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Biomedical subjects

D Milne

Publications and source records attributed to D Milne.

At least 19 recordsLinked to original sources

Meeting the support and information needs of women with advanced breast cancer: a randomised controlled trial.

Addressing psychosocial and quality of life needs is central to provision of excellent care for people with advanced cancer. This study tested a brief nurse-delivered intervention to address the needs of urban women with advanced breast cancer. This study was conducted at four large urban hospitals in Australia. One hundred and five women with advanced breast cancer were recruited and randomised to receive the intervention or usual care, then asked to complete the European Organisation of Research and Treatment of Quality of life Q-C30 version (2.0) (EORTC Q-C30) (version 2) and Supportive Care Needs Survey (SCNS) at 1 month and 3 months postrecruitment. No significant differences were detected between intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale scores. However, when the groups were divided into high needs (score of above 50) and low baseline needs (score of 50 or below) for each SCNS subscale, a significant difference between intervention and usual care groups was found in the psychological/emotional subscale among women with high baseline needs. In conclusions, this study demonstrated that a face-to-face session and follow-up phone call with a breast care nurse significantly reduced the psychological and emotional needs of those with high initial needs. There was no evidence of the intervention influencing the quality of life; or perceived needs of women with low initial psychological/emotional needs or perceived needs in other domains. Possibly, the intervention was not sufficiently intense to achieve an effect.

Adult↗

Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality.

BACKGROUND: Recurrent thromboembolic events after an initial deep vein thrombosis (DVT) are relatively frequent. Residual thrombus in the affected veins on ultrasound scan at the completion of anticoagulant therapy has been described as a recurrence risk factor, and may have utility in stratifying those patients at risk. OBJECTIVES: The aims of the study were to correlate the risk of recurrence of DVT with the results of ultrasound at completion of oral anticoagulant therapy. A secondary aim was to review the mortality in this population. PATIENTS: A cohort of 316 DVT patients was included. The patients were divided into those with completely clear vessels on follow-up scan (45%) and those with residual thrombus identified (55%). RESULTS: The cumulative incidence of recurrence was 10% by 2 years and 23% by 5 years. Patients with residual thrombus on follow-up ultrasound were at higher risk of recurrence (hazard ratio [HR] 2.2, 1.19-4.21; P = 0.012) which remained significant after multivariate adjustment for age, gender and malignancy (HR 2.2, 1.15-4.17; P = 0.018). During follow-up, the cumulative mortality was 12% at 2 years and 27% by 5 years. The risk of death was increased in patients with residual thrombus on follow-up scan (HR 3.9, 1.93-7.71; P < 0.001) and this risk persisted after multivariate analysis of age, gender and malignancy (2.8, 1.37-5.72; P = 0.005). The majority of deaths were due to malignancy (68%) however 10 (18%) died from vascular causes. There was a trend towards increased vascular death in the patients with residual thrombus on follow-up ultrasound scan, which did not reach significance (HR 4.1, 0.87-19.33; P = 0.13). CONCLUSIONS: Consistent with previous cohort studies, recurrence risk is increased in patients with residual thrombus on ultrasound. The increased risk of death in patients with residual thrombus, with a trend towards increased vascular death, may suggest that failure of thrombus resolution is a marker of more global vascular dysfunction.

Anticoagulants↗

Exhaled nitric oxide in sarcoidosis.

BACKGROUND: Increased production of nitric oxide (NO) by the lower respiratory tract is viewed as a marker of airway inflammation in asthma and bronchiectasis. NO is a potentially important immune modulator, inhibiting the release of several key pro-inflammatory cytokines. As sarcoidosis is characterised by granulomatous airway inflammation, we hypothesised that exhaled NO levels might be raised in sarcoidosis and correlate with the morphological extent and functional severity of disease. METHODS: Fifty two patients with sarcoidosis (29 men) of mean age 42 years underwent thin section computed tomography (CT), pulmonary function tests, and measurement of exhaled NO. RESULTS: Exhaled NO levels (median 6.8 ppb, range 2.4-21.8) did not differ significantly from values in 44 control subjects, and were not related to the extent of individual CT abnormalities or the level of pulmonary function impairment. CONCLUSION: Exhaled NO levels are not increased in pulmonary sarcoidosis.

Adult↗

Long-term results of the anterior Délorme's operation in the management of symptomatic rectocele.

PURPOSE: Although the results of surgery for symptomatic rectocele seem satisfactory initially, there is a trend toward deterioration with time. This study was designed to assess the long-term outcome of Anterior Délorme's operation for rectocele. METHODS: Questionnaires were sent to all females who had Anterior Délorme's operation performed in Auckland between 1990 and 2000. The questionnaires included obstructed defecation symptoms and a validated fecal incontinence severity index questionnaire and fecal incontinence quality of life questionnaire. Preoperative and postoperative obstructed defecation symptoms and incontinence score were compared. RESULTS: A total of 150 females (mean age, 56 (range, 30-83) years) who had an Anterior Délorme's operation for a rectocele were identified. One hundred seven patients (71.5 percent; mean age, 56 years) completed the questionnaire. Median follow-up was four (range, 2-11) years. The number of patients with obstructed defecation reduced from 87 preoperatively to 23 postoperatively using Rome II criteria (P < 0.0001). Postoperatively there was a reduction in the number of patients with each of the symptoms of obstructed defecation from 83 to 27 for straining, 87 to 33 for incomplete emptying, 64 to 14 for feeling of blockage, 41 to 10 for digitation (P < 0.0001 for all). The median incontinence score reduced from 20 of 61 preoperatively to 12 of 61 postoperatively (P = 0.0001). CONCLUSIONS: In patients with symptomatic rectocele, Anterior Délorme's operation provides long-term benefit for patients with obstructed defecation and leads to a significant improvement of incontinence scores.

Adult↗

Dietzia strain X: a newly described Actinomycete isolated from confluent and reticulated papillomatosis.

Confluent and reticulated papillomatosis (CRP) is a rare skin disorder. To date its aetiology remains uncertain. The possibility of an infectious aetiology has been supported by case reports of therapeutic response to antibiotic therapy. We have isolated and identified a previously unknown Dietzia strain, an Actinomycete, from skin scrapings of a 17-year-old boy with CRP. We propose that this organism may be the aetiological agent of CRP. Further investigations are necessary to determine the potential role of this Actinomycete in the pathogenesis of CRP.

Actinomycetales↗

Mapping the quality of life and unmet needs of urban women with metastatic breast cancer.

Enhancing quality of life and reducing the unmet needs of women are central to the successful management of advanced breast cancer. The objective of this study was to investigate the quality of life and support and information needs of urban women with advanced breast cancer. This study was conducted at four large urban hospitals in Melbourne, Australia. A consecutive sample of 105 women with advanced breast cancer completed a questionnaire that contained the European Organization of Research and Treatment of Cancer Quality of Life Q-C30 and the Supportive Care Needs Survey. Between one quarter and a third of the women reported difficulties with their physical, role and social functioning, and a little over a quarter of the women reported poor global health status. Fatigue was a problem for most women. The highest unmet needs were in the psychological and health information domains. Almost no differences in unmet needs were detected when comparing different demographic and disease characteristics of women. Health care providers should routinely monitor the quality of life and needs of women with advanced breast cancer to ensure that appropriate treatment, information or supportive services are made available.

Adaptation, Psychological↗

Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study.

BACKGROUND: The frequency and role of risk factors for venous thromboembolism related to air travel is uncertain. We aimed to establish the frequency of this disorder in a group of long distance air travellers and to investigate the role of potential risk factors. METHODS: We designed a prospective study into which we recruited individuals aged between 18 and 70 years, travelling for 4 h or more by aircraft. D-dimer measurement was done before and after travel. Participants with a negative D-dimer (<500 ng/L) before travel were included in the study. Those who became D-dimer positive or developed high clinical probability symptoms during the 3 months after travel were investigated with bilateral compression ultrasonography and CT pulmonary angiography. Suspected clinical and thrombophilic risk factors, and use of prophylactic measures, were assessed. FINDINGS: 1000 individuals were recruited, with 878 meeting inclusion criteria and completing the study. All participants travelled at least 10 h, with a mean total duration of air travel of 39 h (SD 12.5). 112 patients underwent radiological assessment on return. Frequency of venous thromboembolism associated with travel was 1.0% (9/878, 95% CI 0.5-1.9), which included four cases of pulmonary embolism and five of deep venous thrombosis. Six patients with venous thromboembolism had pre-existing clinical risk factors, two had a recognised thrombophilic risk factor, two travelled exclusively in business class, five used aspirin, and four wore compression stockings. INTERPRETATION: Our results suggest an association between multiple long distance air flights and venous thromboembolism, even in individuals at low to moderate risk. The role of traditional risk factors and prophylactic measures in air travel-related venous thromboembolism needs further investigation.

Adolescent↗

Management of solitary pulmonary nodules: how do thoracic computed tomography and guided fine needle biopsy influence clinical decisions?

BACKGROUND: Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule < or = 3 cm in diameter on initial chest radiography. METHODS: Clinical, physiological, and outcome data on 114 patients with an SPN < or = 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later. RESULTS: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median kappa values 0.79-0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (kappa=0.33), rose with CT information (kappa=0.44), and increased further with the addition of the FNB data (kappa=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedman's test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31-70%). FNB data contributed most to the benefit (p<0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy. CONCLUSION: Both CT and FNB make cost effective contributions to the clinical management of SPN < or = 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.

Adult↗

Phosphorylation of murine double minute clone 2 (MDM2) protein at serine-267 by protein kinase CK2 in vitro and in cultured cells.

Murine double minute clone 2 oncoprotein (MDM2) is a key component in the regulation of the tumour suppressor p53. MDM2 mediates the ubiqutination of p53 in the capacity of an E3 ligase and targets p53 for rapid degradation by the proteasome. Stress signals which impinge on p53, leading to its activation, promote disruption of the p53-MDM2 complex, as in the case of ionizing radiation, or block MDM2 synthesis and thereby reduce cellular MDM2 levels, as in the case of UV radiation. It is therefore likely that MDM2, which is known to be modified by ubiquitination, SUMOylation and multi-site phosphorylation, may itself be a target for stress signalling (SUMO is small ubiquitin-related modifier-1). In the present study we show that, like p53, the MDM2 protein is a substrate for phosphorylation by the protein kinase CK2 (CK2) in vitro. CK2 phosphorylates a single major site, Ser(267), which lies within the central acidic domain of MDM2. Fractionation of cellular extracts revealed the presence of a single Ser(267) protein kinase which co-purified with CK2 on ion-exchange chromatography and, like CK2, was subject to inhibition by micromolar concentrations of the CK2-specific inhibitor 5,6-dichlororibofuranosylbenzimidazole. Radiolabelling of cells expressing tagged recombinant wild-type MDM2 or a S267A (Ser(267)-->Ala) mutant, followed by phosphopeptide analysis, confirmed that Ser(267) is a cellular target for phosphorylation. Ser(267) mutants are still able to direct the degradation of p53, but in a slightly reduced capacity. These data highlight a potential route by which one of several physiological modifications occurring within the central acidic domain of the MDM2 protein can occur.

Amino Acid Sequence↗

Managing challenging behaviour in the community: methods and results of interactive staff training.

A necessary condition for a high quality of community care in relation to challenging behaviour is staff training in appropriate methods. This paper describes the application of a practical 'interactive staff training' approach with n = 101 staff, featuring the use of focused and experiential learning in teams. The findings indicated that the course was socially acceptable to the participants, led to a significant improvement in their knowledge of nonphysical methods, and resulted in written guidelines for managing their own clients' challenging behaviour. Furthermore, agreements were clarified on how these guidelines would be implemented by each team following training. Implications are drawn for improved evaluation of this promising training programme, including developing the measures of learning and adding a generalisation assessment.

Adult↗

The national health demonstration projects.

The White Paper Towards a Healthier Scotland pledged 15 million Pounds to support four national health demonstration projects to lead the way in achieving sustained improvement in child health, young people's sexual health, coronary heart disease and cancer. The Starting Well project aims to demonstrate that child health in Glasgow can be improved by a programme of activities which both supports families and provides them with access to enhanced community-based resources. The Healthy Respect project aims to help young people in Lothian develop a positive attitude to their own sexuality and that of others, and a healthy respect for their partners, in order to reduce unplanned teenage pregnancies and sexually transmitted infections. The Have a Heart Paisley project is targeting coronary heart disease among the population of Scotland's largest town. The Cancer Challenge project is piloting a screening programme in the North East of Scotland for the detection of colorectal cancer. Though each project has specific objectives, appropriate to its own topic, all share underlying principles. The projects will act as test beds for action and a learning resource for the rest of Scotland.

Cardiovascular Diseases↗

Is the practice of psychological therapists evidence-based?

An interview-based survey of evidence-based practice (EBP) and the research, continuing professional development (CPD) and audit activity that support it was conducted in the North East of England amongst a representative sample of NHS clinical psychologists and counsellors (n = 30). It profiled their participation in EBP activities over the past year and their intentions for the next year. The findings suggest that the sample had used guidelines and protocols on 56 per cent of occasions, had on average drawn on research, CPD and audit approximately half of the time, but had been only minimally influenced by research, CPD or audit. It is concluded that EBP has occurred in all defined areas and that the conditions for an increased degree of EBP are promising.

Adult↗

A systematic review of effective cognitive-behavioural supervision.

OBJECTIVES: A systematic review was undertaken of studies that have assessed objectively the impact of supervision and consultancy. As well as gauging effectiveness, we examined the methodological rigour of these studies. METHOD: Twenty-eight empirical studies of the change processes occurring between participants within the educational pyramid, 'consultant-->supervisor', 'supervisor-->supervisee' and 'supervisee-->patient', were analysed. The inclusion criteria also required that supervision was analysed under field conditions and there were objective measures of learning outcomes. Each study was analysed by reference to an evaluation manual, with two independent raters obtaining satisfactory reliability. RESULTS: Studies meeting the above criteria came mainly from the intellectual disability specialty and included many studies using cognitive-behavioural methodologies. The studies included in this sample had more rigorous methodologies than those reviewed by Ellis, Ladany, Krengel, and Schult (1996). The findings of the review suggested that the pyramid approach benefited patients. Closely monitoring the supervisee, modelling competence, providing specific instructions, goal setting and providing contingent feedback on performance were the dominant methods of supervision and were associated with benefits to supervisees. CONCLUSION: Despite the large body of literature on supervision, there have been relatively few empirical investigations of the educational pyramid. This work identified a number of studies with good methodological rigour, although these too often failed to provide adequate background and assessment details regarding each of the members of the pyramid, particularly the consultant. The results of cognitive-behavioural supervision were found to be positive.

Cognitive Behavioral Therapy↗

Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm.

OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) occurs in cases of atopic asthma and may result in important lung disease. Early diagnosis is essential as this disease is responsive to steroids. However, while asthma is common, ABPA is infrequently diagnosed. CT allows precision in the diagnosis of central bronchiectasis (which is virtually pathognomonic of ABPA) and may enable earlier diagnosis. DESIGN: A prospective evaluation of 255 patients with asthma for ABPA, using skin prick testing (SPT) for Aspergillus fumigatus (AF) as a screening tool and incorporating CT into the diagnostic algorithm. SETTING: Asthma clinic, Green Lane Hospital, Auckland, New Zealand. PARTICIPANTS: Patients with asthma. INTERVENTIONS: ABPA was diagnosed using "essential" criteria (ie, asthma, SPT positivity to AF, elevated serum total IgE, elevated serum AF-specific IgE, and pulmonary infiltrates seen on chest radiography or central bronchiectasis seen on CT scan) and "minimal essential" criteria (ie, asthma, SPT positivity, and central bronchiectasis). MEASUREMENTS AND RESULTS: Two hundred fifty-five consecutive patients with asthma who consented to SPT were studied: 218 of 255 patients (86.8%) were atopic; and 47 of 255 patients (21.6%) were AF-positive, of whom 35 accepted further evaluation including CT scanning. A secure diagnosis of ABPA, satisfying all essential criteria, was evident in 9 of 35 patients (25.7%), a proportion that increased to 13 of 35 patients (37.1%) by using the minimal essential diagnostic criteria. CONCLUSIONS: SPT positivity to AF was present in approximately 20% of patients in the asthma clinic. A diagnosis of ABPA is disclosed by CT in 25 to 40% of SPT-positive patients, depending on the selection of diagnostic criteria. These findings support the use of SPT as a screening tool in the asthma clinic and indicate that a routine CT scan is warranted in SPT-positive patients.

Adult↗

Rethinking the role of diagnosis in Navajo religious healing.

Diagnosis plays a central, primary role in the therapeutic process across cultures. In this article, the authors examine the role of diagnosis in two Navajo religious healing traditions, the Traditional Navajo religion and the Native American Church (NAC), and examine a case study of a diagnostic encounter between an NAC diagnostician and a Traditional patient. The authors assert that, for Navajos, diagnosis is not merely a prescriptive rite that passively initiates the therapeutic process (as it has been seen in the Navajo literature) but can itself constitute a cure. Claims made about the similarity between Western psychotherapy and religious healing both by scholars and by the healer and patient in this case study are investigated. The authors conclude that such an analogy must be seen against the backdrop of Navajo beliefs about thought, speech, and health. Viewing diagnosis as a "talking cure" and an example of Good's concept of "narrativizing" illness (things it shares with Western psychotherapy) suggests why the analogy is appealing for Navajos themselves.

Adult↗

A one-year follow-up to physical activity and health. A report of the Surgeon General.

OBJECTIVES: A telephone survey of over 2000 American adults was conducted to determine their awareness of Physical Activity and Health: A Report of the Surgeon General and their knowledge of the health messages contained within the report. A related purpose was to determine if awareness and knowledge were a function of age, ethnicity, gender, and education level. METHODS: A random sample of American adults was drawn and a national telephone survey was conducted in the 48 contiguous states and the District of Columbia. RESULTS: Approximately one third of the adult population had heard of the report. Awareness was a function of age, ethnicity, and educational level. Knowledge of the relationship between physical inactivity and specific chronic diseases was a function of age, ethnicity, and gender. CONCLUSIONS: Differential awareness of the Report and its contents by various segments of the population has significant implications for the messages transmitted and interventions developed to help individuals adopt and maintain active lifestyles.

Adolescent↗

Protein kinase CK2-dependent regulation of p53 function: evidence that the phosphorylation status of the serine 386 (CK2) site of p53 is constitutive and stable.

The p53 tumour suppressor protein is regulated by several mechanisms including multisite phosphorylation. One of the protein kinases which has an established role in regulating p53 function is the protein kinase CK2. The regulation by CK2 occurs both through interaction of p53 with CK2 itself (the regulatory beta subunit) and phosphorylation at the penultimate residue of p53, serine 386 (murine p53). Strikingly, this phosphorylation event controls several independent functions of p53 including site-specific DNA binding, strand renaturation, transcriptional repression and the anti-proliferative function of p53. However, CK2 is a constitutively-active enzyme and therefore the mechanism by which the phosphorylation of p53 at serine 386 is itself regulated, or indeed the question as to whether phosphorylation of this site is regulated at all, remains unresolved. In this paper we provide evidence that serine 386 is highly resistant to dephosphorylation in cultured cells, even though this site can be dephosphorylated in vitro by recombinant protein phosphatase 1. These data suggest that, once phosphorylated at the CK2 site, a p53 molecule remains in this modified form throughout its lifespan. To address the issue of whether the level of serine 386 phosphorylation may be regulated through controlling the subcellular compartmentalisation of p53 and CK2, we examined the subcellular localisation of p53 and CK2alpha in C57MG cells and Rat-1 fibroblasts by immunofluorescence staining. Both proteins were present in the cytoplasm and enriched in the nucleus, with minor variations in the intensity of subcellular location over the course of the cell cycle. Similarly, activation of p53 by UV irradiation or DNA damage-inducing drugs had no effect on either the localisation or levels of CK2alpha, even although significant nuclear p53 accumulation was observed. A striking observation arising from these studies was the intense staining of CK2alpha with the centrosomes, suggesting a potentially important role for this kinase in microtubule formation and/or chromosomal segregation.

Amino Acid Sequence↗