Association of cleft palate with Sprengel anomaly: confirmation of the Hodgson-Chiu syndrome.
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Child, Preschool↗
Biomedical subjects
R Stevens
Publications and source records attributed to R Stevens.
Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13.
PURPOSE: To determine if Biafine compared to Best Supportive Care (BSC) is effective in minimizing or preventing radiation-induced dermatitis in women undergoing breast irradiation. METHODS AND MATERIALS: Patients were randomized between Biafine (n = 83) vs. BSC (n = 89). The institutions identified preference for BSC at the time of randomization. A no-treatment arm was allowed (16% received no treatment). Patients were instructed to apply randomized product three times a day, but not within 4 h of their daily RT session. Application began following their first radiation treatment and continued 2 weeks postradiation. Skin dermatitis was scored weekly utilizing the RTOG and ONS (Oncology Nursing Society) skin toxicity scales, a weekly patient satisfaction and quality-of-life questionnaire. RESULTS: Using the RTOG toxicity scale there was no overall difference for maximum dermatitis during RT between Biafine and BSC (p = 0.77). There was no difference in maximum toxicity by arm or breast size. There was an interaction between breast size and toxicity, with large-breasted women exhibiting more toxicity. Large-breasted women receiving Biafine were more likely to have no toxicity 6 weeks post RT. CONCLUSION: There was no overall difference between BSC and Biafine in the prevention, time to, or duration of radiation-induced dermatitis.
Adult↗
Longitudinal changes in CD4+ T cell antigen receptor diversity and naive/memory cell phenotype during 9 to 26 months of antiretroviral therapy of HIV-infected patients.
Although skewing of the CD4+ TCR repertoire in advanced HIV infection is well documented, increases in polyclonality during antiretroviral therapy have been less consistently observed. Ten patients, each with documented abnormalities within the CD4+ TCR repertoire, were studied by CDR3 spectratyping, semiquantitative PCR, and SSCP during 9-26 months of therapy. Naive and memory cell phenotypes were analyzed by flow cytometry. Six of 10 patients showed increased polyclonality of their TCR repertoires, 1 showed no change, and 3 showed increased TCR skewing, despite suppressed viral replication. Overall, there was no significant change in the percentage of abnormal BV subfamilies (from a mean of 25.5 to 17.1%) or the percentage of naive CD4+ T cells (from a mean of 18 to 25%). Further, progression of TCR repertoire disruptions was observed in some patients even with suppression of plasma viral RNA below 500 copies/ml. Although a spectrum of changes may be seen within the CD4+ TCR repertoire in the setting of antiretroviral therapy, increases in polyclonality are observed in some patients.
Anti-HIV Agents↗
Effects of intermittent interleukin-2 therapy on plasma and tissue human immunodeficiency virus levels and quasi-species expression.
To characterize the effects of intermittent interleukin (IL)-2 therapy on human immunodeficiency virus (HIV), 11 patients underwent detailed virological evaluation during a year of IL-2 therapy. Six patients showed a >0.5 log increase in plasma HIV during at least 1 IL-2 cycle, with 2 experiencing an increase in >50% of cycles. Three of the remaining 5 patients had a >0.5 log decrease during at least 1 IL-2 cycle, and the remaining patients exhibited <0.5 log changes. No changes in lymphoid (tonsil) levels of HIV were seen during the year. Quasi-species analysis in a separate cohort demonstrated that the virus induced by IL-2 most commonly resembled pre-IL-2 plasma quasi species. Thus, intermittent IL-2 does not result in sustained increases in either plasma or tissue levels of HIV and does not result in sustained expression of a previously silent quasi species.
Adult↗
Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors.
The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-gamma in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8-18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-term nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.
Adult↗
Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection.
To study human immunodeficiency virus (HIV)-specific cellular immunity in vivo, we transferred syngeneic lymphocytes after ex vivo expansion and transduction with a chimeric receptor gene (CD4/CD3-zeta) between identical twins discordant for HIV infection. Single and multiple infusions of 10(10) genetically modified CD8(+) T cells resulted in peak fractions in the circulation of approximately 10(4) to 10(5) modified cells/10(6) mononuclear cells at 24 to 48 hours, followed by 2- to 3-log declines by 8 weeks. In an effort to provide longer high-level persistence of the transferred cells and possibly enhance anti-HIV activity, we administered a second series of infusions in which both CD4(+ )and CD8(+) T cells were engineered to express the chimeric receptor and were costimulated ex vivo with beads coated with anti-CD3 and anti-CD28. Sustained fractions of approximately 10(3) to 10(4) modified cells/10(6) total CD4(+) or CD8(+) cells persisted for at least 1 year. Assessment of in vivo trafficking of the transferred cells by lymphoid tissue biopsies revealed the presence of modified cells in proportions equivalent to or below those in the circulation. The cell infusions were well tolerated and were not associated with substantive immunologic or virologic changes. Thus, adoptive transfer of genetically modified HIV-antigen-specific T cells was safe. Sustained survival in the circulation was achieved when modified CD4(+ )and CD8(+) T cells were infused together after ex vivo costimulation, indicating the important role played by antigen-specific CD4(+) T cells in providing "help" to cytotoxic effectors. (Blood. 2000;96:467-474)
Adult↗
Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group.
OBJECTIVE: To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes. DESIGN: Incremental cost effectiveness analysis alongside randomised controlled trial. SETTING: 23 UK hospital clinic based study centres. PARTICIPANTS: 3867 patients with newly diagnosed type 2 diabetes (mean age 53 years). INTERVENTIONS: Conventional (primarily diet) glucose control policy versus intensive control policy with a sulphonylurea or insulin. MAIN OUTCOME MEASURES: Incremental cost per event-free year gained within the trial period. RESULTS: Intensive glucose control increased trial treatment costs by pound 695 (95% confidence interval pound 555 to pound 836) per patient but reduced the cost of complications by pound 957 (pound 233 to pound 1681) compared with conventional management. If standard practice visit patterns were assumed rather than trial conditions, the incremental cost of intensive management was pound 478 (-pound 275 to pound 1232) per patient. The within trial event-free time gained in the intensive group was 0.60 (0.12 to 1.10) years and the lifetime gain 1.14 (0.69 to 1.61) years. The incremental cost per event-free year gained was pound 1166 (costs and effects discounted at 6% a year) and pound 563 (costs discounted at 6% a year and effects not discounted). CONCLUSIONS: Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications.
Adult↗
Systematic reviews and meta-analyses on treatment of asthma: critical evaluation.
OBJECTIVE: To evaluate the clinical, methodological, and reporting aspects of systematic reviews and meta-analyses on the treatment of asthma and to compare those published by the Cochrane Collaboration with those published in paper based journals. DESIGN: Analysis of studies identified from Medline, CINAHL, HealthSTAR, EMBASE, Cochrane Library, personal collections, and reference lists. STUDIES: Articles describing a systematic review or a meta-analysis of the treatment of asthma that were published as a full report, in any language or format, in a peer reviewed journal or the Cochrane Library. MAIN OUTCOME MEASURES: General characteristics of studies reviewed and methodological characteristics (sources of articles; language restrictions; format, design, and publication status of studies included; type of data synthesis; and methodological quality). RESULTS: 50 systematic reviews and meta-analyses were included. More than half were published in the past two years. Twelve reviews were published in the Cochrane Library and 38 were published in 22 peer reviewed journals. Forced expiratory volume in one second was the most frequently used outcome, but few reviews evaluated the effect of treatment on costs or patient preferences. Forty reviews were judged to have serious or extensive flaws. All six reviews associated with industry were in this group. Seven of the 10 most rigorous reviews were published in the Cochrane Library. CONCLUSIONS: Most reviews published in peer reviewed journals or funded by industry have serious methodological flaws that limit their value to guide decisions. Cochrane reviews are more rigorous and better reported than those published in peer reviewed journals.
Asthma↗
Life-expectancy projection by modelling and computer simulation (UKPDS 46).
A method is described for estimating the life-expectancy of cohorts of type 2 diabetic patients, based on computer simulation from a parametric model. The method can be used where non-parametric methods, such as the Kaplan-Meier estimate, fail due to lack of the data. The simulation algorithm combines observed and modelled information to estimate the life-expectancy implications of event rates observed within a study. The use of bootstrap methods to estimate confidence intervals is discussed. The methods are illustrated with results that have been previously published, without derivation, in a health economic analysis of tight blood pressure (BP) control in the UK Prospective Diabetes Study (UKPDS), and the application to other health economic analyses of UKPDS data is discussed.
Algorithms↗
Comparison of allogeneic transplant versus chemotherapy for relapsed childhood acute lymphoblastic leukaemia in the MRC UKALL R1 trial. MRC Childhood Leukaemia Working Party.
BACKGROUND: Although reinduction rates are good for children with relapsed acute lymphoblastic leukaemia there is no consensus on whether bone marrow transplantation (BMT) is the most effective treatment to prolong second remission. PATIENTS AND METHODS: Analyses comparing the outcome of related donor allogeneic BMT (related allograft) with chemotherapy are unreliable because of selection biases. To avoid these biases, the MRC UKALL R1 trial was analysed by HLA-matched donor availability. RESULTS: No significant difference in outcome was found between the donor and no donor groups. The donor group had a non-significant eight-year event-free survival (EFS) advantage of 8%, (95% confidence interval -9%-24%) over the no donor group. Patients with a first remission less than two years appeared to benefit most from having a donor, although the effect was only marginally significantly different from patients with longer first remission. Analysis by treatment received gave similar results, with BMT patients having a 5% (P = 0.8) eight-year EFS advantage over patients who received chemotherapy. CONCLUSIONS: Related allograft was not found to be significantly better than chemotherapy, but there was the possibility of a moderate EFS benefit with related allograft. especially in patients with a short first remission.
Adolescent↗
Serum albumin and colorectal cancer risk.
OBJECTIVE: To study the relationship between serum albumin and colorectal cancer occurrence. DESIGN: A case-control study nested within a cohort followed from 1968 to 1991. SUBJECTS AND METHODS: The albumin concentration was determined from serum samples stored at -20 degrees C at baseline in 177 incident colorectal cancer cases and 288 controls matched for sex, age and study region. RESULTS: An elevated risk was present of cancer of the left, distal colon at high serum albumin concentrations. No significant association was observed for the right, proximal colon or the rectum. The relative risks of cancer of the distal and proximal colon among individuals in the highest and lowest quartiles of serum albumin were 17.03 (95% confidence interval 1.48-195) and 0.77 (95% confidence interval 0. 19-3.13), respectively. CONCLUSIONS: The present study lends support to the hypothesis that some dietary factor associated with serum albumin may be a risk factor for distal colon cancer.
Adult↗
The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study.
We have examined the toxicity and overall outcome of the Medical Research Council UKALL R1 protocol for 256 patients with relapsed childhood acute lymphoblastic leukaemia (ALL). Second remission was achieved in over 95% of patients. Two patients died during induction and seven patients died of resistant disease. The overall actuarial event-free survival (EFS) at 5 years for all patients experiencing a first relapse was 46% (95% CI 40-52). Duration of first remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic significance. Five-year EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for those relapsing without bone marrow involvement > 2.5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however, were not comparable with respect to risk factor profile, and therefore direct comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatment groups, but did not suggest benefit for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the difficulties in running randomized trials especially in patients who have relapsed from a previous trial. The optimal treatment for relapsed ALL therefore remains uncertain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.
Antineoplastic Combined Chemotherapy Protocols↗
Wrapping and interoperating bioinformatics resources using CORBA.
Bioinformaticians seeking to provide services to working biologists are faced with the twin problems of distribution and diversity of resources. Bioinformatics databases are distributed around the world and exist in many kinds of storage forms, platforms and access paradigms. To provide adequate services to biologists, these distributed and diverse resources have to interoperate seamlessly within single applications. The Common Object Request Broker Architecture (CORBA) offers one technical solution to these problems. The key component of CORBA is its use of object orientation as an intermediate form to translate between different representations. This paper concentrates on an explanation of object orientation and how it can be used to overcome the problems of distribution and diversity by describing the interfaces between objects.
Amino Acid Sequence↗
Ontology-based knowledge representation for bioinformatics.
Much of biology works by applying prior knowledge ('what is known') to an unknown entity, rather than the application of a set of axioms that will elicit knowledge. In addition, the complex biological data stored in bioinformatics databases often require the addition of knowledge to specify and constrain the values held in that database. One way of capturing knowledge within bioinformatics applications and databases is the use of ontologies. An ontology is the concrete form of a conceptualisation of a community's knowledge of a domain. This paper aims to introduce the reader to the use of ontologies within bioinformatics. A description of the type of knowledge held in an ontology will be given.The paper will be illustrated throughout with examples taken from bioinformatics and molecular biology, and a survey of current biological ontologies will be presented. From this it will be seen that the use to which the ontology is put largely determines the content of the ontology. Finally, the paper will describe the process of building an ontology, introducing the reader to the techniques and methods currently in use and the open research questions in ontology development.
Artificial Intelligence↗
TAMBIS: transparent access to multiple bioinformatics information sources.
UNLABELLED: TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) is an application that allows biologists to ask rich and complex questions over a range of bioinformatics resources. It is based on a model of the knowledge of the concepts and their relationships in molecular biology and bioinformatics. AVAILABILITY: TAMBIS is available as an applet from http://img.cs.man.ac.uk/tambis SUPPLEMENTARY: A full manual, tutorial and videos can be found at http://img.cs.man.ac.uk/tambis. CONTACT: tambis@cs.man.ac.uk
Computational Biology↗
Whole genomic DNA probe for detection of Porphyromonas endodontalis.
The purpose of the present study was to develop a DNA probe for Porphyromonas endodontalis. Pure cultures of P. endodontalis were grown in TYP medium, in an anaerobic chamber. DNA was extracted from the P. endodontalis and labeled using the Genius System by Boehringer Mannheim. The labeled P. endodontalis DNA was used in dot-blot hybridization reactions with homologous (P. endodontalis) and unrelated bacterial samples. To determine specificity, strains of 40 other oral bacterial species (e.g. Porphyromonas gingivalis, Porphyromonas asaccharolytica, and Prevotella intermedia) were spotted and reacted with the P. endodontalis DNA probe. None of the panel of 40 oral bacteria hybridized with the P. endodontalis probe, whereas the blot of the homologous organism showed a strong positive reaction. To determine the sensitivity of the probe, dilutions of a P. endodontalis suspension of known concentration were blotted onto a nylon membrane and reacted with the probe. The results of our investigation indicate that the DNA probe that we have prepared specifically detects only P. endodontalis and can detect at least 3 x 10(4) cells.
Colony Count, Microbial↗
Resistance to replication of human immunodeficiency virus challenge in SCID-Hu mice engrafted with peripheral blood mononuclear cells of nonprogressors is mediated by CD8(+) T cells and associated with a proliferative response to p24 antigen.
High levels of resistance to challenge with human immunodeficiency virus type 1 SF162 were observed in animals engrafted with peripheral blood mononuclear cells of four long-term nonprogressors (LTNPs). Resistance was abrogated by depletion of CD8(+) T cells in vivo and was observed only in LTNPs with proliferative responses to p24. In a subgroup of nonprogressors, CD8(+) T cells mediated restriction of challenge viruses, and this response was associated with strong proliferative responses to p24 antigen.
Animals↗
Do we need a new word for patients? Patients should obviously now be called "Neubergers".
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Patients↗