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)

Surgical treatment of giant abdominal hernias includes reduction of the hernia content and tension-free closure of the abdominal wall. Initial laparoscopy simulates the postoperative abdominal wall tension. Recognizing the need for a preoperative pneumoperitoneum in cases of chronic eventration may help to avoid "abdominal catastrophes" including bowel resection, abdominal compartment, and extended abdominal wall reconstruction. We report a 66-year-old man with an asymptomatic long-standing giant scrotal hernia who was admitted with sepsis and uremia caused by intestinal obstruction.
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PMID:[Pneumoperitoneum in surgical management of giant scrotal hernias]. 1639 76

Conditions such as acidosis, uremia, and sepsis are characterized by insulin resistance and muscle wasting, but whether the insulin resistance associated with these disorders contributes to muscle atrophy is unclear. We examined this question in db/db mice with increased blood glucose despite high levels of plasma insulin. Compared with control littermate mice, the weights of different muscles in db/db mice and the cross-sectional areas of muscles were smaller. In muscle of db/db mice, protein degradation and activities of the major proteolytic systems, caspase-3 and the proteasome, were increased. We examined signals that could activate muscle proteolysis and found low values of both phosphatidylinositol 3 kinase (PI3K) activity and phosphorylated Akt that were related to phosphorylation of serine 307 of insulin receptor substrate-1. To assess how changes in circulating insulin and glucose affect muscle protein, we treated db/db mice with rosiglitazone. Rosiglitazone improved indices of insulin resistance and abnormalities in PI3K/Akt signaling and decreased activities of caspase-3 and the proteasome in muscle leading to suppression of proteolysis. Underlying mechanisms of proteolysis include increased glucocorticoid production, decreased circulating adiponectin, and phosphorylation of the forkhead transcription factor associated with increased expression of the E3 ubiquitin-conjugating enzymes atrogin-1/MAFbx and MuRF1. These abnormalities were also corrected by rosiglitazone. Thus, insulin resistance causes muscle wasting by mechanisms that involve suppression of PI3K/Akt signaling leading to activation of caspase-3 and the ubiquitin-proteasome proteolytic pathway causing muscle protein degradation.
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PMID:Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. 1677 75

Calcinosis cutis, one of the rare manifestations of systemic calcinosis, is characterized by the deposition of calcium and phosphate salts in the skin. Metastatic calcinosis, usually a late complication of chronic renal failure, arises from increased calcium or phosphate levels in the serum or both. Both sexes and all ages may be affected; however, cutaneous involvement is uncommon, particularly in children. We present the youngest patient, to our knowledge, with end-stage renal disease and cutaneous metastatic calcification resulting from secondary hyperparathyroidism. A 2-month-old infant presented to the pediatric service with anuria and uremia. A renal biopsy specimen showed chronic tubulo-interstitial nephritis. Indurated, firm, tender reddish papules were localized to both lower limbs, and extensive irregular nodules and plaques with ulceration and white stony contents were localized to the right upper limb. Topical antibiotic ointment was applied to the skin lesions to prevent secondary infection. However, acute peritonitis developed during peritoneal dialysis, and death occurred as a result of sepsis.
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PMID:Extensive skin calcifications in an infant with chronic renal failure: metastatic calcinosis cutis. 1678 Apr 69

Loss of functional capacity of skeletal muscle is a major cause of morbidity in patients with a number of acute and chronic clinical disorders, including sepsis, chronic obstructive pulmonary disease, heart failure, uremia, and cancer. Weakness in these patients can manifest as either severe limb muscle weakness (even to the point of virtual paralysis), respiratory muscle weakness requiring mechanical ventilatory support, and/or some combination of these phenomena. While factors such as nutritional deficiency and disuse may contribute to the development of muscle weakness in these conditions, systemic inflammation may be the major factor producing skeletal muscle dysfunction in these disorders. Importantly, studies conducted over the past 15 years indicate that free radical species (superoxide, hydroxyl radicals, nitric oxide, peroxynitrite, and the free radical-derived product hydrogen peroxide) play an key role in modulating inflammation and/or infection-induced alterations in skeletal muscle function. Substantial evidence exists indicating that several free radical species can directly alter contractile protein function, and evidence suggests that free radicals also have important effects on sarcoplasmic reticulum function, on mitochondrial function, and on sarcolemmal integrity. Free radicals also modulate activation of several proteolytic pathways, including proteosomally mediated protein degradation and, at least theoretically, may also influence pathways of protein synthesis. As a result, free radicals appear to play an important role in regulating a number of downstream processes that collectively act to impair muscle function and lead to reductions in muscle strength and mass in inflammatory conditions.
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PMID:Free radical-mediated skeletal muscle dysfunction in inflammatory conditions. 1721 25

The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.
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PMID:Congenital nephrotic syndrome. 1765 4

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

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

A functional ubiquitin proteasome system is essential for all eukaryotic cells and therefore any alteration to its components has potential pathological consequences. Though the exact underlying mechanism is unclear, an age-related decrease in proteasome activity weakens cellular capacity to remove oxidatively modified proteins and favours the development of neurodegenerative and cardiac diseases. Up-regulation of proteasome activity is characteristic of muscle wasting conditions including sepsis, cachexia and uraemia, but may not be rate limiting. Meanwhile, enhanced presence of immunoproteasomes in aging brain and muscle tissue could reflect a persistent inflammatory defence and anti-stress mechanism, whereas in cancer cells, their down-regulation reflects a means by which to escape immune surveillance. Hence, induction of apoptosis by synthetic proteasome inhibitors is a potential treatment strategy for cancer, whereas for other diseases such as neurodegeneration, the use of proteasome-activating or -modulating compounds could be more effective. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
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PMID:Role of proteasomes in disease. 1804 40

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in elderly patients. Therefore, efforts to optimize the healthcare process for patients with CAP are warranted. An organized approach to management is likely to improve clinical results. Assessing the severity of CAP is crucial to predicting outcome, deciding the site of care, and selecting appropriate empirical therapy. Unfortunately, current prognostic scoring systems for CAP such as CURB-65 (confusion, uraemia, respiratory rate, low blood pressure and 65 years of age) or the Pneumonia Severity Index have not been validated specifically in older adults, in whom assessment of mortality risk alone might not be adequate for predicting outcomes. Obtaining a microbial diagnosis remains problematic and may be particularly challenging in frail elderly persons, who may have greater difficulties producing sputum. Effective empirical treatment involves selection of a regimen with a spectrum of activity that includes the causative pathogen. Although most cases of CAP are probably caused by a single pathogen, dual and multiple infections are increasingly being reported. Streptococcus pneumoniae remains the overriding aetiological agent, particularly in very elderly people. However, respiratory viruses and 'atypical' organisms such as Chlamydia pneumoniae are being described with increasing frequency in old patients, and aspiration pneumonia should also be taken into consideration, particularly in very elderly subjects and those with dementia. Age >65 years is a well established risk factor for infection with drug-resistant S. pneumoniae. Clinicians should be aware of additional risk factors for acquiring less common pathogens or antibacterial-resistant organisms that may suggest that additions or modifications to the basic empirical regimen are warranted. In addition to administration of antibacterials, appropriate supportive therapy, covering management of severe sepsis and septic shock, respiratory failure, as well as management of any decompensated underlying disease, may be critical to improving outcomes in elderly patients with CAP. Immunization with pneumococcal and influenza vaccines has also been demonstrated to be beneficial in numerous large studies. There is good evidence that implementation of guidelines leads to improvement in clinical outcomes in elderly patients with CAP, including a reduction in mortality. Protocols should address a comprehensive set of elements in the process of care and should periodically be evaluated to measure their effects on clinically relevant outcomes. Assessment of functional clinical outcome variables, in addition to survival, is strongly recommended for this population.
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PMID:Improving outcomes of elderly patients with community-acquired pneumonia. 1858 47

In the setting of sepsis and multiorgan dysfunction syndrome, the development of acute kidney injury can be an ominous event, particularly in the pediatric patient. In this setting, rapid initiation of renal supportive therapy is likely to positively impact on mortality rates. Therapeutic initiation and choice of dialytic modality are dependent on physician beliefs, as well as patient and organizational characteristics. Patient-specific factors including adequacy of nutrition provision, acuity of acute kidney injury, degree of uremia, and severity of fluid overload all must be taken into account during the decision on whether or not to initiate renal supportive therapies. In addition to the utilization of classical renal supportive modalities such as acute hemodialysis, peritoneal dialysis, and continuous renal replacement therapies, the increasing use of plasma exchange therapies and other alternatives are actively being explored for use in sepsis-associated acute kidney injury. This article reviews these concepts and current literature in the context of pediatric specific sepsis-associated acute kidney injury.
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PMID:Renal supportive therapy for pediatric acute kidney injury in the setting of multiorgan dysfunction syndrome/sepsis. 1879 Mar 65


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