Adverse drug reactions in pediatrics with a study of in-hospital intensive surveillance

A two-part prospective study of adverse drug reactions (ADRs) in Indian children was carried out at a teaching general hospital. Using an in-hospital intensive surveillance scheme (IISS) for the detection of ADRs, indoor patients of one of the two units in the pediatric ward were monitored daily for 6 months, with the other unit serving as a control group. A total of 347 patients were monitored, 2781 daily orders written and 24,474 doses of 96 different drugs given. Six patients suffered from ADRs (1.73%), and 1 reaction proved fatal (0.29%), while the control group reported only 1 ADR in the same time period. The frequency of ADRs (p < 0.001) and their resultant mortality in Indian children was less than that in a western prototype study. Though IISS showed a marked increase in ADR reporting, it was too cumbersome for routine use in our country. In the second part of the study, 40 cases of ADRs seen over 2 years were analyzed. Antimicrobials, especially sulphonamides, accounted for a high percentage of cases mostly as skin rashes and fairly severe reactions were common. Patients on anti-tuberculous and anti-convulsant drugs required prolonged supervision for late onset reactions.     

Characterization of atherosclerotic plaques and mural thrombi with intravascular ultrasound elastography: a potential method evaluated in an aortic rabbit model and a human coronary artery

Plaque rupture is correlated with the plaque morphology, composition, mechanical properties, and with the blood pressure. Whereas the geometry can accurately be assessed with intravascular ultrasound (IVUS) imaging, intravascular elastography (IVE) is capable of extracting information on the plaque local mechanical properties and composition. This paper reports additional IVE validation data regarding reproducibility and potential to characterize atherosclerotic plaques and mural thrombi. In a first investigation, radio frequency (RF) data were acquired from the abdominal aorta of an atherosclerotic rabbit model. In a second investigation, IVUS RF data were recorded from the left coronary artery of a patient referred for angioplasty. In both cases, Galaxy IVUS scanners (Boston Scientific, Freemont, CA), equipped with 40 MHz Atlantis catheters, were used. Elastograms were computed using two methods, the Lagrangian speckle model estimator (LSME) and the scaling factor estimator (SFE). Corroborated with histology, the LSME and the SFE both clearly detected a soft thrombus attached to the vascular wall. Moreover, shear elastograms, only available with the LSME, confirmed the presence of the thrombus. Additionally, IVE was found reproducible with consistent elastograms between cardiac cycles (CCs). Regarding the human dataset, only the LSME was capable of identifying a plaque that presumably sheltered a lipid core. Whereas such an assumption could not be certified with histology, radial shear and tangential strain LSME elastograms enabled the same conclusion. It is worth emphasizing that this paper reports the first ever in vivo tangential strain elastogram with regards to vascular imaging, due to the LSME. It is concluded that the IVE was reproducible exhibiting consistent strain patterns between CCs. The IVE might provide a unique tool to assess coronary wall lesions.     

Stress hormones and the immunological responses to heat and exercise

This review focuses on the response of "stress" hormones to heat, exercise (single or repeated bouts), and combinations of these stimuli, with particular reference to their impact upon immune function. Very hot conditions induce a typical stress response, with secretion of catecholamines and cortisol. The catecholamines induce a demargination of leukocytes, and cortisol subsequently causes cells to migrate to lymphoid tissue. Sustained exercise, even in a thermally comfortable environment, induces a larger hormonal response than moderate thermal stress. With moderate exercise, increases in leukocyte numbers are related mainly to plasma norepinephrine concentrations, but with more intense exercise epinephrine concentrations assume a major importance. As exercise continues, plasma cortisol levels also rise, inducing an influx of neutrophils from bone marrow and an efflux of other leukocyte subsets. A combination of exercise and heat stress augments both hormonal and leukocyte responses. But these changes seem to be reversed if temperatures are clamped by exercising in cold water. If a second bout of exercise is performed with an inter-test interval of 30-45 min, neither hormone concentrations nor immune responses show any great cumulative effect under temperate conditions. However, in a hot environment the second exercise bout induces a larger and more persistent neutrophilia. Training influences these various responses mainly by decreasing the stress imposed when exercising at a given absolute work-rate.     

Bacterial degradation of plasticised PVC-effect on some physical properties

Burial tests on plasticised PVC in neutral soil inoculated with species of Pseudomonas and Brevibacterium have shown degradation in 8 weeks that is largely dependent on the nature of the plasticiser. There was no evidence for any attack on the polymer itself. Phthalate and phosphate plasticisers were resistant; adipate, azelate and sebacate plasticisers were susceptible and a number of others, e.g. chlorinated hydrocarbon and epoxy types, occupied an intermediate position. The degree of attack was also dependent on the nature of the stabiliser used in the PVC formulation, lead-based stabiliser conferring less resistance than barium/cadmium-based stabiliser. Degradation has been assessed in terms of loss in weight, change of stiffness and loss of energy during cyclic deformation.     

Use of intranasal IL-12 to target predominantly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin

We have investigated the effects of IL-12 and cholera toxin (CT) on the immune response to tetanus toxoid (TT) given by intranasal or oral routes. CT inhibited IL-12-induced IFN-gamma secretion both in vivo and in vitro. Intranasal administration of IL-12 to mice nasally immunized with the combined vaccine of TT and CT resulted in increased TT-specific IgG2a and IgG3 Abs, while IgG1 and IgE Ab responses were markedly reduced. This shift of the CT-induced immune response toward Th1 type was associated with TT-specific CD4+ T cells secreting IFN-gamma and reduced levels of Th2-type cytokines (i.e., IL-4, IL-5, IL-6, and IL-10). In contrast, intranasal IL-12 enhanced the CT-induced serum IgG1 and IgE Ab responses in mice given the combined vaccine orally. IFN-gamma secretion by TT-specific CD4+ T cells was also enhanced; however, Th2-type cytokine responses were predominant. Mucosal secretory IgA responses to oral or nasal vaccines were not affected by intranasal IL-12. Thus, intranasal IL-12 delivery influences Th cell subset development in mucosal inductive sites that are dependent on the route of vaccine delivery.     

Nosocomial infection following cardiovascular surgery: comparison of two periods, 1987 vs. 1992

BACKGROUND: QT dispersion has been proposed as a simple, noninvasive measure for identifying patients at risk of postinfarction arrhythmia. It is assumed to reflect nonuniform ventricular repolarization, which, in turn, may result from regional differences in repolarization time as well as from localized activation delay. The aim of this study was to examine the relation between QT dispersion and intraventricular conduction abnormalities in patients with acute anterior wall myocardial infarction. METHODS AND RESULTS: Standard 12-lead electrocardiographic and 12-lead signal-averaged electrocardiographic recordings were performed in 25 patients with a first Q-wave anterior wall myocardial infarction. Measures calculated by using the 6 precordial (V1 through V6) leads for QT dispersion were (1) difference between maximum and minimum QT and QTc intervals and (2) standard deviation of QT and QTc intervals. Measures calculated from the signal-averaged electrocardiogram were (1) maximum filtered QRS duration; (2) mean; and (3) standard deviation of filtered QRS duration. No relation was found between any measure of filtered QRS duration and that of QT dispersion by using linear correlation analysis. Similarly, no significant association was demonstrated between the filtered QRS duration and corresponding QT interval measurements (total 131 leads). CONCLUSIONS: The lack of correlation between signal-averaged electrocardiogram indexes of slow intraventricular conduction and electrocardiogram variables of QT dispersion suggests an independent predictive value for the 2 methods in identifying patients at risk of postinfarction arrhythmia. This suggestion is further supported by the finding that altered activation sequence is an unlikely mechanism of QT dispersion in patients with acute myocardial infarction, as indicated by the lack of association between the filtered QRS duration and corresponding QT interval measurements.     

Three-dimensional reconstruction of aqueous channels in human trabecular meshwork using light microscopy and confocal microscopy

Conventional two-dimensional imaging of the trabecular meshwork (TM) provides limited information about the size, shape, and interconnection of the aqueous channels within the meshwork. Understanding the three-dimensional (3-D) relationships of the channels within this tissue may give insight into its normal function and possible changes present in the eye disease glaucoma. The purpose of our study was to compare laser scanning confocal microscopy with standard 1 μm Araldite-embeddedhistologic sections for 3-D analysis of the trabecular meshwork. In addition, the study was done to determine whether computerized 3-D reconstruction could isolate the fluid spaces of the trabecular meshwork and determine the size of interconnections between the fluid spaces. Confocal microscopy appears comparable to 1 μm Araldite-embedded tissue sections and has the advantage of inherent registration of the serial tissue sections. Three-dimensional reconstruction allowed the isolation of the fluid spaces within the trabecular meshwork and revealed the presence of numerous interconnections between larger fluid spaces. The distribution of these interconnections was randomly arranged, with no predilection for specific regions within the trabecular meshwork. This distribution of constrictions and “expansion chambers” may provide a clue to the mechanism by which subtle histologic changes are associated with increased ocular pressure in glaucoma.     

Preparation and characterization of surfactant‐free stimuli‐sensitive microgel dispersions

A surfactant‐free method to produce responsive polymer microgels is introduced. As an example, poly(methacrylic acid) hydrogels with varying crosslinking density have been synthesized in bulk and then chopped using a high shear mechanical cutter to form microgel particles dispersed in water. The mechanical cutting technique enables the concentration and particle size distribution of the microgel suspensions to be easily controlled, therefore making the rheology of the suspensions tuneable. The particle size distribution of the dispersions, characterized using light scattering, was dependent on the speed and duration of mechanical cutting. The particle size distribution also depended on the degree of crosslinking of the hydrogel. The higher the crosslinking density, the lower the average mean diameter of the resulting microgel particles. The lower the crosslinking density of the hydrogel, the larger the difference between the maximum and minimum particle size. The time to complete swelling of the particles upon change in pH was measured to be up to 45 s, depending on the particle size. The rheology of the resulting suspensions as a function of pH was investigated. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 104: 1912–1919, 2007     

The Appropriation of the Material of Places in the Landscape: the case of tufa and springs

Springs have long been recognized as being significant places in the landscape, and there is ample evidence of later-prehistoric and Roman activity at spring sites. The Christian appropriation of springs as 'places', either indirectly by assigning their origin to saints, or directly by building chapels and churches on spring-head sites, is also well evidenced. The possibility that the material of petrifying springs - tufa - was both transplanted and appropriated, and that the symbolic properties of the material may go back well into British prehistory, is explored.