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Biomedical subjects

R English

Publications and source records attributed to R English.

At least 19 recordsLinked to original sources

Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol.

BACKGROUND: To compare the efficacy and safety of budesonide/formoterol (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting beta2-agonist therapy. METHODS: In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV1 40% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 microg), were randomized to receive either budesonide/formoterol (320/9 microg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 microg]) or formoterol (9 microg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 microg]). The primary efficacy variable was the average FEV1 from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured. RESULTS: FEV1 increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated. CONCLUSION: Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting beta2-agonist.

Acute Disease↗

The Practical Approach to Lung Health in South Africa (PALSA) intervention: respiratory guideline implementation for nurse trainers.

AIM: This paper describes the design, facilitation and preliminary assessment of a 1-week cascade training programme for nurse trainers in preparation for implementation of the Practical Approach to Lung Health in South Africa (PALSA) intervention, tested within the context of a pragmatic cluster randomized controlled trial in the Free State province. PALSA combines evidence-based syndromic guidelines on the management of respiratory disease in adults with group educational outreach to nurse practitioners. BACKGROUND: Evidence-based strategies to facilitate the implementation of primary care guidelines in low- to middle-income countries are limited. In South Africa, where the burden of respiratory diseases is high and growing, documentation and evaluation of training programmes in chronic conditions for health professionals is limited. METHOD: The PALSA training design aimed for coherence between the content of the guidelines and the facilitation process that underpins adult learning. Content facilitation involved the use of key management principles (key messages) highlighted in nurse-centred guidelines manual and supplemented by illustrated material and reminders. Process facilitation entailed reflective and experiential learning, role-playing and non-judgemental feedback. DISCUSSION AND RESULTS: Preliminary feedback showed an increase in trainers' self-awareness and self-confidence. Process and content facilitators agreed that the integrated training approach was balanced. All participants found that the training was motivational, minimally prescriptive, highly nurse-centred and offered personal growth. CONCLUSION: In addition to tailored guideline recommendations, training programmes should consider individual learning styles and adult learning processes.

Education, Nursing, Continuing↗

Analysis of clinical decision-making in multi-disciplinary cancer teams.

Management decisions for patients with cancer are frequently taken within the context of a multi-disciplinary team (MDT). There is little known, however, about decision-making at team meetings and whether MDT decisions are all implemented. This study evaluated team decision-making in upper gastrointestinal cancer. Consecutive MDT treatment decisions were recorded for patients with oesophageal, gastric, pancreatic and peri-ampullary tumours. Implementation of MDT decisions was investigated by examining hospital records. Where decisions were implemented it was recorded as concordant and discordant if the decision changed. Reasons for changes in MDT decisions were identified. 273 decisions were studied and 41 (15.1%) were discordant (not implemented), (95% confidence interval 11.1-20.0%). Looking at the reasons for discordance, 18 (43.9%) were due to co-morbid health issues, 14 (34.2%) related to patient choice and 8 (19.5%) decisions changed when more clinical information was available. For one discordant decision, the reason was not apparent. Discordant decisions were more frequent for patients with pancreatic or gastric carcinoma as compared to oesophageal cancer (P = 0.001). Results show that monitoring concordance between MDT decisions and final treatment implementation is useful to inform team decision-making. For upper gastrointestinal cancer, MDTs require more information about co morbid disease and patient choice to truly optimize the implementation of multi-disciplinary expertise.

Adult↗

Predictors of outcome of mammography in the National Health Service Breast Screening Programme.

BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50-64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.

Age Factors↗

Expression of the hypoxia-inducible and tumor-associated carbonic anhydrases in ductal carcinoma in situ of the breast.

Carbonic anhydrases (CA) influence intra- and extracellular pH and ion transport in varied biological processes. We recently identified CA9 and CA12 as hypoxia-inducible genes. In this study we examined the expression of these tumor-associated CAs by immunohistochemistry in relation to necrosis and early breast tumor progression in 68 cases of ductal carcinoma in situ (DCIS) (39 pure DCIS and 29 DCIS associated with invasive carcinoma). CA IX expression was rare in normal epithelium and benign lesions, but was present focally in DCIS (50% of cases) and in associated invasive carcinomas (29%). In comparison, CA XII was frequently expressed in normal breast tissues (89%), in DCIS (84%), and in invasive breast lesions (71%). In DCIS, CA IX was associated with necrosis (P: = 0.0053) and high grade (P: = 0.012). In contrast, CA XII was associated with the absence of necrosis (P: = 0.036) and low grade (P: = 0.012). Despite this, augmented CA XII expression was occasionally observed adjacent to necrosis within high-grade lesions. Neither CA IX nor CA XII expression was associated with regional or overall proliferation as determined by MIB1 staining. Assessment of mammographic calcification showed that CA XII expression was associated with the absence of calcification (n = 43, P: = 0.0083). Our results demonstrate that induction of CA IX and CA XII occurs in regions adjacent to necrosis in DCIS. Furthermore, these data suggest that proliferation status does not influence expression of either CA in breast tissues, that hypoxia may be a dominant factor in the regulation of CA IX, and that factors related to differentiation, as determined by tumor grade, dominate the regulation of CA XII. The existence of differential regulation and associations with an aggressive phenotype may be important in the development of selective inhibitors of CAs, because the latter have recently been shown to prevent tumor invasion.

Antibody Specificity↗

A mammographic dilemma: calcification or haemosiderin as a cause of opacities? Validation of a new digital diagnostic tool.

Core biopsies of an area of microcalcification demonstrated large collections of macrophages containing haemosiderin, with evidence of minimal microcalcification on H&E staining. Algorithms were developed that were capable of differentiating with high accuracy those signs due to calcification, using quantitative measurements such as the apparent volume composition of calcium. Using the linear attenuation coefficients of calcification and assuming an ellipsoid model for the 3-dimensional shape of calcification, we computed the relative calcification volume for each region of interest. The difference in the linear attenuation coefficients of iron and calcification allowed the two to be differentiated on a mammogram based on this measure of relative calcification volume.

Breast↗

Three-dimensional reconstruction of microcalcification clusters from two mammographic views.

Classification of benign/malignant microcalcification clusters is a major diagnostic challenge for radiologists. Clinical studies have revealed that the shape of the cluster, and the spatial distribution of individual microcalcifications within it, are important indicators of its malignancy. However, mammographic images of clustered microcalcifications confound their three-dimensional (3-D) distribution with image projection and breast compression. This paper presents a novel model-based method for reconstructing microcalcification clusters in 3-D from two mammographic views (cranio-caudal and medio-lateral oblique--"shoulder to the opposite hip" or lateral-medio). We develop a 3-D breast representation and a parameterised breast compression model which constraints geometrically the possible 3-D positions of a calcification in a two-dimensional image. Corresponding calcifications in the two views are matched using an estimate of the calcification volume. Both the geometric constraint and the matching criterion are utilized in the final reconstruction step to build the 3-D reconstructed clusters. Validation experiments are described using 30 clusters to verify the individual steps of the model, and results consistent with known ground truth are obtained. Some of the approximations in the model and future work are discussed in the concluding section.

Algorithms↗

Fixed implant rehabilitation of the edentulous maxilla: clinical guidelines and case reports. Part II.

Fixed prosthetic implant reconstruction of the edentulous maxilla demands skill and state-of-the-art techniques of both the surgeon and the restorative dentist. As discussed in Part I (Implant Dent. 1999;8: 186-193), accurate diagnosis and treatment planning are essential to successful, predictable clinical results. How and where implants are placed have a lasting impact on the quality and prognosis of the final restoration. A series of clinical guidelines and considerations is reviewed with illustrative clinical treatment protocols of edentulous maxillae of unfavorable anatomy including attendant prosthetic difficulties. This article addresses the fixed implant rehabilitation of edentulous maxillas with inadequate posterior bone and favorable arch position, inadequate posterior bone and unfavorable arch position, and inadequate anterior and posterior bone and unfavorable arch position.

Adult↗

Taking on the student role: how can we improve the experience of registered nurses returning to study?

Regardless of the number of nurses who undertake graduate certificate courses in critical care nursing in Victoria, Australia, there is still a shortage of skilled nurses in the critical care areas. Preparation for practice in this specialist field has moved from hospital-based programs to tertiary-based courses during the past decade. As a consequence, there has been scrutiny of the clinical ability of graduates to perform the role function. Although this is understandable, anecdotal evidence to date indicates that students in these courses experience many difficulties, yet very little is written about the stressors they encounter. As the future of the critical care work force depends on a constant supply of students undertaking courses, it is essential to gain insight into the student experience, with a view to optimising it for future students and perhaps preventing attrition from courses. This paper describes a qualitative research study involving 14 students undertaking a graduate certificate course in critical care nursing. The aim of the study was to document the students' experience in relation to factors they identified as helping or hindering their progress on the course. Data were obtained at three points during the academic component of the course: on entry, at the end of semester 1 and at the end of semester 2. Interviews and questionnaires were used as the data collection methods. Results indicate that for this group of students, the experience of undertaking the course was adversely affected by stress related to three factors: change of role from clinician back to student; unmet expectations, and exhaustion. Recommendations related to preparation for study, curriculum timelines and peer support are included in this paper.

Attitude of Health Personnel↗

Detecting film-screen artifacts in mammography using a model-based approach.

Microcalcifications can be one of the earliest signs of breast cancer. Unfortunately, their appearance in mammograms can be mimicked by dust and dirt entering the imaging process and this has been shown previously to lead to false positives. We use a model of the imaging process and, in particular, the blurring functions inherent within it to detect the film-screen artifacts caused by dust and dirt and, thus, reduce false-positives. A crucial facet of the work is the choice of the correct image representation upon which to perform the image processing. After extensive testing, our algorithm has identified no microcalcifications as being artifacts and has an artifact detection rate of approaching 96%.

Algorithms↗

Fixed implant rehabilitation of the edentulous maxilla: clinical guidelines and case reports. Part I.

Fixed implant reconstruction is one of the most challenging prosthetic treatment alternatives for the edentulous maxilla. Accurate diagnosis and treatment planning are essential to successful, predictable clinical results. Decisions concerning the placement of implants may have a lasting impact on the quality and prognosis of the final restoration. A series of clinical guidelines and considerations is presented with illustrative clinical treatment protocols of edentulous maxillae that vary in degrees of anatomical and prosthetic difficulty. This article addresses the fixed implant rehabilitation of edentulous maxillas with favorable anatomy and favorable arch position, favorable anatomy, and unfavorable arch position, and unfavorable anatomy and favorable arch position.

Adult↗

Horizontal transmission of feline immunodeficiency virus with semen from seropositive cats.

The AIDS virus of cat species, feline immunodeficiency virus (FIV), has been used extensively as an animal model of HIV-1 infection. This felid lentivirus shares many molecular and biochemical traits with HIV-1 and causes similar immunologic and clinical perturbations, most notably CD4+ cell loss, impaired cell-mediated immunity and increased susceptibility to opportunistic pathogens. Previous reports have shown that FIV is transmitted horizontally by biting and vertically in utero and through nursing. Our objective was to determine whether FIV could be venereally transmitted in domestic cats. In the first experiment, susceptibility of the female reproductive tract to mucosal transmission of the FIV isolate, NCSU1, was demonstrated via intravaginal inoculation with infected cultured cells. We next identified virus in electroejaculates from asymptomatic, chronically FIV-NCSU1-infected, adult males. A fragment of FIV gag provirus DNA was detected by nested polymerase chain reaction (PCR) in nonfractionated seminal cells and in swim-up sperm preparations. Additionally, replication-competent virus was isolated from cell-free seminal plasma and seminal cells by co-cultivation with a feline CD4+ T-cell line. In the third study, queens were artificially inseminated via an intrauterine laparoscopic technique with electroejaculates from FIV-NCSU1-infected males. Of six inseminations carried out with fresh semen, three resulted in infection of queens. Lastly, immunohistochemical studies identified potential virus target cell populations in normal female reproductive tissues. In conclusion, these experiments indicate that FIV infection in domestic cats may provide a unique small animal model of sexual transmission of HIV-1.

Animals↗

Responses to time-varying stimuli in rat auditory cortex.

Responses to frequency modulated (FM) sweeps were recorded in rat primary auditory cortex. Forty-four percent of the cells were direction-selective. For speed selectivity, the majority of the cells preferred faster sweeps. The results suggest that rat auditory cortex may be used for processing communication signals of their predators or for detecting spectral changes in acoustic signals.

Acoustic Stimulation↗

Effect on attendance at breast cancer screening of adding a self administered questionnaire to the usual invitation to breast screening in southern England.

STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.

Breast Neoplasms↗

Cortical cell loss in asymptomatic cats experimentally infected with feline immunodeficiency virus.

Specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) were used to evaluate the development of central nervous system changes during the asymptomatic stages of viral infection. The brains of asyptomatic cats were examined at postinoculation times ranging from 8 weeks to 3 years for changes in neuron density, glutamate receptor density, and synaptophysin immunoreactivity. At 2-3 years postinoculation a small decrease in neuronal density was found in layers 2-3 and layer 5 of the frontal cortex (-14.4%), parietal cortex (-18.1%), and striatum (-29.5%). The only other indications of pathology within these regions were a mild diffuse astrogliosis, occasional microglial nodules, and the accumulation of satellite cells around selected neurons. An average loss of large neurons of 56-68% was seen in the cortex of four random source cats euthanized with AIDS. These values contrasted with the absence of any significant cell loss in FIV-infected cats 18 weeks after inoculation or FIV-negative controls. The loss of neurons in the asymptomatic cats showed a significant positive correlation with a decrease in the blood CD4:CD8 ratios. Morphometric evaluation of synaptic terminal densities immunocytochemically stained with synaptophysin revealed a significant increase in the asymptomatic cats at 2-3 years postinoculation that correlated negatively with the CD4:CD8 ratios. Random source AIDS cats showed a 34% decrease in synaptophysin-immunoreactive profiles. Glutamate binding in the cortex did not change significantly in the asymptomatic cats (4-7% decline). Thus, experimentally infected specific pathogen-free cats show a loss of cortical neurons similar to what has been observed in postmortem studies of humans infected with HIV. The detection of neuronal loss during the asymptomatic stage of disease and the correlation with the peripheral CD4:CD8 cell ratios indicate that neurodegeneration may progress in parallel with peripheral disease.

Animals↗

Enhanced Excitotoxicity in Primary Feline Neural Cultures Exposed to Feline Immunodeficiency Virus (FIV).

The ability of feline immunodeficiency virus (FIV) to induce neurodegenerative changes in vitro similar to those due to HIV was examined as a potential model to examine the mechanisms underlying AIDS dementia. Primary cultures of feline neural tissue (neurons, astrocytes and microglia) were established from E40-E57 fetal cat cortex and challenged by inoculation with the NCSU1 strain of FIV. Proviral FIV was detected in the cultures and correlated with the presence of microglia. No direct toxicity of FIV was seen. Stimulation of FIV-inoculated cortical cultures with 20 uM glutamate resulted in a greatly enhanced acute swelling response in approximately 14-24% of the neurons and an increase in the number of dead cells after 24 h relative to control cultures. The enhanced responses were due to an increase in the sensitivity of the cells to glutamate and were dependent on the presence of a soluble factor in the medium. The similarity of the indirect excitoxic effects of FIV to current models of HIV-gp120 neurotoxicity and the versatility of the in vitro cultures, indicate that FIV should provide a valuable model for the investigation of the mechanisms of neurodegeneration in AIDS dementia.

AIDS Dementia Complex↗