Towards the characterization and validation of alcohol use disorder subtypes: integrating consumption and symptom data.

BACKGROUND: There is evidence that measures of alcohol consumption, dependence and abuse are valid indicators of qualitatively different subtypes of alcohol involvement yet also fall along a continuum. The present study attempts to resolve the extent to which variations in alcohol involvement reflect a difference in kind versus a difference in degree. METHOD: Data were taken from the 2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions. The sample (51% male; 72% white/non-Hispanic) included respondents reporting past 12-month drinking at both waves (wave 1: n = 33644; wave 2: n = 25186). We compared factor mixture models (FMMs), a hybrid of common factor analysis (FA) and latent class analysis (LCA), against FA and LCA models using past 12-month alcohol use disorder (AUD) criteria and five indicators of alcohol consumption reflecting frequency and heaviness of drinking. RESULTS: Model comparison revealed that the best-fitting model at wave 1 was a one-factor four-class FMM, with classes primarily varying across dependence and consumption indices. The model was replicated using wave 2 data, and validated against AUD and dependence diagnoses. Class stability from waves 1 to 2 was moderate, with greatest agreement for the infrequent drinking class. Within-class associations in the underlying latent factor also revealed modest agreement over time. CONCLUSIONS: There is evidence that alcohol involvement can be considered both categorical and continuous, with responses reduced to four patterns that quantitatively vary along a single dimension. Nosologists may consider hybrid approaches involving groups that vary in pattern of consumption and dependence symptomatology as well as variation of severity within group.

Short duration of lamivudine for the prevention of hepatitis B virus transmission in pregnancy: lack of potency and selection of resistance mutations.

This study sought to assess the antiviral efficacy of lamivudine (LMV) administered during third trimester to reduce maternal viraemia and to identify the emergence of LMV resistance. A prospective observational analysis was performed on 26 mothers with high viral load (>107 IU/mL). Twenty-one women received LMV (treated group) for an average of 53 days (range 22-88 days), and the remaining five formed the untreated control group. Serum samples from two time points were used to measure HBV DNA levels and antiviral drug resistance. The LMV-treated women achieved a median HBV DNA reduction of 2.6-log10 IU/mL. Although end-of-treatment (EOT) HBV DNA in four (18%) LMV-treated women remained at >10(7) IU/mL (± 0.5 log IU/mL), no mother-to-baby transmission was observed. In contrast, a baby from the untreated mother was HBsAg positive at 9 months postpartum. Four technologies were used for drug resistance testing. Only ultra-deep pyrosequencing (UDPS) was sufficiently sensitive to detect minor viral variants down to <1%. UDPS showed that LMV therapy resulted in increased viral quasispecies diversity and positive selection of HBV variants with reverse transcriptase amino acid substitutions at sites associated with primary LMV resistance (rtM204I/V and rtA181T) in four (19%) women. These viral variants were detected mostly at low frequencies (0.63-5.92%) at EOT, but one LMV-treated mother had an rtA181T variant that increased from 2.2% pretherapy to 25.59% at EOT. This mother was also infected with the vaccine escape variant (sG145R), which was inhibited by LMV treatment. LMV therapy during late pregnancy only reduced maternal viraemia moderately, and drug-resistant viral variants emerged.

Phytochemical induction of cell cycle arrest by glutathione oxidation and reversal by N-acetylcysteine in human colon carcinoma cells.

Cancer prevention by dietary phytochemicals has been shown to involve decreased cell proliferation and cell cycle arrest. However, there is limited understanding of the mechanisms involved. Previously, we have shown that a common effect of phytochemicals investigated is to oxidize the intracellular glutathione (GSH) pool. Therefore, the objective of this study was to evaluate whether changes in the glutathione redox potential in response to dietary phytochemicals was related to their induction of cell cycle arrest. Human colon carcinoma (HT29) cells were treated with benzyl isothiocyanate (BIT) (BIT), diallyl disulfide (DADS), dimethyl fumarate (DMF), lycopene (LYC) (LYC), sodium butyrate (NaB) or buthione sulfoxamine (BSO, a GSH synthesis inhibitor) at concentrations shown to cause oxidation of the GSH: glutathione disulfide pool. A decrease in cell proliferation, as measured by [(3)H]-thymidine incorporation, was observed that could be reversed by pretreatment with the GSH precursor and antioxidant N-acetylcysteine (NAC). Cell cycle analysis on cells isolated 16 h after treatment indicated an increase in the percentage (ranging from 75-30% for benzyl isothiocyanate and lycopene, respectively) of cells at G2/M arrest compared to control treatments (dimethylsulfoxide) in response to phytochemical concentrations that oxidized the GSH pool. Pretreatment for 6 h with N-acetylcysteine (NAC) resulted in a partial reversal of the G2/M arrest. As expected, the GSH oxidation from these phytochemical treatments was reversible by NAC. That both cell proliferation and G2/M arrest were also reversed by NAC leads to the conclusion that these phytochemical effects are also mediated, in part, by intracellular oxidation. Thus, one potential mechanism for cancer prevention by dietary phytochemicals is inhibition of the growth of cancer cells through modulation of their intracellular redox environment.

Evaluation of four airway training manikins as patient simulators for the insertion of eight types of supraglottic airway devices.

We evaluated the performance of four currently available manikins: Airway Management Trainer (Ambu, UK), Airway Trainer (Laerdal, Norway), Airsim (Trucorp, Ireland), 'Bill 1' (VBM, Germany), with eight supraglottic airway devices: Airway Management Device, Cobra Perilaryngeal Airway, Combitube, i-Gel, Laryngeal Tube, Laryngeal Tube Disposable, Laryngeal Tube Suction II and Streamlined Liner of the Pharynx Airway. Ten anaesthetists inserted each supraglottic airway device twice into each manikin. Each insertion was scored and ranked. Manikin score and rank data showed statistically significant overall performance differences. Post hoc analysis showed the Trucorp manikin performed best, followed by the Laerdal manikin. No one manikin performed best for all individual supraglottic airway devices. The Trucorp manikin performed adequately for all supraglottic airway devices. Comparing supraglottic airway devices, i-Gel insertion was significantly the easiest. Our results show that manikin performance for supraglottic airway device insertion is unequal, which has implications for selecting manikins for supraglottic airway device training and for manikin studies assessing performance of supraglottic airway devices.

Transitioning into and out of large-effect drinking in young adulthood.

As individuals age beyond the college years into young adulthood, many exhibit a tendency to moderate or "mature out of" alcohol involvement. The current study classified effect-drinking statuses in young adults and examined transitions among statuses using latent transition analysis, a latent variable state-sequential model for longitudinal data. At 3 occasions over 7 years (Years 1, 4, and 7), 443 men (47%) and women (mean age of both at baseline = 18.5 years; 51% with family history of alcoholism) responded to 3 past-30-day items assessing drinking and subjective effects of drinking: whether the respondent drank alcohol, felt high, and felt drunk. Latent statuses included abstainers (14% at Year 1), limited-effect drinkers (8%), moderate-effect drinkers (23%), and large-effect drinkers (54%). Respondents with family history of alcoholism were less likely to transition out of large-effect drinking than those without family history. Men exhibited more severe initial effect-drinking statuses and lower transition probabilities into less severe effect-drinking statuses than women.

Quantification and variability analysis of bacterial cross-contamination rates in common food service tasks.

This study investigated bacterial transfer rates between hands and other common surfaces involved in food preparation in the kitchen. Nalidixic acid-resistant Enterobacter aerogenes B199A was used as a surrogate microorganism to follow the cross-contamination events. Samples from at least 30 different participants were collected to determine the statistical distribution of each cross-contamination rate and to quantify the natural variability associated with that rate. The transfer rates among hands, foods, and kitchen surfaces were highly variable, being as low as 0.0005% and as high as 100%. A normal distribution was used to describe the variability in the logarithm of the transfer rates. The mean +/- SD of the normal distributions were, in log percent transfer rate, chicken to hand (0.94 +/- 0.68), cutting board to lettuce (0.90 +/- 0.59), spigot to hand (0.36 +/- 0.90), hand to lettuce (-0.12 +/- 1.07), prewashed hand to postwashed hand (i.e., hand washing efficiency) (-0.20 +/- 1.42), and hand to spigot (-0.80 +/- 1.09). Quantifying the cross-contamination risk associated with various steps in the food preparation process can provide a scientific basis for risk management efforts in both home and food service kitchens.

The factor structure of the Personality Assessment Inventory-Borderline Features (PAI-BOR) Scale in a nonclinical sample.

We evaluated the fit of Morey's (1991) proposed 4-factor structure on Personality Assessment Inventory-Borderline Features Scale (PAI-BOR; Morey, 1991) items in a sample of approximately 5,000 nonclinical participants. The proposed model did not fit the data well. Results from a series of exploratory and confirmatory factor analyses suggested that a 6-factor model provided the best fit to the PAI-BOR item covariances.

A psychosocial model of sun protection and sunbathing in young women: the impact of health beliefs, attitudes, norms, and self-efficacy for sun protection.

A psychosocial model of sun protection and sunbathing as distinct behaviors was developed on 202 young Caucasian women and replicated in an independent sample (n = 207). Proximal outcomes were intention to sun protect and intention to sunbathe; distal outcomes included sun protection and sunbathing behavior measured 5 months later. Objective risk for skin cancer plus 4 classes of psychosocial variables (sun-protective health beliefs, self-efficacy for sun protection, attitudes toward sunbathing, and norms for sunbathing and sun protection) served as predictors. Sun-protective norms and self-efficacy for sun protection predicted only intention to sun protect; sunbathing norms predicted only intention to sunbathe. Susceptibility and advantages of tanning predicted both intention constructs, which, in turn, predicted behavior. These findings distinguish sun protection from sunbathing and provide a basis for intervention design.

Heat-shocked A20 lymphoma cells fail to induce degranulation of cytotoxic T lymphocytes: possible mechanism of resistance.

A20 lymphoma cells were subjected to heat shock for 2 h at 42 and 43 +/- 0.1 degrees C and then evaluated at 37 degrees C for sensitivity to lysis by intact allo-specific cytotoxic T lymphocytes (CTLs), perforin-containing granules isolated from CTLs, and Fas-mediated apoptosis. Heat shock at 42 degrees C caused little change in sensitivity of the lymphoma cell line to lysis by intact CTLs or their isolated cytotoxic granules, but caused increased sensitivity to Fas-mediated apoptosis. However, A20 cells shocked at 43 degrees C declined significantly in sensitivity to lysis by intact CTLs, while remaining very sensitive to perforin granules and to Fas-mediated apoptosis. Expression of the inducible heat shock protein was observed in A20 cells incubated at 43 degrees C, but not in those incubated at 42 degrees C, suggesting a role for heat shock proteins. Furthermore, A20 cells shocked at 43 degrees C did not provoke degranulation and secretion of granzymes by antigen-specific CTLs, although formation of CTL-target conjugates and levels of MHC class I molecules remained unchanged. These observations demonstrate that hyperthermia or febrile conditions may reduce susceptibility of target cells to CTL attack due to failure of antigen presentation and the inability of CTLs to recognize heat stressed targets, thus enabling targets to escape CTL attack.

Trajectories of concurrent substance use disorders: a developmental, typological approach to comorbidity.

BACKGROUND: Although alcohol and tobacco use disorders are highly comorbid, little is known regarding the combined course of these disorders. METHODS: The current study utilized latent class analysis to examine longitudinal patterns of alcohol-tobacco use disorder comorbidity. Participants were 449 young adults (baseline age, 18.5 years; 48% male; 51% with paternal history of alcoholism) assessed five times over 7 years. RESULTS: Five longitudinal types of alcohol or tobacco use disorder over time were identified: nondiagnosing; developmentally limited alcohol use disorder; chronic alcohol use disorder; chronic tobacco use disorder; and comorbid alcohol and tobacco use disorder. These typologies were distinguishable on the basis of family history of alcoholism status and sex. Etiologically important third variables (alcohol expectancies, behavioral undercontrol, childhood stressors) mediated the relation between family history and the latent classes. CONCLUSIONS: Characterizations of alcohol use disorders typically fail to consider important sources of heterogeneity such as course or comorbidity. By simultaneously modeling developmental course and comorbidity with tobacco dependence, we were able to identify distinct trajectories of single and concurrent substance use disorders. Such multi-substance trajectories represent meaningful subtypes that, although sharing substantial common influences, have unique etiologic correlates. Additionally, these subtypes might represent distinct groups from the perspective of intervention strategies.

Prospective analysis of comorbidity: tobacco and alcohol use disorders.

Alcohol use disorders (AUD) and tobacco use disorders (TD) frequently co-occur. The authors examined AUD-TD comorbidity over time using a state-trait (ST) model. The ST model represents variance in AUD/TD as a traitlike factor that spans measurement occasion and identifies distinct sources of variance in AUD-TD comorbidity. The ST model was evaluated on 450 young adults (baseline age = 18.5 years; 51% with family history of alcoholism) assessed 5 times over 7 years. The ST model demonstrated superior fit over a first-order autoregressive model. The tendency to diagnose with AUD and TD was partially explained by family history of alcoholism; this relationship was mediated by childhood stressors, alcohol expectancies, and behavioral undercontrol. Results supported a common third-variable influence (vs. directional) model of comorbidity. The ST model is an important conceptual and methodological approach to the prospective study of comorbidity in general.

Family risk and resiliency factors, substance use, and the drug resistance process in adolescence.

Recent approaches to drug prevention have emphasized risk and resiliency factors. Two models have been developed to explain these factors, one which posits that separate elements make up each set and the other which posits that a single factor can be either a risk or a resiliency factor depending on, for example, if it is present (resiliency) or absent (risk). This study tested these models and attempted to compare the effects of risk and resiliency across gender and ethnicity. Results support the model in which risk and resiliency are discrete sets of factors and demonstrate that overall resiliency factors play a larger role than risk factors in substance use and drug resistance processes. However, gender proved to be an important moderator of these effects. For adolescent males, resiliency has an indirect effect on overall substance use through age of first use, while risk has a direct effect on overall substance use. For adolescent females, resiliency has a direct effect on overall substance use and risk has an indirect effect through age of first use. This indicates that while early interventions are important for both genders, resiliency factors must be dealt with before initiation of substance use for males. Findings did not differ substantially across ethnicity, although the small African-American sample size may have limited power to detect differences.

Ethnic and gender differences and similarities in adolescent drug use and refusals of drug offers.

This paper examines the relationship among ethnicity, gender, drug use, and resistance to drug offers among a sample of 2,622 African American, Mexican American, and White American seventh graders. A number of similarities were noted. First, these adolescents did not seem to possess large or sophisticated repertoires of offer resistance strategies. Second, most offers came from acquaintances in contrast to more intimate offers among older youths. Ethnic and gender differences were also noted. Ethnicity had significant effects on use and the offer process. Mexican Americans received more offers, used more drugs, and were more likely to be offered drugs by peer family members and at parties. European Americans were more likely to receive drug offers from acquaintances and at friends' homes and on the street. African Americans were more likely to receive offers from dating partners and parents, and in the park, and were more likely to resist offers of drugs-using explanations. Gender significantly affected drug offers and types of offers. Males were more at risk for offers and use at a younger age. Offers of drugs to males were more likely to come from parents or other males, while offers to females were more likely to come from other females or dating partners. Males also were more likely to receive drug offers that appeal to their social standing or self-image while females received either simple offers or those that minimize effects. Finally, offers of drugs to males were more likely to be made in public, while those to females were more likely to occur in private. Cultural explanations are offered for these findings.

Hepatic lacI and cII mutation in transgenic (lambdaLIZ) rats treated with dimethylnitrosamine.

The recent introduction of a transgenic rat in vivo mutation assay is a much needed supplement to the transgenic mouse models and offers the tools necessary for collecting target tissue specific genotoxicity data in this species. The utility of the Big Blue(R) rat for the detection of in vivo mutations was investigated by studying spontaneous and dimethylnitrosamine (DMN)-induced hepatic mutations. High molecular weight DNA isolated from Big Blue(R) rat livers typically yielded good transgene rescue efficiency of up to 5x105 plaque forming units per packaging reaction. DMN, when administered by oral gavage at dose levels of 0.2, 0.6, 2.0, and 6.0 mg kg-1 day-1, induced up to a 4.5-fold increase in mutations at the highest dose level. There was no apparent difference between the lacI vs. cII target genes of the shuttle vector in either the background or DMN-induced mutant frequencies. These results suggest that the transgenic rat model is a useful tool for studying potential genotoxicity in target organs and, with further validation, the selectable cII target could be an attractive alternative to the conventional lacI color screening method for the detection of mutations in the lambdaLIZ shuttle vector.

Mammography screening for women under 50: women's response to medical controversy and changing practice guidelines.

The controversy concerning the efficacy of mammography screening for reducing breast cancer mortality among women aged 40 to 49 has continued throughout much of this decade. We examined the impact of this controversy on a community sample of women aged 40 to 60 in 2 data collections (n = 146 and n = 51, respectively), each time following a critical point in the controversy. At initial data collection, only 19% of women identified the specific nature of the debate. Women reported that physicians did not recommend waiting to age 50 to be screened. The women supported screening in the 40s. Those in their 40s intended to continue screening. At 2nd data collection, women showed awareness of inaccuracies in mammography screening, but intended to continue screening nonetheless. These results suggest that health care consumers will not easily relinquish medical innovations that previously have been integrated into usual health care.

Arrest of the cell cycle reduces susceptibility of target cells to perforin-mediated lysis.

Cytotoxic T lymphocytes secrete a pore-forming cytolysin, perforin, that damages membranes of target cells. They also ligate Fas receptors on target cells and provoke apoptotic death. A20 (B lymphoma) and P815 (mastocytoma) cell lines were examined for their susceptibility to perforin-mediated lysis and to Fas-induced apoptosis after blockade of the cell cycle at the G1/S interface. Cells were arrested at the G1/S interface by inhibition of DNA synthesis with thymidine or aphidicolin. Subsequently, the treated cells were incubated either with CTL cytotoxic granules or the Fas-specific monoclonal antibody Jo-2. We show that arrest of the cell cycle at the G1/S interface markedly reduced the susceptibility of target cells to perforin-mediated lysis. In contrast, growth arrest with thymidine or aphidicolin increased susceptibility of A20 and P815 cells to Fas-mediated apoptosis. Susceptibility to lysis by intact CTLs was not affected significantly by blockade of target cells with aphidicolin or thymidine. When cells surviving exposure to perforin-containing granules were isolated on Ficoll density gradients and cell-cycle profiles were examined by flow cytometry, the ratio of G1 to G2 cells increased among the survivors exposed to granules in contrast to controls incubated with buffer alone. The data suggest that cells in G1 phase of the cell cycle are less susceptible to the perforin pathway than cells in G2 and S phases but are more susceptible to the Fas pathway.

Effect of lymphatic and splenic pump techniques on the antibody response to hepatitis B vaccine: a pilot study.

Osteopathic manipulative treatment (OMT) facilitates the movement of lymphatic fluid and may enhance the immunologic response to infection or injected antigen. In this investigation, two groups of volunteers were vaccinated with recombinant hepatitis B vaccine, given at 0, 5, and 25 weeks. The experimental group (n = 20) received OMT (lymphatic and splenic pump) three times per week for 2 weeks after each vaccination. Control subjects (n = 19) received vaccine but no OMT. Resultant serum antibody levels were measured by enzyme immunoassay. Fifty percent of subjects in the treatment group achieved protective antibody titers (> or = 10 mIU/mL) on the 13th week with an average titer of 374 mIU/mL. Only 16% of the control subjects had positive antibody responses, with average titers of 96 mIU/mL. At all time points from week 6 on, the average anti-hepatitis B titer was higher in the treatment group than in the control group. These data suggest an enhanced immunologic response in subjects who received OMT.