Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension

Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc

Theoretical evaluations of therapeutic systemic and local cerebral hypothermia

Purpose: To simulate cerebral temperature behaviour with hypothermia treatment applying different cooling devices and to find the optimal brain temperature monitoring. Methods: Models based on hourly temperature values recorded in patients with severe aneurysmal subarachnoid hemorrhage, taking MRI data, thermal conductive properties, metabolism and blood flow into account were applied to different scenarios of hypothermia. Results: Systemic hypothermia by endovascular cooling leads to an uniform temperature decrease within the brain tissue. Cooling with head caps lead to 33 ◦C only in the superficial brain while the deep brain remains higher than 36 ◦C. Cooling with neckbands lead to 35.8 ◦C for dry and 32.8 ◦C for wet skin in the deep brain. Conclusions: With head caps temperatures below36 ◦C cannot be reached in the deep brain tissue, whereas neckbands, covering the carotid triangles, may lead to hypothermic temperatures in the deep brain tissue. Temperature sensors have to be applied at least 2cm below the cortical surface to give values representative for deep brain tissue

Treatment of resistant fever: New method of local cerebral cooling

BACKGROUND: Fever in neurocritical care patients is common and has a negative impact on neurological outcome. The purpose of this prospective observational study was (1) to evaluate the practicability of cooling with newly developed neck pads in the daily setting of neurointensive care unit (NICU) patients and (2) to evaluate its effectiveness as a surrogate endpoint to indicate the feasibility of neck cooling as a new method for intractable fever. METHODS: Nine patients with ten episodes of intractable fever and aneurysmal subarachnoid hemorrhage were treated with one of two different shapes of specifically adapted cooling neck pads. Temperature values of the brain, blood, and urinary bladder were taken close meshed after application of the cooling neck pads up to hour 8. RESULTS: The brain, blood, and urinary bladder temperatures decreased significantly from hour 0 to a minimum in hour 5 (P < 0.01). After hour 5, instead of continuous cooling in all the patients, the temperature of all the three sites remounted. CONCLUSION: This study showed the practicability of local cooling for intractable fever using the newly developed neck pads in the daily setting of NICU patients