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Biomedical subjects

T Taylor

Publications and source records attributed to T Taylor.

At least 37 records · Page 2Linked to original sources

Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease.

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)

Adolescent↗

Psychosocial influences on older adults' interest in participating in bowel cancer screening.

BACKGROUND: As part of a multicenter, randomized controlled trial of the efficacy of flexible sigmoidoscopy for the prevention of bowel cancer, an investigation of the predictors of screening interest was carried out in a subsample of older adults. METHOD: The aim of the study was to establish the predictive power of the Health Belief Model (HBM) and to evaluate the contribution of HBM elements in mediating the effect of other demographic and health variables which have been found to be associated with screening interest and participation. A total of 5,099 participants were sent a postal questionnaire which examined screening interest, attitudes toward screen ing (benefits and barriers), perceived bowel cancer risk, bowel cancer worry, bowel symptoms, health status, state anxiety, and optimism. A total of 3,648 questionnaires were returned completed, giving a response rate of 71.5%. RESULTS: The results showed that threat, barriers, and benefits explained 47% of the variance in interest. Demographic and health variables were also associated with screening interest, although most of their effect was mediated by the HBM constructs. DISCUSSION: This community study in older adults showed a high level of interest in participating in screening. The large sample size provided the opportunity to test the value of the HBM model and to examine mediation of demographic and health variables. The HBM proved to be a good model of screening interest. These results further our understanding of the decision processes in participating in cancer screening and point to directions to increase the level of participation in community samples.

Attitude to Health↗

Knowledge, skills, and behavior improvements on peer educators and low-income Hispanic participants after a stage of change-based bilingual nutrition education program.

A nutrition education program, entitled La Cocina Saludable, was designed according to the Stage of Change Model and implemented in ten southern Colorado counties. The objectives were to improve the nutrition related knowledge, skills, and behaviors that lead to healthy lifestyles in a low-income Hispanic population. The content of the program included nutrition information designed to help mothers of preschool children provide for their children's nutritional needs. Previous studies suggest that low-income Hispanics often demonstrate low intakes of vitamins A and C, calcium, iron, and protein, and high rates of diabetes, obesity, and infections. Additionally, this population presents many obstacles for nutrition educators including limited resources, child care, transportation, time, language, culture, literacy, health beliefs, and, in some cases, the transient nature of the population. The program attempted to overcome these barriers by incorporating a flexible program format carried out by abuela (Hispanic grandmother) educators using the processes described in the Stage of Change Model. The program was evaluated using a knowledge, skills and behavior pre-test, post-test, and six-month follow-up survey on both the abuela educators as well as the actual class participants. Results of the peer education training sessions suggest that this type of training program can be effective in increasing the knowledge, skills, and behavior of peer educators as well as reduce need for retraining for educators who continuously teach classes. Additionally, the results suggest that this type of program can be effective in changing selected nutrition related knowledge, skills, and behaviors leading to healthy lifestyles for low-income Hispanic mothers of preschool children.

Adult↗

Placental haemozoin and malaria in pregnancy.

Malaria infections in pregnant women cause poor birth outcomes. Malaria pigment (haemozoin) accumulates in the placenta within macrophages and extracellularly, but its pathological significance is not understood. In order to study the potential role of haemozoin in malaria pathogenesis, we enrolled primigravid women at a Malawian government antenatal clinic and followed them through delivery. One hundred and thirteen women (71 per cent) out of 159 women followed through delivery were parasitaemic at least once. Mean placental haemozoin concentrations were significantly higher in women with delivery parasitaemias (223 ng/mg protein) than in women who never had a detectable parasitaemia (43 ng/mg protein; P<0.05), but were not significantly higher in women who were parasitaemic only during the antenatal period (67 ng/mg protein). Haemozoin was not associated with preterm delivery (PTD) or intrauterine growth retardation (IUGR) (P -values, 0.307-0.787). Thus, placental haemozoin is associated with malaria infection at the time of delivery and does not seem to be associated with poor birth outcome.

Adult↗

Combinatorial effect of T-cell receptor ligation and CD45 isoform expression on the signaling contribution of the small GTPases Ras and Rap1.

By using ligands with various affinities for the T-cell receptor (TCR) and by altering the contribution of the CD45 tyrosine phosphatase, the effects of the potency of TCR-induced signals on the function of small GTPases Ras and Rap1 were studied. T cells expressing low-molecular-weight CD45 isoforms (e.g., CD45RO) exhibited the strongest activation of the Ras-dependent Elk-1 transcription factor and the highest sensitivity to the inhibitory action of dominant negative mutant Ras compared to T cells expressing high-molecular-weight CD45 isoforms (ABC). Moreover, stimulation of CD45RO(+), but not CD45ABC(+), T cells with a high-affinity TCR ligand induced suboptimal Elk-1 activation compared with the stimulation induced by an intermediate-affinity TCR-ligand interaction. This observation suggested that the Ras-dependent signaling pathway is safeguarded in CD45RO(+) expressors by a negative regulatory mechanism(s) which prohibits maximal activation of the Ras-dependent signaling events following high-avidity TCR-ligand engagement. Interestingly, the biochemical activity of another small GTPase, the Ras-like protein Rap1, which has been implicated in the functional suppression of Ras signaling, was inversely correlated with the extent of Elk-1 activation induced by different-affinity TCR ligands. Consistently, overexpression of putative Rap dominant negative mutant RapN17 or the physiologic inhibitor of Rap1, the Rap GTPase-activating protein RapGAP, augmented the Elk-1 response in CD45RO(+) T cells. This is in contrast to the suppressive effect of RapN17 and RapGAP on CD45ABC(+) T cells, underscoring the possibility that Rap1 can act as either a repressor or a potentiator of Ras effector signals, depending on CD45 isoform expression. These observations suggest that cells expressing distinct isoforms of CD45 employ different signal transduction schemes to optimize Ras-mediated signal transduction in activated T lymphocytes.

DNA-Binding Proteins↗

Acceptability of flexible sigmoidoscopy screening in older adults in the United Kingdom.

OBJECTIVES: To assess the acceptability of bowel cancer screening using flexible sigmoidoscopy (FS). SETTING: Adults aged 55 to 64 recruited from general practices in Welwyn Garden City and Leicester, which were the pilot and start up centres of a multicentred randomised controlled trial of FS screening (the ICRF/MRC Flexible Sigmoidoscopy Screening Trial). METHODS: Screenees (n=4422) were sent a three month follow up questionnaire that included measures of satisfaction with information given before the test, facilities at the test unit, attitudes of the staff, and explanation of the results. Measures of pain, embarrassment, feelings of being "in control" during the test, willingness to encourage others to have the test, and gladness to have participated were also included. In addition, semistructured telephone interviews were conducted with 60 screenees, stratified by screening outcome and gender. RESULTS: The follow up questionnaire was completed by 94% of screenees. Responses indicated a high level of satisfaction with the procedure: 99% were satisfied with the information given before the test, the facilities, the attitudes of the staff, and the explanation of their results; 91% reported only mild or no pain; 97% reported little or no embarrassment; and 99% were glad they had the test. Satisfaction ratings varied little by gender or outcome group. The quantitative results were reinforced by the qualitative data, which also revealed high acceptability. CONCLUSION: In the context of a clinical trial with dedicated trial staff, FS is a well tolerated procedure. There are high levels of satisfaction with service provision and positive attitudes towards the programme.

Colorectal Neoplasms↗

Predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial.

OBJECTIVE: To investigate predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial. DESIGN: Prospective design in which participants completed a postal questionnaire before being sent their invitation for screening. SETTING: Welwyn Garden City and Leicester, United Kingdom. PARTICIPANTS: A total of 2758 patients aged 55 to 64, registered with general practices in the two centres, who (a) expressed interest in having the screening test, (b) completed a postal questionnaire, and (c) were subsequently invited for screening. MAIN RESULTS: The attendance rate among questionnaire responders was 76.1%. Multiple logistic regression analysis yielded a final model that included nine independent predictors of attendance. Patients with the following characteristics were more likely to attend: men; home owners; non-smokers; those who had regular check ups at the dentist; those with better subjective health; those who minded less about having medical tests; those who said they would definitely rather than probably take up the offer of sigmoidoscopy screening; and those who perceived less barriers and more benefits to having the test. CONCLUSIONS: The findings are broadly consistent with previous studies of screening participation, although subjective health emerged as an important predictor in this study. There was no evidence for "reverse targeting": attenders were not at lower (or higher) risk for colorectal cancer compared with non-attenders. The findings relating to attitudes and beliefs could be used in efforts to improve attendance, for example by developing information leaflets that address barriers to screening. Other findings could be used to target interventions to subgroups that have relatively low rates of screening participation.

Age Factors↗

Association between antihypertensive drug use and hypoglycemia: a case-control study of diabetic users of insulin or sulfonylureas.

Antihypertensive drugs are commonly prescribed for the treatment of patients with both diabetes and hypertension. However, the role of selected agents in the development of hypoglycemia remains controversial. The main objective of this study was to evaluate the effect of antihypertensive agents on the risk of hypoglycemia in diabetic patients receiving insulin or sulfonylurea therapy. A matched case-control study was conducted using Pennsylvania Medicaid data. Five control subjects, matched for sex and age, with no reported medical condition of hypoglycemia, were randomly selected for each case patient admitted for hypoglycemia in 1993, resulting in a total of 404 cases and 1375 controls. With these sample sizes, we were able to detect a difference of 10% (P < 0.05) for our primary outcome measure, hospitalization for hypoglycemia. The relative risk of hypoglycemia was estimated using an unconditional logistic regression. The risk of hypoglycemia was 5.5 times greater (95% confidence interval [CI], 4.0 to 7.6) in insulin versus sulfonylurea users and was not influenced by use of angiotensin-converting enzyme (ACE) inhibitors overall. However, use of the ACE inhibitor enalapril was associated with an increased risk of hypoglycemia (odds ratio, 2.4; 95% CI, 1.1 to 5.3) in sulfonylurea users, suggesting that analyzing the unintended side effects of a class of drugs can sometimes mask the adverse effects of individual drugs. Use of beta-blockers was not associated with an increased risk of hypoglycemia, providing further empiric evidence that beta-blockers are an appropriate treatment for persons with concomitant diabetes and hypertension. Per capita health care costs were approximately 3 times higher in patients hospitalized for hypoglycemia compared with controls (P < 0.05). Hospitalization for hypoglycemia is expensive and may be prevented with appropriate monitoring of diabetic patients taking selected antihypertensive agents such as enalapril.

Adolescent↗

The effect of botulinum toxin A on gastrocnemius length: magnitude and duration of response.

Thirty-nine ambulant children (22 with hemiplegia, 17 with diplegia) with spastic cerebral palsy receiving isolated gastrocnemius muscle injection with botulinum toxin A were studied prospectively. The children had a mean age of 6 years (range 3 to 13 years). Measurement of gastrocnemius muscle length was used to estimate the dynamic component of each child's spasticity and to quantify the response. There was a strong correlation between the dynamic component of spasticity before injection and the corresponding magnitude of the response after injection. Children undergoing repeated injections showed similar correlations. A strong correlation was found between the duration of response and the dynamic component. Children with hemiplegia showed twice the duration for a given dynamic component compared with those with diplegia when injected with the same total dose per unit body weight. Long-term lengthening did not occur for the cohort, although some patients showed a response at a 12-month follow-up. By delaying shortening, the injections may have a role in delaying the need for surgery. Injections were well tolerated with few side effects.

Adolescent↗

Malaria infection during pregnancy: intrauterine growth retardation and preterm delivery in Malawi.

In sub-Saharan Africa, malaria infection in pregnancy contributes to low birth weight through intrauterine growth retardation (IUGR) and preterm delivery (PTD). It was hypothesized that malaria-associated PTD and IUGR have differing etiologies due to timing of infection. In a prospective cohort of primigravid women enrolled at the antenatal clinic of Mangochi District Hospital in Malawi, the associations were investigated between antenatal or delivery parasitemias and IUGR or PTD. Among 178 singleton deliveries, 35% of infants were preterm or had IUGR. Cord blood parasitemia (odds ratio [OR]=3.34; 95% confidence interval [CI], 1.3-8.8], placental parasitemia (OR=2.43; 95% CI, 1.2-5.1), and postdelivery maternal peripheral parasitemia (OR=2.78; 95% CI, 1.3-6.1) were associated with PTD. Parasitemia and/or clinically diagnosed malaria in the antenatal period was associated with IUGR (OR=5.13; 95% CI, 1.4-19.4). Delivery parasitemias had borderline associations with IUGR. The risk patterns observed suggest that the timing and severity of infection influences the occurrence of IUGR or PTD.

Female↗

Cytokine expression in the brain in human cerebral malaria.

Evidence from clinical studies and murine models supports a role for cytokines in the pathogenesis of human cerebral malaria (CM). In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate expression of mRNA for transforming growth factor (TGF)-beta, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in human postmortem tissue. Immunohistochemistry was used to examine the distribution of cytokine protein. TGF-beta was expressed in normal brain, in CM, and in meningitis and encephalitis. IL-1beta was absent from normal brain but was detected in CM and other cerebral infections. TNF-alpha mRNA was expressed only in CM, although TNF-alpha protein was also seen in meningitis. Cytokine mRNA expression in the brain did not correlate with the density of parasitized erythrocytes detected using RT-PCR for major surface protein-2. This report of RT-PCR on postmortem human tissues infected with CM demonstrates induction of the proinflammatory cytokines TNF-alpha and IL-1beta in the brain.

Antigens, Protozoan↗

Differential role of CTLA-4 in regulation of resting memory versus naive CD4 T cell activation.

Regulation of peripheral T cell responses is critical for preserving self tolerance. Memory T cells have a lower threshold for activation through the TCR and are thought to be less dependent on costimulation than naive T cells, suggesting a requirement for more stringent regulation of memory T cells. We have recently shown that CD4 engagement apart from the TCR results in the inactivation of memory, but not naive, CD4 T cells. We show here that this inhibition requires ligation of CTLA-4, in that blocking CTLA-4-B7 interactions restores memory CD4 T cell responsiveness. Early signaling through CTLA-4 is possible because resting memory, but not naive, CD4 T cells contain intracellular stores of CTLA-4 that are continuously recycled between the cytoplasm and the cell surface. This mechanism ensures that low intensity TCR engagements, which are thought to be important for peripheral T cell longevity, do not cause memory T cell activation but instead raise their threshold for costimulatory signals. This may give memory T cells an extended lifespan with a reduced risk of inappropriate activation.

Abatacept↗

Outcome after treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma. DESIGN: Analysis of data from a multicenter study. SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). MEASUREMENTS: Death, disease progression, and disease-free survival. RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.

Adenocarcinoma, Follicular↗