High postoperative portal venous flow pulsatility indicates right ventricular dysfunction and predicts complications in cardiac surgery patients.

BACKGROUND: Right ventricular failure after cardiac surgery is associated with morbidity and mortality. Right ventricular dysfunction results in hepatic venous congestion, which impacts the portal circulation. We aimed to determine whether an increased portal flow pulsatility fraction was associated with right ventricular dysfunction in cardiac surgery patients. We also aimed to describe the haemodynamic factors and postoperative complications associated with an increased portal pulsatility in this setting. METHODS: We conducted a prospective single-centre cohort study, recruiting adults undergoing cardiac surgery. Portal flow was assessed before, during, and after surgery by Doppler ultrasound. A detailed haemodynamic and echocardiographic assessment was performed at the same time points. RESULTS: A total of 115 patients were included. Both systolic and diastolic right ventricular dysfunction were associated with a higher portal pulsatility fraction (P=0.008 and <0.001, respectively). A positive association was present between portal pulsatility fraction and measurements representative of venous pressure (central venous pressure, inferior vena cava diameter). A post-procedural portal pulsatility fraction ≥50% measured in the operating room was present in 21 (18.3%) patients and was associated with an increased risk of major complications (odds ratio=5.83, confidence interval, 2.04-16.68, P=0.001). The addition of portal flow assessment to a predictive model including EuroSCORE II and systolic right ventricular dysfunction improved prediction of postoperative complications. CONCLUSIONS: High portal flow pulsatility fraction is associated with right ventricular dysfunction, signs of venous congestion and decreased perfusion, and an increased risk of major complications. Portal vein Doppler ultrasound appears to be promising for risk assessment in the perioperative period. CLINICAL TRIALS REGISTRATION: NCT02658006.

Estrogen-induced hypothalamic beta-endorphin neuron loss: a possible model of hypothalamic aging.

Over the course of normal aging, all female mammals with regular cycles display an irreversible arrest of cyclicity at mid-life. Males, in contrast, exhibit gametogenesis until death. Although it is widely accepted that exposure to estradiol throughout life contributes to reproductive aging, a unified hypothesis of the role of estradiol in reproductive senescence has yet to emerge. Recent evidence derived from a rodent model of chronic estradiol-mediated accelerated reproductive senescence now suggests such a hypothesis. It has been shown that chronic estradiol exposure results in the destruction of greater than 60% of all beta-endorphin neurons in the arcuate nucleus while leaving other neuronal populations spared. This loss of opioid neurons is prevented by treatment with antioxidants indicating that it results from estradiol-induced formation of free radicals. Furthermore, we have shown that this beta-endorphin cell loss is followed by a compensatory upregulation of mu opioid receptors in the vicinity of LHRH cell bodies. The increment in mu opioid receptors presumably renders the opioid target cells supersensitive to either residual beta-endorphin or other endogenous mu ligands, such as met-enkephalin, thus resulting in chronic opioid suppression of the pattern of LHRH release, and subsequently that of LH. Indeed, prevention of the neuroendocrine effects of estradiol by antioxidant treatment also prevents the cascade of neuroendocrine aberrations resulting in anovulatory acyclicity. The loss of beta-endorphin neurons along with the paradoxical opioid supersensitivity which ensues, provides a unifying framework in which to interpret the diverse features that characterize the reproductively senescent female.

[Sexuality in the psychiatric milieu]. / Sexualité en milieu psychiatrique.

The main goal of this paper is to describe the problems associated with the expression of sexuality of patients in a psychiatric setting. The problem is analyzed according to the normalization principle. The staff's attitude is considered to be a determining factor in this situation. The authors present the principal conclusions of their study and make some practical recommendations.

The 21-aminosteroid antioxidant, U74389F, prevents estradiol-induced depletion of hypothalamic beta-endorphin in adult female rats.

A single intramuscular injection of 2 mg estradiol valerate (EV) results in neuronal degeneration and beta-endorphin depletion in the hypothalamic arcuate nucleus of adult female rats. We have hypothesized that peroxidase-positive astrocytes in this brain region oxidize estrogens and catecholestrogens to semiquinone radicals which mediate oxidative neuronal injury. In the present study, dietary administration of the potent antioxidant 21-aminosteroid, U-74389F, completely blocked EV-induced beta-endorphin depletion in the hypothalami of adult female rats. Neither EV nor 21-aminosteroid treatment had any effect on hypothalamic concentrations of neuropeptide Y and Met-enkephalin, confirming that the estradiol lesion is fairly selective for the beta-endorphin cell population. The present findings support the hypothesis that the toxic effect of estradiol on hypothalamic beta-endorphin neurons is mediated by free radicals.

Quantitative evaluation of neuronal loss in the dorsal hippocampus in rats with long-term pilocarpine seizures.

Systemic administration of the cholinergic agonist pilocarpine (350-400 mg/kg, i.p.) to rats induces acute behavioral and EEG status epilepticus followed by apparent complete neurological recovery. In rats receiving higher doses of pilocarpine (i.e., 380-400 mg/kg), recurrent seizures reappear 2-2.5 weeks later and continue to occur as long as the rats are kept alive. Stereological estimates of neurons in regions CA1, CA3 and the dentate granule cell layer in the dorsal hippocampus show a dose-dependent neuronal loss in the CA3 and CA1 subregions. The granule cell layer of the dentate gyrus is not affected. No progressive neuronal loss was observed in the regions studied after 3, 6 and 12 weeks during which the animals displayed spontaneous recurrent seizures. The temporal profile of the epileptic condition induced by pilocarpine and the resulting pattern of neuronal loss in the rat hippocampus are similar to those seen in many cases of human temporal lobe epilepsy. The neuronal loss is dose-dependent and primarily results from the acute pilocarpine-induced seizures as chronic seizures do not produce any measurable additional cell loss in the regions examined in the experimental model used in this study.

Pathologic effect of estradiol on the hypothalamus.

Estradiol provides physiological signals to the brain throughout life that are indispensable for the development and regulation of reproductive function. In addition to its multiple physiological actions, we have shown that estradiol is also selectively cytotoxic to beta-endorphin neurons in the hypothalamic arcuate nucleus. The mechanism underlying this neurotoxic action appears to involve the conversion of estradiol to catechol estrogen and subsequent oxidation to o-semiquinone free radicals. The estradiol-induced loss of beta-endorphin neurons engenders a compensatory increment in mu opioid binding in the medial preoptic area rendering this region supersensitive to residual beta-endorphin or to other endogenous opioids. The consequent persistent opioid inhibition results in a cascade of neuroendocrine deficits that are ultimately expressed as a chronically attenuated plasma LH pattern to which the ovaries respond by becoming anovulatory and polycystic. This neurotoxic action of estradiol may contribute to a number of reproductive disorders in humans and in animals in which aberrant hypothalamic function is a major component.

Estradiol is selectively neurotoxic to hypothalamic beta-endorphin neurons.

The neurotoxic effects of estradiol on hypothalamic arcuate neurons were examined in a model of chronic estrogenization induced by means of a single injection of estradiol valerate (EV). Eight weeks after EV treatment, a 60% decrease in the total number of beta-endorphin-immunoreactive neurons was detected in the arcuate nucleus. In contrast, the numbers of neurotensin-, somatostatin-, and tyrosine hydroxylase-immunoreactive neurons were unchanged, suggesting that the effects of estradiol were selective for beta-endorphin neurons. Further evidence for the selectivity of estradiol's actions was provided by RIAs indicating decreases in hypothalamic beta-endorphin concentrations, but not in Metenkephalin or neuropeptide-Y concentrations. Cell counts performed in Nissl-stained material using unbiased stereological methods revealed a reduction in the total number of neurons in the EV-treated group compared to that in the controls. The estimated number of neurons lost (approximately 3500) corresponded precisely with the total number of beta-endorphin neurons lost (approximately 3600), as estimated using quantitative immunocytochemistry. These results confirm the selectivity of estradiol's effect on the beta-endorphin cell population and demonstrate that the observed decrease in beta-endorphin immunoreactivity reflects actual cell loss. The evidence indicates that the selective neurotoxic effect of estradiol on hypothalamic beta-endorphin neurons contributes to reproductive senescence, suggesting that steroids may participate in disruption of the biological functions that they normally facilitate.

Vitamin E protects hypothalamic beta-endorphin neurons from estradiol neurotoxicity.

Estradiol valerate (EV) treatment has been shown to result in the destruction of 60% of beta-endorphin neurons in the hypothalamic arcuate nucleus. Evidence suggests that the mechanism of EV-induced neurotoxicity involves the conversion of estradiol to catechol estrogen and subsequent oxidation to free radicals in local peroxidase-positive astrocytes. In this study, we examined whether treatment with the antioxidant, vitamin E, protects beta-endorphin neurons from the neurotoxic action of estradiol. Our results demonstrate that chronic vitamin E treatment prevents the decrement in hypothalamic beta-endorphin concentrations resulting from arcuate beta-endorphin cell loss, suggesting that the latter is mediated by free radicals. Vitamin E treatment also prevented the onset of persistent vaginal cornification and polycystic ovarian condition which have been shown to result from the EV-induced hypothalamic pathology.

Monosodium glutamate-induced reductions in hypothalamic beta-endorphin content result in mu-opioid receptor upregulation in the medial preoptic area.

Estradiol valerate (EV) treatment in the rat induces a lesion of the hypothalamic arcuate nucleus, resulting in significant decreases in hypothalamic beta-endorphin. In addition, the EV treatment causes a selective increase in mu-opioid binding in the medial preoptic area (MPOA). Since beta-endorphin neurons located in the arcuate nucleus project extensively to the MPOA, we have hypothesized that the EV-induced loss of these afferents induces a compensatory upregulation of mu-opioid receptors in opioid target neurons. In order to test this hypothesis, we have utilized monosodium glutamate (MSG) treated animals as a model of beta-endorphin cell loss and hence of beta-endorphin deafferentation of the MPOA. Neonatal MSG treatment has been shown to result in the destruction of 80-90% of arcuate neurons accompanied by pronounced decreases in beta-endorphin concentrations in both arcuate nucleus and MPOA. mu-Opioid binding sites were radioautographically labeled in sections from the MPOA of sham- and MSG-injected animals using the methionine enkephalin analogue 125I-FK 33-824 and quantitated by computer-assisted densitometry. The remainder of the hypothalamus of these same animals was utilized for the determination of the beta-endorphin concentration. The hypothalami of rats treated with MSG exhibited 62% (p < 0.01) less beta-endorphin than saline-injected controls. In addition, the mean mu-opioid-binding densities in the MPOA were 24% (p < 0.05) above controls in the MSG-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease.

The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.

Distribution of mu, delta, and kappa opioid receptors in the hypothalamus of the rat.

The radioautographic distribution of mu, delta and kappa opioid binding sites was examined by in vitro radioautography in the rat hypothalamus using the highly selective ligands [125I]-FK 33-824, [125I]azidoDTLET and [125I]DPDYN, respectively. Levels of mu opioid binding sites varied considerably amongst hypothalamic nuclei. mu Opioid labeling was dense in the medial preoptic area, medial preoptic nucleus, suprachiasmatic nucleus and ventromedial nucleus, whilst the supraoptic nucleus, paraventricular nucleus, arcuate nucleus and dorsomedial nucleus were devoid of labeling. Delta opioid labeling was sparse throughout most of the hypothalamus; however, moderate binding densities were detected in the suprachiasmatic and ventromedial nucleus. kappa Opioid labeling was also scant throughout the hypothalamus with the exception of the suprachiasmatic nucleus which was very densely labeled. Our results indicate that the 3 opioid receptors types are differentially distributed within the hypothalamus, although a significant overlap exists. In general, the distribution of hypothalamic opioid receptors correlates well with that of opioid-containing terminal fibers and may represent the anatomical substrate for opioid involvement in the hypothalamic regulation of autonomic, behavioral and neuroendocrine functions.

Development and maintenance of a polycystic condition in ovaries autotransplanted under the kidney capsule.

A single injection of estradiol valerate (EV) produces a polycystic ovarian (PCO) condition in the rat. The development of the PCO condition coincides with alterations in the endogenous plasma gonadotropin patterns, suggesting that PCO may be a response to abnormal gonadotropin stimulation. Other factors, however, such as direct autonomic innervation, also contribute significantly to the regulation of the ovary and could be important in generating and/or maintaining PCO. We have, therefore, removed and autotransplanted one ovary in each of eight rats under the capsule of the ipsilateral kidney, thus totally disrupting its innervation. The animals were injected with EV and both ovaries of each animal were examined 8 weeks later. In a second group of animals, we induced the PCO condition, autotransplanted one polycystic ovary in each animal under the kidney capsule, and examined the ovaries 2 weeks later. In both groups the autotransplanted ovaries exhibited the full range of polycystic morphology, as did the intact ovary in each animal. We conclude that since a major perturbation in innervation affects neither the development nor the maintenance of PCO, autonomic innervation does not play a crucial role in this disorder.

[Nasotracheal intubation and tracheostomy in acute epiglottitis and laryngotracheal bronchitis]. / L'intubation naso-trachéale et la trachéostomie dans l'épiglottite et la laryngo-trachéo-bronchite aigue.

Acute infectious respiratory distress in children has known different modalities of treatment during these past few years, but controversy remains between tracheostomy and naso-tracheal intubation as ways to cope with the problem. This study, which was undertaken at St. Justine's Hospital in Montreal, reports our complications with the two methods and shows that non-fatal complications are about the same but less serious with naso-tracheal intubation, whereas mortality was 3.2% with tracheostomy and 0% with naso-tracheal intubation. These results entitle us to think that naso-tracheal intubation is the treatment which should be used. This study also reviews different incidence in regards to age, sex, and seasonal prevalence between croup and epiglottitis and also compares the duration of hospital care between the two modalities.