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)

This report describes two patients who developed agranulocytosis while receiving prophylactic amodiaquine treatment. The neutrophil counts returned to normal in one after stopping the drug while the other died of sepsis. Amodiaquine-dependent circulating neutrophil IgG antibodies were demonstrated in both patients using the indirect granulocyte immunofluorescence test. The antineutrophil antibody activity was enhanced with the use of the major amodiaquine metabolite, mono-desethyl amodiaquine. Additional studies showed the activity of the sera to be nondialysable, heat stable, active against autologous as well as allogenic cells, and absent from the convalescent sera. There was no growth inhibition of allogenic myeloid committed progenitor cells (CFU-GM) following incubation with the patients' sera, complement and amodiaquine. These results indicate that agranulocytosis can be mediated by a drug-dependent antibody which affects mature blood cells.
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PMID:Amodiaquine-induced immune agranulocytosis. 291 31

The authors evaluate in a retrospective, non-randomized two-year study the action of 57 granulocyte concentrates from a Fenwal CS 3000 separator in 12 patients used for induction therapy of acute leukaemia, malignant lymphoma and agranulocytosis, as compared with a control group of 18 patients without concentrates. The indication for selection was granulocytopenia of less than 0.5.10(9)/l, temperatures resistant to antibiotics for more than 48 hours, mainly gram-negative sepsis and a severe localized infection. A significant reduction of febrile days was achieved, to 6.08 as compared with 12.44 (p less than 0.001) along with cure of the infection. Survival, evaluated on the 21st day of the investigation in the treated group 66.6%, as compared with 61.1%, and the percentage of complete remissions 58% as compared with 55.56%, were not statistically significant (p greater than 0.05). The mean one-hour rise of granulocytes by 0.37 x 10(9)/l in the recipients had no clinical impact. With the exception of one patient a relationship was observed between the favourable action of transfusions and the trend of recovery of the patient's granulopoiesis and the onset of remission of the disease. Minor pyretic and allergic reactions occurred in three patients (5.2%).
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PMID:[Clinical evaluation of granulocyte concentrates in the treatment of malignant disorders of hematopoiesis]. 292 52

One hundred nineteen patients were entered onto a randomized trial of the role of intravenous hyperalimentation (IVH) in patients with small-cell lung cancer. IVH was given during the first 30 days of induction chemotherapy to 54 patients. IVH did not effect any improvement in response or survival from therapy. In view of the lack of benefits from IVH, an analysis was made of the toxicities suffered by the 54 patients receiving IVH as well as any effects IVH might have made on chemotherapy-induced toxicity. Toxicities observed included mechanical difficulties with the catheter leading to temporary or permanent discontinuation of the IVH (11 patients), subclavian vein thrombosis (one patient), sepsis in nine patients v none of the 62 control patients, fluid overload (27 patients), hyponatremia (25 patients), and hyperglycemia requiring insulin (13 patients). Patients receiving IVH had higher granulocyte counts on days 14 and 21 of the first cycle of chemotherapy. Analysis shows that this difference is likely caused by fever and infection associated with IVH rather than any nutritional effect on granulopoiesis. In this population of patients, IVH had significant complications but did not ameliorate chemotherapy-induced toxicity and it did not effect any clinical benefit. Future studies of adjunctive nutritional therapy must consider the significant risk in this older population and must limit IVH volume or exclude patients with even mild compromise in cardiovascular functions. Further, any new trial must have a significant rationale for adjunctive use to justify the potential risks.
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PMID:Effects of intravenous hyperalimentation during treatment in patients with small-cell lung cancer. 299 75

Patients with severe neutropenia are at increased risk for systemic infection with bacteria or fungi. This risk is in proportion to both the degree and duration of the neutropenic process. Although granulocyte transfusion as a means of augmenting host defenses would appear to be a logical therapeutic intervention in clinical contexts involving severe and prolonged neutropenia, several features of granulocyte physiology and collection complicate such considerations. These include the large numbers of granulocytes normally produced by healthy hosts, the short survival of the granulocyte in the circulation after transfusion, the relatively small number of granulocytes which can be collected using currently available pheresis techniques, problems associated with alloimmunization, and the possibility of transferring disease (CMV, toxoplasmosis, hepatitis) by means of these transfusions. In the mid-1970s, well-designed clinical studies strongly suggested that patients with documented Gram-negative sepsis or tissue infection that failed to respond to appropriate antibiotics were significantly benefited by granulocyte transfusions. With recent advances in potent, broad-spectrum antibiotic availability, some have questioned whether these observations remain valid. Several studies regarding the prophylactic use of granulocyte transfusions in patients undergoing allogeneic bone marrow transplantation and/or induction therapy for leukemia have failed to reveal therapeutic benefits and suggested the possibility of significant side effects. These studies are reviewed.
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PMID:Granulocyte transfusions in neutropenic patients. 304 Feb 82

The pathophysiology of shock associated with sepsis in complex, but granulocyte activation and production of toxic oxygen radicals, is of major importance in producing endothelial cell injury. Multiple organ failure including a reversible cardiomyopathy with impairment of left ventricular ejection fraction, are known factors complicating, and in the latter, perpetuating, shock. When treating the severely shocked patient, a systolic pressure of 100 mmHg and a PaO2 of greater than 8 kPa (60 mmHg) should be aimed for. Non-response to oxygenation, respiratory support, volume, and metabolic control, may be an indication for insertion of a thermodilution catheter into the right heart, so that cardiac output can be measured and oxygen delivery maintained above 10 mmol/kg/min. Where, by manipulation of respiratory indices and inotropic support, achievement of this level is not possible, the prognosis is grave. Antibiotic therapy is discussed, therapy being instituted if at all possible once the haemodynamic state has been improved.
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PMID:Management of patients with shock and sepsis. 304 58

To examine the role of polymorphonuclear neutrophils (PMN) and other granulocytes in the pathogenesis of acute lung injury caused by tumor necrosis factor alpha (TNF), we compared the permeability edema and pulmonary histopathology in normal (granulocyte sufficient) guinea pigs and in granulocytopenic guinea pigs treated with TNF. Circulating granulocytes were depleted with cyclophosphamide. Two groups of normal animals were treated with either saline (PMN+/Control) or 1.4 x 10(6) U/kg recombinant human TNF (PMN+/TNF). Three granulocytopenic groups were treated with either saline (PMN-/Control), TNF (PMN-/TNF), or intravenous infusion of 2 x 10(9) E. coli strain J96 (PMN-/Sepsis). We measured the amount of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid and whole lung tissue and the wet/dry lung weight ratio to assess pulmonary transvascular protein flux and edema. We also quantified PMN in BAL fluid and fixed lung tissue. There were no statistically significant differences in any of these parameters between the PMN+/Control, PMN-/Control, or PMN-/TNF groups, except that the PMN+/Control predictably had more PMN/alveolus than the PMN- groups. However, both the PMN+/TNF and the PMN-/Sepsis groups had increased amounts of 125I-labeled albumin in BAL fluid and lung tissue (p less than 0.01) and increased wet/dry lung weight ratios (p less than 0.05), compared to all other groups. Histopathologically, capillary congestion and moderate inflammation were seen in the PMN+/TNF group, and acute inflammation and gross alveolar hemorrhage were seen in the PMN-/Sepsis group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs. 305 92

Immunoluminometric assays for lactoferrin and elastase-alpha 1-proteinase inhibitor complexes were developed using solid-phase methodology, which has already been published from this laboratory. The aim of the study was to develop a rapid method to see whether elevated granulocyte activity was present in the lung, as for example in neonatal sepsis. The lactoferrin assay gave reliable results within 30 minutes, the elastase-alpha 1-proteinase inhibitor complexes, within 5 hours. The correlation between both analytes was good, so that the lactoferrin assay could replace the elastase-alpha 1-proteinase inhibitor assay in emergency cases. The lactoferrin assay was used for rapid answer, the elastase-alpha 1-proteinase inhibitor complex assay for "fine" monitoring of the progress of the disease. Both assays could be used to measure concentrations in plasma or bronchoalveolar lavage using a 10 microliters sample. Plasma for the elastase-alpha 1-proteinase inhibitor complex determination had to be diluted 1:50 before being assayed. Only EDTA plasma was used in the assay, as either heparin plasma or serum resulted in granulocyte destruction, thus giving rise to elevated, and non-reproducible results. The results from bronchoalveolar lavage show an excellent correlation between elastase-alpha 1-proteinase inhibitor complexes and lactoferrin. No interference was seen from lipaemic or icteric plasma samples. Results from haemolytic samples i.e. where lysis of erythrocytes and leukocytes had occurred, had to be treated with care if no clinical indication of intravascular haemorrhage was present. The assays lend themselves to perinatal diagnosis, as the total volume of plasma or lavage needed is theoretically under 50 microliters, i.e. ethically acceptable for regular monitoring of neonates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development and clinical evaluation of immunoluminometric assays for lactoferrin and elastase-alpha 1-proteinase inhibitor complexes in body fluids with special references to bronchoalveolar lavage and neonatal sepsis. 306 29

The results presented in this paper demonstrate that recombinant human granulocyte-colony stimulating factor (rhG-CSF) is a potent myelopoietic growth and differentiation factor in vivo. RhG-CSF was able to shorten the time period of neutrophil recovery in both cyclophosphamide (CY)-induced myelosuppression and following bone marrow transplantation (BMT) in primates. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect on the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and after bone marrow transplantation.
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PMID:Recombinant human granulocyte-colony stimulating factor: in vitro and in vivo effects on myelopoiesis. 331 Dec 16

Although reactions to granulocyte transfusions in neonates are rarely reported, we observed a near-fatal pulmonary reaction, presumably due to white cell antibodies, in a neonate with Rh hemolytic disease. The hemolytic disease was being treated with exchange transfusions, and at 2 days after the infant's birth, bacterial sepsis was suspected and granulocyte transfusions were begun. The first granulocyte transfusion (Day 3) was uneventful. Five minutes after the beginning of the second granulocyte transfusion (Day 4), severe respiratory distress, hypotension, bradycardia, cyanosis, and acidosis suddenly occurred. The infant's serum obtained after the reaction contained granulocytotoxic and B-lymphocytotoxic antibodies that reacted with leukocytes from the second granulocyte donor. Antibodies could not be detected either in the initial infant serum or in maternal serum. However, an antileukocyte antibody was present in the serum of a parous woman donor. We used plasma from this woman to prepare reconstituted whole blood for the exchange transfusion that we performed immediately preceding the second granulocyte transfusion. Despite the sequence of events, an irrefutable cause-and-effect mechanism could not be established because the properties of the donor and neonatal antibodies were similar, but not identical. However, this catastrophic event emphasizes both the potential for adverse effects of granulocyte transfusions in neonates and the need for caution when transfusing blood from parous women.
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PMID:A near-fatal reaction during granulocyte transfusion of a neonate. 335 47

We reviewed results of intraabdominal operations in 23 patients with acute or chronic leukemia to address morbidity, mortality, and factors associated with complications. We found a higher mortality rate among those who had emergency procedures as opposed to elective procedures. Three of four patients who needed reoperation and all four patients with ischemic or perforated viscus died, all from sepsis. Factors such as age, preoperative leukocyte or granulocyte count, or preoperative use of steroids or antineoplastic drugs did not affect the outcome. We therefore recommend early surgical intervention in these patients, even in the face of granulocytopenia, thrombocytopenia, or active medical treatment.
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PMID:Intraabdominal operations in patients with leukemia. 339 93


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