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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis. Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest. In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta. Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production. Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages. The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth. Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.
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PMID:The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. 1112 11

Reactive oxygen species contribute to diaphragm dysfunction in certain pathophysiological conditions (i.e., sepsis and fatigue). However, the precise alterations induced by reactive oxygen species or the specific species that are responsible for the derangements in skeletal muscle function are incompletely understood. In this study, we evaluated the effect of the superoxide anion radical (O(2)(-).), hydroxyl radical (.OH), and hydrogen peroxide (H(2)O(2)) on maximum calcium-activated force (F(max)) and calcium sensitivity of the contractile apparatus in chemically skinned (Triton X-100) single rat diaphragm fibers. O(2)(-). was generated using the xanthine/xanthine oxidase system;.OH was generated using 1 mM FeCl(2), 1 mM ascorbate, and 1 mM H(2)O(2); and H(2)O(2) was added directly to the bathing medium. Exposure to O(2)(-). or.OH significantly decreased F(max) by 14.5% (P < 0.05) and 43.9% (P < 0. 005), respectively.OH had no effect on Ca(2+) sensitivity. Neither 10 nor 1,000 microM H(2)O(2) significantly altered F(max) or Ca(2+) sensitivity. We conclude that the diaphragm is susceptible to alterations induced by a direct effect of.OH and O(2)(-)., but not H(2)O(2), on the contractile proteins, which could, in part, be responsible for prolonged depression in contractility associated with respiratory muscle dysfunction in certain pathophysiological conditions.
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PMID:Superoxide, hydroxyl radical, and hydrogen peroxide effects on single-diaphragm fiber contractile apparatus. 1113 92

Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses. In suspected sepsis, 2 or 3 days' empiric antibiotic therapy should begin immediately after cultures have been obtained without awaiting results. Antibiotics should be re-evaluated when the results of the cultures and susceptibility tests are available. The initial antibiotic (combination) is determined by the likely causative agent, susceptibility patterns within a specific institution, CNS penetration, toxicity, and the patient's hepatic and renal function. The likely offending micro-organism in turn depends primarily on the patient's age, coexistence of any premorbid condition leading to impaired immune response, and the presenting signs and symptoms. Close attention to cardiovascular, respiratory, fluid and electrolyte, haematological, renal and metabolic/nutritional support is essential to optimise outcome. Fluid resuscitation is of utmost importance to overcome hypovolaemia on the basis of a diffuse capillary leak. Monitoring and normalisation of the heart rate is essential. In case of nonresponse to fluid resuscitation, inotropic and vasoactive agents are commonly used to increase cardiac output, maintain adequate blood pressure and enhance oxygen delivery to the tissue. Because respiratory distress syndrome is seen in about 40% of critically ill children with septic shock, increased inspired oxygen is essential. To provide optimal relief from respiratory muscle fatigue and facilitate the provision of positive airway pressure, early intubation and mechanical ventilation should be considered. Renal support is essential to avoid prolonged renal shutdown in hypoperfusion states. Haematological support comprises replacement therapy of clotting factors to overcome disseminated intravascular coagulation. Metabolic support may include glucose support, extraction of ammonia from the body and recognition of liver dysfunction. Nutritional support may modify the inflammatory host response, and early enteral feeding can improve outcome in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory agents have not shown significant benefit in septic patients.
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PMID:Management of sepsis and septic shock in infants and children. 1122 Apr 6

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m(2), paclitaxel 85 mg/m(2), and topotecan 2.25 mg/m(2)weekly, with G-CSF (5 microg/kg days 3-5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65-92%] ORR. At a 13-month (range, 4-26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches.
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PMID:A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study. 1133 65

Respiratory muscle dysfunction associated with ventilatory loading may be partially attributed to respiratory muscle injury. Exertion-induced muscle injury can be defined as structural alterations of the muscle, however, a better understanding of the biochemical, morphologic, and functional correlates of injured respiratory muscles will facilitate discrimination of how injury, fatigue, and weakness contribute to respiratory muscle dysfunction. In addition to the increased loads associated with lung disease, many factors such as poor arterial blood gases, immobilization, sepsis, decreased nutrition, and corticosteroids may increase susceptibility to exertion-induced respiratory muscle injury. Respiratory muscle injury in humans is not well-described, however, more extensive evidence has been shown in animal models of increased ventilatory loading. Potential mechanisms of respiratory muscle injury are mechanical stress, metabolic stress, and inflammation. In order to optimize therapeutic interventions, a better understanding of these mechanisms and the patients that are most susceptible to respiratory muscle injury needs to be determined.
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PMID:Respiratory muscle injury: evidence to date and potential mechanisms. 1148 9

From 1959-1964 the incidence of puerperal sterilization was 3.5% at the Lady Hardinge Hospital in New Delhi, an increase over the incidence of 2.15% from 1952-1957. The group analyzed in this study consists of 301 women sterilized during the 1959-64 period. Sterilizations were postpartum (191), during caesarean section or hysterotomy (74), and miscellaneous (36, including post-abortion). Average age was 32.5; average parity was 6.0. The majority had at least 2 male children. Indications for sterilization were socioeconomic (90%), obstetric (7%), and medical (3.3%). Immediate postoperative sequelae, studied in the postpartum cases only, included pyrexia and sepsis at rates of 25% and 24% of postpartum women. The most common late sequelae among all the women were chronic fatigue (44%), menstrual disturbances (28.9%), headache (28%), backache (26.5%), and lower abdominal pain (27.5%). The high incidence of chronic pelvic inflammation, 15%, was probably associated with the use of silk sutures. 2 patients became subsequently pregnant; the pregnancy rate was thus an unsurprising 0.7%.
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PMID:A review of 301 cases of sterilisation. 1233 82

Some of the serious side effects of childbirth are described for women in the critical postpartum period in developing countries. These side effects include hemorrhage, anemia, nutrition deficits, infection, family violence, and emotional problems. The postpartum period applies to 42 days after delivery, and it is a time when the healing and return of the reproductive organs to their nonpregnant state occurs. During this time, women should receive extra rest, food, and supplementation. In developing countries, maternal mortality primarily occurs during the puerperium. A study in Bangladesh found that 60% of women die during the postpartum period compared to 20% during pregnancy. Women tend to ignore their health problems in general, and, after the birth of a child, there is a tendency to focus on the newborn. A study in the UK revealed that 50% of women with children have longterm maternal health problems related to childbirth. Most postpartum complications are due to hemorrhage and infection. Normal blood loss after delivery is about 150 ml with a range of 300 ml for heavy loss and 500 ml for postpartum hemorrhage. An Australian study showed that 17% lose 500 ml of blood during delivery, and 4% lose more than 1000 ml. Excessive blood loss is directly related to a risk of anemia, and anemic women are at the highest risk of maternal mortality. The physical condition of women is the most significant feature in determining the seriousness of blood loss. A moderate level of blood loss with anemia is dangerous. Anemia leads to chronic fatigue and increased susceptibility to infection. Assuring high nutritional intake (iron and calcium fortified diets) during the postpartum period counteracts anemia and provides calories for adequate milk production. Adequate nutrition during the pregnancy means storage of nutrients for the postpartum period. Some cultures prescribe food restrictions which can impact deleteriously on women's health. Complications or prolonged delivery often lead to sepsis or infection. Infections may occur with improperly healing of tears. Violence against women can occur due to a stillbirth or failure to produce a male heir. Little is known about maternal stress and depression among postpartum women in developing countries.
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PMID:Postpartum care is crucial for health and survival. 1234 57

Fatigue is the most frequent adverse event encountered in cancer patients and often underestimated by oncologists. This fatigue results in a deterioration of the quality of life physically, psychologically and socio-professionally. We have to distinguish various degrees of fatigue and identify "acute" fatigue from "chronic" fatigue. The acute fatigue appears normal after a physical or psychological effort and requires less than a week of rest to recover; the impact on quality of life is thus minimal. Chronic fatigue is more insidious; the causes are multiple. The patient feels that this fatigue is abnormal and disproportionate. It last several weeks and has a severe impact on the quality of life. Somatic mechanisms of fatigue related to the tumour and/or treatment are: vitaminic or proteic deficiencies due to malnutrition, accumulation of toxic metabolites, infections and septicemia, the abuse of sleeping tablets or antalgics, insomnias, immobilisation, organic insufficiencies or ionic disturbances. Anemia--observed in more than 50% of the cancerous patients--deserves a particular attention. The causes of this anemia are also multiple. It is obvious that anemia interferes with quality of life of the patient, decreases his physical performances and leads to a lack of motivation or energy. Patients with an hemoglobin level higher than 12 g/dl describe significantly less complaints and a higher physical and functional well being. To better assess the treatment of fatigue, it is important to first evaluate if the cause is organic, psychologic or mixed. Among the somatic causes, nutritious deficiencies, pain and anemia, ... all these complications can be treated with appropriate medications. This fatigue is often recognized by the patient as a progression of the tumour or as a treatment failure. Therefore, it is important to inform the patients of the possibility of that adverse event so that it does not generate additional stress and anxiety during the treatment.
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PMID:[Fatigue and quality of life in cancer patients]. 1242 50

Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.
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PMID:Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation. 1242 14

An autopsy case of sepsis following radiofrequency ablation (RFA) for metastatic liver carcinoma after bile duct reconstructive operation is reported. A 72-year-old man underwent pylorus-preserving pancreaticoduodenectomy and reconstruction with the Suzuki-method (PD-III) for extrahepatic bile duct cancer in October 1998. A metastatic lesion was recognized in the liver (S3) in November 2001. Percutaneous RFA was performed for a recurrent lesion. A metastatic lesion was recognized again in the same segment in February 2002. Percutaneous RFA was performed again on February 26 and March 12. The patient was discharged without hemorrhage, infection, or hepatic failure on March 22. He complained of general fatigue on March 26. He was diagnosed with liver abscess, sepsis, acute renal failure, and disseminated intravascular coagulation, and received intensive care, but died on April 1. The autopsy revealed liver necrotic abscess at the RFA locus and multiple microabscesses of the liver, heart, and kidney.
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PMID:[An autopsy case of sepsis following radiofrequency ablation (RFA) for metastatic liver carcinoma after bile duct reconstruction]. 1248 45


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