Choice of local anaesthetic for epidural caesarean section: a Bayesian network meta-analysis.

Rapid-onset epidural local anaesthesia can avoid general anaesthesia for caesarean delivery. We performed a Bayesian network meta-analysis of direct and indirect comparisons to rank speed of onset of the six local anaesthetics most often used epidurally for surgical anaesthesia for caesarean delivery. We searched Google Scholar, PubMed, EMBASE, Ovid, CINAHL and CENTRAL to June 2019. We analysed 24 randomised controlled trials with 1280 women. The mean (95%CrI) onset after bupivacaine 0.5% was 19.8 (17.3-22.4) min, compared with which the mean (95%CrI) speed of onset after lidocaine 2% with bicarbonate, 2-chloroprocaine 3% and lidocaine 2% was 6.4 (3.3-9.6) min faster, 5.7 (3.0-8.3) min faster and 3.9 (1.8-6.0) min faster, respectively. Speed of onset was similar to bupivacaine 0.5% after ropivacaine 0.75% and l-bupivacaine 0.5%: 1.6 (-1.4 to 4.8) min faster and 0.4 (-2.2 to 3.0) min faster, respectively. The rate (95%CrI) of intra-operative hypotension was least after l-bupivacaine 0.5%, 315 (236-407) per 1000, and highest after 2-chloroprocaine 3%, 516 (438-594) per 1000. The rate (CrI) of intra-operative supplementation of analgesia was least after ropivacaine 0.75% 48 (19-118) per 1000 and highest after 2-chloroprocaine 3%, 250 (112-569) per 1000.

Spinal anesthesia performed for cesarean delivery after external ventricular drain placement in a parturient with symptomatology from an intracranial mass.

We describe a case in which spinal anesthesia was undertaken in a pregnant patient with a space-occupying tumor and significant symptomatology. The collaborative efforts of all medical disciplines involved and the willingness of the neurosurgeon to discuss and help determine the safety of neuraxial anesthesia, culminated in placing an external ventricular drain to help monitor and manage intracranial pressure, so that we could proceed with spinal anesthesia and more easily monitor neurologic status.

Monozygotic twins discordant for trisomy 18.

We report on the pre- and postnatal cytogenetic, molecular genetic and clinical findings in monochorionic-diamniotic twins discordant for trisomy 18. Structural anomalies were identified in one of the twins on prenatal ultrasound examination at 20 weeks' gestation and sampling of amniotic fluid from both sacs was performed for karyotyping. This revealed trisomy 18 in the twin with abnormalities and a normal karyotype in the other twin. Elective Cesarean section was performed at 31 + 5 weeks and the aneuploid twin died shortly after delivery. The surviving twin showed low-grade mosaicism for trisomy 18 on postnatal analysis but has shown normal development. For prenatal diagnosis in monochorionic-diamniotic twin pregnancy the sampling of both amniotic sacs is recommended, especially if one twin has structural anomalies on ultrasound scan.

Functions of Fos phosphorylation in bone homeostasis, cytokine response and tumourigenesis.

Mice lacking c-fos develop osteopetrosis due to a block in osteoclast differentiation. Carboxy-terminal phosphorylation of Fos on serine 374 by ERK1/2 and serine 362 by RSK1/2 regulates Fos stability and transactivation potential in vitro. To assess the physiological relevance of Fos phosphorylation in vivo, serine 362 and/or serine 374 was replaced by alanine (Fos362A, Fos374A and FosAA) or by phospho-mimetic aspartic acid (FosDD). Homozygous mutants were healthy and skeletogenesis was largely unaffected. Fos C-terminal phosphorylation, predominantly on serine 374, was found important for osteoclast differentiation in vitro and affected lipopolysaccharide (LPS)-induced cytokine response in vitro and in vivo. Importantly, skin papilloma development was delayed in FosAA, Fos362A and Rsk2-deficient mice, accelerated in FosDD mice and unaffected in Fos374A mutants. Furthermore, the related Fos protein and putative RSK2 target Fra1 failed to substitute for Fos in papilloma development. This indicates that phosphorylation of serines 362 and 374 exerts context-dependent roles in modulating Fos activity in vivo. Inhibition of Fos C-terminal phosphorylation on serine 362 by targeting RSK2 might be of therapeutic relevance for skin tumours.

Effects of eccentric rotation on the human pitch vestibulo-ocular reflex.

CONCLUSION: The pitch plane vestibulo-ocular reflex (VOR) gain and symmetry at low frequencies (< or =0.3 Hz) are enhanced by otoliths and/or somatosensory sensory cues during combined angular and linear stimuli. We conclude that neural processing of these linear motion cues is used to improve the VOR when stimulus frequencies are below the optimal range for the canals. OBJECTIVE: The purpose of this study was to examine the effects of eccentric rotation on the passive pitch VOR responses in humans. SUBJECTS AND METHODS: Eleven subjects were placed on their left sides (90 degrees roll position) and rotated in the pitch plane about an earth-vertical axis at 0.13, 0.3, and 0.56 Hz. The inter-aural axis was either aligned with the axis of rotation (no modulation of linear acceleration) or offset from it by 50 cm (centripetal linear acceleration directed feet-ward). The modulation of pitch VOR responses was measured in the dark with a binocular videography system. RESULTS: The pitch VOR gain was significantly increased and the VOR asymmetry was significantly reduced at the lowest stimulus frequencies during eccentric rotation. There was no effect of eccentric rotation on the pitch gain or asymmetry at the highest frequency tested.

Patent foramen ovale and left atrial appendage: new devices and methods for closure.

Transcatheter closure of atrial septal defects (ASDs) has become a routine procedure in many countries of the world. It spares many patients cardiac surgery and has proven efficacy in long-term studies. Device improvements have resulted in a continuous reduction of complications and of residual shunt frequency. ASD closure devices are also used for transcatheter closure of patent foramen ovale (PFO) for prevention of paradoxical embolism. In the past few years, there has been increasing interest in developing devices specifically designed for PFO closure. Although transcatheter closure of ASDs is well established, interventional closure of the left atrial appendage is in its development stage. Closure of the left atrial appendage is designed to reduce the risk of stroke in patients with atrial fibrillation in whom anticoagulation with Warfarin-type drugs is contraindicated. This article describes the latest developments in catheter closure of PFO and the left atrial appendage.

Assessment of cytomegalovirus infections using neopterin and a new immunoblot.

Human cytomegalovirus (HCMV) infections are a major cause of morbidity and mortality in immunocompromised patients despite advances in diagnostic tests and antiviral therapies. The underlying study investigates the diagnostic value of the immune marker neopterin and a recently developed HCMV-specific western blot to detect HCMV infections and to differentiate them into either syndromes or diseases. The mean period of observation was 1428 days. Thirteen HCMV diseases and nine syndromes were diagnosed retrospectively. The first appearance of clinical signs or symptoms was always associated with a marked increase of serum and urine neopterin. The HCMV-specific IgM response followed in the mean 9 days later. Median values and the course of the neopterin levels were significantly higher during the HCMV diseases. In addition, the strength of the humoral immune response was related to the severity of the HCMV infection. Patients with HCMV diseases developed antibodies against a higher number of epitopes. The anti-HCMV IgM response persisted in more than 80% of the patients for longer than 3 years. In conclusion, combining the HCMV-specific western blot and neopterin permit detection of the immune response against HCMV, reflect the severity of the infection and might guide the anti-viral therapy.

Use of recombinant glycoprotein antigens gB and gH for diagnosis of primary human cytomegalovirus infection during pregnancy.

The major risk factor for intrauterine transmission of human cytomegalovirus (HCMV) is a primary infection during pregnancy. The neutralizing antibody response appeared after an average of 13 weeks after seroconversion and therefore the absence of neutralizing titers in HCMV IgG positive pregnant women is a reliable marker for primary infection. Determination of neutralizing antibody, however, is time-consuming and labor-intensive. For this reason an immunoblot assay for detection of neutralizing antibodies was developed based on the use of recombinant antigens representing neutralizing epitopes of glycoproteins (gp) gB (gpUL55) and gH (gpUL75) of HCMV. In this study, 93.6% of sera of pregnant women with prior infection recognized the gp-specific epitopes corresponding to a nonresponder rate of 6.4% relative to the neutralizing antibody. In primary infection the gp-response in general coincided with the appearance of neutralizing antibody. Intriguingly, lack of HCMV gB-specific antibodies was correlated with a lower risk of intrauterine fetal infection (P < 0.05).

Disruption of postural readaptation by inertial stimuli following space flight.

Postural instability (relative to pre-flight) has been observed in all shuttle astronauts studied upon return from orbital missions. Postural stability was more closely examined in four shuttle astronaut subjects before and after an 8 day orbital mission. Results of the pre- and post-flight postural stability studies were compared with a larger (n = 34) study of astronauts returning from shuttle missions of similar duration. Results from both studies indicated that inadequate vestibular feedback was the most significant sensory deficit contributing to the postural instability observed post flight. For two of the four IML-1 astronauts, post-flight postural instability and rate of recovery toward their earth-normal performance matched the performance of the larger sample. However, post-flight postural control in one returning astronaut was substantially below mean performance. This individual, who was within normal limits with respect to postural control before the mission, indicated that recovery to pre-flight postural stability was also interrupted by a post-flight pitch plane rotation test. A similar, though less extreme departure from the mean recovery trajectory was present in another astronaut following the same post-flight rotation test. The pitch plane rotation stimuli included otolith stimuli in the form of both transient tangential and constant centripetal linear acceleration components. We inferred from these findings that adaptation on orbit and re-adaptation on earth involved a change in sensorimotor integration of vestibular signals most likely from the otolith organs.

Constitutive expression of human cytomegalovirus (HCMV) glycoprotein gpUL75 (gH) in astrocytoma cells: a study of the specific humoral immune response.

The humoral immune response to gpUL75 (gH) was determined in different groups of human cytomegalovirus (HCMV) infected subjects using a full-length glycoprotein constitutively expressed in an astrocytoma cell line. The recombinant molecule consisted of two distinct isoforms resembling the authentic protein of infected cells. Separated from the interactions of other viral gene products gH failed to form an oligomeric complex, thus exhibiting exclusively epitopes present on the monomer. Ninety five percent of serum samples from latently-infected healthy adults revealed the presence of gH-specific IgG. Moreover, examination of sequential sera from immunocompromised and immunocompetent individuals undergoing active HCMV infection demonstrated that antibodies to gH occurred in most cases simultaneously with those to the abundant surface antigen gpUL55 (gB) and at similar titres. Appearance of this response was correlated with a considerable increase of the virus-neutralizing activity and most likely associated with restriction of viral dissemination during subsequent viremic episodes. Together, these results suggest that glycoprotein H of HCMV is like gB, a highly immunogenic component of the infectious particle.

Yaw and pitch visual-vestibular interaction in weightlessness.

Both yaw and pitch visual-vestibular interactions at two separate frequencies of chair rotation (0.2 and 0.8 Hz) in combination with a single velocity of optokinetic stimulus (36 degrees/s) were used to investigate the effects of sustained weightlessness on neural strategies adopted by astronaut subjects to cope with the stimulus rearrangement of spaceflight. Pitch and yaw oscillation in darkness at 0.2 and 0.8 Hz without optokinetic stimulation, and constant velocity linear optokinetic stimulation at 18, 36, and 54 degrees/s presented relative to the head with the subject stationary, were used as controls for the visual-vestibular interactions. The results following 8 days of space flight showed no significant changes in: (1) either the horizontal and vertical vestibulo-ocular reflex (VOR) gain, phase, or bias; (2) the yaw visual-vestibular response (VVR); or (3) the horizontal or vertical optokinetic (OKN) slow phase velocity (SPV). However, significant changes were observed: (1) when during pitch VVR at 0.2 Hz late inflight, the contribution of the optokinetic input to the combined oculomotor response was smaller than during the stationary OKN SPV measurements, followed by an increased contribution during the immediate postflight testing; and (2) when during pitch VVR at 0.8 Hz, the component of the combined oculomotor response due to the underlying vertical VOR was more efficiently suppressed early inflight and less suppressed immediately postflight compared with preflight observations. The larger OKN response during pitch VVR at 0.2 Hz and the better suppression of VOR during pitch VVR at 0.8 Hz postflight are presumably due to the increased role of vision early inflight and immediately after spaceflight, as previously observed in various studies. These results suggest that the subjects adopted a neural strategy to structure their spatial orientation in weightlessness by reweighting visual, otolith, and perhaps tactile/somatic signals.

Effects of body orientation and rotation axis on pitch visual-vestibular interaction.

Spatial transformations of the vestibular-optokinetic system must account for changes in head position with respect to gravity in order to produce compensatory oculomotor responses. The purpose of this experiment was to study the influence of gravity on the vestibulo-ocular reflex (VOR) in darkness and on visual-vestibular interaction in the pitch plane in human subjects using two different comparisons: (1) Earth-horizontal axis (EHA) rotation about an upright versus a supine body orientation, and (2) Earth-horizontal versus Earth-vertical (EVA) rotation axes. Visual-vestibular responses (VVR) were evaluated by measuring the slow phase velocity of nystagmus induced during sinusoidal motion of the body in the pitch plane (at 0.2 Hz and 0.8 Hz) combined with a constant-velocity vertical optokinetic stimulation (at +/- 36 degrees/s). The results showed no significant effect on the gain or phase of the VOR in darkness or on the VVR responses at 0.8 Hz between EHA upright and EHA supine body orientations. However, there was a downward shift in the VOR bias in darkness in the supine orientation. There were systematic changes in VOR and VVR between EHA and EVA for 0.2 Hz, including a reduced modulation gain, increased phase lead, and decreased bias during EVA rotation. The same trend was also observed at 0.8 Hz, but at a lesser extent, presumably due to the effects of eccentric rotation in our EVA condition and/or to the different canal input across frequencies. The change in the bias at 0.2 Hz between rotation in darkness and rotation with an optokinetic stimulus was greater than the optokinetic responses without rotation. During EHA, changes in head position relative to gravity preserve graviceptor input to the VVR regardless of body orientation. However, the modifications in VVR gain and phase when the rotation axis is aligned with gravity indicate that this graviceptive information is important for providing compensatory eye movements during visual-vestibular interaction in the pitch plane.

Effect of cysteine substitutions on dimerization and interfragment linkage of human cytomegalovirus glycoprotein B (gp UL55).

Experiments were carried out to analyze the function of cysteine residues at amino acid positions 506 (cI), 550 (cII), 573 (cIII), and 610 (cIV), in dimerization and/or disulfide linkage of human cytomegalovirus (HCMV) glycoprotein B (gB). Single c-codons or pairs were substituted in the gB sequence of constructs which were used for transfection and selection of stable transfectants. Analysis of gB expression products revealed that single substitutions of cIII or cIV, but neither single nor double substitutions of cI or/and cII prevented gB dimerization. All substituted gB derivatives were, however, no longer processed by proteolytic cleavage. After deletion of the membrane anchor domain, correct proteolytic processing was again observed for anchorless gB forms. Substitutions of cI or cI/cII in secretory gB appeared to interfere with disulfide linkage between gB cleavage fragments. In the case of anchorless gB with substitutions of cII, cIII, or cIII/cIV, however, extracellular gB forms were not recovered. Using the Sindbis expression system recovery of all anchorless gB forms with cysteine substitutions was achieved. Analysis verified involvement of cI/II substitutions in intrachain disulfide linkage between cleavage fragments of HCMV gB.

Posture, locomotion, spatial orientation, and motion sickness as a function of space flight.

This article summarizes a variety of newly published findings obtained by the Neuroscience Laboratory, Johnson Space Center, and attempts to place this work within a historical framework of previous results on posture, locomotion, motion sickness, and perceptual responses that have been observed in conjunction with space flight. In this context, we have taken the view that correct transduction and integration of signals from all sensory systems is essential to maintaining stable vision, postural and locomotor control, and eye-hand coordination as components of spatial orientation. The plasticity of the human central nervous system allows individuals to adapt to altered stimulus conditions encountered in a microgravity environment. However, until some level of adaptation is achieved, astronauts and cosmonauts often experience space motion sickness, disturbances in motion control and eye-hand coordination, unstable vision, and illusory motion of the self, the visual scene, or both. Many of the same types of disturbances encountered in space flight reappear immediately after crew members return to earth. The magnitude of these neurosensory, sensory-motor and perceptual disturbances, and the time needed to recover from them, tend to vary as a function of mission duration and the space travelers prior experience with the stimulus rearrangement of space flight. To adequately chart the development of neurosensory changes associated with space flight, we recommend development of enhanced eye movement systems and body position measurement. We also advocate the use of a human small radius centrifuge as both a research tool and as a means of providing on-orbit countermeasures that will lessen the impact of living for long periods of time with out exposure to altering gravito-inertial forces.

The major open reading frame of the beta2.7 transcript of human cytomegalovirus: in vitro expression of a protein posttranscriptionally regulated by the 5' region.

beta2.7 is the major early transcript produced during human cytomegalovirus infection. This abundantly expressed RNA is polysome associated, but no protein product has ever been detected. In this study, a stable peptide of 24 kDa was produced in vitro from the major open reading frame (ORF), TRL4. Following transient transfection, the intracellular localization was nucleolar and the expression was posttranscriptionally inhibited by the 5' sequence of the transcript, which harbors two short upstream ORFs.

Spatial coding of eye movements relative to perceived earth and head orientations during static roll tilt.

This purpose of this study was to examine the spatial coding of eye movements during static roll tilt (up to +/-45 degrees) relative to perceived earth and head orientations. Binocular videographic recordings obtained in darkness from eight subjects allowed us to quantify the mean deviations in gaze trajectories along both horizontal and vertical coordinates relative to the true earth and head orientations. We found that both variability and curvature of gaze trajectories increased with roll tilt. The trajectories of eye movements made along the perceived earth-horizontal (PEH) were more accurate than movements along the perceived head-horizontal (PHH). The trajectories of both PEH and PHH saccades tended to deviate in the same direction as the head tilt. The deviations in gaze trajectories along the perceived earth-vertical (PEV) and perceived head-vertical (PHV) were both similar to the PHH orientation, except that saccades along the PEV deviated in the opposite direction relative to the head tilt. The magnitude of deviations along the PEV, PHH, and PHV corresponded to perceptual overestimations of roll tilt obtained from verbal reports. Both PEV gaze trajectories and perceptual estimates of tilt orientation were different following clockwise rather than counterclockwise tilt rotation; however, the PEH gaze trajectories were less affected by the direction of tilt rotation. Our results suggest that errors in gaze trajectories along PEV and perceived head orientations increase during roll tilt in a similar way to perceptual errors of tilt orientation. Although PEH and PEV gaze trajectories became nonorthogonal during roll tilt, we conclude that the spatial coding of eye movements during roll tilt is overall more accurate for the perceived earth reference frame than for the perceived head reference frame.

Motion sickness and development of synergy within the spatial orientation system. A hypothetical unifying concept.

Adaptation to research paradigms such as rotating rooms and optical alteration of visual feedback during movement results in development of perceptual-motor programs that provide the reflexive assistance that is necessary to skilled control of movement and balance. The discomfort and stomach awareness that occur during the adaptation process has been attributed to conflicting sensory information about the state of motion. Vestibular signals depend on the kinematics of head movements irrespective of the presence or absence of signals from other senses. We propose that sensory conflict when vestibular signals are at least one component of the conflict are innately disturbing and unpleasant. This innate reaction is part of a continuum that operates early in life to prevent development of inefficient perceptual-motor programs. This reaction operates irrespective of and in addition to reward and punishment from parental guidance or goal attainment to yield efficient control of whole body movement in the operating environment of the individual. The same mechanism is involved in adapting the spatial orientation system to strange environments. This conceptual model "explains" why motion sickness is associated with adaptation to novel environments and is in general consistent with motion sickness literature.

Relationship between selected orientation rest frame, circular vection and space motion sickness.

Space motion sickness (SMS) and spatial orientation and motion perception disturbances occur in 70-80% of astronauts. People select "rest frames" to create the subjective sense of spatial orientation. In microgravity, the astronaut's rest frame may be based on visual scene polarity cues and on the internal head and body z axis (vertical body axis). The data reported here address the following question: Can an astronaut's orientation rest frame be related and described by other variables including circular vection response latencies and space motion sickness? The astronaut's microgravity spatial orientation rest frames were determined from inflight and postflight verbal reports. Circular vection responses were elicited by rotating a virtual room continuously at 35 degrees/s in pitch, roll and yaw with respect to the astronaut. Latency to the onset of vection was recorded from the time the crew member opened their eyes to the onset of vection. The astronauts who used visual cues exhibited significantly shorter vection latencies than those who used internal z axis cues. A negative binomial regression model was used to represent the observed total SMS symptom scores for each subject for each flight day. Orientation reference type had a significant effect, resulting in an estimated three-fold increase in the expected motion sickness score on flight day 1 for astronauts who used visual cues. The results demonstrate meaningful classification of astronauts' rest frames and their relationships to sensitivity to circular vection and SMS. Thus, it may be possible to use vection latencies to predict SMS severity and duration.

Microgravity vestibular investigations: perception of self-orientation and self-motion.

Four astronauts experienced passive whole-body rotation in a number of test sessions during a 7-day orbital mission. Pitch (Y-axis) and roll (X-axis) rotation required subject orientations on the rotator in which the otolith system was at radius of 0.5 m. Thus subjects experienced a constant -0.22 Gz stimulus to the otoliths during the 60 s constant-velocity segments of "pitch" and "roll" ramp profiles. The Gz stimulus, a radius-dependent vector ranging from -0.22 Gz at the otoliths to +0.36 Gz at the feet, generated sensory information that was not interpreted as inversion in any of the 16 tests carried out in flight (12 in pitch and 4 in roll orientation). None of the subjects was rotated with head off-center during the first 33 h of the mission. In the state of orbital adaptation of these subjects, a -0.22 Gz otolith stimulus did not provide a vertical reference in the presence of a gradient of +Gz stimuli to the trunk and legs.