Surgical management of parapharyngeal space tumors: a 10-year review.

OBJECTIVE: The purpose of this article is to describe the diagnostic evaluation and surgical approaches to parapharyngeal space tumors in a tertiary referral center. STUDY DESIGN AND SETTING: The study is a retrospective review of 47 patients diagnosed with tumors of the parapharyngeal space (12 with malignant diseases and 35 with benign lesions) and surgically treated during a 10-year period. The transcervical (40%) and the transcervical-transparotid approaches (46%) were the most commonly performed surgical procedures followed by the orbitozygomatic-middle fossa approach (12%) and the transmandibular approach (2%). RESULTS: The surgical procedures were uneventful and there were no postoperative mortalities. Complications were rare; the most common was transient facial nerve paralysis (5 patients). After an average follow-up of 35 months, only 1 of 35 patients with benign diseases had a recurrence 5 years following transcervical resection of a pleomorphic adenoma. Of 12 patients with malignant tumors, 5 (42%) are alive with no evidence of disease. The sensitivity of preoperative fine needle aspiration biopsy (n = 23 patients) was 87% for detection of malignant disease and specificity was 100%. CONCLUSIONS: Most benign parapharyngeal space tumors can be removed surgically with a low rate of complications and recurrence. Malignant neoplasms, however, carry an ominous prognosis and a low rate of disease-free survival. Fine needle aspiration may be helpful in preoperative diagnostic evaluation of patients with parapharyngeal space tumors.     

Cannabinoid Receptor Activation Prevents the Effects of Chronic Mild Stress on Emotional Learning and LTP in a Rat Model of Depression

Most psychiatric disorders are characterized by emotional memory or learning disturbances. Chronic mild stress (CMS) is a common animal model for stress-induced depression. Here we examined whether 3 days of treatment using the CB1/2 receptor agonist WIN55,212-2 could ameliorate the effects of CMS on emotional learning (ie, conditioned avoidance and extinction), long-term potentiation (LTP) in the hippocampal-accumbens pathway, and depression-like symptoms (ie, coping with stress behavior, anhedonia, and weight changes). We also examined whether the ameliorating effects of WIN55,212-2 on behavior and physiology after CMS are mediated by CB1 and glucocorticoid receptors (GRs). Rats were exposed to CMS or handled on days 1–21. The agonist WIN55,212-2 or vehicle were administered on days 19–21 (IP; 0.5 mg/kg) and behavioral and electrophysiological measures were taken on days 23 and 28. The CB1 receptor antagonist AM251 (IP; 0.3 mg/kg) or the GR antagonist RU-38486 (IP; 10 mg/kg) were co-administered with WIN55,212-2. Our results show that CMS significantly modified physiological and behavioral reactions, as observed by the impairment in avoidance extinction and LTP in the hippocampal-accumbens pathway, and the alterations in depression-like symptoms, such as coping with stress behavior, weight gain, and sucrose consumption. The most significant effect observed in this study was that 3 days of WIN55,212-2 administration prevented the CMS-induced alterations in emotional memory (ie, extinction) and plasticity. This effect was mediated by CB1 receptors as the CB1 receptor antagonist AM251 prevented the ameliorating effects of WIN55,212-2 on extinction and LTP. The GR antagonist RU-38486 also prevented the CMS-induced alterations in extinction and plasticity, and when co-administered with WIN55,212-2, the preventive effects after CMS were maintained. The findings suggest that enhancing cannabinoid signaling could represent a novel approach to the treatment of cognitive deficits that accompany stress-related depression.     

Educational lectures enhance knowledge about the human immunodeficiency virus (HIV) and reduce risky behavior and fear among methadone maintenance treatment patients

Abstract

Background: The aim of this study was to characterize human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related knowledge and stigma among methadone maintenance treatment (MMT) patients and evaluate the contribution of an educational lecture in reducing risky behavior and unjustified overprotective behavior due to fear and stigma among MMT patients. Methods: Patients from an MMT clinic within a tertiary medical center were invited to an educational lecture on HIV/AIDS. Seventy participants (of current 330) were chosen by a random sample (December 2015), plus at-risk patients and HIV patients. Attendee compliance and change in scores of questionnaires on knowledge (modified HIV-K-Q-22) and on sexual and injection behaviors were studied. Results: Forty-six patients (65.7% compliance) attended the lecture, and their knowledge and behavior scores improved 2?weeks post-lecture (knowledge: from 14.2?±?3 to 19.0?±?2.2 [P?<?.0005], sexual behavior: from 12.1?±?2.9 to 8.8?±?3.0 [P?<?.0005], and injection behavior: from 7.3?±?6.2 to 0.2?±?1.3 [P?<?.0005]). The unjustified fear of proximity to HIV carriers reported by 50% attendees fell to 35% post-lecture. Eight months post-lecture, the scores on knowledge and risky behavior of 21 randomly chosen attendees were still better than pre-lecture scores (knowledge: 15.4?±?2.3 vs. 17.2?±?1.8 [paired t test, P?=?.001], sexual behavior: 13.2?±?2.3 vs. 9.7?±?2.9 [P?<?.0005], and injection behavior: 9.3?±?5.6 vs. 2.8?±?3.1 [P?<?.0005]). Drug abuse and treatment adherence were not related to intervention and to risky behavior. Conclusions: More knowledge, less fear, and less risky behavior immediately and at 8?months post-lecture reflect the success and importance of the educational intervention. Future efforts are needed in order to reduce ignorance and fear associated with HIV/AIDS.     

Sp-2-propylthio-ATP-α-B and Sp-2-propylthio-ATP-α-B,β-γ-dichloromethylene are novel potent and specific agonists of the human P2Y11 receptor

The human P2Y₁₁ nucleotide receptor mRNA was found in virtually all human tissues, and the receptor serves many physiological roles, such as immune response regulation. The Ala-87-Thr-P2Y₁₁ receptor single nucleotide polymorphism was linked to increased risk for acute myocardial infarction. To facilitate the development of new therapeutic applications involving cells expressing several P2 receptor subtypes, the availability of specific and potent agonists is mandatory. Here, we synthesized a series of novel adenine nucleotide derivatives, based upon the potent P2Y₁₁ receptor agonists AR-C67085. Features of the novel nucleotide derivatives are a propylthio substitution at C2-adenine and a Pα-borano or Pα-thio substitution of non-bridging oxygen atom. The latter substitutions introduce a chiral center at the α-phosphate. Sp-isomers of Pα-borano- and Rp-isomers of Pα-thio-substituted nucleotides are preferred by the P2Y₁₁ receptor. As recently reported by us, diastereoselectivity of the P2Y₁₁ receptor is opposite to that of the P2Y₁ receptor. Therefore, we exploit this characteristic to increase nucleotide selectivity. At the P2Y₁₁ receptor, the Sp-isomers of 2-propylthio-ATP-α-B (2B) and 2-propylthio-ATP-α-B,β-γ-dichloromethylene (4B) were the most potent of the novel nucleotide series, with EC₅₀ values of 0.03 μM for both, being ca. 80-fold more potent than 2-propylthio-ATP and ATP (EC₅₀ = 2.6 μM). We conclude that the borano-substitution at the α-phosphate of 2-propylthio-ATP enhances nucleotide potency at the P2Y₁₁ receptor. The combination with a Pβ-Pγ-dichloromethylene group in 4B results in a nucleotide, which shows higher selectivity for the P2Y₁₁ receptor over the P2Y₁ receptor than 2B making it the most promising of the novel P2Y₁₁ receptor agonists.