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)

Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and systemic inflammatory states such as sepsis. Accumulating evidence indicates that contractile failure is associated with dysregulation of myoplasmic calcium levels. In a search for biochemical causes for contractile dysfunction, we found that the dipeptide carnosine improves cardiac contractility and tested the possibility that carnosine plays a role in the regulation of intracellular calcium. Carnosine increased contractility in a dose-dependent manner (1-10 mM) in isolated perfused rat hearts. and it also increased free intracellular calcium levels in isolated myocytes. Carnosine increased myocyte tension via calcium release from the ryanodine receptor calcium release channel in skinned myocardial fibers and increased open-state probability and dwell time of the isolated ryanodine receptor calcium release channel in lipid bilayers. In addition. we report that carnosine sensitizes the contractile proteins so calcium. These results suggest a novel role for carnosine as a modulator of intracellular calcium and contractility in cardiac tissue.
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PMID:Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells. 903 68

The purpose of this study was to determine the characteristics of gouty arthritis in an urban Guatemalan population. We reviewed the medical records of 148 (145 males and 3 females) patients with a diagnosis of acute gouty attack seen at an urban rheumatology clinic in Guatemala City between 1982 and 1993. Mean age at diagnosis was 49 years (range 21-87), mean age of onset was 42 years, mean duration of disease 7.4 years, family history of gout 42 (28%), peak prevalence 5th decade 39 (26%). Seventy-one (48%) had monarticular, 49 (33%) oligoarticular, and 22 (15%) polyarticular attacks, respectively. Podagra was seen in 34 (23%) patients; however, 108 (73%) developed it at any moment of their life. Tophaceous gout was seen in 33 (22%). Mean serum urate concentrations (enzymatic method) were higher than 7.0 mg % in 90 (60%) patients. At follow-up, 44 (30%) patients never returned to our clinic, and a large majority of them [66 (45%)] were seen only during acute attacks. Associated disorders included hypertension (43%), obesity (27%), nephrolithiasis (16%), ischaemic heart disease (7%), renal insufficiency (2%), stroke (0.6%), and diabetes mellitus (0.6%), and two died due to sepsis; high alcoholic intake was found in 58 (39%) patients. In conclusion, our findings indicate that gout is not an unusual disorder in the Guatemalan population. It presents with the same characteristics as those reported in Caucasians, with the possible exception of a lower frequency of diabetes mellitus as an associated disorder.
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PMID:Characteristics of gouty arthritis in the Guatemalan population. 913 25

Adults and children have cardiac arrests for very different reasons. The commonest reason for an adult cardiac arrest is a primary arrhythmia in association with ischaemic heart disease, i.e. ventricular fibrillation. Children have cardiac arrests because of respiratory failure, hypovolaemia (due to trauma and dehydration) and sepsis.
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PMID:Resuscitation. IV: Advanced paediatric life support. 948 20

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.
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PMID:Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer. 985 99

Although the short- and medium-term (5-10 years) outcome of patients with lupus nephritis has been studied extensively, there are very few data on the second and subsequent decades. We studied outcome in 110 local patients investigated at a single centre before 1986, who all had potential follow-up of more than 10 years (actual 2-31 years, median 15.5 years). At last follow-up, 40 patients were dead and 70 alive, nine of whom were on maintenance dialysis or transplanted, actuarial survivals being 84%, 72%, 62%, 61% and 54% at 5, 10, 15, 20 and 25 years for the group as a whole. Survival was better in the cohort 1976-86 (n = 60) than in that from 1963-75 (n = 50) (90, 81 and 76% vs. 78, 56 and 43% at 5, 10 and 15 years, p < 0.001). Sepsis (12) and myocardial infarction (8) were the principal causes of death. Of living patients with renal function, 38% had normal urine and renal function, 11 were off all treatment (19%), 62% had persistent proteinuria and 18% had reduced but generally stable renal function. Renal failure, in those patients who developed it, occurred during the first decade and none of 67 patients actually followed more than 10 years subsequently went into renal failure. Induction treatment was with prednisolone, combined with azathioprine in more severe forms of nephritis, and from the middle 1970s to 1986, 30 with methylprednisolone and in 12 cases plasma exchange. Seventeen other patients were treated using oral cyclophosphamide during the 1960s. No patient received i.v. cyclophosphamide as induction therapy, although nine patients had this form of treatment later, largely because of non-compliance. Serious complications of lupus and/or its treatment occurred in 49%: sepsis in 32, ischaemic heart disease in 20, thrombosis in one and avascular necrosis of bone in eight. In contrast, fracturing osteoporosis occurred in only three, and cataracts requiring surgery and diabetes mellitus in none. The very long-term outlook of lupus nephritis, especially its more severe forms, has improved, but that with current management strategies only a minority of patients are able to stop treatment altogether, and the incidence of serious complications is high.
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PMID:The very long-term prognosis and complications of lupus nephritis and its treatment. 1039 9

Coronary complications after aortic root replacement (ARR) with pulmonary autografts have been reported to be more common than with other stentless biological conduits (homografts, xenografts). To verify this hypothesis, results with 84 consecutive patients having stentless ARR between January 1992 and January 1999 were reviewed. Fifty patients had autograft (Group 1) and 34 either homograft or xenograft (Group 2) ARR. Comparison of age (27+/-9 vs. 38+/-22 years, P = ns), prevalence of male sex (86% vs. 79%, P = ns), aortic root disease (30% vs. 44%, P = ns), congenital coronary anomalies (10% vs. 3%, P = ns), prior aortic procedure (16% vs. 15%), and need for associated procedures (26% vs. 24%, P = ns), did not disclose significant differences. Bicuspid aortic valve was more prevalent in Group 1 (56% vs. 9%, P = .001). Mean aortic crossclamp (154+/-28 vs. 120+/-24 minutes, P = .05) and bypass (216+/-30 vs. 192+/-58 minutes, P = .05) times were longer in Group 1. Early mortality was comparable (2% vs. 3%, P = ns) and caused by right ventricular ischemia in both groups. Overall prevalence of coronary complications was higher in Group 1 (10% vs. 3%, P = .04), all resulting in right heart ischemia. Intraoperative partial takedown of repair in 5 Group 1 patients, associated with CABG in 1, resulted in prompt resolution of myocardial ischemia in 4 (80%) and prolonged in 1, which ultimately died as a result of sepsis. Recovery was prompt in all 4 patients (mean ICU stay 35+/-28 hours) with no metabolic or echocardiographic evidence of myocardial infarction. At discharge echocardiography, satisfactory biventricular kinetics was found in all patients. Analysis of preoperative variables showed bicuspid aortic valve (83% vs. 33%, P = .01) and coronary anomalies (67% vs. 3%, P = .001) to be more prevalent in patients suffering from coronary complications. Stentless ARR is a safe procedure with low operative mortality, regardless of the type of biological conduit. Autograft ARR may be at greater risk of right ventricular ischemia in patients with bicuspid aortic valve and coronary anomalies. An aggressive intraoperative approach including partial takedown of repair may limit the morbidity of coronary complications.
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PMID:Risk factors for coronary complications after stentless aortic root replacement. 1066 Jan 80

A stress-activated serine/threonine protein kinase, p38 mitogen-activated protein kinase (p38 MAPK), belongs to the MAP kinase superfamily. Diverse extracellular stimuli, including ultraviolet light, irradiation, heat shock, high osmotic stress, proinflammatory cytokines and certain mitogens, trigger a stress-regulated protein kinase cascade culminating in activation of p38 MAPK through phosphorylation on a TGY motif within the kinase activation loop. p38 MAPK appears to play a major role in apoptosis, cytokine production, transcriptional regulation, and cytoskeletal reorganization, and has been causally implicated in sepsis, ischemic heart disease, arthritis, human immunodeficiency virus infection, and Alzheimer's disease. The availability of specific inhibitors helps to clarify the role that p38 MAPK plays in these processes, and may ultimately offer therapeutic benefit for certain critically ill patients.
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PMID:MAP kinase pathways activated by stress: the p38 MAPK pathway. 1080 18

BACKGROUND: We analyzed the causes and results of utilization of critical care services in the special care unit in patients after surgical procedures performed by the hepatobiliary surgical service during a 23-month period. RESULTS: Thirty-two of 537 patients (6.0%) required postoperative admission to the special care unit. Twenty-one patients were admitted directly from operating room or from recovery room because of inability to wean from ventilator (n = 10), hypovolemic shock (n = 4), myocardial ischemia or infarction (n = 2), sepsis (n = 2), upper gastrointestinal bleeding (n = 2), and acute renal failure (n =1). Eleven postoperative patients were admitted from floor care for respiratory failure (n = 4), cardiac dysrhythmia or infarction (n = 4), sepsis (n = 2), and upper gastrointestinal bleeding (n = 1). Thirty-eight per cent of patients (n = 12) admitted to the special care unit after surgery died. By multivariate analysis, total postoperative stay in the special care unit that was greater than median total duration of stay of 4.5 days was the only independent predictor of mortality (P = 0.041). CONCLUSIONS: Respiratory failure was the predominant component of all complications after hepatobiliary surgery. No clinically useful predictors of eventual outcome could be identified.
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PMID:The critically ill patient after hepatobiliary surgery. 1105 38

The balance between cell survival and death is under tight genetic control. A multiplicity of extracellular signals and intracellular mediators is involved in maintaining this balance. When the cell is exposed to physical, biochemical or biological injury, or deprived of necessary substances, it activates a series of stress-response genes. With minimal insults, the cell may recover. With greater insults, single cell death, or apoptosis, results; the cell dies and is recycled to its neighbours. If the insult overwhelms a large number of cells then necrosis ensues, with an accompanying inflammatory response. Dysregulation of the controlling mechanisms of this system results in disease. Deficient apoptosis is associated with cancer, auto-immunity and viral infections. Excessive apoptosis is associated with ischaemic heart disease, stroke, neurodegenerative disease, sepsis and multiple organ dysfunction syndrome. There are myriad therapeutic options unfolding as understanding is gained of apoptosis and its control.
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PMID:Apoptosis: mechanisms and clinical implications. 1135 Mar 55

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
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PMID:Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? 1113 72


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