Evaluation of a lysostaphin-fusion protein as a dry-cow therapy for Staphylococcus aureus mastitis in dairy cattle.

This study evaluated the efficacy of a recombinant lysostaphin fused to a protein transduction domain (rLYS-PTD) as a dry-cow therapy for the treatment of experimentally induced chronic, subclinical Staphylococcus aureus mastitis. Twenty-two Holstein dairy cows were experimentally infected with Staph. aureus in a single pair of diagonal mammary quarters approximately 45d before dry off. Staphylococcus aureus-infected mammary quarters of cows were randomly assigned to 1 of 2 treatment groups at dry off: (1) 279mg of rLYS-PTD in 50mL of vehicle (n=11 cows; 22 quarters) or (2) 50mL of vehicle solution (n=11 cows; 22 quarters) by intramammary infusion. All cows were followed for 30d postpartum to determine cure rates using bacteriologic culture, somatic cell counts, and clinical mastitis scores. No cures were recorded in either the treatment or control groups. Milk somatic cell count, bacterial colony counts, and mastitis scores did not significantly differ between treatment groups. In conclusion, rLYS-PTD was not an effective dry-cow therapeutic for chronic, subclinical Staph. aureus mastitis at the tested dose and formulation.

Follicular expression of a human beta-cell leukaemia/lymphoma-2 (Bcl-2) transgene does not decrease atresia or increase ovulation rate in swine.

Transgenic (TG) gilts carrying a human Bcl-2 cDNA transgene driven by mouse inhibin-alpha subunit promoter were produced and evaluated to determine if ectopic expression of Bcl-2 in the ovaries would decrease the frequency of atresia in antral follicles and increase ovulation rate. Immunohistochemical analysis showed that the Bcl-2 transgene protein was expressed in granulosa and theca cells, in 86% of healthy and 54% of atretic follicles analysed in TG prepubertal and Day 50 pregnant gilts combined (n = 24). In contrast, Bcl-2 transgene protein was expressed in only 1.4% of healthy and 0% of atretic follicles in non-TG littermates (n = 13). Real-time reverse transcription-polymerase chain reaction analysis confirmed that human Bcl-2 was expressed in follicles of TG gilts. The atresia rate for the TG and non-TG groups did not differ (P > 0.05) for prepubertal (45 v. 59%) and Day 50 pregnant gilts (53 v. 52%) respectively. The mean +/- s.e.m. ovulation rate did not differ (P > 0.5) between TG (15.9 +/- 0.8, n = 12) and non-TG (16.4 +/- 0.6, n = 7) Day 50 pregnant gilts. The molecular basis of the failure of ectopic Bcl-2 expression to increase the ratio of healthy to atretic follicles is unknown, but it is possible that the activity of the mitochondrial-dependent cell death pathway was not neutralized by ectopic expression of human Bcl-2 or that other cell death pathways compensated for the decreased mitochondrial-dependent cell death.

The role of mu-opioid receptors in inflammatory hyperalgesia and alpha 2-adrenoceptor-mediated antihyperalgesia.

The purpose of the present study was to investigate the role of mu-opioid receptor in inflammatory hyperalgesia in intact and in spinalized animals and the interaction between mu-opioid and alpha2-adrenergic receptor in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and heat stimuli were studied in mu-opioid receptor knockout mice and wildtype control mice. Thermal nociception was evaluated by measuring paw withdrawal latencies to radiant heat applied to the hindpaws. Mechanical nociception was measured by von Frey monofilament applications to the hindpaws. Intraplantar carrageenan-induced (1 mg/40 microl) mechanical and heat hyperalgesia were compared in micro-opioid knockout and wildtype mice. The effect of systemically administered alpha2-adrenergic receptor agonist dexmedetomidine (1-10 microg/kg) was evaluated on mechanical and thermal withdrawal responses under normal and inflammatory state in knockout and wildtype mice. The role of micro-opioid receptor in descending modulation of nociception was studied by assessing mechanical and heat withdrawal responses before and after mid-thoracic spinalization. Withdrawal responses to radiant heat and von Frey monofilaments were similar in mu-opioid knockout and wildtype mice before and after the carrageenan induced hindpaw inflammation. Also, antinociceptive effects of dexmedetomidine in thermal and mechanical nociceptive tests were similar before carrageenan induced hindpaw inflammation. However, the potency of dexmedetomidine was significantly reduced in carrageenan-induced mechanical hyperalgesia in mu-opioid knockout mice compared to the wildtype control mice. Thermal and mechanical withdrawal responses were similar between mu-opioid knockout and wildtype mice before and after mid-thoracic spinalization. Our observations indicate that the mu-opioid receptors do not play an important role in alpha2-adrenergic receptor agonist-mediated acute antinociception. In addition, micro-opioid receptors are not tonically involved in the modulation of inflammation-induced mechanical and thermal hyperalgesia, and the supraspinal control of spinal reflexes. However, in the presence of inflammation, mu-opioid receptors play an important role in the antihyperalgesic actions of an alpha2-adrenergic receptor agonist.

Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice.

Mutations in the human ectodysplasin-A (EDA) are responsible for the most common form of the ectodermal dysplasia and the defective orthologous gene in mice produces the tabby phenotype, suggesting its vital role in the development of hair, sweat glands and teeth. Among several EDA splice isoforms, the most common and the longest EDA splice isoforms, EDA-A1 and EDA-A2, differing by only two amino acids, activate NF-kappaB-promoted transcription by binding to distinct receptors, EDAR and XEDAR. The extent to which any particular isoform is sufficient for the formation of hair, sweat glands or teeth has remained unclear. Here we report that transgenic expression of the mouse EDA-A1 isoform in tabby (EDA-less) males rescued development of several skin appendages. The transgenic tabby mice showed almost complete restoration of hair growth, dermal ridges, sweat glands and molars. The number of hair follicles in the transgenic mice is the same as in wild-type; though the development of follicles and associated glands varies from indistinguishable from wild-type to smaller and/or only partially formed. These results suggest that the other EDA isoforms may not be absolutely required for skin appendage formation, but consistent with distinctive temporal and spatial expression of the EDA-A2 isoform, are likely required for appropriate timing and completeness of development. Our data provide the first direct physiological evidence that EDA-A1 is a key regulator of hair follicle and sweat gland initiation; its soluble ligand form could aid in deriving therapeutic reagents for conditions affecting hair and sweat gland formation.

Murine inter-strain polymorphisms alter gene targeting frequencies at the mu opioid receptor locus in embryonic stem cells.

Chromosomal regions near the mu opioid receptor gene are implicated in morphine preference by quantitative trait loci studies. Differences in expression of the mu opioid receptor are expected to contribute to differences in inter-individual (humans) or strain-specific (mice) responses to painful stimuli, opiate drugs, and addictive behaviors. The search for relevant genetic elements is hindered by a lack of inter-strain (or inter-individual) genomic sequence information. This work describes 9.3 kb of DNA sequence surrounding exons 2 and 3 of the murine mu opioid receptor gene from both 129/Sv and C57BL/6 strains. While the exons are perfectly conserved, intronic sequences demonstrate approximately a 2.5% divergence between the strains. Polymorphism within these intronic regions may effect either primary transcript stability or C-terminal splicing. Homologous recombination frequencies of targeting vectors harboring mu opioid receptor gene sequences have also been compared in embryonic stem cells derived from these strains. Non-isogenic targeting reduces homologous recombination in both 129/Sv and C57BL/6 embryonic stem cells by greater than 15-fold. These findings are the first to examine C57BL/6 embryonic stem cells for non-isogenic targeting frequencies and to define polymorphisms that exist between these mouse strains which might contribute to opioid behaviors.

A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity.

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.

Application of cDNA microarrays to examine gene expression differences in schizophrenia.

Using cDNA microarrays we have investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA neuroarray, comprised of genes related to brain function, was used to screen pools of samples from the cerebellum and prefrontal cortex from a matched set of subjects, and middle temporal gyrus, from a separate subject cohort. Samples of cerebellum and prefrontal cortex from neuroleptic naive patients were also included. Genes that passed a 3% reproducibility criterion for differential expression in independent experiments included 21 genes for drug-treated patients and 5 genes for drug-naive patients. Of these 26 genes, 10 genes were increased and 16 were decreased. Many of the differentially expressed genes were related to synaptic signaling and proteolytic functions. A smaller number of these genes were also differentially expressed in the middle temporal gyrus. The five genes that were differentially expressed in two brain regions from separate cohorts are: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide; sialyltransferase; proteasome subunit, alpha type 1; ubiquitin carboxyl-terminal esterase L1; and solute carrier family 10, member 1. Identification of patterns of changes in gene expression may lead to a better understanding of the pathophysiology of schizophrenia disorders.

Region-specific transcriptional response to chronic nicotine in rat brain.

Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978+/-0.0035 from 0.941+/-0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10(-14)) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K(+) channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.

Attrition prevention with individuals awaiting publicly funded drug treatment.

AIMS: To evaluate the effectiveness of a motivational intervention to reduce attrition from a waiting list for substance abusers seeking publicly funded treatment. DESIGN: Randomized clinical trial comparing an "attrition prevention" condition to standard care while awaiting treatment admission. SETTING: A centralized substance abuse assessment and referral center in Seattle, Washington. PARTICIPANTS: Substance abusers (n = 654) eligible for publicly funded drug abuse treatment. MEASUREMENTS: Alcohol and drug use, substance-related negative consequences, areas in need of help, perceived need for help, emotional status, readiness to change, reasons for seeking and perceived barriers to entering treatment. FINDINGS: Overall, approximately 70% of clients entered treatment, and of these approximately 70% completed their assigned treatment. Those who entered treatment showed significant reductions in substance use and improved psychosocial function at a short-term 3-month follow-up. However, the attrition prevention intervention had no differential effect on treatment entry, completion or outcome compared to the standard waiting list. Further, there were no differences across therapists on these outcome measures. CONCLUSIONS: A motivational attrition prevention intervention did not enhance treatment entry, completion or outcome among treatment-seeking substance abusers. It is suggested that alternative strategies, such as contingency management and case management, may help facilitate treatment entry for individuals seeking publicly funded treatment.

Sources of motivation for abstinence: a replication analysis of the reasons for quitting questionnaire.

The Reasons for Quitting Questionnaire (RFQ) as modified by McBride and colleagues (C. M. McBride et al., 1994) for use with substance users other than tobacco smokers, was administered to individuals approved for public-sector addiction treatment. Four motivation dimensions, similar to those found by McBride et al., were identified: self-concept issues, health concerns, legal issues, and social influence. A forced two-component solution yielded dimensions interpretable as intrinsic and extrinsic motivation. Self-concept issues provided the highest levels of motivation for abstinence in this sample, with moderate levels provided by health concerns, and the lowest levels provided by legal and social influence components. Intrinsic motivation was higher than extrinsic motivation. Logistic regression models, with adjustment for total motivation, tested the association of successful abstinence during a follow-up period with baseline extrinsic and intrinsic motivation, and with the difference between intrinsic and extrinsic levels. All three associations were significant: intrinsic motivation (positive association), extrinsic motivation (negative association), and the difference score (positive association). The results suggest the usefulness of the 20-item modified RFQ in evaluating motivation for abstinence among treatment seekers exhibiting severe negative consequences of addiction. Testing with samples varying in severity of addiction consequences is recommended.

Gene expression profile in early stage of retinoic acid-induced differentiation of human SH-SY5Y neuroblastoma cells.

PURPOSE: The human SH-SY5Y cell line is an established model for retinoic acid (RA)-induced neural differentiation. We employed a broad human 15K microarray (15,000 genes) and focused Neuroarray (1152 genes) to examine changes in gene expression early in the process of differentiation (6 hr), before morphology or growth changes are observed. METHODS: 33 P-labeled CDNA probes prepared from RNA extracts of RA-treated and control cultures were hybridized to array membranes, and levels of expression were quantified and compared. RESULTS: In the 15K array, 19 % of the genes were decreased (0.4 % were named genes and the remainder were expressed sequence tags (ESTs) or unknowns), and 9 % were increased (4.2 % named genes). In the Neuroarray, 3 % were decreased and 8 % were increased. CONCLUSIONS: Summary gene profiles are presented, which include transcription factors, genes associated with cell cycle, cell shape, neurotransmission, intermediary filaments, and others. The prevalence of down-regulated genes in the broad 15K array and up-regulated genes in the neuro-focused array suggests a pattern shift in gene expression associated with differentiation. The predominance of ESTs among the down-regulated genes indicates a great number of as-yet-unidentified genes are repressed in early stage neural differentiation.

Assembly and use of a broadly applicable neural cDNA microarray.

cDNA microarrays provide an efficient method to analyze gene expression patterns in thousands of genes in parallel. In some cases, large unfocused collections of cDNAs have been used in hybridization studies, in others small logically defined collections of tissue specific arrays have been used. Here we describe the bioinformatic selection of 1152 named human cDNAs specifically designed for neuroscience applications, arrayed on nylon membranes at high density. cDNAs were chosen which represent all the major cellular types of the brain including; neurons, astrocytes, microglia, and oligodendrocytes. Gene families chosen include cell type specific markers, ion-channels, transporters, receptors, and cell adhesion molecules among many others. These arrays were used with region specific samples from human brain to determine MRNA expression profiles for each region. Used with 33p labeled complex probes, this is a low cost, highly sensitive approach for tbc investigator to focus on tissue specific genes of interest where samples of limiting amounts of RNA are used. This selected set of brain-relevant cDNAs should be widely useful in the analysis of gene expression patterns from brain tissues as well as neural cell lines.

Relationship between follow-up rates and treatment outcomes in substance abuse research: more is better but when is "enough" enough?

AIMS: To examine the effects of different follow-up rates on estimates of treatment outcome and predictive models thereof, and to specify participant characteristics associated with tracking difficulty. DESIGN: An observational study using data collected for a randomized, experimental design. SETTING: The King County Assessment Center in Seattle, Washington, an organization responsible for referral to publicly funded substance abuse treatment. PARTICIPANTS: Substance-addicted individuals referred to publicly funded inpatient or outpatient treatment. MEASUREMENTS: Standardized self-report instruments measuring substance use, substance use consequences and general functioning. Chart review was used to measure treatment entry and completion. FINDINGS: There was a significant association between follow-up difficulty and outcomes related to addiction treatment and later substance use. However, outcome estimates based on 60% of the sample who were easiest to locate were only minimally different from those based on the 90-100% ultimately captured, and predictive models of outcome based on the 60% group were reasonably similar to those based on the final sample. Of baseline characteristics examined, only age was associated with later tracking difficulty. CONCLUSIONS: Studies reporting follow-up rates below 70% may produce valid findings and study attrition may be largely unpredictable from participant characteristics at baseline. However, a number of factors such as type of population studied, geographical location of the sample, reasons for loss to follow-up and sample size must be considered when attempting to generalize the findings of this study.

To thine own self be true: self-concept and motivation for abstinence among substance abusers.

Individuals approved for public-sector addiction treatment were interviewed regarding their reasons for attempting abstinence. Follow-up interviews were completed 3 to 6 months after participants' removal from county-controlled treatment wait-lists. Rates of continuous self-reported abstinence for 90 days preceding follow-up were positively associated with motivation linked to discrepancies between substance use and self-standards. Characteristics associated with high identity-linked motivation were cocaine preference, a history of reducing self-dissatisfaction through substance use, low rewards and high costs associated with using. and low support for the user identity among significant others. The perception of discrepancies between substance use and self-standards was an effective motivator of abstinence even among those who reported previous use of substances to dampen self-dissatisfaction.

Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse.

Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The ability of anti-PC Abs using H chains other than the V1 H chain to protect against pneumococcal infection remains controversial. We generated V1(-/-) knockout mice to determine whether protective anti-PC Abs could be produced in the absence of the V1 gene. No anti-PC Abs were produced in V1(-/-) mice immunized with avirulent SPn; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice. These Abs provided poor protection against virulent SPn; thus, <25% of V1(-/-) mice survived challenge with 10(4) bacteria as compared with 100% survival of V1(+/+) mice. The anti-PC Abs in V1(-/-) mice were heteroclitic, binding to nitrophenyl-PC better than to PC. None of nine hybridomas produced from V1(-/-) mice provided passive protection. However, the V1(-/-) mice produced normal amounts of Ab to SPn proteins that can partially protect mice against SPn. These data indicate that the V1 gene is critical for the production of anti-PC Abs providing optimum protection against infection with SPn, and the V1(-/-) mice could be useful in unmasking epitopes other than the immunodominant PC epitope on SPn capable of providing cross protection.

Esophagogastric adenocarcinoma in an E1A/E1B transgenic model involves p53 disruption.

We studied tumorigenesis and p53 immunostaining in a murine transgenic model introducing E1A/E1B under the control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter in which adenocarcinoma occurs at the squamocolumnar junction in the foregut, predominantly in males, and at no other site. Mutations of p53 are frequent in human esophageal adenocarcinoma and the E1B gene product interferes with p53-mediated apoptosis, inhibiting tumor suppression at the G(1)/S checkpoint. Transgenic animals were generated utilizing a purified linear 6.7 kb fragment of plasmid DNA containing MMTV-LTR/E1A/E1B and were confirmed by dot blot hybridization of tail DNA to (32)P-labeled E1A/E1B probe and polymerase chain reaction (PCR) amplification of E1A. Transgenic and control animals were observed for morbidity and weight changes. Eleven of 45 animals were transgenic (24% efficiency) with an estimated 5 to 57 copies of the gene per genome. Profound weight loss (>20%) led to sacrifice or death of one of five females (at 12 weeks) and four of six males (at 16 to 17 weeks). Grossly visible tumors (2 to 10 mm) were noted in the forestomach at the visible margin between the proximal (squamous-lined) stomach and the distal glandular stomach. Histologic sections confirmed adenocarcinoma arising in each case at the squamocolumnar junction with glandular formation, pleomorphism, and frequent mitotic figures. Immunostaining was positive for p53 indicating accumulation of mutated or altered p53 protein. E1A/E1B transgenic animals developed macroscopic and microscopic adenocarcinoma at the squamocolumnar junction, which corresponds to adenocarcinoma at the human esophagogastric junction. Disruption of p53 was present in the transgenic model as in the human cancer.

"I already stopped": abstinence prior to treatment.

AIMS: To determine pre-treatment abstinence rates among treatment seekers and identify factors associated with pre-treatment abstinence. To evaluate the association between pre-treatment abstinence and subsequent outcome. DESIGN: An observational study using data collected for a randomized, experimental design. SETTING: Conducted with participants immediately after assessment for publicly funded substance abuse treatment at the King County Assessment Center (KCAC) in Seattle. PARTICIPANTS: People referred for outpatient or inpatient treatment by KCAC who had illicit drug use in the previous 90 days (N = 565). Participants waited a median of 12 days (range = 0-108 days) until either treatment entry or waiting-list dropout. MEASUREMENTS: A modified Drug History Questionnaire quantified drug use at baseline, treatment entry or waiting-list dropout and 3 months later. Other measurement methods: Stages of Change Readiness and Treatment Eagerness Scale, participant confidence ratings and KCAC chart review. FINDINGS: Sample-wide, 45% of participants reported abstinence from initial assessment to when they entered or failed to enter treatment. Higher rates of abstinence were associated with shorter waiting periods, less substance use prior to initial assessment and higher scores on change readiness. Pre-treatment abstinence was not associated with either treatment entry or completion. There was a non-significant trend towards less improvement in substance use with pre-treatment abstinence, with the greatest effect observed for short waits. CONCLUSIONS: Participants can become abstinent prior to treatment, but this is not a good predictor of treatment entry, completion or outcome. A decisional balance strategy may be a more productive use of client and treatment program energy.

Mice deficient in the candidate tumor suppressor gene Hic1 exhibit developmental defects of structures affected in the Miller-Dieker syndrome.

HIC1 is a candidate tumor suppressor gene which is frequently hypermethylated in human tumors, and its location within the Miller-Dieker syndrome's critical deletion region at chromosome 17p13.3 makes it a candidate gene for involvement in this gene deletion syndrome. To study the function of murine Hic1 in development, we have created Hic1 -deficient mice. These animals die perinatally and exhibit varying combinations of gross developmental defects throughout the second half of development, including acrania, exencephaly, cleft palate, limb abnormalities and omphalocele. These findings demonstrate a role for Hic1 in the development of structures affected in the Miller-Dieker syndrome, and provide functional evidence to strengthen its candidacy as a gene involved in this disorder.

Alcohol problems in women admitted to a level I trauma center: a gender-based comparison.

BACKGROUND: Male patients constitute such a large proportion of trauma patients that most studies of alcohol problems in trauma patients have been carried out with clinical data largely or totally contributed by male patients. It may be incorrect to assume that the nature of alcoholism in women and men is identical, or that the size of the problem among women is small, eliminating the need to specifically study female patients. The purpose of this study was to perform a gender-based comparison of alcohol problems in trauma patients. METHODS: Admitted injured patients underwent routine screening, including a blood alcohol concentration, serum gamma-glutamyl transpeptidase, and the Short Michigan Alcohol Screening Test. A random sample of screen positive women and men underwent a comprehensive alcohol use and psychosocial assessment, and the results were compared by gender. RESULTS: The screen-positive rate was higher for men, 51% versus 34% (p < 0.01). However, screen-positive women and men had similar problem severity as reflected by mean blood alcohol concentration (162 mg/dL vs. 142 mg/dL, p = 0.16) and Short Michigan Alcohol Screening Test scores (4.6 vs. 5.0, p = 0.32). The Alcohol Use Disorders Identification Test, NIMH-DIS, and Severity of Alcohol Dependence Data form showed that female trauma patients with alcohol problems have the same severity of dependence symptoms as men. However, women were significantly more likely to have liver dysfunction, depression, psychological distress, and recent physical, emotional, or sexual abuse. CONCLUSION: Alcohol problems are more common in male trauma patients, but women with alcohol problems are just as severely impaired, have at least as many adverse consequences of alcohol use as their male counterparts, and have more evidence of alcohol-related physical and psychological harm.