Functional and proteomic analysis of submandibular saliva in rats exposed to chronic stress by immobilization or constant light.

OBJECTIVE: In this study, we have evaluated the effects of stress on functional and proteomic changes in submandibular saliva of rats. DESIGN: Male adult rats were divided in three groups: IMO (2 h/day of immobilization for 7 days), LL (constant light during 20 days), C (unstressed controls submitted to 14 h light-10h dark cycle). Body weight, food intake and the dry weight of submandibular gland were recorded. Saliva samples, collected under anaesthesia following i.p. administration of isoproterenol and pilocarpine (5 mg/kg), were assayed for total proteins (TP), amylase activity and SDS-PAGE electrophoresis. RESULTS: Body weight, food intake and the dry weight of submandibular gland of IMO rats were lower than those of C and LL groups. The salivary volumes secreted in IMO and LL rats, were significantly higher than in controls. The TP output (µg protein/µg saliva/mg of dry tissue) and amylase activity output (AU/µg of saliva/mg of dry tissue) in IMO were significantly higher than in C and LL animals. The electrophoretic pattern of saliva proteins of LL rats, revealed the absence of a protein band of approximately 25 kDa. This band was composed by the common salivary protein-1 and a prolactin-induced protein as identified by peptide mass fingerprinting. CONCLUSIONS: Differences in body weight and food intake between IMO and LL might be attributed to the sort and intensity of stressors stimuli. The changes in the volume of secreted saliva could be a compensatory mechanism in response to stressors. The increase of total protein in IMO rats and the absence of 25 kDa proteins in LL, would suggest that the submandibular glands respond to the sympathetic nervous system stimuli induced by the stress with an increase of activity of the sympathetic nerves in IMO and a reduction in LL rats.

The validity of the interviewer severity ratings in groups of ASI interviewers with varying training.

AIMS: This study evaluated the hypothesis that the subjective interviewer severity rating (ISR) summary indices of the intake Addiction Severity Index (ASI) of less trained interviewers are less valid than those of more highly trained interviewers. DESIGN: Baseline ASIs from three completed studies whose interviewers varied in degree of initial ASI training and subsequent quality assurance monitoring were examined. Associations between baseline ISRs and three other sets of ASI summary indices not based on interviewer ratings-composite scores, clinical indices and evaluation indices-were compared for three groups of interviewers with varying amounts of training. The assumption underlying these analyses was that more reliable ISRs, found in more trained interviewers, would be more highly associated with the other more objective indices. SETTING: Methadone maintenance patients in the Philadelphia and New York City areas. PARTICIPANTS: Thirty-five interviewers with the most intense training who administered 295 interviews; 10 interviewers with an intermediate level of training who administered 763 interviews; and eight identified (and other unidentified) least trained interviewers who administered a total of 276 interviews. Measurements and methods. Four sets of summary indices from the above ASIs. Both bivariate and multivariate analyses were performed. FINDINGS: The study found that the validity of the validity of ISRs was greater in more trained interviewers. CONCLUSIONS: Greater training and subsequent monitoring of ASI interviewers generally appears to be associated with increased ISR validity.

Predictive validity of the Addiction Severity Index's composite scores in the assessment of 2-year outcomes in a methadone maintenance population.

The current research tested the predictive validity of 6 of the 7 Composite Scores (CSs) of the Addiction Severity Index (ASI) in 310 methadone maintenance patients assessed at treatment entry using the ASI and other measures, and followed for 2 years. Logistic regression was used to estimate the sensitivity and specificity of the CSs at intake in predicting their respective validity criterion measures at follow up. Except for the Medical CS, each of the other 5 CS measures significantly predicted its validity criterion measure. The CSs measuring drug use, alcohol abuse, psychopathology, and legal problems had high specificity (88% [corrected] for the Drug CS, 91% for the Alcohol CS, 96% for the Legal CS, and 100% for the Psychological CS). The CSs measuring employment problems had high sensitivity (76%). The results support the predictive validity of most of the ASI CSs as measures of specific problems as well as the validity of the multidimensional construct on which the ASI is based.

Short- and long-term smoking cessation for three levels of intensity of behavioral treatment.

Efficacy and costs of 3 levels of medical-behavioral treatment intensity in conjunction with nicotine replacement therapy (NRT) were compared in 240 one-pack-a-day smokers: (a) a low-intensity (LI) group that received 8 weeks of NRT (n = 80) and 1 advice and education (A&E) session with a nurse practitioner (NP); (b) a moderate-intensity (MI) group that was provided NRT and 4 A&E sessions with an NP (n = 80); and (c) a high-intensity (HI) group that received treatment combining NRT, 4 A&E sessions, and 12 weeks of individualized cognitive-behavioral therapy (n = 80). Biochemically confirmed abstinence rates at 9, 26, and 52 weeks posttreatment initiation were highest for the HI (45%, 37%, 35%) group, followed by the LI (35%, 30%, and 27%) and MI (27%, 12%, 12%) groups. Group differences approached statistical significance at 9 weeks and were statistically significant at both 26 and 52 weeks. The cost of LI treatment was $308, that of MI was $338, and the HI treatment cost was $582.

A community-based trial of vocational problem-solving to increase employment among methadone patients.

UNLABELLED: Unemployment remains a common problem among methadone patients. This study examined the effectiveness of the Vocational Problem-Solving Skills (VPSS) intervention to help unemployed methadone patients obtain employment. METHODS: 109 patients were randomly assigned to receive 10 sessions of either VPSS (n=62) or Interpersonal Problem-Solving (IPS) (n=47). Fourteen counselors from two methadone programs were trained to deliver both the VPSS and IPS counseling sessions. RESULTS: Overall, 93% (101/109) of the patients completed a 6-month follow-up assessment which revealed that 58.6% (34/58) of patients in the VPSS condition were employed, whereas 37.2% (16/43) in the comparison condition worked (chi-square=4.53, 1 df, p<0.05). However, a multinomial regression equation found that the VPSS intervention did not significantly contribute to the prediction of employment. Other factors such as longer length of previous work experience, 40 years of age or older, treatment site, and baseline patient motivation to work emerged as significant predictors. CONCLUSION: Although VPSS alone was not a strong independent predictor of improved employment functioning, improvements in employment functioning were detected at one of the two sites as a function of VPSS.

A comparison of the predictive validity of four sets of baseline ASI summary indices.

This study compared the long-term predictive validity of original and new baseline Addiction Severity Index summary scores in methadone patients. The indices included the original Interviewer Severity Ratings (ISRs) and the new Clinical Indices (CIs), which use both lifetime and recent problem information, and the original Composite Scores (CSs) and Evaluation Indices (EIs), based on recent problems only. Outcomes were medical hospitalization, employment, alcohol intoxication, drug hospitalization, and psychiatric hospitalization in Months 7-24 poststudy entry and criminal charges in Months 0-24. Hierarchical logistic regression analyses were used in which 1 index was entered first and the other in the 2nd step. The reverse order of entry was used in a 2nd analysis. A final analysis set compared the best predictor from each of the 2 prior analysis sets. The CIs were superior to the other indices in predicting 3 of 6 outcomes (psychiatric hospitalization, drug hospitalization, and criminal charges); the EI was the best predictor of alcohol intoxication, and the CS the best predictor of unemployment.

Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity.

Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms, and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms.

State-level treatment outcome studies using administrative databases.

State substance dependence administrative databases contain both administrative and clinical information on large numbers of patients collected over extended time periods. Access to other state databases--employment, criminal behavior, and Medicaid--has also been achieved in some instances. Such data could prove an important source for the evaluation of long-term treatment outcomes and their determinants. This selected review describes and evaluates the treatment outcome and cost-related findings of the most advanced studies using these databases. A number of these studies have shown that completion of substance dependence treatment is associated with reduced societal costs. Some of these studies have focused on significant subpopulations of patients, including pregnant women and adolescents. A shortcoming of the findings of most of these studies concerns their use of noncompleter or non-randomly collected comparison groups. The utility of these databases can be enhanced by coupling them with clinical research treatment outcome evaluation approaches.

Cocaine withdrawal symptoms and initial urine toxicology results predict treatment attrition in outpatient cocaine dependence treatment.

This study evaluated the ability of cocaine withdrawal symptoms, measured by the Cocaine Selective Severity Assessment (CSSA) and initial urine toxicology results, to predict treatment attrition among 128 cocaine dependent veterans participating in a 4-week day hospital treatment program. The CSSA was administered and a urine toxicology screen was obtained at intake and at the start of the day hospital (about 1 week later). The combination of a positive urine toxicology screen and a high CSSA score at intake predicted failure to complete treatment. Urine toxicology results at the start of the day hospital, but not at intake, predicted failure to complete treatment. Among participants without other psychiatric illness, high CSSA scores at intake predicted failure to complete treatment. The presence of cocaine withdrawal symptoms and a positive urine toxicology screen are clinically useful predictors of treatment attrition.

Alcoholism treatment after liver transplantation: lessons learned from a clinical trial that failed.

Alcoholic liver disease is the second most common indication for liver transplantation in the United States. The lack of alcoholism treatment studies led us to study motivational enhancement therapy (MET) plus naltrexone after transplant. The authors could not complete this study. Sixty alcoholic patients were to receive MET plus naltrexone or placebo for 6 months. Fifty men and 5 women were screened. Nine died and 15 were not approached. Of 31 approached, 20 were ineligible, 11 refused, and 5 entered but dropped out before completion. Barriers to posttransplant alcoholism included infirmity, intensive medical management, and denial for alcoholism treatment. Because 30%-50% of alcoholic patients drink after transplant, the authors suggest using MET alone pretransplant.

Continuous, categorical, and time to event cocaine use outcome variables: degree of intercorrelation and sensitivity to treatment group differences.

Although a number of cocaine use variables are available for use in treatment outcome studies, there is little information on how strongly these variables are related or their relative sensitivity for detecting treatment group differences. Eight continuous and categorical variables of cocaine use obtained at 6-, 12-, 18-, and 24-month follow-ups, four event history variables, and one summary measure of cocaine use over the 24-month follow-up period were examined. The variables were generally correlated 0.30--0.50 or greater. An exploratory factor analysis in which the repeated measures were averaged across follow-up points yielded two factors, one made up of incidence of use variables (e.g. percent days cocaine use, monetary value of cocaine, abstinence status, time to relapse, urine toxicology) and a second consisting of perceived severity of use variables (e.g. drug and cocaine composites, craving). This factor solution was supported by confirmatory factor analyses conducted at each follow-up point. None of the variables yielded significant differences between the two treatment conditions in the study, standard group and individualized relapse prevention continuing care. However, monetary value of cocaine used and urine toxicology variables yielded the largest effect sizes (eta(2)=0.020 and 0.010, respectively).

The relationship of psychiatric comorbidity to treatment outcomes in methadone maintained patients.

The authors examined the relationship of comorbid non-substance use psychiatric disorders to preadmission problem status and treatment outcomes in 278 methadone maintenance patients. Recent admissions were assigned DSM-III-R Axis I and II diagnoses according to structured diagnostic interviews. The Addiction Severity Index was administered at admission to assess past and current substance use and psychosocial problems and again 7 months later. Treatment retention and month 7 drug urinalysis results were also obtained. Across substance use and psychosocial domains, participants showed significant and comparable levels of improvement regardless of comorbidity. Comorbid participants received more concurrent psychiatric treatment which may have accounted for the lack of differential improvement among groups. Nevertheless, psychiatric comorbidity was associated with poorer psychosocial and medical status at admission and follow-up and participants with the combination of Axis I and II comorbidity had the most severe problems. Admission and month 7 substance use were, for the most part, not related to psychiatric comorbidity, although there was a trend indicating more treatment attrition for participants with personality disorders.

The effectiveness of two intensities of psychosocial treatment for cocaine dependence.

Structured treatments for cocaine dependence have been shown to be effective despite high attrition rates. What is unclear is what level of treatment intensity is needed to improve and sustain patient outcomes, especially among low SES urban residents. This study evaluated whether there were differences between two levels of treatment intensities for cocaine dependence in reducing substance use and improving health and social indicators. Ninety-four cocaine dependent predominantly African-American male veterans were randomly assigned to either a 12 h/week day hospital program (DH12) or a 6 h/week outpatient program (OP6) and were evaluated at baseline, during treatment and at 4 and 7 months post-treatment. Both treatments stressed abstinence, behavior change and prosocial adjustment and only differed in level of treatment intensity. During treatment measures included urine toxicologies, program attendance, treatment completion and aftercare attendance. Participants reported a 52% reduction in days of cocaine use and experienced significant improvements in employment and psychiatric functioning at seven months post-treatment. However, there was no significant difference between the DH12 and OP6 programs in terms of abstinence during treatment, treatment completion, treatment or aftercare attendance or any Addiction Severity Index (ASI)-related variable assessing level of functioning at 4 and 7 months. While future research with a larger community-based sample that includes female clients is necessary, the current findings demonstrate that a 6 h/week program is just as effective and thus has a significant cost savings compared to a 12 h/week treatment modality for cocaine dependence.

Amantadine in the treatment of cocaine-dependent patients with severe withdrawal symptoms.

OBJECTIVE: The study examined the effectiveness of amantadine in reducing cocaine withdrawal symptoms and improving treatment outcome among cocaine-dependent patients in outpatient treatment. METHOD: Sixty-one cocaine-dependent subjects participated in a double-blind, placebo-controlled trial of amantadine. RESULTS: Among subjects with severe cocaine withdrawal symptoms at the start of treatment, those who received amantadine used significantly less cocaine during the trial than did subjects who received placebo. Compared to subjects who received placebo, subjects who received amantadine submitted significantly more benzoylecgonine-negative urine samples and used cocaine on significantly fewer days during the trial. CONCLUSIONS: Amantadine may be an effective treatment for cocaine-dependent patients with severe cocaine withdrawal symptoms.

The relationship between psychopathology and smoking cessation treatment response.

The study evaluated the relationship of psychopathology to treatment response of 208 smokers prescribed transdermal nicotine (8 weeks). Participants were relatively high functioning (DSM-IV axis V score) outpatients in a university-based clinic. The primary study objective was to determine whether patients with a history of either a DSM-IV axis I or II diagnosis would have poorer during treatment response (patch adherence, smoking) and lower rates of smoking cessation at post-patch follow-up (study weeks 9, 26, 52) than those without a diagnosis. While there was some indication that patients with a history of psychopathology wore the patch less frequently, psychopathology was not associated with during- and post-treatment smoking.

Generalizability of the clinical dimensions of the Addiction Severity Index to nonopioid-dependent patients.

Clinical dimensions (CDs) for the Addiction Severity Index recently have been established for application among opioid-dependent patients in methadone treatment (P. A. McDermott et al., 1996). This article examines the generalizability of the CDs to other substance-dependent patients. A sample of 2,027 adult nonopioid-dependent patients was identified; it comprised 581 primarily cocaine-dependent, 544 primarily alcohol-dependent, and 803 polydrug-dependent patients and 99 patients who were dependent on other varied drugs. Generality of dimensions was assessed through confirmatory components analysis, structural congruence, internal consistency, and variance partitioning in higher order factoring. The CDs were found generalizable overall and to specific nonopioid-dependent subgroups, and across patient gender and age, and to African American and White patients. Preliminary concurrent and predictive validity data supported the CD structure.

Comparison of outcomes by gender and for fee-for-service versus managed care: a study of nine community programs.

During-treatment services and 7-month posttreatment entry outcome of cocaine- or alcohol-dependent men (n = 145) and women (n = 149) Target City patients receiving either standard fee-for-services (n = 183) or managed care treatment funding (n = 111) in nine community outpatient programs were compared. No differences were found in treatment services received by the various subgroups. Regression analyses compared the four described subgroups (Gender x Type of Funding) on their seven Addiction Severity Index composite scores at 7 months postadmission controlling for the respective baseline composite score and several background variables on which the groups differed. Surprisingly few outcome differences were revealed between men and women patients and patients receiving the two forms of treatment funding. The only difference noted was that patients treated via managed care showed more improvement in the drug area. The need for further evaluation of the effects of managed care is emphasized.

Truncated TrkB mediates the endocytosis and release of BDNF and neurotrophin-4/5 by rat astrocytes and schwann cells in vitro.

Binding and cross-linking studies with radiolabeled neurotrophins demonstrate that cultured rat hippocampal astrocytes lack full-length TrkB, but do express high levels of truncated TrkB (tTrkB). In astrocytes and Schwann cells, tTrkB appears to have the novel function of mediating the endocytosis of neurotrophins into an acid-stable, Triton X-100 resistant intracellular pool that is released back into the medium in a temperature-dependent manner. Chloroquine treatment, trichloroacetic acid solubility, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that when incubated with astrocytes or Schwann cells for at least 48 h neither the intracellular nor the released neurotrophins were significantly degraded. The endocytosis and release of neurotrophins may represent a novel mechanism whereby neuroglia can regulate the local concentration of these neurotrophic factors for extended periods of time.

Prognostic significance of antisocial personality disorder in cocaine-dependent patients entering continuing care.

This study examined the relationship of antisocial personality disorder (APD) to response to continuing care treatments in a sample of cocaine-dependent patients. Patients (N = 127) were randomly assigned to 20-week standard group or individualized relapse prevention continuing care interventions after the completion of an initial treatment episode and followed up at 3, 6, and 12 months. APD and non-APD patients did not differ on retention in continuing care, substance use outcomes, social function outcomes, or experiences before or during cocaine relapse episodes. A diagnosis of APD was also not a predictor of differential response to the two continuing care interventions in the study. However, APD patients had worse medical and psychiatric problem severity than non-APD patients at entrance to continuing care and during follow-up. These results suggest that cocaine patients with APD who are in the continuing care phase of outpatient rehabilitation might benefit from additional medical and psychiatric treatment services.

Baseline prediction of 7-month cocaine abstinence for cocaine dependence patients.

A broad range of baseline subject variables was evaluated to identify predictors of 7-month cocaine use for 160 lower socioeconomic cocaine dependent male veteran patients participating in either an intensive 1-month day hospital (DH; n=90) or a 1-month inpatient (INP; n=70) treatment program. The baseline measures included sociodemographic variables, the seven Addiction Severity Index composite scores, cocaine urine toxicology, craving, the SCL-90 total score, and lifetime psychiatric diagnoses. Since a proportion of subjects who reported no use at follow-up had positive urines, both liberal and conservative data estimation strategies were employed for subjects without urine toxicology data at follow-up who had reported no use (21% of subjects). Analyses were done separately for the DH and INP subjects. Under the conservative definition of cocaine abstinence/use, univariate correlations of predictor variables with 7-month cocaine use revealed no statistically significant relationships. Under the liberal definition of cocaine abstinence/use, only one variable, greater severity of alcohol problems at intake predicted cocaine abstinence at outcome. Because of the inability to predict treatment success, originally planned logistic regression analyses were not undertaken. The findings point to the difficulty of predicting long-term outcomes in cocaine dependent patients based on baseline information and to the importance of obtaining objective data on cocaine use.