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

Ms. K., a white, 47-year-old female with a history of hyperthyroidism had been treated with methimazole daily for a period of 9 years. She presented with a 2-day history of fever higher than 103 degrees F and cellulitis of the right arm after a scratch injury. White blood cell count (WBC) was noted at 0.4 x 10(3)/microL and neutrophils at 5.6%, indicating agranulocytosis. Methimazole was discontinued by the patient with the onset of symptoms. Appropriate intravenous antibiotic therapy and reverse isolation were provided in the acute-care setting, as well as administration of the granulocyte colony-stimulating factor (G-CSF) filgrastim. No recovery of the granulocyte count or improvement of clinical condition was noted until her sixth day of admission, at which time her WBC increased to 2.6 x 10(3)/microL. The administration of intravenous antifungals and antibiotics prevented overwhelming sepsis, while giving the G-CSF the opportunity to stimulate growth of granulocytes to finally fight the offending organisms and save this patient.
 ...
PMID:Severe neutropenia as an adverse effect of methimazole in the treatment of hyperthyroidism. 1047 84

Bacterial and fungal sepsis are major causes of morbidity and mortality in the newborn. Multiple factors contribute to this increased susceptibility to infection, including quantitative and qualitative neutrophil defects, with a reduction in neutrophil number and function. Neutropenia in the newborn may occur in association with sepsis and has a poor prognosis. In addition to antibiotic therapy and supportive care, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce morbidity and mortality. Granulocyte CSF is the physiological regulator of neutrophil production and function. Administration of G-CSF results in increased neutrophil production and counts and improved neutrophil function. Several studies of animal and human newborns having neutropenia or suspected sepsis investigated the use of G-CSF and GM-CSF to elevate neutrophil counts and reduce morbidity and mortality in this population. Results of small clinical trials using G-CSF and GM-CSF in very low-birth-weight infants having neutropenia show increased neutrophil counts and a reduced incidence of sepsis during the neonatal period. Despite these promising early results, further studies of the safety and efficacy of G-CSF and GM-CSF administration in neonates are required before their routine use can be recommended as either prophylaxis or treatment for neonatal sepsis.
 ...
PMID:Myeloid colony-stimulating factors: use in the newborn. 1048 17

Dose-intensive chemotherapy appears to be important in the treatment of patients with recurrent solid tumors. Expanding upon our prior experience, we report the results of our most recent approach to administering dose-intensive therapy using four cycles of moderately high-dose chemotherapy with hematopoietic cell support for patients with metastatic breast cancer. This outpatient therapy includes high-dose melphalan, thiotepa, and paclitaxel for two cycles followed by mitoxantrone, thiotepa, and paclitaxel for two cycles, with each cycle supported with autologous peripheral blood progenitor cells (PBPCs). Between December 1994 and June 1996, 16 patients with recurrent or refractory breast cancer were enrolled in this prospective study. They had received a median of two previous chemotherapy regimens, with a median of nine prior cycles of chemotherapy. For mobilization of autologous PBPCs, patients received cyclophosphamide, 4 g/m2, followed by granulocyte colony-stimulating factor (G-CSF). PBPCs were collected by apheresis. Each day's collection was divided into four equal fractions, and each fraction was infused after each cycle of combination therapy. Cycles 1 and 2 consisted of melphalan, 80 mg/m2, thiotepa, 300 mg/m2, and paclitaxel, 200 mg/m2. Cycles 3 and 4 were comprised of mitoxantrone, 30 mg/m2, and thiotepa and paclitaxel at the same doses as in the first two cycles. The cyclophosphamide infusion was administered in the hospital, whereas all subsequent infusions of chemotherapy and PBPCs were performed on an outpatient basis. The first seven patients were randomized to receive alternate cycle G-CSF or placebo on day +1 of each cycle. Including the initial pulse of cyclophosphamide, 67 (84%) of a planned 80 total courses of chemotherapy were delivered. Of the planned 64 cycles of high-dose combination chemotherapy, 52 cycles (81%) were delivered. Treatment was discontinued for progressive disease (one patient) or morbidity (five patients). Twelve of 16 patients completed at least three cycles of therapy. Nine patients completed all four cycles. One death resulted from fungal sepsis. In 20 cycles delivered to the first seven patients, day +1 G-CSF versus placebo was administered, with a median WBC recovery of 10 versus 13 days, respectively (P = 0.048 in cycle 1). The median duration of response was almost 9 months, and the median survival was 18 months after therapy. With a median follow-up of 1.5 years and longest follow-up of 4.2 years, two patients continue to be without evidence of disease. The 3-year event-free survival, freedom from progression, and overall survival are 19%, 20%, and 31%, respectively. This four-cycle regimen of high-dose combination therapy supported with hematopoietic progenitor cells is feasible, but it is associated with a range of posttransplant complications. The efficacy of such a treatment would have to be substantially superior to that of other currently available therapies, including single autologous transplant procedures, to justify the prolonged period of treatment, multiple episodes of pancytopenia, and associated toxicities, including infectious risks. G-CSF administration after each PBPC infusion appears to accelerate time to neutrophil recovery but does not affect red cell or platelet engraftment.
 ...
PMID:A feasibility study of multiple cycle therapy with melphalan, thiotepa, and paclitaxel followed by mitoxantrone, thiotepa, and paclitaxel with autologous hematopoietic cell support for metastatic breast cancer. 1058 52

We present a seven-month-old boy referred to our hospital with a history of recurrent suppurative infections starting in his neonatal period. Anemia, absolute neutropenia absolute neutrophil count (ANC: 500 cells/microl), pneumonia, purulent otitis media and maturational arrest of granulocytes at promyelocyte-myelocyte level in bone marrow were detected on his admission. He was diagnosed as Kostmann syndrome and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy was started at a dose of 10 microg/kg/d, gradually increasing up to 120 microg/kg/d in sequential seven-day courses. As there was no response, rhG-CSF was stopped and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was started subcutaneously with 2.5 microg/kg/d and was escalated by doubling the dose every seven days to 20 mg/kg/d. By this therapy absolute neutrophil count (ANC) transiently reached above 500 cells/microl, but eosinophilia developed with a total white cell count of 88.200 cells/microl, and a differential count showing 86 percent eosinophils. Since eosinophilia of this magnitude has deleterious effects, and neutrophil production did not significantly increase, we tried combined therapy with rhG-CSF and rhGM-CSF at doses of 10-20 microg/kg/d and 5-10 microg/kg/d, respectively, without any effect on absolute neutrophil count. The patient succumbed from sepsis eight months after the diagnosis.
 ...
PMID:Failure of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in a patient with Kostmann syndrome. 1077 Jun 86

Bone marrow aplasia is a frequent complication of colchicine poisoning. This typically occurs on day 3 to 5 postexposure, and the blood cell counts remain depressed for a week or more. Unfortunately, because patients suffering from colchicine toxicity develop multiple organ complications and sepsis, the morbidity and mortality associated with bone marrow depression is high. In this article, we present three cases of colchicine toxicity in which granulocyte colony-stimulating factor (G-CSF) was used to treat bone marrow depression. In all three cases, there was a dramatic increase in the white cell count and, to a lesser extent, the platelet count. In view of the critical nature of the bone marrow depression and multi-organ toxicity induced by colchicine, we believe that consideration of the use of G-CSF to shorten the duration of neutropenia is warranted.
 ...
PMID:Colchicine-induced bone marrow suppression: treatment with granulocyte colony-stimulating factor. 1080 21

Blood levels of tumor necrosis factor (TNF)-alpha were determined in 78 patients with burn sepsis. Of these patients, 51 were managed with additional administration of granulocyte colony-stimulating factor (G-CSF) in addition to routine treatment procedures (group A), while 27 received only routine treatment (group B). G-CSF was administrated for at least nine and at most 14 days; doses were gradually decreased in each 3 day period. On the 1st, 4th, 7th, 10th and 15th days, blood levels of TNF-alpha were determined. We sought to determine whether TNF alpha levels had a prognostic value in the management of burn induced sepsis that was treated with G-CSF. In our study, patients with gradually decreasing TNF-alpha levels in the second 3 day period, were strong candidates for survival, because TNF-alpha levels decreased little in nonsurvivors but decreased greatly in survivors. The survival rate was 42/51 (82.3%) in group A and 9/27 (33.3%) in group B. In conclusion, G-CSF had positive effects on survival, and TNF-alpha was a predictor of prognosis in burn-induced sepsis.
 ...
PMID:The relationship between tumor necrosis factor (TNF)-alpha and survival following granulocyte-colony stimulating factor (G-CSF) administration in burn sepsis. 1086 22

Multiple sclerosis (MS) is an immune-mediated disease that may be amenable to high-dose immunosuppression with peripheral blood stem cell transplantation (SCT) in selected patients. Five MS patients (all women, ages 39-47 years) received granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization, CD34 cell selection for T-cell depletion, a preparatory regimen of busulfan (1 mg/kg x 16 doses) and cyclophosphamide (120 mg/kg), and antithymocyte globulin (10 mg/kg x 3 doses) at the time of stem cell infusion. Days required to recover absolute neutrophil count >500 were 12 to 14 and platelet count >20,000 were 17 to 58. Posttransplantation infectious complications in the first year after SCT occurred in 3 of 5 patients, and 1 patient died at day 22 after SCT from influenza A pneumonia. Neuropathologic study in this patient showed demyelinating plaques with surrounding macrophages but only rare T cells. In 2 patients, MS flared transiently with G-CSF. Magnetic resonance imaging gadolinium enhancement was present in 3 of 5 patients before transplantation and 0 of 4 after SCT. There were cerebrospinal fluid oligoclonal bands at 1 year after SCT, similar to the pretransplantation assays. Sustained suppression of peripheral blood mononuclear cell proliferative responses to myelin antigens occurred after SCT, but new responses to some myelin peptide fragments also developed after SCT. In 1 patient, enzyme-linked immunospot (ELISPOT) assays done 9 months after SCT showed a predominant T helper 2 (Th2) cytokine pattern. Neurological progression of 1 point on the extended disability status scale was seen in 1 patient 17 months after SCT. Another patient who was neurologically stable died abruptly 19 months after SCT from overwhelming S. pneumoniae sepsis. The remaining patients have had stable MS (follow-up, 18 and 30 months). In summary, our experience confirms the high-risk nature of this approach. Further studies and longer follow-up would be needed to determine the significance of new lymphocyte proliferative responses after SCT and the overall effect of this treatment on the natural history of MS.
 ...
PMID:Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. 1107 Dec 62

The inflammatory cascade that ensues after an infectious insult is protean in its manifestations, resulting in mild self-limited illness in some patients, while progressing to fulminant sepsis and multisystem organ failure in others. Research into the pathophysiology of this cascade has been intense, but advances in the treatment of sepsis have been few and far between. Although mortality rates have been impacted slightly in patients with sepsis--with improved survival in certain patient subgroups--overall survival still reaches only 55% to 60%. In this paper we will review some of the most recent advances in the therapy of the sepsis syndrome, specifically the roles of cytokine modifiers, supranormal delivery of oxygen, granulocyte colony-stimulating factor administration in leukopenic patients, and parenteral nutrition. Hopefully, these modalities represent additional steps in the path towards a meaningful improvement in survival from this catastrophic condition.
 ...
PMID:Adjunctive Therapies for Sepsis and Septic Shock. 1109 92

Granulocyte colony-stimulating factor (G-CSF), a central mediator of the endogenous response to infection and inflammation, is approved for use in the prevention of infection-related complications in patients with nonmyeloid malignancies during antineoplastic therapy associated with high risk of severe neutropenia. Administration of granulocyte colony-stimulating factor results in improvement of host defence paired with anti-inflammatory effects. There is evidence from animal and clinical studies that administration of granulocyte colony-stimulating factor may also be beneficial in non-neutropenic infections. This review focuses mainly on the results of different animal and clinical studies of granulocyte colony stimulating factor used in the treatment of severe infections and sepsis.
 ...
PMID:Recombinant granulocyte colony-stimulating factor (G-CSF) in infectious diseases: still a debate. 1125 46

A meta-analysis was used to determine whether administering recombinant granulocyte colony-stimulating factor (rG-CSF) to neonates with bacterial septicemia reduces mortality. Five studies were identified, involving 73 rG-CSF recipients and 82 control subjects. Mortality was lower among the rG-CSF recipients (odds ratio, 0.17; CI, 0.03-0.70; P <.05). However, when the non-randomized studies were excluded, the P value was.13. For the subgroups "<2000 g" or "neutropenia," the P value was <.02. Thus the routine use of rG-CSF cannot be recommended for all neonates with sepsis.
 ...
PMID:Administration of recombinant granulocyte colony-stimulating factor to neonates with septicemia: A meta-analysis. 1139 41


<< Previous 1 2 3 4 5 6 7 8 9 10