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Biomedical subjects

D Taylor

Publications and source records attributed to D Taylor.

At least 181 records · Page 10Linked to original sources

Efficacy of the carbocyclic 2'-deoxyguanosine nucleoside BMS-200475 in the woodchuck model of hepatitis B virus infection.

Daily oral treatment with the cyclopentyl 2'-deoxyguanosine nucleoside BMS-200475 at doses ranging from 0.02 to 0.5 mg/kg of body weight for 1 to 3 months effectively reduced the level of woodchuck hepatitis virus (WHV) viremia in chronically infected woodchucks as measured by reductions in serum WHV DNA levels and endogenous hepadnaviral polymerase activity. Within 4 weeks of daily therapy with 0.5 or 0.1 mg of BMS-200475 per kg, endogenous viral polymerase levels in serum were reduced about 1,000-fold compared to pretreatment levels. Serum WHV DNA levels determined by a dot blot hybridization technique were comparably decreased in these treated animals. In the 3-month study, the sera of animals that had undetectable levels of WHV DNA by the dot blot technique were further analyzed by a highly sensitive semiquantitative PCR assay. The results indicate that BMS-200475 therapy reduced mean WHV titers by 10(7)- to 10(8)-fold, down to levels as low as 10(2) to 10(3) virions/ml of serum. Southern blot hybridization analysis of liver biopsy samples taken from animals during and after BMS-200475 treatment showed remarkable reductions in the levels of WHV DNA replicative intermediates and in the levels of covalently closed circular viral DNA. WHV viremia in BMS-200475-treated WHV carriers eventually returned to pretreatment levels after therapy was stopped. These results indicate that BMS-200475 should be evaluated in clinical trials for the therapy of chronic human hepatitis B virus infections.

Animals↗

Renal cortical Na+-K+-ATPase activity and abundance is decreased in normal pregnant rats.

During late pregnancy, the rat undergoes massive plasma volume expansion due to cumulative renal sodium retention. In the present study, conducted in virgin, mid- (days 11-13), and late-pregnant (days 18-20) rats, we measured both Na+-K+-ATPase activity (by coupled enzyme assay) and abundance of the alpha-subunits of the Na+-K+-ATPase (by Western and slot blot analyses) in renal cortex, medulla, and brain stem. Unexpectedly, Na+-K+-ATPase in renal cortex, in both stages of pregnancy, is reduced versus the virgin, consistent with our finding of a reduced quantity of the alpha1-subunit. In renal medulla, there is a small rise in activity at midterm, but there is no difference in either activity or abundance of the alpha1-subunit in late pregnancy, when renal Na retention is maximal. In brain stem, where only alpha2- and alpha3-subunits are evident, pregnancy has no impact on enzyme activity or abundance of either isoform. In conclusion, the outcome of these experiments was unexpected in that we did not observe increased renal Na+-K+-ATPase activity in late pregnancy in the rat. In fact, in renal cortex, Na+-K+-ATPase activity and abundance are reduced. Whatever promotes net sodium retention in pregnancy must be capable of overwhelming this and several other strong natriuretic signals.

Animals↗

A randomized trial comparing peak expiratory flow and symptom self-management plans for patients with asthma attending a primary care clinic.

Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.

Adult↗

Pindolol augmentation of antidepressant therapy.

BACKGROUND: Antidepressant therapy is not always effective and is slow to take effect. In theory, these shortfalls may be caused by induction of neuronal negative feedback via pre-synaptic 5-HTIA receptors. Pindolol, an antagonist at somatodentritic pre-synaptic 5-HTIA receptors has been investigated as a potential accelerator and augmentor of antidepressant response. METHOD: A Medline search was conducted in November 1997. RESULTS: Six open-label studies and six controlled studies were identified for review. CONCLUSIONS: Open-label studies strongly suggest that pindolol may accelerate and augment antidepressant response, but controlled studies do not wholly support these findings: only three of six studies clearly demonstrate benefit. Larger, well-designed, controlled trials are needed to determine definitively the effectiveness of pindolol in this context.

Adrenergic beta-Antagonists↗

Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy.

Although it is established that small and medium sized arteries undergo extensive radiation damage, the effect on large vessels such as the carotid arteries is less well understood. We sought to determine if an increased severity of carotid artery stenosis is present in patients who have undergone radiotherapy for head and neck tumours. 45 patients aged 43-90 years (average 67) with head and neck malignancies treated with radiotherapy underwent colour Doppler ultrasonographic scanning of the carotid arteries. These patients were compared with a population of asymptomatic historical controls. 60% of patients demonstrated stenosis ranging from 21 to 86%. 38% of patients demonstrated a stenosis greater than or equal to 50%. Carotid artery stenosis appears to be increased in patients who have previously undergone treatment with radiotherapy to the head and neck regions compared with controls (p < 0.001). These findings suggest that radiation has an adverse effect on large vessels. Colour Doppler follow-up may be indicated for patients receiving head and neck radiation therapy.

Adult↗

Coroners' records of rural and non-rural cases of youth suicide in New South Wales.

OBJECTIVE: The aim of this study is to compare the frequency of certain putative risk factors for youth suicide in New South Wales (especially use of alcohol, social class, unemployment, and internal migration) in metropolitan and rural settings. METHOD: A review of 137 files for 10-19-year-old subjects judged by the Coroner to have committed suicide in 1988-1990 was carried out. RESULTS: One hundred and fifteen males and 21 females were identified (one subjects sex was unavailable). The male-female ratio was higher in rural (13.0) areas than non-rural (4.9 chi 2 = 12.14, p < 0.01). Of 27 subjects migrating within Australia, most migrated in a rural direction, and most to rural shires. Unemployment was somewhat more common among rural (38.5%) than non-rural (28.9%) subjects (chi 2 = 0.75, p = 0.39). Eleven of 50 non-rural parents of the deceased, but none of the 11 rural parents, were ranked as being in social classes 2 or 3. Alcohol consumption appeared more common in rural shires (44%) than metropolitan areas (32.9%), but this was not statistically significant. Medical services were less utilised prior to death in rural (15%) than non-rural (25%) areas (chi 2 = 1.69, p = 0.19), and a psychiatric diagnosis was recorded more commonly in non-rural areas. CONCLUSIONS: Incomplete coronial file data and relatively small numbers limit this study's conclusions. Male suicides, principally by firearms, predominated in rural areas. Youth firearm access remains highly relevant to rural communities. Possible trends among rural subjects toward rural migration, higher unemployment, lower social class and lower medical attendance may point to resource deprivation among this group; these matters require further investigation.

Adolescent↗

Crystal ball gazing: back to the future.

This article presents some of the challenges, competencies, and opportunities that advanced practice nurses will face in the near future as the emerging health care system unfolds. Nurses must be knowledgeable about, prepared for, and participate in the creation of a preferred future in health care policy and practice. Advancing educational programs and orienting research and activism in the direction of personal and community health will allow advanced practice nurses to continue to have a significant influence on the transformation of health care and delivery systems.

Delivery of Health Care↗

Effects of phosphodiesterase inhibitors on glucose utilization in isolated cardiac myocytes.

The phosphodiesterase (PDE) inhibitor, enoximone, enhances the oxidation of fatty acids in cardiac myocytes. Since carbohydrate oxidation is tightly coupled and inversely related in cardiac tissue to fatty acid oxidation, this study was designed to investigate enoximone's effects on glucose metabolism in the heart. To determine if enoximone alters this reciprocal relationship, the effects of enoximone on [U-14C]glucose and [2-14C]pyruvate oxidation were determined in isolated cardiac myocytes. The effect of PDE inhibitors was also examined on pyruvate dehydrogenase complex (PDH) activity, a key component of oxidative glucose metabolism. Two PDE inhibitors, enoximone and milrinone, decreased PDH activity by 69 and 64%, respectively at 0.5 mM. This inhibition of PDH activity by enoximone was completely reversed after removing enoximone from the myocyte medium. PDH activity was unaffected by agents which alter cyclic nucleotide signaling: cGMP, dibutyryl cyclic AMP, and AMP. The effect of enoximone on [2-14C]pyruvate oxidation was similar to that on PDH. Interestingly, the oxidation of glucose was decreased 35% by 0.5 mM enoximone. In isolated rat heart mitochondria (RHM), enoximone decreased PDH activity by 37%. These studies suggest that PDE inhibitors decrease carbohydrate utilization by inhibiting the PDH complex in the heart. The inhibition of PDH by PDE inhibitors appears unrelated to their effects on cAMP or cGMP. This inhibition of PDH by PDE inhibitors may occur, at least in part, secondary to stimulating fatty acid oxidation.

Animals↗

Sudden death in septo-optic dysplasia. Report of 5 cases.

OBJECTIVES: To report our experience with sudden death in children with septo-optic dysplasia and to identify specific risk factors and suggest preventive measures to minimize mortality. METHODS: Clinical data from 5 children with septo-optic dysplasia who died suddenly and unexpectedly were evaluated retrospectively. RESULTS: All children had corticotropin deficiency, all had thermoregulatory disturbances, and 4 children had diabetes insipidus. In at least 4 children, clinical deterioration was caused by fever and dehydration from a presumed viral illness, which appeared to precipitate adrenal crisis. CONCLUSIONS: Children with septo-optic dysplasia and hypocortisolism are at risk for sudden death during febrile illness. Thermoregulatory disturbances and dehydration from diabetes insipidus may potentiate clinical deterioration. Prevention of sudden death in septo-optic dysplasia requires early recognition and treatment of these major risk factors.

Adrenocorticotropic Hormone↗

Contribution of birth defects and genetic diseases to pediatric hospitalizations. A population-based study.

OBJECTIVE: To estimate the contribution of birth defects and genetic diseases to pediatric hospitalizations by use of population-based data. DESIGN: Hospital discharges were categorized according to the diagnostic codes of The International Classification of Diseases, Ninth Revision, Clinical Modification. Hospitalizations that were related to birth defects and genetic diseases were compared with hospitalizations for other reasons, with respect to age, race/ethnicity, sex, length of stay, charges, source of payment, and mortality rate. Hospitalization rates and per capita charges were computed with the use of population estimates from 1990 census data. MATERIALS: The 1991 population-based hospital discharge data from California and South Carolina. RESULTS: Nearly 12% of pediatric hospitalizations in the 2 states combined were related to birth defects and genetic diseases. These children were, on average, about 3 years younger, stayed 3 days longer in a hospital, incurred 184% higher charges, and had a 4 1/2 times greater in-hospital mortality rate than children who were hospitalized for other reasons. The rate of hospitalizations that were related to birth defects and genetic diseases was 4 per 1000 children in both states, but these rates varied by age and race. CONCLUSION: These population-based data are the first contemporary findings to show the substantial morbidity rate and hospitalization charges associated with birth defects and genetic diseases in the pediatric population. IMPLICATIONS: This information is important for planning effective health care strategies, especially as the causes, treatments, and prevention of these disorders are being further elucidated by findings from human genome research and epidemiologic studies.

Adolescent↗

Bone maintenance and remodeling: a control system based on fatigue damage.

This paper explores the relationship between damage, repair, and remodeling in compact bone. A model of microcrack growth is developed that takes account of recent findings on the behaviour of small fatigue cracks in other materials. This is combined with a simple model of a repair process, envisaged as a constant rate of decrease in crack length. The system that results is capable of achieving a stable and precise control of crack length without the need to measure it. This is very useful because it implies that bone does not require the complexities of crack-measuring transducers or active decision-making processes. A simple explanation is suggested for the presence of a "lazy zone" of remodeling equilibrium strains, and the limits of this zone are quantified. The model is developed through a necessarily simplified geometry and loading scheme but can be extended to provide a general solution applicable to in vivo conditions.

Bone Remodeling↗

Relationship between bone-prosthesis bonding and load transfer in total hip reconstruction.

The effect of bone-prosthesis bonding on proximal load transfer is investigated using a coupled experimental and finite element analysis on a synthetic femur. Three-dimensional finite element models for an intact femur and a femur implanted with a cementless prosthesis were constructed from the experimental models used, and the proximal femoral strains recorded for two loading conditions approximating a one-legged stance. The approach was used to investigate a press-fitted and a fully bonded bone-prosthesis structure to identify the stem-bone behaviour for both interface conditions and their implications for proximal bone load transfer. Regression slopes close to unity indicated that the finite element predictions were an accurate estimate of the experimental measurements. Physiological surface strains were recorded only when the abductor force was included in the loading. Meanwhile, experimental measurements and numerical predictions showed that a different load transfer pattern is to be expected for normally press-fitted and glued press-fitted stems. The finite element model for the treated femur, modelling both interface conditions correlated very well with the experimental model. These finite element models subsequently modified and used to analyse the effect of different interface conditions predicted a significant increase in the load transfer to the proximal calcar bone when only proximal bonding is achieved. This study suggests that information obtained for the assessment and prediction of total hip arthroplasty longevity by numerical and experimental techniques used together and in parallel is of greater value than either technique used alone. The employment of a femur analogue as featured in this study is also shown to be a suitable alternative to cadaveric specimens in such an analysis.

Biomechanical Phenomena↗

Natriuretic and depolarizing effects of a stable fly (Stomoxys calcitrans) factor on Malpighian tubules.

A two-step HPLC purification procedure resulted in a factor from the stable fly that depolarizes the lumen-negative transepithelial voltage (V(t)) of the adult stable fly Malpighian tubule. When applied to tubules of the female mosquito, Aedes aegypti, this factor partially mimics the electrophysiological actions of the mosquito natriuretic factor (MNF). It also selectively increases active transepithelial Na transport by the mosquito Malpighian tubule. The blood meal causes a transient increase in hemolymph Na and Cl contents and hemolymph volume during the course of the 24-h post-feeding period. The level of a factor that is immunologically cross-reactive with the human atrial natriuretic peptide (ANP) increases more than 6-fold within 6h following a blood meal by the stable fly. The temporal pattern of the levels of the ANP-immunoreactive factor closely parallels the blood meal-induced rise and subsequent fall in hemolymph NaCl content and hemolymph volume, suggesting a functional correlation between the ANP-immunoreactive factor and the rate of NaCl and fluid loss from the hemolymph.

Journal Article↗