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Biomedical subjects

A Webb

Publications and source records attributed to A Webb.

At least 37 records · Page 2Linked to original sources
PubMed2001

Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer.

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg x m(-2)) was given every 2 weeks and PVI 5-FU (300 mg x m(-2) x day(-1)) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15-46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n = 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3-4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7-73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer.

Adult↗
PubMed2001

Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are rare tumours of the gastrointestinal tract characterised by cell-surface expression of the tyrosine kinase KIT (CD117). No effective systemic treatment is available. Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. We did a phase I study to identify the dose-limiting toxic effects of imatinib in patients with advanced soft tissue sarcomas including GISTs. METHODS: 40 patients (of whom 36 had GISTs) received imatinib at doses of 400 mg once daily, 300 mg twice daily, 400 mg twice daily, or 500 mg twice daily. Toxic effects and haematological, biochemical, and radiological measurements were assessed during 8 weeks of follow-up. 18Fluorodeoxy-glucose positron-emission tomography (PET) was used for response assessment in one centre. FINDINGS: Five patients on 500 mg imatinib twice daily had dose-limiting toxic effects (severe nausea, vomiting, oedema, or rash). Inhibition of tumour growth was seen in all but four patients with GISTs, resulting in 19 confirmed partial responses and six as yet unconfirmed partial responses or more than 20% regressions. 24 of 27 clinically symptomatic patients showed improvement, and 29 of 36 were still on treatment after more than 9 months. PET scan responses predicted subsequent computed tomography responses. INTERPRETATION: Imatinib at a dose of 400 mg twice daily is well tolerated during the first 8 weeks, side-effects diminish with continuing treatment, and it has significant activity in patients with advanced GISTs. Our results provide evidence of a role for KIT in GISTs, and show the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers.

Adult↗
PubMed2001

General and task-specific frontal lobe recruitment in older adults during executive processes: a fMRI investigation of task-switching.

Performance deteriorates when subjects must shift between two different tasks relative to performing either task separately. This switching cost is thought to result from executive processes that are not inherent to the component operations of either task when performed alone. Medial and dorsolateral frontal cortices are theorized to subserve these executive processes. Here we show that larger areas of activation were seen in dorsolateral and medial frontal cortex in both younger and older adults during switching than repeating conditions, confirming the role of these frontal brain regions in executive processes. Younger subjects activated these medial and dorsolateral frontal cortices only when switching between tasks; in contrast, older subjects recruited similar frontal regions while performing the tasks in isolation as well as alternating between them. Older adults recruit medial and dorsolateral frontal areas, and the processes computed by these areas, even when no such demands are intrinsic to the current task conditions. This neural recruitment may be useful in offsetting the declines in cognitive function associated with ageing.

Adult↗
PubMed2001

Health informatics.

Health informatics is the development and assessment of methods and systems for the acquisition, processing and interpretation of patient data with the help of knowledge from scientific research. This definition implies that health informatics is not tied to the application of computers but more generally to the entire management of information in healthcare. The focus is the patient and the process of care. The apparent information overload and the imperfection of medical decision making motivate the use of information systems for medical decision support. Health informatics provides tools to control processes in healthcare, acquire medical knowledge and communicate information between all people and organisations involved with healthcare. Although the development of medical information systems may often lag behind the available possibilities, the technological state of the current medical information systems is better than it is generally held to be. Health informatics should help healthcare professionals to provide better and more cost-effective care and enable healthcare systems to be more efficient and to adapt better to our patients' needs. Health informatics may reshape the way we deliver care to meet the demands of the future.

Artificial Intelligence↗
PubMed2001

Attentional selection and the processing of task-irrelevant information: insights from fMRI examinations of the Stroop task.

In this chapter, we discuss our research that reveals how attentional mechanisms can modulate activity of posterior brain regions responsible for processing the unattended attribute of a stimulus. To do so, we utilized fMRI to reveal patterns of regional brain activity for variants of the Stroop task that differ in the nature of the task-irrelevant stimulus attribute. In all variants, individuals had to identify the ink color in which an item was presented. To vary attentional demands, we manipulated whether or not the task-irrelevant information contained conflicting color information. The variants differed in whether the conflicting color information was contained in a word naming a color (e.g. the word 'red' in blue ink), a word naming an object highly associated with a specific color (e.g. the word 'frog' in red ink), or a line drawing of an object highly associated with a specific color (e.g. a drawing of a frog in red ink). When the unattended stimulus attribute contained color information that conflicted with an item's ink color, increased activity was observed in the posterior brain region that processes the aspect of the task-irrelevant attribute related to color. Increased activity was observed in the left precuneus and left superior parietal cortex when the conflicting information arose from a color word; in the middle temporal gyrus and insular cortex when the word named an object highly associated with a specific color, and included extensive regions of early portions of the ventral visual processing stream when a line drawing was highly associated with a specific color. These areas have been implicated in word processing, semantic processing, and visual processing, respectively. Our results suggest that attentional selection can occur by: (1) increasing the gain on all posterior regions responsible for processing information related to the task demands, regardless of whether that information is contained in the task-relevant or task-irrelevant dimension; (2) limiting the processing of task-irrelevant information in order to reduce interference; and (3) modulating the processing of representations varying from those of a low-level perceptual nature up through those of a higher-order semantic nature.

Adult↗
PubMed2001

The relative involvement of anterior cingulate and prefrontal cortex in attentional control depends on nature of conflict.

While numerous studies have implicated both anterior cingulate and prefrontal cortex in attentional control, the nature of their involvement remains a source of debate. Here we determine the extent to which their relative involvement in attentional control depends upon the levels of processing at which the conflict occurs (e.g., response, non-response). Using a combination of blocked and rapid presentation event-related functional magnetic resonance imaging techniques, we compared neural activity during incongruent Stroop trial types that produce conflict at different levels of processing. Our data suggest that the involvement of anterior cingulate and right prefrontal cortex in attentional control is primarily limited to situations of response conflict, while the involvement of left prefrontal cortex extends to the occurrence of conflict at non-response levels.

Adolescent↗
PubMed2001

An oxaliplatin-based chemotherapy in patients with relapsed or refractory intermediate and high-grade non-Hodgkin's lymphoma.

This study was designed to assess the efficacy and safety of substituting cisplatin with oxaliplatin in the DHAP (dexamethasone, cytarabine and cisplatin) regimen for patients with relapsed or refractory non-Hodgkin's lymphoma. Twenty-four evaluable patients with intermediate or high-grade non-Hodgkin's lymphoma were treated at 3-weekly intervals with oxaliplatin (130 mg/m2, d 1), cytarabine (2 g/m2 for two doses, d 2) and dexamethasone (40 mg, d 1-4). The median age of the patients was 58 (range 18-70). Histological subtypes were diffuse large B cell, 20; mantle cell, two; anaplastic large cell, one; and peripheral T cell, one. The overall objective response rate (RR) was 50% [95% confidence interval (CI) = 29-71%] including four complete responses and eight partial responses. RR for those patients treated at first relapse was higher than those treated at second and subsequent relapse (77% versus 29%). Grade 3 and 4 toxicity was mainly haematological: anaemia 17%, neutropenia 75% and thrombocytopenia 75%. No grade 4 non-haematological toxicity was reported. No significant renal and neurotoxicity was demonstrated. Median survival was 10.6 months. Probabilities of 1-year progression-free survival and overall survival were 47% (95% CI = 26-66%) and 50% (95% CI = 23-72%) respectively. In conclusion, dexamethasone, cytarabine and oxaliplatin (DHAX) is a novel combination in salvage therapy for relapsed or refractory non-Hodgkin's lymphoma. It has clinically significant activity with an acceptable toxicity profile. Lack of renal toxicity makes DHAX an attractive cytoreductive regimen before high-dose chemotherapy.

Adolescent↗
PubMed2001

Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria.

We show that the phenotype associated with gro-1(e2400) comprises the whole suite of features that characterize the phenotype of the clk mutants in Caenorhabditis elegans, including deregulated developmental, behavioral, and reproductive rates, as well as increased life span and a maternal effect. We cloned gro-1 and found that it encodes a highly conserved cellular enzyme, isopentenylpyrophosphate:tRNA transferase (IPT), which modifies a subset of tRNAs. In yeast, two forms of the enzyme are produced by alternative translation initiation, one of which is mitochondrial. In the gro-1 transcript there are also two possible initiator ATGs, between which there is a sequence predicted to encode a mitochondrial localization signal. A functional GRO-1::GFP fusion protein is localized diffusely throughout the cytoplasm and nucleus. A GRO-1::GFP initiated from the first methionine is localized exclusively to the mitochondria and rescues the mutant phenotype. In contrast, a protein initiated from the second methionine is localized diffusely throughout the cell and does not rescue the mutant phenotype. As oxygen consumption and ATP concentration have been reported to be unaffected in gro-1 mutants, our observations suggest that GRO-1 acts in mitochondria and regulates global physiology by unknown mechanisms.

Adenosine Triphosphate↗
PubMed2001

A protocol of urokinase infusion and warfarin for the management of the thrombosed haemodialysis catheter.

BACKGROUND: Catheter dysfunction remains a significant cause of catheter loss and interrupted haemodialysis sessions. A number of regimens utilizing urokinase have been used but the optimum management of this common problem remains undetermined. METHODS: The study took place over 2 years and evaluated a protocol of urokinase infusion (25,000 U in 48 ml saline run at 4 ml/h via each limb of the catheter) followed by warfarin for restoration of catheter patency. RESULTS: Forty-eight urokinase infusions were used for 41 episodes of catheter dysfunction. Catheter patency was restored in 95% and only one catheter was lost. Recurrent thrombosis occurred in eight of 10 catheters not anticoagulated. Once anticoagulated, catheters worked well. Further episodes of non-function were related to a sub-therapeutic INR. CONCLUSIONS: Our results show a high success rate for our protocol. We suggest an aggressive approach to the management of catheter thrombosis with urokinase used by infusion and carefully controlled anticoagulation to maintain the INR in the range 2-2.5.

Anticoagulants↗
PubMed2001

Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging.

The aim of this study was to compare functional cerebral hemodynamic signals obtained simultaneously by near infrared spectroscopy (NIRS) and by functional magnetic resonance imaging (fMRI). The contribution of superficial layers (skin and skull) to the NIRS signal was also assessed. Both methods were used to generate functional maps of the motor cortex area during a periodic sequence of stimulation by finger motion and rest. In all subjects we found a good collocation of the brain activity centers revealed by both methods. We also found a high temporal correlation between the BOLD signal (fMRI) and the deoxy-hemoglobin concentration (NIRS) in the subjects who exhibited low fluctuations in superficial head tissues.

Brain↗
PubMed2001

Expulsions following 1000 GyneFix insertions.

CONTEXT: The GyneFix intra-uterine device has been used in our family planning service since 1997. One of the perceived advantages is its low expulsion rate, as reported by clinical trials. OBJECTIVE: To calculate expulsion rates in routine clinical use and to look at possible reasons for expulsion. DESIGN: Retrospective casenote analysis and opportunistic client consultation. SETTING: A city centre family planning clinic. PARTICIPANTS: The first 1000 GyneFix insertions. MAIN OUTCOME MEASURES: Parity of client, experience of clinician carrying out insertion, time from device insertion to expulsion. RESULTS: Overall expulsion rate was 7.6%. There was no significant difference in parity of clients experiencing expulsion. Most (4.7%) expulsions were early, occurring within 3 months of insertion. There was considerable variation in early expulsion rate from one clinician to another. Later expulsions also occurred, up to 28 months after insertion. Increasing experience of the inserting clinician led to lower rates of late expulsion. Unnoticed expulsion led to four unplanned pregnancies. CONCLUSIONS: The GyneFix expulsion rate in our service is higher than quoted in clinical trials. Early expulsions may be related to insertion technique, representing insufficient implantation of the anchoring knot into the fundal myometrium. Late expulsions also occur, often many months after insertion; the reason for these is unclear. Users should be taught to check for the presence of the thread after each menstrual period and unnoticed expulsion should be confirmed by ultrasound and abdomino-pelvic plain X-ray.

Contraception↗
PubMed2001

Introduction of the GyneFix intra-uterine device into the UK: client satisfaction survey and casenotes review.

OBJECTIVE: To assess the first year's use with the GyneFix intra-uterine device. This has been used in Liverpool since early 1997. It is offered mainly to nulliparous women wishing to use an effective non-hormonal method and parous women who have had pain with, or expulsion of, a framed device previously. It is also used as emergency contraception. DESIGN: Retrospective study, by means of casenote review and client questionnaire. PARTICIPANTS: All GyneFix users from February 1997 to January 1998; 215 women in total. MAIN OUTCOME MEASURES: Data were extracted from casenotes to determine reasons for choice of GyneFix, parity, whether the insertion was planned or as an emergency measure, problems reported at follow-up and reasons for removal. Users were asked by questionnaire to comment on insertion procedure, menstrual or other changes since insertion and to state their overall satisfaction. RESULTS: Over half of the users (57%) were nulliparous and a quarter of insertions were for emergency contraceptive use. A third reported that insertion was 'very painful'. Half reported that their periods had become heavier since insertion, but only 8% said that they were now unmanageable. Unacceptable bleeding was the most common reason for removal. Some reported intermenstrual bleeding and dysmenorrhoea. Satisfaction with the GyneFix was high; 86% of questionnaire responders said that they would recommend it to a friend. CONCLUSION: The GyneFix is well accepted in Liverpool inappropriately selected clients, and is an effective non-hormonal method for nulliparous as well as parous women.

Contraception↗
PubMed2001

Ability of Escherichia coli O157:H7 isolates to colonize the intestinal tract of conventional adult CD1 mice is transient.

In an attempt to improve upon a current mouse model of intestinal colonization by Escherichia coli O157:H7 used in this laboratory for vaccine development, nine clinical isolates of the pathogen were screened for their ability to persist in the intestinal tract of conventional adult CD-1 mice. None of the test isolates of E. coli O157:H7 were capable of colonizing these mice for a period of more than two weeks. Most of the isolates appeared to be benign for the experimental host, but one isolate was lethal. This virulence correlated with the ability of the latter isolate to produce large quantities of Shiga-like toxin 2 in vitro.

Animals↗
PubMed2000

Comparison of a specialist retrieval team with current United Kingdom practice for the transport of critically ill patients.

OBJECTIVE: The inter-hospital transfer of critically ill patients in the United Kingdom is commonly undertaken using standard ambulance under junior doctor escort, despite recommendations for the use of specialist retrieval teams. Patients are transferred into University College London Hospitals (UCLH) intensive care unit (ICU) by both methods. We undertook to evaluate the effect of transfer method on acute physiology (within 2 h of ICU admission) and early mortality ( < 12 h after ICU admission). DESIGN: Retrospective review of all transfers over 1 year. SETTING: UCLH ICU. SUBJECTS: 259 transfers; 168 by specialist retrieval team (group A) and 91 by standard ambulance with doctor provided by referring hospital (group B). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Acute physiology (pH, PaO2, PaCO2, heart rate (HR), mean arterial blood pressure (MAP), 24 h severity of illness scores (APACHE II, SAPS II), length of stay and mortality. RESULTS: There were no differences in demographic characteristics or severity of illness between the two groups; nevertheless significantly more patients in group B than in group A were severely acidotic (pH < 7.1: 11% vs. 3%, p < 0.008) and hypotensive (MAP < 60: 18 % vs. 9%, p < 0.03) upon arrival. In addition, there were more deaths within the first 12 h after admission with 7.7 % deaths (7/91) in group B transfers vs. 3% (5/168) in group A. CONCLUSIONS: The use of a specialist transfer team may significantly improve the acute physiology of critically ill patients and may reduce early mortality in ICU.

Ambulances↗
PubMed2000

Prefrontal regions play a predominant role in imposing an attentional 'set': evidence from fMRI.

fMRI was used to determine whether prefrontal regions play a predominant role in imposing an attentional 'set' that drives selection of task-relevant information. While monitoring for an atypical item, individuals viewed Stroop stimuli that were either colored words or colored objects. Attentional demands were varied, being greater when the stimuli contained two distinct and incongruent sources of information about the task-relevant attribute (e.g., when attending to color, seeing the word 'blue' in red ink) as compared to only one source (e.g., seeing the word 'late' in red ink). Prefrontal but not anterior cingulate regions exhibited greater activation on incongruent than neutral trials, suggesting that prefrontal cortex has a major role in imposing an attentional 'set'. In addition, we found that prefrontal activation is most likely to occur when that attentional set is difficult to impose.

Attention↗