Biomedical subjects
Publications and source records attributed to D Robinson.
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BACKGROUND: There is concern about whether cardiac damage occurs as a result of prolonged strenuous exercise. OBJECTIVE: To investigate whether competing in a triathlon is associated with cardiac damage based on a sustained increase in cardiac troponin T (cTnT), and whether such an increase correlates with echocardiographic changes METHODS: cTnT and echocardiographic measurements were made in 38 participants in the 2001 Australian ironman triathlon. cTnT was measured the day before, immediately after, and the day following the race. Echocardiography was done the day before, immediately after, and two to six weeks later for measurement of ejection fraction, stroke volume, cardiac output, wall motion analysis, and global left ventricular function (LVF). RESULTS: No subject had detectable cTnT in the pre-race sample. Following the race, 32 subjects (86.5%) had detectable levels of cTnT (>0.01 ng/ml), with six (16.2%) having >0.10 ng/ml. The day after the race, nine subjects (23.7%) still had detectable cTnT, with two recording a level >0.10 ng/ml. Previously described echocardiographic changes of "cardiac fatigue" were observed in the whole cohort. There was a modest but significant correlation between change in ejection fraction and peak cTnT level (p = 0.02, r = 0.39). Athletes with a post-race cTnT >0.10 ng/ml had a greater decrease in global LVF (p = 0.02) and a trend toward a greater fall in ejection fraction and stroke volume than athletes with cTnT levels <0.10 ng/ml. Cardiac output fell in the group with cTnT >0.10 ng/ml (p>0.05). CONCLUSIONS: Participation in ironman triathlon often resulted in persistently raised cTnT levels, and the troponin rise was associated with echocardiographic evidence of abnormal left ventricular function. The clinical significance and long term sequelae of such damage remains to be determined.
OBJECTIVE: To compare the incidence of subsequent cancers in a cohort of patients with primary Sjögren's syndrome (pSS) with that of the general population in the same region of England. METHODS: A retrospective analysis was carried out on 112 patients who had attended the out-patients department at University College Hospital, London, from 1979 onwards. Patients were followed up from diagnosis of pSS to diagnosis of first subsequent cancer, death, loss to follow-up or 31 December 2003 (the censoring date) to determine the person-years at risk for each individual. The expected numbers of subsequent cancers were calculated from sex-/age-/period-specific rates for the general population of southeast England, derived from registrations at the Thames Cancer Registry. Standardized incidence ratios (SIRs) were then calculated as the ratio of observed to expected numbers of cancers, along with 95% confidence intervals (CIs). Separate analyses were performed for all malignant cancers combined, lymphomas and non-lymphoid cancers. RESULTS: Among the 112 patients with pSS, 25 developed cancer (either before or after development of pSS), with lymphoma occurring in 11 cases. Nine patients had two cancers. There was a significantly elevated incidence of lymphomas in pSS patients compared with the general population (SIR 37.5, 95% CI 20.7-67.6). For non-lymphoid cancer, the observed increase in incidence was small and not statistically significant (SIR 1.5, 95% CI 0.9-2.6). CONCLUSION: This study confirms that there is an increased incidence of lymphoma in patients with pSS. An increase in the incidence of other cancers was not proven but the observation that some patients developed more than one cancer raises the possibility that there may be a subgroup of patients who are at greater risk of developing cancer.
AIM: To assess the dental health and preventive practices of child patients with congenital heart disease treated at the Royal Hospital for Sick Children, Glasgow. STUDY DESIGN: A retrospective study using an audit data collection sheet. METHODS: Data collected for 370 paediatric cardiac patients between January 2002 and December 2003 was analysed to obtain an insight into these patients' tooth brushing methods, use of fluoride (F), dental attendance and past dental treatment. An oral examination assessed the patient's caries experience. RESULTS: There were 195 subjects aged between 1 and 5 years, 105 were 6 - 11 years and 70 were 12 -16 years of whom 291 (78%) children were registered for dental care. Of these children 331 (90%) maintained that they brushed their teeth regularly with F- toothpaste. Experience of dental treatment revealed that 132 (36%) children had undergone previous dental treatment. Oral examination showed that out of 370 patients, 236 (64%) had no active caries. The dental health of the cardiac subjects was poor compared with that of Scottish primary school children (5 year-olds) and the 12 year-olds but compared favourably with the 14-year old group. STATISTICS: The relationship between caries activity and frequency of toothbrushing was significant (p<0.01). The relationship between caries activity and attendance for dental care was not significant. CONCLUSION: Children with cardiac problems should be identified in early infancy through liaison with medical colleagues and the family offered all the preventive advice and regular dental care necessary to prevent dental disease.
Cryptosporidium has become increasingly recognized as a pathogen responsible for outbreaks of diarrhoeal illness in both immunocompetent and immunocompromised persons. In August 2001, an Illinois hospital reported a cryptosporidiosis cluster potentially linked to a local waterpark. There were 358 case-patients identified. We conducted community-based and waterpark-based case-control studies to examine potential sources of the outbreak. We collected stool specimens from ill persons and pool water samples for microscopy and molecular analysis. Laboratory-confirmed case-patients (n=77) were more likely to have attended the waterpark [odds ratio (OR) 16.0, 95% confidence interval (CI) 3.8-66.8], had pool water in the mouth (OR 6.0, 95% CI 1.3-26.8), and swallowed pool water (OR 4.5, 95% CI 1.5-13.3) than age-matched controls. Cryptosporidium was found in stool specimens and pool water samples. The chlorine resistance of oocysts, frequent swimming exposures, high bather densities, heavy usage by diaper-aged children, and increased recognition and reporting of outbreaks are likely to have contributed to the increasing trend in number of swimming pool-associated outbreaks of cryptosporidiosis. Recommendations for disease prevention include alteration of pool design to separate toddler pool filtration systems from other pools. Implementation of education programmes could reduce the risk of faecal contamination and disease transmission.
The aim of this study was to investigate variations in the length of time that patients with cancer wait from diagnosis to treatment with radiotherapy. A total of 57,426 men and 71,018 women diagnosed with cancer between 1992 and 2001 and receiving radiotherapy within 6 months of diagnosis were identified from the Thames Cancer Registry database. In total, 12 sites were identified for which a substantial number or proportion of patients received radiotherapy: head and neck, oesophagus, colon, rectum, lung, nonmelanoma skin cancer, breast, uterus, prostate, bladder, brain and non-Hodgkin's lymphoma. Median waiting times from diagnosis to radiotherapy were calculated, together with the proportion of patients who received radiotherapy within 60 days of diagnosis, and analysed by year of diagnosis, cancer site, deprivation quintile, age at diagnosis, sex and cancer network of either residence or treatment. Logistic regression was used to adjust the proportion receiving treatment within 60 days for the effects of the other factors. There were significant differences in the proportions receiving radiotherapy within 60 days between different networks and different cancer sites, which remained after adjustment. Median waiting times varied from 42 to 65 days across networks of residence, with the adjusted proportion treated within 60 days ranging from 44 to 71%. There was no difference between male and female patients after adjustment for the other factors, particularly site. There was a highly significant trend over time: the median wait increased from 45 days in 1992 to 76 days in 2001, while the adjusted proportion being treated within 60 days declined by almost a half, from 64 to 35%, over the same period.
The occurrence of second primary cancers was explored in patients with squamous cell cancer of the skin (SCC). The excess incidence subsequent to SCC was mainly in cancers related to sunlight and smoking, and in lymphoproliferative malignancies, it was largest (10-fold) in salivary gland cancer.
Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.
Antimuscarinic drug therapy has been shown to be effective in the management of patients with symptoms of the overactive bladder syndrome (OAB), but the bothersome antimuscarinic adverse effects of dry mouth, constipation, somnolence and blurred vision often affect compliance with medication. The development of bladder selective M3 specific antagonists offers the possibility of increasing efficacy whilst minimising adverse effects. The M3 specific antagonist solifenacin has recently been marketed, and darifenacin will soon be available. The purpose of this article is to review the pharmacology and clinical trial data available for darifenacin, in addition to examining its role in the treatment of the OBS.
Overactive bladder (OAB) is the term used to describe the symptom complex of urinary frequency and urgency, with or without urge incontinence. Whilst antimuscarinic drug therapy has proven to be effective in the management of patients with symptoms of the OAB syndrome, compliance with medication is often affected by the bothersome antimuscarinic adverse effects of dry mouth, constipation, somulence and blurred vision. The development of bladder selective M3 specific antagonists offers the possibility of increasing efficacy whilst minimising adverse effects. At present, there are no M3 specific antagonists currently available, although solifenacin and darifenacin are under development and are due to be registered in 2004-2005. The purpose of this article is to review the pharmacology and clinical trial data available for solifenacin in addition to examining its emerging role in the treatment of the OAB syndrome.
With advances in diagnosis and treatment, breast cancer is becoming an increasingly survivable disease resulting in a large population of long-term survivors. Factors affecting the quality of life of such patients include the consequences of breast cancer treatment, which may have involved radiotherapy. In this study, we compare the incidence of second primary cancers in women who received breast radiotherapy with that in those who did not (non-radiotherapy). All women studied received surgery for their first breast cancer. Second cancers of the lung, colon, oesophagus and thyroid gland, malignant melanomas, myeloid leukaemias and second primary breast cancers were studied. Comparing radiotherapy and non-radiotherapy cohorts, elevated relative risks (RR) were observed for lung cancer at 10-14 years and 15 or more (15+) years after initial breast cancer diagnosis (RR 1.62, 95% confidence interval [CI] 1.05-2.54 and RR 1.49, 95% CI 1.05-2.14, respectively), and for myeloid leukaemia at 1-5 years (RR 2.99, 95% CI 1.13-9.33), for second breast cancer at 5-10 years (RR 1.34, 95% CI 1.10-1.63) and 15+ years (RR 1.26, 95% CI 1.00-1.59) and oesophageal cancer at 15+ years (RR 2.19, 95% CI 1.10-4.62).
OBJECTIVE: Three-dimensional (3D) ultrasound facilitates assessment of the anatomy of the urethral sphincter, a decrease in sphincter volume being associated with stress incontinence. Urethral pressure profilometry (UPP) is used to assess urethral sphincter function although it is not diagnostic of stress incontinence. The aim of this pilot study was to determine whether 3D sphincter volume can be correlated with the area under the UPP curve. METHODS: Primigravid women were recruited antenatally between 32 and 42 weeks' gestation. 3D transvaginal ultrasound scans of the urethra were performed in modified lithotomy position with a comfortably full bladder. Length and cross-sectional area were measured allowing the sphincter volume to be calculated. UPP measurements were performed with a Gaeltec solid-state pressure transducer and the area under the curve mapped out and calculated. All scans and measurements were repeated between 3 and 6 months postpartum. RESULTS: Nineteen women participated in the study. Antenatal and postnatal data were available in all cases. There was a statistically significant correlation between antenatal sphincter volumes and area under the UPP curve although this relationship was lost following delivery. CONCLUSIONS: There appears to be a correlation between structural anatomy and functional anatomy in the antenatal period although following delivery this is lost.
Three-dimensional conformal radiotherapy (3D CRT) has become an established treatment for pituitary macroadenomas. This study is an investigation into the possible dosimetric advantages of intensity-modulated radiotherapy for such critically located tumors. Three consecutive patients with pituitary macroadenoma previously treated with 3D CRT were replanned with inverse-planned IMRT using Helax-TMS (V.6.0, Helax AB, Uppsala, Sweden. Fusion of computed tomography (CT) with postoperative magnetic resonance imaging (MRI) was performed within the planning system to define the gross tumor volume (GTV), planning target volume (PTV), and normal structures including the optic chiasm. Dose-volume histograms (DVHs) for the 3D CRT plans were then compared with those of the corresponding prospective IMRT plans. Both techniques maintained critical structure doses below tolerance levels while maintaining a minimum dose of 45 Gy to 100% of the PTV. While IMRT plans deliver consistently more heterogeneous dose distributions to the PTV, the median PTV dose is elevated in the IMRT plans compared with the 3D CRT plans. For critically located tumors like these pituitary macroadenomas, IMRT allows escalation of the median dose to the tumor without an accompanying loss in critical structure sparing or creating unacceptable cold spots within the PTV.
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A polyanhydride implant containing gentamicin sulfate was fabricated using a laboratory-scale injection-molding machine. After injection molding, the implants were subject to heat treatment at 60 degrees C for various time periods with or without nitrogen protection. The impact of this heat treatment on the in vitro properties of the implants including copolymer molecular weights, mechanical properties, and in vitro drug-release profiles was investigated. This heat treatment caused a drastic drop in the molecular weight of the copolymer. Heating without nitrogen protection resulted in the hardening of the implant, but heating in the presence of nitrogen rendered the implant less rigid. It was also found that a faster in vitro drug release profile was shown by implants heated without nitrogen protection and a pronounced slowing down in drug release was exhibited by implants heated with nitrogen protection.
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BACKGROUND: Remifentanil is a short acting, potent synthetic opioid that does not accumulate after infusion or repeated bolus doses. It may be rapidly titrated to the requirements of individual patients. Titrated infusion of remifentanil may be able to provide potent analgesia required for pediatric cardiac surgery and obtund the stress response in theater whilst not having the persistent respiratory depression and sedation seen with longer acting opioids. METHODS: Twenty patients were randomized to receive a titrated infusion of remifentanil (0-1 microg x kg(-1) x min(-1)) or a standard dose of fentanyl (30 microg x kg(-1)) prebypass plus morphine (1 mg x kg(-1)) on rewarming. Blood samples for glucose and cortisol were taken at regular intervals from induction through bypass and into the first 24 h of postoperative intensive care. In addition to biochemical indicators of the stress response we recorded baseline hemodynamic parameters and any acute physiological events. RESULTS: Ten patients received morphine, seven received remifentanil. There were no statistically significant differences between the two treatment groups in cortisol measurements, mean arterial pressure or heart rate recordings. In the last time period the remifentanil group had a larger rise in blood glucose concentration (baseline 3.9, rise 3 mmol x l(-1)) than the fentanyl/morphine group (baseline 4.2 rise 1.9 mmol x l(-1)), CI -4.3 to -0.2. CONCLUSIONS: The only significant difference was in glucose in the postbypass time periods. Although statistically significant, this difference is insufficient evidence of increased stress in the remifentanil group. The results show that in the patients studied there was no clinically important difference between the two techniques.