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Biomedical subjects

L Sharpe

Publications and source records attributed to L Sharpe.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder.

We conducted a 9-cM genome scan in a large bipolar pedigree sample from the National Institute of Mental Health genetics initiative (1060 individuals from 154 multiplex families). We performed parametric and nonparametric analyses using both standard diagnostic models and comorbid conditions thought to identify phenotypic subtypes: psychosis, suicidal behavior, and panic disorder. Our strongest linkage signals (genome-wide significance) were observed on chromosomes 10q25, 10p12, 16q24, 16p13, and 16p12 using standard diagnostic models, and on 6q25 (suicidal behavior), 7q21 (panic disorder) and 16p12 (psychosis) using phenotypic subtypes. Several other regions were suggestive of linkage, including 1p13 (psychosis), 1p21 (psychosis), 1q44, 2q24 (suicidal behavior), 2p25 (psychosis), 4p16 (psychosis, suicidal behavior), 5p15, 6p25 (psychosis), 8p22 (psychosis), 8q24, 10q21, 10q25 (suicidal behavior), 10p11 (psychosis), 13q32 and 19p13 (psychosis). Over half the implicated regions were identified using phenotypic subtypes. Several regions - 1p, 1q, 6q, 8p, 13q and 16p - have been previously reported to be linked to bipolar disorder. Our results suggest that dissection of the disease phenotype can enrich the harvest of linkage signals and expedite the search for susceptibility genes. This is the first large-scale linkage scan of bipolar disorder to analyze simultaneously bipolar disorder, psychosis, suicidal behavior, and panic disorder.

Bipolar Disorder↗
PubMed2004

Modification of attentional biases in chronic pain patients: a preliminary study.

Research suggests that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. This study examined the degree to which a successful cognitive-behavioural program was able to reduce the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow-up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post-treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.

Adult↗
PubMed2004

Validity of the disease repercussion profile in patients with systemic lupus erythematosus.

The Disease Repercussion Profile (DRP) was developed for use with patients with rheumatoid arthritis (RA) and has been shown to be a valid and clinically useful assessment of patient-perceived handicap. This study aimed to determine whether the Disease Repercussion Profile was also suitable for use with patients with systemic lupus erythematosus (SLE). Sixty patients with a definite diagnosis of SLE from a consultant rheumatologist were recruited into the study. They completed a series of questionnaires that assessed quality of life, depression, anxiety, attitudes towards the illness and the DRP. Results showed that patients with SLE endorsed each of the six spheres of the DRP as being frequently affected by their illness. Activity was most often endorsed. Both relationships and social activity were equally frequently adversely affected, and more often affected than the remaining spheres of finance, emotions and appearance. However, as in RA, when any area of function was affected, it was rated as very important to the individual. Indicators of quality of life were reliably related to all areas of function, as was depression and attitudes towards illness. The present study indicates that the DRP does have relevance for patients with SLE. Strong correlations between quality of life indicators, depression, attitudes towards illness and DRP subscales and total score indicate that this measure is a valid tool to assess the effect of illness on individuals with SLE.

Adolescent↗
PubMed2003

Long-term efficacy of a cognitive behavioural treatment from a randomized controlled trial for patients recently diagnosed with rheumatoid arthritis.

OBJECTIVES: This study examined the long-term efficacy of a cognitive behavioural intervention for patients with recent-onset, seropositive rheumatoid arthritis (RA). METHODS: Fifty-three consecutive patients with less than a 2-yr history of classic or definite RA were recruited into the trial. All participants received routine medical management during the study, and half were randomly allocated to receive an 8-week adjunctive psychological intervention. All assessments were conducted blind to the allocation. This paper reports intention-to-treat analyses of the 18-month follow-up. RESULTS: Consistent with short-term results, significant differences were found between the groups in depressive symptoms. The intervention group maintained improvements in joint function, although those in routine care made similar improvements over the ensuing 18 months. At follow-up, group differences emerged for disability and anxiety. CONCLUSIONS: These results indicate that cognitive behavioural intervention offered as an adjunct to standard clinical management early in the course of RA is efficacious in producing improvements in both psychological and physical indices. Furthermore, improvements appear to increase 18 months after a brief, time-limited psychological treatment.

Adolescent↗
PubMed2001

Cooperation, control, and concession in meerkat groups.

"Limited control" models of reproductive skew in cooperative societies suggest that the frequency of breeding by subordinates is determined by the outcome of power struggles with dominants. In contrast, "optimal skew" models suggest that dominants have full control of subordinate reproduction and allow subordinates to breed only when this serves to retain subordinates' assistance with rearing dominants' own litters. The results of our 7-year field study of cooperative meerkats, Suricata suricatta, support the predictions of limited control models and provide no indication that dominant females grant reproductive concessions to subordinates to retain their assistance with future breeding attempts.

Africa, Southern↗
PubMed2001

The course of depression in recent onset rheumatoid arthritis: the predictive role of disability, illness perceptions, pain and coping.

BACKGROUND: This study aimed to investigate the course of depression for patients with recently diagnosed rheumatoid arthritis (RA) and to investigate predictors of depression. METHODS: Twenty-two patients with a history of recently diagnosed RA of less than 2 years were assessed on a variety of clinical outcome and process measures on six assessment occasions over a 21-month period. These 22 patients constituted the control group of a controlled trial and received standard outpatient clinic treatment during follow-up. RESULTS: Patients became significantly more depressed over time. A set of five factors were found to consistently predict depression at the following assessment. These were initial level of depression, disability, pain, beliefs about the consequences of arthritis and coping strategies. CONCLUSIONS: The results confirm the importance of psychological factors in early RA and their relative independence from physical findings. This is the first study to document the importance of illness perceptions in recent onset RA.

Adaptation, Psychological↗
PubMed2001

A blind, randomized, controlled trial of cognitive-behavioural intervention for patients with recent onset rheumatoid arthritis: preventing psychological and physical morbidity.

This study examined the efficacy of a cognitive and behavioural intervention (CBT) for patients with recent onset, seropositive rheumatoid arthritis. Fifty-three participants with a diagnosis of classical or definite rheumatoid arthritis, who were seropositive and had less than 2 years of disease history were recruited into the trial. All participants received routine medical management during the study, although half were randomly allocated to receive an adjunctive psychological intervention. All pre- and post-treatment assessments were conducted blind to the allocation. Analyses were conducted of treatment completers and also by intention-to-treat. Significant differences were found between the groups at both post-treatment and 6-month follow-up in depressive symptoms. While the CBT group showed a reduction in depressive symptoms, the same symptoms increased in the Standard group. At outcome but not follow-up, the CBT group also showed reduction in C-reactive protein levels. However, the CBT group did show significant improvement in joint involvement at 6-month follow-up compared with the Standard group, indicating physical improvements above those achieved with standard care. These results indicate that cognitive-behavioural intervention offered as an adjunct to standard clinical management early in the course of RA is efficacious in producing reductions in both psychological and physical morbidity

Adaptation, Psychological↗
PubMed2001

Characteristics of handicap for patients with recent onset rheumatoid arthritis: the validity of the Disease Repercussion Profile.

OBJECTIVES: To investigate the applicability of the Disease Repercussion Profile (DRP) in the assessment of people with recently diagnosed rheumatoid arthritis. Previous research using this instrument has been confined to chronic samples. METHODS: Fifty-three patients with recent onset rheumatoid arthritis completed the DRP and other commonly used clinical outcome measures. RESULTS: The life areas of the DRP were highly interrelated, with the exception of finance. The total DRP score was associated with joint function, disability, subjective pain and coping, but was most highly associated with emotional disturbance, particularly depressive symptoms. No associations were found between measures of disease or demographic variables and DRP subscales. Activity was the area most often affected, with social life, emotions and appearance all more strongly endorsed than finances and relationships. However, whenever any of the areas was endorsed as affected, its impact was inevitably rated as very important. The pattern of self-perceived handicap was different from that reported in people with chronic arthritis. CONCLUSIONS: These results offer evidence that the DRP provides a valid measure of handicap for patients with early illness even with relatively low levels of disability. However, handicap in early rheumatoid arthritis may be more highly associated with psychological distress than in later stages of the illness.

Adaptation, Psychological↗
PubMed2001

An investigation of symptom-specific muscle hyperreactivity in upper extremity cumulative trauma disorder.

OBJECTIVE: The study examined symptom-specific muscle hyperreactivity in patients with chronic pain with upper limb cumulative trauma disorder (CTD). DESIGN: Four tasks were presented in counterbalanced order and included neutral, general stressor, personal stressor, and pain stressor tasks. Ratings of stressfulness and recordings of skin conductance level confirmed the effectiveness of the experimental manipulations in inducing stress experiences for all subject groups. SETTING: The study was conducted in a university research center. PATIENTS: Thirty patients with CTD were matched as closely as possible for age and gender to control groups of chronic low back pain, arthritis, and pain-free subjects. OUTCOME MEASURES: Surface electromyograph recordings were taken from the frontalis, forearm flexors, trapezius, and lower back during baseline and tasks. RESULTS: The study found no evidence of greater muscle tension increases or extended duration of return to baseline for the CTD or low back pain patients at any of the muscle sites for any of the tasks in comparison to control groups. CONCLUSIONS: The results indicate that symptom-specific psychophysiological responses may be limited to certain subgroups rather than being characteristic of chronic musculoskeletal pain patients in general.

Adult↗
PubMed2000

Second stage of a genome scan of schizophrenia: study of five positive regions in an expanded sample.

In a previous genome scan of 43 schizophrenia pedigrees, nonparametric linkage (NPL) scores with empirically derived pointwise P-values less than 0.01 were observed in two regions (chromosomes 2q12-13 and 10q23) and less than 0.05 in three regions (4q22-23, 9q22, and 11q21). Markers with a mean spacing of about 5 cM were typed in these regions in an expanded sample of 71 pedigrees, and NPL analyses carried out. No region produced significant genomewide evidence for linkage. On chromosome 10q, the empirical P-value remained at less than 0.01 for the entire sample (D10S168), evidence in the original 43 pedigrees was slightly increased, and a broad peak of positive results was observed. P-values less than 0.05 were observed on chromosomes 2q (D2S436) and 4q (D4S2623), but not on chromosomes 9q or 11q. It is concluded that this sample is most supportive of linkage on chromosome 10q, with less consistent support on chromosomes 2q and 4q. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:864-869, 2000.

Alleles↗
PubMed2000

Individual contributions to babysitting in a cooperative mongoose, Suricata suricatta.

Evolutionary explanations of cooperative breeding based on kin selection have predicted that the individual contributions made by different helpers to rearing young should be correlated with their degree of kinship to the litter or brood they are raising. In the cooperative mongoose or meerkat, Suricata suricatta, helpers babysit pups at the natal burrow for the first month of pup life and frequent babysitters suffer substantial weight losses over the period of babysitting. Large differences in contributions exist between helpers, which are correlated with their age, sex and weight but not with their kinship to the young they are raising. Provision of food to some group members raises the contributions of individuals to babysitting. We discuss the implications of these results for evolutionary explanations of cooperative behaviour.

Animals↗
PubMed1998

Genome scan of schizophrenia.

OBJECTIVE: The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHOD: A genomewide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals--126 of them with schizophrenia-related psychoses--from 43 pedigrees. Nonparametric linkage analysis was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirically derived p values reached nominal levels of significance at eight marker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002). CONCLUSIONS: The results do not support the hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychiatric disorders) has limited power to detect genes of small effect or those that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely to contain schizophrenia susceptibility genes.

Chromosome Mapping↗
PubMed1997

Modulation of cisPlatin cytotoxicity by interleukin-1 alpha and resident tumor macrophages.

The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1 alpha) was studied in cultures of SCC-7 tumor cells with and without tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1 alpha in SCC-7 solid tumors. Neither IL-1 alpha nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1 alpha had no direct effect on tumor cell growth in vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC90 = 6.0 microM), but, the addition of IL-1 alpha (500-2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor macrophages increased cell killing (IC90 = 3.1 microM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1 alpha. The modulation of cisPlatin cytotoxicity by IL-1 alpha exhibited a biphasic dose response that paralleled the IL-1 alpha dose dependent release of H2O2 by resident tumor macrophages. Further, IL-1 alpha modification of cisPlatin cytotoxicity was prompt and inhibited by catalase. CisPlatin and exogenous H2O2 (50 microM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response. Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1 alpha treatment for 24 hrs, before cisPlatin, produced drug resistance (IC90 = 11.1 microM). Our study shows that IL-1 alpha can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explantation for the synergistic antitumor activity of cisPlatin and IL-1 alpha in vivo.

Animals↗
PubMed1996

Penetrance of schizophrenia-related disorders in multiplex families after correction for ascertainment.

Penetrance of schizophrenia and related disorders was calculated in 27 multiplex pedigrees ascertained by a consistent set of screening and selection criteria. The rationale for the study was that single major locus linkage models are frequently used on a pragmatic basis to analyze data for schizophrenia which is most likely to have a polygenic mechanism. Penetrance estimates assuming Mendelian inheritance represent maximum values and thus can provide guidance for construction of appropriate linkage models. Four diagnostic models were considered: narrow (schizophrenia and chronic schizoaffective disorder), intermediate (including other non-affective psychoses), broad (including schizotypal and paranoid personality disorders), and broad + suspected (including suspected schizophrenia spectrum disorders). Penetrance was calculated in the youngest affected adult sibship, under both dominant and recessive inheritance assumptions, either without correction, or with a correction that excluded individuals necessary to meet pedigree selection criteria. Without correction, penetrance values ranged from 0.70 to 0.90 assuming dominant and 1.0 to > 1.0 assuming recessive inheritance. After correction, the ranges were 0.30-0.51 for dominant and 0.47-0.59 for recessive models. The corrected values are likely to be overestimates given that the penetrance of any one locus in a multilocus model must be lower. It is suggested that lod score analyses of schizophrenia should attempt to derive information primarily from affected diagnoses, because information derived from unaffecteds under high penetrance models is likely to be spurious.

Adult↗
PubMed1995

Second cancers occurring after cancers of the mouth and pharynx: data from three population-based registries in Australia, Scotland and Slovenia.

Data over at least 20 years from three large population-based registries in Europe and Australasia have been used to assess the risk of second primary tumours occurring after a cancer of the mouth or pharynx. These patients have previously been shown in clinical series to be at a particularly high risk of subsequent tumours, while data from cancer registries have shown conflicting results on the magnitude of the risk. In this study, patients were found to have between a 2-fold (Scotland and New South Wales) and 4-fold (Slovenia) increase in risk of a subsequent tumour over that in the population, although the actual risk in each centre was similar (between 2.8 and 3.1 per 100 person years). The risk remained for 10 years after diagnosis of the original tumour and was primarily in the upper aerodigestive tract. The most elevated risks (approximately 10-fold) were for tumours in the oral cavity and oesophagus. These data provide higher estimates of risk than previously reported from European cancer registries for second primary tumours and emphasize the need for close follow-up of patients who may represent an appropriate population in which to assess possible new chemopreventive agents.

Digestive System Neoplasms↗