Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the study was to correlate degree of hypocholesterolemia to changes in plasma levels of amino acids and other metabolic variables in severely injured septic patients. Measurements included plasma cholesterol, full amino-acidograms, acute phase proteins, complementary variables and blood cell counts. The Fischer plasma molar amino acid ratio (leucine+isoleucine+valine)/(phenylalanine+tyrosine) was calculated. Plasma cholesterol for all measurements (n=145) was 3.1+/-1.1 mmol/L and, upon entry in the study, it was correlated inversely with sepsis severity score (p<0.05). Along the clinical course, changes in cholesterol were clearly paralleled by opposite changes in C-reactive protein, which was the best correlate of cholesterol (r2=0.70, p<0.0001). Furthermore cholesterol was inversely related to phenylalanine, fibrinogen, lactate and white blood cell count, and directly to the Fischer molar amino acid ratio, cystathionine, methionine, glycine and transferrin (r2 between 0.36 and 0.15, p<0.0001 for all). Within this pattern of correlations, cholesterol was also directly related to alkaline phosphatase, which accounted for the effect of cholestasis, when present. For any given value of the other variables, cholesterol increased significantly with increase in alkaline phosphatase (p<0.0001). C-reactive protein (CRP, mg/dl) and alkaline phosphatase (ALKPH, U/L) together in the same regression explained 79% of the variability of cholesterol (CHOL, mmol/L): CHOL=5.90-0.74[Log(e)CRP]+0.004[ALKPH]; multiple r2=0.79, p<0.0001. Inclusion in this regression of other variables did not increase the r2. By using only amino acid variables, the best fit was provided by a regression including the Fischer ratio and cystathionine, which explained 55% of the variability of cholesterol (multiple r2=0.55 p<0.0001), and this result was not improved by the inclusion of other amino acids. These data show that severity of hypocholesterolemia in sepsis is quantifiably related to changes in plasma amino acids, and to severity of acute phase response and metabolic decompensation. More study is needed to understand whether hypocholesterolemia in sepsis has only diagnostic or prognostic implications, or that it may also contribute actively to worsening of the disease.
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PMID:The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis. 1530 77

Bicuculline methiodide attenuates inflammation by inhibiting the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, and by increasing the production of the anti-inflammatory cytokine interleukin-10, both of which play important roles in the pathogenesis of sepsis. The aim of this study was to examine the effects of bicuculline methiodide on sepsis in the cecal ligation and puncture septic-rat model. Cytokine production was measured by enzyme-linked immunosorbent assay. Oxidative stress was assessed by determining serum lipid peroxidation and nitrite levels. Hepatic injury was evaluated by determining the levels of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Mortality was recorded within 24 h. Bicuculline methiodide potently decreased the production of tumor necrosis factor-alpha and interleukin-1beta but increased interleukin-10 in serum. Bicuculline methiodide significantly decreased serum lipid peroxidation and nitrite levels. Further, bicuculline methiodide attenuated hepatic injury and reduced mortality after cecal ligation and puncture. Therefore, the alteration of cytokine production may be involved in the effects of bicuculline methiodide on hepatic injury and mortality in septic rats.
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PMID:Bicuculline methiodide attenuates hepatic injury and decreases mortality in septic rats: role of cytokines. 1537 90

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology. Despite advances in understanding the pathophysiology underlying this disorder, no effective medical therapy has been identified for halting disease progression. The aim of this investigation was to determine the safety and estimated efficacy of mycophenolate mofetil (MMF) for the treatment of PSC. Thirty patients with PSC received MMF 1 g daily to a maximum of 3 g daily for 1 yr. Liver tests were determined at 3-month intervals with the Mayo risk score calculated at baseline and at the end of therapy. Twenty-three (77%) patients completed 1 yr of therapy. Significant but clinically marginal improvement in serum alkaline phosphatase level after 1 yr of therapy was observed (1135 +/- 581 U/L vs 912 +/- 463 U/L, p= 0.02). No other significant changes in liver biochemistries or Mayo risk score was observed. Seven patients (23%) discontinued MMF due to adverse events possibly related to therapy. Adverse reactions resolved spontaneously or with dose reduction in 10 (33%) patients. One patient developed pancreatitis, bacterial cholangitis, and sepsis during the eighth month of MMF therapy. No patient developed cytopenia on therapy. In conclusion, MMF does not appear to have clinically important benefits for PSC despite being tolerated by most patients. The results of this pilot study do not support further study of MMF as a single agent in the treatment of PSC.
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PMID:Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. 1566 87

A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical measurements were prospectively performed on 92 liver resection patients, and processed to assess the correlations between ALB, other plasma proteins, additional variables and clinical events. The measurements were performed preoperatively and at postoperative day 1, 3 and 7 in all patients, and subsequently only in those who developed complications or died. In patients who recovered normally ALB was 4.3 +/- 0.4 g/dl (mean +/- SD) preoperatively, 3.7 +/- 0.7 at day 1 and 3, and 3.9 +/- 0.4 at day 7. In patients with complications its decrease was more prolonged. In non-survivors it was 3.4 +/- 0.4 preoperatively, 3.0 +/- 0.4 at day 1, and then decreased further. Regression analysis showed direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300-13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl), prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables and dose of exogenous albumin. An inverse relationship found between ALB and age (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing larger age-related decreases in ALB associated with complications (COMPL: sepsis, liver insufficiency) or death (DEATH). Main overall correlations: CHE = 287.4(2.014)(ALB), r = 0.73; CHOL = 16.5(1.610)(ALB) (1.001)(ALKPH), r = 0.71; IBC = 68.6(1.391)(ALB), r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 + 20.2(CREAT) - 6.2(ALB), r = 0.91; ALB = 5.0-0.013(AGE) - {0.5 + 0.003(AGE)( COMPL ) + 0.012(AGE)( DEATH )}( POSTOP ), r = 0.74 [p < 0.001 for each regression and each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent determinant of CHOL; discontinuous variables in italics label the change in regression slope or intercept associated with the corresponding condition]. These results suggest that altered albumin synthesis (or altered synthesis unable to compensate for albumin loss, catabolism or redistribution) is an important determinant of hypoalbuminemia after hepatectomy. The correlations with age and postoperative outcome support the concept that hypoalbuminemia is a marker of pathophysiologic frailty associated with increasing age, and amplified by the challenges of postoperative illness.
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PMID:The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man. 1658 10

Alkaline phosphatase is a promising therapeutic agent in the Gram-negative bacterial lipopolysaccharide (LPS) mediated acute and chronic diseases. Contrary to other alkaline phosphatase isozymes, purified tissue-nonspecific alkaline phosphatase (TNAP) is not available in large quantities from tissue sources, which would enable to analyse its efficacy in animal sepsis models. Two transgenic rabbit lines were created by pronuclear microinjection with the whey acidic protein promoter-humanTNAP minigene (WAP-hTNAP). Lactating females of both lines produced biologically active human TNAP. As indicated by fractionation of milk samples the recombinant alkaline phosphatase was associated with the membrane of milk fat globules. Alkaline phosphatase enzymatic activity was two orders of magnitude higher compared to normal human serum levels. The demonstration that this TNAP is physiologically active would provide the clue to use transgenic animals as bioreactor for bulk production of the human tissue-nonspecific alkaline phosphatase in milk. This may be a valuable and possibly viable option with important implication in attenuating LPS mediated inflammatory responses.
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PMID:High level expression of tissue-nonspecific alkaline phosphatase in the milk of transgenic rabbits. 1682 24

A prospective study of two types of total parenteral nutrition (TPN) was carried out in 34 patients suffering from sepsis and complicated liver dysfunction. Group 1 (18 patients) received non-protein energy as glucose plus fat emulsion in a caloric ratio of 19:1, while group 2 (16 patients) received the same energy intake but with a ratio of 1:1. Group 1 exhibited higher levels of bilirubin and alkaline phosphatase with values of 93.5 +/- 25.5 mumol/l and 160 +/- 30 IU/l respectively compared to Group 2, in which the corresponding values were 81.6 +/- 32.3 mumol/l and 120 +/- 10 IU/l (p < 0.05). On the other hand, group 1 had lower levels of serum albumin and serum transferrin with values 25 +/- 1.3 g/l and 40 +/- 20% of normal, compared to group 2 in whom the corresponding values were 28 +/- 8 g/l and 48 +/- 30% of normal (p < 0.05). There were no differences between the two groups, in the absolute number of T-lymphocytes and in transaminase levels. In sepsis complicated by liver dysfunction a 50:50 glucose: fat regimen caused less disturbance of liver function than one consisting almost entirely of glucose.
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PMID:Glucose-based versus fat-based total parenteral nutrition (TPN): effects on hepatic function in septic patients complicated with cholestatic jaundice. 1683 62

Fasciolosis is recognized as an important human disease. Wistar rats experimentally infected with Fasciola hepatica were examined using data obtained in the advanced chronic state of the disease (200, 300 and 400 days post-infection, dpi). Pigment stones (PS) and bile specimens were collected. The same procedure was applied in control rats. Liver tests were determined using stored serum samples. Bacteriological bile culture revealed viable bacteria (Escherichia coli, 45% of cases, Enterococcus faecalis, 45% and Klebsiella pneumoniae, 10%). The presence of bacterobilia was associated with liver serum enzymes, including aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT), alkaline phosphatase (AP) and total bilirubin levels. Multivariate analysis suggested an association between bacterobilia and the following factors: duration of parasitic infection and intensity of parasitic infection supported the impression that the obstruction caused by advanced chronic fasciolosis in the rat may be related to biliary sepsis. Extrapolation to human infection in fasciolosis hyperendemic areas is discussed. In conclusion, the results of the rodent model should lead to a reconsideration of treatment features in human disease, i.e. therapeutic strategies should not only include a parasitic treatment but also consider the possibility of bacterial co-infection.
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PMID:High risk of bacterobilia in advanced experimental chronic fasciolosis. 1706 56

Biliary complications after liver transplantation (LT) using organs retrieved from donors after cardiac death are not well characterized. The aim of this study was to evaluate the severity of biliary complications and outcomes after donation after cardiac death liver transplantation (DCD-LT). A retrospective evaluation of 20 DCD-LTs from 1997-2006 was performed. The recipient age was 53+/-8.7, and the donor age was 35+/-11 years. The warm ischemia time, cold ischemia time, peak alanine aminotransferase level, and peak aspartate aminotransferase level were 33+/-12 minutes, 8.7+/-2.7 hours, 1757+/-1477 U/L, and 4020+/-3693 U/L, respectively. The bilirubin and alkaline phosphatase levels at hospital discharge after LT were 3.2+/-5.4 mg/dL and 248+/-200 U/L, respectively. During a median follow-up of 7.5 months (range: 1-73), 5 patients (25%; 1 death after re-LT) died (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from a cardiac event at 46 months), and additionally, 4 patients (20%) required re-LT (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction, and 2 because of biliary strictures). Twelve (60%) developed biliary complications, and of these, 11 (55%) had serious biliary complications. The biliary complications were as follows: a major bile leak for 2 patients (10%; both eventually underwent retransplantation), anastomotic strictures for 5 patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%), stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients (10%). More than 1 biliary complication was seen in most patients, and these were unpredictable and required multiple diagnostic or therapeutic procedures. Serious biliary complications are common after DCD-LT, and research should focus on identifying donor and recipient factors that predict and prevent serious biliary complications.
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PMID:Biliary complications and outcomes of liver transplantation from donors after cardiac death. 1804 64

Results of prospective study of 398 patients with abdominal sepsis are analyzed. It is demonstrated that acute hepatic failure occurs at 45% of these patients and it is direct cause of death at 28% of them. Blood level of triglycerides and alkaline phosphatase are reliable markers of hepatic dysfunction at abdominal sepsis. Concentrations of these markers are associated with severity of patients and systemic inflammation syndrome, and also with the number of performed laparotomies.
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PMID:[Diagnosis of hepatic failure at the patients with abdominal sepsis]. 1816 11

The purpose of this study was to evaluate liver function tests as potential indicators of bacteremia. We examined 156 patients with laboratory-confirmed bacteremia (bacteremia group) and 211 bacteremia-negative patients with bacterial infections (control group). The patients of the two groups had no underlying liver diseases. For patients in the bacteremia group, we analyzed liver function tests results obtained the day when the first positive blood culture was ordered. For those in the control group, the same data were obtained on the day when the first of multiple negative blood cultures was ordered. At t-test analyses, serum levels of gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase (ALP) were significantly higher, and those of albumin, total cholesterol, and cholinesterase were significantly lower in the bacteremia group than in the control group. Multivariate analyses found serum cholinesterase as an independent factor with adjusted odds ratio of 0.319 (per 65 U/L, standard deviation [SD] size). Serum level of C-reactive protein (CRP), on the other hand, showed no significant difference between the two groups. Serum levels of gamma-GT, ALP, albumin, total cholesterol, and cholinesterase more rapidly altered when various bacterial infections accompanied bacteremia. Therefore, they may be useful in detecting sepsis in its early stages.
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PMID:Liver function tests in patients with bacteremia. 1820 May 69


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