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Biomedical subjects

Sarah Crawford

Publications and source records attributed to Sarah Crawford.

4 recordsLinked to original sources

Estrogen dependent growth inhibitory effects of tamoxifen but not genistein in solid tumors derived from estrogen receptor positive (ER+) primary breast carcinoma MCF7: single agent and novel combined treatment approaches.

While many studies have documented tamoxifen's benefits as an adjuvant therapy in the treatment and prevention of recurrent breast cancer in estrogen receptor positive (ER+) breast carcinoma, this beneficial effect may decrease with long-term tamoxifen use. This experimental study was designed to compare the cytotoxic responses of ER+ primary breast cancer solid tumors derived from the MCF7 cell line to experimental therapeutics, including genistein, tamoxifen, all-trans retinoic acid (ATRA) and parthenolide in the presence and absence of exogenous beta-estradiol. The results of this study suggest that the growth inhibitory effects of tamoxifen, were dependent on beta-estradiol levels. In contrast, the cytotoxic effects of the isoflavone soy derivative, genistein, were observed to be independent of exogenous estrogen. Moreover, combined therapy using tamoxifen and genistein produced enhanced cytotoxic effects also independent of beta-estradiol levels. Additional studies involving the use of the novel agents all trans retinoic acid (ATRA) and parthenolide produced notable tumor responses and combined effects that were also estrogen-independent. Overall, these preclinical research findings suggest possible clinical applications suggesting that genistein might be a useful clinical adjuvant, particularly in post-menopausal women in whom breast cancer occurs more frequently. Moreover, this research suggests that combined treatment approaches involving the use of tamoxifen in conjunction with agents that inhibit NFkappaB pathway signaling, such as parthenolide and genistein, warrant further study.

Anticarcinogenic Agents↗

Tourette's syndrome: performance on tests of behavioural inhibition, working memory and gambling.

BACKGROUND: Tourette's syndrome (TS) is a neurodevelopmental disorder associated with fronto-striatal dysfunction. There is debate as to the extent to which TS is associated with cognitive impairment. Some authors argue that any impairments seen are attributable to comorbid psychiatric symptomatology, whilst others have suggested that uncomplicated TS is associated with mild deficits limited primarily to inhibitory processes. The present study was designed to examine this issue using carefully screened participants with TS and experimental measures thought to involve different areas of the frontal lobes. METHODS: Adolescents with TS who were screened for comorbid psychiatric disorder were compared with a healthy control group on a set of executive measures. Two tasks involving behavioural inhibition were used: a Sentence Completion task in which sentences had to be completed first with straightforward and then with nonsensical endings, and a Flanker task in which a central stimulus was surrounded by either compatible or incompatible flankers. Working memory was assessed using an N-back task, and reward learning was assessed using a Gambling task. Both accuracy and reaction times were measured for each task. RESULTS: The TS group differed significantly from the control group on both the Sentence Completion task and on the Flanker task. On the Sentence Completion task, they were slower to make both sensible and nonsensical completions, and they had higher error scores on the nonsensical completions. On the Flanker task, the TS participants were less accurate than the control group, since they were poorer on the incompatible but not the compatible trials. A similar interaction with trial type was found for speed, where the TS participants were slowed more by the incompatible versus compatible trials, although overall their performance tended to be faster than the controls. The TS group did not differ significantly from the control group on measures of working memory or reward learning. CONCLUSIONS: The findings provide further evidence that uncomplicated TS is not associated with widespread executive impairments. However, it was not clear that any differences between the groups could be attributed solely to selective inhibitory impairment.

Adolescent↗

Real-life-type problem solving in Tourette syndrome.

OBJECTIVE: The main objective of the study was to examine social problem solving in real-life-type situations in Tourette syndrome (TS). BACKGROUND: Studies of cognitive functioning in TS have usually focused on nonsocial, abstract tasks, with mixed findings as to whether there is evidence of impairment in executive functions in those without comorbid disorders. The current study focuses primarily on social functioning, using a problem-solving task known to be sensitive to frontal lobe lesions. METHODS: TS participants without comorbid diagnoses were compared with matched healthy control participants on a problem-solving task, using a range of interpersonal problem scenarios presented on video. A set of more abstract executive tests was also included. RESULTS: Participants with TS were found to perform below a matched control group on the problem-solving task both in generating a range of potential problem solutions, and in selecting appropriate final solutions. They also performed more poorly on aspects of executive function. CONCLUSIONS: This study provides evidence of difficulties in both social and nonsocial aspects of functioning in TS. The implications of the findings for our understanding of TS and problem solving are discussed.

Adult↗

Psychological needs of patients in low awareness states, their families, and health professionals.

Patients who have emerged from low awareness states may present with psychological needs that can be addressed via adapted formal clinical psychological interventions, or by behavioural techniques. Families of these patients may experience similar psychological reactions to relatives of any patients with severe brain injury, but there are also additional factors that are unique to patients in low awareness states. These sources of psychological distress for relatives are discussed. The needs of clinicians working with these clients are also discussed. It is important that services attending to the needs of clients in low awareness states also have adequate support for both relatives and clinicians.

Attitude of Health Personnel↗