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 are three clinical presentations of anthrax in humans: cutaneous (>95% of cases), orogastric and inhalational. The infectious form, the spore, enters the body and is thought to germinate within macrophages either at the site of inoculation (cutaneous or orogastric) or in the regional lymph node (inhalational). The bacillus then synthesizes its antiphagocytic capsule and the lethal and oedema toxins which interfere with the non-specific host defences leading to the characteristic locally destructive lesion and spread by lymphatics to the systemic circulation and other organs. The cutaneous form begins as a papule which progresses over several days to a vesicle and then ulcerates. There is often oedema, sometimes massive, probably due to the oedema toxin that surrounds the lesions which then develop a characteristic black eschar. The patient may be febrile with mild to severe systemic symptoms of malaise, headache and toxicity. Oropharyngeal anthrax presents with severe sore throat or an ulcer in the oropharyngeal cavity associated with neck swelling, fever, toxicity and dysphagia. Gastrointestinal anthrax begins with anorexia, nausea, vomiting and abdominal pain which may be similar to an acute abdomen. There may be diarrhoea and ascites, both of which may be haemorrhagic. Inhalational anthrax begins with non-specific symptoms of malaise, fever, myalgia and non-productive cough. After a period of 2-3 days, this is followed by a sudden onset of severe respiratory distress associated with diaphoresis, cyanosis and increased chest pain. There may be a widened mediastinum and pleural effusions on chest X-ray. Death follows in 24-36 h from respiratory failure, sepsis and shock. The diagnosis of anthrax is easy if it is considered. The organism is readily observed by Gram or Wright stain in local lesions or blood smear and can be easily cultured from the blood and other body fluids. However, because of its rarity, it is not often included in the differential diagnosis and in inhalational disease the diagnosis is rarely made until the patient is moribund. More rapid diagnostic tests are under development. Penicillin, combined with supportive care, remains the mainstay of treatment, although the organism is susceptible in vitro to many antibiotics. In recent years, there have been significant advances in our knowledge of the organism and its toxins and it is anticipated that similar progress will be made in the future in developing more rapid diagnostic tests and new modalities of treatment.
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PMID:Clinical aspects, diagnosis and treatment of anthrax 1047 74

During sepsis, catabolism of proteins and associated changes in plasma amino acids occur. Tryptophan and tyrosine, and their derivatives serotonin (5-HT) and dopamine (DA), influence hypothalamic feeding-related areas and are associated with the onset of anorexia. We hypothesized that anorexia of sepsis is associated with changes in serotonin and dopamine in the ventromedial nucleus (VMN) of the hypothalamus. The aim of this study was to test our hypothesis by measuring intra-VMN changes of these two neurotransmitters at the onset of anorexia during sepsis. Fischer 344 male rats had an intracerebral guide cannula stereotaxically implanted into the VMN. Ten days later, in awake, overnight-food-deprived rats, a microdialysis probe was inserted through the in situ VMN cannula. Two hours thereafter, serial baseline serotonin and dopamine concentrations were measured. Then cecal ligation and puncture to induce sepsis or a control laparotomy was performed under isoflurane anesthesia. VMN microdialysis samples were serially collected every 30 min for 8 h after the surgical procedure to determine 5-HT and DA changes in response to sepsis. During the hypermetabolic response to sepsis, a strong association occurred between anorexia and a significant reduction of VMN dopamine concentration (P < 0.05; constant rate of dopamine decrease in the Study group of 0.99 pg per 2 h); no changes occurred in 5-HT in association with anorexia of sepsis. Six hours after operation, a single meal was offered for 20 min to assess the response of neurotransmitters to food ingestion. Food intake was minimal in anorectic septic rats (mean size of the after food-deprived meal in the Septic group was 0.03+/-0.01 g, that of the Control group was 1.27+/-0.14 g; P = 0.0001), while Control rats demonstrated anticipated changes in neurotransmitters in response to eating. We conclude that the onset of anorexia in septic rats is associated with a reduction in VMN dopamine.
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PMID:VMN hypothalamic dopamine and serotonin in anorectic septic rats. 1071 77

The treatment and cure of patients exposed to sulfur mustard is a remaining challenge despite on-going research in this field. A severe suppression of the immune system still remains the major cause of opportunistic infections, septicemia and death in patients injured by sulfur mustard. In this report, we present a model of sulfur mustard contamination in mice, which exhibit clinical signs similar to that exhibited by patients during the Iran-Iraq war. Dose response studies were performed to determine the most appropriate dose for our model i.e., 6.35 micrograms/kg. Animals contaminated with sulfur mustard intraperitoneally showed symptoms of anorexia, diarrhea, loss of weight and blindness. Autopsy of animals showed a severe necrosis in gut and degeneration of spleen. Results shows that sulfur mustard caused an over all suppression of the immune response to sRBC as indicated by agglutination titer and DTH tests. These studies present a rodent model of sulfur mustard exposure, which can be used for further studies in this area.
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PMID:Modeling for immunosuppression by sulfur mustard. 1136 43

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.
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PMID:[Chronic experimental bacteremia in Yucatan micropigs]. 1164 22

Bacterial infection alters whole-body protein homeostasis. Although immune cells are of prime importance for host defense, the effect of sepsis on their protein synthesis rates is poorly documented. We analyzed protein synthesis rates in rat primary lymphoid tissues and circulating lymphocytes after infection. Male Sprague-Dawley rats were studied 1, 2, 6 or 10 d after an intravenous injection of live Escherichia coli. Control healthy rats consumed food ad libitum (d 0) or were pair-fed to infected rats. Protein synthesis was quantified using a flooding dose of L-(4,4,4-(2)H(3))valine. Sepsis induced a delayed increase in total blood leukocytes and a rapid and persistent inversion of the counts. Basal fractional rates of protein synthesis (ks) were 117, 73 and 29%/d in bone marrow, thymus and circulating lymphocytes, respectively. Pair-feeding strongly depressed the absolute protein synthesis rates (ASR) of bone marrow (d 2 and 10) and thymus (d 2-10). The infection per se increased bone marrow, thymus and circulating lymphocyte ks but at various postinfection times. It decreased bone marrow (d 1) and thymus (d 1 and 2) ASR but increased lymphocyte (d 2 and 10) and bone marrow (d 10) ASR. Our results reflect the deleterious effect of anorexia on primary lymphoid tissues. The host defense against bacterial infection exhibited time- and tissue-dependent modifications of protein synthesis, indicating that blood lymphocyte protein data are not representative of the immune system as a whole. Optimization of nutritional supports would be facilitated by including protein synthesis measurements of the immune system.
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PMID:Bacterial infection affects protein synthesis in primary lymphoid tissues and circulating lymphocytes of rats. 1209 87

A 49-kg (107.8-lb) sexually intact male Arabian foal was evaluated at 3 days of age because of profuse watery diarrhea, anorexia, and signs of abdominal pain. Physical examination findings were unremarkable except for evidence of diarrhea. A catheter was placed in the right jugular vein for administration of antimicrobials and lactated Ringer's solution. The foal was discharged with instructions to the owner to continue antimicrobial administration and fluid therapy; at home, the owner inadvertently cut the catheter at the level of the hub during attempted removal, and the catheter fragment migrated distally in the jugular vein and subsequently lodged in the pulmonary artery. The foal was readmitted to the hospital for retrieval of the fragment, using a percutaneous retrieval technique. Catheter fragmentation is a well-recognized risk of catheterization in horses. Catheter fragments can be retrieved somewhat easily from the jugular vein; however, if the fragment migrates to the heart or pulmonary artery, imaging the fragment to locate and retrieve it can be difficult. Complications associated with catheter fragmentation include septicemia, endocarditis, lung abscesses, pulmonary embolism, dysrhythmias, cardiac perforation, pulmonary or caval thrombosis, and death. To our knowledge, this is the first report of successful retrieval of a catheter fragment from the pulmonary artery in a horse.
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PMID:Percutaneous retrieval of a jugular catheter fragment from the pulmonary artery of a foal. 1212 33

Intravenous busulfan (i.v. BU) has demonstrated safety when administered at 0.8 mg/kg per dose i.v. every 6 hours x 16 doses. We evaluated the safety and pharmacokinetics (PK) of giving the same total daily i.v. BU dose (3.2 mg/kg) either divided as a twice-daily infusion or as a single infusion to patients undergoing hematopoietic stem cell transplantation (HSCT). Twelve patients with hematologic malignant disease were treated; 7 patients had non-Hodgkin's lymphoma, 4 patients had acute myeloid leukemia, and 1 patient had chronic myelogenous leukemia. The first cohort (group A) received, on the basis of actual body weight, i.v. BU at 1.6 mg/kg per dose over 4 hours every 12 hours for 4 days (day -7 to day -4). The second cohort (group B) received 3.2 mg/kg per dose of i.v. BU (same total dose as group A) as a single infusion over 4 hours daily for 4 days. In both groups the i.v. BU was followed by cyclophosphamide 60 mg/kg daily for 2 days (day -3 and day -2). Blood specimens were collected on the first, fifth, and seventh doses for group A and on the first and fourth doses for group B to determine the disposition of i.v. BU. Peripheral blood stem cells (autologous in 7 cases and HLA-matched allogeneic in 5 cases) were given 2 days after completion of cyclophosphamide administration (day 0), and granulocyte colony-stimulating factor 5 microg/kg was started on the same day. GVHD prophylaxis consisted of tacrolimus plus methotrexate for recipients of allogeneic stem cells. One patient developed presumed fungal pneumonia and died of multisystem organ dysfunction on day +21 before hematologic reconstitution could be evaluated. Another was reported to have sudden death of undetermined cause at home on day 40. The remaining patients had engraftment (absolute neutrophil count >500/microL) at a median of 11 days and sustained platelet counts >20,000/microL at a median of 14 days. Significant regimen-related toxicity (grade III-IV) was limited to hepatic toxicity (2 cases) catheter infection (2 cases), epistaxis (3 cases), diarrhea (1 case), anorexia (1 case), mucositis (1 case), hyperglycemia (1 case), pneumonia (1 case), and sepsis (1). In group B there was 1 case of mild venoocclusive disease, which resolved without sequelae. No central nervous system or pulmonary toxicity was noted. Pharmacokinetic parameters, including clearance, half-life, maximum concentration, and area under the curve, demonstrated that the first dose profile was highly predictive of later dose PK profiles. No accumulation of the drug was noted. The change in dosing schedule did not increase toxicity or end-organ damage despite higher plasma concentration-times. Although further study for long-term efficacy is warranted, i.v. BU can be given safely with reproducible results on a twice-daily divided or single-daily dosing schedule to patients undergoing HSCT.
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PMID:Evaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation. 1237 50

Severe sepsis and septic shock are among the most complex and challenging conditions treated by critical care practitioners. Although the pathophysiology of severe sepsis and septic shock is not fully understood, bacteria and immune responses are known to trigger the release of cytokines. These cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and sleepiness, as well as a host of physiologic events such as activation of the coagulation cascade, vasodilation, hypotension, and increased vessel permeability. As research advances the understanding of severe sepsis and septic shock, practitioners must become aware of the cellular basis of events so that treatments can be implemented knowledgeably and evaluated.
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PMID:The cellular basis of septic shock. 1259 36

High mobility group box 1 (HMGB), a ubiquitous DNA-binding protein, has been implicated as a proinflammatory cytokine and late mediator of lethal endotoxemia. HMGB1 is released by activated macrophages. It amplifies and extends the inflammatory response by inducing cytokine release and mediating acute lung injury, anorexia, and the inflammatory response to tissue necrosis. The kinetics of HMGB1 release provide a wide therapeutic window for endotoxemia because extracellular levels of HMGB1 begin to increase 12 to 24 h after exposure to inflammatory stimuli. Here, we demonstrate that a DNA-binding domain of HMGB1, the B box, recapitulates the cytokine activity of full length HMGB1 and efficiently activates macrophages to release tumor necrosis factor (TNF) and other proinflammatory cytokines. Truncation of the B box revealed that the TNF-stimulating activity localizes to 20 amino acids (HMGB1 amino acids 89 to 108). Passive immunization of mice with antibodies raised against B box conferred significant protection against lethal endotoxemia or sepsis, induced by cecal perforation. These results indicate that a proinflammatory domain of HMGB1 maps to the highly conserved DNA-binding B box, making this primary sequence a suitable target in the design of therapeutics.
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PMID:Structural basis for the proinflammatory cytokine activity of high mobility group box 1. 1276 38

A case of pio-pneumothorax complicating a splenic flexure colonic carcinoma is herein presented. The patient was a 58 years old male and was submitted 3 months earlier to a colo-colic bypass for a locally advanced tumor infiltrating stomach, spleen, tail of the pancreas and left emidiaphragm. Few days before the admittance in our ward, he experienced fever, anorexia, and severe dispnoea. Treatment was a water seal drainage of the chest evacuating nearly 8 Liters of purulent material where Escherichia coli was found. Death occurred 2 weeks after drainage. From the analysis of the literature thoracic empyema is an extremely rare complication of colonic carcinoma: 5 other cases have been reported so far. Pathogenesis in half of the cases was due to septicemia and in the others to infectious local spreading.
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PMID:[Left pyo-pneumothorax: a rare complication of colon carcinoma]. 1290 72


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