Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A community-based incidence case-referent study was undertaken in a rural and an urban setting in Zimbabwe in order to define risk factors associated with maternal deaths at family, community, primary and referral health care levels. Referent subjects were drawn from place or area of delivery for each consecutive maternal death. Using a multiple source confidential reporting network for all maternal deaths, the maternal mortality rate for the rural setting was 168/100,000 live births and that for the urban setting was 85/100,000 live births. A model for interacting factors contributing to maternal mortality was designed. Haemorrhage and abortion sepsis were the major direct causes while malaria was the leading indirect cause in the rural setting. In the urban setting, eclampsia, abortion and puerperal sepsis were the leading causes of maternal deaths. It was found that all situations associated with diminished, or absent social support, that is, being single (Odds Ratio = 4.7, 95% CI = 2.2-9.8) divorced, widowed, one of several wives, cohabiting, or self-supporting carried an increased risk for maternal mortality, especially in the rural area. Income and level of education for index and referent subjects were comparable, probably because of the limited part of the population under study that belonged to a more affluent class. Distribution of cases and referents by religious-affiliation was also comparable. Age > 35 years and parity > 6 were significant risk factors for maternal mortality in the rural setting, whereas bad reproductive history with reported stillbirth or abortion constituted a high risk both in the city and in the rural areas (Odds Ratios 4-6).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maternal mortality in rural and urban Zimbabwe: social and reproductive factors in an incident case-referent study. 851 49

The pattern of postoperative pyrexia in Khartoum was prospectively studied in 260 patients who underwent a variety of surgical operations. Ninety four patients (36.1%) developed postoperative pyrexia. The commonest causes of pyrexia encountered were wound sepsis (10%), malaria (9.6%) and respiratory tract infection (7.3%). Less frequent causes were urinary tract infection, thrombophlebitis, intra-abdominal sepsis and deep vein thrombosis. In 14.6% of the patients, the cause of pyrexia was undetermined. The risk factors for postoperative pyrexia were the patient's age, diabetes mellitus, obesity, preoperative chest infection, smoking, duration of surgery, operator's surgical experience and urethral catheterisation. The postoperative pyrexia was associated with 7.4% mortality rate which was due to intra-abdominal sepsis and pulmonary embolism. The incidence of postoperative pyrexia can be minimised by adequate preoperative preparation, meticulous surgical technique and good postoperative care.
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PMID:Pattern of postoperative pyrexia in Khartoum. 862 71

Liposomes have been used therapeutically to deliver drugs to certain anatomical sites. The use of liposomes to deliver antigens, although not a new concept, has received less attention. At least two vaccines of nearly identical liposome base composition to our vaccines have been tested in humans. A malaria vaccine study showed that the liposomal preparation is quite safe: reaction profiles of volunteers receiving the vaccine demonstrated little reactivity and virtually no pyrogenicity (14). The concentration of MPLA in the vaccine was substantially higher (nearly 50,000 times) than the pyrogenic dose of free lipid A. The same vaccine, but different antigen (gp120, an HIV protein), was tested in volunteers and had the same lack of toxicity (27). In both studies, antibodies and cytotoxic cells specific for the respective antigens were produced. We have several subunit vaccines under development for infectious diseases (gram negative sepsis, fungal infections, protozoan infections), metabolic disorders (hypercholesterolemia, diabetic retinopathy, macular degeneration), and neoplastic diseases (multi-drug resistant cancer, primary and metastatic tumors, and angiogenic hyperproliferative disorders). In each case, one or more antigens were identified that might be useful in immunologic control of biologic proliferation (i.e., pathogen or tumor growth, rise in serum cholesterol, growth of blood vessels). We anticipate that at least one of these vaccines will be ready for testing in humans in the next calendar year.
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PMID:Liposomal vaccines. 864 17

It is increasingly evident that sepsis triggers a complex host reaction that is responsible for a variety of pathophysiologic changes during the inflammatory process. Pentoxifylline (PTX) is a methylxanthine with selective anti-inflammatory activity. Because of the current concept of an exaggerated immune response during severe inflammatory response syndrome (SIRS), this drug has received interest as a potential beneficial modulator of SIRS. Animal studies suggest that randomized clinical trials should be carefully planned with regard to dose-response relationship, disease severity, etiologic pathogens, and mechanisms that result in SIRS. The efficacy of PTX has been promising in human malaria. It is probably also effective in other hyper-tumor necrosis factor (TNF) states. The effective dosage is unclear to date, and its use is restricted by intolerance. Potential adverse effects may be related to the selective depression of TNF expression and to the depression of granulocyte phagocytic activity and the neutrophil/endothelium interaction. However, it is unlikely that any single agent will prove to be the magic bullet in the therapy of sepsis and SIRS. Multiple agents, perhaps tailored to individual circumstances, will most probably be needed, raising dramatic economic and ethical challenges.
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PMID:Pentoxifylline in severe inflammatory response syndrome. 869 53

Community information based on causes and circumstances of death in infants and young children in Malawi was obtained in a prospective cohort of babies delivered to women enrolled in a malaria-prevention-in-pregnancy study. Vital status information was obtained through home visits every two months; for children who died, questions were asked concerning age and date of death, symptoms preceding death, care sought, location of death (home versus facility), and duration of illness. Of 3,274 liveborn singleton infants, 181, 397, and 152 deaths occurred in the neonatal, postneonatal, and second year of life, respectively. For neonates, proportionate mortality was greatest for sepsis/tetanus (16.7%) and fever (8.6%); however, for more than half of neonatal deaths evaluated the cause was not identified. Up to 30% of neonatal deaths may have been related to prematurity. In the postneonatal period, gastrointestinal illness (39.6%), fever (18.3%), and respiratory illness (14.7%) were the leading causes. Most postneonatal illnesses lasted 1 week or less. Two-thirds of postneonatal deaths occurred outside of a health care facility, although 80% were brought to a facility for care during their illness. Infectious disease syndromes continued to be important in the second year of life, with gastrointestinal (31.6%), fever (23.5%), and measles (20.6%) the most commonly reported causes of death. In this area of rural sub-Saharan Africa, neonatal mortality contributes substantially to infant mortality, and prematurity is considered to be an important component of early neonatal deaths; infectious disease syndromes predominate in the postneonatal and second year of life. Strategies to reduce infant deaths in sub-Saharan Africa must consider these factors, as well as the observations that most children who died had brief illnesses, were taken to a health care facility before death, yet died at home.
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PMID:Infant and second-year mortality in rural Malawi: causes and descriptive epidemiology. 870 42

Tumor necrosis factor (TNF) is recognized as a central mediator of sepsis, septic shock, and multiple organ failure. These host reactions are associated with increased TNF levels in circulation, presumably due to increased TNF production. A previously described nucleotide variation at position -308 in the promoter region of the human TNF gene was shown to be associated with the clinical outcome of malaria. In this study we addressed the relevance of the -308 polymorphism for expression of the human TNF gene in response to bacterial endo- toxin in vivo and in vitro. First, we typed 80 patients suffering from severe sepsis and 153 healthy individuals and found no association of the -308 variation with incidence of the disease. In contrast, the NcoI marker in the closely linked lymphotoxin-alpha (LT-alpha) gene showed association with survivaL This discrepancy can be explained by the linkage of the TNFB2(NcoI) allele to the common TNF1 (-308) allele. Second, we generated reporter gene constructs with the promoter deletions and with both -308 variation in the context of the extended human TNF promoter region. Although such constructs were highly inducible by lipopolysaccharide (LPS) in transient transfections into a macrophage cell line, the -308 variation had no significant effect on transcription, consistent with the promoter deletion study. We conclude that the functional consequence of the -308 polymorphism may be unrelated to transcriptional response of the TNF gene to bacterial endotoxin.
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PMID:-308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter. 883 66

We assessed the clinical characteristics of newly-diagnosed diabetic patients presenting to the Mulago Hospital Diabetic Clinic for the first time between 1 January 1993 and 10 August 1994. There were 252 patients: 117 men and 135 women. Mean age at onset of diabetes was 45 years (range 2-87 years) and peak incidence was at 40-49 years. Body mass index (BMI) was available in only 71 patients, of whom 53.5% (33.8% female, 19.7% male) were overweight (BMI > 25 in women, in > 27 men) and 11.3% (8.5% men, 2.8% women) were underweight (BMI < 20). Obesity was more marked in young women. Almost all patients presented with the classical symptoms of diabetes, and the majority were severely hyperglycaemic. A family history of diabetes was identified in 16%. Concurrent illnesses at diagnosis of diabetes were unusual. Sepsis was commonest (11.9%), followed by malaria (7.8%), tuberculosis (1.2%), AIDS (1.2%) and pancreatitis (0.8%). Peripheral neuropathy was present in 46.4% of patients, hypertension (BP > 150/100) in 27.3%, impotence in 22.2% of the men, proteinuria in 17.1%, ischaemic heart disease in 4.8%, foot ulcers in 4.0% and cataracts in 3.2%. Insulin was the most commonly prescribed treatment (52.8%); 31% of patients received oral hypoglycaemic agents, only 15.1% were managed on diet only, and 1.2% opted for herbal medicine.
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PMID:The presentation of newly-diagnosed diabetic patients in Uganda. 891 47

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.
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PMID:TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. 912 3

Procalcitonin, the precursor of calcitonin, is elevated in patients with sepsis and infection (base-line values <0.1 ng/ml). We determined PCT in 38 hospitalised patients with suspected malaria. All of them had signs of infection and had recently returned from Africa. Plasmodium vivax was proven in 15, Plasmodium falciparum in one and an infection with both species was found in another case (n = 17). PCT was determined on admission and the days thereafter. In one patient PCT was determined every 4 hours on the first day. The maxima of the PCT concentration on day 0 and 1 were 5.3 ng/ml with proven Malaria and 0.43 ng/ml without. At the following days we found a decrease to normal values (<0.5 ng/ml) which correlated with the general condition of the patient. At a cut-off point of 2 ng/ml we found a sensitivity of 52%, positive predictive value of 74%, specificity of 86%, negative predictive value of 71%. procalcitonin, malaria
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PMID:Procalcitonin in acute malaria. 915 45

A total of 638 patients with acute renal failure (ARF) of diverse etiology were studied over a period of 9 years (July 1985-Dec, 1994) of which 96 (15%) patients were classified as elderly ARF with mean age of 72.5 years. Medical causes accounted for 80% of geriatric ARF while 20% patients, had ARF of surgical origin. Decreased renal perfusion resulting from gastroenteritis was the predominant (52.8%) cause of ARF in the medical group. Nephrotoxic ARF and ARF due to F. malaria were seen in 10 and 7 patients respectively. Obstructive uropathy was observed in 12 patients in surgical group and in remaining 8 patients ARF developed following various surgical procedures. ARF in association with multiorgan failure was not observed in our study. Mortality was seen in 24 patients (25%). The causes of mortality were GI bleed (6), peripheral circulatory failure (5), hyperkalemia (4) and sepsis (4). Thus medical ARF remains the major cause of acute renal failure in elderly patients in our study in contrast to ARF associated with multiorgan failure and surgery in developed countries.
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PMID:Acute renal failure in the elderly: a demographic and clinical study of patients in eastern India. 942 1


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