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T Jones

Publications and source records attributed to T Jones.

At least 37 records · Page 2Linked to original sources
PubMed2003

A trial-based cost-effectiveness analysis of letrozole followed by tamoxifen versus tamoxifen followed by letrozole for postmenopausal advanced breast cancer.

BACKGROUND: Third-generation aromatase inhibitors are being considered as an alternative to tamoxifen as first-line therapy for advanced breast cancer. These newer therapies are more expensive, and will gain greater acceptance if they can demonstrate cost-effectiveness. METHODS: Life table analyses are used to compare the costs and benefits [life years gained and quality-adjusted life years (QALYs) gained] of treating postmenopausal women with advanced breast cancer with first-line letrozole (with the option of second-line tamoxifen) compared with first-line tamoxifen (with the option of second-line letrozole). Patient-level data from a large clinical trial describes the effectiveness of the therapy options, clinicians estimate resource usage and utility values are obtained from the literature. RESULTS: The mean cost of providing first- and second-line hormonal therapy is pound 4765 if letrozole is the first-line therapy and pound 3418 if tamoxifen is provided first (a difference of pound 1347). However, patients receiving letrozole as first-line therapy gain an additional 0.228 life years, or 0.158 QALYs. The cost-effectiveness analysis found that first-line hormonal therapy with letrozole gains additional life years at a cost of pound 5917, whilst the cost per additional QALY gained is pound 8514. CONCLUSION: The strategy of letrozole as first-line hormonal therapy not only provides an opportunity for extending and improving patient's quality of life, but also is highly cost-effective compared with other generally accepted medical treatments.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Emergency asthma inhalers in school.

Despite there being a lack of direct evidence of the effectiveness of providing emergency inhalers to schools, the balance of evidence at present suggests the benefits outweigh any possible harm. However, unless UK prescribing law or its interpretation is changed, this will remain an action which opens teachers, nurses, and doctors to possible legal and professional sanctions, and may nullify their institutional or professional indemnity. As a consequence, provision will remain patchy and research into the value of emergency inhalers will be inhibited. A position statement from one or more responsible organisations such as the Royal College of Paediatrics and Child Health, the British Thoracic Society, or the British Paediatric Respiratory Society could persuade a reassessment from the Medicines Control Agency. This is also an issue which could be addressed in the forthcoming National Service Framework for children.

Acute Disease↗
PubMed2003

Paramedic accuracy in using a decision support algorithm when recognising adult death: a prospective cohort study.

BACKGROUND: Prolonged advanced life support for cardiac arrest victims who present with non-shockable arrhythmias in an out of hospital setting is associated with extremely poor survival rates. This and the risks associated with rapid ambulance transport to hospital have resulted in the development of decision support algorithms, enabling paramedics to recognise when adult death has occurred. The aim of the study was to assess the accuracy with which paramedics used such an algorithm. METHOD: This prospective 16 month cohort study evaluated 188 events of recognition of adult death (ROAD) by paramedics in the period from November 1999 to February 2001. RESULTS: Of 188 ROAD applications, errors were made in 13 cases (6.9%, 95% CI 3.7 to 11.5. Additionally, there was one adverse clinical incident associated with a case in which ROAD was applied (0.5%, 95% CI 0.01 to 2.9%). ECG strips were unavailable for eight cases, although ambulance records indicated a rhythm of asystole for each of these. Assuming this diagnosis was correct, ROAD was used 174 times without errors (93%, 95% CI 88 to 96%). Assuming that it was not, the ROAD protocol was applied without errors in 166 cases (88.3%, 95% CI 82.8 to 92.5%). None of the errors made appeared to be attributable to poor clinical decision making, compromised treatment, or changed patient outcome. The mean on-scene time for ambulance crews using the ROAD policy was 60 minutes. CONCLUSION: Paramedics can accurately apply a decision support algorithm when recognising adult death. It could be argued that the attendance of a medical practitioner to confirm death is therefore an inappropriate use of such personnel and may result in unnecessarily protracted on-scene times for ambulance crews. Further research is required to confirm this, and to determine the proportion of patients suitable for recognition of adult death who are actually identified as such by paramedics.

Adult↗
PubMed2002

Measurement of spin-transfer observables in p p-->Lambda Lambda at 1.637 GeV/c.

Spin-transfer observables for p p-->Lambda Lambda have been measured using a transversely polarized frozen-spin target and a beam momentum of 1.637 GeV/c. Current models of the reaction near threshold are in good agreement with existing measurements performed with unpolarized particles in the initial state but produce conflicting predictions for the spin-transfer observables Dnn and Knn (the normal-to-normal depolarization and polarization transfer), which are measurable only with polarized target or beam. Measurements of Dnn and Knn presented here are found to be in disagreement with predictions from these models.

Journal Article↗
PubMed2002

Cancer Research UK procedures in manufacture and toxicology of radiotracers intended for pre-phase I positron emission tomography studies in cancer patients.

Radiolabelled compounds formulated for injection (radiopharmaceuticals), are increasingly being employed in drug development studies. These can be used in tracer amounts for either pharmacokinetic or pharmacodynamic studies. Such radiotracer studies can also be carried out early in man, even prior to conventional Phase I clinical testing. The aim of this document is to describe procedures for production and safety testing of oncology radiotracers developed for imaging by positron emission tomography in cancer patients. We propose strategies for overcoming the inability to produce compounds in sufficient quantities via the radiosynthetic routes for full chemical characterisation and toxicology testing including (i) independent confirmation as far as possible that the stable compound associated with the radiopharmaceutical is identical to the non-labelled compound, (ii) animal toxicity studies with > or = 10 times (typically 100 times) the intended tracer dose in humans scaled by body surface area, and (iii) patient monitoring during the radiotracer positron emission tomography clinical trial.

Animals↗
PubMed2002

Molecular conformation-activity relationship of decamethonium congeners.

BACKGROUND: Of the polymethylene bismethonium congeners (C5-C12 and C18), decamethonium (C10) is the most potent neuromuscular blocking agent. We tested the hypothesis that these congeners act as straight molecules and will not bend easily in spite of the flexible connecting chain between the methonium heads. For congeners higher than C10, we also hypothesized that the relative difficulty with which the molecules to bend to conform to the interonium distance of C10 proportionately reduces their neuromuscular blocking potency. METHODS: Each congener was modelled and subjected to computer searches for representative low-energy molecular conformers. The conformation-potency relationship of the congeners was examined. RESULTS: For all congeners, we found that the lowest energy conformer (the 'global minimum') has a straight-chain conformation. Reduction of the interonium distance (by bending) incurs a steep energy penalty linearly related to the distance reduced. The global minimum of C10 has an interonium distance of 14.03 A and a total molecular length of 20.10 A. For other congeners, the interonium distance differential from that of C10 and the energy penalty required to conform to the interonium distance of C10 (where applicable) correlate with the reported logarithmic (mmol kg(-1)) dose requirement for neuromuscular block. CONCLUSIONS: The C10 congeners strongly prefer a straight conformation. Their molecular length and resistance to bending is key to their neuromuscular blocking potency. A molecular length of approximately 20 A should best fit the space available to neuromuscular blocking agents between the two receptive sites of the endplate acetylcholine receptor.

Decamethonium Compounds↗
PubMed2002

The intracranial complications of rhinosinusitis: can they be prevented?

OBJECTIVES/HYPOTHESIS: Reference textbooks on the intracranial complications of rhinosinusitis imply that many of the intracranial complications of rhinosinusitis can be prevented. We sought to examine whether or not this is true. STUDY DESIGN: A retrospective case series. METHODS: The study included 47 consecutive patients presenting with intracranial complications secondary to rhinosinusitis between 1992 to 1999 with a mean follow-up of 5 years and 1 month. RESULTS: The most common presenting symptoms of intracranial involvement were an altered mental state, headache, fever, seizure, vomiting, a unilateral weakness or hemiparesis, or a cranial nerve sign. These justify an urgent magnetic resonance imaging or computed tomography scan. The importance of imaging before a lumbar puncture cannot be overemphasized. Of particular note was the finding that 21 patients (45%) presented with a periorbital cellulitis or frontal swelling. Therefore, it does not follow that because a collection of pus presents anteriorly it precludes any intracranial involvement. More than half of our patients (55%) had visited their primary care physician with an upper respiratory tract infection and had been treated appropriately. Once any central symptoms or signs developed, there was little evidence of any significant delay in referral to our unit. Only six patients had a history of nasal disease, three having had recent sinus surgery and three having had nasal polyps. Nine patients had significant long-term morbidity, seven patients had epilepsy, one patient had dysphasia, and one patient had right arm weakness. The single death in our series was associated with a cavernous sinus thrombosis. CONCLUSIONS: The report emphasizes the need for surgeons to be alert to the diagnosis, particularly in patients with a periorbital abscess or frontal swelling. Sinus surgery has a role in obtaining pus for culture, as well as draining the sinus if it is in continuity with an intracranial collection. Intracranial infections secondary to rhinosinusitis occur sporadically and, although it appears that this cannot be prevented, early recognition and treatment are essential to reduce any subsequent morbidity or mortality.

Adolescent↗
PubMed2002

Hitting them where it hurts? Low dose nalbuphine therapy.

OBJECTIVE: To determine if low dose nalbuphine provides an adequate reduction in pain with minimal side effects. METHODS: Prospective cohort of 115 patients given nalbuphine by paramedics in Wales and the English borders. OUTCOME MEASURES: (1) Mean total dose of nalbuphine administered, change in pain score, time to adequate pain relief (score below four), and change in respiratory rate and systolic blood pressure; (2) proportion of patients continuing to suffer moderate to severe pain on arrival at hospital; (3) incidence of adverse events. RESULTS: Full data were obtained for all patients. The mean total dose of nalbuphine administered was 6.09 mg (range 2.5 to 12.5 mg). This was significantly higher in trauma than ischaemic chest pain patients (7.03 versus 5.13 mg). The mean reduction in pain score was -3.97 (95% CI -4.38 to -3.57, p<0.001). The mean time to adequate pain relief (where this was achieved) was 15.7 minutes (95% CI 13.4 to 17.9 minutes). On arrival at hospital 60% of patients (n=69, 95% CI 50.9 to 68.5%) still met ambulance criteria for analgesia (70.7% of trauma patients and 49.1% with ischaemic chest pain). Systolic blood pressure fell by a mean of -3.67 (95% CI -6.76 to -0.58, p=0.02) and respiratory rate increased by a mean of 1.63 (95% CI 1.08 to 2.17, p<0.001). Two patients complained of nausea (1.74%, 95% CI 0.5 to 6.0%). No other adverse events were reported. CONCLUSION: Low dose nalbuphine results in few adverse events, but offers poor pain control for a high proportion of patients.

Analgesics, Opioid↗
PubMed2002

Effects of wearing knitted or rubber gloves on the transfer of Escherichia cohi between hands and meat.

On eight occasions, five volunteers each handled five pieces of meat with bare hands or while wearing dry or wet knitted gloves or rubber gloves after hands had been inoculated with Escherichia coli or after handling a piece of meat inoculated with E. coli. On each occasion, after all meat was handled, each piece of meat, glove, and hand were sampled to recover E. coli. When hands were inoculated, E. coli was recovered from all meat handled with bare hands, in lesser numbers from some pieces handled with knitted gloves, and from only one piece handled with rubber gloves. When pieces of inoculated meat were handled, the numbers of E. coli transferred to uninoculated meat from bare hands or rubber gloves decreased substantially with each successive piece of uninoculated meat, but decreases were small with knitted gloves. The findings indicate that, compared with bare hands, the use of knitted gloves could reduce the transfer of bacteria from hands to meat but could increase the transfer of bacteria between meat pieces, whereas the use of rubber gloves could largely prevent the first and greatly reduce the second type of bacteria transfer.

Bacterial Adhesion↗
PubMed2001

Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury.

Limb denervation leads to reorganization of the representational zones of the somatosensory cortex. Using [11C](R)-PK11195, a sensitive in vivo marker of glial cell activation, and PET, we provide first evidence that limb denervation induces a trans-synaptic increase in [11C](R)-PK11195 binding in the human thalamus but not somatosensory cortex: these brain structures appeared morphologically normal on magnetic resonance imaging (MRI). The increased thalamic signal was detectable many years after nerve injury, indicating persistent reorganization of the thalamus. This glial activation, beyond the first-order projection area of the injured neurons, may reflect continually altered afferent activity. Our findings support the view that long-term rearrangement of cortical representational maps is significantly determined within the thalamus.

Adult↗
PubMed2001

Nasal immunization with subunit proteosome influenza vaccines induces serum HAI, mucosal IgA and protection against influenza challenge.

The immunogenicity of a mucosally delivered subunit influenza vaccine was assessed in mice. Split influenza virus vaccine (sFlu) was formulated with proteosomes (Pr-sFlu), administered intranasally, and the induced immunity was compared with the responses elicited by sFlu alone given either intramuscularly or intranasally. Intranasal (i.n.) immunization with Pr-sFlu induced specific serum IgG and hemagglutination inhibition (HAI) titers comparable to or better than those induced by intramuscular (i.m.) sFlu, and in contrast to sFlu alone, i.n. Pr-sFlu also induced high levels of influenza-specific IgA in lung and nasal washes. Mice receiving i.n. Pr-sFlu were completely protected against live virus challenge, as were mice immunized by injection with sFlu alone. The i.n. Pr-sFlu elicited cytokine responses polarized towards a type 1 phenotype whereas those elicited by sFlu alone were of a mixed type 1/type 2 phenotype. The data strongly suggest that i.n. proteosome-formulated influenza antigens are highly effective and are excellent candidates for a non-invasive human vaccine.

Administration, Intranasal↗
PubMed2001

In-vivo measurement of activated microglia in dementia.

BACKGROUND: Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease. METHODS: We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site. FINDINGS: In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex. INTERPRETATION: In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.

Adult↗
PubMed2001

Nucleotide sequence and predicted functions of the entire Sinorhizobium meliloti pSymA megaplasmid.

The symbiotic nitrogen-fixing soil bacterium Sinorhizobium meliloti contains three replicons: pSymA, pSymB, and the chromosome. We report here the complete 1,354,226-nt sequence of pSymA. In addition to a large fraction of the genes known to be specifically involved in symbiosis, pSymA contains genes likely to be involved in nitrogen and carbon metabolism, transport, stress, and resistance responses, and other functions that give S. meliloti an advantage in its specialized niche.

Agrobacterium tumefaciens↗
PubMed2001

The composite genome of the legume symbiont Sinorhizobium meliloti.

The scarcity of usable nitrogen frequently limits plant growth. A tight metabolic association with rhizobial bacteria allows legumes to obtain nitrogen compounds by bacterial reduction of dinitrogen (N2) to ammonium (NH4+). We present here the annotated DNA sequence of the alpha-proteobacterium Sinorhizobium meliloti, the symbiont of alfalfa. The tripartite 6.7-megabase (Mb) genome comprises a 3.65-Mb chromosome, and 1.35-Mb pSymA and 1.68-Mb pSymB megaplasmids. Genome sequence analysis indicates that all three elements contribute, in varying degrees, to symbiosis and reveals how this genome may have emerged during evolution. The genome sequence will be useful in understanding the dynamics of interkingdom associations and of life in soil environments.

Bacterial Adhesion↗