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Biomedical subjects

Robert Harrison

Publications and source records attributed to Robert Harrison.

33 records · Page 2Linked to original sources

A grafting approach to obtain site-specific metal-binding properties of EF-hand proteins.

The EF-hand calcium-binding loop III from calmodulin was inserted with glycine linkers into the scaffold protein CD2.D1 at three locations to study site-specific calcium binding properties of EF-hand motifs. After insertion, the host protein retains its native structure and forms a 1:1 metal-protein complex for calcium and its analog, lanthanum. Tyrosine-sensitized Tb3+ energy transfer exhibits metal binding and La3+ and Ca2+ compete for the metal binding site. The grafted EF-loop III in different environments has similar La3+ binding affinities, suggesting that it is largely solvated and functions independently from the host protein.

Animals↗

Cleaning products and work-related asthma.

To describe the characteristics of individuals with work-related asthma associated with exposure to cleaning products, data from the California-, Massachusetts-, Michigan-, and New Jersey state-based surveillance systems of work-related asthma were used to identify cases of asthma associated with exposure to cleaning products at work. From 1993 to 1997, 236 (12%) of the 1915 confirmed cases of work-related asthma identified by the four states were associated with exposure to cleaning products. Eighty percent of the reports were of new-onset asthma and 20% were work-aggravated asthma. Among the new-onset cases, 22% were consistent with reactive airways dysfunction syndrome. Individuals identified were generally women (75%), white non-Hispanic (68%), and 45 years or older (64%). Their most likely exposure had been in medical settings (39%), schools (13%), or hotels (6%), and they were most likely to work as janitor/cleaners (22%), nurse/nurses' aides (20%), or clerical staff (13%). However, cases were reported with exposure to cleaning products across a wide range of job titles. Cleaning products contain a diverse group of chemicals that are used in a wide range of industries and occupations as well as in the home. Their potential to cause or aggravate asthma has recently been recognized. Further work to characterize the specific agents and the circumstances of their use associated with asthma is needed. Additional research to investigate the frequency of adverse respiratory effects among regular users, such as housekeeping staff, is also needed. In the interim, we recommend attention to adequate ventilation, improved warning labels and Material Safety Data Sheets, and workplace training and education.

Adult↗

Work-related reactive airways dysfunction syndrome cases from surveillance in selected US states.

The objective was to elaborate the descriptive epidemiology of work-related cases of reactive airways dysfunction syndrome (RADS). Cases of work-related asthma (WRA) were identified in four states in the United States during 1993-1995 as part of the Sentinel Event Notification Systems for Occupational Risks (SENSOR). Information gathered by follow-back interview was used to describe 123 work-related RADS cases and to compare them to 301 other WRA cases whose onset of disease was associated with a known asthma inducer. RADS represented 14% of all new-onset WRA cases identified by the state SENSOR surveillance systems. RADS cases had significant adverse medical and occupational outcomes identified by follow-back interview. In particular, 89% still had breathing problems, 78% had ever sought emergency care and 39% had ever been hospitalized for work-related breathing problems, 54% had applied for worker compensation benefits, and 41% had left the company where they experienced onset of asthma. These values equaled or exceeded the comparable figures for those WRA cases whose onset was attributed to a known inducer. Work-related RADS represents a minority of all WRA cases, but the adverse impact of this condition appears to equal that of other WRA cases.

Adult↗

Characterization of the role of the divalent metal ion-dependent transcriptional repressor MntR in the virulence of Staphylococcus aureus.

DtxR-type metal ion-dependent repressors, present in many bacterial pathogens, may regulate expression of virulence genes such as that encoding diphtheria toxin. SirR, a DtxR homologue initially identified in Staphylococcus epidermidis, governs the expression of the adjacent sitABC operon encoding a putative metal ion ABC transporter system. We identified a sirR homologue, mntR, in Staphylococcus aureus and demonstrated by gel shift assay that the corynebacterial repressor DtxR binds to the S. aureus mntABC operator in the presence of Fe(2+) or Mn(2+). Since a mutant DtxR, DtxR(E175K), functions as an iron-independent hyperrepressor in certain settings, we constructed a heterodiploid S. aureus strain expressing dtxR(E175K) from the native mntR promoter. Transcription of the S. aureus mntABC operon was repressed in the presence of Fe(2+) or Mn(2+) in wild-type and heterodiploid S. aureus strains. Under metal ion-limiting conditions, mntABC transcription was reduced but not abolished in S. aureus isolates expressing dtxR(E175K) compared with an isogenic control, suggesting that DtxR(E175K) binds the S. aureus MntR box in vivo. Under all conditions tested, mntABC transcription in the dtxR(E175K)-expressing strain was reduced relative to the isogenic control, indicating that DtxR(E175K) function was constitutively active. In the mouse skin abscess model, dtxR(E175K)-expressing S. aureus recombinants showed significantly reduced CFU levels compared with the isogenic wild-type control. We conclude that the S. aureus MntR box is recognized by corynebacterial DtxR proteins and thus belongs to the DtxR family of metal-dependent operator sites. Moreover, constitutive repression by DtxR(E175K) reduces the virulence of S. aureus in the mouse skin abscess model.

Abscess↗

Why do telemedicine systems fail to normalize as stable models of service delivery?

Two groups independently carried out qualitative studies of the development, implementation and evaluation of telehealth systems and services in the UK. The data collected (in more than 600 discrete data collection episodes) included semistructured interviews, observations and documents. We conducted a conjoint reanalysis of the data. The objective was to identify the conditions which dispose a telehealth service to be successful or to fail. There appear to be four conditions necessary for a telemedicine system to stabilize and then normalize as a means of service delivery. When one or more is absent, failure can be expected. These conditions are often overlooked by local proponents of telemedicine, who seem to rely on demonstrations that the equipment works as the primary criterion of success.

Delivery of Health Care↗

Protecting innovation in bioinformatics and in-silico biology.

Commercial success or failure of innovation in bioinformatics and in-silico biology requires the appropriate use of legal tools for protecting and exploiting intellectual property. These tools include patents, copyrights, trademarks, design rights, and limiting information in the form of 'trade secrets'. Potentially patentable components of bioinformatics programmes include lines of code, algorithms, data content, data structure and user interfaces. In both the US and the European Union, copyright protection is granted for software as a literary work, and most other major industrial countries have adopted similar rules. Nonetheless, the grant of software patents remains controversial and is being challenged in some countries. Current debate extends to aspects such as whether patents can claim not only the apparatus and methods but also the data signals and/or products, such as a CD-ROM, on which the programme is stored. The patentability of substances discovered using in-silico methods is a separate debate that is unlikely to be resolved in the near future.

Computational Biology↗

Prostate brachytherapy postimplant dosimetry: a comparison of prostate quadrants.

PURPOSE: To investigate postimplant dosimetry for different regions of the prostate gland in patients treated with transperineal 125Iodine brachytherapy implants for low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Two hundred eighty-four patients treated with permanent interstitial prostate brachytherapy comprised the study population. A nonuniform, urethral-sparing algorithm was used to plan all patients. Prostate contours were outlined on postimplant CT images. Prostate volumes were then divided into four quadrants: anterior-superior quadrant (ASQ), posterior-superior quadrant (PSQ), anterior-inferior quadrant (AIQ), and posterior-inferior quadrant (PIQ). Dose-volume histograms (DVHs) were calculated for the whole prostate and each quadrant. RESULTS: The mean postimplant V(100) +/- 95% confidence (the percent prostate volume encompassed within the isodose surface comprising the prescription dose = 144 Gy) for the ASQ was 78.5 +/- 1.9, which was significantly lower than that of the PSQ, AIQ, and PIQ in which the V(100) plus minus 95% confidence values were 94.9 +/- 0.8, 92.6 +/- 1.2, and 98.7 +/- 0.3, respectively. The mean V(100) +/- 95% confidence for the whole prostate was 90.4 +/- 0.8. Mean values for V(150) and D(90) (the minimum dose in Gy received by 90% of the target volume) for the four quadrants and the whole prostate showed similar results. CONCLUSIONS: Underdosed areas of the planning target volume (PTV), if present, were largely confined to the ASQ, which received a significantly lower dose, on average, compared to the other three quadrants of the prostate.

Aged↗

Design and performance of a multi-centre randomised controlled trial and economic evaluation of joint tele-consultations [ISRCTN54264250].

BACKGROUND: Appropriate information flow is crucial to the care of patients, particularly at the interface between primary and secondary care. Communication problems can result from inadequate organisation and training, There is a major expectation that information and communication technologies may offer solutions, but little reliable evidence. This paper reports the design and performance of a multi-centre randomised controlled trial (RCT), unparalleled in telemedicine research in either scale or range of outcomes. The study investigated the effectiveness and cost implications in rural and inner-city settings of using videoconferencing to perform joint tele-consultations as an alternative to general practitioner referral to the hospital specialist in the outpatient clinic. METHODS: Joint tele-consultation services were established in both the Royal Free Hampstead NHS Trust in inner London, and the Royal Shrewsbury Hospitals Trust, in Shropshire. All the patients who gave consent to participate were randomised either to joint tele-consultation or to a routine outpatients appointment. The principal outcome measures included the frequency of decision by the specialist to offer a follow-up outpatient appointment, patient satisfaction (Ware Specific Questionnaire), wellbeing (SF12) and enablement (PEI), numbers of tests, investigations, procedures and treatments. RESULTS: A total of 134 general practitioners operating from 29 practices participated in the trial, referring a total of 3170 patients to 20 specialists in ENT medicine, general medicine (including endocrinology, and rheumatology), gastroenterology, orthopaedics, neurology and urology. Of these, 2094 patients consented to participate in the study and were correctly randomised. There was a 91% response rate to the initial assessment questionnaires, and analysis showed equivalence for all key characteristics between the treatment and control groups. CONCLUSION: We have designed and performed a major multi-centre trial of teleconsultations in two contrasting centres. Many problems were overcome to enable the trial to be carried out, with a considerable development and learning phase. A lengthier development phase might have enabled us to improve the patient selection criteria, but there is a window of opportunity for these developments, and we believe that our approach was appropriate, allowing the evaluation of the technology before its widespread implementation.

Adult↗

Implementation of telemedicine: the problem of evaluation.

In the UK, few telemedicine applications have endured beyond the trial phase. It is commonly said that lack of evidence is responsible for the lack of implementation. This assumes that evidence will lead to implementation. Studies show that this is naive, especially in organizations like health-care systems, which are characterized by professional dominance. Furthermore, other research indicates that the nature of the changes experienced by clinicians in telemedicine experiments is sometimes limiting compared with conventional practice. This presents a dilemma for evaluation since it cannot reliably take place until a particular technique has become stable and accepted into the daily routine. A programme of selected case studies is recommended to develop knowledge of how telemedicine can become a taken-for-granted part of medical care.

Attitude of Health Personnel↗

The benefits of a qualitative approach to telemedicine research.

We used qualitative research to evaluate the experience of the participants in teleconsultations between primary and secondary care. Semistructured interviews were conducted with 15 hospital specialists, 24 general practitioners and 30 patients. Focus groups were also held with hospital specialists (two groups), general practitioners (six groups) and administrative staff (five groups). Sixty teleconsultations in six different specialties were video-recorded. Early findings show that the participants (hospital specialists, general practitioners and patients) had different perceptions of the same teleconsultations. Furthermore, the participants perceptions of consultations differed from those of the researchers.

Attitude of Health Personnel↗

Geographic Information System mapping of snakebite incidence in northern Ghana and Nigeria using environmental indicators: a preliminary study.

Snakebite is an important health problem in many parts of rural West Africa where the carpet or sawscaled viper, Echis ocellatus, is responsible for most of the morbidity and mortality. Marked seasonal and geographical variation in the incidence of snakebite suggests an association with environmental factors that could potentially identify high-risk areas and inform health care decision making. This preliminary investigation describes a Geographic Information System (GIS) approach to risk mapping that identifies environmental variables potentially associated with variation in snakebite incidence rates at a number of health facilities in northern Ghana and Nigeria and which has been used to create a preliminary risk map of the potential probability of high snakebite incidence for West Africa. Detailed and extensive further studies will enable the more reliable estimation of snakebite incidence at a local level across the region.

Environmental Health↗