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

A 38-year-old Ghanaian man presented with a 6-month history of worsening pruritus, jaundice, and ascites. He was previously fit and well and rarely drank alcohol. Screening tests for chronic liver disease including viral, autoimmune, and other metabolic causes including iron overload were unremarkable. A liver biopsy performed at the referring hospital demonstrated intralobular cholestasis and cirrhosis. He was listed for liver transplantation but subsequently developed sepsis with multiple organ failure and died. The sickle solubility test was positive. Blood smear showed cells consistent with liver failure and no sickle cells. Hemoglobin electrophoresis revealed HbA2 2.8%, HbF 0.5%, and HbS greater than HbA (49.6% vs. 41.3%) in the absence of blood transfusion. Sequence analysis of the beta-globin genes showed he was a compound heterozygote for the Hbs mutation at codon 6 (CAG --> GTG) and a novel mutation at position 844 of intron 2 (betaIVS2-844 C --> A). A diagnosis of sickle hepatopathy causing decompensated cirrhosis was made. This case is unusual insomuch as this patient was asymptomatic for over 35 years and represents a novel presentation of sickle cell disease. Sickle cell disease should be considered in appropriate patients when unusual presentations of liver disease arise.
 ...
PMID:Sickle liver disease--an unusual presentation in a compound heterozygote for HbS and a novel beta-thalassemia mutation. 1756 24

Pancreatic lipomatosis is defined as deposition of fat cells in pancreatic parenchyma. Although the etiology of this condition is still unclear, it is not uncommon in the elderly, obese individuals, and a variety of transfusion-dependent hematologic diseases such as beta-thalassemia major. Pancreatic lipomatosis associated with transfusion-dependent myelodysplastic syndrome (MDS) has never been reported. We present a 17-year-old male patient with transfusion-dependent MDS. He received transfusion of a total of 345 units of blood in a period of 18 months but without iron chelating agent. Progressive fatty replacement of the pancreas parenchyma was found by a series of computed tomography images over seven hospital admissions due to repeated infections. Bone marrow biopsy revealed hemosiderin deposition. Because of his poor response to induction chemotherapy, stem cell transplantation was suggested, but the patient died of sepsis before the therapeutic procedure could take place. Although most patients with pancreatic lipomatosis have neither clinical symptoms nor abnormal laboratory data, it may cause endocrine and exocrine pancreas dysfunction. In this reported case, mild exocrine dysfunction was noted on the last admission. Clinicians should be cautious of hemosiderin deposition after large amount of blood transfusion and chelating therapy should be given to avoid iron overload.
 ...
PMID:Rapidly progressive pancreatic lipomatosis in a young adult patient with transfusion-dependent myelodysplastic syndrome. 1771 3

Hepcidin is a small protein comprised of 25 amino acids, synthesized in the liver. It was first described in 2001 as a component of the innate immunity due to its antimicrobial activity. Soon after, hepcidin was recognized as a key component in iron homeostasis, involved in maladies of iron overload or iron deficiency. Hepcidin acts by binding to the transmembrane protein ferroportin, in charge of exporting iron from cells. Upon binding to ferroportin, the latter is internalized into cytoplasmic lysosomes and is hydrolyzed, thus iron is accumulating in cells, and hypoferremia ensues. In hereditary and juvenile types of hemochromatosis, iron overload could be partially due to the down-regulation of hepcidin by the mutated genes HFE and HJV. In ferroportin disease, hepcidin synthesis is not inhibited, yet cells are still overloaded with iron due to mutations in ferroportin, preventing the binding of hepcidin and iron export from cell to the blood. Hepcidin has also been implicated in the scenario related to as "anemia of inflammation". In this condition significant hypoferremia develops as a result of acute sepsis, but also in wake of infections, chronic inflammation, rheumatic diseases and in certain malignancies. Such scarcity of iron leads to anemia that may not be corrected by erythropoietin treatment, and hepcidin synthesis in such anemic state is dramatically elevated. Future therapeutic approach may attempt administering synthetic hepcidin, or its antagonists, to correct states of iron overload or scarcity.
 ...
PMID:[Hepcidin--the discovery of a small protein with a pivotal role in iron homeostasis]. 1848 71

We report a case of Vibrio vulnificus sepsis developed during deferoxamine therapy for transfusional iron overload due to secondary hemochromatosis of myelodysplastic syndrome. The patient was treated with adjuvant deferasirox in combination with ciprofloxacin, after rapid diagnosis of V. vulnificus sepsis using real-time polymerase chain reaction (PCR). This case suggests that since V. vulnificus DNA can be detected by real-time PCR for several days even after patients receive antibiotics, real-time PCR for V. vulnificus is a very useful test for establishing an early diagnosis, even if a patient has been treated with antibiotics prior to admission.
 ...
PMID:Deferasirox plus ciprofloxacin combination therapy after rapid diagnosis of Vibrio vulnificus sepsis using real-time polymerase chain reaction. 1893 Mar 21

There are several reports of persons with hemochromatosis and Vibrio vulnificus primary septicemia, but few accounts of persons with hemochromatosis and V. vulnificus wound infection. A 58-year-old white man developed infection of a forearm injury exposed to seawater in the Gulf of Mexico near the Alabama coast. At age 66, he was diagnosed to have hemochromatosis. Transferrin saturation was 89% and serum ferritin was 4761 pmol/L. HFE genotype was C282Y/C282Y. Serum levels of hepatic enzymes, glucose, IgG, IgA, and IgM, and blood levels of T, B, and natural killer cells were normal. We identified previous reports of only 2 similar cases: a woman from Alabama and a man from northern Australia. Mean age of the 3 subjects was 51 years at diagnosis of infection. Each had elevated serum iron measures or iron overload complications; both men were diagnosed to have hemochromatosis after they developed infection. Each of the 3 had recent exposure of a wound on an extremity to seawater, rapid development of a necrotizing soft tissue infection that required debridement and skin grafting, and positive wound or blood cultures. Each subject survived the infection. V. vulnificus wound infection occurs in some persons with hemochromatosis, but the risk of infection may be small. All patients with V. vulnificus infections should be evaluated for hemochromatosis, iron overload, and liver disorders.
 ...
PMID:Hemochromatosis and Vibrio vulnificus wound infections. 1934 2

Lipoproteins (Lpp) are ligands of TLR2 and signal by the adaptor MyD88. As part of the bacterial cell envelope, Lpp are mainly involved in nutrient acquisition for Staphylococcus aureus. The impact of Lpp on TLR2-MyD88 activation for S. aureus in systemic infection is unknown. S. aureus strain SA113 deficient in the enzyme encoded by the prolipoprotein diacylglyceryl transferase gene (Deltalgt), which attaches the lipid anchor to pro-Lpp, was used to study benefits and costs of Lpp maturation. Lpp in S. aureus induced early and strong cytokines by TLR2-MyD88 signaling in murine peritoneal macrophages. Lpp contributed via TLR2 to pathogenesis of sepsis in C57BL/6 mice with IL-1beta, chemokine-mediated inflammation, and high bacterial numbers. In the absence of MyD88-mediated inflammation, Lpp allowed bacterial clearing from liver devoid of infiltrating cells, but still conferred a strong growth advantage in mice, which was shown to rely on iron uptake and storage in vitro and in vivo. With iron-restricted bacteria, the Lpp-related growth advantage was evident in infection of MyD88(-/-), but not of C57BL/6, mice. On the other hand, iron overload of the host restored the growth deficit of Deltalgt in MyD88(-/-), but not in immunocompetent C57BL/6 mice. These results indicate that iron acquisition is improved by Lpp of S. aureus but is counteracted by inflammation. Thus, lipid anchoring is an evolutionary advantage for S. aureus to retain essential proteins for better survival in infection.
 ...
PMID:Lipoproteins in Staphylococcus aureus mediate inflammation by TLR2 and iron-dependent growth in vivo. 1945 8

Vibrio vulnificus infection is an uncommon but potentially fatal disease in children such that prompt recognition has prognostic implications. We describe here the case of a 9-year-old female with thalassemia and iron overload who presented with septic arthritis as an atypical initial manifestation of fatal V. vulnificus septicemia. This report underscores the possibility of septic arthritis as an early manifestation of V. vulnificus septicemia. Pediatricians should be alert to this extremely invasive disease, especially in children with iron overload.
 ...
PMID:Septic arthritis as the initial manifestation of fatal Vibrio vulnificus septicemia in a patient with thalassemia and iron overload. 1959 Dec 24

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in normal hepatocytes and are critical for normal physiologic processes, including oxidative respiration, growth, regeneration, apoptosis, and microsomal defense. When the levels of oxidation products exceed the capacity of normal antioxidant systems, oxidative stress occurs. This type of stress, in the form of ROS and RNS, can be damaging to all liver cells, including hepatocytes, Kupffer cells, stellate cells, and endothelial cells, through induction of inflammation, ischemia, fibrosis, necrosis, apoptosis, or through malignant transformation by damaging lipids, proteins, and/or DNA. In Part I of this review, we will discuss basic redox biology in the liver, including a review of ROS, RNS, and antioxidants, with a focus on nitric oxide as a common source of RNS. We will then review the evidence for oxidative stress as a mechanism of liver injury in hepatitis (alcoholic, viral, nonalcoholic). In Part II of this review, we will review oxidative stress in common pathophysiologic conditions, including ischemia/reperfusion injury, fibrosis, hepatocellular carcinoma, iron overload, Wilson's disease, sepsis, and acetaminophen overdose. Finally, biomarkers, proteomic, and antioxidant therapies will be discussed as areas for future therapeutic interventions.
 ...
PMID:Nitric oxide and redox regulation in the liver: part II. Redox biology in pathologic hepatocytes and implications for intervention. 2040 Jan 12

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in normal hepatocytes and are critical for normal physiologic processes, including oxidative respiration, growth, regeneration, apoptosis, and microsomal defense. When the levels of oxidation products exceed the capacity of normal antioxidant systems, oxidative stress occurs. This type of stress, in the form of ROS and RNS, can be damaging to all liver cells, including hepatocytes, Kupffer cells, stellate cells, and endothelial cells, through induction of inflammation, ischemia, fibrosis, necrosis, apoptosis, or through malignant transformation by damaging lipids, proteins, and/or DNA. In Part I of this review, we will discuss basic redox biology in the liver, including a review of ROS, RNS, and antioxidants, with a focus on nitric oxide as a common source of RNS. We will then review the evidence for oxidative stress as a mechanism of liver injury in hepatitis (alcoholic, viral, nonalcoholic). In Part II of this review, we will review oxidative stress in common pathophysiologic conditions, including ischemia/reperfusion injury, fibrosis, hepatocellular carcinoma, iron overload, Wilson's disease, sepsis, and acetaminophen overdose. Finally, biomarkers, proteomic, and antioxidant therapies will be discussed as areas for future therapeutic interventions.
 ...
PMID:Nitric oxide and redox regulation in the liver: Part I. General considerations and redox biology in hepatitis. 2044 70

Septicaemia and septic arthritis due to Yersinia pseudotuberculosis are rare diseases with high mortality rates. Reactive arthritis caused by Yersinia infection is a well-known complication but septic arthritis is found at a much lower frequency. It has already been established that there is a relationship between yersiniosis and iron but there are currently no data about yersiniosis and haematological disorders such as haemophilia. We report a case of septic arthritis due to Y. pseudotuberculosis as an early manifestation of Yersinia septicaemia in a patient with severe haemophilia A. The patient had no history of immunosuppression and presented with a repeat case of haemarthrosis with a fever of unknown origin. Furthermore, he suffered from acute-on-chronic renal failure and non-ST segment elevation myocardial infarction. Arthrocentesis and blood culture tested positive for Y. pseudotuberculosis. Iron deposits at localized sites in the synovium in patients with haemophilia have been described, and as Yersinia infections are common in patients with secondary iron overload, we felt that a review of the literature was in order. Severe Yersinia infection is often associated with iron overload, a condition that might occur as a side effect in the treatment of haemophilia. Iron overload, which plays an important role in the pathogenesis of haemophilic arthropathy, may have increased the virulence of Y. pseudotuberculosis in the present case.
 ...
PMID:Haemophilia-associated Yersinia pseudotuberculosis serotype O:1 septicaemia: the role of iron. 2218 9


<< Previous 1 2 3 4 5 6 Next >>