RÉSUMÉ
Five patients with breakage of instrumentation when using the cannulated 3.5 mm screw system for fracture fixation are reported. Four 1.25 mm guide wires were sheared off by the cannulated drill and one 3.5 mm cannulated tap sleeve fractured. This article presents potential dangers when using the cannulated 3.5 mm screw system for general fracture care.
Sujet(s)
Vis orthopédiques/effets indésirables , Ostéosynthèse interne , Adolescent , Traumatismes de la cheville/chirurgie , Traumatismes du pied/chirurgie , Fractures fermées/chirurgie , Humains , Fractures de l'humérus/chirurgie , Mâle ,RÉSUMÉ
Dopamine D3 receptors have been implicated in pathophysiological substrates of schizophrenia, and neuroleptic drugs which are antagonists primarily at D2 receptors possess therapeutic activity in this disorder. In the present study, rats tested for hypomotility induced by 7-hydroxy-DPAT (7OH, a selective D3 agonist) were pretreated with the neuroleptic haloperidol. These animals showed an attenuated agonist-induced suppression of behavior compared with rats receiving 7OH alone. The drug combination also 'normalized' dopamine metabolism in the frontal cortex, as turnover ratios which are typically enhanced by acute neuroleptic administration were no longer significantly increased when 7OH was also given. These observations suggest that the effects of haloperidol in cortical regions regulating limbic locomotor systems may be important for therapeutic efficacy in schizophrenic symptoms generated from a D3 substrate.
Sujet(s)
Agonistes de la dopamine/pharmacologie , Halopéridol/pharmacologie , Activité motrice/effets des médicaments et des substances chimiques , 1,2,3,4-Tétrahydro-naphtalènes/pharmacologie , Acide 3,4-dihydroxy-benzèneacétique/métabolisme , Analyse de variance , Animaux , Neuroleptiques/pharmacologie , Dopamine/métabolisme , Lobe frontal/effets des médicaments et des substances chimiques , Lobe frontal/métabolisme , Acide homovanillique/métabolisme , Système limbique/physiologie , Mâle , Rats , Rat Sprague-Dawley , 1,2,3,4-Tétrahydro-naphtalènes/antagonistes et inhibiteursRÉSUMÉ
1. Negative symptoms of schizophrenia are characterized by amotivation, anhedonia and anergia. These aspects of the symptom profile can be modeled by D3 agonism in animal behavioral models. 2. Serotonergic systems have been implicated in pathophysiologic substrates for this disorder; most notably, in deficit state schizophrenia, as newer 'atypical' neuroleptics which are especially efficacious for treating this syndrome antagonize central 5-HT2 receptors. 3. FC regions may also be important in chronic negative symptoms, as hypofrontality has been associated with these schizophrenic features. 4. The author examined effects of a behaviorally-active dose of the D3 agonist, 7OH, on 5-HT metabolism in FC, and the ability of a low-dose neuroleptic treatment to antagonize this biochemical effect. 5. Acute administration of 7OH induced a selective decrease of 5-HT turnover in the FC without affecting metabolism of this transmitter in more subcortical DA regions. 6. Hal, which has previously been demonstrated to antagonize electrophysiologic, biochemical and behavioral effects of 7OH, was without effect on agonist-induced decreases in 5-HT turnover. 7. The biochemical association between D3 agonism and reductions of FC 5-HT may be significant for pathophysiologic mechanisms of negative symptoms, and antagonism of this effect may differ for neuroleptics with varying efficacy in alleviating these symptoms.
Sujet(s)
Neuroleptiques/pharmacologie , Agonistes de la dopamine/pharmacologie , Halopéridol/pharmacologie , Schizophrénie/physiopathologie , Sérotonine/métabolisme , Animaux , Agonistes de la dopamine/administration et posologie , Interactions médicamenteuses , Mâle , Cortex préfrontal/effets des médicaments et des substances chimiques , Cortex préfrontal/physiologie , Rats , Rat Sprague-Dawley , Schizophrénie/traitement médicamenteuxRÉSUMÉ
FES is a non-receptor protein tyrosine kinase expressed in hematopoietic progenitors and differentiated myeloid cells. It has recently been implicated in granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and erythropoietin signal transduction. To better understand the role played by FES in normal and neoplastic hematopoiesis, we used cell fractionation techniques to examine the subcellular localization of FES in myeloid cells and cell lines. FES was observed in the nuclear, granular and plasma membrane fractions of primary human neutrophils and the myeloid leukemia cell line, HL-60. The nuclear localization was confirmed by immunocytochemistry of neutrophils.
Sujet(s)
Noyau de la cellule/enzymologie , Protein-tyrosine kinases/génétique , Protéines proto-oncogènes/génétique , Animaux , Lignée cellulaire , Clonage moléculaire , Humains , Protein-tyrosine kinases/métabolisme , Protéines proto-oncogènes/métabolisme , Protéines proto-oncogènes c-fes , Fractions subcellulaires/enzymologie , Cellules cancéreuses en cultureRÉSUMÉ
Investigations linking sudden infant death syndrome (SIDS) and type II intrauterine growth retardation (IUGR) have thus far failed due in part to technical limitations. Recently developed stereological methods for the unbiased estimation of total nephron number in the human kidney are capable of detecting deviations from normal values of greater than 10%. We compared the total number of nephrons in the kidneys of 24 SIDS victims with those from 16 controls with the same age range. Mean nephron number was significantly (P < 0.001) reduced in ex-IUGR SIDS cases (birthweight under the 10th centile, n = 9, mean number 635,000, range 327,000-1,010,000) in comparison with controls (903,000, 740,000-1,060,000). A similarly significant (P < 0.01) reduction in the "normal birthweight" SIDS group (birthweight over 10th centile, n = 15, 690,000, 361,000-1,040,000) was found. This hitherto unreported renal developmental arrest may be only one manifestation of a general, somatic developmental defect, reflecting adverse intrauterine conditions; other organ systems, similarly critical to homeostasis may be comparably affected. The findings, although not proposed as direct cause of SIDS, may represent a potential explanation for the recognized association of IUGR and SIDS, and provide--we believe--the first quantitative evidence of intrauterine growth retardation in, at least a number of, children of average birthweight.
Sujet(s)
Retard de croissance intra-utérin/anatomopathologie , Néphrons/anatomopathologie , Mort subite du nourrisson/épidémiologie , Mort subite du nourrisson/anatomopathologie , Poids de naissance , Femelle , Retard de croissance intra-utérin/complications , Humains , Nourrisson , Mâle , Facteurs de risqueRÉSUMÉ
OBJECTIVE: To investigate the effect of Type II (asymmetrical) intrauterine growth retardation (IUGR) on renal development. DESIGN: A prospective descriptive study. SETTING: Department of Fetal and Infant Pathology, Liverpool Children's Hospital. SUBJECTS: Six (severely) affected IUGR stillbirths of known gestational age with a control group of stillbirths with birthweight greater than 10th centile, and eight liveborn IUGR infants who died within a year of birth with a control group of appropriately grown infants who died within a year of birth (postnatal groups). TECHNIQUES: The kidneys from all the groups studied were analysed using unbiased, reproducible and objective design-based stereological techniques. MAIN OUTCOME MEASURES: Total renal nephron (glomerular) numbers and average volumes of total nephron and cortical and medullary nephron segments. RESULTS: Nephron number estimates lay below the control group's 5% prediction limit in five out of the six growth-retarded stillbirths, and were significantly (P less than 0.005, IUGR at 65% of the control mean) reduced in the postnatal group. Estimates of nephron (segment) volume did not differ between control and IUGR groups. CONCLUSIONS: Type II intrauterine growth retardation may exert a profound effect on renal development. The reduced nephron number at birth, together with the lack of any early postnatal compensation in either nephron number or nephron size, emphasizes the need for vigorous antenatal surveillance for IUGR and consideration of elective preterm delivery of affected fetuses. A systematic review of other organs, which develop in a similarly rapid fashion during the late intrauterine period, is indicated by this work. With one exception, all birthweights in the growth-retarded groups were below the third centile, thus the precise quantitative relation between progressive IUGR and renal function requires further assessment.
Sujet(s)
Retard de croissance intra-utérin/embryologie , Néphrons/embryologie , Poids de naissance , Femelle , Mort foetale/embryologie , Retard de croissance intra-utérin/anatomopathologie , Humains , Nourrisson , Nouveau-né , Néphrons/anatomopathologie , Grossesse , Études prospectivesRÉSUMÉ
Negative symptoms have been associated with structural impairment in the PFC, and hypothesized to arise from a central hypodopaminergic substrate. Corticofugal PFC neurons, which are inhibited by VTA DA innervation, exert a tonic excitatory modulation on DA activity in the NAS. Lesions of ascending DA forebrain projections "uncouple" the functional link between D1 and D2 receptors, permitting independent activation of D1 sites in generating behavioral output. A previously identified absence of this D1/D2 link in schizophrenic brain suggests that functional activation of PFC D1 receptors may induce hyperinhibition of descending corticofugal efferents to the NAS. Consequent hypoactivity of DA in the NAS is proposed to give rise to negative symptoms of schizophrenia, and low dose DA agonist treatments may mimic behavioral features of this symptom profile via direct PFC D1 stimulation. It follows that clozapine's efficacy for negative symptoms may be attributable, in part, to blockade of PFC D1 receptors, with subsequent enhancement of glutamate-facilitated NAS DA activity.
Sujet(s)
Récepteurs dopaminergiques/métabolisme , Schizophrénie/métabolisme , Psychologie des schizophrènes , Neuroleptiques/usage thérapeutique , Humains , Récepteur dopamine D1 , Schizophrénie/traitement médicamenteuxRÉSUMÉ
Animals in the present investigation were trained for conditioned place preference by pairing the non-preferred compartment of a two chamber apparatus with either 1.5 mg kg-1 D-amphetamine or 0.05 mg kg-1 scopolamine. Some of the amphetamine-conditioned rats were injected with 0.05 mg kg-1 scopolamine as an acute treatment on the test day which followed conditioning. Although the scopolamine by itself did not induce either a preference or an aversion to the drug-paired side, it enhanced the expression of place preference in animals conditioned with amphetamine. Potentiation of this conditioned response (CR) was observed in the absence of changes in locomotor activation which would implicate general arousal as a potential mechanism. Hypotheses regarding anticholinergic mediation of CR expression via central reward mechanisms, memory retrieval, cue function and stimulus saliency are discussed, and possible neurosubstrates considered.
Sujet(s)
Conditionnement opérant/effets des médicaments et des substances chimiques , Dexamfétamine/pharmacologie , Récompense , Scopolamine/pharmacologie , Comportement spatial , Animaux , Éveil/effets des médicaments et des substances chimiques , Dopamine/physiologie , Synergie des médicaments , Locomotion/effets des médicaments et des substances chimiques , Mâle , Motivation , Rats , Lignées consanguines de rats , Activation chimiqueRÉSUMÉ
Animals were treated either acutely, or chronically for 21 days, with a low dose (0.1 mg/kg) of haloperidol, then sacrificed to obtain trunk blood for radioimmunoassay of prolactin (PRL) level. PRL concentrations on day 21 of chronic treatment were greater than two-fold those produced by acute neuroleptic. Challenge with apomorphine to rats withdrawn for 48 hours revealed similar PRL reductions as a group withdrawn from chronic vehicle injections.
Sujet(s)
Halopéridol/pharmacologie , Prolactine/sang , Animaux , Apomorphine/pharmacologie , Halopéridol/administration et posologie , Mâle , Rats , Lignées consanguines de ratsRÉSUMÉ
1. Low dose dopaminergic agonist effects have been used as a behavioral screen for identifying compounds with selective autoreceptor activity. 2. However, results from several recent investigations suggest that these behaviors may not be generated from an autoreceptor substrate but rather from a subpopulation of postsynaptic dopamine receptors with a high affinity for the agonist. 3. In support of this hypothesis, the present investigation reports that both hypomotility and yawning, induced in the rat with 0.07 mg/kg apomorphine, were not paralleled by autoreceptor-induced reductions in transmitter metabolism from either mesolimbic or neostriatal dopamine regions.
Sujet(s)
Apomorphine/pharmacologie , Comportement animal/effets des médicaments et des substances chimiques , Récepteurs dopaminergiques/physiologie , Acide 3,4-dihydroxy-benzèneacétique/métabolisme , Animaux , Apomorphine/administration et posologie , Comportement animal/physiologie , Dopamine/métabolisme , Acide homovanillique/métabolisme , Mâle , Noyau accumbens/métabolisme , Bulbe olfactif/métabolisme , Rats , Lignées consanguines de rats , Récepteurs dopaminergiques/effets des médicaments et des substances chimiquesRÉSUMÉ
Animals responding for biphasic square wave stimulation to the VTA were treated for 26 days with a low dose (0.07 mg/kg) of the neuroleptic haloperidol and tested at 1 h post-injection. Initially the drug induced a pronounced lateral displacement of the baseline rate-intensity function, concomitant with a depression in slope. Over the course of chronic treatment, partial tolerance was observed to the drug-induced increases in threshold concomitant with the onset of a significant suppression in peak response rate. Biochemical tolerance to stimulated dopamine metabolism (as per cent non-drug control) was significant only for mesolimbic (versus neostriatal) regions, in animals receiving haloperidol according to pre- and post-test administration schedules. The observation of sensitization to peak rate reductions parallels previous reports for spontaneous locomotor activity measures and is compatible with depolarization inactivation mechanisms proposed to account for delayed-onset clinical effects. Further, selective biochemical tolerance in mesolimbic regions supports suggestions that mesolimbic dopamine is important as a substrate for subtle low dose neuroleptic effects which may be relevant for studying pharmacotherapeutic treatment issues.
Sujet(s)
Halopéridol/pharmacologie , Autostimulation/effets des médicaments et des substances chimiques , Animaux , Encéphale/anatomie et histologie , Chimie du cerveau/effets des médicaments et des substances chimiques , Dopamine/métabolisme , Relation dose-effet des médicaments , Mâle , Rats , Lignées consanguines de rats , Programme de renforcementRÉSUMÉ
When treated chronically with haloperidol, rats show progressively enhanced behavioral suppression, mimicking the delay of onset seen clinically with neuroleptics. To investigate potential neurochemical mechanisms underlying this delay, low-dose apomorphine treatment was administered after withdrawal from 21 days of 0.1 mg/kg haloperidol, to probe for depolarization inactivation or autoreceptor supersensitivity. This haloperidol treatment was subthreshold for inducing either dopamine autoreceptor supersensitivity or postsynaptic supersensitivity as evidenced by equivalent metabolic reductions in chronically treated neuroleptic versus vehicle groups, and an absence of stereotypical responding in either condition. However, haloperidol treated rats appeared subsensitive to yawning induced by 0.07 mg/kg apomorphine. This latter response appears to be generated from an as yet unidentified postsynaptic dopaminergic substrate. The present observation suggests that, within a therapeutically relevant dose range, repeated neuroleptic administration induces a complex set of neuroadaptive processes (both up- and down-regulation of pre- and postsynaptic sites) in the underlying substrate for these drugs' behavioral and biochemical effects.
Sujet(s)
Comportement animal/effets des médicaments et des substances chimiques , Halopéridol/pharmacologie , Récepteurs dopaminergiques/effets des médicaments et des substances chimiques , Animaux , Apomorphine/pharmacologie , Chimie du cerveau/effets des médicaments et des substances chimiques , Antagonistes de la dopamine , Mâle , Activité motrice/effets des médicaments et des substances chimiques , Prolactine/sang , Rats , Lignées consanguines de rats , Récepteur D2 de la dopamine , Comportement stéréotypé/effets des médicaments et des substances chimiques , Synapses/effets des médicaments et des substances chimiques , Bâillement/effets des médicaments et des substances chimiquesRÉSUMÉ
Early postlesion amphetamine-induced contralateral rotation has been linked to intraneuronal dopamine (DA) accumulation and transmitter release associated with axonal degeneration. Animals in the present study sustained severe unilateral depletion of striatal DA with or without a near-complete loss of ipsilateral mesolimbic DA. Contralateral rotation to 1.0 mg/kg (+)-amphetamine was observed on days 1 and 4 postlesion, and was greatly enhanced in mesolimbic-lesioned animals on day 4. On days 7 and 14, very little contralateral turning was observed and there was an emergence of low-rate ipsilateral rotation. These changes in direction and magnitude of rotational response suggest neurochemical adaptations which continue beyond initial periods of intraneuronal accumulation and degeneration-induced release.
Sujet(s)
Dexamfétamine/pharmacologie , Hydroxydopamines/pharmacologie , Système limbique/effets des médicaments et des substances chimiques , Mésencéphale/effets des médicaments et des substances chimiques , Récepteurs dopaminergiques/effets des médicaments et des substances chimiques , Comportement stéréotypé/effets des médicaments et des substances chimiques , Acide 3,4-dihydroxy-benzèneacétique/métabolisme , Animaux , Corps strié/effets des médicaments et des substances chimiques , Dominance cérébrale/effets des médicaments et des substances chimiques , Dopamine/métabolisme , Acide homovanillique/pharmacologie , Mâle , Voies nerveuses/effets des médicaments et des substances chimiques , Noyau accumbens/effets des médicaments et des substances chimiques , Bulbe olfactif/effets des médicaments et des substances chimiques , Oxidopamine , Rats , Lignées consanguines de rats , Substantia nigra/effets des médicaments et des substances chimiquesRÉSUMÉ
Bilateral lesions of mesolimbic dopamine (DA) reliably produce an attenuated response to amphetamine's locomotor stimulatory effects when administered after two weeks of surgical recovery. Several studies have revealed enhanced amphetamine-induced hyperactivity during the first postlesion week, however. In the present study, animals with bilateral 6-OHDA lesions of nucleus accumbens and olfactory tubercle DA showed an exaggerated response to 1.0 mg/kg amphetamine during this early period but were hypoactive in the absence of drug treatment. Neurochemical assay at 5 days revealed increased DA metabolism in the tubercle. Shifting patterns of postlesion amphetamine response under conditions of reduced mesolimbic DA are suggestive of dynamic adaptations in nondopaminergic systems.
Sujet(s)
Dexamfétamine/pharmacologie , Dopamine/physiologie , Hydroxydopamines/pharmacologie , Système limbique/physiologie , Acide 3,4-dihydroxy-benzèneacétique/métabolisme , Animaux , Dopamine/métabolisme , Acide homovanillique/métabolisme , Système limbique/effets des médicaments et des substances chimiques , Système limbique/métabolisme , Mâle , Activité motrice/effets des médicaments et des substances chimiques , Oxidopamine , Rats , Lignées consanguines de ratsSujet(s)
Comportement d'exploration/effets des médicaments et des substances chimiques , Halopéridol/pharmacologie , Activité motrice/effets des médicaments et des substances chimiques , Animaux , Éveil/effets des médicaments et des substances chimiques , Attention/effets des médicaments et des substances chimiques , Relation dose-effet des médicaments , RatsRÉSUMÉ
As low-dose amphetamine stimulation of locomotor activity in the rat depends upon a mesolimbic dopaminergic substrate, neuroleptic antagonism of this behavior has been suggested as a model for studying antipsychotic activity. Animals in the present study received 21 days of chronic treatment with 1.0 mg/kg amphetamine, 0.1 mg/kg haloperidol or a combination of these two drugs. On day 21, mesolimbic (but not striatal) dopamine (DA) concentrations were positively related to locomotor activity in an open field. DA metabolites in this region were inversely correlated with the behavior. The combined drug group showed saline-like levels of both behavioral activity and mesolimbic DA. Metabolic indices in this group suggested that increased DA availability partially competed with the neuroleptic receptor blockade in mesolimbic regions. In contrast to tolerance previously observed with cataleptic doses of neuroleptics, 21 days of 0.1 mg/kg haloperidol did not induce behavioral or biochemical tolerance. This finding is consistent with the lack of tolerance development to antipsychotic effects and suggests that animal models incorporating chronic low-dose neuroleptic regimens may be useful for the study of chronic treatment issues.
Sujet(s)
Dexamfétamine/pharmacologie , Halopéridol/pharmacologie , Système limbique/effets des médicaments et des substances chimiques , Mésencéphale/effets des médicaments et des substances chimiques , Récepteurs dopaminergiques/effets des médicaments et des substances chimiques , Animaux , Corps strié/effets des médicaments et des substances chimiques , Relation dose-effet des médicaments , Mâle , Activité motrice/effets des médicaments et des substances chimiques , Voies nerveuses/effets des médicaments et des substances chimiques , Rats , Lignées consanguines de ratsRÉSUMÉ
Rats receiving 0.1 mg/kg haloperidol showed a progressive decline in their rate of spontaneous motor activity in an open field environment, suggesting that incentive motivational properties of stimuli in the experimental situation may be blunted by neuroleptic treatment. After removal for a short time-out in the home cage they were re-tested in this, or a novel stimulus environment, for a second observation session. Under novel (but not familiar) stimulus conditions haloperidol-treated rats showed an enhancement of spontaneous activity, similar to that observed in vehicle-treated animals, and exceeded their previous low rates of crossing and rearing responses. As drug conditions were similar for the two haloperidol groups, it is likely that neuroleptic-induced effects on spontaneous motor behavior are sensitive to the stimulus complexity of the environmental situation.
Sujet(s)
Environnement , Extinction (psychologie)/effets des médicaments et des substances chimiques , Halopéridol/pharmacologie , Animaux , Mâle , Activité motrice/effets des médicaments et des substances chimiques , Rats , Lignées consanguines de ratsRÉSUMÉ
A rapid latex agglutination slide test for group A beta-hemolytic streptococcal throat infections was prospectively evaluated. Resident physicians, working in an adult non-acute emergency room, recorded clinical data and collected throat swabs from 729 adult patients with sore throats. Research assistants obtained throat swabs from 329 control patients. Sensitivity and specificity, compared with routine cultures, were 96% and 97%, respectively. Analyses of clinical predictions and of test results for control patients, however, suggest that this test may perform better than routine culture. The test provides a rapid, accurate, potentially useful alternative for diagnosing group A beta-hemolytic streptococcal pharyngitis in adults.
Sujet(s)
Service hospitalier d'urgences , Tests au latex , Pharyngite/diagnostic , Infections à streptocoques/diagnostic , Adolescent , Adulte , Analyse de variance , Techniques bactériologiques , Études d'évaluation comme sujet , Humains , Études prospectives , Streptococcus pyogenes/isolement et purificationRÉSUMÉ
The effect of direct intrastriatal injection of three organophosphate cholinesterase inhibitors, DFP (diisopropylphosphorofluoridate), soman (pinacolyl methylphosphonofluoridate) and sarin (isopropyl methylphosphonofluoridate) has been studied on locomotor activity in the rat. The degree of ChE inhibition has been monitored in the striatum, as well as in surrounding brain areas and blood, in order to verify the selectivity of the treatment and rule out effects attributable to actions in these areas and/or the periphery. It has been determined that while enzyme activity is inhibited in the striatum by all three compounds, only DFP significantly reduces locomotor activity at doses that produce no other observable behavioral deficits, or significant leakage into the periphery. Behavioral recovery occurs before enzyme activity returns to control levels. Possible contributions of DFP's action on other neurotransmitters and on ChE in other brain areas to the inhibition of locomotor activity are discussed.