ABSTRACT
We report a case of a 51-year-old woman with newly diagnosed glioblastoma multiforme (GBM) who was treated with surgery followed by the standard concomitant temozolomide (TMZ) and radiotherapy (RT). Although TMZ is generally safe and well-tolerated, she developed a sudden onset of prolonged and severe thrombocytopenia as the most prominent event of pancytopenia during the combined treatment, leading to discontinuation of the combined therapy. Thrombocytopenia lasted for more than 2 months with intensive, intermittent platelet transfusions. A bone marrow aspiration and biopsy performed after recovery of severe suppression still revealed reduced number of megakaryocytes. O(6)-methylguanine-DNA methyltransferase (MGMT) analyses showed methylated MGMT promoter in GBM, but unmethylated promoters in both peripheral blood leukocytes and bone marrow cells. This is the first report suggesting the irrelevance of MGMT status of normal hematopoietic cells to TMZ-induced severe thrombocytopenia and pancytopenia.
Subject(s)
Brain Neoplasms/therapy , DNA Modification Methylases/drug effects , DNA Repair Enzymes/drug effects , Glioblastoma/therapy , Pancytopenia/etiology , Thrombocytopenia/etiology , Tumor Suppressor Proteins/drug effects , Antineoplastic Agents, Alkylating/adverse effects , Base Sequence , Blotting, Western , Brain Neoplasms/pathology , Combined Modality Therapy , DNA Methylation/drug effects , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Dacarbazine/adverse effects , Dacarbazine/analogs & derivatives , Female , Glioblastoma/pathology , Humans , Magnetic Resonance Imaging , Middle Aged , Neurosurgical Procedures , Polymerase Chain Reaction , Radiotherapy/adverse effects , Temozolomide , Tumor Suppressor Proteins/geneticsABSTRACT
OBJECTIVE: Recent data suggest that the concentration of interleukin-10 (IL-10) is higher than that of interleukin-6 (IL-6) in the vitreous of eyes of patients with non-Hodgkin's lymphoma. In this study, we evaluated the utility of measuring intravitreal IL-10 and IL-6 concentrations in the diagnosis of intraocular lymphoma. METHODS: Specimens of undiluted vitreous were collected at the time of pars plana vitrectomy and IL-10 and IL-6 concentrations were determined. Vitreous specimens were obtained from 5 patients with suspected intraocular lymphoma and 10 patients with uveitis presumed to be unrelated to a neoplasm. RESULTS: In all 5 patients eventually diagnosed with intraocular lymphoma, the vitreous IL-10 concentration ranged from 3,040 to 11,200 pg/ml, and was higher than the vitreous IL-6 concentration in all cases. In 9 of the 10 patients with uveitis, the vitreous IL-10 concentrations ranged from less than 2 to 97 pg/ml, with an IL-10/IL-6 ratio of less than 0.11. However, in the remaining case diagnosed as uveitis of unknown etiology, the vitreous IL-10/IL-6 ratio was greater than 1. CONCLUSION: Our data suggest that the measurement of vitreous IL-10 concentrations would aid in the diagnosis of intraocular lymphoma.
Subject(s)
Biomarkers, Tumor/analysis , Eye Neoplasms/diagnosis , Interleukin-10/analysis , Interleukin-6/analysis , Lymphoma, Non-Hodgkin/diagnosis , Vitreous Body/chemistry , Adolescent , Adult , Aged , Child , Child, Preschool , Cytodiagnosis , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Vitreous Body/pathologyABSTRACT
BACKGROUND: Shear stress generated in stenosed arteries promotes platelet thrombi formation at the stenosed sites by accelerating the binding of von Willebrand factor (vWF) to platelets. Shear-induced platelet aggregation (SIPA) has been studied in acute coronary syndromes, but not in chronic coronary disease. HYPOTHESIS: We investigated the effect of both the site and severity of coronary stenosis on SIPA in patients with chronic coronary artery disease. METHODS: Shear-induced platelet aggregation was measured using platelet-rich plasma in 49 patients (41 men and 8 women; mean age 61+/-10 years) with coronary artery disease to evaluate the association between the extent of SIPA and coronary angiographic findings. Stenoses > 75% were considered severe. In all, 62 healthy individuals (54 men and 18 women; mean age 45+/-7 years) served as controls. The correlation between SIPA and the site and severity of the coronary lesion, and parameters of coagulation and fibrinolysis were evaluated. RESULTS: Shear-induced platelet aggregation was increased in the stenosis group (69.0+/-10.6%) compared with the controls (57.7+/-10.3%, p < 0.0001). Patients with severe stenosis in the proximal segments had significantly increased SIPA (p< 0.0001) and vWF larger multimer concentration (p<0.0001) compared with the control group. A significant correlation existed between SIPA and the vWF larger multimer concentration in all subjects studied (r = 0.422, p < 0.0001). CONCLUSIONS: Shear-induced platelet aggregation is increased in patients with severe stenosis of the proximal coronary arteries and correlates with plasma concentrations of vWF larger multimers, suggesting that severe stenosis in the proximal segments is not only associated with an increased risk of significant myocardial ischemia, but may also generate high shear stress in the stenosed artery and increase plasma vWF larger multimers, thereby promoting the formation of platelet thrombi.
