d-Amphetamine increases choice of cigarette smoking over monetary reinforcement

RATIONALE: Psychomotor stimulants previously have been found to increase the frequency of cigarette smoking, but it is unclear whether this is due to a non-specific increase in general activity or a specific increase in the reinforcing effects of smoking. OBJECTIVES: To investigate whether d-amphetamine increases the relative reinforcing effects of cigarette smoking. METHODS: Ninety minutes after d-amphetamine (7.5, 15 mg/70 kg) or placebo administration, 13 male and female subjects participated in 3-h sessions during which they could make a maximum of 20 choices between cigarette smoking (two puffs per choice), earning money ($0.25 per choice), or neither. In separate sessions, using the same subjects, the effects of d-amphetamine on the frequency of ad libitum smoking was assessed. RESULTS: During choice sessions, d-amphetamine dose-dependently increased smoking choices from 4.2 +/- 0.6 to 5.7 +/- 0.6. During sessions in which subjects smoked ad libitum, d-amphetamine increased number of cigarettes smoked from 2.8 +/- 0.4 to 3.8 +/- 0.6. Breath carbon monoxide (CO) levels, a measure of smoke exposure, showed corresponding dose-related increases. CONCLUSIONS: These results are consistent with previous findings that d-amphetamine increases smoking and provide evidence that this effect is due to a drug-produced increase in the relative reinforcing effects of cigarette smoking.     

Suppression of tumorigenicity of rat liver tumor cells by human chromosome 13: evidence against the involvement of pRb and BRCA2.

Aberrations of chromosome 13, including large-scale deletions and rearrangements, have been implicated in the development of a significant fraction of human hepatocellular carcinomas, suggesting that liver tumor suppressor genes may be located on this chromosome. In this study, we have employed a microcell hybrid-based model system to investigate the presence of liver tumor suppressor loci on human chromosome 13. The parental GN6TF rat liver epithelial tumor cells are highly tumorigenic in vivo and exhibit altered cellular morphology and growth characteristics in vitro. The GN6TF cells form tumors in 100% of syngeneic animals with short latency, are not contact inhibited or anchorage-dependent in cell culture, and do not express mRNAs for rat Rb1 and BRCA2. Microcell-mediated introduction of human chromosome 13 into the rat liver tumor cell line GN6TF resulted in the generation of clonal microcell hybrid (MCH) cell lines that differentially exhibited tumor suppression and/or alteration of other transformation-associated phenotypes in vitro. Two GN6TF-13neo MCH lines exhibited characteristics indicative of suppression by the human chromosome, including a normalized cellular morphology and growth pattern, loss of anchorage-independent growth potential, partial restoration of contact inhibition, reduction in tumorigenic potential in vivo, and dramatic elongation of tumor latency. In contrast, three GN6TF-13neo MCH cell lines were minimally affected by the introduction of the human chromosome and were nearly indistinguishable from the parental GN6TF tumor cells, exhibiting a highly aggressive tumorigenic phenotype in vivo. Both suppressed and non-suppressed GN6TF-13neo MCH cell lines express Rb1 and BRCA2 mRNA in vitro, and tumors derived from the non-suppressed GN6TF-13neo MCH cell lines continue to express Rb1 and BRCA2 mRNA in vitro, and express pRb in vivo. The results suggest that: i) human chromosome 13 contains a liver tumor suppressor locus, ii) expression of Rb1 and/or BRCA2 is insufficient to produce tumor suppression in this rat liver tumor cell line, and iii) that the human chromosome 13 liver tumor suppressor may represent a novel tumor suppressor gene, distinct from Rb1 and BRCA2.     

Interpreting and using the dietary references intakes in dietary assessment of individuals and groups

For individuals, a statistical approach is available to compare observed intakes to the EAR or AI (to assess adequacy), and the UL (to assess risk of excess). A more qualitative assessment of intakes involves comparison directly to the RDA to evaluate adequacy, but this is accurate only if long-term usual intake is known. For groups of people, the prevalence of inadequacy can usually be estimated as the proportion with intakes below the EAR, while the prevalence of potentially excessive intakes is estimated as the proportion above the UL. The accuracy of all assessments depends on unbiased and accurate intake estimates as well as a consideration of the effects of day-to-day variation in intake. Nutrition practitioners will find the new DRIs useful for assessing diets in a variety of settings. Computerized assessment systems will be important tools when incorporating these theoretical concepts into dietetic practice.     

The A-OCDS predicts both craving and alcohol cue reactivity in adolescent alcoholics

Adolescents with alcohol dependence may experience marked craving and physiologic reactivity in the presence of alcohol cues which could undermine treatment gains. The Adolescent Obsessive Compulsive Drinking Scale (A-OCDS) was developed to help quantify the severity of alcohol craving in adolescents with alcohol use disorders. The A-OCDS is a relatively new instrument, and empirical data are needed to support its value in clinical trials. The present investigation uses data collected as part of a clinical laboratory study examining alcohol craving and cue reactivity in adolescents with and without alcohol dependence. A-OCDS total and subscale scores from adolescent alcoholics (N = 28) were examined regarding their relationship to drinking and several indices of craving and alcohol cue reactivity. In addition, regression analyses were performed to characterize the predictive ability of A-OCDS total scores and drinking indices (drinks per drinking day and percent days abstinent) on two measures of alcohol craving and cue reactivity. Results showed that the A-OCDS total scores, but not drinks per drinking day or percent days abstinent, predicted scores on both indices of craving. The study uses a small but well-defined sample of adolescents with alcohol dependence and supports the construct validity of the A-OCDS and suggests that, as in adults, alcohol craving and drinking behavior are related but separate elements of alcohol dependence. The results are intended to guide future studies in which the A-OCDS may be employed to measure craving and changes in craving over the course of treatment for adolescents with alcohol dependence.     

Psychiatric symptoms, health services, and HIV risk factors among homeless women

The authors determined whether psychiatric symptoms and lack of health and/or social services contacts were associated with HIV risk behaviors among a probability sample of homeless women. Women were interviewed regarding socioeconomic indicators, psychiatric symptoms, health and/or social services contacts, and past-year HIV risk behaviors. Overall, 8 percent of the women injected drugs, 64 percent engaged in unprotected sex, and 22 percent traded sex. Multiple logistic regression results revealed that substance abuse was positively associated with injection drug use and trading sex. Homeless women with case managers were less likely to inject drugs. Although barriers to obtaining drug treatment were associated with trading sex, women attending self-help meetings for substance abuse were also more likely to trade sex. Homeless women who are substance abusers are vulnerable to HIV risk behaviors. Risk reduction interventions for homeless women should be implemented through substance abuse and intensive case management programs.     

EEG and Seizure Outcome After Epilepsy Surgery

Summary: The significance of the EEG after epilepsy surgery is not fully understood. We investigated the as- sociation between postoperative EEG abnormalities and persistent seizures after epilepsy surgery as they relate to pathologic lesions. Among 254 patients who underwent epilepsy surgery between 1987 and 1991, we identified 78 patients who had mesiotemporal sclerosis (MTS) and 47 patients who had low-grade brain tumors, all of whom had 6-to 18-month postoperative follow-up including EEG. Patients who had other pathology, multiple operations, callosotomy, or hemispherectomy, or who were aged <18 years or who had insufficient EEG data, were excluded. Patients were classified as having persistent seizures or being seizure-free since operation. EEG abnormalities were abstracted from EEG reports 6–18 months postoperatively. Seizures persisted in 24% of the MTS group and in 27% of the tumor group. Of those with normal EEGs, none of the MTS patients and only 1 of the tumor patients had persistent seizures (p = 0.03 for MTS and p = 0.42 for tumor). Epileptiform discharges and focal slowing were associated with seizure persistence in both groups, but to a significant extent only in the MTS group. In the MTS group, patients who had both epileptiform discharges and focal slowing were more likely to have persistent seizures than were those with either abnormality alone.     

Enhanced nitric oxide activity offsets peripheral vasoconstriction during acute hypoxaemia via chemoreflex and adrenomedullary actions in the sheep fetus

We tested the hypothesis that enhanced nitric oxide (NO) opposes fetal peripheral vasoconstrictor responses to acute hypoxaemia via actions involving the carotid chemoreflex and the adrenal medulla. The hypothesis was tested in the late gestation ovine fetus using a novel NO clamp technique, which involves fetal combined treatment with the NO synthase inhibitor, l -NAME, and the NO donor, sodium nitroprusside. In contrast to treatment with l -NAME alone, combined fetal treatment with l -NAME and nitroprusside prevents generalized vasoconstriction and pronounced hypertension, not only maintaining basal cardiovascular function, but also permitting blockade of the de novo synthesis of NO during hypoxaemia while compensating for the tonic production of the gas. Under general anaesthesia, seven sheep fetuses were surgically prepared with catheters and a femoral Transonic flow probe. Five days after surgery, fetuses were subjected to a 3 h protocol: 1 h normoxia, 1 h hypoxaemia and 1 h recovery. Fetal hypoxaemia was induced during either fetal infusion with saline or treatment with the NO clamp. During saline infusion, fetuses responded to hypoxaemia with transient bradycardia, femoral vasoconstriction and increases in plasma noradrenaline and adrenaline. During fetal treatment with the NO clamp, bradycardia persisted and there were greater peripheral vasoconstrictor and catecholaminergic responses to hypoxaemia. Further analysis showed that NO clamp treatment enhanced the chemoreflex component of the fetal cardiovascular defence to acute hypoxaemia. These data support the hypothesis that enhanced NO synthesis during acute hypoxaemia offsets fetal peripheral vasoconstrictor responses to hypoxaemia via chemoreflex and adrenomedullary actions.     

Measuring the impact of health research

Measuring the decision-making impact of applied health research should constitute a core function for many research funders and research organizations. Different target audiences warrant different measures of impact. The target audiences for applied health research include the general public, patients (and their families), clinicians, managers (in hospitals, regional health authorities and health plans), research and development officers (in biotechnology firms) and public policy-makers (i.e. elected officials, political staff and civil servants). Making meaningful assessments within peer groups that fund or produce similar types of research knowledge for similar types of target audiences makes more sense than a one-size-fits-all approach to impact assessment. User-pull and interactive measures of impact (i.e. measures of cultural shifts that would facilitate the on-going use of research knowledge to inform decision-making) can supplement more traditional producer-push measures that assess researchers' active efforts to inform decision-making and the outcome of these efforts. Cultural shifts may include the creation of a research-attuned culture among decision-makers and a decision-relevant culture among researchers. Moving beyond whether research was used to examine how it was used is also important. Research knowledge may be used in instrumental, conceptual or symbolic ways. These actions, coupled with on-going refinements to the proposed assessment tool as research evidence evolves, would take us a long way towards assessment and accountability in the health sector.     

Single nucleotide polymorphisms in the matrix metalloproteinase gene family and the frequency and duration of gastroesophageal reflux disease influence the risk of esophageal adenocarcinoma

The matrix metalloproteinase (MMP) family of proteins mediates various cellular pathways, including apoptosis and angiogenesis. Polymorphisms of MMP genes are associated with increased esophageal adenocarcinoma (EAC) risk. Gastroesophageal reflux disease (GERD) is an established EAC risk factor. We examined whether MMP polymorphism-EAC risk is modified by GERD. In total, 309 EAC patients and 279 frequency-matched healthy controls underwent MMP1 1G/2G, MMP3 6A/5A, MMP12 -82A/G and MMP12 1082A/G genotyping. Questionnaires collected GERD history. EAC risk was analyzed using logistic regression, adjusted for key covariates and stratified by GERD. Joint effects models explored GERD severity and duration, whereas additional models explored genotype-GERD interactions in EAC risk. We determined that each MMP1 and MMP3 minor (variant) allele was independently associated with increased EAC risk (adjusted odds ratio (AOR) 3.2, 95% confidence interval (CI) 2.0-5.1, p < 0.001 and AOR 1.8, 95% CI 1.1-2.7, p = 0.01, respectively) only among those with GERD but not in GERD-free individuals (all p = nonsignificant). There were significant interactions between the MMP1 variants and the presence of GERD (p = 0.002) and between MMP3 variants and GERD (p = 0.04). There was an equally strong interaction between cumulative GERD severity and MMP1 (p = 0.002). The AOR of each variant allele was 14.9 (95% CI 1.6-136) for individuals with severe GERD, 1.7 (95% CI 1.0-2.7) for mild-moderate GERD and 0.98 (95% CI 0.7-1.4) for those without GERD. This was further reflected in separate analyses of frequency and duration of GERD. In conclusion, MMP1 1G/2G (and possibly MMP3 6A/5A) polymorphisms alter EAC risk differentially for GERD and GERD-free individuals.     

Linking measures of adolescent nicotine dependence to a common latent continuum

Using the theoretical model of nicotine dependence (ND) operationalized within the Diagnostic and Statistical Manual of Mental Disorder, fourth Edition (DSM-IV: American Psychiatric [American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC]) as a frame of reference, we used methods based in item response theory to link alternative instruments assessing adolescent nicotine dependence severity to a common latent continuum. A multi-ethnic cohort of 6th-10th graders selected from the Chicago Public Schools (CPS) completed five household interviews over 2 years. Youth who reported at least some cigarette use in the last 30 days prior to the interviews at waves W3-W5 completed measures of DSM-IV ND, the Modified Fagertrom Tolerance Questionnaire (mFTQ: Prokhorov et al., 1998) and the Nicotine Dependence Syndrome Scale (NDSS: Shiffman et al., 2004), yielding samples of 253, 241, and 296 respondents at W3-W5, respectively. Confirmatory factor analysis supported a primary dimension of ND. Each instrument's items had complementary and stable relationships to ND across multiple waves of assessment. By aligning symptoms along a common latent ND continuum, we evaluated the consistency of symptoms from different instruments that target similar content. Further, these methods allowed for the examination of the DSM-IV as a continuous index of ND, evaluation of the degree of heterogeneity in levels of ND within groups above and below diagnostic thresholds, and the utility of using the pattern or particular DSM-IV symptoms that led to each score in further differentiating levels of ND. Finally, we examined concurrent validity of the ND continuum and levels of current of smoking at each wave of assessment.