Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice.

During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1ß, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1ß concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1ß, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1ß and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1ß, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.

Hypoventilation does not explain the impaired quality of sleep in postpolio patients ventilated noninvasively vs. invasively.

In a previous study, it was found that patients treated with noninvasive ventilation (NIV) reported larger dysfunctions in sleep-related parameters as assessed with the Sickness Impact Profile (SIP) and Health Index questionnaires than those treated with tracheostomy. The aim of the current study was to further evaluate these sleep limitations and relate these limitations to blood gas analyses in the groups to investigate, if the differences could be related to differences in the efficacy of ventilation. We compared postpolio patients treated with tracheostomy (PPT, n = 17), NIV (PPN, n = 14) and patients with neuromuscular disorders treated with NIV (NMN, n = 15). Significantly fewer patients in the PPT group scored large dysfunctions in the SIP sleep (SIP score >10 points) compared with the PPN and NMN patients. The PPT patients scored significantly higher regarding quality of sleep and less sense of tiredness than the PPN and NMN patients. No differences were found between the groups regarding blood gas parameters neither before nor during or after the study period. In conclusion, postpolio patients treated with invasive home mechanical ventilation seem to experience better sleep and less sense of tiredness than patients on NIV. These differences cannot be explained by differences in alveolar ventilation as assessed with blood gas analyses.

Prolonged exposure to inhaled nitric oxide does not affect haemostasis in piglets.

OBJECTIVE: To examine possible adverse effects on haemostasis from prolonged exposure to inhaled nitric oxide (iNO). DESIGN AND SETTING: Blinded, randomised, experimental animal study in a university animal laboratory. INTERVENTIONS: Anaesthetised and intubated piglets received central venous, arterial, and transabdominal urinary catheters. Twelve piglets were studied with triggered pressure support ventilation breathing with an air-oxygen mixture for 30 h with nitric oxide (NO), 40 parts per million (ppm) (n = 6) or without NO gas (n = 6) added. The tests of platelet function were assessed in a separate 1-h experiment in which 12 additional animals were blindly randomised to receive intravenous acetylsalicylic acid (ASA) (n = 7) or placebo (n = 5). MEASUREMENTS AND RESULTS: All 12 animals were clinically stable during the study period of 30 h. Haemostasis was assessed in terms of bleeding time and platelet function by Adeplat-S, reflecting platelet adhesion. Prothrombin fragment 1 + 2, fibrin D-dimer, tissue plasminogen activator and prothrombin complex were measured to investigate whether inhaled NO (iNO) had any effects on thrombin formation, fibrin formation, fibrinolysis or coagulation. All parameters including bleeding time and Adeplat-S were unaffected by iNO. ASA significantly increased bleeding time, but did not affect Adeplat-S. Nitrate in plasma and NOx (nitrate and nitrite) in urine increased significantly in pigs receiving iNO compared with controls. CONCLUSIONS: Prolonged exposure to iNO at 40[Symbol: see text]ppm did not affect bleeding time or coagulation parameters in healthy piglets. The findings do not support the hypothesis that iNO increases the risk of bleeding in humans.

Neuraxial opioids as analgesia in labour, caesarean section and hysterectomy: A questionnaire survey in Sweden.

Background: Neuraxial opioids improve labour analgesia and analgesia after caesarean section (CS) and hysterectomy. Undesirable side effects and difficulties in arranging postoperative monitoring might influence the use of these opioids. The aim of the present survey was to assess the use of intrathecal and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A questionnaire was sent to 47 anaesthesiologists at obstetric units in Sweden concerning the use and postoperative monitoring of morphine, sufentanil and fentanyl in spinal/epidural anaesthesia. Results: A total of 32 units responded representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units use intrathecal morphine, the most common dose of which was 100 µg (17/21). Intrathecal fentanyl (10-20 µg) was used by 21 units and sufentanil (2.5 -10 µg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural fentanyl (50-100 µg) or sufentanil (5-25 µg) were commonly used (25/32), and 12/32 clinics used epidural morphine, the majority of units used a 2 mg dose. Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 µg as the most common dose (9/32). Postoperative monitoring was organized in adherence to the National Guidelines; the patient is in postoperative care or an obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward. Risk of respiratory depression/difficult to monitor was a reason for not using intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in CS and hysterectomy, but is still restricted in some units because of the concern for respiratory depression and difficulties in monitoring.