Gastroschisis revisited: role of intraoperative measurement of abdominal pressure

Background

Animal studies have shown that visceral circulation is well preserved when intraabdominal pressure does not exceed 20 mm Hg. Our aim was to analyze the outcomes of a series of infants with gastroschisis whose surgical management was directed by the intraoperative measurement of bladder pressure.

Methods

Forty-two neonates with gastroschisis were surgically managed using intraoperative measurement of bladder pressure at a tertiary care center between July 31, 1992, and March 20, 2004, and their outcome was evaluated. Primary closure with or without prosthetic material was performed when pressures measured 20 mm Hg or less. Delayed closure using a silon pouch was performed when pressures measured more than 20 mm Hg. Categorical variables were analyzed including mode of delivery, associated anomalies, type of closure, complications, and mortality. Continuous variables were analyzed including gestational age, birth weight, bladder pressure, time to full feeds, and length of hospital stay. Categorical and continuous variables for both groups were compared using Fisher's Exact and Wilcoxon's rank-sum tests, respectively, and a significance level of .05 was used. Preapproval of this study was obtained from the Institutional Review Board (No. 6690).

Results

Thirty-three (79%) neonates with a mean bladder pressure of 16 mm Hg underwent primary closure and 9 neonates with a mean bladder pressure of 27 mm Hg underwent delayed closure with a silon pouch that was not spring loaded (P < .03). Patients treated with primary closure had faster return to full feeds and significantly shorter hospital length of stay compared with patients treated by delayed closure (P = .04). Surgical morbidity and mortality was nil in patients after primary closure. One patient with total abdominal evisceration died during attempted delayed closure and another patient required reoperation for bowel necrosis after delayed closure.

Conclusion

Primary closure was safely accomplished in 100% of neonates with gastroschisis whose bladder pressure measured 20 mm Hg or less. Further, this group of patients had a faster return to full feeds and a significantly shorter hospital length of stay compared with neonates who required delayed closure.     

Lesion-induced synaptogenesis in the dentate gyrus of aged rats: I. Loss and reacquisition of normal synaptic density

Quantitative electron microscopy was used to examine the ability of aged (2-year-old) and young adult (90-day-old) rats to replace those synapses lost (85-90%) in the outer two-thirds of the molecular layer of the dentate gyrus after a complete unilateral lesion of the entorhinal cortex. In aged rats the synaptic density is significantly lower than that of young adults at 10 days postlesion. Synaptic replacement begins between 2 and 4 days postlesion in young adults, whereas there is a delay until after 10 days postlesion in aged rats. Once synapse replacement begins in aged rats, the rate of synapse reappearance is about equal that of young adults. Thus the initial 10 days postlesion appears critical to growth of responding afferents and reformation of synaptic contacts. Analysis of synapses in terms of noncomplex and complex synaptic types shows that the noncomplex type accounts for the significant synaptic density difference between the two age groups. Replacement of complex synapses is nearly indistinguishable between age groups and is complete by 60 days postlesion. In contrast the initial replacement rate of noncomplex synapses in aged rats is much slower than young adults, though the control synaptic density is achieved by the end of the time course.     

Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord

Kynurenic acid, a tryptophan metabolite, inhibits excitatory synaptic transmission in the rat hippocampal slice and the isolated immature rat spinal cord, but does not affect membrane potential or input resistance of hippocampal CA1 pyramidal cells. Kynurenic acid also antagonizes responses induced in the dentate gyrus by excitatory amino acids, particularly N-methyl-DL-aspartate and the endogenous excitant quinolinic acid. These results indicate that kynurenic acid antagonizes synaptic transmission probably by blocking postsynaptic transmitter receptors at putative amino acid mediated synapses.     

Subcellular distribution of transmitter-related enzyme activities in discrete areas of the rat dentate gyrus

To investigate the possibility that synaptic boutons which utilize acetylcholine or GABA as neurotransmitters are present in the outer two-thirds of the molecular layer of the rat dentate gyrus, the subcellular distribution of choline acetyltransferase, acetylcholinesterase and glutamate decar?ylase activities was determined. In this area and in the remainder of the dentate gyrus, where cholinergic and GABAnergic connections are reportedly present, choline acetyltransferase and glutamate decar?ylase activities were recovered primarily in synaptosomal fractions. Acetylcholinesterase activity was also recovered mainly in synaptosomal fractions, but membrane fractions also possessed high activity. When the crude mitochondrial fraction was resolved on a discontinuous Ficoll-sucrose gradient, relatively higher glutamate decar?ylase activity than choline acetyltransferase activity was found in the denser synaptosomal reactions. These findings suggest that acetylcholine and GABA serve as neurotransmitters in the outer two-thirds of the molecular layer. They exemplify one type of information which can be provided by subcellular fractionation of very small regions of the central nervous system.     

Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain

N-methyl-D-aspartate (NMDA) is an acidic amino acid which depolarizes neurons by selectively interacting with a distinct class of excitatory amino acid receptor. Recent evidence has indicated that this receptor is a neurotransmitter receptor in the spinal cord, cerebral cortex, and hippocampus for which the endogenous ligand is likely to be L-glutamate or a structurally related compound. Using quantitative autoradiography, we have studied the anatomical distribution of the class of L-[3H]glutamate-binding sites displaced by NMDA, which appear to correspond to NMDA receptors. The CA1 region of the hippocampus contains the highest density of sites. In general, telencephalic regions have high levels of binding sites. The cerebral cortex shows significant density variations among the differing layers and regions, with the highest levels found in the frontal cortex layers I to III. Within the basal ganglia, the highest levels are found in the nucleus accumbens, intermediate levels are found in the caudate/putamen, and very low levels are found in the globus pallidus. Thalamic regions have moderate levels with variations among differing regions. Midbrain and brainstem have low levels of binding sites, but within these regions there are structures exhibiting higher levels, e.g., the nucleus of the solitary tract and the inferior olive. The distribution of NMDA sites is consistent with most, but not all, of the regions previously proposed to use glutamate as an excitatory transmitter. Thus, the distribution of NMDA-sensitive L-[3H]glutamate-binding sites suggests that the NMDA receptor represents a major, distinct subset of excitatory amino acid receptors and indicates regions in which neurotransmission may be mediated or modulated by this receptor.     

Exercise-induced gene expression changes in the rat spinal cord

There is growing evidence that exercise benefits recovery of neuromuscular function from spinal cord injury (SCI). However, the effect of exercise on gene expression in the spinal cord is poorly understood. We used oligonucleotide microarrays to compare thoracic and lumbar regions of spinal cord of either exercising (voluntary wheel running for 21 days) or sedentary rats. The expression data were filtered using statistical tests for significance, and K-means clustering was then used to segregate lists of significantly changed genes into sets based upon expression patterns across all experimental groups. Levels of brain-derived neurotrophic factor (BDNF) protein were also measured after voluntary exercise, across different regions of the spinal cord. BDNF mRNA increased with voluntary exercise, as has been previously shown for other forms of exercise, contributed to by increases in both exon I and exon III. The exercise-induced gene expression changes identified by microarray analysis are consistent with increases in pathways promoting neuronal health, signaling, remodeling, cellular transport, and development of oligodendrocytes. Taken together these data suggest cellular pathways through which exercise may promote recovery in the SCI population.     

Caspase-cleaved tau accumulation in neurodegenerative diseases associated with tau and α-synuclein pathology

Alzheimers disease (AD), Picks disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or -synuclein. In AD, -amyloid (A)-associated caspase activation and cleavage of tau at Asp⁴²¹ (Tau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether Tau accumulates in other diseases not characterized by extracellular A accumulation, we examined PiD, PSP, and CBD cases in comparison to those without extensive tau accumulation including frontotemporal lobar degeneration without Pick bodies (FTLD) and control cases. Additionally, we studied Tau accumulation in DLB cases associated with intracellular -synuclein. Tau was observed in all disease cases except non-PiD FTLD and controls. These results demonstrate that the accumulation of Tau may represent a common pathway associated with abnormal accumulation of intracellular tau or -synuclein and may be relatively less dependent on the extracellular accumulation of A in non-AD dementias.     

Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury

After spinal cord injury, there is a chemoattractant-mediated inflammatory response that is associated with secondary degeneration. The chemoattractant CXCL10 recruits CD4 Th1 cells via the CXCR3A receptor and inhibits growth and chemotaxis of endothelial cells via the CXCR3B receptor. To test the hypothesis that CXCL10 inhibits angiogenesis following spinal cord injury, we assayed the brainstems and spinal cords of spinal cord-injured mice treated with anti-CXCL10 antibodies for expression of angiogenesis-associated genes and quantified blood vessels within their spinal cords. Brainstem microarray analysis indicated eight angiogenesis-associated genes that had significantly higher expression levels in the treated mice than in the untreated mice. Ribonuclease protection assays of the spinal cords showed a significant increase in eight angiogenesis-associated genes in treated animals compared with untreated animals. Histological analysis of the spinal cords of treated and untreated mice showed a significant increase in the number of blood vessels in treated animals. We conclude that CXCL10 plays a critical role in vasculature remodeling following spinal cord injury and that angiogenesis is enhanced following anti-CXCL10 treatment of spinal cord injuries. Improved blood flow and oxygen supply to the injury site may contribute to the functional improvement associated with this treatment.