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)

We examined serum transthyretin levels after thermal injury in a longitudinal study of 61 patients with burn injury from day 2 to day 28 after trauma. All the patients had a maximal decrease in transthyretin levels between days 6 and 8. Transthyretin values remained lower during the recovery phase in patients who died than in patients who survived. In addition, persistently low transthyretin values were associated with sepsis in the survivors. Finally, transthyretin levels were only slightly dependent on the extent of the burn injury. These results emphasize the interest of transthyretin monitoring in patients with burn injuries.
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PMID:Serum transthyretin levels in patients with burn injury. 202 Sep 9

Plasma levels of interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL-6), and markers of protein metabolism were determined in 12 burn patients throughout the healing period (day 2 to 21 post-injury) to determine the pattern of variations in plasma cytokine concentration. To establish the relationship between cytokine production and the nutritional status a wide range of severity standpoints (burn surface area ranging from 9% to 82%) was chosen. Interleukin 6 levels were increased in all patients throughout the study period; maximum concentrations (615 +/- 198 pg/mL) were reached on day 4 and correlated (p < 0.01) with the extent of burn injury. Tumor necrosis factor alpha levels were also elevated; they were significantly higher on day 7 in the patients who developed sepsis than in the other patients (67 +/- 21 pg/mL vs. 20 +/- 7 pg/mL; p < 0.05) but did not correlate with the extent of burn injury. Interleukin 1 beta was rarely detected. Cortisolemia on day 7 was inversely correlated with levels of TNF alpha but not with those of IL-6. Interleukin 6 levels correlated positively with protein turnover (phenylalaninemia) and catabolism (3-methylhistidine/creatinine ratio) and negatively with levels of fibronectin and transthyretin. Our data indicate that the systemic cytokine response to burn injury is mainly represented by IL-6. These data also support the hypothesis that IL-6 is a key mediator of the variations in protein metabolism following burn injury.
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PMID:Cytokine response to burn injury: relationship with protein metabolism. 818 61

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.
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PMID:Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons. 930 58

Inflammatory stimulation of hepatic acute phase protein expression is, in part, modulated by tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-beta), and IL-6. These cytokines also may mediate some aspects of the persistent inflammation and metabolic dysregulation of sepsis. Cecal ligation and puncture (CLP) sepsis in male Sprague-Dawley rats inappropriately decreases hepatocellular transcription of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), carnitine palmitoyltransferase II (CPTII), acetyl CoA acyltransferase (ACA), and ornithine transcarbamylase (OTC). We hypothesize that 1) transcriptional reprogramming does not occur after simple inflammation induced by subcutaneous turpentine injection, 2) the pattern of acute phase gene expression after CLP differs from that following turpentine injection, and 3) the different responses reflect differences in the intrahepatic activity of TNFalpha/IL-1beta or IL-6. Gene expression, transcription factor activity, and cytokine abundance were determined after either a subcutaneous injection of turpentine or CLP. After turpentine injection, PEPCK, G6Pase, CPTII, ACA, and OTC expression were unchanged, different from previously reported data following CLP. Both turpentine injection and CLP increased expression of TNFalpha/IL-1beta-regulated alpha1-acid glycoprotein, and IL-6-regulated alpha2-macroglobulin and decreased expression of transthyretin (a negative acute phase protein). However, the magnitude and temporal pattern of expression differed. Turpentine injection increased the activity of the TNFalpha/IL-1beta-linked transcription factor NF-kappaB and the intrahepatic abundance of TNFalpha in a manner similar to that observed after CLP but only slightly altered the activity of the IL-6-linked transcription factor Stat-3 and intrahepatic IL-6 abundance. This differed significantly from observations after CLP. We conclude that CLP-induced alterations in hepatic gene expression may reflect differences in IL-6 activity.
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PMID:Hepatic gene expression and cytokine responses to sterile inflammation: comparison with cecal ligation and puncture sepsis in the rat. 1035 41

The principal thyroxine (T4) binding proteins were measured in 8 septic patients and 8 controls to determine the extent to which a decrease in their concentration contributes to the decrease in serum T4 in sepsis. T4 binding globulin (TBG) evaluated by radioimmunoassay (RIA) and radial immunodiffusion (RID) was 61% and 66%, respectively, of the normal mean value in sera from septic patients. Decreases of albumin and transthyretin (TTR) to 55% and 29%, respectively, of the normal mean concentration contributed to the loss of T4 binding power in these sera. Total serum binding of T4, calculated from the normal contribution of each protein to T4 binding and the reduction of its concentration in septic patients, was 55% of that in the normal controls. This decrease in the estimated protein binding of T4 was proportional to the decrease of serum T4 from a mean of 8.4 microg/dL in the normal controls to 4.7 microg/dL (56% of the control) in the septic patients. Because TBG binds most of the serum T4, the decrease in the TBG concentration was the major factor in the decrease of total T4 binding power. Since the concentration of the major T4 binding proteins decreased sufficiently to account for the decrease in serum T4, it is unnecessary to postulate the effects of additional factors such as binding inhibitors or modification of T4 binding protein affinity.
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PMID:Concordant decreases of thyroxine and thyroxine binding protein concentrations during sepsis. 1087 1

Familial amyloid polyneuropathy type I (FAP-I) is an inherited amyloidosis secondary to systemic deposition of amyloid fibrils containing mutant transthyretin (TTR) variants. The disease has a progressive clinical course and is usually fatal 10 years after its onset. TTR is mainly produced in hepatocytes, and liver transplantation (LT) has been proposed as an effective treatment for FAP-I. The aim of this study is to evaluate the results of LT for FAP-I in Brazil and analyze prognostic factors associated with survival after surgery. Twenty-four patients (median age, 36 years; range, 25 to 52 years) who underwent LT with the diagnosis of FAP-I were evaluated. Surgery was uneventful in all but six patients who died of complications of primary liver nonfunction (n = 1), cardiogenic shock (n = 1), sepsis (n = 3), and hepatic artery thrombosis (n = 3). Overall 1- and 5-year survival rates were 70% and 58%, respectively. Most patients had stabilization or improvement of symptoms after a median follow-up of 36 months (range, 14 to 82 months). Survivors had a shorter disease duration before LT (median, 6 years; range, 2 to 17 years v 9 years; range, 7 to 12 years; P =.02), greater albumin levels (median, 4 g/dL; range, 3 to 4.7 g/dL v 3.6 g/dL; range, 2.6 to 4.1 g/dL; P =.03), and greater modified body mass index scores (median, 735; range, 502 to 1,432 v 659; range, 411 to 803; P =.04) compared with nonsurvivors. However, only disease duration and albumin levels were independently associated with survival in multivariate analysis. In conclusion, LT is an effective therapy for FAP-I. Mortality after surgery is associated with poor nutritional status and long-standing disease before LT. Thus, LT should be performed as early as possible after the onset of FAP-I symptoms to avoid major disability and improve survival.
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PMID:Results of liver transplantation for familial amyloid polyneuropathy type I in Brazil. 1179 83

Few cases of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy have been reported, and the technique for the operation is far from being consolidated. Three patients with amyloidogenic transthyretin (ATTR)-related (variant Glu89Gln to ATTR Glu89Gln) cardiomyopathy underwent CHLT at our institution. Patient 1 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All three patients underwent cardiac and sequential hepatic transplantation using the piggyback technique with organs procured from the same donor. Venovenous bypass (VVB) was used only in patient 1, with an uncomplicated procedure. After CHLT, his cardiac performance remained normal, and no progression of amyloidosis was observed. Patient 2 had no intraoperative complications, but experienced postoperative bleeding, renal failure, sepsis, and heart failure and eventually died of multiorgan failure 2 months after transplantation. In patient 3, right hemicolectomy was required intraoperatively because of intestinal ischemia without significant hemodynamic perturbations, whereas extracardiac symptoms of amyloidosis gradually worsened postoperatively. Two patients (no. 1 and 3) currently are alive after 38 and 18 months, respectively. CHLT for ATTR Glu89Gln can be performed successfully, even in patients with advanced disease. However, the most compromised patients are more exposed to intraoperative risks, postoperative complications, and worsening of extracardiac and extrahepatic symptoms. The need for VVB remains to be evaluated.
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PMID:Combined heart and liver transplantation for familial amyloidotic neuropathy: considerations from the hepatic point of view. 1294 63

There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy (FAP). The technique for the operation remains to be defined. Four CHLTs were performed for amyloidogenic transthyretin-related (variant Glu89Gln-ATTR Glu89Gln) cardiomyopathy in our center. Patients 1 and 4 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All four patients underwent cardiac and sequential hepatic transplantation with organs procured from the same donor. Venovenous bypass was used in patients 1 and 4 who experienced uncomplicated procedures. The amyloidotic liver of patient 4 was successfully utilized for a domino procedure to treat a patient with hepatocellular carcinoma on cirrhosis. The cardiac performance of patients 1 and 4 remains normal; there has been no progression of amyloidosis at 42 and 1 months after transplantation. Patient 2 had no intraoperative complications but experienced postoperative bleeding, renal failure, sepsis, and heart failure, and finally died of multiorgan failure 2 months after transplant. In patient 3, right hemicolectomy was required intraoperatively due to intestinal ischemia, without significant hemodynamic instability, while extracardiac symptoms of amyloidosis gradually worsened postoperatively. In conclusion, CHLT for ATTR Glu89Gln may be performed even in patients with advanced disease. However, the most compromised patients are more likely to display intraoperative risks, postoperative complications, and worsening of extracardiac, extrahepatic symptoms.
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PMID:Combined heart and liver transplantation in four adults with familial amyloidosis: experience of a single center. 1511 Jun 20

Classical familial amyloid polyneuropathy may have a course with progressive renal impairment. We studied 62 patients (24 males, 38 females) with FAP, transthyretin variant V30M, and end-stage renal disease (ESRD) treated with hemodialysis, all referred to a single center over a period of 11 years. Clinical course, morbidity and survival after dialysis were analyzed. Patient's mean age at first dialysis was 51.5 +/- 10.7 years, and mean duration of neuropathy was 10.2 +/- 3.8 years. The most frequent form of presentation of FAP nephropathy was nephrotic proteinuria with renal dysfunction. In the year prior to dialysis, renal function declined rapidly, and fluid overload was the main indication to initiate treatment. The presence of decubitus ulcers, significant disability, venous catheter for definitive vascular access for long-term treatment, and permanent bladder catheter, were related to death during the first year of dialysis. The mean duration of renal replacement therapy was 21 months, with a 54.5% one year, and 38.4% two year treatment survival. However, when the duration of neurological symptoms at first dialysis exceeded 10 years, survival was significantly lower. Infections, (41% were decubitus ulcers with sepsis) were the cause of early, as well as late mortality. Early creation of vascular access for hemodialysis, surveillance of skin wounds, and intervention on neurogenic bladder are essential to improve the prognosis of ESRD in FAP.
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PMID:End-stage renal disease and dialysis in hereditary amyloidosis TTR V30M: presentation, survival and prognostic factors. 1518 96

Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.
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PMID:Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience. 2020 91


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