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

Groups of newborn rats were transthoracically inoculated with 1 X 10(6) type III group B streptococci/g body wt, either alone or in combination with 1.5 microgram/g body wt of type-specific antibody derived from hybridoma cell lines. Ninety-four percent of the animals who received bacteria alone died. In contrast, none of those treated with antibody died (P less than 0.005). Kinetic studies suggested that antibody may have offered protection, In part, by facilitating the neutrophil response. Animals who received only bacteria exhibited a marked neutropenia (20 +/- 18/mm3, mean +/- S.E.M.) whereas infected animals treated with antibody did not (3800 +/- 30/mm3, P less than 0.001). Furthermore, within 2 h of inoculation, antibody-treated animals mobilized and stored neutrophils, whereas significant neutrophil mobilization did not occur in the animals which received bacteria alone until 6 h. In the animals receiving bacteria alone, exhaustion of the neutrophil supply quickly occurred (remaining storage neutrophils at 6 h, 0.2 +/- 0.1 X 10(6) cells). In contrast, animals, which received antibody, maintained an adequate supply of stored neutrophils (7.0 +/- 0.4 X 10(6) P less than 0.001). The migration of neutrophils to the site of inoculation was measured by assaying the lungs' content of myeloperoxidase, a marker enzyme for granulocytes. The right and left lungs of animals not receiving antibody accumulated the same quantity of neutrophils, with peak pulmonary neutrophil accumulation occurring 6 h after the infection. In antibody recipients, however, the inoculated lung accumulated significantly more neutrophils than the opposite lung and peak pulmonary neutrophil accumulation occurred at 2 rather than 6 h.
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PMID:The effect of hybridoma antibody administration upon neutrophil kinetics during experimental type III group B streptococcal sepsis. 635

When neutropenia due to exhaustion of the marrow neutrophil reserve, develops in a neonate with bacterial sepsis the likelihood of survival is very small. We report such a case who was treated with a double-volume exchange transfusion using fresh unstored whole blood. We were able to determine a net gain of 5 x 10(8) neutrophils per kg. Then, in neutropenic neonatal animals, neutrophil transfusion by double-volume exchange transfusion with unstored blood was investigated.
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PMID:Use of whole blood exchange transfusion to supply neutrophils to septic, neutropenic neonates. 675 23

Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
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PMID:A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. 752 Jul 70

Eleven adult patients with chronic neutropenia have been treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Seven patients had idiopathic sporadic neutropenia, 2 idiopathic congenital neutropenia and 2 cyclic neutropenia. Treatment was started with 3 micrograms/kg s.c. daily and was modified according to response. All patients had a rapid increase of neutrophils. The cycle length shortened from 21 to 14 days in patients with congenital cyclic neutropenia. Doses required for maintenance ranged from 0.1 to 8 micrograms/kg. One patient with idiopathic sporadic neutropenia recovered after 151 days with an absolute neutrophil count (ANC) of > 2000/microliters and had no need for further treatment. The overall efficacy of the treatment was good with abrogation of severe infections. Treatment has been continuously given to a maximum of 4.5 years. No loss of efficacy was observed during long-term treatment. There was no evidence for lineage drain or stem cell exhaustion with prolonged treatment. Cytogenetic analyses in seven of eleven patients did not reveal the development of abnormal cell-clones. G-CSF is safe and efficient in long-term treatment of adult patients with chronic neutropenias.
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PMID:G-CSF in the long-term treatment of cyclic neutropenia and chronic idiopathic neutropenia in adult patients. 858 68

The first report on the administration of the chemoprotective agent Ethyol (amifostine) in conjunction with high dose carboplatin to a patient in the pediatric/adolescent age group is presented. A 17 year old teenager with recurrent cerebellar medulloblastoma received a total of five courses of high dose carboplatin 2 x 600 mg/m2 (1200 mg/m2 total) in each cycle. A complete response has been observed following the third treatment cycle. However, cumulative grade IV hematological toxicity developed following each of the first four treatments. Therefore, the fifth treatment was administered in conjunction with amifostine, at a dose of 2 x 740 mg/m2. Time to complete hematological recovery (Hb > 100 g/l, granulocytes > 2.0 G/l, platelets > 100 G/l) was 52, 58, 72, 78 and 50 days, respectively, following treatments nos 1, 2,,3, 4 and 5. The duration of grade III-IV neutropenia (< 1.0 G/l) was 3, 7, 8, 10 and 5 days, respectively. The duration of grade II-IV thrombocytopenia (platelets < 75 G/l) was 10, 25, 35, 40 and 32 days, respectively. Grade IV thrombocytopenia (platelets < 25 G/l) lasted for 5, 10, 12, 18 and 3 days, respectively, after each consecutive treatment. The total number of platelet transfusions was 1, 2, 2, 3 and 1, with the transfusion of 6, 9, 11, 11 and 5 units of platelets. The administration of amifostine has not been accompanied by any serious side effect. A short decrease in body temperature and a transient drop of blood pressure have been observed. Although hematological toxicity of high dose carboplatin has not been eliminated by amifostine, we conclude that significant protection was achieved in this situation of progressive bone marrow exhaustion.
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PMID:Administration of Ethyol (amifostine) to a child with medulloblastoma to ameliorate hematological toxicity of high dose carboplatin. 874 9

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant benefits in patients with cancer.
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PMID:A risk-benefit assessment of epoetin in the management of anaemia associated with cancer. 980 42

The purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P <. 01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.
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PMID:Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b. 1115 11

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.
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PMID:Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders? 1843 26

We report a 20-year-old male who suffered smoke inhalation injury and burns covering 26% of his TBSA, including his face, dorsal chest, and both the arms. The Abbreviated Burn Severity Index was 5 (likelihood of survival 95%). He underwent burn surgery, requiring massive transfusion. Postoperatively, he appeared increasingly hyperthermic, showed respiratory exhaustion, and was neutropenic (lowest white blood cell count was 0.8 Gpt with a normal granulocyte count). He developed acute respiratory distress syndrome, renal failure, and severe inflammatory response syndrome. Aggressive ventilation patterns, intermittent prone positioning, and high-dose catecholamine therapy were performed. Hydrocortisone therapy and antibiotic prophylaxis did not improve his clinical status. He died after 12 days of septic multiple organ failure. Legal medicine autopsy identified aggressive Candida famata mycosis. The organism mainly affected the alimentary canal, and there were multiple pyemic abscesses in tissues of the heart, liver, spleen, kidneys, lungs, and meninges. Histology confirmed gastric ulcers as the source of the Candida infection. Despite the autopsy findings, all intravital specimens collected (blood, urine, and tracheal mucus) and all clinical Candida antigen tests were unsuspicious. Postoperative neutropenia may be a warning sign of severe infection even in survivable burns. Suppression of immune response and possible previous gastric Candida colonization may contribute to hazardous outcomes. However, delayed and unreliable methods to detect fungal infections remain a major problem in burn care. Occult aggressive fungal sepsis resulting in early multiple organ failure should be kept in mind.
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PMID:Fulminant, undetected Candida sepsis after an apparently survivable burn injury. 1969 26

In May 2005, a 79-year-old woman was referred to our hospital with complaints of right lower quadrant mass and feces mixed with blood. After examination, she was diagnosed with ascending colon cancer and synchronous multiple liver metastases. Postoperative diagnosis after right hemicolectomy and D3 lymph node dissection was T2, N1, H2, P0, M0, and Stage IV. One month after the operation, we started a combination chemotherapy using 5-FU plus UFT as pharmacokinetic modulating chemotherapy with hepatic arterial infusion (HAI-PMC). But abdominal CT scan revealed the increase of multiple liver metastases, PD, after 4 courses of treatment. We then changed to modified HAI-PMC (additional CPT-11, once every four weeks), but had to cancel it due to her exhaustion and inappetence. Therefore, S-1 was started from October, 2005. Each course consisted of daily oral administration of 80 mg S-1 for 4 weeks and withdrawal for 2 weeks. After 4 courses, abdominal CT scan revealed a reduction in the number of multiple liver metastases, PR. PR has continued for a long term to date. As an adverse event, we had grade 3 neutropenia and grade 2 diarrhea in January 2009, and we changed the administration method (80 mg S-1 for 2 weeks and withdrawal for 1 week). She continues to undergo outpatient treatment with good QOL without a lesion for 4 years and 6 months. S-1 is expected to be an effective agent for the treatment of advanced colon cancer.
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PMID:[Long survival of a colon cancer case with synchronous multiple liver metastases responding to S-1]. 2049 32


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