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

The effect of repeated cycles of tetracycline and oleandomycin administration on the complement titer, content of lysozyme and bactericidal properties of the serum in rabbits with experimental staphylococcal sepsis was studied. It was shown that the septic process induced by intravenous inoculation of staphylococci was accompanied by stimulation of the host nonspecific resistance. However, repeated inoculations of the animals resulted in exhaustion of the host protective forces and decreased non-specific resistance. The use of tetracycline in experimental staphylococcal sepsis was accompanied by an increase in the complement titer, lysozyme content and bactericidal properties of the serum after both the 1st and 2nd cycles of the drug administration. The use of oleaudomycin induced an increase in the contents of the complement, lysozyme and bactericidal properties of the serum at the background of staphylococcal sepsis only after the 1st cycle. The repeated cycle of oleandomycin administration was accompanied by a decrease in the above indices. Such conditions should be taken into account in choosing the antibiotic for treatment of septic cases especially when repeated cycles of the drug administration are used.
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PMID:[Effect of repeated cycles of tetraolean and oleandomycin administration on the indices of nonspecific resistence of the body in experimental staphylococcal sepsis]. 111 93

The aim of the study was to find out in which way lung permeability and polymorphonuclear leukocyte (PMNL) functions are modulated under recurrent endotoxin challenge, as it might occur in clinical septic patients. In a sheep model with chronic lung lymph fistula, performing bronchoalveolar lavage (BAL), we investigated the relationship between PMNL function and endothelial as well as epithelial damage in the lung in a sepsis syndrome, using a protocol of recurrent endotoxemia induced by 1 microgram/kg body weight Escherichia coli endotoxin treatment every 12 h over a 5-day period. Pulmonary response showed constantly increased pulmonary arterial pressure at mean values of 24-30 mm Hg. Also, lymph flow did not return to baseline, but remained on a level of 6-9 ml/30 min, after an increase to 12-15 ml/30 min following each endotoxin injection. In contrast, a lower increase in protein clearance was noted upon subsequent endotoxin administration. After initial values of 7-8 ml/30 min following the first endotoxin injection, almost baseline values were measured on the 5th day (3-4 ml/30 min). In systemic hemodynamics, we noted a decrease in cardiac output to 3.0 l/min after the first endotoxin injection, followed by a significant increase to 7 l/min under subsequent endotoxin administration. In PMNL function, we observed an attenuation of the acute response of the decrease in PMNL count, in vitro chemiluminescence response and plasma beta-N-acetylglucosaminidase level. The plasma urea concentration revealed a transient reduction in kidney function. In the epithelial lining fluid (ELF) of the alveoli, total cell count did not change significantly, but the fraction of PMNL increased from 2 to 20% during the 5 days. The ELF/plasma ratios of albumin and total protein did not change significantly. In conclusion, recurrent endotoxemia in a sheep model can produce a hyperdynamic state like in a sepsis syndrome which is further characterized by an initial leakage of the endothelial barrier, only minor affection of the epithelial barrier and by an exhaustion of PMNL function.
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PMID:Effect of recurrent endotoxemia on hemodynamics, lung function and neutrophil activation in sheep. 149 2

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.
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PMID:Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma. 199 8

After major trauma, including burns, patients develop a multitude of immunologic alterations, including impaired cellular immunity (CMI). Because of conflicting reports on the relationship of in vitro lymphocyte activity to the clinical course of burn patients, we studied CMI in 29 patients with a mean burn size of 41% and a mean age of 32 years. The patients' cellular response to the mitogen phytohemagglutinin and the ability of the patients' serum to suppress a normal lymphocyte mitogenic response were measured. The endogenous level of lymphocyte activity spontaneous blastogenic transformation (SBT) was measured immediately after the cells were harvested from the blood. During the first 72 hours postburn, the ability of the patients' cells to respond to mitogens in vitro decreased, while the endogenous activity (SBT) increased. Subsequent changes in the SBT, but not the mitogen-stimulated response, predicted sepsis. Although the patients' serum was mildly suppressive, these changes were not of statistical or clinical significance. It is postulated that the in vivo and in vitro CMI defects are not primarily due to a defect in the ability of the cell to be activated, but instead are due to exhaustion, desensitization, or down-regulation of these in vivo-activated cells.
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PMID:Postburn impaired cell-mediated immunity may not be due to lazy lymphocytes but to overwork. 315 54

To evaluate the availability of the fibrinolytic system in patients suffering from acute respiratory distress syndrome, ARDS, induced by septicemia or trauma, the following parameters were analysed: fibrinogen, FG, antithrombin III, AT III, plasma prekallikrein, PPK, plasminogen, PG, alpha 2-antiplasmin, alpha 2-AP, alpha 2-macroglobulin, alpha 2-MG, urokinase-inhibitor, UK-I, streptokinase-inhibitor, SK-I, C1-inhibitor, C1-I, alpha 1-antitrypsin, alpha 1-AT, and fibrinogen-fibrin degradation products, FDP. Survivors and non-survivors of septicemia induced ARDS showed a characteristic feature: marked increase of FG and pronounced decrease of AT III and PPK in the coagulation system; concerning the fibrinolytic system a decrease of PG, alpha 2-AP and alpha 2-MG as well as an increase of inhibitors of PG-activators (PG-antiactivators) UK-I, SK-I, C1-I and alpha 1-AT; the FDP-titer was elevated. This constellation of parameters is interpreted as indicative of a marked procoagulant stimulation rendering the organism a state of hypercoagulability coinciding with a diminished availability of the fibrinolytic system, due to exhaustion of the fibrinolytic potential and increase of PG-antiactivators. In the trauma group initially the rise of FG, SK-I, C1-I and alpha 1-AT is absent independent of the outcome, but develops with progression of the disease. As ARDS is more frequently associated with septicemia, diminished availability of the fibrinolytic system simultaneously with increased procoagulant stimulation may be a particular pathophysiologic mechanism in the pathogenesis of ARDS.
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PMID:Fibrinolysis inhibition in acute respiratory distress syndrome. 386 24

Thrombocytopenia is characteristically associated with septicemia and hemolytic uremic syndrome (HUS), a subset of which has been shown to be associated with endotoxemia and shigellosis. An experimental model that closely resembles these clinical conditions is the generalized Shwartzman reaction modified with a continuous intravenous infusion of endotoxin for 5 hr in rabbits. In addition to exhibiting the triad of HUS (thrombocytopenia, hemolytic anemia, and azotemia), these animals also had circulating platelet aggregates, leukocytosis, lipidemia, hemoglobinemia, hyperfibrinogenemia, and prolonged partial thromboplastin time. Platelets that remained in circulation were chemically exhausted in serotonin content and functionally impaired in aggregation activities. Plasma from animals during thrombocytopenia and platelet functional deficiency had no effect of the aggregation responses of normal platelets. Although the single triggering event of endotoxin infusion was stopped at hour 5, recovery from abnormalities was only partial on day 2 and within normal limits by day 3. In vitro studies supported platelet exhaustion as a mechanism for decreased platelet function after endotoxin infusion. The presence of circulating platelet aggregates and exhausted platelets suggested that the process of platelet activation took place at as long as 24 hr after the cessation of LPS infusion. Endotoxin and other mechanism(s) are likely to be operative in the pathogenesis leading to platelet activation. Further studies to reveal the mechanism of platelet exhaustion in the experimental model may help our understanding of corresponding events in clinical endotoxic injury and HUS associated with endotoxemia.
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PMID:Impaired and exhausted platelets in modified generalized Shwartzman reaction: an analogue of hemolytic uremic syndrome associated with endotoxemia. 664 55

When neutropenia due to exhaustion of the marrow neutrophil reserve, develops in a neonate with bacterial sepsis the likelihood of survival is very small. We report such a case who was treated with a double-volume exchange transfusion using fresh unstored whole blood. We were able to determine a net gain of 5 x 10(8) neutrophils per kg. Then, in neutropenic neonatal animals, neutrophil transfusion by double-volume exchange transfusion with unstored blood was investigated.
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PMID:Use of whole blood exchange transfusion to supply neutrophils to septic, neutropenic neonates. 675 23

Depletion of the mature neutrophil reserve during bacterial sepsis is rare in adults but common in neonates; when it occurs, a fatal outcome is likely. Neutrophil reserve depletion was investigated in groups of premature, 1-day-old and 1-, 2-, and 4-week-old rats by measuring: (1) the size of the neutrophil storage pool, and (2) the proportion of this pool which was released from the storage compartment when a weight-standardized release stimulus was applied. It was found that the premature rat has a small neutrophil storage pool containing 1.29 +/- 0.07 X 10(6) cells/g body weight (mean +/- SE). This pool size increases to contain 4.35 +/- 0.23 X 10(6) cells/g in the 4-week-olds (p less than 0.001). With a standard neutrophil storage pool release stimulus, the premature rats depleted 68 +/- 4% of their neutrophil stores, vs. a depletion o only 13 +/- 6% of the stores in the 4-week-olds (p less than 0.001). The small neutrophil reserve and the exaggerated release of stored neutrophils in neonatal animals are factors which predispose neonates to neutrophil reserve exhaustion during bacterial sepsis.
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PMID:Supply and release of storage neutrophils. A developmental study. 706 44

Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
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PMID:A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. 752 Jul 70

The authors present the results of denervation procedures treatment for 70 patients with persistent knee pain after total knee replacement, trauma, or osteotomy. In patients with total knee arthroplasty, aseptic loosening, sepsis, ligamentous instability, malalignment, and polyethylene wear had to be systematically ruled out as the source of pain. In patients with nontotal knee arthroplasty, arthrosis, synovitis, ligamentous instability, and meniscal derangement had been excluded as a source of pain. All candidates for the procedure had a successful selective nerve block. Sixty of the 70 (86%) patients were satisfied with the denervation procedure as judged by direct questioning and a reduction in their preoperative pain visual analog score of 5 or more points. The average Knee Society score improved from a preoperative mean of 51 points (range, 40-62 points) to a followup mean of 82 points (range, 15-100 points). Forty-nine of 70 (70%) patients had final Knee Society objective scores greater than 80. There was no difference in patient satisfaction whether the followup period was less than 2 years or more than 2 years. Selective knee denervation is indicated in the management of intractable knee pain after exhaustion of traditional approaches to any structural or infectious etiologies and after successful selective nerve block.
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PMID:Partial denervation for persistent neuroma pain around the knee. 876 55


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