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R O'Rahilly

Publications and source records attributed to R O'Rahilly.

At least 19 recordsLinked to original sources

Prenatal ages and stages-measures and errors.

BACKGROUND: The confusing term "gestational age" is generally either not defined or is used for menstrual "age," postovulatory age, or postfertilizational age. The designation (post)menstrual weeks and/or days is very useful in obstetrics but, because prenatal age extends from fertilization to birth, menstrual "age" is a misnomer. The term "stage" has a specific morphological meaning in embryology and should not be used either for ages or for lengths. METHODS: Embryonic age is best assessed, when possible, from the 23 internationally recognized morphological stages. A morphological staging system is not available for the fetal period, and fetal age is assessed mainly from measurements. RESULTS: Among these, the unsatisfactory designation crown-rump length (CRL) should be replaced, in ultrasonic biometry as well as in embryology, by the greatest length (GL), exclusive of the lower limbs. These points are discussed in detail, and justification for the views expressed is provided. CONCLUSIONS: The continuing confusion concerning prenatal age is shown to be unnecessary once the ambiguous and superfluous term "gestational age" is abandoned.

Crown-Rump Length

Making planes plain.

The major anatomical planes (horizontal, coronal, and sagittal, including the median plane) are discussed from a historical perspective, and their correct usage is clarified. Unofficial and unnecessary terms to be avoided (for reasons explained) include midsagittal, parasagittal, and midline.

Anatomy

Philatelic introduction to the history of anatomy.

Representative postage stamps reproduced here provide an idea of the scope available for introducing the history of human anatomy. Included are ancient Greek pioneers, the reformer of human anatomy (Vesalius), the discoverer of the circulation of the blood (Harvey), the compound microscope, and well-known names in histology, neurohistology, and topographical anatomy.

Anatomy

"Gestational age"?

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Embryonic and Fetal Development

The timing and sequence of appearance of neuromeres and their derivatives in staged human embryos.

Serial sections of 215 human embryos from Carnegie stages 6-17 were investigated, and 85 graphic reconstructions were prepared. It is proposed that neuromeres be defined as morphologically identifiable transverse subdivisions perpendicular to the longitudinal axis of the embryonic brain and extending onto both sides of the body. It is proposed further that primary neuromeres be redefined as the early-appearing larger divisions of the open neural folds, and secondary neuromeres as the smaller subdivisions that are found both before and after closure of the neural tube. In the light of these definitions, 6 primary neuromeres can be detected in the human brain at stage 9, and a maximum of 16 secondary neuromeres at stage 14. The relationships of the 8 rhombomeres to the associated neural crest, as well as to the pharyngeal arches and the exits of the cranial nerves, are tabulated. Rhombomere 8 (Rh. 8) is intermediate between the more rostral neuromeres and the spinal cord, and its neural relationships indicate that the four occipital somitic pairs do not impress a strictly repetitive pattern as in the spinal cord. Hence, it is suggested that Rh. 8 depends on both intrinsic and extrinsic factors. The synencephalon, parencephalon, and isthmic neuromere can be distinguished in stage 13. In stage 14, rostral and caudal portions of the parencephalon are recognizable, and the full complement of 16 neuromeres is now present. The medial ventricular eminence appears in the diencephalon (D1). A longitudinal organisation begins to be superimposed on the neuromeres, as now indicated by the appearance of the hypothalamic cell cord. This continues in stage 15, when the hypothalamic sulcus develops. That groove, however, is not continuous with the sulcus limitans. In the diencephalon, five longitudinal zones can be discerned. In stage 16, fibre tracts, such as the habenulo-interpeduncular (fasciculus retroflexus) and the tract of the posterior commissure, outline the boundaries of the synencephalon. In stage 17, the tract of the zona limitans intrathalamica (along the marginal ridge in the parencephalon) is an important landmark. This is the last stage in which all the neuromeres can be distinguished. The supramamillary recess becomes defined and is the termination of the sulcus limitans: the alar/basal distinction is inappropriate in the human forebrain. The number and identity of the neuromeres in the human brain, their precise sequence of appearance, and the stages at which they appear are here clarified for the first time. The results of various studies of domains of gene expression indicate that, although in some instances such territories follow the morphological neuromeres, in others they may cross interneuromeric boundaries. It is concluded that the precise morphological study of neuromeres in any given species is necessary for correlative investigations of gene expression.

Anatomy, Comparative

Neurulation in the normal human embryo.

The neural groove and folds are first seen during stage 8 (about 18 postovulatory days). Two days later (stage 9) the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open. Two days later (stage 10) the neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm. The rostral (or cephalic) neuropore closes within a few hours during stage 11 (about 24 days). The closure is bidirectional; it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently. The caudal neuropore takes a day to close during stage 12 (about 26 days) and the level of final closure is approximately at future somitic pair 31, which corresponds to the level of sacral vertebra 2. At stage 13 (4 weeks) the neural tube is normally completely closed. Secondary neurulation, which begins at stage 12, is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.

Embryonic and Fetal Development

Occipitocervical segmentation in staged human embryos.

Serial sections of 108 human embryos from stage 11 to stage 23 were investigated, and 33 reconstructions were prepared. The existence of 4 occipital somites was confirmed. The important developmental distinction between axial (central) and lateral components obtains in the occipital as well as in the vertebral region. The lateral occipital components begin to show dense areas as the cervical region is approached. The lateral occipital and vertebral components arise in registration with the initial sclerotomes. In both the occipital and the vertebral region the related nerves and intersegmental arteries traverse the loose areas of the sclerotomes. The axial occipital region is not segmented, whereas the cervical components develop from perinotochordal loose areas. Three complete centra (known as XYZ) develop in the atlanto-axial region, although they are related to only 2 1/2 sclerotomes and only 2 neural arches. The height of the XYZ complex equals that of 3 centra elsewhere, and not 2 1/2, as previously maintained. The experimental findings in the occipitocervical region of the chick embryo show both similarities to, as well as differences from, the data for the human embryo. A scheme showing the early development of the entire vertebral column is included.

Atlanto-Occipital Joint

Commemorating the Fabrica of Vesalius.

It is an appropriate time to commemorate the Fabrica of Andreas Vesalius, which was published in Basel 450 years ago. In addition, a dozen key references in English (books and articles) are listed for those who wish to learn more about Vesalius and particularly concerning the wonderful woodcuts in the Fabrica.

Anatomy

Development of anencephaly and its variants.

Extreme variants of anencephaly in two human embryos of the same stage, namely 22 (54 days), shed new light on problems such as craniocerebral interrelationships and the timing of developmental events. Embryo X had a chondrocranium that possessed features typical of a holoacranial anencephalic skull and an extremely well-preserved brain, in which some of the neural tracts were comparable to those in a normal control. On the other hand, embryo Y of the same stage had a completely degenerated brain, although the chondrocranium was more nearly normal and represented the precursor of a meroacranial skull. A comparison of the two cases seems to indicate a certain independence between skull and brain. Moreover, it appears possible that the disturbances are related primarily to the skeletal, and only secondarily to the nervous, component. Comparisons with experimental data allow the conclusion that the maldevelopment involves mostly paraxial mesenchyme and little or no disturbance of neural crest. The timing of the mesenchymal defect is probably as early as stages 8 and 9 (18-20 days). This is also the time at which mesenchymal defects can result in failure of the neural tube to close.

Abnormalities, Multiple

The human rhombencephalon at the end of the embryonic period proper.

The human rhombencephalon at 8 postovulatory weeks (stage 23) is described and illustrated for the first time with the aid of silver-impregnated sections and graphic reconstructions. The motor and sensory trigeminal nuclei were among those studied, and the latter was found to be almost contiguous to the dentate nucleus. Fibers to the principal sensory nucleus join the mesencephalic trigeminal tract, which also seems to be connected with the motor fibers. Fine fibers from the sensory root join the tractus solitarius, which appears to receive connections from the facial, glossopharyngeal, and vagal nerves. Main and accessory abducent nuclei are evident. A part (the Kappenkern des Facialisknies) of the nucleus funiculi teretis is particularly prominent. The presence of the pyramidal decussation during the embryonic period is noted for the first time. The arrangement of nuclei and tracts at 8 weeks is shown to be closely similar to that present in the newborn, and it is likely that the rapid growth of the rhombencephalon during the embryonic period proper is associated with correspondingly early functional activity.

Cell Movement

Ventricular system and choroid plexuses of the human brain during the embryonic period proper.

This morphological study, based on serial sections and graphic reconstructions at 4-8 postovulatory weeks (stages 11-23), is believed to be the first account of the ventricular system in staged human embryos. Closure of the caudal neuropore at stage 12 heralds the onset of the ventricular system and separates the ependymal from the amniotic fluid. After the appearance of the optic ventricle at stage 11, the cavity of the telencephalon medium is discernible at stage 13. At stage 14 the future cerebral hemispheres and lateral ventricles begin, and the rhomboid fossa becomes apparent. The medial and lateral ventricular eminences cause indentations in the lateral ventricle by stage 15. The hypothalamic sulcus is evident at stage 16. At stages 17-18 the interventricular foramina are becoming relatively smaller, and cellular accumulations indicate the future choroid villi of the fourth and lateral ventricles. The areae membranaceae rostralis and caudalis are visible in the roof of the fourth ventricle at stage 18, and the paraphysis is appearing. At stage 19 choroid villi are seen in the fourth ventricle, and a mesencephalic evagination (Blindsack) is detectable. Choroid villi are noticeable in the lateral ventricle at stage 20. An olfactory ventricle is present by stage 21. At about stages 21-23 the lateral ventricle has become C-shaped, so that anterior and inferior horns are visible. Several recesses, e.g., the optic, infundibular, and pineal, develop in the third ventricle during the embryonic period. Features of the ventricular system that do not become apparent until the fetal period include the posterior horn of the lateral ventricle, choroid plexus of the third ventricle, suprapineal recess, interthalamic adhesion, aqueduct, and apertures in the roof of the fourth ventricle.

Cerebral Ventricles

The human brain at stages 18-20, including the choroid plexuses and the amygdaloid and septal nuclei.

The development of the human brain during the seventh embryonic week was studied in serial sections of 88 embryos, and graphic reconstructions were prepared. From stages 18 to 20 the cerebral hemispheres expand rapidly and become more and more distinct entities. The longitudinal fissure between them occupies approximately half of their rostrocaudal extent. In stage 20 they have progressed so far in organization that functional aspects (based on synapses in the primordial plexiform layer) are of importance. An advanced differentiation is also present in the amygdaloid body, which has at least four individual nuclei, and in the forebrain septum, which shows the nucleus of the diagonal band and the medial septal nucleus. This has a bearing on recent experimental studies that document the fundamental role of the septal nuclei with regard to behavioural and cognitive functions. Fibre connections between septal nuclei and hippocampus have appeared. A definitive internal capsule, however, is not yet present. The main connections with diencephalon and other parts of the brain are chiefly by fibres to or from the amygdaloid body by way of the lateral forebrain bundle. The olfactory areas are connected with the habenular nuclei by a well developed stria medullaris thalami. Globus pallidus externus, entopeduncular nucleus, and subthalamic nucleus are prominent features in the subthalamus. The main nucleus of the oculomotor nerve shows a dorsolateral and a ventromedial portion. The rhombic lip is mitotically active in all parts of the rhombencephalon, and seems to participate significantly in the formation of the intermediate layer of the cerebellum and of the cochlear nuclei. The sensory nucleus of the trigeminal nerve has appeared. In the cerebellum the cell layer thought to contain the future Purkinje cells develops. The cerebellar plate is organized into external and internal bulges, and is now connected with mid- and hindbrain through fibre bundles. The area thought to be the dentate nucleus and the supposed floccular region are especially rich in fibres. The accessory olivary nucleus appears in stage 19, and accessory nuclei of the abducent and hypoglossal nerves are evident in stage 20. The choroid plexuses of the fourth and lateral ventricles have appeared. In view of their advanced features, the study of embryos of stages 19-21 becomes increasingly relevant to questions of tissue transplantation.

Amygdala

The human brain at stages 21-23, with particular reference to the cerebral cortical plate and to the development of the cerebellum.

The development of the human brain during the eighth embryonic week was studied in serial sections of 22 embryos, and graphic reconstructions were prepared. The cortical plate appears in stage 21 in the area of the future insula and is an excellent feature for staging. The internal capsule contains neocortical fibres. Its three main outlets begin to be present in stage 22 and lead to epithalamus, to dorsal thalamus, and to mesencephalon. At this time a well developed lateral olfactory tract can be seen. The anterior commissure appears in stage 23. A clear developmental relationship between claustrum and olfactory area is described for the first time in human embryos. The optic tract reaches the ventral area of the lateral geniculate body. Scattered fibres of the lateral lemniscus reach at least as far as the caudal mesencephalon, in which superior and inferior colliculi can be distinguished at stage 23; two caudal Blindsäcke containing ventricular recesses form in stage 23. The cerebellum is still present as a plate, but its internal bulge is considerably enlarged. It possesses radially- and tangentially-arranged cells; the latter form the external germinal layer. The dentate nucleus, as well as the inferior and superior cerebellar peduncles and some of the cerebellar commissures, are present. Compared with the highly developed and probably already functional remainder of the hindbrain, the cerebellar plate shows far less differentiation. Two caudal migratory streams (marginal and submarginal) are present and represent the corpus pontobulbare. The decussation of the pyramids appears in stage 23. This article concludes the study of the developing human brain during the embryonic period, from stage 8 to stage 23. The series was based on 340 serially-sectioned embryos and graphic reconstructions from 89 brains. No comparable investigation of the fetal brain is available.

Amygdala