Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apheresis therapy such as plasma exchange and plasma adsorption has become therapeutic tools in critical care. The indications for apheresis therapy in ICU patients include fulminant hepatic failure, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), autoimmune disease, and sepsis. During the past 11 years, 150 patients with various kinds of critical illnesses were treated with apheresis therapy in our ICU, and the overall survival rate was 50%. Apheresis therapy is especially useful in the treatment of a patient with fulminant hepatic failure because liver transplantation is seldom performed in Japan; therefore, the patient should be treated with artificial liver support. When plasma exchange is performed on the critically ill, continuous hemodiafiltration should be performed simultaneously to overcome the adverse effects of plasma exchange such as hypernatremia, metabolic alkalosis, and abrupt changes in colloid osmotic pressure and to enhance the removal rate of the causative middle molecular weight substances of hepatic failure or hepatic coma.
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PMID:Efficacy and limitation of apheresis therapy in critical care. 1022 44

Before de novo synthesized von Willebrand factor (vWF) leaves the endothelial cell, it undergoes endoproteolytic cleavage of its propeptide (vW antigen II). The processed vWF and propeptide are either released constitutively or, following activation of the endothelium, released through the regulated pathway. In a recent study (Borchiellini et al, Blood 88:2951, 1996), we showed that the half-life of mature vWF and of its propeptide differ fourfold to fivefold. We postulated that the molar ratio of the propeptide to mature vWF could serve as a tool to assess the extent of endothelial cell activation under physiologic and clinical conditions. To test this hypothesis, we measured mature vWF and propeptide in patients with documented acute and chronic vascular disease, including patients with thrombotic thrombocytopenic purpura (TTP), acute septicemia, and diabetes mellitus. These data were compared with experimental conditions in healthy subjects in which perturbation of the endothelium was simulated by physical exercise or by administration of 1-deamino-8-D-arginine vasopressin (DDAVP) or endotoxin. In all individuals of the latter study group, both vWF and propeptide levels were elevated during the acute phase of the experimentally induced vascular perturbation; at later time points after stimulation, only vWF levels remained elevated. In patients with sepsis and TTP, both vWF and propeptide were elevated several-fold. Thus, this pattern can readily be explained in terms of acute perturbation of the endothelium. In contrast, in patients with diabetes mellitus propeptide levels were only slightly elevated, whereas vWF levels were elevated twofold to threefold. This pattern is a typical feature of chronic, low-grade activation of the endothelium. These observations support our hypothesis that measurement of both propeptide and vWF levels allows to discriminate between chronic and acute phases of endothelial cell activation in vivo. Measurement of only vWF is less indicative in this respect.
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PMID:von Willebrand factor propeptide in vascular disorders: A tool to distinguish between acute and chronic endothelial cell perturbation. 1038 11

Continuous venovenous hemofiltration/hemodiafiltration (CVVH/D) is commonly used to provide renal replacement therapy for critically ill patients who are hemodynamically unstable. Occasionally, the addition of plasmapheresis therapy is necessary for some conditions, including immune-mediated acute renal failure, sepsis, fulminant hepatic failure, and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Most tertiary care facilities provide centrifugation plasmapheresis instead of membrane plasmapheresis, because of the requirement for both therapeutic plasma exchange and pheresis of cellular blood products. We report a new technique where centrifugation plasmapheresis and CVVHD (P-CVVHD) are combined and used concurrently. Blood from the patient was concurrently filtered utilizing a Hospal BSM 22 machine with a Multiflow 60 hemofilter and a Cobe Spectra continuous cell separator in a parallel configuration. P-CVVHD is technically possible and can be used for long periods of time with limited risks. There may be advantages to P-CVVHD compared with discontinuous combined CVVH/D and plasmapheresis therapy.
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PMID:Concurrent centrifugation plasmapheresis and continuous venovenous hemodiafiltration. 1065 23

The application of laparoscopic techniques for abdominal procedures has been achieved with varying success. The general acceptance of laparoscopic splenectomy (LS) may be hindered by its infrequent performance and difficulty in manipulating the spleen. A retrospective review of splenectomies performed for primary splenic pathology was done to assess the role and outcome of LS. One hundred fifty LSs were performed from July 1995 through September 1999. Over that time period the proportion of LS performed increased steadily from 17 to 75 per cent of all splenectomies. The primary indications for splenectomy included immune thrombocytopenic purpura in 75 (50%), lymphoma/leukemia 36 (24%), and splenomegaly 19 (13%). There were 86 females and 64 males. Immediately before operation 36 patients (4%) had a platelet count <50,000/ mL, and 24 patients (16%) a hemoglobin <10 mg per cent. The mean operative time was 161 minutes with an average blood loss of 138 cm3 (<50-800). The mean morcellated weight of the entire group was 411 g (33-3300) indicating generally large splenic size. In the 37 patients with splenomegaly the mean weight was 735 g (293-3300). There were two conversions to open splenectomy. Two patients with hematologic malignancy, splenomegaly, and cytopenias died from overwhelming post-splenectomy sepsis (1.3%). Morbidity occurred in 14 (9%) with the most common complication being pancreatitis in seven (5%). The median length of postoperative stay was 2.4 days (range 1-5). In summary LS has rapidly replaced the open approach for nearly all elective splenectomies in adults and children. When performed with the patient in the lateral position it can be accomplished with minimal morbidity, even in complex patients, including those with splenomegaly.
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PMID:The ascendance of laparoscopic splenectomy. 1120 97

Platelet-derived microparticles (PMPs) are released from platelets through the platelet activation by high shear stress, collagen, or calcium ionophore (A23187). PMPs are observed in patients with acute myocardial infarction, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, heparin-induced thrombocytopenia and other thrombotic disorders, but the importance of circulating PMPs in the pathogenesis of these diseases is still debated. Numbers of PMPs are usually determined by flowcytometry (FCM), but easier and reproducible PMP assay systems are needed. To develop a better ELISA for PMPs, we used antibodies against the platelet antigens anti-GPIb (NNKY5-5), anti-GPIIb/IIIa (NNKY2-11, anti-CD41), anti-GPIX (KMP-9), and anti-CD9 (NNKY1-19). PMPs were detected with all combinations of these antibodies, but the ELISA having the highest and most specific absorbance was obtained with a combination of KMP-9 (capture antibody) and NNKY5-5 (detecting antibody). PMPs in blood samples were measured by ELISA and FCM. ELISA correlated with PMPs quantitated by FCM. By shaking ELISA plates during incubation, nonspecific binding of platelets was eliminated. The level of PMPs was not increased in diabetes mellitus, thrombotic thrombocytopenic purpura, antiphospholipid syndrome, or sepsis. The concentration of PMP was elevated in hemolytic uremic syndrome. Activated PMPs were absorbed to 0.8 microm filter, but circulating PMPs were not absorbed. These results suggest that activated PMPs are likely to adhere to leukocytes or endothelial cells at the activation site and that the circulating form of PMPs are likely to be a residue of activated PMPs. To detect only the activated form of PMPs, a new ELISA needs to be developed, and it will likely use a combination of antibodies that detect platelet activation markers such as P-selectin (CD62P) or activated GPIIb/IIIa.
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PMID:Development and assessment of enzyme immunoassay for platelet-derived microparticles. 1124 56

A 66-year-old man developed a hemolytic uremic syndrome (HUS) with acute renal failure, thrombocytopenia, fragmented red cells in the blood film and elevated serum LDH following a capnocytophaga canimorsus (DF-2) infection after a dog bite. He was treated with antibiotics, plasmapheresis and hemodialysis. Although hematologic values improved, the patient remained hemodialysis-dependent for six months. In the literature several cases of renal failure following capnocytophaga canimorsus septicemia have been described, caused by hypotension or disseminated intravascular coagulation (DIC). In our patient there were no signs of hypotension or extensive DIC. A few case reports described HUS and thrombotic thrombocytopenic purpura (TTP) following DF-2 sepsis.
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PMID:Hemolytic uremic syndrome after capnocytophaga canimorsus (DF-2) septicemia. 1126 82

In this study, we examined changes in the plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I complex in patients with disseminated intravascular coagulation (DIC) and in those with thrombotic thrombocytopenic purpura (TTP) to investigate the fibrinolytic function and its relation to organ failure. The plasma levels of total PAI-1 and tPA/PAI-I complex were significantly higher in patients with DIC, pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher in patients with organ failure than in those without organ failure. The plasma levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients with acute leukemia. The plasma levels of total PAI-I, but not those of tPA/PAI-I complex, were significantly increased in patients with sepsis or with solid cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I complex may be useful in the diagnosis of DIC.
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PMID:Plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tPA/PAI-1 complex in patients with disseminated intravascular coagulation and thrombotic thrombocytopenic purpura. 1144 85

Von Willebrand factor (VWF) is a multifunctional plasma protein that plays a prominent role in haemostasis. In endothelial cells, processing of its precursor pro-VWF results in the formation of two large polypeptides, mature VWF and a propeptide. These proteins are co-secreted on an equimolar basis but are cleared from the circulation at different rates. VWF levels are frequently elevated in response to vascular disorders. Similarly, propeptide levels are increased under these conditions, although primarily in fulminant vascular disease, such as thrombotic thrombocytopenic purpura and septicemia. In chronic vascular disease, e.g. diabetes or peripheral vascular disease, propeptide levels are much less elevated. The differential response of VWF and propeptide levels to vascular disease could provide a means to assess the extent and time course of endothelial cell activation. After secretion, the propeptide may play a role in modulating cellular adhesion processes. Thus, enhanced propeptide secretion seems not to be of merely diagnostic significance.
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PMID:Von Willebrand factor propeptide in vascular disorders. 1148 4

Since idiopathic (immune) thrombocytopenic purpura (ITP) in adults is usually a chronic condition with few spontaneous remissions, the goal of treatment is not cure, but to maintain a hemostatically safe platelet level. The indication for treatment should be based not merely on platelet counts, but also clinical indices of bleeding. Although most patients show good initial response to prednisone, the side effects of steroids limit this treatment. Currently, long-term management usually involves splenectomy. Since splenectomy has surgical risks and may also predispose the patient to sepsis, a clinical trial using anti-D (WinRho-SDR) has been performed to determine whether this treatment can safely delay or avoid the need for surgery. The use of WinRho may also reveal the occurrence of spontaneous remissions, a previously unrecognized subgroup of adults with chronic ITP.
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PMID:Initial management of adults with idiopathic (immune) thrombocytopenic purpura. 1191 92

A severe deficiency in von Willebrand factor-cleaving protease (ADAMTS13) activity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in various thrombocytopenic and other conditions. We studied 68 patients with thrombocytopenia due to severe sepsis or septic shock (n = 17), heparin-induced thrombocytopenia (n = 16), idiopathic thrombocytopenic purpura (n = 10), or other hematologic (n = 15) or miscellaneous conditions (n = 10). Twelve of the 68 patients had subnormal levels of ADAMTS13 activity (<or= 30%), but none had less than 10%. Thus, the study showed that ADAMTS13 activity is decreased in a substantial proportion of patients with thrombocytopenia of various causes. A severe deficiency of ADAMTS13 (< 5%), identified in more than 120 patients during 1996 to 2001 in our laboratory, is specific for a thrombotic microangiopathy commonly labeled TTP.
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PMID:Von Willebrand factor-cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. 1241 28


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