Au nanoparticles modified with 21-base thiolated-oligonucleotides have been evaluated as delivery vehicles for the development of a nonviral transfection platform. The electromigration combined with electroporation for DNA delivery in an osteoblast like cell was employed to test on microchips. Electroporation introduces foreign materials into cells by applying impulses of electric field to induce multiple transient pores on the cell membrane through dielectric breakdown of the cell membrane. On the basis of the characteristic surface plasmon of the Au particles, UV-vis absorption was utilized to qualitatively judge the efficiency of delivery. Transmission electron microscopy images and atomic absorption measurements (quantitative analysis) provided evidence of the bare Au and Au/oligonucleotide nanoparticles before and after electroporation and electromigration function. The experiments demonstrated that electrophoretic migration followed by electroporation significantly enhanced the transportation efficiency of the nanoparticle-oligonucleotide complexes as compared with electroporation alone. Most interestingly, Au capped with oligonucleotides led to optimal performance. On the other hand, the bare Au colloidal suspensions resulted in aggregation, which might be an obstacle to the internalization process. In addition, analytical results demonstrated an increase in the local particle concentrations on the cell surface that provided additional support for the mechanism underlying the improved Au nanoparticle transportation into cells in the presence of electromigration function.
Candidal meningitis is a rare infectious disease that usually leads to substantial morbidity and mortality. We present a case of candidal meningitis refractory to systemic antifungal therapy (amphotericin B and fluconazole). A 63-year-old female with lymphoblastic lymphoma and myelodysplasia with leukemia transformation developed prolonged fever and headache on the seventh day following intrathecal prophylactic chemotherapy. A lumbar puncture showed neutrophilic pleocytosis, and a cerebrospinal fluid culture yielded Candida albicans. The clinical course was complicated by brain edema, subarachnoid hemorrhage, and hydrocephalus. Parenteral therapy with amphotericin B alone or amphotericin B in combination with fluconazole or intrathecal administration of amphotericin B failed to eradicate C. albicans in the cerebrospinal fluid. After 7 days of caspofungin therapy, however, the cerebrospinal fluid became sterile and the patient gradually regained consciousness. She was discharged 1 month after completing 4 weeks of caspofungin therapy. There were two critical issues we thought to be relevant to the favorable outcome of this case. First, isolation of C. albicans was achieved by inoculating enriched liquid medium with cerebrospinal fluid. Second, there is a potential therapeutic benefit of caspofungin in treating a fungal infection of the central nervous system.
CASE REPORTA 63-year-old woman had lymphoblastic lymphoma and myelodysplasia with leukemia transformation, initially presenting as a neck mass, anemia, and thrombocytopenia. She received the first course of chemotherapy, consisting of a hyperCVAD regimen (cyclophosphamide, vincristine, epirubicin, and dexamethasone), on 23 December 2002 and the second course of chemotherapy on 14 February 2003 (day 1). The latter treatment included intrathecal methotrexate (day 2) and intrathecal cytosine arabinoside (day 8). Neutropenic fever developed 8 days after initiation of chemotherapy, accompanied by progressive headache and vomiting. The fever did not subside under parenteral treatment with vancomycin and meropenem. A lumbar puncture was therefore done on day 23, and study of the cerebrospinal fluid (CSF) revealed neutrophilic pleocytosis (white blood cell count, 1,500/mm 3 ; 87% neutrophils). The patient's consciousness deteriorated following the lumbar puncture, a phenomenon thought to be related to a subarachnoid hemorrhage and brain edema (Fig. 1A). The patient was treated for bacterial meningitis on the basis of the initial CSF data. An Omaya reservoir was inserted on day 27 because of hydrocephalus. CSF drawn from the Omaya reservoir on day 33 yielded Candida albicans. Amphotericin B (1 mg/kg of body weight per day) was given for central nervous system (CNS) candidiasis, starting on day 39. Brain magnetic resonance imaging (MRI) scans on day 41 showed hydrocephalus and hematoma over the premedullary space, which was thought to be the result of a rupture of a mycotic aneurysm (Fig. 1B). However, after 29 days of amphotericin B therapy, with a cumulative dose of...
Hypersensitivity syndrome associated with teicoplanin has rarely been reported. We report a case with a preceding episode of vancomyin-related neutropenia. A 47-year-old female with cervical spine infection was treated with vancomycin. Neutropenia occurred after 17 days of vancomycin therapy. Vancomycin was changed to teicoplanin, and the neutropenia resolved 4 days later. After 11 days of teicoplanin therapy, a new episode of hypersensitivity syndrome manifested as fever, bilateral neck lymphadenopathy, mild wheezing, hepatitis and increased CRP occurred. Neutropenia and thrombocytopenia developed 3 days later. The patient's symptoms settled over 1 week following withdrawal of teicoplanin. Naranjo's ADR algorithm categorized the neutropenia associated with vancomycin and the hypersensitivity syndrome associated with teicoplanin as 'probable'.
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