Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

Transesophageal echocardiographic monitoring for transcatheter closure of atrial septal defect.

BACKGROUND AND PURPOSE: Transcatheter closure of atrial septal defect (ASD) is generally performed under fluoroscopy alone. Recently, we have used transesophageal echocardiography (TEE) monitoring as an aid in performing this procedure. The purpose of this study was to evaluate the efficacy and complications associated with this use of TEE. METHODS: Transcatheter closure of ASD was accomplished under TEE guidance simultaneously with fluoroscopic imaging in 11 patients aged 3 to 33 years (weight, 15.4-62.9 kg). TEE was successfully performed in all patients after endotracheal general anesthesia. The ASDs were reexamined before catheterization. The appropriate placement of the occluder device was evaluated. RESULTS: Seven cases were uneventful with successful ASD occluder implantation, but one failed because of a large ASD (24.7 mm). In three cases, transcatheter closure was aborted after TEE examination, one with a large ASD (27.05 mm), one with an ASD that was too small, and one with multiple fenestrated ASDs. CONCLUSIONS: Routine TEE monitoring for transcatheter closure of ASDs is effective for evaluation of ASD before implantation of an occluder, to ensure the proper seating of the occluder after the defect occlusion is complete.

Spinal anesthesia in MELAS syndrome: a case with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is one of the classic mitochondrial encephalomyopathies with variable clinical presentation and multisystem involvement. Enhanced sensitivity to neuromuscular blockade or anesthetic agents and susceptibility to malignant hyperthermia in these patients have ever been reported, all of which complicate the management of general anesthesia. To avoid these appalling troubles in general anesthesia, we chose spinal anesthesia for a patient with MELAS syndrome receiving appendectomy. The patient obtained adequate anesthesia and good recovery without neurologic sequelae. Although there is little information about the application of regional anesthesia in MELAS patients, we demonstrate that it may be a satisfactory choice. However, it is suggested that regional anesthesia is performed only when neurological abnormalities of spinal cord or peripheral nerves are definitely ruled out.