for this transendothelial passage of large fluid-type liposomes involves a PS-specific transient interaction with the endothelial cells followed by a forced squeezing of the fluid liposomes through the fenestrations, possibly mediated by an endothelial cell-surface-located scavenger receptor. An alternative explanation, involving a pharmacological widening effect of the PS on the fenestrations, could be discarded on the basis of experiments in which radiolabeled PG liposomes and nonlabeled PS liposomes were simultaneously injected: under those conditions still no uptake of large PG liposomes by hepatocytes was observed.The endothelial scavenger receptor is able to recognize and internalize PS liposomes in vitro but not in vivo, due to the masking effect of liposome-adsorbed plasma proteins.</p