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Biomedical subjects

Sarah Brown

Publications and source records attributed to Sarah Brown.

11 recordsLinked to original sources
PubMed2005

Minimization--reducing predictability for multi-centre trials whilst retaining balance within centre.

Minimization is often used to assign patients to treatment groups to ensure good balance in patient numbers within centre and other prognostic factors. Balance within centre is preferable since large imbalances between treatment arms may have logistical implications for centres, such as cost and resource implications. However, recent concern over high predictability of treatment allocation by centres when using minimization has caused this method to be questioned. We used data from current clinical trials to assess predictability and summarize subsequent within-centre imbalances with the aim of finding the most effective minimization method for reducing predictability whilst still retaining sufficient balance within centre, when randomization is to one of two treatments. We compared prediction rates and imbalances for deterministic minimization, and minimization incorporating various random elements, p (p=0.95,0.90,0.80,0.75,0.70). We also compared prediction rates and imbalance when centre was and was not included as a stratification factor. Incorporating a random element proved successful in reducing prediction rates whilst minimizing the inevitable increase in within-centre imbalance, whereas excluding centre as a stratification factor incurred major within-centre imbalance. We therefore suggest that minimization can still be used, and that centre can be included as a stratification factor, but a random element has to be incorporated into the minimization algorithm. Minimization incorporating a random element of 0.80 is the most efficient method to use based upon the simulations undertaken in this study of real clinical trial data using different probabilities of allocation.

Algorithms↗
PubMed2005

Recruitment of a foreign quinone into the A1 site of photosystem I. Consecutive forward electron transfer from A0 TO A1 to FX with anthraquinone in the A1 site as studied by transient EPR.

In photosystem I (PS I), phylloquinone (PhQ) acts as a low potential electron acceptor during light-induced electron transfer (ET). The origin of the very low midpoint potential of the quinone is investigated by introducing anthraquinone (AQ) into PS I in the presence and absence of the iron-sulfur clusters. Solvent extraction and reincubation is used to obtain PS I particles containing AQ and the iron-sulfur clusters, whereas incubation of the menB rubA double mutant yields PS I with AQ in the PhQ site but no iron-sulfur clusters. Transient electron paramagnetic resonance spectroscopy is used to investigate the orientation of AQ in the binding site and the ET kinetics. The low temperature spectra suggest that the orientation of AQ in all samples is the same as that of PhQ in native PS I. In PS I containing the iron sulfur clusters, (i) the rate of forward electron transfer from the AQ*- to F(X) is found to be faster than from PhQ*- to F(X), and (ii) the spin polarization patterns provide indirect evidence that the preceding ET step from A0*- to quinone is slower than in the native system. The changes in the kinetics are in accordance with the more negative reduction midpoint potential of AQ. Moreover, a comparison of the spectra in the presence and absence of the iron-sulfur clusters suggests that the midpoint potential of AQ is more negative in the presence of F(X). The electron transfer from the AQ- to F(X) is found to be thermally activated with a lower apparent activation energy than for PhQ in native PS I. The spin polarization patterns show that the triplet character in the initial state of P700)*+AQ*- increases with temperature. This behavior is rationalized in terms of a model involving a distribution of lifetimes/redox potentials for A0 and related competition between charge recombination and forward electron transfer from the radical pair P700*+A0*-.

Anisotropy↗
PubMed2003

An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder.

BACKGROUND: Despite the increasing recognition of comorbid attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) in adults, there are no prospective trials of pharmacological agents to treat ADHD in these patients. Given the efficacy of bupropion for ADHD in adults, as well as its use in the management of bipolar depression, we studied the tolerability and efficacy of sustained-release (SR) bupropion in adults with ADHD plus BPD. METHODS: This was an open, prospective, 6-week trial of bupropion SR (up to 200 mg b.i.d.) in adults with DSM-IV ADHD plus historical bipolar I disorder (BPD I) (10%) or bipolar II disorder (BPD II) (90%). Adults receiving adjunct antimanic agents (mood stabilizers and antipsychotics) at baseline were included in the study. We used standardized psychiatric instruments for diagnosis and outcome. Efficacy was based primarily on the Clinical Global Impression Scale (CGI) for ADHD and the ADHD symptom checklist. RESULTS: Of 36 patients entered (75% male, mean age 34 years), 30 patients (83%) completed the protocol. At end point (last observation carried forward [LOCF]) compared to baseline, treatment with bupropion SR resulted in significant reductions in the ADHD symptom checklist (-55%, z = 5.63, p <.001) and CGI severity of ADHD (-40%, z = 6.285, p <.001). Bupropion was associated with reductions in ratings of mania and depression. CONCLUSIONS: The results from this open study of adults with ADHD plus BPD suggest that sustained-release bupropion may be effective in treating ADHD in the context of a lifetime diagnosis of BPD, without significant activation of mania. Further controlled trials are warranted.

Adult↗
PubMed2003

Cord blood serum affects T cells ability to produce and respond to IL-2.

The current literature suggests that cord blood (CB) cells are functionally immature. We previously reported that CB sera inhibit T cell proliferation and suggested that the microenvironment in which CB T cells reside may be, in part, responsible for their reduced function. In this study we have tried to explain some of the actions of the CB sera on peripheral blood mononuclear cells (PBMC). We showed that, as expected CB sera decreased the anti-CD3 and anti-CD28-induced proliferative response of PBMC (p < 0.01) but unexpectedly, increased the interleukin-2 (IL-2) specific proliferation of both a human T cell line (p < 0.005) and T cells within a mononuclear cell population (p < 0.05). These findings prompted us to analyse the effect of CB sera on the T cell ability to make and respond to IL-2. Stimulation of T cells in the presence of CB sera increased the frequency of IL-2 producing cells (p < 0.005) (but not the amount of IL-2 secreted) and resulted in a higher expression of CD25 (p < 0.05). Furthermore CB sera (in the presence and absence of IL-2) made the cells apoptose less (p < 0.005) than adult sera. Our results go some way to explaining the effect of the CB microenvironment on CB cellular function.

Apoptosis↗
PubMed2003

A genetic map of the lettuce downy mildew pathogen, Bremia lactucae, constructed from molecular markers and avirulence genes.

The genetic map of Bremia lactucae was expanded utilizing 97 F(1) progeny derived from a cross between Finnish and Californian isolates (SF5xC82P24). Genetic maps were constructed for each parent utilizing 7 avirulence genes, 83 RFLP markers, and 347 AFLP markers, and a consensus map was constructed from the complete data set. The framework map for SF5 contained 24 linkage groups distributed over 835cM; the map for C82P24 contained 21 linkage groups distributed over 606cM. The consensus map contained 12 linkage groups with markers from both parents and 24 parent-specific groups. Six avirulence genes mapped to different linkage groups; four were located at the ends of linkage groups. The closest linkages between molecular markers and avirulence genes were 3cM to Avr4 and 1cM to Avr7. Mating type seemed to be determined by a single locus, where the heterozygote determined the B(2) type and the homozygous recessive genotype determined the B(1) type.

Chromosome Mapping↗
PubMed2002

Psychological profiles of sexually abusive adolescents in Ireland.

OBJECTIVE: This study aimed to profile the psychological and psychosocial characteristics of a group of Irish adolescents who had sexually abused other youngsters. METHOD: Levels of behavior problems, personal adjustment, anger management, and psychosocial adjustment were compared in 27 Irish adolescents with a history of sexually abusing another youngster (SA group), 20 clinical controls who had significant behavioral problems but no history of sexual offending (CC group), and 29 normal controls who were without significant psychological problems (NC group). Measures used included the Child Behavior Checklist (CBCL), the Youth Self-Report Form (YSR), selected scales from Beckett (1997) Adolescent Sex Offender Assessment Pack (ASOAP), and the Family Environment Scale (FES). RESULTS: Compared with the CC group, the SA group displayed fewer problems overall on the CBCL and the YSR. The SA group showed problems with self-esteem, emotional loneliness, and perspective-taking similar to those of the CC group, but their impulsivity scores were similar to those of the NC group. The locus of control scores of the SA group fell between those of the CC and NC groups. The SA group showed an anger management profile that fell at an intermediate position between those of the NC and CC groups. The SA group showed problematic family functioning in the areas of expressiveness, behavior control, and social support, similar to those of the CC group. Their difficulties with family cohesion were less severe than those of the CC group but worse than those of the NC group. CONCLUSIONS: Overall, the psychological adjustment of adolescents with a history of sexually abusing others was more problematic than that of normal controls but less problematic than that of youngsters who had significant behavioral problems but no history of sexual offending.

Adolescent↗
PubMed2002

Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD.

OBJECTIVE: Although the literature documents that attention-deficit/hyperactivity disorder (ADHD) commonly onsets prior to age 6, little is known about the disorder in preschool children. We evaluated the clinical characteristics, psychiatric comorbidity, and functioning of preschool children and school-age youths with ADHD referred to a pediatric psychiatric clinic for evaluation. METHOD: Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed with parents about their children. Family, social, and overall functioning were also assessed at intake. RESULTS: We identified 165 children with ADHD aged 4 to 6 years (preschool children) and 381 youths aged 7 to 9 years (school-age) with ADHD. Despite being younger, preschool children had similar rates of comorbid psychopathology compared with school-age youths with ADHD. There was an earlier onset of ADHD and co-occurring psychopathology in the preschool children compared to school-age youths. Both preschool children and school-age youths had substantial impairment in school, social, and overall functioning. CONCLUSIONS: The results of this study suggest that despite being significantly younger, clinically referred preschool children with ADHD are reminiscent of school-age youths with ADHD in the quality of ADHD, high rates of comorbid psychopathology, and impaired functioning. Follow-up of these clinically referred preschool children with ADHD to evaluate the stability of their diagnoses, treatment response, and their long-term outcome are necessary.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Patterns of psychopathology and dysfunction in clinically referred preschoolers.

Despite the growing interest in the use of psychotropic medications in preschoolers, little is known about the clinical presentation of young children referred for psychiatric services. We describe the clinical characteristics, psychiatric disorders, and functioning of preschoolers referred for pediatric psychiatry evaluation. Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed on clinically referred youth. Family, social, and overall functioning were assessed at intake. From the pool of 1658 consecutive referrals, we identified 200 children less than or equal to (<or=) 6 years of age (12%). The most common psychopathology identified was attention deficit hyperactivity disorder (ADHD) (86%), followed by other disruptive behavioral (61%), mood (43%), and anxiety disorders (28%). Co-occurring psychiatric disorders were common with preschoolers manifesting a mean of two major psychiatric disorders per child. Despite their young age, the onset of psychopathology preceded evaluation by a mean (+/-SD) of 2.2 +/- 1.3 years. Preschoolers referred for psychiatric services had high rates of psychopathology with prominent comorbidity and associated dysfunction. These preschoolers are likely to require aggressive interventions including psychopharmacology.

Anxiety Disorders↗