Multidisciplinary learning in family planning clinics.
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Education↗
Biomedical subjects
S Webb
Publications and source records attributed to S Webb.
Congenital bilateral ureteral stenosis and hydronephrosis in a neonatal puppy.
Three days after an uneventful parturition, a Brittany spaniel/beagle puppy (Canis familiaris) was nursing but not gaining weight as rapidly as were its littermates. Although its diet was supplemented, the puppy died 10 days after birth. The renal pelves were enlarged and filled with urine. Both ureters were thin throughout their length, and urine could not be expressed from either kidney into its respective ureter. The bladder contained no urine and was firmly embedded in the umbilicus. Histologically, both kidneys were hydronephrotic and contained hypoplastic collecting tubules. The diameter of the right (0.55 mm) and left (0.57 mm) ureters at the uteropelvic junction were narrower than those of an age-matched control of the same breed (1.03 mm and 1.02 mm) and were lined by hypoplastic urothelium. Trichrome staining of the ureters revealed excessive collagen and disorganized smooth muscle fibers; in contrast, the control had predominantly circular smooth muscle fibers and less fibrous tissue. Although neither blood nor aqueous humor could be evaluated for urea nitrogen, we suspect that the puppy died from uremia. The congenital bilateral ureteral stenosis and hydronephrosis of the described puppy is similar to a form of uteropelvic obstruction in humans.
Animals↗
Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors.
PURPOSE: Intensity-modulated radiotherapy (IMRT) offers the potential to more closely conform dose distributions to the target, and spare organs at risk (OAR). Its clinical value is still being defined. The present study aims to compare IMRT with stereotactically guided conformal radiotherapy (SCRT) for patients with medium size convex-shaped brain tumors. METHODS AND MATERIALS: Five patients planned with SCRT were replanned with the IMRT-tomotherapy method using the Peacock system (Nomos Corporation). The planning target volume (PTV) and relevant OAR were assessed, and compared relative to SCRT plans using dose statistics, dose-volume histograms (DVH), and the Radiation Therapy Oncology Group (RTOG) stereotactic radiosurgery criteria. RESULTS: The median and mean PTV were 78 cm3 and 85 cm3 respectively (range 62-119 cm3). The differences in PTV doses for the whole group (Peacock-SCRT +/-1 SD) were 2%+/-1.8 (minimum PTV), and 0.1%+/-1.9 (maximum PTV). The PTV homogeneity achieved by Peacock was 12.1%+/-1.7 compared to 13.9%+/-1.3 with SCRT. Using RTOG guidelines, Peacock plans provided acceptable PTV coverage for all 5/5 plans compared to minor coverage deviations in 4/5 SCRT plans; acceptable homogeneity index for both plans (Peacock = 1.1 vs. SCRT = 1.2); and comparable conformity index (1.4 each). As a consequence of the transaxial method of arc delivery, the optic nerves received mean and maximum doses that were 11.1 to 11.6%, and 10.3 to 15.2% higher respectively with Peacock plan. The maximum optic lens, and brainstem dose were 3.1 to 4.8% higher, and 0.6% lower respectively with Peacock plan. However, all doses remained below the tolerance threshold (5 Gy for lens, and 50 Gy for optic nerves) and were clinically acceptable. CONCLUSIONS: The Peacock method provided improved PTV coverage, albeit small, in this group of convex tumors. Although the OAR doses were higher using the Peacock plans, all doses remained within the clinically defined threshold and were clinically acceptable. Further improvements may be expected using other methods of IMRT planning that do not limit the treatment delivery to transaxial arcs. Each IMRT system needs to be individually assessed as the paradigm utilized may provide different outcomes.
Algorithms↗
Mechanisms of deficient cardiac septation in the mouse with trisomy 16.
It used to be thought that the atrioventricular septum was predominantly the product of the atrioventricular endocardial cushions. In a previous study, we have shown that multiple developmental primordia are of importance in its formation. With this in mind, we have evaluated cardiac morphogenesis in the mouse with trisomy 16, an animal model with a high incidence of atrioventricular septal defects. Normal and trisomic fetuses from an Rb(11.16)2H/Rb(16.17)7Bnr x C57BL/6J cross were collected on days 10 to 15 of gestation and examined by scanning electron microscopy and histological serial sectioning. No evidence was found to suggest that atrioventricular septal defect could be explained simply on the basis of "failure of fusion" between the atrioventricular endocardial cushions. Rather, our findings supported two other developmental elements as being important in the genesis of atrioventricular septal defect. The first is an alteration in the configuration of the heart tube, with inadequate remodeling of the inner heart curvature. This resulted in the failure of the atrioventricular junction to expand to the right, with subsequent malalignment of the atrioventricular endocardial cushions with the proximal outflow cushions. The second is a variability in the connection of the primary atrial cardiac segment to the body of the embryo, the so-called dorsal mesocardium, which influences its relationship to the extracardiac mediastinal mesoderm. There appeared little difference in the connection between normal and trisomic embryos at the stage of 20 to 25 somites, but the area subsequently showed marked changes. In most trisomic embryos, the connection with the mediastinal mesoderm of the body was over a larger area than seen in normal embryos. As this area of attachment encloses the pulmonary pit, the entry point of the pulmonary vein, this gives potential for variation in the connection of the pulmonary vein. In addition, in the majority of trisomic embryos, the right pulmonary ridge (the spina vestibuli) did not accumulate extracardiac mesoderm, nor did it undergo the pronounced forward growth seen in normal embryos of equivalent stages. Consequently, the trisomic embryos show incomplete formation of both the atrial and the atrioventricular septal structures.
Animals↗
Is it possible to optimize a radiotherapy treatment plan?
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Algorithms↗
Clinical anatomy of the atrial septum with reference to its developmental components.
Knowledge of development is of crucial importance and can help clarify mechanisms of maldevelopment, but it must be properly validated. Concepts of development must be consistent with the anatomy seen in postnatal life. Such consistency is not always achieved. We have reviewed new and old accounts of cardiac embryology with regard to the definitive structure of the atrial septum. The key to understanding is to distinguish between folds of the atrial wall and true interatrial partitions. The flap valve of the oval foramen, and its inferior rim, are true septal structures, whereas the other rims, particularly the antero-superior rim, are infoldings enclosing extracardiac fat. During embryonic life, the systemic venous tributaries must achieve entrance only to the right side of the primary atrium. Development of the pulmonary venous component is a late event, with the canalizing vein using the dorsal mesocardium to gain access to the left side of the atrium. Once the systemic venous tributaries have achieved their rightward shift, the primary septum, together with the mesenchymal cap, grows between the systemic and pulmonary venous orifices. Closure of the primary foramen is achieved by fusion of the mesenchymal cap of the primary septum with the atrioventricular endocardial cushions and the vestibular spine (an additional mesenchymal structure carried on the right side of the pulmonary venous orifice). The superior margin of the newly formed secondary foramen is produced by an infolding of the atrial walls. Historically these mechanisms received appropriate recognition, but not all receive their proper due in current writings.
Endocardium↗
LAMS(TM)--a laboratory animal management system.
The LAMStrade mark database stores data on a colony of breeding animals. Forms are hierarchial and show details of internal codes, matings, litters, and offspring. The identifier given to each animal can be subdivided as such. Each form shows an abbreviated list of the related data from the form one level down, and some special fields, when double-clicked, cause the related record to be displayed. The print button allows the user to print the current record and its related records. Other buttons on each form allow the user to amend, delete, find, and add records within certain rules. User-defined lists are created to allow the selection of various characteristics during data entry. The offspring form contains a section where the user can define the label of a comment and/or a text field. This name is then always subsequently available as an option in a list of user-defined labels. Reports are available for tailtipping dates (if applicable) and calculation of genetic ratios. A queryform allows the user to filter the records in the offspring form to the criteria specified, and a display of the actual query submitted is shown. An integrated HELP is available. The LAMStrade mark database is available at http://www.hgu.mrc.ac.uk/Softdata/Lams
Animals↗
An overview of quality control practices in Ontario with particular reference to cholesterol analysis.
BACKGROUND: The Laboratory Proficiency Testing Program (LPTP) assesses the analytical performance of all licensed laboratories in Ontario. The LPTP Enzymes, Cardiac Markers, and Lipids Committee conducted a "Patterns of Practice" survey to assess the in-house quality control (QC) practices of laboratories in Ontario using cholesterol as the QC paradigm. DESIGN AND METHODS: The survey was questionnaire-based seeking information on statistical calculations, software rules, review process and data retention, and so on. Copies of the in-house cholesterol QC graphs were requested. A total of 120 of 210 laboratories were randomly chosen to receive the questionnaires during 1995 and 1996; 115 laboratories responded, although some did not answer all questions. RESULTS: The majority calculate means and standard deviations (SD) every month, using anywhere from 4 to >100 data points. 65% use a fixed mean and SD, while 17% use means calculated from the previous month. A few use a floating or cumulative mean. Some laboratories that do not use fixed means use a fixed SD. About 90% use some form of statistical quality control rules. The most common rules used to detect random error are 1(3s)/R4s while 2(2s)/4(1s)/10x are used for systematic errors. About 20% did not assay any QC at levels >5.5 mmol/L. CONCLUSIONS: Quality control data are reviewed daily (technologists), weekly and monthly (supervisors/directors). Most laboratories retain their QC records for up to 3 years on paper and magnetic media. On some QC graphs the mean and SD, QC product lot number, or reference to action logs are not apparent. Quality control practices in Ontario are, therefore, disappointing. Improvement is required in the use of clinically appropriate concentrations of QC material and documentation on QC graphs.
Chemistry, Clinical↗
A comparison of coplanar four-field techniques for conformal radiotherapy of the prostate.
BACKGROUND AND PURPOSE: Conformal radiotherapy of the prostate is an increasingly common technique, but the optimal choice of beam configuration remains unclear. This study systematically compares a number of coplanar treatment plans for four-field irradiation of two different clinical treatment volumes: prostate only (PO) and the prostate plus seminal vesicles (PSV). MATERIALS AND METHODS: A variety of four-field coplanar treatment plans were created for PO and PSV volumes in each of ten patients. Plans included a four-field 'box' plan, a symmetric plan having bilateral anterior and posterior oblique fields, a plan with anterior oblique and lateral fields, a series of asymmetric plans, and a three-field plan having anterior and bilateral fields for comparison. Doses of 64 and 74 Gy were prescribed to the isocentre. Plans were compared using the volume of rectum irradiated to greater than 50% (V50), 80% (V80) and 90% (V90) of the prescribed dose. Tumour control probabilities (TCP) and normal tissue complication probabilities (NTCP) for the rectum, bladder and femoral heads were also evaluated. Femoral head dose was limited such that less than 10% of each femoral head received 70% of the prescribed dose. RESULTS: For the PO group, the optimal plan consisted of anterior oblique and lateral fields (Rectal V80 = 23.8+/-5.0% (1 SD)), while the box technique (V80 = 26.0+/-5.8%) was less advantageous in terms of rectal sparing (P = 0.001). Similar results were obtained for the PSV group (Rectal V80 = 43.9+/-5.0% and 47.3+/-5.5% for the two plan types, respectively, P = 0.001). The three-field plan was comparable to the optimal four-field plan but gave higher superficial body dose. With dose escalation from 64 to 74 Gy, the mean TCP for the optimal plan rose from 52.0+/-2.8% to 74.1+/-2.0%. Meanwhile, rectal NTCP for the optimal plan rose by 3.5% (PO) or 8.4% (PSV), compared to 4.7% (PO) or 10.1% (PSV) for the box plan. CONCLUSIONS: For PO volumes, a plan with gantry angles of 35 degrees, 90 degrees, 270 degrees and 325 degrees offers a high level of rectal sparing and acceptable dose to the femoral heads for all patients, while for PSV volumes, the corresponding plan has gantry angles of 20 degrees, 90 degrees , 270 degrees and 340 degrees. Using these plans, the gain in TCP resulting from dose escalation can be achieved with a smaller increase in anticipated rectal NTCP.
Algorithms↗
Improved methods for adding transaxial two-dimensional margins to the superior and inferior regions of a clinical target volume.
When adding laminar or 2-D margins to the clinical target volume (CTV), additional borders are required superiorly and inferiorly. Two common strategies for adding these margins, the cylindrical method (CYL) and the chamfer method (CHR), are discussed, and improved 2-D methods are presented. The improved cylindrical method (ICYL) extends the PTV superiorly and inferiorly, but the uppermost and lowermost PTV outlines are limited laterally to the extent of the CTV. If the required 3-D margin is M, the improved chamfer method (ICHR) constructs a transaxial margin of the square root of M2-d2 on a CT plane which is a distance d above the most superior CTV outline. For a theoretical tumor, CYL and CHR overestimate and underestimate the superior target margin by 8.1 cm3 and 9.6 cm3, respectively, whereas ICYL overestimates by only 2.2 cm3 and ICHR provides the desired margin. For eight esophageal tumors (specified margin 20 mm), CHR systematically underestimates the margin on the slice immediately inferior to the CTV by 7 mm (median, range 7-27 mm, p<0.01), while CYL overestimates the margin two slices inferior to the CTV by 20 mm in all cases. ICYL removes the overestimation of CYL, but retains an overestimation of 3 (-17-3) mm (p<0.01) on the first slice inferior to the CTV. ICHR performs most accurately, the margin width being equal to that of a true 3-D margin, except for occasional underestimations (0-33 mm, p<0.01). Similar results are demonstrated for eight prostatic tumors (specified margin 10 or 15 mm), but with the more irregular tumor shape causing all 2-D methods to underestimate the margin, most notably by 4.5 (0-21) mm (p<0.01) on the inferior CTV slice for a 15-mm margin. In general, both improved 2-D methods produce significantly more accurate margins than the conventional methods, the margin produced by the improved chamfer method most closely approximating a true 3-D margin.
Esophageal Neoplasms↗
Placebo-controlled n-of-1 trials in cystic fibrosis.
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Administration, Inhalation↗
Experimental 3D dosimetry around a high-dose-rate clinical 192Ir source using a polyacrylamide gel (PAG) dosimeter.
It is well known that the experimental dosimetry of brachytherapy sources presents a challenge. Depending on the particular-dosimeter used, measurements can suffer from poor spatial resolution (ion chambers), lack of 3D information (film) or errors due to the presence of the dosimeter itself distorting the radiation flux. To avoid these problems, we have investigated the dosimetry of a clinical 192Ir source using a polyacrylamide gel (PAG) dosimeter. Experimental measurements of dose versus radial distance from the centre of the source (cross-line plots) were compared with calculations produced with a Nucletron NPS planning system. Good agreement was found between the planning system and gel measurements in planes selected for analysis. Gel dosimeter measurements in a coronal plane through the phantom showed a mean difference between measured absorbed dose and calculated dose of 0.17 Gy with SD = 0.13 Gy. Spatially, the errors at the reference point remain within one image pixel (1.0 mm). The use of polymer gel dosimetry shows promise for brachytherapy applications, offering complete, three-dimensional dose information, good spatial resolution and small measurement errors. Measurements close to the source, however, are difficult, due to some of the limiting properties of the polyacrylamide gel.
Acrylic Resins↗
Constrained customization of non-coplanar beam orientations in radiotherapy of brain tumours.
A methodology for the constrained customization of non-coplanar beam orientations in radiotherapy treatment planning has been developed and tested on a cohort of five patients with tumours of the brain. The methodology employed a combination of single and multibeam cost functions to produce customized beam orientations. The single-beam cost function was used to reduce the search space for the multibeam cost function, which was minimized using a fast simulated annealing algorithm. The scheme aims to produce well-spaced, customized beam orientations for each patient that produce low dose to organs at risk (OARs). The customized plans were compared with standard plans containing the number and orientation of beams chosen by a human planner. The beam orientation constraint-customized plans employed the same number of treatment beams as the standard plan but with beam orientations chosen by the constrained-customization scheme. Improvements from beam orientation constraint-customization were studied in isolation by customizing the beam weights of both plans using a dose-based downhill simplex algorithm. The results show that beam orientation constraint-customization reduced the maximum dose to the orbits by an average of 18.8 (+/-3.8, ISD)% and to the optic nerves by 11.4 (+/-4.8, ISD)% with no degradation of the planning target volume (PTV) dose distribution. The mean doses, averaged over the patient cohort, were reduced by 4.2 (+/-1.1, ISD)% and 12.4 (+/-3.1, ISD)% for the orbits and optic nerves respectively. In conclusion, the beam orientation constraint-customization can reduce the dose to OARs, for few-beam treatment plans, when compared with standard treatment plans developed by a human planner.
Adenoma↗
Conformal intensity-modulated radiotherapy (IMRT) delivered by robotic linac--testing IMRT to the limit?
In this paper it is proposed that intensity-modulated radiotherapy (IMRT) could be delivered optimally by a short-length linac mounted on a robotic arm. The robot would allow the linac to 'plant' narrow pencils of photon radiation with any orientation (excluding zones within which the linac and couch might collide) relative to the planning target volume (PTV). The treatment is specified by the trajectory of the robot and by the number of monitor units (MUs) delivered at each robotic orientation. An inverse-planning method to determine the optimum robotic trajectory is presented. It is shown that for complex PTVs, specifically those with concavities in their outline, the conformality of the treatment is improved by the use of a complex trajectory in comparison with a less complex constrained trajectory and this improvement is quantified. It is concluded that robotic linac delivery would lead to a great flexibility in those IMRT treatments requiring very complicated dose distributions with complex 3D shapes. However, even using very fast computers, the goal of determining whether robotic linac delivery is the ultimate IMRT cannot be conclusively reached at present.
Models, Theoretical↗
Dynamics of polymerization in polyacrylamide gel (PAG) dosimeters: (I) ageing and long-term stability.
Few quantitative data are available on the kinetics of polymerization reactions in polymer gel (PAG) dosimeters and their long-term stability. Post-irradiation polymerization reactions have been found to continue for several weeks, posing questions regarding dosimeter stability and its achievement. In this paper we report an investigation of polymerization kinetics in PAG dosimeters and the effect of diffusing oxygen into the dosimeter, post irradiation, as a potential method of inhibiting further polymerization and stabilizing the dose distribution. Results show continuous post-irradiation changes in transverse relaxation rate R2 with time over the five week study period and that a steady-state may not be reached for a period of months. An assessment is made of the appropriate time to image the dosimeter which shows that after three to four days the polymerization change is slow compared with imaging time. The implications of the time delay between irradiation and imaging are discussed in terms of the resultant sensitivity of the dosimeter and accuracy of the dose measured. In pairs of dosimeters, one sealed the other open to air, oxygen diffusing into the dosimeter arrests polymerization. However, the diffusion rate is too slow to make this method practicable. The slow diffusion means that while in regions near the air/gel interface polymerization is quickly arrested, in deeper regions it may continue for many hours, causing artefacts in the dose distribution. In the companion paper to this from a collaborating team, a study focusing on modelling oxygen diffusion in dosimeter gel will be presented.
Acrylic Resins↗
Beam-orientation customization using an artificial neural network.
A methodology for the constrained customization of coplanar beam orientations in radiotherapy treatment planning using an artificial neural network (ANN) has been developed. The geometry of the patients, with cancer of the prostate, was modelled by reducing the external contour, planning target volume (PTV) and organs at risk (OARs) to a set of cuboids. The coordinates and size of the cuboids were given to the ANN as inputs. A previously developed beam-orientation constrained-customization (BOCC) scheme employing a conventional computer algorithm was used to determine the customized beam orientations in a training set containing 45 patient datasets. Twelve patient datasets not involved in the training of the artificial neural network were used to test whether the ANN was able to map the inputs to customized beam orientations. Improvements from the customized beam orientations were compared with standard treatment plans with fixed gantry angles and plans produced from the BOCC scheme. The ANN produced customized beam orientations within 5 degrees of the BOCC scheme in 62.5% of cases. The average difference in the beam orientations produced by the ANN and the BOCC scheme was 7.7 degrees (+/-1.7, 1 SD). Compared with the standard treatment plans, the BOCC scheme produced plans with an increase in the average tumour control probability (TCP) of 5.7% (+/-1.4, 1 SD) whilst the ANN generated plans increased the average TCP by 3.9% (+/-1.3, 1 SD). Both figures refer to the TCP at a fixed rectal normal tissue complication probability (NTCP) of 1%. In conclusion, even using a very simple model for the geometry of the patient, an ANN was able to produce beam orientations that were similar to those produced by a conventional computer algorithm.
Humans↗
Massachusetts Medical Society Seminar Series on Domestic Violence.
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Domestic Violence↗
Adenovirus-mediated expression of a ribozyme to c-myb mRNA inhibits smooth muscle cell proliferation and neointima formation in vivo.
Smooth muscle cell (SMC) proliferation is an important component of restenosis in response to injury after balloon angioplasty. Inhibition of proliferation in vivo can limit neointima hyperplasia in animal models of restenosis. Ribozymes against c-myb mRNA have been shown to be effective inhibitors of SMC proliferation in vitro. The effectiveness of adenovirus as a gene therapy vector in animal models of restenosis is well documented. In order to test the utility of ribozymes to inhibit SMC proliferation by a gene therapy approach, recombinant adenovirus expressing ribozymes against c-myb mRNA was generated and tested both in vitro and in vivo. This adenovirus ribozyme vector is shown to inhibit SMC proliferation in culture and neointima formation in a rat carotid artery balloon injury model of restenosis.
Adenoviridae↗