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Biomedical subjects

J Edwards

Publications and source records attributed to J Edwards.

At least 73 records · Page 4Linked to original sources

Seeking a simple measure of analgesia for mega-trials: is a single global assessment good enough?

We sought to investigate the potential of using a simple global estimation ('How effective do you think the treatment was?') as a measure of efficacy by comparing it with at least 50%maxTOTPAR (at least 50% of the maximum possible pain relief) in acute pain studies. One hundred and fifty randomized, double-blind trials included in 11 systematic reviews of single dose, oral analgesics for postoperative pain were used as a source of data. The relationship between the proportion of patients reporting the top two or three values on a five-point global scale and the proportion with at least 50%maxTOTPAR was investigated. Twenty-six trials provided data on the proportion reporting the top two categories (very good or excellent) and 27 gave data on the top three categories (good, very good or excellent). The relationship between the percentage of patients recording the top two categories on a five-point global scale and the proportion with at least 50%maxTOTPAR was fair (r(2)=0.67). That for the top three categories was less good (r(2)=0.57). Similar numbers-needed-to-treat were calculated for aspirin 600/650 mg and ibuprofen 400 mg using at least 50%maxTOTPAR and the top two categories. No real difference was seen in the correlation for standard wording compared to non-standard wording. Individual patient data were also used from four randomized, placebo-controlled, double-blind trials in postoperative pain. The frequency distribution for %maxTOTPAR was plotted for patients reporting each of the five categories on the global scale. A global assessment provides similar measures of analgesic efficacy as TOTPAR derived from hourly measurements, but the effects of adverse effects have yet to be understood.

Analgesia↗

Selection analyses of insertional mutants using subgenic-resolution arrays.

We describe a method of genome-wide analysis of quantitative growth phenotypes using insertional mutagenesis and DNA microarrays. We applied the method to assess the fitness contributions of Escherichia coli gene domains under specific growth conditions. A transposon library was subjected to competitive growth selection in Luria-Bertani (LB) and in glucose minimal media. Transposon-containing genomic DNA fragments from the selected libraries were compared with the initial unselected transposon insertion library on DNA microarrays to identify insertions that affect fitness. Genes involved in the biosynthesis of nutrients not provided in the growth medium were found to be significantly enriched in the set of genes containing negatively selected insertions. The data also identify fitness contributions of several uncharacterized genes, including putative transcriptional regulators and enzymes. The applicability of this high-resolution array selection in other species is discussed.

Culture Media↗

Chemiluminescence detection of ATP release from red blood cells upon passage through microbore tubing.

A novel approach for the determination of adenosine triphosphate (ATP) released from red blood cells (RBCs) after passage through microbore capillaries is described. ATP is often released from RBCs in vessels and has been linked to the production of nitric oxide, a known vasodilator. The system described here uses a syringe pump to deliver microliter flow rates (5-15 microl min(-1)) of reagent and sample through fused silica capillary tubing of varying dimensions (25-75 microm) to a photomultiplier tube. The released ATP is characterized by the detection of chemiluminescent emission from the luciferin-luciferase reaction. The amount of ATP released is directly proportional to the number of RBCs injected into the system. Results also suggest that the amount of released ATP decreases from 6.9 microM to 1.4 microM as the tubing diameter is increased from 25 microm to 75 microm. An investigation of capillary lengths ranging from 15 to 35 cm resulted in ATP concentrations of 1.5 microM to 2.4 microM being released. Results also indicate that increases in flow rate also induce increased amounts of ATP release. These results are consistent with those of previous systems attempting to model the physiological release of ATP from red blood cells.

Adenosine Triphosphate↗

Is processing speed related to severity of language impairment?

Children with specific language impairment (SLI) typically respond more slowly on many tasks than do their typically developing peers. This paper addresses the question of whether speed of response is linearly related to severity of language impairment as measured by standardized test score. To address this question, we performed post hoc analyses of data from a study on lexical processing involving 66 children with SLI (mean age 6 years 9 months) and 66 typically developing children matched for age and nonverbal IQ. Response times derived from a series of tasks were correlated with language test scores. None of the Pearson correlations reached significance when corrected for number of correlations run, nor did a canonical correlation analysis reach significance. If these results are replicated in other studies, then they suggest that there is no direct linear relation between speed of processing and severity of language impairment as it is estimated from scores on standardized tests of language.

Child↗

Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer.

OBJECTIVE: To examine the role of androgen receptor (AR) gene amplification and aneusomy of the X chromosome in the development of antiandrogen-resistant prostate cancer. PATIENTS AND METHODS: Twenty patients with prostate cancer resistant to androgen-deprivation therapy were selected for study. The records of patients with tumours before and after antiandrogen therapy, and with a full clinical follow-up, were retrieved. AR gene amplification and X chromosome copy number were assessed by fluorescence in situ hybridization using a labelled probe at locus Xq11-13 for the AR gene and a labelled alpha-satellite probe for the X chromosome. At least 20 nuclei were scored over three tumour areas by two independent observers. RESULTS: Aneusomy of the X chromosome was reported respectively in seven (35%) and 11 (55%) tumours before and after hormone relapse, the AR gene copy number was increased in seven (35%) and 13 (65%), respectively, and AR gene amplification was detected in one (5%) and three (15%), respectively. Neither increased AR copy number nor AR amplification in primary tumours precluded a biological response to androgen-deprivation therapy. CONCLUSION: The rate of AR gene amplification is too low to be solely responsible for the development of antiandrogen-resistant prostate cancer. Also, the presence of amplified AR and cells aneusomic for the X chromosome in primary tumours that respond to androgen-deprivation therapy suggests that an increase in AR gene copy number does not prevent a tumour from responding to this therapy. Therefore other mechanisms which could cause hormone-refractory prostate cancer must be investigated before it is understood why so many patients relapse with this disease.

Aged↗

Characteristics of hospitals and infection control professionals participating in the National Nosocomial Infections Surveillance System 1999.

The National Nosocomial Infections Surveillance (NNIS) system is the oldest and largest monitoring system for health care-acquired infections in the United States. This report describes both the characteristics of NNIS hospitals compared with those of US hospitals with 100 beds or more and their infection control programs. Overall, NNIS hospitals tend to have more hospital beds than the average for-comparable US hospitals. The majority of NNIS hospitals have affiliations with academic medical centers, and most have substantial intensive care units. Even though infection control professionals in NNIS hospitals spend most of their time in inpatient settings, 40% of their time is also spent in a variety of other settings, including home health, outpatient surgery or clinics, extended care facilities, employee health and quality management, and other clinical or administrative activities. As described in this report, the infrastructure of the NNIS system offers a national resource on which to build improved voluntary patient safety monitoring efforts, as outlined in the recent Institute of Medicine report on medical errors.

Cross Infection↗

Traumatic renal artery dissection identified with dynamic helical computed tomography.

Intimal tears in the renal arteries typically result from traumatic mechanisms that produce rapid deceleration. These injuries usually progress to secondary thrombosis of the vessel. When the tear leads to dissection with luminal stenosis, early diagnosis and repair will preserve parenchymal function. Computed tomography has replaced intravenous pyelography as the radiographic study of choice for renal trauma. We present two patients with unilateral delay of renal contrast enhancement during dynamic helical computed tomography scan due to arterial stenosis from intimal dissection confirmed with arteriography. Both vessel injuries were successfully managed with endovascular stent placement. No previous description of this diagnostic strategy is reported in the literature.

Adult↗

CD34 selection using three immunoselection devices: comparison of T-cell depleted allografts.

BACKGROUND: T-cell depletion of allografts markedly reduces the incidence of GvHD following BMT. The approach taken at our Center has utilized the physical separation method of counterflow centrifugal elutriation (CCE), augmented by recovery of stem cells from lymphocyte-rich fractions by immunoaffinity selection of CD34(+) stem cells. We wanted to compare the performance characteristics of three commercially available selection devices, as well as the clinical outcomes of patients who received allografts engineered by the different devices. METHODS: BM allografts were prepared for patients undergoing BMT for hematologic malignancies. BM cells were separated into lymphocyte-rich and lymphocyte-depleted fractions using CCE, followed by recovery of CD34(+) cells from the lymphocyte-rich fraction using one of three immunoselection devices [CellPro CEPRATE, Nexell Isolex 300i (software version 2.5) and AmCell CliniMACS]. Allografts consisted of the lymphocyte-depleted fraction plus the CD34-selected fraction. RESULTS: Yields of CD34(+) cells were comparable for the three devices. However, there were significant differences in purity (CEPRATE < Isolex 300i < CliniMACS) and time from start of fractionation to infusion (CEPRATE < CliniMACS < Isolex 300i). More technical problems were encountered with the Isolex 300i device. Allograft compositions were comparable. Transplant outcomes (engraftment and incidence of GvHD) also were comparable. DISCUSSION: Qualitatively and quantitatively, allografts prepared with the CEPRATE, Isolex 300i (v 2.5) and CliniMACS devices should be considered comparable for use in this setting and probably also for direct T-cell depletion of BM.

Adolescent↗

A comparison of the prevalence of respiratory illness and non-specific health symptoms in two Victorian cities.

OBJECTIVE: To compare the prevalence of respiratory illness and non-specific health symptoms among adults and children aged 4-15 years living in Portland and Warrnambool, Victoria. METHODS: A postal survey of 3,903 adults in Portland and Warrnambool systematically selected from the electoral roll was undertaken. Both an adults and children's questionnaire were enclosed in the mailing to each adult. If there were children aged 4-15 years in the household, an adult was asked to complete a questionnaire for the child who would next celebrate a birthday. Questionnaires were returned by 2,111 adults (54%) and for 585 children. RESULTS: No significant differences in the prevalence of self-reported asthma or wheeze were observed among adults or children residing in Portland and Warrnambool. The likelihood of itchy eyes, skin rash and stuffy nose was significantly higher in Portland adults and children compared with those in Warrnambool. Dry cough at night was increased among Portland children, but not significantly so. CONCLUSIONS: Higher rates of non-specific symptoms were observed in Portland but from a cross-sectional survey such as this, it is not possible to identify the cause of these higher rates. They may be related to environmental factors such as pollens or emissions from aluminium production, fertiliser production or bulk handling activities on the wharf, or they may be attributable to other factors such as response or recall bias.

Adolescent↗

Medical education with the Internet: a pilot training programme in reproductive medicine.

Following a detailed information technology survey in the South West Deanery, an Internet educational programme in reproductive medicine was constructed, delivered and assessed. The course followed a problem-based approach using case studies, using an education website and electronic mail (e-mail) to communicate between trainees and trainers. Independent evaluation revealed a high level of satisfaction for both trainees and trainers with an increase in trainees' confidence to deal with patients following the course. This study suggests that the Internet may be used effectively to deliver postgraduate medical education, if the training programme is designed appropriately to computer infrastructure and the computer literacy of the users.

Education, Distance↗

vimA gene downstream of recA is involved in virulence modulation in Porphyromonas gingivalis W83.

A 0.9-kb open reading frame encoding a unique 32-kDa protein was identified downstream of the recA gene of Porphyromonas gingivalis. Reverse transcription-PCR and Northern blot analysis showed that both the recA gene and this open reading frame are part of the same transcriptional unit. This cloned fragment was insertionally inactivated using the ermF-ermAM antibiotic resistance cassette to create a defective mutant by allelic exchange. When plated on Brucella blood agar, the mutant strain, designated P. gingivalis FLL92, was non-black pigmented and showed significant reduction in beta-hemolysis compared with the parent strain, P. gingivalis W83. Arginine- and lysine-specific cysteine protease activities, which were mostly soluble, were approximately 90% lower than that of the parent strain. Expression of the rgpA, rgpB, and kgp protease genes was the same in P. gingivalis FLL92 as in the wild-type strain. In contrast to the parent strain, P. gingivalis FLL92 showed increased autoaggregration in addition to a significant reduction in hemagglutinating and hemolysin activities. In in vivo experiments using a mouse model, P. gingivalis FLL92 was dramatically less virulent than the parent strain. A molecular survey of this mutant and the parent strain using all known P. gingivalis insertion sequence elements as probes suggested that no intragenomic changes due to the movement of these elements have occurred in P. gingivalis FLL92. Taken together, these results suggest that the recA downstream gene, designated vimA (virulence-modulating gene), plays an important role in virulence modulation in P. gingivalis W83, possibly representing a novel posttranscriptional or translational regulation of virulence factors in P. gingivalis.

Adhesins, Bacterial↗

Fourth-generation enzyme-linked immunosorbent assay for the simultaneous detection of human immunodeficiency virus antigen and antibody.

The VIDAS HIV DUO Ultra, a fourth-generation immunoassay under development for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 and HIV-2, was evaluated. The enzyme-linked fluorescence immunoassay, performed on the automated VIDAS instrument, is claimed to detect early and established HIV infection. The assay was challenged with a total of 2,847 samples that included 74 members of 10 seroconversion panels, 9 p24 antigen-only-reactive members of a panel of group M clades, 503 consecutively collected samples from individuals seeking care in the University of Maryland Medical System, 1,010 samples from U.S. blood donors, 1,141 samples from patients in a high-incidence population in Trinidad, 83 samples from a clinic for sexually transmitted diseases in the Bahamas, 10 confirmed HIV-1 group O samples, and 16 confirmed HIV-2 samples from the Cote d'Ivoire. Reference tests were U.S. Food and Drug Administration-licensed HIV antibody screening, p24 antigen tests, HIV confirmatory assays, and the Roche Diagnostics Amplicor HIV-1 Monitor. The VIDAS HIV DUO Ultra demonstrated 100% sensitivity and 99.5% specificity overall, with a 99.7% specificity in low-risk individuals. The analytical sensitivity, as assessed by seroconversion panels and p24 antigen in samples, was equivalent to the sensitivity of the reference assays used to characterize these panels. The VIDAS HIV DUO Ultra is accurate, offers potential advantages over conventional HIV testing for time and cost savings, has walk-away capability, and correctly identifies both early and established HIV infections.

Enzyme-Linked Immunosorbent Assay↗

Dentists' opinions of an online orthodontic advice service.

An online teledentistry service was tested for eight months to determine whether it could help to reduce the high level of inappropriate orthodontic referrals to consultants and provide general dental practitioners (GDPs) with quick access to advice that would enable them to tackle a wider range of cases themselves. Six GDPs took part in the trial and were interviewed after it had been running for four months. The most important conclusions from the interviews were that the process of sending cases was quite straightforward, that teledentistry was a good way of getting advice and that it was popular with both patients and their parents. The GDPs enjoyed the experience and felt that there had been significant benefits, especially in educational terms.

Attitude of Health Personnel↗

A model of palliative care for the adolescent with cancer.

Adolescents are a distinct group in paediatric and adult cancer and palliative care specialities. The process that is experienced by the patient and his/her family of the transition from health to living with a life-threatening illness and from a life-threatening to a life-limited illness raises specific issues for service provision. The adolescent population presents with a wide variety of physical and emotional maturity that highlights the need for health professionals to be equipped with skills in adolescent care, cancer care and specialist palliative care. Due to the small number of patients who will require such a service in any one health district in the UK this is not usually realistic. This article discusses a model of care that promotes collaborative professional practice in a cancer centre between the paediatric department and adult specialist palliative care team that in turn extends a philosophy of care into cancer units and the community setting.

Adolescent↗

Cognitively oriented psychotherapy for early psychosis (COPE): a 1-year follow-up.

OBJECTIVES: Cognitively oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. DESIGN: A total of 80 people participated in the initial trial and completed assessments on a range of outcome measures. Post-treatment assessment results from a non-randomized controlled trial of COPE have been previously reported. The present paper describes the results obtained from 51 patients who attended a follow-up assessment 1 year subsequent to the end-of-treatment assessment. METHOD: The 51 patients formed three groups: (1) those who were offered and accepted COPE; (2) those who were offered COPE but refused it, and continued to receive other services from the Early Psychosis Prevention and Intervention Centre (EPPIC) (refusal subjects); and (3) those who were offered neither COPE nor any other continuing treatment from EPPIC (control subjects). RESULTS: At 1-year follow-up, there was only one significant difference and this was between the COPE and refusal groups on the Integration/Sealing Over (I/SO) measure (p = .008). End-of-treatment differences were mostly sustained over the 1-year follow-up period. When the complete sample of 80 was considered, there were no differences between the three groups in terms of hospital admissions, community episodes, or time taken to first in-patient re-admission. CONCLUSIONS: The study was weakened by the poor follow-up rates in the two control groups. This reduced power to detect differences between groups on the seven major measures. However, the relapse data gathered on the complete set of 80 patients were discouraging and suggest that the present formulation of COPE does not confer any advantage to those patients receiving the therapy over those not receiving the therapy.

Adolescent↗

Upper-airway collapsibility: measurements and sleep effects.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. Several techniques have been proposed to assess the collapsibility of the upper airway in awake humans, but sleep-wake comparisons have rarely been attempted and there are few studies comparing OSA patients to control subjects. We sought to compare two collapsibility measurement techniques between normal and apneic subjects, and between wakefulness and sleep. DESIGN: We conducted three studies. First, we examined whether collapsibility assessed by negative pressure pulses (NPPs) during wakefulness reflected values during sleep in 21 normal subjects. Second, we determined in these normal subjects whether collapsibility during sleep assessed by NPPs was predictive of collapsibility measured by inspiratory resistive loading (IRL). Finally, we compared upper-airway collapsibility between apnea patients (n = 22) and normal volunteers (n = 38) during wakefulness by NPPs. SETTING: Clinical and research laboratories at the Brigham and Women's Hospital. PARTICIPANTS: Two populations of normal subjects (n = 21 and n = 38) and OSA patients (n = 22). MEASUREMENTS AND RESULTS: Collapsibility during wakefulness, as measured by NPPs, correlated significantly with collapsibility during sleep (r = 0.62; p = 0.003). There was also a significant correlation between the two measures of collapsibility (IRL and NPP) during sleep (r = 0.53; p = 0.04). Both measures revealed a significant increase in pharyngeal collapsibility during sleep as compared to wakefulness. Finally, apnea patients had significantly greater pharyngeal collapsibility than control subjects during wakefulness (p = 0.017). CONCLUSIONS: These data suggest that upper-airway collapsibility measured during wakefulness does provide useful physiologic information about pharyngeal mechanics during sleep and demonstrates clear differences between individuals with and without sleep apnea.

Adult↗