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Biomedical subjects

C McLeod

Publications and source records attributed to C McLeod.

At least 19 recordsLinked to original sources
PubMed2007

Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of pemetrexed disodium in combination with cisplatin for the treatment of unresectable pleural mesothelioma in chemotherapy-naive patients. DATA SOURCES: Electronic databases were searched up to May 2005. REVIEW METHODS: The systematic review was conducted following accepted guidelines. An assessment of the economic submission received from the manufacturer of pemetrexed was also carried out. This comprised two sections, each employing an economic model. One of these models was then reformulated in order to carry out a separate exploration of economic performance. RESULTS: One randomised controlled trial comparing pemetrexed and cisplatin with cisplatin alone, and involving a total study population of 448 patients, met the inclusion criteria. Pemetrexed in combination with cisplatin in this trial showed a 2.8-month gain in median survival compared with cisplatin alone in an intention-to-treat (ITT) population (12.1 and 9.3 months, respectively, p = 0.020, hazard ratio of 0.77). During the trial, increased reporting of severe toxicity in the pemetrexed arm led to a change in the protocol to add folic acid and vitamin B12 supplementation to therapy. For fully supplemented patients (n = 331) the hazard ratio for median survival in favour of pemetrexed plus cisplatin was also comparable (0.75), but of borderline significance between treatment arms (p = 0.051). The trial inclusion criteria restricted recruitment to those with a Karnofsky performance status of 70 or greater (equivalent to ECOG/WHO 0 or 1 scales more widely used in the UK). Quality of life scores using the Lung Cancer Symptom Scale demonstrated significantly greater improvement for pain and dyspnoea for patients in the combination group compared with those in the cisplatin group. In the ITT population, the incidence of serious toxicities with pemetrexed plus cisplatin was higher compared with cisplatin alone. However, the grade 3/4 toxicities of the combination arm, particularly leucopenia, neutropenia and diarrhoea, were found to be greatly improved by the addition of vitamin B12 and folic acid. The existing published economic literature was very limited. The economic evaluation conducted by the study (and that submitted by the manufacturer) suggested that pemetrexed is unlikely to be considered cost-effective at conventionally accepted thresholds in the UK for all patients, mainly because of the high cost of pemetrexed itself compared with cisplatin. These findings were better for some patient subgroups, e.g. especially for fully supplemented (FS) patients with good performance status (0/1) and advanced disease (AD). These findings seem robust. The estimated cost-effectiveness results were for the FS population, incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained = pound59,600; for the FS with AD population, ICER per QALY = pound47,600; for the FS with performance status 0/1 population, ICER per QALY = pound49,800; and for the FS with performance status 0/1 and AD population, ICER per QALY = pound36,700. CONCLUSIONS: The new therapy examined in this document demonstrates an extension of life expectancy and palliation, as measured by time to progression of disease and other end-points. However, the absolute benefit obtained is small, and it needs to be weighed against the benefits of effective palliative care services. The limited benefit was also at the expense of considerable toxicity to patients. The economic evaluation conducted in this study and that of the manufacturers suggest that pemetrexed is not cost-effective at conventional thresholds for all patients. Cost-effectiveness seems better for some patient subgroups, e.g. especially for patients with good performance status and with advanced diseases, where it is estimated the ICER per QALY would be pound36,700. Given the relatively small number of patients with mesothelioma, albeit increasing, the overall budget impact of pemetrexed would be unlikely to be more than pound5 million per year at present costs. Much more research is needed into the optimum chemotherapy for patients with mesothelioma and a clear definition of what constitutes best supportive care.

Antineoplastic Agents↗
PubMed2006

The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews.

OBJECTIVES: The aim of this review is to examine the clinical and cost-effectiveness of screening for lung cancer using computed tomography (CT) to assist policy making and to clarify research needs. DATA SOURCES: Electronic databases and Internet resources. REVIEW METHODS: A systematic review was undertaken and selected studies were assessed using the checklists and methods described in NHS Centre for Reviews and Dissemination (CRD) Report 4. Separate narrative summaries were performed for clinical effectiveness and cost-effectiveness. Cost-effectiveness analysis resulting in a cost per quality-adjusted life-year was not feasible, therefore the main elements of such an appraisal were summarised and the key issues relating to the existing evidence base were discussed. RESULTS: Twelve studies of CT screening for lung cancer were identified, including two randomised controlled trials (RCTs) and ten studies of screening without comparator groups. The quality of reporting of these studies was variable, but the overall quality was adequate. The two RCTs were of short duration (1 year) and therefore there was currently no evidence that screening improves survival or reduces mortality. The proportion of people with abnormal CT findings varied widely between studies (5-51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number need to screen to detect one lung cancer = 31-249). Incidence rates of lung cancer were lower (0.1-1% per year). Detection of stage I and resectable tumours was high, 100% in some studies. Adverse events, as a result of investigation or surgery, or the screening process per se were poorly reported. Incidental findings of other abnormalities requiring medical follow-up were reported to be as high as 49%. Six full economic evaluations of population CT screening programmes for lung cancer were included in the review. The magnitude of cost-effectiveness ratios reported varied widely. None was set in the UK and generalisation was complicated by wide variation in the data used in different countries and a paucity of UK data for comparison. All six made the fundamental assumption that screening with CT for lung cancer reduced mortality. At the current time, there is no evidence to support that assumption. In the absence of evidence of health gains from screening for lung cancer, in terms of either quantity or quality of life, and faced with a range of uncertainties, from the frequency of abnormal screening findings within a population to the natural history of screening detected lung cancers, it is not feasible at the current time to develop accurately and meaningfully an economic argument for CT screening for lung cancer in the UK. For subgroups, in particular certain occupational groups, there is evidence of increased risk of lung cancer, but the role of screening has not been demonstrated by the current studies. CONCLUSIONS: The accepted National Screening Committee criteria are not currently met, with no RCTs, no evidence to support clinical effectiveness and no evidence of cost-effectiveness. RCTs are needed to examine the effect of CT screening on mortality, either with whole-population screening or for particular subgroups; to determine the rate of positive screening and detected lung cancers. Research is also needed to understand better the natural history and epidemiology of screening-detected lung cancers, particularly small, well-differentiated adenocarcinomas; as well as the impacts on quality of life. Increased collection is needed of UK health service data regarding resource use and safety data for lung cancer management and services. Research is also needed into the feasibility and logistics of tracing people who have in the past worked in industry where there was exposure to lung carcinogens.

Adult↗
PubMed2005

A novel bipolar-drive circuit for medical applications.

A novel drive circuit, useful for medical electronics, is capable of supplying a sample of human tissue, across which there should be zero direct voltage (dc), with a well-defined test current from a source having an output impedance exceeding 16 MOmega at 100 kHz.

Electric Impedance↗
PubMed2002

Levels and risk assessment for humans and ecosystems of platinum-group elements in the airborne particles and road dust of some European cities.

Traffic is the main source of platinum-group element (PGE) contamination in populated urban areas. There is increasing concern about the hazardous effects of these new pollutants for people and for other living organisms in these areas. Airborne and road dusts, as well as tree bark and grass samples were collected at locations in the European cities of Göteborg (Sweden), Madrid (Spain), Rome (Italy), Munich (Germany), Sheffield and London (UK). Today, in spite of the large number of parameters that can influence the airborne PGE content, the results obtained so far indicate significantly higher PGE levels at traffic sites compared with the rural or non-polluted zones that have been investigated (background levels). The average Pt content in airborne particles found in downtown Madrid, Göteborg and Rome is in the range 7.3-13.1 pg m(-3). The ring roads of these cities have values in the range 4.1-17.7 pg m(-3). In Munich, a lower Pt content was found in airborne particles (4.1 pg m(-3)). The same tendency has been noted for downtown Rh, with contents in the range 2.2-2.8 pg m(-3), and in the range 0.8-3.0 and 0.3 pg m(-3) for motorway margins in Munich. The combined results obtained using a wide-range airborne classifier (WRAC) collector and a PM-10 or virtual impactor show that Pt is associated with particles for a wide range of diameters. The smaller the particle size, the lower the Pt concentration. However, in particles <PM-10, some of the highest values correspond to the fraction <0.39 microm. Considering an average Pt content in all particles of approximately 15 pg m(-3), which is representative for all countries and environmental conditions, the tracheobronchial fraction represents approximately 10% and the alveolar fraction approximately 8% of the total particles suspended in air. However, from the environmental risk point of view, an exposure to PGEs in traffic-related ambient air is at least three orders of magnitude below the levels for which adverse health effects might theoretically occur (of approx. 100 ng m(-3)). Therefore, today inhalation exposure to PGEs from automotive catalysts does not seem to pose a direct health risk to the general population. Even though the data available today indicate no obvious health effects, there are still a number of aspects related to PGEs and catalysts that justify further research. First, continual monitoring of changes in PGE levels in air and road dust is warranted, to make sure that there is no dramatic increase from today's levels. Secondly, more detailed information on the chemical composition of the PGE-containing substances or complexes leaving the catalyst surface and the size distribution of the PGE-containing particles released during driving will facilitate a more in-depth human risk assessment.

Air Pollutants↗
PubMed2002

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

A comparison of platinum-group element (PGE) emission between gasoline and diesel engine catalytic converters is reported within this work. Whole raw exhaust fumes from four catalysts of three different types were examined during their useful lifetime, from fresh to 80,000 km. Two were gasoline engine catalysts (Pt-Pd-Rh and Pd-Rh), while the other two were diesel engine catalysts (Pt). Samples were collected following the 91441 EUDC driving cycle for light-duty vehicle testing, and the sample collection device used allowed differentiation between the particulate and soluble fractions, the latter being the most relevant from an environmental point of view. Analyses were performed by inductively coupled plasma-mass spectrometry (ICP-MS) (quadrupole and high resolution), and special attention was paid to the control of spectral interference, especially in the case of Pd and Rh. The results obtained show that, for fresh catalysts, the release of particulate PGE through car exhaust fumes does not follow any particular trend, with a wide range (one-two orders of magnitude) for the content of noble metals emitted. The samples collected from 30,000-80,000 km present a more homogeneous PGE release for all catalysts studied. A decrease of approximately one order of magnitude is observed with respect to the release from fresh catalysts, except in the case of the diesel engine catalyst, for which PGE emission continued to be higher than in the case of gasoline engines. The fraction of soluble PGE was found to represent less than 10% of the total amount released from fresh catalysts. For aged catalysts, the figures are significantly higher, especially for Pd and Rh. Particulate PGE can be considered as virtually biologically inert, while soluble PGE forms can represent an environmental risk due to their bioavailability, which leads them to accumulate in the environment.

Air Pollutants↗
PubMed2001

Realistic 2D human thorax modelling for EIT.

Electrical impedance tomography is a technique that permits estimation of resistivity within a subject by reconstructing from boundary measurements. Due to the ill conditioning of the problem, images are greatly affected by boundary errors. Reconstruction algorithms account for boundary shape and electrode position by using a forward solver. In this paper is presented the realization of a 2D realistic thoracic model as a better approach compared to circular meshing. Several meshes with different discretizations are compared in terms of accuracy with a complete electrode model forward solver. By comparing the different discretizations it is possible to choose an appropriate mesh density for the 2D EIT problem.

Algorithms↗
PubMed2000

Sound transmission between 50 and 600 Hz in excised pig lungs filled with air and helium.

This study measured transit time (TT) and attenuation of sound transmitted through six pairs of excised pig lungs. Single-frequency sounds (50-600 Hz) were applied to the tracheal lumen, and the transmitted signals were monitored on the tracheal and lung surface using microphones. The effect of varying intrapulmonary pressure (Pip) between 5 and 25 cmH(2)O on TT and sound attenuation was studied using both air and helium (He) to inflate the lungs. From 50 to approximately 200 Hz, TT decreased from 4.5 ms at 50 Hz to 1 ms at 200 Hz (at 25 cmH(2)O). Between approximately 200 and 600 Hz, TT was relatively constant (1.1 ms at upper and 1.5 ms at lower sites). Gas density had very little effect on TT (air-to-He ratio of approximately 1.2 at upper sites and approximately 1 at lower sites at 25 cmH(2)O). Pip had marked effects (depending on gas and site) on TT between 50 and 200 Hz but no effect at higher frequencies. Attenuation was frequency dependent between 50 and 600 Hz, varying between -10 and -35 dB with air and -2 and -28 dB with He. Pip also had strong influence on attenuation, with a maximum sensitivity of 1.14 (air) and 0.64 dB/cmH(2)O (He) at 200 Hz. At 25 cmH(2)O and 200 Hz, attenuation with air was about three times higher than with He. This suggests that sound transmission through lungs may not be dominated by parenchyma but by the airways. The linear relationship between increasing Pip and increasing attenuation, which was found to be between 50 and approximately 100 Hz, was inverted above approximately 100 Hz. We suggest that this change is due to the transition of the parenchymal model from open to closed cell. These results indicate that acoustic propagation characteristics are a function of the density of the transmission media and, hence, may be used to locate collapsed lung tissue noninvasively.

Acoustics↗
PubMed1997

Absorption, social desirability, and symptoms in a behavioral medicine population.

The relationships among absorption, social desirability, and psychological and somatic symptoms were examined in a clinical population of patients at a behavioral medicine clinic. Absorption, as measured by the Tellegen Absorption Scale, was significantly and positively related to the somatization and global distress indices of the Brief Symptom Inventory. However, absorption was negatively related to social desirability, as measured by the Marlowe-Crowne Scale. Global distress, but not somatization, also was negatively related to social desirability. After controlling for social desirability, global distress was marginally related to absorption. In addition, absorption interacted with a measure of how much patients were bothered by their primary symptom. Patients who had high absorption reported more somatic and global distress if they also reported being very bothered by their primary symptom than if they were less bothered by it. The results are discussed with respect to related research on absorption, social desirability, and symptoms.

Adult↗
PubMed1993

The optimal current direction for excitation of human cervical motor roots with a double coil magnetic stimulator.

Upper limb muscles can easily be excited using magnetic stimulation with a circular coil over the cervical vertebrae. Double coil magnetic stimulators generate a more focal and directed form of stimulus and may offer an advantage in the more specific stimulation of individual motor roots. The aims of this study were to determine the optimal rostro-caudal locations and orientations of a double coil magnetic stimulator for excitation of the human 5th cervical to 1st thoracic motor roots. Compound muscle action potentials (CMAPs) evoked by magnetic stimuli were recorded from deltoid, brachioradialis, extensor digitorum communis and first dorsal interosseus muscles. Optimal rostro-caudal location was determined with the coil current flowing horizontally towards the midline. Optimal orientation was determined by rotating the coil in increments of 22.5 degrees about the optimal rostro-caudal location. In all subjects with all muscles examined, the best orientation was with the coil current flowing downwards towards the midline at a mean angle between 14.9 degrees and 27.6 degrees to the horizontal. Review of the anatomy of motor roots reveals a short upwardly directed segment within the intervertebral foramen and it is postulated that excitation occurs exclusively within this segment.

Action Potentials↗
PubMed1984

Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity.

Four mouse monoclonal antibodies specific for human epidermal growth factor (EGF) receptors have been prepared using EGF receptor protein from human A431 epidermoid carcinoma cells as immunogen. We have determined the effect of these antibodies on two known functions of the EGF receptor: EGF binding and tyrosine kinase. Three of these antibodies (225, 528, and 579) are inhibitors of EGF binding, whereas the fourth (455) does not compete for binding but immunoprecipitates the EGF receptor. Inhibition is of the mixed competitive and noncompetitive type. The three competing monoclonal antibodies are antagonists of EGF-stimulated tyrosine protein kinase activity assayed both in intact cells and using an exogenous peptide substrate in solubilized membranes. These immunoglobulins are partial agonists in self-phosphorylation of the EGF receptor in solubilized membranes but exhibit only antagonist activity for this reaction in intact cells. The three competing monoclonal immunoglobulins recognize receptors in variant A431 cells with the same efficiency as in parental A431 cells. Such antagonist monoclonal antibodies can be used to control the concentration of receptors which can be activated by EGF.

Animals↗
PubMed1983

Plasma and endometrial progesterone content following exogenous progesterone administration in mares.

Intact and ovariectomized pony mares were treated with either progesterone in-oil or repositol progesterone. Serum progesterone, endometrial progesterone and endometrial histology were examined. There were no differences in serum or tissue progesterone between intact and ovariectomized mares. Serum and tissue progesterone were greater for progesterone in-oil treated mares than for repositol treated mares. Both progesterone in-oil and repositol progesterone initiated endometrial gland proliferation with no difference in response observed between the two preparations.

Journal Article↗
PubMed1983

Oesophageal multipurpose monitoring probe.

An oesophageal probe which incorporates facilities for pressure, temperature, electrocardiographic and stethoscopic monitoring is described. Actual and potential uses are outlined.

Body Temperature↗
PubMed1982

Effect of ovarian hormones on the phagocytic response of ovariectomized mares.

The reaction between ovarian hormones and experimental uterine infection (Streptococcus zooepidemicus) was investigated in 3 groups, each containing 6 ovariectomized mares. Group 1 served as controls ('anoestrus'), Group 2 mares were injected with oestrogen ('oestrus') and Group 3 with progesterone ('dioestrus') over a period of 5 weeks. All mares received an intrauterine inoculation of the bacteria 1 week after the start of hormonal treatment, and the results of the challenge were examined by endometrial biopsy and swabs once weekly. At the end of Week 1 no bacteria were recovered from the mares in Group 2. Group 1 mares were free of bacteria at the end of Week 2 but all Group 3 mares remained infected at least for the total period examined. Streptococcal phagocytosis was quantitated by chemiluminescence. Before the challenge-inoculation, phagocytosis was not significantly different in the 3 groups of mares. Bacterial cultures were negative for all three groups. However, within 48 h after infection, there was a significant increase (P less than 0.01) in phagocytosis in Group 2 and a significant suppression (P less than 0.05) in Group 3 mares. Patterns of streptococcal clearance from the uterus closely paralleled the changes in the magnitude of chemiluminescence response. The results suggest that ovarian hormonal status can modulate the phagocytic response in episodes of streptococcal-induced endometritus in mares.

Animals↗