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Biomedical subjects

C D Collins

Publications and source records attributed to C D Collins.

At least 19 recordsLinked to original sources
PubMed2006

The application of genomic and proteomic technologies in predictive, preventive and personalized medicine.

The long asymptomatic period before the onset of chronic diseases offers good opportunities for disease prevention. Indeed, many chronic diseases may be preventable by avoiding those factors that trigger the disease process (primary prevention) or by use of therapy that modulates the disease process before the onset of clinical symptoms (secondary prevention). Accurate prediction is vital for disease prevention so that therapy can be given to those individuals who are most likely to develop the disease. The utility of predictive markers is dependent on three parameters, which must be carefully assessed: sensitivity, specificity and positive predictive value. Specificity is important if a biomarker is to be used to identify individuals either for counseling or for preventive therapy. However, a reciprocal relationship exists between sensitivity and specificity. Thus, successful biomarkers will be highly specific without sacrificing sensitivity. Unfortunately, biomarkers with ideal specificity and sensitivity are difficult to find for many diseases. One potential solution is to use the combinatorial power of a large number of biomarkers, each of which alone may not offer satisfactory specificity and sensitivity. Recent technological advances in genetics, genomics, proteomics, and bioinformatics offer a great opportunity for biomarker discovery. The newly identified biomarkers have the potential to bring increased accuracy in disease diagnosis and classification, as well as therapeutic monitoring. In this review, we will use type 1 diabetes (T1D) as an example, when appropriate, to discuss pertinent issues related to high throughput biomarker discovery.

Biomarkers↗
PubMed2006

A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer.

PURPOSE: Multi-drug resistance mediated by ATP-binding cassette trans-membrane protein pumps is an important cause of cancer treatment failure. Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti-cancer activity of substrate chemotherapeutic agents, e.g. anthracyclines. METHODS: We conducted a dose-escalating, single arm, prospective, open label, non-randomised phase I trial of epirubicin (75 mg/m(2)) in combination with escalating oral doses of sulindac (0-800 mg) in patients with advanced cancer to identify an appropriate dose of sulindac to use in future resistance studies. Anthracycline and sulindac pharmacokinetics were studied in cycles 1 and 3. RESULTS: Seventeen patients (8 breast, 3 lung, 2 bowel, 1 melanoma, 1 renal, 1 ovarian and 1 of unknown primary origin, 16/17 having had prior chemotherapy) were enrolled. Eight patients received a full six cycles of treatment; 14 patients received three or more cycles. Dose-limiting toxicity was observed in two patients at 800 mg sulindac (1 renal impairment, 1 fatal haemoptysis in a patient with advanced lung cancer), and sulindac 600 mg was deemed to be the maximum tolerated dose. Sulindac had no effect on epirubicin pharmacokinetics. Among 15 patients with evaluable tumour, two partial responses were seen (malignant melanoma and breast cancer). Four others had prolonged stable disease. CONCLUSION: Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Pelvic radiotherapy in patients with hydronephrosis in stage IIIB cancer of the cervix: renal effects and the optimal timing for urinary diversion?

BACKGROUND AND PURPOSE: Many patients with Stage IIIB cervix cancer (Ca) and hydronephrosis will require ureteral stenting. The timing is important as delays or prolonged overall treatment times adversely affect outcome. Our aim was to measure the effect of pelvic radiotherapy (R/T) on renal function and identify a subset of patients at high risk of acute urinary obstruction during R/T. PATIENTS AND METHODS: From 1/1/2000 to 1/1/2002, all patients with Stage IIIB cervix Ca and hydronephrosis were analysed retrospectively. To quantify the impact of pelvic R/T, all eligible patients from 1/7/2002-1/7/2004 had prospectively recorded baseline biochemistry, creatinine clearance and renal ultrasounds; these were repeated weekly to detect any change in renal function or degree of hydronephrosis. RESULTS: 13 eligible patients were analysed retrospectively, 5 with unilateral hydronephrosis with 40% requiring urinary diversion (UD). 8 had bilateral hydronephrosis, with 75% requiring UD; 50% before R/T and 35% during R/T. Average creatinine clearance (CrCl) was 74 mL/min (1.24 mL/s) in unilateral hydronephrosis , bilateral = 52 mL/min (0.87 mL/s), in those stented during R/T it was < 40 mL/min (0.67 mL/s). The resulting break in R/T was 6 and 19 days. In the prospective study, 5 patients were eligible and 4 consented. 75% had unilateral hydronephrosis and did not require UD with an average CrCl = 71 mL/min (1.19 mL/s). 1 patient with bilateral hydronephrosis had a CrCl of < 20 mL/min (0.33 mL/s) with bilateral stents placed before R/T. CONCLUSIONS: Patients with bilateral hydronephrosis and a low CrCl < 50 mL/min (0.84 mL/s) should be considered for elective UD prior to R/T. Pelvic R/T did not induce any deterioration in renal function or degree of hydronephrosis.

Acute Kidney Injury↗
PubMed2004

The deposition and translocation of methyl iodide by crops.

Organic forms of radioactive iodine are released during routine and accidental releases from the nuclear industry. Methyl iodide is often the predominant species in these releases. This paper describes the results of a study to determine the deposition, allocation, and loss of radioiodine after crops of bean, carrot, and cabbage were exposed to CH3 125I. The deposition velocity ranged from 0.14-7.10 x 10(-4) cm s(-1), which is in line with previous studies. Translocation of radioiodine away from the leaves to other crop components was observed post exposure. The partition of radioiodine was to those crop components growing most actively at the time of exposure. This finding contradicts some previous studies and will have implications for dose assessments. Losses of radioiodine were only observed as a consequence of leaf fall. The consequences of these findings for the modeling the movement of radioiodine in crops following the deposition of methyl iodide are discussed.

Air Pollutants, Radioactive↗
PubMed2004

Reduction in the proportion of patients with colorectal cancer presenting as an emergency following the introduction of fast-track flexible sigmoidoscopy: a three-year prospective observational study.

OBJECTIVE: We established a fast-track flexible sigmoidoscopy service to meet the two-week target for colorectal cancer, and have performed a prospective observational study over three years to assess its impact on the proportion of patients with colorectal cancer presenting as an emergency. METHODS: The fast-track system was established on 1 November 1999 using six screening criteria to select high-risk patients. Data on all high-risk patients referred through the fast-track system and all patients diagnosed with colorectal cancer were recorded prospectively in two time periods: six months before fast-track (1 November 1998 to 30 April 1999, Period 1) and three years following fast-track (1 November 1999 to 31 October 2002, Period 2). RESULTS: In Period 2, 2294 fast-track referrals were received. A total of 635 cases (321 male, 314 female) of colorectal cancer were diagnosed in Period 2 vs. 84 cases (43 male, 41 female) in Period 1. In Period 1, 30 patients with colorectal cancer (35.7% of the total) presented as an emergency vs. 165 patients (25.9%) in Period 2 (P = 0.059, chi(2)test). CONCLUSION: Introduction of a fast-track service to meet the two-week target has resulted in a trend towards fewer emergency presentations with colorectal cancer.

Appointments and Schedules↗
PubMed2003

Intradermal radioisotope injection optimises sentinel lymph node identification in breast cancer.

AIM: Currently there is no consensus on the optimal technique for sentinel lymph node (SLN) identification in patients with breast cancer. The aim was to compare the efficacy of intraparenchymal and intradermal isotope injection in sentinel lymph node mapping for breast cancer. METHODS: One hundred and twenty-five patients with histologically confirmed invasive breast cancer underwent SLN mapping using radioisotope and isosulphan blue dye followed by a back-up axillary dissection. The first 80 patients had intraparenchymal (IP) injection of radioisotope given in four portions around the tumor. The remaining 45 patients had an intradermal (ID) injection given at a single site over the tumour. Both groups had isosulphan blue dye injected around the tumour. Sentinel node(s) were identified using a combination of lymphoscintigraphy, blue dye and an intra-operative hand held gamma probe. RESULTS: The preoperative lymphoscintigram (LSG) demonstrated a SLN significantly more often in the ID isotope group compared to the IP isotope group (P=0.002). A combination of blue dye and isotope successfully located the SLN in 96% of the intraparenchymal group and 100% of the intradermal group. CONCLUSION: Our results suggest that intradermal isotope injection in combination with intraparenchymal blue dye optimises the localization of the sentinel lymph node in breast cancer.

Axilla↗
PubMed2002

The importance of the short-term leaching dynamics of wood preservatives.

The potential environmental impacts from the use of treated timber in aquatic areas is under scrutiny as a result of environmental legislation and reports of the deleterious environmental effects around treated structures. In this study leaching experiments of up to 3 weeks duration were conducted on two species of chromated copper arsenate treated timber, dried for different periods of time. Increased drying time significantly reduced leaching of Cr and As. The addition of a synthetic humic acid increased leaching of Cu and As, but reduced leaching of Cr. Putative risk assessments conducted using short-term copper leaching data suggested protocol design may influence decisions made regarding the environmental acceptability of such preservatives.

Arsenates↗
PubMed2001

Deposition of gaseous radionuclides to fruit.

14C, 35S and 3H are released to the environment during the operation of gas-cooled reactors and were identified as radionuclides of interest by the BIOMASS Fruits Working Group. This paper provides a review of the deposition, uptake, allocation and loss of these radionuclides with respect to fruit and conceptual models for gaseous radionuclides. It is concluded that the mechanisms for the uptake of CO35S, HTO and 14CO2 are well understood and that their deposition velocities have been quantified. There is also a reasonable body of work on the translocation of 14C once in the crop, but much less for 35S and 3H, which are considered to follow source-sink relationships. The loss rates of the three radionuclides show large differences, with tritium lost rapidly in the form of HTO but retained longer when converted to OBT. The losses of 14C are less and those of sulphur are minimal post fixation. When fruit crops alone are considered, the quantity of information is further reduced but predictions on possible behaviour of these radionuclide species can be made from the current knowledge.

Air Movements↗
PubMed2001

Experimental studies on the deposition to crops of radioactive gases released from gas-cooled reactors--III. Carbon-14 dioxide.

Experimental studies were performed under controlled environmental conditions to determine the deposition and subsequent allocation of carbon-14, following a short-term fumigation of major British crops with 14CO2. The deposition velocities varied between 0.075 and 1.32 cm3 g-1 s-1 and 0.0008 and 0.157 cm s-1 on weight and area bases, respectively. The primary sites of deposition were leaves, although other organs, e.g. ears and pods, were increasingly important as the crops developed. Activity was allocated post-deposition to those crop components actively growing at the time of deposition. The allocation was generally completed 24 h after fumigation, the exceptions to this being those crops where reproductive organs developed after the fumigation. A single exponential function was the best fit for the loss of activity from the crops. The data are discussed in the context of modelling carbon-14 contamination of crops following radioactive discharges.

Carbon Dioxide↗
PubMed2001

Leaching of chromated copper arsenate wood preservatives: a review.

Recent studies have generated conflicting data regarding the bioaccumulation and toxicity of leachates from preservative-treated wood. Due to the scale of the wood preserving industry, timber treated with the most common preservative, chromated copper arsenate (CCA), may form a significant source of metals in the aquatic environment. The existing literature on leaching of CCA is reviewed, and the numerous factors affecting leaching rates, including pH, salinity, treatment and leaching test protocols are discussed. It is concluded from the literature that insufficient data exists regarding these effects to allow accurate quantification of leaching rates, and also highlights the need for standardised leaching protocols.

Arsenates↗
PubMed2001

The assessment of irradiated bladder carcinoma using dynamic contrast-enhanced MR imaging.

AIM: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) in distinguishing residual or recurrent tumour from radiation change in patients with bladder carcinoma. MATERIALS AND METHODS: Forty patients with biopsy proven bladder carcinoma were imaged before and at 4 and 12 months after radiotherapy (XRT) using conventional and dynamic contrast-enhanced magnetic resonance imaging at 0.5 Tesla. An enhancement of >1.54 times above baseline at 80 s post-contrast injection proved a reliable indicator of tumour before radiotherapy and was therefore applied to the assessment of patients after XRT. Conventional MR images and dynamic enhancement profiles (DEPs) from the site of previous tumour were scored by three radiologists for the presence of tumour at 4 and 12 months after XRT. Findings were compared with cystoscopic biopsy. RESULTS: Dynamic contrast-enhanced magnetic resonance imaging had negative predictive values of 100% and 93% for tumour recurrence at 4 and 12 months, respectively. The positive predictive values, sensitivity and specificity were 48, 100 and 48% at 4 months and 50, 80 and +76% at 12 months post XRT, respectively. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging may prove reliable in excluding the presence of persistent or recurrent tumour up to 12 months after XRT.

Contrast Media↗
PubMed2000

Benzene accumulation in horticultural crops.

In this study apple, blackberry and cucumber crops were exposed to elevated levels of benzene under controlled conditions. Benzene was retained in fruits of all crops, but only accumulated in leaves of blackberries and apples. The retention by cucumber fruits is suggested to result from the longer pathway for the desorption of benzene as a consequence of their increased tissue depth compared to leaves. The process of accumulation in blackberry and apple leaves is unknown. The ingestion of benzene via the food-chain pathway on the basis of this study is concluded not to be significant.

Benzene↗
PubMed2000

Relationship of MRI and clinical staging to outcome in invasive bladder cancer treated by radiotherapy.

AIM: To compare MRI and clinical staging of invasive bladder cancer prospectively and identify additional prognostic features on MRI before radiotherapy. METHODS AND MATERIALS: 143 patients with a pathological diagnosis of transitional cell carcinoma underwent MRI (1.0 T) of the abdomen and pelvis before radical radiotherapy. Tumour size, site, degree of infiltration, presence of adenopathy and hydronephrosis were assessed and an appropriate radiological stage assigned. Following radiotherapy all patients received regular cystoscopic follow-up. Date of first relapse and date of death were recorded. RESULTS: The median follow-up was 2.8 years for survivors. Those patients upstaged from T2a clinically to T3b on MRI had a significantly worse outcome (P = 0.0078). In univariate analysis a number of MRI features were significantly associated with adverse outcome: tumour size, circumferential tumour extent, and presence of hydronephrosis (all P < 0.05). After adjustment for clinical T stage and histological grade, all these MRI features and the MRI T stage were found to confer additional prognostic information in predicting early disease relapse and death (P < 0.05). CONCLUSION: This study demonstrates that MRI before radiotherapy provides valuable additional prognostic information compared to clinical staging.

Aged↗
PubMed2000

Magnetic resonance imaging in the management of suspected spinal canal disease in patients with known malignancy.

AIM: The aim of this study was to examine the spectrum of spinal canal disease in patients with known malignancy using magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred and fifty-five patients underwent a total of 159 spinal MRI examinations over a three-year period. Patients were examined using a 1.0T magnet and a phased array surface spine coil. Sagittal T1 weighted spin echo and STIR sequences were routinely employed. Axial T1 and T2 weighted spin echo images were obtained at sites of identified pathology. Contrast enhanced sagittal and axial T1 weighted spin echo images were acquired when the unenhanced appearances did not correlate with the clinical findings or when the images suggested intradural or intramedullary disease. RESULTS: Malignant disease affecting the spinal cord or cauda equina was noted in 104/159 (65%) patients (extradural n= 78, intradural n= 20, intramedullary n= 7); one patient had evidence of both intradural and intramedullary deposits. Multiple levels of extradural cord/cauda equina compression were present in 18/78 patients (23%). The thoracic spine was the most frequently affected (74%). Bone elements were the major component of extradural compression in 11/78 patients (14%). Intradural metastases were multiple in 15/20 patients (75%). Four of the six solitary intramedullary metastases were situated in the conus medullaris. CONCLUSION: Magnetic resonance imaging of the entire spine is the investigation of choice in patients with known malignancy and suspected spinal canal disease. Contrast-enhanced images should be acquired when the unenhanced appearances do not correlate with the clinical findings or when they suggest intradural or intramedullary disease.Loughrey, G. J. (2000). Clinical Radiology55, 849-855.

Adolescent↗
PubMed2000

NHS reforms in the United Kingdom and learning from developing country experience.

The NHS has been the object of much international interest from its inception and through its periodic reforms. However, UK policy-makers have expressed only limited and selective concern for health sector reforms in other countries. This paper seeks to identify key elements of the present process and content of reforms to the UK NHS and examine the extent to which international learning would be important in developing these reforms. Particular emphasis is placed on learning from developing country experience. The paper therefore considers the policy process in the UK, the focus on primary care, the shift from competitive to collaborative strategies in addition to prioritising and planning. Each is considered in relation to developing country experience and the opportunities for learning. The paper concludes by setting out four areas leading to an international opening in NHS policy processes: developing political space in policy making, developing mechanisms for international exchanges, understanding policy context, and broadening international experience and changing values. The notion of a one-way process in international policy learning is rejected: while the South can learn from the North, so too can the North from the South.

Cooperative Behavior↗
PubMed1999

Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine.

Administration, Oral↗