Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A 43 year old woman was admitted to our hospital in April 1987 due to shortness of breath and pedal edema. She had a history of sepsis associated with the crisis of hyperthyroidism 15 years prior to the admission. Physical examination revealed a badly nourished with ascites: weight was 56 kg and height 156 cm. The heart sounds were distant with mild holosystoric murmur (grade I/VI) at xiphoisternum. The chest X-ray showed cardiomegaly (CTR: 72.3%) with pleural effusion. The electrocardiogram showed atrial fibrillation, low voltage and right ventriculer hypertrophy. The echocardiogram showed marked dilatation of right atrium and ventricle with very short septal leaflet of tricuspid valve. The anterior and posterior leaflets were undetected. The tricuspid regurgitant doppler signal was recorded up to hepatic vein. No other abnormalities were noted in other valves. The white cell count was 4900 with lymphocytopenia (26%; T-cell 82%, B-cell 13%). Serum total protein was reduced to 3.4 g/dl with albumin 1.64 g/dl. Immunoelectrophoresis showed normal IgG, IgA and IgM. Proteinuria was not recognized. Fecal excretion of polyvinylpyrrolidone-131I (PVP) was elevated to 2.8%, The systolic pressure in pulmonary artery, right ventricle, right atrium, superior and inferior vena cave were almost equal as 26 mmHg. The pulmonary arterial scintigraphy disclosed multiple peripheral defects in both lungs. Two weeks after the operation of tricuspid valve replacement based on the diagnosis of protein-losing enteropathy due to isolated tricuspid regurgitation, serum total protein and albumin were normalized to 6.8 g/dl and 3.6 g/dl respectively, but the lymphocytopenia was persistent. She become very well, with free of ascites and edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of isolated tricuspid regurgitation associated with protein-losing gastroenteropathy]. 273 14

Bradykinin (BRADY) is hypothesized to cause the "capillary leak" syndrome in patients with sepsis, trauma, and burns. Our purpose was to determine if isoproterenol (ISO) reversed a BRADY-produced accelerated loss of intravascular fluid and protein into the interstitium of skin. An increase in microvascular permeability in canine hind paw skin was sustained by a continuous femoral artery infusion of BRADY (0.2 micrograms/kg/min). After 2 hours of BRADY, skin lymph flow (LYM FLOW microliters/min) increased nine-fold and skin lymph-to-plasma total protein concentration ratio (RTP) was substantially increased. Mean blood flow in the femoral arteries was increased four-fold by the BRADY infusion. After 2 hours of BRADY-induced increased permeability, five of the ten dogs were started on intravenous ISO (2 micrograms/min continuously) which increased heart rate from 182 +/- 15 to 222 +/- 11 beats/min. ISO reversed the increase in RTP produced by the BRADY. After 8 hours of BRADY, there was less tissue albumin in the dogs given ISO (14.5 +/- 2.0 vs. 29.5 +/- 6.6 mg/gram dry wgt, p less than 0.05 unpaired t-test). ISO can reverse the sustained increase in skin microvascular permeability produced by BRADY.
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PMID:Isoproterenol inhibits the increase in microvascular membrane permeability produced by bradykinin. 276 Sep 47

Forty-eight piebald-lethal (PL) mice with distal aganglionosis and 42 normal littermates (LM) were studied to determine the cause of early death. PL mice were noted to be smaller than their LM and to have normal albumin and immunoglobulin levels for the first 30 days of age. As PL mice aged, a significant decline in albumin with a concomitant rise in immunoglobulin levels was demonstratable. Systemic sepsis with enteric organisms was found in 10% of sacrificed PL mice and in 38% of spontaneously dying PL animals. Histologic examination of PL aganglionic and ganglionic colon demonstrated no evidence of enterocolitis. Ganglionic colon of PL mice contained a flattened, thinned mucosa. The early death of PL mice is related to generalized debilitation from prolonged distal colonic obstruction resulting in a decrease in immunologic integrity and an increased susceptibility to sepsis.
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PMID:The piebald-lethal murine strain: investigation of the cause of early death. 277 85

Twenty patients with extensive thermal injury were entered into a prospective randomized double-blind trial of prophylactic intravenous immunoglobulin administration. Ten patients received intravenous immunoglobulin and ten, albumin controls. No statistically significant difference was found between mortality rates, mortality rates from sepsis, the incidence of positive blood cultures, the positive quantitative wound biopsies, urine cultures, or positive intravenous line cultures. No significant improvement was noted in assays of neutrophil chemotactic index or intracellular kill, assays of lymphocyte function, or helper/suppressor ratio. We did, however, note significant improvement in the incidence of polymicrobial blood cultures, cytomegalovirus titers, and blood endotoxin concentration in treated patients. While the high incidence of inhalation injury (16 out of 20 patients) and, therefore, the disproportionately high mortality rate (40% overall) in the study group do not permit extension of these observations to the burn patient population at large, certain cautious recommendations may be made with regard to the use of intravenous immunoglobulin G in the management of burn patients.
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PMID:Prophylactic intravenous immunoglobulin replacement in high-risk burn patients. 282 23

The efficacy of ceftazidime in the treatment of neonatal sepsis was studied in 42 low birthweight premature babies. Forty-nine courses of ceftazidime (25 mg/kg bd, iv or im were administered. In 19 babies, treatment was stopped after 48 h, the remainder were treated for 5 days or more. Six neonates had bacteriological evidence of infection, one other was pyrexial and 29 had radiological evidence compatible with respiratory tract infection. Eight of the study population died. Only one death was attributed to infection which arose 3 days after completion of a 5-day course of ceftazidime. Two babies developed clinical signs of necrotizing enterocolitis (NEC). Clostridium difficile (7) and Cl. perfringens (2) were isolated from 34 post-treatment faecal samples but not from the two babies with NEC. No faecal sample contained Cl. difficile toxin. Post-treatment cultures from 12 neonates yielded ceftazidime-resistant micro-organisms. Ceftazidime therapy was not associated with significant alteration in serum alanine aminotransferase, urea, creatinine, protein or albumin. Four babies had an eosinophilia, three transient and one following two intrauterine transfusions. Coombs' tests were performed on 17 babies. There were no false positives. The abnormal clotting studies observed in one baby were not due to ceftazidime. In a concurrent pharmacokinetic study, the half-life of ceftazidime was 7.4 (SD +/- 4.1) h following iv administration. Other pharmacokinetic values were C max 74 (SD +/- 20) mg l-1 trough concentration 20 (SD +/- 10) mg l-1. Total body clearance ranged from 0.13 to 2.10 ml min-1 per kg and increased with increasing postnatal age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ceftazidime in the treatment of neonatal infection. 286 90

Sixty patients with inoperable non-small-cell lung cancer (NSCLC) were entered into a phase II study that tested the combination of cisplatin (80 mg/m2, day, etoposide intravenously (IV) (100 mg, days 1 and etoposide orally (200 mg/m2, days 3 and 5). The regimen was repeated every 28 days for six courses, after which patients were allowed to receive additional treatment at the discretion of their physician. Overall objective response rate in 51 evaluable patients was 69% (95% confidence interval: range, 56% to 81%), with 16% sustaining complete remission (CR), 53% partial remission (PR), 17% stable disease (SD), and 14% progressive disease (PD). CR was pathologically confirmed by bronchoscopy and biopsy. One patient with a clinical PR underwent surgery and was shown to have a pathologic CR. Median survival of all evaluable patients was 52 weeks, greater than 75 weeks for CR patients, 52 weeks for PR patients, 42 weeks for SD patients, and 13 weeks for PD patients. Eleven patients (21.5%) developed CNS metastases, which resulted in the deaths of ten. Survival was significantly correlated with extent of disease, performance status, and albumin level, but not with histology or weight loss. Tumor response was significantly correlated only with histology (squamous-cell and large-cell undifferentiated carcinoma greater than adenocarcinoma). Side effects were nausea, vomiting, anorexia, alopecia, bone marrow suppression, and nephrotoxicity. One patient died from leukopenia and sepsis. Pharmacokinetic studies in ten patients showed the continuous presence of etoposide in plasma for six days at a level of at least 220 to 480 ng/mL. In order to investigate whether this very effective combination of cisplatin and etoposide can prolong survival in NSCLC, it will be tested as preoperative chemotherapy in a randomized trial in operable patients with T1N1 and T2N0-1 disease.
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PMID:A multicenter phase II trial of cisplatin and oral etoposide (VP-16) in inoperable non-small-cell lung cancer. 302 Jul 7

The purpose of this study was to identify which of the biochemical, immunological, or functional parameters derived before surgery as part of a systemic evaluation were helpful in predicting the frequency of rejection episodes, the chance of survival, and the cause risk of death (should death occur) of patients after orthotopic liver transplantation (OLTx). Ninety-eight adult patients who had an extensive preoperative protocol evaluation were studied before OLTx. The biochemical parameters assessed were albumin, prothrombin time, bilirubin, and ICG clearance. The immunologic parameters assessed included total lymphocytes, T3 cells, T4 cells, T8 cells, and the T4/T8 ratio. The degree of histocompatibility antigen (HLA) matching between the donor and the recipient was also evaluated in 80 of the 98 patients studied. Most postoperative deaths occurred within 12 weeks of the procedure (24%; 24 of 98 patients); 13 patients (13%) died within the first 6 postoperative weeks, of either bacterial or fungal sepsis. An additional 14 patients (14%) died after the initial 6 postoperative weeks due, primarily of an acquired viral and/or protozoan infection (p less than 0.01). During the first 6 weeks, survival was better for patients with cholestatic liver disease (ChLD, 93%, n = 45) and miscellaneous liver diseases (MISC, 100%, n = 10) than it was for those with parenchymal liver diseases (PLD, 77%, n = 43). Although albumin, prothrombin time, T4/T8 ratios, and per cent T8 cells were statistically different in patients with PLD as compared with those with ChLD, these parameters, as well as the per cent T4 cells, serum bilirubin level, per cent retention of ICG at 15 minutes, and the plasma ICG disappearance rate were not found to be of substantial help in predicting patient survival or non-survival. Moreover, neither the degree of HLA matching nor the number of rejection episodes differed between surviving and nonsurviving patients. The results of this study suggest that patients with PLD are at increased risk of early postoperative death after OLTx because of bacterial and/or fungal sepsis, as compared with patients operated upon for ChLD. Better pre-, intra-, and postoperative predictors of risk of death and complications are needed to reduce the early mortality observed after orthotopic liver transplantation.
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PMID:Relationship between the diagnosis, preoperative evaluation, and prognosis after orthotopic liver transplantation. 304 26

Tumor necrosis factor alpha (TNF), a monokine produced by mononuclear cells in response to bacterial endotoxin (LPS), creates a syndrome similar to septic shock in animal models. To study whether TNF could induce acute lung injury similar to that seen in gram-negative sepsis, we injected recombinant human TNF (rHuTNF alpha) into guinea pigs and monitored arterial blood gases, leukocyte counts, and left atrial (Pla), pulmonary artery (Ppa), and mean arterial pressures (MAP) serially for 8 h. Pulmonary histopathology was assessed microscopically, and cell counts and 125I-labeled albumin (125I-albumin) in bronchoalveolar lavage (BAL) fluid and lung wet/dry weight ratios were determined. Five groups of animals were studied; the 2 TNF groups received high (1.4 X 10(6) U/kg) or low (1.0 X 10(6) U/kg) doses of rHuTNF alpha, the sepsis group received 2 X 10(9) Escherichia coli/kg intravenously, and the control group received saline. An LPS control group receiving 40 ng/kg E. coli LPS was also included because the rHuTNF alpha contained a small amount of LPS as a contaminant. Pulmonary permeability was assessed by studying the Pla and the BAL fluid/plasma 125I-albumin ratio (permeability index). The permeability index was significantly increased in the high-dose TNF (0.0408 +/- 0.0041, p less than 0.05) and sepsis groups (0.0466 +/- 0.0068, p less than 0.01) relative to controls (0.0215 +/- 0.0028). The wet/dry lung weight ratios were also significantly increased in the high-dose TNF (6.07 +/- 0.29, p less than 0.05) and sepsis groups (6.22 +/- 0.30, p less than 0.05) relative to the control group (5.18 +/- 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor causes increased pulmonary permeability and edema. Comparison to septic acute lung injury. 305 59

To examine the role of polymorphonuclear neutrophils (PMN) and other granulocytes in the pathogenesis of acute lung injury caused by tumor necrosis factor alpha (TNF), we compared the permeability edema and pulmonary histopathology in normal (granulocyte sufficient) guinea pigs and in granulocytopenic guinea pigs treated with TNF. Circulating granulocytes were depleted with cyclophosphamide. Two groups of normal animals were treated with either saline (PMN+/Control) or 1.4 x 10(6) U/kg recombinant human TNF (PMN+/TNF). Three granulocytopenic groups were treated with either saline (PMN-/Control), TNF (PMN-/TNF), or intravenous infusion of 2 x 10(9) E. coli strain J96 (PMN-/Sepsis). We measured the amount of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid and whole lung tissue and the wet/dry lung weight ratio to assess pulmonary transvascular protein flux and edema. We also quantified PMN in BAL fluid and fixed lung tissue. There were no statistically significant differences in any of these parameters between the PMN+/Control, PMN-/Control, or PMN-/TNF groups, except that the PMN+/Control predictably had more PMN/alveolus than the PMN- groups. However, both the PMN+/TNF and the PMN-/Sepsis groups had increased amounts of 125I-labeled albumin in BAL fluid and lung tissue (p less than 0.01) and increased wet/dry lung weight ratios (p less than 0.05), compared to all other groups. Histopathologically, capillary congestion and moderate inflammation were seen in the PMN+/TNF group, and acute inflammation and gross alveolar hemorrhage were seen in the PMN-/Sepsis group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs. 305 92

The effects of sepsis on lipid metabolism may be summarized as follows: The increased plasma catecholamine concentration stimulates adipose tissue FFA release. The increased FFA mobilization and plasma concentration results in an enhanced FFA uptake by the liver which promotes TGFA synthesis and output. Thus, triglyceride appearance rate also can be increased during hypermetabolic sepsis. In severe sepsis, the regulatory signals to increase FFA release from adipose tissue may be counterbalanced by blood flow limitations that inhibit FFA release, possibly due to the inadequate availability of the plasma carrier, albumin. Under such conditions, the arterial FFA concentration may be unchanged or decreased along with similar changes in the rate of peripheral FFA utilization. Triglyceride metabolism can also be altered during septic conditions in which plasma levels of cytokines are very high. Cytokines, notably TNF and IL-1, suppress synthesis of lipoprotein lipase which decreases the rate of TGFA clearance. Thus, hypertriglyceridemia can develop in the absence of elevated plasma FFA levels. The plasma concentration of cytokines necessary to inhibit LPL and how often this form of hypertriglyceridemia occurs in human sepsis are unknown at present. The sequence of events describing the influence of sepsis on carbohydrate metabolism is postulated to be the following: The presence of bacteria, or their products (eg, endotoxin) either directly or indirectly (via stimulating mononuclear phagocytes to release cytokines) activate the immune tissues. Glucose utilization by these tissues, which are predominantly glycolytic, is thereby stimulated resulting in increased lactate production. At the same time, glucose uptake by skeletal muscle and lactate release are also elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in lipid and carbohydrate metabolism in sepsis. 306 39


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