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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 109 records · Page 6Linked to original sources
PubMed1999

The importance of qualitative vitreous examination in patients with acute posterior vitreous detachment.

OBJECTIVE: To determine whether patients with acute posterior vitreous detachment with pigmented vitreous granules or hemorrhage have a higher likelihood of retinal tear compared with those with qualitatively normal vitreous examination findings. METHODS: A multicenter cross-sectional study was performed in 3 peripheral ophthalmic clinics. Patients with acute posterior vitreous detachment were examined for the presence or absence of vitreous pigment granules, vitreous hemorrhage, and horseshoe retinal tear. RESULTS: Fifty-nine consecutive patients with acute posterior vitreous detachment met our eligibility criteria. Eight patients had a retinal tear, and thus its prevalence in our study was almost 14%. Thirteen patients (22%) had a high likelihood because they had evidence of either pigmented vitreous granules or hemorrhage. The prevalence of retinal tear in the setting of acute posterior detachment associated with vitreous hemorrhage alone, pigment alone, or vitreous hemorrhage and pigment was 54%. Patients with posterior vitreous detachment with pigmented vitreous granules or hemorrhage were significantly more likely to have a retinal tear (odds ratio, 52.0; 95% confidence interval, 5.4-497.0). Patients with a retinal tear were 7 times more likely to have pigmented vitreous granules or hemorrhage (LR + ve = 7.4, in which LR + ve indicates positive likelihood ratio; 95% confidence interval, 3.3-16.4). CONCLUSION: Patients with posterior vitreous detachment with vitreous pigment granules or hemorrhage are 52 times more likely to have a retinal tear compared with those who have normal findings on qualitative vitreous examination.

Acute Disease↗
PubMed1999

The significance of excursions above the ADI: duration in relation to pivotal studies.

The significance of excursions of intake above the ADI, TDI, or PTWI can only be assessed by reference to the database which led to the derivation of these, most particularly the duration of the pivotal study (chronic, subchronic, acute), the pharmacokinetic parameters, and the nature of toxicity and mechanism of action. Although this implies a case by case assessment, a number of typical situations may be recognized: (1) The substance (usually a contaminant, not an additive) has a very long half-life leading to accumulation in target organs/tissues, e.g., Cd or dioxin. The chronic toxicity is manifested when critical concentrations are achieved in these tissues and there is a large difference between the acutely toxic dose and the chronic NOAEL. In such a case, the effect of excursions above the PTWI on tissue levels is readily calculated; peak excursions of several times the PTWI for short periods (days, weeks, or even months) or lower peak intakes for even longer periods (months to years) may be inconsequential provided that the integrated exposure over longer periods does not lead to critical steady-state tissue concentrations being achieved. (In such cases, it is clearly inappropriate to divide the PTWI by 7 and treat this as an ADI.) (2) A more common situation for food additives is where the ADI is based on a chronic study, but the t1/2 is short, i.e., the situation is one of chronic stress rather than cumulative toxicity. In such cases, e.g., BHA or BHT, the effects on the target organ (hyperplasia, foci of altered cells, etc.) can usually be identified in subchronic studies, although progressive changes may occur in chronic studies. Two subsituations then arise. First, when the effects seen at the LOAEL in subacute/subchronic studies are truly reversible (e.g., methemoglobinemia), short-term studies with a reversibility component may become pivotal in assessing the consequences of short-term excursions above the ADI. Second, when the short-term effects are not fully reversible, or are even progressive, the consequences of short-term peaks of intake above the ADI would require careful evaluation against the NOAEL or LOAEL in subacute or subchronic studies. (3) A rare situation might arise where the ADI is based on a chronic toxicity study but the margins between the chronic NOAEL and some aspects of acute toxicity may be small. For example, for a compound which behaved like retinol, the ADI might be based on chronic effects on the liver but at maternally nontoxic doses the substance may be teratogenic following acute exposure during early pregnancy. Clearly in such a situation, the acute NOAEL for teratogenicity would be used appropriately to evaluate the risks associated with short-term peaks of exposure, i.e., a different study may be pivotal in determining the effects of large excursions above the ADI than that which was used to calculate it. Clearly, these cases are not comprehensive but do provide a framework against which to discuss the potential effects of excursions above the ADI and to reach rational conclusions which are not based on the misapprehension that the ADI (or worse, the PTWI x 7) is a lower bound of toxicity.

Abnormalities, Drug-Induced↗
PubMed1999

The significance of excursions above the ADI. Case study: monosodium glutamate.

Monosodium glutamate (MSG) has been allocated an "ADI not specified" by the JECFA, which indicates that no toxicological concerns arise associated with its use as a food additive in accordance with good manufacturing practice (GMP) and for that reason it is not necessary to allocate a numerical ADI. The question in this case, then, is not whether excursions above a numerical ADI might occur but whether high peak intakes might arise which could invalidate the assumption of absence of hazard. Two major issues have arisen in relation to high intakes of MSG: (1) What is the significance of neural damage (focal necrosis in the hypothalamus) seen following high parenteral or intragastric doses of MSG to neonatal animals and is this a particular risk for children? (2) What is the role of MSG in "Chinese Restaurant Syndrome" (flushing, tightness of the chest, difficulty in breathing, etc.) following consumption of Chinese foods? In relation to the first issue, human studies have been crucial in resolving the question. The threshold blood levels associated with neuronal damage in the mouse (most sensitive species) are 100-130 mumol/dl in neonates rising to > 630 mumol/dl in adult animals. In humans, plasma levels of this magnitude have not been recorded even after bolus doses of 150 mg/kg body wt (ca. 10 g for an adult). Additionally, studies in infants have confirmed that the human baby can metabolize glutamate as effectively as adults. It is concluded that blood levels of glutamate + aspartate do not rise significantly even after abuse doses and babies are no more at risk than adults. Intake levels associated with the use of MSG as a food additive and natural levels of glutamic acid in foods therefore do not raise toxicological concerns even at high peak levels of intake. It is not envisaged that use of MSG according to GMP requires the allocation of a numerical ADI. With regard to the second issue, controlled double-blind crossover studies have failed to establish a relationship between Chinese Restaurant Syndrome and ingestion of MSG, even in individuals reportedly sensitive to Chinese meals, and MSG did not provoke bronchoconstriction in asthmatics. Thus, high usage of MSG in ethnic cuisines does not represent a situation in which intakes might achieve unsafe levels, even among individuals claiming idiosyncratic intolerance of such foods. In the light of the toxicological studies, the human metabolic studies in neonates and adults, and the physiological and nutritional role of glutamic acid and the fact that food additive use does not markedly increase the total dietary burden, no foreseeable circumstances arise in which intakes would be such as to invalidate the appropriateness of allocating an ADI not specified to MSG.

Adult↗
PubMed1999

Development and evaluation of a phantom for morphometric X-ray absorptiometry.

Morphometric X-ray absorptiometry (MXA) provides the potential to assess vertebral deformity using a technique with much lower radiation dose to the patient than standard radiographic procedures. MXA overcomes many other limitations such as cone beam distortion observed in conventional plane radiographs. A phantom has been designed to assess the accuracy of the MXA technique, to monitor long-term precision and to assess inter- and intra-operator variability. The phantom consists of two columns of 12 cylinders representing the vertebral bodies, one of regular components and one representing vertebral deformities. Each column may be inserted, as required, into a Perspex torso-mimicking block. Initial assessment on the Lunar Expert-XL demonstrates that the phantom provides image parameters reflecting those found clinically. Measurement of vertebral height was found to be consistently underestimated by 4.9%. Operator precision ranged from 0.6% for posterior height measurement to 1.0% for middle height measurement of the regular component column. The corresponding precision range for the column representing vertebral deformation was 0.6% (posterior) and 1.1% (middle). Analysis of 10 scans of each column by two independent operators demonstrated a few significant differences in height assessment confined to the 'thoracic' region of the regular column. However, inter-operator variability was found to increase with increasing complexity of vertebral shape producing several differences, particularly in posterior height assessment of the deformed column.

Absorptiometry, Photon↗
PubMed1999

Detection of EWS-FLI-1 fusion in Ewing's sarcoma/peripheral primitive neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed paraffin-embedded tissue.

The balanced translocation t(11;22)(q24;q12) is specific for the Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/PNETs) and results in the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription polymerase chain reaction (RT-PCR). Recent studies also have used fluorescence in situ hybridization (FISH) to show the translocation; however, most of these have been performed on cell lines or touch preparations and short-term cultures of tumors. Moreover, the existing probes generally have shown only the break in the specific chromosomes rather than the translocation itself. We describe our findings with a new set of probes that localize to 22q12 (EWS) and 11q24 (FLI-1) and directly show the translocation as juxtaposed red-green signals on der(22) in nuclei extracted from formalin-fixed, paraffm-embedded tissues. After establishing the specificity of the probes (on metaphase spreads and interphase nuclei in two translocation-positive cell lines and normal peripheral blood lymphocytes), we evaluated 11 ES/PNETs and 10 other tumors (four alveolar rhabdomyosarcomas, three neuroblastomas, two lymphomas, one extramedullary myeloid tumor) using a two-color FISH assay. All 11 ES/PNETs showed fusion signals in 20% to 80% of evaluable nuclei. In two lymphoma cases, random overlapping signals were present in 2% and 4% of nuclei, whereas the remaining eight tumors were negative. The presence of t(11;22) was confirmed by RT-PCR in 10 of 11 ES/PNETs. We conclude that FISH analysis with this newly designed probe pair is a specific and sensitive method of detecting t(11;22) on routinely processed tissue and can be useful in the differential diagnosis of ES/PNETs from other small round blue cell tumors when only fixed tissue is available.

Adolescent↗
PubMed1999

The application of in vitro data in the derivation of the acceptable daily intake of food additives.

The acceptable daily intake (ADI) for food additives is commonly derived from the NOAEL (no-observed-adverse-effect level) in long-term animal in vivo studies. To derive an ADI a safety or uncertainty factor (commonly 100) is applied to the NOAEL in the most sensitive test species. The 100-fold safety factor is considered to be the product of both species and inter-individual differences in toxicokinetics and toxicodynamics. Although in vitro data have previously been considered during the risk assessment of food additives, they have generally had no direct influence on the calculation of ADI values. In this review 18 food additives are evaluated for the availability of in vitro toxicity data which might be used for the derivation of a specific data-derived uncertainty factor. For the majority of the food additives reviewed, additional in vitro tests have been conducted which supplement and support the short- and long-term in vivo toxicity studies. However, it was recognized that these in vitro studies could not be used in isolation to derive an ADI; only when sufficient in vivo mechanistic data are available can such information be used in a regulatory context. Additional short-term studies are proposed for the food additives which, if conducted, would provide data that could then be used for the calculation of data-derived uncertainty factors.

Animals↗
PubMed1999

A model of saccade generation based on parallel processing and competitive inhibition.

During active vision, the eyes continually scan the visual environment using saccadic scanning movements. This target article presents an information processing model for the control of these movements, with some close parallels to established physiological processes in the oculomotor system. Two separate pathways are concerned with the spatial and the temporal programming of the movement. In the temporal pathway there is spatially distributed coding and the saccade target is selected from a "salience map." Both pathways descend through a hierarchy of levels, the lower ones operating automatically. Visual onsets have automatic access to the eye control system via the lower levels. Various centres in each pathway are interconnected via reciprocal inhibition. The model accounts for a number of well-established phenomena in target-elicited saccades: the gap effect, express saccades, the remote distractor effect, and the global effect. High-level control of the pathways in tasks such as visual search and reading is discussed; it operates through spatial selection and search selection, which generally combine in an automated way. The model is examined in relation to data from patients with unilateral neglect.

Attention↗
PubMed1999

Seizure-alert dogs--fact or fiction?

Anecdotal evidence suggests that some dogs may be able to sense the onset of seizures and other medical conditions in humans, although this has never been explored scientifically. There is, however, evidence that dogs can be specially trained to recognize specific changes preceding a seizure and give an overt signal enabling the dog to warn his/her owner. The introduction of the use of dogs to detect and accurately predict the onset of a seizure, giving sufficient time for a person to take control of the situation will have a dramatic impact on quality of life. Support Dogs, a registered charity which trains dogs to assist disabled people, has successfully trained several 'Seizure-alert dogs'. As training progressed, the dogs were able to provide overt signals to their owners within time periods varying from 15 to 45 minutes prior to a seizure occurring. Each dog had an accurate prediction time and, in each case, the owner's seizure frequency was reduced.

Adolescent↗
PubMed1999

Ignorance about Chlamydia among sexually active women--a two centre study.

Chlamydia trachomatis is the micro-organism causing the most common sexually transmitted disease in the UK and Europe. The majority of female infections are asymptomatic and recognized sequelae include pelvic inflammatory disease, infertility, and ectopic pregnancy. Over 1200 sexually active women from two urban centres in the UK were questioned about awareness and knowledge of Chlamydia genito-urinary infection. Awareness was poor, as half of the study population had never heard of Chlamydia. Overall, less than one-quarter demonstrated adequate knowledge regarding transmission, immunity, symptoms, and sequelae. Better knowledge was found in women over the age of 25 years, in those cohabiting, in those with a professional/management occupation, and in those attending family planning clinics. The Chief Medical Officer's Expert Advisory Group on Chlamydia (1998) has recommended opportunistic screening of asymptomatic sexually active women in the UK. This study gives insight into the considerable task facing the Department of Health, as only an informed public will take up the offer of screening. Research is urgently needed to assess the impact of different approaches to education regarding sexually transmitted infection.

Chlamydia Infections↗
PubMed1999

Adherence of Candida albicans to oral epithelial cells differentiated by Papanicolaou staining.

OBJECTIVE: To examine the relative adherence of Candida albicans to oral epithelial cells differentiated by Papanicolaou staining. METHODS: Oral epithelial cells were collected from 10 healthy adults (five male, five female) and counted. Equal volumes of oral epithelial cells and candida were mixed and incubated. The epithelial cells from this mix were collected by filtration through 10 microns polycarbonate membrane filters. Cells retained on the membrane filters were stained with crystal violet followed by Papanicolaou stain. The number of yeast attached to each of 100 red, orange, and green staining oral epithelial cells was determined by direct microscopic examination. RESULTS: C albicans had a higher level of adherence (p < 0.001) to red staining oral epithelial cells (mean (SD) number of candida attached to 100 oral epithelial cells 562 (159)) than to cells staining either orange (105 (47)) or green (161 (66)). CONCLUSIONS: Oral epithelial cell variability for candidal adherence is confirmed. The technique provides an opportunity to examine the relation between oral epithelial cell type and oral candidosis in specific groups, such as tobacco smokers, where increased epithelial cell keratinisation and candidal colonisation has been reported.

Adult↗
PubMed1999

'Niche Selection' and the evolution of a complex behavior in a changing environment--a simulation.

One of the key problems in theoretical biology is the identification of the mechanisms underlying the evolution of complexity. This paper suggests that some difficulties in current models could be avoided by taking account of"niche selection"as proposed by Waddington [21] and subsequent authors [2]. Computer simulations, in which an evolving population of artificial organisms"selects"the niche(s) that maximize their fitness, are compared with a Control Model in which"Niche Selection"is absent. In the simulations the Niche Selection Model consistently produced a greater number of"fit"organisms than the Control Model; although the Niche Selection Model tended, in general, to produce organisms occupying simple niches, it was nonetheless more effective than the Control Model in producing well-adapted organisms inhabiting complex niches. It is shown that the production of these organisms is critically dependent on the rate of environmental change: Slow change leads to fit but undifferentiated populations, dominated by organisms occupying simple niches; differentiated populations, including well-adapted organisms living in complex niches, require rates of environmental change lying just beyond a mathematically well-defined critical value. In simulation"Niche Selection,"unlike conventional"Natural Selection,"provides a permanent selective bias in favor of simplicity. This tendency is counterbalanced by statistical forces favoring shifts from rare"simple niches"to commoner niches of greater complexity. Fit organisms inhabiting complex niches only emerge in conditions where the rate of environmental change is high enough to avoid the concentration of the population in very simple niches, but slow enough to permit step-by-step adaptation to niches of gradually increasing complexity. This result appears to be robust to changes in simulation parameters and assumptions, and leads to interesting conjectures about the real world behavior of biological organisms (and other complex adaptive systems). It is suggested that some of these conjectures might be relatively easy to test.

Animals↗
PubMed1999

Heading off boundary problems: clinical supervision as risk management.

The effective management of risk in clinical practice includes steps to limit harm to clients resulting from ethical violations or professional misconduct. Boundary problems constitute some of the most damaging ethical violations. The authors propose an active use of clinical supervision to anticipate and head off possible ethical violations by intervening when signs of boundary problems appear. The authors encourage a facilitative, Socratic method, rather than directive approaches, to help supervisees maximize their learning about ethical complexities. Building on the idea of a slippery slope, in which seemingly insignificant acts can lead to unethical patterns of behavior, the authors discuss ten cues to potential boundary problems, including strong feelings about a client; extended sessions with clients; gift giving between clinician and client; loans, barter, and sale of goods; clinician self-disclosures; and touching and sex. The authors outline supervisory interventions to be made when the cues are detected.

Ethics, Professional↗