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Biomedical subjects

Peter W Jones

Publications and source records attributed to Peter W Jones.

34 records · Page 2Linked to original sources

Associations between prostate cancer susceptibility and parameters of exposure to ultraviolet radiation.

Low sunlight exposure confers increased prostate cancer risk. In a study conducted in northern England, we investigated how combinations of exposure measures affect this risk. Recursive partitioning was used to identify combinations of exposure parameters that distinguished 453 prostate cancers from 312 benign hypertrophy patients. Sunbathing score most significantly defined cancer patients; 78.7% men with low scores (</=3.0) and 40.2% men with high scores (>8.0) had cancer. These subgroups were stratified by childhood sunburning, holidays in a hot climate and skin type such that subgroups with a 13.0-fold increased risk of cancer were identified.

Adenocarcinoma↗

Unexpected nocturnal hypoxia in patients with acute stroke.

BACKGROUND AND PURPOSE: Patients who have had a stroke are at risk of hypoxia through alterations in the central regulation of respiration, through aspiration, and through respiratory muscle weakness. Sleep-related breathing disorders are common and may lead to episodes of nocturnal hypoxia even when daytime oxygenation is normal. The aim of this study was to assess the prevalence of unexpected nocturnal hypoxia in stroke patients. METHODS: Consecutive adult patients with stroke were recruited within 72 hours of admission to hospital. Patients with indications for oxygen treatment were excluded. Older adults from the local community were recruited as control subjects. Oxygenation was assessed by pulse oximetry (Minolta 3i) for 5 minutes when awake before bedtime and continuously from 11 pm until 7 am. RESULTS: Of the 238 potentially eligible stroke patients, 120 were excluded because they required oxygen, 118 were recruited, and 100 had adequate pulse oximetry data. The mean+/-SD age was 74+/-8 years for stroke patients and 72+/-8 years for control subjects (n=85). Mean awake oxygen saturation (So2) was 94.5+/-1.7% for the stroke group and 95.8+/-1.7% for the control group (P<0.001). Mean nocturnal So2 was 93.5+/-1.9% in stroke patients and 94.3+/-1.9% in control subjects (P<0.01). Stroke patients had a higher oxygen desaturation index (ODI 4%) (8.9 versus 2.1, P<0.001). In addition, 23% of stroke patients spent >30 minutes with So2 <90% during the night. CONCLUSIONS: Oxygen saturation at night is approximately 1% lower than when awake. Almost a quarter of stroke patients who are normoxic at screening during the day spend >30 minutes with an oxygen saturation <90%.

Acute Disease↗

A method for comparing two normal means using combined samples of correlated and uncorrelated data.

A method is proposed for comparing two normal means when the data consist of some observations that are correlated and others that are uncorrelated. Typically, such data will consist of one subsample in which the observations for treatment 1 and treatment 2 are independent of each other, and another subsample which consists of paired observations taken under both treatments. The proposed method is developed using asymptotic results and is evaluated using simulation. The simulation results indicate that the proposed method can provide substantial improvement in type I error rate and power when compared with standard methods of analysis.

Antihypertensive Agents↗

Prostate cancer risk and exposure to ultraviolet radiation: further support for the protective effect of sunlight.

Recent studies have suggested that exposure to ultraviolet (UV) radiation may be protective to some internal cancers including that in the prostate. We describe a confirmatory study in 212 prostatic adenocarcinoma and 135 benign prostatic hypertrophy patients designed to determine whether previous findings showing a protective effect for UV exposure could be reproduced. We used a validated questionnaire to obtain data on aspects of lifetime exposure to UV. The data confirmed that higher levels of cumulative exposure, adult sunbathing, childhood sunburning and regular holidays in hot climates were each independently and significantly associated with a reduced risk of this cancer.

Adenocarcinoma↗

Combined effects of gender, skin type and polymorphic genes on clinical phenotype: use of rate of increase in numbers of basal cell carcinomas as a model system.

Patients with a basal cell carcinomas (BCC) have an increased risk of further tumors. We studied the individual and combined impact of gender, skin type and allelic genes cytochrome P450 (CYP2D6), vitamin D receptor (VDR), tumor necrosis factor-alpha, TNF-alpha) on the rate of increase in BCC numbers after first presentation. Individually, male gender, skin type 1, CYP2D6 EM, VDR TT and TNF-alpha GG were associated with more BCC/year (rate ratio (RR) 1.20-1.36) while RR for associations of combinations of two, three and four variables were greater than in their reference categories (RR 1.32-1.90, 2.20-2.84, 3.06-5.49, respectively). The data show that different factors mediate the numbers of BCC/year in males and females and, the individual contributions of variables to risk is modest.

Adult↗

The association of maternal but not paternal genetic variation in GSTP1 with asthma phenotypes in children.

Maternal factors including atopy and smoking during pregnancy are associated with asthma risk during childhood. Suggested mechanisms include transmission of specific maternal alleles and maternal influences on the intrauterine environment. We have previously shown that polymorphism in glutathione S-transferase, GSTP1 is associated with airway hyperresponsiveness (AHR) and atopy in adults. We now hypothesise that GSTP1 genotypes in the mother and child, but not the father, mediate asthma phenotypes in the child. One hundred and forty-five Caucasian families were recruited via an asthmatic proband aged 7-18 years. Atopy and asthma were assessed using a questionnaire, skin prick testing, serum IgE, spirometry and methacholine challenge (PC20, dose-response slope--DRS). GSTP1 genotyping was determined using PCR. GSTP1 Val105/Val105 genotype in the child was associated with a reduced risk of atopy (P = 0.038) and AHR (PC20, P = 0.046; DRS, P = 0.032). In mothers (P = 0.014) but not fathers (P = 0.623), Val105/Val105 was associated with a reduced risk of AHR in the child. We have identified, for the first time, an association between maternal genotype and the child's asthma phenotype that appears not to be due to transmission of specific maternal alleles. This preliminary data supports the view of in utero effects of maternal genotype and adds new insights into the possible mechanisms by which maternal factors may influence development of childhood asthma.

Adolescent↗

Correction of bronchial challenge data for age and size may affect the results of genetic association studies in children.

Meaningful studies of asthma genetics require careful definition of airway hyperresponsiveness (AHR). In children, several studies have emphasized the need for correction of bronchial challenge data for baseline parameters, such as age, gender, lung function and atopic status, when undertaking airway responsiveness measurements. However, few studies have suggested how this should be performed in practice. This study describes a method for the correction of dose-response slopes (DRS) and PC20 values for baseline parameters in children, and illustrates the effect of such corrections on the association of AHR with the glutathione S-transferase GSTP1 Ile105Val polymorphism in children. Skin prick and methacholine challenge testing, measurement of total serum IgE concentration and GSTP1 genotyping were performed in 145 unrelated British children aged 7-18 years. Correction of bronchial challenge results, expressed as both DRS and PC20 values, for age, gender, baseline lung function and atopic status was performed using linear regression and discriminant analysis, respectively. Adjusting bronchial challenge results for the age and size of the child altered AHR status, defined as a PC20 methacholine <8 mg/ml, in 37% of children. Correction for baseline parameters also resulted in a significant reduction in mean DRS (original uncorrected DRS 83.6, corrected DRSc 27.4). This had a marked effect on the results of the association study, unmasking a previously unidentified association between the GSTP1 genotype and AHR in children. Age and size adjustment of bronchial challenge data has a significant effect on AHR status and may influence the results of genetic association studies in children.

Adolescent↗

Susceptibility to prostate cancer: studies on interactions between UVR exposure and skin type.

Recent studies have proposed that exposure to ultraviolet radiation (UVR) protects against development of some internal cancers including that in prostate. This effect may be mediated by UVR-induced cutaneous synthesis of vitamin D. It is also proposed that ability to pigment in response to UVR will influence susceptibility to prostate cancer through its effects on vitamin D synthesis. We wished to determine first, whether ability to pigment, as assessed by skin type, influences the extent of exposure to UVR, secondly, whether skin type is associated with prostate cancer susceptibility and thirdly, whether such an effect is mediated by the extent of UVR exposure. We studied 453 prostatic adenocarcinoma and 312 benign prostatic hypertrophy (BPH) patients using a validated questionnaire to assess two parameters of exposure; months of cumulative exposure per year and adult sunbathing score. We used analysis of variance to show that cancer cases with sun-sensitive skin (skin type 1) had lower cumulative exposure per year (P = 0.014) and sunbathing scores (P < 0.0001) than those with type 4, possibly because of a tendency to avoid exposure. Further, cumulative exposure per year and sunbathing score were significantly lower in cancer compared with BPH patients (P < 0.001 and P < 0.001, respectively). While the proportion of subjects with skin types 1 and 2 was lower in cancer than BPH patients, these were not significantly different (logistic regression analysis, skin type 1 versus type 4; P = 0.11). We used recursive partitioning to determine if skin type influenced susceptibility to prostate cancer in subgroups stratified by exposure. Analysis of the data showed that in men with low sunbathing scores, skin type 1 conferred protection compared with skin types 2-4 (OR = 4.78, 95% CI 3.01-8.25, P < 0.0009). These findings indicate that susceptibility to prostate cancer is in part determined by extent of exposure to UVR and that ability to pigment mediates this effect.

Adenocarcinoma↗

Analysis of a Bayesian repeated measures model for detecting differences in GP prescribing habits.

A linear mixed model is used to detect a change, if any, in the prescribing habits in the UK at the general practice (family medicine) level due to an educational intervention given repeated measures data before and after the intervention and a control group. Inferences are corrected for general practice size and fundholding status. The estimates of the model parameters are obtained using Bayesian inference by applying Gibbs sampling. We develop three different priors for the parameters of the model. These three priors correspond to 'sceptical,' 'reference' and 'enthusiastic' priors in terms of the opinion about the treatment effects that they represent. We compare the results obtained by using these three priors for the parameters in the random effects model.

Anti-Inflammatory Agents, Non-Steroidal↗

Randomised study of long term outcome after epidural versus non-epidural analgesia during labour.

OBJECTIVE: To determine whether epidural analgesia during labour is associated with long term backache. DESIGN: Follow up after randomised controlled trial. Analysis by intention to treat. SETTING: Department of obstetrics and gynaecology at one NHS trust. PARTICIPANTS: 369 women: 184 randomised to epidural group (treatment as allocated received by 123) and 185 randomised to non-epidural group (treatment as allocated received by 133). In the follow up study 151 women were from the epidural group and 155 from the non-epidural group. MAIN OUTCOME MEASURES: Self reported low back pain, disability, and limitation of movement assessed through one to one interviews with physiotherapist, questionnaire on back pain and disability, physical measurements of spinal mobility. RESULTS: There were no significant differences between groups in demographic details or other key characteristics. The mean time interval from delivery to interview was 26 months. There were no significant differences in the onset or duration of low back pain, with nearly a third of women in each group reporting pain in the week before interview. There were no differences in self reported measures of disability in activities of daily living and no significant differences in measurements of spinal mobility. CONCLUSIONS: After childbirth there are no differences in the incidence of long term low back pain, disability, or movement restriction between women who receive epidural pain relief and women who receive other forms of pain relief.

Adult↗

Management of obstetric anal sphincter injury: a systematic review & national practice survey.

BACKGROUND: We aim to establish the evidence base for the recognition and management of obstetric anal sphincter injury (OASI) and to compare this with current practice amongst UK obstetricians and coloproctologists. METHODS: A systematic review of the literature and a postal questionnaire survey of consultant obstetricians, trainee obstetricians and consultant coloproctologists was carried out. RESULTS: We found a wide variation in experience of repairing acute anal sphincter injury. The group with largest experience were consultant obstetricians (46.5% undertaking > or = 5 repairs/year), whilst only 10% of responding colorectal surgeons had similar levels of experience (p < 0.001). There was extensive misunderstanding in terms of the definition of obstetric anal sphincter injuries. Overall, trainees had a greater knowledge of the correct classification (p < 0.01). Observational studies suggest that a new 'overlap' repair using PDS sutures with antibiotic cover gives better functional results. However, our literature search found only one randomised controlled trial (RCT) on the technique of repair of OASI, which showed no difference in incidence of anal incontinence at three months. Despite this, there was a wide variation in practice, with 337(50%) consultants, 82 (55%) trainees and 80 (89%) coloproctologists already using the 'overlap' method for repair of a torn EAS (p < 0.001). Although over 50% of colorectal surgeons would undertake long-term follow-up of their patients, this was the practice of less than 10% of obstetricians (p < 0.001). Whilst over 70% of coloproctologists would recommend an elective caesarean section in a subsequent pregnancy, only 22% of obstetric consultants and 14% of trainees (p < 0.001). CONCLUSION: An agreed classification of OASI, development of national guidelines, formalised training, multidisciplinary management and further definitive research is strongly recommended.

Anal Canal↗

Repeated measures models for prescribing change.

Linear mixed models are used to detect a change, if any, in prescribing habits at the primary care practice level due to an educational intervention given repeated measures data before and after intervention and a control group. Inferences are corrected for general practice size, fundholding status and baseline prescribing. The correlation structure is discussed and the results for multilevel modelling using MLwiN and NLME version 3.0 are compared.

Anti-Inflammatory Agents, Non-Steroidal↗

Glutathione S-transferase GSTP1 genotypes are associated with response to androgen ablation therapy in advanced prostate cancer.

We determined whether the glutathione S-transferase GSTP1 Ile105 --> Val105 substitution is associated with response to androgen ablation therapy in patients with advanced prostate cancer. As response may be associated with tumor grade, Gleason score, clinical T stage and presence of metastases we also determined if GSTP1 genotypes were associated with these prognostic parameters. We speculated that GSTP1 Ile105/Ile105 would be linked with good response to androgen ablation therapy and, low/moderate tumor grade, 1/2 clinical T-stage, Gleason score < 6 and, no metastases. Genotype frequencies in cases and controls were not significantly different (P = 0.70) indicating that allelism in GSTP1 is not associated with susceptibility. There was no association between GSTP1 (Ile105/Ile105 versus Ile105/Val105 and Val105/Val105) and grade (P = 0.28, OR = 0.92), Gleason score (P = 0.84, OR = 0.94) or metastatic state (P = 0.68, OR = 0.88) though the frequency of GSTP1 Ile105/Ile105 was higher in cases with stage 1/2 tumors than those with stage 3/4 tumors (P = 0.03, OR = 1.89). GSTP1 Val105/Val105 was also associated with response to hormone ablation therapy. Thus, the GSTP1 Ile105/Ile105 frequency was significantly higher in 86/118 patients who demonstrated a good response than in those with poor response (P = 0.03, OR = 2.70). We speculate that the association of GSTP1 with response results from an effect of the gene product early in carcinogenesis.

Adenocarcinoma↗

The rate of increase in the numbers of primary sporadic basal cell carcinomas during follow up is associated with age at first presentation.

Basal cell carcinoma (BCC) patients demonstrate marked variation in tumour numbers and site. Previous studies also show an association between age at first BCC presentation and development of BCC on the trunk. In this study we have investigated the association between age at first presentation and the rate of development of truncal and non-truncal tumours in 747 patients with BCC. We used negative binomial regression analysis to show that increasing age at first presentation was associated with an increased rate of BCC development (rate ratio 1.01/year, 95% CI 1.01-1.02, P < 0.001). In particular, development of tumours was greater in cases aged 60.0-69.9, 70.0-79.9 and 80.0-89.9 years than in those 40.0-49.9 years (P = 0.05, 0.01 and 0.039, respectively). While few cases aged over 70 years of age first present with a truncal BCC, the numbers of BCC/year were greater than in those with a head/neck BCC. The data suggest different genetic factors mediate the appearance of BCC in patients of different ages particularly those aged above and below 60 years.

Adult↗

Clinical and radiographic predictors of scoliosis in patients with myelomeningocele.

BACKGROUND: The prevalence of scoliosis in patients with myelomeningocele has been reported to be as high as 80% to 90% in some studies. However, those studies included patients with both congenital and developmental curves. The variation in the patient population as well as the definition of scoliosis in those studies made it difficult to predict the true prevalence of scoliosis in these patients. The purpose of the present study was to identify clinical and radiographic factors that may predict the onset of developmental scoliosis in patients with myelomeningocele. METHODS: A retrospective review of the charts and radiographs of all patients with a diagnosis of myelomeningocele who were seen in our clinic between 1990 and 1995 was performed. The criteria for inclusion in the study included a diagnosis of myelomeningocele or lipomeningocele, an age of more than ten years at the time of the review, serial documentation of motor power, and radiographic documentation of spinal deformity primarily in the coronal plane. The radiographs were examined to assess the degree of scoliosis and to document the last intact laminar arch. The relationship between the degree of scoliosis and the last intact laminar arch was evaluated. Statistical analysis was performed to assess the association between scoliosis and the clinical motor level, the ambulatory status, spasticity, motor asymmetry, and hip instability. RESULTS: One hundred and forty-one patients satisfied the criteria for inclusion in the study. Seventy-four patients (52%) had scoliosis. The average duration of follow-up was 9.4 years (range, three to thirty years), and the average age of the patients was nineteen years (range, ten to forty-two years). Scoliosis developed before the age of nine years in forty-three patients and after the age of nine years in thirty-one patients, with new curves continuing to develop until the age of fifteen years. Curves of <20 degrees degrees often resolved. The clinical motor level, ambulatory status, and last intact laminar arch were all found to be predictive factors for the development of scoliosis in these patients. CONCLUSIONS: In the population of patients with myelomeningocele, the term scoliosis should be reserved for curves of >20 degrees. New curves may continue to develop until the age of fifteen years. The level of the last intact laminar arch is a useful early predictor of the development of scoliosis in these patients.

Adolescent↗