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)

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a relatively recently known and not very often diagnosed form of ischemic bowel disease of low incidence und unknown etiology. We present the case of a patient who after presentation of inconclusive signs of epigastric pain and rectal bleeding suddenly developed right abdominal pain with local peritonism. Suspecting intestinal ischemia or perforated appendicitis we first performed laparoscopy, which showed an inflammable tumor of cecum, ascending colon and appendix with massive adhesions to the abdominal wall. We performed an open right hemicolectomy with primary anastomosis. The patient developed a deep vein thrombosis of the vena tibialis post. and vena saphena parva. After 12 months our patient is free of complaints and recurrence. Investigations carried out showed no evidence of hypercoagulopathy. The presentation of MIVOD can range from chronic inflammatory bowel disease with recurrent abdominal pain in combination with nausea, emesis and bloody diarrhea to acute abdomen. Therefore diagnostic misinterpretation and mistherapy as well as underdiagnosis is common. Histologic investigation shows a variable inflammatory infiltration of multiple veins of the intestinal wall and the mesentery as well as thrombotic vessel occlusion in different stages without involvement of the arteries. All forms of hypercoagulopathy, parasitic disease, sepsis and malignancy have to be excluded. Therapeutic success can only be achieved with surgical resection of the affected bowel, whereon in general no recurrence will occur.
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PMID:[Mesenteric inflammatory veno-occlusive disease (MIVOD)--a rare cause of intestinal ischemia]. 1639 91

Although adenocarcinoma is a well known complication of chronic inflammatory bowel disease, primary gastrointestinal lymphoma occurring in Crohn's disease is rare. A 40-year-old man with 10 year-history of Crohn's disease had multiple longitudinal ulcerative lesions on descending colon in follow-up colonoscopic examination. Microscopic examination of proximal descending colon revealed peripheral T cell lymphoma and other site of the descending colon was consistent with Crohn's disease. The patient reached complete remission of malignant lymphoma after three cycles of combined chemotherapy. He has been well for 10 months with sulfasalazine maintenance therapy but was admitted to the hospital due to spontaneous bowel perforation of ascending colon. Right hemicolectomy was done, but the patient died of post-surgical recurrent mesenteric abscess and sepsis. To the best of our knowledge, this is the first case of Non-Hodgkin's lymphoma complicating Crohn's disease in Korea which was confirmed by immunohistochemical studies.
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PMID:[A case of Non-Hodgkin's lymphoma in a patient with Crohn's disease]. 1655 79

The unexpected discovery of a second form of the estrogen receptor (ER), designated ERbeta, surprised and energized the field of estrogen research. In the 9 yr since its identification, the remarkable efforts from academic and industrial scientists of many disciplines have made significant progress in elucidating its biology. A powerful battery of tools, including knockout mice as well as a panel of receptor-selective agonists, has allowed an investigation into the role of ERbeta. To date, in vivo efficacy studies are limited to rodents. Current data indicate that ERbeta plays a minor role in mediating estrogen action in the uterus, on the hypothalamus/pituitary, the skeleton, and other classic estrogen target tissues. However, a clear role for ERbeta has been established in the ovary, cardiovascular system, and brain as well as in several animal models of inflammation including arthritis, endometriosis, inflammatory bowel disease, and sepsis. The next phase of research will focus on elucidating, at a molecular level, how ERbeta exerts these diverse effects and exploring the clinical utility of ERbeta-selective agonists.
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PMID:Estrogen receptor-beta: recent lessons from in vivo studies. 1655 37

The plasma kallikrein-kinin system (KKS) participates in the pathogenesis of inflammatory reactions involved in cellular injury, coagulation, fibrinolysis, kinin formation, complement activation, cytokine secretion and release of proteases. It has been shown that KKS activation in the systemic inflammatory response syndrome results in decrease of its component plasma proteins. Similar changes have been documented in diabetes, sepsis, children with vasculitis, allograft rejection, disseminated intravascular coagulation, patients with recurrent pregnancy losses, hereditary angioedema, adult respiratory distress syndrome and coronary artery disease. Direct involvement of the KKS in the pathogenesis of experimental acute arthritis and acute and chronic enterocolitis has been documented by previous studies from our laboratory using experimental animal models. It has been found that in HK deficient Lewis rats, experimental IBD was much less severe. We showed a genetic difference in kininogen structure between resistant Buffalo and susceptible Lewis rats, which results in accelerated cleavage of HK and it is responsible for the susceptibility to the inflammatory process in the Lewis rats. It has been demostrated that therapy with a specific plasma kallikrein inhibitor (P8720) modulated the experimental enterocolitis, arthritis and systemic inflammation. Furthermore, it has been shown that a bradykinin 2 receptor (B2R) antagonist attenuates the inflammatory changes in the same animal model. We have showed that a monoclonal antibody targeting HK decreases angiogenesis and arrests tumor growth in a syngeneic animal model. In summary, these results indicate that the plasma KKS plays a central role in the pathogenesis of chronic intestinal inflammation, arthritis and angiogenesis.
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PMID:[High molecular weight kininogen in inflammation and angiogenesis: a review of its properties and therapeutic applications]. 1670 6

This registry describes a multicentre experience of Home Parenteral Nutrition (HPN) in nine European countries covering 27 centres and 194 patients. The main purpose of this study was to evaluate the quality of life and prognosis of patients on HPN. Patients started HPN at 44 +/- 1 years old (mean +/- SEM), and received 200 courses of HPN for a mean of 12 +/- 1 months representing a cumulative duration of 207 years. The four commonest indications for HPN were inflammatory bowel disease (30%), mesenteric vascular disease (21%), malignancy (17%) and radiation enteritis (13%). The nutritional status during HPN was clinically normal or subnormal in 93% of cases. The yearly incidence of catheter related complications leading to a catheter change was 0.74, sepsis accounting for half of this. The duration of hospital readmission for HPN complications was 4 +/- 1% of time spent at home, which represents 2 weeks per year and 41% of the total readmission time. Mortality was mainly influenced by the underlying disease since only 3% of patients died of HPN complications. A good social rehabilitation was observed in 52% of patients who during treatment recovered their pre-HPN occupational status. The poorest social rehabilitation was observed in patients over 65 years of age, and patients with malignancies and radiation enteritis, who also had the poorest prognosis. Caution seems necessary before recommending HPN in these patients.
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PMID:Home parenteral nutrition in adults: a multicentre survey in Europe. 1683 59

High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namely HKa. BK promotes angiogenesis by upregulation of bFGF through the B1 receptor or by stimulation of VEGF formation via the B2 receptor. Kininogen-deficient rats show diminished angiogenesis when neovascularization is stimulated. The formation of HKa results in exposure of domain 5 (D5). HKa or D5 inhibit endothelial cell migration and proliferation, both of which are needed for angiogenesis. In the chicken chorioallantoic membrane assay when neovascularization is stimulated by bFGF or VEGF, HKa or D5 inhibit angiogenesis. Monoclonal antibody C11C1, which prevents binding of HK to endothelial cells, also limits its conversion to BK thus downregulating angiogenesis. In vivo, mAb C11C1 inhibits tumor angiogenesis in mice as well as in experimental inflammatory arthritis and inflammatory bowel disease in Lewis rats. In vitro HKa or D5 inhibits endothelial cell adhesion to vitronectin and fibrinogen, resulting in anokis and apoptosis. The HKa receptor, uPAR, forms a signaling complex containing the integrin alphavbeta3 or alpha5beta1, caveolin, Src kinase Yes, focal adhesion kinase and paxcillin. HKa physically disrupts the complex by interfering with the binding of vitronectin to uPAR. Both mAb C11C1 and D5 have potential applications for controlling unwanted angiogenesis in inflammation and cancer.
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PMID:Regulation of angiogenesis by the kallikrein-kinin system. 1684 60

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients' treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro. The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis. There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events. In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women. Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.
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PMID:Safety of etanercept in psoriasis: a critical review. 1687 41

Azathioprine, an analog of 6-mercaptopurine has been used as a steroid-sparing agent in the treatment of inflammatory bowel disease for over 30 years. Hypersensitivity reactions to azathioprine including fever, myalgia, arthralgia, rash are well documented in the literature. Here, we report 2 cases of azathioprine hypersensitivity in patients with inflammatory bowel disease manifesting with the unusual symptom of profound muscular weakness resulting in inability to perform simple tasks such as lifting even light objects, sitting upright, and walking a few steps. Development of severe weakness raised concern about myositis, rhabdomyolysis, myopathy, and sepsis in these patients. Discontinuation of azathioprine resulted in prompt improvement of muscular weakness, and rechallenge led to recurrence of similar symptoms within hours. These observations suggest that the development of muscular weakness in patients on azathioprine should be considered as an adverse effect of the drug. Failure to recognize this adverse outcome can lead to prolonged periods of muscular weakness in this group of patients.
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PMID:Severe muscular weakness: an unusual adverse effect of azathioprine therapy. 1691 6

Colorectal cancer is the most common malignant complication in patients who have IBD. The disease is difficult to diagnose because there is an overlap in symptoms in patients who have colon cancer and those who have IBD. Much has been learned about the incidence of colorectal cancer in patients who have IBD and its correlation with disease activity, duration, and anatomic location; however, almost no data are available regarding specific therapeutic considerations during adjuvant or palliative chemotherapy for these patients with respect to their underlying disease. Patients who have IBD who develop colorectal cancer are at higher risk for developing severe diarrhea during chemotherapy that may be due to the toxic effects of cytotoxic drugs or a flare of the IBD. Continuous infusional 5-FU alone, in combination with leucovorin, or in combination with oxaliplatin (FOLFOX) seems to be tolerated best. Bolus infusions of 5-FU (Roswell Park or Mayo regimens) and combination therapy of irinotecan with 5-FU should be avoided because of severe diarrhea and the possibility of sepsis. When diarrhea develops or worsens, empiric aminosalicylates may be given. Although it is theoretically possible that anti-EGFR therapies could affect IBD activity adversely, clinical experience with cetuximab in patients who have colorectal cancer has not shown any significant gastrointestinal side effects. Therefore, it seems reasonable to use it in patients who have colorectal cancer and IBD. The administration of bevacizumab has been associated with rare episodes of intestinal perforation; it should be used with great care in patients who have IBD. More studies and an integrative, multidisciplinary approach from oncologists and gastroenterologists are needed to provide optimal care for patients who have IBD during chemotherapy for colorectal cancer
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PMID:Systemic treatment of patients who have colorectal cancer and inflammatory bowel disease. 1695 47

The induction of immune tolerance is critical for the prevention of autoimmunity and the maintenance of immune homeostasis. The identification of factors involved in the maintenance or restoration of such tolerance has become the focus of new therapies for inflammatory and autoimmune diseases. Cortistatin, a recently discovered cyclic neuropeptide related to somatostatin, has emerged as a potential endogenous antiinflammatory factor based on its production by, as well as its binding to, immune cells. Thus, cortistatin has been found to downregulate the inflammatory response mediated by activated macrophages. The present work reviews various recent studies involving different experimental models of sepsis, rheumatoid arthritis and inflammatory bowel disease, demonstrating that cortistatin treatment offers great benefits at both the clinical and pathological levels. These include the downregulation of both inflammatory and Th1-mediated autoimmune disease components and the emergence of regulatory T cells (Treg) that suppress autoreactive T cells, both of which contribute to the restoration of immune tolerance. While many questions need to be resolved, cortistatin appears to be an exciting and promising candidate for the treatment of several chronic inflammatory diseases and autoimmune disorders.
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PMID:Cortistatin as a potential multistep therapeutic agent for inflammatory disorders. 1708 Feb 2


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