Dingcai Cao

Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking

CONTEXT Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse. OBJECTIVE To prospectively assess the relationship of acute alcohol responses to future binge drinking. DESIGN Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses. SETTING Participants recruited from the community. PARTICIPANTS High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86). INTERVENTION We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520). MAIN OUTCOME MEASURES Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences-Recent, and DSM-IV alcohol abuse and dependence. RESULTS Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence. CONCLUSIONS The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00961792.

Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine.

Background : Many non‐responders to azathioprine or mercaptopurine (6‐mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6‐methylmercaptopurine instead of the active 6‐tioguanine (6‐tioguanine) metabolites.

A Randomized Phase II Trial of the Antiangiogenic Agent SU5416 in Hormone-Refractory Prostate Cancer

Purpose: To assess the activity of the antiangiogenic agent and VEGFR2 inhibitor SU5416 in hormone-refractory prostate cancer. Patients and Methods: Thirty-six chemotherapy naïve patients were randomized to treatment with SU5416 (145 mg/m2) and dexamethasone premedication or dexamethasone alone. Patients in the control arm could cross over to experimental therapy after progression. Prostate-specific antigen (PSA) was measured every 2 weeks, and radiological evaluation was performed every 8 weeks. In vitro assessment of SU5416 on PSA secretion was assessed in the LNCaP cell line. Baseline serum basic fibroblast growth factor and plasma vascular endothelial growth factor (VEGF) were explored as prognostic factors. Results: VEGF receptor-2 expression is detectable in prostate cancer cell lines, and SU5416 inhibited in vitro PSA secretion. No effect of SU5416 on PSA secretion or time to progression is detectable in patients. VEGF and basic fibroblast growth factor were not prognostic. Headache and fatigue were the most common SU5416 toxicities, but hyperglycemia, hyponatremia, lymphopenia, infection, and adrenal suppression, all attributable to steroids and the required central line, were common. Conclusion: No disease modifying effects of SU5416 were detectable in this small study. Modest toxicity, an inconvenient administration schedule, and availability of other VEGFR-targeted agents support the decision to halt further evaluation of SU5416 in prostate cancer.

Need-service matching in substance abuse treatment: Racial/ethnic differences

This study examines the impact of ancillary health and social services matched to client needs in substance abuse treatment for African Americans, Latinos and Whites. The study uses data collected from 1992 to 1997 for the National Treatment Improvement Evaluation Study, a prospective cohort study of substance abuse treatment programs and their clients. The analytic sample consists of 3142 clients (1812 African Americans, 486 Latinos, 844 Whites) from 59 treatment facilities. Results show that racial/ethnic minorities are underserved compared to Whites in the substance abuse service system. Different racial/ethnic groups come into treatment with distinct needs and receive distinct services. Although groups respond differentially to service types, substance abuse counseling and matching services to needs is an effective strategy both for retaining clients in treatment and for reducing post-treatment substance use for African Americans and Whites. Receipt of access services was related to reduced post-treatment substance use for Latinos. Study findings are relevant to planning special services for African Americans and Latinos.

Efficacy of naltrexone in smoking cessation : A preliminary study and an examination of sex differences

This double-blinded, placebo-controlled trial evaluated the efficacy of naltrexone as an adjunct to standard smoking cessation treatment. Participants (N = 110) were adult male and female nicotine-dependent smokers who expressed interest in quitting smoking. All subjects received six sessions of behavioral counseling (1 hr/session for 6 weeks), and 1 month of the nicotine patch (21 mg for the first 2 weeks, 14 mg the third week, 7 mg the fourth week). Subjects were randomly assigned to the naltrexone or placebo group. The naltrexone group started at 25 mg daily for 3 days prior to the quit date, and increased to 50 mg/day on the quit date and following 8 weeks. At the end of medication treatment, the naltrexone group had better quit rates versus the placebo group (48% quit on naltrexone vs. 41% on placebo), but this difference was not statistically significant. However, men and women differed on several measures: in the placebo group, women had significantly lower quit rates than men (39% vs. 67%, p<.05), but in the naltrexone group, women had quit rates comparable with those of men (58% vs. 62%, p = ns). Further examination revealed that naltrexone significantly reduced mens and womens cessation-related weight gain and selectively reduced womens urge to smoke to relieve negative affect and withdrawal. The results suggest continued examination of naltrexone as an adjunct in smoking cessation, particularly in female smokers, who have historically shown worse outcomes with traditional treatment methods.

Responses of Primate Retinal Ganglion Cells to Perimetric Stimuli

PURPOSE Perimetry is used clinically to assess glaucomatous ganglion cell loss. It has been proposed that frequency-doubling stimuli are better than the conventional size III perimetric stimulus in preferentially stimulating magnocellular (M) versus parvocellular (P) ganglion cells. However, little is known about how primate ganglion cells respond to perimetric stimuli. The authors recorded contrast responses of M and P ganglion cells to size III and frequency-doubling stimuli and compared contrast gain of M and P cells to these stimuli to assess the ability of these stimuli to preferentially stimulate M versus P cells. METHODS Data were recorded from 69 macaque retinal ganglion cells, by an in vivo preparation, at eccentricities of 5° to 15°. The size III stimulus was a circular luminance increment 26 min arc in diameter, 200 ms in duration. The frequency-doubling stimulus was a sinusoidal grating (0.5 cyc/deg) temporally modulated in counterphase at 13 Hz. A Michaelis-Menten function was fit to each cells contrast responses to assess contrast gain. RESULTS For both size III and frequency-doubling stimuli, ganglion cell responses increased linearly at low contrasts, and then the increase slowed at high contrasts (saturation). The mean (± SE) difference in estimated log contrast gain between M and P cells for the size III stimulus was significantly higher than that for the frequency-doubling stimulus (1.24 ± 0.09 vs. 0.89 ± 0.13; P < 0.01). CONCLUSIONS The size III stimulus was superior to the frequency-doubling stimulus in preferentially stimulating M cells versus P cells.

Rod contributions to color perception: Linear with rod contrast

At mesopic light levels, an incremental change in rod activation causes changes in color appearance. In this study, we investigated how rod mediated changes in color perception varied as a function of the magnitude of the rod contrast. Rod-mediated changes in color appearance were assessed by matching them with cone-mediated color changes. A two-channel four-primary colorimeter allowed independent control of the rods and each of the L-, M- and S-cone photoreceptor types. At all light levels, rod contributions to inferred PC, KC and MC pathway mediated vision were linearly related to the rod incremental contrast. This linear relationship could be described by a model based on primate ganglion cell responses with the assumption that rod signals were conveyed via rod-cone gap junctions at mesopic light levels.

Matching rod percepts with cone stimuli

Traditional methods for studying the effects of rod activity on color vision make it hard to assess the underlying physiological mechanisms. In this study, rod-mediated changes in color appearance were assessed by matching them with cone-mediated color changes. A four-primary photostimulator allowed independent control of rod and cone stimulation and identification of the cone types that generate color sensations equivalent to rod color sensations. The results showed that increases in rod stimulation required matches with cone stimuli that excited M-cones more than L-cones for all conditions. Matches for low-luminance conditions also required some S-cone stimulation. A subsidiary experiment showed that increases in rod modulation of an inducing field produced chromatic contrast effects like those produced by the M-cone system. The data are consistent with a hypothesis of perceptual normalization of scotopic vision to the chromatic appearance of objects under photopic conditions.

Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women.

Abstract This study examined whether the opioid receptor antagonist naltrexone is efficacious in smoking cessation and whether sex moderates the response. We assessed smoking quit rates and weight gain in a double-blind randomized trial comparing oral naltrexone (n = 162) with placebo (n = 154) in nicotine-dependent participants who wanted to quit smoking. The medication was gradually titrated up to 50 mg during the week before the quit date and then maintained at this dose for 12 weeks. For the first 4 weeks after the quit date, all participants received a nicotine patch to mitigate tobacco withdrawal and attended weekly individual cognitive-behavioral smoking cessation counseling sessions. After this time, participants continued with naltrexone or placebo through 12 weeks. Follow-up assessments were conducted at 26 and 52 weeks. During treatment, naltrexone (vs placebo) increased quit rates, attenuated smoking urge, and reduced weight gain. At follow-up, after medication discontinuation, the effect of naltrexone on improving quit rates was no longer evident. Men and women experienced different benefits from naltrexone; men showed greater reductions in smoking, whereas women showed greater reductions in weight gain. In sum, naltrexone showed acute efficacy in treating nicotine dependence, but after the medication was discontinued, the effect on quit rate was not maintained. Further study of naltrexone in smoking cessation treatment and reduction of cessation-related weight gain, as well as preclinical investigation of mechanisms underlying sex differences, is warranted.

Vision under mesopic and scotopic illumination

Evidence has accumulated that rod activation under mesopic and scotopic light levels alters visual perception and performance. Here we review the most recent developments in the measurement of rod and cone contributions to mesopic color perception and temporal processing, with a focus on data measured using a four-primary photostimulator method that independently controls rod and cone excitations. We discuss the findings in the context of rod inputs to the three primary retinogeniculate pathways to understand rod contributions to mesopic vision. Additionally, we present evidence that hue perception is possible under scotopic, pure rod-mediated conditions that involves cortical mechanisms.