Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and laboratory features of 72 patients with Felty's syndrome described within the last ten years have been compared with Felty's five original patients. Felty's syndrome appears to be a variant of rheumatoid arthritis with extra-articular manifestations in which leukopenia (usually due to neutropenia) and splenomegaly occur, although not always at the same time. Both are manifestations of the underlying disease process and are not necessarily otherwise related. The mechanism of the leukopenia is complex and abnormalities in leukocyte function appear to be as important as the leukopenia in predisposing patients with Felty's syndrome to infection. Functional abnormalities of the leukocytes in this syndrome are due in part to immune complex formation. Hypocomplementemia associated with this process may be another cause for the increased susceptibility to infection. It is proposed, therefore, that therapy in Felty's syndrome be directed at the underlying disease process, and gold salts and penicillamine should be considered for this purpose. Splenectomy should be reserved for specific situations, such as hemolytic anemia, severe thrombocytopenia, leg ulcers, and infections associated with profound leukopenia that are not responsive to medical therapy.
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PMID:Felty's syndrome: an analytical review. 33 Sep 14

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ticlopidine are reviewed. Ticlopidine appears to inhibit platelet aggregation induced by adenosine diphosphate. Ticlopidine hydrochloride is rapidly absorbed after oral administration, and maximum antiplatelet effects occur one to three hours after the dose. In multicenter, randomized, double-blind trials, ticlopidine was more effective than aspirin or placebo in preventing stroke, myocardial infarction, or death caused by vascular events. Ticlopidine was more effective than aspirin in preventing recurrent transient ischemic attacks after six months of therapy. Ticlopidine has also been used to prevent occlusion and improve patency of aortocoronary bypass grafts, to prevent ischemic ulcers in patients with chronic arterial occlusive disease, and to slow the progression of diabetic microangiopathy. The most serious adverse effect, neutropenia, occurred in about 1% of patients. The most frequently reported adverse effects are diarrhea, nausea, vomiting, and abdominal cramps. Ticlopidine is indicated for reducing the risk of thrombotic stroke in patients who have experienced a minor stroke, transient ischemic attack, or completed thrombotic stroke. The recommended dosage is 500 mg/day in two divided doses taken with food. Ticlopidine is an alternative agent for the primary and secondary prevention of stroke. Because of the risk of neutropenia and agranulocytosis and the high cost of therapy, ticlopidine should be reserved for patients who are intolerant of or lack benefit from aspirin.
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PMID:Ticlopidine: a new platelet aggregation inhibitor. 161 11

Gram-negative bacillary pneumonia is common in all groups of iatrogenically immunosuppressed patients. Mortalities are directly proportional to the degree of neutropenia. Those at particular risk for gram-negative pneumonia are neutropenic patients, patients residing in the hospital setting for prolonged periods, and patients in postoperative periods (eg, organ transplant recipients). The most frequent pathogenesis for pneumonia appears to be airway colonization with gram-negative bacilli, followed by lowe respiratory tract infection. Thus, attention to infection control measures and surveillance culture data is important. Because sputum production is scant or absent, and blood cultures positive in only 30% to 40% of patients, it is often difficult to identify specific etiologic agents. If bacterial pneumonia is suspected in the immunocompromised host, empiric antibiotic coverage should include drugs active against all common aerobic gram-negative bacilli (including P aeruginosa), plus S aureus. Most advocate a beta-lactam plus aminoglycoside combination. Adjunctive treatment with granulocyte transfusions should be reserved for patients not responding to traditional regimens. Immune therapy or prophylaxis has not been fully evaluated for the immunocompromised patient population.
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PMID:Gram-negative bacterial pneumonia in the immunocompromised host. 331 7

Standard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we conducted two consecutive phase II studies. From March 1986 to February 1991, 64 patients with advanced untreated but resectable head and neck cancer who would require total laryngectomy were enrolled on one of two cisplatin-based induction regimens: cisplatin-bleomycin-5-fluorouracil (PBF) in 31 patients and cisplatin-5-fluorouracil (PF) in 33; all received definitive radiotherapy. Surgery was reserved for patients who achieved less than a partial response to chemotherapy and patients with residual or recurrent disease after sequential chemotherapy plus radiotherapy. Overall complete plus partial response rates to both cisplatin-based regimens were comparable. The combined PF and PBF overall response rates were 75% for laryngeal cancer, 78% for hypopharyngeal cancer, and 75% for oropharyngeal cancer. Complete response rates after radiotherapy were 88%, 83%, and 50%, respectively. Neutropenia (< 1,000 cells/mm3) was the most common hematologic toxic effect: it occurred in 44% of patients who received PF and 16% of those who received PBF. Grade > or = 3 mucositis occurred in 50% of patients who received PF and 4% who received PBF. The data suggest that laryngeal preservation was feasible in all three primary-site subgroups. With follow-up of 15+ to 54+ months, 44% of patients with laryngeal cancer, 28% with hypopharyngeal cancer, and 22% with oropharyngeal cancer are alive with laryngeal preservation. The overall 2-year survival rates for patients with cancer of the larynx, hypopharynx, and oropharynx were 71%, 46%, and 38%, respectively.
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PMID:Laryngeal preservation by induction chemotherapy plus radiotherapy in locally advanced head and neck cancer: the M. D. Anderson Cancer Center experience. 751 Feb 76

Since an earlier review in the Journal substantial additional data have accumulated, further clarifying the in vitro activity, pharmacokinetic profile, clinical efficacy and tolerability of teicoplanin. Recent therapeutic trials confirm the efficacy of teicoplanin in the treatment of microbiologically confirmed Gram-positive infections, including septicaemia, endocarditis, and infections of skin and soft tissue, bone and joints, and the lower respiratory tract. As teicoplanin can be administered once daily intramuscularly as well as intravenously, it has potential for outpatient treatment of severe Gram-positive infections. Teicoplanin is appropriate as treatment of patients with fever and neutropenia, but there is still controversy over the timing for introduction of glycopeptide antibiotics into therapeutic regimens. Teicoplanin is generally reserved for secondary therapy of patients with documented bacteraemia who fail to respond to initial empirical antibiotic regimens, but probably should be part of the initial empirical regimen in the setting of a high incidence of methicillin-resistant staphylococci. Teicoplanin has a lower propensity than vancomycin to impair renal function when either drug is combined with an aminoglycoside, causes fewer anaphylactoid reactions, and appears to be of comparable efficacy. Thus, teicoplanin may be preferred to vancomycin in the treatment of Gram-positive infections, and where a glycopeptide antibiotic is deemed a necessary inclusion in a regimen for empirical treatment in patients with fever and neutropenia.
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PMID:Teicoplanin. A reappraisal of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. 752 Aug 60

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.
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PMID:Clinical use of hematopoietic growth factors in allogeneic bone marrow transplantation. 752 6

Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), has identical biological activity to that of endogenous human G-CSF, but differs in that it contains an N-terminal methionine residue and is not glycosylated. It principally stimulates activation, proliferation and differentiation of neutrophil progenitor cells and has been evaluated in the treatment of patients with various neutropenic conditions, both iatrogenic and disease-related. Two comparative studies have demonstrated that prophylactic administration of filgrastim 230 micrograms/m2/day significantly reduces the incidence, duration and severity of neutropenia in patients with previously untreated small-cell lung cancer receiving standard-dose chemotherapy with CDE (cyclophosphamide, doxorubicin plus etoposide). Concomitant with the amelioration of neutropenia, the incidence of febrile neutropenia was significantly reduced by 50% and there were 35 and 50% decreases in hospitalisation rates and intravenous antibiotic requirements. Since not all patients receiving standard-dose chemotherapy are at risk of infectious complications, prophylactic filgrastim use may be reserved for those patients who have developed febrile neutropenia during a previous cycle of the same regimen. This strategy may prove less costly, although potential savings must be weighed against a greater risk of patient morbidity and reduced quality of life. When combined with standard intravenous antibiotic therapy, filgrastim further decreases morbidity in patients with established febrile neutropenia and may have a positive impact on overall treatment costs by shortening the length of hospitalisation. Attention is focused on the use of haematopoietic growth factors to support dose-intensification of chemotherapy with a view to improving treatment outcomes in patients with chemo-responsive tumours. Filgrastim, used alone, permits modest increases in dose-intensity and/or dose-escalation of some standard-dose chemotherapy regimens. Moreover, the drug has proven useful as an adjunct to myeloablative chemotherapy followed by stem cell rescue with autologous bone marrow transplantation and/or peripheral blood progenitor cells. However, the impact of these dose-intensification approaches on survival remains to be determined in well-controlled clinical studies. Filgrastim is effective in increasing the neutrophil count and decreasing morbidity in patients with severe chronic neutropenia, including Kostmann's syndrome, and in idiopathic and cyclic neutropenia. In addition, filgrastim has accelerated neutrophil recovery in patients with idiosyncratic drug-induced agranulocytosis. Available data indicate that filgrastim is generally well tolerated. The most frequent adverse reaction is mild to moderate medullary bone pain, reported by approximately 20% of patients, although this can generally be controlled using simple analgesics without the need to discontinue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Filgrastim. A review of its pharmacological properties and therapeutic efficacy in neutropenia. 753 Jun 30

The approach to the diagnostic evaluation of a patient with neutropenia can be guided largely by clinical history and physical examination and does not always require an extensive laboratory evaluation. Based on the history and bone marrow morphology, most children with chronic neutropenia can be classified and managed. Most patients with chronic neutropenia are free of infections and are able to maintain a normal lifestyle with no or minimal medical intervention. On the other hand, for patients with recurrent or severe infections, careful follow-up and institution of treatment are mandatory. The Food and Drug Administration has approved the use of rhG-CSF in patients with chronic neutropenia. As mentioned previously, the use of colony-stimulating factors has dramatically improved the outcome for many patients with the more severe neutropenia; however, this cytokine is expensive, so treatment should be reserved for more severely affected patients and not given just because the ANC is low. Although concerns exist regarding leukemogenic effects or eventual loss of the progenitor cell compartment driven by the continuous stimulation of rhG-CSF, at this moment, the long-term data available suggest that the chronic administration of rhG-CSF is safe.
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PMID:Diagnosis and management of chronic neutropenia during childhood. 864 9

Haematopoietic growth factors are glycosylated proteins involved in the differentiation of pluripotent stem cells into committed progenitor cells, which eventually give rise to distinct haematopoietic cell lineages. Three recombinant hematopoietic growth factors--G-CSF, GM-CSF and erythropoietin--are currently commercially available for clinical use. G-CSF and GM-CSF are lineage-specific growth factor that regulate the production and function of granulocytic and monocytic cells. They have been shown to reduce the incidence of febrile neutropenia. Primary prophylactic administration is reserved for patients in which the expected incidence of febrile neutropenia is greater than 40% without haematopoietic growth factor. After a documented occurrence of febrile neutropenia in an earlier cycle, the secondary prophylactic administration of G-CSF or GM-CSF may be considered. However, in the absence of clinical data supporting maintenance of chemotherapy dose-intensity, dose reduction should be considered as an alternative to the use of haematopoietic growth factors. G-CSF and GM-CSF also shorten the period of neutropenia in patients undergoing high-dose chemotherapy with autologous bone marrow support. Erythropoietin is currently approved for treatment of anemia associated with cisplatin-based chemotherapy with the aim to reduce transfusion requirements.
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PMID:[Haematopoietic growth factors and solid tumors]. 936 42

This study retrospectively evaluated the use of parenteral ciprofloxacin (PC) under the influence of a reserved antimicrobial drug program and an intravenous-oral stepdown program. During the first three months following its formulary introduction, 92 PC treatment courses were initiated. Fifty of these treatment courses in 49 adults were randomly selected for study. The hematology service accounted for 50% of the courses reviewed. The balance were initiated in the intensive care unit (16%), and six other services (34%). PC was used for the treatment of febrile neutropenia (50%), respiratory tract infections (20%), gram-negative sepsis (10%), and five other indications. Initial use of the intravenous formulation was considered appropriate in 92% of courses. Stepdown therapy occurred in 17 (34%) of treatment courses. Of the 26 patients considered candidates for oral therapy, seven patients (27%) were eligible for earlier stepdown and nine patients (35%) did not receive oral drug. According to our criteria, unnecessary use of the intravenous route occurred in 20% of PC treatment days. Mean total cost (acquisition plus delivery) of therapy per course was $668. This cost was higher in the hematology service (mean $990) than any other service (p = 0.0015). When stepdown therapy was employed the mean daily cost of therapy was $43.63 vs. $55.61 when the oral dosage form was not used (p = 0.04). Parenteral drug costs totalling $6245 were avoided by subsequent use of the oral dosage form. If full compliance with stepdown criteria had occurred, an estimated total savings of $10,769 could have been realized.
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PMID:Ciprofloxacin use under a reserved drug and stepdown promotion program. 1014 Oct 61


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