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Biomedical subjects

Richard Cowan

Publications and source records attributed to Richard Cowan.

8 recordsLinked to original sources

The quality of life of men with locally advanced prostate cancer during neoadjuvant hormone therapy: data from the Medical Research Council RT01 trial (ISRCTN 47772397).

OBJECTIVE: To explore patients' quality of life (QoL) during neoadjuvant hormone therapy (HT) using data from the Medical Research Council RT01 trial of standard- (64 Gy/32-fraction) and high- (74 Gy/37-fraction) dose radiotherapy (RT, both given conformally). PATIENTS AND METHODS: Of the 843 patients randomized to the RT01 trial, 316 completed the Functional Assessment Of Cancer Therapy core questionnaire with its additional prostate subscale, and the Short Form-36 Health Survey questionnaire with the University of California-Los Angeles Prostate Cancer Index before HT and again before starting RT. Three predefined QoL hypotheses were generated to focus the analyses. RESULTS: For the three primary QoL analyses there was evidence that sexual functioning deteriorated, urinary function did not change, and there was a slight decline in physical well-being after > or = 3 months of HT. Sensitivity analyses confirmed these findings. Exploratory analyses also suggested that role functioning deteriorated, sleep was more disturbed, and there was an increase in fatigue. However, overall QoL was not reported to be affected and patients indicated an improvement in attitude and satisfaction with treatment. CONCLUSIONS: In this group of men, many of whom reported reduced sexual functioning before treatment, the additional decline during HT seemed to be generally accepted as the price to pay for an appropriate cancer treatment. Nevertheless, these changes need to be discussed with patients before HT is commenced.

Aged↗

The role of language in mathematical development: evidence from children with specific language impairments.

A sample (n=48) of eight-year-olds with specific language impairments is compared with age-matched (n=55) and language matched controls (n=55) on a range of tasks designed to test the interdependence of language and mathematical development. Performance across tasks varies substantially in the SLI group, showing profound deficits in production of the count word sequence and basic calculation and significant deficits in understanding of the place-value principle in Hindu-Arabic notation. Only in understanding of arithmetic principles does SLI performance approximate that of age-matched-controls, indicating that principled understanding can develop even where number sequence production and other aspects of number processing are severely compromised.

Child↗

X-ray volume imaging in bladder radiotherapy verification.

PURPOSE: To assess the clinical utility of X-ray volume imaging (XVI) for verification of bladder radiotherapy and to quantify geometric error in bladder radiotherapy delivery. METHODS AND MATERIALS: Twenty subjects undergoing conformal bladder radiotherapy were recruited. X-ray volume images and electronic portal images (EPIs) were acquired for the first 5 fractions and then once weekly. X-ray volume images were co-registered with the planning computed tomography scan and clinical target volume coverage assessed in three dimensions (3D). Interfraction bladder volume change was described by quantifying changes in bladder volume with time. Bony setup errors were compared from both XVI and EPI. RESULTS: The bladder boundary was clearly visible on coronal XVI views in nearly all images, allowing accurate 3D treatment verification. In 93.5% of imaged fractions, the clinical target volume was within the planning target volume. Most subjects displayed consistent bladder volumes, but 25% displayed changes that could be predicted from the first three XVIs. Bony setup errors were similar whether calculated from XVI or EPI. CONCLUSIONS: Coronal XVI can be used to verify 3D bladder radiotherapy delivery. Image-guided interventions to reduce geographic miss and normal tissue toxicity are feasible with this technology.

Aged↗

Calendrical savants: exceptionality and practice.

The exceptionality of the skills of calendrical savants and the role of practice were investigated. Experiment 1 compared four autistic calendrical savants to Professor Conway, a distinguished mathematician with calendrical skills. Professor Conway answered questions over a greater range of years but some savants knew more calendrical regularities. Experiment 2 studied the development of a calendrical savant's ability to answer date questions for very remote future years. He started by making written calculations and progressed to mental calculation. His variation in response time for remote dates was similar to that for near dates. The findings are consistent with the view that calendrical savants develop their skills through practice.

Adult↗

Physical characteristics of small intestinal submucosa scaffolds are location-dependent.

Using biodegradable scaffolds as an alternative to engineer new tissues has become an attractive candidate in various transplantation protocols. In particular, small intestinal submucosa (SIS), a dense connective matrix harvested from the small intestine, has gained attention due to a number of favorable properties. However, use of SIS is constrained by obtaining reliable, reproducible products in large-scale preparations that affect the regenerative process. To better understand the heterogeneous nature of SIS, this study focused on evaluating the location-dependent alterations in the physical characteristics of the matrices harvested from distal and proximal ends and processed in-house (referred as hand-made). Additionally, results were compared with a commercially available machine-made Cook SIS. Tensile properties during monotonic loading and cyclical loading were compared in wet conditions. Furthermore, permeability of these membranes to urea was analyzed using a custom-built chamber, and the microarchitecture was analyzed via scanning electron microscopy. These results showed that distal samples were more elastic and less permeable to urea relative to other samples. However, permeability in each sample was direction-dependent, that is, mucosal to serosal direction was less permeable compared to sorasal to mucosal direction in all the samples. Cook SIS was more susceptible to cyclical loading and had a shorter range of load carrying capacity. In summary, results show that physical characteristics of SIS are location-dependent.

Absorbable Implants↗

Safety and tolerability of PCK3145, a synthetic peptide derived from prostate secretory protein 94 (PSP94) in metastatic hormone-refractory prostate cancer.

BACKGROUND: The safety, tolerability, and pharmacokinetic and preliminary efficacy of PCK3145 were determined in patients with metastatic hormone-refractory prostate cancer. PATIENTS AND METHODS: PCK3145 was administered in ascending doses of 5, 20, 40, and 80 mg/m2 3 times per week for 4 weeks to cohorts of 4 patients. Dose escalation was based on dose-limiting toxicity (DLT). Pharmacokinetic profiles, tumor burden, and tumor markers (including prostate-specific antigen [PSA] and matrix metalloproteinase-9 [MMP-9] levels) were assessed. Sixteen patients received PCK3145. The median age was 66 years, and the median PSA level was 232.5 microg/L. A total of 32 cycles of therapy were administered. RESULTS: The most common adverse events reported were pain and nausea. The only DLT was a grade 4 cardiac arrhythmia in a patient treated at the 80-mg/m2 dose level. Pharmacokinetic analysis using a 2-compartment model indicated that the mean area under the curve values increased as the dose range increased, and the mean elimination half-life ranged from 0.35 hours to 1.45 hours. The best tumor response was stable disease in 10 patients and progressive disease in 5 patients. No PSA responses were observed, but 1 patient showed a marked reduction in PSA of 41% at cycle 2. A substantial reduction in MMP-9 levels was observed in patients with baseline levels of MMP-9 > 100 microg/L. CONCLUSION: PCK3145 was safe and well tolerated at all doses. Efficacy observations were encouraging, and the biologic activity of PCK3145 in reducing MMP-9 level may suggest a potential role of this peptide in the regulation of metastatic tumor growth.

Adenocarcinoma↗

Telephone first post-intervention follow-up for men who have had radical radiotherapy to the prostate: evaluation of a novel service delivery approach.

The increasing prevalence of prostate cancer places pressure on services, leading to questions about how best to configure services, so as to maintain quality and best utilise the skills of the multi-disciplinary team. There have been positive evaluations of specialist nursing roles, nurse-led service provision and telephone consultations, leading us to consider whether telephone follow-up led by a specialist nurse might be an acceptable alternative to traditional follow-up in hospital-based out-patient clinics for patients receiving radical radiotherapy for prostate cancer. Thirty-six men were included in a pilot introduction of telephone follow-up, evaluated via a questionnaire survey. The evaluation explored patients' satisfaction with practical arrangements; satisfaction with the nurse; acceptability of telephone follow-up and acceptability of this being nurse-led. Patients reported high levels of satisfaction with practical arrangements. Thirty-five patients considered the nurse to be knowledgeable and found nurse-led care acceptable. Only one patient was unhappy with telephone follow-up, whilst 27 were "very happy". Only one patient felt that telephone follow-up was poorer than traditional follow-up, whilst 27 found it "as good" and three "better". Particular advantages were reported in terms of convenience and time savings. Telephone follow-up appears to have potential for this patient group and merits wider, research-based consideration.

Aftercare↗

A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer.

The use of definitive radiotherapy for treatment of invasive bladder cancer has the advantage of preserving bladder function, but tumour regression is only achieved in approximately 40-50% of patients. Knowledge of the molecular basis of sensitivity to ionizing radiation and identification of potential molecular predictors will provide useful information regarding patient response and thus help clinicians to individualize treatment. The recent application of cDNA expression array technology provides a useful tool to investigate hundreds or even thousands of genes in a single experiment. In our study, we have used the Atlas human stress cDNA array trade mark to investigate the expression profile of stress-related and DNA repair genes in a radioresistant bladder carcinoma cell line (MGH-U1) and its radiosensitive subclone (S40b). This provides an ideal situation to study genes related to radiation because the genotypes of both cell lines are basically similar and differential changes detected are likely to be related to the different radiosensitivity phenotype. Of 234 genes blotted on the array, 3 genes (Heat shock protein 90, Heat shock protein 27 and Nicotinamide N-methyl transferase) showed consistent downregulation in the radiosensitive clone in 2 independent experiments. These results were further confirmed for HSP27 and NNMT using Sybr Green I-based real-time QRT-PCR. The role of heat shock proteins (HSPs) in response to radiation remains to be determined; however, the results of our present work suggest a possible role of HSP27 in determining radiosensitivity. Our study also opens avenues for the investigation of genes, such as NNMT, which has not previously been linked to response to radiation.

Base Sequence↗