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Biomedical subjects

D Atkins

Publications and source records attributed to D Atkins.

At least 19 recordsLinked to original sources
PubMed2006

Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications.

Adult↗
PubMed2006

Laser microdissection and microarray analysis of breast tumors reveal ER-alpha related genes and pathways.

About 70-80% of breast cancers express estrogen receptor alpha (ER-alpha), and estrogens play important roles in the development and growth of hormone-dependent tumors. Together with lymph node metastasis, tumor size, and histological grade, ER status is considered as one of the prognostic factors in breast cancer, and an indicator for hormonal treatment. To investigate genes and pathways that are associated with ER status and epithelial cells in breast tumor, we applied laser capture microdissection (LCM) technology to capture epithelial tumor cells from 28 lymph node-negative breast tumor samples, in which 17 patients had ER-alpha+ tumors, and 11 patients have ER-alpha- tumors. Gene expression profiles were analysed on Affymetrix Hu133A GeneChip. Meanwhile, gene profiles using total RNA isolated from bulk tumors of the same 28 patients were also generated. In total, 146 genes and 112 genes with significant P-value and having significant differential expression between ER-alpha+ and ER-alpha- tumors were identified from the LCM data set and bulk tissue data set, respectively. A total of 61 genes were found to be common in both data sets, while 85 genes were unique to the LCM data set and 51 genes were present only in the bulk tumor data set. Pathway analysis with the 85 genes using Gene Ontology suggested that genes involved in endocytosis, ceramide generation, Ras/ERK/Ark cascade, and JAT-STAT pathways may play roles related to ER. The gene profiling with LCM-captured tumor cells provides a unique approach to study epithelial tumor cells and to gain an insight into signaling pathways associated with ER.

Breast Neoplasms↗
PubMed2003

[Intraoperative histological sections in obstetric brachial plexus lesions--comparison of macroscopic appearance, HE staining and toluidine blue staining].

In brachial plexus lesions and their revision, evaluation of nerve stumps is very important for the reconstructive strategy. We intraoperatively perform cryostat sections, Haematoxilin-Eosin (HE) stained, and compare the clinical appearance of the nerves to the microscopic results. Toluidine blue staining is later used to validate the structural details. Intraneural fibrosis can be traced safely with both staining methods, in root avulsions a histology is helpful, too. For more proximal, intraforaminal lesions semithin section stained with toluidine-blue are less informative than are HE-stained cryostat sections. In these lesions the clinical control by electrical stimulation and evoked potentials is superior.

Adult↗
PubMed2001

Metal distribution in Clark Fork River sediments.

Accurate sampling of pore waters and sediments in gravel river beds is problematic because cobbles preclude most coring techniques, while the angularity of sand grains destroys the membranes of standard pore water samplers. In the Clark Fork River, the recipient of over 100 years of mining activity, a modified single tube core-freezing device was used to profile bed sediment (approximately 65% cobbles and 35% gravel substrate), and a novel pore water sampler was developed to collect interstitial water. In the sediment, the <63 microm fraction comprised <4 wt % yet contained approximately an order of magnitude higher metal concentrations compared to the 63 microm-2 mm fraction (constituting approximately 20% of the mass). However, on a mass basis the sand fraction contained 60% of the metals, compared to 40% in the clay/silt fraction in the gravels, while in point bars the distribution was approximately 50:50. The metals occur predominantly in sulfides frequently armored with an oxide rim and other sparingly soluble phases that may explain the low pore water metal concentrations. These data demonstrate that consideration of multiple particle size cutoffs is necessary to accurately characterize fluvial bed sediment metal conditions and that the form of the metal is important in understanding metal solubility in the benthos.

Animals↗
PubMed2001

Screening and treating adults for lipid disorders.

CONTEXT: Screening and treatment of lipid disorders in people at high risk for future coronary heart disease (CHD) events has gained wide acceptance, especially for patients with known CHD, but the proper role in people with low to medium risk is controversial. OBJECTIVE: To examine the evidence about the benefits and harms of screening and treatment of lipid disorders in adults without known cardiovascular disease for the U.S. Preventive Services Task Force. DATA SOURCES: We identified English-language articles on drug therapy, diet and exercise therapy, and screening for lipid disorders from comprehensive searches of the MEDLINE database from 1994 through July 1999. We used published systematic reviews, hand searching of relevant articles, the second Guide to Clinical Preventive Services, and extensive peer review to identify important older articles and to ensure completeness. DATA SYNTHESIS: There is strong, direct evidence that drug therapy reduces CHD events, CHD mortality, and possibly total mortality in middle-aged men (35 to 65 years) with abnormal lipids and a potential risk of CHD events greater than 1% to 2% per year. Indirect evidence suggests that drug therapy is also effective in other adults with similar levels of risk. The evidence is insufficient about benefits and harms of treating men younger than 35 years and women younger than 45 years who have abnormal lipids but no other risk factors for heart disease and low risk for CHD events (less than 1% per year). Trials of diet therapy for primary prevention have led to long-term reductions in cholesterol of 3% to 6% but have not demonstrated a reduction in CHD events overall. Exercise programs that maintain or reduce body weight can produce short-term reductions in total cholesterol of 3% to 6%, but longer-term results in unselected populations have found smaller or no effect. To identify accurately people with abnormal lipids, at least two measurements of total cholesterol and high-density lipoprotein cholesterol are required. The role of measuring triglycerides and the optimal screening interval are unclear from the available evidence. CONCLUSIONS: On the basis of the effectiveness of treatment, the availability of accurate and reliable tests, and the likelihood of identifying people with abnormal lipids and increased CHD risk, screening appears to be effective in middle-aged and older adults and in young adults with additional cardiovascular risk factors.

Adult↗
PubMed2001

Current methods of the US Preventive Services Task Force: a review of the process.

The U.S. Preventive Services Task Force (USPSTF/Task Force) represents one of several efforts to take a more evidence-based approach to the development of clinical practice guidelines. As methods have matured for assembling and reviewing evidence and for translating evidence into guidelines, so too have the methods of the USPSTF. This paper summarizes the current methods of the third USPSTF, supported by the Agency for Healthcare Research and Quality (AHRQ) and two of the AHRQ Evidence-based Practice Centers (EPCs). The Task Force limits the topics it reviews to those conditions that cause a large burden of suffering to society and that also have available a potentially effective preventive service. It focuses its reviews on the questions and evidence most critical to making a recommendation. It uses analytic frameworks to specify the linkages and key questions connecting the preventive service with health outcomes. These linkages, together with explicit inclusion criteria, guide the literature searches for admissible evidence. Once assembled, admissible evidence is reviewed at three strata: (1) the individual study, (2) the body of evidence concerning a single linkage in the analytic framework, and (3) the body of evidence concerning the entire preventive service. For each stratum, the Task Force uses explicit criteria as general guidelines to assign one of three grades of evidence: good, fair, or poor. Good or fair quality evidence for the entire preventive service must include studies of sufficient design and quality to provide an unbroken chain of evidence-supported linkages, generalizable to the general primary care population, that connect the preventive service with health outcomes. Poor evidence contains a formidable break in the evidence chain such that the connection between the preventive service and health outcomes is uncertain. For services supported by overall good or fair evidence, the Task Force uses outcomes tables to help categorize the magnitude of benefits, harms, and net benefit from implementation of the preventive service into one of four categories: substantial, moderate, small, or zero/negative. The Task Force uses its assessment of the evidence and magnitude of net benefit to make a recommendation, coded as a letter: from A (strongly recommended) to D (recommend against). It gives an I recommendation in situations in which the evidence is insufficient to determine net benefit. The third Task Force and the EPCs will continue to examine a variety of methodologic issues and document work group progress in future communications.

Advisory Committees↗
PubMed2001

Priorities among recommended clinical preventive services.

BACKGROUND: Many recommended clinical preventive services are delivered at low rates. Decision-makers who wish to improve delivery rates, but face competing demands for finite resources, need information on the relative value of these services. This article describes the results of a systematic assessment of the value of clinical preventive services recommended for average-risk patients by the U.S. Preventive Services Task Force. METHODS: The assessment of services' value for the U.S. population was based on two dimensions: burden of disease prevented by each service and cost effectiveness. Methods were developed for measuring these criteria consistently across different types of services. A companion article describes the methods in greater detail. Each service received 1 to 5 points on each of the two dimensions, for total scores ranging from 2 to 10. Priority opportunities for improving delivery rates were determined by comparing the ranking of services with what is known of current delivery rates nationally. RESULTS: The highest ranked services (scores of 7+) with the lowest delivery rates (< or =50% nationally) are providing tobacco cessation counseling to adults, screening older adults for undetected vision impairments, offering adolescents an anti-tobacco message or advice to quit, counseling adolescents on alcohol and drug abstinence, screening adults for colorectal cancer, screening young women for chlamydial infection, screening adults for problem drinking, and vaccinating older adults against pneumococcal disease. CONCLUSIONS: Decision-makers can use the results to set their own priorities for increasing delivery of clinical preventive services. The methods provide a basis for future priority-setting efforts.

Adult↗
PubMed2001

Methods for priority setting among clinical preventive services.

Methods used to compare the value of clinical preventive services based on two criteria-clinically preventable burden (CPB) and cost effectiveness (CE)-are described. A companion article provides rankings of clinical preventive services and discusses its uses for decision-makers; this article focuses on the methods, challenges faced, and solutions. The authors considered all types of data essential to measuring CPB and CE for services recommended by the U.S. Preventive Services Task Force and developed methods essential to ensuring valid comparisons of different services' relative value.

Bias↗
PubMed2001

Variation in melanin content and composition in type V and VI photoexposed and photoprotected human skin: the dominant role of DHI.

A combination of techniques, including high-performance liquid chromatography (HPLC), spectrophotometric measurements, and a novel method for quantifying melanosome morphology, were applied to the analysis of melanin content and composition in highly pigmented (Fitzpatrick type V and VI) human skin. We found that total epidermal melanin content is significantly elevated in photoexposed type V and VI skin (approximately 1.6 x), while analysis of individual melanin components suggests that pheomelanin content increases only slightly, whereas 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-eumelanin and to a greater extent 5,6-dihydroxyindole (DHI)-eumelanin content are both markedly elevated. Analysis of the relative composition of epidermal melanin in these subjects revealed that DHI-eumelanin is the largest single component (approximately 60-70%), followed by DHICA-eumelanin (25-35%), with pheomelanin being a relatively minor component (2-8%). Moreover, there was a comparative enrichment of DHI-eumelanin at photoexposed sites, with a corresponding decline in the relative contributions from DHICA-eumelanin and pheomelanin. There was also a good correlation and close agreement between the concentration of spheroidal melanosomes determined by morphological image analysis and the concentration of pheomelanin determined by a combination of HPLC and spectrophotometric analysis (r = 0.89, P < 0.02). This study demonstrates the usefulness of melanosome morphology analysis as a sensitive new method for the quantification of melanin composition in human skin. The data also suggest that DHI-eumelanin formation is the dominant pathway for melanin synthesis in heavily pigmented (Fitzpatrick V and VI) skin types in vivo, and is the favoured pathway when melanin production is increased in chronically photoexposed skin.

Biopsy↗
PubMed2000

HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels independently of tumor grading and staging and can be recognized by HLA-A2.1-restricted cytotoxic T lymphocytes.

The HER-2/neu oncoprotein, a 185 kDa membrane-associated tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGF-R), is overexpressed in breast and ovarian carcinomas. Its overexpression is closely associated with poor prognosis in the course of disease. Here we demonstrate HER-2/neu overexpression in both established cell lines and biopsy material obtained from renal epithelial tumors. Immunohistochemical analysis of human kidney tumor lesions using 2 HER-2/neu-specific antibodies revealed HER-2/neu expression in more than 40% of primary epithelial renal tumors and more than 30% of primary renal cell carcinoma (RCC) specimens. A distinctive HER-2/neu expression pattern was found in different subtypes of kidney tumors with the highest frequency in chromophilic and chromophobic RCC, but neither associated with disease stage nor tumor grade. Eight of 10 RCC cell lines expressed significant levels of HER-2/neu mRNA and protein, but at a lower level compared with HER-2/neu overexpressing ovarian carcinoma cells. To evaluate the immune response against HER-2/neu expressing HLA-A2-positive (HLA-A2(+)) RCC cells, allogeneic HLA-A2-restricted cytotoxic T-lymphocyte (CTL) lines generated by pulsing dendritic cells with 3 different HER-2/neu-derived peptides, (HER-2(9.369), HER-2(9.435) and HER-2(9.689), were utilized in chromium-release assays. Specific lysis of HER-2/neu expressing HLA-A2(+) RCC cell lines was mediated by CTL lines specific for each of these 3 HER-2/neu-derived epitopes. The fine specificity of 2 CTL clones was defined to the epitopes HER-2(9.435) and HER-2(9.689). Their specificity was then confirmed by cold target inhibition assays. In addition, CTL-mediated lysis was enhanced by pulsing tumor cells with exogenous HER-2/neu-specific peptides. Our data suggest that (i) HER-2/neu is heterogeneously expressed in different subtypes of RCC, (ii) HER-2/neu is naturally processed by RCC and (iii) HER-2/neu epitopes presented by RCC can be recognized by HLA-A2-restricted, HER-2/neu-specific CTL.

Antigens, Neoplasm↗
PubMed2000

A rapid genetic screening system for identifying gene-specific suppression constructs for use in human cells.

We describe a rapid cell-based genetic screen using fission yeast for identifying efficient gene suppression constructs (GSCs) from large libraries (10(5)) for any target sequence for use in human cells. In this system, target sequences are fused to the 5' end of the lacZ reporter gene and expressed in yeast. Random fragment expression libraries derived from the target sequence are screened in the fusion gene-expressing strain using the lacZ gene-encoded colony color phenotype. We demonstrate the utility of this screening assay by identifying a range of different GSCs for the fission yeast ura4 gene and human c-myc and Chk1 sequences, including rare efficient suppressors. GSCs specific for c-myc were shown to regulate expression of both a c-myc-lacZ fusion gene and the endogenous c-myc gene in human cells.

Cells, Cultured↗
PubMed2000

Comparative analysis of artificial antisense RNA regulation in fission yeast and human cells.

The fission yeast Schizosaccharomyces pombe has recently been established as an experimental model for the study of antisense RNA-mediated gene suppression. To validate the use of S. pombe as a host for identifying antisense genes for use in human cells, it was important to determine if sequences identified in yeast were as equally effective in a human cell line. This report describes the comparison of a range of lacZ antisense RNAs targeting a lacZ gene expressed in HeLa cells in a comparable manner to its expression in S. pombe cells in earlier studies. In both cell types, the same lacZ gene target was expressed using the same promoter. Antisense genes were expressed episomally in both experimental systems and the levels of suppression determined. In all cases, the relative level of suppression of the lacZ gene was similar in the mammalian and yeast cells. This result indicates that, at least for lacZ antisense RNA, results obtained in fission yeast are predictive of their behavior in the mammalian cellular environment.

Base Sequence↗
PubMed2000

Interventions for treating plantar heel pain.

BACKGROUND: Ten percent of people may experience pain under the heel (plantar heel pain) at some time. Injections, insoles, heel pads, strapping and surgery have been common forms of treatment offered. The absolute and relative effectiveness of these interventions are poorly understood. OBJECTIVES: The objective of this review was to identify and evaluate the evidence for effectiveness of treatment in treating plantar heel pain. SEARCH STRATEGY: MEDLINE (from 1966 to December 1997), EMBASE and the Cochrane Library were searched. Three podiatry journals (The Foot, The Chiropodist (later The Journal of British Podiatric Medicine), and The British Journal of Podiatric Medicine) were handsearched. We contacted known investigators in the field to identify unpublished data or research in progress. Non English language reports were excluded from the review. SELECTION CRITERIA: Randomised and quasi randomised trials of interventions for plantar heel pain in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated studies for inclusion, extracted data and assessed study quality. Additional information was obtained by direct contact with investigators. No poolable data were identified. Where measures of variance were available we have calculated the weighted mean differences based on visual analogue scale (VAS) scores. MAIN RESULTS: Eleven randomised trials involving 465 participants were included. Study quality was generally poor, and pooling of data was not possible. All studies measured a reduction in heel pain as the primary outcome. Seven trials evaluated interventions against placebo/dummy or no treatment. There was limited evidence for the effectiveness of topical corticosteroid, administered by iontophoresis in reducing pain. There was no evidence for the effectiveness of injected corticosteroid. There was limited evidence for the effectiveness of low energy extracorporeal shock wave therapy in reducing night pain, resting pain and pressure pain in the short term (12 weeks). In individuals with chronic pain (longer than six months), there was limited evidence for the effectiveness of dorsiflexion night splints in reducing pain. There was no evidence to support the effectiveness of therapeutic ultrasound, low-intensity laser therapy, exposure to an electron generating device or insoles with magnetic foil. No randomised trials evaluating orthotic devices, surgery, or radiotherapy against a control population were identified. There was limited evidence for the superiority of corticosteroid injections over orthotic devices. REVIEWER'S CONCLUSIONS: Although there is limited evidence for the effectiveness of local corticosteroid therapy, the effectiveness of other frequently employed treatments in altering the clinical course of plantar heel pain has not been established in comparative studies. Well designed and conducted randomised studies are required.

Adrenal Cortex Hormones↗
PubMed2000

Mandated coverage for cancer-screening services: whose guidelines do states follow?

OBJECTIVES: To determine the prevalence and nature of state coverage mandates for cancer screening. METHODS: We contacted insurance departments in 50 states, Washington, DC, and Puerto Rico for copies of state codes that mandate coverage of screening for breast, cervical, prostate, and colorectal cancer by private insurers. We further compared mandates, when identified, with American Cancer Society (ACS) and U.S. Preventive Services Task Force (USPSTF) guidelines for likely sources of screening recommendations. RESULTS: Forty-three states and the District of Columbia currently mandate coverage of cancer screening. Breast cancer-screening coverage was most frequently mandated (n =44), followed by cervical (n =22), prostate (n =18), and colorectal cancer screening (n =1). Twenty-three states used ACS guidelines only, 18 states used ACS and non-ACS/non-USPSTF guidelines, and 3 states used only non-ACS/non-USPSTF guidelines in development of coverage mandates. No state screening coverage mandate reflected USPSTF-screening guidelines. Of 85 mandates in place, 57 have been passed since 1990. CONCLUSIONS: Although state mandates for insurer coverage of cancer screening are common and increasing, we found noticeable inter- and intra-state variation in coverage, selection, and use of screening guidelines.

Adolescent↗
PubMed2000

The influence of antisense gene location on target gene suppression in the fission yeast Schizosaccharomyces pombe.

A fission yeast model was employed to investigate the influence of antisense gene location on the efficacy of antisense RNA-mediated target gene suppression. Fission yeast transformants were generated that contained the target lacZ gene at a fixed position and a single copy antisense lacZ gene integrated into various genomic locations, including the same locus as the target gene. No significant difference in lacZ suppression was observed when the antisense gene was integrated in close proximity to the target gene locus compared with other genomic locations, indicating that target and antisense gene colocalization is not a critical factor for efficient antisense RNA-mediated gene expression in vivo. Instead, increased lacZ downregulation correlated with an increase in antisense dose, with the steady-state levels of antisense RNA being dependent on genomic position effects and transgene copy number.

Down-Regulation↗