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)

There is no doubt that acute renal failure (ARF) is associated with enhanced protein breakdown. It has been shown that protein split products can be measured in plasma samples of these patients. On the other hand, ARF frequently occurs in conditions of increased metabolic stress which leads to enhanced protein catabolism. Muscle wasting, loss of lean body weight, and a negative nitrogen balance result in malnutrition which considerably increases morbidity and mortality. Besides the accumulation of uremic toxins, several other factors are involved in the accelerated proteolysis in ARF. Metabolic acidosis appears to be one of the major catabolic factors in chronic renal failure, and probably in ARF as well. Insulin resistance, which is commonly attributed to uremia, also increases protein degradation. However, this derangement of carbohydrate metabolism is not directly accessible to therapy, in contrast to acidosis, which can be easily corrected by bicarbonate administration. There is further evidence that glucocorticoid excess contributes to the enhanced muscle proteolysis in ARF. Moreover, several studies have demonstrated that only in the presence of both glucocorticoids and acidosis could proteolysis occur. Investigation of the cellular mechanism by which muscle proteins are degraded indicates the importance of the cytosolic, soluble ATP- and ubiquitin-dependent proteolytic system. Successful treatment of various catabolic conditions with recombinant human growth hormone and insulin-like growth factor-I seems to be a promising strategy in severely catabolic patients with ARF. Anticytokine therapy appears to be another promising treatment in the course of catabolic illness due to sepsis; however, clinical application is still in its infancy.
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PMID:Protein catabolism in acute renal failure. 938 14

The daily turnover of protein amounts to 280 g in an adult weighing 70 kg but the metabolic processes responsible for protein turnover are only just beginning to be understood. In cells, the major pathway of protein degradation is the ubiquitin-proteasome pathway and protein flux through this pathway is precisely regulated. In catabolic conditions such as uremia, activity of the ubiquitin-proteasome pathway increases, resulting in degradation of muscle protein. In addition to increased protein degradation, gene transcription is activated, resulting in higher levels of the mRNAs encoding ubiquitin and proteasome subunits. The signals activating this pathway include metabolic acidosis and glucocorticoids but must be more diverse since the pathway is also activated in response to starvation, sepsis, cancer, muscle denervation, thermal injury, and acute diabetes. Understanding how the pathway is controlled could lead to the prevention of muscle loss in uremia and other conditions.
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PMID:Cellular mechanisms controlling protein degradation in catabolic states. 938 15

Loss of lean body mass is common in patients with acute or chronic renal failure but the mechanisms causing this loss are only beginning to be understood. One mechanism involves an inability of uremic patients to activate the critical metabolic responses that maintain protein balance when dietary protein is limited. Metabolic responses to dietary protein restriction include a sharp reduction in the degradation of essential amino acids and protein; changes in protein synthesis are less reliable. If uremia prevents suppression of essential amino acid or protein degradation when dietary protein is reduced by anorexia, negative nitrogen balance and loss of lean body mass will ensue. One complication of uremia, metabolic acidosis, stimulates the degradation of branched-chain amino acids and proteins and therefore blocks the ability of the patient to respond to a low-protein diet. The mechanisms require glucocorticoids and involve increased activity of branched-chain keto acid dehydrogenase and the ubiquitin-proteasome proteolytic pathway; there also is increased transcription of genes encoding components of enzymes involved in the pathways. Besides acidosis, a low insulin concentration and cytokines activate the ubiquitin-proteasome proteolytic pathway. Understanding how proteolysis is activated, including how these genes are stimulated, is important because the same pathways are activated in diabetes, cancer, sepsis, burns, starvation, and muscle denervation. Activation of the ubiquitin-proteasome pathway leads to reduced lean body mass.
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PMID:Robert H Herman Memorial Award in Clinical Nutrition Lecture, 1997. Mechanisms causing loss of lean body mass in kidney disease. 949 77

A total of 140 pathoanatomic conclusions and files collected by the author are analyzed. Morphological signs of the DIC syndrome were detected in 55% of patients who died. In 42% of lethal outcomes this syndrome was the final direct cause of death after such conditions as terminal stage of cancer, sepsis, extensive myocardial infarction, mechanical jaundice, uremia, bacteremia, etc. In 13% of autopsies fatal intravascular coagulation was a complication of the intervention or hemorrhage which was arrested before death. The DIC syndrome is diagnosed during autopsy due to a complex of peculiar changes in the viscera which are called "shock" in such cases. The signs of a shock liver are as follows: a characteristic red net pattern of the sliced surface and histological phenomena related to blocking of the sinusoidal bloodflow and lobular ischemia: abnormal hepatocyte complexes, fragmentation of liver bulks, and necrosis of the central lobules.
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PMID:[Morphological diagnosis of DIC syndrome. Shock liver]. 951 Dec 43

As with most liver diseases, the symptoms of hepatitis in dogs are nearly always aspecific: the dogs eat less, are apathetic, sometimes have polyuria/polydipsia, and sometimes have diarrhoea. Hepatoencephalopathy and ascites only occur with these symptoms in very advanced stages of chronic hepatitis. Only a part of the dogs have jaundice. Because of these aspecific symptoms, the diagnosis hepatitis is often not taken into consideration, even though the presence of a liver disease can be easily detected by measuring plasma concentrations of alkaline phosphatase and bile acids, one or both of which are elevated. The diagnosis is confirmed by histological examination of a liver biopsy sample. The most common forms of hepatitis are non-specific reactive hepatitis, acute hepatitis, and chronic hepatitis. Non-specific reactive hepatitis is a reaction against endotoxin as a result of sepsis or an increased gastrointestinal absorption. Treatment is directed to the primary process. Leptospirosis also causes non-specific reactive hepatitis, but then renal insufficiency is the most prominent feature. The diagnosis is made not on the basis of a liver biopsy but on the basis of increased IgM titres against Leptospira. Immediate treatment with antibiotics and infusions at the first signs (jaundice and uraemia) can save the animal's life. Acute hepatitis can develop as a result of infection, toxins, or liver hypoxia. There is no specific treatment, but adequate recovery often occurs with supportive treatment. Corticosteroids are contraindicated. Chronic hepatitis, which can lead to cirrhosis, is the most common form of hepatitis. It is an autoimmune inflammatory reaction that is usually caused by a virus infection but sometimes by poisoning (intoxication). Long treatment with prednisolone or azathioprine is usually successful, but early recognition of the disease increases the likelihood of success. Nowadays, chronic hepatitis due to hepatic copper accumulation in Beddlington terriers can be detected by DNA tests. Such tests make it possible to distinguish between carriers and non-carriers. Affected animals can be kept symptom-free by life-long treatment with zinc gluconate or penicillamine.
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PMID:[Hepatitis in dogs; a review]. 958 48

Eight hemodialysis (HD) patients with convulsions of unknown cause were monitored for serum levels of uremic toxins such as methylguanidine(MG), and polymorphonuclear leukocyte elastase (PMNE). Twenty HD patients without convulsions served as controls. In the convulsion group, MG and PMNE were high. In 2 patients, convulsions subsided after daily hemodiafiltration (HDF). Although PMNE was thought to be a mediator of injury in the present series, no significant correlation was found between PMNE and either neutrophil numbers or endotoxin levels. PMNE may indicate the over production of cytokines not associated with serious infection or septicemia. In patients with renal failure and complications of unknown cause, intensified dialysis therapy such as frequent HDF may be useful when combined with treatment of the underlying disease producing the toxins. PMNE measurement is useful in assessing the uremia caused by high cytokine levels and, together with methylguanidin (MG) serum levels, can indicate the severity of the convulsion.
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PMID:Convulsions in hemodialysis (HD) patients with elevated polymorphonuclear leukocyte elastase (PMNE) levels. 960 30

Severe acute renal failure (SARF) occurs when renal dysfunction is such that haemodialysis or haemofiltration becomes necessary to maintain homeostasis. SARF is increasingly seen in association with multiorgan failure and has become a predominantly Intensive Care Unit disorder. Because of this change in epidemiology, the treatment of SARF has evolved from being exclusively nephrologist and intermittent haemodialysis-based to being mostly intensivist and continuous haemofiltration-based, particularly in European countries with a strong ICU tradition and in Australia. Continuous renal replacement therapy (CRRT) has several advantages in critically ill patients, including greater flexibility, excellent haemodynamic tolerance, outstanding fluid balance control, excellent control of uraemia, prevention of cerebral oedema, ability to provide full and aggressive nutrition, and a possible anti-inflammatory effect. The blood purification effect of CRRT may, in fact, go beyond the simple control of uraemia. Several animal studies have now shown that CRRT attenuates the haemodynamic consequences of bacteraemia or endotoxaemia. Such studies have also shown that increasing the intensity of fluid exchange may offer further beneficial effects in the setting of sepsis. In the light of these findings, CRRT is moving into the area of adjuvant treatment of sepsis, and pilot randomized controlled trials are being conducted to test the hypothesis that CRRT, either in standard or high fluid exchange volumes, attenuates the inflammatory effects of sepsis in humans. In the future, the use of CRRT may extend beyond its initial scope into the area of adjuvant management of sepsis and continuous blood purification may become part of a complex multifaceted approach to multiorgan dysfunction.
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PMID:Continuous renal replacement therapy: continuous blood purification in the intensive care unit. 977 92

Prophylactic hemodialysis has been employed in the treatment of 15 patients with acute renal failure due to acute tubular necrosis (12), bilateral renal cortical necrosis (two), and poststreptococcal glomerulonephritis (one). Dialyses, usually lasting six hours each, were begun before clinical evidence of uremia developed in each patient and/or before the nonprotein nitrogen reached 200 mg.%, and were repeated daily or often enough to maintain the nonprotein nitrogen below 150 mg.%. The hypothesis underlying this technic postulates (1) that wasting, sepsis and impaired wound healing in these patients may reflect tissue injury by the same dialyzable toxic agents which produce the uremic symptoms that are readily reversible by dialysis, and (2) that repeated dialyses should therefore prevent both clinical uremia and the later, often lethal sequelae. The results contrast dramatically with our own past experience in treating patients with acute renal failure with a carefully executed medical regimen together with hemodialysis on conventional indications. Except in one instance of crush injury with progressive intracerebral damage, and one brief occasion in another individual, these patients experienced a stable, convalescent clinical course, remained free of uremic symptoms or chemical imbalances, ate at least three meals daily which were unrestricted in amount and composition, and were ambulatory between dialyses unless confined to bed by associated disease. Wounds healed well. Infection either did not occur, or subsided after appropriate therapy. Fluid restriction was liberalized by means of ultrafiltration with dialysis. Regional heparinization of only the extracorporeal circuit eliminated actual or impending bleeding as a contraindication to dialysis. Chronic vessel cannulation made the frequent dialyses possible, but may have provided the route for repeated, transient bacterial contamination of the blood stream in the first hour of many dialyses. Marked anemia, despite reticulocytosis, moderate to mild weight loss and some mental deficit persisted in spite of the general clinical improvement and well-being. Three patients with tubular necrosis died after seven, 11 and 26 days of oliguria; both patients with bilateral renal cortical necrosis also succumbed, on the seventy-third and ninety-second days of renal failure, and after 29 and 40 dialyses, respectively. At autopsy, evidence of sepsis was conspicuously absent. The remaining 10 patients survived. Thus some, but not all, clinical manifestations of acute renal failure appear to be favorably influenced by prophylactic dialysis treatment. Our initial experience in this group of 15 patients does not of course prove that freedom from complications and a significantly better outlook for survival can be assured to patients with acute renal failure by these methods. However, it seems to offer a reasonable hope of this possibility which we cannot attach to management by medical measures alone, or by dialysis on conventional indications. If this hope is realized in greatly extended, subsequent series, then it seems inevitable that some form of prophylactic dialysis, or some equally effective alternative, should be adopted in treating the majority of patients with acute renal failure.
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PMID:Prophylactic hemodialysis in the treatment of acute renal failure. Annals of Internal Medicine, 53:992-1016, 1960. 984 96

To determine the clinical usefulness of the autopsy in elderly patients, we studied a total of 231 autopsies performed during 1986 and 1995 at Jikeikai hospital. Autopsies were done after 231 of 609 deaths (38%). The autopsy rate in our hospital fell from 63% in 1986 to 17% in 1995. Most primary causes of deaths as established by clinicians before autopsy were pulmonary, neoplastic, and cardiovascular diseases. The probability of a major unexpected finding at autopsy was higher in acute pneumonia, acute myocardial infarction, and cerebrovascular disease. No primary pathological cause of death was established by pathologists at autopsy in 13 cases (The clinical diagnoses in those patients were acute pneumonia in 5 patients, acute myocardial infarction in 2 patients, sepsis in 2 patients, bronchiale asthma, cerebral infarction, uremia, gastrointestinal bleeding each in 1 patient.) The mean age of these 13 patients was higher by 5 years than the age of the group as a whole. This indicate that elderly patients have many complications and that these deaths were caused by many small changes that were not be detected at autopsy. Latent cancer was found in 23 cases (12%): thyroid and colon cancer in 6 patients each, gastric cancer in 4, prostate cancer in 3, ovarian cancer in 2, and other cancers (renal, uterine, lung, urethral, pancreatis and liver) each 1 in patient.
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PMID:[Clinical usefulness of the autopsy in elderly patients]. 1021 66

Renal failure with severe uremia is still an important cause of mortality, despite effective renal replacement therapy. Cardiopulmonary arrest (CPA) is the most severe complication during hemodialysis (HD). To acquire more information about cardiopulmonary resuscitation (CPR) during HD, we retrospectively enrolled 24 patients (11 males and 13 females) who had CPR during HD in a medical center during a 3-year period. Their mean age was 66.8 +/- 16.8 years. The CPR rate of the patients from our outpatient department (0.02%) was significantly lower than that from general wards (0.11%), the intensive care unit (ICU, 0.16%), or the emergency room (ER, 0.38%). Eighteen patients (75%) were initially resuscitated successfully. Only 11 patients (45.8%) survived more than 24 h after CPR, and 2 patients (8.3%) survived more than 1 month, but none survived until discharge. The rates of surviving 24 h and surviving to discharge during HD were lower than those in the general wards, the ICU or the ER. Sepsis (33.3%) and cardiogenic shock (25%) were the two leading causes of death. For analyzing factors affecting the outcome of CPR, we divided the patients into 2 groups by survival time (<==24 vs. >24 h). Patients with heart disease or with prolonged CPR durations (>30 min) had shorter survival. No significant survival difference between the 2 groups was found due to factors of age, sex, diabetic nephropathy, pre-arrest morbidity scores, pre-arrest laboratory data, renal failure pattern, HD duration, the preceding HD time and ultrafiltrated volume.
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PMID:Clinical findings and outcomes of intra-hemodialysis cardiopulmonary resuscitation. 1046 Sep 36


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