Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors.

Ultrasound (US) is an effective tool for local delivery of genes into target tumors or organs. In combination with microbubbles, US can temporarily change the permeability of cell membranes by cavitation and facilitate entry of plasmid DNA into cells. Here, we demonstrate that repeated US-mediated delivery of anti-angiogenic genes, endostatin or calreticulin, into muscle significantly inhibits the growth of orthotopic tumors in the liver, brain or lung. US-mediated anti-angiogenic gene therapy also seems to function as an adjuvant therapy that significantly enhances the antitumor effects of the chemotherapeutic drug doxorubicin and adenovirus-mediated cytokine gene therapy. Significantly higher levels of tumor apoptosis or tumor-infiltrating lymphocytes were observed after combined therapy consisting of either anti-angiogenic therapy and chemotherapy, or anti-angiogenic therapy and immunotherapy. Taken together, our experiments demonstrate that intramuscular delivery of anti-angiogenic genes by US exposure can effectively treat distant orthotopic tumors, and thus has great therapeutic potential in terms of clinical treatment.

Multiple deep-seated cavernomas in the third ventricle, hypothalamus and thalamus.

BACKGROUND: Cavernomas are rarely located in the third ventricle, hypothalamus, or thalamus. In this report, we present our experience managing a patient with three cavernomas, one each in the floor of the third ventricle, hypothalamus, and left thalamus. CASE PRESENTATION: This 62-year-old woman had had an unsteady gait and weakness of both legs for six months. Magnetic resonance imaging (MRI) revealed multiple intracranial tumours in the third ventricle, hypothalamus, and left thalamus. The third ventricle tumour was found to be a cavernoma by intra-operative endoscopic examination and then was excised via a transcortical, transventricular approach. Pathology revealed a cavernoma. The other two tumours were assumed to be cavernomas because of their MRI features. Three days after surgery, the patient developed right hemiparesis and disturbance of consciousness. Computed tomography revealed a left thalamic haemorrhage. After conservative treatment, her conscious level gradually recovered and she could walk with support seven months after surgery. INTERPRETATION: Our experience with this rare case of multiple, deep-seated cavernomas suggests that management of such patients requires specific consideration of the clinical manifestations, location, size, and previous bleeding history.

Treatment of chronic pain by spinal cord stimulation.

Chronic pain after injury of the nervous system is difficult to treat. This report describes our experience in the treatment of chronic pain by spinal cord stimulation (SCS) in four patients (three men and one woman, with ages ranging from 61 to 73 yr). One patient had chronic intractable pain due to a spinal cord injury, one had post-herpetic neuralgia, one had failed back surgery syndrome, and one had brachial plexus and spinal cord injuries. A permanent spinal cord stimulator was implanted in the patient with spinal cord injuries. In the other three patients, a permanent spinal cord stimulator was implanted after a successful trial stimulation with temporarily implanted electrodes. After 19 to 25 months (mean, 21 mo) of follow-up, three patients had satisfactory improvement of pain and one patient had temporary pain relief, but pain recurred two months after implantation. One patient had recurrence of pain after migration of an electrode, and the pain-relieving effects of SCS returned after repositioning the electrode. According to this preliminary experience, SCS is effective for pain reduction in selected patients with chronic pain. Long-term follow-up is mandatory to evaluate the benefits and complications of SCS for relief of chronic pain.

A randomized clinical trial of combined topical-intracameral anesthesia in cataract surgery.

OBJECTIVE: To evaluate the level of patient discomfort during phacoemulsification and implantation of a foldable intraocular lens (IOL) while under topical lidocaine, alone or in combination with intracameral lidocaine. DESIGN: A prospective, randomized, controlled trial. PARTICIPANTS: Between January and July 1997, a total of 162 patients (162 eyes) scheduled for cataract surgery were randomly assigned to either the placebo group (topical anesthesia with intracameral balanced salt solution [group 1, n = 81]) or the interventional group (combined topical-intracameral anesthesia [group 2, n = 81]). INTERVENTIONS: All patients underwent temporal clear corneal phacoemulsification and implantation of a foldable silicone IOL. All patients received a minimum total of five doses (two drops per dose) of 2% topical lidocaine hydrochloride. Three doses were administered before surgery into the superior and inferior cul-de-sac at 10 minutes, 5 minutes, and immediately before the initial corneal incision. One dose was administered before the commencement of phacoemulsification and another dose before implantation of the IOL. In addition, all patients received an intracameral injection immediately after entrance into the anterior chamber. Patients in group 1 received a 0.5-ml injection of balanced salt solution, and those in group 2 received a 0.5-ml injection of 1% lidocaine. MAIN OUTCOME MEASURE: A 10-point visual analogue scale was used immediately after the surgery to assess each patient's overall severity of pain intraoperatively. RESULTS: Ninety percent of patients in group 1 and 95% in group 2 assigned a score of 0 or 1 to the level of intraoperative discomfort. The mean pain score +/- 1 standard deviation for group 1 was 0.63 +/- 0.68 and for group 2 was 0.37 +/- 0.58. The difference between the pain scores for the two groups was statistically significant (P = 0.0053). A small but significant proportion (15%) of patients in group 1 expressed distress when the ciliary body was stretched or the iris was manipulated with instruments. CONCLUSION: Although topical lidocaine alone provides adequate anesthesia for phacoemulsification and implantation of a foldable IOL, combined topical and intracameral administration of lidocaine can further minimize intraoperative discomfort.