Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model.

BACKGROUND: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. METHODS: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O2 (FiO2) of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. RESULTS: During tidal ventilation, the expiratory lung collapse increased when I:E <1 [mean (standard deviation) lung collapse=15.7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). CONCLUSIONS: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.

Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test.

The degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive 'gas-distribution' type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on 'GOLD' classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ([Formula: see text]). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

Ancient genetic variation in one of the world's rarest seabirds.

The Chatham Island Taiko (Tchaik, Pterodroma magentae) is one of the world's rarest seabirds. In the past there were millions of breeding pairs of Taiko and it was the most abundant burrowing petrel on Chatham Island. The present population consists of just 120-150 birds, including only 8-15 breeding pairs. Surprisingly high genetic variation was revealed by DNA sequencing of almost every known adult Taiko (N=90). Given the massive population decline, genetic variation may have been even larger in the past. Therefore, we investigated past genetic diversity by sequencing regions of the mitochondrial cytochrome b gene in 44 ancient Taiko bones. We identified a total of 12 haplotypes in Taiko. Eight haplotypes were revealed in the ancient DNA: four were unique to the bones and four corresponded to those found in the modern Taiko population. Surprisingly, despite the critically endangered status of the Taiko, no significant reduction in mitochondrial DNA haplotype diversity was observed between ancient samples (N=44) and modern adult Taiko (N=90). The modern population may have however lost four haplotypes present in the ancient populations.

Plantar motoneuron columns in the rat.

In the rat, the numbers and locations of motoneurons innervating the short plantar muscles of the hindlimb (supplied by the medial and lateral plantar nerves, as well as a branch of the sural nerve) were determined by using both horseradish peroxidase (HRP) and fluorochromes as retrograde labels. Topographical organization within the plantar motor nucleus was examined by exposing individually the cut ends (encapsulated in low melting-point paraffin) of medial plantar, lateral plantar, and sural nerves to HRP. In addition, double-labeling experiments were conducted in which the medial plantar nerve was labeled with one fluorochrome (either true blue or diamidino yellow) and the lateral plantar nerve with another. The plantar motor pool is located in the extreme dorsolateral portion of the ventral horn, usually concentrated in the fifth lumbar (L5) spinal segment. Labeled motoneurons extended caudally into the sixth lumbar (L6) segment and rostrally into portions of the fourth lumber (L4) segment. Motoneurons of the medial plantar, lateral plantar, and sural nerve have overlapping territories. Sural motoneurons (about 70 cells per side) are generally confined to L5, medial plantar motoneurons (about 180 cells per side) tend to be concentrated in caudal L5 and rostral L6, whereas the lateral plantar motoneurons (about 310 cells per side) extend throughout the entire length of the plantar motor pool. The distribution of motoneuronal cell size is unimodal (mean cross-sectional area = 610 +/- 150 microns2). Cell bodies of plantar motoneurons tend to have similar geometries in all three major planes of sectioning. In all, the combined plantar plus sural nerve population amounts to about 560 motoneurons on each side of the spinal cord. On the basis of these data, and those published by others, the innervation of the small muscles of the foot accounts for about 25% of the motor axons carried by the entire sciatic nerve.

Computer-assisted three-dimensional reconstructions of [14C]-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot.

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by [14C]-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1, were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: 1) Three-dimensional volume images were color-coded to represent different levels of functional activity. 2) On the reconstructed volumes, "virtual" sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. 3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.

Somatotopic organization of the dorsal column nuclei in the rat: transganglionic labelling with B-HRP and WGA-HRP.

To analyze the patterns of cutaneous primary afferent fibers projecting to the dorsal column nuclei in the rat, horseradish peroxidase (HRP)-based tracers were injected intracutaneously into a number of discrete regions of the forelimbs and hindlimbs. Three-4 days following the HRP injections, the rats were perfused transcardially; 60 microns transverse sections were cut, and the HRP was reacted using the tetramethyl benzidine method. Comparisons were made of projections following injections with choleragenoid-conjugated horseradish peroxidase (B-HRP) or with wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). B-HRP and WGA-HRP produced similar patterns of labelling, but B-HRP produced greater intensity of labelling and slightly larger projection areas. In the cuneate nucleus (CN), HRP labelling of primary afferents from small, delimited regions, e.g., from a portion of the skin of a single digit, appeared to be precisely restricted in rostrocaudally oriented columns, with little or no overlap (in the mediolateral and dorsoventral plane) into adjacent regions. With respect to rostrocaudal organization, a region in the CN containing a dense population of cutaneous primary afferent fibers appeared to be similar to the middle, or cluster, region in cats and in raccoons and the pars rotunda in primates. Projection patterns were very consistent from rat to rat, but their somatotopic organization differed from that suggested by electrophysiological studies: cutaneous afferents from forelimb digit 1 projected near the ventral border of the CN; those from digit 5 projected dorsomedially to those from digit 1; the projections from the remaining digits formed a crescent between the projections from digits 1 and 5. In the gracile nucleus, the organization of cutaneous afferent projections from hindlimb digits was more variable and complex than that found in the CN.

Organization of cutaneous primary afferent fibers projecting to the dorsal horn in the rat: WGA-HRP versus B-HRP.

Primary afferent projections from cutaneous afferents in the forelimb and hindlimb digits to the dorsal horn (DH) were examined using 4 tracers: (1) 25% free horseradish peroxidase (HRP), (2) 2.5% wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), (3) a mixture of 25% free HRP and 2.5% WGA-HRP (WGA-HRP/HRP) or (4) 0.1% HRP conjugated to cholera toxin (B-HRP). The tracer was injected intracutaneously into the digits. Three to 4 days later, the rats were perfused transcardially, transverse sections (60-microns thick) were cut and the HRP was reacted using the tetramethyl benzidine (TMB) method. The location of the label was reconstructed by camera lucida drawings. In rats which received an injection of HRP alone, no label was detected in the DH. Rats injected with WGA-HRP had projection patterns similar to those injected with WGA-HRP/HRP. Patterns of labelling with WGA-HRP differed markedly from those with B-HRP. WGA-HRP labelled cutaneous afferents projecting to Rexed's laminae I-III, with the densest label in lamina II; in contrast, B-HRP labelled cutaneous afferents projecting to laminae II-V, with the densest label in laminae III-IV. These results indicate that, for cutaneous primary afferents projecting to the DH, WGA-HRP and B-HRP labelled different subpopulations of fibers, with the B-HRP-labelled subpopulation biased toward afferents of larger diameter. Rostrocaudally, the extent of the densest fiber projections, whether labelled by WGA-HRP or by B-HRP, was essentially the same, but the extent of the less densely labelled projections was much greater with B-HRP than with WGA-HRP. Comparisons of the projection maps from each of the five digits, using either WGA-HRP or B-HRP, indicated that, as seen in transverse sections through the DH, there was extensive overlapping among the labelled cutaneous afferent fibers from adjacent, or even non-adjacent digits.

Synaptophysin immunoreactivity and distributions of calcium-binding proteins highlight the functional organization of the rat's dorsal column nuclei.

The mammalian dorsal column nuclei (DCN) are principally composed of the cuneate (CN) and gracile (GN) nuclei. Data presented here support previously published anatomical and functional evidence that the longitudinal organization of the CN and GN reflect the complex role of the DCN in somatosensory processing. The CN is organized longitudinally into three parts. Within the middle portion of this nucleus, primary afferent projections and cuneothalamic cells are concentrated. Although traditional cytoarchitectonic analyses had failed to detect this tripartite organization in rats, we found evidence for it, with a functional middle region, extending approximately 0.2-0.9 mm caudal to the obex, characterized by precise somatotopy of primary afferent terminations and corresponding somatotopy of cytochrome oxidase (CO) blotches. Additional evidence is presented here consistent with a functionally distinct middle region within the rat's CN: (1) patches of dense synaptophysin (a synaptic-vesical-associated protein)-immunoreactivity (SYN-IR) are limited to the middle CN region, coincident with the dense CO blotches; (2) neurons immunoreactive for the calcium-binding proteins calbindin-D28 (CB), calretinin (CR) and parvalbumin (PV) are concentrated in the middle CN region. Furthermore, in adult rats subjected to perinatal forepaw removal, (1) the patterns of SYN-IR in the middle region of the CN are disrupted, as had previously been shown for the patterns of CO blotches; (2) in contrast, however, distributions of CN cells with PV-, CB- and CR-IR are unaffected. Evidence for a tripartite division in the GN is also presented, based on the distributions of cells with PV-, CB- and CR-IR.

Somatotopic organization of the cuneate nucleus in the rat: transganglionic labelling with WGA-HRP.

A novel somatotopic map of primary cutaneous afferents projecting to the cuneate nucleus in the rat was determined by transganglionic transport of wheat-germ agglutinin conjugated to horseradish peroxidase and free horseradish peroxidase. Intracutaneous injections of tracer into different limited regions of the forelimb resulted in discrete areas of label for each injection site, with little or no overlap into other projection areas. The map of cutaneous projections onto the cuneate nucleus revealed by our anatomical tracing provided much more detail than any previous study in the rat, and demonstrated some significant differences from earlier maps based on electrophysiological recordings.

Enhanced cytochrome-oxidase staining of the cuneate nucleus in the rat reveals a modifiable somatotopic map.

Existing cytochrome oxidase (CO)-staining techniques were modified to enhance sensitivity and contrast in order to examine patterns of CO-activity in the dorsal column nuclei (DCN) of adult Long-Evans rats. Within a rostrocaudally limited region in the middle of the cuneate nucleus (CN) distinctive blotches of intense CO-activity were observed. The CO-staining was maximally differentiated approximately 0.3-0.7 mm caudal to the obex. No CO-blotches were observed anywhere else in the DCN. Transganglionic labelling (WGA-HRP) demonstrated that some of the CO-blotches in the rat CN are related to the terminal projection fields of primary afferents from the skin of the forepaws. The corresponding location of primary afferent termination fields and CO-staining patterns supports a tripartite rostrocaudal division in the rat CN, similar to that described by other investigators in cats, monkeys and raccoons. Comparing the patterns of CO-staining to (1) the cytoarchitecture (Nissl-stained sections), or to (2) the dendritoarchitecture (distribution of microtubule-associated protein 2 (MAP2) or to (3) the organization of retrogradely labelled (WGA-HRP/HRP) cuneothalamic cells, revealed no topographical organization corresponding to the CO-blotches. Postnatal (at least up to 11 days postpartum) forepaw deafferentation or removal disrupted the CO-staining pattern in the CN.

The mutability of low-affinity nerve growth factor receptor (p75NGFR) expression in the rat cuneate nucleus following perinatal injury and adult deafferentations: comparisons with cytochrome oxidase.

In normal adult rats, intense immunostaining for the 75 kDa low-affinity receptor for nerve growth factor and other neurotrophins (p75NGFR) is concentrated in the middle region of the cuneate nucleus (CN), distributed in a blotchy pattern similar to that of cytochrome oxidase (CO) activity. In the adult rats, partial dorsal rhizotomies (centered around the 7th and 8th cervical spinal segments) resulted in the complete disappearance of p75NGFR-like immunoreactivity within the ipsilateral CN, but did not affect the distribution of the CO blotches. Perinatal (postnatal day 1-8) damage to the ipsilateral forepaw and subsequent rearing to adulthood also resulted in significant disruption of the topographical expression of p75NGFR-like immunoreactivity within the CN, as well as--as previously reported--disruption of the CO blotches. Although the patterns of staining in intact adult rats are similar for CO staining and for p75NGFR-like immunoreactivity within the CN, the CO staining appears to be primarily associated with postsynaptic cells, while the p75NGFR-like immunostaining appears to be associated with primary afferent terminals.

Immunocytochemical localization of the low-affinity nerve growth factor receptor (p75NGFR) in the cuneate nucleus of the rat and its relationship to cytochrome-oxidase activity.

Immunohistochemical staining for the 75-kDa, low-affinity nerve growth factor receptor (p75NGFR), within the cuneate nucleus (CN) of the adult rat revealed that this receptor is concentrated rostrocaudally in the middle CN (approximately 0.2-0.9 mm caudal to the obex), corresponding to that portion of the CN receiving densest projections of cutaneous primary afferent terminals. Furthermore, dense patches of p75NGFR-like immunoreactivity appear to correspond to the 'blotches' of cytochrome-oxidase activity observed in the middle region of the CN. This close correspondence between the localization pattern of p75NGFR in the CN and its functional organization suggests an important role for trophic factors in the CN's development and/or maintenance.

The cuneate nucleus in the rat does have an anatomically distinct middle region.

Recently obtained anatomical evidence supports the division of the rat cuneate nucleus (CN) into three rostrocaudal regions, with the middle region receiving a disproportionately greater share of the primary sensory input. The CN in the rat conforms to the basic rostrocaudal CN pattern described in other mammals, including cat, monkey and raccoon.

The up-regulation of trkA and trkB in dorsal column astrocytes following dorsal rhizotomy.

One week after rat dorsal root fibers were severed, immunoreactivity for the high affinity neurotrophin receptors, trkA and trkB, was up-regulated on glial cells in the spinal cord dorsal column. Immunoreactivity for glial fibrillary acidic protein (GFAP) also increased. In contrast, no changes in immunoreactivity for trkA or trkB, or for GFAP were observed in the brainstem cuneate nucleus, a principal termination site for many of the severed dorsal root fibers.

The structure of posttraumatic stress symptoms.

Posttraumatic stress disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. and 4th ed.; American Psychiatric Association, 1987, 1994, respectively), is characterized by 17 symptoms, descriptively clustered into 3 groups: (a) intrusions, (b) hyperarousal, and (c) avoidance and numbing. The present study sought to identify the basic dimensions (factors) that underlie these symptoms. Two samples were assessed: 103 victims of motor vehicle accidents and 419 United Nations peacekeepers deployed in Bosnia. A principal axis factor analysis was conducted for each sample. In each sample, 2 correlated factors were obtained, which were very similar across samples. Factor 1 was labeled Intrusions and Avoidance, and Factor 2 represented Hyperarousal and Numbing. These factors loaded on a single higher order factor. The higher order factor accounted for 13% to 38% of variance in symptom severity, and the lower order factors accounted for an additional 8% to 9% of variance. If the authors assume that each factor corresponds to a distinct mechanism (R. B. Cattell, 1978), then the results suggest that posttraumatic stress reactions arise from a general mechanism, with contributions from 2 specific mechanisms.

Severity of impairment or specific types of aphasia: an empirical investigation.

This study examined empirical means of clustering aphasic patients into relatively homogenous and identifiable groups. The method included: (1) examining the intercorrelations of the subtests of the Neurosensory Comprehensive Examination for Aphasia by the means of factor analysis; (2) allowing the subjects to group themselves in homogenous subgroups by means of hierarchical cluster analysis; and (3) comparing the profiles of these groups on the derived dimensions. Four factors accounting for 79.3% of their total test variance were derived which reflected attention/memory; reading ability; verbal-naming ability; and elementary writing skills. With five groups the hierarchical grouping analysis indicated that only 21.5% of the total variability could be ascribed to within group variability. An analysis of variance of the four factor scores found that 66%, 93%, 81% and 79% of the between group variance of each of the respective factors was associated with group membership and the accuracy of membership prediction was 94.1%. Four groups appeared to be distributed on the basis of a severity model of impairment. One group representing 6.3% of the total sample demonstrated a pattern of specific impairment involving a mild level of impairment on attention/memory tasks, a moderate level of impairment on verbal naming tasks and writing skills, and a profound level of impairment on measures of reading skills. The high inter-factor correlations indicated the general nature of language functioning. The results were discussed in terms of the concept of aphasia as a general cognitive deficit.

The effects of supraceliac aortic clamping on the anticoagulant effects of heparin.

BACKGROUND: Coagulopathy is frequently encountered during supraceliac aortic clamping. Patients are routinely heparinized during these operations. This experiment was undertaken to evaluate the effect of supraceliac aortic cross-clamping (XC) on heparin pharmacodynamics. MATERIAL AND METHODS: Fourteen mongrel dogs were randomly divided into three groups: Group 1 (X; n = 6), 90 minutes aortic XC; Group 2 (SH; n = 4), sham operation and heparin, 100 mg/kg intravenously; and Group 3 (XH; n = 4), heparin, 100 mg/kg intravenously 3 minutes before XC. Prothrombin time (PT) and partial prothrombin time (PTT) were measured serially. Heparin concentrations were estimated via automated titration with protamine sulfate. RESULTS: After XC, PTT is increased during reperfusion. Heparin administration (XH) before aortic XC increases PTT above those with X or SH. Anticoagulation was potentiated and prolonged by XC. There was no difference in heparin concentration or PT. CONCLUSION: Supraceliac aortic clamping significantly affects heparin pharmacodynamics and may contribute to coagulopathy.

Risk of respiratory failure after repair of thoracoabdominal aortic aneurysms.

BACKGROUND: Multiple complications occur after repair of a thoracoabdominal aortic aneurysm, the most common of which is respiratory failure. METHODS: One hundred consecutive thoracoabdominal aneurysm repairs were studied retrospectively using univariate, bivariate, and multiple logarithmic regression analyses to identify factors associated with respiratory failure. RESULTS: The mean of days of intubation was 5.8 +/- 0.8 (mean +/- SEM), with a median of 2 days. Patients who developed respiratory failure (21%) had a 42% mortality compared with a 6% mortality in patients who did not develop respiratory failure (P < 0.001). Statistical analysis demonstrated a significant (P < 0.01) age difference between those with respiratory failure (71.9 +/- 1.6 years) and those without (65.5 +/- 1.3 years). Type II aneurysms occurred in 32% of patients, a 3.2-fold increase in relative risk compared with all other types of aneurysm. Seventy-nine percent of patients had a significant smoking history. Low forced vital capacity and forced expiratory volume were both significant variables in predicting respiratory failure, but neither chronic obstructive pulmonary disease nor emphysema was a predictive variable. Intraoperative blood transfusion (mean 10.5 +/- 0.8 units) was associated with respiratory failure (P = 0.05). Postoperative complications associated with respiratory failure were creatinine elevation and pneumonia. CONCLUSION: We conclude that the independent variables affecting respiratory failure after thoracoabdominal aneurysm repair are age, type of aneurysm, excessive intraoperative blood transfusions, creatinine elevation, and postoperative pneumonia.

Agonistic behavior of the weakly electric fish, Gnathonemus petersii (Mormyridae, Osteoglossomorpha).

The role played by the electric organ discharge (EOD) in eliciting and maintaining social behavior was assessed. First, a description of the motor acts associated with agonistic encounters between resident and intruder Gnathonemus petersii was provided: The temporal distribution of these acts depended on the aggressiveness of the resident. Second, half of the residents and half of the intruders were rendered electrically "silent" by cutting the nerves to the electric organ. Encounters were staged between pairs of intact fish, pairs of silent fish, and pairs in which one fish was intact and the other silent. Silent residents chased and attacked their opponents less often than the intact fish. Silent and intact residents did not differ in their rates of social probing. Intact intruders elicited higher rates of social probing, and the silent animals elicited more attacks. The effects of the fish's ability to emit EODs and perceive conspecific discharges on different motor acts are discussed.

Social influences on factored dimensions of the McGill Pain Questionnaire.

The McGill Pain Questionnaire (MPQ) was administered to 268 subjects following electrical stimulation to pain-tolerance limits. Subjects received stimulation under four social modeling conditions: tolerant, intolerant, control, and no model. The number of factors and degree of obliqueness most appropriate for the MPQ scores were determined using multiple criteria. Five factors, reflecting 46.6% of the total variance, were derived and labelled as follows: affective-arousal, sensory-pressure, perception of harm, somesthetic pressure, and cutaneous sensitivity. The various modeling conditions did not produce any significant between-group differences on the factors. The repeated demonstration that the MPQ assesses substantially more than the three components originally proposed suggests that considerable caution is warranted with respect to using the 'sensory-evaluative-affective' method of scoring this test. Considered in relation to previous research, the present findings are consistent with the conclusion that social influences affect fundamental components of subjective reactions to pain.