MIP-3α expression in macrophages is NOD dependent.

BACKGROUND: The first identified susceptibility gene for Crohn's disease, NOD2, acts as a sensor for the bacterial-wall peptidoglycan fragment muramyl dipeptide (MDP) and activates the transcription factor nuclear factor-κB (NF-κB). Upon NF-κB activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3α to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3α induction. METHODS: Human embryonal kidney HEK293 cells were transfected with NOD2 wild-type (NOD2(WT)) and the NOD2 SNP13 variant (NOD2(L1007fsinsC)) and stimulated with MDP. Recruitment of CD45R0+ and Th17 cells was determined by immunohistochemistry. RESULTS: Endogenous NOD2 stimulation was followed by a dose-dependent increase in MIP-3α secretion in MONO-MAC-6 (MM6) cells. MIP-3α mRNA was also significantly (*p < 0.05) induced in HEK293 transfected with NOD2(WT) via MDP ligation. In vivo cell-cell contacts between IMACs and CD45R0+ memory T cells as well as recruitment of Th17 cells in patients of NOD2 variants were unchanged as compared to wild-type patients. CONCLUSION: Our data demonstrate a dose-dependent increase in MIP-3α secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3α-driven recruitment of Th17 cells or CD45R0+ memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants.

[Additional treatment in chronic pain syndrome due to hip and knee arthritis with the selective serotonin reuptake inhibitor fluvoxamine (Fevarin]. / Eine additive Therapie chronischer Schmerzen bei fortgeschrittener Gon-/Coxarthrose mit dem selektiven Serotonin-Reuptake-Hemmer Fluvoxamin (Fevarin).

OBJECTIVE: The aim of this study was to investigate the effectiveness and safety of the selective serotonin reuptake inhibitor fluvoxamine (Flevarin) in patients with a chronic pain syndrome due to hip and knee arthritis. METHODS: We prospectively investigated 60 patients in a single-centre double-blind study. The group was divided into two groups (M1 fluvoxamine; M2 placebo) each containing 30 patients, age ranging from 30 to 80 years. During treatment results were evaluated using several scales once at the beginning (V1) followed by weekly evaluations (V1-V8) and one final investigation at the end of treatment (V9). The investigated medication consisted of 50-150 mg fluvoxamine. In addition other drugs such as NSAID were administered (diclofenac, piroxicam, ibuprofen). RESULTS: Both groups (M1 and M2) showed a reduction of pain during treatment using the visual analogue scale (VAS). However, no statistical difference was found between both groups concerning pain reduction at any time. A significant pain relief was monitored in the patients of the M1 group towards the end of treatment. Concerning the daily impairment because of pain measured by the Griss scale an improvement was seen in 70 % of the patients receiving fluvoxamine versus 44 % in patients receiving placebo. Additionally, an improvement in the M1 group was seen in the WOMAC scale and in factors such as pain, stiffness and mobility compared to the M2 group. Using the CGI scale, 56.6 % of the M1 group compared to 37.9 % of the M2 group were stating that their overall status had improved "much" or "very much" at the end of the treatment (V9). A depression had been excluded in all patients. No statistical differences were seen in the Bf scale (von Zerssen) during all evaluations (V1 to V9). During the whole study 127 side effects were registered in 49 patients. None of the 5 severe events were related to the investigated drug. CONCLUSION: Considering the good effects in combination with very few side effects, a positive cost-effectiveness relation for the usage of fluvoxamine can be stated in patients with chronic pain syndrome due to hip and knee arthritis.

Levosimendan in patients with acute myocardial ischaemia undergoing emergency surgical revascularization.

BACKGROUND AND OBJECTIVE: Levosimendan is a calcium-sensitizing drug that enhances myocardial contractility without increasing intracellular calcium. By activating adenosine triphosphate-dependent potassium channels it exerts cardioprotective and vasodilatory effects. METHODS: A retrospective matched pair analysis was performed in 52 patients undergoing emergency coronary artery bypass grafting for acute myocardial ischaemia with or without cardiogenic shock. A total of 27 patients received levosimendan (bolus 6 microg kg(-1); continuous infusion 0.2 microg kg(-1) min(-1)) in addition to catecholamines, while 25 patients were treated with catecholamines only. RESULTS: Predicted mortality by logistic EuroSCORE was 42% (14-90%) in the levosimendan group and 38% (9-90%) in the control group (median, range). Cardiogenic shock was diagnosed in 52% of the patients in both groups. Compared to the control group, levosimendan-treated patients had fewer intra-aortic balloon pumps inserted (33% vs. 76%, P 0.05) and need for dialysis (11% levosimendan; 32% control, P > 0.05) did not reach statistical significance. Length of hospital stay did not differ (14 +/- 18 days, levosimendan; 13 +/- 19 days, control; P > 0.05) between the two groups. CONCLUSION: In this retrospective matched pair analysis of 52 patients undergoing emergency coronary artery bypass grafting for acute ischaemia, levosimendan reduced morbidity. The reduced morbidity did not translate into reductions in mortality or length of stay. A larger, prospective randomized trial is warranted to confirm the potentially beneficial effects of levosimendan in patients with acute ischaemia.

Bispectral index and electroencephalographic entropy in patients undergoing aortocoronary bypass grafting.

BACKGROUND AND OBJECTIVE: This study was conducted to compare bispectral index, state entropy and response entropy in patients undergoing coronary artery bypass grafting. METHODS: In 66 patients, anaesthesia was maintained at two different levels using bispectral index. Doses of sufentanil and midazolam were adjusted to achieve a bispectral index in the range of 45-55 in 33 patients (BIS 50 group) and 35-44 in another 33 patients (BIS 40 group). Simultaneously, state entropy and response entropy were recorded. RESULTS: The targeted values of bispectral index were achieved in both groups and the bispectral index values differed significantly during whole anaesthesia. Median response entropy and state entropy fell to 19-26 during anaesthesia in both groups. Response entropy and state entropy values in the two groups differed significantly only after induction of anaesthesia and did not differ during further anaesthesia. There was no explicit intraoperative recall in both groups. Patients in Group BIS 40 received significantly (P<0.05) more sufentanil than the BIS 50 group (704+/-181 microg vs. 490+/-107 microg, respectively) and midazolam (18.5+/-6.1 mg vs. 15.6+/-3.8 mg, respectively). After cardiopulmonary bypass, significantly (P<0.05) more patients in Group BIS40 needed inotropic support with dobutamine (79%) than in the BIS50 group (52%). Time to extubation did not differ between the two groups. CONCLUSION: In patients undergoing coronary artery bypass grafting, no relationship was found between bispectral index levels and state entropy and response entropy at two different stages of a sufentanil-midazolam anaesthesia. A bispectral index level of 45-55 reduced anaesthetic medications used and the need for inotropic support.

[A comparison of the Arndt endobronchial blocker with a double lumen tube in robotic cardiac surgery]. / Ein Vergleich des Arndt-Bronchusblockers mit einem Doppellumentubus im Rahmen robotergestützter Eingriffe in der Herzchirurgie.

OBJECTIVE: In this prospective, randomised study a double lumen tube (DLT) or an Arndt bronchial blocker (BB) was used for one lung ventilation (OLV). Intraoperative oxygenation, ventilation, haemodynamics, and ease of placement were compared. METHODS: In 32 patients undergoing robotic harvesting of the left internal thoracic artery (ITA) a left-sided DLT or a BB controlled by bronchoscopy was used for OLV of the right lung. In 2 patients randomised for DLT, a single lumen tube and BB was used for difficult visualisation of the larynx. These 2 patients were excluded from the study. RESULTS: Correct placement of DLT (8.8 +/- 5.4 min, 87.5 % of the patients) as well as BB (6.5 +/- 4.0 min; n. s.; 100 % of the patients) was achieved rapidly. The Cormack-Lehane score for visualisation of the larynx was 2, 1 - 3 (median, range) in group DLT and 3, 1 - 4 (median, range) in group BB (p < 0.05). OLV lasted for 93 +/- 29 min in group DLT and 88 +/- 34 min in group BB (n. s.). Satisfactory conditions for harvesting ITA were achieved in all patients of both groups. There was no difference in any haemodynamic parameter at any time between the two groups. Mean pulmonary arterial pressure and pulmonary vascular resistance were increased without significant differences between the two groups during thoracoscopy for robotic preparation of left ITA. During OLV, index of paO (2)/FiO (2) was significantly (p < 0.05) lower in DLT patients compared to BB patients. Time to extubation did not differ between the two groups (DLT 14.3 +/- 4.6 h; BB 11.8 +/- 3.8 h). CONCLUSION: OLV in patients undergoing robotic cardiac surgery was safely achieved either by BB or by left-sided DLT. Positioning of the BB was easier than that of a DLT when intubation was difficult and tube exchange at the end of surgery is avoided. Therefore, we prefer a BB in patients undergoing robotic harvesting of left ITA.

Comparison of two different anesthesia regimens in patients undergoing aortocoronary bypass grafting surgery: sufentanil-midazolam versus remifentanil-propofol.

OBJECTIVE: To compare intraoperative hemodynamics and depth of anesthesia using sufentanil-midazolam (SM) versus remifentanil-propofol (RP) anesthesia. DESIGN: Prospective, randomized study. SETTING: Clinical investigation in an urban, university-affiliated hospital. PARTICIPANTS: Forty patients undergoing elective first-time coronary artery bypass graft surgery. INTERVENTIONS: Twenty patients were anesthetized using SM and 20 patients using RP. MEASUREMENTS AND MAIN RESULTS: Hemodynamic monitoring included a 5-lead electrocardiogram, a radial artery catheter, and a pulmonary artery catheter. Depth of anesthesia was assessed using bispectral index (BIS). Data were obtained after induction of anesthesia (T1), after sternotomy (T2), after pericardiotomy (T3), 5 minutes after cardiopulmonary bypass (CPB) (T4), after closure of thorax (T5), and at the end of surgery (T6). The 2 groups were comparable with regard to demographic and perioperative data. There were no significant differences of any hemodynamic parameter at any time between the 2 groups. In both groups, systemic vascular resistance increased at T2 and decreased at T4 from baseline value (p < 0.05). Cardiac index increased at T4 in both groups from baseline value (p < 0.05); 55% of the patients of both groups needed low-dose dobutamine after CPB. During CPB, 40% of the RP patients needed norepinephrine versus 35% of the SM patients. BIS was lower in the RP than in the SM group at T2 and T3 (p < 0.05). BIS values indicating intraoperative awareness were not noted. CONCLUSION: Both anesthesia regimens provided stable hemodynamics and adequate anesthesia in patients undergoing coronary artery bypass graft surgery.

Total intravenous anesthesia with remifentanil and propofol for implantation of cardioverter-defibrillators in patients with severely reduced left ventricular function.

OBJECTIVE: To determine the cardiocirculatory effects of total intravenous anesthesia (TIVA) using remifentanil and propofol in high-risk cardiac surgical patients. DESIGN: Prospective study of 20 patients undergoing first-time implantation of a cardioverter-defibrillator (ICD). SETTING: Major, community, university-affiliated hospital. PARTICIPANTS AND INTERVENTIONS: In 20 patients with severely reduced left ventricular function (left ventricular ejection fraction <30%) undergoing first-time implantation of an ICD, TIVA using remifentanil and propofol was performed. MEASUREMENTS AND MAIN RESULTS: Extensive hemodynamic monitoring using a pulmonary artery catheter was performed: (T1) before induction of anesthesia, (T2) after intubation, (T3) after skin incision, (T4) after first defibrillation, and (T5) 10 minutes after extubation. Propofol, 3.0 +/- 0.6 mg/kg/h (range, 1.9 to 4.4 mg/kg/h), and remifentanil, 0.30 +/- 0.05 microg/kg/min (range, 0.21 to 0.40 microg/kg/min), were used. Total costs added up to US $44.60 per patient. Patients could be extubated within 12.5 +/- 4.2 minutes after stopping anesthesia. There were significant decreases in heart rate (HR; from 77 +/- 12 to 57 +/- 10 beats/min [T3]), mean arterial blood pressure (MAP; from 98 +/- 14 to 70 +/- 12 mmHg [T2]), and systemic vascular resistance (from 1,551 +/- 309 to 1,233 +/- 274 dyne x s x cm(-5) [T2]). Cardiac index (CI) slightly decreased only at T3 (from 2.46 +/- 0.42 to 1.92 +/- 0.29 L/min/m2; p = 0.04). The decrease in MAP could easily be treated by volume infusion in most patients (17 patients). Sixty-five percent of the patients needed dobutamine to increase CI to greater than 2.0 L/min/m2 (mean dose, 2.2 +/- 1.8 microg/kg/min). Dobutamine could be stopped before extubation in all patients. No patient needed sustained inotropic or ventilatory support and intensive care therapy could be avoided. CONCLUSION: TIVA using remifentanil and propofol in patients with severely reduced left ventricular function is safe, well-controllable, and allows early extubation after implantation of an ICD. Because patients without complications did not need a postoperative intensive care stay, costs may be considerably reduced.

The active site structure of E. coli HPII catalase. Evidence favoring coordination of a tyrosinate proximal ligand to the chlorin iron.

E. coli produces 2 catalases known as HPI and HPII. While the heme prosthetic group of the HPII catalase has been established to be a dihydroporphyrin or chlorin, the identity of the proximal ligand to the iron has not been addressed. The magnetic circular dichroism (MCD) spectrum of native ferric HPII catalase is very similar to those of a 5-coordinate phenolate-ligated ferric chlorin complex, a model for tyrosinate proximal ligation, as well as of chlorin-reconstituted ferric horseradish peroxidase, a model for 5-coordinate histidine ligation. However, further MCD comparisons of chlorin-reconstituted myoglobin with parallel ligand-bound adducts of the catalase clearly rule out histidine ligation in the latter, leaving tyrosinate as the best candidate for the proximal ligand.