The nicotinic alpha 4 beta 2 receptor selective agonist,TC-2559, increases dopamine neuronal activity in the ventral tegmental area of rat midbrain slices

The ability of alpha4beta2 nicotinic acetylcholine receptors to modulate dopaminergic (DA) cell activity in the ventral tegmental area (VTA) in rat midbrain slices was assessed using a selective alpha4beta2 receptor agonist, TC-2559 ((E)-N-methyl-4-[3-(5-ethoxypyridin)y1]-3-buten-1-amine). The selectivity of TC-2559 was characterized across 6 recombinant human nicotinic receptors (alpha4beta2, alpha2beta4, alpha4beta4, alpha3beta4, alpha3beta2 and alpha7) stably expressed in mammalian cell lines. Using a fluorescent imaging plate reader and fluo-3 to monitor changes in intracellular calcium, TC-2559 was found to be at least 69 fold more potent on alpha4beta2 than on other heteromeric subtypes, with an efficacy of 33%. No activity on the homomeric alpha7 subtype was detected. TC-2559 also showed selectivity for alpha4beta2 over the alpha4beta4 and alpha7 subtypes expressed in Xenopus oocytes. When bath applied to VTA slices, TC-2559 increased the firing of DA cells in a dose-dependent manner, in the same concentration range that activates alpha4beta2 receptors in recombinant cell lines or oocytes. The effect of TC-2559 was blocked by 2 microM dihydro-beta-erythroidine (an alpha4beta2-preferring antagonist), but not by 10 nM methyllycaconitine (an alpha7 antagonist). Glutamate receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione and D(-)-2-amino-5-phosphonopentanoic acid) did not reduce TC-2559-induced responses, suggesting that the increase in DA cell firing induced by TC-2559 is caused by direct postsynaptic depolarisation via the activation of alpha4beta2 receptors and not by enhancement of glutamate release.     

Treatment options for brain metastases in patients with non-small cell lung cancer

Opinion statement Brain metastases are a common complication for patients with non-small cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than three metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and patients with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.     

Retrocaval ureter

Two cases of retrocaval ureter are reported. A 22 years old male patient presented to us with the complaints of right flank pain and hematuria and a child of 2 years referred to us for evaluation of right side moderate hydronephrosis detected on ultrasound. The diagnosis was confirmed on intravenous urography and retrograde pyelography. Both the ends were transected and anastomosed above a JJ stent in front of the inferior vena cava. Postoperatively the patients remained asymptomatic and the hydronephrosis improved.     

To study voice quality before and after thyroplasty type 1 in patients with symptomatic unilateral vocal cord paralysis

PURPOSE: The purpose of this study was to evaluate voice quality before and after thyroplasty type 1 in patients with symptomatic unilateral vocal cord paralysis. METHODS: Fifteen consecutive cases of unilateral symptomatic vocal cord paralysis of a known or idiopathic etiology with the duration of 6 months who have failed conventional speech therapy. The voice quality was assessed by perceptual evaluation, acoustic measures, and aerodynamic measures. The position of the cord was assessed by using fiberoptic laryngoscope. The procedure was done under local anesthesia. RESULTS: Among 15 patients, on the first postoperative day, 7 patients were changed to moderate dysphonia and 8 patients had a near-normal voice. On the 30th postoperative day, 3 patients had persistent moderate dysphonia, nine patients had near-normal voice, and 3 patients had normal voice. CONCLUSION: Thyroplasty type 1 successfully reduces glottic gap and improves voice quality in patients with unilateral vocal cord paralysis. Improved maximum phonation time, signal-to-noise ratio, shimmer, jitter, fundamental frequency, and intensity of voice appear to be directly related to medialization of the paralyzed vocal cord.     

Hyperopic refractive surgery

Although the first attempts at hyperopia correction were made more than 100 years ago, it is only in the past several years that the success of hyperopic refractive surgery has begun to approach the efficacy of myopia surgery. Corneal surgery for the correction of hyperopia includes older lamellar techniques such as automated lamellar keratoplasty and epikeratophakia, and more recently photorefractive keratectomy and laser in situ keratomileusis. The latter two procedures have shown the most success. Using large diameter laser ablations and improved keratomes, laser in situ keratomileusis has become a realistic alternative for corrections of up to 4 or 5 diopters with astigmatic corrections. Laser thermal keratoplasty using the Holmium or diode laser and contact techniques also have gained popularity and shown some potential. Collagen shrinkage procedures are easy to perform and have relatively few complications, but over correction and regression are problems. Crystalline lens surgery and phakic intraocular lenses are being investigated actively and are promising; however, safety issues persist. The surgical treatments of hyperopia present a significant challenge and reward for the ophthalmic surgeon.     

Memory creation and the treatment of psychiatric disorders

False-memory syndrome describes the 'recovery' of memories of traumatic events which did not take place. 'Recovered' memories are created as a result of suggestion or other psychological maneuvers. This means that memories can be implanted. The author suggests that the possibility of use of implantation of 'good' memories for the treatment of certain psychiatric disorders should be explored and that implantation of 'good' memories may be called 'positive memory creation therapy'. The author also suggests that memory creation treatment should be used under strict ethical and legal control.     

The transosteal implant: A 17-year review and report

The survival percentage for the transosteal implant is 80.9% +/- 0.04 and predictably satisfactory host site responses may be anticipated at the 100% level after the second successful year in situ. The benefits of the transosteal implant are its unsophisticated design with a straight uncomplicated cervix, a simple surgical technique, economy, immediate fixation and readiness for use, modesty of size, versatility (it may be used singly or in diverse multiples in association with teeth or other implants), ease of removal when indicated, and universality of application to a broad variety of anatomic and prosthetic situations.