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81.
82.
Georgios Papakonstantinou Helmut Loeffler Torsten Haferlach Wolfram Brugger 《European journal of haematology》2010,84(6):547-549
Erythroblastic synartesis is a very rare disorder, considered to be caused by autoimmune mechanisms, leading to aggregation of erythroid precursor cells in the bone marrow and subsequently to acquired dyserythropoiesis with severe, transfusion‐dependent anemia. An association with lymphoproliferative or autoimmune diseases has been reported or strongly suggested in all six published cases. Here, we report a young patient with severe idiopathic erythroblastic synartesis without an underlying disease, who was successfully treated with rituximab, an anti‐CD20 monoclonal antibody. The patient received rituximab at a dose of 375 mg/m2 once weekly for 4 wk after failure of both immunosuppressive therapies with corticosteroids and intravenous immunoglobulins. At a follow‐up of 30 months after treatment, the patient is still in continuous complete remission without any further treatment, suggesting that rituximab may induce prolonged remissions and eventually cure in this rare disease. 相似文献
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84.
L M Patrias A C Klaver M P Coffey D A Loeffler 《Clinical and experimental immunology》2010,161(3):527-535
Alpha‐synuclein is the major protein in Lewy bodies, the hallmark pathological finding in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although normally intracellular, it also can be secreted, so extracellular alpha‐synuclein may contribute to neuronal injury. Serum antibodies to alpha‐synuclein could exert protective effects by increasing alpha‐synuclein's movement out of the brain and, if they cross the blood–brain barrier, by inhibiting its neurotoxic effects. The objective of this study was to measure antibody concentrations to alpha‐synuclein monomer and soluble oligomers in three intravenous immunoglobulin (IVIG) preparations, Gamunex (Talecris Biotherapeutics), Gammagard (Baxter Healthcare) and Flebogamma (Grifols Biologicals). Antibodies were measured in native IVIG preparations and after antibody–antigen complex dissociation. IVIG's non‐specific binding was subtracted from its total binding to alpha‐synuclein to calculate specific anti‐alpha‐synuclein antibody concentrations. Specific antibodies to alpha‐synuclein monomer and/or soluble oligomers were detected in all IVIG products. In native IVIG preparations, the highest anti‐monomer concentrations were in Gammagard and the highest anti‐oligomer concentrations were in Gamunex; the extent to which lot‐to‐lot variation may have contributed to these differences was not determined. Antibody–antigen complex dissociation had variable effects on these antibody levels. The IVIG preparations did not inhibit alpha‐synuclein oligomer formation, although they changed the distribution and intensity of some oligomer bands on Western blots. The presence of antibodies to soluble alpha‐synuclein conformations in IVIG preparations suggests that their effects should be studied in animal models of synucleinopathies, as a first step to determine their feasibility as a possible treatment for PD and other synucleinopathies. 相似文献
85.
NU Jerath JS Newman & CJ Boes 《Cephalalgia : an international journal of headache》2009,29(10):1028-1033
The aim of this study was to review the life of Mary E. O'Sullivan and to summarize her important contributions to the study of migraine. Mary E. O'Sullivan underwent extensive training to become a neurologist at a time when only 5% of women in America were physicians. She published five papers on migraine. In a 1936 Journal of the American Medical Association article, she described a patient with ergotamine overuse headache and recommended that daily doses of oral ergotamine should be avoided. Three years later she described migraine as a 'complex' syndrome with multiple causes and multiple cures. Mary E. O'Sullivan, an ambitious female headache specialist of the 1930s, was an early advocate of the use of ergotamine to treat migraine, yet she was one of the first to report ergotamine overuse headache. Although her life was short, her research, knowledge and ambition at a time when women had limited opportunities in medicine have left a mark. 相似文献
86.
Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? 总被引:2,自引:0,他引:2
Michael Weller Hilmar Berger Christian Hartmann Johannes Schramm Manfred Westphal Matthias Simon Roland Goldbrunner Dietmar Krex Joachim P Steinbach Christoph B Ostertag Markus Loeffler Torsten Pietsch Andreas von Deimling 《Clinical cancer research》2007,13(23):6933-6937
PURPOSE: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy. EXPERIMENTAL DESIGN: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification. RESULTS: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender. CONCLUSIONS: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress. 相似文献
87.
88.
Recent trends in the radiotherapy of pediatric gliomas 总被引:3,自引:0,他引:3
The management of pediatric gliomas is controversial, and is greatly influenced by the site of origin of the tumor. For example, cerebellar low grade tumors are often cured by surgery alone. This is in contrast to the hypothalamic and optic system tumors which are usually not amenable to complete resection. For the low grade astrocytomas, the usual indications for adjuvant treatment include: recurrent tumors after initial complete resection or symptomatic tumors that have been incompletely excised. In addition, treatment is generally indicated in tumors with growth on follow-up imaging, even in the absence of symptoms. In selecting the optimal treatment, the relative efficacies of surgery, chemotherapy and irradiation must be balanced by the potential complications of therapy. The potential risks of delayed intervention include irreversible neurologic impairment and potential lower probability of tumor control. This chapter reviews recent trends in the radiotherapeutic management of pediatric low-grade and malignant astrocytomas, particularly the new more conformal techniques that hold the promise of reduced toxicity in children requiring irradiation. 相似文献
89.
OBJECTIVE: Previous reports of seizure outcomes after arteriovenous malformation (AVM) treatment have involved single-treatment modality (surgery, radiosurgery, or embolization) series. Such series reflect only selected lesions, of certain sizes, locations, and other clinical and anatomic characteristics, that are amenable to the single therapy, limiting the analysis of those factors. We report the results of AVM treatment using a multimodality approach that we think encompasses a broader spectrum of treatable brain AVMs. We tested for factors associated with seizure presentation and seizure outcomes. METHODS: Between 1991 and 1999, the multidisciplinary neurovascular unit at Massachusetts General Hospital treated 424 patients with brain AVMs. Treatment consisted of surgical resection, radiosurgery, or embolization, either alone or in combination. One hundred forty-one patients (33%) experienced seizures before treatment. We studied the following factors: sex, age, AVM size, AVM location, occurrence of intracranial hemorrhage, seizure type, duration of seizure history, treatment modality, and AVM obliteration. We tested for statistical associations between these factors and seizure presentation and outcomes. Clinical follow-up monitoring was via mailed questionnaires. RESULTS: When we compared the 141 patients with seizures with the 283 patients who did not experience seizures (total of 424 patients), male sex, age of less than 65 years, AVM size of more than 3 cm, and temporal lobe AVM location were statistically associated with seizures (P < 0.01, P < 0.05, P < 0.0001, and P < 0.01, respectively). Posterior fossa and deep locations were statistically associated with no seizures (P < 0.0001). One hundred ten (78%) of the 141 patients who experienced seizures before treatment responded to the mailed questionnaires, with a mean follow-up period of 2.9 years. A detailed comparison of responders and nonresponders demonstrated no statistically significant differences in pertinent characteristics. As determined with the Engel Seizure Outcome Scale, there were 73 (66%) Class I (free of disabling seizures), 11 (10%) Class II (rare disabling seizures), 1 (0.9%) Class III (worthwhile improvement), and 22 (20%) Class IV (no worthwhile improvement) outcomes. Three patients died during the follow-up period. We tested for factors associated with Engel Class I outcomes. Sex, age, and AVM size were not associated with Class I outcomes. Short seizure history, association of seizures with intracranial hemorrhage, generalized tonicoclonic seizure type, deep and posterior fossa AVM locations, surgical resection, and complete AVM obliteration were statistically associated with Class I outcomes (P < 0.0001, P < 0.05, P < 0.05, P < 0.05, P < 0.001, and P < 0.001, respectively). When only completely obliterated AVMs were considered, there were no statistically significant differences between surgery, radiosurgery, and embolization. CONCLUSION: Certain factors, as identified in an analysis of a wide spectrum of treatable brain AVMs, can facilitate predictions of the incidence of seizure presentation with AVMs, as well as seizure outcomes after multimodality treatment. 相似文献
90.
Chapman G Beaman BL Loeffler DA Camp DM Domino EF Dickson DW Ellis WG Chen I Bachus SE LeWitt PA 《Experimental neurology》2003,184(2):715-725
Our previous studies found that experimental infection of BALB/c mice with the Gram-positive bacterium Nocardia asteroides induced a parkinsonian-type syndrome with levodopa-responsive movement abnormalities, loss of nigrostriatal dopaminergic neurons, depletion of striatal dopamine, and intraneuronal inclusions in the substantia nigra (SN) with an appearance similar to Lewy bodies. In the present study, an in situ hybridization technique was developed to detect nocardial 16S ribosomal RNA (rRNA), using a Nocardia-specific probe (B77). Cerebral cortical specimens from cynomolgus monkeys were examined for the presence of nocardial RNA 48 h, 3.5 months, and 1 year after experimental infection with N. asteroides. Hybridization reactions were detected within Nocardia-like structures 48 h after infection and within intracellular inclusion bodies (immunoreactive for α-synuclein and ubiquitin) in one of two 3.5-month-infected monkeys. The in situ hybridization procedure was then applied in a blinded fashion to 24 human SN specimens with Lewy bodies and 11 human SN specimens without Lewy bodies (including five normal controls). Hybridization reactions were detected in nine Lewy body-containing specimens and none of the others. Reactivity was limited to inclusions with the appearance of Lewy bodies, with the exception of one specimen in which intracellular reactivity was also observed in Nocardia-like structures. These results suggest a possible association between Nocardia and neurodegenerative disorders in which Lewy bodies are present. 相似文献