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Biomedical subjects

Kathleen Carroll

Publications and source records attributed to Kathleen Carroll.

15 recordsLinked to original sources
PubMed2006

Naltrexone and disulfiram in patients with alcohol dependence and comorbid post-traumatic stress disorder.

BACKGROUND: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, the effect of these medications on alcohol use outcomes and on psychiatric symptoms is still unknown in patients with co-occurring disorders post-traumatic stress disorder (PTSD). METHODS: Patients (n = 254) with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in a medication study at three Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram; and (2) double-blind randomization to naltrexone or placebo. This resulted in four groups: (1) naltrexone alone; (2) placebo alone; (3) disulfiram and naltrexone; or (4) disulfiram and placebo. Outcomes were measures of alcohol use, PTSD symptoms, alcohol craving, GGT levels and adverse events. RESULTS: 93 individuals (36.6%) met DSM-IV criteria for PTSD. Subjects with PTSD had better alcohol outcomes with active medication (naltrexone, disulfiram or the combination) than they did on placebo; overall psychiatric symptoms of PTSD improved. Individuals with PTSD were more likely to report some side effects when treated with the combination. CONCLUSIONS: The results of this study suggest that disulfiram and naltrexone are effective and safe for individuals with PTSD and comorbid alcohol dependence.

Adult↗
PubMed2006

Global translational responses to oxidative stress impact upon multiple levels of protein synthesis.

Global inhibition of protein synthesis is a common response to stress conditions. We have analyzed the regulation of protein synthesis in response to oxidative stress induced by exposure to H(2)O(2) in the yeast Saccharomyces cerevisiae. Our data show that H(2)O(2) causes an inhibition of translation initiation dependent on the Gcn2 protein kinase, which phosphorylates the alpha-subunit of eukaryotic initiation factor-2. Additionally, our data indicate that translation is regulated in a Gcn2-independent manner because protein synthesis was still inhibited in response to H(2)O(2) in a gcn2 mutant. Polysome analysis indicated that H(2)O(2) causes a slower rate of ribosomal runoff, consistent with an inhibitory effect on translation elongation or termination. Furthermore, analysis of ribosomal transit times indicated that oxidative stress increases the average mRNA transit time, confirming a post-initiation inhibition of translation. Using microarray analysis of polysome- and monosome-associated mRNA pools, we demonstrate that certain mRNAs, including mRNAs encoding stress protective molecules, increase in association with ribosomes following H(2)O(2) stress. For some candidate mRNAs, we show that a low concentration of H(2)O(2) results in increased protein production. In contrast, a high concentration of H(2)O(2) promotes polyribosome association but does not necessarily lead to increased protein production. We suggest that these mRNAs may represent an mRNA store that could become rapidly activated following relief of the stress condition. In summary, oxidative stress elicits complex translational reprogramming that is fundamental for adaptation to the stress.

Eukaryotic Initiation Factor-2↗
PubMed2006

Family members' perceptions of augmentative and alternative communication device use.

PURPOSE: Although advancements in technology have expanded the use of augmentative and alternative communication (AAC) devices for children with disabilities, the use of AAC devices in school and home settings is often inconsistent. The purpose of this study was to examine family members' perceptions regarding the use of AAC devices. Factors that were perceived to affect student's use of AAC devices, family expectations, and benefits of AAC device use were explored. METHOD: Semistructured interviews were conducted with 6 family members (primary caregivers) of 7 youth who primarily use AAC devices to communicate in the school environment. The interviews were analyzed using cross-case analysis. RESULTS: A variety of common perspectives emerged from the data, including four thematic categories: expectations, facilitators, barriers, and benefits of AAC device use. IMPLICATIONS: Information gained in this investigation may be used to improve professional-family and teaming relationships and serve to benefit AAC users in school and home settings.

Adolescent↗
PubMed2006

The relation of brain ouabain-like compounds and idiopathic intracranial hypertension.

OBJECTIVES: To determine the relationship between levels of ouabain-like compounds (OLC) in the cerebrospinal fluid (CSF) and the occurence of idiopathic intracranial hypertension (IIH). BACKGROUND: OLC are naturally occurring inhibitors of the sodium-potassium ATPase that are found in the CSF of mammals. Since the production of CSF is dependent upon sodium-potassium ATPase activity, and since there is evidence that the increased intracranial pressure found in the condition of IIH may be the result of increased CSF production, we hypothesized that the level of endogenous OLC would be reduced in the CSF of patients with IIH. METHODS: CSF samples were obtained from n = 7 patients with IIH and n = 31 patients with neurological disorders other than IIH ("control" patients) who had lumbar puncture as part of their routine evaluation or treatment. The concentration of OLC in the CSF samples was measured using an established ELISA. RESULTS: Patients with IIH exhibited a concentration of OLC in the CSF of 0.11 +/- 0.03 ng/mL. In comparison, the concentration of OLC in CSF samples from non-IIH control patients was 0.12 +/- 0.01 ng/mL. These values were not statistically different when compared with a t-test (P= 0.31). However, the concentration of OLC did negatively correlate to the opening pressure on lumbar puncture, but only in the IIH group (r=-0.80, P= .03). Furthermore, IIH patients who were newly diagnosed or who were unsuccessfully treated (n = 5 of 7 IIH patients) exhibited OLC concentrations of 0.06 +/- 0.1 ng/mL, which is nearly lower than that of the control group (P= .06). CONCLUSIONS: The average concentration of OLC in IIH patients (treated and untreated) is unlikely to be distinguishable from that in non-IIH control patients with other neurological conditions. However, the concentration of OLC may be inversely related to the intracranial pressure in patients with IIH, and it may prove to be lower in the subgroup of untreated and unsuccessfully treated IIH patients.

Adult↗
PubMed2005

Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample.

BACKGROUND: Auditory hallucinations are often resistant to treatment and can produce significant distress and behavioral difficulties. A preliminary report based on 24 patients with schizophrenia or schizoaffective disorder indicated greater improvement in auditory hallucinations following 1-hertz left temporoparietal repetitive transcranial magnetic stimulation (rTMS) compared to sham stimulation. Data from the full 50-subject sample incorporating 26 new patients are now presented to more comprehensively assess safety/tolerability, efficacy and moderators of this intervention. METHODS: Right-handed patients experiencing auditory hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 132 minutes of rTMS was administered over 9 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. RESULTS: Hallucination Change Score was more improved for rTMS relative to sham stimulation (p = .008) as was the Clinical Global Impressions Scale (p = .0004). Hallucination frequency was significantly decreased during rTMS relative to sham stimulation (p = .0014) and was a moderator of rTMS effects (p = .008). There was no evidence of neurocognitive impairment associated with rTMS. CONCLUSIONS: Left temporoparietal 1-hertz rTMS warrants further study as an intervention for auditory hallucinations. Data suggest that this intervention selectively alters neurobiological factors determining frequency of these hallucinations.

Adult↗
PubMed2005

Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders.

BACKGROUND: Disulfiram and naltrexone are approved by the Food and Drug Administration (FDA) for the treatment of alcoholism, but these agents have not been rigorously evaluated in dually diagnosed individuals. METHOD: Two-hundred and fifty-four patients with an Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at three Veterans Administration outpatient clinics. Randomization included assignment to one of four groups: 1) naltrexone alone; 2) placebo alone; 3) (open-label) disulfiram and (blinded) naltrexone; or 4) (open-label) disulfiram and (blinded) placebo. Medication compliance was evaluated using the Microelectric Events Monitoring System. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms, alcohol craving, g-GGT levels and adverse events. RESULTS: There was a high rate of abstinence across groups. Subjects treated with an active medication had significantly more consecutive weeks of abstinence and less craving than those treated with placebo, but there were no significant group differences in other measures of alcohol consumption. There was no advantage of the combination of both medications. CONCLUSIONS: These data suggest a modest advantage for the use of disulfiram and naltrexone for this group of dually diagnosed alcohol-dependent individuals but did not suggest an advantage in the combination.

Alcohol Deterrents↗
PubMed2005

Global gene expression profiling reveals widespread yet distinctive translational responses to different eukaryotic translation initiation factor 2B-targeting stress pathways.

Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.

Amino Acids↗
PubMed2004

PEDRo: a database for storing, searching and disseminating experimental proteomics data.

BACKGROUND: Proteomics is rapidly evolving into a high-throughput technology, in which substantial and systematic studies are conducted on samples from a wide range of physiological, developmental, or pathological conditions. Reference maps from 2D gels are widely circulated. However, there is, as yet, no formally accepted standard representation to support the sharing of proteomics data, and little systematic dissemination of comprehensive proteomic data sets. RESULTS: This paper describes the design, implementation and use of a Proteome Experimental Data Repository (PEDRo), which makes comprehensive proteomics data sets available for browsing, searching and downloading. It is also serves to extend the debate on the level of detail at which proteomics data should be captured, the sorts of facilities that should be provided by proteome data management systems, and the techniques by which such facilities can be made available. CONCLUSIONS: The PEDRo database provides access to a collection of comprehensive descriptions of experimental data sets in proteomics. Not only are these data sets interesting in and of themselves, they also provide a useful early validation of the PEDRo data model, which has served as a starting point for the ongoing standardisation activity through the Proteome Standards Initiative of the Human Proteome Organisation.

Animals↗
PubMed2004

The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast.

Dcs1, the m7GpppX pyrophosphatase of Saccharomyces cerevisiae, has been reported to 'scavenge' capped 5' end fragments generated by 3'-->5' mRNA degradation. We now show that the absence of Dcs1, and the closely related Dcs2 protein, compromises cellular responses to glucose-deprivation stress as well as to step changes in glucose availability. Dcs1 and Dcs2 form homo- and heterodimers, with the heterodimer appearing as cells enter diauxie. Despite the previously observed increase in abundance of the mRNA encoding the neutral trehalase (Nth1) in the stationary phase, the total enzyme activity of Nth1 decreases in this phase of growth. Changes in trehalase activity are significant because the non-reducing disaccharide trehalose is thought to stabilize cellular components under stress conditions. In the dcs1Delta and dcs1Deltadcs2Delta mutants, normal regulation of trehalase activity is lost. Nutrient stress induces DCS1 and DCS2 transcription via the cAMP-PKA signalling pathway. Dcs1 also becomes phosphorylated as the availability of glucose diminishes, and we test the role of this phosphorylation in the stress response. Further evidence indicates that Dcs1 plays a complementary role to the translation factor eIF4E in preventing capped 5' fragments of mRNA from interfering with translation initiation. We conclude that Dcs1 function influences cellular responses to changes in nutrient avialability, while Dcs2 seems to act as a modulator of Dcs1 function.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations.

BACKGROUND: Neuroimaging studies suggest that auditory hallucinations (AHs) of speech arise, at least in part, from activation of brain areas underlying speech perception. One-hertz repetitive transcranial magnetic stimulation (rTMS) produces sustained reductions in cortical activation. Recent results of 4-day administration of 1-Hz rTMS to left temporoparietal cortex were superior to those of sham stimulation in reducing AHs. We sought to determine if a more extended trial of rTMS could significantly reduce AHs that were resistant to antipsychotic medication. METHODS: Twenty-four patients with schizophrenia or schizoaffective disorder and medication-resistant AHs were randomly allocated to receive rTMS or sham stimulation for 9 days at 90% of motor threshold. Patients receiving sham stimulation were subsequently offered an open-label trial of rTMS. Neuropsychological assessments were administered at baseline and during and following each arm of the trial. RESULTS: Auditory hallucinations were robustly improved with rTMS relative to sham stimulation. Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement. Duration of putative treatment effects ranged widely, with 52% of patients maintaining improvement for at least 15 weeks. Repetitive transcranial magnetic stimulation was well tolerated, without evidence of neuropsychological impairment. CONCLUSIONS: These data suggest that the mechanism of AHs involves activation of the left temporoparietal cortex. One-hertz rTMS deserves additional study as a possible treatment for this syndrome.

Adult↗
PubMed2003

Exposure to 17 alpha-ethinylestradiol and bisphenol A--effects on larval moulting and mouthpart structure of Chironomus riparius.

The effects of the endocrine-disrupting chemicals 17alpha-ethinylestradiol (EE) and bisphenol A (BPA) on the development of the aquatic life-cycle stages (eggs to pupa) of Chironomus riparius were investigated. The test species was exposed to sublethal concentrations of EE and BPA (10 ng/L-1mg/L) and effects on larval weight and moulting success were recorded. In addition, three mouthpart structures (mentum, mandibles, and pecten epipharyngis) present on the head capsules of fourth-instar larvae were examined for structural deformities. Moulting was delayed and larval wet weight significantly reduced (P<0.05) at the highest treatment concentration (1mg/L) of both chemicals. No significant effect on either of these parameters was noted in the remaining treatments. However, deformities in the mouthparts of C. riparius were observed at very low exposure concentrations (10 ng/L), although the incidence of deformities was greater in the chironomids exposed to EE than BPA. Effects were mainly associated with the mentum, with statistically significant differences in median deformity score (Kruskal-Wallis P<0.001) recorded for both chemicals. At similar effect concentrations, an increased percentage of exposed animals had deformities of the pecten epipharyngis; however, little evidence of deformity was noted for the mandibles. At high concentrations, where moulting and wet weight were affected, no incidence of mouthpart deformity was noted. The relevance of these results in relation to the identification of an "endocrine-sensitive" endpoint for invertebrates is discussed.

Animals↗
PubMed2002

Characteristics, beliefs, and practices of community clinicians trained to provide manual-guided therapy for substance abusers.

The successful dissemination of empirically supported addiction therapies to community providers requires an appreciation of the characteristics of those practitioners who might be willing participants in this process of technology transfer. Clinicians (N = 66) from 11 community treatment programs associated with six research-clinic partnerships of the National Drug Abuse Clinical Trials Network volunteered to be trained in Motivational Interviewing or Motivational Enhancement Therapy (MET/MI) and were assessed prior to training. The sample of clinicians was heterogeneous in education and credentials, had a high level of counseling experience, reported using a wide range of counseling techniques and orientations, but had limited prior exposure to MET/MI or to the use of treatment manuals of empirically supported therapies. In general, many of the clinicians reported beliefs and techniques that were consistent with their stated theoretical orientation and recovery status. Relatively few participants reported relying on one dominant orientation or set of techniques.

Adult↗
PubMed2002

Dual Diagnosis Motivational Interviewing: a modification of Motivational Interviewing for substance-abusing patients with psychotic disorders.

Motivational Interviewing (MI) is a brief treatment approach for helping patients develop intrinsic motivation to change addictive behaviors. While initially developed to target primary substance using populations, professionals are increasingly recognizing the promise this approach has for addressing the motivational dilemmas faced by patients who have co-occurring psychiatric and psychoactive substance use disorders. Unfortunately, this recognition has not lead to a clear explication of how MI might be adopted for specific diagnostic populations of dually diagnosed patients. In this article we describe how we have applied the principles and practices of MI to patients who have psychotic disorders and co-occurring drug or alcohol use problems. Specifically, we provide two supplemental guidelines to augment basic MI principles (adopting an integrated dual diagnosis approach, accommodating cognitive impairments and disordered thinking). We present recommended modifications to primary MI skill sets (simplifying open-ended questions, refining reflective listening skills, heightening emphasis on affirmation, integrating psychiatric issues into personalized feedback and decisional balance matrices). Finally, we highlight other clinical considerations (handling psychotic exacerbation and crisis events, recommended professional qualifications) when using MI with psychotic disordered dually diagnosed patients.

Adult↗
PubMed2002

Population responses of the freshwater amphipod Gammarus pulex (L.) to an environmental estrogen, 17alpha-ethinylestradiol.

The effects of the environmental estrogen 17alpha-ethinylestradiol (EE) on mixed populations of 90 individual Gammarus pulex were examined following a 100-d exposure in a flow-through system. Counts of total animal numbers revealed that, in all treatment groups, population size dramatically increased due to recruitment, with neonate and juvenile gammarids the most abundant. At concentrations of 1 and 10 microg/L EE, the recorded mean population sizes of 385 and 411, respectively, were significantly greater (p = 0.018) than the control (169). Mean population sizes in the solvent control (257) and 100 ng/L EE treatment (267) were not significantly different (p > 0.05) from the control. In addition to total counts, detailed image analysis of each individual animal allowed the assessment of length-frequency distributions, adult sex ratio, number of precopula pairs/ovigerous females, and measurement of secondary antenna and gnathopod length (secondary sex characteristics). The sex ratio of adults at 100 ng, 1 microg, and 10 microg/L EE was greater than 2:1 (female:male), and significantly more females (p = 0.008) were recorded at these concentrations compared with the control. The number of male adults, precopula guarding pairs, and ovigerous females did not differ between treatments (p > 0.05). Secondary antennal and gnathopod length in males was consistently greater than in females (p < or = 0.001), but comparison between groups revealed no difference in these parameters.

Animals↗