Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kostmann's syndrome is a congenital disorder characterized by impairment of myeloid differentiation in bone marrow with severe absolute neutropenia. A 17-month-old girl was admitted to the hospital with complaints of recurrent skin infections since birth and severe pneumonia of the right lung which had been resistant to antibiotics since the patient was eight months old. Anemia, severe neutropenia and maturational arrest of granulocytes at the myelocyte stage in bone marrow were detected. At the age of 20 months, a right pneumonectomy was performed because of resistant cystic infection. Postoperatively, she was diagnosed with Kostmann's syndrome. Recombinant human granulocyte-colony-stimulating factor (rhG-CSF) was administered intravenously at a dose of 3 micrograms/kg/day, gradually increasing to 60 micrograms/kg/day in sequential seven-day courses to obtain a neutrophil count of more than 500 cells/mm3. Absolute neutrophil counts increased to greater than 1000 cells/mm3 at a dose of 60 micrograms/kg/day, and at that time bone marrow aspiration revealed an increase in neutrophilic granulocytic precursors beyond the myelocyte stage. In order to maintain the neutrophil response, a dose of 20 micrograms/kg/day rhG-CSF subcutaneously was continued successfully. The patient has tolerated rhG-CSF treatment without complications, and infectious attacks have significantly decreased.
 ...
PMID:Kostmann's syndrome with chronic pneumonia and lymphocytosis: effect of recombinant human G-CSF. 751 21

Administration of G- and GM-CSF increases the neutrophil counts in a number of clinical situations. GM-CSF shows the additional effect of increasing the number of monocytes and eosinophil granulocytes. Both G- and GM-CSF affect of neutrophil functions, in the case of GM-CSF there are some potentially negative effects on neutrophil migration and adhesiveness. The clinical relevance of the various effects on mature haematopoietic cells is not fully understood. Clinical data with G-CSF treatment indicate that increased levels of neutrophil granulocytes following cytotoxic chemotherapy may translate into clinical benefit such as a decreased rate of neutropenic infection and an increased cytotoxic chemotherapy dose even though the data are conflicting and the risk of "laboratory cosmetics" is apparent. Regarding treatment with GM-CSF following chemotherapy, the clinical benefit is unclear. The clinical benefit of GM-CSF-induced monocytes and eosinophils is unknown. G- and GM-CSF accelerates neutrophil recovery following autologous or allogeneic BMT. The influence on neutropenic infections is, however, less impressive. Pretreatment with G- or GM-CSF increases the yield of peripheral stem cell harvest, thereby reducing the number of leukaphereses needed. Transplantation of G- and GM-CSF primed autologous peripheral stem cells tends to reduce the period of post-transplant cytopenia, particularly thrombocytopenia, in comparison with traditional ABMT. In patients with MDS, G- and GM-CSF appear to increase the number of neutrophil granulocytes and there is some evidence that patients with severe infectious problems will benefit from this treatment. However, little influence was seen on the main clinical problems with these patients, which are anaemia and thrombocytopenia. In conclusion, G- and GM-CSF are two different proteins with different properties in vivo and in vitro. GM-CSF has, compared with G-CSF, more complex pharmacological effects and a more trouble-some side-effect profile. Early clinical development indicates that both compounds have a substantial influence on the levels of certain blood cells. Whether the increases in different blood cells translate into long-term clinical benefit for greater patient groups is the focus of ongoing research. The effects of G- and GM-CSF may be potentiated by other cytokines, an area which is presently being explored.
 ...
PMID:G- and GM-CSF in oncology and oncological haematology. 751 79

This retrospective study was undertaken to investigate whether paclitaxel was associated with cumulative bone marrow toxicity in patients undergoing salvage chemotherapy for refractory ovarian cancer. Seventy-seven patients were treated with paclitaxel 135 mg/m2 every 21 days, with granulocyte-colony-stimulating factor (G-CSF) support as necessary according to standard criteria. The mean white blood cell nadir was significantly higher and the incidence of severe leukopenia (Gynecologic Oncology Group grade 3-4) significantly lower after ten cycles than after the first cycle for the entire study population (3.4 vs. 1.6 x 10(3)/mm3 and 29 vs. 77%, respectively) and the patients who received G-CSF (3.5 vs. 1.4 x 10(3)/mm3 and 33 vs. 89%, respectively), but did not differ significantly for the patients who did not require G-CSF (2.9 vs. 2.5 x 10(3)/mm3 and 40 vs. 59%, respectively). The mean hematocrit and platelet nadirs, as well as the incidence of severe anemia and thrombocytopenia, did not differ significantly after ten cycles from those after the first cycle for the entire study population and both subgroups. Thirty-two (42%) patients received G-CSF, each initiated within four cycles. The indications for initiating G-CSF support were febrile leukopenia (53%) and treatment delay (47%). The average duration of G-CSF support was 4.6 days, and did not increase significantly as the number of paclitaxel cycles increased. We conclude that paclitaxel was not associated with cumulative bone marrow toxicity in patients undergoing salvage chemotherapy for refractory ovarian cancer.
 ...
PMID:Absence of cumulative bone marrow suppression in heavily pretreated ovarian cancer patients undergoing salvage chemotherapy with paclitaxel. 754 68

Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established.
 ...
PMID:[Cytokines in the treatment of blood diseases]. 754 26

Monosomy 7 (Mo7) and leukaemia predisposition are associated with Kostmann's disease (KD). The recent introduction of long-term recombinant HuG-CSF treatment in patients with KD, whilst showing significant reductions in infectious complications and improved quality of life, might also be associated with an increased risk of developing karyotypic abnormalities, myelodysplasia (MDS) and acute myeloid leukaemia (AML). We describe a case of an identical twin with probable autosomal dominant KD who developed anaemia, Mo7/MDS and AML at 18, 30 and 50 months respectively from starting r-metHuG-CSF (filgrastim) treatment. Further patient analyses are required to establish the natural history of KD and to determine what role, if any, filgrastim plays in altering the pathobiology of this disorder.
 ...
PMID:Kostmann's disease, recombinant HuG-CSF, monosomy 7 and MDS/AML. 757 23

Thymoma has been associated with a variety of autoimmune disorders. We report a case of agranulocytosis and anemia in a 68-year-old woman with a spindle cell thymoma. She was unresponsive to treatment with antibiotics, granulocyte-colony stimulating factor (G-CSF), prednisone, and high-dose intravenous immunoglobulin. Serial bone marrow examinations on this therapy showed progression from a cellular marrow with mild myeloid and erythroid hyperplasia and lymphocytosis, to granulocyte aplasia and severe erythroid hypoplasia. Her serum contained granulocyte-specific antibodies and inhibited the growth in culture of her own marrow cells and marrow cells from a normal donor. An IgG fraction from her serum also inhibited the growth of marrow cells. Although the patient's spindle cell thymoma was surgically removed, she remained neutropenic. She was treated with six plasma exchanges followed by 1,000 milligrams of intravenous cyclophosphamide 2 days after the final plasma exchange and daily G-CSF. Three weeks later her peripheral blood showed marked leukocytosis with pronounced neutrophilia and a left shift. Although her agranulocytosis resolved, she died of fungal sepsis. This case demonstrates that aggressive plasma exchange and immunosuppressive therapy may benefit patients with agranulocytosis associated with thymoma.
 ...
PMID:Immune mediated agranulocytosis and anemia associated with thymoma. 763 79

A 4-year-old male mixed-breed dog from the Sierra Nevada mountains in California was referred because of epistaxis and signs of cervical pain. Dermacentor variabilis ticks were found on the dog at the time of physical examination. Clinicopathologic abnormalities included nonregenerative anemia, thrombocytopenia, and rare intracytoplasmic morulae within circulating neutrophils. Abnormalities of the CSF included pleocytosis and intracytoplasmic morulae in approximately 9% of neutrophils. Serum antibody titers for Ehrlichia canis (40,960) and Rickettsia rickettsii (5,120) were high, and titer for E equi (40) was moderate. Treatment included administration of tetracycline, chloramphenicol, doxycycline, and prednisone. The dog had several relapses, but long-term remission was eventually achieved. Granulocytic ehrlichiosis has previously been associated with anemia, thrombocytopenia, and polyarthritis in dogs. This case suggests that granulocytic ehrlichiosis may be associated with meningitis and that the organisms that cause granulocytic ehrlichiosis may have the same vector as do the spotted fever-group rickettsiae.
 ...
PMID:Granulocytic ehrlichiosis and meningitis in a dog. 773 Jan 22

Growth and differentiation of hematopoietic progenitor cells is regulated by a complex network of stimulatory and inhibitory cytokines. Bone marrow failures can be due to a decrease of stimulators or an increase of inhibitors. T cells produce both, hematopoiesis stimulating and inhibiting cytokines. Therefore, a role of T cells in regulating hematopoiesis can only be assumed if the gene expression of these antagonistic acting cytokines can be differentially induced in T cells. To establish a model of selective cytokine induction, we investigated the induction of IFN gamma as inhibitor and GM-CSF as stimulator of hematopoiesis in T cells. Our results showed that IFN gamma mRNA accumulates in T cells which have been pre-activated via the signal transduction unit CD3, but not in unstimulated T cells. This accumulation depends on the expression of the high affinity IL2 receptor which is including the IL2 receptor alpha-chain (IL2R alpha, CD25). In a study on children with constitutional (CAA) versus acquired aplastic (EAA) anemia, we investigated the relevance of this model for the pathogenesis of aplastic anemia in childhood. We compared the following parameters: 1. Incidence of hematopoietic progenitor cells and cloning efficiency, 2. activation status and IL2R alpha expression of bone marrow T cells, 3. T cell cytokine expression profile. Our results show: 1. The relative incidence of bone marrow progenitor cells is decreased in children with CAA and normal in children with EAA. 2. Clonogenic growth of hematopoietic progenitor cells is suppressed in children with EAA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Experimental principles of therapy-oriented pathogenetic classification of aplastic anemia in childhood]. 796 17

We present a case of meningoencephalitis due to EBV in a 2-month-old infant, without mononucleosis, which persisted for more than 5 months. Evidence for persistence of the infection was provided by a convulsive disorder and prolonged CSF pleocytosis, combined with persistent moderate anemia. Despite the persistence of the infection, the child continued to develop normally. This case demonstrates that EBV meningoencephalitis occurring in young patients may present with only subtle clinical findings and may have a favorable prognosis.
 ...
PMID:Prolonged meningoencephalitis due to Epstein-Barr virus with favorable outcome in a young infant. 813 72

Cytokines are decisive for the regulation of the immune system as well as the renewal and maturation of the haematopoietic cells. The most important groups of substances, several of which are already produced by gentechnology, are the interferons, the interleukins and the haematopoietic growth factors. The main indications for the application of alpha-(less often beta-)Interferon in children are the juvenile larynx papillomatosis, chronic hepatitis B, viral encephalitis, and also chronic myeloic leukemia, extended haemangiomas, recurrent Langerhans cell histiocytosis and nasopharynx carcinomas. gamma-Interferon is administered successfully for chronic granulomatous disease and has recorded positive effects in therapy resistant rheumatoid arthritis, in kidney cell carcinoma and in osteopetrosis. G-CSF, GM-CSF and Interleukin 3 are the most effective haematopoietic growth factors currently in use. Through G-CSF congenital agranulocytosis (Kostmann syndrome) has become a treatable disease. Other proven applications are in the reduction of aplastic phases after chemotherapy and in critical situations of primary bone marrow failure as well as myelodysplastic syndromes, for prevention of transplant rejections after bone marrow transplantation and for mobilisation of stem cells into peripheral blood before apheresis. Erythropoietin is established in the treatment of chronic renal anaemia and is currently used in the treatment of anaemia in preterm infants. Finally, Interleukin 2 is also used for adoptive immunotherapy in children with minimal residual tumors. The future will show us, whether the spectrum of indications will expand and whether a definite benefit for sick children will result from a wider application of these substances. As long as the cost/benefit ratio for certain indications is not clear, the use of these drugs should be tested in prospective studies.
 ...
PMID:[Clinical applications of cytokines in pediatrics]. 815 1


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