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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The availability of potent and stable bradykinin antagonists has had a tremendous impact on kinin research. This article reviews the current status of research on kinin antagonists, describes their chemical properties, and delineates recent advances that have occurred with the advent of the second generation of kinin antagonists. The data collected with these antagonists support the assumption that kinins are implicated in inflammation and tissue injury as endogenous agents. Their importance, however, is not limited to the role as mediators of tissue injury and inflammation, as kinin antagonists have enabled the identification kinins as potential endogenous cardioprotective substances, also contributing to the effects of angiotensin converting enzyme inhibitors. Clinical studies are currently being performed in asthma, postoperative pain, anaphlyactoid reactions during low density lipoprotein apheresis, systemic inflammatory response syndrome, and suspected sepsis, head injury, and hantavirus infections to investigate the utility of kinin antagonists as therapeutic agents.
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PMID:Kinin receptor antagonists: unique probes in basic and clinical research. 884 12

Burn injury and sepsis produce acute gastrointestinal derangements that may predispose patients to bacterial translocation. We studied the effects of enalapril, an angiotensin converting enzyme inhibitor (ACEI), on gastrointestinal anatomic alterations, bacterial translocation, and related mortality during gut-derived sepsis in burned mice that had received a prior bacterial challenge. BALB/c mice (n = 111) were treated with enalapril 10 or 1 mg/kg body weight or sterile saline as control twice daily for 3 days. They were then gavaged with 10(a)111 in radiolabeled or unlabeled Escherichia coli and given a 20% total body surface area (TBSA) burn injury. Animals gavaged with unlabeled bacteria were observed for survival (n = 60). Survival was significantly higher in the group receiving enalapril 10 mg/Kg compared with control (75% vs. 10%). Mice treated with enalapril maintained small intestine weight, measured 4 h postburn, and ileal mucosal height was preserved, whereas burned untreated animals lost intestinal weight and mucosal height. Bacterial translocation was decreased in mice treated with enalapril, but killing was unaffected. This study suggests that treatment with enalapril positively affects the outcome in gut-derived sepsis by ameliorating gastrointestinal structural and functional damage and decreasing bacterial translocation.
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PMID:Effects of the angiotensin converting enzyme inhibitor enalapril on bacterial translocation after thermal injury and bacterial challenge. 885 42

HIV-infected patients may present with a variety of patterns of renal involvement. Acute renal failure is common and most often a result of sepsis, hypotension, and nephrotoxic agents. It is potentially avoidable, and support through the period of renal failure may lead to resolution of the renal dysfunction. HIV-associated nephropathy is a unique pattern of sclerosing glomerulopathy that ranges in prevalence from 1 to 10% of the HIV-infected population in different geographic locales. This complication of HIV infection will likely present a growing challenge to the medical community as HIV infection continues to spread worldwide. Deciphering the pathogenetic mechanisms of this most rapidly progressive form of focal segmental sclerosis is not only clinically relevant, but will hopefully provide valuable insights into the mediation of the more common idiopathic form of the disease. The potential for improved renal survival of patients with HIV-associated nephropathy has become more realistic with the development and use of antiretroviral agents, as well as studies on the role of immunosuppression and ACE inhibition in this population. An awareness of other glomerular lesion and tubulointerstitial lesions has broadened our understanding of populations with renal disease who have been infected by HIV. Moreover, as prolonged survival of HIV-infected individuals is being achieved with modern antiviral therapy, the percentage of patients surviving with nephropathy will likely grow in coming years. Awareness of the growth of this population and those requiring short- and long-term hemodialysis and peritoneal dialysis will allow appropriate planning for ESRD in the HIV-infected population.
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PMID:HIV infection and the kidney. 901 59

Ten of 26 patients with sepsis were given a combination of dexamethasone (0.15 mg/kg, intravenously, once on admission), colchicine (0.5 mg, orally, daily, for 3 days) and pentoxifylline (DCP) (400 mg, orally, daily, for 3 days), together with best medical therapy. Serum tumour necrosis factor-alpha (TNF-alpha) levels were undetectable at 24 h compared with about 4 IU/ml (mean) in 16 similar control patients who were not given DCP (P < 0.06). Although the clinical course in the two groups was not significantly different, this simple, well-tolerated and inexpensive regimen should be further evaluated as a possible means of preventing the deleterious effects of TNF-alpha in sepsis.
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PMID:Triple anti-TNF-alpha therapy in early sepsis: a preliminary report. 910 Jan 67

Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates.
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PMID:POMB/ACE chemotherapy for mediastinal germ cell tumours. 929 97

Diabetes mellitus carries a great burden on healthcare costs due to its growing population and high co-morbidity. This adverse effect sustains even when patients develop end-stage renal disease (ESRD). We here present data showing the effect of diabetes on economic costs in dialysis therapy in Taiwan. As of the end of 1997, we have 22,027 ESRD patients with a prevalence and incidence rate of 1013 and 253 per million populations, respectively. Diabetic nephropathy is the second most common cause of the underlying renal diseases, but accounts for 24.8% of the prevalent patients and 35.9% of the incident cases. The diabetic patients engendered 11.8% more expense for care of dialysis than the non-diabetic patients (US $26,988 vs. US $24,146 per patient-year). Higher inpatient cost mainly account for the difference. As compared to non-diabetic patients, the diabetic patients had 3.5 times more inpatients costs (US $1325 vs. US $4677 per patient-year), and higher proportion of inpatient-to-annualized cost ratio (5.5 vs. 17.3%) resulting from their more frequent hospitalization (0.59 vs. 1.13 times per patient-year) and longer hospital stay (6.7 vs. 18.9 days per patient-year). The major causes responsible for a more frequent hospitalization were cardiovascular disease, poorly controlled hyperglycemia, sepsis and failure of vascular access. The annualized costs for care of dialysis patients in Taiwan, including inpatient and outpatient costs, averaged US $25,576 per patient-year. This value is approximately half of that in most of the western countries and Japan. Thus, a more cost-effective way to achieve savings is to reduce the high incidence rate of dialysis population and to maximize the quality of dialysis treatment for avoiding hospitalization. Recent studies had shown that tight blood pressure control, intensive glycemic control, and use of angiotensin converting enzyme inhibitors in diabetic patients significantly reduced not only the rate of progressive renal failure, but also substantially reduced the cost of complications and led to higher cost effectiveness. Once diabetic patients reach stage of ESRD, an optimized pre-ESRD care and consideration of kidney transplantation are essential in terms of better patient survival and cost savings.
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PMID:The impact of diabetes on economic costs in dialysis patients: experiences in Taiwan. 1158 Sep 69

Plasmapheresis is a general term involving extracorporeal plasma separation by centrifugation or primary membrane plasma separator (MPS). Further plasma processing can be accomplished by the use of secondary membrane plasma fractionation (PF), as in double filtration plasmapheresis, also called cascade filtration, low-density lipoprotein pheresis, thermofiltration, and cryofiltration apheresis. Otherwise, the separated plasma is replaced by colloid solution as in plasma exchange (PE). PE is used, unselectively, to treat patients with immunological, neurological, hematological, renal, and metabolic disorders. Secondary PF may be a more selective alternative. In general, the primary MPS and secondary PF are safe, effective, and biocompatible. The advantages of the primary MPS include its simplicity to use with blood pumps and no observed white blood cell or platelet loss, compared with centrifugation. The disadvantages are lack of versatility, the need to monitor transmembrane pressure to prevent hemolysis, and possible biocompatibility issues such as use of polyvinyl alcohol membranes. The advantages of secondary PF, compared with PE, include selective removal of macromolecules according to molecular weight and filter pore size. No deficiency syndromes or sepsis are observed, nor is replacement solution required. More than 1 plasma volume may be processed, and it is less expensive than PE. Cryofiltration apheresis, using the cryoglobulin filter, selectively removes cryoproteins and is a specific treatment for cryoprecipitate-induced diseases. The disadvantages of PF include biocompatibility, especially with concomitant ACE inhibitor use, and membrane plugging. An important disadvantage is that most PFs are investigational in the United States. This article reviews the availability, safety, efficacy, and biocompatibility of primary MPSs and secondary PF in the United States.
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PMID:Membrane plasmapheresis in the United States: a review over the last 20 years. 1172 18

Despite major advances in nutritional support, membrane technology and dialytic techniques, the mortality of patients with acute renal failure (ARF) who require dialysis is still almost 50% (1). Increased patient age and co-morbidity confer a poorer prognosis, and the condition is certainly commoner in this patient group. Hence, one study showed that the age-related annual incidence of ARF increased from 17 per million in adults under 50 years to 949 per million in the 80-89 age group (2). Over 60% of cases of ARF ultimately result from renal hypoperfusion and consequent intra-renal ischaemic damage, which leads to acute tubular necrosis (ATN) (3). Ischaemic ARF may thus result from a diversity of systemic and intra-renal circulatory stresses including acute losses of blood and extra-cellular fluids, from low cardiac output states such as following ischaemic or toxic myocardial damage, and even from drug-induced renal perfusion shutdown (ACE inhibitors, non-steroidal anti-inflammatory agents). Many cases of ARF have a multi-factorial aetiology (e.g. post-surgical sepsis with hypovolaemia, hypotension and injudicious antibiotic use), and these patients, who often have other organ failure, fit into the poorer prognostic category. A large number of patients with ischaemic ARF pass through a phase of potentially reversible pre-renal oliguria; early recognition and prompt, appropriate treatment of these pre-renal factors can prevent progression to established ARF, with the genuine prospect of improved patient morbidity and mortality, and this is the main scope of this article. Early diagnosis in other patients with ARF, such as those with acute inflammatory renal disease (e.g. vasculitis) or urinary tract obstruction, will allow appropriate prompt treatment and the possibility for reversal of the ARF. The following account, which is composed of personal experience, that of colleagues, and the literature (1,4), is not intended to provide a comprehensive guide to the management of ARF, but seeks to highlight important common pitfalls and fundamental principles in the recognition and subsequent preventive treatment of these patients.
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PMID:Early management and prevention of acute renal failure. 1237 20

Glucose-6-phosphate dehydrogenase (G-6-PDH) deficiency is the most common known human genetic polymorphism. This study tested the hypothesis that G-6-PDH deficiency worsens sepsis-induced erythrocyte dysfunction. Sepsis (24 h) was induced by cecal ligation and puncture in wild-type (WT) and G-6-PDH-deficient (G-6-PDH activity 15% of WT) mice. Erythrocyte responses were tested in whole blood as well as in subpopulations of circulating erythrocytes. Whereas erythrocyte deformability was similar in unchallenged deficient and WT animals, sepsis decreased erythrocyte deformability that was more pronounced in deficient than WT animals. Sepsis also resulted in anemia and hemolysis in deficient compared with WT animals. Mean corpuscular hemoglobin content and erythrocyte deformability decreased in younger erythrocyte subpopulations from septic deficient compared with WT animals. Sepsis decreased the reduced-to-oxidized glutathione ratio in erythrocytes from both deficient and WT animals; however, plasma glutathione increased more in deficient than in WT animals. Erythrocyte content of band 3 associated with the cytoskeleton was elevated in deficient compared with WT erythrocytes. The antioxidant N-acetyl-l-cysteine in vivo alleviated the sepsis-induced decrease in erythrocyte deformability in deficient animals compared with sham-operated control animals. This study demonstrates that a mild degree of G-6-PDH deficiency (comparable to the human class III G-6-PDH deficiencies) worsens erythrocyte dysfunction during sepsis. Increased erythrocyte rigidity and tendency for hemolysis together with alterations in band 3-spectrin interactions may contribute to the immunomodulatory effects of G-6-PDH deficiency observed after major trauma and infections in humans.
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PMID:Red blood cell dysfunction in septic glucose-6-phosphate dehydrogenase-deficient mice. 1475 57

Besides cyclooxygenase and NO-synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization (EDHF), is involved in the relaxation of the vascular smooth muscle cells. EDHF has been demonstrated unequivocally in various blood vessels from different species, including human, and is likely to play an important role in cardiovascular physiology. This alternative pathway involves the activation of two populations of endothelial potassium channels, the small conductance and intermediate conductance calcium-activated potassium channels (SK(Ca) and IK(Ca), respectively). EDHF-mediated responses are clearly altered in various pathological conditions (ageing, hypertension, atherosclerosis, hypercholesterolemia, heart failure, ischemia-reperfusion, angioplasty, eclampsia, diabetes, sepsis). Therapeutic or adjutant interventions (angiotensin converting enzyme inhibitors, antagonist of the angiotensin receptor, estrogen, omega-3 polyunsaturated fatty acids, polyphenol derivatives, potassium and/or calcium intake) can restore these responses, suggesting that the improvement of the EDHF pathway contributes to the observed beneficial effect of these various substances. However, the improvement or restoration of EDHF responses has not been, yet, the direct purpose of any pharmaceutical effort. Activating endothelial IK(Ca) and/or SK(Ca) or increasing their expression as well as improving myo-endothelial communication, for instance by increasing the expression of connexin(s), could become interesting therapeutic targets.
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PMID:EDHF: new therapeutic targets? 1502 34


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