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)

Thirty patients with primary hepatocellular carcinoma or liver metastases were entered into a program of chemoembolization with cisplatin, lipiodol, and escalating doses of thiotepa. Doses of cisplatin were 100/m2, and thiotepa doses ranged from 9 mg/m2 to 24 mg/m2. Two of three patients with ocular melanoma had partial responses in the liver metastases for 3+ and 16 months. In patients with either hepatocellular carcinoma (15 patients) or primary cholangiocarcinoma of the liver (three patients), there were two partial responses, for 22 and 33 months. Five patients had minor responses: four with a 40% reduction in tumor and one with a mixed response. There were four early deaths, which involved sepsis in two patients, respiratory failure in one, and acute myocardial infarction in one. Otherwise, toxicity was tolerable and reversible and included abdominal pain and transient elevation of serum creatinine, bilirubin, and transaminases. Less common toxicities included ototoxicity and peripheral neuropathy. Chemoembolization of the liver with cisplatin, thiotepa, and lipiodol can produce responses, but toxicity can be significant. The recommended starting phase II dose for future studies is thiotepa 24 mg/m2 and cisplatin 100 mg/m2.
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PMID:A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer. 1044 Jan 93

The purpose of this study was to observe the prevalence of hypocholesterolaemia in a hospital population and also the causes and clinical outcome of this condition. Fifty-seven patients were found with a plasma cholesterol of < or = 3.0 mmol/L, which was less than 0.50% of all plasma cholesterol requests; there were 39 men and 18 women (P < 0.05, Chi-squared test). The mean age was 53.8 [21.3] (range 3-83 years). The mean plasma cholesterol concentration was 2.28 [0.56] mmol/L (1.16-3.0) and the mean triglyceride concentration was 1.58 [1.09] mmol/L (0.49-7.35). There was a significant correlation between plasma cholesterol concentration and plasma albumin (Rs = 0.48, P < 0.01) and between plasma total protein concentration (Rs = 0.49, P < 0.01). However, there was no relationship between the concentrations of plasma cholesterol and triglyceride (Rs = 0.10, P > 0.05). Eighteen per cent of patients with hypocholesterolaemia died during their hospitalization. Thirty-nine per cent of those who had a plasma cholesterol of < or = 2.0 mmol/L died whereas 71% of those who had a plasma cholesterol concentration of < 1.5 mmol/L died. Hypocholesterolaemia was more commonly seen in the intensive care unit and in post-operative patients, those with malignancy, sepsis, acute myocardial infarction, those who had inflammatory bowel disease and diabetics on insulin. Hypocholesterolaemia may be a useful predictor of mortality in hospital patients.
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PMID:Hypocholesterolaemia in a hospital population. 1050 11

C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary angioedema caused by a deficiency of C1-Inh. There is now accumulating evidence, obtained from studies in animals and observations in patients, that administration of C1-Inh may have a beneficial effect as well in other clinical conditions such as sepsis, cytokine-induced vascular leak syndrome, acute myocardial infarction, or other diseases. Activation of the complement system, the contact activation system, and the coagulation system has been observed in these diseases. A typical feature of the contact and complement system is that on activation they give rise to vasoactive peptides such as bradykinin or the anaphylatoxins, which in part explains the proinflammatory effects of either system. C1-Inh, belonging to the superfamily of serine proteinase inhibitors (serpins), is a major inhibitor of the classical complement pathway, the contact activation system, and the intrinsic pathway of coagulation, respectively. It is, therefore, endowed with anti-inflammatory properties. However, inactivation of C1-Inh occurs locally in inflamed tissues by proteolytic enzymes (e.g., elastase) released from activated neutrophils or bacteria thereby leading to increased local activation of the various host defense systems. Here we will give an overview on the biochemistry and biology of C1-Inh. We will discuss studies addressing therapeutic administration of C1-Inh in experimental and clinical conditions. Finally, we will provide an explanation for the therapeutic benefit of C1-Inh in so many different diseases.
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PMID:C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. 1069 56

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.
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PMID:Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin. 1089 75

Cardiovascular and cerebrovascular diseases are common causes of morbidity and mortality in women with systemic lupus erythematosus (SLE) and are also common in patients with end-stage renal disease (ESRD). To determine whether women with ESRD caused by lupus nephritis are at greater risk for morbidity from these conditions than women with other causes of ESRD, data from the US Renal Data System were used to compare incidence rates of hospitalizations for acute myocardial infarction and cerebrovascular accident between women with ESRD caused by lupus nephritis and women with ESRD from other causes. The age- and race-adjusted incidences of hospitalizations for acute myocardial infarction during dialysis were 16.4 hospitalizations/1,000 patient-years among women with ESRD caused by lupus nephritis and 17.3 hospitalizations/1,000 patient-years among women in the comparison group (adjusted hazard ratio, 0.80; 95% confidence interval [CI], 0.58 to 1.08; P = 0.14). Adjusted incidence rates for acute myocardial infarction after renal transplantation also did not differ between these groups. Adjusted incidence rates for hospitalizations for cerebrovascular accident during dialysis were 18.5 hospitalizations/1,000 patient-years among women with ESRD caused by lupus nephritis and 19.2 hospitalizations/1,000 patient-years among women in the comparison group (adjusted hazard ratio, 0.87; 95% CI, 0.66 to 1.14; P = 0.30); incidence rates after transplantation also did not differ between groups. Risks for death from cardiovascular or cerebrovascular diseases also were not increased among women with ESRD caused by lupus nephritis. Sepsis was the most common cause of death in this group. Morbidity and mortality from acute myocardial infarction and cerebrovascular accident were substantially greater among women with ESRD caused by diabetes mellitus. Although morbidity and mortality from cardiovascular and cerebrovascular diseases are common among women with SLE, risks for these outcomes are not greater among women with ESRD caused by lupus nephritis than among other women without diabetes with ESRD.
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PMID:Cardiovascular and cerebrovascular morbidity and mortality among women with end-stage renal disease attributable to lupus nephritis. 1097 83

Data were collected retrospectively on 1,681 consecutive isolated coronary artery bypass graft patients at Millard Fillmore Hospital (Buffalo, New York, USA) undergoing coronary artery bypass. No patients were excluded. There were 616 patients in the open circuit group and 1,065 in the closed circuit group. Patients in the closed circuit group exhibited a trend towards a higher incidence of most pre-existing comorbidities, with acute myocardial infarction, pre-existing cerebrovascular disease and the incidence of extensively calcified aortas all being significantly higher. Significantly different postbypass outcomes favored the closed circuit group, with levels of sepsis of 1% for open and 0% for closed and respiratory failure of 4% for open and 1% for closed. The length of stay approached significance with a p-value of 0.057 (open 9.85 days and closed 7.53). Use of an open circuit was a significant, independent predictor for increased use of units of packed red blood cells and total units of blood products. This study provides evidence that closed venous reservoirs can favorably impact surgical outcomes and reduce resulting healthcare costs.
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PMID:Impact of closed versus open venous reservoirs on patient outcomes in isolated coronary artery bypass graft surgery. 1100 Nov 71

Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role.
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PMID:Newer uses of glucose-insulin-potassium regimen. 1120 54

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

Both undetected and clinically evident venous thrombosis and venous thromboembolism (VTE) can seriously impact the prognosis of acutely and/or critically ill patients. Pulmonary embolism (PE) is harder to diagnose in the acutely and/or critically ill, many of whom also have developed respiratory failure for other reasons. Deep vein thrombosis (DVT) of the upper and lower extremities can subsequently complicate insertion of central venous catheters, leading to PE, sepsis and septic shock. Recovery from the original critical illness (e.g. weaning from mechanical ventilation) can be adversely affected by these complications. There are recent data suggesting that, for prophylaxis, low-molecular-weight heparin (LMWH) is more effective than unfractionated heparin (UFH) in critically ill trauma patients, and that high-dose LMWH is more effective than placebo or low-dose LMWH in seriously ill medical patients. In both populations, LMWH appeared safe. While LMWH appears superior to UFH in acute stroke patients to prevent venographically-proven lower-extremity DVT, whether it provides a superior long-term outcome after acute stroke is uncertain. One study found that a high dosage of the LMWH dalteparin was more effective than placebo in preventing left ventricular thrombi after acute myocardial infarction, but there was a significant safety cost. Current questions surrounding prophylaxis of VTE and the use of LMWH in acutely and/or critically ill patients include whether monitoring levels and dosage adjustment in some of these patients would improve outcome, and whether the diagnosis of VTE can be improved so that treatment can be instituted when prophylaxis has failed.
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PMID:Risk assessment and prophylaxis of venous thromboembolism in acutely and/or critically ill patients. 1125 46

I suggest that insulin suppresses the secretion and antagonizes the harmful effects of tumor necrosis factor-alpha, macrophage migration-inhibitory factor, and superoxide anion. Therefore, the glucose-insulin-potassium regimen might be beneficial in acute myocardial infarction and useful in the management of patients with septicemia, septic shock, and other inflammatory diseases in which tumor necrosis factor-alpha and macrophage migration-inhibitory factor have important roles.
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PMID:Is insulin an antiinflammatory molecule? 1204 30


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