Calcipotriol poisoning in dogs.
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Biomedical subjects
Publications and source records attributed to A Campbell.
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Bilateral local microinfusion of serotonin (5-hydroxytryptamine; 5-HT) into the ventrolateral striatum (VLS) of the rat forebrain induces quantifiable stereotyped orofacial behaviors. The role of presynaptic dopamine (DA) and structural requirements of indoles for expression of this behavioral effect and for inhibition of neuronal transport of [3H]DA were examined. Bilateral local injection of 6-OHDA (8 micrograms/side) into VLS depleted DA and markedly diminished the behavioral effects of 5-HT. Intracerebral pretreatment with the potent DA transport inhibitors GBR-12909 (6 micrograms/side) or nomifensine (4 micrograms/side) also markedly decreased behavioral responses to 5-HT. A series of indoles and tyramine were examined for ability to induce stereotypy following infusion into the VLS. Of compounds tested, only p-tyramine, 5-HT, tryptamine and L-5-hydroxytryptophan (5-HTP) elicited strong orofacial behaviors; indoles lacking a free amino group or containing other substituents were virtually inactive in vivo, and the effect of 5-HTP was prevented by systemic pretreatment with the decarboxylase inhibitor NSD-1015, indicating its required conversion to 5-HT. Uptake of [3H]DA (0.1 microM) into rat striatal synaptosomes was inhibited in a concentration-dependent manner in the following apparent rank-order: p-tyramine, N-methyl-5-HT, tryptamine, 5-HT, N-methyltryptamine (IC50 = 44-718 nM), other indoles (IC50 = 10-100 microM). These results support the conclusion that oral stereotypy induced by microinjection of 5-HT or other aromatic amines into rat VLS is mediated by local release of endogenous DA. These results extend previous findings indicating that this effect of 5-HT was not blocked by 5-HT receptor antagonists, and suggest mediation by a neuronal transport process involved in the uptake or storage of DA.
OBJECTIVE: To compare hydrodynamic characteristics of a new bileaflet heart valve, the CarboMedics kinetic cardiac valve prosthesis, with those of a St. Jude Medical (SJM) heart valve. METHODS: Hydrodynamic characteristics were determined in the mitral and aortic positions of a Vivitro Systems pulse duplicator for size 23 Kinetic aortic values, size 23 SJM aortic valves, size 29 Kinetic mitral valves and size 29 SJM mitral valves. Test conditions were 72 beats per min with cardiac outputs of 2, 5 and 7 l/min. Values of forward flow pressure drop (delta P), regurgitant and energy loss were determined for each valve. The test results for the two valve designs were compared by valve size. RESULTS: The test results show that both the size 23 and size 29 Kinetic valves have 8-14% lower delta P values and 5-10% greater effective orifice area (EOA) values. The size 29 Kinetic mitral valve has a 1-2 ml lower regurgitant volume, while the size 23 Kinetic aortic valve has a 0.5 ml greater regurgitant volume than the corresponding SJM values. These factors combine to provide a 5-10% lower energy loss for size 23 Kinetic aortic valves and a 15-25% lower energy loss for size 29 Kinetic mitral valves over the cardiac cycle than for corresponding sizes of SJM valves. CONCLUSIONS: The Kinetic valve's fluid dynamics are superior to equivalent sizes of SJM valves. This is especially impressive considering that the tissue annulus diameters for Kinetic valves are approximately 0.5 mm less than equivalent size SJM valves. The primary reasons for the superior hydrodynamic performance of Kinetic valves are (1) the larger orifices which result in lower forward flow delta P values and (2) the opening angles, which have been customized for each valve size to minimize energy loss.
OBJECTIVE: To determine the annual cost of implementing and maintaining a respiratory personal protective equipment (PPE) program at an urban hospital. SETTING: St Clare's Hospital and Health Center, a 250-bed hospital in Manhattan that treats 60 to 100 cases of tuberculosis annually. METHODS: Review of Purchasing Department records for all masks acquired by the hospital from 1992 to 1995, and an estimate of administrative time spent developing and implementing the guidelines recommended by various agencies during the study interval. RESULTS: Respiratory isolation was provided for 6,360 to 10,883 days annually during the 4-year interval. Yearly costs for the PPE program ranged from $86,560 to $175,690. Of note, the daily cost for a respiratory isolation day decreased dramatically between 1994 and 1995 ($25/day to $13/day), when the high-efficiency particulate air-filter (HEPA) respirator was used by all staff. The decrease occurred because of lower administrative costs and a sharp decrease in the numbers of HEPA units purchased. Objective measures of worker compliance with HEPA respirators demonstrated the decrease was not due to less HEPA use but rather that employees were using each HEPA unit for several weeks, as recommended. CONCLUSION: We found a significant decrease in cost in the second year of our HEPA program due to increasing employee familiarity with the program. Newly approved, cheaper, but less durable, N-95 masks are unlikely to withstand multiple wearings and may be discarded after a few uses. Thus, cheaper masks may result in a more expensive PPE program.
ICAM-1, a transmembrane glycoprotein promoting adhesion in immunologic and inflammatory reactions, was found to be increased on nasal epithelial cells of patients with allergic rhinitis. Loratadine, an H1-blocker, was found to reduce in vitro the expression of ICAM-1 on nasal epithelial cells. A double-blind, parallel-group study was carried out during the pollen season to compare the effect of two H1-blockers, cetirizine (10 mg OD) and loratadine (10 mg OD), on the release of soluble ICAM-1 in nasal secretions. A group of untreated patients was used as a control group. sICAM-1 was measured by enzyme immunoassay before and after 2 weeks of treatment. Symptoms were significantly decreased in the actively treated groups. sICAM-1 levels were unchanged in the control group but were significantly reduced in the two treated groups (P < 0.015, Wilcoxon's W test). This study shows that two H1-blockers, loratadine and cetirizine, have a similar effect on sICAM-1 released in nasal secretions during the pollen season.
The aim of the present study was to test the reliability of theory of mind task performance by individuals with a learning disability. Across a series of three false belief tasks and two belief-desire reasoning tasks reliability was moderate--although it was no lower than has been found over a period of 3 weeks in normally developing children. The overall level of performance on the tasks was also only moderate, with approximately half the subjects passing on any one false belief task, and one quarter on any one belief-desire reasoning task. Reliable passers had higher VMA and NVMA than unreliable passers and subjects who failed. Given the important interpretations made regarding the representational skills of individuals on the basis of their responses in such experimental tasks, further work investigating the psychometric properties of the tasks is required with both typically and atypically developing individuals.
In contrast to the usual pattern of higher male aggression, girls have been shown to exceed boys on frequency measures of indirect aggression. Women also tend to view aggression in terms of an expressive social representation whereby it is seen to result from loss of self-control, in contrast to men who tend to describe it as an instrumental act aimed at exerting control over others. Sixteen items measuring different forms of aggressive behaviour were given to 105 undergraduates together with Expagg, a psychometric measure of social representation of aggression. Factor analysis of the aggression items revealed three scales: direct (verbal and physical), indirect instrumental and indirect expressive aggression. The only aggression scale showing a significant sex difference was indirect expressive aggression on which women scored higher than men. There was also a significant sex difference on Expagg with women showing a more expressive representation of aggression. However the point biserial correlation between sex and indirect expressive aggression was not diminished when expressive representation of aggression was partialled out. It is argued that indirect expressive aggression (involving bitching and avoiding) fails to show a relationship with social representation because it lacks the formal requirements of intentional harm and consequently is not an act of 'aggression'.
It was shown previously that phage 21 and the defective element e14 integrate at the same site within the icd gene of Escherichia coli K-12 but that 21 integrase and excisionase excise e14 in vivo very infrequently compared to excision of 21. We show here that the reverse is also true: e14 excises itself much better than it excises an adjacent 21 prophage. In vitro integrase assays with various attP substrates delimit the minimal attP site as somewhere between 366 and 418 bp, where the outer limits would include the outermost repeated dodecamers suggested as arm recognition sites by S. J. Schneider (Ph.D. dissertation, Stanford University, Stanford, Calif., 1992). We speculate that the reason 21 attP is larger than lambda attP (240 bp) is because it must include a 209-bp sequence homologous to the 3' end of the icd transcript in order to allow icd expression in lysogens. Alteration of portions of 21 attP to their e14 counterparts shows that 21 requires both the arm site and core site sequences of 21 but that replacements by e14 sequences function in some positions. Consistent with Schneider's in vivo results, and like all other known integrases from lambdoid phages, 21 requires integration host factor for activity.
BACKGROUND/AIMS: Regional differences in the biology of the colonic epithelium may determine the extent of involvement by ulcerative colitis. Novel monoclonal antibodies (MAbs) were used in this study to investigate regional heterogeneity in the colonic mucosa. METHODS: MAbs generated using a method of tolerisation against common antigens in the proximal colon and distal colon were used for immunoperoxidase staining, comparative histochemistry, immunoblotting, and slot-blot analysis. RESULTS: The colon specific MAbs 5F1 (IgG3) and 6G4 (IgM) stained goblet cell contents throughout the normal distal colon but staining was markedly reduced in the proximal colon (p < 0.0001). In the distal colon of patients with ulcerative colitis, whether quiescent or actively inflamed, reactivity was reduced compared with controls (p < 0.05, p < 0.001 respectively). By contrast, an overall increase in staining was seen in the uninflamed proximal colon in ulcerative colitis compared with controls (p < 0.02). Comparative staining with high iron diamine and biochemical analyses indicated that MAb 6G4 was reactive with mucin bearing sulphate or O-acetylated sialic acid groups, or both. CONCLUSIONS: Regional differences in the staining characteristics of normal colonic mucin have been shown using novel monoclonal antibodies. The pattern of mucin expression throughout the colon in ulcerative colitis is altered even in the absence of histological changes.
Cytokines are proteins with pleiotropic biological effects, but the pathophysiologic role of cytokine inhibitors in advanced cardiac disease remains unclear. We assessed the levels of tumor necrosis factor (TNF)-alpha and its soluble receptors I (sTNF-RI) and II (sTNF-RII), soluble interleukin-1 receptor antagonist (sIL-1 Ra), and interleukin-6 soluble receptor (IL-6 sR) in sera from 11 patients with severe chronic congestive heart failure (mean left ventricular ejection fraction 19 +/- 6%; mean symptom-limited oxygen consumption 13 +/- 4 ml/min per kg) and 11 healthy volunteers. The serum concentrations of TNF, sTNF-RI, and sIL-1 Ra, but not of sTNF-RII and IL-6 sR, were significantly increased in heart failure patients. Importantly, their symptom-limited oxygen consumption was strongly associated with both sTNF-RI (R = -0.68, p = 0.04) and sIL-1 Ra (R = -0.77, p = 0.01). These results suggest that cytokine inhibitors from different receptor families may be involved in functional disability, a characteristic feature in patients with severe congestive heart failure. Understanding the response of cytokine inhibitors to heart failure might have therapeutic value as interventions against cytokines become available.
Controversy abounds as to whether the Hooper Visual Organization Test (VOT) is a measure of hemisphere-specific, region-specific, or non-specific brain damage. The present study examines this issue in a group of African Americans with acute unilateral brain damage and non-brain-injured controls. Consistent with the idea that the VOT is a measure of "organic" cerebral pathology, non-brain damaged controls earned significantly higher VOT scores than brain-damaged patients. While other studies have noted that the VOT is primarily sensitive to damage in the right parietal region of the brain, the present study shows that VOT performance is especially vulnerable to acute lesions in the right anterior quadrant of the brain. This latter finding supports the idea that VOT performance is differentially sensitive to regional cerebral pathology, but challenges the region specific claim of poorer VOT performance among patients with right posterior cerebral damage.
Little is known of the influence race has on the development of leg ulceration, with most studies being performed in almost exclusively white populations. As part of a wider audit of leg ulcer services, health care professionals were contacted to give details of age, sex and ethnic background of all patients who attended for treatment of leg ulceration over a one year period in an area of west London. West London Health Care Trust provides services to a population of 275,000 of whom 53,000 have an ethnic background from the Indian subcontinent (South Asian). In all, 280 patients were identified, of whom 264 (94%) had details of age and sex. This gave a crude ascertainment rate of 1.02 per 1000 population. Of the 264 patients, five were classified as South Asians, with one patient classified as Afro-caribbean. The Mantel Haenzsel test demonstrated a significantly higher proportion of whites suffering from leg ulceration than South Asians, giving an odds ratio of 4.43, with 95% confidence intervals between 1.94 and 10.13 (P = 0.0004). The expected frequency of South Asian patients should be 23, based on rates from the white population, of which 13 would be women and 10 men. Only five South Asian men were identified, and no Asian women with leg ulceration. Reasons for this low ascertainment are two-fold. Either there is a real difference between the white and South Asian populations, or South Asian patients are not presenting for treatment. Further work must be performed to determine whether this is an effect of low prevalence, or unmet need in the community.
Transforming growth factor beta 1 null mice (TGF-beta 1-/-) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels in controls, peaking at 15-17 d of life. Shortterm treatment of TGF-beta 1-/- mice with NG-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-beta 1-/- mice. These findings demonstrate that TGF-beta 1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-beta 1 in vitro.
The production of reactive oxygen species may have an important role in the pathogenesis of inflammatory bowel disease, yet the cells responsible in colonic mucosa have not been clearly defined. We studied 28 patients with ulcerative colitis and 13 controls to determine the cells generating reactive oxygen species, using a combined method for determining nitroblue tetrazolium reducing activity and immunohistochemical characterization. In contrast to the proportion of EBM11-positive cells (tissue macrophages), which did not increase in inflamed mucosa, the proportions of PMN-13F6 positive cells, CD11b-positive cells, and eosinophils were significantly increased in inflamed mucosa. PMN-13F6 positive cell and eosinophil counts were significantly correlated with CD11b positivity. Eosinophils, however, showed a stronger correlation with CD11b positivity than PMN-13F6-positive cells. The majority of CD11b-positive cells were eosinophils. Although some nitroblue tetrazolium reducing leukocytes were positively stained with EBM11 or PMN-13F6, eosinophils were the major subset of nitroblue tetrazolium reducing leukocytes. Recruitment and activation of eosinophils may play an important role in the pathogenesis of ulcerative colitis.
A gene at 42 min on the Escherichia coli chromosome, identified as the locus of pseudoreversion of knockout mutations in the biotin sulfoxide reductase gene, bisC, has 64% base sequence identity with bisC. This makes it a member of a multigene family of molybdopterin enzymes that includes genes for anaerobic reduction of trimethylamine oxide (torA) and dimethylsulfoxide (dmsA). Disruption of this gene eliminates the background activity of biotin sulfoxide reduction observed in bisC mutants. Sequence comparison of the new gene (bisZ) with bisC indicates that certain ts mutants of bisC arise by gene conversion between the two loci.
OBJECTIVE: To determine the energy loss attributable to prosthetic valve size and design in double valve replacement, energy consumption of mitral valves (size #25 to #29), of two different designs (Bjork Shiley tilting disc and Carbomedics bileaflet valves), in combination with a small (#21) and large sized (#27) aortic prosthesis, were analyzed in a flow simulator. METHODS: A pulsatile flow simulator was used to reproduce physiological ventricular dynamics and to match the input and output impedances of the human left ventricle. Hydrodynamic performance was determined as stroke work, closing work and leak work for each combination of valves at low flow (5 liters per minute) and high flow (9 liters per minute) conditions. RESULTS: At low flow no decrease of energy requirement was found with the use of a mitral valve larger than #25. At high flow the #27 and #29 mitral valves required less energy compared to a #25 mitral valve, in combination with a large aortic prosthesis. The #29 mitral prosthesis revealed similar results as the #27. With the use of a large aortic prosthesis a remarkable reduction of total flow work was shown. These results were found in both designs. In comparison of the two designs, tilting disc valves required more energy for stroke and closure of the valve, although less energy for leakage. In total, energy requirements were higher for tilting disc valves. COMMENTS: A hydrodynamic advantage for the use of a mitral valve larger than #25 was found only with the combination of a large aortic prosthesis and high flow. Hydrodynamic data favor the use of bileaflet prosthesis especially for a patient who is expected to exercise.
Histamine antagonists together with topical steroids are the treatment of choice in allergic rhinitis. Many of these histamine antagonists exhibit effects in addition to blockade of the histamine receptor. In this study we have investigated the effects of ebastine and carebastine on the release of eicosanoids and cytokines from human dispersed polyp cells and the effect of these compounds on the release of inflammatory mediators into nasal lavage fluid after allergen challenge. Ebastine was shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 mumol/L, respectively) and to inhibit the release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14 mumol/L) but had little effect on cytokine release. When patients underwent nasal provocation tests with allergen, ebastine significantly increased the mean number of pollen grains required to induce an allergic response. In addition, the drug inhibited the release of granulocyte-macrophage colony-stimulating factor but had no effect on any other mediators measured.
One of the strategies identified by the NHS to achieve improvements in the health status of the Scottish population is to implement health promotion programmes through the general medical practitioner service. Grampian Local Health Council undertook a survey of Grampian residents to identify factors which might encourage greater public participation in such programmes. The results which are analysed and discussed in this paper show that factors identified by the public include: a preference for doctors to carry out health checks; the need for public education on the roles of different health professionals; the need for information on health checks and their benefits to be supplied in advance; a choice of appointment times and the offer of a follow-up appointment to discuss test results. These results are of interest to health professionals as they are likely to contribute to higher levels of patient involvement in health promotion programmes.