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C Parker

Publications and source records attributed to C Parker.

At least 19 recordsLinked to original sources
PubMed2007

Perspectives on ethics.

In his recent paper about understanding ethical issues, Boyd suggests that traditional approaches based on principles or people are understood better in terms of perspectives, especially the perspective-based approach of hermeneutics, which he uses for conversation rather than controversy. However, we find that Boyd's undefined contrast between conversation and controversy does not point to any improvement in communication: disputes occur during conversation and controversy may be conducted in gentle tones. We agree with Boyd, that being prepared to listen and learn are excellent attitudes, but his vague attempts to establish these and similar virtues in hermeneutic theory are not plausible. Additionally, the current controversy about the use of human embryos in stem cell therapy research shows Boyd missing the opportunity to illustrate how conversation would improve understanding.

Communication↗
PubMed2006

Comparative genomics of the lactic acid bacteria.

Lactic acid-producing bacteria are associated with various plant and animal niches and play a key role in the production of fermented foods and beverages. We report nine genome sequences representing the phylogenetic and functional diversity of these bacteria. The small genomes of lactic acid bacteria encode a broad repertoire of transporters for efficient carbon and nitrogen acquisition from the nutritionally rich environments they inhabit and reflect a limited range of biosynthetic capabilities that indicate both prototrophic and auxotrophic strains. Phylogenetic analyses, comparison of gene content across the group, and reconstruction of ancestral gene sets indicate a combination of extensive gene loss and key gene acquisitions via horizontal gene transfer during the coevolution of lactic acid bacteria with their habitats.

Animals↗
PubMed2006

Neospora caninum detected in feral rodents.

The role of rodents in the epidemiology of neosporosis was investigated by assaying brain tissue of feral mice (Mus musculus) and rats (Rattus norvegicus) for Neospora caninum. Both mouse and rat brain tissue were extracted for total DNA, and subjected to two different N. caninum-specific nested polymerase chain reaction (PCR) assays. A portion of brain tissue from the mice and rats were also assayed for N. caninum in gerbils or gamma-interferon gene knockout (KO) mice. Of the 105 feral mice tested, 10% were positive in the N. caninum-specific PCR assays. Of the 242 rats tested, 30% were positive in both assays. Although mice and rats had N. caninum by PCR testing, clinical signs of N. caninum infection were not observed nor were N. caninum parasites observed in gerbils or KO mice inoculated with the rodent brain tissue.

Animals↗
PubMed2006

Improving the outcome of patients with castration-resistant prostate cancer through rational drug development.

Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Although docetaxel has recently been shown to extend the survival of patients with CRPC in two large randomised phase III studies, subsequent treatment options remain limited for these patients. A greater understanding of the molecular causes of castration resistance is allowing a more rational approach to the development of new drugs and many new agents are now in clinical development. Therapeutic targets include the adrenal steroid synthesis pathway, androgen receptor signalling, the epidermal growth factor receptor family, insulin growth factor-1 receptor, histone deacetylase, heat shock protein 90 and the tumour vasculature. Drugs against these targets are giving an insight into the molecular pathogenesis of this disease and promise to improve patient quality of life and survival. Finally, the recent discovery of chromosomal translocations resulting in the upregulation of one of at least 3 ETS genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this disease.

Antineoplastic Agents↗
PubMed2006

A model of the natural history of screen-detected prostate cancer, and the effect of radical treatment on overall survival.

The lead time and over-detection associated with prostate-specific antigen (PSA) screening, and generational improvements in all-cause mortality, make prostate cancer outcome studies from the pre-PSA era difficult to interpret in a contemporary setting. We developed a competing-risks hazard model to estimate the natural history of screen-detected prostate cancer, and the impact of radical treatment on overall survival. The model of hazard of mortality was fitted to clinical outcome data from the pre-PSA era, and the effects of screening, generational mortality improvements and radical treatment were incorporated. Sensitivities to the choice of baseline data and values of key parameters were assessed. Lead-time estimates in men diagnosed aged 55-59 years were 14.1, 9.3 and 5.0 years for men with Gleason scores <7, 7 and >7, respectively, assuming biennial screening with 100% attendance. Central estimates of 15-year prostate cancer mortality for conservative management of screen-detected prostate cancer ranged from 0 to 2% for Gleason scores <7, 9 to 31% for Gleason score 7 and 28-72% for Gleason scores >7. For men aged 55-59 years at diagnosis, the predicted absolute 15-year survival benefit from curative treatment was 0, 12 and 26% for men with Gleason scores <7, 7 and >7, respectively. Estimates of the survival benefit of radical treatment were relatively insensitive to values of key parameters. The case for curative treatment, rather than conservative management, of screen-detected localised prostate cancer is strongest in men with high-grade disease. This conclusion contrasts with current patterns of care.

Aged↗
PubMed2006

Multiple sites of impingement of a tracheal tube as it is advanced over a fibreoptic bronchoscope or tracheal tube introducer in anaesthetized, paralysed patients.

Impingement of the tracheal tube on upper airway structures occurs commonly during advancement over a fibreoptic bronchoscope or introducer. In this descriptive study a fibrescope was used to assess the site and mechanism of tracheal tube impingement during advancement over a variety of fibreoptic bronchoscopes and introducers during orotracheal intubation in anaesthetized adults. The effect of the 90 degree counterclockwise rotation manoeuvre in overcoming impingement was also assessed. We recorded impingement at the right arytenoid, left arytenoid, epiglottis, interarytenoid tissue and the left pyriform fossa. Our study found a wider range of sites at which impingement may occur than in previous studies. We also found that when 90 degree counterclockwise rotation of the tip of the tracheal tube was achieved, the impingement was reliably overcome.

Adolescent↗
PubMed2005

Construction of tissue microarrays from prostate needle biopsy specimens.

Needle biopsies are taken as standard diagnostic specimens for many cancers, but no technique exists for the high-throughput analysis of multiple individual immunohistochemical (IHC) markers using these samples. Here we present a simple and highly reliable technique for constructing tissue microarrays (TMAs) from prostatic needle biopsies. Serial sectioning of the TMAs, called 'Checkerboard TMAs', facilitated expression analysis of multiple proteins using IHC markers. In total, 100% of the analysed biopsies within the TMA both preserved their antigenicity and maintained their morphology. Checkerboard TMAs will allow the use of needle biopsies (i) alongside other tissue specimens (trans-urethral resection of prostates and prostatectomies in the case of prostate cancer) in clinical correlation studies when searching for new prognostic markers, and (ii) in a diagnostic context for assessing expression of multiple proteins in cancers from patients prior to treatment.

Biopsy, Needle↗
PubMed2005

Fertility, gonadal and sexual function in survivors of testicular cancer.

Modern treatments cure most testicular cancer patients, so an important goal is to minimise toxicity. Fertility and sexual functioning are key issues for patients. We have evaluated these outcomes in a cross-sectional study of long-term survivors of testicular cancer. In total, 680 patients treated between 1982 and 1992 completed the EORTC Qly-C-30(qc30) questionnaire, the associated testicular cancer specific module and a general health and fertility questionnaire. Patients have been subdivided according to treatment received: orchidectomy either alone (surveillance, S n = 169), with chemotherapy (C, n = 272), radiotherapy (R, n = 158), or both chemotherapy and radiotherapy (C/RT n = 81). In the surveillance group, 6% of patients had an elevated LH, 41% an elevated FSH and 11% a low (< 10 nmol l(-1)) testosterone. Hormonal function deteriorated with additional treatment, but the effect in general was small. Low testosterone was more common in the C/RT group (37% P = 0.006), FSH abnormalities were more common after chemotherapy (C 49%, C/RT 71% both P < 0.005) and LH abnormalities after radiotherapy (11% P < 0.01) and chemotherapy (10%, P < 0.001). Baseline hormone data were available for 367 patients. After treatment, compared to baseline, patients receiving chemotherapy had significantly greater elevations of FSH (median rise of 6 (IQR 3-9.25) iu l(-1) compared to 3 (IQR 1-5) iu l(-1) for S; P < 0.001) and a fall (compared to a rise in the surveillance group) in median testosterone levels (-2 (IQR -8.0 to -1.5) vs 1.0. (IQR -4.0-4.0) P < 0.001). Patients with low testosterone (but not elevated FSH) had lower quality of life scores related to sexual functioning on the testicular cancer specific module and lower physical, social and role functioning on the EORTC Qly C-30. Patients with a low testosterone also had higher body mass index and blood pressure. Treatment was associated with reduction in sexual activity and patients receiving chemotherapy had more concerns about fathering children. In total, 207 (30%) patients reported attempting conception of whom 159 (77%) were successful and a further 10 patients were successful after infertility treatment with an overall success rate of 82%. There was a lower overall success rate after chemotherapy (C 71%; CRT 67% compared to S 85% (P = 0.028)). Elevated FSH levels were associated with reduced fertility (normal FSH 91% vs elevated 68% P < 0.001). In summary, gonadal dysfunction is common in patients with a history of testicular cancer even when managed by orchidectomy alone. Treatment with chemotherapy in particular can result in additional impairment. Gonadal dysfunction reduces quality of life and has an adverse effect on patient health. Most patients retain their fertility, but the risk of infertility is likely to be increased by chemotherapy. Screening for gonadal dysfunction should be considered in the follow-up of testicular cancer survivors.

Adolescent↗
PubMed2005

Ratio spectra derivative spectrophotometry for the determination of furosemide and spironolactone in a capsule formulation.

The determination of furosemide and spironolactone in a capsule formulation has been investigated using techniques such as Vierordt's method and derivative spectroscopy dA/d lambda and d2A/d lambda2 applying the zero-crossing technique following reported methods. In our hands, using standard mixtures, these methods gave unreliable results. We have therefore investigated the use of ratio spectra derivative spectrophotometry for this determination. The technique of ratio spectra derivative spectrophotometry was developed in 1990, and has recently been used for a number of analyses of co-formulated products. The method was applied to the analysis of standard mixtures of the two drugs and the combined contents of 20 capsules resulting in values (mean +/- standard deviation) of 102.1 +/- 1.9% and 101.4 +/- 4.0% of the stated content for furosemide and spironolactone, respectively. Similarly, the analysis of individual capsules resulted in values of 101.5 +/- 1.6% and 102.2 +/- 1.4% of the stated content for furosemide and spironolactone, respectively.

Calibration↗
PubMed2005

Docetaxel for the treatment of prostate cancer.

Prostate cancer accounts for 12% of male cancer deaths, amounting to almost 10,000 deaths per year in the UK. Patients that develop metastatic disease may have their prostate cancer controlled for approximately 2 years with androgen deprivation but invariably progress to a castrate-independent state and succumb to metastatic disease. The previous experience of cytotoxic chemotherapy in hormone-refractory prostate cancer has yielded modest improvements in quality of life, with mitoxantrone in widest use. However, following encouraging Phase II data, two Phase III trials have demonstrated a survival advantage associated with the use of the synthetic taxoid cytotoxic docetaxel (Taxotere) over mitoxantrone and prednisolone. Moreover, this treatment was well tolerated. Therefore, docetaxel is set to be the standard by which future interventions are judged and a platform for future trials containing novel molecular therapies.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Individual patient data meta-analysis of randomized controlled trials of community occupational therapy for stroke patients.

BACKGROUND AND PURPOSE: Trials of occupational therapy for stroke patients living in the community have varied in their findings. It is unclear why these discrepancies have occurred. METHODS: Trials were identified from searches of the Cochrane Library and other sources. The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) score at the end of intervention. Secondary outcome measures included the Barthel Index or the Rivermead ADL (Personal ADL), General Health Questionnaire (GHQ), Nottingham Leisure Questionnaire (NLQ), and death. Data were analyzed using linear or logistic regression with a random effect for trial and adjustment for age, gender, baseline dependency, and method of follow-up. Subgroup analyses compared any occupational therapy intervention with control. RESULTS: We included 8 single-blind randomized controlled trials incorporating 1143 patients. Occupational therapy was associated with higher NEADL scores at the end of intervention (weighted mean difference [WMD], 1.30 points, 95% confidence intervals [CI], 0.47 to 2.13) and higher leisure scores at the end of intervention (WMD, 1.51 points; 95% CI, 0.24 to 2.79). Occupational therapy emphasizing activities of daily living (ADL) was associated with improved end of intervention NEADL (WMD, 1.61 points; 95% CI, 0.72 to 2.49) and personal activities of daily living (odds ratio [OR], 0.65; 95% CI, 0.46 to 0.91), but not NLQ. Leisure-based occupational therapy improved end of intervention NLQ (WMD, 1.96 points; 95% CI, 0.27 to 3.66) but not NEADL or PADL. CONCLUSIONS: Community occupational therapy significantly improved personal and extended activities of daily living and leisure activity in patients with stroke. Better outcomes were found with targeted interventions.

Activities of Daily Living↗
PubMed2004

An evaluation of Beam cath in the verification process for prostate cancer radiotherapy.

AIMS: As the trend towards more conformal treatment continues, the accuracy of treatment delivery becomes more important. Conventionally, treatment set-up for prostate cancer patients is verified in relation to the bony anatomy. However, there can be prostate movement independent of bony anatomy. This study tested the feasibility of using Beam cath to enable online correction of treatment set-up in relation to the prostate position, and to assess inter-fraction and intra-fraction prostate movement. MATERIALS AND METHODS: Beam cath is a urethral catheter containing radio-opaque markers, which can be seen on electronic portal imaging, enabling verification of prostate rather than bony anatomy position. The Beam cath was used for planning and treatment of a boost phase of 10 Gy in 5 fractions, delivered before the conventional conformal plan of 60 Gy in 30 fractions. Patients were scanned by computed tomgography (CT), with and without the catheter, and a radio-opaque marker in the catheter was used as the isocentre of the boost phase to enable accurate and rapid pre-treatment isocentre adjustment. The set-up errors between the Beam Cath and bony images were compared to identify the magnitude of prostate movement, independent of bony anatomy. Post-treatment portal images were taken to assess intra-fraction prostate movement. RESULTS: Of 29 patients approached to take part in the study, 18 patients gave informed consent, but only five completed the intended 5 fractions of the boost phase using Beam cath. Pre- and post-treatment portal images were obtained for a total of 29 fractions in six patients. Inter-fraction prostate movement, independent of bony anatomy, was identified. The mean movements were 0.2 mm (standard deviation [SD] 1.2 mm), 2.9 mm (SD 3.1 mm) and 0.7 mm (SD 2.3 mm) in the right left (RL), cranio-caudal (CC) and anterior posterior (AP) direction, respectively. The mean intra-fraction movement was 0.2 mm (SD 1.2 mm), 2.9 mm (SD 3.1 mm) and 0.7 mm (SD 2.3 mm) in the RL, CC and AP direction, respectively. CONCLUSION: Although independent prostate movement was identified, the use of Beam cath was poorly tolerated. Alternative methods of identifying and correcting for prostate movement should be investigated.

Aged↗
PubMed2004

Current opinion on adjuvant and salvage treatment after radical prostatectomy.

AIMS: The role of postoperative radiotherapy and hormone treatment after radical prostatectomy is uncertain, with no good evidence base to guide practice. In particular, it is not known whether a blanket policy of adjuvant therapy offers any advantage over a selective approach using salvage treatment in people who develop biochemical failure. Furthermore the technique for postoperative radiotherapy to the prostate bed has not been well described. We surveyed the opinion of UK clinical oncologists to describe current practice, with a view to informing the design of clinical trials in this setting. MATERIALS AND METHODS: A questionnaire was designed to elicit the opinion and clinical practice of UK clinical oncologists on the use of radiotherapy and hormone therapy after radical prostatectomy. The questionnaire was distributed to the delegates at the British Institute of Radiology Conference 'Contemporary issues in Prostate Cancer Radiotherapy' on 9 May 2003. RESULTS: Forty-nine out of 70 (70%) clinical oncologists completed the questionnaire. With an undetectable postoperative prostate-specific antigen (PSA) less than 0.04 ng/ml, opinion was divided on the role of adjuvant therapy. For example, adjuvant radiotherapy was recommended by 51% (25/49) of respondents for cases with pT3 margin positive disease. When recommending adjuvant radiotherapy, 60% (59/99) recommended hormone therapy in addition. In cases with an asymptomatic rising PSA after radical prostatectomy who had not received adjuvant therapy, 93% (43/46) recommended salvage radiotherapy, but the PSA threshold for recommending such treatment varied widely. The two most common dose-fractionation regimens for salvage radiotherapy to the prostate bed were 62-64 Gy in 2 Gy daily fractions (47%), and 50-55 Gy in 20 fractions (30%). CONCLUSIONS: Opinion is varied within the UK on the role of radiotherapy and hormone therapy after radical prostatectomy. The results of this survey should inform the design of future clinical trials.

England↗
PubMed2004

Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.

BACKGROUND: The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS: During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS: Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS: Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.

Abdominal Pain↗
PubMed2004

Active surveillance of early prostate cancer: rationale, initial results and future developments.

Active surveillance is a new strategy that aims to individualise therapy by selecting only those men with significant cancers for curative therapy based on early evidence of disease progression. Active surveillance must be distinguished from watchful waiting, which for decades has described a policy of observation with the use of palliative treatment for symptomatic progression. The rationale for active surveillance is discussed, based on our knowledge of the natural history of PSA-detected early prostate cancer. The initial results of active surveillance have demonstrated its feasibility. Ongoing studies seek to optimise the active surveillance protocol, and to determine the long-term outcomes. Looking ahead, dietary intervention in men on active surveillance could become an important new paradigm for prostate cancer management.

Humans↗
PubMed2003

Modulation of human swallowing behaviour by thermal and chemical stimulation in health and after brain injury.

Few data support thermal or chemical stimulation as therapy for neurogenic dysphagia. Our aims were to explore the behavioural effects of thermal (cold) and chemical (citrus) modalities on water swallowing in health (n = 65, mean age 45 years, 44 females) and acute stroke (n = 22, mean age 67 years, eight females). Multiple randomized timed 50-mL swallowing tests were performed for each of four water conditions: (a) room temperature (RT), (b) cold (CD), (c) citrus (CT) and (d) combined cold and citrus (CD + CT). The inter-swallow interval (ISI), swallowing volume velocity (speed), and volume per swallow (capacity) were measured. In health, compared to RT, only CD + CT slowed the speed (12.3 +/- 0.5 vs 10.3 +/- 0.5 mL s(-1), P < 0.03) and decreased the capacity (16.4 +/- 0.9 vs 14.6 +/- 0.7 mL per swallow, P < 0.02) of swallowing. ISI was unaffected, except by CD + CT in healthy young subjects (<60 years) where it was reduced (1.44 +/- 0.02 vs 1.30 +/- 0.02 s, P < 0.02). Despite smaller volumes ingested by stroke patients, CD + CT, compared to RT, again slowed both the speed (3.8 +/- 0.4 vs 4.5 +/- 0.5 mL s(-1), P < 0.03) and capacity (7.6 +/- 0.7 vs 8.5 +/- 0.7 mL per swallow, P < 0.03) of swallowing but had no effect on ISI. We conclude that combined thermal and chemical modification of water consistently alters swallowing behaviour in health and after cerebral injury. These findings have relevance in the management of neurogenic swallowing problems.

Adult↗