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T Ford

Publications and source records attributed to T Ford.

At least 19 recordsLinked to original sources

Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans.

ATI-7505, an investigational 5-HT(4) receptor agonist, was designed to have similar activity as cisapride without the cardiac adverse effects, i.e. without QT prolongation. In addition, ATI-7505 is not metabolized by CYP450. The aim of the study was to assess the effect of ATI-7505 on gastrointestinal (GI) and colonic transit in healthy humans. A randomized, parallel-group, double-blind, placebo-controlled study evaluated effects of 9-day treatment with ATI-7505 (3, 10 or 20 mg t.i.d.) on scintigraphic GI and colonic transit in healthy volunteers (12 per group). Primary endpoints were gastric-emptying (GE) T(1/2), colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T(1/2). Daily stool diaries were kept. Analysis of covariance assessed overall treatment group differences, followed by post hoc unadjusted pairwise comparisons. There were borderline overall treatment effects (decrease) on GE T(1/2) (P = 0.154); the 20 mg t.i.d. of ATI-7505-accelerated GE vs placebo (P = 0.038). ATI-7505 increased colonic transit (GC24, P = 0.031) with fastest transit at 10 mg t.i.d. vs placebo (P = 0.065). ATI-7505 accelerated AC emptying T(1/2) (overall P = 0.075) with 10 mg dose vs placebo (P = 0.042). There was looser stool (Bristol stool form scale, overall P = 0.056) with the 10 and 20 mg t.i.d. doses. No safety issues were identified. ATI-7505 accelerates overall colonic transit and tends to accelerate GE and AC emptying and loosen stool consistency.

Adolescent↗

Prevalence of pervasive developmental disorders in the British nationwide survey of child mental health.

OBJECTIVE: The prevalence of pervasive developmental disorders (PDD) is not well established and needs monitoring. The prevalence of PDD in the 1999 nationwide British survey of child and adolescent mental health was investigated. METHOD: A randomized, stratified sample of children (N= 12,529) aged 5 to 15 years was generated from the Child Benefit Register. Trained interviewers interviewed parents and youths aged 11 or older with a standardized diagnostic interview (Development and Well-Being Assessment), and questionnaire data (Strengths and Difficulties Questionnaire) were obtained from teachers and parents, who also completed self-report measures of psychological distress. Final diagnostic determination was achieved by a team of experienced clinicians using all data sources. RESULTS: A total of 10,438 (83%) interviews were conducted. There were 2 girls with Rett syndrome (weighted prevalence: 3.8/10,000 girls) and 27 children with other PDD (weighted prevalence: 26.1/10,000). Compared with children with a psychiatric disorder other than PDD, social but not behavioral problems were more frequent in the PDD group. Parents of children with PDD had higher rates of psychological distress than those from the two comparison groups. CONCLUSIONS: Consistent with other recent surveys, PDD rates are higher than those reported 30 years ago. The burden associated with PDD is very high.

Adolescent↗

Prevalence of obsessive-compulsive disorder in the British nationwide survey of child mental health.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disorder that appears to be underdiagnosed and undertreated, despite the evidence for effective treatments. There are variable estimates of OCD prevalence in the under-16s and published rates give little indication of age trends. AIMS: To establish the prevalence and associates of OCD in young people aged 5-15 years. METHOD: A nationwide (UK) epidemiological study of rates of psychiatric disorder in 5- to 15-year-olds (1999 British Child Mental Health Survey): 10 438 children were assessed. RESULTS: Twenty-five children with OCD were identified (weighted overall prevalence 0.25%; 95% CI 0.14-0.35), with prevalence rising exponentially with increasing age. Compared with normal controls, children with OCD were more likely to be from lower socio-economic class and of lower intelligence. Only three of these children had been seen by specialist children's services. CONCLUSIONS: Although OCD is rare in young children, the rate increases towards the adult rates at puberty. Children with OCD have additional psychosocial disadvantage. The majority of the childhood cases identified in this survey appear to have been undetected and untreated.

Adolescent↗

Marine swimming-related illness: implications for monitoring and environmental policy.

There is increasing evidence that environmental degradation may be contributing to an increase in marine-related diseases across a wide range of taxonomic groups. This includes a growing number of reports of both recreational and occupational users of marine waters developing gastrointestinal, respiratory, dermatologic, and ear, nose, and throat infections. The duration and type of exposure, concentration of pathogens, and host immunity determine the risk of infection. Public health authorities may not be able to accurately predict the risk of waterborne disease from marine waters due to the limitations of conventional monitoring, as well as erroneous perceptions of pathogen life span in marine systems. Pathogens undetectable by conventional methods may remain viable in marine waters, and both plankton and marine sediments may serve as reservoirs for pathogenic organisms, which can emerge to become infective when conditions are favorable. In this paper we address the environmental factors that may contribute to illness, the types of associated economic costs, the issues of water quality monitoring and the policy implications raised by the apparent rise in incidence of marine water-related illnesses.

Animals↗

Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: results of the ELITE ventricular function substudy.

BACKGROUND: The mechanism by which angiotensin-converting enzyme inhibitors reduce mortality rates and disease progression in patients with heart failure is likely mediated in part through prevention of adverse ventricular remodeling. This study examined the effects of the angiotensin-converting enzyme inhibitor captopril and the angiotensin II type 1 receptor antagonist losartan on ventricular volumes and function in elderly patients with heart failure and reduced left ventricular ejection fraction (< or =40%). METHODS: Patients underwent radionuclide ventriculograms (RVG) at baseline and were randomized to either captopril (n = 16) or losartan (n = 13). After 48 weeks, another RVG was obtained. Therapy was then withdrawn for at least 5 days, and the RVG was repeated while the patient was not receiving the drug. RESULTS: At 48 weeks both captopril and losartan significantly reduced left ventricular (LV) end-diastolic volume index (135 +/- 26 to 128 +/- 23 mL/m(2) for losartan, P <.05 vs baseline; 142 +/- 25 to 131 +/- 20 mL/m(2) for captopril, P <.01; mean (SD). Captopril also reduced LV end-systolic volume index (98 +/- 24 to 89 +/- 21 mL/m(2), P <.01 vs. baseline), whereas a nonsignificant trend was observed for the losartan group (97 +/- 23 to 90 +/- 16 mL/m(2), P = not significant). The between-group differences in the changes in LV volumes were not statistically significant. After drug withdrawal, LV end-diastolic volume index remained significantly lower than baseline in the captopril group (P <.01). CONCLUSIONS: Both captopril and losartan prevent LV dilation, representing adverse ventricular remodeling, previously seen with placebo treatment. Reverse remodeling was observed in the captopril group. On the basis of these results, the relative effects on LV remodeling do not provide a rationale for a survival benefit of losartan over captopril.

Aged↗

Case study: bipolar disorder after head injury.

A case of bipolar disorder subsequent to a mild head injury in a 15-year-old girl is reported. Review of the literature indicates that this is an extremely rare outcome. Lack of adequate follow-up studies makes it difficult to accurately predict type and severity of psychiatric outcome. Assessment and management involves ongoing consideration of both organic and psychosocial factors even after initial negative investigations.

Adolescent↗

Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample.

BACKGROUND: Child psychiatric disorders are common and treatable, but often go undetected and therefore remain untreated. AIMS: To assess the Strengths and Difficulties Questionnaire (SDQ) as a potential means for improving the detection of child psychiatric disorders in the community. METHOD: SDQ predictions and independent psychiatric diagnoses were compared in a community sample of 7984 5- to 15-year-olds from the 1999 British Child Mental Health Survey. RESULTS: Multi-informant (parents, teachers, older children) SDQs identified individuals with a psychiatric diagnosis with a specificity of 94.6% (95% Cl 94.1-95.1%) and a sensitivity of 63.3% (59.7-66.9%). The questionnaires identified over 70% of individuals with conduct, hyperactivity, depressive and some anxiety disorders, but under 50% of individuals with specific phobias, separation anxiety and eating disorders. Sensitivity was substantially poorer with single-informant rather than multi-informant SDQs. CONCLUSIONS: Community screening programmes based on multi-informant SDQs could potentially increase the detection of child psychiatric disorders, thereby improving access to effective treatments.

Adolescent↗

The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology.

The Development and Well-Being Assessment (DAWBA) is a novel package of questionnaires, interviews, and rating techniques designed to generate ICD-10 and DSM-IV psychiatric diagnoses on 5-16-year-olds. Nonclinical interviewers administer a structured interview to parents about psychiatric symptoms and resultant impact. When definite symptoms are identified by the structured questions, interviewers use open-ended questions and supplementary prompts to get parents to describe the problems in their own words. These descriptions are transcribed verbatim by the interviewers but are not rated by them. A similar interview is administered to 11-16-year-olds. Teachers complete a brief questionnaire covering the main conduct, emotional, and hyperactivity symptoms and any resultant impairment. The different sorts of information are brought together by a computer program that also predicts likely diagnoses. These computer-generated summary sheets and diagnoses form a convenient starting point for experienced clinical raters, who decide whether to accept or overturn the computer diagnosis (or lack of diagnosis) in the light of their review of all the data, including transcripts. In the present study, the DAWBA was administered to community (N = 491) and clinic (N = 39) samples. There was excellent discrimination between community and clinic samples in rates of diagnosed disorder. Within the community sample, subjects with and without diagnosed disorders differed markedly in external characteristics and prognosis. In the clinic sample, there was substantial agreement between DAWBA and case note diagnoses, though the DAWBA diagnosed more comorbid disorders. The use of screening questions and skip rules greatly reduced interview length by allowing many sections to be omitted with very little loss of positive information. Overall, the DAWBA successfully combined the cheapness and simplicity of respondent-based measures with the clinical persuasiveness of investigator-based diagnoses. The DAWBA has considerable potential as an epidemiological measure, and may prove to be of clinical value too.

Adolescent↗

Interactions between metals and microbial communities in New Bedford Harbor, Massachusetts.

The fate of toxic metals in marine sediments depends on a combination of the physical, chemical, and biologic conditions encountered in any given environment. These conditions may vary dramatically, both spatially and temporally, in response to factors ranging from seasonal changes and storm events to human activities such as dredging or remediation efforts. This paper describes a program designed to evaluate the interrelationships between the microbial community and pollutants in the New Bedford Harbor, Massachusetts, area, a U.S. Environmental Protection Agency designated Superfund site. Research has focused on establishing distributional relationships between contaminant metals, fluxes of metals between sediments and the overlying water, changes in microbial diversity in response to metals, and potential use of the microbial community as a biomarker of contaminant availability. This research has shown that a significant flux of metals to the water column is mediated by benthic biologic activity, and that microbial communities may be a responsive marker of contaminant stress. A combination of biogeochemical studies and the use of molecular tools can be used to improve our understanding of the fate and effect of heavy metals released to aquatic systems.

Animals↗

A novel method for the rapid separation of plasma lipoproteins using self-generating gradients of iodixanol.

We describe a new method for the rapid fractionation of plasma lipoproteins, which makes use of a new non-ionic, iodinated, density gradient medium, iodixanol, commercially available as Optiprep(TM). The method is simple: plasma or serum is mixed with iodixanol followed by centrifugation in a vertical or near vertical rotor. Separation of VLDL, LDL and HDL can be achieved in 3 h and the lipoprotein fractions are comparable in density and composition with those prepared using conventional salt based gradients. Each class of lipoprotein can be removed in a single fraction, or a profile of lipoprotein distribution can be obtained using a gradient fractionator. Because the medium is inert, fractions from the gradient can be analysed by agarose gel electrophoresis or assayed for lipid content or apolipoprotein composition by SDS-PAGE without removing the iodixanol. Small differences in electrophoretic mobility of HDL and LDL across several gradient fractions suggest that subfractionation of these classes may occur. The new method is simple, rapid and versatile with potential application for preparation of lipoproteins and for analysis of lipoprotein profiles in the research or clinical laboratory.

Apolipoproteins↗

Methylphenidate euphoria.

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Attention Deficit Disorder with Hyperactivity↗

Phospholipase A2-activating protein induces the synthesis of IL-1 and TNF in human monocytes.

Phospholipase A2-activating protein (PLAP) is an important mediator of eicosanoid generation. PLAP can also be found in high concentrations in synovial fluid from patients with rheumatoid arthritis, and injection of PLAP into animal joints results in an inflammatory, rheumatoid-like lesion. We have demonstrated previously that TNF-alpha and IL-1 beta stimulate formation of PLAP before phospholipase A2 (PLA2) enzyme activation and production of eicosanoids. To further explore the mechanisms found in the inflammatory response, we examined the ability of PLAP to stimulate release of TNF and IL-1 from human peripheral blood monocytes. TNF and IL-1 protein levels were measured by ELISA, and IL-1 and TNF mRNA were determined by Northern blotting. PLAP, PLAP peptide, and melittin, a bee venom PLA2 activator with homology with PLAP, all increased IL-1 and TNF production in a time- and dose-dependent manner. Heat-denatured PLAP and actin (an irrelevant protein) failed to exert this effect. PLAP stimulation of TNF and IL-1 could be enhanced with co-treatment of cells with free fatty acids, such as arachidonic or linoleic acid, but it was not blocked completely by PLA2 inhibitors. These results demonstrate not only that synthesis of PLAP can be stimulated by cytokines, but also that PLAP may regulate cytokine synthesis and thus perpetuate an immune or inflammatory response.

Amino Acid Sequence↗

Toxic metals in aquatic ecosystems: a microbiological perspective.

Microbe-metal interactions in aquatic environments and their exact role in transport and transformations of toxic metals are poorly understood. This paper will briefly review our understanding of these interactions. Ongoing research in Lake Chapala, Mexico, the major water source for the City of Guadalajara, provides an opportunity to study the microbiological aspects of metal-cycling in the water column. Constant resuspension of sediments provides a microbiologically rich aggregate-based system. Data indicate that toxic metals are concentrated on aggregate material and bioaccumulate in the food chain. A provisional model is presented for involvement of microbial aggregates in metal-cycling in Lake Chapala.

Animals↗

Iodixanol: a nonionic iso-osmotic centrifugation medium for the formation of self-generated gradients.

The physical and biological properties of Iodixanol, a new nonionic density gradient medium, are described in this paper. It is effectively a dimer of Nycodenz and it exhibits two significant advantages over previous iodinated density gradient media--its aqueous solutions are iso-osmotic up to a density of 1.32 g/ml and it is capable of forming self-generating gradients in 1 to 3 h. It has a very low toxicity toward biological material and enzyme assays can be carried out in its presence.

Cell Line↗

The preparation of subcellular organelles from mouse liver in self-generated gradients of iodixanol.

This paper reports the use of a new density gradient compound, Iodixanol, for the resolution of the major organelles from mouse liver. A major advantage of Iodixanol over other iodinated density gradient media is its ready ability to form self-generated gradients. Gradient-forming conditions have been modulated to provide optimal recoveries of Golgi membranes, lysosomes, mitochondria, and peroxisomes. The organelles were isolated in high yield (80-90% of gradient input) and high purity. Nycodenz and Iodixanol were compared using preformed gradients. Iodixanol provided resolution superior to that of Nycodenz, notably of peroxisomes and mitochondria and the separation of lysosomes from endoplasmic reticulum. Because Iodixanol does not interfere significantly with marker enzyme activities, gradient fractions can be analyzed without removal of the gradient medium.

Animals↗