Biomedical subjects
Publications and source records attributed to P M Wilson.
Lightning strikes kill 1,000 people per year worldwide. Cardiac arrests resulting from lightning strikes have good survival rates but there is a significant degree of morbidity amongst the survivors. This is the case report of a 13-year-old boy who had a cardiac arrest following a direct lightning strike, and his subsequent management.
The rise in chronic illness and comorbidity in Western society has resulted in an increasing emphasis on self-care initiatives. In the United Kingdom this is exemplified by the Expert Patient policy. This paper discusses the Expert Patient initiative as an example of the State's third way approach to public health. The extent to which this policy challenges conventional power relationships between professional and patient, and fosters equal partnership is examined. In particular, how expert is defined and whether a professional understanding of the term is reconcilable with a patient's expertise is debated. The paper argues that the Expert Patient initiative is unlikely to reconstruct chronic illness and may further complicate the State's responsibility in meeting the needs of those with chronic illness. Issues of power within self-care are explored to illuminate the policy, and this paper argues that the Expert Patient initiative is an example of Foucault's notion of pastoral power. Although the Expert Patient policy focuses on the rights and responsibilities of those with chronic illness, this paper concludes that there is no corresponding strategy to challenge professionals' assumptions toward those with chronic illness.
OBJECTIVE: To review the safety and efficacy of fluoridation of drinking water. DESIGN: Search of 25 electronic databases and world wide web. Relevant journals hand searched; further information requested from authors. Inclusion criteria were a predefined hierarchy of evidence and objectives. Study validity was assessed with checklists. Two reviewers independently screened sources, extracted data, and assessed validity. MAIN OUTCOME MEASURES: Decayed, missing, and filled primary/permanent teeth. Proportion of children without caries. Measure of effect was the difference in change in prevalence of caries from baseline to final examination in fluoridated compared with control areas. For potential adverse effects, all outcomes reported were used. RESULTS: 214 studies were included. The quality of studies was low to moderate. Water fluoridation was associated with an increased proportion of children without caries and a reduction in the number of teeth affected by caries. The range (median) of mean differences in the proportion of children without caries was -5.0% to 64% (14.6%). The range (median) of mean change in decayed, missing, and filled primary/permanent teeth was 0.5 to 4.4 (2.25) teeth. A dose-dependent increase in dental fluorosis was found. At a fluoride level of 1 ppm an estimated 12.5% (95% confidence interval 7.0% to 21.5%) of exposed people would have fluorosis that they would find aesthetically concerning. CONCLUSIONS: The evidence of a beneficial reduction in caries should be considered together with the increased prevalence of dental fluorosis. There was no clear evidence of other potential adverse effects.
Activities of daily living scales can be a useful tool in assessing change in people with dementia, either as the disease progresses or in response to treatment. However, little data exist as to the sensitivity to change of instruments used. The Bristol Activities of Daily Living Scale was developed with assistance from the carers of community dwelling people with dementia to be completed by such people and has been shown to have internal consistency as well as face and construct validity. This study aimed to analyse the sensitivity to change of the Bristol Activities of Daily Living Scale in people with Alzheimer's disease receiving anticholinesterase medication. Using the Clinician's Global Rating of Change as a gold standard for change, differences between Bristol Activities of Daily Living Scale scores before and after medication were compared with change in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale - Cognitive and the Nurses Observation Scale for Geriatric Patients, in 61 older adults receiving anticholinesterase medication for Alzheimer's disease. Both the Bristol Activities of Daily Living Scale and the Nurses Observation Scale for Geriatric Patients are sensitive and specific in predicting improvement or stability as measured by the clinician's global rating of change. However, unlike the Nurses Observation Scale for Geriatric Patients, change over time in the Bristol Activities of Daily Living Scale significantly correlates with change in the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale - Cognitive. The Bristol Activities of Daily Living Scale is sensitive to change in activities of daily living and shows the expected and desirable relationship with measures of cognition.
The avascular cornea has limited access to plasma proteins, including plasminogen, a protein that is synthesized by the liver and supplied to most tissues via the blood. Recent experiments by others using plasminogen-deficient mice revealed the importance of plasmin, the active form of plasminogen, for the maintenance of the normal cornea and for corneal wound healing [Kao, Kao, Bugge, Kaufman, Kombrinck, Converse, Good and Degan (1998) Invest. Ophthalmol. Vis. Sci. 39, 502-508; Drew, Kaufman, Kombrinck, Danton, Daugherty, Degen and Bugge (1998) Blood 91, 1616-1624]. In the present experiments, plasmin was identified as a major serine proteinase in the human cornea. The major plasminogen and plasmin forms on non-reducing zymograms and Western blots had Mr values of 76x10(3) and 85x10(3), with minor forms of Mr 200x10(3), 135x10(3), 68x10(3) and 45x10(3). Angiostatin-like peptides with Mrs of 48x10(3), 45x10(3) and 38x10(3) were observed which bound to lysine-Sepharose and reacted with anti-plasminogen monoclonal antibodies directed towards kringle domains 1-3 of plasminogen. The cornea contained 1.1+/-0.15 microgram of plasminogen+plasmin/cornea, or 0.54+/-0.05 microgram of plasminogen+plasmin/mg of protein. Cornea conditioned medium contained nine times the amount of plasminogen+plasmin that could be extracted from the cornea. These data suggested that corneal cells, unlike most extrahepatic cells, synthesize plasminogen. The synthesis of plasminogen by the cornea was confirmed by immunoprecipitation of metabolically labelled plasminogen, sequencing of its cDNA obtained by reverse transcriptase-PCR and inhibition of protein synthesis. Interleukins-1alpha and -1beta stimulated corneal plasminogen synthesis 2-3-fold; however, interleukin-6 decreased corneal plasminogen synthesis by approx. 40% at early times after addition of the cytokine. By 24 h of culture, no differences were noted in the presence and absence of interleukin-6. Thus the cornea can synthesize plasminogen and regulate its synthesis in response to its environment, including cytokines induced in the cornea by injury and inflammation. Therefore the cornea can control the amount of plasminogen, the precursor of both plasmin and angiostatin.
Neuronal death can be induced by DNA-damaging agents and occurs by apoptosis involving a specific signal-transduction pathway. However, to our knowledge, methods for the quantitative determination of DNA damage in individual neurons have not yet been described. Here we optimize the single-cell gel electrophoresis (SCGE) or "comet"-assay to measure DNA damage within individual neurons growing in dissociated cell culture. In addition, we have written a macro for the NIH Image program to determine the tail moment of individual comets. We have calibrated this method using gamma-irradiated (0-16 Gy) cerebral cortical neurons from the rat central nervous system. Neuronal DNA damage (in the form of DNA strand breaks) occurs in a linear, dose-dependent manner, which can be quantitatively determined in vitro using the SCGE assay. These data demonstrate that the SCGE assay is an effective method to measure DNA damage in individual neurons and may be highly useful for the study of neuronal DNA damage formation, repair and apoptosis.
Conjugation of bacterial polysaccharides (PS) to protein carriers confers the ability to elicit protective serum Ab in infants, who respond poorly to plain PS. The serum Ab of young children immunized with Haemophilus influenzae type b (Hib) PS conjugate vaccine varies with age and Ag formulation. To understand these age-related changes in human anti-Hib PS immune responses we determined the variable region gene sequences encoding anti-Hib PS mAbs of infants immunized with Hib oligosaccharide-diphtheria toxin vaccine. The anti-Hib PS repertoire of children differs from that of adults. A smaller proportion of mAbs from children have high affinity for Hib PS, and the overall variable region gene repertoire of infants is more diverse than that in adults. Variable region genes encoding high affinity mAbs of infants are similar to the restricted repertoire described in adults. Low affinity anti-Hib PS mAbs of infants are encoded by a heterogeneous group of genes that are uncommonly observed in the adult repertoire. Abs with high affinity for Hib PS from infants, like most mAbs from adults, react only with Hib PS and the structurally similar PS of Escherichia coli K100, whereas low affinity mAbs of infants are polyreactive. The low affinity anti-Hib PS mAbs of infants immunized with Hib oligosaccharide-diphtheria toxin vaccine vaccine are not reflected in serum Ab. However, the differences between the variable region gene repertoires of adults and infants may account for the distinct immunologic characteristics of the anti-Hib PS responses in young children immunized with other vaccine formulations.
PURPOSE: Vitamin A deficiency alters the transparency of the cornea due to epithelial cell keratinization and increases the susceptibility of the cornea to ulceration. The purpose of this study was to determine the effect of vitamin A deficiency on rat corneal matrix metalloproteinases and serine proteinases. METHODS: Four dietary groups of male WAG/RijMCW rats were prepared: (1) Vitamin A deficient rats were raised on a casein-based retinoid deficient diet; (2) Retinol repleted rats were raised on the retinoid deficient diet. On the eighty-sixth day on this diet, the rats were fed retinyl palmitate and then given free access to the retinyl palmitate-supplemented control diet; (3) The weight-matched, pair-fed rats were restricted in their intake of the retinyl palmitate-supplemented diet so that their weight gain matched that of the A-rats; (4) The non-restricted rats were given free access to the retinyl palmitate-supplemented diet. The animals were killed at the late plateau stage for weight of the deficiency (102-106 days). Zymography was used to study proteinases in the corneal extracts. RESULTS: Vitamin A deficient and control rat corneas contain multiple matrix metalloproteinases and serine proteinases. The matrix metalloproteinases at 90/92 kDa (gelatinase B) and 66/63/57 kDa (gelatinase A) were significantly decreased in the corneas of the vitamin A deficient rats relative to the control corneas. Corneas from the four groups of rats contained 76, 45, 38, 28 and 22 kDa proteinases that cleaved casein. Only the vitamin A deficient corneas contained a 50 kDa casein cleaving enzyme. The 76, 45, 38 and 28 kDa serine proteinases were significantly lower in the vitamin A deficient corneas. The major 22 kDa enzyme was not altered by the deficiency. All casein cleaving proteinases were inhibited by phenylmethylsulfonyl fluoride and chymostatin except for a minor 76 kDa band. The activity of this band was not altered by inhibitors for the other classes of proteinases, ethylenediaminetetraacetic acid, E-64 or pepstatin. The concentrations of the 61, 52 and 40 kDa plasminogen activators were not altered by the deficiency. CONCLUSIONS: Alterations in corneal proteinases under vitamin A deficiency conditions may be involved in the characteristic changes observed in the cornea under vitamin A deficiency conditions: decreased exfoliation of epithelial cells, increased levels of keratofibrils in the corneal keratocytes, increased stromal keratocyte degradation and increased susceptibility towards ulceration.
Previous studies showed a higher percentage of neutrophils from vitamin A deficient rats are hypersegmented and contain lower levels of cathepsin G than the neutrophils from control rats. In this study chemotaxis, phagocytosis and oxidant generation were studied using either isolated neutrophils or neutrophils in whole blood from four dietary groups of rats: 1) vitamin A deficient rats; 2) vitamin A deficient rats that received vitamin A for 16, 8, 4 or 2 d prior to killing; 3) weight-matched rats pair-fed a vitamin A-complete diet; and 4) rats fed nonrestricted, vitamin A complete diet. Chemotaxis towards P. aeruginosa conditioned medium and formylated methinyl leucinyl phenylalanine was significantly lower for neutrophils from vitamin A-deficient rats than for neutrophils from weight-matched pair-fed rats, nonrestricted vitamin A sufficient rats and vitamin A deficient rats that received vitamin A for 16 d prior to killing. No differences in chemotaxis towards activated rat serum were noted among the neutrophils from the four groups of rats. Adhesion of P. aeruginosa organisms, phagocytosis of these organisms and generation of active oxidative molecules were significantly lower in the neutrophils from the vitamin A-deficient rats relative to these functions in the neutrophils from the vitamin A deficient rats that received vitamin A for 16 d, weight-matched rats pair-fed a vitamin A complete diet; and rats fed nonrestricted, vitamin A-complete diet. Eight days after vitamin A administration to vitamin A deficient rats, the ability of the neutrophils to phagocytose P. aeruginosa organisms and to generate active oxidant molecules was restored to the levels observed for weight-matched, pair-fed rats and rats fed nonrestricted, vitamin A complete diet. The elucidated alterations in neutrophil function in vitamin A deficient rats probably contribute to the altered ability of vitamin A deficient rats to fight infections.
The times of origin of neurons in the septum, amygdala and hippocampus of the marsupial brushtailed possum, Trichosurus vulpecula, were determined with 3H thymidine autoradiography. The long time period for neurogenesis in the brushtailed possum facilitated analysis of neurogenetic gradients in the brain. A series of 20 possums were injected with 3H thymidine from postnatal (P) days 5-95 and were allowed to survive until brain cytoarchitecture was mature. Our results indicate that septal neurogenesis was complete by P21 (38 days after conception) with a medial to lateral gradient of neurogenesis evident in the lateral septal division. Neurogenesis in the amygdala was complete in the basal, central and medial amygdaloid nuclei by P21, and in the lateral amygdaloid nucleus by P46, with a medial to lateral gradient of neurogenesis evident in basal, central and lateral amygdaloid nuclei. In the hippocampus, neurogenesis of pyramidal cells was complete in field CA3 by P50, and in field CA1 by P55. Early forming pyramidal cells (P5-12) were distributed adjacent to the stratum oriens in fields CA1 and CA3, with later forming pyramidal cells distributing in the middle of the stratum pyramidale (P21-32) and on the edge adjacent to the stratum radiatum (P46). Neurogenesis of dentate granule cells extended over a long period of time, from P5, at least until P82, with the earliest forming granule cells (P5-12) distributed adjacent to the stratum moleculare, and the latest forming granule cells (P82) adjacent to the hilus.
Vitamin A deficiency leads to an increased susceptibility to infections, increased severity of infections and increased mortality. Because the neutrophil is the first cell to respond to infection, this study explores the effect of vitamin A deficiency on neutrophil proteinases. We found that neutrophils from vitamin A-deficient rats had lower levels of two cathepsin G-like enzymes (28 and 24 kDa) when compared to neutrophils from weight-matched pair-fed rats, vitamin A-deficient rats which were repleted with retinyl palmitate and nonrestricted vitamin A complete diet rats. The 28 kDa cathepsin G-like enzyme, which migrated with the same mobility as elastase on SDS-polyacrylamide gels, was quantified using Western blots. The 24 kDa cathepsin G-like enzyme was quantified using zymogram gels. This activity was inhibited by chymostatin. Other neutrophil proteinases, elastase, plasminogen activators and gelatinase, were not altered significantly by vitamin A deficiency. The low levels of cathepsin G may contribute to differences in the inflammatory process observed under vitamin A deficiency.
Using gas chromatography/mass spectrometry for detection of hemoglobin adducts, and 32P-postlabelling for DNA adducts, we examined macromolecular binding in Fischer-344 rats administered 2,4-or 2,6-toluene diamine (TDA). The dose-response and correlative relationship between the two macromolecules were investigated over a range of doses (0-250 mg/kg). The time course of adduct formation and removal was also examined. Both TDA isomers induced formation of hemoglobin adducts, but only the 2,4-isomer induced DNA binding. Maximum hemoglobin and DNA adduct levels were detected 24 h following administration. Both hemoglobin and DNA binding increased in a dose-dependent manner. Hemoglobin adduct clearance demonstrated a nonlinear decay, with adduct loss occurring faster than normal erythrocyte clearance. The effects of metabolic inhibitors on adduct formation were examined using piperonyl butoxide and pentachlorophenol to inhibit p450 isozymes and sulfotransferase, respectively. Microsomal enzymatic activation was critical to hemoglobin adduct formation with inhibition by piperonyl butoxide reducing adduct yields by over 90%. Sulfation did not appear to play a significant role in TDA-induced hemoglobin adduct formation.
Retinoic acid bound to the nuclear retinoic acid receptor-alpha is required for the differentiation of promyelocytes to mature neutrophils. However, severely vitamin A-deficient rats have normal numbers of neutrophils in the blood and inflamed tissues. This paradox was explored using four dietary groups of rats: 1) vitamin A-deficient rats; 2) vitamin A-deficient rats subsequently receiving vitamin A; 3) weight-matched pair-fed rats; and 4) nonrestricted, vitamin A-complete diet-fed rats. Plasma and liver retinol concentrations of the vitamin A-deficient rats were < 1 % of those of the other three groups. In contrast, the bone marrow retinol concentrations of the vitamin A-deficient rats were fourfold higher than those in the other three groups. The distribution of myeloid-derived cells in the bone marrow was similar in all four groups of rats with the exception of a significantly greater (P < 0.05) occurrence of hypersegmented neutrophils (six or more lobes) in the vitamin A-deficient rats (2. 1 %) relative to the control groups (0-0.1%). The blood of the vitamin A-deficient rats also contained significantly higher numbers (P < 0.01) of hypersegmented neutrophils (67%) relative to those in the control groups (2-7%). The hypersegmentation of the neutrophils in this group of rats was not due to a concurrent deficiency of vitamin B-12 or folate. The importance of bone marrow-derived cells to the survival of the animal is suggested by retinol sequestration in the bone marrow of vitamin A-deficient rats, allowing the differentiation of myeloid cells to neutrophils.
PURPOSE: Vitamin A-deficient humans and animals are more susceptible to infections than are healthy humans and animals. This study compares the early corneal response (within 24 hours) to an experimental Pseudomonas aeruginosa infection between vitamin A deficient and control rats. METHODS: Male WAG/Rij/MCW rats were fed either a vitamin A- deficient diet (A-) or the same diet with retinyl palmitate added back in a nonrestricted manner (N) or under pair-fed conditions (A+) to yield weight-matched rats. Some A-rats were repleted wih retinyl palmitate 16 days before being killed and then given free access to the retinyl palmitate-supplemented diet (R). Twenty-four hours before being killed, the corneas of anesthetized rats were scratched and P. aeruginosa organisms were applied to the corneal surface. The rats were killed using an overdose of sodium pentobarbital. Corneas were either processed for light and electron microscopic examination or extracted for proteinase and myeloperoxidase determination. Corneal myeloperoxidase concentrations relative to neutrophil myeloperoxidase concentrations were used to determine the number of neutrophils in the cornea. Zymography was used to study caseinases, gelatinases, and plasminogen activators. Reverse zymography was used to detect proteinase inhibitors. Similar results were noted at early, mid, and late weight plateau stages of vitamin A deficiency. RESULTS: Ulceration occurred within 24 hours when low numbers of P. aeruginosa (10(4) cpu) were applied topically onto scratched A- corneas, whereas no ulceration was observed in the A+, R, and N corneas. When higher numbers of P. aeruginosa (10(7)-10(8)) were applied to the scratched corneas, all corneas became ulcerated within 24 hours. The extent of ulceration in the control corneas was greater than that in A- corneas by a factor of two. Only the A- corneas contained inflammatory cells with unusual striated deposits in phagolysosomes. The total number of neutrophils in the cornea and the concentrations of caseinases, plasminogen activators, and gelatinases in the infected corneal extracts were similar; however, the concentrations of cysteine proteinase inhibitors were elevated under A- conditions. CONCLUSIONS: Vitamin A deficiency alters the response of the cornea to a P. aeruginosa infection during the first 24 hours. The alterations observed are probably due to multiple factors: an insufficient tear film for bacterial clearance and migration of neutrophils, epithelial keratinization, alterations in corneal wound healing, and changes in polymorphonuclear function.
Two days after returning with its owners from a 60-day visit to Liberia, an 8-year-old 6.5-kg spayed female Miniature Schnauzer was examined by a veterinarian in the United States. A 1.0 x 1.0-cm raised erythematous nodule was noticed on the medial aspect of the right pinna. In the center of the nodule was a 1.0 x 1.0-mm pore from which a 0.5 x 0.5 x 1.0-cm white larva was extracted. The larva was identified as a third-stage larva of Cordylobia anthropophaga, the African Tumbu fly, a fly restricted to sub-Saharan Africa. Cordylobia anthropophaga does have zoonotic potential, but the owners did not have any skin lesions. Detection of C anthropophaga in the United States warranted reports to state and federal authorities and personnel at the Centers for Disease Control and Prevention. The situation described here illustrated the potential of tourists' pets to import foreign diseases.
A procedure to determine hemoglobin adduct yields resulting from exposure to the carcinogen 2,4-diaminotoluene (2,4-TDA) was developed using gas chromatography-electron impact positive-ion mass spectrometry. Liberated 2,4-TDA was quantified following alkaline hydrolysis of hemoglobin. Optimized derivatization of free 2,4-TDA with hepatafluorobutyric anhydride allowed detection of hemoglobin adduct levels as low as 5 ng/g Hb. Pure HFBA-2,4-TDA showed a linear dynamic range of 50 to 5000 pg. The quantitative extraction and recovery of liberated 2,4-TDA (ca. 100%) following hemoglobin hydrolysis allows accurate and precise determinations of adduct yields.
BACKGROUND: A patient's satisfaction with a consultation may be influenced by many factors relating to both patient and doctor. AIM: This study set out to examine the effects of emotional disturbance and its detection on general practice patients' satisfaction with the consultation. METHOD: A prospective study involving 893 adult patients attending 12 general practitioners in Glasgow was carried out. Questionnaires were completed by general practitioners after consecutive surgery consultations. Patients completed forms assessing mental state and satisfaction with inter-personal aspects of the consultation. RESULTS: Patients reporting frank psychological disturbance tended to express more dissatisfaction with the inter-personal aspects of the consultation. This effect was alleviated in the majority by recognition of the disturbance by the general practitioner. General practitioners differed markedly in their assessment of the psychological component of consultations. Fewer dissatisfied patients were found in the surgeries of doctors who tended to rate the psychological component of consultations more highly. In contrast, the general practitioner's overall accuracy of diagnosis of psychological distress was a poor predictor of the proportion of dissatisfied patients. CONCLUSION: This preliminary study suggests that a tendency among doctors to assign importance to the psychological component of consultations may enhance elements of patient satisfaction. It is not clear whether this [psychological-mindedness' is an attribute which can be learnt. To resolve this uncertainty, studies are needed of the effects on patients of educational interventions designed to increase general practitioners' sensitivity to psychological distress.
The proteinase inhibitor alpha 1-antichymotrypsin is present in the epithelial, stromal and endothelial layers of the human cornea. This was determined by immunolocalization in corneal sections and by Western blot analysis of extracts from the three separated layers. The inhibitor was quantified in the extracts by immunodot blot analysis. The levels observed were 1.3 +/- 0.3 microgram/cornea for the epithelial layer, 22.8 +/- 3.8 micrograms/cornea for the stromal layer and an average of 0.17 micrograms/cornea for the endothelial layer. alpha 1-Antichymotrypsin is being synthesized by the cornea. Metabolically labeled inhibitor was immunoprecipitated from the three layers following organ culture of the intact cornea. Two major forms were detected. These were the native, mature 64 kDa form and a 50 kDa form which is either a degradation product or an incompletely glycosylated form. These results indicate that the cornea has the ability to locally control degradation through synthesis of this inhibitor. Local synthesis of this inhibitor releases the cornea from total dependance upon the vascular system for its supply of alpha 1-antichymotrypsin.