Surgical treatment of spontaneous intracerebral hemorrhage in a full-term infant with coagulopathy--case report.
(57/402)An 11-week-old male infant presented with intracerebral hemorrhage associated with coagulopathy manifesting as left hemiparesis, lethargy, and vomiting. Computed tomography demonstrated extensive right frontoparietal intracerebral hemorrhage extending into the ventricular system. Liver function tests revealed abnormal values of transaminases and bilirubin. Blood coagulation studies showed prolonged prothrombin time (PT) and activated partial thromboplastin time (APPT). PT and APTT immediately normalized after the administration of vitamin K and fresh frozen plasma. Right parietal craniotomy and evacuation of the hematoma were performed because of the deterioration in consciousness and left hemiparesis. No vascular abnormality was observed in the hematoma cavity. After surgery, he became alert and the left hemiparesis improved. There is a risk of intracerebral hemorrhage due to vitamin K deficiency even if prophylactic administration of vitamin K was given. Surgical treatment should be considered for the treatment of infantile spontaneous intracerebral hemorrhage, especially if neurological deterioration is present. (+info)
Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets.
(58/402)Arterial occlusive disorders are a leading cause of human morbidity. We hypothesized that ectopic expression of fibrinolytic proteins in platelets could be used to favorably alter the hemostatic balance at sites of thrombosis. To test our hypothesis, we directed murine urokinase-type plasminogen activator transgene expression to platelets using a platelet factor 4 promoter. Urokinase was selectively expressed and stored in the platelets of these mice. These transgenic mice had altered platelet biology and a bleeding diathesis similar to that seen in patients with Quebec platelet disorder, affirming the role of ectopic urokinase expression as the etiology of this inherited disease. These mice were resistant to the development of occlusive carotid artery thrombosis in the absence of systemic fibrinolysis and displayed rapid resolution of pulmonary emboli. Moreover, transfusion of urokinase-expressing platelets into wild-type mice prevented formation of occlusive arterial thrombi. These studies show the feasibility of delivering fibrinolytic agents to sites of incipient thrombus formation through selective storage in platelets and offer a new strategy to prevent thrombosis and hemorrhage. (+info)
Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement.
(59/402)BACKGROUND: Total knee arthroplasty (TKA) is often carried out using a tourniquet and shed blood is collected in drains. Tranexamic acid decreases the external blood loss. Some blood loss may be concealed, and the overall effect of tranexamic acid on the haemoglobin (Hb) balance is not known. METHODS: Patients with osteoarthrosis had unilateral cemented TKA using spinal anaesthesia. In a double-blind fashion, they received either placebo (n=24) or tranexamic acid 10 mg kg(-1) (n=27) i.v. just before tourniquet release and 3 h later. The decrease in circulating Hb on the fifth day after surgery, after correction for Hb transfused, was used to calculate the loss of Hb in grams. This value was then expressed as ml of blood loss. RESULTS: The groups had similar characteristics. The median volume of drainage fluid after placebo was 845 (interquartile range 523-990) ml and after tranexamic acid was 385 (331-586) ml (P<0.001). Placebo patients received 2 (0-2) units and tranexamic acid patients 0 (0-0) units of packed red cells (P<0.001). The estimated blood loss was 1426 (1135-1977) ml and 1045 (792-1292) ml, respectively (P<0.001). The hidden loss of blood (calculated as loss minus drainage volume) was 618 (330-1347) ml and 524 (330-9620) ml, respectively (P=0.41). Two patients in each group developed deep vein thrombosis. CONCLUSIONS: Tranexamic acid decreased total blood loss by nearly 30%, drainage volume by approximately 50% and drastically reduced transfusion. However, concealed loss was only marginally influenced by tranexamic acid and was at least as large as the drainage volume. (+info)
Identification of amino acids in antiplasmin involved in its noncovalent 'lysine-binding-site'-dependent interaction with plasmin.
(60/402)The lysine-binding-site-mediated interaction between plasmin and antiplasmin is of great importance for the fast rate of this reaction. It also plays an important part in regulating the fibrinolytic enzyme system. To identify structures important for its noncovalent interaction with plasmin, we constructed seven single-site mutants of antiplasmin by modifying charged amino acids in the C-terminal part of the molecule. All the variants were expressed in the Drosophila S2 cell system, purified, and shown to form stable complexes with plasmin. A kinetic evaluation revealed that two mutants of the C-terminal lysine (K452E or K452T) did not differ significantly from wild-type antiplasmin in their reactions with plasmin, in either the presence or absence of 6-aminohexanoic acid, suggesting that this C-terminal lysine is not important for this reaction. On the other hand, modification of Lys436 to Glu decreased the reaction rate about fivefold compared with wild-type. In addition, in the presence of 6-aminohexanoic acid, only a small decrease in the reaction rate was observed, suggesting that Lys436 is important for the lysine-binding-site-mediated interaction between plasmin and antiplasmin. Results from computerized molecular modelling of the C-terminal 40 amino acids support our experimental data. (+info)
The use of the rapid D-dimer test for the exclusion of acute venous thromboembolism in a regional hospital.
(61/402)BACKGROUND: The performance of rapid D-dimer ELISA assay has been validated as a part of various diagnostic work-ups in tertiary care hospitals for the exclusion of acute thromboembolism in the medical emergency department. In order to measure the performance of this test outside of predetermined protocols and in a different medical setting, we retrospectively analysed a cohort of adult patients admitted to the emergency department of a regional hospital with a suspicion of acute venous thromboembolism. METHODS: All D-dimer assays performed during an 18-month period were retrieved. The patients' data were collected from hospital charts. Six-month follow-up was determined either by a written or telephone questionnaire or after contact with the patient's physician. The patients for whom this process was completed were included in the study and a retrospective diagnostic assessment was performed using a combination of clinical probability and objective testing. The diagnosis was then compared to the result of the initial D-dimer assay. RESULTS: During the study period 494 patients were included with 110 venous thromboembolic episodes. The sensitivity and negative predictive value of the D-dimer assay were respectively 94.5% (95% CI 88.4 to 97.7%) and 96.8% (95% CI 93.2 to 98.7%). CONCLUSIONS: The yield of the rapid D-dimer assay in this study is comparable to the results of management studies performed in tertiary centres. D-dimer ELISA assay can be used to exclude venous thromboembolism, particularly in cases with a low clinical probability, in the emergency department and for larger populations in various clinical settings, even in the absence of a formal diagnostic work-up. False negative results can occur, particularly in the presence of a high clinical probability of acute thromboembolism. (+info)
Immunoglobulins G could prevent adherence of Candida albicans to polystyrene and extracellular matrix components.
(62/402)Immunocompromised patients are at high risk of developing Candida infections. Although cell-mediated immunity is generally believed to play the main role in defence against fungi, antibodies could also be effective in immune defence by different mechanisms of action. The adherence capacity of four strains of Candida albicans to polystyrene and to some extracellular matrix components was investigated after incubation of the yeasts with non-specific and specific anti-C. albicans IgG. Experiments were carried out using a colorimetric method based upon the reduction of XTT tetrazolium (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) by mitochondrially active blastospores in the presence of menadione. Incubation of the yeasts with IgG, specific or not, caused a decrease in the capacity for adherence to the surfaces studied. There was no significant effect of the specificity of the tested antibodies on the reduction of adherence capacity. In conclusion, total IgG could play a role in blocking the binding of C. albicans to host and medical device surfaces. These results suggest that regular survey of levels of total IgG in patients suffering from severe hypogammaglobulinaemia could be of interest for the prevention of systemic candidiasis. (+info)
Control of ascorbic acid efflux in rat luteal cells: role of intracellular calcium and oxygen radicals.
(63/402)In luteal cells, prostaglandin (PG)F2a mobilizes intracellular calcium concentration ([Ca]i), generates reactive oxygen species (ROS), depletes ascorbic acid (AA) levels, inhibits steroidogenesis, and ultimately induces cell death. We investigated the hypothesis that [Ca]i mobilization stimulates ROS, which results in depletion of cellular AA in rat luteal cells. We used a self-referencing AA-selective electrode that noninvasively measures AA flux at the extended boundary layer of single cells and fluorescence microscopy with fura 2 and dichlorofluorescein diacetate (DCF-DA) to measure [Ca]i and ROS, respectively. Menadione, a generator of intracellular superoxide radical (O2-), PGF2a, and calcium ionophore were shown to increase [Ca]i and stimulate intracellular ROS. With calcium ionophore and PGF2a, but not menadione, the generation of ROS was dependent on extracellular calcium influx. In unstimulated cells there was a net efflux of AA of 121.5 +/- 20.3 fmol x cm-1 x s-1 (mean +/- SE, n = 8), but in the absence of extracellular calcium the efflux was significantly reduced (10.3 +/- 4.9 fmol x cm-1 x s-1; n = 5, P < 0.05). PGF2a and menadione stimulated AA efflux, but calcium ionophore had no significant effect. These data suggest two AA regulatory mechanisms: Under basal conditions, AA efflux is calcium dependent and may represent recycling and maintenance of an antioxidant AA gradient at the plasma membrane. Under luteolytic hormone and/or oxidative stress, AA efflux is stimulated that is independent of extracellular calcium influx or generation of ROS. Although site-specific mobilization of calcium pools and ROS cannot be ruled out, the release of AA by PGF2a-stimulated luteal cells may occur through other signaling pathways. (+info)
Laboratory tests in the diagnosis of pulmonary embolism.
(64/402)The diagnosis of pulmonary embolism (PE) requires objective testing. However, all imaging techniques have their own limitations and costs and cannot be performed in every patient with suspected PE. After decades of unfruitful research, several laboratory tests have been evaluated for suspected PE, the most promising being the D-dimer test. As a general rule, the specificity of D-dimers is too low to confirm PE. Conversely, several (but not all) D-dimer assays have a high sensitivity for diagnosing PE. Outcome studies indicate that the Vidas D-dimer and SimpliRED D-dimer can be used safely to withdraw anticoagulation when the pretest probability of PE is low (SimpliRED) or when it is low or moderate (Vidas). These results may however not apply to other D-dimer assays and clinicians should know the characteristics of the test used in their hospital. Blood gas analysis does not have sufficient sensitivity and specificity to confirm or exclude PE, but it may be used to evaluate the clinical probability of PE before other testing is done. The diagnostic value of the alveolar dead space fraction in patients with suspected PE is currently investigated. Initial data suggest that it needs to be combined with a D-dimer test to safely exclude PE. Brain natriuretic peptide and cardiac troponin have limited usefulness for diagnosing PE, but both tests may identify patients with a poor prognosis, in whom more aggressive treatment may be warranted. (+info)