Menkes disease mimicking non-accidental injury.
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Child Abuse↗
Biomedical subjects
L Henderson
Publications and source records attributed to L Henderson.
Testing strategies in mutagenicity and genetic toxicology: an appraisal of the guidelines of the European Scientific Committee for Cosmetics and Non-Food Products for the evaluation of hair dyes.
The European Scientific Committee on Cosmetics and Non-Food Products (SCCNFP) guideline for testing of hair dyes for genotoxic/mutagenic/carcinogenic potential has been reviewed. The battery of six in vitro tests recommended therein differs substantially from the batteries of two or three in vitro tests recommended in other guidelines. Our evaluation of the chemical types used in hair dyes and comparison with other guidelines for testing a wide range of chemical substances, lead to the conclusion that potential genotoxic activity may effectively be determined by the application of a limited number of well-validated test systems that are capable of detecting induced gene mutations and structural and numerical chromosomal changes. We conclude that highly effective screening for genotoxicity of hair dyes can be achieved by the use of three assays, namely the bacterial gene mutation assay, the mammalian cell gene mutation assay (mouse lymphoma tk assay preferred) and the in vitro micronucleus assay. These need to be combined with metabolic activation systems optimised for the individual chemical types. Recent published evidence [D. Kirkland, M. Aardema, L. Henderson, L. Müller, Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens. I. Sensitivity, specificity and relative predictivity, Mutat. Res. 584 (2005) 1-256] suggests that our recommended three tests will detect all known genotoxic carcinogens, and that increasing the number of in vitro assays further would merely reduce specificity (increase false positives). Of course there may be occasions when standard tests need to be modified to take account of special situations such as a specific pathway of biotransformation, but this should be considered as part of routine testing. It is clear that individual dyes and any other novel ingredients should be tested in this three-test battery. However, new products are formed on the scalp by reaction between the chemicals present in hair-dye formulations. Ideally, these should also be tested for genotoxicity, but at present such experiences are very limited. There is also the possibility that one component could mask the genotoxicity of another (e.g. by being more toxic), and so it is not practical at this time to recommend routine testing of complete hair-dye formulations as well. The most sensible approach would be to establish whether any reaction products within the hair-dye formulation penetrate the skin under normal conditions of use and test only those that penetrate at toxicologically relevant levels in the three-test in vitro battery. Recently published data [D. Kirkland, M. Aardema, L. Henderson, L. Müller, Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens. I. Sensitivity, specificity and relative predictivity, Mutat. Res. 584 (2005) 1-256] suggest the three-test battery will produce a significant number of false as well as real positives. Whilst we are aware of the desire to reduce animal experiments, determining the relevance of positive results in any of the three recommended in vitro assays will most likely have to be determined by use of in vivo assays. The bone marrow micronucleus test using routes of administration such as oral or intraperitoneal may be used where the objective is extended hazard identification. If negative results are obtained in this test, then a second in vivo test should be conducted. This could be an in vivo UDS in rat liver or a Comet assay in a relevant tissue. However, for hazard characterisation, tests using topical application with measurement of genotoxicity in the skin would be more appropriate. Such specific site-of-contact in vivo tests would minimise animal toxicity burden and invasiveness, and, especially for hair dyes, be more relevant to human routes of exposure, but there are not sufficient scientific data available to allow recommendations to be made. The generation of such data is encouraged.
Amines↗
Diagnostic tools for animal diseases.
While traditional testing methods are still widely used in veterinary diagnostic laboratories exciting new technologies, such as biosensors and microarray techniques, are being developed. Nucleic acid diagnostic techniques such as polymerase chain reaction (PCR) have become routine diagnostic tools in veterinary laboratories not only to make specific typing determinations but also to rapidly screen large numbers of samples during disease outbreaks. In addition, nanotechnologies, although not yet implemented in veterinary laboratories, hold the promise of screening for numerous pathogens in a single assay. Other biotechnologies are likely to be widely used in the future as they can improve diagnostic capabilities while reducing the time and perhaps, the costs, associated with conventional technologies. This paper describes some of these new technologies and concludes that although a lot of developmental work is still required, biotechnology and its applications hold great promise for improving the speed and accuracy of diagnostics for veterinary pathogens.
Animal Diseases↗
A survey to assess physical activity promotion by Registered Dietitians.
BACKGROUND: Convincing evidence has emerged in recent years for the role of physical activity (PA) in the prevention and treatment of many chronic diseases. These include both physical and mental health problems, which are likely to be encountered by practicing dietitians. This study aimed to identify whether NHS based Registered Dietitians (RDs) currently promote PA to their patients and if so, how they do it and with which patients. METHOD: An anonymous questionnaire sent to 516 RDs in NHS teaching hospitals achieved a 77% (n = 397) return rate. RESULTS: Ninety-three per cent of respondents reported regularly promoting PA particularly with new patients. Among active PA promoters, 87% reported encouraged daily accumulation of PA, 50% focused on sport and exercise and 52% referred patients to GPs or Physiotherapists for advice. Distinctive levels and styles of PA promotion were found to be related to levels of recent training in the field although fewer than one in four had actually received any formal training. CONCLUSIONS: A high interest in further PA-specific training (95% of all respondents), together with high variability in the type and quality of advice suggests the need to develop further in-service training specifically for RDs.
Adult↗
Preliminary findings in the neurophysiological assessment of intercostal nerve injury during thoracotomy.
OBJECTIVE: Previous work has suggested that intercostal nerve injury is a major factor in the aetiology of chronic post-thoracotomy pain. The aim of this study was to establish if there was identifiable intercostal nerve injury during thoracotomy. METHODS: Intercostal nerves were stimulated and motor evoked potentials were recorded from intercostal muscles in 13 patients undergoing thoracotomy. Measurements were taken before and after entering the pleural space, after removal of the rib retractor and after intercostal space closure. RESULTS: Intercostal nerves functioned normally before and after entering the pleural space. After the rib retractor was removed, there was a total conduction block in the nerve immediately above the incision in every patient. In the nerves above this, six had a total block, one a partial block and three had normal conduction. There was a total conduction block in the nerve immediately below the incision in all but one patient. Of the nerves below this, four had a total block, two a partial block and three had normal conduction. In the cases of total conduction block, there was either a discrete block at the level of the distal end of the rib retractor or impairment throughout the whole nerve. Intercostal space closure did not injure any previously uninjured nerve. In a solitary patient where rib retraction was not employed, there was no impairment of the intercostal nerves throughout the operation. CONCLUSIONS: This study demonstrates for the first time that intercostal nerve injury occurs routinely due to rib retraction during thoracotomy. We believe that it may be an important step toward understanding the cause of post-thoracotomy neuralgia.
Evoked Potentials, Motor↗
St John's wort (Hypericum perforatum): drug interactions and clinical outcomes.
AIMS: The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible. METHODS: A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken. RESULTS: A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions. CONCLUSIONS: In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.
Contraceptives, Oral↗
Are all noisy quantum states obtained from pure ones?
We ask what type of mixed quantum states can arise when a number of separated parties start by sharing a pure quantum state and then this pure state becomes contaminated by noise. We show that not all mixed states arise in this way. This is even the case if the separated parties actively try to degrade their initial pure state by arbitrary local actions and classical communication.
Journal Article↗
The validity of a short version of the Body Shape Questionnaire.
This study investigated the 'construct validity' (which includes the extent to which a test conforms to predictions from previous observations) of a 14-item version of the Body Shape Questionnaire (BSQ) in 75 patients with psychogenic low weight and a history of full or partial anorexia nervosa (AN). Various predictions were confirmed, i.e. ratings on the BSQ (designed to measure concern about body image) were significantly correlated with ratings for the Eating Attitudes Test, the Bulimia Investigatory Test and the Beck Depression Inventory, and with the body mass index at referral. Also, the binge eating/purging subtype of AN was associated with increased body-image psychopathology. In contrast to a previous report using another questionnaire, this association was independent of body weight. The findings indicate that this shorter version of the BSQ can be used to assess body image psychopathology in patients with psychogenic low weight and to confirm an increased concern about body-image in the binge-eating/purging subtype of AN.
Adult↗
Porcine dermatitis and nephropathy syndrome.
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Animals↗
Oral health of patients with hepatitis C virus infection: a pilot study.
OBJECTIVES: This study examined the oral health of a cohort of hepatitis C virus (HCV) patients. In particular, the prevalence of lichen planus and xerostomia were determined. Experiences of discrimination against HCV-infected patients by their dentists were also recorded. METHODS: Forty patients infected with HCV, who were not undergoing anti-viral treatment, were examined. Patient information collected included demographic details together with patients' perception of their oral health and access to dental care since being diagnosed with hepatitis C. Both extra-oral and intra-oral examinations were conducted. Teeth present and visible caries were recorded, periodontal condition was measured using a Community Periodontal Index of Treatment Need (CPITN) probe and denture fit and hygiene were assessed where appropriate. The soft tissues were examined and lichen planus diagnosed clinically. Salivary flow rates were estimated by the Salivette system. RESULTS: The oral health of this cohort was poor. Eight patients had clinical evidence of oral lichen planus (OLP), although this was not confirmed histologically. The salivary flow rates were significantly lower (P < 0.001) than in previously reported healthy controls. Of the 15 (37.5%) regular dental attenders, two had encountered problems accessing dental care. CONCLUSIONS: Chronic hepatitis C patients have significant oral health needs. More effective oral health education is required for both HCV-infected patients and their carers, including dental practitioners.
Adult↗
Selectively impaired reaction time in Parkinson's disease: persistent absence of simple reaction advantage in a patient with frontal complications.
The search for specific patterns of impaired reaction time in Parkinson's disease has yielded conflicting results. We propose subtypes that exhibit different patterns of impairment and report the case of a patient, Jobe, whose simple and binary choice reaction times were tested repeatedly in a variety of stimulus-response paradigms over a period of 4 years. Jobe consistently failed to exhibit the normal simple reaction advantage even though his choice reaction times fell well within the normal range. While his general intellectual status was above average, he had great difficulty with some neuropsychological tests. He was seldom able to acquire a new category in the Wisconsin Card Sort Test and also had difficulty with the Tower of London Test. We ascribe Jobe's selective impairment of simple reactions to an inability to engage in the off-line preparatory processing that confers an advantage on simple reactions.
Aged↗
Monitoring gastrointestinal intraluminal PCO2: problems with airflow methods.
UNLABELLED: Gastrointestinal intraluminal PCO2 (PiCO2) information is used to assess the adequacy of trauma patient resuscitation and to assist in choosing resuscitative interventions. Therefore, determining the limitations and potential caveats of different PiCO2 monitoring systems is clinically important. This study compared two PCO2 monitoring systems. The airflow device adds and then removes air samples to quantitate PCO2, whereas the fiber-optic device does not. METHODS: Airflow (TRIP Tonometer/Tonocap) and fiber-optic (Neotrend) systems were used. In vitro they were compared with each other and to two end-tidal CO2 monitors measuring the PCO2 of humidified air containing 5% and then 10% CO2. In vivo the two systems' catheters were surgically juxtaposed in 15 dogs' stomachs; paired PiCO2 readings were taken throughout hemorrhage and resuscitation. RESULTS: In vitro, paired PCO2 values from the airflow and fiber-optic devices correlated with each other (r = 0.99) and with end-tidal values (r = 0.99 with airflow, r = 0.95 with fiber-optic). In vivo, paired values differed significantly (P < 0.0001), correlating poorly for two devices simultaneously measuring the same variable (r = 0.61). Fiber-optic PiCO2 values were higher than airflow values (mmHg +/- SEM): 69.3 +/- 4.8 vs. 61.3 +/- 5.6 at the start of hemorrhage, 141.3 +/- 12.9 vs. 87.7 +/- 7.9 by end of hemorrhage, and 104.3 +/- 9.6 vs. 82.8 +/- 7.0 by end of resuscitation for fiber-optic and airflow, respectively. CONCLUSIONS: Despite agreement in vitro, airflow methods can influence PiCO2 values obtained in vivo. Passive sensing methods used to monitor PiCO2, such as fiber-optic methods, are preferable because they neither deliver O2 to, nor remove CO2 from the local microenvironment.
Animals↗
Control of impurities in diphenhydramine hydrochloride by an ion-pairing, reverse liquid chromatography method.
A precise, sensitive, repeatable and robust reverse-phase liquid chromatographic method has been developed for the control of seven possible impurities of diphenhydramine hydrochloride. The robustness of the method was examined by varying, in turn, each of four mobile-phase parameters (acetonitrile content, buffer salt concentration, ion-pair reagent concentration and pH). The method was linear in the range 0-0.14 mg mL(-1) for diphenhydramine hydrochloride with an acceptable precision and accuracy, and a limit of detection of 0.17 microg mL(-1). Five samples of diphenhydramine hydrochloride from two sources were analysed with the developed liquid chromatographic method.
Chromatography, High Pressure Liquid↗
Representing infant feeding: content analysis of British media portrayals of bottle feeding and breast feeding.
OBJECTIVE: To examine how breast feeding and bottle feeding are represented by the British media. DESIGN: Content analysis. SUBJECTS: Television programmes and newspaper articles that made reference to infant feeding during March 1999. SETTING: UK mass media. MAIN OUTCOME MEASURES: Visual and verbal references to breast or bottle feeding in newspapers and television programmes. RESULTS: Overall, 235 references to infant feeding were identified in the television sample and 38 in the newspaper sample. Bottle feeding was shown more often than breast feeding and was presented as less problematic. Bottle feeding was associated with "ordinary" families whereas breast feeding was associated with middle class or celebrity women. The health risks of formula milk and the health benefits of breast feeding were rarely mentioned. CONCLUSIONS: The media rarely present positive information on breast feeding, even though this feeding practice is associated with the most health benefits. Health professionals and policy makers should be aware of patterns in media coverage and the cultural background within which women make decisions about infant feeding.
Attitude to Health↗
Clinical outcomes, quality of life, and costs in the North Thames Dialysis Study of elderly people on dialysis: a prospective cohort study.
BACKGROUND: Evidence-based health policy is urgently needed to meet the increasing demand for health services among elderly people, particularly for expensive technologies such as renal-replacement therapy. Age has been used to ration dialysis, although not always explicitly, despite the lack of rigorous empirical evidence about how elderly people fare on dialysis. We undertook a comprehensive assessment of outcomes in patients 70 years or over. METHODS: We did a 12-month prospective cohort study of outcomes in 221 patients with end-stage renal failure aged 70 years or over recruited from four hospital-based renal units. We assessed 1-year survival in 125 incident patients (70-86 years) and disease burden (hospital admissions, quality of life, costs) in 174 prevalent patients (70-93 years). FINDINGS: 1-year survival rates were: 71% overall; 80%, 69%, and 54% in patients 70-74 years, 75-79 years, and 80 years and older, respectively (p=0.008); and 88%, 71%, and 64% in patients with no, one, or two or more comorbid conditions, respectively (p=0.056). Cox regression analyses showed that mortality was significantly associated with age 80 years and older (relative risk 2.79 [95% CI 1.28-6.93]) and peripheral vascular disease (2.83 [1.29-6.17]), but not with diabetes, ischaemic heart disease, cerebrovascular disease, chronic obstructive airways disease, sex, or treatment method. In terms of disease burden, hospital admissions represent a low proportion of costs and was not required by a third of patients, mental quality of life in elderly dialysis patients was similar to that of elderly people in the general population, and the average annual cost per patient of 20802 (US$31200) (68% dialysis treatment, 1% transport, 19% inpatient hospital admissions, 12% medications) was within the range of other life-extending interventions. INTERPRETATION: Our results suggest that age alone should not be used as a barrier to referral and treatment and emphasise the need to consider the benefits of dialysis in elderly people. Indicators of the ability to benefit from treatment, rather than chronological age, should be used to develop policies that ensure equal access to care for all.
Aged↗
Information, relative entropy of entanglement, and irreversibility.
Previously proposed measures of entanglement, such as entanglement of formation and assistance, are shown to be special cases of the relative entropy of entanglement. The difference between these measures for an ensemble of mixed states is shown to depend on the availability of classical information about particular members of the ensemble. Based on this, relations between relative entropy of entanglement and mutual information are derived.
Journal Article↗
Thresholds in genotoxicity responses.
It has been commonly accepted that risk assessments of genotoxic chemicals are based on linear extrapolation methods. However, there is substantial evidence that some chemicals may be genotoxic only at high doses by mechanisms that do not occur at low doses, or only under specific conditions in genotoxicity assays, but are inactive at concentrations within the range of human exposure levels. There are a variety of possible mechanisms of thresholded genotoxicity, including disruption of cell division and chromosome segregation, inhibition of DNA synthesis, overloading of oxidative defence mechanisms, metabolism or plasma binding capacity, disturbances of metal homeostasis, cytotoxicity and physiological perturbations in in vivo assays. The degrees of evidence supporting the proposed mechanisms are variable and not all are sufficiently robust to be universally accepted as yet by the scientific community. However, a survey of industrial companies indicated that data have been accepted by some regulatory authorities indicating thresholds contributing to genotoxicity responses.
Animals↗
Thresholds in genetic toxicology - concluding remarks.
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Animals↗