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Biomedical subjects

T Johnson

Publications and source records attributed to T Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Continuous pH and Pco2 monitoring during respiratory failure in children with the Paratrend 7 inserted into the peripheral venous system.

CONTEXT: The Paratrend monitor provides continuous arterial blood gas monitoring after insertion through a >/=20-gauge arterial cannula. OBJECTIVE: To determine the correlation of arterial blood gas values and the Paratrend monitor placed through a peripheral intravenous catheter. DESIGN: Prospective, open-label evaluation. SETTING: University-based pediatric intensive care unit. PATIENTS: Infants and children with respiratory failure and arterial access. RESULTS: The cohort included 23 infants and children. A total of 100 sample sets (Paratrend/ABG Pco(2) and pH values) were collected. The absolute difference between the arterial and Paratrend Pco(2) was 2. 9 +/- 1.8 mm Hg (range 0 to 9 mm Hg). Linear regression analysis of Paratrend Pco(2) versus arterial Pco(2) resulted in r = 0.97 and r(2) = 0.9479 (P <.001). Bland-Altman analysis of Pco(2) values demonstrated a bias +/- precision of -2.1 +/- 2.7 mm Hg. The absolute difference between arterial and Paratrend pH was 0.04 +/- 0. 02 units (range 0 to 0.15 units). Linear regression analysis of Paratrend pH versus arterial pH resulted in r = 0.83 and r(2) = 0. 7016 (P <.0001). Bland-Altman analysis of pH values revealed a bias +/- precision of 0.03 +/- 0.03 units. CONCLUSIONS: Inserted through a peripheral intravenous cannula, the Paratrend monitor can be used to provide an accurate estimation of arterial blood gas values in children with respiratory failure.

Adolescent↗
PubMed2000

Intravenous azathioprine in severe ulcerative colitis: a pilot study.

OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerative colitis were enrolled. Patients 1-3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4-6 received 40 mg/kg i.v. azathioprine over 36 h. Patients 7-9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erythrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Response was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 x 10(8). Two patients had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.

Adult↗
PubMed2000

Gay and lesbian couples in therapy: perspectives for the contemporary family therapist.

This paper outlines the major concerns of gay and lesbian couples who seek therapy. Presenting problems are classified as either internal to the relationship or as external (contextual) ones that reflect the influence of oppressive cultural and gender biases. Throughout the article, distinctive therapy methods are described that address the unique concerns of lesbian and gay couples, with special sensitivity to heterosexist and homophobic bias.

Adult↗
PubMed2000

Requirement for TAF(II)250 acetyltransferase activity in cell cycle progression.

The TATA-binding protein (TBP)-associated factor TAF(II)250 is the largest component of the basal transcription factor IID (TFIID). A missense mutation that maps to the acetyltransferase domain of TAF(II)250 induces the temperature-sensitive (ts) mutant hamster cell lines ts13 and tsBN462 to arrest in late G(1). At the nonpermissive temperature (39.5 degrees C), transcription from only a subset of protein encoding genes, including the G(1) cyclins, is dramatically reduced in the mutant cells. Here we demonstrate that the ability of the ts13 allele of TAF(II)250 to acetylate histones in vitro is temperature sensitive suggesting that this enzymatic activity is compromised at 39.5 degrees C in the mutant cells. Mutagenesis of a putative acetyl coenzyme A binding site produced a TAF(II)250 protein that displayed significantly reduced histone acetyltransferase activity but retained TBP and TAF(II)150 binding. Expression of this mutant in ts13 cells was unable to complement the cell cycle arrest or transcriptional defect observed at 39.5 degrees C. These data suggest that TAF(II)250 acetyltransferase activity is required for cell cycle progression and regulates the expression of essential proliferative control genes.

Acetyltransferases↗
PubMed2000

Socioeconomic status and the expectation of disability in old age: estimates for England.

OBJECTIVES: The longer life expectancy in old age of more privileged socioeconomic groups is well established, but less clear is whether the net effect of additional years of life is a lengthened, stable or reduced duration of disability. Estimates of healthy and disabled life expectancy (using definitions including dependency in activities of daily living and cognitive impairment) were made, contrasting occupational classes I and II (professional and managerial) with the rest. DESIGN: Disability prevalence was estimated from the Medical Research Council Cognitive Function and Ageing study. Sullivan's method was used to calculate health expectancy. SUBJECTS: 10,377 people aged 65 years or over in Cambridgeshire, Newcastle, Nottingham and Oxford. Subjects were classified as disabled if they had evidence of dementia (using the Automated Geriatric Examination Computer Assisted Taxonomy) or scored 11 or more on the modified Townsend Disability scale, at baseline screen. RESULTS: The prevalence of disability overall and need for "constant care" was lower in both men and women in social classes I and II compared with the rest. Men aged 65 to 69 in classes I and II can expect nearly 14 years of life free of disability compared with 11.5 years for those in classes III to V: for women the equivalent expectations are 15.5 and 13.8 years. Men aged 65 to 69 in classes I and II can also expect a shorter duration of disability: 1 year compared with 1.6 years for classes III to V. In women expectation of disability is higher overall, but shows little difference by occupational class. CONCLUSIONS: Relatively privileged socioeconomic groups in England, especially men, can expect fewer years of disability despite longer overall life expectancy. These findings lend weight to optimistic scenarios for the future numbers of older people with disability.

Aged↗
PubMed2000

The prevalence of breast-feeding in south Leicestershire.

The consultative document, 'Our Healthier Nation' (Department of Health, 1998a), outlined areas for health improvement, and offers health professionals an opportunity to use the Government's programme to raise breast-feeding rates. This article reports the results of an audit to establish local breast-feeding prevalence rates in south Leicestershire, and when and why women stop breast-feeding. A simple questionnaire was used by health visitors to collect data on all babies born over a 3-month period (October 1997 - December 1997). The audit found that 57% of mothers were breast-feeding at birth compared with national breast-feeding figures of 64%. The rate at which women stopped breast-feeding substantially increased between 10 days and 6-8 weeks postpartum. Women stopped breast-feeding for a variety of reasons. The information provided by the audit will be used to inform health-visiting practice and in the long term will hopefully help to increase breast-feeding rates in this area.

Breast Feeding↗
PubMed2000

Longitudinal study of the influence of life events and personality status on diagnostic change in three neurotic disorders.

It has been known for many years that diagnosis within the neurotic spectrum of disorders is temporally unstable and also that life events can be major precipitants of change in symptoms. Reasons for this instability could include inherent inadequacy of current diagnostic practice, the influence of life events as an agent of diagnostic shift, and an innate course of disorder with features dependent on the stage at which disorder presents (e.g., development of panic to agoraphobia). These possibilities were examined in a prospective study that was initially a randomised controlled trial. Two hundred ten patients recruited from primary care psychiatric clinics with DSM-III diagnosed dysthymic, generalised anxiety, and panic disorders were randomly allocated to either drug treatment (mainly antidepressants), cognitive-behaviour therapy, or self-help therapy over a 2 year period, irrespective of original diagnosis. Life events were recorded by using a standard procedure over the period 6 months before starting treatment and at five occasions over 2 years; 181 (86%) of the patients had follow-up data and 76% maintained compliance with the original treatment allocated over the 2 years; and 155 of the 181 patients (86%) had at least one diagnostic change in this period. There was no difference in the number of diagnostic changes between the three original diagnostic groups, but dysthymic disorder changed more frequently to major depressive episode than did GAD or panic disorder (20; 11; 12) (%) and panic disorder changed more frequently to agoraphobia (with or without panic) than did dysthymia or GAD (18; 8; 6) (%). There was no relationship between loss events and depressive diagnoses or between addition events and anxiety diagnoses, but greater numbers of conflict events were associated with diagnostic change. More life events were associated with the flamboyant and dependent personality disorders, reinforcing other evidence that many life events are internally generated by personality characteristics and cannot be regarded as truly independent.

Cognitive Behavioral Therapy↗
PubMed2000

Oral paclitaxel and concurrent cyclosporin A: targeting clinically relevant systemic exposure to paclitaxel.

Oral paclitaxel is not inherently bioavailable because of the overexpression of P-glycoprotein by intestinal cells and the significant first-pass extraction by cytochrome P450-dependent processes. This study sought to simulate the toxicological and pharmacological profile of a clinically relevant schedule of paclitaxel administered on clinically relevant i.v. dosing schedules in patients with advanced solid malignancies using oral paclitaxel administered with cyclosporin A, an inhibitor of both P-glycoprotein and P450 CYP3A. Nine patients were treated with a single course of oral paclitaxel in its parenteral formulation at a paclitaxel dose level of 180, 360, or 540 mg. Cyclosporin A was administered at a dose of 5 mg/kg p.o. 1 h before and concurrently with oral paclitaxel. Blood sampling was performed to evaluate the pharmacokinetics of paclitaxel, 6-alpha-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and cyclosporin A. The pharmacokinetic behavior of paclitaxel was characterized using both compartmental and noncompartmental methods. Model-estimated parameters were used to simulate paclitaxel concentrations after once daily and twice daily oral administration of paclitaxel and cyclosporin A. Aside from an unpleasant taste, the oral regimen was well tolerated, and there were no grade 3 or 4 drug-related toxicities. The systemic exposure to paclitaxel, as assessed by maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) values, did not increase as the dose of paclitaxel was increased from 180 to 540 mg, and there was substantial interindividual variability (4-6-fold) at each dose level. Mean paclitaxel Cmax values approached plasma concentrations achieved with clinically relevant parenteral dose schedules, averaging 268+/-164 ng/ml. AUC values averaged 3306+/-1977 ng x h/ ml, which was significantly lower than AUC values achieved with clinically relevant i.v. paclitaxel dose schedules. However, computer simulations using pharmacokinetic parameters derived from the present study demonstrated that pharmacodynamically relevant steady-state plasma paclitaxel concentrations of at least 0.06 microM would be achieved after protracted once daily and twice daily dosing with oral paclitaxel and cyclosporin A. Paclitaxel metabolites were detectable in three patients, and the 6-alpha-hydroxypaclitaxel: paclitaxel and 3-p-hydroxypaclitaxel:paclitaxel AUC ratios averaged 0.63 and 0.86, respectively; these values were substantially higher than values reported in patients treated with i.v. paclitaxel. Oral paclitaxel was bioavailable in humans when administered in combination with oral cyclosporin A 5 mg/kg 1 h before and concurrently with paclitaxel treatment, and plasma paclitaxel concentrations achieved with this schedule were biologically relevant and approached concentrations attained with clinically relevant parenteral dose schedules. However, treatment of patients with oral paclitaxel using a single oral dose administration schedule failed to achieve sufficiently high systemic drug exposure and pharmacodynamic effects. In contrast, computer simulations demonstrated that clinically relevant pharmacodynamic effects are likely to be achieved with multiple once daily and twice daily oral paclitaxel-cyclosporin A dosing schedules.

Administration, Oral↗
PubMed2000

Increasing productivity and reducing errors through usability analysis: a case study and recommendations.

The usability problems of a system often occur due to inattention to well-documented and well-established design guidelines and heuristics. These problems often lead to increased errors, user dissatisfaction, and often user abandonment. Although there are a plethora of design principles, programs are still being constructed without integration of these principles. One family history-tracking program was examined for usability compliance. In addition to a user analysis, a task analysis was conducted comparing the designers' conceptualization of tasks with the users' conceptualization of these tasks. A cognitive walk-through was then conducted on these tasks. Finally, a keystroke level model was used to show the differences between the execution times of these tasks. This model showed a serious mismatch between the designers and users conceptions of the task. The suggested redesign showed timesaving for each of these tasks.

Attitude to Computers↗
PubMed2000

A comprehensive interactive competency program. Part I: Development and framework.

The department of medicine/oncology nursing of an academic medical center developed and implemented a comprehensive interactive competency program. The program proved to be valuable to nurses and the organization. Part I of this two-part series describes the process of program development and the resulting framework.

Academic Medical Centers↗
PubMed1999

The approach to mutation-selection balance in an infinite asexual population, and the evolution of mutation rates.

A method is described for calculating the dynamics of the distribution of fitness in an infinite asexual population which is subject to unconditionally deleterious mutations with independent effects. This method is applied to the problem of calculating the frequency of a mutator subpopulation, at equilibrium between mutation and indirect selection due to association with deleterious mutations. Many mutator alleles are produced by loss-of-function mutations in polymerase or mismatch repair genes. Previous calculations have ignored the fact that this creates a flux of higher fitness individuals into the mutator subpopulation. This flux raises the mean fitness of the mutator subpopulation, and when this factor is taken into account, the frequency of the mutator may be more than an order of magnitude greater than recent theoretical work has suggested.

Alleles↗
PubMed1999

Profile of disability in elderly people: estimates from a longitudinal population study.

OBJECTIVES: To provide estimates of the numbers of cognitively impaired and physically disabled elderly people in England and Wales, subdivided by a range of sociodemographic, dependency, care receipt, and survival variables, to support debates on the form and funding of health and welfare programmes. DESIGN: Interviews at baseline and 2 year follow up plus data on resource use extracted from records for those with disability. SUBJECTS: 10 377 people aged 65 years and over in Cambridgeshire, Newcastle, Nottingham, and Oxford. All estimates weighted to population of England and Wales in 1996. RESULTS: 11% of men and 19% of women aged 65 and over were disabled, totalling 1.3 million people; 38% of these were aged 85 or over and a similar percentage were cognitively impaired. Overall, more than 80% of elderly disabled people needed help on at least a daily basis. Over a third of people with limitations to daily activity living in private households were wholly or partly dependent on formal services for help. 63% of disabled elderly people used acute hospitals during the 2 year follow up, 43% as inpatients. 53% of those with cognitive impairment and limitations to daily activity were living in institutions. CONCLUSIONS: Very elderly people and those with cognitive impairment make up a large proportion of those in need of long term care. A large proportion of even the most disabled elderly people currently live outside institutions and depend on formal services as well as informal care givers. Disabled elderly people use acute hospitals extensively, underlining the interrelations between acute and long term care.

Activities of Daily Living↗
PubMed1999

A NF-kappa B/c-myc-dependent survival pathway is targeted by corticosteroids in immature thymocytes.

Glucocorticoid hormones modulate T cell maturation in vivo. While low levels of hormones are required for appropriate T cell development, high levels of glucocorticoid hormones target immature developing thymocytes for cell death during systemic stress. In this report, we propose a molecular mechanism for the induction of apoptosis in CD4+CD8+ double-positive thymocytes by dexamethasone in vivo. Dexamethasone injection induced the expression of IkappaBalpha and IkappaBbeta in thymocytes and down-regulated NF-kappaB DNA binding activated by intrathymic signals. Down-regulation of NF-kappaB DNA binding preceded cell death, suggesting that NF-kappaB may be important for the survival of immature thymocytes. In addition, ex vivo treatment of thymocyte single-cell suspension with dexamethasone accelerated p65/RelA down-regulation and cell death. Conversely, NF-kappaB induction diminished dexamethasone-induced death. Expression of the c-myc proto-oncogene, a NF-kappaB target, was also reduced in thymocytes of dexamethasone-treated animals, and ectopic transgenic expression of c-myc in mice provided partial rescue of double-positive thymocytes from dexamethasone mediated cell death. These observations suggest that viability of CD4+CD8+ thymocytes may be maintained by an NF-kappaB/c-myc-dependent pathway in vivo.

Animals↗