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1.
Br J Clin Pharmacol ; 78(6): 1354-65, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24976291

ABSTRACT

AIM: Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers. METHODS: The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value). RESULTS: All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports. CONCLUSIONS: In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.


Subject(s)
Blood Platelets/drug effects , Cerebrovascular Circulation/drug effects , Macula Lutea/drug effects , Propylene Glycols/pharmacology , Sphingosine/analogs & derivatives , Adult , Blood Flow Velocity , Blood Platelets/physiology , Double-Blind Method , Female , Fingolimod Hydrochloride , Humans , Macula Lutea/anatomy & histology , Male , Middle Aged , Propylene Glycols/adverse effects , Propylene Glycols/pharmacokinetics , Receptors, Lysosphingolipid/drug effects , Sphingosine/adverse effects , Sphingosine/pharmacokinetics , Sphingosine/pharmacology
2.
Clin Appl Thromb Hemost ; 20(7): 735-40, 2014 Oct.
Article in English | MEDLINE | ID: mdl-23832064

ABSTRACT

BACKGROUND: Rivaroxaban (Xarelto, Bayer HealthCare, Leverkusen, Germany) is a new oral anticoagulant drug. Anticoagulants may cause bleeding, thereby requiring reliable monitoring and efficient therapy. We investigated thromboelastometry versus routine coagulation tests to measure prophylactic and therapeutic concentrations of rivaroxaban and their reversal with prothrombin complex concentrate (PCC) and activated recombinant factor VII (rFVIIa) in vitro. METHODS: Rivaroxaban was solubilized, and PCC and rFVIIa were added in 2 concentrations to the rivaroxaban-spiked blood samples, and thromboelastometry and measurements were performed. RESULTS: Rivaroxaban increased tissue factor-activated clotting time (CT(ExTEM)) dose dependently. Activated partial prothrombin time (aPTT), prothrombin time ratio (PTR), and prothrombin time (PT) were changed significantly in both concentrations. Reversal with PCC in both dosages caused no significant change in the measured parameters. For prophylactic rivaroxaban dosage, rFVIIa changed the PT significantly but not CT(ExTEM), aPTT, and PTR. For therapeutic rivaroxaban dosage, the CT(ExTEM) was significantly reduced. The other parameters remained unaffected. CONCLUSIONS: Thromboelastometry can detect rivaroxaban effects. In vitro rFVIIa seems highly effective for reversal in contrast to PCC.


Subject(s)
Blood Coagulation Factors/metabolism , Factor VIIa/metabolism , Factor Xa Inhibitors/pharmacokinetics , Morpholines/pharmacokinetics , Thiophenes/pharmacokinetics , Thrombelastography , Adult , Dose-Response Relationship, Drug , Factor Xa Inhibitors/pharmacology , Female , Humans , Male , Morpholines/pharmacology , Rivaroxaban , Thiophenes/pharmacology
4.
Ann Rheum Dis ; 71(7): 1163-9, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22267327

ABSTRACT

OBJECTIVE: Fibrinogen is a target of autoimmune reactions in rheumatoid arthritis (RA). Fibrin(ogen) derivatives are involved in inflammatory processes and the generation of a stable fibrin network is necessary for sufficient inflammation control. As the density and stability of fibrin networks depend on complex interactions between factor XIIIA (F13A) and fibrinogen genotypes, the authors studied whether these genotypes were related to C-reactive protein (CRP) levels during acute-phase reactions. METHODS: Association between α-fibrinogen (FGA), ß-fibrinogen (FGB) and F13A genotypes with CRP levels was tested in two cohorts with longitudinal CRP measurements. Discovery and replication cohorts consisted of 288 RA (913 observations) and 636 non-RA patients (2541 observations), respectively. RESULTS: Genotype FGB -455G>A (rs1800790) was associated with CRP elevations (≥ 10 mg/l) in both cohorts (RA, OR per allele 0.69, p=0.0007/P(adj)<0.015; non-RA, OR 0.70, p=0.0004/p(adj)<0.02; combined, OR 0.69, p<10(-5)/p(adj)=0.001). Genotype F13A 34VV (rs5985) was conditional for the association of FGB -455G>A with CRP as indicated by a clear restriction on F13A 34VV individuals and a highly significant heterogeneity between F13A 34VV and F13A 34L genotypes (p<10(-5), p(adj)=0.001). In both cohorts, mean CRP levels significantly declined with ascending numbers of FGB -455A alleles. Genotype FGA T312A (rs6050) exhibited opposite effects on CRP compared with FGB -455G>A. Again, this relation was dependent on F13A V34L genotype. CONCLUSION: Novel genetic determinants of CRP completely unrelated to previously known CRP regulators were identified. Presumably, these haemostatic gene variants modulate inflammation by influencing fibrin crosslinking. These findings could give new perspectives on the genetic background of inflammation control.


Subject(s)
Acute-Phase Reaction/genetics , C-Reactive Protein/analysis , Factor XIIIa/genetics , Fibrinogen/genetics , Acute-Phase Reaction/blood , Adult , Factor XIIIa/analysis , Female , Fibrinogen/analysis , Genotype , Humans , Male , Middle Aged
5.
Clin Appl Thromb Hemost ; 17(4): 340-5, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20460343

ABSTRACT

Thoracic mobile aortic mural thrombus (TAMT) of the aortic arch is a rare condition. We report 3 cases of symptomatic TAMT treated with systemic alteplase (tissue plasminogen activator [t-PA]) thrombolysis. The first patient was symptomatic with repetitive thromboembolism to the left brachial artery. She was treated with repetitive thrombolysis after surgical embolectomy of the brachial artery. The second patient was symptomatic with splenic infarction and mesenteric ischemia. She was treated with a single cycle of systemic thrombolysis followed by ileocoecal resection. The third patient presented with a TAMT obstructing the left common carotid artery, causing ischemic stroke. After systemic thrombolysis, a reduction in thrombus size was documented; however, the patient died later, of acute heart failure, during the clinical course. On follow-up 6 months after the incidences, the 2 surviving patients were in good condition and free of thromboembolic events. We show that systemic thrombolytic therapy can be performed successfully in patients with TAMT.


Subject(s)
Aorta, Thoracic/pathology , Thrombolytic Therapy/methods , Thrombosis/drug therapy , Aged, 80 and over , Aorta, Thoracic/diagnostic imaging , Echocardiography , Female , Humans , Middle Aged , Thrombosis/diagnostic imaging , Thrombosis/pathology , Tomography, X-Ray Computed , Treatment Outcome
6.
Ann Rheum Dis ; 69(11): 1951-7, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20511612

ABSTRACT

OBJECTIVE: To assess and analyse nutritional status in patients with systemic sclerosis (SSc) and identify possible associations with clinical symptoms and its prognostic value. METHODS: Body mass index (BMI) and parameters of bioelectrical impedance analysis (BIA) were assessed in 124 patients with SSc and 295 healthy donors and matched for sex, age and BMI for comparisons. In patients with SSc, BMI and BIA values were compared with clinical symptoms in a cross-sectional study. In a prospective open analysis, survival and changes in the nutritional status and energy uptake induced by nutritional treatment were evaluated. RESULTS: Patients with SSc had reduced phase angle (PhA) values, body cell mass (BCM), percentages of cells, increased extracellular mass (ECM) and ECM/BCM values compared with healthy donors. Malnutrition was best reflected by the PhA values. Of the patients with SSc, 69 (55.7%) had malnutrition that was associated with severe disease and activity. As assessed by multivariate analysis, low predicted forced vital capacity and high N-terminal(NT)-proBNP values discriminated best between good and bad nutritional status. Among different clinical parameters, low PhA values were the best predictors for SSc-related mortality. BMI values were not related to disease symptoms or mortality. Fifty per cent of patients with SSc had a lower energy uptake related to their energy requirement, 19.8% related to their basal metabolism. Nutritional treatment improved the patients' nutritional status. CONCLUSIONS: In patients with SSc, malnutrition is common and not identified by BMI. BIA parameters reflect disease severity and provide best predictors for patient survival. Therefore, an assessment of nutritional status should be performed in patients with SSc.


Subject(s)
Malnutrition/etiology , Nutritional Status , Scleroderma, Systemic/complications , Adolescent , Adult , Aged , Body Composition , Body Mass Index , Electric Impedance , Epidemiologic Methods , Germany/epidemiology , Humans , Malnutrition/mortality , Malnutrition/physiopathology , Middle Aged , Prognosis , Scleroderma, Systemic/mortality , Scleroderma, Systemic/physiopathology , Young Adult
7.
Subst Use Misuse ; 45(7-8): 1216-29, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20441459

ABSTRACT

Alcohol use disorder patients have a five-fold higher risk of postoperative bleeding complications. We measured the perioperative von Willebrand factor and factor VIII levels in consecutive patients with alcohol use disorder. In one university hospital, 105 patients scheduled for arthroplasty were screened, and 25 fulfilled inclusion criteria. Postoperatively, we found significantly decreased von Willebrand factor ristocetin cofactor values over time among alcohol use disorder patients and significantly different time courses of factor VIII levels between patients with and without a diagnosed alcohol use disorder. Blood loss was significantly increased among alcohol use disorder patients on their first postoperative day.


Subject(s)
Alcoholism , Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Factor VIII/analysis , Perioperative Care , Postoperative Complications/blood , von Willebrand Diseases , Aged , Female , Humans , Male , Middle Aged
8.
Thromb Res ; 125(5): e190-6, 2010 May.
Article in English | MEDLINE | ID: mdl-20116087

ABSTRACT

INTRODUCTION: Elevated platelet reactivity despite antiplatelet therapy is associated with an increased cardiovascular risk after percutaneous coronary interventions. Current guidelines recommend uniform antiplatelet maintenance regimen after percutaneous coronary interventions for patients with myocardial infarction and elective patients. We sought to demonstrate that there is a persistent enhancement of residual platelet reactivity after myocardial infarction, requiring an intensified antiplatelet maintenance therapy. MATERIALS AND METHODS: A total of 66 patients after coronary stenting for myocardial infarction (n=36) or elective coronary stenting (n=30) were included in this prospective, controlled study. Platelet reactivity to adenosine-5-diphosphate and arachidonic acid under treatment with clopidogrel (75 mg) and acetyl salicylic acid (100mg) were assessed 48 hours and 30 days after coronary stenting using light transmission aggregometry and multiple electrode platelet aggregometry (Multiplate analyzer) simultaneously. RESULTS: Fourty-eight hours after coronary stenting all measures of residual platelet reactivity were significantly elevated in the infarction group. After a mean follow up of 37 days, residual platelet reactivity to adenosine-5-diphosphate was still consistently elevated, albeit statistically not significant. Contrarily, residual platelet reactivity to arachidonic acid significantly decreased and returned to normal by the time of follow up. Regression analyses revealed myocardial infarction, C-reactive protein and fibrinogen as predictors of enhanced platelet reactivity 48 hours after coronary stenting. CONCLUSIONS: Patients undergoing coronary stenting for acute myocardial infarction exhibit an enhancement of residual platelet reactivity sustaining for at least 48 hours following coronary stenting. This finding provides a rationale for a continued intensified antiplatelet therapy after myocardial infarction.


Subject(s)
Coronary Vessels/physiopathology , Coronary Vessels/surgery , Myocardial Infarction/physiopathology , Myocardial Infarction/surgery , Platelet Activation , Platelet Aggregation , Stents , Female , Humans , Male , Middle Aged , Treatment Outcome
9.
Clin Hemorheol Microcirc ; 40(3): 167-76, 2008.
Article in English | MEDLINE | ID: mdl-19029642

ABSTRACT

The study's objective was to determine the effects of the administration of combinations of C1 esterase inhibitor (C1-INH) with coagulation factor XIII (F XIII) and N-acetylcysteine (NAC) with tirilazad mesylate (TM) on leukocyte adherence and on intestinal functional capillary density during experimental endotoxemia in rats. In a prospective, randomized, controlled animal study, 40 male Wistar rats were divided into 4 groups. Group 1 (CON group) served as control group. Group 2 (LPS group), group 3 (C1-INH+F XIII group) and group 4 (NAC+TM group) received endotoxin infusions (10 mg/kg/h for 2 h). In C1-INH+F XIII group, 100 U/kg b.w. C1-INH and 50 U/kg b.w. F XIII were administered after the first 30 min of endotoxemia. In the NAC+TM group, 150 mg/kg b.w. N-acetylcysteine and 10 mg/kg b.w. Tirilazad mesylate were administered after 30 min of endotoxemia. Leukocyte adherence at venules of the intestinal submucosal layer and functional capillary density in the villi intestinales and in the longitudinal and circular muscle layers were estimated by intravital fluorescence microscopy (IVM). C1-INH+F XIII reduced the count of firmly adherent leukocytes that was increased after LPS administration in the V3 venules (CON group 69 (17-160)/mm2; LPS group 635 (556-814)/mm2; C1-INH+F XIII group 503 (337-646)/mm2). NAC+TM reduced the firmly adherent leukocytes in the V3 venules (NAC+TM group 403 (309-572)/mm2) and in the V1 venules (CON group 55 (16-131)/mm2; LPS group 368 (306-475)/mm2; NAC+TM group 270 (216-308)/mm2) as well. FCD was not impaired after LPS challenge and there was no influence of both combinations on the FCD. We conclude that both drug combinations can reduce the leukocyte adherence in a sepsis model in rats.


Subject(s)
Acetylcysteine/pharmacology , Complement C1 Inhibitor Protein/pharmacology , Endotoxemia/metabolism , Factor XIII/pharmacology , Free Radical Scavengers/pharmacology , Leukocytes/metabolism , Pregnatrienes/pharmacology , Animals , Cell Adhesion/drug effects , Endotoxemia/chemically induced , Endotoxemia/drug therapy , Leukocytes/pathology , Lipopolysaccharides/toxicity , Male , Rats , Rats, Wistar
10.
Crit Care ; 12(1): R14, 2008.
Article in English | MEDLINE | ID: mdl-18279513

ABSTRACT

BACKGROUND: The purpose of this study was to determine the role of recombinant activated factor VII (rFVIIa) in abdominal, vascular, and urological surgery. METHODS: We conducted meta-analyses of case series and placebo-controlled studies reporting on the treatment or prophylaxis of bleeding with rFVIIa regarding 'reduction or cessation of bleeding', 'mortality', and 'thromboembolism'. RESULTS: All case reports (n = 15 case reports and 17 patients) documented an effect of rFVIIa in the treatment of bleeding. A meta-analysis of 10 case series revealed a reduction or cessation of bleeding in 39 out of 50 patients after administration of rFVIIa (estimated mean effect 73.2%, 95% confidence interval [CI] 51.0% to 95.4%) and a mean probability of survival of 53.0% (95% CI 26.4% to 79.7%). Among the rFVIIa responders, 19 out of 29 patients (66%) survived versus 1 out of 10 rFVIIa nonresponders (P = 0.003). Six out of 36 patients from the case series had a thromboembolic complication (estimated mean probability 16.5%, 95% CI 1.2% to 31.8%). Compared with a meta-analysis of eight placebo-controlled studies, no increased risk of thromboembolism was seen after administration of rFVIIa. CONCLUSION: The meta-analysis of case series showed that, in a mean of 73% patients, rFVIIa achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa. rFVIIa was not associated with an increased risk of thromboembolism compared with placebo.


Subject(s)
Factor VIIa/therapeutic use , Intraoperative Complications/drug therapy , Postoperative Hemorrhage/prevention & control , Abdomen/surgery , Cardiovascular Surgical Procedures , Factor VIIa/adverse effects , Female , Humans , Male , Postoperative Hemorrhage/drug therapy , Postoperative Hemorrhage/mortality , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Thromboembolism/chemically induced , Urologic Diseases/surgery
12.
Ren Fail ; 29(3): 271-7, 2007.
Article in English | MEDLINE | ID: mdl-17497439

ABSTRACT

PURPOSE: The aim of this pilot study was to compare the effect of heparin anticoagulation with and without iloprost administration during continuous renal replacement therapy (CRRT) in critically ill patients. MATERIAL AND METHODS: In a prospective, randomized, controlled pilot study at an intensive care unit at a university hospital, 20 patients requiring CRRT were investigated. Patients were allocated into two groups: group 1, the heparin group; and group 2, the heparin plus 1 ng/kg/min iloprost. In both groups, activated partial thromboplastin time (aPTT) was adjusted to 40-50 sec. Observation time was a maximum of 7 days. RESULTS: Median filter run time was significantly prolonged by iloprost administration to a median of 14 h (13-26 h) compared to 10 h (4-12 h) in the heparin group (p = 0.004). A decrease in platelet count was attenuated by iloprost administration (p = 0.012). There were no bleeding complications in either group. Hemofiltration efficiency did not differ significantly between the groups. CONCLUSION: Additional administration of iloprost prolonged the filter run time of continuous veno-venous hemofiltration (CVVH) in this setting and attenuated the fall in platelet count during CRRT.


Subject(s)
Anticoagulants/therapeutic use , Hemofiltration , Heparin/therapeutic use , Iloprost/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Acute Kidney Injury/blood , Acute Kidney Injury/therapy , Aged , Aged, 80 and over , Analysis of Variance , Biomarkers/blood , Blood Coagulation/drug effects , Drug Therapy, Combination , Female , Hemofiltration/instrumentation , Humans , Infusions, Intravenous , Male , Middle Aged , Partial Thromboplastin Time , Pilot Projects , Platelet Activation/drug effects , Platelet Count , Prospective Studies , Treatment Outcome
13.
BJU Int ; 99(6): 1427-31, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17355366

ABSTRACT

OBJECTIVE: To show the effect of different results for total prostate specific antigen (tPSA) and percentage free/total PSA (%fPSA) obtained with different assays for differentiating between benign and malignant prostate diseases. PATIENTS AND METHODS: Data were used for tPSA and fPSA levels from 596 patients with prostate cancer (314) or no evidence of cancer (282) within the PSA range 0.5-10 ng/mL, analysed with assays from Abbott (AxSYM), Beckman Coulter (Access), DPC (Immulite 2000), and Roche (Elecsys 2010), and with tPSA and complexed PSA (cPSA) assays from Bayer (ADVIA Centaur), as already reported. Receiver operating characteristics (ROC), specificities at assay-dependent and fixed thresholds, and the percentages of correct classification rates of patients were calculated. RESULTS: Whereas the areas under the ROC curves were no different among all tPSA assays, the assay-specific thresholds at 90% sensitivity were 2.5-3.1 ng/mL. When using fixed 2.5 or 4 ng/mL tPSA thresholds there was a wide sensitivity range, with significant differences among almost all assays, resulting in significantly different classification rates of patients. These differences were even larger when using fixed %fPSA thresholds. CONCLUSIONS: The current situation of differences among PSA values measured with different assays do not allow the recommendation of uniform PSA limits as biopsy criteria. For that purpose, better harmonization of PSA values between the different PSA test systems must be realized.


Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Reagent Kits, Diagnostic/standards , Adult , Aged , Aged, 80 and over , Area Under Curve , Biopsy , Humans , Male , Middle Aged , Predictive Value of Tests , Prostate/pathology , ROC Curve , Sensitivity and Specificity
14.
Anesth Analg ; 103(4): 969-74, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17000814

ABSTRACT

BACKGROUND: In this study, we evaluated the effects of the thawing process of 2 commercially available devices on the activity of clotting factors, inhibitors and activation markers of the hemostatic system in fresh-frozen plasma (FFP). In an experimental procedure, FFP was thawed under running warm water at 42 degrees C. METHODS: Plasma of 20 healthy donors was sampled, separated, and distributed in 3 plasma bags. Within 2 h after sampling plasma bags was frozen at a temperature of -30 degrees C to -40 degrees C and stored for at least 8 wk. After sampling (baseline) as well as immediately and 1, 2, 4, and 6 h after thawing, the activity of FV, FVII, FVIII, fibrinogen, fibrin monomers (FM), d-dimers (DD), alpha2-antiplasmin (alpha2-AP), and protein S (PS) was determined from each plasma bag. RESULTS: From 1 h to 6 h after thawing, no significant differences in the activity of the investigated coagulation markers dependent on the thawing procedure were found. However, immediately after thawing and independent of the thawing procedure, the activity of FVII was significantly decreased (P < 0.01), whereas FM were significantly increased (P = 0.001). CONCLUSION: The thawing procedures studied exhibited no significant influence on activity and stability of the investigated markers of coagulation over the study period. The decreased activity of FVII and the clinical significance of the increase in FM require further research.


Subject(s)
Blood Coagulation Factors/physiology , Blood Coagulation/physiology , Blood Preservation/methods , Cryopreservation/methods , Plasma , Adult , Female , Heating/methods , Humans , Male , Middle Aged
15.
Pediatr Crit Care Med ; 7(4): 383-5, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16738494

ABSTRACT

BACKGROUND: Heparin-induced thrombocytopenia type II (HIT II) is a rare but potentially life-threatening complication of heparin therapy. Hitherto, only few reports on HIT II in infants and children have been published. In particular, infants and children who have to be operated under cardiopulmonary bypass are at risk as an alternative anticoagulation is required. CASE PRESENTATION: We report on an infant with a congenital heart defect who was scheduled for cardiac surgery (Damus Kaye-Stansel procedure) with cardiopulmonary bypass. In the intensive care unit, an HIT II was diagnosed. Before surgery, the infant was pretreated with epoprostenol sodium (incrementally increasing up to a maximum dose of 30 ng/kg/min) before heparin was administered shortly after sternotomy. Mean arterial pressure was kept stable with an infusion of norepinephrine and the course of the cardiopulmonary bypass showed no signs of thrombosis. Drainage loss in the postoperative period was moderate. CONCLUSION: In HIT II infants, pretreatment with epoprostenol sodium before reexposure to heparin may offer a safe and effective anticoagulation for cardiopulmonary bypass.


Subject(s)
Anticoagulants/adverse effects , Cardiopulmonary Bypass , Epoprostenol/administration & dosage , Heparin/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Premedication , Thrombocytopenia/chemically induced , Thrombocytopenia/prevention & control , Anticoagulants/administration & dosage , Drug Therapy, Combination , Female , Heart Defects, Congenital/surgery , Heparin/administration & dosage , Humans , Infant
16.
Am J Respir Crit Care Med ; 174(4): 408-14, 2006 Aug 15.
Article in English | MEDLINE | ID: mdl-16728716

ABSTRACT

RATIONALE: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity. OBJECTIVES: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients. METHODS: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 mug/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery. MEASUREMENTS AND MAIN RESULTS: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients. CONCLUSIONS: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.


Subject(s)
Alcoholism/physiopathology , Antifungal Agents/administration & dosage , Cushing Syndrome/prevention & control , Ethanol/administration & dosage , Hypothalamo-Hypophyseal System/drug effects , Ketoconazole/administration & dosage , Pituitary-Adrenal System/drug effects , Pneumonia/immunology , Postoperative Complications/immunology , Stress, Physiological/immunology , APACHE , Aged , Alcoholism/epidemiology , Alcoholism/immunology , Comorbidity , Cushing Syndrome/immunology , Digestive System Neoplasms/epidemiology , Digestive System Neoplasms/surgery , Double-Blind Method , Female , Humans , Hydrocortisone/blood , Hypothalamo-Hypophyseal System/immunology , Interferon-gamma/blood , Interleukin-10/blood , Length of Stay , Male , Middle Aged , Morphine/administration & dosage , Pituitary-Adrenal System/immunology , Pneumonia/prevention & control , Postoperative Complications/prevention & control , ROC Curve , Stress, Physiological/prevention & control , Th1 Cells , Th2 Cells
17.
Crit Care ; 10(1): R29, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16507148

ABSTRACT

INTRODUCTION: The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia. METHODS: In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM. RESULTS: The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group. CONCLUSION: Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.


Subject(s)
Endotoxemia/drug therapy , Factor XIII/pharmacology , Intestine, Small/blood supply , Intestine, Small/drug effects , Leukocytes/drug effects , Animals , Capillaries/drug effects , Capillaries/physiology , Capillary Permeability/drug effects , Capillary Permeability/physiology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Endotoxemia/physiopathology , Factor XIII/therapeutic use , Intestine, Small/physiology , Leukocytes/physiology , Male , Mesenteric Veins/drug effects , Mesenteric Veins/physiology , Microcirculation/drug effects , Microcirculation/physiology , Prospective Studies , Rats , Rats, Wistar
18.
Pacing Clin Electrophysiol ; 29(12): 1346-51, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17201841

ABSTRACT

BACKGROUND: Pacemaker-induced superior vena cava (SVC) syndrome is a rare but serious complication of permanent pacemaker implantation. Because of its rarity, little is known about the long-term prognoses of such patients. METHODS: Five patients, mean age 62 +/- 11.4 years, with pacemaker-induced SVC syndrome for more than 10 years were investigated. The clinical evaluation included: exercise testing, thrombophilia lab tests, and a chest CT. RESULTS: Two of the patients manifested complications of SVC syndrome which included thoracoabdominal subcutaneous collaterals. One of these patients simultaneously developed an increase in the pacing threshold which required the implantation of epicardial leads. Three of the five patients had normal age-adjusted VO(2) AT und VO(2) max. Four of the patients were both heterozygous for a polymorphism of PAI-1 and were homozygous for a polymorphism of t-PA. One of these patients also was heterozygous for a polymorphism of factor V and glycoprotein IIb/IIIa. The chest CTs revealed extensive and varying collateral circulation patterns in all of the patients. CONCLUSIONS: The development of pacemaker-induced SVC syndrome is the result of various predisposing factors including thrombophilia. Many patients retain normal age-adjusted cardiopulmonary capacity and demonstrate stable clinical findings on the long-term as the result of the development of extensive collateral vessel systems. The most serious complication was the combination of SVC syndrome and the simultaneous malfunctioning of one of the leads requiring implantation of a new lead.


Subject(s)
Cardiac Pacing, Artificial/adverse effects , Pacemaker, Artificial/adverse effects , Superior Vena Cava Syndrome/etiology , Superior Vena Cava Syndrome/prevention & control , Aged , Equipment Failure , Equipment Failure Analysis , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Superior Vena Cava Syndrome/diagnosis , Treatment Outcome
19.
Crit Care Med ; 33(10): 2241-6, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16215377

ABSTRACT

OBJECTIVE: Analysis of safety and efficacy of recombinant activated factor VII (rFVIIa) used as the last resort for refractory bleeding after cardiac surgery. DESIGN: Retrospective cohort analysis and matched pairs analysis with historic controls were performed. In the rFVIIa group, which also received conventional hemostatic therapy, data were collected for a median of 14 hrs from admission to the intensive care unit (ICU) to the administration of rFVIIa and for the following 24 hrs. In the control group, which received only conventional hemostatic therapy, data were collected for 14 and then for 24 hrs after admission to the ICU. SETTING: University hospital. PATIENTS: Twenty-four patients matched with historic controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: No thromboembolic complications were observed in the rFVIIa group. Blood loss and transfusion requirements were significantly reduced in the period after the administration of rFVIIa. However, in the 24-hr period after rFVIIa administration, blood loss (p = .140) and transfusion of packed red blood cells (p = .442) and fresh frozen plasma (p = .063) were not different between the rFVIIa and control groups. Platelet concentrates (p = .004) were transfused less in the control group. Mortality and 6-month survival rates were not different between the groups. CONCLUSIONS: When used as a last resort, rFVIIa was safe but not incrementally efficacious over conventional hemostatic therapy.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Factor VII/therapeutic use , Hemostatics/therapeutic use , Postoperative Hemorrhage/drug therapy , Postoperative Hemorrhage/etiology , Aged , Aged, 80 and over , Blood Transfusion , Cohort Studies , Factor VIIa , Female , Humans , Male , Middle Aged , Postoperative Hemorrhage/mortality , Recombinant Proteins/therapeutic use , Retrospective Studies , Survival Rate , Treatment Outcome
20.
Artif Organs ; 29(6): 507-10, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15926989

ABSTRACT

Heparin-induced thrombocytopenia type II (HIT II) requires alternative anticoagulation. Hirudin has been effectively used in patients with HIT II scheduled for cardiac surgery. However, bleeding complications were observed in patients with renal impairment. In vitro hemodialysis (HD) has been questioned over its efficacy in eliminating hirudin. Another approach to stop bleeding is the application of recombinant factor VIIa (rFVIIa). We report on a patient with HIT II and chronic renal failure who suffered from severe hirudin-induced bleeding after cardiac surgery who was safely treated with a combined approach of surgical hemostasis, substitution of blood products, HD, and rFVIIa to stop finally bleeding.


Subject(s)
Anticoagulants/therapeutic use , Aortic Valve Stenosis/surgery , Hemorrhage/etiology , Hirudin Therapy , Kidney Failure, Chronic/complications , Mitral Valve Insufficiency/surgery , Thrombocytopenia/complications , Anticoagulants/adverse effects , Aortic Valve Stenosis/complications , Heparin/adverse effects , Humans , Male , Middle Aged , Mitral Valve Insufficiency/complications , Thrombocytopenia/prevention & control
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