Development and organization of ocular dominance bands in primary visual cortex of the sable ferret.

Thalamocortical afferents in the visual cortex of the adult sable ferret are segregated into eye-specific ocular dominance bands. The development of ocular dominance bands was studied by transneuronal labeling of the visual cortices of ferret kits between the ages of postnatal day 28 (P28) and P81 after intravitreous injections of either tritiated proline or wheat germ agglutinin-horseradish peroxidase. Laminar specificity was evident in the youngest animals studied and was similar to that in the adult by P50. In P28 and P30 ferret kits, no modulation reminiscent of ocular dominance bands was detectable in the pattern of labeling along layer IV. By P37 a slight fluctuation in the density of labeling in layer IV was evident in serial reconstructions. By P50, the amplitude of modulation had increased considerably but the pattern of ocular dominance bands did not yet appear mature. The pattern and degree of modulation of the ocular dominance bands resembled that in adult animals by P63. Flat mounts of cortex and serial reconstructions of layer IV revealed an unusual arrangement of inputs serving the two eyes in the region rostral to the periodic ocular dominance bands. In this region, inputs serving the contralateral eye were commonly fused along a mediolateral axis, rostral to which were large and sometimes fused patches of ipsilateral input.

Death due to unrecognised myocardial infarction causing left ventricular rupture: can we improve the diagnostic rate?

AIM: To investigate the clinical presentations of ruptured myocardial infarction, where the initial diagnosis of myocardial infarction was missed, to enhance the diagnostic rate of primary care physicians. METHODS: We studied 67 cases of myocardial infarction, terminating with left ventricular rupture, between January 1988 and December 1996. The study was restricted to sudden death where, at coroner-directed autopsy, a ruptured myocardial infarction was determined as the cause of death. It was also restricted to patients who consulted a doctor within the two weeks prior to death. The report made to the coroner by attending police and the autopsy report was studied, and the requisite data were abstracted. RESULTS: Half of our study group did not present with chest pain. Of the atypical presentations: 15/67 cases (22%) were from referred pain (neck, arm, abdomen or back), 12/ 67 patients presented with "flu-like illness" (18%), 4/67 cases had respiratory presentations (cough or shortness of breath) (6%) and 2/67 falls (3%). Of those with chest pain, 16/34 (47%) were diagnosed or referred and 2/15 infarcts with atypical or referred pain were diagnosed. None of those presenting with "flu like illness" or respiratory symptoms was diagnosed or referred. CONCLUSION: Fifty per cent of our patients had "silent" myocardial infarcts. A large proportion of this group complained of a flu-like illness, which is currently not considered a presentation of this disease. Patients at higher risk of a myocardial infarct, should be treated with a high index of suspicion when unwell, especially when complaining of a flu-like illness. Pathologically, posterior and lateral infarcts accounted for over half the cases.

Spatial-frequency tuning and geniculocortical projections in the visual cortex (areas 17 and 18) of the pigmented ferret.

We have examined the spatial-frequency selectivity of neurons in areas 17 and 18 of the adult pigmented ferret, by measuring how the amplitude of response depends on the spatial-frequency of moving sinusoidal gratings of optimal orientation and fixed contrast. Neurons in area 17 of the ferret respond optimally to low spatial frequencies [average 0.25 cycles per degree (c/deg)], much lower than the optima for cat area 17. The tuning curves are of the same form as those found in cat and monkey: unimodal with bandwidths in the range 0.8-3.5 octaves. Neurons in area 18 of the ferret respond optimally to even lower spatial frequencies (average 0.087 c/deg) than area 17 neurons, and the distributions of optimal spatial frequency for areas 17 and 18 hardly overlap. In both cortical areas, the bandwidth of the tuning curves is inversely correlated with optimal spatial frequency. This marked difference in tuning between the two cortical areas is probably attributable to differential geniculo-cortical projections. Small injections of fluorescent latex microspheres or horseradish peroxidase (HRP) were made into area 17 or area 18 in order to investigate the populations of geniculate neurons projecting to the two cortical areas. After injections into area 17, labelled neurons are found predominantly in the geniculate A layers, with a few neurons labelled in the C layers. Conversely, after an area 18 injection, similar numbers of labelled neurons are found in the C layers as in the A layers. Soma-size analysis of the neurons in the A-layers suggests the existence of two populations of relay neurons, which project differentially to areas 17 and 18. The different geniculate inputs and the different spatial-frequency tuning in areas 17 and 18 may imply that the two cortical areas process visual information more in parallel than in series.

Emergency department management of sunburn reactions.

The medical records of fifteen patients presenting to the emergency department of a university hospital for sunburn were reviewed. Patients with sunburn had a mean age of 27 years and injury was most likely to occur in July. Six patients had blisters secondary to the ultraviolet injury. Treatment with nonsteroidal anti-inflammatory drugs was used for nine of fifteen patients. Although eight instances of patient education about the primary prevention of future sunburn were documented in the medical records, only one patient record had documentation of her being warned about her increased risk for skin cancer.

Topography of fibre organisation in the corticofugal pathways of rats.

The organisation of the long descending corticofugal pathways is poorly understood. We have examined these pathways to determine the fibre relationships along the extent of their course through the internal capsule, cerebral peduncle, longitudinal pontine fasciculus, pyramid, pyramidal decussation, and dorsal column of the spinal cord. Different cytoarchitectonic regions (e.g., lateral agranular and granular) of the rat's neocortex were injected with the axonal tracer biotinylated dextran. In other experiments, each animal had different-coloured fluorescent tracers (Fluoro Ruby and dextran-fluorescein) injected into separate cortical areas. Our results show that in the anterior and posterior limbs of the internal capsule, axons arising from spatially separate sites in rat neocortex occupy distinct regions of the cross-sectional area of the pathway. More caudally, within the cerebral peduncle and the longitudinal pontine fasciculus, axons from more distant cortical areas remain largely separate, but those from adjacent cortical areas begin to overlap. By the medullary pyramid, the pyramidal decussation, and the dorsal column of the spinal cord, the representations of all the cortical regions injected overlap completely; in these structures, the axons arising from each cortical area are widely intermingled. Thus, along the rostral-to-caudal course of the corticofugal pathways, there is a change in the organisation of axons. At rostral levels, the order corresponds roughly to the spatial distribution of the cells of origin, but more caudally, this changes to an arrangement of axons that has no readily apparent order. A similar change has been observed along the course of the retinofugal pathway, where a decrease of spatial order in the fibre distribution has been associated with a reordering of axons according to their temporal sequence of outgrowth.

Therapeutic approaches to papillomavirus infections.

Human papillomaviruses (HPVs) cause benign tumors (i.e., warts) and are occasionally responsible for malignant tumors such as squamous-cell carcinomas. Therapy for most warts is commonly via surgical or cytodestructive methods. Presently, only one antiviral/immunomodulatory drug is available for wart therapy; this agent, interferon alpha (IFN alpha), is approved only for genital warts (condylomata acuminata) and is expensive, relatively difficult to use, associated with systemic side effects, and somewhat slow acting. Two new antiviral/immunomodulatory drugs, imiquimod and cidofovir, have been proved to be effective and able to overcome many of the shortcomings of IFN alpha. While these two agents are pending approval, other treatments are being evaluated, such as antisense oligonucleotides and therapeutic HPV vaccines. In contrast to surgical and cytodestructive therapies, the goal of these new antiviral/immunomodulatory agents is not just to remove the tumor but also to reduce sufficiently the amount of latent and subclinical HIV so as to reduce the rate of recurrence.

Maturational gradients in the retina of the ferret.

In the present set of studies, we have examined the site for the initiation of retinal maturation in the ferret. A variety of maturational features across the developing inner and outer retina were examined by using standard immunohistochemical, carbocyanine dye labelling, and Nissl-staining techniques, including 1) two indices of early differentiation of the first-born retinal ganglion cells, the presence of beta-tubulin and of neuron-specific enolase; 2) the receding distribution of chondroitin sulfate proteoglycans within the inner retina; 3) the distribution of the first ganglion cells to grow axons along the optic nerve; 4) the emergence of the inner plexiform layer; 5) the emergence of the outer plexiform layer and 6) the onset of synaptophysin immunoreactivity within it; 7) the differentiation of calbindin-immunoreactive horizontal cells; and 8) the cessation of proliferative activity at the ventricular surface. Although we were able to define distinct maturational gradients that are associated with many of these features of inner and outer retinal development (each considered in detail in this report), with dorsal retina maturing before ventral retina, and with peripheral retina maturing last, none showed a clear initiation in the region of the developing area centralis. Rather, maturation began in the peripapillary retina dorsal to the optic nerve head, which is consistent with previous studies on the topography of ganglion cell genesis in the ferret. These results make clear that the order of retinal maturation and the formation of the area centralis are not linked, at least not in the ferret.

Effect of intravenous administration of fluids on packed cell volume, blood pressure, and total protein and blood glucose concentrations in healthy halothane-anesthetized dogs.

OBJECTIVE: To determine the effects of IV administration of fluids on PCV, serum total protein and blood glucose concentrations, and systolic arterial pressure in healthy anesthetized dogs undergoing elective surgical procedures. DESIGN: Prospective, randomized controlled trial. ANIMALS: 70 clinically normal dogs. PROCEDURE: Dogs received i.v. administration of 0, 5, 10, or 15 mL/kg of body weight/h of a polyionic crystalloid solution or 5% dextrose in water. Blood samples were collected before and after administration of medication, prior to anesthetic induction, after anesthetic induction, at the end of the surgical procedure, and 2 hours after surgery to determine PCV and serum total protein and blood glucose concentrations. Blood pressure was measured before and after anesthetic induction and at the end of the surgery. RESULTS: There were not any significant differences in PCV, total protein concentration, or systolic arterial pressure among treatment groups. Hyperglycemia developed in dogs receiving 5% dextrose in water, but resolved 2 hours after discontinuing administration of fluids. CLINICAL IMPLICATIONS: Intravenous administration of fluids may not be necessary to maintain normal blood pressure in young, healthy dogs undergoing elective surgery.

Cells of the perireticular nucleus project to the developing neocortex of the rat.

The perireticular nucleus is a recently described thin sheet of small cells among the fibres of the internal capsule, lying lateral to the thalamic reticular nucleus and medial to the globus pallidus (Clemence and Mitrofanis [1992]. J. Comp. Neurol. 322:167-180). During development, the perireticular nucleus is relatively large, lying in the path of the growing corticofugal and thalamocortical axons and filling the area of the internal capsule lateral to the thalamic reticular nucleus. After these axons have formed their connections, the perireticular nucleus rapidly decreases in size, leaving only a few cells in the adult (Mitrofanis [1992] J. Comp. Neurol. 320:161-181). In this study, we aimed to investigate the connections between the developing cortex and thalamus by making injections of tracer into the cortical plate. Injections of Horse Radish Peroxidase (HRP), Wheat Germ Agglutinin bound to HRP (WGA-HRP) and 1'dioctadecyl-3,3,3',3 tetramethycarbocyanine perchlorate (DiI) were made in vivo between embryonic day (E) 18 and adult and DiI was placed in the fixed brains of rats aged between E16 and postnatal day (P)1. Between E17 and P10, the retrograde perikaryal labelling resulting from these injections revealed a transient projection from the perireticular nucleus to the ipsilateral cortical plate. No cells were labelled in the thalamic reticular nucleus. This suggests that the perireticular nucleus must be regarded as a group of cells distinct from the thalamic reticular nucleus and having a separate role in development. Comparisons between the perireticular cells and the cells of the cortical subplate suggest that both may be playing comparable roles in early development, possibly guiding fibres towards their end stations or serving to rearrange the complex mapped projections linking the thalamus and cortex.

Development of the thalamic reticular and perireticular nuclei in rats and their relationship to the course of growing corticofugal and corticopetal axons.

This study examines the connections of the thalamic reticular and perireticular nuclei during development. In addition, because these nuclei lie directly in the path of corticofugal and corticopetal axons during development, we have examined the relationship of these growing axons to the reticular and perireticular cell groups. Neurones were labelled by applying DiI, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), or HRP to the dorsal thalamus and/or cerebral cortex of rats at different stages of development. The axons of neurons in the reticular nucleus reach the dorsal thalamus as early as embryonic day (E) 14. At this age, and during later prenatal development, a small DiI implant limited to the presumptive lateral geniculate nucleus labels reticulothalamic and thalamocortical axons which travel in a clearly defined bundle through the thalamus. During late gestation, thalamocortical (approximately E15) and corticothalamic (approximately E17) axons pass directly through the reticular nucleus toward their targets. It is not until birth that collaterals are seen extending into the nucleus from the parent axons. Neurones in the perireticular nucleus, in contrast to those in the reticular nucleus, are not labelled from the lateral geniculate nucleus until after birth. The perireticular nucleus is very large at a stage when the first thalamocortical axons leave and when the first corticothalamic axons approach the thalamus. These axons are seen to change course sharply in the region of the internal capsule, where there are many perireticular cells. Corticothalamic axons turn toward the reticular nucleus, and thalamocortical axons turn toward the cortical subplate. Corticospinal and corticobulbar axons, on the other hand, pass directly through the perireticular region toward their more caudal targets. After these axons have reached their targets, the perireticular nucleus reduces dramatically in size.

Differential action of the albino mutation on two components of the rat's uncrossed retinofugal pathway.

The development of the uncrossed retinofugal pathways in normally pigmented and albino rats, aged from embryonic day (E) 14.5 to E18.5, was investigated. DiI was placed into one optic tract and the retinal origin of the uncrossed component, as well as its course in the optic stalk, was studied. The results show that, as in the mouse, the uncrossed retinal projection has two components. The first component is seen at E15.5 in normally pigmented animals. It develops exclusively in the central parts of the retina and is normal in albino littermates. The second component, which arises from the peripheral parts of the ventrotemporal retina, is seen two days later at E17.5 in all animals but is significantly smaller in albinos than in their pigmented littermates. Studies of axons in the optic stalk labelled retrogradely with DiI placed in the optic tract indicate that the uncrossed axons have no preference for any position in the stalk except when they approach the chiasm, where they tend to accumulate at the caudal region of the stalk. The uncrossed axons intermingle with the crossed axons along the entire length of the stalk. In albino embryos, no obvious difference in the prechiasmatic course of uncrossed axons was seen at any age examined. It is concluded that the albino mutation in rats affects the late ventrotemporal component of the uncrossed pathway selectively. It does not act on the early central component. Further, the intermingling of crossed and uncrossed axons in the stalk and the apparently unaffected prechiasmatic course of uncrossed axons in albinos indicate that the albino gene has its primary action in the retina.

The re-establishment of the representation of the dorso-ventral retinal axis in the chiasmatic region of the ferret.

This study has examined the representation of the dorso-ventral retinal axis in the optic nerve and tract of the ferret, as well as the associated fiber transformations which take place within the chiasmatic region. In one series of experiments, dorsal or ventral retinal lesions were made to induce fiber degeneration along the pathway, from which semi-thin sections were then stained for degenerating myelin. In a second series, implants of the carbocyanine dye, DiI, were made into the caudo-medial or rostro-lateral optic tract in order to label retrogradely the axons as they course through the chiasmatic region. Additional observations were made from the optic pathways of ferrets that had been similarly lesioned or implanted, but employing either a reduced-silver technique to reveal the degenerating axons or horseradish peroxidase as the retrograde label. The axons arising from the dorsal and ventral retina course in the dorsal and ventral parts of the optic nerve posterior to the eye, but as they continue along the nerve they disperse producing a highly impoverished retinotopy in the prechiasmatic portion of the nerve. As they course through the chiasmatic region, however, they become segregated again: dorsal fibers cross the midline relatively caudally while ventral fibers cross further rostrally, although there is overlap between them. Nearer the threshold of the optic tract, the fibers from dorsal and ventral retina undergo a further and more striking segregation, placing the dorsal fibers caudo-medially and the ventral fibers rostro-laterally within the tract. This re-emergence of retinotopic order implicates a fiber-substrate interaction as being responsible for the axonal reordering, and suggests that fiber pre-ordering in the tract contributes to the formation of the orderly projection of the dorso-ventral retinal axis upon central visual targets.

Chiasmatic course of temporal retinal axons in the developing ferret.

Recent studies on the distribution of optic axons in the mature visual pathways, as well as on the genesis of their ganglion cells of origin, suggest that the time of axonal arrival at the optic chiasm determines the side of the brain to which a temporal retinal axon will project. The present study has examined this issue directly in fetal ferrets, by determining the projection of the temporal retina at different developmental stages. Fetuses of known gestational age were fixed with paraformaldehyde and subsequently implanted with crystals of the carbocyanine dye, DiI, into either the temporal retina, or into one optic tract. The lipophilic diffusion of the dye within the plasma membrane of the axons revealed the course of temporal retinal fibers through the fetal chiasm, as well as the distribution of ganglion cells across the two retinae projecting to one optic tract. During early fetal stages, the temporal retina extends axons preferentially into the ipsilateral optic tract: the early retinal projection shows a classical partial decussation pattern. During later fetal stages, temporal retinal axons can be traced into both optic tracts, and the distribution of cells with crossed and uncrossed optic axons in the temporal retina is overlapping. These results indicate that the mature decussation patterns of retinal ganglion cell classes are not primarily the consequence of regressive phenomena such as cell death; rather, they are formed as axons navigate the chiasmatic region during development. The differences in decussation pattern between cell classes arise from the fact that the mechanisms producing the segregation of nasal and temporal retinal axons at the chiasm must change as development proceeds.

Pharmacist work activity before and after pharmacy department computerization.

The effects of a dedicated computer system on pharmacists' daily activities at a 363-bed hospital were studied. A one-group pretest-posttest design was used. Twenty-four pharmacists recorded activity frequency and time for seven consecutive days several months before and after a pharmacy computer system was implemented. The computer system could be used for printing unit dose fill lists and i.v. labels, entering data, and printing patient profiles. An admissions, discharge, and transfer interface between the hospital system and the pharmacy system was also operational. The data were organized into 28 activities for analysis. For seven activities that were considered directly affected by computerization, a net 0.1-minute increase in the average time was found. Four of those seven showed an increase in average time (a total of 1.86 minutes): (1) calculating the composition of total parenteral nutrient or i.v. solution, (2) compounding large-volume i.v. solution, (3) profiling orders, and (4) checking the work of pharmacy technicians. The other three showed a decrease in average time (a total of 1.76 minutes): (1) preparing syringe or small-volume i.v. solution, (2) monitoring drug profiles, and (3) dispensing unit dose medications. However, with all 28 activities considered, a 1.03-minute decrease occurred in the average time per activity. Installation of a dedicated pharmacy computer decreased the amount of time pharmacists spent performing 28 activities by an average of 1.03 minutes per activity but increased the amount of time spent on activities directly affected by the computer by an average of 0.1 minute per activity.

Retinofugal fibres change conduction velocity and diameter between the optic nerve and tract in ferrets.

In earlier studies of central nervous fibre tracts, it was tacitly assumed that individual axons are relatively uniform along their length. In the retinofugal pathway in particular, axon diameter, myelin thickness and correlated conduction properties have been treated as constant throughout the optic nerve, chiasm and tract. We report here that the conduction velocities of fibres contributing to the early components of the compound action potential are significantly greater in the optic tract than in the optic nerve of ferrets, and also that the diameters of the largest retinofugal fibres increase from nerve to tract. This observation raises significant questions about the developmental mechanisms in the central nervous system that relate the axons, their diameters, and the glia with which they are myelinated. In addition, it indicates that studies that have relied on the constancy of conduction velocity along the retinofugal course may require reappraisal.

Prechiasmatic Reordering of Fibre Diameter Classes in the Retinofugal Pathway of Ferrets.

This study examines the distribution of fibre diameter classes at various sites along the retinofugal pathway of adult ferrets. Light microscopic observations were made on semi-thin sections, and regional fibre diameter spectra were constructed from diameter measurements taken from electron micrographs of thin sections of the intraorbital optic nerve (2.5 mm from the optic disc), the intracranial optic nerve (1 mm rostral to the fusion of the nerves), and the optic tract (just caudal to the optic chiasm). Whereas diameter types are relatively evenly distributed behind the eye in the postoptic nerve, they begin to segregate along its prechiasmatic course. Within this prechiasmatic region, coarse and fine calibre fibres are confined increasingly to more ventral locations in the nerve, leaving a dorsal band populated predominantly by intermediate calibre fibres. In conjunction with this redistribution of axon size classes, the fascicular arrangement of axons which is present distally, changes to a non-fascicular organization. The prechiasmatic organization of fibre types approximates that found in the optic tract where the coarse and fine calibre fibres lie further ventrally towards the pial surface. The prechiasmatic region can be viewed as a region of transition where the order of fibres in the nerve (retinotopic) starts to change to that present in the optic tract (chronotopic), resulting in the first-born beta cell axons becoming segregated dorsally, and rostral to the coarse and fine calibre classes which segregate at further caudal locations. Further, since the sorting of fibres according to diameter appears before the fibres reach the optic chiasm, the segregation of diameter classes is not dependent on the chiasmatic sorting of fibres according to their crossed or uncrossed course.

The Course of Fibre Diameter Classes Through the Chiasmatic Region in the Ferret.

The present study has examined the transition of fibre order from the optic nerve through the optic chiasm and into the optic tract in the ferret's retinofugal pathway. Semi-thin sections through the chiasmatic region were examined in normal and in monocularly enucleated ferrets in order to display the segregation of the different axon diameter classes as the fibres pass from the optic nerve into the optic tract, and to determine, for each diameter class, where the crossed and uncrossed components become separated in the chiasmatic region. As demonstrated in the preceding manuscript, fine and coarse optic axons begin to segregate from the medium optic axons rostral to the fusion of the two optic nerves. This segregation continues in the chiasmatic region where the different axon diameter classes decussate at different rostro-caudal levels: the fine and coarse diameter axons decussate rostrally, accumulating along the ventral, superficial surface of the contralateral half-chiasm, while the medium diameter axons continue caudally before crossing the midline. These two populations, a ventral, crossed (fine and coarse) population and a dorsal, yet-to-cross (medium) population are discriminable not only by their size in the chiasmatic region, but also by a thin invagination of hypothalamic neuropil separating them at their lateral extreme. The population of ipsilaterally projecting fibres is composed of both fine and medium optic axons. No coarse optic axons project ipsilaterally in the ferret: these fibres all decussate rostrally in the optic chiasm, intermingled with many of the decussating fine fibres. The fibre ordering in the adult ferret's optic chiasm is interpreted as reflecting a gradient of axonal arrival during development, with successively later arriving optic axons entering one of the two optic tracts at a progressively more superficial, rostral and ventral, location in the chiasmatic region. A fibre's position and time of arrival may influence its subsequent crossed or uncrossed course during the period of axonal ingrowth in development.

Distribution of uncrossed axons along the course of the optic nerve and chiasm of rodents.

The distribution of the ipsilaterally projecting population of retinofugal axons has been analyzed following injections of horseradish peroxidase (HRP) into the optic tract of adult hamsters and rats to determine whether the topographical segregation of the cells of origin seen in the retina is maintained by their axons throughout the course of the optic nerve and chiasm. Axons are limited to a roughly appropriate topographic location within the intraorbital course of the nerve but this organization changes at levels progressively closer to the optic chiasm. Immediately rostral to the chiasm labelled profiles are found dispersed across most of the cross-sectional area of the nerve. This dispersal is maintained within the region of the optic chiasm where a complex rearrangement of ipsilaterally projecting axons takes place. The results show that axons are not retinotopically organized along the entire length of the optic nerve. The order of axons changes along the course of the nerve and in the optic chiasm. The change seen within the intracranial course may indicate a chronotopic re-sorting of axons prior to the optic tract where the organization of axons has previously been interpreted as a map of time of axon arrival.