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Biomedical subjects

A Kneebone

Publications and source records attributed to A Kneebone.

14 recordsLinked to original sources

Radiotherapy in the management of recurrent synovial chondromatosis.

Synovial chondromatosis is a rare, benign condition characterized by the formation of multiple cartilaginous nodules that are generally intra-articular and can lead to chronic pain and limit the function of involved joints. We report on the novel use of radiotherapy that was used to treat a 42-year-old man with rapid recurrences of extensive synovial chondromatosis in the knee refractory to multiple operations. Based on follow-up MRI scans and clinical findings, the disease process was halted with no progression seen over 5 years.

Adult↗

Information for gene networks in inner ear development: a study centered on the transcription factor gata2.

The search for molecular mechanisms to stimulate sensory regeneration in the mammalian inner ear is commonly based upon developmental studies. This has revealed many genes that regulate the differentiation of sensory cells. A major challenge is to place these genes into the context of functional networks that describe developmental processes more fully and increase the chances of identifying useful therapeutic targets. We used a novel approach to identify genes that are functionally related to the transcription factor gata2. Temporal profiles of gene expression were derived from three conditionally immortal cell lines and clustered to those of gata2 by applying the gamma model for oligonucleotide signals, a statistical method that allows quantitative analysis of oligonucleotide array data. We derived an objective list of 28 genes that clustered with gata2 in all three cell lines. A number of these genes have known functional links with gata2. Genes encoding CCAAT/enhancer binding proteins (C/EBP) and signal transducer and activation of transcription 3 (Stat3) are especially interesting as they are known to bind gata proteins directly. The results provide strong evidence that our experimental approach can reveal functional relationships between genes that regulate fundamental processes in the differentiation of sensory cells in the inner ear.

Animals↗

Australia-wide comparison of intensity modulated radiation therapy prostate plans.

The aim of this study was to investigate the ability of Australian centres to produce high-dose intensity modulated radiation therapy (IMRT) prostate plans, and to compare the planning parameters and resultant dose distributions. Five Australian radiation therapy departments were invited to participate. Each centre received an identical 5 mm-slice CT data set complete with contours of the prostate, seminal vesicles, rectum, bladder, femoral heads and body outline. The planning team was asked to produce the best plan possible, using published Memorial Sloan-Kettering Cancer Centre prescription and dose constraints. Three centres submitted plans for evaluation. All plans covered the planning target volume adequately; however, only one plan met all the critical organ dose constraints. Although the planning parameters, beam arrangements and planning systems were different for each centre, the resulting plans were similar. In Australia, IMRT for prostate cancer is in the early stages of implementation, with routine use limited to a few centres.

Australia↗

Surgical management of colorectal cancer in south-western Sydney 1997-2001: a prospective series of 1293 unselected cases from six public hospitals.

BACKGROUND: The aim of the present study is to provide local data for the management of colorectal cancers in the south-western Sydney health area from 1997 to 2001. METHODS: The data were collected prospectively. Follow up was conducted in late 2001 and early 2002. Data were cross-validated with hospital and area databases and with data from the New South Wales Registry of Births, Deaths and Marriages. RESULTS: This was an unselected series of 1293 patients from 36 surgeons; 16.5% of patients presented as emergencies. Only 3% presented as a result of bowel cancer screening. Of the 1293 patients, 1270 received an operation. There were 598 elective colonic resections with the mortality rate of 1.2%, reoperation rate of 2.7% and anastomotic leak rate of 0.8%. For the 410 elective rectal resections, the rates were 2.9%, 2.7% and 1.2%, respectively. For the 290 emergency operations, the rates were much worse at 7.7%, 6.6% and 4.8%, respectively. The corrected overall 3-year survival rate was 64%. For Dukes' A, B, C and D, the figures were 94%, 87%, 61% and 7%, respectively. CONCLUSIONS: Colorectal cancer is a major cause of mortality and morbidity in our community. Very few bowel cancers were discovered at the asymptomatic stage. This paper strongly supports community bowel cancer screening and early diagnosis. The local database has provided a rich source of information to benchmark management and outcomes of bowel cancer patients treated in the South Western Sydney Area Health Service. An area-wide computer network with online data input facilities at individual workplaces will improve data integrity and data collection efficiency.

Adult↗

Direct comparison of 18F-fluorodeoxyglucose coincidence gamma camera tomography with gallium scanning for the staging of lymphoma.

BACKGROUND: The present study compared the performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) using a coincidence dual-head gamma camera (FDG Co-PET) with 67gallium scinti graphy (GS) in pretreatment staging of lymphoma. METHODS: A total of 46 patients underwent FDG Co-PET, computed tomography (CT) scanning and GS for pretreatment staging of lymphoma (40 newly diagnosed and recurrence) between November 1997 and December 1999. RESULTS: Histological subgroups comprised low grade (8 patients), intermediate grade (25) high-grade (3) non-Hodgkin's lymphoma and Hodgkin's disease (10). Based on clinical assessment, CT scan findings and biopsy, 100 nodal sites and 15 extra-nodal sites were deemed positive. FDG Co-PET was superior to GS in nodal site positivity rate (97%vs 79%, P < 0.0001). Compared with GS, FDG Co-PET detected 39 more abnormal sites in 22 patients (48%), of which 28 sites were validated by biopsy, CT and/or progress FDG Co-PET scanning. There was only one proven false negative FDG site in the spleen. CT + FDG Co-PET led to upstaging in 2 patients (4%), compared to CT + GS. CONCLUSION: FDG Co-PET shows potential for providing an accurate means for pretreatment staging of lymphoma and can detect extra sites of disease activity compared to GS.

Adult↗

Differentiation of an auditory neuronal cell line suitable for cell transplantation.

The auditory neuroblast cell line US/VOT-N33 (N33), which is conditionally immortal, was studied as an in vitro model for the differentiation of spiral ganglion neurons (SGNs) and as a candidate for cell transplantation in rodents. It expresses numerous molecular markers characteristic of auditory neuroblasts, including the transcription factors GATA3, NeuroD, Brn3a and Islet1, as well as the neuronal cytoskeletal protein beta3-tubulin. It displays active migratory behaviour in vitro and in vivo. In the presence of the fibroblast growth factors FGF1 or FGF2 it differentiates bipolar morphologies similar to those of native SGNs. In coculture with neonatal cochlear tissue it is repelled from epithelial surfaces but not from native SGNs, alongside which it extends parallel neuronal processes. When injected into the retina in vivo, EGFP-labelled N33 cells were traced for 1-2 weeks and migrated rapidly within the subretinal space. Cells that found their way into the retinal ganglion cell layer extended multiple processes but did not express beta3-tubulin. The ability of N33 to migrate, to differentiate, to localize with native SGNs in vitro and to survive in vivo suggests that they provide an effective model for SGN differentiation and for cell transplantation into the ear.

Animals↗

Australian and New Zealand three-dimensional conformal radiation therapy consensus guidelines for prostate cancer.

Three-dimensional conformal radiation therapy (3DCRT) has been shown to reduce normal tissue toxicity and allow dose escalation in the curative treatment of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group initiated a consensus process to generate evidence-based guidelines for the safe and effective implementation of 3DCRT. All radiation oncology departments in Australia and New Zealand were invited to complete a survey of their prostate practice and to send representatives to a consensus workshop. After a review of the evidence, key issues were identified and debated. If agreement was not reached, working parties were formed to make recommendations. Draft guidelines were circulated to workshop participants for approval prior to publication. Where possible, evidence-based recommendations have been made with regard to patient selection, risk stratification, simulation, planning, treatment delivery and toxicity reporting. This is the first time a group of radiation therapists, physicists and oncologists representing professional radiotherapy practice across Australia and New Zealand have worked together to develop best-practice guidelines. These guidelines should serve as a baseline for prospective clinical trials, outcome research and quality assurance.

Australia↗

Three-dimensional conformal radiotherapy in the treatment of prostate cancer in Australia and New Zealand: Report on a survey of radiotherapy centres and the proceedings of a consensus workshop.

There is an increasing use of 3-D conformal radiotherapy (3DCRT) in the radiotherapeutic management of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group carried out a survey of Australian and New Zealand radiotherapy centres in the preparation of a consensus workshop. Of the 19 centres that were represented, there were 24 radiation oncologists, 16 radiation therapists and 12 medical physicists. The survey collected demographic information and data on the practices undertaken at those centres when delivering curative radiotherapy in the treatment of prostate cancer. There was much variation in the delivery of treatment in the areas of patient set-up, contouring of target volumes and organs of interest during computer planning, the techniques and the dose constraints used in these techniques, the use of adjuvant androgen deprivation therapy and the quality assurance processes used in monitoring effects of treatment. This variability reflects the range of data in the published literature. Emerging trends of practices were also identified. This is a first report on a multi-disciplinary approach to the development of guidelines in 3DCRT of prostate cancer.

Australia↗

The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial.

PURPOSE: Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. METHODS AND MATERIALS: A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. RESULTS: One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). CONCLUSION: This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation proctitis and may increase acute bleeding. The cause of the increased bleeding in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic evaluation, is currently being performed on this cohort of patients.

Administration, Oral↗

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.

Adenocarcinoma↗

Managing malignant spinal cord compression.

BACKGROUND: Spinal malignancy can present as low back pain and accounts for most cases of spinal cord compression (SCC). OBJECTIVE: To assist the clinician in the diagnosis of malignant SCC and to increase awareness of various treatment modalities. A clinical approach for the workup of patients with 'metastatic carcinoma of unknown primary' is also outlined. DISCUSSION: It is important to diagnose SCC early and initiate urgent treatment to obtain optimum patient outcomes. Further management includes workup for the primary tumour source if unknown.

Combined Modality Therapy↗

Localization of temporal lobe epileptic foci with iodine-123 iododexetimide cholinergic neuroreceptor single-photon emission computed tomography.

There is evidence suggesting that muscarinic cholinergic neuroreceptors (mChR) are reduced at seizure foci. Iodine-123 (I-123) iododexetimide (IDEX) single-photon emission computed tomography (SPECT) permits in vivo imaging of mChR. We assessed 23 patients with temporal lobe epilepsy (TLE) undergoing preoperative assessment. Regions of interest were placed over the amygdala, hippocampus, and lateral temporal cortex on IDEX SPECT images. Eighteen patients had unilateral TLE. In these, IDEX binding in the ipsilateral hippocampal region was reduced by 19.1 +/- 12%. This was significantly greater than blood flow asymmetry (p < 0.02 by Wilcoxon's signed-rank test). Changes were less marked in the amygdala (11.3 +/- 6.4%) and lateral cortex (7.6 +/- 12.1%). Blinded visual analysis gave correct localization in 14 (78%) patients, and hexamethylpropylenamine oxide (HMPAO) SPECT gave correct localization in 50%. MRI revealed hippocampal sclerosis in 13 (72%) patients and was normal in 5 patients. Of the latter group, four were correctly localized by IDEX. This study confirms that mChR receptors are altered in medial temporal lobe structures in TLE. IDEX SPECT appears to be superior to interictal HMPAO SPECT and complimentary to MRI for seizure focus localization.

Adult↗