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Biomedical subjects

L Buckley

Publications and source records attributed to L Buckley.

At least 19 recordsLinked to original sources
PubMed2001

Tamoxifen and cardiac risk factors in healthy women: Suggestion of an anti-inflammatory effect.

-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all P:<0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen. The potential for beneficial cardiovascular effects of tamoxifen in healthy women is suggested.

Administration, Oral↗
PubMed1999

Dynamically heterogenous partitions and phylogenetic inference: an evaluation of analytical strategies with cytochrome b and ND6 gene sequences in cranes.

ki ctes over whether molecular sequence data should be partitioned for phylogenetic analysis often confound two types of heterogeneity among partitions. We distinguish historical heterogeneity (i.e., different partitions have different evolutionary relationships) from dynamic heterogeneity (i.e., different partitions show different patterns of sequence evolution) and explore the impact of the latter on phylogenetic accuracy and precision with a two-gene, mitochondrial data set for cranes. The well-established phylogeny of cranes allows us to contrast tree-based estimates of relevant parameter values with estimates based on pairwise comparisons and to ascertain the effects of incorporating different amounts of process information into phylogenetic estimates. We show that codon positions in the cytochrome b and NADH dehydrogenase subunit 6 genes are dynamically heterogenous under both Poisson and invariable-sites + gamma-rates versions of the F84 model and that heterogeneity includes variation in base composition and transition bias as well as substitution rate. Estimates of transition-bias and relative-rate parameters from pairwise sequence comparisons were comparable to those obtained as tree-based maximum likelihood estimates. Neither rate-category nor mixed-model partitioning strategies resulted in a loss of phylogenetic precision relative to unpartitioned analyses. We suggest that weighted-average distances provide a computationally feasible alternative to direct maximum likelihood estimates of phylogeny for mixed-model analyses of large, dynamically heterogenous data sets.

Algorithms↗
PubMed1999

Personality dimensions in chronic fatigue syndrome and depression.

Chronic fatigue syndrome (CFS) is a poorly understood condition. Possible etiological factors include infectious agents, psychiatric disorders, and personality characteristics. We examined personality dimensions in 30 nondepressed patients with CFS, 20 patients with major depressive disorder (MDD), and 15 healthy controls. On the NEO-FFI, patients with CFS scored significantly lower than healthy controls on the extroversion subscale. On the neuroticism dimension of the Eysenck Personality Questionnaire (EPQ), patients with MDD scored higher than those with CFS, who in turn scored significantly higher than the healthy controls. CFS patients rated themselves as higher on neuroticism and less extroverted when ill than when they were well. Our results suggest that high scores on neuroticism and low scores on extroversion in CFS could be a reaction to chronic illness.

Adult↗
PubMed1998

Rib lesions and tuberculosis: the palaeopathological evidence.

SETTING: Tuberculosis diagnosis in past populations relies on lesions in the spine and major weight bearing joints of the body. Bone formation on visceral surfaces of ribs has also been suggested to be the result of chronic pulmonary disease. OBJECTIVE: To test whether these lesions are the result of pulmonary infection (most likely tuberculosis), by reviewing past work, and to discuss whether these lesions could be considered another diagnostic criterion for pulmonary tuberculosis. DESIGN: A review of the literature on new bone formation on ribs, and consideration of further evidence from archaeological skeletal material from the UK. RESULTS: Results from modern studies suggest that bone formation on ribs is often the result of pulmonary tuberculosis, that lesions are relatively common in archaeological skeletal material, and that some skeletons have rib lesions plus pathognomonic changes of tuberculosis. CONCLUSION: Evidence suggests that new bone formation on visceral surfaces of ribs should be considered a possible indicator of tuberculosis. If accepted, historical evidence, when correlated with rib data, produces closer approximations to the frequency of the disease in the past. This study indicates the importance of palaeopathology in identifying sometimes subtle lesions that may not be noted by clinicians because of their non-visibility on radiographs.

Humans↗
PubMed1997

DNA phylogeny of the marsupial wolf resolved.

The phylogenetic position of the recently extinct marsupial 'wolf', or thylacine (Thylacinus cynocephalus), has been a source of contention in mammalian systematics for nearly a century. Thylacines were endemic to Australasia, but possessed striking anatomical similarities to Oligo-Miocene borhyaenid marsupials of South America. At issue has been whether these features are indicative of common ancestry or convergent adaptation to carnivory. Recent morphological studies have supported both conclusions. Although current marsupial classifications group thylacines with Australian dasyuromorphians, this putative clade is characterized by mostly primitive morphological features. Attempts to determine thylacine affinities with ancient protein and DNA analyses have supported, but not resolved, a dasyuromorphian placement. We report 1546 bp of mitochondrial DNA sequence (from cytochrome b and 12S rRNA genes) and 841 bp of nuclear protamine gene sequence from the thylacine and representatives of all or most other marsupial orders. Phylogenetic analysis of these sequences shows unambiguously that thylacines are members of Dasyuromorphia, and suggests a late Oligocene or very early Miocene divergence of familial lineages.

Animals↗
PubMed1997

A multigene assessment of phylogenetic relationships within the dasyurid marsupial subfamily Sminthopsinae.

We report sequences of the mitochondrial cytochrome b (1146 bp) and 12S rRNA (961 bp) genes, as well as the nuclear protamine P1 (608 bp) gene, from 13 species representing all four genera of the dasyurid marsupial subfamily Sminthopsinae. Mitochondrial sequences are partitioned into five categories (three codon positions in cytochrome b, and stems and loops in 12S rRNA) with distinct substitution rates, transition biases, and base compositions. We extract estimates of these biases from the sequences and employ them to calculate two overall distances based on the DNAML model. Phylogenetic analyses using distance and parsimony methods yield trees with different topologies for mtDNA and protamine. These trees are compatible with respect to highly resolved nodes, but incompatible with respect to length differences in a parsimony framework. The tree from combined-data analysis is dominated by the larger data set (mtDNA). The balance of evidence favors a basal separation of Planigale from other sminthopsines. Within Planigale, Pl. maculata is sister to the remaining species. Although the precise intergeneric affinities of Antechinomys are unresolved, A. laniger does not appear to be part of the genus Sminthopsis as suggested by morphological data. The 12S rRNA resolves Ningaui ridei and N. yvonnae as sister species.

Amino Acid Sequence↗
PubMed1997

Radiographic results from the Minocycline in Rheumatoid Arthritis (MIRA) Trial.

OBJECTIVE: To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and final visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease. RESULTS: Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 placebo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference. CONCLUSION: Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted "newly involved" joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.

Adult↗
PubMed1995

Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group.

OBJECTIVE: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. DESIGN: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. SETTING: 6 clinical centers in the United States. PATIENTS: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. MEASUREMENTS: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. RESULTS: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. CONCLUSIONS: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.

Administration, Oral↗
PubMed1992

A health survey of toll booth workers.

The prevalence of respiratory and other health problems in a cohort of highway toll booth workers was surveyed by mailed questionnaire. In a low proportion of respondents (43.2%), a high prevalence of central nervous system complaints (headaches, irritability, or anxiety, and unusual tiredness), mucous membrane irritation (eye irritation, nasal congestion, and dry throat), and musculoskeletal problems (joint and back pains) was found. We believe these symptoms are reflective of the acute irritant and central nervous system effects of exposure to motor vehicle exhaust. The musculoskeletal complaints are likely the result of bending, reaching, and leaning out of the toll booth. The need for in-depth evaluation of the ventilation systems and the ergonomic and job stressors of work at toll booths is suggested by these results.

Adult↗
PubMed1990

Effect of blood upon the selective ablation of atherosclerotic plaque with a pulsed dye laser.

Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques.

Animals↗
PubMed1988

31P NMR studies of the diabetic lens.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic analyses of the crystalline lens from the experimental diabetic rat were performed. Qualitative and quantitative alterations in the phosphorus-31 NMR metabolic profile were observed over the course of 3 weeks after the induction of diabetes mellitus. Most striking was the appearance of two new, as yet unidentified, metabolites. These metabolites which resonate at 6.6 and 5.8 ppm were not detected in the normal lens. Compared to the normal lens, glycerol-3-phosphate (G3P) underwent an eightfold increase in concentration and phosphorylcholine decreased to one-third its initial level. The phosphodiesters, glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE), decreased to barely detectable levels. Oral treatment of the diabetic animal with an aldose reductase inhibitor resulted in the preservation of an essentially normal lens 31P NMR spectrum. Except for the changes observed in glycerol-3-phosphate, these alterations have not been previously reported and raise new questions about the metabolic consequences of diabetes mellitus and the dependence of these alterations on the action of a single enzyme, aldose reductase.

Aldehyde Reductase↗
PubMed1987

Cloning of genes that suppress an Escherichia coli K-12 alanine auxotroph when present in multicopy plasmids.

To facilitate molecular analyses of a previously uncharacterized gene involved in alanine synthesis, attempts were made to clone the wild-type allele of this gene, alaA, with a mini-Mu plasmid element used for in vivo cloning. Seventy-six independent Ala+ plasmids were isolated and characterized. Physiological, enzymological, and restriction endonuclease analyses indicated that three different genes, none of them alaA, were cloned. These genes were avtA+, which encodes the alanine-valine transaminase (transaminase C); tyrB+, which encodes the tyrosine-repressible transaminase (transaminase D); and a previously undescribed gene, called alaB, which encodes an alanine-glutamate transaminase.

Alanine↗
PubMedDate not supplied

Perceptions of pharmacists about adverse effects of corticosteroid therapy: focus on osteoporosis.

OBJECTIVE: To assess the perceptions of pharmacists regarding the adverse effects of corticosteroids, in particular corticosteroid-induced osteoporosis. DESIGN: Mailed survey of a random sample of pharmacists. SETTING: Richmond, Virginia. PARTICIPANTS: 350 community and hospital pharmacists. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Respondents' knowledge of adverse effects of corticosteroid therapy in men, premenopausal women, and postmenopausal women; the content of respondents' usual patient counseling for low- and high-dose therapy; and respondents' opinions of regimens for prevention of osteoporosis. RESULTS: Pharmacists associated gastritis, weight gain, and mood changes with corticosteroid use in a hypothetical 45-year-old man or 45-year-old premenopausal woman. For a hypothetical 65-year-old postmenopausal woman, pharmacists more frequently counseled about weight gain, osteoporosis, and gastritis. Patient counseling focused on these adverse effects for both low-dose (5 to 10 mg/day) and high-dose (> or = 30 mg/day) prednisone use. Osteoporosis was considered more likely in patients receiving high-dose corticosteroids on a long-term basis. CONCLUSION: Pharmacists responding to this survey frequently overlooked the association between low- and high-dose corticosteroid use and decreased bone density. Educational efforts are needed so that pharmacists can fulfill their potential for educating patients, monitoring corticosteroid therapy, and detecting drug-induced complications.

Adrenal Cortex Hormones↗