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-1β, 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)-1β 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-1β, 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-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, 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.

Background-Antibodies to endothelial cells (aECs) and to cardiolipin (aCLs) are implicated in autoimmune diseases like systemic lupus erythematosus vasculitis. ␤ 2 -Glycoprotein 1 (␤2GP1) is a cofactor for aCLs. The present study investigated the possible role of aECs, aCLs, and a␤2GP1 in borderline hypertension. Methods and Results-Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure, 85 to 94 and Ͻ80 mm Hg, respectively) were recruited from a population screening program. Antibody levels were determined by ELISA. Presence of carotid atherosclerosis was determined by B-mode ultrasonography, and 29 individuals had atherosclerotic plaques. BHT men had significantly higher aEC and a␤2GP1 levels of IgG class than NT control subjects (Pϭ0.029 and Pϭ0.0001, respectively). aEC levels of IgM class were higher in BHT (Pϭ0.012), but not a␤2GP1 levels. There was no correlation between aCL levels and BHT. Individuals with atherosclerotic plaques had significantly higher aEC levels of both IgG (Pϭ0.042) and IgM subclasses (Pϭ0.018) than those without plaques, but no difference was found in aCL and a␤2GP1 levels. Endothelin and aECs of IgM class were significantly associated. Conclusions-We demonstrate the first evidence of a significant elevation of aEC and a␤2GP1 levels in borderline hypertension. These findings provide a new link between hypertension and atherosclerosis and indicate that humoral immune reactions to the endothelium may play an important role in both conditions.

Intrathecal morphine supplementation to bupivacaine reduces first 24 h PCA-morphine consumption after abdominal hysterectomy under general anesthesia, and we found no benefit from increasing the dose over 200 μg.

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.

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 all anaesthetic obstetric units in Sweden concerning the use and postoperative monitoring of morphine, sufentanil and fentanyl in spinal/epidural anaesthesia. Results: A total of 32 of 47 (68%) 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 monitored 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.