Seven ways to get a grip on implementing Competency-Based Medical Education at the program level.

Competency-based medical education (CBME) curricula are becoming increasingly common in graduate medical education. Put simply, CBME is focused on educational outcomes, is independent of methods and time, and is composed of achievable competencies.1 In spite of widespread uptake, there remains much to learn about implementing CBME at the program level. Leveraging the collective experience of program leaders at Queen's University, where CBME simultaneously launched across 29 specialty programs in 2017, this paper leverages change management theory to provide a short summary of how program leaders can navigate the successful preparation, launch, and initial implementation of CBME within their residency programs.

Les programmes de formation médicale fondée sur les compétences (FMFC) sont de plus en plus répandus dans les études supérieures en médecine. En termes simples, la FMFC est centrée sur les résultats scolaires, elle est indépendante des méthodes et du temps, et est constituée de compétences réalisables.1 Malgré cette adoption généralisée, il reste encore beaucoup à apprendre sur la mise en œuvre de la FMFC au niveau des programmes. Tirant profit de l'expérience collective des responsables de programmes à l'Université Queen, où la FMFC a été lancée simultanément dans 29 programmes de spécialité en 2017,le présent article s'appuie sur la théorie de la gestion du changement pour produire un court résumé de la manière dont les responsables de programmes peuvent gérer avec succès la préparation, le lancement et la mise en œuvre initiale de la FMFC au sein de leurs programmes de résidence.

Effect of 4 weeks of aerobic or resistance exercise training on arterial stiffness, blood flow and blood pressure in pre- and stage-1 hypertensives.

The benefits of aerobic exercise (AE) training on blood pressure (BP) and arterial stiffness are well established, but the effects of resistance training are less well delineated. The purpose of this study was to determine the impact of resistance vs aerobic training on haemodynamics and arterial stiffness. Thirty pre- or stage-1 essential hypertensives (20 men and 10 women), not on any medications, were recruited (age: 48.2 +/- 1.3 years) and randomly assigned to 4 weeks of either resistance (RE) or AE training. Before and after training, BP, arterial stiffness (pulse wave velocity (PWV)) and vasodilatory capacity (VC) were measured. Resting systolic BP (SBP) decreased following both training modes (SBP: RE, pre 136 +/- 2.9 vs. post 132 +/- 3.4; AE, pre 141 +/- 3.8 vs. post 136 +/- 3.4 mm Hg, P = 0.005; diastolic BP: RE, pre 78 +/- 1.3 vs post 74 +/- 1.6; AE, pre 80 +/- 1.6 vs. post 77 +/- 1.7 mm Hg, P = 0.001). Central PWV increased (P = 0.0001) following RE (11 +/- 0.9-12.7 +/- 0.9 ms(-1)) but decreased after AE (12.1 +/- 0.8-11.1 +/- 0.8 m s(-1). Peripheral PWV also increased (P = 0.013) following RE (RE, pre 11.5 +/- 0.8 vs. post 12.5 +/- 0.7 ms(-1)) and decreased after AE (AE, pre 12.6 +/- 0.8 vs post 11.6 +/- 0.7 m s(-1)). The VC area under the curve (VC(AUC)) increased more with RE than that with AE (RE, pre 76 +/- 8.0 vs. post 131.1 +/- 11.6; AE, pre 82.7 +/- 8.0 vs. post 110.1 +/- 11.6 ml per min per s per 100 ml, P = 0.001). Further, peak VC (VCpeak) increased more following resistance training compared to aerobic training (RE, pre 17 +/- 1.9 vs. post 25.8 +/- 2.1; AE, pre 19.2 +/- 8.4 vs post 22.9 +/- 8.4 ml per min per s per 100 ml, P = 0.005). Although both RE and AE training decreased BP, the change in pressure may be due to different mechanisms.

Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons.

Calcitonin gene-related peptide (CGRP) increases in sensory neurons after inflammation and plays an important role in abnormal pain responses, but how this neuropeptide is regulated is not well understood. Both activin A and nerve growth factor (NGF) increase in skin after inflammation and induce CGRP in neurons in vivo and in vitro. This study was designed to understand how neurons integrate these two signals to regulate the neuropeptide important for inflammatory pain. In adult dorsal root ganglion neurons, NGF but not activin alone produced a dose-dependent increase in CGRP mRNA. When added together with NGF, activin synergistically increased CGRP mRNA, indicating that sensory neurons combine these signals. Studies were then designed to learn if that combination occurred at a common receptor or shared intracellular signals. Studies with activin IB receptor or tyrosine receptor kinase A inhibitors suggested that each ligand required its cognate receptor to stimulate the neuropeptide. Further, activin did not augment NGF-initiated intracellular mitogen-activated protein kinase signals but instead stimulated Smad phosphorylation, suggesting these ligands initiated parallel signals in the cytoplasm. Activin synergy required several NGF intracellular signals to be present. Because activin did not further stimulate, but did require NGF intracellular signals, it appears that activin and NGF converge not in receptor or cytoplasmic signals, but in transcriptional mechanisms to regulate CGRP in rat sensory neurons after inflammation.

Systematic structural coordination chemistry of p-tert-butyltetrathiacalix[4]arene: 1. Group 1 elements and congeners.

Determinations of the crystal structures of complexes of the alkali metal ions with, in the case of Li, the dianion and, in the cases Na-Cs, the monoanion of p-tert-butyltetrathiacalix[4]arene have shown that both the sulfur atoms which form part of the macrocyclic ring, as well as the pendent phenolic/phenoxide oxygen donor atoms, are involved in coordination to these metals. Although the Li and Na complex structures are similar to those of the corresponding complexes of p-tert-butylcalix[4]arene, there is no similarity in the structures of the Cs complexes, with the present structure showing no evidence of polyhapto Cs(+)-pi interactions. Instead, the complex crystallizes as a ligand-bridged (S-, O-donor) aggregate of three Cs ions, solvent molecules, and four calixarenes, somewhat like the Rb complex, though here four Rb ions are present, and higher in aggregation than the K+ complex, where two K+ ions are sandwiched between two calixarene moieties. The triethylammonium complex of the thiacalixarene monoanion, though formally analogous in that it involves a monocation, has a simpler structure than any of the alkali metal derivatives, based formally on proton coordination (H-bonding). However, interestingly, it can be isolated in both solvated (dmf, dmso) and unsolvated forms, as indeed can the "free", p-tert-butyltetrathiacalix[4]arene ligand itself.

Skin cell induction of calcitonin gene-related peptide in embryonic sensory neurons in vitro involves activin.

Target skin cells induce the neuropeptide calcitonin gene-related peptide (CGRP) in naïve embryonic dorsal root ganglion (DRG) neurons in vitro, but the molecular basis of that induction is not known. Recombinant activin or bone morphogenetic proteins (BMPs) dramatically increase the number of sensory neurons with CGRP and substance P in vitro (X. Ai et al., 1999, Mol. Cell. Neurosci. 14, 506-518). These experiments were designed to test if activin or BMPs accounted for the CGRP-inductive activity by skin cells. To identify factors from skin that induce CGRP, we developed a bioassay in which embryonic DRG neurons isolated before peripheral target contact in vivo are challenged in vitro with specific factors. Conditioned medium from an embryonic rat skin cell line induced neuronal CGRP expression, and induction was blocked by follistatin, implicating transforming growth factor family members. Immunoblot analysis revealed that the skin cell line medium contained several activin and bone morphogenetic protein moieties. Antibody specific to activin neutralized most of the CGRP-inductive activity in skin conditioned medium. These data indicate that the CGRP-inductive action of skin cells involves activin and establish activin as a candidate regulator of this sensory neuropeptide phenotype during development.

Influence of non-neuronal cells on establishment of neuropeptide Y expression by sympathetic neurons in vitro.

Sympathetic ganglion precursors were used to test the role of non-neuronal cell-derived factors in the establishment of mature neuronal phenotypes. In control conditions, characteristic neuronal populations with and without neuropeptide Y (NPY) expression developed after 1 week, but following removal of non-neuronal cells, virtually all neurons expressed NPY. Thus, ganglionic non-neuronal cells downregulated NPY expression in some but not all neurons in vitro. Conditioned medium from non-neuronal cells restored heterogeneous NPY expression, a finding that suggests the factors are soluble. A non-neuronal cell-derived cytokine, leukemia inhibitory factor, dramatically reduced NPY expression in all neurons, but no concentration tested could recapitulate heterogeneous neuronal NPY expression. Sympathetic precursors that incorporated BrdU early in the culture were more likely to develop NPY expression than neurons that became postmitotic later in vitro. Together, these findings support the notion that the environment in which neurons become postmitotic contributes to neuronal phenotype.

Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro.

The neuropeptide calcitonin gene-related peptide (CGRP) expressed by one-third of rat dorsal root ganglion (DRG) neurons mediates pain sensation and vasodilation. The developmental regulation of CGRP is poorly understood, but may involve target-derived factors from skin or viscera. Few embryonic DRG neurons in defined culture express CGRP, indicating inductive signals are required. Follistatin blocked CGRP expression induced by serum or skin-conditioned medium, implicating transforming growth factor beta (TGFbeta) family members. Activin or bone morphogenetic proteins (BMPs) 2, 4, or 6 stimulated CGRP expression in 60% of DRG neurons. Brief BMP4 application supported maximal CGRP induction, suggesting that BMP4 is a "switch" rather than a continuous modulator of neuropeptide phenotype. DRG expressed corresponding receptor subunits and exhibited Smad1 transcription factor nuclear translocation following BMP stimulation. BMP mRNAs were present in embryonic targets innervated by CGRP-expressing neurons. Thus, specific TGFbeta family members are candidate regulators of CGRP expression in sensory neurons.

Depolarization stimulates initial calcitonin gene-related peptide expression by embryonic sensory neurons in vitro.

The neuropeptide calcitonin gene-related peptide (CGRP) is expressed by one-third of adult rat lumbar dorsal root ganglion (DRG) neurons, many of which mediate pain sensation or cause vasodilation. The factors that regulate the developmental expression of CGRP are poorly understood. Embryonic DRG neurons initially lack CGRP. When these neurons were stimulated in culture by serum or persistent 50 mM KCl application, the same percentage of CGRP-immunoreactive (CGRP-IR) neurons developed in vitro as was seen in the adult DRG in vivo. The addition of the L-type calcium channel blockers, 5 microM nifedipine or 10 microM verapamil, dramatically decreased the proportion of CGRP-IR neurons that developed, although the N-type calcium channel blocker, 2.5 microM omega-conotoxin, was less effective. By contrast, the sodium channel blocker 1 microM tetrodotoxin had no effect on CGRP expression after depolarization. Fura-2 ratiometric imaging demonstrated that mean intracellular free calcium levels increased from 70 to 135 nM with chronic depolarization, and the addition of nifedipine inhibited that increase. Only a subpopulation of neurons had elevated calcium concentrations during chronic depolarization, and they were correlated with CGRP expression. Key signal transduction pathways were tested pharmacologically for their role in CGRP expression after depolarization; the addition of the CaM kinase inhibitor KN-62 reduced the proportion of CGRP-IR neurons to basal levels. By contrast, protein kinase A and protein kinase C were not implicated in the depolarization-induced CGRP increases. These data suggest that depolarization and the subsequent Ca2+-based signal transduction mechanisms play important roles in the de novo expression of CGRP by specific embryonic DRG neurons.

Regeneration of adult axons in white matter tracts of the central nervous system.

It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons. In addition to physical or molecular barriers presented by glial scarring at the lesion site, it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors or lacks growth-promoting molecules. Here we investigate whether adult CNS white matter can support long-distance regeneration of adult axons in the absence of glial scarring, by using a microtransplantation technique that minimizes scarring to inject minute volumes of dissociated adult rat dorsal root ganglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons immediate access to the host glial terrain, where we found that they rapidly extended for long distances in white matter, eventually invading grey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transplant interface, whereas successfully regenerating transplants were associated with minimal upregulation of these molecules. Our results demonstrate, to our knowledge for the first time, that reactive glial extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter tracts beyond the glial scar can be highly permissive for regeneration.

The generation of neuronal heterogeneity in a rat sensory ganglion.

Adult sensory neurons differ chemically, morphologically, and functionally, but the factors that generate their diversity remain unclear. For example, neuropeptides are generally found in small neurons, whereas abundant neurofilament is common in large neurons. Neurons containing the neuropeptides calcitonin gene-related peptide (CGRP) or substance P were quantified using immunohistochemistry in rat lumbar dorsal root ganglion (DRG) at times before and after sensory neurons contact central and peripheral targets in vivo. No neurons in the newly formed DRG expressed neuropeptide or neuropeptide mRNA, but neuropeptides were detectable about the time that axons connect with peripheral targets. To determine the requirement for target in neuropeptide regulation, embryonic DRG neurons were isolated at times before central and peripheral connections had formed, placed in culture, and immunocytochemically assayed for CGRP and substance P. Cultured neurons expressed neuropeptides with a time course and in proportions similar to those in vivo. Thus, some neurons in the embryonic DRG seem to be intrinsically specified to later express CGRP and substance P. The percentage of CGRP-immunoreactive neurons was not changed by cell density, non-neuronal cells, neurotrophins in addition to nerve growth factor (NGF), or antibody inactivation of neurotrophin-3 in the presence of NGF. To test the role of extrinsic cues on CGRP expression, DRG neurons were co-cultured with potential target tissues. Co-culture with a rat epidermal or smooth muscle cell line increased the proportion of CGRP-containing neurons, whereas primary skeletal muscle and 3T3 cells had no effects. Thus, multiple appropriate sensory neuron phenotypes arise in a regulated fashion in cultured neurons isolated before target connections have formed, and some candidate target tissues can modulate that intrinsic expression pattern.

A comparison of imitation strategies in observational learning of action patterns.

The effects of different arrangements of demonstration and imitation of modeled actions on the learning of the 26 handshapes of the American manual alphabet were investigated. A concurrent group (N =16), which imitated handshapes concurrently with their demonstration, was compared with a delayed group (N = 16), which delayed imitation until 3 handshapes had been displayed, and with a combination group (N = 16), which practiced under a combination of concurrent conditions early in acquisition and delayed conditions later in acquisition. Following acquisition, learning was assessed by means of immediate and long-term recall and recognition tests. The delayed group was superior to the concurrent group in long-term serial recall and in immediate and long-term recognition of 3-letter sequences (in nonserial order); the performance of the combination group was between those of the delayed and concurrent groups. Therefore, delaying imitation in acquisition required subjects to expend more cognitive effort to retain and produce handshapes when requested than did concurrent imitation. This was beneficial to development of task knowledge that could be relied on for postacquisition recall and recognition of handshapes.

Developing sympathetic neurons express a neuronal trait before a catecholaminergic synthetic enzyme in vivo.

How multiple mature phenotypic traits are regulated in developing neurons remains a central problem in developmental neurobiology. Mature sympathetic neurons express general neuronal epitopes, including neuron specific tubulin (NST) as well as markers involved in neurotransmitter synthesis including tyrosine hydroxylase (TH). To investigate the relationship between neuronal differentiation and neurotransmitter development, the order of appearance of NST and TH was determined in both chick and rat embryonic sympathetic ganglia by double-label immunohistochemistry. In differentiated ganglia, these two markers were expressed in virtually all sympathetic neurons examined. By contrast, at early stages of embryonic development in both chick and rat, sympathetic ganglia contained many NST immunoreactive (IR) cells, but few precursors were TH-IR. With further development, more NST-IR cells were also TH-IR, and these two markers gradually became coexpressed with subsequent development. These data provide evidence that general neuronal and neurotransmitter differentiation events are separable and independently regulated during cellular diversification in the adrenergic lineage.

Liarozole amplifies retinoid-induced apoptosis in human prostate cancer cells.

Beta-carotene, canthaxanthin and retinoic acid (RA) inhibited growth of human DU145 prostate cancer cells by 45, 56 and 18%, respectively. Lycopene was also found to inhibit cell growth. Other carotenoids including xanthophyll (lutein), cryptoxanthin and zeaxanthin were less effective. Liarozole (a novel imidazole-derived inhibitor of intracellular RA catabolism) had a modest effect upon cell growth, this drug significantly amplified the pro-apoptotic actions of beta-carotene and RA. RA-induced expression of thymosin beta-10, an apoptotic accelerant, was associated with increased nuclear DNA nicking as measured using TUNEL. Liarozole enhanced the proapoptotic actions of RA upon DNA fragmentation in a dose-dependent manner. These actions were accompanied by inhibition of the cell survival factor bcl-2. Liarozole may thus prove useful as a novel chemotherapeutic/chemopreventive agent by boosting retinoid-induced apoptosis in the prostate.

Multiple mechanisms regulate sympathetic neuronal phenotype.

Adult rat sympathetic neurons can possess specific neuropeptides utilized as cotransmitters along with norepinephrine, but the factors that regulate their expression remain unknown. 60% of adult rat superior cervical ganglion (SCG) neurons express neuropeptide Y (NPY) in vivo. To determine whether the restricted expression was an intrinsic property of sympathetic ganglia, we examined if embryonic sympathetic precursors gave rise to NPY immunoreactive (-IR) neurons in vitro. After one week in culture, 60% of neurons derived from the E14.5 rat SCG were NPY-IR. Thus, ganglia isolated before peripheral target contact or preganglionic innervation were capable of regulating NPY expression both in the number of neurons with NPY and in the developmental timing of NPY expression. To determine if the restricted expression of NPY was a reflection of neuroblasts committed to an NPY fate, SCG precursors were labeled with a replication incompetent retrovirus carrying lacZ, and NPY expression in lacZ-labeled clones examined after one week. Two thirds of neuronal clones obtained were uniformly NPY-IR; that is, all neurons in a clone either possessed or lacked NPY. One-third of the neuronal clones were mixed and contained both neurons with and without NPY. We provide a novel demonstration that both lineage and environmental cues contribute to neuropeptide phenotype.

Proliferation, differentiation, and survival of rat sensory neuron precursors in vitro require specific trophic factors.

To determine critical periods of action, the effects of trophic factors on rat lumbar dorsal root ganglion (DRG) neurons were evaluated during neurogenesis, and after neurogenesis, before and after target contact. Brain-derived neurotrophic factor and neurotrophin-4 increased E12.5 DRG neuronal survival. Leukemia inhibitory factor enhanced neuronal differentiation. NGF and NT3 increased BrdU incorporation in neurons derived from E12.5 DRG neuroblasts. By contrasts, neurotrophin dependence switched at E14.5 such that BDNF had no survival activity but NGF, NT3, and NT4 supported survival of the same neurons. At birth, DRG neurons were supported by NGF and to a lesser extent, leukemia inhibitory factor. Thus, specific trophic factors discretely regulate proliferation, differentiation, and survival in DRG at different ages. This study complements genetic studies of neurotrophin and trk activity by identifying the critical period of action for and the specific events regulated by each neurotrophin.

Dividing neuron precursors express neuron-specific tubulin.

Neuronal differentiation involves specific molecular and morphological changes in precursors and results in mature, postmitotic neurons. The expression of neuron-specific beta tubulin, as detected by the monoclonal antibody TuJ1, begins during the period of neurogenesis. Indeed, TuJ1 expression precedes that of the 160 kD neurofilament protein in both the central and peripheral nervous systems. In the embryonic rat spinal cord, bipolar cells and some mitotic cells in the ventricular zone were TuJ1 immunoreactive (IR). Sensory ganglia also contained cells with TuJ1-IR mitotic spindles in situ. In embryonic rat sensory and sympathetic ganglion cell cultures pulsed with the thymidine analog bromodeoxyuridine (BrdU), TuJ1 label was detected in the spindle of mitotic cells and in the midbody of cells joined at cytokinesis, indicating that neuron-specific tubulin expression was initiated during or before the final mitosis of neuronal progenitors. Dorsal root ganglion cultures included TuJ1-IR cells with several shapes that may reflect morphological transitions, from flattened stellate neural crest-like cells to differentiated bipolar neurons. Indeed, the presence of flattened TuJ1-IR cells was correlated with neurogenesis. Some sympathetic neuron precursors possessed long TuJ1-IR neurites, as well as TuJ1-IR spindle microtubules and BrdU-labeled chromosomes, indicating that these precursors can possess long processes during metaphase. These results support the hypothesis that neuron-specific tubulin expression represents an early molecular event in neuronal differentiation exhibited by a wide range of neuronal precursors. The cessation of proliferation can occur at different points during neuronal differentiation, as TuJ1-IR was detected in cells undergoing mitosis. Future studies directed toward understanding the molecules that initiate neuron-specific tubulin expression may lead to the factors that control the initial phases of neuronal differentiation.

Lectin binding distinguishes between neuroendocrine and neuronal derivatives of the sympathoadrenal neural crest.

Lectin cytochemistry was used to identify surface epitopes selectively expressed by chromaffin cell chemoreceptors (glomus cells) in the rat carotid body. Unexpectedly, these studies revealed that binding sites for peanut agglutinin (PNA; Arachis hypogea) were highly expressed by all neuroendocrine-derivatives of the sympathoadrenal neural crest, including glomus cells, small, intensely fluorescent cells, and adrenal chromaffin cells in situ. In contrast, principal sympathetic neurons did not express PNA receptors. PNA binding was inhibited by 2% galactose. To determine whether expression of PNA receptors was selectively induced by neuroendocrine differentiation of sympathoadrenal precursors, we compared PNA labeling of embryonic sympathoblasts in the presence of either nerve growth factor (NGF) or the synthetic glucocorticoid dexamethasone (DEX). DEX-treated cells, which expressed several neuroendocrine traits, bound PNA, whereas NGF-treated neuronal derivatives did not. In addition, to examine whether expression of existing PNA receptors was down-regulated by neuronal differentiation of chromaffin cells, we compared labeling of PC12 cells, which normally bind PNA, in the presence and absence of NGF. Although PC12 cells acquired characteristic neuronal morphologies in the presence of NGF, they did not lose PNA labeling, even after 8 days of NGF treatment. These findings indicate that neuronal and neuroendocrine derivatives of the sympathoadrenal lineage can be distinguished by differential expression of carbohydrate epitopes and suggest that PNA receptors are induced by neuroendocrine differentiation.

Thymosin beta-10 accelerates apoptosis.

The 5 Kd (MW), retinoic acid responsive thymosin beta-10 protein is expressed at relatively high levels in embryonic tissues, and its mRNA is abundant in a variety of tumors and tumor cell lines. Recently this protein (together with other members of the same protein family) was found to be a major intracellular G-actin binding protein. In the present study, plasmid-driven overexpression of thymosin beta-10 gene results in increased susceptibility of permanently transfected fibroblasts to undergo apoptosis. Conversely, knockout of the endogenous gene via overexpression of the antisense mRNA inhibited cell death induced by TNF-alpha and calcium ionophore A23187. Differential expression of thymosin beta-10 influenced cell proliferation, cell morphology, and expression/distribution of the antiapoptotic protein bcl-2. The presence of increased cytoplasmic thymosin beta-10 precipitated significant disruption of phalloidin-stained actin stress fibers while knockout of thymosin expression promoted F-actin assembly. These and other observations suggest that thymosin beta-10 (a) plays a significant and possibly obligatory role in cellular processes controlling apoptosis possibly by acting as an actin-mediated tumor suppressor, (b) perhaps functions as a neoapoptotic influence during embryogenesis, and (c) may mediate some of the pro-apoptotic anticancer actions of retinoids.

Changing epidemiology and management of deliberate self poisoning in Christchurch.

AIMS: To review the epidemiology and emergency management of deliberate self poisoning by substance ingestion in Christchurch for 1992, with comparison to 1989. METHOD: A retrospective analysis of case records was conducted for the year 1992, and compared with published data from 1989. RESULTS: There were 622 presentations (compared to 531 in 1989) of deliberate self poisoning by substance ingestion, representing 1.2% (cf 0.96%) of the total emergency department consultations. The female to male ratio was 1.5:1.0 (cf 2.1:1), with three quarters of patients being under the age of 35. The principle drugs ingested were antidepressants (24.4% cf 15.7%), hypnotic/anxiolytics 23.6% (benzodiazepines 18% cf 22.8% in 1989), paracetamol (16.9% cf 10.6%) and antipsychotics (16.1%, not reported 1989). Stomach emptying procedures were used in 27% of patients (cf 78%). Ipecacuanha was administered in 1% (cf 25%). Activated charcoal alone was used as the method of gastrointestinal decontamination in 46% (cf 0.4%). No attempt at decontamination was made for 27% of patients. Fifty nine percent (cf 66%) were admitted, 11% (cf 18%) to the intensive care unit. There were two inpatient deaths in both 1992 and 1989. CONCLUSIONS: Antidepressants have become the most frequently misused medication, and misuse of paracetamol has increased. However, self poisoning remains a phenomenon of low morbidity and mortality. Stomach emptying procedures are used much less frequently, making for substantial savings of time, resources and patient discomfort.

Molecular interactions between G-actin, DNase I and the beta-thymosins in apoptosis: a hypothesis.

The beta-thymosins are a family of < 5kDa (MW), mostly acidic, proteins which were originally defined in the immune system. Recently, specific members of this family of cytoplasmic polypeptides, namely beta-4 and beta-10, were shown to bind monomeric G-actin both in vitro and in vivo. Whilst many aspects of programmed cell death or 'apoptosis' remain to be defined, the Ca2+/Mg(2+)-dependent endonuclease, DNase I does feature in this process. Monomeric G-actin binds to and inhibits the DNA-degrading activity of DNase I. Given that the intracellular abundance of thymosins beta-4 and beta-10 is related to cell division and differentiation and that anticancer/morphogenic agents such as retinoic acid (RA) and cyclic AMP modulate expression of their respective genes, it is possible that these G-actin sequestering proteins play significant roles in apoptosis perhaps mediated via DNase I.