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)

The activity of complement-mediated opsonin was measured by the whole blood chemiluminescence method in 17 children with hematologic malignancy (including 6 with ALL, 7 with ANLL and 4 with non-Hodgkin's lymphoma) during remission induction therapy. The activity of opsonin, which was at the normal level before chemotherapy, decreased in all of the children during the therapy. This phenomenon was especially marked in the children treated with L-asparaginase. Although no clear relationship was found between the decrease in opsonin activity and the susceptibility to infection, it was confirmed that in 4 children having an episode of sepsis or septic fever, the infection started when the granulocyte decreased to the nadir, and simultaneously the activity of opsonin decreased. Therefore, it may be reasonable to suspect the decrease in opsonin activity when treating children with such infections.
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PMID:Impairment of opsonic function in children with hematologic malignancy during remission induction therapy. 399 81

Burns wound sepsis is not only the most common but also the most severe complication following extensive thermal injury. One conceivable explanation of this problem is a reduced capacity of the polymorphonuclear neutrophil leucocytes of these patients to combat the invading microbes. Fifty patients (42 male and 8 female) with deep dermal burns, covering 20-90 per cent of the total body surface area, were investigated from immediately after the injury until death or until healing of the wounds. The following functions of the neutrophil granulocytes were studied: chemotaxis and random migration utilizing a modified Boyden chamber technique, phagocytosis of Staph. aureus and IgG-coated latex particles, bactericidal capacity, e.g. killing of Staph. aureus and the neutrophil granulocyte content of: myeloperoxidase, lactoferrin, and chymotrypsin-like cationic protein. The presence of stimulators and inhibitors of the granulocyte functions was studied using gel filtration of the patient's serum on Sephacryl gel columns. Sera from all patients obtained within the first 1-3 days post-burn contained significantly increased amounts of heat-labile chemokinetic stimulating activity. Sera obtained between days 4 and 10 after injury contained significantly decreased amounts of heat-stable chemokinetic stimulating activity. Reduced chemokinetic activity was found during the third and fourth weeks following major burns (greater than or equal to 40 per cent) due to the presence of one or both heat-stable chemokinetic inhibitory activities. During the second week post-burn patients with burns larger than 40 per cent of the body surface area who showed an inhibition of chemotaxis, also had defects in phagocytosis, and often impaired bactericidal capacity concomitant with lower contents than normal of the granular enzymes. A hyaluronic acid preparation in low concentrations was found to counteract the migration inhibitory effect demonstrated in vitro in sera from patients with severe burns. Based upon these results a series of patients with severe burns and impaired functions of the neutrophil granulocytes have been treated with small amounts of this hyaluronic acid preparation subcutaneously. Very promising results have been noticed, similar to those found in vitro.
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PMID:Neutrophil granulocyte functions in severely burned patients. 402 46

The immunologic status and the occurrence of alloimmunization against granulocytes, platelets, lymphocytes, and red cells was evaluated in 33 babies who received granulocyte transfusion because of neonatal sepsis. Nine age-matched babies were examined as control. A first group of 19 infants was examined only once between 6 and 23 months of age. Alloantibodies were searched by the following serologic methods: standard techniques for red cell antibodies; lymphocytotoxicity test; agglutination and immunofluorescence tests on granulocytes and platelets. No antibodies were demonstrated. The immunologic profile was investigated by determining the Ig levels, the percentage of E rosette-forming cells, and the lymphocyte blastic response to phytohemagglutinin and concanavalin A. Granulocyte function was studied by phagocytosis and killing of Candida. No significant differences were observed between treated and control babies. In a second group of 14 infants the occurrence of early immunization within 3 to 9 weeks after the last transfusion was investigated. No evidence of early immunization was found. The present data suggest that following neonatal granulocyte transfusion the risk of adverse immune reactions should be low.
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PMID:Immunologic follow-up of infants treated with granulocyte transfusion for neonatal sepsis. 404 93

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.
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PMID:Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon. 407 11

The kinetics of human autologous granulocytes, separated and labelled with 111In without isolation from plasma, have been studied in subjects with and without sepsis with the aim of identifying the fate and sites of destruction of granulocytes in man. In subjects without inflammatory disease, 111In granulocyte recovery in faeces, urine and saliva over 4 d was less than 1% of the dose, so that the activity visualized by the gamma camera represented almost 100% of the dose. On images taken at 24 and 48 h, this activity was distributed between spleen, bone marrow and liver, with foci of additional abnormal activity in subjects with inflammatory disease. Splenic activity fell between 40 min and 24 h, consistent with the presence of a splenic granulocyte pool, but remained constant after 24 h. Since granulocyte clearance from the blood was predominantly completed by 24 h, the residual splenic activity at that time reflected splenic granulocyte destruction. In patients with sepsis, the fall in splenic activity was greater than in those without, implying diversion of granulocytes from splenic destruction to tissue utilization when inflammation is present. Bone marrow activity increased between 40 min and 24 h and then remained stable. Granulocytes that were extensively manipulated in saline prior to labelling failed to localize in marrow, suggesting that visualization of the latter reflected destruction of intact, normal granulocytes. Although the changes in splenic and marrow activities terminated at 24 h, at which time granulocyte clearance from blood was at least 80% completed, plasma 111In remained essentially unchanged between 40 min and 48 h at less than 5% of the dose, discounting it as the source of splenic and marrow activities.
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PMID:The kinetics of 111indium distribution following injection of 111indium labelled autologous granulocytes in man. 408 57

Since the age of nine weeks a red haired girl suffered from purulent dermatitis and recurrent, systemic E. coli infections. She had an excessive hyperimmunoglobulinemia E, as well as impaired granulocyte adherence and chemotaxis. Though a sepsis was evident, the granulocytes exhibited a random FITC-Concanavalin A fluorescence. In spite of intensive treatment with various antibiotics and several granulocyte transfusions the child died at the age of 2 years and 11 months. As shown by the FITC-Concanavalin A distribution, the hyperimmunoglobulinemia E may have caused a decreased membrane fluidity causing the impaired adherence and chemotaxis. This could explain the pathophysiology of the Job's Syndrome.
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PMID:[Membranes properties of granulocytes in Job's-Syndrome with E. coli-septicemia (author's transl)]. 611 94

Pneumococci have been shown to induce granulocytopenia and pulmonary leukostasis which might contribute to morbidity and mortality in pneumococcal sepsis. We studied whether other gram-positive species (groups A and B streptococci, Staphylococcus aureus, Bacillus cereus, and Clostridium perfringens) could also induce these phenomena. Rabbits were challenged with nonviable preparations of each species, and all five species induced profound granulocytopenia (mean decrease of 90%) and pulmonary leukostasis. In vitro studies of serum incubated with these species of bacteria showed a mean consumption of total hemolytic complement of 90%, a mean increase of chemotactic activity for granulocytes of 204%, and a mean augmentation of granulocyte adherence of 45% (compared with 18% for the control). Infusion of sonicate-exposed sera induced granulocytopenia in recipient rabbits. Thus, several nonviable gram-positive species can interact with serum to activate the complement system, generate C5a bioactivity, augment granulocyte adherence, and generate a neutropenia-inducing factor. These alterations may contribute to granulocytopenia or pulmonary leukostasis, which may play a role in the morbidity and mortality associated with gram-positive bacterial infections.
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PMID:Gram-positive bacteria-induced granulocytopenia and pulmonary leukostasis in rabbits. 628 93

The complement (C) system evolved as a beneficial antimicrobial system. However, when activated during extracorporeal perfusion as with haemodialysis or cardiopulmonary bypass modest pulmonary dysfunction associated with granulocyte aggregation and embolization can occur. When C activation is massive and prolonged, as with severe sepsis, trauma, or acute pancreatitis, severe pulmonary damage which is recognized as shock lung, or adult respiratory distress syndrome, may occur. Since ulcerating atherosclerotic plaques can also activate C, a mechanism by which myocardial infarcts may extend during the first few hours after infarction is also implied. Therapeutic ramifications of these conclusions are evident. Thus, high doses of corticosteroids or of nonsteroidal anti-inflammatory agents such as ibuprofen share the ability to prevent aggregation and embolization of stimulated granulocytes to patent vessels downstream and also inhibit their production of toxic oxygen radicals. These properties suggest the use of these agents in myocardial infarction and shock states, particularly shock lung, and appropriate clinical trials are awaited with interest.
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PMID:Complement-mediated leucoembolization: a mechanism of tissue damage during extracorporeal perfusions, myocardial infarction and in shock--a review. 635 25

To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Pretreatment demographic, clinical, and laboratory variables that were found to be insignificant in prognosis between newborns who received transfusions and newborns who did not receive transfusions included weight, gestational and postnatal age, hypoxia, acidosis, hypotension, initial absolute granulocyte count (AGC), initial levels of immunoglobulins (IgA, IgG, and IgM), and total hemolytic complement. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group (13/13, 100%) compared with the group that did not receive transfusions (6/10, 60%, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved survival of newborns receiving leukocyte transfusions for sepsis. 638 16

The current incidence of neonatal sepsis in the United States varies from less than 1 to 8.1 per 1000 live births. The incidence of bacterial meningitis is about one-third of the number of infants with sepsis. The mortality is 20 to 30% and many survivors are severely impaired. Group B streptococcus and Escherichia coli are the most frequent causes of meningitis. Because of the difficulty of clinical diagnosis, many infants receive presumptive therapy for suspected sepsis or meningitis although few have documented infection. Between 5 and 10% of newborn infants born in the United States receive antimicrobial agents in the nursery, usually a penicillin and an aminoglycoside. To lower the continued high mortality and morbidity of meningitis due to gram-negative enteric bacilli, collaborative randomized trials evaluated the efficacy of gentamicin administered via the intrathecal route, gentamicin administered into the ventricle and most recently, the efficacy of moxalactam. Neither intrathecal or intraventricular drug, both in combination with parenteral drug, was advantageous when compared with parenterally administered drug alone. The mortality rate and number of days of culture positive cerebrospinal fluid were similar in infants who received moxalactam and ampicillin and infants who received amikacin and ampicillin. Adjunctive therapies including granulocyte transfusion, administration of hyperimmune gamma globulin and exchange transfusion are now under investigation. Initial studies of prevention of systemic bacterial infection by prophylactic ampicillin administered to the mother at delivery and use of group B streptococcal vaccine administered to susceptible women in the child bearing age show promise.
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PMID:Recent advances in management of bacterial meningitis in neonates. 639 49


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