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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

The effect of stair-step leaf transmission on the 'tongue-and-groove problem' in dynamic radiotherapy with a multileaf collimator.

When intensity-modulated fields are created using a multileaf collimator with dynamic leaf movement the potential problem for underdosage beneath the tongue-and-groove interleaf regions has been identified and a solution based on leaf-movement synchronization has been provided by Van Santvoort and Heijmen. Their first-order analysis ignored the transmission through an exposed stair-step. In this brief Note we provide the extended analysis including this contribution and show the effect on irradiation with synchronization. The result is that the synchronization approach of Van Santvoort and Heijmen solves the tongue-and-groove problem even when the transmission through the stair-step is considered, but partial synchronization is generally sufficient.

Health Physics↗

A family with hereditary spastic paraparesis and epilepsy.

PURPOSE: We describe a family with hereditary spastic paraparesis (HSP) in which 4 of 6 affected members also have epilepsy. METHODS: All family members were examined by 2 neurologists. Four affected and 3 unaffected family members had EEG recordings. Four affected members were investigated for other causes of spastic paraparesis and epilepsy. RESULTS: Epileptic symptoms varied among family members: 1 had complex partial seizures, another had focal myoclonic epilepsy, and 2 had simple partial seizures secondarily generalized. All 4 had clinical or EEG evidence to support a focal origin for the epilepsy, and 2 had photoparoxysal responses on EEG. Symptoms were more severe and occurred earlier in the younger generation, suggesting genetic anticipation in this family. The onset of epilepsy developed simultaneously with, or < or = 18 years before, onset of gait disturbance. Three unaffected family members had normal EEGs. CONCLUSIONS: The association of HSP and epilepsy should no longer be assumed to be fortuitous.

Adolescent↗

Intensity-modulated radiotherapy by means of static tomotherapy: a planning and verification study.

There is currently much research interest in developing, evaluating, and verifying intensity-modulation techniques. Of particular interest is how well the delivery of intensity-modulated profiles can be simulated by planning algorithms, and how accurately these profiles can be delivered given the specification constraints of linear accelerators. In this paper we present a planning and verification study based on delivering radiation in "static-tomotherapy" mode via the NOMOS MIMiC (Multileaf intensity-modulation collimator), which sheds some light on these issues. An inverse-planning algorithm was used to compute intensity-modulated profiles for a 9-coplanar-field plan for a body phantom. The algorithm makes several approximations about the form of the elementary fluence profile through bixels during delivery. Specifically, it is independent of the state of adjacent bixels (i.e., open or closed) and obeys the superposition principle. From the standpoint of comparing the predicted versus the delivered dose, these assumptions were made irrelevant by a final one-step forward dose calculation performed using the optimized intensity profiles. This forward dose calculation took into account the penumbral characteristics of the delivery system by decomposing the intensity profiles into the set of delivery components. Each component was assigned the appropriate penumbral functions thereby ensuring that the calculated dose distribution closely predicted the delivered dose distribution. The nine intensity modulated fields were delivered to a perspex phantom with the same geometry, containing a verification film. In general good agreement was found between the predicted and the measured delivered dose distributions. All the main features of the predicted dose distribution are seen in the delivered. The 90% isodoses were consistently in spatial agreement to within 3 mm. At the 50% isodose level consistent spatial agreement was again found to within 3 mm, the largest deviation being about 5 mm. The close correspondence between the predicted and measured dose distribution demonstrates the potential of the MIMiC delivery system. Our results indicate the level of dose conformation that is achievable in practice and the accuracy of the dose computation algorithm. However, this study only concerned delivery of radiation to a 2 cm thick slice, and the dose distribution was only verified in the central plane of the phantom where the film was placed. We therefore cannot comment as yet on what happens to the dose distribution away from the central film-plane.

Algorithms↗

Two families with autosomal recessive spastic paraplegia, pigmented maculopathy, and dementia.

OBJECTIVE: Two families with autosomal recessive hereditary spastic paraplegia and pigmented maculopathy are described. METHODS: All family members were examined by two neurologists. An assessment of cognitive function in affected members was made using the mini mental state examination (MMSE) or Cambridge cognitive examination (CAMCOG). RESULTS: Six patients from two families presented with a slowly progressive, autosomal recessive, spastic tetraplegia. Although they were always considered to be intellectually slower than their peers, further intellectual deterioration was noted during the second decade. Five had a pigmented maculopathy with mild decrease in visual acuity and all had distal amyotrophy, mild cerebellar signs, and developed faecal and urinary incontinence late in the course of the disease. CONCLUSION: The association of hereditary spastic paraplegia and pigmented maculopathy has rarely been described; only 11 families with 32 affected members have been reported, showing considerable heterogeneity in presentation. These described conditions may be allelic or more probably reflect mutations at different genetic loci.

Adult↗

Outcome of anxiety and depressive disorders in primary care.

BACKGROUND: Factors related to the outcome of depression and anxiety in primary care are not fully understood. METHOD: Adult patients in general practice with depressive, anxiety or panic disorder (n = 148; DSM-III-R criteria) were studied prospectively for six months to determine the factors most closely associated with outcome. The Psychiatric Assessment Schedule, Hamilton Depression Rating Scale, Clinical Anxiety Scale and Life Events and Difficulties Schedule interviews were performed at index consultations and repeated six months later. Variables associated with outcome were assessed by multiple regression analysis. RESULTS: Good outcome was predicted by mild depression at initial assessment, high educational level, and being in employment. At follow-up the most important predictor of improvement was reduction in marked difficulties over the six months. Recognition and management by the GP was most frequent in patients with severe disorder; such patients were least likely to improve because of the severity of their depression and marked social difficulties. CONCLUSIONS: This naturalistic study helps to provide a framework for further studies with more precisely defined groups of people with depression. An effective treatment strategy for people with marked depression and ongoing social difficulties is especially needed.

Adolescent↗