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Biomedical subjects

David Robinson

Publications and source records attributed to David Robinson.

At least 19 recordsLinked to original sources
PubMed2007

Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study.

BACKGROUND: Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right. METHODS: All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD) or any cardiovascular disease (CVD). A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis. RESULTS: A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21-2.08; p = 0.001) and all CVD (hazard ratio 1.27; 95% confidence interval 1.07-1.51; p = 0.006). When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95-1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05-1.49; p = 0.014). CONCLUSION: We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long-term cardiac toxicity. In absolute terms, the increase in cardiovascular mortality induced by radiotherapy may be substantial, as these mortality events are relatively common.

Aged↗
PubMed2006

A novel function for selenium in biological system: selenite as a highly effective iron carrier for Chinese hamster ovary cell growth and monoclonal antibody production.

As the market for biopharmaceuticals especially monoclonal antibodies (MAbs) rapidly grows, their manufacturing methods are coming under increasing regulatory scrutiny, particularly due to concerns about the potential introduction of adventitious agents from animal-sourced components in the media used for their production in mammalian cell culture. Chinese hamster ovary (CHO) cells are by far the most commonly used production vehicles for these recombinant glycoproteins. In developing animal-component free media for CHO and other mammalian cell lines, the iron-transporter function of serum or human/bovine transferrin is usually replaced by certain organic or inorganic chelators capable of delivering iron for cell respiration and metabolism, but few of them are sufficiently effective. Selenium is a well-known essential trace element (TE) for cell growth and development, and its positive role in biological system includes detoxification of free radicals by activating glutathione peroxidase. In cell culture, selenium in the form of selenite can help cells to detoxify the medium thus protect them from oxidative damage. In this presentation, we describe the discovery and application of a novel function of selenite, that is, as a highly effective carrier to deliver iron for cell growth and function. In our in-house-developed animal protein-free (APF) medium for CHO cells, using an iron-selenite compound to replace the well-established tropolone delivery system for iron led to comparable or better cell growth and antibody production. A high cell density of >10 x 10(6) viable cells/mL and excellent antibody titer of approximately 3 g/L were achieved in 14-day fed-batch cultures in shake flasks, followed by successful scale-up to stirred bioreactors. The preparation of the commercially unavailable iron-selenite compound from respective ions, and its effectiveness in cell-culture performance, were dependent on reaction time, substrates, and other conditions.

Animals↗
PubMed2006

A modification to the flow method to estimate completeness in cancer registries with delayed registration.

OBJECTIVE: For registries that routinely delay case registration, the flow method does not accurately describe their completeness over time. A modification to allow for such a delay is proposed and tested. METHODS: Using original data set from Ticino Cancer Registry, Switzerland, a new data set (the delayed data set) was created by adding two years to the date of registration for each case in the original data set, to emulate the situation in a registry where registration is delayed by two years. Both the original and modified methods were then applied to both the original and the delayed data set. RESULTS: When applied to the delayed data, the original method produced estimates of completeness of 32 and 43% at one and two years after diagnosis. When the modified method was applied to the delayed data, the completeness at one and two years was correctly estimated at 0%. After the initial two-year time lag, completeness was consistently estimated by both methods. When applied to the original data, the modified method produced the same results as the original method. CONCLUSIONS: The proposed modification allows the method to be applied even when registration is delayed long after diagnosis-thus extending the range of registries for which the flow method can be used.

Databases as Topic↗
PubMed2006

Trends in the treatment of breast cancer in Southeast England following the introduction of national guidelines.

There is little published evidence on trends in the treatment of breast cancer in England following the publication of the Calman-Hine report in 1995. Reliable national data are available for women with screen-detected breast cancer, but data on women presenting symptomatically have been difficult to collect. Using data from both a clinical audit database and a population-based cancer register, we show that between 1996 and 2003 the rates of mastectomy and chemotherapy treatment for women with breast cancer in Southeast England have increased marginally, whereas there has been a steady decline in the use of hormone therapy and radiotherapy recorded within 6 months of diagnosis.

Antineoplastic Agents↗
PubMed2006

Microfluidic electroporation of robust 10-microm vesicles for manipulation of picoliter volumes.

We present a new way to transport and handle picoliter volumes of analytes in a microfluidic context through electrically monitored electroporation of 10-25 microm vesicles. In this method, giant vesicles are used to isolate analytes in a microfluidic environment. Once encapsulated inside a vesicle, contents will not diffuse and become diluted when exposed to pressure-driven flow. Two vesicle compositions have been developed that are robust enough to withstand electrical and mechanical manipulation in a microfluidic context. These vesicles can be guided and trapped, with controllable transfer of material into or out of their confined environment. Through electroporation, vesicles can serve as containers that can be opened when mixing and diffusion are desired, and closed during transport and analysis. Both vesicle compositions contain lecithin, an ethoxylated phospholipid, and a polyelectrolyte. Their performance is compared using a prototype microfluidic device and a simple circuit model. It was observed that the energy density threshold required to induce breakdown was statistically equivalent between compositions, 10.2+/-5.0 mJ/m2 for the first composition and 10.5+/-1.8 mJ/m2 for the second. This work demonstrates the feasibility of using giant, robust vesicles with microfluidic electroporation technology to manipulate picoliter volumes on-chip.

Electroporation↗
PubMed2006

Ocular findings in Gillespie-like syndrome: association with a new PAX6 mutation.

BACKGROUND: Gillespie syndrome is a rare variant form of aniridia, characterized by mental retardation, nonprogressive cerebellar ataxia, and iris hypoplasia. Unlike the more common dominant and sporadic forms of aniridia, there have been no associated PAX6 mutations or Wilms' tumor reported in Gillespie syndrome patients. Ocular findings in 21 cases published since Gillespie's initial description in 1965 include iris and foveal hypoplasia, nystagmus, and small optic discs with pigmentary retinopathy. CASE REPORT: We herein report a case of atypical Gillespie syndrome associated with bilateral ptosis, exotropia, corectopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation. Neurologic evaluation revealed a mild hand tremor and learning disability, but no ataxia or cerebellar abnormalities on neuroimaging. Sequencing studies revealed a substitution in intron 2 of the PAX6 gene (IVS2 + 2T > A). To our knowledge, this is the first mutation of PAX6 gene reported in association with a Gillespie-like syndrome.

Abnormalities, Multiple↗
PubMed2006

Evaluation of corneal sensitivity to mechanical and chemical stimuli after LASIK: a pilot study.

PURPOSE: To evaluate the effect of laser in situ keratomileusis (LASIK) on corneal sensitivity, nerve morphology, and tear film characteristics. METHODS: A cross-sectional study design was used. Eighteen patients (eight men and 10 women with a mean age of 36.9 +/- 11.2 years) who had undergone bilateral LASIK for low myopia within 18 months of the study and 28 control subjects (16 men and 12 women with a mean age of 27.2 +/- 7.7 years) were enrolled. Central and inferior corneal thresholds to mechanical (air) and chemical (air plus carbon dioxide) stimuli were determined by using a staircase technique. Stimuli of a 1-second duration at 34 degrees C were delivered with a CRCERT-Belmonte aesthesiometer. Images of subbasal nerves in the central cornea were captured with confocal microscopy. Nerve morphology was classified as no nerves, short nerves (<175 microm), or long nerves (>175 microm), with or without interconnections. Noninvasive tear break up time was measured. The phenol red thread test was used to indicate basal tear secretion. Differences between groups were evaluated with analysis of variance, and associations between variables were evaluated with parametric or nonparametric correlation, when appropriate. RESULTS: Central corneal mechanical sensitivity was significantly reduced in the post-LASIK group compared with the control subjects (P < 0.001). Nerve morphology was associated with mechanical threshold. Nerve morphology, mechanical sensitivity, and tear breakup time improved during the first 1 to 3 months after surgery, with little change thereafter. Chemical sensitivity was associated with tear secretion (P < 0.05). CONCLUSIONS: Central corneal mechanical sensitivity is reduced in patients after LASIK, with partial recovery seen 3 months after surgery. A similar recovery trend is seen for nerve morphology.

Adult↗
PubMed2006

A dynamic model of Rubisco turnover in cereal leaves.

A simple, improved model of Rubisco synthesis and degradation in cereal leaves is developed using data obtained over the leaf lifespan to return maximum likelihood values for Rubisco proteolysis and biosynthesis. It assumes that the time course of leaf Rubisco content can be described using a log-normal curve, and degradation of the Rubisco pool occurs exponentially. Curve parameters give an insight into how Rubisco dynamics differ among treatments or genotypes; also, statistical analyses can be performed more easily, requiring fewer data and allowing more flexibility in sampling than previous studies. Predicted patterns of synthesis correlate well with independent rbc gene transcript data. Rubisco degradation is a first-order decay process, and biosynthesis correlates with leaf elongation rates. As Rubisco degradation takes place according to first-order kinetics, control of leaf Rubisco concentration must be exerted by adjustment of biosynthetic, rather than proteolytic, rates.

Data Interpretation, Statistical↗
PubMed2005

A 13-year follow-up of patients with breast cancer presenting to a District General Hospital breast unit in southeast England.

The purpose of this clinical cohort study was to examine long-term survival in groups of screen-detected and symptomatic breast cancer patients attending a specialist breast unit, and to determine the factors affecting this survival. A total of 3239 breast cancer cases (1252 screen-detected and 1987 symptomatic) diagnosed between 1989 and 2002 were followed up until the end of 2002, and breast cancer-specific survival was examined in the screened and symptomatic groups, in relation to patient age, tumour size, nodal status and histological grade. Long-term survival in this clinical cohort was high. Relative survival values in the symptomatic group were similar to population-based estimates for southeast England derived from data held at the Thames Cancer Registry, whilst survival values in the screening group were 11-12 percentage points higher at 4 years after diagnosis and onwards. Ten-year relative survival estimates were 88% in the screening group and 77% in symptomatic cases. In groups of comparable age, the difference in breast cancer-specific survival at 10 years was 19 percentage points. Survival was significantly related to tumour characteristics (size, nodal status and grade), but not to morphological tumour type or deprivation score of the subject. After adjustment for other factors, the difference in survival between the two groups was much attenuated and became statistically non-significant. The higher survival seen in the screening group can be almost entirely accounted for in terms of the detection of early stage and lower grade tumours which screening provides.

Age Distribution↗
PubMed2005

Rupture process of the 2004 Sumatra-Andaman earthquake.

The 26 December 2004 Sumatra-Andaman earthquake initiated slowly, with small slip and a slow rupture speed for the first 40 to 60 seconds. Then the rupture expanded at a speed of about 2.5 kilometers per second toward the north northwest, extending 1200 to 1300 kilometers along the Andaman trough. Peak displacements reached approximately 15 meters along a 600-kilometer segment of the plate boundary offshore of northwestern Sumatra and the southern Nicobar islands. Slip was less in the northern 400 to 500 kilometers of the aftershock zone, and at least some slip in that region may have occurred on a time scale beyond the seismic band.

Journal Article↗
PubMed2005

Survival in prostate carcinoma--outcomes from a prospective, population-based cohort of 8887 men with up to 15 years of follow-up: results from three countries in the population-based National Prostate Cancer Registry of Sweden.

BACKGROUND: To decide on screening strategies and curative treatments for prostate carcinoma, it is necessary to determine the incidence and survival in a population that is not screened. METHODS: The 15-year projected survival data were analyzed from a prospective, complete, population-based registry of 8887 patients with newly diagnosed prostate carcinoma from 1987 to 1999. RESULTS: The median patient age at diagnosis was 75 years (range, 40-96 years), and 12% of patients were diagnosed before the age 65 years. The median follow-up was 80 months for patients who remained alive. In total, 5873 of 8887 patients (66.1%) had died, and 2595 of those patients (44.2%) died directly due to prostate carcinoma. The overall median age at death was 80 years (range, 41-100 years). The projected 15-year disease-specific survival rate was 44% for the whole population. In total, 18% of patients had metastases at diagnosis (M1), and their median survival was 2.5 years. Patients with nonmetastatic T1-T3 prostate carcinoma (age < 75 years at diagnosis; n=2098 patients) had a 15-year projected disease-specific survival rate of 66%. Patients who underwent radical prostatectomy had a significantly lower risk of dying from prostate carcinoma (relative risk, 0.40) compared with patients who were treated with noncurative therapies or radiotherapy. CONCLUSIONS: The disease-specific mortality was comparatively high, but it took 15 years to reach a disease-specific mortality rate of 56%. These data form a truly population-based baseline on how prostate carcinoma will affect a population when screening is not applied and can be used for comparison with other health care strategies.

Adult↗
PubMed2005

Operation for adult patent ductus arteriosus using an aortic stent-graft technique.

Patent ductus arteriosus is a condition usually diagnosed and treated in childhood but in some instances is not detected until adult life. Although surgical closure remains the accepted treatment in most cases, stent-grafting has emerged as a possible alternative treatment for persistent ductus arteriosus in the adult. We describe a case of elective repair of a patent ductus arteriosus using an aortic stent-graft technique in a young man. Successful use of the endoprosthetic approach may allow more widespread use of this technique in adult patent ductus arteriosus.

Adult↗
PubMed2005

The 50 ml syringe training aid should be utilized immediately before cricoid pressure application.

OBJECTIVE: Cricoid pressure, applied during rapid sequence induction of anaesthesia, should be performed only by trained staff. Recommended training intervals vary from weekly to every 3 months, but this is unrealistic in day-to-day practice. Performance, when assessed, is often shown to be unacceptable before training. Unfortunately, most training aids are either expensive or unavailable. Assessment and training in previous studies was carried out on the same cricoid pressure simulator, introducing learning bias. In our study, we tested whether a 50 ml syringe utilized as a training aid immediately before the assessment of simulated rapid sequence induction on a different cricoid pressure simulator would improve staff performance. METHODS: A total of 64 volunteers were randomly allocated into two equal groups. Group 1 (control group) was assessed on the cricoid pressure simulator only. Group 2 (training group) was pretrained to defined criteria using the 50 ml syringe. Next, the group was assessed on the cricoid pressure simulator. RESULTS: A satisfactory force was applied in only 19% (6/32) of the control group, but in 47% (15/32) of the syringe pretrained group (P=0.03). Both groups applied, on average, excessive force. CONCLUSION: Brief training with a 50 ml syringe will increase the likelihood of satisfactory force application during Sellick's manoeuvre. Applied to clinical practice, this will make cricoid pressure both more effective and reliable, and may improve patient safety. Therefore, the 50 ml syringe should be utilized before any clinical application of cricoid pressure.

Anesthesiology↗
PubMed2004

Ablation with an internally irrigated radiofrequency catheter: learning how to avoid steam pops.

OBJECTIVES: The aim of this study was to assess the feasibility of using electrode temperature, impedance, and power to predict and thereby potentially prevent steam pops during cooled radiofrequency (RF) ablation. BACKGROUND: When myocardial temperature reaches 100 degrees C during RF catheter ablation, steam explosions are seen. Saline-cooled RF ablation reduces temperatures at the electrode-tissue interface, but excessive intramyocardial heating still may occur. METHODS: In anesthetized swine, 26 cooled RF applications were made in the right and left atria while observing with intracardiac echocardiography (ICE). Power delivery was increased gradually until a steam explosion was seen or a maximum output of 50 W was reached. RESULTS: ICE identified steam explosions in 21 RF applications. Steam explosions were associated with a large impedance increase, >25 Omega in only three cases, whereas small increases <10 Omega (mean 5.3 +/- 2.6 Omega) occurred in 18 cases. Mean electrode temperature at the time of steam explosion was 43.6 degrees C +/- 5.3; 18 of 21 explosions occurred when temperature reached >/=40 degrees C. Mean power and impedance drop were similar for applications with and without steam explosions. Five steam explosions were associated with a sudden drop in electrode temperature. CONCLUSIONS: Steam explosions are common when cooled electrode temperature exceeds 40 degrees C and are not predictable from power or impedance drop. Small impedance rises and sudden drops in measured electrode temperature indicate possible steam formation. Maintaining cooled electrode temperature <40 degrees C during RF likely will reduce the risk of steam explosions.

Animals↗
PubMed2004

Completeness of ascertainment by cancer registries: putting bounds on the number of missing cases.

BACKGROUND: When comparing cancer incidence or mortality rates between different regions, it is important to know how complete the registration data are on which these figures are based. A number of ways of estimating completeness have been proposed, but it is often difficult to say how precise these estimates are. We describe a computer program developed to produce measures of precision for estimates of completeness obtained by one such method, the flow method. METHODS: The program works by resampling the required data sets, and repeatedly calculating completeness estimates until convergence of the standard errors occurs. It was tested on colorectal tumours from a single health district, and empirical confidence limits for 1 and 5 year completeness were compared with those obtained by applying various normalizing transformations and a beta distribution. The method was then applied to tumours of the head and neck, breast and lung and the results compared with those from a capture-mark-recapture exercise carried out 4 years previously. RESULTS: The sampling distribution was close to normal for 1 year completeness, but much less so for 5 year completeness, as assessed by quantile plots. Approximation by a beta distribution was better than by normalizing transformation. Although there were differences between the results produced by the flow method and capture-recapture, the flow method is more reproducible and easier to apply. CONCLUSION: It is now possible to estimate confidence limits for the results of the flow method, and thus determine whether comparative results between registries are likely to be affected by sampling error.

Bias↗
PubMed2004

Goal-directed ultrasound in the detection of long-bone fractures.

BACKGROUND: New portable ultrasound (US) systems are capable of detecting fractures in the remote setting. However, the accuracy of ultrasound by physicians with minimal ultrasound training is unknown. METHODS: After one hour of standardized training, physicians with minimal US experience clinically evaluated patients presenting with pain and trauma to the upper arm or leg. The investigators then performed a long-bone US evaluation, recording their impression of fracture presence or absence. Results of the examination were compared with routine plain or computer aided radiography (CT). RESULTS: 58 patients were examined. The sensitivity and specificity of US were 92.9% and 83.3%, and of the physical examination were 78.6% and 90.0%, respectively. US provided improved sensitivity with less specificity compared with physical examination in the detection of fractures in long bones. CONCLUSION: Ultrasound scans by minimally trained clinicians may be used to rule out a long-bone fracture in patients with a medium to low probability of fracture.

Adult↗