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Biomedical subjects

D M Donovan

Publications and source records attributed to D M Donovan.

At least 37 records · Page 2Linked to original sources

Alcohol interventions in a trauma center as a means of reducing the risk of injury recurrence.

OBJECTIVE: Alcoholism is the leading risk factor for injury. The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism. METHODS: This study was a randomized, prospective controlled trial in a level 1 trauma center. Patients were screened using a blood alcohol concentration, gamma glutamyl transpeptidase level, and short Michigan Alcoholism Screening Test (SMAST). Those with positive results were randomized to a brief intervention or control group. Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records, and 6- and 12-month interviews were conducted to assess alcohol use. RESULTS: A total of 2524 patients were screened; 1153 screened positive (46%). Three hundred sixty-six were randomized to the intervention group, and 396 to controls. At 12 months, the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week; in the control group, the decrease was 6.7+/-5.8 (p = 0.03). The reduction was most apparent in patients with mild to moderate alcohol problems (SMAST score 3 to 8); they had 21.6+/-4.2 fewer drinks per week, compared to an increase of 2.3+/-8.3 drinks per week in controls (p < 0.01). There was a 47% reduction in injuries requiring either emergency department or trauma center admission (hazard ratio 0.53, 95% confidence interval 0.26 to 1.07, p = 0.07) and a 48% reduction in injuries requiring hospital admission (3 years follow-up). CONCLUSION: Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism. Given the prevalence of alcohol problems in trauma centers, screening, intervention, and counseling for alcohol problems should be routine.

Adult↗

Detection of acute alcohol intoxication and chronic alcohol dependence by trauma center staff.

BACKGROUND: Trauma patients with acute alcohol intoxication or chronic alcohol dependence are at greater risk for morbidity and mortality. We hypothesized that relying on clinical suspicion to detect acute alcohol intoxication and chronic alcohol dependence in trauma patients is inaccurate, influenced by injury factors, and biased by race, gender, age, and socioeconomic status. METHODS: Trauma patients were screened with a blood alcohol concentration and with the Short Michigan Alcohol Screening Test and CAGE questionnaire. Before screening, physicians and emergency department nurses were asked whether the patient was acutely intoxicated (blood alcohol concentration > 100 mg/ dL) or had a chronic alcohol problem. Sensitivity, specificity, positive, and negative predictive values were determined by comparing responses with blood alcohol concentration, Short Michigan Alcohol Screening Test, and CAGE questionnaire results, stratified by injury and demographic factors. RESULTS: Clinical evaluations were obtained on 462 patients. Overall, 23% of acutely intoxicated patients were not identified by physicians. The miss rate increased to one third in severely injured, chemically paralyzed, or intubated patients. Specificity was also poor. Patients with a negative blood alcohol concentration were more likely to be falsely suspected of intoxication if they were either young, male, perceived as disheveled, uninsured, or having a low income (p < 0.05). Staff identified < 50% of patients with a positive Short Michigan Alcohol Screening Test or CAGE, and falsely identified 26% of patients as alcoholic. CONCLUSIONS: Formal alcohol screening should be routine because clinical detection of acute alcohol intoxication and dependence is inaccurate. Screening should also be routine to avoid discriminatory bias attributable to patient characteristics.

Acute Disease↗

Internal validity of Project MATCH treatments: discriminability and integrity.

Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) is a multisite collaborative project designed to evaluate patient-treatment interactions in alcoholism treatment. To evaluate whether major threats to the internal validity of the independent (treatment) variable in Project MATCH could be ruled out, we investigated several aspects of treatment integrity and discriminability. In this study, 1,726 alcohol-dependent participants at 10 sites were randomized to 3 treatments: cognitive-behavioral treatment (CBT), motivational enhancement therapy (MET), and 12-step facilitation (TSF). Participants received treatment either as outpatients or as aftercare following a more intensive inpatient or day hospital treatment. For both the outpatient and aftercare arms of the study, treatments were discriminable in that therapists implemented each of the treatments according to manual guidelines and rarely used techniques associated with comparison approaches. Participants received a high level of exposure to their study treatments, and the intended contrast in treatment dose between MET and the 2 more intensive treatments (CBT and TSF) was obtained. Alcoholics Anonymous involvement was significantly higher for participants assigned to TSF versus MET or CBT, whereas the treatments did not differ in utilization of other nonstudy treatments. Nonspecific aspects of treatment such as therapist skillfulness and level of the therapeutic alliance were comparable across treatment conditions.

Adult↗

Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia.

Morphine produces analgesia at opiate receptors expressed in nociceptive circuits. mu, delta, and kappa opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands. The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however. We produced homologous, recombinant mu, opiate receptor, heterozygous and homozygous knockout animals that displayed approximately 54% and 0% of wild-type levels of mu receptor expression, respectively. These mice expressed kappa receptors and delta receptors at near wild-type levels. Untreated knockout mice displayed shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with mu opiate receptors in normal nociceptive processing. Morphine failed to significantly reduce nociceptive responses in hot plate or tail flick tests of homozygous mu receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships. These results implicate endogenous opioid-peptide actions at mu opiate receptors in several tests of nociceptive responsiveness and support mu receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia.

Analgesia↗

The therapeutic alliance and its relationship to alcoholism treatment participation and outcome.

The relationship between the therapeutic alliance and treatment participation and drinking outcomes during and after treatment was evaluated among alcoholic outpatient and aftercare clients. In the outpatient sample, ratings of the working alliance, whether provided by the client or therapist, were significant predictors of treatment participation and drinking behavior during the treatment and 12-month posttreatment periods, after a variety of other sources of variance were controlled. Ratings of the alliance by the aftercare clients did not predict treatment participation or drinking outcomes. Therapists ratings of the alliance in the aftercare sample predicted only percentage of days abstinent during treatment and follow-up. The results document the independent contribution of the therapeutic alliance to treatment participation and outcomes among alcoholic outpatients.

Adult↗

Intrastriatal grafting of Cos cells stably expressing human aromatic L-amino acid decarboxylase: neurochemical effects.

To study the possibility that increasing striatal activity of aromatic L-amino acid decarboxylase (AADC; EC 4.1.1.28) can increase dopamine production in dopamine denervated striatum in response to L-3,4-dihydroxy-phenylalanine (L-DOPA) administration, we grafted Cos cells stably expressing the human AADC gene (Cos-haadc cells) into 6-hydroxydopamine denervated rat striatum. Before grafting, the catalytic activity of the enzyme was assessed in vitro via the generation of 14CO2 from L-[14C]DOPA. The Km value for L-DOPA in intact and disrupted cells was 0.60 and 0.56 mM, respectively. The cofactor, pyridoxal 5-phosphate, enhanced enzymatic activity with maximal effect at 0.1 mM. The pH optimum for enzyme activity was 6.8. Grafting Cos-haadc cells into denervated rat striatum enhanced striatal dopamine levels measured after systemic administration of L-DOPA. When measured 2 h after L-DOPA administration, the mean dopamine level in the striata of Cos-haadc-grafted animals was 2 micrograms/g of tissue, representing 31% of normal striatal dopamine concentration. The mean dopamine concentration in the striata grafted with untransfected Cos cells (Cos-ut cells) was 1 microgram/g. At 6-8 h after L-DOPA administration, striatal dopamine content in the Cos-haadc-grafted animals was 0.67 microgram/g of tissue weight, representing 9% of intact striatum dopamine content. By contrast, the average dopamine content in the Cos-ut-grafted animals was undetectable. These findings demonstrate that enhancing striatal AADC activity can improve dopamine bioformation in response to systemically administered L-DOPA.

Animals↗

Practical guidelines for performing alcohol interventions in trauma centers.

Nearly 50% of trauma patients are injured while under the influence of alcohol; however, addressing alcohol problems is not considered a routine component of trauma care. A public health approach to trauma prevention should include attention to underlying risk factors in the same way that advice regarding smoking cessation is offered in adult respiratory medicine clinics, and blood pressure, cholesterol, dietary, and exercise advice is provided in coronary care units. The Department of Health and Human Services, in its recent report to Congress, stated that efforts to reduce death and disability from injuries must be combined with efforts to reduce alcohol abuse, and called for an increase in the use of alcohol interventions in trauma patients. According to the National Academy of Sciences, the responsibility to provide counseling for patients with uncomplicated cases of mild to moderate alcohol abuse lies not with specialized alcohol treatment centers, but with physicians and other health care staff in general hospital settings trained to provide brief interventions. This paper provides practical guidelines for the administration of alcohol interventions that are suitable for trauma center use, and that have documented efficacy in reducing alcohol consumption.

Adult↗

Alcohol abuse in urban Indian adolescents and women: a longitudinal study for assessment and risk evaluation.

Empirical studies of American Indian health and mental health have focused primarily on reservation samples or small cross-sectional school-based or treatment samples. Few studies have addressed these issues among urban American Indian populations. This paper introduces an ongoing ten-year prospective longitudinal study of alcohol abuse, drug abuse, and mental health status in a community sample of urban American Indian adolescents and women. The study uses structured interviews and diagnostic assessments to identify risk factors for, and measure prevalence of, alcohol abuse, drug abuse, and psychopathology in 523 Indian youth and 276 Indian women. Study aims, rationale, research design, methods, sample characteristics, assessment instruments, and substance use prevalence are described, and methodological issues related to conducting longitudinal research are discussed.

Adolescent↗

Conceptualizations of relapse: a summary of psychological and psychobiological models.

While substance use disorders have long been recognized as chronic relapsing conditions, it has mainly been in the last two decades that clinical researchers have been systematically attending to the nature and processes of relapse. These efforts have led to the development of a variety of psychological and psychobiological models of relapse. These models are summarized in the present article, with particular attention placed on each model's basic principles and on the precipitants of relapse predicted by the respective models. The delineation of these models may help facilitate subsequent cross-referencing and cross-fertilization of thinking in this important area.

Alcoholism↗

Assessment issues and domains in the prediction of relapse.

The present paper provides a brief overview of methodological issues involved in the process of assessment related to the classification and prediction of relapse. These include conceptual and operational definitions of relapse, retrospective versus prospective assessment, attributional biases in recalling relapse events, single versus multiple determinants of relapse, static versus dynamic assessment models, and the necessary level of specificity involved in the assessment of relapse categories. Additionally, general domains representing distal personal characteristics, intermediate background variables and factors proximal in time to relapse situations are reviewed. Potential variables appropriate for assessment within each of these domains are described. It is concluded that relapse is best understood as a complex process having multiple and interactive determinants that vary in their temporal proximity from and their relative influence on relapse. An adequate assessment model must be sufficiently comprehensive to include theoretically relevant variables from each of the multiple domains and different levels of potential predictors.

Alcoholism↗

Marlatt's classification of relapse precipitants: is the Emperor still wearing clothes?

The present paper provides comments on the series of papers dealing with the reliability and validity of Marlatt's taxonomy of relapse precipitants. The results of these papers suggest that the degree of reliability and predictive validity of the original relapse taxonomy, as operationalized and employed in the present studies, is lower than would be hoped for. Both methodological factors in the studies and limitations in the taxonomy are discussed. While the original taxonomic system has provided a useful heuristic model and a guide for clinical intervention, it is recommended that it be modified to improve its utility in research and practice. A number of specific recommendations are provided for modifying the system.

Alcoholism↗

Alcohol interventions in trauma centers. Current practice and future directions.

Nearly half of all trauma beds are occupied by patients who were injured while under the influence of alcohol. Alcoholism plays such a significant role in trauma that efforts to reduce injury recurrence are unlikely to be successful if it remains untreated. An injury requiring hospitalization creates a unique opportunity to intervene and to motivate patients to alter their drinking behavior, thereby making trauma centers ideal sites to implement an alcohol screening, intervention, and referral program. However, despite emphasis on injury control and prevention, little has been done to incorporate alcohol intervention programs into care of the injured patient. Effective means of intervention exist that are consistent with the time, financial, and staffing constraints of trauma centers, and they should be implemented.

Alcoholism↗

Murine transcription factor alpha A-crystallin binding protein I. Complete sequence, gene structure, expression, and functional inhibition via antisense RNA.

alpha A-crystallin binding protein I (alpha A-CRYBP1) is a ubiquitously expressed DNA binding protein that was previously identified by its ability to interact with a functionally important sequence in the mouse alpha A-crystallin gene promoter. Here, we have cloned a single copy gene with 10 exons spanning greater than 70 kb of genomic DNA that encodes alpha A-CRYBP1. The mouse alpha A-CRYBP1 gene specifies a 2,688-amino acid protein with 72% amino acid identity to its human homologue, PRDII-BF1. Both the human and the mouse proteins contain two sets of consensus C2H2 zinc fingers at each end as well a central nonconsensus zinc finger. The alpha A-CRYBP1 gene produces a 9.5-kb transcript in 11 different tissues as well as a testis-specific, 7.7-kb transcript. alpha A-CRYBP1 cDNA clones were isolated from adult mouse brain and testis as well as from cell lines derived from mouse lens (alpha TN4-1) and muscle (C2C12). A single clone isolated from the muscle C2C12 library contains an additional exon near the 5'-end that would prevent production of a functional protein if the normal translation start site were utilized; however, there is another potential initiation codon located downstream that is in frame with the rest of the coding region. In addition, we identified multiple cDNAs from the testis in which the final intron is still present. Finally, we used an antisense expression construct derived from an alpha A-CRYBP1 cDNA clone to provide the first functional evidence that alpha A-CRYBP1 regulates gene expression. When introduced into the alpha TN4-1 mouse lens cell line, the antisense construct significantly inhibited expression from a heterologous promoter that utilized the alpha A-CRYBP1 binding site as an enhancer.

Amino Acid Sequence↗