Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactivation of fetal hemoglobin (HbF, alpha 2 gamma 2) synthesis was previously reported in normal human adult erythroblast colonies ("bursts") generated by erythroid progenitors (BFU-E) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated with erythropoietin (Ep). Our studies focused on the reactivation of HbF synthesis in normal adult erythroid bursts generated by peripheral blood mononuclear cells (PBMCs) seeded in FCS+ methylcellulose culture. Reactivation is almost totally suppressed when (a) PBMCs are grown in optimized FCS- culture, or (b) PBMCs are first stringently depleted of monocytes and then plated in FCS+ medium (ie, BFU-E growth in FCS+ Mo- culture). In both experimental conditions, the proliferation of lymphocytes and macrophages interspersed among colonies is drastically reduced, and the cloning efficiency of granulocyte-macrophage (GM) progenitors is sharply diminished. In either case, addition of biosynthetic GM colony-stimulating factor (GM-CSF) induces a dose-related increase of HbF synthesis up to the level in FCS+ culture, with even more elevated values on delayed addition of Ep. A dose-related increase was also observed in erythroblast clones generated by highly purified BFU-E. These results suggest that reactivation of HbF synthesis in normal adults is at least in part mediated by GM-CSF. Furthermore, they imply intriguing hypotheses on the mechanism(s) of perinatal Hb switching. Finally, they raise the possibility of reactivation of HbF synthesis in beta-thalassemia and sickle cell anemia by GM-CSF therapy.
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PMID:Granulocyte-macrophage colony-stimulating factor reactivates fetal hemoglobin synthesis in erythroblast clones from normal adults. 247 26

We tested various shunt systems for pressure/flow characteristics and long-term reliability. In addition, we used a model to simulate activities of daily life postural changes, blood and airway pressure changes and their impact on CSF pressure and flow through various ventriculo-peritoneal shunt systems. In the recumbent position, the changes in flow rate and CSF pressure depended on the valve resistance. Various valves showed deviations from the pressure/flow characteristics claimed for them and proved to be unreliable during long-term perfusion. The flow rate increased in the head-up position. Negative intracranial CSF pressure was due to the continued flow through the shunt system afforded by the siphon effect. The siphon effect was so marked in the upright position that valves of various kinds and with various resistances did not make any significant difference in the resulting intracranial pressure (ICP). The shunt systems, however, differed in the maximum flow rate in the upright position, leading to a different steep fall in ICP following elevation of the body. Ball-and-spring valves had the highest flow rates (> 500 ml/h), leading to negative ICP within seconds. Diaphragm valves, and especially the self-adjusting diaphragm valve, demonstrated a slower drop in ICP, taking several minutes to reach negative ICP. ASD and SCD, however, did prevent any siphoning effects, leading to an ICP within the corresponding valve opening/closing pressure range. Our results demonstrate that in most patients there is no significant difference in various different shunting systems as long as the patient is mobile.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is there a reasonable differential indication for different hydrocephalus shunt systems? 762 78

Two children affected by severe aplastic anaemia and sickle cell anaemia rejected the allogeneic bone marrow transplantation from an HLA-matched unrelated volunteer and an HLA-identical sibling, respectively. In both cases a second transplant using granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) was performed. Donors were the HLA-haploidentical mother and the same HLA-identical sibling who was employed for the first marrow allograft, respectively. Treatment with G-CSF and PBSC collection were well tolerated. Both patients had engraftment of donor haemopoiesis and did not experience severe graft-versus-host disease. These cases confirm that PBSC transplant should be considered as a feasible treatment to reverse graft failure in paediatric patients.
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PMID:Recombinant human G-CSF-mobilized peripheral blood stem cells for second allogeneic transplant after bone marrow graft rejection in children. 860 13

The vaso-occlusive process (VOC) in sickle cell disease is of a complex nature. It involves intricate interactions between sickle red blood cells, endothelium and probably also leukocytes. As these interactions are regulated by cytokines, we analyzed the role of the potent neutrophil chemokine IL-8 by measuring serum levels in sickle cell patients during sickle cell crisis. These results were compared to nonsymptomatics and healthy controls. In patients having a vaso-occlusive crisis both HbSS and HbSC patients showed significantly enhanced serum IL-8 levels compared to healthy controls. Several of these patients showed extremely elevated serum IL-8 levels which were independent of the crisis inducing factor. Furthermore, a sickle cell patient with VOC as a complication of rhGM-CSF treatment similarly showed high IL-8 serum levels at crisis onset. Nonsymptomatic sickle cell patients serum IL-8 levels were comparable to healthy controls. These results implicate a role for IL-8 at or during (the initiation of) sickle cell crisis.
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PMID:Elevated IL-8 levels during sickle cell crisis. 985 44

There is great interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, based on the good results seen with autologous PBSC infusion. Reasonable caution exists regarding the use of allogeneic PBSC for transplantation because of donor toxicities due to rhG-CSF administration and the risk of graft-versus-host-disease (GVHD) in the recipient because of the large number of T-cell infused. We present preliminary data on allogeneic PBSC collections and transplantation in ten patients affected by advanced leukemia (eight patients), severe aplastic anemia (one patient) and sickle cell anemia (one patient). Seven donors were HLA-identical siblings, while the other three were mismatched for three, two and one locus, respectively. All donors received rhG-CSF at a dose of 12 micrograms/kg for a mean of 5 days. Leukaphereses were performed with the aim of collecting a minimum of 5 x 10(6)/kg (recipient's weight) CD 34+ cells. Collection timing was determined by monitoring CD 34+ cells in the donor's peripheral blood from the second day of rhG-CSF therapy. The PBSC collections yielded a mean of 10.05 x 10(8) MNCs/kg and of 10.48 x 10(6) CD 34+ cells/kg (recipient's weight). PBSC were immediately infused after collection in patients given myeloablative therapy. Engraftment was observed in each patient at a mean of 13.2 days for an absolute neutrophil count (ANC) more than 0.5 x 10(9)/L and of 26.5 days for a platelet count of more than 20 x 10(9)/L. Eight patients experienced no or moderate acute GVHD, whereas two patients died of grade 4 GVHD, notwithstanding GVHD prophylaxis with cyclosporine and prednisone. Two other patients died of viral and fungal infections, respectively, despite prophylaxis. The remaining six patients are alive between 58 and 430 days after transplant. Our results document that allogeneic PBSC are capable of engraftment after a myeloablative regimen. Controlled trials are necessary to compare the potential benefits of this approach with the results obtained in allogeneic bone marrow transplantation.
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PMID:Peripheral blood stem cell collection from healthy donors for allogeneic transplantation. 1016 49

Cerebral internal venous thrombosis are rare and diagnosis is difficult. We report three cases in male adults. Clinical data were headaches, vomiting, dizziness and coma, in relation with an intracranial hypertension, or in a case, cardiocirculatory arrest. Cerebral internal veinous thrombosis was diagnosed by a CT scan and cerebral angiography twenty four hours after the admission in neurosurgical intensive care. CT scan showed hemorrhagic and ischemic lesions of thalami in two cases, diffuse cerebral edema in two patients, early or delayed hydrocephaly in two cases. No patient survived despite intensive treatment including heparinotherapy, ventricular CSF drainage, osmotherapy, dehydration, barbiturate, other antiepileptic drugs and mechanical ventilation. In two cases, general or local illness was found, sickle cell disease or radiotherapy for pineal tumor, and in case 3 clinical signs evoked autoimmune disease, not demonstrated by biological samples.
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PMID:[Cerebral deep vein thrombosis: three cases]. 1048 48

We aimed to use an established murine model of sickle cell anemia to develop an unambiguous method for testing new therapies, with survival as an end point. Survival rates following various challenges were compared for three different groups of mice: (a) sickle cell mice expressing human hemoglobin-S exclusively ((h)beta(s)); (b) littermates that expressed both human hemoglobin S and murine beta major globin ((h)beta(s)(m)beta); and (c) wild-type C57BL/6 mice (wt). Two types of challenge were tested. The first set of studies was based upon recent observations indicating that granulocyte-colony stimulating factor (G-CSF) can precipitate severe complications in patients with sickle cell disease. While (h)beta(s) mice had higher neutrophil counts than (h)beta(s)(m)beta mice at baseline, (h)beta(s) mice tolerated several different doses and schedules of either human or murine G-CSF without adverse effects. A second type of challenge tested whether sickle cell mice exhibit an enhanced susceptibility to hemoglobin deoxygenation. Acute hemoglobin deoxygenation was accomplished either by a single intraperitoneal injection of sodium bisulfite or by a 1-h exposure to hypoxia. Neither intervention resulted in a significantly different survival rate for (h)beta(s) mice compared to either (h)beta(s)(m)beta or wt mice. Chronic twice-weekly exposures to hypoxia (1 h per exposure) also failed to produce significant differences in survival rates between (h)beta(s) mice, (h)beta(s)(m)beta, and wt mice over a period of 12 weeks. Our results demonstrate that neither G-CSF administration nor hypoxia accentuates survival differences between this model of sickle cell mouse and normal controls.
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PMID:Limitations of a mouse model of sickle cell anemia. 1206 10

Granulocyte colony-stimulating factor (G-CSF) has been reported to exacerbate vaso-occlusive crises in sickle cell disease. It has been recommended to avoid its use for stem cell mobilization in this population, yet autologous transplant is the standard of care and at times a life-saving treatment for patients with various hematologic malignancies such as relapsed aggressive lymphoma or multiple myeloma. We report 5 cases of patients with sickle cell disease and related hemoglobinopathies who underwent granulocyte-colony stimulating factor (G-CSF)-mobilization of peripheral blood stem cells (PBSC). Three of them developed manageable vaso-occlusive pain symptoms requiring parenteral narcotics alone. The 2 others had no complications. These cases demonstrate that stem cell mobilization using G-CSF, although complicated and not without risk, is feasible in patients with sickle cell syndromes.
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PMID:Granulocyte colony-stimulating factor-based stem cell mobilization in patients with sickle cell disease. 1848 98

The purpose of this retrospective study was to describe epidemiological, clinical, bacteriological and outcome features of purulent meningitis caused by Streptococcus pneumoniae in adult patients hospitalized in the infectious diseases clinic of the Fann University Hospital in Dakar, Senegal from 1995 to 2004. A total of 73 cases of pneumococcal meningitis were recorded during the study period. Streptococcus pneumoniae was the second cause of purulent meningitis after meningococcal infection. Sickle-cell disease (n=3) and HIV infection (n=9) were the main underlying factors and pneumonia was the main portal of entry into the CNS (51.8%). Coma was a frequent complication (61.6%). Penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) accounted for 27.3% of isolated strains. However strains were sensitive to third-generation cephalosporin (100%) and chloramphenicol (68.2%) which were the most frequently used antibiotics. The mortality rate was 69.8% and neurological complications occurred in 13.7% of patients. The main unfavorable prognostic factors were cardiovascular collapse and/or coma at the time of admission and detection of pneumococcal strains by direct examination of CSF. The high mortality of pneumococcal meningitis in adult patients in Dakar shows the need to improve intensive care facilities and the growing incidence of PNSP underlines the requirement for better control of antibiotic prescription.
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PMID:[Adult purulent meningitis caused by Streptococcus pneumoniae in Dakar, Senegal]. 1963 33

Fever is defined as a rectal temperature greater than 38.0 degrees C (>100.4 degrees F). A recently documented fever at home should be considered the same as a fever in the ED and should be managed similarly. All febrile infants younger than 28 days should receive a "full sepsis workup" and be admitted for parenteral antibiotic therapy. Clinical and laboratory criteria can be used to identify a low-risk population of febrile infants aged 1 to 4 months who have not received 2 doses of conjugate vaccines for bacterial meningitis. Children with sickle cell disease are at high risk and require special evaluation. MRSA infections are now common and should be considered in all patients with pyoderma, severe pneumonia, and catheter-related sepsis. HSV infection of the CNS should be considered whenever a patient has altered mental status and CSF findings are not diagnostic of bacterial meningitis. Fever rarely represents life-threatening pathology; however, a handful of less common serious causes of pediatric fever exist with the potential for morbidity and mortality.
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PMID:Pediatric emergencies associated with fever. 1994 99


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