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Biomedical subjects

D Norris

Publications and source records attributed to D Norris.

At least 19 recordsLinked to original sources
PubMed2005

Autografting followed by rituximab for chemosensitive mantle cell lymphoma: a pilot study and literature review.

Mantle cell lymphoma (MCL) is rarely cured with either conventional-dose chemotherapy or autografting. Recent evidence suggests that anti-CD20 monoclonal antibody therapy (rituximab) in combination with chemotherapy may improve the response rate. We report a pilot study of autografting using busulfan-melphalan conditioning followed by rituximab in 9 patients (median age 52 years) with chemosensitive MCL. Rituximab was given for 4 doses of 375 mg/m(2) between 4 and 10 weeks post-transplant. Three of 5 patients autografted after induction therapy remain alive in clinical and molecular complete remission at 33-50 months post-transplant. Only 1 of 4 patients autografted after relapse remains in complete remission. Two of the 3 patients with persistent marrow molecular positivity post-autograft became negative after rituximab therapy. Molecular negativity was first observed in 2 patients only after rituximab therapy. Overall, 2 patients have relapsed and the remaining 3 died of late-onset respiratory failure, probably reflecting infection and/or aggressive conditioning in an older patient population. These preliminary results, together with a review of the literature, suggest that the combination of autografting and rituximab may lead to durable molecular remissions in patients with chemosensitive MCL. Further studies are required to clarify whether the administration of rituximab: (1) is optimal pre- or post-autograft and (2) impacts on the incidence of infection and idiopathic pneumonitis in this context.

Antibodies, Monoclonal↗
PubMed2005

Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV potency.

The goal of this study was to optimize the hydroxyurea dosage in HIV-infected patients, and to minimize the toxicity and maximize the antiviral efficacy of the hydroxyurea-didanosine combination. In a randomized, open-label study (RIGHT 702, a multicenter trial performed in private and institutional practices), three daily doses (600 microg, 800-900 microg, and 1200 microg) of hydroxyurea were administered in combination with didanosine and stavudine to 115 chronically HIV-infected patients, one-third antiretroviral drug naive, with viremia between 5000 and 200,000 copies/ml regardless of CD4+ cell count. The primary efficacy end point was the proportion of patients with plasma HIV-1 RNA levels below 400 copies/ml after 24 weeks of therapy. In the RIGHT 702 intent-to-treat population the lowest (600 mg) dose of hydroxyurea was better tolerated, associated with fewer adverse events, and more potent by all efficacy parameters, including the primary end point (76 versus 60% patients with viremia<400 copies/ml at week 24 for the 600-mg and 800- to 900-mg dose groups, respectively; p=0.027), the mean area under the curve (60.3 versus 65.8; p=0.016), and the mean log10 decrease (-1.95 versus -0.77; p=0.001). Patients receiving 600 mg of hydroxyurea daily also had the highest CD4+ cell count, CD4+/CD8+ cell ratio, and lowest CD8+ cell count and percentage (p=0.035). The RIGHT 702 trial provides an explanation for the increased toxicity and decreased efficacy of hydroxyurea when it was used at high dosage (1200 mg daily). At the optimal dosage of 600 mg daily, hydroxyurea, in combination with didanosine, deserves reevaluation for the long-term management of HIV/AIDS worldwide, because of its excellent resistance profile, durability, and affordability.

Anti-HIV Agents↗
PubMed2004

Relationships between longevity and linear type traits in Holstein cattle population of Southern Africa.

Relationships between longevity and linear type traits were estimated using data on 34,201 cows with lifetime information and linear type scores. The longevity trait considered was the number of lactations initiated and the linear type traits were rump height, body depth, angularity, rear udder height, fore udder attachment, udder depth, fore teat placement and fore teat length. Fixed effects included in the models were herd year, season of calving and herd-date of classification-classifier and days in milk. Age at first calving and age at classification were included as linear and quadratic covariates. Heritability estimates were low for longevity and moderate for most type traits except rump height and fore teat length. All the phenotypic correlations between longevity and the linear type traits were slightly positive (0.01 to 0.09) except the relationships with rump height and fore teat length which were -0.01 and -0.02, respectively. Genetic correlations between longevity and udder traits as well as angularity were moderate to high and positive (0.22 to 0.48). The only notable negative genetic correlations were longevity with body depth and fore teat length (-0.15 and -0.07, respectively). The genetic correlations suggest that selection for udder traits and angularity should improve longevity in the Holstein cattle population.

Age Factors↗
PubMed2004

Estimation of genetic parameters and variance components for growth traits of Nguni cattle in Limpopo Province, South Africa.

Estimates of (co)variance and genetic parameters of birth, weaning (205 days) and yearling (365 days) weight were obtained using single-trait animal models. The data were analysed by restricted maximum likelihood, fitting an animal model that included direct and maternal genetic and permanent environmental effects. The data included records collected between 1976 and 2001. The pedigree information extended as far back as early 1960s. The heritabilities for direct effects of birth, weaning and yearling weights were 0.36, 0.29 and 0.25, respectively. Heritability estimates for maternal effects were 0.13, 0.16 and 0.15 for birth, weaning and yearling weights, respectively. The correlations between direct and maternal additive genetic effects were negative for all traits analysed. The results indicate that both direct and maternal effects should be included in a selection programme for all the traits analysed.

Analysis of Variance↗
PubMed2004

Changes in vegetation and soil characteristics in coastal sand dunes along a gradient of atmospheric nitrogen deposition.

A field survey was conducted to detect signals of atmospheric nitrogen (N) in 11 dune systems along a nitrogen deposition gradient in the United Kingdom. In the mobile and semi-fixed dunes, above-ground biomass was positively related to N inputs. This increase was largely due to increased height and cover of Ammophila arenaria. In the long term, this increased biomass may lead to increased organic matter accumulation and consequently accelerated soil development. In the fixed dunes, above ground biomass also showed a positive relationship with N inputs as did soil C : N ratio while soil available N was negatively related to N inputs. Plant species richness was negatively related to N inputs. In the dune slacks, while soil and bulk vegetation parameters showed no relationship with N inputs, cover of Carex arenaria and Hypochaeris radicata increased. Site mean Ellenberg N numbers showed no relationship with N deposition either within habitats or across the whole dataset. Neither abundance-weighting nor inclusion of the Siebel numbers for bryophytes improved the relationship. The survey reveals that the relationships of soil and vegetation with atmospheric N deposition vary between sand dune habitats but, despite this variability, clear correlations with N inputs exist. While this survey cannot establish causality, on the basis of the relationships observed we suggest a critical load range of 10 - 20 kg N ha(-1) yr(-1) for coastal sand dunes in the UK.

Atmosphere↗
PubMed2001

Twice-daily triple nucleoside intensification treatment with lamivudine-zidovudine plus abacavir sustains suppression of human immunodeficiency virus type 1: results of the TARGET Study.

This open-label, multicenter, single-arm clinical trial assessed the 48-week efficacy of a twice-daily triple nucleoside reverse-transcriptase inhibitor regimen containing a lamivudine (150 mg)-zidovudine (300 mg) combination tablet (COM) and abacavir (ABC; 300 mg) in 87 antiretroviral therapy-experienced, protease inhibitor-naive patients infected with human immunodeficiency virus type 1 (HIV-1). At baseline, the median plasma HIV-1 RNA level was 3.10 log(10) copies/mL, and the median CD4 cell count was 506 cells/mm(3). An intent-to-treat&rcolon;observed analysis showed that, at weeks 24 and 48 of treatment, HIV-1 RNA level was <400 copies/mL in 48 (76%) of 63 and 45 (82%) of 55 patients, respectively, and <50 copies/mL in 37 (59%) of 63 and 31 (56%) of 55 patients, respectively. Previous zidovudine or lamivudine use and presence at baseline of the M184V reverse-transcriptase mutation did not impact virologic response. Median CD4 cell counts were maintained above baseline throughout the study. COM plus ABC was generally well tolerated.

Adult↗
PubMed2001

Finding and using rural aging data: an international perspective.

This article reports on a workshop in which participants identified sources of data on rural aging. Such sources are typically part of larger data collection efforts or special aging studies with large rural components. Finding and using data on rural aging are not only two different processes but they also face somewhat different obstacles and the solutions are likewise different. The workshop addressed both of these issues. Participants shared many innovative and creative means for collecting, finding and adapting more general data sources, and analyzing and using these data, to further our understanding of rural aging phenomena.

Aged↗
PubMed2001

A comparison of medication errors between two storage sites.

This prospective single-blinded study aimed to compare the types of medication errors and medication error rates of two medication delivery systems. The setting was a 30 bed surgical ward that was divided into two identical areas. In one area medications were stored and issued in a ward bay workstation immediately outside the patients' rooms. The alternate area used a medication trolley at the patients' bedside. Three hundred and forty opportunities for errors were observed using five nurse educators. Twenty administration errors (5.8% error rate) and two dispensing errors (0.6% error rate) were detected. A statistically significant difference was found between the two systems, where four errors occurred from the medication trolley (2.6% error rate), and fifteen errors occurred from the ward bay (9.2% error rate). These results suggest that medications were less likely to be omitted and more likely to be given on time when they were issued at the patient's bedside using the medication trolley.

Drug Storage↗
PubMed2000

Hsl7p, the yeast homologue of human JBP1, is a protein methyltransferase.

The yeast protein Hsl7p is a homologue of Janus kinase binding protein 1, JBP1, a newly characterized protein methyltransferase. In this report, Hsl7p also is shown to be a methyltransferase. It can be crosslinked to [(3)H]S-adenosylmethionine and exhibits in vitro protein methylation activity. Calf histones H2A and H4 and bovine myelin basic protein were methylated by Hsl7p, whereas histones H1, H2B, and H3 and bovine cytochrome c were not. We demonstrated that JBP1 can complement Saccharomyces cerevisiae with a disrupted HSL7 gene as judged by a reduction of the elongated bud phenotype, and a point mutation in the JBP1 S-adenosylmethionine consensus binding sequence eliminated all complementation by JBP1. Therefore, we conclude the yeast protein Hsl7p is a sequence and functional homologue of JBP1. These data provide evidence for an intricate link between protein methylation and macroscopic changes in yeast morphology.

Animals↗
PubMed2000

Yeast cell-free system that catalyses joint-molecule formation in a Rad51p- and Rad52p-dependent fashion.

One of the central reactions of homologous recombination is the invasion of a single strand of DNA into a homologous duplex to form a joint molecule. Here we describe the isolation of a cell-free system from meiotic yeast cells that catalyses joint-molecule formation in vitro. The active components in the system required ATP and homologous DNA and operated in both 0.5 and 13 mM MgCl(2). When the cell-free system was prepared from rad51/rad51 and rad52/rad52 mutants and joint-molecule formation was assayed at 0.5 mM MgCl(2), the specific activity decreased to 6% and 13.8% respectively of the wild-type level. However, when the same mutant extracts were premixed, joint-molecule formation increased 4-8-fold, i.e. the mutant extracts exhibited complementation in vitro. These results demonstrated that Rad51p and Rad52p were required for optimal joint-molecule formation at 0.5 mM MgCl(2). Intriguingly, however, Rad51p and Rad52p seemed to be more dispensable at higher concentrations of MgCl(2) (13 mM). Further purification of the responsible activity has proven problematical, but it did flow through a sizing column as a single peak (molecular mass 1.2 MDa) that was co-eluted with Rad51p and RFA, the eukaryotic single-stranded DNA-binding protein. All of these characteristics are consistent with the known properties of the reaction in vivo and suggest that the new cell-free system will be suitable for purifying enzymes involved in homologous recombination.

Cell-Free System↗
PubMed2000

Merging information in speech recognition: feedback is never necessary.

Top-down feedback does not benefit speech recognition; on the contrary, it can hinder it. No experimental data imply that feedback loops are required for speech recognition. Feedback is accordingly unnecessary and spoken word recognition is modular. To defend this thesis, we analyse lexical involvement in phonemic decision making. TRACE (McClelland & Elman 1986), a model with feedback from the lexicon to prelexical processes, is unable to account for all the available data on phonemic decision making. The modular Race model (Cutler & Norris 1979) is likewise challenged by some recent results, however. We therefore present a new modular model of phonemic decision making, the Merge model. In Merge, information flows from prelexical processes to the lexicon without feedback. Because phonemic decisions are based on the merging of prelexical and lexical information, Merge correctly predicts lexical involvement in phonemic decisions in both words and nonwords. Computer simulations show how Merge is able to account for the data through a process of competition between lexical hypotheses. We discuss the issue of feedback in other areas of language processing and conclude that modular models are particularly well suited to the problems and constraints of speech recognition.

Cognition↗
PubMed2000

Benign melanocytic proliferative nodule within a congenital naevus.

A neonate presented with a deeply pigmented papule within a medium-sized congenital naevus. Histologically, this proved to be a benign proliferative nodule in a congenital naevus. This case is presented to highlight the occurrence of this lesion, the main differential of which is the rare entity of true congenital melanoma.

Diagnosis, Differential↗
PubMed2000

Evaluation of simplified protease inhibitor dosing regimens for the treatment of HIV infection.

Complicated dosing regimens can unfavorably affect patient adherence and drug efficacy. In an effort to increase adherence while maximizing the benefits of the protease inhibitor (PI) component of HAART, the efficacy and safety of less frequent PI dosing regimens have recently been under scrutiny. Limiting the number of drugs required in antiretroviral therapy regimens may also minimize toxicity and drug-drug interactions. This article reviews the current movement toward twice-daily regimens and examines the efficacy and safety data available on twice-daily dosing of amprenavir, indinavir, nelfinavir, saquinavir soft-gel capsules, and ritonavir. Future trends in dosing are also discussed.

Dose-Response Relationship, Drug↗
PubMed2000

Phase I trial of XR9576 in healthy volunteers demonstrates modulation of P-glycoprotein in CD56+ lymphocytes after oral and intravenous administration.

XR9576 is a novel inhibitor of P-glycoprotein (P-gp) that has been shown to reverse P-gp-dependent multidrug-resistance in tumor cell lines and tumor-bearing animals. Here we report the first i.v. and p.o. administration to healthy volunteers of XR9576 in dose-escalating studies with the aim of investigating its effects on safety, its pharmacokinetics, and a surrogate marker of efficacy. XR9576 was administered as a single dose-upward titration of 0.1, 0.2, 0.5, 1.0, and 2 mg/kg XR9576 i.v. or 50, 100, 200, 500, and 750 mg/volunteer p.o. The surrogate marker for in vivo efficacy examined the accumulation of the P-gp substrate Rhodamine-123 (Rh-123) in P-gp-expressing CD56+ lymphocytes by flow cytometry. Addition of Rh-123 to blood samples from subjects given XR9576 or a placebo demonstrated drug-dependent modulation of P-gp activity. Even at the lowest doses, significant effects were observed on Rh-123 accumulation in CD56+ cells. Maximal effects were seen during the i.v. infusion or 4-6 h after oral administration. As the dose was increased, a concomitant rise in the level and duration of P-gp blockade was observed. A dose of 2.0 mg/kg i.v. and > or = 200 mg/volunteer p.o. gave approximately 100% inhibition of P-gp for in excess of 24 h. All doses of XR9576 were well tolerated. Inhibition increased with XR9576 plasma concentration, and maximal activity was achieved at 150-200 ng/ml XR9576. In conclusion, XR9576 has demonstrated sustained inhibition of P-gp after i.v. and oral administration and, supported by the elimination half-life of about 24 h, XR9576 is being taken into Phase II as a once-daily agent.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Information exchange in an epilepsy forum on the World Wide Web.

The Partners Healthcare Epilepsy Service hosts an epilepsy 'Webforum'. In this paper, we describe our observations regarding who uses it, what kind of information is exchanged, how much misinformation is present and how we can better serve our patients. We examined a sample of 155 posts to the forum and 342 responses to those posts. The individual making the post and the type of questions were categorized. We also determined whether any information was objectively inaccurate. The principal users were care-givers (49%) and patients (34%). Eighty percent of the primary posts were questions. Answers were given largely by patients (38%) and care-givers (34%). The most commonly asked questions were about treatment options (31%) and the natural history of the illness (28%). In 20% of the questions, the user incidentally remarked that a health-care provider had not met their information needs. Six percent of the information was objectively inaccurate. The Web can serve as an effective means for the exchange of information between individuals with a common medical condition. We found that a small amount of misinformation is exchanged and that health-care providers are sometimes perceived as unable or unwilling to supply important health-related information.

Computer-Assisted Instruction↗
PubMed1999

Naming cAsE aLtErNaTeD words.

A dual-route approach was used as an initial framework to examine the relation between presentation format and lexical processing in a naming task. In Experiments 1 and 3, words were presented in lowercase versus case-alternated format. Presentation format interacted with word frequency and regularity: For irregular words (e.g., pint), case alternation was additive with frequency, whereas for regular words (e.g., mint), case alternation and frequency interacted. Experiment 2 dissociated the locus of case-alternation effects from those of stimulus intensity. Stimulus intensity was additive with frequency and regularity, suggesting that whereas stimulus intensity affects encoding, case alternation affects lexical processing at a postencoding stage in the word recognition system. It was concluded that a dual-route approach provides a suggestive but incomplete account of how case alternation influences lexical processing. As an alternative to a dual-route approach, we show that the present results can be addressed and successfully simulated using an implemented version of Norris's (1994) multilevel model.

Female↗
PubMed1998

The primacy model: a new model of immediate serial recall.

A new model of immediate serial recall is presented: the primacy model. The primacy model stores order information by means of the assumption that the strength of activation of successive list items decreases across list position to form a primacy gradient. Ordered recall is supported by a repeated cycle of operations involving a noisy choice of the most active item followed by suppression of the chosen item. Word-length and list-length effects are attributed to a decay process that occurs both during input, when effective rehearsal is prevented, and during output. The phonological similarity effect is attributed to a second stage of processing at which phonological confusions occur. The primacy model produces accurate simulations of the effects of word length, list length, and phonological similarity.

Humans↗