Epidemiologic studies have identified cocaine as a cofactor for development of acquired immunodeficiency syndrome (AIDS). To evaluate this interaction, human peripheral blood leukocytes (PBL) were implanted into severe combined immunodeficient mice and infected with human immunodeficiency virus (HIV) in both the presence and absence of cocaine. Concurrent administration of cocaine resulted in significantly more PBL becoming infected with HIV in vivo (38.85% vs. 18.5%). The number of CD4(+) cells recovered from HIV-infected, cocaine-treated animals was significantly lower than that from mice infected with HIV in the absence of cocaine (6.5 x 10(4) vs. 19 x 10(4)) and was associated with a lower CD4:CD8 ratio and a dramatic increase in virus load. Exposure to cocaine alone did not affect the implantation of PBL, suggesting a specific interaction between cocaine and HIV. This report describes a model for evaluating HIV cofactors and supports cocaine's role in the development and progression of AIDS.

Cocaine is associated with an increased risk for, and progression of, clinical disease associated with human immunodeficiency virus (HIV) infection. A human xenograft model, in which human peripheral blood mononuclear cells were implanted into severe combined immunodeficiency mice (huPBL-SCID) and infected with a HIV reporter virus, was used to investigate the biological interactions between cocaine and HIV infection. Systemic administration of cocaine (5 mg/kg/d) significantly increased the percentage of HIV-infected PBL (two- to threefold) and viral load (100- to 300-fold) in huPBL-SCID mice. Despite the capacity for cocaine to increase corticosterone and adrenocorticotropic hormone levels in control mice, the hypothalamic-pituitary-adrenal axis was suppressed in HIV-infected animals, and corticosterone levels were further decreased when animals were exposed to HIV and cocaine. Activating huPBL in vitro in the presence of 10(-8) M cocaine increased expression of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptors. Expression of CCR5 was also increased at early time-points in the huPBL-SCID model following systemic exposure to cocaine (54.1+/-9.4% increase over control, P<0.01). This effect preceded the boost in viral infection and waned as HIV infection progressed. Cocaine has been shown to mediate immunosuppressive effects by activating sigma-1 receptors in immune cells in vitro and in vivo. Consistent with these reports, a selective sigma-1 antagonist, BD1047, blocked the effects of cocaine on HIV replication in the huPBL-SCID mouse. Our results suggest that systemic exposure to cocaine can enhance HIV infection in vivo by activating sigma-1 receptors and by modulating the expression of HIV coreceptors.

—The kinetics of plasma choline (Ch) and the uptake of plasma Ch into the brain were studied by means of intravenous infusion of [2H4]Ch at various rates into anaesthetized and conscious rats. [2H4]Ch levels in both arterial and venous plasma at steady state were linearly related to the infusion rate; however, unlabelled Ch levels were independent of infusion rate. [2H4]Ch levels were higher in the arterial plasma than in the venous plasma, while unlabelled Ch levels were higher in the venous plasma than in the arterial plasma. It was concluded that Ch is being generated in the brain and is released into the venous effluent. The supply of Ch to the plasma is not decreased if the plasma Ch level is increased. The clearance and turnover of Ch in the compartment of its initial distribution are 75 ml kg‐1 min‐1 and 716 nmol kg‐1 min‐1, respectively. The uptake of plasma Ch into the brain is not saturated even at very high levels of plasma Ch.

Objectives To compare long‐term oncologic outcomes and adjuvant therapies for patients treated with transoral robotic surgery (TORS), nonrobotic surgery, or transoral laser microsurgery (TLM). Study Design A retrospective analysis of the National Cancer Database (2010–2014). Methods Patients with clinical tumor (T)1 and T2 oropharyngeal squamous cell carcinomas (OPSCC) were classified into those receiving TORS versus nonrobotic surgery versus TLM. Univariate and multivariate survival analyses were conducted with chi‐square tests; Kaplan‐Meier log‐rank test; and Cox multivariate, logistic regression, and multinomial regression modeling. Results We identified 2,224 OPSCC TORS patients; 6,697 nonrobotic surgery patients; and 333 TLM patients. The majority of patients were white males with a mean age of approximately 59 years. No significant difference was noted between the cohorts in tumor stage; however, TORS patients were more likely to have nodal (N)1 to N3 disease than nonrobotic surgery and TLM patients, respectively (69.8% vs. 62.0% vs. 59.7%, P < 0.001). TORS was associated with a lower likelihood of positive margins when compared to nonrobotic surgery, although not TLM (nonrobotic surgery: hazard ratio [HR] 1.51, P < 0.001, TLM: HR 1.13, P = 0.582). TORS was associated with lower likelihood of postsurgical chemoradiotherapy (TLM: HR 2.07, P < 0.001, nonrobotic surgery: 1.65, P < 0.001) but not adjuvant radiotherapy alone (TLM: HR 1.06, P = 0.569, nonrobotic surgery: 0.96, P = 0.655). On multivariate Cox analysis of overall survival, the use of TORS was not associated with increased survival (TLM: HR 1.31, P = 0.233, nonrobotic surgery: HR 1.12, P < 0.303). Conclusion The advantages of TORS for early‐stage OPSCC may be a lower likelihood of postsurgical positive margins and subsequent need for adjuvant chemoradiotherapy. Level of Evidence NALaryngoscope, 129:1844–1855, 2019

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