Biomedical subjects

A D Milner

Publications and source records attributed to A D Milner.

At least 19 recordsLinked to original sources

PubMed2006

A phase I/II trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer.

BACKGROUND: The study's aim was to determine the maximum tolerated dose (MTD) of celecoxib combined with chemoradiotherapy (CRT) for locally advanced oesophageal cancer (OC). METHODS: CRT comprised of 5FU (1000 mg/m(2)/day, days 1-4, weeks 1 & 5), cisplatin (75 mg/m(2), days 1 & 29) and radiotherapy (50 Gy in 25 fractions or 50.4 Gy in 28 fractions). Celecoxib was given daily during CRT at one of five doses (200 mg bd to 600 mg bd). Three to six patients were assigned per dose. RESULTS: Thirteen patients were recruited before trial closure due to external safety concerns regarding celecoxib. Median follow up was 17 months (95% CI 9 - >39). The highest administered dose was 400 mg bd (n=4) with one dose-limiting toxicity at this level: grade 3 rash. Five (38%) and 8(62%) patients had grade 3 non-haematological and haematological toxicities respectively. No grade 4 toxicities occurred. Radiological response rate was 54% (n=7: all CR). Six patients had resection with one pathological CR. Median progression-free and overall survival were 8.8 (95% CI 5.1 - >24.8) and 19.6 months (95% CI 7.3 - >39) respectively. CONCLUSIONS: A MTD was not reached. The regimen was tolerable, indicating that celecoxib can be safely administered with CRT for locally advanced OC.

Adenocarcinoma↗

PubMed2006

Reaching errors in optic ataxia are linked to eye position rather than head or body position.

When reaching towards a visual stimulus, spatial information about the target must be transformed into an appropriate motor command. Visual information is coded initially in retinotopic coordinates, while the reaching movement ultimately requires the specification of the target position in limb-centred coordinates. It is well established that the posterior parietal cortex (PPC) plays an important role in transforming visual target information into motor commands. Lesions in the PPC can result in optic ataxia, a condition in which the visual guidance of goal-directed movements is impaired. Here, we present evidence from two patients with unilateral optic ataxia following right PPC lesions, that the pattern of reaching errors is linked to an eye-centred frame of reference. Both patients made large errors when reaching to visual targets on the left side of space, while facing and fixating straight ahead. By varying the location of fixation and the orientation of the head and body, we were able to establish that these large errors were made specifically to targets to the left of eye-fixation, rather than to the left of head-, body-, or limb-relative space. These data support the idea that visual targets for reaching movements are coded in eye-centred coordinates within the posterior parietal cortex.

Aged, 80 and over↗

PubMed2005

A phase I trial of high-dose palliative radiotherapy plus concurrent weekly Vinorelbine and Cisplatin in patients with locally advanced and metastatic NSCLC.

The role of concurrent chemoradiotherapy (CRT) in patients with non-small-cell lung cancer (NSCLC) unsuitable for radical therapy but who require locoregional treatment has not been defined. The aims of this phase I trial were thus to develop a novel regimen of weekly chemotherapy concurrent with high-dose palliative RT (40 Gy/20 fractions) and assess its tolerability, objective and symptomatic response rates. Eligible patients had stage I-IIIB NSCLC unsuitable for radical RT or limited stage IV disease, ECOG PS<or=1 and required locoregional therapy. Treatment was RT (40 Gy/20 fractions/5 per week) and weekly Vinorelbine plus Cisplatin escalated in six planned dose levels (DLs). At 4 weeks post-RT, patients received two cycles of Cisplatin 80 mg m-2 day 1+Vinorelbine 25 mg m-2 days 1, 8, 15. Dose-limiting toxicities (DLTs) were defined in the CRT phase. Disease-related symptoms were assessed by the Lung Cancer Symptom Scale. In all, 24 patients accrued, stage IIIB (n=12) and IV disease (n=10). The highest administered dose was at DL 4, Vinorelbine 30 mg m-2+Cisplatin 20 mg m-2 with DLTs of grade 4 neutropenia in two of three patients. No grade 3 or 4 nonhaematological toxicities were observed. The overall radiological response rate was 65% (n=23: complete response 4% and partial response 61%) and infield FDG-PET responses were seen in 89% (n=18). There was an improvement or stabilisation of symptoms and quality of life. Dose level 3, Vinorelbine 25 mg m-2+Cisplatin 20 mg m-2, is recommended for further assessment. This regimen was tolerable and produced meaningful responses for patients for whom locoregional control is required, but who are unsuitable for radical CRT.

Adult↗

PubMed2005

Dampened ventilatory response to added dead space in newborns of smoking mothers.

BACKGROUND: Term newborns can compensate fully for an imposed dead space (tube breathing) by increasing their minute ventilation. OBJECTIVE: To test the hypothesis that infants of smoking mothers would have an impaired response to tube breathing. DESIGN: Prospective study. SETTING: Perinatal service. PATIENTS: Fourteen infants of smoking and 24 infants of non-smoking mothers (median postnatal age 37 (11-85) hours and 26 (10-120) hours respectively) were studied. INTERVENTIONS: Breath by breath minute volume was measured at baseline and when a dead space of 4.4 ml/kg was incorporated into the breathing circuit. MAIN OUTCOME MEASURES: The maximum minute ventilation during tube breathing was determined and the time constant of the response calculated. RESULTS: The time constant of the infants of smoking mothers was longer than that of the infants of non-smoking mothers (median (range) 37.3 (22.2-70.2) v 26.2 (13.8-51.0) seconds, p = 0.016). Regression analysis showed that maternal smoking status was related to the time constant independently of birth weight, gestational or postnatal age, or sex (p = 0.018). CONCLUSIONS: Intrauterine exposure to smoking is associated with a dampened response to tube breathing.

Female↗

PubMed2005

Visually guided reaching: bilateral posterior parietal lesions cause a switch from fast visuomotor to slow cognitive control.

The visually guided reaching of two patients with bilateral optic ataxia was explored in two experiments. In Experiment 1 simple delayed pointing was compared with immediate pointing. In the immediate pointing task both variable and constant errors increased with target eccentricity. In contrast to the performance of control subjects and contrary to their own beliefs, the patients both showed improved accuracy in the delay condition. This improvement was manifest as a reduction in both pointing variability and in the constant angular error towards the point of fixation. Both angular errors and their improvement with the delay were proportional to target eccentricity. Experiment 2 used a task in which the target was pre-viewed 5s prior to its re-exposure for pointing ('delayed real pointing'). On some trials a conflict was introduced between the present and previous visual information by changing the target's location during the delay. In contrast to control subjects, who ignored the pre-viewed location and aimed directly at the current target, both patients with optic ataxia initiated their movements towards the previously viewed target location. Evidently they relied on off-line information in preference to on-line visual information. In addition, the patients often failed to detect the changes in target location. One of the patients sometimes even guessed incorrectly that the target had changed its location, and her movement trajectory was then more affected by her false belief than by the target's actual location. These findings confirm that posterior parietal lesions severely disrupt direct visuomotor transformations, and suggest that the residual performance is mediated indirectly by expectations or beliefs about target position.

Acoustic Stimulation↗

PubMed2005

Parotid-sparing radiotherapy: does it really reduce xerostomia?

AIMS: Parotid-sparing radiotherapy (PSRT) was introduced for patients with selected head and neck cancer requiring bilateral upper-neck irradiation at our centre in 2000. The aim of this study was to compare the subjective degree of xerostomia in patients treated with PSRT between January 2000 and June 2003 with patients treated using conventional techniques (radiotherapy) over the same period. MATERIALS AND METHODS: Eligible patients were required to have completed treatment 6 months previously and be recurrence-free at the time of interview. PSRT was defined as conformal radiotherapy, in which the mean dose to at least one parotid gland was 33 Gy or less, as determined by the dose-volume histogram. Patients receiving radiotherapy were treated with standard parallel-opposed fields, such that both parotids received a minimum of 40 Gy. Xerostomia was assessed using a validated questionnaire containing six questions with a rating between 0 and 10. Lower scores indicated less difficulty with xerostomia. RESULTS: Thirty-eight eligible patients treated with PSRT were identified: 25 with oropharyngeal cancer and 13 with nasopharyngeal cancer (NPC). The mean overall questionnaire score (Q1-5) for this group was 4.20 (standard error = 0.33). Forty-four patients (24 oropharyngeal, 21 NPC) treated with radiotherapy over the same period were eligible. The mean overall questionnaire score (Q1-5) for this group was 5.86 (standard error = 0.35). The difference in mean overall scores between the two groups of patients was statistically significant (P < 0.001), as were the scores for four of the six individual questions. CONCLUSION: These results suggest that PSRT offers improved long-term xerostomia-related quality of life compared with conventional radiotherapy.

Adult↗

PubMed2004

Synchronized mechanical ventilation for respiratory support in newborn infants.

BACKGROUND: During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. Thus, if synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing barotrauma and hence airleak and chronic lung disease. Synchronous ventilation can be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient assisted ventilation. OBJECTIVES: To compare (i) the efficacy of synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation or triggered ventilation (patient triggered ventilation (PTV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation(ii) different types of triggered ventilation SEARCH STRATEGY: Searches from 1985-2004 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), Oxford Database of Perinatal Trials, MEDLINE, previous reviews, abstracts and symposia proceedings; hand searches of journals in the English language and contact with expert informants. SELECTION CRITERIA: Randomized or quasi randomized clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (PTV/SIMV) to conventional mechanical ventilation (CMV) in neonates. Randomized trials comparing different triggered ventilation modes (PTV and SIMV) in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, airleaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intracerebral haemorrhage (grades 3 and 4), chronic lung disease (oxygen dependency beyond 28 days) and duration of weaning/ventilation. Three comparisons were made: (i) HFPPV vs CMV; (ii) PTV/SIMV vs CMV; (iii) PTV vs SIMV. Data analysis was conducted using relative risk for categorical outcomes, weighted mean difference for outcomes measured on a continuous scale. MAIN RESULTS: Eleven studies were eligible for inclusion. The meta-analysis demonstrate that HFPPV compared to CMV was associated with a reduction in the risk of airleak (typical relative risk for pneumothorax was 0.69, 95% CI 0.51, 0.93). PTV/SIMV compared to CMV was associated with a shorter duration of ventilation (weighted mean difference -34.8 hours, 95% CI -62.1, -7.4). PTV compared to SIMV was associated with a trend to a shorter duration of weaning (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of chronic lung disease. There was a non-significant trend towards a lower mortality rate using HFPPV versus CMV, but a non-significant trend towards a higher mortality rate using triggered ventilation versus CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. REVIEWERS' CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in airleak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits, but optimization of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials.

Humans↗

PubMed2004

Avoidance of obstacles in the absence of visual awareness.

The spatial character of our reaching movements is extremely sensitive to potential obstacles in the workspace. We recently found that this sensitivity was retained by most patients with left visual neglect when reaching between two objects, despite the fact that they tended to ignore the leftward object when asked to bisect the space between them. This raises the possibility that obstacle avoidance does not require a conscious awareness of the obstacle avoided. We have now tested this hypothesis in a patient with visual extinction following right temporoparietal damage. Extinction is an attentional disorder in which patients fail to report stimuli on the side of space opposite a brain lesion under conditions of bilateral stimulation. Our patient avoided obstacles during reaching, to exactly the same degree, regardless of whether he was able to report their presence. This implicit processing of object location, which may depend on spared superior parietal-lobe pathways, demonstrates that conscious awareness is not necessary for normal obstacle avoidance.

Brain Injuries↗

PubMed2004

Preserved obstacle avoidance during reaching in patients with left visual neglect.

We asked 12 patients with left visual neglect to bisect the gap between two cylinders or to reach rapidly between them to a more distal target zone. Both tasks demanded a motor response but these responses were quite different in nature. The bisection response was a communicative act whereby the patient indicated the perceived midpoint. The reaching task carried no imperative to bisect the gap, only to maintain a safe distance from either cylinder while steering to the target zone. Optimal performance on either task could only be achieved by reference to the location of both cylinders. Our analysis focused upon the relative influence of the left and right cylinders on the lateral location of the response. In the bisection task, all neglect patients showed qualitatively the same asymmetry, with the left cylinder exerting less influence than the right. In the reaching task, the neglect group behaved like normal subjects, being influenced approximately equally by the two cylinders. This was true for all bar two of the patients, who showed clear neglect in both tasks. We conclude that the visuomotor processing underlying obstacle avoidance during reaching is preserved in most patients with left visual neglect.

Aged↗

PubMed2004

Covert processing of visual form in the absence of area LO.

The patient D.F., who suffers from severe visual form agnosia, has been found to have a bilateral lesion of area LO, an area known to be intimately involved in the perception of object shape. Despite her perceptual impairment, however, D.F. retains residual form processing abilities that can provide distal visuomotor control, for example in the configuration of her grasp when reaching to pick up objects of different shapes and sizes. This dissociation has been interpreted as reflecting the sparing of a dedicated system for processing the physical properties of objects solely for purposes of guiding action. Here we test this hypothesis in two studies designed to examine whether or not spared shape processing capacities might be revealed under other kinds of indirect test conditions. First, we exploited the fact that a redundant shape cue will speed search for a coloured stimulus within an array, and vice versa. Unlike our control subjects, D.F. showed no facilitation effect of either kind. Second, we used two Stroop tasks in which single coloured uppercase letters were presented. Our intention was to determine (a) whether naming the colour would be influenced by whether the letter was the initial letter of the correct or incorrect colour name (e.g. 'R' or 'G'); and (b) whether the reverse might be true, that is that D.F.'s guesses at letter identity might be influenced by their colour. We found no evidence for a Stroop effect of the former (standard) kind in D.F., but we did find evidence for reverse-Stroop effects. This result may reflect a partial sparing of ventral stream areas specialised for letter-form processing.

Agnosia↗

PubMed2003

Delayed reaching and grasping in patients with optic ataxia.

A series of experiments documenting the reaching and grasping of two patients with optic ataxia is presented. We compare their immediate responses with their behavior when required to delay for a few seconds before responding. When the delayed response is 'pantomimed', i.e. made in the absence of the target object, their performance typically improves. This pattern was predicted from a two-visual-systems model in which the cortical dorsal stream mediates normal visually guided actions while the ventral stream deals with visual information that has to be held in memory. We further found that when a 'preview' task was used in which the patients could use memorized information to guide a response to a still-present target object, they did so in preference to using the visual information facing them.

Adult↗

PubMed2002

Airway resistance estimation by best fit analysis in very premature infants.

Plethysmographic measurement of airway resistance (R(aw)) has been determined by single-point analysis, usually at 50% of maximum inspiratory flow (MIF). Computer-assisted (best fit) analysis, however, allows R(aw) to be calculated by applying a regression line to any portion of the plethysmograph pressure-flow loop. We determined whether the results of best fit analysis using a computer program, sampling at 200 Hz, were influenced by the portion of the inspiratory loop analysed and if best fit or single-point analysis gave more reproducible results. Twenty infants of median gestational age 26 (range 24-28) weeks, were studied at a median age of 12 (12-14) months corrected for prematurity. R(aw) was calculated by best fit analysis between 0 and 33% MIF, 0 and 50% MIF and 0 and 67% MIF and single-point analysis at 50% of MIF. Similar mean R(aw) values were obtained by best fit analysis between 0 and 33% MIF (2.79 kPa/(l/s)) and 0 and 50% MIF (3.01 kPa/(l/s)) and single-point analysis at 50% MIF (2.86 kPa/(l/s)), but best fit analysis between 0 and 67% gave higher results (3.60 kPa/(l/s)), p < 0.0001. Within the linear portion of the inspiratory loop, the mean intrasubject coefficient of variation was lowest for best fit analysis between 0 and 50% MIF. Best fit computerized analysis between 0 and 50% MIF is recommended as the analysis of choice.

Airway Resistance↗

PubMed2002

Bronchodilator therapy and hyperactivity in preschool children.

The common report of parents of asthmatic children that inhaled/nebulised salbutamol causes overactive behaviour was investigated. Nineteen children were assessed in a standardised setting before and after the administration of nebulised salbutamol and placebo. Neither parental report nor observer ratings suggested any significant increase in the child's level of activity.

Administration, Inhalation↗

PubMed2001

Grasping the past. delay can improve visuomotor performance.

"Optic ataxia" is caused by damage to the human posterior parietal cortex (PPC). It disrupts all components of a visually guided prehension movement, not only the transport of the hand toward an object's location, but also the in-flight finger movements pretailored to the metric properties of the object. Like previous cases, our patient (I.G.) was quite unable to open her handgrip appropriately when directly reaching out to pick up objects of different sizes. When first tested, she failed to do this even when she had previewed the target object 5 s earlier. Yet despite this deficit in "real" grasping, we found, counterintuitively, that I.G. showed good grip scaling when "pantomiming" a grasp for an object seen earlier but no longer present. We then found that, after practice, I.G. became able to scale her handgrip when grasping a real target object that she had previewed earlier. By interposing catch trials in which a different object was covertly substituted for the original object during the delay between preview and grasp, we found that I.G. was now using memorized visual information to calibrate her real grasping movements. These results provide new evidence that "off-line" visuomotor guidance can be provided by networks independent of the PPC.

Animals↗

PubMed2001

The role of size and binocular information in guiding reaching: insights from virtual reality and visual form agnosia III (of III).

Reaching out to grasp an object requires information about the size of the object and the distance between the object and the body. We used a virtual reality system with a control population and a patient with visual form agnosia (DF) in order to explore the use of binocular information and size cues in prehension. The experiments consisted of a perceptual matching task in addition to a prehension task. In the prehension task, control participants modified their reach distance in response to step changes in vergence in the absence of any clear reference for relative disparity. Their reach distance was unaffected by equivalent step changes in size, even though they used this information to modify grasp and showed a size bias in a distance matching task. Notably, DF showed the same pattern of results as the controls but was far more sensitive to step changes in vergence. This finding complements previous research suggesting that DF relies predominantly on vergence information when gauging target distance. The results from the perceptual matching tasks confirmed previous findings suggesting that DF is unable to make use of size information for perceptual matching, including distance comparisons. These data are discussed with regard to the properties of the pathways subserving the two visual cortical processing streams.

Agnosia↗

PubMed2001

Monocular and binocular distance cues: insights from visual form agnosia I (of III).

The human nervous system constructs a Euclidean representation of near (personal) space by combining multiple sources of information (cues). We investigated the cues used for the representation of personal space in a patient with visual form agnosia (DF). Our results indicated that DF relies predominantly on binocular vergence information when determining the distance of a target despite the presence of other (retinal) cues. Notably, DF was able to construct an Euclidean representation of personal space from vergence alone. This finding supports previous assertions that vergence provides the nervous system with veridical information for the construction of personal space. The results from the current study, together with those of others, suggest that: (i) the ventral stream is responsible for extracting depth and distance information from "monocular" retinal cues (i.e. from shading, texture, perspective) and (ii) the dorsal stream has access to binocular information (from horizontal image disparities and vergence). These results also indicate that DF was not able to use size information to gauge target distance, suggesting that intact temporal cortex is necessary for "learned size" to influence distance processing. Our findings further suggest that in neurologically intact humans, object information extracted in the ventral pathway is combined with the products of dorsal stream processing for guiding prehension. Finally, we studied the "size-distance paradox" in visual form agnosia in order to explore the cognitive use of size information. The results of this experiment were consistent with a previous suggestion that the paradox is a cognitive phenomenon.

Agnosia↗

PubMed2001

Vertical gaze angle as a distance cue for programming reaching: insights from visual form agnosia II (of III).

It has been shown that a patient with visual form agnosia (DF) relies predominantly on vergence information when gauging target distance in an open-loop pointing task. This finding suggested that the programming of prehension might be severely disrupted if DF viewed target objects through ophthalmic prisms. An initial experiment showed that this prediction was not upheld; DF was able to programme reasonably accurate movements to objects located on a tabletop despite large changes in vergence angle. A second experiment, however, showed that placing the target objects at eye height whilst manipulating vergence angle caused gross disruption to prehension, with DF mis-programming the reach component in a predictable manner. Notably, the evidence for DF's reliance on vergence distance information was obtained in a task where the targets were viewed at eye height. These experiments indicate that DF uses vertical gaze angle to gauge target distance in normal prehension and suggest that this extra-retinal cue may be a useful source of distance information for the human nervous system, especially where pictorial cues are impoverished.

Agnosia↗

PubMed2001

Characterisation of the Hering-Breuer deflation reflex in the human neonate.

Human infants have been observed making inspiratory efforts in response to chest compression. These may be a manifestation of the Hering-Breuer deflation reflex. We sought to stimulate the reflex in 33 term infants by rapidly reducing lung volume using an inflatable jacket. The effect of altering the timing, magnitude or rate of application of the lung deflation on the strength of the inspiratory response was investigated. Inspiratory effort was quantified by measuring (1) the rate of fall in oesophageal pressure on inspiration; and (2) the mean inspiratory flow (MIF) in response to lung deflation. Variables which significantly affected (1) and resulted in increased inspiratory effort were, in order of importance: larger rises in oesophageal pressure on chest compression (38%) (percentage of variance explained), greater reductions in lung volume below functional residual capacity (FRC) (26%), faster rates of lung deflation (19%) and slower respiratory rates (11%). Increased inspiratory efforts, as assessed by response (2), were generated by greater reductions in FRC (23%), larger rises in oesophageal pressure (11%) and faster rates of lung deflation (10%). Increasing deflation pressures eventually resulted in a plateau in both measures of inspiratory response. These results were consistent with the Hering-Breuer deflation reflex being activated which could have a role in protecting the FRC of the newborn infant.

Constriction↗