Sympatric divergence and clinal variation in multiple coloration traits of Ficedula flycatchers.

Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (PST ) was higher than that in neutral genetic markers (FST ), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non-independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.

Candidate genes for colour and vision exhibit signals of selection across the pied flycatcher (Ficedula hypoleuca) breeding range.

The role of natural selection in shaping adaptive trait differentiation in natural populations has long been recognized. Determining its molecular basis, however, remains a challenge. Here, we search for signals of selection in candidate genes for colour and its perception in a passerine bird. Pied flycatcher plumage varies geographically in both its structural and pigment-based properties. Both characteristics appear to be shaped by selection. A single-locus outlier test revealed 2 of 14 loci to show significantly elevated signals of divergence. The first of these, the follistatin gene, is expressed in the developing feather bud and is found in pathways with genes that determine the structure of feathers and may thus be important in generating variation in structural colouration. The second is a gene potentially underlying the ability to detect this variation: SWS1 opsin. These two loci were most differentiated in two Spanish pied flycatcher populations, which are also among the populations that have the highest UV reflectance. The follistatin and SWS1 opsin genes thus provide strong candidates for future investigations on the molecular basis of adaptively significant traits and their co-evolution.

Midazolam premedication reduces propofol dose requirements for multiple anesthetic endpoints.

PURPOSE: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG). METHODS: In a double blind, controlled, randomized and prospective study, 24 ASA I-II patients received either midazolam 0.05 mg x kg(-1) (PM; n = 13) or saline placebo (PO; n = 11) i.v. as premedication. Twenty minutes later, anesthesia was induced by propofol infusion at 30 mg x kg(-1) x hr(-1). ED50, ED95 and group medians for times and doses were determined and compared at multiple anesthetic endpoints. RESULTS: At the hypnotic, motor and EEG endpoints, midazolam premedication significantly and similarly reduced propofol ED50 (reduction: 18%, 13% and 20% respectively; P <0.05 vs unpremedicated patients) and ED95 (reduction: 20%, 11% and 20% respectively; P <0.05 vs unpremedicated patients). For antinociception (LRP), dose reduction by premedication was greater for propofol ED95 (reduction: 41%; P <0.05 vs unpremedicated patients) than ED50 (reduction: 18%; P <0.05 vs unpremedicated patients). Hemodynamic values were similar in both groups at the various endpoints. CONCLUSIONS: Midazolam premedication 20 min prior to induction of anesthesia reduces the propofol doses necessary to attain the multiple anesthetic endpoints studied without affecting hemodynamics in this otherwise healthy population. The interaction differs for different anesthetic endpoints (e.g., antinociception vs hypnosis) and propofol doses (e.g., ED50 vs ED95).

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points.

We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n = 12) or no midazolam (group T0, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED50 and ED95 values at all end-points (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED95 +52%, ED50 +23%, median +39%), and smallest for painful stimulation (LRP) (median +18%; ED50 +13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points.

[Oncotic pressure and hemodilution]. / Pression oncotique et hémodilution.

The appropriate fluid therapy in neurosurgical patients remains an area of disagreement between neurosurgeons and anaesthesiologists. Fluid restriction has long been practiced in patients with brain pathology, in order to reduce or prevent the formation of cerebral oedema. This grows from a fear that rapid administration of fluids, particularly noncolloidal fluids, can enhance cerebral oedema, although there is a lack of experimental evidence to substantiate this belief. On the other hand, fluid restriction can lead to relative hypovolaemia, causing haemodynamic instability during anaesthesia and influence defavourably cerebral perfusion. The appropriate fluid management of patients with brain pathology requires a careful review of the Starling's law and a clear understanding of osmolality, oncotic pressure (OP) and the nature of the blood-brain barrier (BBB). The Starling equation of ultrafiltration states that the net movement of fluid between the intra- and extravascular compartments is the result of the summated influences of the pressure gradients (hydrostatic pressure, OP, and osmotic pressure) between those compartments and the properties of the barriers (capillary endothelium) that separate them. In most peripheral tissues this barrier is freely permeable to small molecules and ions and net fluid movement depends on intravascular hydrostatic pressure and OP. Under normal circumstances, intraluminal hydrostatic pressure is higher than interstitial pressure, favouring water egress. By contrast, intraluminal OP is higher than interstitial OP, favouring water retention. These forces do not balance exactly, and fluid accumulation is prevented by the lymphatics. If this net movement exceeds the capacity of the lymphatic clearance mechanisms, fluid accumulates, which is the definition of oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

[Subarachnoid hemorrhage: cerebral damage, fluid balance, intracranial pressure and pressure-volume relation]. / Hémorragie sous-arachnoïdienne: lésion cérébrale, équilibre hydrique, pression intracrânienne et relation pression-volume.

Changes in osmolality and electrolyte concentrations are observed frequently in patients with subarachnoid haemorrhage (SAH). Intracranial pressure (ICP) plays a determinant role in the development of secondary brain damage following SAH and may be caused by haemorrhage itself, oedema formation and disturbance of cerebrospinal fluid (CSF) dynamics. The relationships among these factors are the aim of this investigation. In 17 comatose SAH patients, ICP was monitored through a ventricular catheter; serial of pressure-volume index (PVI) and CSF formation and reabsorption were performed. Arterio-jugular differences for oxygen and lactate were measured. The average ICP recorded for each 12 hour interval was 18.9 mmHg (SD = 5.9); mean cerebral perfusion pressure (CPP) was 75 mmHg (SD = 13); the lowest CPP value was 30 mmHg. Mean PVI was 22.7 mL (SD = 7.4), ranging from 5 to 36. Eleven patients however, showed a PVI less than 15 mL at some point during testing. Values of CSF dynamics indicated disturbances of CSF reabsorption in 11 cases. When the cause of ICP rise was identified in CSF disturbances, treatment was successful, even in case of reduced PVI. Mean C(a-v)O2, corrected for a PaCO2 of 40 mmHg, was 3.7 mL.dL-1 (SD = 1.1) ranging from the extremely low value of 0.2 to 6.8 mL.L-1. Three patients with extremely low C(a-v)O2 values showed a cerebral production of lactate and developed areas of ischaemia on the CT scan. Hyponatraemia, considered as a sodium plasma concentration of less than 135 mmol.L-1, was detected in seven patients. Hyponatraemia was treated by infusion of hypertonic sodium solutions. Mannitol (1 g.kg-1.d-1 in four doses) was infused if the sodium plasma concentration was not corrected by the former treatment or if ICP exceeded 20 mmHg. Treatment was aimed at preserving cerebral perfusion by providing adequate pre-load, low viscosity (Ht 30%) and sustained arterial pressure. Correction of hyponatraemia was therefore achieved more through hypertonic fluids infusion than by using diuretics.

[Treatment of hypovolemia in brain injured patients]. / Traitement de l'hypovolémie chez le traumatisé craniocérébral.

The appropriate administration of intravenous fluids in neurosurgical patients remains an area of disagreement between neurosurgeons and anaesthetists. Fluid restriction has long been advocated by the former and is widely believed to reduce or prevent the formation of cerebral oedema. However, such restriction can lead to hypovolaemia which in turn can result in haemodynamic instability. Thus, brain homeostasis should be aimed for through adequate fluid administration and normal or slightly elevated mean arterial pressure. The properties of the endothelium differ between the brain and the remainder of the body. In most non CNS tissues the size of the junctions between endothelial cells averages 65 A. Proteins do not cross these gaps while sodium does. In the brain, the junction size is only 7 A, which is too small to allow crossing by sodium. Investigations with changes in osmotic and oncotic pressure have demonstrated that: 1) reducing osmolality results in oedema formation in all tissues including normal brain; 2) a decrease in oncotic pressure is only associated with peripheral oedema but not in the brain; 3) in case of brain injury, a decrease in osmolality elicits oedema in the part of brain which remained normal; 4) similarly, a decrease in oncotic pressure does not cause an increase in brain oedema in the injured part of the brain. Thus, a major reduction in oncotic pressure is unimportant for the brain, whereas changes in total osmolality are the dominant driving force at this level. To conclude, in a hypovolaemic patient with severe head injury, the crystalloid of choice is NaCl 0.9% and the colloid of choice is hydroxyethylstarch, both with an osmolality > 300 mosm.kg-1. Ringer-lactate is hypoosmotic (255 mosm.kg-1) and may cause or increase cerebral oedema. Mean arterial pressure should be maintained above 80 mmHg.

[Physiopathological consequences of blood-brain barrier involvement]. / Conséquences physiopathologiques d'une atteinte de la barrière hématoencéphalique.

Most of the adverse effects of cerebral injury derive result from the formation of cerebral oedema, which causes brain swelling, brain shift and intracranial hypertension. The mechanisms of cerebral oedema are specific of the type of cerebral injury and the effectiveness of treatments such as corticosteroids depend on the type of cerebral oedema. Recent magnetic resonance imaging studies of the brain in patients with acute intracranial injury have confirmed that anatomical brain shifts accompany the clinical syndromes of brain herniation. In particular, specific neurological syndromes can effectively identify rostro-caudal herniation, both transtentorially (uncal and central syndrome) and through the foramen magnum. Signs of upward transtentorial herniation are less specific. Early detection of these syndromes is essential if therapeutic measures to reduce intracranial pressure are to be taken before secondary neurological injury occurs.

[Role of blood-brain barrier in cerebral homeostasis]. / Rôle de la barrière hématoencéphalique dans l'homéostasie cérébrale.

By a variety of mechanisms, the cerebral endothelium isolates the extracellular fluid space in the central nervous system from the plasma. The combination of physical and enzymatic mechanisms which prevent macromolecules, polar solutes, neurotransmitters, peptides, and electrolytes from passively entering the brain has been termed the blood-brain barrier (BBB). Specific mechanisms provide facilitated transport across the BBB and active secretion of extracellular fluid and CSF maintain homeostasis for nutrients and for cation and H+ respectively. Consequently, interstitial fluid volume in the CNS does not increase when the total extracellular fluid volume is increased. Total tissue volume is sensitive to osmotic forces, while oncotic forces are relatively unimportant. Most anaesthetic drugs are sufficiently lipid soluble that they enter the CNS easily by passive diffusion. Differences in the rates of CNS penetration between drugs can be predicted from their lipid solubility. Anaesthetic drugs have little effect on BBB permeability and their effects on brain oedema formation derive principally from their haemodynamics effects.

[Flumazenil and peroperative awakening in surgery of scoliosis]. / Flumazénil et réveil peropératoire lors de la chirurgie de la scoliose.

Motor and sensory function must be assessed during surgery of scoliosis so as to avoid possible damage to the spinal cord. The intraoperative awakening by a specific benzodiazepine antagonist, flumazenil, was studied prospectively in 20 patients (mean age 17 years) undergoing surgery for severe scoliosis. Premedication consisted in 0.02 mg.kg-1 atropine and 0.15 mg.kg-1 midazolam. Anaesthesia was induced with a mean dose of 0.42 +/- 0.1 mg.kg-1 midazolam, 1.6 +/- 0.6 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 pancuronium. Maintenance was obtained with a continuous infusion of 0.22 +/- 0.1 mg.kg-1.h-1 midazolam, 66% nitrous oxide in oxygen, and fentanyl (1.6 +/- 0.5 micrograms.kg-1.h-1). Nitrous oxide and midazolam were respectively stopped 10 and 1 min before giving the antagonist (5 micrograms.kg-1 flumazenil) if required (17 out of the 20 patients). Eye opening occurred a mean 42 +/- 32 s after giving the antagonist. At this time, there was a significant increase in mean arterial blood pressure (+ 11 mmHg) and heart rate (+ 7 b.min-1). Thiopentone, 66% nitrous oxide in oxygen and 0.5% halothane were given to re-induce and maintain anaesthesia for completion of the procedure. The day following surgery, 19 patients were unable to remember the period of intraoperative awakening. One patient, although remembering the episode, did not experience any pain or any other disagreement in relation to it. Two patients were given a second dose of flumazenil at extubation so as to improve the quality of their recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Use of flumazenil (RO 15-1788) after prolonged infusion of midazolam in anesthesia for intracranial surgery]. / Utilisation du flumazénil (Ro 15-1788) après perfusion prolongée de midazolam en anesthésie pour chirurgie intracrânienne.

Midazolam, with a half-life of about 1.5-3.5 h, is inappropriate for the maintenance of anaesthesia during long procedures, especially when rapid recovery is necessary. The efficacy of flumazenil, a specific benzodiazepine antagonist, in the treatment of patients with benzodiazepine overdose suggests that rapid recovery from anaesthesia induced and maintained with midazolam might be obtained in patients needing immediate assessment. The rate of recovery, the side-effects and the feasibility of an early and accurate neurological assessment were studied in 18 ASA III patients after craniotomy in whom the prolonged effects of midazolam had been antagonized by flumazenil. Surgery lasted 5.5 +/- 1.3 h (means +/- SD). The induction dose of midazolam was 0.32 +/- 0.08 mg.kg-1 and the infusion rate was 0.2 +/- 0.08 mg.kg-1.h-1. Fentanyl was added at a dose and rate of 5.0 +/- 3.6 micrograms.kg-1 and 2.0 +/- 0.9 micrograms.kg-1.h-1 respectively. At the end of the dressing, 0.5 mg of flumazenil (t0) was injected, followed by 0.1 mg every minute up to a total of 1 mg. After 2 min, 14 patients (78%) opened their eyes (p less than 0.05) and 13 (72%) obeyed orders (p less than 0.05). After 10 min, 16 patients (89%) were extubated and speaking. During the first 10 min, the Glasgow score and the sedation score used for this study showed the same progression, with 13 patients (72%) having a Glasgow score of 14-15 (p less than 0.05). Thereafter, both scores decreased progressively till t60, then increased again, reaching their t10 level at t120. Three patients required another dose of antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)