Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PMN elastase, a proteolytic enzyme, is a biochemical marker for pathologic granulocyte stimulation. In the presence of sepsis, excessive neutrophil stimulation occurs and significant amounts of PMN elastase are released into the plasma and serve as an indicator for the severity of the disease and the prognosis. PMN elastase is also a useful parameter for preoperative diagnostic management and postoperative follow-up of bone and joint infections. In patients with osteomyelitis and joint empyema (n = 48) PMN elastase had a sensitivity of 77%, which was only exceeded by that of the unspecific erythrocyte sedimentation rate (sensitivity 89%). Sensitivities of other inflammation parameters were lower: C-reactive protein (CRP) 67%, fibrinogen 50%, neopterin 32% and leukocyte count 21%. Determination of PMN elastase levels was also helpful in postoperative follow-up of patients with bone and joint infections. In the early postoperative period PMN elastase levels normalized more quickly than the other parameters unless patients actually developed complications. At the first postoperative determination (day 2-4 after surgery) 38% of the patients (n = 24) already had PMN elastase levels within the normal range (less than or equal to 40 micrograms/l) (CRP 13%). After 10 days PMN elastase was normal in 57% and CRP in 30% of the patients. Later on both parameters reacted similarly: by the time of discharge from hospital levels of PMN elastase were normal in 70% and CRP levels in 74%.
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PMID:[PMN-elastase as a marker in diagnosis and follow-up of bone and joint infections]. 171 43

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.
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PMID:Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group. 172 Apr 52

The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy. The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60%. In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses. It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%). The administration of antibiotics was required for about 7 days to patients with febrile episodes. Sepsis was experienced in five courses, in which the neutrophils were all zero. All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy.
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PMID:The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor. 172 56

We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis.
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PMID:Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis. 151 35

In order to achieve the maximum therapeutic benefit in the treatment of malignancies, doses of chemotherapeutic agents are pushed to the point of severe marrow toxicity. This aggressive therapy can lead to iatrogenic complications including haemorrhage and sepsis due to the depletion of platelets and granulocytes. Prior to the advent of platelet transfusions, haemorrhage was the leading cause of death in these patients. Advances in blood banking and the availability of platelet transfusions have markedly decreased the incidence of fatal haemorrhage. As a result, infection has become the leading cause of death in patients with marrow failure. Although the risk of infection in patients with neutropenia has been well documented, the role of granulocyte transfusions in the treatment and prevention of these infections remains controversial. This paper will attempt to review the currently available literature regarding granulocyte procurement techniques and the efficacy of granulocyte transfusions.
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PMID:Granulocyte transfusions--a review for the intensive care physician. 175 Jun 30

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in patients infected with human immunodeficiency virus (HIV). Ganciclovir, a guanosine nucleoside, has been found to be effective in the short-term treatment of CMV retinitis and in the delay of progression to recurrence of the disease. However, ganciclovir has no intrinsic activity against HIV, and patients with the acquired immune deficiency syndrome often require treatment with zidovudine, the only currently approved therapy for HIV infection. Both agents have been associated with dose-limiting granulocytopenia in such patients, and death from sepsis in the setting of profound decreases in absolute granulocyte counts has been reported. However, recent investigation suggests that with careful patient selection and monitoring, relatively safe concomitant therapy may be possible. This article reviews the toxicity issues that influence the decision to employ concomitant therapy with ganciclovir and zidovudine. An approach to dosing ganciclovir, including a schema for modifying or interrupting the zidovudine dosage based on hematologic status, is also presented. A prospective study is presently under way to determine whether combined therapy in selected patients leads to prolonged survival and a decreased incidence of recurrence of active CMV retinitis.
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PMID:Concomitant ganciclovir and zidovudine treatment for cytomegalovirus retinitis in patients with HIV infection: an approach to treatment. 184 17

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.
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PMID:Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study. 191 29

Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300-400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma.
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PMID:Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia. 193 5

Severe thermal injury results in impairment of granulocyte production and function. The ability to improve the functional capacity of neutrophils could contribute to a reduced morbidity and mortality from sepsis following thermal injury. Previous studies from this laboratory have shown that rhG-CSF increases the number of femoral marrow granulocyte progenitor cells and circulating neutrophils as well as the survival rate following burn wound infection. The studies reported here examine the effect of in-vivo administration of rhG-CSF on neutrophil chemotaxis following a burn injury and also following superimposed Pseudomonas burn wound sepsis in mice. Casein-elicited peritoneal neutrophils were harvested 72 hours after burn injury and 24 hours after infection. Chemotaxis was assessed using microchemotaxis chambers and 10(-5) M fMet-Phe as a chemoattractant. The number of neutrophils that migrated into the filter was used as an index of directed chemotaxis. Burn injury resulted in depressed chemotaxis compared with sham or sham/G-CSF-treated animals (p less than 0.05). Administration of rhG-CSF to burned animals resulted in a level of neutrophil chemotaxis comparable with that in control animals. The presence of a burn wound infection caused no further impairment of chemotaxis. Administration of rhG-CSF to animals with a burn wound infection resulted in improved chemotaxis compared with sham, burned, and burned/infected animals. The beneficial effect of G-CSF following burn wound infections from this and previous studies appears to be a combination of expanded numbers of myeloid elements and preservation of their function.
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PMID:The effect of granulocyte colony-stimulating factor (G-CSF) upon burn-induced defective neutrophil chemotaxis. 202 39

Typical alterations of the white blood cell count are often missed during the acute course of infectious diseases. Activiation and degranulation of granulocytes are followed by elevation of E alpha 1 PI and lactoferrin plasma concentrations under these conditions. The aim of our study was the evaluation of the diagnostic significance of these granulocyte parameters in relation with the absolute granulocyte count in infected pediatric patients. A total number of 106 patients at the age of 1 day to 16 years were studied. 25 children suffered from viral, 26 from localized and 23 from systemic bacterial infections, 32 children exhibiting no signs of infection served as controls. Results of the study are given as medians and ranges. Total granulocyte count was elevated above controls (4.8; 2.2-12.7/nl) only in patients with localized bacterial infections (13.3; 5.5-36.5/nl). E alpha 1 PI and lactoferrin plasma concentrations correlated well (r = 0.72) and were found to be significantly elevated in patients with localized bacterial infections (856; 363-4820 micrograms/l and 748; 206-2078 micrograms/l) and septicemia respectively (661; 256-2078 micrograms/l and 871; 160-9550 micrograms/l). A clearcut differentiation of septic and locally infected patients was given by the ratio of E alpha 1 PI and total granulocyte counts. Significantly elevated E alpha 1 PI concentrations of patients exhibiting viral infections (295; 86-690 micrograms/l) may suggest effective granulocyte activation under this condition. Finally we conclude that E alpha 1 PI and lactoferin plasma concentration related to total granulocyte counts in infected patients may serve as a helpful indicator of granulocyte activation during the acute course of the disease.
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PMID:[Elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI) and lactoferrin plasma concentrations in viral and bacterial infections]. 203 54


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