Clinical outcome of closed isolated subtalar dislocations.

INTRODUCTION: Subtalar dislocation (SD) is an uncommon injury accounting for 1-2% of all dislocations. It involves simultaneous disruption of the talocalcaneal and talonavicular joints, without involvement of the calcaneocuboid or tibiotalar joints or talar neck fracture. We present a retrospective study of pure medial and lateral SDs treated conservatively and discuss the pathogenesis, classification, prognostics and therapeutic aspects of SD. MATERIALS AND METHODS: Thirty patients, 24 men and 6 women (mean age 33 years; range 18-55) with closed isolated SD were treated conservatively and re-evaluated at 5-12 years. There were 20 medial and 10 lateral dislocations. All patients were managed with immediate closed reduction under general anaesthesia. Open dislocations and SDs associated with fractures were excluded. RESULTS: The mean AOFAS Ankle-Hindfoot score was 78.8. Seven patients (all with medial SDs) had an AOFAS score of 100; 14 patients (11 with medial and 3 with lateral SD) had a mean AOFAS score of 85; 6 patients (three with medial and three with lateral SD) had a mean AOFAS score of 65; and 3 patients (all with lateral SDs) had a mean AOFAS score of 28. The latter patients subsequently underwent subtalar fusion, with a fair outcome. The mean AOFAS scores of patients with lateral and medial SD were not significantly different (P = 0.05). CONCLUSION: Various factors adversely affect outcome, including type of dislocation (lateral/medial, open/closed), severity of the injury, associated fractures, length of immobilization. Management of closed isolated SD is by immediate conservative treatment in order to avoid or reduce the incidence of early soft-tissue and vascular complications and poor long-term outcomes due to post-traumatic arthritis, talus necrosis and subtalar joint stiffness. However, complications may still arise despite correct treatment.

Sub-neurotoxic neonatal anoxia induces subtle behavioural changes and specific abnormalities in brain group-I metabotropic glutamate receptors in rats.

Anoxia in the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. We set-up a model of subneurotoxic anoxia based on repeated exposures to 100% nitrogen during the first 7 days of post-natal life. This mild post-natal exposure to anoxia specifically modified the behaviour of the male adult rats, which showed an attention deficit and an increase in anxiety, without any impairment in spatial learning and any detectable brain damage (magnetic resonance imaging and histological analysis). Post-anoxic rats showed a reduction in the expression of group-I metabotropic glutamate receptors (i.e. mGlu1 and mGlu5 receptors) in the hippocampus and cerebral cortex, whereas expression of the mGlu 2/3 receptors, the NR1 subunit of NMDA receptors, and the GluR1 subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors was unchanged. mGlu1 and mGlu5 receptor signalling was also impaired in postanoxic rats, as revealed by a reduced efficacy of the agonist (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) to stimulate polyphosphoinositide hydrolysis in hippocampal slices. We conclude that rats subjected to subneurotoxic doses of anoxia during the early post-natal life develop behavioural symptoms that are frequently encountered in the inattentive subtype of the attention deficit hyperactivity disorder, and that group-I mGlu receptors may be involved in the pathophysiology of these symptoms.

Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms and in some binary mixtures.

Thermogravimetry (TG) and differential scanning calorimetry (DSC) were used to assess the compatibility between acetaminophen (Ac) and some excipients (polyvinylpyrrolidone (P), magnesium stearate (M), citric acid (C), aspartame (As), mannitol (Mn), cellulose (Cll) and starch (S)) in several of the more commercially available pharmaceutical formulations and in solid binary mixtures. The present study compared thermodynamic data on acetaminophen melting and vaporization processes of pure acetaminophen with those found for several solid mixtures and in some commercially available acetaminophen-based dosage forms. Appreciable modifications occur only for solid mixtures with high content of excipient. Acetaminophen-based dosage forms and its solid binary mixtures usually show "additivity" of calorimetric peaks number of pure components in their calorimetric curve profiles, thus revealing a good thermoanalytical compatibility between acetaminophen and the excipients examined, except for samples containing appreciable content of mannitol.

Reduced activity of hippocampal group-I metabotropic glutamate receptors in learning-prone rats.

Following the hypothesis of the "signal-to-noise" ratio we examined whether changes in the activity of group-I metabotropic glutamate (mGlu) receptors in the hippocampus are associated with a condition that specifically enhances the learning capacity in rats. As a model, we used rats that had been nursed by mothers drinking a solution of corticosterone (13.5 mg of daily intake of corticosterone hemisuccinate) during the lactation period. These rats were prone to learn, as indicated by a better performance in a passive avoidance test. Stimulation of polyphosphoinositide (PI) hydrolysis by the mGlu receptor agonist, 1S,3R-1-amino-cyclopentan-1,3-dicarboxylic acid (1S,3R-ACPD), was attenuated in hippocampal slices prepared from corticosterone-nursed male and female rats at 30 or 60 days of postnatal life, an age at which an increased learning capacity could be demonstrated. This effect was specific because the PI response to carbamylcholine was unchanged. A reduced PI hydrolysis in corticosterone-nursed rats was also observed when group-I mGlu receptors (i.e. mGlu1 and -5 receptors) were selectively activated using 3,5-dihydroxyphenylglycine or 1S,3R-APCD combined with the selective group-II mGlu receptor antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)propionate. Western blot analysis showed a selective reduction in the expression of mGlu1a receptor protein in the hippocampus of corticosterone-nursed rats, whereas expression of mGlu5 and mGlu2/3 receptors was unchanged. The reduction in mGlu-receptor mediated PI hydrolysis in the hippocampus may contribute to the greater learning capacity of corticosterone-nursed rats by reducing the background noise over which a specific signal must be superimposed during learning. This hypothesis was supported by the evidence that mGlu-receptor stimulated PI hydrolysis was amplified in hippocampal slices from rats subjected to a passive avoidance learning paradigm, and that this amplification was greater in slices from corticosterone-nursed rats of both sexes.

Relationship between learning, stress and hippocampal brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) expression in the hippocampus is reduced in response to acute, as well as repeated immobilization stress. This effect might be mediated by corticosterone, because corticosterone administration is known to reduce hippocampal BDNF. However, rats subjected to a learning paradigm showed an increased BDNF expression in the hippocampus despite the high corticosterone levels found during the test. To dissect the relative contributions of learning and stress to the overall changes in BDNF levels we set up an experimental model in which two groups of rats received the same amount of stress, but only one group had the possibility to learn how to avoid it. Using this model, we now report that learning and stress exert an opposite modulation on BDNF levels in the hippocampus, and that the increasing effect of learning predominates over the decreasing effect of stress.

Maternal corticosterone influences behavior, stress response and corticosteroid receptors in the female rat.

In infancy, glucocorticoids have been shown to affect hypothalamus-pituitary-adrenal (HPA) axis activity and behavior. Both the activity of the HPA axis and many aspects of behavior exhibit important gender-dependent differences physiologically. In our previous studies, male offspring of hypercorticosteronemic mothers show long-lasting changes of learning as well as adrenocortical activity. In the light of these findings, this study aims to determine the long-term effects of glucocorticoids in the early stages of life in female rats. Corticosterone (200 microg/ml) was added to the drinking water of the dams. Female offspring exhibited lower adrenocortical secretory response to stress, improvement in learning (water maze at 21, 30 and 90 days; active avoidance at 15 months) and reduced fearfulness in anxiogenic situations (dark-light test at 1 and 15 months; conditioned suppression of drinking at 3 months; plus maze at 15 months) after weaning, from 21 days up to 15 months of age, but not before. No difference in hippocampal adrenocorticoid receptors was observed. These results, together with previous data on male offspring, show that the outcomes of maternal hypercorticosteronemia on hormonal stress response and behavior are similar in males and females, but the effects on some aspects of the HPA axis activity are gender-dependent. Possible explanations for these differences are discussed.

Increased maternal corticosterone levels in rats: effects on brain 5-HT1A receptors and behavioral coping with stress in adult offspring.

This study examined the consequences of elevated corticosterone levels in lactating rats on their offspring's serotonergic 5-hydroxytryptamine (5-HT)1A receptor system and behavioral coping with stress. The mothers received normal drinking water or water with corticosterone, which, via the milk, enters the circulation and brains of the pups. In adulthood, the corticosterone-nursed offspring showed a consistently more passive way of coping with environmental challenges. However, they did not seem to be more anxious. Autoradiographic analysis of the 5-HT1A receptor system revealed a decrease in the adult 5-HT1A receptor binding in the hippocampal CA1 region. The results support the hypothesis that differences in behavioral coping with stress by adult rats are associated with differences in the serotonergic system. At the same time, it suggests that adult coping and its neuronal substrates are not solely determined by genes but depend on subtle developmental factors as well.

Maternal glucocorticoid hormone influences nerve growth factor expression in the developing rat brain.

Rat pups nursed from birth by mothers with increased plasma corticosterone show long-lasting biochemical and behavioral modifications. Here we have investigated nerve growth factor (NGF) concentrations in the basal forebrain, prefrontal cortex and hippocampus of both male and female offspring at 11 days of age. Maternal hypercorticosteronemia was achieved by giving corticosterone-enriched water (200 microg/ml) from delivery. There was a significant increase of NGF in the basal forebrain of both sexes and no changes in the prefrontal cortex. In the hippocampus, an increase in NGF was found in males. These results indicate that a moderate increase of corticosterone in the lactating mother modulates NGF in the developing rat. We propose that these effects contribute directly to the long-lasting behavioral and biochemical modifications in pups nursed by hypercorticosteronemic mothers.

Maternal corticosterone during lactation permanently affects brain corticosteroid receptors, stress response and behaviour in rat progeny.

The long-term consequences of a physiological-range increase of maternal corticosterone during lactation were investigated on the 15-month-old progeny. The offspring of rats drinking water supplemented with corticosterone (200 microgram/ml of corticosterone hemisuccinate) from day 1 postpartum to weaning exhibited: (i) better performance in a conditioned learning test; (ii) reduction of fearfulness in two conflict situations; (iii) lower stress-induced corticosterone secretion and (iv) higher number of corticosteroid receptors in the hippocampus. The results of this study show that the effects of maternal physiological-range hypercorticosteronemia during lactation are lifelong. Moreover, these data suggest that corticosteroids, secreted during neonatal life, may constitute a factor directing the neurobiological development of the infant. In line with this hypothesis, glucocorticoid-induced early events have consequences on the behavioral and physiological status of adulthood. These consequences may be either "beneficial" or "detrimental" depending on the plasma levels of corticosterone induced by the early life occurrences, as well as on the kind of the stimulus and the developmental stage at which the neonate experiences the event. The present study demonstrates that, when the increase of corticosterone in infancy is moderate, the adult rats show reduced anxiety, improved learning and a better coping strategy to deal with stressful situations.

Orphanin FQ reduces morphine-induced dopamine release in the nucleus accumbens: a microdialysis study in rats.

The effects induced by orphanin FQ (OFQ) on morphine-induced dopamine (DA), 3,4-dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA) release in the nucleus accumbens were studied in rats by using microdialysis with electrochemical detection. Morphine administered intraperitoneally (i.p., 2, 5 and 10 mg/kg) dose-dependently increased DA and metabolites release in the nucleus accumbens. OFQ intracerebroventricularly (i.c.v.) administered at doses of 2, 5 and 10 nmol did not change DA and metabolites release in the nucleus accumbens. OFQ (10 nmol) administered i.c.v. 15 min before morphine (5 and 10 mg/kg, i.p.) significantly reduced morphine-induced DA and metabolites release in the nucleus accumbens. These effects suggest that OFQ may regulate the stimulant action linked to morphine-induced DA release in the nucleus accumbens.

Day-surgery. The "Regina Elena" National Cancer Institute experience.

The Authors thorough analyse the subject of day-surgery underscoring the advantages this procedure represents in the light of the experience gained at "R.Elena" National Cancer Institute. The aims of ambulatorial surgery are, in broad terms, the safety of procedures, patients' compliance as well as organisational and economic savings for the health structure. In the future, one-day surgery might represent an important contribution to surgical therapeutical strategies allowing, if well organized, an excellent compromise between safety, convenience and reduced costs.

Effect of increased maternal corticosterone during lactation on hippocampal corticosteroid receptors, stress response and learning in offspring in the early stages of life.

The influence of maternal corticosterone during lactation on the development of the hippocampal corticosteroid receptor system, hypothalamus-pituitary-adrenal axis activity and spatial learning/retention performance was investigated in the rat during postnatal days 11 to 30. We increased the plasma levels of corticosterone by adding the hormone (200 microg/ml) to the drinking water of the dams. When compared to controls corticosterone-nursed offspring displayed: i) higher number of hippocampal type I and type II corticosteroid receptors at 30 days of life, but no changes at 11 and 16 days; ii) higher plasma levels of corticosterone in the basal condition and after 15 min of maternal separation at 11 but not at 16 days: iii) lower adrenal weights at 11 and 16 days, but which were no longer present at the age of 30 days; iv) no difference in performance in the place learning version of the Morris water task and T aquatic maze at 16 days. The present results, together with our previous findings showing that 90-day-old corticosterone-nursed rats have lower basal and restraint stress corticosterone levels and improved learning performance, indicate that the effects of maternal treatment appears only after weaning, thereby suggesting that increased corticosteroid receptors may be responsible, at least partially, for the endocrine and learning modifications induced by pre-weaning corticosterone exposure. The role played by maternal circulating corticosterone during the period of lactation in shaping the characteristics of the hypothalamus-pituitary-adrenal axis and brain of the offspring is outlined.

Reduced hippocampal in vitro CA1 long-term potentiation in rat offsprings with increased circulating corticosterone during neonatal life.

A moderate increase in plasma level of corticosterone was induced in dams by adding the hormone (200 micrograms/ml) to the drinking water from the day after delivery to weaning. This procedure produces a parallel increase in plasma levels of the hormone in the pups (from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml) at 10 days of lactation. A significant (P < 0.01) reduction in the magnitude of the long-term potentiation (LTP) of the CA1 population spike occurred in hippocampal slices obtained from 30-45 day old male corticosterone-nursed rats with respect to controls, while no significant difference occurred in the magnitude of the basal CA1 evoked extracellular somatic field potentials with respect to controls. The results demonstrate that a moderate increase in plasma corticosterone during neonatal life, obtained through maternal milk, has long-lasting effects on the hippocampal CA1 synaptic plasticity. In addition, these results together with our previous findings [Catalani, A. et al., Brain Res., 624 (1993) 209-215], demonstrating that 30 day old corticosterone-nursed offsprings perform better than controls in the place learning version of the Morris water maze, show no relationships between in vitro CA1 LTP induction and spatial learning in agreement with literature data.

Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance.

In order to test the hypothesis that maternal corticosterone influences hypothalamus-pituitary-adrenal (HPA) system activity in the adult rat and behaviors related to it, we induced a moderate increase in maternal plasma level of corticosterone by adding the hormone to the drinking water of the dams (200 micrograms/ml) from the day after delivery to weaning. Our previous experiments have shown that this procedure produces plasma levels of the hormone in the range of those following a mild psychic stress (from 4.3 +/- 0.5 to 9.5 +/- 1.8 micrograms/100 ml in the dams, and from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml in the pups at 10 days of lactation). Adrenal weights were slightly and temporarily decreased by treatment in both mothers and offspring. Only the male progeny was investigated in this study. Corticosterone-nursed rats had significantly less corticosterone and ACTH in basal conditions and after a 2 min restraint stress at 3 months of age, and showed better performances at weaning and at 1, 2 and 3 months of life in the Morris water maze. Our results demonstrate that a moderate increase in maternal corticosterone during lactation influences the activity of HPA axis and improves spatial learning ability of the adult offspring.

Maternal adrenalectomy and adult offspring in a conflict situation in the rat.

The effects of the absence of maternal adrenals during pregnancy (P), during lactation (L), during pregnancy and lactation (PL) were studied on pain suppressed behavior (punished drinking test) of the adult offspring in comparison with controls (C). The female L offspring showed a lower responsiveness to the anxiogenic stimulus, as demonstrated by increased water intake, decreased percentage of ineffective licks, and decreased time to perform 300 licks compared to C. The male L behavior was not affected. Reduced growth was not responsible for the reduced anxiogenic reactivity because also both male and female PL offspring had lower weight than C, but did not show any significant effect. Pain threshold in the tail flick test was the same in all types of offspring. Thus, absence of maternal adrenals, specifically during lactation, significantly affects behavior of female offspring. It is discussed whether this is due to the lack of a physiological influence of maternal adrenal hormones on brain ontogenesis (hippocampal glucocorticoid receptors), or on the development of the brain-pituitary-adrenal system during neonatal life of the offspring.