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)

Adrenomedullin (AM) is a potent vasodilator peptide in plasma at picomolar levels. Polymorphisms in the human AM gene have been associated with genetic predisposition to diabetic nephropathy and proteinuria with essential hypertension, and numerous studies have demonstrated that endogenous AM plays a role in protecting the heart and kidneys from fibrosis resulting from cardiovascular disease. Elevated plasma levels of AM are associated with pregnancy and sepsis and with cardiovascular stress and hypertension. However, there are no reports of the effects of genetic differences in the expression of the endogenous AM gene and of gender on blood pressure in these circumstances or on the pathological changes accompanying hypertension. To address these questions, we have generated mice having genetically controlled levels of AM mRNA ranging from approximately 50% to approximately 140% of wild-type levels. These modest changes in AM gene expression have no effect on basal blood pressure. Although pregnancy and sepsis increase plasma AM levels, genetically reducing AM production does not affect the transient hypotension that occurs during normal pregnancy or that is induced by treatment with lipopolysaccharide. Nor does the reduction of AM affect chronic hypertension caused by a renin transgene. However, 50% normal expression of AM enhances cardiac hypertrophy and renal damage in male, but not female, mice with a renin transgene. These observations suggest that the effect of gender on the role of AM in counteracting cardiovascular damage in humans merits careful evaluation.
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PMID:Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males. 1736 Jun 61

Acute renal failure (ARF) occurs in wide range of conditions, making the evaluation of its prognosis a difficult task. Data regarding prognostic factors in ARF in a general population in developing countries are scarce. The objective of the study was to describe predictors of mortality in ARF that are relevant in the developing world. This prospective study was carried out over a one-year period; all hospitalized adults with ARF were included in the study. Predictors of mortality studied included causes of ARF, pre-existing diseases, and severity as well as complications of ARF. Of 33,301 patients admitted during the study period, 294 (0.88%) were either admitted with or developed ARF after hospitalization. Mean age was 43.9 +/- 16.9 (18-86 yrs). Sepsis was the most common cause (63.26%). Pre-existing diseases like cardiovascular disease (CVSD), respiratory system disease (RSD), central nervous system disease (CNSD), hypertension, diabetes mellitus (DM), and malignancy were significantly higher in elderly as compared to younger patients. On univariate analysis sepsis, hypoperfusion as a cause of ARF and hospital-acquired ARF were associated with higher mortality. Pre-existing diseases viz. RSD, CVSD, CNSD, and DM had higher mortality. Among the severity and complications of ARF, oliguria, bleeding and infection during the course of ARF and critical illness were predictors of poor outcome. Age > 60 yrs was associated with significantly higher mortality. However, on multivariate analysis, only critical illness (odds ratio 37.3), age > 60 years (odds ratio of 5.6), and sepsis as cause of ARF (odds ratio of 2.6) were found to be independent predictors of mortality.
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PMID:Predictors of mortality in acute renal failure in a developing country: a prospective study. 1749 70

Dual-lumen cuffed central venous catheter proved an important alternative vascular access compared to conventional arteriovenous (Cimino-Brescia) shunt in a selected group of patients on regular dialysis treatment. Typically, these catheters are used as bridging access, until fistula or graft is ready for use, or as permanent access when an arteriovenous fistula or graft is not planned (NKF-DOQI). We conducted a prospective study on IJV permanent catheter insertion and its related earlier and long-term complications. From February 1991 to February 2001 we inserted in 124 patients in end stage renal disease 135 cuffed catheters (130 in the right IJV and 5 in the left IJV), 92 of which were Permcath, 27 Vascath, and 16 Ash-Split. We performed the insertion of catheters by puncturing the IJV under ultrasonographic guid-ance in the lower side of the Sedillot triangle and checking the accurate position of the tip by endocavitary electrocardiography (EC-ECG). The duration of catheter use was from 60 to 1460 days, mean 345 days. The actuarial survival rate at 1 year was 82%, at 2 years 56%, at 3 years 42% and at 4 years 20%. The exit site infection and septicemia rates were 5.2 and 2.86 per 1000 catheter days respectively. Catheter sepsis was implicated in the death of three patients, all of whom had multiple medical problems. Several episodes of thrombosis (6% of dialyses) occurred which required urokinase treatment, and catheter replacement in 12 patients (9.6%). In 3 cases the catheters were displaced and correct repositioning was performed. Two catheters (Ash-Split) were replaced due to accidental damage of the external portion of catheters (alcoholic disinfectant). Catheter tip embolism occurred on one occasion during elective catheter exchange over guide-wire. One of the common problems encountered with cuffed tunneled catheters is poor blood flow, most often secondary to the formation of a fibrin sheath around the lumen. Even if we conducted a non-randomized study, in our experience, the higher rate of malfunctioning catheters was in the group with no anticoagulation therapy. Therefore, we suggest anticoagulation treatment in all patients wearing central vascular catheters with no contraindication. Just one year ago, we followed NKF-DOQI clinical practice guidelines for vascular access that indicated that for patients who have a primary AV fistula maturing, but need im-mediate hemodialysis, tunneled cuffed catheters are the access of choice and the preferred insertion site is the right IJV. Considering recent reports of permanent central venous stenosis or occlusion after IJV can-nulation, currently, our first choice is femoral vein cannulation with smooth silicone rubber catheters, tunneled if long-term utilization is needed (more the 3-4 weeks). In our opinion, the right IJV puncture is to be avoided as much as the venipuncture of arm veins suitable for vascular access placement, particularly the cephalic vein of the non-dominant arm. Our data confirm that permanent venous catheters might rep-resent an effective long-term vascular access for chronic hemodialysis, particularly for older patients with cardiovascular disease and for cancer patients.
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PMID:Implantation of permanent jugular catheters in patients on regular dialysis treatment: ten years' experience. 1763 64

The innate immune system detects highly conserved, relatively invariant structural motifs of pathogens. Toll-like receptors (TLRs) have been identified as the primary innate immune receptors. TLRs distinguish between different patterns of pathogens and activate a rapid innate immune response; however, TLRs can also be activated by host-derived molecules. In addition to being expressed in immune cells, TLRs are expressed in other tissues, such as those of the cardiovascular system. TLRs could, therefore, be a key link between cardiovascular disease development and the immune system. Indeed, evidence that TLR activation contributes to the development and progression of atherosclerosis, cardiac dysfunction in sepsis, and congestive heart failure, is convincing. Although much has been learned about TLR activation in cellular components of the cardiovascular system, the role individual TLR family members have in the pathophysiology of cardiovascular diseases and hence in clinical practice remains to be defined. Here we review the rapid progress that has been made in this field, which has improved our understanding of vascular as well as myocardial TLR function in basic and clinical science.
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PMID:Mechanisms of disease: Toll-like receptors in cardiovascular disease. 1765 17

There has been a notable lack of research activity regarding major infections in patients with advanced chronic kidney disease. To an outsider, this might seem unexpected, because uremia has long been considered a state of immune hyporesponsiveness and rates of major bacterial infection, like septicemia and pneumonia, are known to be orders of magnitude more likely in dialysis populations than in the general population. This article reviews recent literature on the topic, focusing predominantly on the clinical epidemiology of major bacterial infections in dialysis patients, the links between bacterial infections and cardiovascular disease, and randomized trials of interventions designed to prevent these infections.
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PMID:Infections in patients with chronic kidney disease. 1782 17

Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single-center study. In 113 patients with impaired left ventricular function (ejection fraction <50%; nonischemic cardiomyopathy, n=52; ischemic cardiomyopathy, n=61), MPO plasma levels were elevated (24.5 [IR:15.8-54.0] vs 15.5 [IR:8.9-39.2] ng/ml in controls, P<0.01) as was elastase (111.5 [IR:63.8-233.3] vs 70.5 [IR:45.0-129.0] ng/ml, P<0.01) and NT-proBNP plasma levels (747.4 [IR:216.3-1958.3] vs 264.1 [IR:82.5-671.8] ng/L, P<0.01). Elevation of circulating MPO was irrespective of the etiology of heart failure and independent of traditional confounding variables. No association was observed between MPO -463 promoter polymorphism genotype and LV dysfunction. MPO plasma levels correlated with ejection fraction (P<0.01) and left ventricular end-diastolic diameter (P<0.01), respectively. Myeloperoxidase mRNA expression levels obtained from circulating leukocytes were significantly increased in patients with LV dysfunction. Systemic leukocyte activation with increased transcription of MPO mRNA and augmented release of MPO appears to represent a so far underrecognized characteristic in LV dysfunction, which was revealed to be irrespective of the underlying pathology. Given its potent proinflammatory properties, MPO may represent an important mechanistic link to LV dysfunction and deserves to be evaluated as both marker and therapeutic target in this disease.
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PMID:Activation of polymorphonuclear neutrophils in patients with impaired left ventricular function. 1785 14

Chronic kidney disease (CKD) is associated with a highly atherogenic lipid profile, characterized by elevated triglycerides, low high-density lipoprotein (HDL) cholesterol and accumulation of small dense low-density lipoprotein (LDL) particles. Diverse mechanisms are responsible: uraemia, dialysis, immunosuppressive drugs and concomitant diseases exert their effect on the activity of key enzymes, transfer proteins and receptors involved in lipid metabolism. Post hoc analyses from large scale randomized controlled trials suggest a benefit of statin therapy with respect to cardiovascular and renal endpoints in patients with early CKD comparable to the effect in people without renal disease. Observational studies found a reduction in the risk of contrast media induced nephropathy and a reduction in the risk of hospitalization for sepsis in patients who had CKD and were treated with statins. In contrast, prospective, randomized, controlled statin trials in patients with diabetes on haemodialysis and in renal transplant recipients have not conclusively shown improvements in hard cardiovascular endpoints. This review will focus on lipid disturbances in renal disease, their impact on cardiovascular disease, existing endpoint studies and current treatment guidelines.
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PMID:Dyslipidaemia in chronic kidney disease. 1791 26

Infection is the most common cause of death in hemodialysis patients, after cardiovascular disease. Dialysis access infections, with secondary septicemia, contribute significantly to patient mortality. The most common source is temporary catheterization. Bacteremia occurs commonly in patients receiving hemodialysis, with infective endocarditis being a relatively uncommon, but potentially lethal complication. Valvular calcification is the most significant risk factor. The diagnosis of infective endocarditis is made clinically and confirmed with the echocardiographic modified Duke's criteria. The most common pathogen is Staphylococcus aureus and the mitral valve is the most common site. Staphylococcus aureus infective endocarditis is commonly associated with embolic phenomenon. A high index of suspicion is critical in the early recognition and management of infective endocarditis. However, prevention of bacteremia is undoubtedly the best strategy with the early placement of arteriovenous fistulae. In the case of temporary catheterization, the use of topical mupirocin or polysporin and gentamicin and/or citrate locking is beneficial. Although catheter salvage has not been studied in randomized trials, catheter removal remains standard therapy during bacteremia.
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PMID:Infective endocarditis in a hemodialysis patient: a dreaded complication. 1792 31

In Italy, the mortality rate of hemodialysis patients is approximately 14% per year. Cardiovascular disease is the most important cause of morbidity and mortality in hemodialysis patients. High plasma homocysteine levels are commonly detected in these patients, but hyperhomocysteinemia and cardiovascular mortality are not always strictly correlated. The Dialysis Outcomes and Practice Pattern Study (DOPPS) showed a direct association between regular use of water-soluble vitamins and lower cardiovascular mortality. We recently performed a long-term prospective trial to study the effects of folic acid therapy on cardiovascular events in hemodialysis patients. We observed not only a lower rate of combined cardiovascular events in patients treated with folate, but also a direct correlation between hyperhomocysteinemia and cardiovascular morbidity. On the contrary, the distribution of deaths was similar in treated and untreated patients, because, almost certainly, sudden death is not always due to atherosclerotic events, and non-cardiovascular deaths, such as cachexia, septicemia and malignancy were characterized by low levels of homocysteine, which may be, in addition, a nutritional index similar to albumin and protein catabolic rate. As it is known that diabetic hemodialysis patients have a higher mortality rate, but lower homocysteine levels as compared to non-diabetic patients, we performed an equal allocation of diabetic patients in treated and untreated groups. We observed a similar homocysteine reduction rate in diabetic patients as compared to non-diabetic patients, and a trend towards a lower rate of composite cardiovascular events in treated diabetic patients as compared to untreated diabetic patients. To summarize, the strong relationship between homocysteine and nutritional, inflammatory markers may hide its association with cardiovascular disease. Homocysteine-lowering vitamin B therapy may lower cardiovascular events in dialysis patients. It is mandatory to perform large prospective trials to confirm our results.
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PMID:Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. 1793 6

A role for PRRs (pattern-recognition receptors) in immune cell function is now well established. In macrophages and other immune cells, activation of TLRs (Toll-like receptors) and cytosolic NLRs [NOD (nucleotide oligomerization domain) proteins containing a leucine-rich repeat] results in the induction of genes and release of imunoregulator hormones including cytokines and NO (nitric oxide). In addition to immune cells, structural cells of the cardiovascular system including endothelial cells, vascular smooth muscle and cardiac myocytes express functional PRRs and sense PAMPs (pathogen-associated molecular patterns). Furthermore, bacteria and PAMPs activate the coagulation system and platelets. TLRs are now implicated in a range of cardiovascular diseases and syndromes including atherosclerosis and sepsis. Our group is working on the hypotheses that differences exist in how tissues of the cardiovascular system, including vessels, endothelium, heart and blood, sense pathogens compared with immune cells (principally macrophages) and that identifying such differences will reveal new therapeutic targets for the treatment of cardiovascular disease. We have identified examples of similarities and differences in how cardiovascular tissues and macrophages sense PAMPs. These findings will be discussed together with our interpretation of how this information may lead to new treatments.
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PMID:Role of pattern-recognition receptors in cardiovascular health and disease. 1803 Dec 43


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