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Biomedical subjects

G Wilson

Publications and source records attributed to G Wilson.

At least 19 recordsLinked to original sources
PubMed2007

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a phase I study.

The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24-79) years, World Health Organisation performance status 0-2 and median four marker lesions, received irinotecan 180 mg m(-2) on day 1, oxaliplatin 85-100 mg m(-2) on day 15 and UFT 200-300 mg m(-2) day(-1) with LV 90 mg day(-1), days 1-21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 300 mg m(-2) day(-1)), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 250 mg m(-2) day(-1)). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m(-2) on day 1, oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) day(-1) with LV 90 mg day(-1) on days 1-21 of a 28-day cycle for future studies.

Administration, Oral↗
PubMed2007

Shifts in metabolic parameters surrounding glucose homoeostasis resulting from tricyclic antidepressant therapy: implications of insulin resistance?

This study displayed the physiological effects the tricyclic antidepressants amitriptyline or trimipramine have on glucose homoeostasis in male Wistar rats. An insulin secreting cell line (INS-1) was also used to determine effects tricyclic antidepressants have on insulin secretion and insulin displacement. Thirty rats each received a 1 mg kg-1 dose of amitriptyline or trimipramine for a period of 14 weeks; another 14 rats served as the control group. Blood glucose, serum insulin and muscle and liver glycogen levels were determined. Kidney, liver and muscle insulin degradation was measured and compared with insulin degrading enzyme concentrations in the latter two tissues. INS-1 cells were used to determine the effect 1 microM amitriptyline has on insulin secretion. Displacement studies for [3H]glibenclamide by amitriptyline or trimipramine were undertaken on INS-1 cells. A significant increase in blood glucose (P<0.01) was found for both test groups after 6 and 14 weeks of receiving the medication, which may be related to a significant decrease in liver and muscle glycogen levels (P<0.001). Serum insulin levels remained unchanged, although a significant increase in insulin degradation was observed in the muscle, liver and kidney, which may be related to a significant increase in insulin degrading enzyme (P<0.001) that was found. A significant increase in insulin secretion was observed for the INS-1 cells treated with amitriptyline, although no significant displacement for the [3H]glibenclamide was evident for amitriptyline or trimipramine. The significant alterations in glucose homoeostasis observed, as well as the significant changes associated with insulin secretion and degradation associated with amitriptyline or trimipramine treatment, imply that prolonged use of these medicines may lead to insulin resistance and full blown diabetes.

Amitriptyline↗
PubMed2006

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

Adult↗
PubMed2005

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

Carcinogens↗
PubMed2005

Quantification of secondary CPP insult severity in paediatric head injured patients using a pressure-time index.

This paper describes and validates a new Cumulative Pressure-Time Index (CPT) which takes into account both duration and degree of cerebral perfusion pressure (CPP) derangement and determines critical thresholds for CPP, in a paediatric head injury dataset. Sixty-six head-injured children, with invasive minute-to-minute intracranial pressure (ICP) and blood pressure monitoring, had their pre-set CPP derangement episodes (outside the normal range) identified in three childhood age-bands (2-6, 7-10, and 11-16 years) and global outcome assessed at six months post injury. The new cumulative pressure-time index more accurately predicted outcome than previously used summary measures and by varying the threshold CPP values, it was found that these physiological threshold values (< or = 48, < or = 52 and < or = 56 mmHg for 2-6, 7-10, and 11-16 years respectively) best predicted brain insult in terms of subsequent mortality and morbidity.

Adolescent↗
PubMed2004

Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer.

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.

Adult↗
PubMed2004

Patients' perceptions of treatment with anti-TNF therapy for rheumatoid arthritis: a qualitative study.

OBJECTIVES: Anti-tumour necrosis factor (anti-TNF) therapy is a highly effective treatment for rheumatoid arthritis (RA), as documented using standard outcome measures in clinical trials. Anecdotal experience suggests health benefits for patients other than those measured in this way. We wished to explore Patients' experience of and views about this treatment and the British Society for Rheumatology Biologics Registry (BSR BR) process. METHODS: Separate focus groups for patients treated with infliximab (n = 7) and etanercept (n = 12) were undertaken. They were taped and transcribed verbatim, analysed and subjected to peer review and themes were identified. RESULTS: Five main themes were identified: expectations of treatment, experience of treatment and its effects, concerns about taking a new class of drug, views about the BSR Biologics Registry process and costs. CONCLUSIONS: Patients' experience of anti-TNF therapy was good, particularly in terms of physical function and well-being, although it did not live up to the very high expectations of some patients. The BSR BR process caused initial apprehension but patients had personal and altruistic reasons for being happy to comply with monitoring requirements. Qualitative methods add to our understanding of the effects of anti-TNF therapy for people with RA.

Adult↗
PubMed2004

Removal of ocular artifacts from electro-encephalogram by adaptive filtering.

The electro-encephalogram (EEG) is useful for clinical diagnosis and in biomedical research. EEG signals, however, especially those recorded from frontal channels, often contain strong electro-oculogram (EOG) artifacts produced by eye movements. Existing regression-based methods for removing EOG artifacts require various procedures for preprocessing and calibration that are inconvenient and time-consuming. The paper describes a method for removing ocular artifacts based on adaptive filtering. The method uses separately recorded vertical EOG and horizontal EOG signals as two reference inputs. Each reference input is first processed by a finite impulse response filter of length M (M = 3 in this application) and then subtracted from the original EEG. The method is implemented by a recursive least-squares algorithm that includes a forgetting factor (lambda = 0.9999 in this application) to track the non-stationary portion of the EOG signals. Results from experimental data demonstrate that the method is easy to implement and stable, converges fast and is suitable for on-line removal of EOG artifacts. The first three coefficients (up to M = 3) were significantly larger than any remaining coefficients.

Algorithms↗
PubMed2004

Weight changes, medical complications, and performance during an Ironman triathlon.

BACKGROUND: Subjects exercising without fluid ingestion in desert heat terminated exercise when the total loss in body weight exceeded 7%. It is not known if athletes competing in cooler conditions with free access to fluid terminate exercise at similar levels of weight loss. OBJECTIVES: To determine any associations between percentage weight losses during a 224 km Ironman triathlon, serum sodium concentrations and rectal temperatures after the race, and prevalence of medical diagnoses. METHODS: Athletes competing in the 2000 and 2001 South African Ironman triathlon were weighed on the day of registration and again immediately before and immediately after the race. Blood pressure and serum sodium concentrations were measured at registration and immediately after the race. Rectal temperatures were also measured after the race, at which time all athletes were medically examined. Athletes were assigned to one of three groups according to percentage weight loss during the race. RESULTS: Body weight was significantly (p<0.0001) reduced after the race in all three groups. Serum sodium concentrations were significantly (p<0.001) higher in athletes with the greatest percentage weight loss. Rectal temperatures were the same in all groups, with only a weak inverse association between temperature and percentage weight loss. There were no significant differences in diagnostic indices of high weight loss or incidence of medical diagnoses between groups. CONCLUSIONS: Large changes in body weight during a triathlon were not associated with a greater prevalence of medical complications or higher rectal temperatures but were associated with higher serum sodium concentrations.

Blood Pressure↗
PubMed2003

Carcinosarcoma of the ovary.

We report our experience in the management of patients with carcinosarcoma of the ovary, a rare but aggressive variant of ovarian cancer. Forty patients were treated at a single centre, which is the largest reported series. The median age at diagnosis was 65 years (range 45-86) and the median Karnofsky performance (KP) status was 70. Thirty-two patients (80%) presented with FIGO stage III or IV disease. Twenty-four had heterologous and 14 homologous carcinosarcoma on review of histopathology, but there was no significant difference in survival between these groups (P=0.28). Twenty-seven of the 40 patients had bulk residual disease present after surgery and this was associated with a worse prognosis (P=0.045). Chemotherapy was given to 32 patients (80%) of whom 26 (81%) received platinum-based regimens. Of these 32 patients, three (9.4%) achieved a complete response (CR), 10 (31%) a partial response (PR), five (16%) had stable disease, 10 (31%) had progressive disease and four were not assessable. Of the 19 patients who had a CR, PR or stable disease after chemotherapy or were unevaluable (stage Ic), the median survival was 29.6 months. Currently, seven patients are still alive although one has cancer. The overall censored median survival was 8.7 months after a median follow-up of 34 months, and the 1- and 5-year survival were 40 and 7.5%, respectively.

Aged↗
PubMed2002

A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer.

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified 'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of 400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48 h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial.

Adenocarcinoma↗
PubMed2002

Paediatric liver transplantation [corrected] in Melbourne: the first 50 patients.

To report the outcomes of the first 50 paediatric patients who have undergone liver transplantation (LT) at the Victorian Liver Transplant Unit, a retrospective review of case records was carried out. From December 1988 to December 2000, 108 patients 18 years or younger were referred for LT; 50 of these underwent a total of 53 transplants. The most common indications were biliary atresia (32%), metabolic disease (26%), and acute hepatic necrosis (26%). The majority of deaths (6/7) occurred in the 1st week after LT. The actuarial survival at 1 year was 88% (95% CI 75% to 94%) and at 10 years 85% (95% CI 71% to 93%). Survival rates were highest for children aged 3 to 14 years (95%) and lowest in those weighing less than 8 kg at the time of LT (66%). All 43 survivors are attending age-appropriate activities including kindergarten, school, and employment. The survival of patients undergoing LT in this unit compares favourably with those recorded by the Australia and New Zealand Transplant Registry and is commensurate with that reported by larger paediatric transplant programs overseas.

Adolescent↗
PubMed2002

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation.

Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1-N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88 +/- 4%) than in the CF (57+/- 9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60 +/- 10% vs 46 +/- 9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. T(pot) showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of T(pot) as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between T(pot) and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively.

Adult↗