Evaluation of Plasmapheresis on the Removal of Tobramycin

A 26-year-old man with thrombotic thrombocytopenic purpura resulting in respiratory and renal failure was treated with plasmapheresis (PP). Coexisting pulmonary infiltrates were empirically treated as pneumonia with various antibiotics, including vancomycin and tobramycin. The half-life of tobramycin was 6.93 hours. During PP the half-life of tobramycin decreased to 4.47 hours as determined by three random levels. The fraction eliminated due to PP was 35.5% and the fraction cleared by PP was 10.9%. We conclude that PP contributed significantly to the total clearance of tobramycin. The need for supplemental doses must be evaluated in each patient based on post-PP serum concentrations.     

Modification of depressant and disinhibitory action of flurazepam during short term treatment in the rat

Employing a fixed-interval schedule of reinforcement (temporal discrimination), alternated punished (fixed-ratio) and unpunished (variable-ratio) schedules of reinforcement, a Conditioned Avoidance Response, and studying its interaction with Pentobarbital on general anaesthesia, it has been shown that flurazepam hydrochloride after a single treatment induces very intense depressant effects and slight disinhibitory effects. Short term treatment at longer than daily intervals reduces the depressant effect and unmasks the disinhibitory effect. The phenomenon is probably caused by selective tolerance concerning the depressant action. The results are discussed from the point of view of the significance to be attached to this tolerance and of the importance of this characteristic in the therapeutic use of flurazepam.     

Bone cements: review of their physiochemical and biochemical properties in percutaneous vertebroplasty

Percutaneous vertebroplasty is an effective treatment for aggressive vertebral hemangiomas, osteoporotic vertebral compression fractures, spinal metastases, and myelomas. As percutaneous vertebroplasty is more commonly performed to treat various forms of back pain, new or modified cements are being used. This review examines the physiochemical and biomechanical properties of various bone cements and additives.     

Neonatal myasthenia gravis: Clinical and immunological study of seven mothers and their newborn infants

We studied 7 mothers with myasthenia gravis (MG) and their infants. We confirmed that the development of neonatal MG was not related to the serum titer of maternal anti-acetylcholine receptor antibody (anti-AChR ab). To investigate the possibility that specific immunization of the newborn infant had occurred, serial serum determinations of total and 'specific' anti-AChR IgG and IgM were performed. We found that: the decay in total IgG was within the normal range in all the babies; there was a shorter half-life of 'specific' IgG, compared to total IgG, in 3 of the cases, 2 of which did have neonatal MG; no difference was found between the decay of anti-AChR ab in the babies who had neonatal MG and those who did not; there was no anti-AChR IgM-associated activity. Our data suggest that neonatal MG is due to maternal anti-AChR abs and that affected infants do not produce specific antibodies.     

Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes

Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17, frequently are observed as targets of tumor infiltrating lymphocytes (TIL) originated from HLA-A*0201-expressing patients with melanoma. Furthermore, particular clinical relevance was attributed to gp100/pMel17 based on the impression that the adoptive transfer of gp100-recognizing TIL was associated with clinical responses in a small group of patients. However, the actual frequency of specific T cells for these melanoma differentiation antigens has never been directly enumerated in ex vivo or in vitro expanded TIL cultures. Here, we enumerated melanoma differentiation antigen-specific T-cell precursor frequency in TIL using tetrameric HLA/epitope complexes, functionally characterizing their responsiveness to cognate epitope by cytokine release assay. T-cell precursor frequencies were enumerated in 11 fresh-tumor preparations and 17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100-specific T cells could be detected respectively in 5 and 2 of the 11 fresh preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one exception, melanoma differentiation antigen-specific T-cell precursor frequency in fresh material and TIL ranged between 5,000 to 21,000/10(6) CD8+ T cells. T-cell precursor frequency was not significantly higher in TIL whose administration was associated with clinical response. These data provide direct enumeration of MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of HLA-A*0201.     

Physical and Chemical Enhancement of and Adaptive Resistance to Irreversible Electroporation of Pancreatic Cancer

Irreversible electroporation (IRE) can be used to treat cancer by electrical pulses, with advantages over traditional thermal approaches. Here we assess for the first time the IRE response of pancreatic cancer, one of the deadliest forms of cancer, both in vitro and in vivo. We demonstrate that both established and primary cancer cell lines can be destroyed by IRE, but with differential susceptibility and thresholds. We further demonstrate in vitro that viability for a given IRE dose can vary with the local chemistry as outcomes were shown to depend on suspending medium and reduction of glucose in the media significantly improved IRE destruction. Data here also demonstrate that repeated IRE treatments can lead to adaptive resistance in pancreatic carcinoma cells thereby reducing subsequent treatment efficacy. In addition, we demonstrate that physical enhancement of IRE, by re-arranging the pulse sequences without increasing the electrical energy delivered, achieve reduced viability in vitro and decreased tumor growth in an in vivo xenograft model. Together, these results show that IRE can destroy pancreatic cancer in vitro and in vivo, that there are both chemical and physical enhancements that can improve tumor destruction, and that one should guard against adaptive resistance when performing repeated treatments.