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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic neutropenia (CN) is an inherited disease known to occur in both humans and Gray Collie dogs. In dogs, the disease is characterized by a profound and cyclic decrease in circulating granulocytes at 12-day intervals. Other formed elements of the blood also show cyclic changes and thus the disease is also called cyclic hematopoiesis (CH). In this study, daily serum levels of lysozyme and a factor with macrophage migration inhibitory (MIF) activity were assayed. Both MIF activity and lysozyme levels were elevated more than 2-fold and fluctuated cyclically in CH dogs during the 12-day cycle: CH dogs CH 490 and CH 491, had 32.7 +/- 16.8% and 35.9 +/- 18.3% migration inhibitory activity, respectively, as compared to 15.1 +/- 1.4% in normal dog N 492; CH 490 and CH 491 had 78.7 +/- 43.7 units and 86.9 +/- 58.7 units of lysozyme, respectively, as compared to 33.4 +/- 1.7 units in N 492. The change of MIF activity tended to precede that of lysozyme activity in CH dogs. Furthermore, MIF levels and monocyte counts correlated significantly during the 12-day neutropenia cycle (CH 490, r = 0.677, P less than 0.001; CH 491, r = 0.583, P less than 0.01).
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PMID:Increase in the serum macrophage migration inhibitory activity and lysozyme in dogs affected with cyclic hematopoiesis. 675 48

Cyclic neutropenia is a rare hematological disorder characterized by periodical severe granulocytopenia. A stem cell defect and/or immunological abnormalities are considered to play a role in this disease. Here we describe the case of an adult woman who was diagnosed as having both cyclic neutropenia and severe hypogammaglobulinemia. Her clinical history revealed that one or both abnormalities had been present since childhood. Normal in vitro growth of the patient's bone marrow CFU-GM was observed, while immunological analysis revealed the presence of a persistent excess of activated (HLA-DR+) CD8+ T lymphocytes in both bone marrow and peripheral blood. These T lymphocytes have been shown to be polyclonal by DNA analysis, and their role in determining the clinical picture of our patient remain uncertain since they could not be shown to produce inhibitors of in vitro CFU-GM growth. Intermittent low doses of human recombinant G-CSF were able to improve neutropenia and completely prevent infectious symptoms, thus confirming the efficacy of this cytokine in cyclic neutropenia patients.
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PMID:Cyclic neutropenia and severe hypogammaglobulinemia in a patient with excess of CD8-positive T lymphocytes: response to G-CSF therapy. 768 13

Cyclic neutropenia is characterized by periodic episodes of neutropenia that are often associated with infectious complications. A patient with cyclic neutropenia experienced two pregnancies with an amelioration of her infectious complications and an increase in neutrophil count. Cyclic neutropenia may follow a benign course during pregnancy.
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PMID:Pregnancy in patients with cyclic neutropenia. 836 53

Cyclic neutropenia is a rare disease in which blood neutrophils periodically decrease and almost disappear, ensuing acute infections of variable severity. We report a 37 years old female presenting with severe abdominal pain, fever and neutropenia. During a surgical abdominal exploration, an acute ileitis was found. During a follow-up of 6.5 months, transient episodes of neutropenia (mean count of 0.33 x 10(9)/l), every 22-28 days, were detected. Coinciding with these episodes, band and segmented neutrophils disappeared from the bone marrow and its response to functional stimulation with prednisone was insufficient. No cyclical changes in lymphocytes, monocytes and packed red cell volume were observed. The episodes of severe transient neutropenia and infections persist after three years of follow up.
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PMID:[Adult cyclic neutropenia: acute ileitis as an initial clinical manifestation]. 852 30

Granulocyte colony-stimulating factor (G-CSF) regulates granulocyte precursor cell proliferation, neutrophil survival, and activation. Cyclic hematopoiesis, a disease that occurs both in humans and grey collie dogs is characterized by cyclical variations in blood neutrophils. Although the underlying molecular defect is not known, long-term daily administration of recombinant G-CSF eliminates the severe recurrent neutropenia, indicating that expression of G-CSF by gene therapy would be beneficial. As a prelude to preclinical studies in affected collie dogs, we monitored hematopoiesis in rats receiving vascular smooth muscle cells transduced to express G-CSF. Cells transduced with LrGSN, a retrovirus expressing rat G-CSF, were implanted in the carotid artery and control animals received cells transduced with LASN, a retrovirus expressing human adenosine deaminase (ADA). Test animals showed significant increases in neutrophil counts for at least 7 weeks, with mean values of 3,670 +/- 740 cells/microliter in comparison to 1,870 +/- 460 cells/microliter in controls (p < 0.001). Thus, in rats G-CSF gene transfer targeted at vascular smooth muscle cells initiated sustained production of 1,800 neutrophils/microliter, a cell number that would provide clinical benefit to patients. Lymphocytes, red cells and platelets were not different between control and test animals (p > 0.05). These studies indicate that retrovirally transduced vascular smooth muscle cells can provide sustained clinically useful levels of neutrophils in vivo.
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PMID:Granulocyte colony-stimulating factor expression from transduced vascular smooth muscle cells provides sustained neutrophil increases in rats. 884 2

Granulocyte colony-stimulating factor (G-CSF) acts on precursor hematopoietic cells to control the production and maintenance of neutrophils. Recombinant G-CSF (re-G-CSF) is used clinically to treat patients with neutropenia and has greatly reduced the infection risk associated with bone marrow transplantation. Cyclic hematopoiesis, a stem cell defect characterized by severe recurrent neutropenia, occurs in man and grey collie dogs, and can be treated by administration of re-G-CSF. Availability of the rat G-CSF cDNA would benefit the use of rats as models of gene therapy for the treatment of cyclic hematopoiesis. In preliminary rat experiments, retroviral-mediated expression of canine G-CSF caused neutralizing antibody formation which precluded long-term increases in neutrophil counts. To overcome this problem we cloned the rat G-CSF cDNA from RNA isolated from skin fibroblasts. The rat G-CSF sequence shared a high degree of identity in both the coding and non-coding regions with both the murine G-CSF (85%) and human G-CSF (74%). The signal peptides of murine and human G-CSF both contained 30 amino acids (aa), whereas the deduced signal sequence for rat G-CSF possessed 21 aa. A retrovirus encoding the rat G-CSF cDNA synthesized bioactive G-CSF from transduced vascular smooth muscle cells.
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PMID:Cloning and expression of the cDNA encoding rat granulocyte colony-stimulating factor. 891 83

Cyclic hematopoiesis, (CH, or cyclic neutropenia) is a rare disease manifested by transient severe neutropenia that recurs approximately every 21 days. The hematologic profile of families with the autosomal dominant form (ADCH) has not been well characterized, and it is unknown if the phenotype is distinct from the more common sporadic congenital or acquired forms of CH. We studied nine ADCH families whose children displayed typical CH blood patterns. Pedigrees confirmed dominant inheritance without evidence of heterogeneity or decreased penetrance; three pedigrees suggested new mutations. Families were Caucasian with exception of one with a Cherokee Native American founder: A wide spectrum of symptom severity, ranging from asymptomatic to life-threatening illness, was observed within families. The phenotype changed with age. Children displayed typical neutrophil cycles with symptoms of mucosal ulceration, lymphadenopathy, and infections. Adults often had fewer and milder chronic neutropenia without distinct cycles. While CH is commonly described as "benign", four children in three of the nine families died of Clostridium or E. coli colitis, documenting the need for urgent evaluation of abdominal pain. Misdiagnosis with other neutropenias was common but can be avoided by serial blood counts in index cases. Genetic counseling requires specific histories and complete blood counts in relatives at risk to assess status regardless of symptoms, especially to determine individuals with new mutations. We propose diagnostic criteria for ADCH in affected children and adults. Recombinant human granulocyte colony-stimulating factor treatment resulted in dramatic improvement of neutropenia and morbidity. The differential diagnosis from other forms of familial neutropenia is reviewed.
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PMID:Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis. 898 58

Cyclic neutropenia is a rare hematologic disorder of unknown origin. Periodic decreases in blood leukocytes with relative neutropenia and lymphocytosis are typical. These episodes appear in regular intervals of 15-35 days and last three to seven days. They are associated with physical weakness, fever, septic complications and necrosis of mucous membranes. Between the episodes, the patients are in complete clinical and laboratory remission. We report the case of a 34 year-old patient suffering from cyclic neutropenia with ulcerous lesions of the oral mucosa.
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PMID:[Recurrent episodes of ulcerative gingivostomatitis associated with cyclic neutropenia]. 1046 84

Cyclic neutropenia (CN) is a congenital hematopoietic disorder characterized by remarkably regular oscillations of blood neutrophils from near normal to extremely low levels at 21-day intervals. Recurring episodes of severe neutropenia lead to repetitive and sometimes life-threatening infections. To investigate the cellular mechanism of CN, the ultrastructure and the proliferative and survival characteristics of bone marrow-derived CD34(+) early progenitors, CD33(+)/CD34(-) myeloid progenitors, and CD15(+) neutrophil precursors from CN patients and healthy volunteers were studied. The ultrastructural studies showed profound apoptotic features in bone marrow progenitor cells in CN. Colony-forming assays demonstrated a 75% decrease in the number of early myeloid-committed colonies compared with controls. Long-term culture-initiating cell assays demonstrated a 6-fold increase in production of primitive progenitor cells in CN. To determine whether accelerated apoptosis might account for the underproduction of myeloid progenitors, the hematopoietic subpopulations were labeled with fluorescein isothiocyanate-annexin V and analyzed by flow cytometry. Short-term culture of CN cells resulted in apoptosis of approximately 65% of CD34(+) cells, 80% of CD33(+)/CD34(-) cells, and more than 70% of CD15(+) cells, as compared with 20%, 7%, and 15% apoptosis in respective control subpopulations. Evidence of accelerated apoptosis of bone marrow progenitor cells was observed in all 8 patients participating in the study, regardless of the stage in the CN cycle in which bone marrow aspirations were obtained. Granulocyte colony-stimulating factor therapy of CN patients significantly improved survival of bone marrow progenitor cells. These data indicate that ineffective production of neutrophils is due to accelerated apoptosis of bone marrow myeloid progenitor cells in CN.
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PMID:Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia. 2499 67

Cyclic neutropenia (CN) is a rare hematologic disorder characterized by regular cycling of the absolute neutrophil count and a symptom complex presenting during the neutropenic nadirs. Despite the profound cyclic neutropenia, most patients have a benign course of recurrent fever, malaise, oral ulceration, and minor skin and upper respiratory tract infections. Recurrent infections, inflammation, and ulcers can lead to significant chronic morbidity. Severe dental disease is common, pregnancy complications are increased, and overwhelming infections, bowel necrosis, and mortality, although rare, are potential sequelae. We report a 10-year-old boy with a classical presentation of CN that had remained undiagnosed for 10 years. The difficulty in diagnosing this unusual disorder is highlighted. Treatment with daily recombinant granulocyte colony-stimulating factor (rG-CSF) resulted in a complete clearing of symptoms and a significant increase in quality of life. The excellent clinical response of CN to rG-CSF, in the absence of major adverse effects, is strongly demonstrated by this case and supports rG-CSF as a first-line therapy for CN. The physiologic and adverse effects of rG-CSF use in CN and other neutropenic disorders, including potential leukemic induction, are reviewed. The need for long-term follow-up to investigate the effects of chronic hematopoietic stimulation by rG-CSF is emphasized.
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PMID:Cyclic neutropenia: an unusual disorder of granulopoiesis effectively treated with recombinant granulocyte colony-stimulating factor. 1173 91


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