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Adam Cohen

Publications and source records attributed to Adam Cohen.

8 recordsLinked to original sources
PubMed2007

Functional neuroimaging of word priming in males with chronic schizophrenia.

Word-priming studies have suggested that the associative disturbance of schizophrenia may reflect aberrant spread of activation through the lexicon of the brain. To explore this, we examined lexical activation using a semantic word-priming paradigm coupled with functional magnetic resonance imaging (fMRI). We also wanted to determine whether brain activation to this paradigm correlated with relevant clinical symptom measures. In addition to completing clinical symptom measures, twelve chronic patients and twelve demographically matched control subjects completed a lexical-decision semantic-priming paradigm developed as an event-related BOLD fMRI task. This paradigm consisted of words that differed in connectivity. Words with many connections between shared semantic associates are considered high in connectivity and produce the largest behavioral semantic priming effects in control subjects, while words with few connections between shared semantic associates are considered low in connectivity and produce a relatively smaller amount of semantic priming. In fMRI, a respective step-wise increase in activation from high connectivity to low connectivity to unrelated word pairs was expected for normal subjects. Controls showed the expected pattern of activation to word connectivity; however, patients showed a less robust pattern of activation to word connectivity. Furthermore, this aberrant response correlated with measures of Auditory Hallucinations, Distractive Speech, Illogicality, and Incoherence. The patients did not display left frontal and temporal activation as a function of the degree of word connectivity as seen in healthy controls. This may reflect a disease-related disturbance in functional connectivity of lexical activation, which in turn may be associated with clinical symptomatology.

Adult↗
PubMed2006

Evaluation of proinflammatory cytokines and inflammation markers as biomarkers for the action of thiazolidinediones in Type 2 diabetes mellitus patients and healthy volunteers.

AIMS: Thiazolidinediones (TZDs) not only enhance cellular glucose transport but are reported to have potent anti-inflammatory effects. These effects may play an important role in the insulin sensitizing mechanism, and possibly precede the effects on parameters of glucoregulation. We sought to investigate whether these anti-inflammatory effects could yield early responding biomarkers for TZD action in Type 2 diabetes mellitus (T2DM) patients and healthy volunteers (HV) to expedite early clinical development of novel compounds. METHODS: We investigated the timing of treatment effects on several proinflammatory cytokines and markers of inflammation in comparison with effects on typical measures of glucoregulation in T2DM patients and HV receiving rosiglitazone 4 mg or placebo twice daily for 6 weeks. RESULTS: We found a significant reduction in interleukin (IL)-6 [-39.4%, confidence interval (CI) - 60.0, - 8.2] and white blood cell count (-18.4%, CI - 30.2, - 4.5) after 4 weeks of treatment in the T2DM group. These anti-inflammatory effects did not precede the effects on typical parameters of glucoregulation in the T2DM group and there was no significant anti-inflammatory response in the HV group. CONCLUSION: We could not identify biomarkers that precede the effects of rosiglitazone on parameters of glucoregulation in T2DM or that have a significant response in HV. However, the IL-6 response observed in this study indicates a potential role for this cytokine as complementary biomarker in clinical 'proof of concept' studies with novel TZDs.

Adult↗
PubMed2006

Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma.

Among the drug combinations designed for the initial treatment of multiple myeloma, none has been unequivocally shown to be superior. However, a regimen leading to a high response rate and a low incidence of adverse events is highly desirable. We report the results of a phase II clinical trial involving 45 patients with Durie-Salmon stage II and III multiple myeloma. Doxorubicin and dexamethasone were given for 2 or 3 months followed by thalidomide and dexamethasone for 2 months (AD-TD regimen) with prophylactic antibiotics and daily aspirin (81 mg/d). Among the 42 patients whose response could be assessed, 38 responded to therapy (90.5%). The intent-to-treat response rate was 84.4% with seven complete responses (CR 15.5%), nine near complete responses (nCR 20.0%), and 22 partial responses (PR 48.9%). Two patients had stable disease (4.4%), and two progression of disease (4.4%). Normalization of the free light chain ratio after one or two cycles of treatment was highly predictive of achievement of CR or nCR. Patients tolerated the treatment well although five patients developed thromboembolic complications (11%). AD-TD administered with low dose aspirin for deep vein thrombosis prophylaxis was well tolerated and yielded a high response rate with minimal treatment-related morbidity.

Adult↗
PubMed2006

Acting intentionally and the side-effect effect.

The concept of acting intentionally is an important nexus where theory of mind and moral judgment meet. Preschool children's judgments of intentional action show a valence-driven asymmetry. Children say that a foreseen but disavowed side effect is brought about "on purpose" when the side effect itself is morally bad, but not when it is morally good. This is the first demonstration in preschoolers that moral judgment influences judgments of whether something was done on purpose (as opposed to judgments of purpose influencing moral judgment). Judgments of intentionality are usually assumed to be purely factual. That these judgments are sometimes partly normative-even in preschoolers-challenges current understanding. Young children's judgments regarding foreseen side effects depend on whether the children process the idea that the character does not care about the side effect. As soon as preschoolers effectively process the theory-of-mind concept "not care that P," children show the side-effect effect.

Affect↗
PubMed2004

A phylogeny of caenorhabditis reveals frequent loss of introns during nematode evolution.

Since introns were discovered 26 years ago, people have wondered how changes in intron/exon structure occur, and what role these changes play in evolution. To answer these questions, we have begun studying gene structure in nematodes related to Caenorhabditis elegans. As a first step, we cloned a set of five genes from six different Caenorhabditis species, and used their amino acid sequences to construct the first detailed phylogeny of this genus. Our data indicate that nematode introns are lost at a very high rate during evolution, almost 400-fold higher than in mammals. These losses do not occur randomly, but instead, favor some introns and do not affect others. In contrast, intron gains are far less common than losses in these genes. On the basis of the sequences at each intron site, we suggest that several distinct mechanisms can cause introns to be lost. The small size of C. elegans introns should increase the rate at which each of these types of loss can occur, and might account for the dramatic difference in loss rate between nematodes and mammals.

Amino Acid Sequence↗
PubMed2004

Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life.

PURPOSE: This study was designed to assess whether sleep disturbance is more frequent among patients with partial seizures and what impact on quality of life (QoL) sleep disturbance may have on patients with partial seizures. METHODS: Questionnaire booklets were mailed to 1,183 patients from four Dutch clinics. Each patient was asked to find two age- and gender-matched controls to complete the same set of questionnaires [Sleep Diagnosis List (SDL), Medical Outcomes Study (MOS)-Sleep Scale, Groningen Sleep Questionnaire, Epworth Sleepiness Scale, and the SF-36 Health Survey]. The prevalence of sleep disturbance, based on the SDL, was compared between those with partial epilepsy and controls. Mean scores on sleep and the SF-36 Physical (PCS) and Mental (MCS) Component Summary scales were compared. RESULTS: Responses from 486 patients and 492 controls were analyzed. Respondents with partial epilepsy had a highly significant, twofold higher prevalence of sleep disturbance compared with controls (38.6 vs. 18.0%; p < 0.0001). Most sleep-disorder subscales showed significant abnormalities in respondents with epilepsy, compared with controls. Mean SF-36 MCS and PCS scores were significantly lower in respondents with epilepsy compared with controls in both the strata with sleep disturbance and without (all p values <0.05). The presence of a sleep disturbance in respondents with epilepsy was associated with the greatest impairment in QoL. CONCLUSIONS: Sleep disturbance is more than twice as prevalent in persons with partial epilepsy compared with controls, and most domains of sleep are significantly disturbed. Persons with partial epilepsy have significant QoL impairment, and sleep disturbance further compounds this.

Adult↗