Gap-stepped MLC leaves with filler blades can eliminate tongue-and-groove underdoses when delivering IMRT with maximum efficiency.
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Equipment Design↗
Biomedical subjects
S Webb
Publications and source records attributed to S Webb.
Generation of discrete beam-intensity modulation by dynamic multileaf collimation under minimum leaf separation constraints.
An algorithm to generate discrete beam-intensity modulation by dynamic multileaf collimation is presented which incorporates constraints on minimum allowed leaf separations. MLC positioning information is derived simultaneously for all leaf pairs and back-up diaphragms as they progress across the field. A feedback mechanism allows corrections to be applied to eliminate potential violations of minimum separation conditions and any underexposure in the interleaf tongue-and-groove region as they are encountered. The resulting motion correctly delivers the intended modulation and is physically realizable. Implementation of the algorithm is described. Results of the algorithm can also alternatively be interpreted as defining a series of static fields to deliver the same modulation.
Algorithms↗
Autosomal dominant hereditary spastic paraparesis with cognitive loss linked to chromosome 2p.
A family initially considered to have 'pure' autosomal dominant hereditary spastic paraparesis (HSP), was found on neuropsychological testing to have evidence of late onset cognitive impairment. This family showed genetic linkage to the SPG4 locus on chromosome 2p previously reported for pure HSP. Of 56 living members, 44 were examined, 30 of whom were > 30 years of age and 12 members were found to be affected with HSP including four asymptomatic cases. One other family member (III-5), aged 62 years, died prior to this study of a 4-year dementing illness. Neuropsychological assessment of 11 affected members and 11 matched, unaffected, family controls showed no significant differences between the two groups. However, the neuropsychological test profile in four of 11 affected members tested (mean age 47.2 years) and one of 11 family controls (mean age 41.5 years) showed global cognitive impairment. The pattern of cognitive dysfunction was the same for all five family members identified and was similar to that found in subcortical dementia. The presence of cognitive impairment appeared to be related to age and not the severity of the paraplegia. Both the severity of the paraplegia and the age of onset (21-60 years) varied considerably in this family.
Adult↗
Cognitive impairment in families with pure autosomal dominant hereditary spastic paraparesis.
In the course of a study of a large family with pure autosomal dominant hereditary spastic paraparesis (AD-HSP), mild cognitive impairment was found in older family members. In order to determine if cognitive impairment occurred more frequently in families with pure AD-HSP than normally expected, a case control study of cognitive function in HSP was undertaken. Thirty-one patients, from 12 kindreds with pure AD-HSP, matched with 31 healthy control subjects for age, sex and years of education, were assessed for evidence of cognitive impairment using the Cambridge Cognitive Examination (CAMCOG). Twenty unaffected siblings matched with twenty healthy control subjects were similarly assessed. The total CAMCOG score in the affected group (mean 89.26/107, SD 11.08, 95% confidence interval 85.2-94.49) compared with the control group (mean 96.52/107, SD 5.52, 95% confidence interval 94.49-98.54) was significantly reduced (P = 0.0003). There were also significant abnormalities in three out of the nine subsets including memory (P = 0.0002), language comprehension (P = 0.0166) and language expression (P = 0.0025). The differences between the groups were due to cognitive impairment appearing after the age of 50 years in patients with AD-HSP; CAMCOG scores before this age were similar to control scores. There was also a minor non-significant difference in total CAMCOG score for the unaffected siblings (mean 93.7/107, SD 8.54, 95% confidence interval 89.70-97.70) compared with the control group (mean 97.9/107, SD 4.61, 95% confidence interval 95.7-100.1) (P < 0.02). This study demonstrates that mild cognitive impairment develops after the age of 50 years in patients with pure AD-HSP and is further evidence of degeneration in other systems in this disorder.
Adult↗
Improvements in prostate radiotherapy from the customization of beam directions.
A methodology for optimizing the beam directions in radiotherapy treatment planning has been developed and tested on a cohort of twelve prostate patients. An optimization algorithm employing a an objective cost function was used, based on beam's-eye-view volumetrics but also employing a simple dose model and biological considerations for organs-at-risk (OARs). The cost function embodies information about the volume of OARs in a single field and their position relative to the planning target volume (PTV). The proximity of the PTV to the surface of the patient is also included. Within the algorithm "importance factor" were used to model the clinical importance of different organs-at-risk so that all organs-at-risk were included in a single objective score. "Gantry-angle-windows" were introduced to restrict the available beam directions. The methodology was applied to twelve prostate patients to determine the optimum beam directions for three-field direction plans. Orientation-optimized and standard treatment plans were compared via measures of tumor control probability (TCP) and normal tissue complication probability (NTCP). Standard plans had fixed beam directions whereas orientation-optimized plans contained beam directions chosen by the algorithm. The beam-weights of both the orientation-optimized and standard plans were optimized using a dose-based simulated annealing algorithm to allow the improvements by optimizing the beam directions to be studied in isolation. The results of the comparison show that optimization of the beam directions yielded better plans, in terms of TCP and NTCP, than the standard plans. When the dose to the isocenter was scaled to produce a rectal NTCP of 1%, the average TCP of the orientation-optimized plans was (5.7 +/- 1.4)% greater than that for the standard plans. In conclusion, the customization of beam directions in the treatment planning of prostate patients using and objective cost function and allowed gantry-angle-windows produces superior three-field direction plans compared to standard treatment plans.
Algorithms↗
Rapid portal imaging with a high-efficiency, large field-of-view detector.
The design, construction, and performance evaluation of an electronic portal imaging device (EPID) are described. The EPID has the same imaging geometry as the current mirror-based systems except for the x-ray detection stage, where a two-dimensional (2D) array of 1 cm thick CsI(Tl) detector elements are utilized. The approximately 18% x-ray quantum efficiency of the scintillation detector and its 30 x 40 cm2 field-of-view at the isocenter are greater than other area-imaging EPIDs. The imaging issues addressed are theoretical and measured signal-to-noise ratio, linearity of the imaging chain, influence of frame-summing on image quality and image calibration. Portal images of test objects and a humanoid phantom are used to measure the performance of the system. An image quality similar to the current devices is achieved but with a lower dose. With approximately 1 cGy dose delivered by a 6 MV beam, a 2 mm diam structure of 1.3% contrast and an 18 mm diam object of 0.125% contrast can be resolved without using image-enhancement methods. A spatial resolution of about 2 mm at the isocenter is demonstrated. The capability of the system to perform fast sequential imaging, synchronized with the radiation pulses, makes it suitable for patient motion studies and verification of intensity-modulated beams as well as its application in cone-beam megavoltage computed tomography.
Equipment Design↗
Hyponatraemia in a prepubertal middle-aged woman.
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Aged↗
The derivation of tissue-maximum ratio from percentage depth dose requires peak scatter factor to be considered a function of source-to-surface distance.
A formula for the calculation of tissue-maximum ratio (TMR) from percentage depth dose (PDD) and peak scatter factor (PSF) is derived from first principles using a simple geometric model for the case when the field size for PDD and PSF is defined at the surface. The derivation is carried out in two ways: (a) taking field size for PDD and PSF as defined at the depth of maximum dose and then applying a conversion factor, and (b) by a direct derivation. The first of these methods yields a formula which agrees with BJR Supplement 25, but the latter yields a result which differs from it. Numerically, this difference is insignificant, but it has implications for the theoretical basis of the conversion formulae. The difference arises due to the translation of field size from one depth to another when calculating PSF: two different values of source-to-surface distance (SSD) yield two apparently different PSFs for the same size of field at the depth of maximum dose. Disagreements of this type are prevalent throughout the standard conversion formulae given in BJR Supplement 25 when field size for PDD and PSF is defined at the surface rather than at the depth of dose maximum. These disagreements are illustrated here using the conversion of PDD from one SSD to another as an example. The difficulty is overcome by considering PSF to be a function of SSD as well as field size.
Humans↗
A comparison of conventional and conformal radiotherapy of the oesophagus: work in progress.
A retrospective treatment planning study was carried out in five patients to assess the effectiveness of conformal radiotherapy of the oesophagus. A two-phase conventional treatment plan was created for each patient, with a prescribed dose of 55 Gy. This plan was compared with a single-phase conformal plan consisting of the same field arrangement as the second phase of the conventional treatment, but with conformal blocks shaped to the beam's eye view of the planning target volume. A further comparison was made between the conventional plan and a two-phase plan using the same beam angles and weights as the conventional plan, but with conformal field shapes. The effectiveness of each treatment plan was assessed using dose--volume histograms and normal tissue complication probabilities for the lungs. On average, the single-phase conformal technique increased the mean lung dose from 22.5% (+/- 6.2 SD) of the prescribed dose to 29.5% (+/- 5.2 SD) compared with the conventional technique (p = 0.0001). This indicates that this technique did not offer any benefit in terms of reducing the risk of pneumonitis. However, the two-phase conformal technique reduced the mean lung dose from 22.5% (+/- 6.2 SD) of the prescribed dose to 19.8% (+/- 4.6 SD)(p = 0.03), showing that this technique should reduce the risk of pneumonitis. Further work is underway to study more patients and to investigate tumour control probability and dose escalation.
Antimetabolites, Antineoplastic↗
Untangling the Web. Staying afloat in a sea of information.
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Computer Communication Networks↗
Proficiency testing of creatine kinase and creatine kinase-2: the experience of the Ontario Laboratory Proficiency Testing Program.
The Ontario Laboratory Proficiency Testing Program has regularly monitored the analytical performance of total creatine kinase (CK) (approximately 230 participants) and CK isoenzyme-2 (CK-MB) (approximately 160 participants) throughout the entire province. Consistently, a wide dispersion of results has been observed not only between different analyzer systems but also among identical analyzers. Accordingly, the results of the last three proficiency surveys for these analytes were examined statistically to establish both the extent of these variations and the range of values reported for the male upper reference ranges. The results of many of the analyzer systems were significantly different from each other, as were many of the reference ranges. This unsatisfactory situation may only be remedied by the use of reference materials as shown by others. The consequences of these findings also effect the reliability of epidemiological surveys such as the WHO MONICA Project (Circulation 1994;90:583-612), which monitors deaths due to heart disease and includes cardiac enzyme results in its criteria.
Clinical Enzyme Tests↗
Intensity-modulated radiation therapy: dynamic MLC (DMLC) therapy, multisegment therapy and tomotherapy. An example of QA in DMLC therapy.
Intensity-modulated radiation therapy will make a quantum leap in tumor control. It is the new radiation therapy for the new millennium. The major methods to achieve IMRT are: 1. dynamic multileaf collimator (DMLC) therapy, 2. multisegment therapy, and 3. tomotherapy. The principles of these 3 techniques are briefly reviewed. Each technique presents unique QA issues which are outlined. As an example this paper will present the results of a recent new study of an important QA concern in DMLC therapy.
Humans↗
Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22.
An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We mapped the disease locus to an approximately 26-cM region of chromosome 17q21-22 with a maximum two-point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP-17 candidate region, were also sequenced. This analysis included the microtubule-associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed.
Adult↗
Management of cervical intraepithelial neoplasia during pregnancy with LOOP excision.
OBJECTIVE: Management of severe cervical dysplasia/possible microinvasive carcinoma during pregnancy is frequently associated with significant morbidity. The purpose of this study is to determine the efficacy of LOOP excision performed during pregnancy, and also to record the nature and frequency of complications of the procedure. METHODS: Twenty women underwent LOOP excision during pregnancy. The gestational age range was 8-34 weeks. Data concerning indications, complications, and histopathologic results were recorded. RESULTS: Fourteen of 20 (70%) had dysplastic changes in the LOOP specimen. Eight of 14 (57%) had involved margins. Nine of 19 (47%) had residual dysplasia 3 months postpartum, including 3 patients whose initial LOOP specimens were negative for dysplasia. Significant morbidity included 3 preterm births, 2 patients who required blood transfusion following LOOP, and 1 unexplained intrauterine fetal demise documented 4 weeks post-LOOP. The gestational age range of those patients who had significant morbidity was 27-34 weeks. CONCLUSIONS: LOOP excision of the cervix during pregnancy does not consistently produce diagnostic specimens and is associated with a significant rate of residual disease. Morbidity appears similar to that of cone biopsy during pregnancy and occurs primarily when the procedure is performed in the third trimester. Until refinements in technique occur, LOOP excision during pregnancy should be reserved for limited indications.
Adult↗
Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple sclerosis.
The magnetisation transfer (MT) ratio of eight multiple sclerosis lesions has been studied serially. Initially, when the lesions showed gadolinium enhancement, there was a marked reduction in their MT ratio compared with normal white matter. Follow-up a mean of 11 months later (range 3-23 months), when the lesions no longer enhanced, revealed a consistent and usually marked recovery of the MT ratios towards normal. The MT ratio is thought to reflect the structural integrity of tissues with an important contribution from myelin and axons. MT imaging is a promising tool for elucidating pathophysiology and monitoring treatment in multiple sclerosis.
Adult↗
Cardiac morphology at late fetal stages in the mouse with trisomy 16: consequences for different formation of the atrioventricular junction when compared to humans with trisomy 21.
OBJECTIVE: The mouse with trisomy 16 (Ts16) is held to be a genetic model for humans with Down's syndrome (Ts21). Both trisomies are associated with atrioventricular septal defects, but the precise morphology in the mouse remains unclear. We have therefore characterised cardiac morphology in the mouse with Ts16. METHODS: Ts16 fetuses, from a Rb(11.16)2H/Rb(16.17)7Bnr x C57BL/6J cross, were collected on gestational days 17 or 18 (full term = 19 days) and studied using scanning electron microscopy and serial sections. RESULTS: The hearts showed a spectrum of deficient atrioventricular septation which we categorised into two types. In one, a common atrioventricular junction was separated into right and left orifices by a tongue of tissue joining two valvar leaflets that bridged the ventricular septum to varying extent. In the other, a common atrioventricular junction was connected exclusively to the left ventricle. All hearts had ostium primum atrial and ventricular septal defects, together with abnormal ventriculo-arterial connections. No heart had the typical morphology seen in the human with Down's syndrome, namely a balanced common atrioventricular junction, guarded by a common valve, with the aorta connected exclusively to the left ventricle. CONCLUSIONS: The cardiac defects seen in Ts16 mice show marked differences from the typical anatomy in human Ts21, suggesting more complex mechanisms of cardiac dysmorphogenesis in Ts16. The mouse model will prove valuable in elucidating the mechanism of normal expansion of the atrioventricular junctions, and help in charting the precise steps involved in atrial and ventricular septation.
Animals↗
Analysis of the cost of population screening for haemochromatosis using biochemical and genetic markers.
AIMS: To estimate the cost of population screening for haemochromatosis in Australia and to compare the cost of alternative screening strategies. METHODS: The costs of screening for haemochromatosis were analysed in a hypothetical study using transferrin saturation as the primary screening test, with confirmation of the diagnosis by either liver biopsy or DNA testing for the recently-described haemochromatosis gene. RESULTS: Screening, with confirmation of the diagnosis by liver biopsy, would cost between US$5079 and US$8813 per case detected (excluding administrative costs), depending on the screening strategy (Aust$ = US$0.80). If a DNA test were used instead of liver biopsy, the cost would be reduced to an estimated US$3954-US$4410 per case. This would be further reduced to US$2457 by detection of additional cases by screening family members. The least costly strategy utilised a transferrin saturation threshold of 55% and DNA testing for confirmation of the diagnosis; however, a transferrin saturation threshold of 45% increased the cost only marginally. The initial screening step (transferrin saturation) accounted for 74%-94% of the estimated cost of the screening programme. CONCLUSIONS: Screening for haemochromatosis using transferrin saturation involves relatively modest costs which may be recovered if complications of haemochromatosis can be prevented by early detection and treatment. The most cost-effective strategies utilised transferrin saturation for initial screening, followed by DNA testing. Reduction in the cost of transferrin saturation would lead to a significant reduction in total screening costs. Additional benefits of a screening programme include detection of other iron overload disorders and iron deficiency.
Biopsy↗
The safety profile of GH replacement therapy in adults.
OBJECTIVE: The benefits of GH replacement in GH-deficient adult patients are becoming accepted but the safety profile continues to be defined. The GH deficiency in adults may have arisen i either childhood or during adult life and these two groups differ with regard to history of disease. The aid of the present report was to study differences in safety profile between these two groups during long-term replacement therapy with recombinant human GH (hGH). Possible factors which placed a patient at risk of experiencing an adverse event were also examined. PATIENTS AND DESIGN: GH-deficient adult patients were randomized into two study protocols, differing only in age of onset of the GH deficiency syndrome. There were 98 patients with adult-onset and 67 patients with childhood-onset GH deficiency. Each study consisted of a 6-month double-blind placebo-controlled phase followed by an open-label hGH treatment phase. Glucose tolerance, incidence of treatment-emergent adverse events and relationship to IGF status were studied throughout the 36 months of treatment. RESULTS: Human growth hormone-related adverse events were reported less commonly in childhood-onset patients compared with adult-onset patients. Adult-onset patients who continued into the open-label therapy phase reported an increased incidence of arthralgia, myalgia and paraesthesia. There were significant increases in fasting glucose with hGH therapy but values remained within the normal range. Hypertension was reported in 7.7% of adult-onset patients at 18 months of hGH, which was within the expected prevalence for the number of patients, but was not reported for any childhood-onset patients. Only in adult-onset patients were sufficient adverse events reported to enable analysis of risk factors. Patients reporting hGH-related adverse events were significantly heavier and, therefore, received more hGH. There was a significantly greater increase in IGF-I and IGFBP-3 in the first month in patients who experienced hGH-related adverse events compared with those who did not. CONCLUSION: The risks of replacement therapy with hGH in GH-deficient adults varied with pathogenesis of disease; hGH-related adverse events occurred more frequently in patients with adult-onset compared with those childhood-onset GH deficiency. In the adult-onset patients there was an increased risk of adverse events in heavier patients and those who had the greatest increases in IGF-I and IGFBP-3 at 1 month of therapy.
Adult↗