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Biomedical subjects

Louise Howard

Publications and source records attributed to Louise Howard.

14 recordsLinked to original sources
PubMed2006

Patient preference randomised controlled trials in mental health research.

The relationship between psychiatric patients'preferences for different treatments and the outcome of interventions is unclear, as the few relevant trials have tended to be underpowered. Strong patient preferences result in patients refusing to enter a trial. This leads to bias and limits generalisability, and the patient preference randomised controlled trial (RCT) design has been proposed as an alternative. Limitations and advantages of patient preference RCTs are discussed.

Humans↗
PubMed2005

Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine.

Here, we exploit an absolute differential between stem and progeny cells in their ability to express Cre from a somatically inducible transgene to determine the longevity of intestinal Paneth cells. In the Ahcre transgenic line induction of Cre recombinase allows constitutive activation of a Cre-activated reporter in intestinal precursors but not in Paneth cells. The time taken for Paneth cells to inherit the reporter (EYFP) was measured in adult Ahcre/R26R-EYFP animals. Using confocal microscopy of TOPRO-3-stained sections, both precursors and Paneth cells were identified and subsequently scored for EYFP expression. It takes up to 57 days for Paneth cells to inherit the reporter, making them three times longer-lived than previously indicated using nucleotide incorporation and suggesting that such determinations of cell turnover may be significant underestimates.

Animals↗
PubMed2005

Postnatal depression.

Explore the source record for details and available documents.

Antidepressive Agents, Second-Generation↗
PubMed2004

Elimination of background recombination: somatic induction of Cre by combined transcriptional regulation and hormone binding affinity.

Somatically inducible Cre lines are used extensively to study gene function. However, a background level of spontaneous recombination due to unregulated expression of Cre is particularly confounding for cancer models in which following the pathogenesis of the disease requires the introduction of sporadic mutations that are monitored over time. In three transgenic mouse lines, two with Cre activity controlled at the transcriptional level (Ahcre, Mx1cre), and one controlled at the protein level (R26creER(T)), we have identified sporadic recombination at the R26R reporter locus in multiple tissues. Detailed analysis of the intestinal epithelium suggests that recombination can occur both during development and as an ongoing process in adult life. Here we present a new inducible Cre transgenic line, AhcreER(T), in which control of Cre activity is regulated at two levels: by transcriptional control of the Ah promoter and by a requirement for Tamoxifen binding. There is no detectable background intestinal recombination in adult AhcreER(T) mice on the R26R background. Inducible and dose-dependent recombination can be achieved by a single combined treatment with beta-napthoflavone and Tamoxifen.

Animals↗
PubMed2004

Quantitative phenotyping as an efficient means to estimate C-cell number in a knock-in mouse model of MEN2B.

Over the last two decades we have witnessed the generation of hundreds, if not thousands, of lines of genetically altered mice, large numbers of which are being produced in order to model human disease. Given that their creation is still rather technically demanding and labour intensive, the time taken analysing the resultant phenotypes should be such that the maximal amount of information can be gleaned efficiently in an unbiased manner so as to be as close to the 'true' value as possible. In an attempt to characterise a cell-specific phenotype in a genetically defined knock-in mouse model of multiple endocrine neoplasia type 2B (MEN2B) we used a modern, unbiased, stereological approach called the optical fractionator to estimate total cell number in 3-D space. By applying a sampling technique to tissue blocks in a systematic random uniform manner, we demonstrate that the total number of calcitonin-immunoreactive C-cells in the thyroid glands of littermate mice harbouring activating mutations in one or both alleles of ret does not vary significantly (p = 0.46) from an unbiased estimate of 23,000 in wild-type controls; likewise, neither does mean thyroid volume (p = 0.78) when estimated using Cavalieri's principle. We demonstrate that the variation associated with the quantitative phenotyping method is negligible. Using this efficient, unbiased stereological method our results provide new insights into cell number and positioning with consequences for both normal and disease states. In summary, this unbiased stereological technique is conceptually simple, can be applied efficiently, and is pertinent to quantitating a wide variety of cell phenotypes thereby bridging specialisation boundaries. We propose the adoption of this technique to mouse experimental geneticists and recommend its horizontal transmission across all fields within experimental biology.

Animals↗
PubMed2004

Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.

BACKGROUND & AIMS: A system for introducing specific gene mutations into the epithelia of the adult murine gastrointestinal tract by the transcriptional regulation of Cre recombinase is presented and applied to delete beta-catenin, a central mediator of Wnt signaling, within the small intestine (SI). METHODS: In a transgenic line (Ahcre), cre expression is inducible from a cytochrome P450 promoter element that is transcriptionally up-regulated in response to lipophilic xenobiotics such as beta-napthoflavone. RESULTS: Recombination at a lacZ reporter locus showed extensive expression of beta-galactosidase in liver, intestine, pancreas, gallbladder, esophagus, and stomach in response to beta-napthoflavone treatment. Expression patterns were stable in renewing epithelia for at least 6 months, implying that long-lived stem cells undergo recombination. Analysis of the intestinal epithelium showed dose responsiveness in the extent of recombination and that villus and crypt populations could be targeted differentially by varying the route of administration of beta-napthoflavone. The use of this system to delete beta-catenin in the SI caused crypt ablation, increased apoptosis, depleted numbers of goblet cells, and detachment of villus absorptive cells from the villus core as intact sheets. CONCLUSIONS: The Ahcre model provides a simple route for introducing specific gene mutations into many of the epithelia of the gastrointestinal tract of the mouse. It has been used here to show that beta-catenin is required for the maintenance of intestinal cell proliferation and is implicated in goblet cell differentiation and enterocyte-matrix attachment.

Animals↗
PubMed2004

Postnatal depression.

Explore the source record for details and available documents.

Antidepressive Agents, Second-Generation↗
PubMed2003

Predictors of social services supervision of babies of mothers with mental illness after admission to a psychiatric mother and baby unit.

BACKGROUND: There is insufficient information on the predictors of parenting difficulties in mothers with severe mental illness. Using data from mother and baby units in the UK we aimed to examine the social and clinical characteristics of mothers whose babies were supervised by social services on discharge. METHOD: A case-control study was carried out using data from mother and baby units and facilities entered onto the Marce database. RESULTS: Of 1197 mothers, 23% were discharged with their babies under some form of social services supervision. Factors independently associated with an increased risk of supervision included social class (OR 3.16, 95% CI 1.99-5.03), single marital status (OR 2.10, 95% CI 1.38-3.20), behavioural disturbance (OR 1.69, 95% CI 1.08-2.65) and psychiatric illness in the partner (OR 2.67, 95% CI 1.59-4.49). The diagnostic groups independently associated with the highest risk of having a supervised baby were schizophrenia (OR 5.16, 95% CI 2.61-10.21) and personality disorder (OR 9.29, 95% CI 3.46-24.91). CONCLUSIONS: Mothers with schizophrenia are at particularly high risk of having their baby supervised by social services. Preventative interventions should be targeted at socio-economic difficulties, early detection of psychiatric disorders postpartum and treatment of perinatal mental illness in the context of the whole family.

Adult↗
PubMed2002

Gender differences in living with schizophrenia. A cross-sectional European multi-site study.

The EPSILON project (European Psychistric Services: Inputs Linked to Outcomes and Needs) is a cross-sectional study of the clinical and social characteristics, needs, satisfaction with services, quality of life, and service utilisation and costs for people with schizophrenia in five European sites (Amsterdam, Copenhagen, London, Santander, and Verona). This study examined five hypotheses: (1) Men will have more total needs and more unmet needs for: 'accommodation', 'substance misuse', 'psychotic symptoms', 'harm to others', and 'sexual expression', whereas women will have more total needs and more unmet needs in the domains of 'childcare' and 'harm to self'. (2) Caregivers of male patients will show higher rates of psychological distress, and higher scores for 'supervision' and 'urging' than caregivers of female patients. (3) Male and female patients will show similar levels of satisfaction with services, both in total scores and subscores. (4) Male patients will show lower objective quality of life, but similar subjective quality of life compared with women. (5) Service utilization for men and women will differ, and patterns will vary by site. The results confirmed hypotheses 1 (in part) and 3, but failed to support hypotheses 2, 4 and 5. Graphical models were used to generate hypotheses for future research. The implications for planning separate services for male and female schizophrenic patients are discussed.

Adult↗
PubMed2002

A rapid effect of caffeinated beverages on two choice reaction time tasks.

Though consumers of tea and coffee can report feeling beneficial subjective effects of consumption virtually immediately, tests for objective effects of caffeine immediately post-consumption have been rare. Two experiments examined caffeine's ability to influence reaction time in choice reaction time tasks, using a dose of caffeine typical of a cup of tea or instant coffee, and testing at short post-consumption delays. Two groups of participants were given 60 mg of caffeine, after overnight abstinence, either in a hot tea drink, or a hot water drink. Two control groups also received hot tea or water, but without caffeine. In Experiment 1, participants were given a keypress task before the drink (baseline), immediately after the drink, and 40 min after the drink. In Experiment 2, a touch-screen test was given either 1, 14, or 27 min post consumption. Caffeine was found to reduce the effect of a distracter on reaction time in the keypress test and to reduce reaction time in a component of the touch-screen task; however, in neither experiment were these effects significantly modulated by post-consumption delay length. Thus, the speed of caffeine's action on psychomotor performance was shown to be on the order of minutes.

Adolescent↗