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Biomedical subjects

Richard Gordon

Publications and source records attributed to Richard Gordon.

17 recordsLinked to original sources

Cluster randomized trial of a multifaceted primary care decision-support intervention for inherited breast cancer risk.

BACKGROUND: GPs are increasingly expected to meet the needs of patients concerned about their risk of inherited breast cancer, but may lack skills or confidence to use complex management guidelines. We developed an evidence-based, multifaceted intervention intended to promote confidence and skills in this area. OBJECTIVE: To evaluate the effectiveness of the intervention in improving GP confidence in managing patients concerned about genetic risk of breast cancer. METHODS DESIGN: Cluster randomized controlled trial. SETTING: General practices in the Grampian region of Scotland. SUBJECTS: GPs and the patients they referred for genetic counselling for risk of breast cancer. MAIN OUTCOME MEASURES: GPs' self-reported confidence in four activities related to genetics; rates of referral of patients at elevated genetic risk; and referred patients' understanding of cancer risk factors. RESULTS: No statistically significant differences were observed between intervention and control arms in the primary or secondary outcomes. A possible effect of the intervention on the proportion of referred patients who were at elevated risk could not be discounted. Only a small proportion of intervention GPs attended the educational session, were aware or the software, or made use of it in practice. CONCLUSIONS: No convincing evidence of the effectiveness of the intervention was found, probably reflecting barriers to its use in routine practice.

Breast Neoplasms↗

Diagnosis and management of partial small bowel obstruction after laparoscopic antecolic antegastric Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: The resultant derangement of the normal gastrointestinal anatomy after a gastric bypass procedure increases the incidence of, and level of difficulty diagnosing, partial small bowel obstruction (SBO) in morbidly obese patients. We evaluated the diagnostic methods for partial SBO and the clinical characteristics according to the time after initial operation. STUDY DESIGN: Data of 1,400 consecutive patients who underwent antecolic antegastric laparoscopic Roux-en-Y gastric bypass between 2001 and 2004 were retrospectively analyzed. RESULTS: Partial SBO developed in 21 (1.5%) patients after laparoscopic Roux-en-Y gastric bypass. Five of 15 patients were preoperatively diagnosed with SBO by a gastrograffin study and CT scan diagnosed 17 of 19 patients (p = 0.002). Causes of SBO included jejunojejunostomy stenosis (n = 6), adhesions (n = 5), incarcerated ventral hernia (n = 5), internal hernia (n = 3), and other (n = 2). The majority of patients (n = 19) underwent surgical treatment. CONCLUSIONS: The most frequent cause of early SBO is jejunojejunal anastomotic stenosis. CT scan is a more accurate diagnostic tool for detecting partial SBO, compared with use of a gastrograffin study. Operation remains the most appropriate and definitive treatment for this complication and the laparoscopic approach is a feasible and safe surgical treatment option.

Adult↗

A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton.

Neural tube defects are serious congenital malformations which can be prevented by periconceptional folic acid supplementation. We hypothesize that folic acid provides the methyl group used for post-translational methylation of arginine and histidine in the highly conserved regulatory domains of the cytoskeleton and that these are required for neural tissue differentiation. Presumptive neural tissue has an unusually high need for folates due to the activity of phosphoethanolamine methyl transferase in producing neural tissue specific lipids at a time when the cytoskeleton is also competing for methylation. According to the cell state splitter hypothesis, the cytoskeleton is required to coordinate the spatial and temporal component of differentiation. When folate supply is low and the cytoskeleton is not methylated properly, the result is a neural tube defect due to failure of this coordination.

Animals↗

Mechanics in embryogenesis and embryonics: prime mover or epiphenomenon?

Mechanics is shown to be an important, perhaps central component to the differentiation and development of embryos. Mechanics of the nucleus may also be involved in determining which genes are expressed in a given cell. There are two major approaches at present to the mechanics of differentiation in embryos: morphomechanics and differentiation waves. These are compared in detail, to provide a starting point for future experimental work to bring them into one conceptual framework. This may rationalize the present cookbookery of stem cell production by placing it in the context of differentiation waves and the differentiation code. Embryonics, the realization of concepts from embryology in computer hardware and software, might be considerably enhanced by incorporating mechanical concepts of embryogenesis. Segmented robots, modular robotics, cellular microrobotics, flexible electronics, wearable computers, diatom nanotechnology and waves in active media point to a synthesis that we could call embryonic robotics.

Animals↗

Modeling the effect of tumor size in early breast cancer.

SUMMARY BACKGROUND DATA: The purpose of this study was to determine the type of relationship between tumor size and mortality in early breast carcinoma. METHODS: The data was abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results Program of women diagnosed with primary breast carcinoma between 1988 and 1997 presenting with a T1-T2 lesion and no metastasis in whom axillary node dissection was performed: 58,070 women were node-negative (N0) and 25,616 were node-positive (N+). End point was death from any cause. Tumor size was modeled as a continuous variable by proportional hazards using a generalized additive models procedure. RESULTS: Functionally, a Gompertzian expression exp(-exp(-(size-15)/10)) provided a good fit to the effect of tumor size (in millimeters) on mortality, irrespective of nodal status. Quantitatively, for tumor size between 3 and 50 mm, the increase of crude cumulative death rate (number of observed deaths divided by the number of patients at risk) increased with size from 10% to 25% for N0 and from 20% to 40% for N+. CONCLUSIONS: The functional relationship of tumor size with mortality is concordant with current knowledge of tumor growth. However, its qualitative and quantitative independence of nodal status is in contradiction with the prevailing concept of sequential disease progression from primary tumor to regional nodes. This argues against the perception that nodal metastases are caused by the primary tumor.

Breast Neoplasms↗

Potential roles for diatomists in nanotechnology.

Diatoms produce diverse three-dimensional structures that, due to their exponential rate of growth, may be of use in the manufacture of components for nanotechnology as an alternative to present linear lithographic techniques. Vapor replacement of the silicon permits the conversion of diatom silica valves and other structures to metal/ceramics, with no loss of structure. The literature on diatom nanotechnology is reviewed, along with suggestions on how diatomists might enhance this emerging technology. There is a need for a systematics based catalog of parts (via genomics technologies), improved diatom culture techniques, better understanding of the mechanisms of diatom morphogenesis and motility, and genetic manipulation, mutagenesis, and selection, as via the chemostat-like compustat. Given the self-motility of raphid diatoms, they could form the basis for industrially useful nanobots.

Biomimetics↗

Quantitative target sizes for breast tumor detection prior to metastasis: a prerequisite to rational design of 4D scanners for breast screening.

It is important to determine a breast cancer tumor target size for new screening equipment and molecular detection. Records of women aged 40-69 years diagnosed in 1988-1997 with a nonmetastasized, node-negative, or node-positive T1-stage breast cancer were abstracted from the Surveillance, Epidemiology, and End Results (SEER) public-use database. The linear, Gompertzian, lognormal, and power-exponential models of the effect of tumor size on breast cancer specific mortality were compared using corresponding transforms of size in multivariate Cox proportional hazard models. Criteria for comparison were the linearization of the size transforms and the Nagelkerke R2N index for the Cox models. Our results show that the assumption of a linear effect of tumor size was rejected by the linearity test (P=0.05). The Gompertzian, lognormal, and power-exponential transforms satisfied the test with P-values of 0.08, 0.29, and 0.14, respectively. The corresponding R2N were 0.08410, 0.08420, and 0.08414, respectively, showing a marginally best fit with the lognormal model, which was selected as a model for small tumors. The lognormal function with unadjusted crude death rates gave a lognormal-location parameter of 25 and shape parameter of 1.7, while the corresponding values in multivariate models were 18 and 2, respectively. The derivation of the lognormal model indicates tumor growth acceleration starting at 3 mm (unadjusted crude data) or 2 mm (multivariate model). The breast cancer tumor target size for screening equipment, whether by imaging or molecular detection, is therefore 2 mm.

Adult↗

Density estimation for positron emission tomography.

PET (positron emission tomography) scans are still in the experimental phase, as one of the newest breast cancer diagnostic techniques. There are two traditional approaches to the computation of images from data collected in PET. In the first, standard CT (computed tomography) algorithms are used on rays designated by pairs of detectors receiving coincidence events. The problem generated by this approach is that generally only the mean can be used by such algorithms. With the relatively small numbers of events in PET, and with Poisson statistics for which variance equals the mean, the noise sensitivity of standard CT algorithms becomes limiting. This is exasperated further by 3D imaging with cylindrical arrays of detectors. Statistical CT algorithms take the variance into account. As in the list-mode approach, we consider each coincidence event individually. However, we estimate the location of the annihilation event that caused each coincidence event, one by one, based on the previously assigned location of events processed earlier. The estimated annihilation locations form the image. To accomplish this, we construct a probability distribution along each coincidence line. This is generated from previous annihilation points by density estimation. In this paper we present our density estimation approach to positron emission tomography. Nonparametric methods of density estimation are overviewed followed by numerical examples. Our goal here is to determine which density estimation approach is most suitable for PET.

Algorithms↗

Topical anesthesia-induced methemoglobinemia in bariatric surgery patients.

Methemoglobinemia leads to rapid oxygen desaturation, requiring prompt recognition and treatment. We present two severely obese patients who developed methemoglobinemia following the use of topical or local anesthetic. This complication was detected by analysis of arterial blood gases, and was successfully treated with methylene blue i.v. and 100% O2 supplementation.

Anastomosis, Roux-en-Y↗

Experiments with the nonlinear and chaotic behaviour of the multiplicative algebraic reconstruction technique (MART) algorithm for computed tomography.

Among the iterative reconstruction algorithms for tomography, the multiplicative algebraic reconstruction technique (MART) has two advantages that make it stand out from other algorithms: it confines the image (and therefore the projection data) to the convex hull of the patient, and it maximizes entropy. In this paper, we have undertaken a series of experiments to determine the importance of MART nonlinearity to image quality. Variants of MART were implemented aiming to exploit and exaggerate the nonlinear properties of the algorithm. We introduce the Power MART, Boxcar Averaging MART and Bouncing MART algorithms. Power MART is linked to the relaxation concept. Its behaviour is similar to that of the chaos of a logistic equation. There appears to be an antagonism between increasing nonlinearity and noise in the projection data. The experiments confirm our general observation that regularization as a means of solving simultaneous linear equations that are underdetermined is suboptimal: it does not necessarily select the correct image from the hyperplane of solutions, and so does not maximize the image quality:x-ray dose ratio. Our investigations prove that there is scope to optimize CT algorithms and thereby achieve greater dose reduction.

Algorithms↗

Star Trek replicators and diatom nanotechnology.

Diatoms are single celled algae, the 10(5)-10(6) species of which create a wide variety of three-dimensional amorphous silica shells. If we could get them to produce useful structures, perhaps by compustat selection experiments (i.e. forced evolution of development or evodevo), their exponential growth in suspension cultures could compete with the lithography techniques of present day nanotechnology, which have limited 3D capabilities. Alternatively, their fine detail could be used for templates for MEMS (micro electro mechanical systems), or their silica deposition systems isolated for guiding silica deposition. A recent paper has demonstrated that silica can be replaced atom for atom without change of shape--a step towards the Star Trek replicator.

Cell Culture Techniques↗

Reverse engineering the embryo: a graduate course in developmental biology for engineering students at the University of Manitoba, Canada.

Our desire to educate engineers to be able to understand the component processes of embryogenesis, is driven by the notion that only when principles borrowed from mathematics, fluid mechanics, materials science, etc. are applied to classical problems in developmental biology, will sufficient comprehension be achieved to permit successful understanding and therapeutic manipulation of embryos. As it now stands, biologists seldom possess either skills or interest in those areas of endeavor. Thus, we have determined that it is easier to educate engineers in the principles of developmental biology than to help biologists deal with the complexities of engineering. We describe a graduate course that has been taken, between 1999 and 2002, by 17 engineering students. Our goal is to prepare them to reverse engineer the embryo, i.e., to look at it as an object or process whose construction, albeit self-construction, might be explicable in terms of engineering principles applied at molecular, cellular and whole embryo levels.

Developmental Biology↗

Electrorotation of axolotl embryos.

The frequency dependent dielectric properties of individual axolotl embryos (Ambystoma mexicanum) were investigated experimentally utilizing the technique of electrorotation. Individual axolotl embryos, immersed in low conductivity media, were subjected to a known frequency and fixed amplitude rotating AC electric field and the ensuing rotational motion of the embryo was monitored using a conventional optical microscope. None of the embryos in the pregastrulation or neurulation stages of development exhibited any rotational motion over the field frequency range (10 Hz-5 MHz). Over the same frequency range, the embryos in the gastrulation stage of development exhibited both co-field and counterfield rotation over different ranges of the applied field frequency. Typically, the counterfield rotation exhibited a peak in the rotation spectrum at similar 1 KHz while the co-field peak was located at similar 1-2 MHz. The rotational spectral data was analyzed using a multishelled spherical embryo model to determine the electrical character of embryos during the early development stages (Stages 5-16; i.e., 16 cell through open neural plate stages).

Ambystoma mexicanum↗