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Biomedical subjects

C Reid

Publications and source records attributed to C Reid.

At least 19 recordsLinked to original sources

A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis.

BACKGROUND: Human papillomavirus (HPV) may play a role in the pathogenesis of non-melanoma skin cancer (NMSC) in epidermodysplasia verruciformis (EV) patients, but in the general population no specific HPV types have been associated with these lesions. Objectives To examine the spectrum of HPV types present in the skin and tumours of Australian patients with NMSC or solar keratosis (SK). METHODS: Biopsies from tumours, and cotton swab samples of perilesional skin and buttock skin from each of 59 Australian patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or SK were tested for HPV DNA by polymerase chain reaction (PCR) using HPV consensus (FAP) primers and by type-specific primers for HPV 38 and candidate HPV 92. The identification of HPV type from consensus PCR was performed by sequencing and comparison with GenBank. RESULTS: In total, 49 of 59 (83%) patients harboured HPV DNA, which was detected in 28 of 64 (44%) biopsies, 48 of 64 (75%; P < 0.001) perilesional swabs and 36 of 59 (61%; P = 0.04) buttock swabs. Forty-five different HPV types/putative types were detected: 15 were previously characterized HPV types, 17 were earlier described putative types and 13 were new putative types. In addition, six subtypes and four variants of HPV sequences were identified. HPV types within the B1 group (EV HPV types) were found in 26 of 64 (40%) lesions, 44 of 64 (69%) perilesional swabs and 35 of 59 (59%) buttock swabs. HPV 38 was detected in 23 of 59 (39%) patients, and was found in seven of 16 (43%) SKs, but was less common in SCCs [three of 23 (13%); P = 0.037] and BCCs [four of 25 (16%); P = 0.056]. Candidate HPV 92 was found in seven of 59 (12%) patients. CONCLUSIONS: A broad spectrum of HPV types, the majority from the B1 group, was found in skin of Australian patients with skin tumours. HPV 38 was found significantly more often in SK than in SCC. However, the role of cutaneous HPV infection in the pathogenesis of NMSC remains elusive.

Adult↗

A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study.

BACKGROUND: Actinic keratosis (AK) is a very common condition, which has the potential of progressing to squamous cell carcinoma. The present study is a prospective, randomized study comparing the lesion response, cosmetic outcome, patient satisfaction and tolerability of a new treatment modality, photodynamic therapy (PDT), using topical methyl aminolevulinate (Metvix), with the most commonly used standard therapy for AK, cryotherapy. METHODS: A total of 204 patients with clinically diagnosed AK were randomized to either cryotherapy or PDT. The PDT patients were further assigned to an active or placebo group in a random, double-blind manner. Cryotherapy was performed using liquid nitrogen spray in a single freeze-thaw cycle. PDT was performed using 160 mg/g methyl aminolevulinate cream or placebo, a 3-hour application time, red light (570-670 nm) and a total light dose of 75 J/cm(2). PDT was repeated after 7 days. Two sessions of PDT were undertaken, as a previous study had shown a single session had similar efficacy to cryotherapy. Lesion response was assessed clinically after 3 months (complete response or non-complete response). RESULTS: The lesion response rate was 91% in the methyl aminolevulinate PDT group, 68% in the cryotherapy group and 30% in the placebo PDT group. Methyl aminolevulinate PDT was statistically significantly better than both cryotherapy and placebo PDT in terms of response rates and cosmetic outcome. Most patients preferred PDT to other treatments. CONCLUSIONS: PDT with methyl aminolevulinate is an excellent treatment option, particularly for patients with widespread damage or AK lesions in cosmetically sensitive areas.

Administration, Cutaneous↗

National audit of emergency department child protection procedures.

OBJECTIVE: To assess the compliance with national guidelines on child protection procedures and provision of paediatric services in major English emergency departments. BACKGROUND: Victims of child abuse may present to emergency departments, and successful detection and management depends on adequate child protection procedures being in place. Two official documents published in 1999 provide recommendations for child protection procedures and staffing arrangements in emergency departments, and these can be used as standards for audit. METHODS: Structured telephone questionnaire survey of English emergency departments receiving at least 18 000 child attenders per year. RESULTS: Many of the standards are being met. Areas for improvement include: better access to child protection registers with clearer indications for their use; improved communication with other professionals such as the school nurse; more formal training for medical and nursing staff in the identification of potential indicators of child abuse; and improved awareness of local named professionals with expertise in child protection. More consultants with training in paediatric emergency medicine and more registered children's nurses are needed. CONCLUSION: Many nationally agreed recommendations are being met, but there is a need for improved training, increased numbers of specialised staff, and improved communication between professionals. There is considerable variation in practice between departments.

Child↗

Effect of sunlight and season on serotonin turnover in the brain.

Alterations in monoaminergic neurotransmission in the brain are thought to underlie seasonal variations in mood, behaviour, and affective disorders. We took blood samples from internal jugular veins in 101 healthy men, to assess the relation between concentration of serotonin metabolite in these samples and weather conditions and season. We showed that turnover of serotonin by the brain was lowest in winter (p=0.013). Moreover, the rate of production of serotonin by the brain was directly related to the prevailing duration of bright sunlight (r=0.294, p=0.010), and rose rapidly with increased luminosity. Our findings are further evidence for the notion that changes in release of serotonin by the brain underlie mood seasonality and seasonal affective disorder.

Adolescent↗

Do not attempt resuscitation decisions in a cancer centre: addressing difficult ethical and communication issues.

Talking to patients about 'Do Not Attempt Resuscitation' decisions is difficult for many doctors. Communication about 'Do Not Attempt Resuscitation' decisions should occur as part of a wider discussion of treatment goals at an earlier stage in the patient's illness. A doctor should not initiate any treatment, including cardio-pulmonary resuscitation if he/she does not believe it will benefit the patient. An ethical framework is offered which may be of practical help in clarifying decision-making.

Cancer Care Facilities↗

A systematic review of predictors of maintenance of normotension after withdrawal of antihypertensive drugs.

BACKGROUND: The identification and treatment of hypertension in the general community has contributed to the reduction in strokes and coronary heart disease observed during the past 30 years. However, concerns have arisen that some patients may be receiving unnecessary antihypertensive drug therapy leading to wasted resources and the potential for adverse drug effects. Once therapy has been started, treating physicians have difficulty in selecting patients for withdrawal and have concerns regarding patient safety and their own legal liability. PROCEDURES: This study reviews and consolidates information from published studies to identify known predictors of the successful maintenance of normotension after antihypertensive drug withdrawal. The predictors were identified by determining the proportion of subjects with various baseline characteristics who remained normotensive while off medication for at least 12 months. From these data we have developed a clinical algorithm to help identify patients in whom antihypertensive drug withdrawal might be considered. This may assist primary care physicians in achieving successful withdrawal of antihypertensive therapy among selected hypertensive patients. RESULTS: The most consistent predictors identified were blood pressure (BP) (lower pretreatment, on treatment, and after withdrawal), nature of pharmacotherapy (fewer agents and lower dose), and preparedness to accept dietary intervention (weight and sodium reduction). CONCLUSIONS: On the basis of this information, a trial of withdrawal of antihypertensive medication might be recommended for patients who have mildly elevated, uncomplicated BP that is well controlled on a single agent, and who are motivated and likely to accept lifestyle changes.

Antihypertensive Agents↗

How covert are covertly manipulated diets?

OBJECTIVE: To quantitatively assess subjects' ability to detect hedonic (palatability), sensory and nutritional differences between covertly manipulated high-fat (HF) and low-fat (LF) diets. SUBJECTS AND DIETS: This study examined the response of 16 subjects (eight men, eight women) to 20 LF and 20 HF versions of manipulated foods. Average percentage protein:fat:carbohydrate (by energy) and energy density (ED) of the two diets were 13:25:62, 371 kJ/100 g and 13:50:37, 672 kJ/100 g, respectively. PROTOCOL: Subjects were asked to simultaneously assess the HF and LF versions of each food in terms of (i) subjective pleasantness of each food, (ii) perceived differences in appearance, smell, taste and texture of the foods, and (iii) for each sample to assess whether it was high or low in energy, protein, carbohydrate, fat, fibre, sugar and salt. ANALYSIS: Perceived pleasantness of HF and LF versions of the foods was compared by analysis of variance. Comparisons used chi-squared tests of independence to assess departure from the null hypothesis of no perceived difference in remaining parameters (ii-iii). RESULTS: On average, subjects exhibited no significant preference for LF or HF versions of the foods (no difference 15 foods, three HF foods more pleasant, two LF foods more pleasant (P<0.03)). On average there were no general differences in comparison of sensory attributes that were consistently ascribable to the LF or HF foods, although there were numerous significant differences for individual foods. Subjects appeared unable to distinguish the HF foods as being HF (66% of estimates) and guessed correctly 33% of the time. They were better able to categorize the LF foods correctly (53% correct). On aggregate 43% of HF and LF foods were correctly identified. Subjects appeared able to detect sensory differences between foods but not to relate them to energy or nutrient content of these foods. CONCLUSIONS: These data suggest that subjects are on average not able to perceive large differences in the fat content of diets manipulated in this manner. In general the assumption that the manipulation of such foods is covert appears to hold, but subjects were far better at correctly identifying certain food types (dairy-based) over others.

Adult↗

Ypel1: a novel nuclear protein that induces an epithelial-like morphology in fibroblasts.

BACKGROUND: Embryonic development depends on the regulation of cell morphology and behaviour to carry out morphogenesis. One example of this is the development of the face, which is constructed from independent blocks of tissue that must grow in a coordinated way and then fuse to form a continuous tissue. RESULTS: We have isolated a novel gene of unknown function from mouse and quail embryos in a search for genes involved in craniofacial development. Sequence analysis of this gene, known as Ypel1, demonstrates a striking level of amino acid conservation between vertebrates and invertebrates but no significant homology with any other characterized genes. Ypel1 is expressed in the ventral half of early embryos including the branchial arches from which the face derives. Ypel1 localizes to the nucleus, and transfection into fibroblasts induces an epithelial-like transition, which is accompanied by alterations to the cytoskeleton and cell adhesion machinery. In addition, human YPEL1 localizes to chromosome 22q11.2, a region associated with a number of syndromes involving malformation of the craniofacial complex. CONCLUSION: These data suggest a role in regulation of cellular morphology and behaviour that is important for development of the craniofacial complex.

Amino Acid Sequence↗

Caudal ropivacaine in infants: population pharmacokinetics and plasma concentrations.

BACKGROUND: Ropivacaine is a new long-acting amino-amide local anesthetic. However, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infants younger than 12 months. METHODS: Two groups of infants (group 1 [n = 15], aged 0-3 months; group 2 [n = 15], aged 3-12 months) were given a caudal bolus dose of 0.2% ropivacaine (2 mg/kg) and a standardized general anesthetic technique. Serial blood samples taken for up to 12 h were analyzed for total and free ropivacaine using high-performance liquid chromatography. Population pharmacokinetic modeling was performed to yield estimates of clearance, volume of distribution, and absorption rate constant. An analysis of covariates on the kinetic parameters also was made. RESULTS: Median maximum free ropivacaine concentration was significantly higher in group 1 (99 micog/l) than in group 2 (38 microg/l) (P = 0.0002), as was the median free fraction of ropivacaine (10% vs. 5%; P = 0.01). Pharmacokinetic variables of the total population were best described by a one-compartment model with first-order absorption. Mean clearance was 0.31 l.h(-1).kg(-1) (coefficient of variation [CV], 51%), volume of distribution was 2.12 l/kg (CV, 34%), and absorption rate constant was 1.61 h(-1) (CV, 46%). Mean absorption and elimination half-lives were 0.43 and 5.1 h, respectively. Age and percentage of free ropivacaine were significant covariates for clearance. Posterior Bayesian estimates of clearance were significantly higher (38%) in older children. CONCLUSION: Total and free plasma ropivacaine concentrations after caudal ropivacaine (0.2%, 2 mg/kg) in infants were within the range of concentrations previously reported in adults and older children. Age and percentage of free ropivacaine were significant covariates of clearance.

Age Factors↗

Emergency medicine terminology in the United Kingdom--time to follow the trend?

OBJECTIVE: To determine the frequency of use of the terms "accident and emergency" and "emergency medicine" and their derivatives in original articles in the Journal of Accident and Emergency Medicine. METHODS: Hand search of all articles in the Journal of Accident and Emergency Medicine from September 1995 to July 2000, categorising the first use of terminology in each original article to describe the specialty, its departments, or their staff into either accident and emergency or emergency medicine groups. RESULTS: There is a clear trend towards increasing use of the terms emergency medicine, emergency physician and emergency department, with decreasing use of the terms accident and emergency medicine, accident and emergency department and accident and emergency doctor, although the latter group still constitutes the majority. CONCLUSION: The use of emergency medicine to describe the specialty in the United Kingdom is increasing, although this may reflect the Journal's growing international standing. This trend should be taken into account in the debate over the specialty's name in this country.

Accidents↗

Dose-dependent effects of flumazenil on cognition, mood, and cardio-respiratory physiology in healthy volunteers.

OBJECTIVES: To assess the possible effects of flumazenil on cognitive processing, physiology, and mood. Design A double-blind, placebo controlled, four-way cross-over study, using healthy volunteers. METHODS: On each of 4 separate visits, 16 participants received 0.5 mg, 2.5 mg, 5.0 mg of flumazenil, or normal saline. They then performed a computerised test battery assessing cognitive function. Measures of pulse rate, arterial oxygen saturation and mean arterial pressure were also taken. Finally, participants completed visual analogue scales assessing their subjective mood state. RESULTS: The majority of cognitive tasks showed dose-dependent declines in performance. Mean arterial pressure was significantly reduced, as was pulse rate. Subjective alertness showed a similar decline. CONCLUSIONS: Flumazenil has been clinically described as an agent with few intrinsic properties, whose primary effect lies in its ability to reverse benzodiazepine-induced states. This study has shown that flumazenil does possess intrinsic activity which have a significant effect on cognition, cardiovascular physiology and mood. Clinicians need to be aware of these effects.

Adult↗

Linkage analysis for major histocompatibility complex-related genetic susceptibility in familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blood. 2000;96:3982-3984)

Adult↗

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings.

This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal:noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.

Appetite↗

Liarozole fumarate (R85246): a novel imidazole in the treatment of receptor positive postmenopausal metastatic breast cancer.

This phase II study of liarozole fumarate (R85246, liarozole), a novel imidazole with retinomimetic and aromatase inhibitory effects, was designed to determine the efficacy and tolerability in postmenopausal women with advanced breast cancer in progression, to correlate these effects with hormonal levels, and to evaluate quality of life. Twenty-nine women with ER-positive or unknown metastatic disease who received > or = 2 prior hormonal therapies were treated with 150-300 mg liarozole twice daily until disease progression. All patients were evaluable for toxicity and 25 for response. Four patients (16.0%, 95% CI 5.3-37.4%) had partial remission (PR) of their disease for a median of 7.4 months (range 1.2-12.9) and 7 (28%) had disease stabilization for a median of 4.8 months (1.6-16.0). Estradiol decreased from pre-treatment levels of 9.2-52 pM (mean 17.1) to below detection (9.2 pM, p = 0.0005) after 1 month. Similarly estrone levels fell from 14-307 pM (mean 92.7) to below detection (9.2 pM, p = 0.0001). The most common toxicity was dermatological (96.6%) with features compatible with hypervitaminosis A syndrome such as rash, pruritus, dry skin, and brittle nails. The majority of these were mild to moderate in severity. No significant improvement in quality of life scores (FLI-C) were noted. Liarozole is an active new treatment for breast cancer in patients heavily pre-treated with hormone therapies. Further studies are needed to confirm its relative efficacy in both receptor positive and negative postmenopausal breast cancer.

Aged↗