Drug-related problems identified during medication review before and after the introduction of a clinical decision support system.

WHAT IS KNOWN AND OBJECTIVE: To facilitate the identification of drug-related problems (DRPs) during medication review, several tools have been developed. Explicit criteria, like Beers criteria or STOPP (Screening Tool of Older Peoples' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) criteria, can easily be integrated into a clinical decision support system (CDSS). The aim of this study was to investigate the effect of adding a CDSS to medication review software on identifying and solving DRPs in daily pharmacy practice. METHODS: Pre- to post-analysis of clinical medication reviews (CMRs) performed by 121 pharmacies in 2012 and 2013, before and after the introduction of CDSS into medication review software. Mean number of DRPs per patient, type of DRPs and their resolution rates were compared in the pharmacies pre- and post-CDSS using paired t tests. RESULTS AND DISCUSSION: In total, 9151 DRPs were identified in 3100 patients pre-CDSS and 15 268 DRPs were identified in 4303 patients post-CDSS. The mean number of identified DRPs per patient (aggregated per pharmacy) was higher after the introduction of CDSS (3.2 vs 3.6 P < .01). The resolution rate was lower post-CDSS (50% vs 44%; P < .01), which overall resulted in 1.6 resolved DRPs per patient in both groups (P = .93). After the introduction of CDSS, 41% of DRPs were detected by the CDSS. The resolution rate of DRPs generated by CDSS was lower than of DRPs identified without the help of CDSS (29% vs 55%; P < .01). The two most prevalent DRP types were "Overtreatment" and "Suboptimal therapy" in both groups. The prevalence of "Overtreatment" was equal in both groups (mean DRPs per patient: 0.84 vs 0.77; P = .22), and "Suboptimal therapy" was more frequently identified post-CDSS (mean DRPs per patient: 0.54 vs 1.1; P < .01). WHAT IS NEW AND CONCLUSION: The introduction of CDSS to medication review software generated additional DRPs with a lower resolution rate. Structural assessment including a patient interview elicited the most relevant DRPs. Further development of CDSS with more specific alerts is needed to be clinical relevant.

Anatomical evidence for an endocrine activity of the vomeronasal organ in humans.

The mammalian vomeronasal organ (VNO) is a well-adjusted chemosensory structure that facilitates social and reproductive behavior in mammals. The existence, locality, and function of this organ in human adults remain a matter of discussion. Most authors now agree that a neuroreceptive function of the adult human VNO can be excluded due to the absence of both neural receptive cells associated with the VNO in other mammals despite the enigmatic reports on the effects of pheromones on human behavior. Adult cadavers form European (Caucasoid) descent were used in this article and parasagittal dissection of the heads allowed access to the nasal septa, which were grossly examined for the VNO openings. Tissue samples were collected, embedded in gelatin and serially sectioned through cryomicrotomy. Nissl staining was performed as well as immunohistochemically stained with an antibody against calcium-binding protein. The findings presented here confirm the bilateral presence of the VNO in adult cadavers and demonstrate morphological connections of VNO receptor cells with the underlying capillaries. In addition, possible endocrine activity associated with the epithelium of this chemosensory structure has been demonstrated by the expression of calcium-binding protein in a part of these receptor cells.

The posterior intercostal vein: a thermoregulatory gateway to the internal vertebral venous plexus.

The internal vertebral venous plexus (IVVP) plays a putative role in thermoregulation of the spinal cord. Cold cutaneous venous blood may cool, while warm venous blood from muscles and brown fat areas may warm the spinal cord. The regulating mechanisms for both cooling and warming are still unknown. Warm venous blood mainly enters the IVVP via the intervertebral veins. In the thoracic area these veins are connected to the posterior intercostal veins. In this study, anatomical structures were investigated that might support the mechanisms by which warmed venous blood from the intercostal muscles and the recently described paravertebral patches of brown adipose tissue are able to drain into the vertebral venous plexus. Therefore, tissue samples from human cadavers (n = 21) containing the posterior intercostal vein and its connections to the IVVP and the azygos veins were removed and processed for histology. Serial sections revealed that the proximal parts of the posterior intercostal veins contained abundant smooth muscle fibers at their opening into the azygos vein. Furthermore, the walls of the proximal parts of the posterior intercostal veins contain plicae that allow the vessel to dilate, thereby allowing it to serve as a pressure chamber. It is suggested that a cold induced closure of the intercostal/azygos opening can result in retrograde blood flow from the proximal posterior intercostal vein towards the IVVP. This blood flow would be composed of warm blood from the paravertebral brown adipose tissue and blood containing metabolic heat from the muscles draining into the intercostal veins.

Possible thermoregulatory functions of the internal vertebral venous plexus in man and various other mammals: evidence from comparative anatomical studies.

Comparative anatomy was used to collect more evidence for a thermoregulatory function of the internal vertebral venous plexus (IVVP). The venous connections of the IVVP were studied and compared in various mammals in order to find evidence for the existence of climate related anatomical adaptations. Humans and vervet monkeys were chosen as representatives of mammals living in moderate climates, the IVVP of the dolphin was studied because this animal is always surrounded by cold water. The springbok was chosen as a representative of mammalian species living under very hot conditions. The present study was exclusively performed on post mortem material. After filling the venous system with latex the IVVP and its venous connections were dissected. It appeared that in the dolphin, veins from the trunk muscles were directly and exclusively connected to the IVVP in the absence of an azygos vein. In the vervet monkey and human specimens, veins originating in the muscles drained both into the caval veins and into the IVVP. In these mammals veins draining from brown fat areas were also connected to the IVVP. In the springbok, drainage of blood from the muscles was prevented to enter the IVVP by the presence of valves. In humans and vervet monkeys we found that the lumbar parts of the IVVP were connected to subcutaneous veins of the back. It was concluded that the anatomy of the IVVP and its connecting veins may serve to thermoregulate the spinal cord and that climate related anatomical adaptations were present in the species studied.

Extraforaminal ligament attachments of the thoracic spinal nerves in humans.

An anatomical study of the extraforaminal attachments of the thoracic spinal nerves was performed using human spinal columns. The objectives of the study are to identify and describe the existence of ligamentous structures at each thoracic level that attach spinal nerves to structures at the extraforaminal region. During the last 120 years, several mechanisms have been described to protect the spinal nerve against traction. All the described structures were located inside the spinal canal proximal to the intervertebral foramen. Ligaments with a comparable function just outside the intervertebral foramen are mentioned ephemerally. No studies are available about ligamentous attachments of thoracic spinal nerves to the spine. Five embalmed human thoracic spines (Th2-Th11) were dissected. Bilaterally, the extraforaminal region was dissected to describe and measure anatomical structures and their relationships with the thoracic spinal nerves. Histology was done at the sites of attachment of the ligaments to the nerves and along the ligaments. The thoracic spinal nerves are attached to the transverse process of the vertebrae cranial and caudal to the intervertebral foramen. The ligaments consist mainly of collagenous fibers. In conclusion, at the thoracic level, direct ligamentous connections exist between extraforaminal thoracic spinal nerves and nearby structures. They may serve as a protective mechanism against traction and compression of the nerves by positioning the nerve in the intervertebral foramen.

[Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study in Dutch community pharmacies]. / Medicatiebeoordelingen bij ouderen met polyfarmacie.

OBJECTIVE: To investigate the nature and prevalence of drug related problems (DRPs) in older patients with polypharmacy identified by community pharmacists in daily practice through means of a clinical medication review (CMR) and assess the implementation rate of proposed interventions to solve DRPs. DESIGN: A cross-sectional study METHOD: We analysed the CMR data of 3,807 older patients (≥ 65 years) with polypharmacy (≥ 5 drugs) completed in January-August 2012. Using the "Service Apotheek Medicatie Review Tool" (SAMRT, Service Pharmacy Medication Review Tool), pharmacists in 258 community pharmacies registered the patients' year of birth, gender, dispensing data, DRPs, and proposed and implemented interventions. RESULTS: Pharmacists identified a median of two DRPs (interquartile range 1-4; mean 3.0) per patient. The DRP categories overtreatment (25.5 %) and undertreatment (15.9 %) were found to occur most frequently. On average, 46.2 % of the proposed interventions to address DRPs were implemented as proposed. In 22.4 % of cases the intervention differed from the proposal, whereas in 31.3 % of cases no intervention was implemented. CONCLUSION: In daily practice, community pharmacists identified a mean of three DRPs in older patients with polypharmacy, a number comparable to that found in controlled studies. Over- or undertreatment caused nearly half of the identified DRPs. The majority (69.9%) of the proposed interventions led to an intervention for the patient.

A 43-year-old male with untreated panhypopituitarism due to absence of the pituitary stalk: from dwarf to giant.

A 43-yr-old male was referred because of an x-ray made after a fall, which showed open epiphysis of the arm. The man had always been short for his age; during childhood he once consulted a pediatrician because of short stature, but thereafter he never sought medical attention. At age 18 yr he was not allowed to join the army because of his height of 147 cm. He continued to grow steadily and finally reached 193 cm. He had no complaints and considered himself reasonably fit. Physical examination showed a disproportional man with a body mass index of 29.3 kg/m(2) and Tanner stage P1G1. Laboratory investigations showed hormone levels consistent with multiple pituitary deficiency, with dynamic tests consistent with hypothalamic or pituitary stalk disease. Magnetic resonance scanning of the brain showed a small anterior pituitary remnant, no pituitary stalk, and an ectopic neurohypophysis. This case of untreated panhypopituitarism shows a particular growth curve with an average growth velocity of 2 cm/yr, resembling patients with estrogen receptor mutation or aromatase deficiency. A literature study of other adult patients with untreated panhypopituitarism shows a variable growth pattern. Some speculations about possible reasons for this variability in clinical characteristics are presented.

Spinothalamic projections in a lizard, Varanus exanthematicus: an HRP study.

In the present study HRP injections have been placed in various thalamic areas in order to investigate spinothalamic projections in the lizard Varanus exanthematicus. It appeared that the spinal cord projects to three different thalamic areas: nucleus dorsomedialis, nucleus ventrolateralis, and an area that includes both the nucleus dorsolateralis and nucleus intermediodorsalis. Spinal neurons projecting to nucleus dorsomedialis are localized bilaterally at the medial side of the dorsal horn. Following injections in nucleus ventrolateralis, labeled neurons were found bilaterally in area VII and VIII, whereas nucleus dorsolateralis and nucleus intermediodorsalis receive a bilateral input mainly from areas V and VI.

Brainstem afferents to the thalamus in a lizard, Varanus exanthematicus.

HRP was injected into various thalamic nuclei in order to investigate the brainstem projections to the thalamus in the lizard Varanus exanthematicus. Nucleus dorsomedialis receives afferents from the septal area, nucleus entopeduncularis anterior, nucleus periventricularis hypothalami, area triangularis, nucleus raphes superior, nucleus reticularis inferior, and locus coeruleus. Nucleus dorsolateralis receives afferents from septal area, nucleus dorsomedialis, nucleus entopeduncularis anterior, nucleus periventricularis hypothalami, and the torus semicircularis. Nucleus rotundus receives an input from the tectum mesencephali, the pretectal area, and from the mesencephalic reticular formation. Nucleus intermedius dorsalis receives afferents from the dorsal column nuclei and nucleus periventricularis hypothalami. Nucleus ventrolateralis receives afferents from the dorsal column nuclei, the trigeminal complex, locus coeruleus, and the reticular formation. Nucleus ventromedialis also receives afferents from the trigeminal complex and the reticular formation. Afferents to the habenula have been demonstrated from the septal area, nucleus entopeduncularis anterior, triangular area, nucleus periventricularis hypothalami, nucleus interpeduncularis, nucleus raphes superior, locus coeruleus, nucleus isthmi, nucleus dorsalis motorius nervi vagi, and the mesencephalic tegmentum. The laminar part of the torus semicicularis projects to nucleus medialis.

Efferent connections of the lateral cortex of the lizard Gekko gecko: evidence for separate origins of medial and lateral pathways from the lateral cortex to the hypothalamus.

The lateral cortex of the lizard Gekko gecko is composed of three parts: a dorsal and ventral part located rostrally and a posterior part located caudally. In order to obtain detailed information about the efferent connections of these lateral cortex subdivisions, iontophoretic injections of the anterograde tracers Phaseolus vulgaris leucoagglutinin and biotinylated dextran were made in the various parts. The main projection from the dorsal part terminates in the caudal part of the medial cortex. Other cortical projections were noted to the ipsi- and contralateral lateral cortex, the large-celled part of the medial cortex, and the dorsal cortex. Additional fibers were found bilaterally in the anterior olfactory nucleus and the external amygdaloid nucleus. The ventral part of the lateral cortex projects mainly to the ipsilateral, posterior part of the dorsal ventricular ridge and the external amygdaloid nucleus. Minor contralateral projections to these nuclei were also found. Other projections were observed to travel to the caudal part of the medial cortex, to the nucleus sphericus, and bilaterally to the lateral cortex and the anterior olfactory nucleus. The posterior part of the lateral cortex has similar efferent connections as the dorsal part and should be regarded as the caudal continuation of the dorsal part. Because previous studies have shown that the medial cortex and the amygdaloid complex project to different hypothalamic areas, we conclude that the dorsal and ventral parts of the lateral cortex transmit olfactory information to separate hypothalamic areas that are probably involved with different types of behavior.

Efferent connections of the dorsal cortex of the lizard Gekko gecko studied with Phaseolus vulgaris-leucoagglutinin.

The efferent connections from the dorsal cortex of the lizard Gekko gecko have been studied with the anterograde tracer Phaseolus vulgaris-leucoagglutinin. It appeared that the dorsal cortex is not a homogeneous structure as far as the efferent connections are concerned. All parts of the dorsal cortex project to the septum. All parts except the most medial project to the dorsal ventricular ridge, amygdala, nucleus periventricularis hypothalami, area lateralis hypothalami, and the anterior olfactory nucleus. The most medial part, in addition to the septal projections, is connected with the medial cortex and the contralateral medial and dorsal cortices. From the rostral part additional projections could be traced to the nucleus dorsolateralis hypothalami, nucleus ventromedialis thalami, nucleus dorsolateralis thalami, striatum, pallial thickening, medial cortex, nucleus olfactorius anterior, and the main and accessory olfactory bulbs. From the caudal part additional projections exist to the nucleus dorsomedialis thalami, nucleus accumbens, and the contralateral dorsal cortex. A system of intrinsic connections exists that can be subdivided into four subsystems, each of which subserves the interconnections within four subdivisions of the cortex: 1) the superficial medial part, 2) the deep medial part, 3) the caudal lateral and caudal intermediate parts, and 4) the rostral lateral and rostral intermediate parts. Connections between these four areas are scarce. From the present results the conclusion is drawn that the dorsal cortex of the lizard Gekko gecko has many hodological aspects in common with the ventral subiculum of mammals. The present results do not support the hypothesis that the dorsal cortex is the reptilian equivalent of the mammalian neocortex.

Medial cortex of the lizard Gekko gecko: a hodological study with emphasis on regional specialization.

There is increasing evidence that the archicortex in mammals and reptiles is not a homogeneous structure. However, little is known about the regional specialization of this cortical area in reptiles. Therefore, the efferent connections of the medial cortex of the lizard Gekko gecko were studied with the anterograde tracer Phaseolus vulgaris-leucoagglutinin. The small-celled part of the medial cortex (Cxms) projects to various parts of the septum in a topological way: the rostral part projects to the anterior septal nucleus, whereas the caudal part projects to the lateral septal nucleus and the nucleus septi impar. In addition, Cxms projects to the large-celled part of the medial cortex (Cxml). Axons that originate from the dorsal part of Cxms terminate at the proximal parts of the apical and basal dendrites of the neurons of Cxml caudal to the injection site. In contrast, fibers originating from the ventral part terminate on more distal parts of the dendrites of neurons of Cxml rostral to the injection site. Other projections from Cxms to the dorsal cortex (Cxd) and the external amygdaloid nucleus were found. The Cxml projects bilaterally to Cxms. These projections terminate in the superficial and deep plexiform layers. In addition, projections to the cell plate of Unger, Cxd, and to the lateral septal nucleus were found. It appears, on the basis of the efferent connections, that Cxms can be divided into a rostral and caudal part, while hodological differences also exist between the dorsal and ventral parts of Cxms. The results of the present study do not suggest a subdivision of Cxml. The regional variations of the medial cortex in the lizard Gekko gecko differ from the regional variations described in other reptilian species.

The distribution of dopamine immunoreactivity in the forebrain and midbrain of the lizard Gekko gecko: an immunohistochemical study with antibodies against dopamine.

The distribution of dopamine (DA) immunoreactivity in the forebrain and the midbrain of the lizard Gekko gecko was studied by using recently developed antibodies against DA. Dopamine-containing cells were found around the glomeruli of the olfactory bulb, in several parts of the periventricular hypothalamic nucleus, in the periventricular organ, the ependymal wall of the infundibular recess, the lateral hypothalamic area and the pretectal posterodorsal nucleus of the diencephalon, and in the ventral tegmental area, the substantia nigra, and the presumed reptilian equivalent of the mammalian A8 cell group of the mesencephalon. Dopaminergic fibers and terminals were observed throughout the whole brain, but particularly in the diencephalon and the telencephalon. The nucleus accumbens appears to have the most dense innervation, but also the striatum, amygdaloid complex, olfactory tubercle, septum, and dorsal ventricular ridge (especially its superficial zone) show numerous DA-containing fibers and terminals. Except for the lateral cortex, cortical areas are not densely innervated by DA fibers. In several respects DA distribution in the gekkonid brain differs from that in other reptiles studied. For instance, in the Gekko the dorsal ventricular ridge is densely innervated by DA fibers, whereas in turtles and crocodiles the same structure shows only weak catecholaminergic histofluorescence. When compared to the distribution of DA immunoreactivity in mammals, it appears that the DA system in the gekkonid telencephalon resembles the distribution of DA in the limbic forebrain and striatum of mammals. Whether these similarities in distribution of DA also imply similarities in function will be discussed.

Tectal connections in Python reticulatus.

The origins of the axons terminating in the mesencephalic tectum in Python reticulatus were examined by unilateral tectal injections of horseradish peroxidase. Retrogradely labeled cells were observed bilaterally throughout the spinal cord in all subdivisions of the trigeminal system, with the exception of nucleus principalis, which showed labeled cells only on the ipsilateral side. Labeling of the reticular formation occurred bilaterally in nucleus reticularis inferior magnocellularis, nucleus reticularis lateralis, nucleus reticularis, and the mesencephalic reticular formation. The tectum also receives bilateral projections from the dorsal tegmental field, the nucleus of the lateral lemniscus, and nucleus isthmi, and ipsilateral projections from nucleus profundus mesencephali. A few labeled cells were found ipsilaterally in the locus coeruleus and in nuclei vestibulares ventrolateralis and ventromedialis. In the diencephalon labeled cells were observed ipsilaterally in nucleus ventrolateralis thalami, nucleus ventromedialis thalami, nucleus suprapeduncularis, and in the dorsal and ventral lateral geniculate nuclei. Bilateral labeling was observed in nucleus periventricularis hypothalami. Furthermore, labeling was ipsilaterally present in the ventral telencephalic areas. The tectum in Python reticulatus receives a wide variety of afferent connections which confirm the role of the tectum as an integration center of visual and exteroceptive information.

Histochemical identification of pallidal and striatal structures in the lizard Gekko gecko: evidence for compartmentalization.

The present study provides a description of the distribution patterns of enkephalin, substance P and dopamine immunoreactivity, and acetylcholinesterase activity in the striatum, nucleus accumbens, globus pallidus, and ventral pallidum of the Gekko gecko. The pallidal structures were identified on the basis of characteristic enkephalin and substance P immunoreactive plexus. The globus pallidus contains a very dense enkephalin immunoreactive woolly fiber plexus and a light and less extensive substance P immunoreactive plexus. The ventral pallidum is characterized by substance P and enkephalin immunoreactive woolly fiber plexus, which show a dense and moderate staining, respectively. The striatum and the nucleus accumbens were found to be inhomogeneous with respect to staining intensities for all four markers. Except for the enkephalin immunoreactivity distribution pattern in the striatum, the compartments that can be distinguished in material stained for these markers appear to coincide quite well.

A forebrain atlas of the lizard Gekko gecko.

An atlas of the forebrain of the lizard Gekko gecko has been provided, which will serve as the basis for subsequent experimental tracing and immunohistochemical studies. Apart from a strongly developed medial cortex and septal area, the Tokay gecko shows all the main features of the forebrain of the lacertid-type lizards. When its convenience as an experimental animal is also taken into account, this species seems to be very suitable for studying the limbic system in reptiles. The atlas comprises topographical reconstructions of the telencephalon and diencephalon and a series of transverse sections of which the levels have been indicated in the reconstructions. The results obtained in the Gekko are briefly compared with those found in other lizards studied.

Distribution of choline acetyltransferase immunoreactivity in the brain of the lizard Gallotia galloti.

The aim of the present study is to provide a complete description of the distribution of choline acetyltransferase (ChAT) immunoreactivity (i) in the brain of the lizard Gallotia galloti, on the basis of two different primary antisera: rat anti-ChAT and rabbit anti-chicken ChAT. Considering that the brain is a segmented structure, we have analysed our data with respect to transverse segmental domains (or neuromeres), which have been previously described by several authors in the brain of vertebrates. In the telencephalon, ChATi neurons are seen in the cortex, anterior dorsal ventricular ridge, basal ganglia, diagonal band, and bed nucleus of the stria terminalis. Further caudally, ChATi cell bodies are located in the preoptic area, hypothalamus, habenula, isthmus, and all motor efferent centers of the brainstem and spinal cord. Plexuses of ChATi fibers are observed in the areas containing cholinergic cell bodies. In addition, distinct plexuses are found in the cortex, the posterior dorsal ventricular ridge, the neuropiles of all primary visual centers of the diencephalon and mesencephalon, and several non-visual nuclei of the brainstem. The distribution of ChAT immunoreactivity in the brain of G. galloti resembles in many respects that of other vertebrates, and differences are mainly observed in the pretectum and midbrain tectum. Transverse segmental domains were identified in the brainstem and forebrain of Gallotia when the cranial nerve roots and fiber tracts were used as a reference, and most cranial motor nuclei were found to occupy the same segmental positions as have been reported in the chick.

Septal complex of the telencephalon of the lizard Podarcis hispanica. II. Afferent connections.

The afferent connections to the septal complex were studied in the lizard Podarcis hispanica (Lacertidae) by means of a combination of retrograde and anterograde tracing. The results of these experiments allow us to classify the septal nuclei into three main divisions. The central septal division (anterior, lateral, dorsolateral, ventrolateral, and medial septal nuclei plus the nucleus of the posterior pallial commissure) receives a massive, topographically organized, cortical projection (medial, dorsal, and ventral areas) and widespread afferents from the tuberomammillary hypothalamus and the basal telencephalon. Moreover, it receives discrete projections from the dorsomedial anterior thalamus, the ventral tegmentum, the midbrain raphe, and the locus coeruleus. The ventromedial septal division (ventromedial septal nucleus) receives a massive projection from the anterior hypothalamus, dense serotonergic innervation, and a faint amygdalohypothalamic projection, but it is devoid of direct cortical input. The midline septal division (nucleus septalis impar and dorsal septal nucleus) receives a nontopographic cortical projection (dorsomedial and dorsal cortices) and afferents from the preoptic hypothalamus, the dorsomedial anterior thalamus, the midbrain central gray, and the reptilian A8 nucleus/substantia nigra. Our results indicate that the cortex provides a physiologically complex, massive input to the septum that terminates over the whole dendritic tree of septal cells. In contrast, most of the ascending afferents make axosomatic contacts by means of pericellular nests. The chemical nature of the main septal afferents and the comparative implications of the available hodological data on the organization of the septal complex of tetrapod vertebrates are discussed.

Septal complex of the telencephalon of lizards: III. Efferent connections and general discussion.

The projections of the septum of the lizard Podarcis hispanica (Lacertidae) were studied by combining retrograde and anterograde neuroanatomical tracing. The results confirm the classification of septal nuclei into three main divisions. The nuclei composing the central septal division (anterior, lateral, medial, dorsolateral, and ventrolateral nuclei) displayed differential projections to the basal telencephalon, preoptic and anterior hypothalamus, lateral hypothalamic area, dorsal hypothalamus, mammillary complex, dorsomedial anterior thalamus, ventral tegmental area, interpeduncular nucleus, raphe nucleus, torus semicircularis pars laminaris, reptilian A8 nucleus/substantia nigra and central gray. For instance, only the medial septal nucleus projected substantially to the thalamus whereas the anterior septum was the only nucleus projecting to the caudal midbrain including the central gray. The anterior and lateral septal nuclei also differ in the way in which their projection to the preoptic hypothalamus terminated. The midline septal division is composed of the dorsal septal nucleus, nucleus septalis impar and nucleus of the posterior pallial commissure. The latter two nuclei projected to the lateral habenula and, at least the nucleus of the posterior pallial commissure, to the mammillary complex. The dorsal septal nucleus projected to the preoptic and periventricular hypothalamus and the anterior thalamus, but its central part seemed to project to the caudal midbrain (up to the midbrain central gray). Finally, the ventromedial septal division (ventromedial septal nucleus) showed a massive projection to the anterior and the lateral tuberomammillary hypothalamus. Data on the connections of the septum of P. hispanica and Gecko gekko are discussed from a comparative point of view and used for better understanding of the functional anatomy of the tetrapodian septum.

The septal complex of the telencephalon of the lizard Podarcis hispanica. I. Chemoarchitectonical organization.

In this paper we study the septal complex architecture in the lizard Podarcis hispanica (Lacertidae). Histochemical and immunohistochemical techniques were used to define the distribution of zinc (Timm stain), acetyl cholinesterase (AChase), gamma-aminobutyric acid (GABA), tyrosine hydroxylase (TH), dopamine (DA), serotonin (5-HT), and two neuropeptides: leu-enkephalin (L-ENK) and substance P (SP). These reactions delineate a coherent map of nine septal nuclei that are named with a topographical nomenclature: anterior, lateral, ventromedial, medial, dorsolateral, ventrolateral, and dorsal septal nuclei, nucleus septalis impar, and nucleus of the posterior pallial commissure. The anterior septal nucleus is characterized by intense reaction for zinc and the presence of fibers immunoreactive for GABA, 5-HT, and L-ENK, which form pericellular nests. The lateral septal nucelus shows intense reaction for zinc, a high density of GABA-immunoreactive cells, and L-ENK-immunoreactive fibers forming basketlike figures around unstained somata. The ventromedial septal nucleus shows intense AChase reactivity, a dense network of 5-HT-immunoreactive fibers, and virtually no labeling for the other histochemical stains. The medial septal nucleus is defined by heavy reactivity for zinc, dense DA/TH and L-ENK innervations, and the presence of L-ENK-immunoreactive cells. The dorsolateral septal nucleus shows intense AChase staining in the neuropile and a dense network of fibers immunoreactive for 5-HT and DA/TH, but it shows low staining for zinc. The ventrolateral septal nucleus shows L-ENK-immunoreactive cells and a dense L-ENK innervation, but low reactivity for zinc. The dorsal septal nucleus, intermingled with the fimbrial fibers, shows a dense population of GABA-immunoreactive cells and terminals, but it is unreactive for zinc. Two subdivisions can be established in this dorsal septal nucleus: the dorsal part, intensely reactive for AChase and innervated by 5-HT fibers, and the central part, which shows L-ENK-immunoreactive neurons and fibers without reactivity for either AChase or 5-HT. The nucleus septalis impar, traversed by the fibers of the anterior pallial commissure (mildly reactive for zinc), shows reaction for AChase but low (if present) reactivity for the remaining markers. The nucleus of the posterior pallial commissure shows a generally low reactivity for the histochemical reactions employed. The distribution of these markers is similar to that found in other squamate reptiles and allows for a direct comparison with the septal formation of mammals. Such a comparison reinforces the view that the limbic system has undergone a conservative evolution within vertebrates.