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Head and neck cancer represents the sixth most common malignancy worldwide. (1) In the United States, cancers of the oral cavity and pharynx are among the top 10 most common [...], * Context.--Tumors of the head and neck commonly arise from the squamous and respiratory mucosa that lines the nasal and oral cavity, sinuses, pharynx, and larynx. The rate of oropharyngeal cancers diagnosed among Americans younger than 50 years is increasing. Infection of the oropharynx and tonsils by the human papillomavirus (HPV) has been linked to preneoplasia and cancer. Objectives.--To evaluate the Roche Linear Array HPV Genotyping test kit to identify, and then specifically genotype, HPV in formalin-fixed, paraffin-embedded tissues. Design.--We evaluated the performance of this assay for accuracy, for intra-assay and interassay precision, and for its limit of detection, using materials with known HPV status. Sixteen tumor tissues with the following origins were evaluated: 1 ocular, 1 hypopharynx, 8 tonsil, 1 retromolar trigone, 3 tongue, 1 anal, and 1 lymph node. DNA from formalin-fixed, paraffin-embedded tumor sections was isolated and amplified in duplicate, with positive and negative controls, using primers specific to the polymorphic L1 region of the HPV genome. Thirty-seven genotypes were tested using the linear array. The amplified product (450 base pairs) was visualized by gel electrophoresis and, if positive, reflexed to HPV genotyping. Results.--Nine of the 16 tumors analyzed were HPV positive. The detected genotypes included HPV 6, 16, and 69. Conclusions.--The Roche Linear Array HPV Genotyping test is an easy-to-use method for determining HPV genotype in the routine analysis of formalin-fixed, paraffin-embedded tumors. This assay is robust and can be performed routinely in a clinical laboratory setting. (Arch Pathol Lab Med. 2010;134:1813-1817)

Context  The effect on recurrence rate between patients with juvenile nasopharyngeal angiofibroma (JNA), treated by an endoscopic versus open approach, has not been well established. Objective  A meta-analysis of the available literature concerning recurrence rate in patients who underwent surgery for JNA. Methods  A retrospective meta-analysis of studies analyzing recurrence rate after endoscopic or open surgery for patients with JNA was performed using the DerSimonian–Laird random-effects method. English and non-English articles were reviewed using Embase, Medline, and Cochrane databases. Results  Among nine studies, including 362 patients from 1981 to 2015, with a mean follow-up of 49.4 months, a total of 89 patients (24.5%) had recurrence. Our analysis revealed a total effect size of −0.16 in favor of endoscopic approach (−0.25 to −0.06, CI [confidence interval] 95%). When analyzing tumor by stage (Radkowski's IA–IIIB n  = 299), the endoscopic approach proved to be superior independent of tumor stage (2 vs. 17% for tumors stage IA–IIA, and 26 vs. 32% for tumor stage IIB–IIIB for endoscopic and open approaches respectively; p  < 0.05). The endoscopic approach has a statistical significant lower recurrence rate in patients without intracranial compromise when compared with the open approach (13 vs. 28%; p  < 0.02). No statistical difference was seen in patients with intracranial compromise (p  = 0.5) Conclusion  The use of an endoscopic approach to treat JNA has a significantly lower recurrence rate when compared with open approaches. Independent of disease stage, an endoscopic approach should be the standard of care to surgically treat JNA. For cases with intracranial compromise, either approach can be used for surgical resection. [ABSTRACT FROM AUTHOR]

Objectives This study aims to introduce a novel technique for the reconstruction of the anterior skull base using a free vascularized anterolateral thigh fascia lata free flap (FLFF) anastomosed to the superior trochlear artery (STA). Methods The diameter of the STA was measured in 38 (76 sides) computed tomography angiographies (CTAs). Independently, six cadaver heads were used to measure the diameter of the supratrochlear system, and the model was applied to one of them. Results In women, the average diameter of the STA was 2.5 and 2.8mm² for the right and left sides, respectively; for men, it was 3.0 and 3.2 mm², respectively. In cadavers, the average diameter of both STA was 2.5 mm². There was no statistical difference when comparing the right and left STA diameters between the CTA from women and men (p < 0.208 and < 0.492, respectively). An FLFF advanced through the nose was anastomosed to the STA to reconstruct the anterior skull base. Conclusion The STA is a constant vessel with a 2.5 to 3.0 mm² diameter in men and women that can be used as a recipient free flap vessel. The FLFF can cover the entire skull base. This is a novelmethod to reconstruct the anterior skull base when local flaps are not available. [ABSTRACT FROM AUTHOR]

Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Δ-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size=0.60; p=0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.Neuropsychopharmacology (2009) 34, 672–680; doi:10.1038/npp.2008.120; published online 6 August 2008 [ABSTRACT FROM AUTHOR]

Cyclin E is a critical G1-S cell cycle regulator aberrantly expressed in bronchial premalignancy and lung cancer. Cyclin E expression negatively affects lung cancer prognosis. Its role in lung carcinogenesis was explored. Retroviral cyclin E transduction promoted pulmonary epithelial cell growth, and small interfering RNA targeting of cyclin E repressed this growth. Murine transgenic lines were engineered to mimic aberrant cyclin E expression in the lung. Wild-type and proteasome degradation-resistant human cyclin E transgenic lines were independently driven by the human surfactant C (SP-C) promoter. Chromosome instability (CIN), pulmonary dysplasia, sonic hedgehog (Shh) pathway activation, adenocarcinomas, and metastases occurred. Notably, high expression of degradation-resistant cyclin E frequently caused dysplasia and multiple lung adenocarcinomas. Thus, recapitulation of aberrant cyclin E expression as seen in human premalignant and malignant lung lesions reproduces in the mouse frequent features of lung carcinogenesis, including CIN, Shh pathway activation, dysplasia, single or multiple lung cancers, or presence of metastases. This article reports unique mouse lung cancer models that replicate many carcinogenic changes found in patients. These models provide insights into the carcinogenesis process and implicate cyclin E as a therapeutic target in the lung. [ABSTRACT FROM AUTHOR]

Among English-speaking adults, HIV-associated neuropsychological (NP) impairments have been associated with problems in everyday functioning, including ability to function at work and drive an automobile. Latinos account for a disproportionate number of HIV/AIDS cases nationwide and a significant segment of this population is primarily Spanish speaking. We have previously developed an assessment that evaluated English-speakers on a variety of instrumental activities of daily living. In this pilot study, we used Spanish-language translations of our functional battery to investigate the cultural relevance of such measures and to explore relationships between NP status and ability to perform important everyday tasks in HIV-infected Spanish-speakers. Sixteen HIV-infected monolingual Spanish-speaking adults received comprehensive, Spanish language NP testing and functional assessmenets included the following domains: Medication Management, Cooking, Finances, Shopping and Restaurant Scenario. Results revealed that most of the functional tasks appeared culturally relevant and appropriate with minor modifications. NP-impaired participants were significantly more functionally impaired compared to NP-normals (88% vs. 13%, p<.01). Performances on the functional assessment and the NP battery were also related to indicators of real world functioning, including employment status and quality of life. These results, though preliminary, suggest that Spanish language functional assessments are potentially valid tools for detecting everyday functioning deficits associated with NP impairments in HIV-infected Spanish-speakers. [ABSTRACT FROM AUTHOR]

Background: Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin., Methods: In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed., Results: Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests., Conclusions: This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.

HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction/Executive Function, Learning, Attention/Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of "real-world" functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons.