Cranial conjoined twins: surgical and anesthetic challenges for a routine procedure: adenoidectomy and examination of ears.

Craniopagus conjoined twins have long been the subject of interest because of the rarity and peculiarity of their juxtaposition. We present the surgical, airway and anesthetic challenges in craniopagus conjoined twins, in which one of the twins underwent adenoidectomy for obstructive sleep breathing disorder. The surgical procedure required a special setting from an anesthetic perspective whereby both children needed anesthesia due to the complex physiology of their brains and cardiovascular systems.

Safety and efficacy of continuous morphine infusions following pediatric cranial surgery in a surgical ward setting.

Purpose: Morphine is avoided by many neurosurgeons following cranial surgery. There exists a concern regarding the potential complications and a perception that cranial surgery is less painful than other surgical procedures. At British Columbia Children's Hospital continuous morphine infusions (CMI) have been used to control pain in pediatric neurosurgical patients.

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys.

Positive modulation of GABA(A) and antagonism of N-methyl-D-aspartate receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol, suggesting that these steroids may modulate ethanol addiction. The four isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3alpha,5alpha-P), pregnanolone (3alpha,5beta-P), epiallopregnanolone (3beta,5alpha-P), and epipregnanolone (3beta,5beta-P)], a synthetic analog of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3alpha,5beta-P HS)], and a structurally similar, adrenally derived steroid [3alpha-hydroxy-5-androstan-17-one (3alpha,5alpha-A, androsterone)] were assessed for ethanol-like discriminative stimulus effects at 30 or 60 min after administration in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.

A Jehovah's Witness child with hemophilia B and factor IX inhibitors undergoing scoliosis surgery.

Purpose: To describe the successful perioperative hemostatic management of a Jehovah's Witness patient with hemophilia B and anaphylactic inhibitors to factor IX, undergoing scoliosis surgery.

Clinical Features: A 14 (1/2)-yr-old boy with severe hemophilia B who had a history of anaphylactic inhibitors to factor IX was scheduled to undergo corrective scoliosis surgery. He was initially started on epoetin alfa and iron supplementation to maximize preoperative red cell mass.

Allopregnanolone decrease with symptom improvement during placebo and gonadotropin-releasing hormone agonist treatment in women with severe premenstrual syndrome.

Background: Neurosteroids such as allopregnanolone and pregnanolone are suggested to be of importance for the pathophysiology of premenstrual dysphoric disorder. The aim of this study was to investigate whether the luteal-phase serum concentrations of these neurosteroids are associated with improvement of premenstrual symptoms in 12 women with severe premenstrual syndrome after treatment with low-dose gonadotropin-releasing hormone agonist and placebo.

Methods: Daily ratings for mood and physical symptoms were made prior to treatment and throughout the study.

Steroid pregnenolone sulfate enhances NMDA-receptor-independent long-term potentiation at hippocampal CA1 synapses: role for L-type calcium channels and sigma-receptors.

Severe stress elevates plasma and CNS levels of endogenous neuroactive steroids that can contribute to the influence of stress on memory formation. Among the neuroactive steroids, pregnenolone sulfate (PREGS) reportedly strengthens memories and is readily available as a memory-enhancing supplement. PREGS actions on memory may reflect its ability to produce changes in memory-related neuronal circuits, such as long-term potentiation (LTP) of excitatory transmission in hippocampus.

Discriminative stimulus effects of 5.6 mg/kg pregnanolone in DBA/2J and C57BL/6J inbred mice.

Neurosteroids represent a class of endogenous compounds that exert rapid, nongenomic effects through neurotransmitter receptor systems such as gamma-aminobutyric acid(A) (GABA(A)). Two neurosteroids, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) and pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), possess anxiolytic and sedative properties and show substitution for ethanol, benzodiazepines, and barbiturates in drug discrimination assays. A previous study examining the discriminative stimulus effects of 10 mg/kg pregnanolone in DBA/2J and C57BL/6J mice showed pregnanolone's discriminative stimulus to be mediated primarily through GABA(A) positive modulation.

3alpha-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period.

Allopregnanolone (ALLO) and pregnanolone (PREG), the 3alpha-reduced metabolites of progesterone (PROG), are potent modulators of gamma-aminobutyric acid type A receptors that may function as endogenous anxiolytics. They are purported to be involved in the etiology or expression of clinical depression. In the present study we quantified ALLO and PREG, as well as PROG, 5alpha-dihydroprogesterone (5alpha-DHP), 5beta-dihydroprogesterone (5beta-DHP), epiallopregnanolone and pregnenolone (PREGNEN), in plasma from healthy women at five time points during pregnancy and the postpartum period.

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women.

Rationale: The behavioral effects of allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) in women are not known.

Objective: Allopregnanolone, a neuroactive steroid secreted by the mammalian ovary, exerts its anesthetic, anxiolytic, and sedative/hypnotic effects through potentiation of GABAA receptors. The purpose of this study was to evaluate the behavioral effects of allopregnanolone in healthy women.

Plasma concentrations of anxiolytic neuroactive steroids in men with panic disorder.

Plasma concentrations of neuroactive steroids in men with panic disorder (PD) were measured to evaluate their relations to psychopathology both before and during treatment. Participants comprised 13 men with PD and 10 normal controls. Patients were evaluated while drug-free as well as after 1 and 2 months of paroxetine therapy.

Endogenous gamma-aminobutyric acid (GABA)(A) receptor active neurosteroids and the sedative/hypnotic action of gamma-hydroxybutyric acid (GHB): a study in GHB-S (sensitive) and GHB-R (resistant) rat lines.

In the rat brain, gamma-hydroxybutyric-acid (GHB) increases the concentrations of 3alpha-hydroxy,5alpha-pregnan-20-one (allopregnanolone, 3alpha,5alpha-THP) and 3alpha,21-dihydroxy,5alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone/3alpha,5alphaTHDOC), two neurosteroids acting as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors. This study was aimed at assessing whether neurosteroids play a role in GHB-induced loss of righting reflex (LORR). Basal and GHB-stimulated brain concentrations of endogenous 3alpha,5alpha-THP and 3alpha,5alpha-THDOC were analyzed in two rat lines, GHB-sensitive (GHB-S) and GHB-resistant (GHB-R), selectively bred for opposite sensitivity to GHB-induced sedation/hypnosis.

Characterization of the discriminative stimulus effects of the neuroactive steroid pregnanolone in DBA/2J and C57BL/6J inbred mice.

Neurosteroids represent a class of endogenous compounds that exert rapid, nongenomic effects through neurotransmitter receptor systems such as GABA(A). Two neurosteroids, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) and pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), possess anxiolytic and sedative properties and show substitution for ethanol, benzodiazepines, and barbiturates in drug discrimination assays. This study aimed to examine the effects of strain and sex on the discriminative stimulus effects of pregnanolone.

Electrophysiological effects of allopregnanolone in rats with a history of ethanol exposure.

Background: Sensitivity to the anticonvulsant effects of allopregnanolone (ALLO) is enhanced during the early phase of ethanol (EtOH) withdrawal. However, it is unclear whether this enhanced sensitivity generalizes to ALLO's neurobehavioral effects during protracted abstinence. The purpose of this study was to examine the neurophysiological effects of ALLO in rats with a history of chronic EtOH exposure after a protracted period of abstinence.

Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.

Neurosteroids are modulators of neuronal function that may play important roles in brain maturation. We determined whether chronic prenatal ethanol exposure altered neurosteroid levels in the developing brain. Rat dams were exposed to: (i) a 5% ethanol-containing liquid diet that produces peak maternal blood alcohol levels near the legal intoxication limit (approximately 0.

Brain steroidogenesis mediates ethanol modulation of GABAA receptor activity in rat hippocampus.

An interaction with the GABA type A (GABA(A)) receptor has long been recognized as one of the main neurochemical mechanisms underlying many of the pharmacological actions of ethanol. However, more recent data have suggested that certain behavioral and electrophysiological actions of ethanol are mediated by an increase in brain concentration of neuroactive steroids that results from stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. Neuroactive steroids such as 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) are, in fact, potent and efficacious endogenous positive modulators of GABA(A) receptor function.

Plasma concentrations of anxiolytic neurosteroids in men with normal anxiety scores: a correlation analysis.

Neurosteroids are physiological regulators of anxiety in experimental animals, but there are no data for humans about the modulatory effects of the hormones on normal aspects of this emotional parameter. Plasma concentrations of four neurosteroids, pregnenolone, progesterone (PROG), allopregnanolone and tetrahydrodeoxycorticosterone, suggested to be major anxiety regulators in experimental animals, were measured in a group of 58 physically and psychologically normal adult male subjects. In parallel, trait (genotypical) and state (phenotypical) anxiety scores were measured by the State-Trait Anxiety Inventory.

Failure of gamma-hydroxybutyric acid both to increase neuroactive steroid concentrations in adrenalectomized-orchiectomized rats and to induce tolerance to its steroidogenic effect in intact animals.

Gamma-Hydroxybutyric acid (GHB), a drug proposed in the treatment of alcohol withdrawal syndrome, increases the cerebrocortical and plasma concentrations of the neuroactive steroids allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC). In the present study, we examined the role of hypothalamic-pituitary-adrenal (HPA) axis in the effect of GHB by measuring the concentrations of these steroids in the brain and plasma of adrenalectomized-orchiectomized (Adx-Orx) rats. The acute administration of GHB (500 mg/kg, i.

Social isolation increases the response of peripheral benzodiazepine receptors in the rat.

Social isolation of rats for 30 days immediately after weaning reduces the cerebrocortical and plasma concentrations of progesterone, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG), and 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-TH DOC). The percentage increases in the brain and plasma concentrations of these neuroactive steroids apparent 30 min after intraperitoneal injection of the peripheral benzodiazepine receptor (PBR) ligand CB 34 (25 mg/kg) have now been shown to be markedly greater in isolated rats than in group-housed controls. The CB 34-induced increase in the abundance of 3alpha,5alpha-TH PROG was more pronounced in the brain than in the plasma of isolated rats.

Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats.

Peripheral administration of alcohol has been demonstrated to cause significant increases in neurosteroid levels in the brain and periphery. These findings have led to several theories suggesting a role for neurosteroids in the actions of alcohol. However, the anatomical sources of these steroids (e.

Administration of progesterone produces mild sedative-like effects in men and women.

The goal of this study was to investigate the behavioral and subjective effects of a single dose of progesterone in men and women. Certain metabolites of progesterone (e.g.

Neuroactive steroids: new biomarkers of cognitive aging.

Intensive studies in animals established that neuroactive steroids display neuronal actions and influence behavioral functions. We describe here investigations on the role of neuroactive steroids in learning and memory processes during aging and suggest their role as biomarkers of cognitive aging. Our work demonstrated the role of the steroid pregnenolone (PREG) sulfate as a factor underlying an individual's age-related cognitive decline in animals.

Neurosteroid secretion in panic disorder.

Evidence that neurosteroids have anxiolytic effects in animal models of anxiety has suggested that alterations of neurosteroid secretion might be implicated in the pathogenetic mechanisms of anxiety disorders in humans. In 25 female patients with panic disorder (PD) and 11 healthy female controls, we measured plasma concentrations of progesterone (PROG), pregnenolone (PREG), allopregnanolone (3alpha,5alpha-tetrahydroprogesterone=3alpha,5alpha-THPROG), dehydroepiandrosterone (DHEA) and tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) during a drug-free month and during the following month of paroxetine therapy. The neurosteroids were measured during the early follicular phase, the mid-luteal phase and the premenstrual phase of both months (days 7, 22 and 27 from the beginning of the cycle).

Social isolation-induced increase in the sensitivity of rats to the steroidogenic effect of ethanol.

Social isolation of rats for 30 days immediately after weaning results in marked decreases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG), and 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-TH DOC), as well as a moderate increase in the plasma concentration of corticosterone. This mildly stressful condition has now been shown to increase the sensitivity of rats to the effect of acute ethanol administration on the cerebrocortical and plasma concentrations of neuroactive steroids. The percentage increases in the brain and plasma concentrations of pregnenolone, progesterone, 3alpha,5alpha-TH PROG, and 3alpha,5alpha-TH DOC, apparent 20 min after a single intraperitoneal injection of ethanol (1 g/kg), were thus markedly greater in isolated rats than in group-housed animals.