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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 91 records · Page 5Linked to original sources
PubMed1998

Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2.

The HSPDE4A gene spans 50 kb, consists of at least 17 exons and is orientated 5'-3', telomere to centromere. It is located at chromosome 19p13.2, being 350 kb proximal to the gene encoding TYK2 and 850 kb distal to the gene encoding the low-density lipoprotein receptor. Its structure is consistent with the production of active 'long' and 'short' isoenzymes as the result of alternative mRNA splicing at two splice junctions. Identified is the single alternatively spliced 5' exon encoding the unique N-terminal region of the long isoenzyme HSPDE4A4B (pde46). The upstream conserved regions, UCR1 and UCR2, which form characteristic domains of PDE4 long forms are each encoded by three exons. The PDE4A-subfamily-specific linker region LR1, which joins UCR1 and UCR2, is encoded by two exons, whereas LR2, which joins UCR2 to the catalytic unit, is encoded by a single exon. Identification of exons encoding an enzymically inactive product of this gene, HSPDE4A8A (2el), indicates that this is an authentic gene product. The 5' exon encoding the unique N-terminal region of the human homologue of the rodent isoform RNPDE4A1A (RD1) was located, and the splice junction used to produce this short PDE4A isoform shown to occur at a different position from that seen in both the rat PDE4B and PDE4D genes. Reverse transcriptase PCR analysis indicates that RD1 homologues are conserved across species, having a conserved membrane-targeting region and a hypervariable LR2 region. Human RD1 was expressed transiently in COS-7 cells and detected as an 83 kDa species primarily associated with the high-speed membrane fraction. Human RD1 exhibited a Km for cAMP of about 3 microM, an IC50 value for inhibition by the PDE4-selective inhibitor rolipram of about 0.3 microM and was considerably more thermostable than rat RD1. Human RD1 was generated as a mature 80 kDa species in an in vitro transcription-translation system and shown to be capable of binding to membranes. Knowledge of the gene structure and the associated sequence information should facilitate analysis of the involvement of PDE4A in hereditary disorders that may result from alterations in enzyme expression, activity, regulation and intracellular targeting and serve as a resource for determining authenticity of cloned PDE4A species.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Intrathoracic tracheal avulsion and pseudodiverticulum following pneumomediastinum in a cat.

A case of tracheal avulsion with pneumomediastinum and pseudodiverticulum formation in a cat is described. Radiographs taken at initial presentation showed a pneumomediastinum with fractures of the right first to sixth ribs. Conservative treatment resolved the pneumomediastinum but following initial improvement the cat developed dyspnoea. Radiography and image intensification at this time showed a tracheal diverticulum at the level of the fourth rib. Surgical resection of the diverticulum and stenotic tracheal ends was performed via a right fourth intercostal lateral thoracotomy. The airway was maintained throughout the procedure using a bridging endotracheal tube. The cat made an unremarkable recovery following surgery.

Anastomosis, Surgical↗
PubMed1998

RNA folding at millisecond intervals by synchrotron hydroxyl radical footprinting.

Radiolysis of water with a synchrotron x-ray beam permits the hydroxyl radical-accessible surface of an RNA to be mapped with nucleotide resolution in 10 milliseconds. Application of this method to folding of the Tetrahymena ribozyme revealed that the most stable domain of the tertiary structure, P4-P6, formed cooperatively within 3 seconds. Exterior helices became protected from hydroxyl radicals in 10 seconds, whereas the catalytic center required minutes to be completely folded. The results show that rapid collapse to a partially disordered state is followed by a slow search for the active structure.

Animals↗
PubMed1998

Malnutrition and food intake in relation to quality of life in head and neck cancer patients.

BACKGROUND: The quality of life (QL) of cancer patients has attracted an increasing interest in recent years. Patients with head and neck cancer often have troublesome symptoms due to the disease and to treatment side effects, which will have an impact on the patient's QL. The aim of this study was to evaluate the possibility of studying QL in relation to well-known clinical parameters. METHODS: Patient's QL was evaluated according to the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) combined with a diagnosis-specific questionnaire. Quality of life was measured in a cross section of head and neck cancer patients (n = 48) and related to nutritional status, energy intake, severity of disease, and 2-year survival. RESULTS: Fifty-one percent of the patients (mean age, 67 years) fulfilled the criteria proposed for malnutrition, and 55% had a negative energy balance. We did not find any correlation between the severity of the cancer disease and the patient's self-rated QL. However, we found significantly better QL ratings among the 2-year survivors (mean, 63; range 52-76 versus mean, 42; range, 31-54; p < .05). There were few correlations between the QL items and malnutrition. CONCLUSIONS: Quality of life measurements offer objective information on well-being, sometimes quite opposite that of other clinical parameters, such as tumor stage. Furthermore, QL measurements may be of prognostic value concerning the survival of head and neck cancer patients.

Adult↗
PubMed1998

Obturator prostheses after cancer surgery: an approach to speech outcome assessment.

PURPOSE: This article describes a speech assessment protocol for patients using either obturator prostheses or speech aid prostheses for surgically acquired defects due to cancer of the maxilla and/or soft palate. METHODS: This protocol is structured according to the executive summary of "Disability in America: Toward a National Agenda For Prevention" a report formulated by the Institute of Medicine that describes four levels of disorder: (1) pathology, (2) impairment, (3) functional limitation, and (4) disability. Assessment instruments included (1) the Sentence Intelligibility Test to measure the rate and understandability of speech, (2) a speech physiology system to measure appropriate separation of the nasal/nasopharyngeal and oral compartments, (3) a 13-point interval scale to rate speech nasality, and (4) a scale to rate self-perceptions of communication effectiveness. RESULTS: The results from two patients are reported to illustrate the outcome assessment protocol.

Disability Evaluation↗
PubMed1998

Following the folding of RNA with time-resolved synchrotron X-ray footprinting.

The rapid mixing synchrotron X-ray footprinting technique described in this article allows nucleic acid folding and ligand binding reactions to be followed on a millisecond time resolution with single nucleotide resolution. In principle, the change in .OH protection of every nucleotide in a nucleic acid hundreds of nucleotides long can be monitored separately. In addition, a wide range of solution conditions are compatible with the radiolytic generation of .OH. These characteristics of synchrotron X-ray footprinting create opportunities for conducting thermodynamic and kinetic studies of nucleic acids that are both comprehensive and detailed. Kinetic footprinting studies of a number of systems have been initiated by the Center for Synchrotron Biosciences using this technique.

Flow Injection Analysis↗
PubMed1998

The need to redefine the practice of health promotion in the United Kingdom.

It is argued that since the late 1970s the practice of health promotion within the UK has become, at least in part, bound up with the ideological bias of Conservative political thinking. The shift in political thought that occurred with the advent of Thatcherism, a shift characterised by individualism as opposed to collectivism and consensus politics of earlier decades, has heralded a belief in the paramount importance of the responsibility of the individual for maintaining a healthy lifestyle. This strategy fails to consider the social, cultural, and economic context within which individuals find themselves over which little or no control can be exercised. A politicisation of the concept of health promotion has thus taken place which has placed the emphasis on the over-riding responsibility of the individual for his or her health. Such a selective approach to health is inefficient. It is further argued that a purely structuralist perspective, one that negates the influence of the individual, is equally inefficient. If the new Labour administration is to promote the population's health to any more effective manner it must be recognised that while the individual does have a distinct role to play in his or her own health, that individual must also be considered within his or her social, cultural and economic context. An holistic approach to promoting the health of the population must be multi-factorial acknowledging the influence of social, cultural, economic and medical factors, as well as the role of the individual.

Attitude to Health↗
PubMed1998

An audit of patient acceptance of one-stop diagnosis for symptomatic breast disease.

AIMS: The impetus for optimizing outpatient provision of breast-care services has come both from the patient and management in order to reduce anxiety and make full use of scarce resources. The one-stop diagnostic clinic for the investigation of symptomatic breast lesions is a relatively recent concept with well-known service benefits. However, acceptance to the patient has not been previously investigated. RESULTS: The results of this prospective audit demonstrate a high level of patient satisfaction with the multi-disciplinary, one-stop breast clinic.

Ambulatory Care↗
PubMed1998

Translating health status questionnaires and evaluating their quality: the IQOLA Project approach. International Quality of Life Assessment.

This article describes the methods adopted by the International Quality of Life Assessment (IQOLA) project to translate the SF-36 Health Survey. Translation methods included the production of forward and backward translations, use of difficulty and quality ratings, pilot testing, and cross-cultural comparison of the translation work. Experience to date suggests that the SF-36 can be adapted for use in other countries with relatively minor changes to the content of the form, providing support for the use of these translations in multinational clinical trials and other studies. The most difficult items to translate were physical functioning items, which used examples of activities and distances that are not common outside of the United States; items that used colloquial expressions such as pep or blue; and the social functioning items. Quality ratings were uniformly high across countries. While the IQOLA approach to translation and validation was developed for use with the SF-36, it is applicable to other translation efforts.

Cross-Cultural Comparison↗
PubMed1998

Cross-cultural comparisons of the content of SF-36 translations across 10 countries: results from the IQOLA Project. International Quality of Life Assessment.

Increasingly, translated and culturally adapted health-related quality of life measures are being used in cross-cultural research. To assess comparability of results, researchers need to know the comparability of the content of the questionnaires used in different countries. Based on an item-by-item discussion among International Quality of Life Assessment (IQOLA) investigators of the content of the translated versions of the SF-36 in 10 countries, we discuss the difficulties that arose in translating the SF-36. We also review the solutions identified by IQOLA investigators to translate items and response choices so that they are appropriate within each country as well as comparable across countries. We relate problems and solutions to ratings of difficulty and conceptual equivalence for each item. The most difficult items to translate were physical functioning items that refer to activities not common outside the United States and items that use colloquial expressions in the source version. Identifying the origin of the source items, their meaning to American English-speaking respondents and American English synonyms, in response to country-specific translation issues, greatly helped the translation process. This comparison of the content of translated SF-36 items suggests that the translations are culturally appropriate and comparable in their content.

Cross-Cultural Comparison↗
PubMed1998

Testing the equivalence of translations of widely used response choice labels: results from the IQOLA Project. International Quality of Life Assessment.

The similarity in meaning assigned to response choice labels from the SF-36 Health Survey (SF-36) was evaluated across countries. Convenience samples of judges (range, 10 to 117; median = 48) from 13 countries rated translations of response choice labels, using a variation of the Thurstone method of equal appearing intervals. Judges marked a point on a 10-cm line-representing the magnitude of a response choice label (e.g., "good" relative to the anchors of "poor" and "excellent"). Ratings were evaluated to determine the ordinal consistency of response choice labels within a response scale; the degree to which differences between adjacent response choice labels were equal interval; and the amount of variance due to response choice label, country, judge, and interaction between response choice label and country. Results confirmed the hypothesized ordering of response choice labels; the percentage of ordinal pairs ranged from 88.7% to 100% (median = 98.2%) across countries and response scales. Examination of the average magnitudes of response choice labels supported the "quasi-interval" nature of the scales. Analysis of variance (ANOVA) results supported the generalizability of response choice magnitudes across countries; labels explained 64% to 77% of the variance in ratings, and country explained 1% to 3%. These results support the equivalence of SF-36 response choice labels across countries. Departures from the assumption of equal intervals, when observed, were similar across countries and were greatest for the two response scales that are recalibrated under standard SF-36 scoring. Results provide justification for scoring translations of individual items using standard SF-36 scoring; whether these items form the same scales in other countries as they do in the United States is evaluated with tests of scaling assumptions.

Analysis of Variance↗
PubMed1998

The Swedish SF-36 Health Survey II. Evaluation of clinical validity: results from population studies of elderly and women in Gothenborg.

The validity of the Swedish SF-36 Health Survey was examined, replicating techniques used in the U.S. validation. Principal components analysis was used to test the internal structure of the eight SF-36 scales in relation to hypothesized associations with the two major dimensions of health--physical and mental. Hypothesized relationships between scales and external criteria were also examined by means of clinical group contrasts. Both the principal components analysis and clinical group contrasts largely replicated U.S. findings, which supported the cross-cultural stability of the SF-36 in Sweden. As expected, the Physical Functioning and Mental Health scales were most sensitive to clinical manifestations of medical and mental health, respectively. The General Health scale was associated more with physical than mental health. However, the Social Functioning scale and particularly the Vitality scale were more related to mental health in Sweden than in the corresponding U.S. study. Cultural differences and variation in study samples and selection criteria were suggested as possible explanatory factors for these differences.

Adult↗
PubMed1998

The Swedish SF-36 Health Survey III. Evaluation of criterion-based validity: results from normative population.

Assumptions of the variation in SF-36 scale scores were tested in relation to external criteria in 8930 respondents comprising the Swedish norming population. Physical health scales were strongly associated with age, while small differences were found for the Mental Health scale across age groups. Females reported poorer health than males, particularly in ages between 30-40 and over 70. Worse health profiles were associated with social risk factors (unemployment, divorce, etc.). The disability pension rate was strongly related to reduced Physical Functioning and increased Bodily Pain. The use of medical care was reflected in general health scores (i.e., the lower the scale score, the higher the care consumption). Self-reported physical and psychological symptoms were selectively related to SF-36 scales. All SF-36 scales, except Mental Health, were more strongly related to ratings of health satisfaction than to global quality of life. Combinations of the SF-36 well-being scales explained a substantial part of the variance of these ratings. In conclusion, the performed criterion-validity tests support the cross-cultural stability of the SF-36.

Adolescent↗
PubMed1998

Tests of data quality, scaling assumptions, and reliability of the SF-36 in eleven countries: results from the IQOLA Project. International Quality of Life Assessment.

Data from general population samples in 11 countries (n = 1483 to 9151) were used to assess data quality and test the assumptions underlying the construction and scoring of multi-item scales from the SF-36 Health Survey. Across all countries, the rate of item-level missing data generally was low, although slightly higher for items printed in the grid format. In each country, item means generally were clustered as hypothesized within scales. Correlations between items and hypothesized scales were greater than 0.40 with one exception, supporting item internal consistency. Items generally correlated significantly higher with their own scale than with competing scales, supporting item discriminant validity. Scales could be constructed for 93-100% of respondents. Internal consistency reliability of the eight SF-36 scales was above 0.70 for all scales, with two exceptions. Floor effects were low for all except the two role functioning scales; ceiling effects were high for both role functioning scales and also were noteworthy for the Physical Functioning, Bodily Pain, and Social Functioning scales in some countries. These results support the construction and scoring of the SF-36 translations in these 11 countries using the method of summated ratings.

Cross-Cultural Comparison↗
PubMed1998

The factor structure of the SF-36 Health Survey in 10 countries: results from the IQOLA Project. International Quality of Life Assessment.

Studies of the factor structure of the SF-36 Health Survey are an important step in its construct validation. Its structure is also the psychometric basis for scoring physical and mental health summary scales, which are proving useful in simplifying and interpreting statistical analyses. To test the generalizability of the SF-36 factor structure, product-moment correlations among the eight SF-36 Health Survey scales were estimated for representative samples of general populations in each of 10 countries. Matrices were independently factor analyzed using identical methods to test for hypothesized physical and mental health components, and results were compared with those published for the United States. Following simple orthogonal rotation of two principal components, they were easily interpreted as dimensions of physical and mental health in all countries. These components accounted for 76% to 85% of the reliable variance in scale scores across nine European countries, in comparison with 82% in the United States. Similar patterns of correlations between the eight scales and the components were observed across all countries and across age and gender subgroups within each country. Correlations with the physical component were highest (0.64 to 0.86) for the Physical Functioning, Role Physical, and Bodily Pain scales, whereas the Mental Health, Role Emotional, and Social Functioning scales correlated highest (0.62 to 0.91) with the mental component. Secondary correlations for both clusters of scales were much lower. Scales measuring General Health and Vitality correlated moderately with both physical and mental health components. These results support the construct validity of the SF-36 translations and the scoring of physical and mental health components in all countries studied.

Cross-Cultural Comparison↗
PubMed1998

The equivalence of SF-36 summary health scores estimated using standard and country-specific algorithms in 10 countries: results from the IQOLA Project. International Quality of Life Assessment.

Data from general population surveys (n = 1771 to 9151) in nine European countries (Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) were analyzed to test the algorithms used to score physical and mental component summary measures (PCS-36/MCS-36) based on the SF-36 Health Survey. Scoring coefficients for principal components were estimated independently in each country using identical methods of factor extraction and orthogonal rotation. PCS-36 and MCS-36 scores were also estimated using standard (U.S.-derived) scoring algorithms, and results were compared. Product-moment correlations between scores estimated from standard and country-specific scoring coefficients were very high (0.98 to 1.00) for both physical and mental health components in all countries. As hypothesized for orthogonal components, correlations between physical and mental components within each country were very low (0.00 to 0.12) for both estimation methods. Mean scores for PCS-36 differed by as much as 3.0 points across countries using standard scoring, and mean scores for MCS-36 differed across countries by as much as 6.4 points. In view of the high degree of equivalence observed within each country, using standard and country-specific algorithms, we recommend use of standard scoring algorithms for purposes of multinational studies involving these 10 countries.

Algorithms↗
PubMed1998

Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment.

Data from general population surveys (n = 1483 to 9151) in nine European countries (Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) were analyzed to cross-validate the selection of questionnaire items for the SF-12 Health Survey and scoring algorithms for 12-item physical and mental component summary measures. In each country, multiple regression methods were used to select 12 SF-36 items that best reproduced the physical and mental health summary scores for the SF-36 Health Survey. Summary scores then were estimated with 12 items in three ways: using standard (U.S.-derived) SF-12 items and scoring algorithms; standard items and country-specific scoring; and country-specific sets of 12 items and scoring. Replication of the 36-item summary measures by the 12-item summary measures was then evaluated through comparison of mean scores and the strength of product-moment correlations. Product-moment correlations between SF-36 summary measures and SF-12 summary measures (standard and country-specific) were very high, ranging from 0.94-0.96 and 0.94-0.97 for the physical and mental summary measures, respectively. Mean 36-item summary measures and comparable 12-item summary measures were within 0.0 to 1.5 points (median = 0.5 points) in each country and were comparable across age groups. Because of the high degree of correspondence between summary physical and mental health measures estimated using the SF-12 and SF-36, it appears that the SF-12 will prove to be a practical alternative to the SF-36 in these countries, for purposes of large group comparisons in which the focus is on overall physical and mental health outcomes.

Cross-Cultural Comparison↗