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D Jones

Publications and source records attributed to D Jones.

At least 19 recordsLinked to original sources
PubMed2007

Cueing training in the home improves gait-related mobility in Parkinson's disease: the RESCUE trial.

OBJECTIVES: Gait and mobility problems are difficult to treat in people with Parkinson's disease. The Rehabilitation in Parkinson's Disease: Strategies for Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait-related activity. METHODS: A single-blind randomised crossover trial was set up, including 153 patients with Parkinson's disease aged between 41 and 80 years and in Hoehn and Yahr stage II-IV. Subjects allocated to early intervention (n = 76) received a 3-week home cueing programme using a prototype cueing device, followed by 3 weeks without training. Patients allocated to late intervention (n = 77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a 6-week follow-up without training. Posture and gait scores (PG scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain. RESULTS: Small but significant improvements were found after intervention of 4.2% on the PG scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests (p = 0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p = 0.04), no carry-over effects were observed in functional and quality of life domains. Effects of intervention had reduced considerably at 6-week follow-up. CONCLUSIONS: Cueing training in the home has specific effects on gait, freezing and balance. The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow-up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson's disease.

Aged↗
PubMed2006

Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate.

Mutations of the BCR-ABL kinase domain are a common mechanism of resistance to imatinib in chronic myeloid leukemia. We screened for mutations 171 patients failing imatinib therapy. Sixty-six mutations in 23 amino acids were identified in 62 (36%) patients not responding to imatinib. Phosphate-binding loop (P-loop) mutations were the most frequent (n=24; 36%). By multivariate analysis, factors associated with development of mutations were older age (P=0.026) prior interferon therapy (P=0.026), and accelerated phase or blast phase at time of imatinib failure (P=0.001). After a median follow-up of 38 months (range, 4-68 months) from the start of imatinib therapy, seven patients with non-P-loop and two with P-loop mutation died. By multivariate analysis, development of clonal evolution and higher percentage of peripheral blood basophils were associated with worse survival from the time of imatinib failure. Mutation status had no impact on survival. When survival was measured from the time therapy started, non-P-loop mutations together with duration of response and transformation at the time of failure to imatinib were associated with shorter survival. In conclusion, P-loop mutations were not associated with poor outcome, suggesting that the prognosis of patients who fail imatinib is multifactorial.

Adult↗
PubMed2006

Addition of drug/s to a chemotherapy regimen for metastatic breast cancer.

BACKGROUND: The addition of a chemotherapy drug or drugs to an established regimen is one method used to increase the dose and intensity of treatment for metastatic breast cancer. OBJECTIVES: To identify and review the randomised trial evidence in the first line management of women with metastatic breast cancer that evaluates the addition of one or more chemotherapy drugs to an established regimen. SEARCH STRATEGY: We searched the specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group on 3rd August 2004 (updated search on 2nd August 2005) using the codes for "advanced breast cancer" and "chemotherapy". Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library. SELECTION CRITERIA: Randomised trials that evaluated a first line regimen of at least two chemotherapy drugs, and compared it to that same regimen plus the addition of one or more chemotherapy drugs in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: We collected data from published trials and assessed studies for eligibility and quality. Two reviewers extracted data independently. We derived hazard ratios (HR) from time-to-event outcomes where possible, and a fixed effect model was used for meta-analysis. We analysed response rates as dichotomous variables and extracted toxicity data where available. MAIN RESULTS: We identified 17 trials reporting on 22 treatment comparisons (2674 patients randomised). Fifteen trials (20 treatment comparisons) reported results for tumour response and 11 trials (14 treatment comparisons) published time-to-event data for overall survival. There were 1532 deaths in 2116 women randomised to trials of the addition of a drug to the regimen and control (the regimen alone). There was no detectable difference in overall survival between these patients, with an overall HR of 0.96 (95% CI 0.87 to 1.07, P = 0.47) and no statistically significant heterogeneity. We found no difference in time to progression between these regimens, with an overall HR of 0.93 (95% CI 0.81 to 1.07, P = 0.31) and no statistically significant heterogeneity. Addition of a drug to the regimen was favourably associated with overall tumour response rates (OR 1.21, 95% CI 1.01 to 1.44, P = 0.04) although we observed statistically significant heterogeneity for this outcome across the trials. Where measured, acute toxicities such as alopecia, nausea and vomiting and leukopenia were more common with the addition of a drug. AUTHORS' CONCLUSIONS: The addition of one or more drugs to the regimen shows a statistically significant advantage for tumour response in women with metastatic breast cancer but the results suggest no difference in survival time or time to progression. The positive effect on tumour response observed with addition of a drug to the regimen was also associated with increased toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

The use of rhythmic auditory cues to influence gait in patients with Parkinson's disease, the differential effect for freezers and non-freezers, an explorative study.

PURPOSE: To study the effect of rhythmic auditory cues on gait in Parkinson's disease subjects with and without freezing and in controls. METHOD: A volunteer sample of 20 patients (10 freezers, 10 non-freezers) and 10 age-matched controls performed five randomized cued walking conditions in a gait-laboratory. Auditory cues were administered at baseline frequency, at an increased step frequency of 10 and 20% above baseline and at a decreased step frequency of 10 and 20% below baseline. Mean step frequency, walking speed, stride length and double support duration were collected. RESULTS: Rhythmical auditory cueing induced speed changes in all subjects. Stride length was not influenced by rhythmical auditory cues in controls, whereas patients showed a larger stride length in the -10% condition (p < 0.01). Freezers and non-freezers showed the same response to rhythmical auditory cues. Within group analysis for stride length showed different cueing effects. Stride length decreased at the +10% condition for freezers (p < 0.05), whereas it increased for non-freezers. CONCLUSIONS: This study points to fact that physiotherapists might need to carefully adjust the cueing frequency to the needs of patients with and without freezing. On the basis of the present results we recommend to lower the frequency setting for freezers, whereas for non-freezers an increase of up to +10% may have potential therapeutic use.

Acoustic Stimulation↗
PubMed2006

The effect of rhythmic somatosensory cueing on gait in patients with Parkinson's disease.

BACKGROUND AND AIMS: Gait and gait related activities in patients with Parkinson's disease (PD) can be improved with rhythmic auditory cueing (e.g. a metronome). In the context of a large European study, a portable prototype cueing device was developed to provide an alternative for rhythmic auditory cueing: rhythmic somatosensory cueing (RSC, a miniature vibrating cylinder attached to the wrist). We investigated whether PD patients could adapt their walking pattern using RSC under conditions of changing walking speed and the presence of potentially distracting visual flow while walking on a treadmill. METHODS: A total of 17 patients with PD participated (mean age 63.4+/-10.3 years; Hoehn-Yahr score 2.5+/-0.9, mean Unified Parkinson's Disease Rating Scale score 49.8+/-13.7, mean disease duration 7.7+/-5.1 years). They performed systematic walking speed manipulations under 4 conditions in a random order: (1) no cue, no visual flow, (2) no cue, visual flow, (3) cue, no visual flow and (4) cue, visual flow. Visual flow in the form of a virtual corridor that moved at the current walking speed was projected on a 2 x 2 m rear-projection screen. The cueing rhythm was set at -10% of preferred stride frequency at each speed. Stride frequency was assessed using peaks in the trajectories of thigh sagittal plane segmental angles. RESULTS: Walking with RSC resulted in lower stride frequencies, and thus larger step lengths (p-values <0.05), regardless of walking speed. The presence of visual flow did not impair the use of RSC, as evidenced by the lack of differences between conditions 3 and 4 (p>0.05). CONCLUSION: Rhythmic somatosensory cueing may be a viable alternative for auditory cueing and is robust to changes in walking speed and visual distractors.

Aged↗
PubMed2006

Radiation sources based on laser-plasma interactions.

Plasma waves excited by intense laser beams can be harnessed to produce femtosecond duration bunches of electrons with relativistic energies. The very large electrostatic forces of plasma density wakes trailing behind an intense laser pulse provide field potentials capable of accelerating charged particles to high energies over very short distances, as high as 1GeV in a few millimetres. The short length scale of plasma waves provides a means of developing very compact high-energy accelerators, which could form the basis of compact next-generation light sources with unique properties. Tuneable X-ray radiation and particle pulses with durations of the order of or less than 5fs should be possible and would be useful for probing matter on unprecedented time and spatial scales. If developed to fruition this revolutionary technology could reduce the size and cost of light sources by three orders of magnitude and, therefore, provide powerful new tools to a large scientific community. We will discuss how a laser-driven plasma wakefield accelerator can be used to produce radiation with unique characteristics over a very large spectral range.

Journal Article↗
PubMed2006

Retinoic acid and oncostatin M combine to promote cartilage degradation via matrix metalloproteinase-13 expression in bovine but not human chondrocytes.

OBJECTIVES: Retinoic acid (RetA) and oncostatin M (OSM) have both been shown to mediate potent effects with respect to extracellular matrix integrity. This study assesses the effects of a RetA + OSM combination on cartilage catabolism. METHODS: Animal and human cartilage samples were used to assess the ability of RetA + OSM to promote the release of collagen and proteoglycan fragments, which was determined by measuring glycosaminoglycan and hydroxyproline, respectively. Total collagenolytic and tissue inhibitor of metalloproteinases (TIMP) inhibitory activities were determined by bioassay, whilst gene expression of matrix metalloproteinases (MMPs) and TIMP-1 were determined by northern blotting. Immunohistochemistry was used to assess the presence of MMP-1 and -13 in resorbing cartilage explants. RESULTS: Both agents alone induced proteoglycan release from bovine cartilage, whilst RetA-induced collagen release was variable. Reproducible and synergistic collagenolysis was observed with RetA + OSM, which appeared to be due to MMP-13. Similar collagen release was observed from porcine cartilage. Conversely, no collagen release was seen with human articular cartilage. In primary human chondrocytes, RetA + OSM failed to induce MMP-1 or -13 but caused a significant increase in TIMP-1 expression. CONCLUSIONS: These novel observations show that the combination of RetA + OSM has profound effects on cartilage matrix turnover, but these effects are species-specific. A better understanding of the mechanism by which this combination differentially regulates MMP and TIMP expression in human chondrocytes could provide valuable insight into new therapeutic strategies aimed at the prevention of cartilage destruction.

Animals↗
PubMed2006

Activation of STAT3 in thymic epithelial tumours correlates with tumour type and clinical behaviour.

The STAT3 (signal transducers and activators of transcription 3) signalling pathway plays a pivotal role in oncogenesis and appears essential for postnatal maintenance of thymic architecture and thymocyte survival. The association of STAT3 activation with thymic epithelial tumours (TETs) and myasthenia gravis (MG) has not been elucidated. In this study, 118 cases of TET and 25 non-neoplastic thymic tissue samples were evaluated for STAT3 and phospho-STAT3 (pSTAT3) expression immunohistochemically. In addition, 44 normal thymuses of different ages were included for comparison. It was found that STAT3 activation in thymic epithelial cells (TECs), as evidenced by pSTAT3 expression and/or nuclear STAT3, was present in the majority of non-neoplastic thymuses (88%, 22/25), including those from young children, but not in fetal thymus. In thymoma (n = 73), activated STAT3 was noted at a significantly higher frequency in the cases of lymphocyte-rich thymoma (ie types AB, B1, and B2, 46%, 23/50) in comparison with lymphocyte-depleted thymoma (types A and B3, 1/23) (p = 0.009). Thymoma with activated STAT3 tended to present at an earlier stage, show complete resectability and less aggressive behaviour, and have a higher correlation with MG than the STAT3-negative/inactive group (p < 0.05). In contrast, thymic carcinoma with activated STAT3 (14/45, 31%) had significantly higher rates of unresectability, vascular invasion, and regional lymph node metastasis (p < 0.05). These data provide the first evidence that constitutive STAT3 activation is seen in both benign and neoplastic thymic tissue and is associated with the persistence of thymic tissue and the presence of MG. It is likely to be induced by different factors in thymoma and thymic carcinoma.

Adolescent↗
PubMed2006

TCL1 shows a regulated expression pattern in chronic lymphocytic leukemia that correlates with molecular subtypes and proliferative state.

Expression of the human oncogene TCL1 in transgenic mice produces B-cell tumors that resemble chronic lymphocytic leukemia (CLL) suggesting its role in B-cell tumorigenesis. To clarify the expression pattern and regulation of TCL1 in CLL, we assessed 213 primary tumors by immunohistochemistry (IHC), flow-cytometry and/or Western blot, using a new monoclonal antibody. TCL1 protein was detectable in the majority of CLL (90% by IHC) but showed marked variations across cases with virtual absence in approximately 10% of tumors. Higher TCL1 levels correlated with markers of the 'pre-germinal center' CLL subtype including unmutated VH status (P=0.005), ZAP70 expression (P=0.007), and presence of chromosome 11q22-23 deletions (P=0.04). Intratumoral heterogeneity in TCL1 levels was also prominent and explained in part by markedly lower TCL1 expression in proliferating tumor cells. In vitro exposure of CLL cells to interleukin-4 (but not other growth factors) produced progressive and irreversible decrease in TCL1 protein levels in association with the onset of proliferation. TCL1 expression patterns in CLL are complex and highly dynamic and appear to reflect both the histogenetic subtypes of the disease and the growth parameters of individual tumors. The observed regulation pattern suggests that TCL1 may exert its effects predominantly in the unmutated/ZAP70-positive tumor subset.

Animals↗
PubMed2006

Effect of an education programme on the utilization of a medical emergency team in a teaching hospital.

BACKGROUND: Medical Emergency Teams (MET) have been developed to identify, review and manage acutely unwell ward patients. Previous studies have suggested that there may be obstacles to the utilization and activation of the MET. AIMS: To determine the effect of a detailed education programme on the rate of utilization of the MET system 3.5 years after its introduction in a University teaching hospital. METHODS: Prospective interventional study involving a detailed programme of education, feedback and decision support for nursing and medical staff given before, during and after implementation of a MET system. We measured the number of MET calls per month for both medical and surgical patients for 109 250 consecutive admissions to the acute care campus of Austin Health from August 2000 to June 2004. RESULTS: Overall activation of the MET increased from 25 calls per month to a peak of 79 calls per month over the study period (average increase of one MET call/month). After standardization for monthly admissions, the increase in MET utilization for surgical patients (increase by 1.13 MET/1000 admissions/month) was 4.9-fold greater than for medical patients (increase by 0.23 MET/1000 admissions/month; P < 0.0001). At the peak level of activity (April 2004), the MET was called to review 8.4% of surgical and 2.7% of medical admissions (P < 0.0001). CONCLUSIONS: There was a progressive increase in the utilization of the MET service in the 3.5 years after implementation, with the rate of uptake 4.9 times greater for surgical than for medical patients. Sustained uptake of the MET system is possible, but increased utilization may take several years to develop. Short-term studies testing the efficacy of the MET system are likely to significantly underestimate its effect on reducing adverse events. Intensive care unit resource adjustments will become necessary to meet increased demand.

Critical Illness↗
PubMed2006

Nurses' attitudes to a medical emergency team service in a teaching hospital.

BACKGROUND: Cultural barriers including allegiance to traditional models of ward care and fear of criticism may restrict use of a medical emergency team (MET) service, particularly by nursing staff. A 1-year preparation and education programme was undertaken before implementing the MET at the Austin Hospital, Melbourne, Australia. During the 4 years after introduction of the MET, the programme has continued to inform staff of the benefits of the MET and to overcome barriers restricting its use. OBJECTIVE: To assess whether nurses value the MET service and to determine whether barriers to calling the MET exist in a 400-bed teaching hospital. METHODS: Immediately before hand-over of ward nursing, we conducted a modified personal interview, using a 17-item Likert agreement scale questionnaire. RESULTS: We created a sample of 351 ward nurses and obtained a 100% response rate. This represents 50.9% of the 689 ward nurses employed at the hospital. Most nurses felt that the MET prevented cardiac arrests (91%) and helped manage unwell patients (97%). Few nurses suggested that they restricted MET calls because they feared criticism of their patient care (2%) or criticism that the patient was not sufficiently unwell to need a MET call (10%). 19% of the respondents indicated that MET calls are required because medical management by the doctors has been inadequate; many ascribed this to junior doctors and a lack of knowledge and experience. Despite hospital MET protocol, 72% of nurses suggested that they would call the covering doctor before the MET for a sick ward patient. However, 81% indicated that they would activate the MET if they were unable to contact the covering doctor. In line with hospital MET protocol, 56% suggested that they would make a MET call for a patient they were worried about even if the patient's vital signs were normal. Further, 62% indicated that they would call the MET for a patient who fulfilled MET physiological criteria but did not look unwell. CONCLUSIONS: Nurses in the Austin Hospital value the MET service and appreciate its potential benefits. The major barrier to calling the MET appears to be allegiance to the traditional approach of initially calling parent medical unit doctors, rather than fear of criticism for calling the MET service. A further barrier seems to be underestimation of the clinical significance of the physiological perturbations associated with the presence of MET call criteria.

Adult↗
PubMed2006

Perioperative pulse contour cardiac output analysis in a patient with severe cardiac dysfunction.

We describe a patient with severe left ventricular dysfunction simultaneously monitored with pulse contour cardiac output (PiCCO) analysis, a continuous cardiac output pulmonary artery catheter (continuous COPAC) and intraoperative transoesophageal echocardiography (TOE). There was good agreement between cardiac output (CO) measurements obtained by the three techniques prior to cardiopulmonary bypass (CPB). Agreement of CO measurements following CPB was initially pool; but improved following recalibration of PiCCO. PiCCO-derived global end-diastolic volume index (GEDVI) and cardiac function index (CFI), were assessed as markers of left ventricular preload and myocardial contractility, respectively. GEDVI correlated well with CO in the postoperative period. CFI increased more than two-fold following coronary revascularization and milrinone administration, and there was also a temporal relationship between the CFI and the dose of milrinone in the first 24 hours of treatment. Global end-diastolic volume and cardiac function index may be useful additional measures of left ventricular preload and myocardial contractility in patients with severe left ventricular dysfunction.

Cardiac Output↗
PubMed2006

An introductory guide to survey research in anaesthesia.

Surveys allow convenient and inexpensive research. Surveys include mail-out questionnaires, email questionnaires, telephone interviews, and personal interviews. Despite a widespread perception that surveys are easy to conduct, good surveys need rigorous design, implementation and analysis. This requires substantial planning, time and effort. The most important step in designing a survey is to clearly define the question(s) the survey aims to answer The target population, measured variables and types of associations being investigated should be specific and unambiguous. Investigators should concentrate on what they 'need to know' rather than what would be 'nice to know'. During development surveys should be piloted to identify problems. The main goal when implementing a survey is to maximize the response rate to avoid misleading results. Evidence-based strategies, including brief personalized surveys with stamped return envelopes, can be used to maximize the response rate. A poorly conducted survey can lead to misleading or invalid conclusions and may undermine participation in subsequent surveys by the target population.

Anesthesiology↗
PubMed2006

Relative adrenal insufficiency in etomidate-naïve patients with septic shock.

A recent study reported that 77% of patients with septic shock had relative adrenal insufficiency. However, all patients were mechanically ventilated and received high-dose inotropes. In addition, at least 24% had prior exposure to etomidate, a drug known to suppress adrenal function. We studied the incidence of relative adrenal insufficiency in etomidate-naïve patients with septic shock by analysing the adrenal response to high-dose short synacthen test in 113 consecutive patients from three university-affiliated intensive care units in Australia. Patients were allocated to three groups according to severity of illness and inclusion criteria of the trial of low dose hydrocortisone supplementation using information from patient records. Of the 113 patients, 98 had septic shock (Group A). The incidence of relative adrenal insufficiency in this subpopulation was 24.5%. Eighty-one per cent of patients with septic shock were mechanically ventilated (Group B). In this group, the incidence of relative adrenal insufficiency was 27.8%. Only 38 of the 98 patients with septic shock (39%) fulfilled inclusion criteria for the steroid supplementation trial (Group C). In this group, the incidence of relative adrenal insufficiency was only 34.2%. In all groups its presence was associated with a higher mortality. We conclude that the incidence of relative adrenal insufficiency in etomidate-naive septic shock patients was lower than observed in the steroid supplementation trial. Further, in those who fulfilled inclusion criteria for the trial, the incidence of relative adrenal insufficiency was half that reported by the trial. Our observations raise concerns about the generalizability of the findings of the above trial to etomidate-naïve patients.

APACHE↗
PubMed2006

Oblique pelvic osteotomy in the exstrophy/epispadias complex.

We reviewed retrospectively 45 patients (46 procedures) with bladder exstrophy treated by bilateral oblique pelvic osteotomy in conjunction with genitourinary repair. The operative technique and post-operative management with or without external fixation are described. A total of 21 patients attended a special follow-up clinic and 24 were interviewed by telephone. The mean follow-up time was 57 months (24 to 108). Of the 45 patients, 42 reported no pain or functional disability, although six had a waddling gait and two had marked external rotation of the hip. Complications included three cases of infection and loosening of the external fixator requiring early removal with no deleterious effect. Mid-line closure failed in one neonate managed in plaster. This patient underwent a successful revision procedure several months later using repeat osteotomies and external fixation. The percentage pubic approximation was measured on anteroposterior radiographs pre-operatively, post-operatively and at final follow-up. The mean approximation was 37% (12% to 76%). It varied markedly with age and was better when external fixation was used. The wide range reflects the inability of the anterior segment to develop naturally in spite of close approximation at operation. We conclude that bilateral oblique pelvic osteotomy with or without external fixation is useful in the management of difficult primary closure in bladder exstrophy, failed primary closure and secondary reconstruction.

Age Factors↗