Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM.

Efficacy and safety of biological agents in adult-onset Still's disease.

OBJECTIVES: To describe the efficacy and safety of different biological agents in a large cohort of 20 patients with adult-onset Still's disease (AOSD). METHOD: We retrospectively evaluated 20 patients with severe or refractory AOSD treated with at least one biological agent (anakinra, etanercept, tocilizumab, and adalimumab), followed up for at least 12 months at our Institution. We collected and analysed data on the disease course, treatment outcome, and adverse effects, and compared our data with other published series. RESULTS: The median duration of follow-up was 5 years. In 12 patients a single biological drug induced a clinical response. In eight patients the biological agent that was first administered proved ineffective, and a switch to a different biologic was necessary. In three patients a third biologic was necessary to achieve disease control. The biologics eventually determined a clinical response in all patients. Patients with systemic disease showed better responses than patients with chronic articular disease (p < 0.05). Biological agents allowed either the withdrawal or the tapering of corticosteroid therapy (p < 0.0001) and of disease-modifying anti-rheumatic agents (DMARDs; p < 0.05). Three patients experienced herpes zoster reactivation. CONCLUSIONS: This is the longest follow-up of a cohort of AOSD patients treated with biological agents. Our data show that biologics are safe and generally effective in the long-term management of AOSD, particularly in cases with systemic disease, and suggest that a clinical response can be obtained in almost all AOSD patients, although a switch to drugs with a different mechanism of action may be necessary.

A multidrug combination designed for reversing resistance to BCNU in glioblastoma multiforme.

BACKGROUND: Nitrosoureas constitute the main resource of chemotherapy for glioblastoma. However, because of chemoresistance, which is intrinsic or rapidly acquired after the first administration of chemotherapy, there have been few improvements in survival. Because O(6)-alkylguanine-DNA alkyltransferase (AGT) is the main target for increasing cell sensitivity to the nitrosoureas, we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells. OBJECTIVE: To investigate the response rate, toxic effects, time from start of chemotherapy to progression of disease or exit from the study for any reason (TTP), and progression-free survival at 6 months (PFS-6) associated with a multidrug combination that could reverse resistance to carmustine (BCNU) through AGT depletion. METHODS: We conducted a phase 2 study of patients with glioblastoma at first relapse or progression after surgery and standard radiotherapy. Patients were treated with 100 mg/m(2) of procarbazine on days 1 to 5, 80 mg/m(2) of BCNU on days 3 to 5, and 1.4 mg/m(2) of vincristine on day 3 every 8 weeks. RESULTS: Fifty-eight patients were enrolled in the study, and all were assessable for response and toxic effects. Six patients (10.3%) had a complete response, 11 (19%) had a partial response, and 17 (29.3%) had stable disease. The median TTP was 4.8 months; 42.3% of patients had PFS-6, and 15.4% had PFS at 12 months. Response to chemotherapy was the only significant prognostic factor for TTP. Neutropenia was grade 3 in 8.6% of patients and grade 4 in 5.2% of patients, and thrombocytopenia was grade 3 in 17.2% of patients and grade 4 in 12% of patients; hepatic and pulmonary toxic effects were grade 3 in 5.2% and 8.6% of patients, respectively. CONCLUSION: This regimen proved active in chemotherapy-naive patients with recurrent glioblastoma even though toxic effects were substantial.

Isozyme pattern of glycogen phosphorylase in the rat nervous system and rat astroglia-rich primary cultures: electrophoretic and polymerase chain reaction studies.

Of the three isozymes of glycogen phosphorylase (GP) known, the brain (B) and muscle (M) isoforms have been reported to occur in brain. We investigated the regional and cellular occurrence of the three isozymes in various parts of the rat nervous system, fetal brain and astroglia-rich primary cultures by means of electrophoresis of native proteins with subsequent activity stain and by reverse transcriptase polymerase chain reaction. In the cortex, cerebellum, olfactory bulb, brainstem, spinal cord and dorsal root ganglia, both mRNA and enzyme protein were found for the B and M isozymes. In addition, the liver (L) isoform mRNA was detected in fetal brain and cultured astrocytes. Our studies indicate that there is no regional difference in distribution pattern between brain regions, spinal cord and dorsal root ganglia. In immature brain and cultured glial cells, the additional presence of the L isozyme is possible. These results support the idea that astrocytes express two or even three GP isozymes simultaneously.

Chemotherapy in patients with recurrent and progressive central neurocytoma.

BACKGROUND: Recurrent central neurocytoma is very rare and to the authors' knowledge data regarding its response to chemotherapy currently are not available. METHODS: Three patients with progressive neurocytoma received chemotherapy after their informed consent was obtained. Disease recurred in two patients after surgery and radiotherapy and in one patient after surgery. The treatment regimen was comprised of etoposide, 40 mg/m(2)/day, for 4 days; cisplatin, 25 mg/m(2)/day, for 4 days; and cyclophosphamide, 1,000 mg/m(2), on Day 4; this cycle was repeated every 4 weeks. RESULTS: Stabilization of disease was observed in 2 patients and complete remission was observed in 1 patient; at last follow-up, these responses had been maintained for 15 months, 18 months, and 36 months, respectively. CONCLUSIONS: In this small series, this therapeutic regimen led to long term disease reduction, and merits further study.