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Managing a national pilot site project. The Derby Theatre Project experience.

The National Theatre Project was set up in March 2001 by the Modernization Agency to improve the patient and carer experience, improve employee satisfaction, optimise theatre utilisation and reduce cancelled operations. This is the first in a series of four articles, looking at issues involved in managing a national project, improving operating theatre performance and how to engage the organisation in innovation and change.

Benchmarking↗

Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age <32 weeks): the Project On Preterm and Small for Gestational Age Infants 1983 and the Leiden Follow-Up Project on Prematurity 1996-1997.

OBJECTIVE: To determine changes in peri- and neonatal care concerning neonatal mortality and morbidity by comparing 2 cohorts of very prematurely born infants (gestational age [GA] <32 weeks), 1 from the 1980s and 1 from the 1990s. METHODS: The Leiden Follow-Up Project on Prematurity (LFUPP-1996/97), a regional, prospective study, includes all infants who were born alive after a GA <32 weeks in 1996 and 1997 in the Dutch health regions Leiden, The Hague, and Delft. The Project On Preterm and Small for Gestational Age Infants (POPS-1983), a national, prospective study from the presurfactant era, includes all liveborn infants <32 weeks' GA and/or <1500 g from 1983 (n = 1338). For comparison, infants from the POPS-1983 cohort with a GA <32 weeks from the same Dutch health regions were selected (n = 102). RESULTS: The absolute number of preterm births in the study region increased by 30%: 102 in 1983 to on average of 133 in 1996-1997. Centralization of perinatal care improved: the percentage of extrauterinely transported infants decreased from 61% in 1983 to 35% in 1996-1997. A total of 182 (73%) of the LFUPP-1996/97 infants were treated antenatally with glucocorticosteroids compared with 6 (6%) of the POPS-1983 infants. A total of 112 (42%) of the LFUPP-1996/97 infants received surfactant. In-hospital mortality decreased from 30% in the 1980s to 11% in the 1990s. Mortality of the extremely preterm infants (<27 weeks) decreased from 76% to 33%. The incidence of respiratory distress syndrome remained the same: approximately 60% in both groups. Mortality from respiratory distress syndrome, however, decreased from 29% to 8%. The incidence of bronchopulmonary dysplasia increased from 6% to 19%. For the surviving infants, the average length of stay in the hospital and the mean number of NICU days stayed approximately the same ( approximately 67 days total admission time and 44 NICU days in both groups); including the infants who died, the mean NICU admission time increased from 27 days in the 1980s to 41 days in the 1990s. Equal percentages of adverse outcome (dead or an abnormal general condition) at the moment of discharge from hospital were found (+/-40% in both groups). CONCLUSIONS: An increase in the absolute number of very preterm births in this study region was found, leading to a greater burden on the regional NICUs. Improvements in peri- and neonatal care have led to an increased survival of especially extremely preterm infants. However, increased survival has resulted in more morbidity, mainly bronchopulmonary dysplasia, at the moment of discharge from the hospital.

Bronchopulmonary Dysplasia↗

Morphology, axonal projection pattern, and response types of tectal neurons in plethodontid salamanders. I: tracer study of projection neurons and their pathways.

In three salamander species (Hydromantes italicus, H. genei, Plethodon jordani), the tectobulbospinal and tectothalamic pathways and their cells of origin were studied by means of anterograde and retrograde biocytin and tetramethylrhodamine tracing. In plethodontid salamanders, five types of tectal projection neurons were identified. TO1 neurons have widefield dendritic trees that arborize in the layers of retinal afferents and form a neuropil in the superficial layer; axons constitute the crossed tectospinal tract. Dendrites of TO2 cells have the largest dendritic trees that arborize in the intermediate and deep layers of retinal afferents; axons constitute a lateral uncrossed tectospinal tract. TO3 cells have widefield dendritic trees that arborize in the deep layer of retinal afferents and in the layer of tectal efferents; axons constitute a superficial uncrossed tectospinal tract. TO4 cells have slender primary dendrites and small-field dendritic trees that arborize in the intermediate layers of retinal afferents; axons constitute another lateral uncrossed tectospinal tract. TO2, TO3, and TO4 cells also have ascending axons that run to the ventral and dorsal thalamus. TO5 cells have slender primary dendrites and small-field dendritic trees that extend into the superficial layers of retinal afferents; their fine axons constitute the bulk of the pathways ascending to the ipsilateral and contralateral thalamus. These morphological types of projection neurons and their ascending and descending axonal pathways closely resemble those found in frogs, reptiles, and birds. Their role in visual and visuomotor functions is discussed.

Animals↗

Autoradiographic studies of the projections of the midbrain reticular formation: ascending projections of nucleus cuneiformis.

The ascending projections of the cuneiform nucleus in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of (3)H-leucine. The ascending fibers are almost exclusively ipsilateral and enter the diencephalon as a wide radiation. At the mesodiencephalic junction fibers enter the nucleus of the posterior commissure and pretectal nuclei, and others cross in the posterior commissure to distribute to these structures on the contralateral side. More ventrally directed fibers distribute to the fields of Forel and then spread into the posterior hypothalamus and zona incerta. At the caudal level of the ventral thalamic group, the ascending fibers diverge and follow two separate courses. One division of fibers continues forward beneath the ventral thalamic group and distributes to the zpna incerta and dorsal hypothalamic area. It rapidly diminishes in size as it attains more rostral levels where it is found in the bed nuclei of the stria terminalis and the anterior commissure. Other fibers of this division spread laterally to innervate the ventral lateral geniculate nucleus, the lateral hypothalamus, and preoptic area, and still others follow the entire confirmation of the thalamic reticular nucleus. The second division of fiber ascends through midline and intralaminar nuclei, completely encircling the mediodorsal nucleus, which is uninnervated except for a small ventral region. The distribution of this division is heaviest to the paraventricular, parafascicular, and central dorsal nuclei. Neither division is conspicuous rostral to the anterior commissure. No projections to neostriatum or specific thalamic nuclei were evident.

Afferent Pathways↗

The olivocerebellar projection in the cat as studied with the method of retrograde axonal transport of horseradish peroxidase. II. The projection to the uvula.

Following injections of small quantities of horseradish peroxidase (HRP) suspension in the uvula of the cat, the distribution of labeled cells in the inferior olive has been mapped. The findings confirm the conclusion made on the basis of studies of retrograde cell loss in the olive following ablations of the uvula (Brodal, '40b) that two small olivary subdivisions, the nucleus beta and the dorsomedial cell column project heavily to the uvula. In addition the HRP-study shows that the uvula receives a smaller number of fibers from two circumscribed areas of the contralateral medial accessory olive. These areas appear to project to the lateralmost parts of the uvula (fig. 4). The findings thus support the presence of a longitudinal zonal subdivision in the uvula. Labeled cells are found in the nucleus beta and the dorsomedial cell column also following injections of the fastigial nucleus and to a lesser degree of lobulus VII of the vermis (Hoddevik et al. 76). This may be due to collateral branching of olivary efferents. There is some evidence for a topographical correlation between dorsal and ventral parts of the uvula and rostral and caudal parts, respectively, of the nucleus beta and the dorsomedial cell column. This may be related to functional differences between the two parts of the uvula.

Animals↗

The olivocerebellar projection studied with the method of retrograde axonal transport of horseradish peroxidase. V. The projections to the flocculonodular lobe and the paraflocculus in the rabbit.

HRP was injected in the flocculonodular lobe and the paraflocculus in the rabbit to determine the areas of the inferior olive which project onto these cerebellar regions. Following injections in the flocculus labeled cells occurred in the dorsal cap and the rostralmost tip of the medial accessory olive. Following injections in the nodulus labeled cells were likewise found in the dorsal cap, but in addition in the rostralmost part of the dorsomedial cell column and the adjoining part of the medial accessory olive. Injections in the dorsal paraflocculus gave rise to labeling in the rostrolateral part of the medial accessory olive, while injections in the ventral paraflocculus resulted in labeling in the principal olive, mainly in the lateral part of the ventral lamella. Injections in the lateral third of the dentate nucleus gave rise to labeling mainly in the dorsal lamella of the principal olive. The results are discussed with reference to those obtained by previous authors. There are both similarities and discrepancies. It appears from what is known of afferents from areas mediating visual impulses to the inferior olive that the olivary areas projecting onto the flocculonodular lobe, and possibly the dorsal paraflocculus, may mediate visual impulses to these lobules.

Afferent Pathways↗

Central projections of the brachial nerve in bullfrogs: muscle and cutaneous afferents project to different regions of the spinal cord.

The central projections of muscle and cutaneous sensory neurons in the bullfrog were labeled by filling their peripheral axons in the forelimb with horseradish peroxidase (HRP). Muscle afferent fibers were found to project exclusively to the ventral neuropil of the brachial spinal cord in the intermediate gray zone. Cutaneous afferent axons had their arbors limited to the dorsal neuropil. There is therefore a topography in the central representation of two classes of sensory modalities.

Animals↗

Callosal projections from area SII to SI in monkeys: anatomical organization and comparison with association projections.

The present research was aimed at ascertaining in the macaque monkey the reciprocity of the heterotopical callosal connections between SI and SII, with particular regard to the connectivity of the hand representation, and at comparing the topographical and laminar pattern of these callosal connections with those of association connections entertained by these areas. Horseradish peroxidase (HRP) was unilaterally injected into area SI in five monkeys. The sites of HRP delivery included the trunk and the hand zones preliminarily identified by recording multi-unit responses to peripheral stimulation by means of microelectrodes. Anterograde and retrograde labelling was studied in SII of both sides. The results showed the complete reciprocity of the heterotopical callosal connections between SI and SII. In the latter area both callosal axon terminals and neurones were found, which were labelled from either the trunk or the hand zone of contralateral SI. Labelling of callosal axon terminals occurred mainly in layer IV and in the lowermost part of layer III. Labelled callosal neurones were mainly in the lower half of layer III, whereas few occurred in infragranular layers. Topographically, the distribution of callosal terminals and cell bodies duplicated the distribution of association terminals and cell bodies labelled in SII on the side ipsilateral to HRP injection. The laminar pattern of termination of association fibres from SI was similar to that of callosal fibres. However, the distribution of association-projecting neurones in SII showed a striking difference from that of callosal-projecting neurones. Unlike the latter neurones, which were mainly located in supragranular layers, association cell bodies overwhelmingly dwelt in layers V and VI and were less numerous in layers II and III. This laminar pattern of association SII-SI cells corresponds to the "feed-backward" model and fits the laminar pattern of their axon terminations (Friedman: Brain Res. 273: 147-151, '83). The association and callosal inputs and outputs of area SII are discussed in relation to the function of the forward and backward type of reciprocal connections entertained with SI in the ipsilateral hemisphere and to the function of SII in the interhemispheric exchange of somatosensory information.

Animals↗

Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina.

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Spinally projecting neurons in the dorsal column nuclei: distribution, dendritic trees and axonal projections. A retrograde HRP study in the cat.

The distribution, dendritic trees and axonal courses of spinally projecting cells in the dorsal column nuclei were studied after labelling by retrograde HRP transport. The region of densest distribution was at the base of the two nuclei and in the area between them, extending for about 2 mm caudally from the obex. Only very few cells were found inside the cell cluster regions of the nuclei, where their dendrites had a free stellate form. The great majority, lying between, deep, or rostral to the cluster regions, also had a stellate form, except where they impinged on the boundaries of the cluster regions or on other nuclear borders; the spread of dendrites was dramatically restricted at such boundaries, often leading to a fusiform appearance in transverse sections which however was not evident in the parasagittal plane. No justification was therefore found for subdividing the population on morphological grounds. Axons of these cells descended ipsilaterally in either the medial part of the dorsolateral fascicle or in the adjacent lateral part of the cuneate fascicle, at cervical levels, and probably in about equal numbers. Most axons destined for the DLF followed a deep caudolateral trajectory, while many destined for the DC had a more dorsal or lateral course. Collateral branches were seen within the nuclei but could not be followed far. The fact that few if any cells lying in the region of maximum distribution of the spinally projecting cells were labelled following injections of HRP into the thalamic ventroposterior nucleus emphasizes that they form a distinctive entity within this medullary nuclear complex, and that any axon branches they give into the contralateral brainstem must have some other destination than the VPL. Two other groups of neurons were labelled by HRP implants into the dorsal columns - one in the ventrolateral medullary reticular formation, and the other in the nucleus of the solitary tract.

Afferent Pathways↗

Compressed retinotectal projection in hamsters: fewer ganglion cells project to tectum after neonatal tectal lesions.

After partial ablation of the superior colliculus (tectum) in neonatal hamsters, the whole extent of the visual field comes to be represented in a compressed map on the remaining tectal fragment. However, the total volume of tectal tissue in which retinotectal fibers arborize is less than normal. These observations suggests that the retinal ganglion cells which arborize in this reduced volume might arise throughout the whole extent of the retina but be fewer in number than normal. Alternatively, the ganglion cells which project to the tectum might be normal in number but reduced in terminal arbor size. To distinguish between these possibilities, we have used tectal injections of horseradish peroxidase to label retinal ganglion cells which project to the tectum. The numbers of labelled cells per mm2 of retina were counted in selected regions. In hamsters with small lesions, which left 80--85% of the tectum intact, the density of labelled retinal ganglion cells was normal. However, in hamsters with larger lesions, the density of labelled cells was significantly lower than normal.

Animals↗

An ultrastructural study of the projections from the midbrain periaqueductal gray to spinally projecting, serotonin-immunoreactive neurons of the medullary nucleus raphe magnus in the rat.

In this triple-label, electron microscopic study in the rat, a lesion of the midbrain periaqueductal gray (PAG) was made so that the distribution and targets of degenerating PAG terminals could be identified in the medullary nucleus raphe magnus (NRM). Spinally projecting NRM neurons were identified by the retrograde transport of wheat germ agglutinin-horseradish peroxidase from the cervical cord. We also used immunocytochemistry to define the subpopulation of NRM neurons which were serotonin-immunoreactive. We report that both serotonergic and non-serotonergic neurons of the medulla, which project to the spinal cord, receive monosynaptic inputs from the PAG.

Animals↗

Subpallidal-pedunculopontine projections but not subpallidal-mediodorsal thalamus projections contribute to spontaneous exploratory locomotor activity.

The contribution of the pedunculopontine nucleus to exploratory locomotion was investigated in rats. Locomotor activity recorded in a standard open-field apparatus was increased more than two-fold when wooden panels were inserted. This novelty-elicited locomotion was reduced significantly when procaine was injected bilaterally into the pedunculopontine nucleus but not when procaine was injected bilaterally into the mediodorsal thalamus, a second major projection site of the subpallidal area. These results support observations from earlier studies implicating hippocampal-accumbens-subpallidal-pedunculopontine projections in exploratory locomotion.

Animals↗

Quantification of branched neuronal projections labelled by retrograde fluorescent tracing. A study of olivo-cerebellar projections.

A method for estimating the number of branched and unbranched neurones projecting from a nucleus to two target sites is presented, based on the retrograde transport of fluorescent tracers. The method initially involves stereological corrections for the size of cytoplasm and nuclei respectively labelled by the two tracers. A second correction is applied to account for doubly labelled cells whose cytoplasm, but not nuclei, are in the plane of section. Finally, the detection rates of the two tracers are determined and appropriate corrections are applied. The projection from the medial accessory olive to the cerebellar vermis was studied using true blue and diamidino yellow to illustrate the method. Application of the method increased the number of branched neurones detected by 18.5%. Of the total increase, 48.4% was due to the correction for size, 9.2% to the correction for doubly labelled cells with nuclei outside the plane of the section and 42.4% to the correction for detection rates. There was no significant masking of one tracer by another, but true blue enhanced the fluorescence of diamidino yellow.

Amidines↗

Reduction of transiently expressed acetylcholinesterase activity in developing thalamocortical projections does not affect the mature pattern of basal forebrain projections to visual cortex.

Experiments tested the hypothesis that acetylcholinesterase (AChE) activity, expressed transiently in developing thalamocortical projections, serves to limit the growth of basal forebrain cholinergic projections into thalamocortical recipient zones. Newborn rats were subjected to enucleation, a procedure that eliminates transient AChE activity in developing visual cortex. After 3-8 weeks survival, AChE histochemical techniques revealed no alteration in the pattern of AChE positive basal forebrain axons in visual cortex. These data indicate that transient AChE activity in developing sensory cortex does not limit ingrowth of basal forebrain cholinergic axons.

Acetylcholinesterase↗

The relationship between descending serotonin projections and ascending projections in the nucleus raphe magnus: a double labeling study.

The nucleus raphe magnus and rostral parts of the nucleus raphe obscurus were found to have extensive efferent projections: a major ascending non-serotonergic (5-HT) projection through the median forebrain bundle, and a descending system consisting of both 5-HT and non-5-HT neurons. Differences in the localizations of their cells of origin suggest that they form two distinct efferent systems from the caudal medullary raphe nuclei.

Animals↗

The locus of optic nerve head representation in the retinotopic projection over nucleus geniculatus lateralis ventralis and nucleus griseum tectalis in the chick also lacks a retinal projection.

Recently we have demonstrated the presence of a gap in the avian retinotectal projection, that corresponds with the locus of retinotopic representation of the elongated optic nerve head. The present report describes an equivalent gap in the optic neuropiles of the avian ventral geniculate nucleus and griseum tectalis formation, detected after filling optic terminals anterogradely from the contralateral eye with peroxidase. A projection-less strip appears at the expected retinotopic position in both grisea intersecting radially all the strata of the corresponding neuropiles. It is speculated that a common synaptogenetic mechanism must account for these gaps.

Animals↗

Multi-dimensional treatment planning: II. Beam's eye-view, back projection, and projection through CT sections.

Three features of a fully three-dimensional treatment planning program are presented: (1) The beam's-eye-view provides the user with an accurate reproduction of anatomic features from the viewpoint of a treatment source. The source can be moved to any feasible position relative to the patient, permitting a choice which allows sensitive organs to be excluded from the beam. In this view a field defining aperture can readily be designed. (2) Back-projection of such an aperture shows the parts of the original transverse CT sections, or reconstructed sagittal or coronal sections, which may be covered by the selected beam. (3) Projection through the CT data from any desired origin provides an alignment film simulation which can be used to confirm accuracy of treatment, as well as help establish anatomic relationships relative to the margins of a treatment field.

Computers↗