Rendimiento de los marcadores tumorales séricos en la recaída peritoneal por cáncer colorrectal / Serum tumor markers efficiency for colorectal cancer peritoneal relapse

El cáncer colorrectal es una de las formas más habituales de neoplasia a nivel mundial y el peritoneo representa su tercera localización metastásica más frecuente. La resección quirúrgica continua siendo la primera opción de tratamiento curativo en asociación con una terapia citostática. El antígeno carcinoembrionario (CEA) representa el marcador sérico más estudiado en el cáncer colorrectal. En los últimos años, se ha sumado el análisis de otros biomarcadores tumorales a modo de contribución predictiva de recaída peritoneal en pacientes intervenidos. Su evaluación sérica preoperatoria está afianzándose como indicador de recurrencia y localización de la misma. No obstante, existen muy pocos estudios que evalúen su valor pronóstico en el postoperatorio de la enfermedad, especialmente cuando se carece de alguna determinación previa a la cirugía. Ofrecemos una interpretación del significado predictivo del CEA y del antígeno carbohidrato (Ca 19.9) séricos obtenidos en el postoperatorio de estos pacientes cuando son contextualizados de una forma individualizada con otros factores de riesgo clínico para recaída peritoneal. (AU)

Colorectal cancer is one of the most common worldwide neoplasia and peritoneum represents its third metastatic site. Surgicalresection remains to be the first curative treatment option in association with cytostatic therapy. Carcinoembryonic antigen (CEA)appears to be the most studied serum marker in colorectal cancer. In present years, other tumor biomarkers analysis has been added as a predictive contribution of peritoneal relapse in operated patients. A preoperative serum assessement of them is becoming established as an indicator of recurrence and location. Nevertheless, there are very few studies that evaluate its prognostic value during the postoperative follow-up of disease, especially when there is no determination prior to surgery. We reflect on the predictivesignificance of serum both CEA and carbohydrate antigen (Ca19.9) that were taken in the postoperative follow-up of these patients, establishing an individualized relationship of their value with other clinical risk factors for peritoneal relapse. (AU)

Late maternal hypothyroidism alters the expression of Camk4 in neocortical subplate neurons: a comparison with Nurr1 labeling.

Maternal thyroid hormones (THs) are essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. This is particularly relevant for preterm children who are deprived of maternal THs following birth, are at risk of suffering hypothyroxinemia, and develop attention-deficit/hyperactivity disorder. Expression of neocortical Ca(2+)/calmodulin kinase IV (Camk4), a genomic target of thyroid hormone, and nuclear receptor-related 1 protein (Nurr1), a postnatal marker of cortical subplate (SP) cells, was studied in euthyroid fetuses and in pups born to dams thyroidectomized in late gestation (LMH group, a model of prematurity), and compared with control and developmentally hypothyroid pups (C and MMI groups, respectively). In LMH pups, the extinction of heavy Camk4 expression in an SP was 1-2 days delayed postnatally compared with C pups. The heavy Camk4 and Nurr1 expression in the SP was prolonged in MMI pups, whereas heavy Camk4 and Nurr1 expression in layer VIb remains at P60. The abnormal expression of Camk4 in the cortical SP and in layer VIb might cause altered cortical connectivity affecting neocortical function.

Interleukin-6 as a predictor of cardiovascular events in troponin-negative non-ST elevation acute coronary syndrome patients.

AIM: Risk stratification in acute coronary syndrome without ST-segment elevation (NSTE-ACS) and troponin-negative remains a challenge. We evaluated the value of interleukin-6 (IL-6) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognosis assessment of low-moderate risk NSTE-ACS and troponin-negative, and whether these biomarkers could improve the predictive performance of the established thrombolysis in myocardial infarction (TIMI) risk score. METHODS: A total of 212 low-moderate risk patients with NSTE-ACS and troponin-negative were prospectively studied. Clinical follow up at 6 months was performed for adverse endpoints. RESULTS: A total of 28 patients (13.5%) presented adverse clinical events. Those with adverse clinical events were associated with higher levels of IL-6 [8.58 (5.13-20.95) ng/l vs. 6.12 (4.16-9.14) ng/l, p = 0.043] and NT-proBNP [275.3 (108.6-548.2) ng/l vs. 126.8 (55.97-430.20) ng/l, p = 0.046]. In moderate risk group, we observed a higher event rate in patients with troponin-negative but elevated levels of IL-6 (p = 0.024). Only elevated IL-6 (> 12.40 ng/l) was an independent predictor of adverse outcomes [hazard ratios: 3.62, 95% confidence interval (CI) 1.69-7.75, p = 0.001]. The addition of IL-6 and history of ischaemic heart disease (IHD) to TIMI risk score significantly improved both the discrimination (integrated discrimination improvement, p = 0.003) and reclassification (Clinical Net reclassification improvement, p = 0.010) of the model for adverse events. CONCLUSIONS: Interleukin-6 is an independent predictor of adverse events in low-moderate risk patients with NSTE-ACS and troponin-negative. Its use identifies a higher risk population in moderate-risk patients. This provides together with history of IHD a better discrimination and reclassification beyond that achieved with clinical risk variables from TIMI risk score in these patients.

De la antisepsia a la asepsia / No disponible

Revisamos la antisepsia obstétrica, desarrollada a mediados del siglo XIX por O.W. Holmes y especialmente por I. Semmelweis, con una aportación fundamental en el control de infecciones, el lavado de manos previo a la atención al parto, lo que supuso un avance definitivo en la lucha contra la infección puerperal. Aproximadamente dos décadas más tarde, J. Lister introduce la antisepsia quirúrgica, que supuso asimismo un gran avance en el desarrollo de la cirugía, al reducir sustancialmente las infecciones y permitir intervenciones que hasta entonces no era posible realizar. En las postrimerías del siglo XIX, el método de Lister se fue modificando y la introducción de la esterilización dio paso a la asepsia que, junto con otros avances, como la introducción de guantes, primero de algodón y posteriormente de goma, así como gorro y mascarilla, permitieron modificar sustancialmente la práctica quirúrgica

In this paper we do a revision of obstetric antisepsis developed in the XIX century by O.W. Holmes and especially by I. Semmelweis. He did a fundamental contribution in controlling infections by introducing the washing of hands before the act of child bearing. This meant a definite advance in the fight against puerperal infection. J. Lister introduced the surgical antisepsis about two decades later. This also meant a significant advance in the development of surgery by reducing infections substantially and allowing surgical interventions hard to perform until then. By the end of the 19th century, Lister's method was modified and sterilization introduced. This gave way to antisepsis. The introduction of gloves- which were made out of cotton at first and of rubber later on - as well as surgical caps and masks, allowed substantial modifications to the surgical practice

Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity.

Hypothyroxinemia affects 35-50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats. Pups born to LMH dams, thyroxine treated from E17 to postnatal day (P) 0, were also studied. In developing LMH pups, the cortical lamination was abnormal. At P40, heterotopic neurons were found in the subcortical white matter and in the hippocampal stratum oriens and alveus. The Zn-positive area of the stratum oriens of hippocampal CA3 was decreased by 41.5% showing altered mossy fibers' organization. LMH pups showed delayed learning in parallel to decreased phosphorylated cAMP response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression in the hippocampus. Thyroxine treatment of LMH dams reverted abnormalities. In conclusion, maternal THs are still essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. Our data suggest that thyroxine treatment of premature neonates should be attempted to compensate for the interruption of the maternal supply.

Contribución al estudio histórico del paludismo / No disponible

Realizamos una revisión histórica del paludismo, enfermedad que supone un auténtico problema de Salud Pública, especialmente en países tropicales en vías de desarrollo, donde se registran 300 a 500 millones de casos y 2 a 3 millones de muertes por año. Se revisa la etiología, con distintas aportaciones realizadas a lo largo de la historia, hasta llegar a 1880, en que Laveran descubrió el parásito producto de la enfermedad. En España, todavía durante el siglo XX, la endemia palúdica fue importante, realizándose una lucha contra la enfermedad que permitió certificar su erradicación en 1964. Asimismo, realizamos una revisión histórica de la quinina, pilar fundamental en el tratamiento de la enfermedad (AU)

We present a historic revision of malaria. This condition is a real problem in public health, especially in undeveloped countries in tropical areas. In these countries between 300 and 500 million cases of malaria and from 2 to 3 million deaths are registered per year. We go over the ethiology of this condition as studied through the years concluding at the moment in which Laveran discovers the parasite producing malaria in 1880. Up to the XX century malaria was and important endemic entity in Spain. A persistent fight against malaria resulted in its eradication in 1964. Along with our study concerning malaria, we also present a historic revision of the appearance and development of quina, the fundamental pillar in the treatment of this pathologic entity (AU)

Vacunas e iconografía / No disponible

Mucho antes de que el médico inglés Edward Jenner descubriera la vacuna antivariólica ya se utilizaba de forma empírica algún método mediante el cual se padecía de forma atenuada la enfermedad y se lograba la inmunización frente a la misma. Este método, sin embargo, no estaba exento de complicaciones, que en ocasiones revestían importante gravedad, lo que contribuyó a que no lograra gran aceptación. Además de la viruela, revisamos desde una perspectiva histórica la rabia, la poliomielitis, la fiebre tifoidea y paratifoidea, la difteria y el tétanos, incluyendo cierta iconografía alusiva a estas enfermedades, sus vacunas o figuras o instituciones relacionadas con las mismas (AU)

There was some kind of method used in an empiric way that helped to suffer the small pot disease in a milder way long before the English physician E. Jenner were to discover the vaccine. This method also achieved immunity against the disease. The method was not exempt to complications, however. Sometimes these complications were serious enough as to compromise the general acceptance of the method. Besides the smallpox, we do a historic revision of rage, poliomyelitis, typhoid and partyphoid fever, as well as, that of diphtheria and tetanus. We include an iconography regarding these diseases, its vaccines and persons and institutions relate to then (AU)

[Music versus diazepam to reduce preoperative anxiety: a randomized controlled clinical trial]. / Estudio comparativo de la eficacia de la música frente al diazepam para disminuir la ansiedad prequirúirgica: un ensayo clínico controlado y aleatorizado.

OBJECTIVES: To compare the effectiveness of music to that of diazepam in reducing preoperative anxiety. PATIENTS AND METHODS: Patients were randomized to 2 groups to receive diazepam or listen to music on the day of surgery and the previous day. Just before the operation, anxiety was assessed with the State-Trait Anxiety Inventory. Cortisol levels, heart rate, and blood pressure were also recorded. RESULTS: Two hundred seven patients were enrolled. No significant differences in any of the outcome measures (anxiety, cortisol level, heart rate, or blood pressure) were found between the 2 groups (music vs sedative). CONCLUSIONS: Our findings indicate that music is as effective as sedatives for reducing preoperative anxiety.

Estudio comparativo de la eficacia de la música frente al diazepam para disminuir la ansiedad prequirúrgica: un ensayo clínico controlado y aleatorizado / Music versus diazepam to reduce preoperative anxiety: a randomized controlled clinical trial

OBJETIVOS: Comparar la efectividad de la músicafrente al diazepam en reducir la ansiedad prequirúrgica.SUJETOS Y MÉTODOS: Los pacientes fueron aleatorizadosen dos grupos. El primer grupo recibió diazepam,mientras el segundo escuchó música tanto el día anteriorcomo el mismo día de la cirugía. Inmediatamente antesde la intervención la ansiedad se evaluó mediante elSTAI (State-Trait Anxiety Inventory). Se registraron elcortisol, la frecuencia cardiaca y la presión arterial.RESULTADOS: Se incluyeron 207 pacientes. No seencontraron diferencias significativas entre ambos grupos(música y sedantes) en cuanto a las variables estudiadas(ansiedad, cortisol, frecuencia cardiaca y presiónsanguínea).CONCLUSIONES: Nuestros resultados indican que lamúsica es tan efectiva como los sedantes para reducir laansiedad prequirúrgica (AU)

OBJECTIVES: To compare the effectiveness of music to that of diazepam in reducing preoperative anxiety. PATIENTS AND METHODS: Patients were randomized to 2 groups to receive diazepam or listen to music on the day of surgery and the previous day. Just before the operation, anxiety was assessed with the State–Trait Anxiety Inventory. Cortisol levels, heart rate, and blood pressure were also recorded. RESULTS: Two hundred seven patients were enrolled. No significant differences in any of the outcome measures (anxiety, cortisol level, heart rate, or blood pressure) were found between the 2 groups (music vs sedative). CONCLUSIONS: Our findings indicate that music is as effective as sedatives for reducing preoperative anxiety (AU)

Crossmodal audio-visual interactions in the primary visual cortex of the visually deprived cat: a physiological and anatomical study.

Blind individuals often demonstrate enhanced non-visual perceptual abilities. Neuroimaging and transcranial magnetic stimulation experiments have suggested that computations carried out in the occipital cortex may underlie these enhanced somatosensory or auditory performances. Thus, cortical areas that are dedicated to the analysis of the visual scene may, in the blind, acquire the capacity to participate in other sensory processing. However, the neural substrate that underlies this transfer of function is not fully characterized. Here we studied the synaptic and anatomical basis of this phenomenon in cats that were visually deprived by dark rearing, either early visually deprived after birth (EVD), or late visually deprived after the end of the critical period (LVD); data were compared with those obtained in normally reared cats (controls). The presence of synaptic and spike responses to auditory stimulation was examined by means of intracellular recordings in area 17 and the border between areas 17 and 18. While none of the cells recorded in control and LVD cats showed responses to sound, 14% of the cells recorded in EVD cats showed both subthreshold synaptic responses and suprathreshold spike responses to auditory stimuli. Synaptic responses were of small amplitude, but well time-locked to the stimuli and had an average latency of 30+/-12ms. In an attempt to identify the origin of the inputs carrying auditory information to the visual cortex, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling examined in the cortex and thalamus. No significant retrograde labeling was found in auditory cortical areas. However, the proportion of neurons projecting from supragranular layers of the posteromedial and posterolateral parts of the lateral suprasylvian region to V1 was higher than that in control cats. Retrograde labeling in the lateral geniculate nucleus showed no difference in the total number of neurons between control and visually deprived cats, but there was a higher proportion of labeling in C-laminae in deprived cats. Labeled cells were not found in the medial geniculate nucleus, a thalamic relay for auditory information, in either control or visually deprived cats. Finally, immunohistochemistry of the visual cortex of deprived cats revealed a striking decrease in pavalbumin- and calretinin-positive neurons, the functional implications of which we discuss.

Role of thyroid hormones in the maturation and organisation of rat barrel cortex.

The influence of thyroid hormones on cortical development was analysed in rat somatosensory cortex. Maternal and foetal hypothyroidism was induced and maintained by methimazole treatment from embryonic day 13 onwards. 5-Bromo-2'-deoxyuridine (BrdU) labelling in hypothyroid rats showed that cell positioning during corticogenesis followed an inside-out pattern. The radial neurogenetic gradients were more diffuse at all ages with respect to normal rats due to the inappropriate location of many cells, including those of the subcortical white matter. Most (62%) of the cells in the subcortical white matter of hypothyroid rats were labelled at embryonic day 15. Nissl staining of the primary somatosensory cortex showed blurred cortical layer boundaries and an abnormal barrel cytoarchitecture. Cytochrome oxidase and peanut agglutinin staining showed that the tangential organisation of the posteromedial barrel subfield and its layer IV specificity was not lost in hypothyroid rats. However the temporal pattern of peanut agglutinin labelling was delayed 3-4 days with respect to normal rats. In hypothyroid rats, the total barrelfield tangential area was reduced by 27% with respect to normal. The total tangential barrel area, corresponding to peanut agglutinin-negative labelling, occupied 77% of the barrelfield area and only 66% in hypothyroid rats. This reduction was larger with cytochrome oxidase staining where the total barrel area occupied 69% of the barrelfield area in normal and 46% in hypothyroid rats. Our data stress the importance of maternal and foetal thyroid hormones during development, and demonstrate the irreversible effects that maternal and foetal hypothyroidism may have on the intrinsic organisation and maturation of the neocortex.

Protracted expression of serotonin transporter and altered thalamocortical projections in the barrelfield of hypothyroid rats.

In humans, thyroid hormone deficiency during development causes severe neurological diseases but the underlying mechanisms are unclear. We have examined the effects of thyroid hormones on the development of somatosensory thalamocortical projections, by inducing hypothyroidism in rats by methimazole treatment at embryonic day 13 and subsequent thyroidectomy at postnatal day 6 (P6). Initial development of the thalamocortical projections and their tangential and laminar patterning were similar in normal and hypothyroid rats from birth to P4. The tangential spread of the thalamocortical arbors is reduced in hypothyroid rats after P4, paralleling the overall cortical atrophy. Anterograde tracing and single axon reconstructions indicate that thalamic afferents reached layer IV but that they had fewer and shorter branches, with a 42% reduction in the number of boutons. The transient serotonin (5-HT) immunostaining and 5-HT transporter (5-HTT) expression were both prolonged by 5 days in hypothyroid rats. This does not reflect a delayed maturation of the thalamus because other transiently expressed genes such as the vesicular monoamine transporter and the 5-HT1B receptor are not modified. Protracted 5-HTT expression also occurred in other areas with transient expression, but no changes were observed in the raphe nuclei where the 5-HTT is expressed permanently. Thus, thyroid hormones appear to be important in regulating the extinction of the 5-HTT in nonserotoninergic neurons. The transient stabilization of 5-HT reuptake in hypothyroid rats could affect the growth of thalamic axons. Our data stress the importance of maternal and foetal thyroid hormones for the normal development of sensory systems.

The development of auditory callosal connections in normal and hypothyroid rats.

Previous studies have shown that hypothyroidism modifies the development of callosal connections. In particular, adult hypothyroid rats have fewer callosally projecting neurons in layers II-III of the auditory cortex and more in layer V. This might be due to disturbance in the stabilization/elimination of juvenile callosal axons, or to abnormal neuronal migration during cortical histogenesis. To distinguish between these possibilities we have studied the distribution of callosally projecting auditory neurons at different postnatal ages using retrogradely transported tracers, and the cortical neurogenetic gradients using DNA labelling with 5-bromo-2'-deoxiuridine. In hypothyroid rats, injected at postnatal day 5 (P5) and killed at P18-20, most of the neurons retrogradely labelled from the contralateral hemisphere are distributed between layers IV and VI, as in older rats. In hypothyroid rats, many neurons are at locations inappropriate for their birthdate, including the subcortical white matter, resulting in more diffuse radial neurogenetic gradients. These results indicate that early induced hypothyroidism alters neuronal migration and prevents the establishment of callosal connections from cortical layers II-III.

Anatomy of the ventral nucleus of the lateral lemniscus in rats: a nucleus with a concentric laminar organization.

The lateral lemniscus contains relay nuclei of the auditory pathway in which the neurons have been grouped into dorsal and ventral (VNLL) nuclei. The data about the cytoarchitecture of the VNLL are controversial and no agreement exists concerning its tonotopical organization. In this paper, the cytoarchitecture of VNLL and the spatial distribution of its neurons projecting to the central nucleus of the inferior colliculus (CNIC) have been studied by using different tracers. Rats were iontophoretically injected in the CNIC and grouped in three sets. Group 1 rats received large injections of biotinylated dextran amine (BDA). Group 2 animals received restricted single injections of BDA in the low-, medium-, or high-frequency regions of the CNIC. Group 3 rats were double injected, with horseradish peroxidase placed in the high-frequency region of the CNIC, and with biocytin in the low-frequency one. The distribution of retrogradely labeled neurons in the ipsilateral VNLL was three-dimensionally reconstructed by use of a computer microscope. The analysis of labeled neurons and Nissl material suggests that the VNLL contains flat stellate neurons. Labeled flat stellate neurons and fibers are oriented in parallel and form fibrodendritic laminae. The projection from the VNLL to the CNIC is topographically organized: neurons in peripheral laminae project to dorsolateral, low-frequency regions of the CNIC, and those of central laminae project to ventromedial, high-frequency regions. Each VNLL lamina forms a continuous ventrodorsal structure which resembles a helicoid.

Distribution of parvalbumin immunoreactivity in the neocortex of hypothyroid adult rats.

Early hypothyroidism produces a generalized damage in the brain and in particular, changes in the connectivity of neocortical sensory areas. In this paper, the potential alterations in local neocortical circuits have been explored using immunocytochemistry for parvalbumin (PV) in normal and hypothyroid adult rats. The number and radial distribution of PV-positive cells were similar in both groups, but in hypothyroid rats, the density of PV-positive terminal-like puncta and processes was dramatically reduced, especially in layers II-III and the lower part of layers IV-V and VI. These results suggest that thyroid hormones are necessary for normal development of cortical circuits in which PV-positive cells are involved.

Role of thyroid hormones in the maturation of interhemispheric connections in rats.

Hypothyroidism causes mental retardation secondary to changes in the organization of the CNS. These changes affect higher brain functions for which interhemispheric transfer of information is crucial. In present study, the anterior commissure (AC) and corpus callosum (CC) of normal (C) and hypothyroid (H) rats has been examined using quantitative electron microscopy. H rats received an antithyroid treatment with methimazole from embryonic day 14 (E14) and surgical thyroidectomy at postnatal day 6 (P6). In the AC, the number of axons (unmyelinated and myelinated) increased from 0.17 x 10(6) axons at E18 to 1.08 x 10(6) axons at P4 and it was almost the same at P180 (1.01 x 10(6) axons). In H rats the number of axons between P14 and P180 was similar to that of C rats. In contrast, there were only 0.11 x 10(6) myelinated axons at P180 resulting in a 66% reduction with respect to C rats (0.36 x 10(6) axons). In the CC of C rats, the number of myelinated axons increased from 1.76 x 10(3) axons at P12 to 3.34 x 10(6) axons at P184. In H rats, there were only 0.84 x 10(6) axons at P184 resulting in a 76% reduction with respect to C rats. This reduction was more important in the posterior sector of the CC (95%) than in the rest (on average 63%). Therefore these results show that thyroid hormones play an important role in the processes involved in the maturation of commissural axons.

The development of the anterior commissure in normal and hypothyroid rats.

The development of axon number in the anterior commissure (AC) was analyzed in 39 normal and 37 hypothyroid rats using conventional electron microscopy. Hypothyroid rats underwent antithyroid treatment with methimazole from embryonic day (E) 14 onwards, followed in a fraction of the animals by thyroidectomy at postnatal day (P) 6. In normal rats, the midsagittal cross-sectional anterior commissure area (ACA) increased throughout their life; in hypothyroid rats, ACA was stationary from P4 onwards and at P174-180 it was reduced by 39% relative to normal rats. In normal rats, the number of AC axons increased rapidly from 168,500 at E18 to, on average, 1,049,000 from P4 onwards. Similarly, in hypothyroid rats, the number of axons increased from 135,000 at E18 to, on average, 1,052,000 from P4 onwards. At all ages, the number of axons was similar in normal and hypothyroid rats. During development of the AC, the evolution of axon number observed in normal and hypothyroid rats is different from what was reported for other telencephalic commissures, including the AC of the monkey, where an important fraction of the axons are eliminated postnatally. Antithyroid treatment dissociated ACA from total number of AC axons.

Organization of auditory callosal connections in hypothyroid adult rats.

Callosal connections were studied with tracers (horseradish peroxidase (HRP) and wheat germ agglutinin-horseradish peroxidase (WGA-HRP)) in normal rats and rats deprived of thyroid hormones with methimazole (Sigma) since embryonic day 14 and thyroidectomized at postnatal day 6. In hypothyroid rats, the auditory areas, in particular the primary auditory area, showed cytoarchitectonic changes including blurred lamination and decrease in the size of layer V pyramidal neurons. In control rats, callosally-projecting neurons were found between layers II and VI with a peak in layer III and upper layer IV. In hypothyroid rats, labelled neurons were found between layers IV and VI with two peaks corresponding to layer IV and upper layer V, and in upper layer VI. Quantitative analysis of radial distribution of callosally-projecting neurons confirmed their shift to infragranular layers in hypothyroid rats. Three-dimensional reconstructions showed a more continuous tangential distribution of callosally-projecting neurons in hypothyroid rats which may be due to the maintenance of a juvenile 'exuberant' pattern of projections. These changes in cortical connectivity may be relevant for understanding epilepsy and mental retardation associated with early hypothyroidism in humans and to clarify basic mechanisms of cortical development.

Analysis of an experimental cortical network: I). Architectonics of visual areas 17 and 18 after neonatal injections of ibotenic acid; similarities with human microgyria.

Lesions of cortical areas 17 and 18 have been produced in newborn kittens by local injections of the excitotoxin ibotenic acid (ibo). Twenty-four hours after an injection on postnatal days 2 or 3, the gray matter of areas 17 and 18 near the center of the injection appears completely destroyed, with the exception of a one-to-two cell-thick layer at the bottom of layer I. Intact migrating neurons and radial glia can be found light- and electron-microscopically in the region affected. During the following weeks a several hundred micron thick cortex reforms. In the adult, this cortex consists of superficial layers I, II and III as proven by cytoarchitectonics, continuity with the corresponding layers of the normal cortex and cellular composition. We believe that the recovery is due to completion of migration by neurons spared by the ibo injection. More severe destruction of cerebral cortex, i.e. complete loss of the neuronal layers or their reduction to a few cell-thick mantles can be obtained with ibo injections at the end of the second or, respectively, first postnatal week. Severity of lesion also depends on the dose of ibo injected. There are interesting similarities between the ibo-injured cortex and two human neocortical displasias: microgyria and ulegyria.

Analysis of an experimental cortical network: II). Connections of visual areas 17 and 18 after neonatal injections of ibotenic acid.

Lesions of cortical areas 17 and 18 were produced in newborn kittens by local injections of the excitotoxin ibotenic acid. In the adult this results in a microcortex which consists of superficial layers I, II and III, in the absence of granular and infragranular layers. Horseradish peroxidase, alone or wheat germ agglutinin conjugated, was injected in the microcortex or in the contralateral, intact areas 17 and 18. The microcortex maintains several connections characteristic of normal areas 17 and 18 of the cat. It receives afferents from the dLGN, and several visual areas of the ipsilateral and contralateral hemisphere. However, it has lost its projections to dLGN, superior colliculus, and, at least in part, those to contralateral visual areas. Thus some parts of the microcortex receive from, but do not project into, the corpus callosum. In addition, the microcortex maintains afferents from ipsilateral and contralateral auditory areas AI and AII which are normally eliminated in development.