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PubMed2001

Y2K affiliation, immediate pedestrian density, and helping responses to lost letters.

Of 75 letters "lost" in Florida, 41 were returned in the mail (the helpful response). Immediate pedestrian density was significantly related to nonhelping responses. The greater the number of subjects passing by a lost letter, the less likely any one of them would respond to it. The rates of return did vary with the addressees' affiliations. Returned responses for the affiliates, Y2K Arkbuilders and the Believers of God's Judgement Against Homosexuals: Y2K Millennium Bug, were substantially lower than for the affiliate, Y2K Computer Repair & Programming, Inc. Returns for the Believers of God's Judgement Against Homosexuals: Y2K Millennium Bug affiliate were significantly lower than for the Y2K Arkbuilders affiliate. Variables such as sex, race, and estimated age of subjects were not associated with helping to return a lost letter. The rate of return of lost letters is not the only important measure to be examined in studies using lost letters.

Chronology as Topic↗
PubMed2005

Plasma/blood pharmacokinetics and metabolism after dermal exposure to para-aminophenol or para-phenylenediamine.

The pharmacokinetics and metabolism following dermal application of [(14)C]-para-aminophenol (PAP) or [(14)C]-para-phenylenediamine (PPD) were investigated. Groups of rats were treated under occlusion for 24 h with 12.5 mg/kg [(14)C]-PAP, or for 4h with 50 mg/kg [(14)C]-PPD on 10% or 20% of their body surface area, respectively. A female minipig was also treated dermally (24 h, occlusion) with 4.7 mg/kg [(14)C]-PAP on 10% of its body surface area. Blood and plasma samples were analysed for radioactivity and presence of metabolites. In PAP-treated rats, mean plasma levels at 0.5, 1, 2, 4, 8 or 24h were 0.16, 0.24, 0.38, 0.50, 0.36 or 0.14 microg [(14)C]-PAP equivalents/ml, respectively. The plasma half-life was 5.95 h, the C(max) was 0.5 microg/ml, the t(max) was 4 h, and the AUC(0-infinity) was 9.27 microg-equivalentsh/ml. No free PAP was detected in the plasma, but 3 metabolites (M1, M2 and M3) were found in 2-, 4- or 8-h samples at ranges from 0% to 17.7% (M1), 27.6% to 45.0% (M2) or 46.9% to 70% (M3) of the total plasma radioactivity. M2 was identified as acetylated PAP (paracetamol, acetaminophen, APAP), whereas M1 and M3 were identified as O-glucuronide or O-sulfate conjugates of APAP, respectively. In the pig, very low levels of radioactivity (C(max) of approximately 10 ng/ml) were found in the blood, and identified as APAP. Analysis of plasma of PPD-treated rats at 4 h after topical treatment revealed levels of 1.41 +/- 0.34 microg/ml [(14)C]-PPD-equivalents in males, and 7.40 +/- 1.83 microg/ml in females. Radioactivity, reflected a single metabolite, which was identified to be N,N'-diacetylated PPD. Comparison of the plasma APAP levels in rats or the pig following topical PAP with corresponding human plasma levels after a single oral therapeutic dose of APAP suggested a substantial margin of safety. Overall, the results suggest that topically applied PAP or PPD are metabolised in the skin, presumably by N-acetyltransferase-1 resulting in systemic exposure to acetylated metabolites, and not to their parent arylamines.

Absorption↗
PubMed1994

Chemopreventive action by an extract from Ocimum sanctum on mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid soluble sulfydryl level.

We report the chemopreventive property of an ethanolic extract of the leaves of Ocimum sanctum (a traditional medicinal plant) on 7,12-dimethylbenz[a]anthracene induced skin papillomagenesis in male Swiss albino mice. A significant reduction in the values of tumor incidence, average number of tumors per tumor bearing mice and the cumulative number of papillomas was observed in mice treated topically with the leaf extract of O. sanctum at either the peri-initiational, post-initiational stages or continuously at peri- and post-initiational stages of papillomagenesis as compared to the corresponding control group. Topical application of Ocimum leaf extract for 15 days resulted in significant 2-fold elevation of reduced glutathione content in the skin of mice (p < 0.05). Similarly, glutathione S-transferase activity was also observed to be significantly elevated by 25% compared with the control group (p < 0.05) following Ocimum extract treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Microvascular clearance of macromolecules in skeletal muscle of spontaneously diabetic rats.

Microvascular clearance of FITC-Dextran 150 (fluorescein isothiocyanate dextran, MW 150,000) was studied in cremaster muscles of control (BB/W-R) and diabetic (BB/W-DM) rats following daily injections of a full (FD) or a 1/2 (reduced; RD) dose of insulin. The cremaster muscle was placed in an intravital chamber and superfused with bicarbonate buffer (pH 7.4, equilibrated with 95% N2-5% CO2). A 1-hour period of stabilization was followed by the i.v. injection of FITC-dextran 150 and an equilibration period of 45 min. Suffusate samples were collected for 1 h for control measurements. Following this period, bradykinin was applied topically at a concentration of 10(-7) M. Samples were collected for a final hour for the assessment of clearance. The mean +/- SEM FITC-dextran 150 clearance values (microliter/60 min/g) for BB/W-R, BB/W-DM FD, and BB/W-DM RD were 11.5 +/- 1.8, 14.8 +/- 3.4, and 90.5 +/- 12.0, respectively. The corresponding values after topical application of 10(-7) M bradykinin were 23.7 +/- 5.9, 24.2 +/- 4.4, and 98.7 +/- 25.0. Our results indicate that bradykinin evokes a twofold increase in FITC-dextran 150 clearance in the BB/W-R (control) animals and in the BB/W-DM rats receiving full-dose insulin. In contrast, bradykinin does not further enhance the eightfold increase in FITC-Dextran 150 clearance observed in the reduced-insulin dose-treated BB/W-DM group. Thus, our data show that insulin, administered at a full dose, protects the functional integrity of microvascular perm-selectivity in diabetes mellitus.

Administration, Topical↗
PubMed1994

The effects of topical hypothermia and steroids on ATP levels in an in vivo liver ischemia model.

Complex hepatic surgery often requires occlusion of the portal triad in order to decrease parenchymal bleeding. This study was undertaken to evaluate the effects of topical hypothermia and intravenous steroids on liver ischemia by measuring adenosine triphosphate (ATP) levels within the hepatic parenchyma. Forty New Zealand white rabbits were divided into four experimental and four control groups. All experimental animals underwent laparotomy and ligation of the porta hepatis. Serial liver biopsy specimens were obtained at predetermined time intervals. Group I received no further intervention. Group II were topically cooled until intrahepatic temperature reached 30 degrees C. Group III received preligation intravenous methylprednisolone (30 mg/kg). Group IV received both steroids and topical hypothermia. The corresponding control groups underwent laparotomy and isolation of the porta without ligation. Adenosine triphosphate was extracted from the liver parenchyma and quantified by high-performance liquid chromatography (HPLC). The data were analyzed using a three-factor mixed analysis of variance (ANOVA). There was a statistically significant protective effect on ATP levels provided by topical hypothermia at 15 and 30 minutes of ischemia (p < 0.01), but not at 60 minutes (p > 0.05). Steroids were not found to have any protective effect on ATP levels at any time point. The combination of steroids and topical hypothermia provided significant preservation of hepatic parenchymal ATP levels, although less than that of hypothermia alone, at 15 and 30 minutes of ischemia (p < 0.01).

Adenosine Triphosphate↗
PubMed1994

Effects of topical methylene blue on cyclic GMP level, blood flow, and O2 consumption in focal cerebral ischaemia.

We hypothesized that a decrease in cyclic GMP, a second messenger in the glutamate-nitric oxide pathway, would reduce oxygen consumption and improve O2 balance in the ischaemic cerebral cortex. To test this hypothesis, a study was performed in unilateral middle cerebral artery occluded rats which were assigned to either a control or methylene blue (10(-3) M) group. Regional cerebral blood flow was determined using 14C-iodoantipyrine and regional arterial and venous O2 saturations were determined by microspectrophotometry (n = 6). Cyclic GMP level was measured by radioimmunoassay (n = 8). Guanylate cyclase and cyclic GMP-phosphodiesterase activities were determined in an additional set of control rats (n = 10). The cyclic GMP levels were not different between the ischaemic and contralateral areas in the control group. Compared to the cyclic GMP in the control ischaemic cortex, topical methylene blue significantly decreased the cyclic GMP level by 56% in the ischaemic cortex of the methylene blue group. Ischaemia did not alter the activities of guanylate cyclase but mildly decreased cyclic GMP-phosphodiesterase. The regional cerebral blood flow and O2 consumption in the control group were 50% and 32% lower than those in corresponding contralateral cortex. Topical methylene blue did not alter regional cerebral blood flow and O2 consumption in the ischaemic cortex. Our data showed that cyclic GMP is not a major controller on O2 supply or O2 consumption in the ischaemic brain.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1981

Preselecting literature for routine delivery to physicians in a community hospital-based patient care related reading program.

Health sciences librarians have been actively responding to the changing information needs of users by extending services which involve the selection of literature in response to specific requests from health care personnel. A further development is Patient Care Related Reading (PCRR), a hospital-based program of continuing medical education in which the librarian actively participates in the preselection, packaging, and routine delivery of literature for use by physicians caring for patients with certain clinical disorders. Criteria for selection of literature packet topics were developed jointly by librarians and physicians at their own hospitals. Librarians compiled bibliographic material, reviewed articles, and prepared preliminary packets. Physicians reviewed these packets and made suggestions for each article. Librarians then prepared final packets following reviewers' recommendations and distributed them as a routine procedure to all physicians caring for patients with a diagnosis corresponding to prepared topics. Librarians were notified of patients with PCRR clinical problems by admitting office personnel, floor nurses, nursing supervisors, utilization review, and Professional Standards Review Organization personnel as a part of their usual activities. Packets are used by physicians to add to their fund of knowledge, and for review and teaching purposes. PCRR has provided increased visibility of the library and its many services. Recognition of the librarian's role in the program reinforces the concept of the community hospital library as a service-oriented entity, and helps to establish the library as an active partner in the development and implementation of hospital-based continuing education programs.

Hospitals, Community↗
PubMedDate not supplied

Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor, in rabbits following single and multiple doses.

MK-417, a potent carbonic anhydrase inhibitor capable of reducing intraocular pressure after topical application, is currently under investigation for the treatment of glaucoma. The purposes of this study were to characterize dose-dependent pharmacokinetics of MK-417 and to determine the accumulating effect of the drug during chronic topical administration in rabbits. Because the drug resided primarily in the erythrocytes, kinetic analyses were performed on whole blood concentration data. Following i.v. administration, both total blood clearance and apparent volume of distribution for MK-417 increased disproportionately between the low and high dose, while the half-life of the drug appeared to be independent of dose. Total blood clearance and apparent volume of distribution increased from 0.993 +/- 0.224 ml/hr/kg (mean +/- SD) and 88.6 +/- 9.4 ml/kg at a dose of 0.05 mg/kg to 2.73 +/- 0.17 ml/hr/kg and 272 +/- 5.5 ml/kg at a dose of 1 mg/kg. The dose-dependent kinetics of MK-417 are probably due to the saturable binding of carbonic anhydrase. Upon instillation of MK-417 into the eyes, the drug was rapidly and well absorbed. At the low dose of 0.05 mg/kg, the bioavailability varied from 58% to 98.5% with a mean value of 76.5 +/- 20.5%. Prediction of concentrations of MK-417 during chronic topical administration were performed based on the corresponding concentrations after a single topical dose using an overlay technique. Good agreement between the experimental data and the predicted blood concentrations of MK-417 during chronic dosing at 0.05 mg/kg, but not at 1 mg/kg, strongly suggests that linear kinetics apply in the case of the low dose but not in the case of the high dose.

Animals↗
PubMedDate not supplied

[Comparative histomorphometry of subchondral bone density and articular cartilage thickness in the tibial head in early human arthritis].

The articular cartilage thickness and subchondral bone density of 50 human tibial heads were histomorphometrically measured by an image analysing system and topographically examined in relation to age, sex and grade of osteoarthrosis (OA). Altogether we evaluated 12,000 items. Independent of OA the lateral tibial plateau shows a significant thicker cartilage layer than the medial. In central joint areas we find a thicker cartilage cover than in marginal. Corresponding to the literature cartilage fibrillation according to OA grade 1 and 2 (Otte 1969, Fassbender 1975) accumulates in the lateral and dorsal tibial head including the meniscus covered area. The cartilage thickness decreases with age independent of OA. Without major alterations of the topographical pattern the cartilage thickness however shows a significant increase in early OA (grade 1). For that reason measurements of the cartilage thickness and joint space narrowing are not appropriate for defining early OA. The subchondral bone density shows high values ventromedially and dorsolaterally independent of sex, age or OA. Beneath central joint areas higher values are found than marginally. Corresponding to the topical literature our results point at the model of the real loaded knee joint, which says that the mean loading forces do not act on the middle of the joint but on the medial plateau. The dorsolateral density centre could be an expression of the functional adaptation of the bended knee joint. In joint areas with cartilage fibrillation (OA grade 1) we find a significant higher subchondral bone density without major alterations of the topographical pattern. It is not possible to define cause and effect, we interpret both as result of higher joint loading.

Adolescent↗
PubMed2006

Hierarchical structures induce long-range dynamical correlations in written texts.

Thoughts and ideas are multidimensional and often concurrent, yet they can be expressed surprisingly well sequentially by the translation into language. This reduction of dimensions occurs naturally but requires memory and necessitates the existence of correlations, e.g., in written text. However, correlations in word appearance decay quickly, while previous observations of long-range correlations using random walk approaches yield little insight on memory or on semantic context. Instead, we study combinations of words that a reader is exposed to within a "window of attention," spanning about 100 words. We define a vector space of such word combinations by looking at words that co-occur within the window of attention, and analyze its structure. Singular value decomposition of the co-occurrence matrix identifies a basis whose vectors correspond to specific topics, or "concepts" that are relevant to the text. As the reader follows a text, the "vector of attention" traces out a trajectory of directions in this "concept space." We find that memory of the direction is retained over long times, forming power-law correlations. The appearance of power laws hints at the existence of an underlying hierarchical network. Indeed, imposing a hierarchy similar to that defined by volumes, chapters, paragraphs, etc. succeeds in creating correlations in a surrogate random text that are identical to those of the original text. We conclude that hierarchical structures in text serve to create long-range correlations, and use the reader's memory in reenacting some of the multidimensionality of the thoughts being expressed.

Language↗
PubMed2000

George Huntington (1850-1916) and hereditary chorea.

Although Huntington's disease has existed since at least the seventeenth century, and although several physicians provided earlier descriptions of hereditary chorea, Huntington's disease was not generally recognized until the classic description by George Huntington (1850-1916) in 1872. This paper--on the sesquicentennial of Huntington's birth--reviews Huntington's original and later contributions to the description of this disorder, his professional presentations and correspondence on the topic, and his publications, as well as his background, medical training, and clinical practice. The characteristics of Huntington's disease recognized by George Huntington in 1872--i.e., the distinct clinical profile, midlife onset, and autosomal dominant inheritance pattern--made the disease ideal for investigation by genetic linkage analysis a century after Huntington's description. Subsequent breakthroughs have identified the genetic defect as an unstable expanded CAG trinucleotide repeat mutation in a novel gene on the short arm of chromosome 4. The rapidity of recent discoveries bodes well for further significant progress in understanding, and hopefully treating, this profoundly debilitating neurodegenerative disorder.

Disease Progression↗
PubMed1990

Two cell kinetic methods studied on the rat corneal epithelium.

A stathmokinetic method (using Colcemid) and the [3H]thymidine technique (pulse labelling with tritiated thymidine, [3H]TdR) have been evaluated in the rat corneal epithelium. The dose is not of critical importance for the Colcemid method, thus indicating an all or nothing effect within the dose range studied. A one point estimate is sufficient to calculate the mitotic rate (MR), and in the rat corneal epithelium a 4 h accumulation period is recommended. After administration of [3H]TdR there is an increasing response with increasing dose, followed by a levelling off at higher doses. It seems reasonable to use the lowest maximal effective dose. The labelling index (LI) can be reliably registered 1 h after administration of the drug. For each of the drugs we found corresponding results after topical application and intraperitoneal injection. Hence, topical application of small doses of both Colcemid and [3H]TdR makes interesting in vivo experiments on larger animals and even on human beings possible. Due to the extreme regularity of the corneal epithelium this part of the eye is an interesting organ for cell kinetic studies and provides an excellent tool for evaluating cell kinetic methods.

Administration, Topical↗
PubMed1977

A study of chemically induced acute inflammation in the skin of the rat.

Oedema due to application of benzene to the skin was reduced following prior sensory denervation and in animals systemically pre-treated with capsaicine (which is known to confer resistance to chemical irritants) or compound 48/80 (which depletes the body of mast cells). Increased degranulation of mast cells in the benzene-treated skin was unaffected by denervation but did not occur after treatment with capsaicine. Antidromic stimulation of a cutaneous nerve caused oedema and degranulation of mast cells, both of which were less severe than the corresponding effects of topically applied benzene. These effects were completely prevented by prior treatment with capsaicine and the oedema was less severe in 48/80-treated rats. Hence, the presence of mast cells was necessary for full development of the effects of antidromic stimulation. These observations indicate that axon reflexes in sensory fibres contribute to, but are not entirely responsible for, the development of oedema in chemically irritated skin. The prophylactic action of capsaicine may be due to the prevention of degranulation of mast cells rather than to a direct effect on cutaneous nerve endings. These conclusions are embodied in an hypothesis purporting to explain the involvement of axon reflexes, mast cells and various humoral mediators in chemically induced acute inflammation.

Animals↗
PubMedDate not supplied

Investigating users' requirements: computer-based anatomy learning modules for multiple user test beds.

OBJECTIVE: User data and information about anatomy education were used to guide development of a learning environment that is efficient and effective. The research question focused on how to design instructional software suitable for the educational goals of different groups of users of the Visible Human data set. The ultimate goal of the study was to provide options for students and teachers to use different anatomy learning modules corresponding to key topics, for course work and professional training. DESIGN: The research used both qualitative and quantitative methods. It was driven by the belief that good instructional design must address learning context information and pedagogic content information. The data collection emphasized measurement of users' perspectives, experience, and demands in anatomy learning. MEASUREMENT: Users' requirements elicited from 12 focus groups were combined and rated by 11 researchers. Collective data were sorted and analyzed by use of multidimensional scaling and cluster analysis. RESULTS: A set of functions and features in high demand across all groups of users was suggested by the results. However, several subgroups of users shared distinct demands. The design of the learning modules will encompass both unified core components and user-specific applications. The design templates will allow sufficient flexibility for dynamic insertion of different learning applications for different users. CONCLUSION: This study describes how users' requirements, associated with users' learning experiences, were systematically collected and analyzed and then transformed into guidelines informing the iterative design of multiple learning modules. Information about learning challenges and processes was gathered to define essential anatomy teaching strategies. A prototype instrument to design and polish the Visible Human user interface system is currently being developed using ideas and feedback from users.

Anatomy↗
PubMedDate not supplied

Searches and content of the OTseeker database: informing research priorities.

BACKGROUND: A strategic and prioritized approach to occupational therapy research is needed, particularly given the limited research funding available. Comparing occupational therapists' information needs with the research evidence available can potentially inform research debate within the profession. This study aimed to identify research topics most often sought by users of the OTseeker database and to compare these with the quantity of topics available in the database. METHOD: A random sample of keyword search terms submitted to OTseeker (n= 4,500) was coded according to diagnostic and intervention categories, and compared with the amount of research contained in OTseeker in 2004. RESULTS: Most frequently sought topics were relevant to the diagnostic categories of pediatric conditions (19%), neurology and neuromuscular disorders (17%), and mental health (17%). Most frequently sought intervention topics included modes of service delivery, sensory interventions, and physical modalities. Although many frequently sought topics had a correspondingly high volume of research in OTseeker, a few areas had very little content (e.g., fine motor skill acquisition, autistic spectrum disorder). This information is offered to inform discussions about research priorities and resource allocation for research within occupational therapy.

Biomedical Research↗
PubMed1986

Oral health of individuals aged 3-80 years in Jönköping, Sweden in 1973 and 1983. I. A review of findings on dental care habits and knowledge of oral health.

The aim of the present study was to present data from dental care habits and knowledge of oral health in two cross-sectional studies carried out in 1973 and 1983. A random sample of approximately 1000 individuals evenly distributed in the age groups 3, 5, 10, 15, 20, 30, 40, 50, 60 and 70 years was studied for each of these two years. In the 1983-year examination 80 individuals 80 years of age were also included. All subjects were inhabitants of the community of Jönköping, Sweden. A questionnaire about dental care habits and knowledge was used in combination with a clinical and radiographical examination. The participants answered 23-101 questions. The same questions were raised in 1973 and 1983. For most age groups more then 80 per cent visited a dentist yearly in 1983. This yearly attendance was higher than that for 1973. In the 20-year-old group 14 per cent of the individuals received dental care in the PDS in 1973 compared to 63 per cent in 1983. The main reason to visit a dentist in 1973 was by the patient's own initiative while in 1983 the appointments were based on the dentist's initiative. The number of subjects that felt discomfort in connection with a visit to the dentist had decreased between 1973 and 1983. Knowledge about the etiology of caries had increased between 1973 and 1983 was not the case for gingivitis and periodontitis. An increase had occurred in toothbrushing frequency and the use of toothpicks and disclosing tablets but this between 1973 and 1983. In 1983, 98 to 93 per cent of the subjects in the age groups 10-30 years had been exposed to topical fluorides. The corresponding figure for 30-year-olds in 1973 was 1 per cent. It is obvious that during the period 1973 to 1983 there has been an increase in dental attendance, knowledge of dental diseases, oral health and the use of preventive measures.

Adolescent↗
PubMed1998

[Candida and the gastrointestinal tract. A medical-research evaluation].

In immunocompetent persons, Candida species are members of the normal flora of the gastrointestinal tract. Budding yeasts, in particular Candida albicans, can, however, in patients with a corresponding disposition, spread topically and systemically, that is, they may become pathogenic. In hematological/oncological patients with severe immunodeficiency, for example, the mycelium may infiltrate the muscularis mucosae, with involvement also of the vascular system. The relationships between recurrent diarrhea and Candida are still discussed controversial; various data do, however, suggest that massive colonization with Candida might well represent a(n additional) diarrhea-provoking factor. Similar considerations may also be assumed to apply to diarrhea induced by antibiotic therapy. For immunocompetent persons, guidelines exist for the yeast cell count in the stools. The interpretation of quantitative findings must, however, always be made on an individual basis and against the background of clinical symptoms and/or any particular predisposition of the patient. Reliable treatment of superficial candidasis can be achieved with oral polyene antifungal antibiotics (nystatin, amphotericin B).

Candidiasis↗