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)

Neopterin is a low-molecular mass substance synthesized from guanosine triphosphate (GTP) in monocytes/macrophages due to IFNgamma stimulation. The cellular immune system is involved in or affected by the disease process in various conditions such as viral infections (AIDS), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosis, Crohn's disease), malignancy and monitoring after solid organ transplants. Similar to procalcitonin, neopterin determination can assist in the differential diagnosis between viral and bacterial infection and as an indicator for impending septic complications (MODS vs. sepsis). Because of fact that reduced glamerular filtration rate neopterin accumulates in the blood, neopterin determination in multiorgan failure or sepsis patients are limited. The aim of this study was to evaluate the usefulness of neopterin in clinical diagnostics.
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PMID:[Role of neopterin in clinical diagnostics]. 1646 8

The genetic predisposition to many autoimmune diseases is inherited as a polygenic trait. It is conceivable that some of the causative alleles in these diseases became prevalent in the population by conferring a survival benefit against environmental assaults, such as infections. We used mice cogenic for genetic loci predisposing to systemic lupus erythomatosus to test the hypothesis that some of these genetic loci protect the host from bacterial infections. Mice with the Sle3 lupus-susceptibility locus on a wild-type background were found to have enhanced antibacterial responses in the context of pneumonia and intra-abdominal sepsis than wild-type animals. This was associated with markedly augmented accumulation of neutrophils in infected tissues, and was bone marrow transferable and dependent on the presence of neutrophils, but not lymphocytes. There was no difference in in vitro leukocyte killing of bacteria nor influx of phagocytes between lupus-susceptible and wild-type animals, but neutrophils from lupus-susceptible mice displayed markedly reduced rate of apoptosis, associated with altered expression of Bcl-2 family proteins, contributing to their greater accumulation. Importantly, deliberate inhibition of apoptosis in wild-type animals significantly boosted the accumulation of neutrophils at the site of infection and resulted in an enhanced antimicrobial response. These observations support the concept that some of the genetic loci that mediate autoimmunity may also confer augmented antimicrobial innate immunity.
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PMID:The lupus-susceptibility locus, Sle3, mediates enhanced resistance to bacterial infections. 1649 84

Reactive hemophagocytic syndrome (HS) occurs mainly in the setting of serious infections and lymphomas. HS can occur in the course of 2 active systemic diseases, without simultaneous infection: adult Still disease and systemic lupus erythematosus (SLE). Observations of specific lupus-associated HS are rare, and the long-term outcome of these patients with active SLE is unknown. We retrospectively studied 15 episodes of SLE-associated HS in 12 patients (10 women, 2 men) and noted the long-term outcome. HS occurred at a mean age of 25 years. All patients were febrile with >or=2 cytopenias, and bone marrow aspiration indicated hemophagocytosis. HS revealed SLE in 9 patients and recurred in 3. The main features of SLE-associated HS were a low frequency of hepatosplenomegaly, a high frequency of heart involvement (5 pericarditis, 4 myocarditis requiring transfer to intensive care unit), and a low C-reactive protein level (mean, 15 mg/L). Cutaneous-mucous symptoms of SLE, arthritis, and nephritis were present respectively in 8 (53%), 6 (40%), and 4 (27%) episodes, but symptoms of SLE were absent in 4 episodes at admission. All patients had anti-nuclear antibodies when the HS occurred. Anti-double-stranded DNA antibodies were present in 12 episodes. Treatment was steroids in 14 cases but cyclophosphamide was the only treatment able to control HS in 2 cases. All the cases of SLE-associated HS were controlled by the immunosuppressive regimen. Intravenous immunoglobulins seemed poorly effective. No infectious agent was found. Clinical presentations of the 23 patients with SLE-associated HS described in the literature were reviewed and were similar to those of the current series. The mean follow-up was 88 months (range, 7-240 mo). One patient died at 15 months (sepsis). Among the 5 patients with a follow-up >8 years, 4 always had active disease. During the follow-up of SLE, immunosuppressive drugs were added in 8 patients (cyclophosphamide in 7, azathioprine in 3, mycophenolate mofetil in 2) with significant adverse drug reactions. In the long-term, SLE-associated HS seems to define a severe SLE form with frequent flares, possible HS recurrences, and the need for prolonged immunosuppression.
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PMID:Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. 1672 Dec 59

It is generally accepted that antiphospholipid syndrome remains a major medical problem characterised by hypercoagulability, arterial and venous thrombosis and thrombocytopenia. It is unclear how best to treat these patients should they require emergency surgery. If a lupus anticoagulant is present, hypercoagulability may occur de novo but surgical interventions along with sepsis are two important predisposing factors. We describe three patients with primary antiphospholipid syndrome and discuss the implications for surgery.
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PMID:Antiphospholipid syndrome: a series of surgical emergencies and the current evidence for its management. 1683 58

TLR4 is the receptor for the Gram-negative bacterial cell wall component LPS. TLR4 signaling is controlled by both positive and negative regulators to balance optimal immune response and potential sepsis. Unchecked TLR4 activation might result in autoimmune diseases, a hypothesis that has not been formally resolved. In this study, we found that TLR4 signaling to LPS can be positively enforced by expressing gp96 on cell surfaces through the chaperone function of, but not the direct signaling by, gp96; TLR4 as well as the commensal flora are essential for the production of anti-dsDNA Ab and the immune complex-mediated glomerulonephritis in transgenic mice that express surface gp96. Moreover, a similar constellation of autoimmunity was evident in mice that encode multiple copies of tlr4 gene. Our study has revealed that increased TLR4 signaling alone without exogenous insult can break immunological tolerance. It provides a strong experimental evidence for TLR4 dysregulation as an etiology of lupus-like renal disease.
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PMID:TLR4 up-regulation at protein or gene level is pathogenic for lupus-like autoimmune disease. 1708 2

To save their patients from dialysis and transplantation, neurologists need simply remain alert to the possibility of renal failure, particularly in the context of systemic disease, diabetes, sepsis and drugs. Of the numerous territories shared by our respective specialities, we outline a pragmatic approach to the diagnosis and treatment of the vasculitides, underpinned by knowing which questions to ask, equally importantly when to ask them, and in the art of obtaining a tissue diagnosis. We consider the current evolving trial evidence that directs the usage of a growing arsenal of therapies in the induction and maintenance stages of vasculitis treatment, and extend this consideration to Lupus and Sjogren's.
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PMID:Notes on the kidney and its diseases for the neurologist. 1743 83

Two recent trials concluded that the use of oral contraceptives (OC) did not induce flares in lupus patients. We record our experience with OC in patients with stable lupus. Eight patients were enrolled in an open trial. Six received a combined contraceptive pill and two were allocated to the control arm. During a 12 month follow-up, 3 patients in the active arm experienced 4 major flares. One patient died as a result of uncontrolled disease complicated by sepsis. At this point, we abandoned the trial. The 2 patients in the control arm experienced no disease exacerbation during the 7 months of observation. We would urge that patients who are placed on OC be closely monitored.
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PMID:Major flares in women with SLE on combined oral contraception. 1748 47

Perinatal thrombosis in infants born to mothers with antiphospholipid antibodies (aPL) is a rare event, but with risk of death or severe sequelae. We analysed 16 infants with such perinatal thrombosis reported in the literature in the last 20 years. Thromboses were arterial (13/16), mostly strokes (8/16). Hydrops fetalis with left renal vein thrombosis was associated to a lupus anticoagulant (LA) present only in the child. Risk factors additional to aPL: either prenatal (preeclampsia and/or intra-uterine growth retardation) or perinatal (asphyxia, sepsis, arterial or venous catheter and congenital thrombophilia) were present (one to four of them) in nine out of the 14 evaluable babies. aPL were the only risk factor found in five full term babies who suffered from stroke in four cases and from renal thrombosis in another. Eleven of these infants with aPL in their serum presented a neonatal APS with the same antibody (LA or aCL IgG) found in neonates and their mothers, while the other infants had thrombosis with aPL only in their mother's blood. aCL IgM was only found in one neonate who suffered from sepsis. Thrombosis treatments were diverse. This analysis suggests that women with aPL should be investigated for other thrombophilic risk factors and that aPL should be detected systematically at birth in the offspring of mothers with APS.
Lupus 2007
PMID:Infant perinatal thrombosis and antiphospholipid antibodies: a review. 1771

The objective of this study was to determine the frequency and clinical characteristics of selective IgA deficiency (SIgAD) in children and adults with systemic lupus erythematosus (SLE), and evaluate potential differences in presentation and course of the SLE. IgA deficiency was defined as a serum IgA concentration < or =0.01 mg/mL determined on two sera by radial diffusion. SLE was classified by the 1982 criteria of the American College of Rheumatology. Seventy-seven children with SLE followed prospectively for > or =20 years and 152 adults surveyed during a one-year period were assayed for serum IgA levels. Disease characteristics were compared among the deficient patients and the IgA-normal patients. Twelve patients with SIgAD were identified: 1) Juvenile(J)-SLE: four children with juvenile onset (< or =18 years) and four others encountered as adults; and 2) Adult(A)-SLE: four patients with adult onset. No significant differences were found in clinical presentation or course except for a possible increase in recurrent infections and the observation that there were only two African-Americans. Five patients had received blood transfusions with no reactions; three of these patients had serum anti-IgA antibodies. One pediatric patient developed low levels of IgA (<or =1 mg/mL) during a follow-up of three years. Two adult patients died (septicemia, carcinoma); one was on dialysis. SIgAD was identified in 5.2% of children and 2.6% of adults with SLE for an estimated 35-fold increase in frequency. This small number of patients did not appear to have an altered clinical presentation or course from that expected in patients with SLE who did not have SIgAD.
Lupus 2007
PMID:Selective IgA deficiency in children and adults with systemic lupus erythematosus. 1771 2

Tumour necrosis factor (TNF) ligand members and their associated TNF receptor (TNFR) superfamilies have many diverse physiological roles. TNF is thought to play a critical role in the pathophysiology of a range of diseases including refractory asthma, sepsis, ankylosing spondylitis, lupus, type II diabetes, multiple sclerosis and psoriasis. The recent continued expansion of the novel anti-TNF therapeutic agents (etanercept and infliximab) has seen major improvements in the treatment of some inflammatory-based human diseases including notably rheumatoid arthritis and Crohn's disease, with other conditions currently being trialled using anti-TNF agents. The cellular signalling machinery used by TNFRs to achieve their many cellular responses are discussed, as is the gonadotrophin-releasing hormone (GnRH) receptor signalling mechanisms. TNF is known to have many actions throughout the body including effects on the hypothalamic-pituitary-adrenal/gonadal axes, with many anti-gonadotrophic effects including a role in the development of endometriosis. These interactions between TNF, GnRH and gonadotrophs are discussed.
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PMID:Interactions between TNF and GnRH. 1798 35


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