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E Dale

Publications and source records attributed to E Dale.

At least 19 recordsLinked to original sources
PubMed2005

Comparative analyses of the dynamic properties of the bladder wall studied by repetitive pelvic CT scans of patients and cryo-sections of cadavers.

In radiotherapy planning systems, delineation of hollow normal tissue organs, such as the bladder, is time-consuming. Automated delineation may presuppose two assumptions: (1) the bladder resembles a spherical shell and (2) the volume of bladder tissue is preserved regardless of the volume of urine (luminal volume) inside. The purpose of the present study was to test these assumptions. 22 CT scans from 7 patients were studied retrospectively. Transverse cross-sectional areas enclosed by the outer contour (A(out)) and inner contour of the bladder (A(in)) were recorded from the images. Hence, the transverse cross-sectional area of the wall, A(wall)=A(out)-A(in), and the volume of bladder tissue at various luminal volumes, could be calculated. To quantify the method uncertainty, the same procedure was applied on three spherical plastic phantoms. The results were also compared with data from the Visible Human Project's photographs of cadaver cryo-sections. Assumption no. 1 stated above, implies that A(wall) is constant regardless of the level of intersection of the sphere. The data from cryo-sections revealed a positive correlation for A(wall) and A(out), in contradiction to assumption no. 1 (p<0.001). The corresponding association derived from the repetitive CT scans of patients was also statistically significant (p<0.001) although linear regression revealed a less steep slope. A relationship was found between the volume of bladder tissue and luminal volume, hence contradicting assumption no. 2 (p<0.001). In conclusion the cross-sectional wall areas of the bladder, measured from patient CT scans, increase slightly with luminal cross-sectional areas in contradiction to expected values derived from a simplistic spherical shell model. In addition, the volume of bladder tissue is related to the luminal volume. Our results may be of practical value when developing automated delineation tools in radiotherapy planning systems.

Cryopreservation↗
PubMed2003

Comparative analyses of the dynamic properties of the rectum studied by cryo-sections of human cadavers and pelvic CT scans of patients.

Optimization of radiotherapy treatment plans based on dose-volume histograms relies on accurate organ delineation. Hollow organs, such as the rectum, are difficult and time-consuming to delineate owing to unclear visualization of the border between wall tissue and filling. Automated hollow organ delineation would be a valuable tool, but its development depends upon improved understanding of the dynamics of the rectum in response to filling. Two reasonable assumptions proposed in the literature are that (1) the rectal wall tissue along a constant length of the rectal cylinder is preserved over time and (2) the rectal wall tissue is distributed homogeneously along the cylinder. Therefore, variations in wall thickness can be explained by variable rectal filling. To investigate these assumptions, transversal cross-sectional areas enclosed by the outer contour (A(out)) and inner contour (A(in)) of the rectum were recorded from digital photographs of cadaver cryo-sections from the U.S. National Library of Medicine's Visible Human Project. In addition, A(out) and A(in) were recorded from 19 CT scans of 5 of our own patients. The transversal cross-sectional area of the wall of the rectum, A(wall)=A(out)-A(in), was calculated. The data derived both from cryo-sections and repetitive CT scans of patients, revealed that there was a significant correlation between A(wall) and A(out), in contradiction to assumption (1) stated above (male cryo-sections: p<0.001, female cryo-sections: p=0.03, repetitive CT scans p<0.001). Moreover, the mean A(wall) calculated from one CT scan differed significantly from the mean A(wall) from other CT scans and was correlated with the mean A(out), i.e. rectal filling (p<0.001). This finding was confirmed by careful analysis of another study (p=0.001) and opposes assumption (2). Hence, the amount of wall tissue within a constant length of rectum is not preserved over time, but increases with increased filling. This implies that the longitudinal length of the rectum decreases in response to distension of the organ.

Cadaver↗
PubMed2001

Inter fraction variations in rectum and bladder volumes and dose distributions during high dose rate brachytherapy treatment of the uterine cervix investigated by repetitive CT-examinations.

PURPOSE: To evaluate variation of dose to organs at risk for patients receiving fractionated high dose rate gynaecological brachytherapy by using CT-based 3D treatment planning and dose-volume histograms (DVH). MATERIALS AND METHODS: Fourteen patients with cancer of the uterine cervix underwent three to six CT examinations (mean 4.9) during their course of high-dose-rate brachytherapy using radiographically compatible applicators. The rectal and bladder walls were delineated and DVHs were calculated. RESULTS: Inter fraction variation of the bladder volume (CV(mean)=44.1%) was significantly larger than the inter fraction variation of the mean dose (CV(mean)=19.9%, P=0.005) and the maximum dose (CV(mean)=17.5%, P=0.003) of the bladder wall. The same trend was seen for rectum, although the figures were not significantly different. Performing CT examinations at four of seven brachytherapy fractions reduced the uncertainty to 4 and 7% for the bladder and rectal doses, respectively. A linear regression analysis showed a significant, negative relationship between time after treatment start and the whole bladder volume (P=0.018), whereas no correlation was found for the rectum. For both rectum and bladder a linear regression analysis revealed a significant, negative relationship between the whole volume and median dose (P<0.05). CONCLUSION: Preferably a CT examination should be provided at every fraction. However, this is logistically unfeasible in most institutions. To obtain reliable DVHs the patients will in the future undergo 3-4 CT examinations during the course of brachytherapy at our institution. Since this study showed an association between large bladder volumes and dose reductions, the patients will be treated with a standardized bladder volume.

Adult↗
PubMed2000

Modeling normal tissue complication probability from repetitive computed tomography scans during fractionated high-dose-rate brachytherapy and external beam radiotherapy of the uterine cervix.

PURPOSE: To calculate the normal tissue complication probability (NTCP) of late radiation effects on the rectum and bladder from repetitive CT scans during fractionated high-dose-rate brachytherapy (HDRB) and external beam radiotherapy (EBRT) of the uterine cervix and compare the NTCP with the clinical frequency of late effects. METHODS AND MATERIALS: Fourteen patients with cancer of the uterine cervix (Stage IIb-IVa) underwent 3-6 (mean, 4.9) CT scans in treatment position during their course of HDRB using a ring applicator with an Iridium stepping source. The rectal and bladder walls were delineated on the treatment-planning system, such that a constant wall volume independent of organ filling was achieved. Dose-volume histograms (DVH) of the rectal and bladder walls were acquired. A method of summing multiple DVHs accounting for variable dose per fraction were applied to the DVHs of HDRB and EBRT together with the Lyman-Kutcher NTCP model fitted to clinical dose-volume tolerance data from recent studies. RESULTS: The D(mean) of the DVH from EBRT was close to the D(max) for both the rectum and bladder, confirming that the DVH from EBRT corresponded with homogeneous whole-organ irradiation. The NTCP of the rectum was 19.7% (13.5%, 25. 9%) (mean and 95% confidence interval), whereas the clinical frequency of late rectal sequelae (Grade 3-4, RTOG/EORTC) was 13% based on material from 200 patients. For the bladder the NTCP was 61. 9% (46.8%, 76.9%) as compared to the clinical frequency of Grade 3-4 late effects of 14%. If only 1 CT scan from HDRB was assumed available, the relative uncertainty (standard deviation or SD) of the NTCP value for an arbitrary patient was 20-30%, whereas 4 CT scans provided an uncertainty of 12-13%. CONCLUSION: The NTCP for the rectum was almost consistent with the clinical frequency of late effects, whereas the NTCP for bladder was too high. To obtain reliable (SD of 12-13%) NTCP values, 3-4 CT scans are needed during 5-7 fractions of HDRB treatments.

Algorithms↗
PubMed2000

Impact of progesterone receptor on cell-fate decisions during mammary gland development.

Mammary epithelium contains lineage-limited progenitors that give rise to cells that form distinct morphological structures, ducts vs. lobules, depending on the endocrine status of the female. Progesterone signaling through progesterone receptor (PR) is essential for lobulo-alveolar development that accompanies pregnancy, but not for ductal growth accompanying puberty. PR exists in two molecular forms, A and B, and an imbalance in the native ratio of the two isoforms can lead to alterations in PR signaling. Indeed, as we reported previously, in transgenic mice carrying additional A form of PR, mammary development is abnormal, characterized by excessive lateral ductal branching. This suggests that alterations in PR signaling may have important consequences to mammary development, particularly with regard to ductal vs. alveolar growth. To test this further, we created transgenic mice carrying additional B form of PR and report that mammary development in these mice is also abnormal, characterized by inappropriate alveolar growth. More importantly, these mammary glands, on serial transplantation, undergo a premature arrest in ductal growth without any alteration in the potential for lobulo-alveolar growth. Such an arrest in ductal growth does not occur with transgenics carrying additional A form of PR. These studies, therefore, provide strong evidence to indicate that PR signaling may be of paramount importance for appropriate cell-fate decisions during normal mammary development, and also that this requires a regulated expression of the two isoforms.

Animals↗
PubMed1999

Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy.

PURPOSE: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. METHODS AND MATERIALS: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. RESULTS: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p<0.01 level. The correlation coefficients based on histograms of the whole rectum were larger than those derived from histograms of the rectum wall. Also, simpler descriptive measures as Dmax, of the whole rectum, correlated better to observed late toxicity than Dmax derived from histograms of the rectum wall. Correlation coefficients from "high-dose" measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p<0.01 level. CONCLUSIONS: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late effects in the rectum as measured with questionnaires. This is compatible with a more serial organisation of the rectal tissue architecture than previously reported. 2) Reducing the Lyman-Kutcher model's volume parameter, thus allowing small high-dose regions to determine the NTCP, improved the correlation, but not beyond that of high-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms.

Diarrhea↗
PubMed1998

Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands.

In this report we document the creation of transgenic mice in which the native ratio of A and B forms of progesterone receptor (PR) has been altered by the introduction of additional A form as transgene. We also show that in these mice there is an aberration in mammary development. In ovariectomized prepubertal PR-A transgenic mice, end buds with unusual morphology persist after ovariectomy, and in young adult nonovariectomized mice, mammary glands have extensive lateral branching. The glands of adult mice also exhibit ductal hyperplasia with a disorganized basement membrane and decreased cell-cell adhesion, features commonly associated with neoplasia. Because progesterone is a mitogenic hormone in mammary glands and PR is required for mammary development, these data provide direct evidence that in vivo a regulated expression of the two isoforms of PR is critical for appropriate cellular response to progesterone and that for mammary glands this may have major implications to carcinogenesis.

Animals↗
PubMed1997

Specification of the dose to organs at risk in external beam radiotherapy.

Reporting of the clinical relevant dose to organs at risk (OR) and other normal tissues is crucial in trials and protocols where the aim is to assess late complications and to increase the therapeutic ratio for external beam radiotherapy. The dose distribution in normal tissues and ORs are, however, most often heterogeneous, at least when more than two opposing beams are applied. To decide the most clinical relevant dose with respect to late occurring complications is therefore not a straight forward problem. In this work we discuss what parameters characterise the dose-volume-histogram (DVH) best by calculating normal tissue complication probabilities (NTCPs) by using the Lyman model and various sets of statistical parameters drawn out from the DVHs. These NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of parameters are evaluated. Our calculations indicate that the NTCP based on the Lyman model is best correlated to the Dmax value for serially organised tissues such as the spinal cord. For organs, described largely as tissues organised in parallel, the Dmedian or Dmean of the DVH may be applied. Our calculations reveal that Dmean is the parameter of choice when Dmedian is quite small, but when the two parameters approach each other. Dmedian will be a better choice, using a unity volume fraction. For ORs characterised by a mixed serial and parallel functional structure, as the heart, neither Dmax, Dmedian nor Dmean may predict the actual NTCP.

Dose-Response Relationship, Drug↗
PubMed1996

Resting metabolic rate and obesity in childhood acute lymphoblastic leukaemia.

The present study described excess weight gain in children with acute lymphoblastic leukaemia (ALL) treated without cranial radiotherapy, and tested the hypothesis that reduced resting metabolic rate (RMR) predisposes children with ALL to excess weight gain. Changes in relative weight in 35 children were expressed as BMI standard deviation (s.d.) scores from diagnosis to 2 y post diagnosis. RMR was measured by ventilated hood indirect calorimetry in 27 patients who had been in positive energy balance and 27 healthy control children matched pairwise for gender and fat free mass (FFM). Mean change in BMI s.d. score to 2 y was +1.0 (s.d. 1.3), 95% CI +0.5 to +1.5 (paired t, P < 0.01). No significant differences in RMR were observed between patients and controls (paired t-test; analysis of covariance). We conclude that excess weight gain occurs during ALL therapy, even in the absence of cranial radiotherapy. Children with ALL who have been in positive energy balance do not appear to show abnormalities in RMR.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Intra-chromosomal rearrangements generated by Cre-lox site-specific recombination.

Chromosomal rearrangements are useful genetic and breeding tools but are often difficult to detect and characterize. To more easily identify and define chromosome deletions and inversions, we have used the bacteriophage P1 Cre-lox site-specific recombination system to generate these events in plants. This involves three steps: (i) the introduction of two lox sites into one locus in a plant genome, including one site within a modified Ds transposon; (ii) Ac transposase-mediated transposition of the Ds-lox element to a new locus on the same chromosome; (iii) Cre-mediated site-specific recombination between the two lox sites that bracket a chromosome segment. We report the production of a deletion and three inversion events in tobacco. The utility of chromosomal segments bracketed by lox sites for targeted manipulation and cloning is discussed.

Base Sequence↗
PubMed1986

An evaluated programme of rheumatology training for general practitioners.

The management of painful, upper-limb disorders by 34 general practitioners (GPs) was examined 3 months before and 3 months after personal instruction of GPs by a consultant rheumatologist. Tuition was conducted either in GP surgeries or a hospital out-patient department. Following instruction there were significant increases in the application of appropriate treatments (p less than 0.0005) and of local corticosteroid injections by GPs (p less than 0.005), fewer requests for investigations and less-frequent hospital referrals for consultant rheumatology opinions. Hospital out-patient instruction was associated with a significant reduction of patients' time off work (p less than 0.005) and, in general, differences of management appeared to be more pronounced amongst those GPs instructed in the hospital than in GP surgeries. The study showed that personal instruction of GPs by a consultant rheumatologist may result in modifications of practice, at least in the short term. The evidence indicates that such alterations of GP management may significantly reduce patient morbidity.

Arm↗