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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many questions are raised in this review about the role of adult donor granulocyte transfusions in the setting of overwhelming bacterial neonatal sepsis. There clearly exists a number of variables, which influence the survival and morbidity associated with bacterial sepsis. The important differences in these studies highlight the need for prospective large multicenter studies to definitely clarify these issues. Important criteria, which are yet to be established and which impact significantly, include the time of administration of adjuvant granulocytes, the number of granulocytes that need to be harvested, which group of neonates require early granulocyte transfusions, the best method for optimal and easy granulocyte collection, the frequency and intervals of granulocyte transfusions, and improved methods for the early identification of neonatal candidates who would benefit from the granulocyte transfusions. The benefits of granulocyte transfusions (ie, the improvement in morbidity and mortality) in septic neutropenic neonates must be weighed against the possible and reported side effects associated with such transfusions. Adverse reactions including graft-versus-host disease, CMV, HIV and hepatitis infection, fluid retention and pulmonary edema, blood group sensitization, and pulmonary insufficiency may all result from the use of granulocyte transfusions in a host who has evidence of developmental immaturity. All future studies must continue to evaluate these potential complications to balance and analyze the true benefits of survival with reported treatment results. Recently, a number of investigators including ourselves, have begun to examine the role of alternate adjuvant immunotherapy in enhancing neonatal host defense in the clinical setting of overwhelming bacterial sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of granulocyte transfusion in neonatal sepsis. 213 12

Neonatal host defense simulates a clinical state of immunodeficiency that predisposes the preterm and term newborn to overwhelming bacterial sepsis. There are various immunologic components that are deficient in the newborn and new methods to enhance their function. Defects in both the quantitative and qualitative aspects of the neonatal phagocyte contribute substantially to the immaturity of neonates' immune systems. The neonate lacks an adequate number of granulocyte bone marrow progenitor cells, and has a decreased neutrophil storage pool and an increased tendency to peripheral neutropenia during neonatal sepsis. Additionally, the neonatal granulocyte demonstrates altered physiologic function compared with that found in the adult with respect to chemotaxis, phagocytosis, oxidative metabolism, and bacterial killing. Some recent clinical studies have suggested the benefit of using adult neutrophil transfusions as adjuvant treatment during neonatal bacterial sepsis, yet other studies have found the use of polymorphonuclear neutrophil leukocyte transfusions to be inconclusive. Reduced circulating immunoglobulins and impaired production of specific antibody have also led to recent trials in the use of prophylactic intravenous immunoglobulin in preterm infants predisposed to sepsis. Recently, hematopoietic colony-stimulating factors have been demonstrated to improve in vitro neonatal neutrophil physiologic activity. Future therapy of neonatal sepsis will depend on new nontoxic methods for enhancing neonatal host defense.
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PMID:Neonatal neutrophil host defense. Prospects for immunologic enhancement during neonatal sepsis. 264 45

Neonatal host defense simulates a clinical state of immunodeficiency that predisposes the preterm and term newborn to overwhelming bacterial sepsis. Defects in both the quantitative and the qualitative aspects of the neonatal phagocyte contribute significantly to the immaturity of their immune system. The neonate lacks adequate numbers of granulocyte bone marrow progenitor cells and has a decreased neutrophil storage pool and an increased tendency to peripheral neutropenia during neonatal sepsis. Additionally, the neonatal granulocyte demonstrates altered physiological function compared with that found in the adult with respect to chemotaxis, phagocytosis, oxidative metabolism, and bacterial killing. Reduced circulating immunoglobulins and impaired production of specific antibody are additional hallmarks of altered neonatal immunity. The use of adult neutrophil transfusions for the treatment of neonatal sepsis has shown promise in some clinical studies and no difference in others. Recent investigations have examined the use of intravenous gamma-globulin for prophylaxis and treatment of neonatal sepsis. The following review summarizes the state of immunodeficiency in the newborn and the potential role of polymorphonuclear leukocyte transfusions in the treatment of overwhelming neonatal bacterial sepsis.
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PMID:Neutrophil transfusions in the treatment of neonatal sepsis. 266 51

The purpose of this study was to evaluate the efficacy of a prescreened CMV seronegative blood donor group in preventing transfusion-acquired CMV infection in premature infants in the perinatal period. Group 0 donors with known CMV seronegative status were recruited to supply blood to the neonatal intensive care nurseries. One hundred and twenty-seven low birth weight infants born of CMV seronegative mothers remained seronegative when blood for transfusion was screened for CMV antibody. Twenty two infants shared six units of CMV seropositive blood due to technical errors or poor sensitivity of the test kit in the initial phase of the study. Fifteen of these patients were in the study group. One infant died of immaturity at four weeks of age and two of the remaining 14 showed asymptomatic CMV infection. Another infant who received granulocyte concentrates from CMV seropositive donors had symptomatic CMV infection. Throughout the 24 month study period, blood supply to the ICN was adequate and timely. The donor seroconversion rate was 0.7% per annum. Only one infant was exposed to the risk of CMV infection due to donor seroconversion. We conclude that the prescreening donor program is a sensible and efficient approach for providing CMV seronegative blood in neonatal transfusion therapy.
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PMID:Evaluation of a prescreening blood donor program for prevention of perinatal transfusion-acquired cytomegalovirus (CMV) infection. 284 45

Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detailed marrow cytology and cytochemistry score have been analysed. Poorer remission rates have been found in older patients, in those with lower Karnofsky scores and in patients with a platelet count of less than 25 X 10(9)/l. Leukaemias showing evidence of cytoplasmic maturation along the granulocyte and monocyte lines, as evidenced by granules, Auer rods, a high percentage of Sudan black positive blast cells and morphological and cytochemical abnormalities of neutrophils were associated with a higher remission rate. Marrow eosinophilia was a good prognostic feature. Nuclear features of immaturity, i.e. increasing numbers and prominence of nucleoli were associated with a low remission rate. Abnormalities of the erythroid series, notably Periodic acid-Schiff positivity which was present in 133 cases (22% of the total), was associated with a low remission rate. Patient age and pretreatment Karnofsky score were the most useful predictors of treatment outcome.
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PMID:Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients. 346 40

Studies on proliferation and differentiation of granulocyte-monocyte progenitor cells in Chediak-Higashi syndrome (CHS) were done on a 1-month-old patient, using the soft-agar bone marrow culture technique. The number of granulocyte-macrophage colony-forming cells (GM-CFC) was markedly increased, but with a normal distribution into granulocyte, macrophage, or mixed colonies. Morphologic, cytochemical, and ultrastructural studies showed that 70% of the colonies consisted of cells with giant lysosomes typical of CHS, and in the remaining 30% abnormal cells were not detected. The supply of granulocyte-macrophage colony-stimulating factor (GM-CSF) by the patient's peripheral blood leukocytes was markedly decreased. Inhibition of normal in vitro granulopoiesis by the patient's lymphocytes or serum was not demonstrated. It appears that granulocyte progenitors in CHS proliferate normally, or even in excess, probably in response to intramedullary destruction of granulocytes. The majority of the progenitors are intrinsically defective and give rise to colonies that contain the abnormality. In others the defects are unidentifiable, probably due to the immaturity of the specific fusion process of the cytoplasmic granules. The abnormal leukocytes in CHS are also defective in their capacity to provide GM-CSF, and this may account in part to the overt neutropenia. These studies demonstrate that the basic cytoplasmic abnormalities of the granulocytes and monocytes in CHS are embedded in the granulocytic-monocytic committed stem cell.
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PMID:Chediak-Higashi syndrome. Expression of the cytoplasmic defect by in vitro cultures of bone marrow progenitors. 374 Mar 66

We have previously shown that degranulated guinea pig basophils in vitro do not die. Rather, they recover, and these mature cells rebuild granules in the absence of nuclear changes of immaturity or of mitoses. This ability to survive the explosive release of cytoplasmic granules and to rebuild granules was the first such demonstration for a mature granulocyte. We utilized this model of antigen-induced basophil degranulation and recovery in vitro, in conjunction with a specific antibasophil serum (ABS) and indirect immunoferritin electron microscopy, in order to localize the anatomic sites of expression of the antigen(s) recognizing ABS during the secretory and recovery events. Basophil surface membranes were labeled prior to degranulation, during degranulation, after degranulation, and as mature, polynuclear, granule-free cells began to rebuild new granules. In addition, the plasma membranes of non-granule-containing, glycogen positive, small mononuclear cells were labeled. These were few in number and were thought to be precursor cells in the basophil lineage. Controls, either nondegranulated basophils at a variety of culture intervals, or basophils following degranulation and during recovery, were done using normal rabbit serum (NRS) and an indirect immunoferritin electron microscopic technique. These were all negative. Moreover, contaminating eosinophils, neutrophils, and lymphocytes were also negative. Extruded granules were labeled with ferritin (ABS) on their membrane-free, finely granular exteriors, but not within the lamellar array of their matrixes. Extruded granules were not labeled in control experiments. When tested with ABS, membrane-bound granules in the cytoplasm prior to release and membrane-free, released granules contained within degranulation sacs, were negative, as was the membrane of sacs. Immature, membrane-bound granules were also negative. Ferritin binding to membranes was seen in narrow channels, vesicles, and larger vacuoles, as well as in multivesicular bodies, present in the peripheral cytoplasm. This distribution of labeled sites was not observed in neutrophils, eosinophils, and lymphocytes which were also routinely present in these preparations. These sites were not labeled in basophils or other cells in control studies using ferritin and NRS. This indicates the necessity for specific binding to basophils in order to visualize this process. Whether most such sites represent residual endocytosis at 4 degrees C or binding to open invaginations near surfaces of cells does not detract from their specificity and thus expression of specific antigen(s)-binding sites in basophils.
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PMID:Immunoferritin electron microscopic studies with antibasophil serum of guinea pig basophil degranulation and regranulation in vitro. 402 21

Ten patients under 20 yr of age with the usual (adult) type of chronic myelogenous leukemia (CML) were seen at the University of Rochester Medical Center from 1970 to 1982. The mean white cell count in these 10 patients at presentation was 360,000/microliter, as compared to a mean of 137,000/microliter in 80 CML patients over 20 yr of age seen during the same time interval (p less than 0.02). Analyses of all 90 cases revealed a significant decrease in the average leukocyte count at presentation with increasing age. The childhood cases also had a significantly higher proportion of blood blasts, promyelocytes, and myelocytes than did the adult subjects (p less than 0.01). Signs of leukostasis were present in 12% of adult cases as compared to 60% of the 10 childhood cases, and in these 6 subjects, the mean white cell count was 510,000/microliter. In these 6 patients, leukapheresis and/or chemical therapy was initiated rapidly, and this was followed by complete resolution of the clinical signs of leukostasis. A review of the literature from 1960 to 1982 identified 61 childhood cases that were reported with the usual type of CML. In this group, the frequency of hyperleukocytosis and the distribution of white cell counts corresponded very closely to the 10 cases studied at the University of Rochester. Thus, the usual type of CML presenting in childhood differs from that of adults in that hyperleukocytosis, blood granulocyte immaturity, and leukostatic central nervous system, retinal, and respiratory signs are significantly more common and extreme and merit rapid cytoreductive treatment.
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PMID:Hyperleukocytosis and leukostasis: common features of childhood chronic myelogenous leukemia. 658 36

A quantitative cytochemical study has been made, using scanning-integrating microdensitometry, of 1000 toxic granulation blood neutrophils from 20 infected patients, in comparison with 1250 normal blood neutrophils. Myeloid precursor cells in 10 normal marrows were also studied. Normal bone marrow granulocyte maturation was associated with a progressive decrease in azurophilic granule enzymes (myeloperoxidase, beta-glucuronidase, acid phosphatase, chloroacetate esterase), and also Alcian blue staining from acid mucosubstance, but an increase in the specific granule marker lactoferrin. Toxic granulation blood neutrophils showed minor changes in the enzyme content of their azurophilic and specific granules, consistent with cell immaturity, and an increase in acid mucosubstance in azurophilic granules. Abnormal maturation of azurophilic granules, with persistence of acid mucosubstance, is the likely explanation for the intense Romanowsky dye staining of the toxic granulation neutrophil.
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PMID:Quantitative cytochemistry of the toxic granulation blood neutrophil. 684 17

By rigid cytological and cytochemical criteria, the diagnosis of acute and undifferentiated leukemia was established in 22 patients. According to defined criteria, the leukemic cells could not be classified by conventional light microscopic techniques employed in the study of hematopoietic tissue. Cytochemical studies including peroxidase, periodic acid schiff (PAS) and nonspecific esterase (alpha napthyl butyrate-reacting esterase) stains were done on fresh bone marrow samples, and the percentage of positive leukemia cells for each of these stains was determined on 200 cells. In this series of leukemias, cytochemistry at the light microscope level did not contribute to further classification. Subsequent electron microscopic examination of bone marrow samples from these patients confirmed the immaturity and nuclear/cytoplasmic asynchrony of the leukemic cells. Several in vivo neoplastic markers, such as nuclear blebs, increased nuclear bodies, and cytoplasmic fibrillar bundles could be demonstrated in these cells. Fourteen cases from this series exhibited peroxidase-positive developmental granule formation at the ultrastructural level and were reclassified as acute granulocyte leukemia (AGL). One case was reclassified as lymphoma (poor differentiated type), one case was diagnosed as acute monocytic leukemia (AmonoL), and six cases remained in the undifferentiated category (AUL). Clinical and laboratory features, response to treatment, and survival data were evaluated for these patients. This study demonstrated that electron microscopy is useful in the cytological diagnosis of human leukemia.
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PMID:Acute unclassified leukemia: A clinicopathologic study with diagnostic implications of electron microscopy. 743 2


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