Biomedical subjects
Publications and source records attributed to I Kjaer.
The sella turcica and pituitary gland in a human fetus (18 weeks gestation) with unilateral oro-ocular cleft combined with unilateral cleft lip and palate are described histologically. In this fetus the sella turcica was not a normal sella but a caudally open funnel. The adenopituitary gland tissue was positioned ectopically within the funnel canal and in the pharyngeal submucosa.
The aim of the present study was to compare, both radiographically and histologically, malformed vertebral lumbar corpora in trisomies 21, 18 and 13 with earlier reported normal corporal development in the axial lumbar region. Axial skeletons of human fetuses (GA 15-22 wk) derived from therapeutically induced abortion were investigated in connection with requested autopsy. The number of lumbar vertebral corpora examined for each genotype was as follows: 20 from trisomy 21, 10 from trisomy 18, and 10 from trisomy 13. After radiography in frontal, lateral and axial projections, the individual vertebral corpora were decalcified and horizontally embedded in paraffin. The blocks were serially sectioned and stained with toluidine blue and alcian blue/van Gieson. The radiographic characteristics of the vertebral corpora varied from an almost normal appearance of the corporal bone to complete clefting of the bony corpora. Histological examination showed accumulations of cartilage centrally, in some cases associated with amorphous material. Pronounced metachromatic differences were observed in the cartilaginous ground substance. The study showed identical phenotypic characteristics in the corpora from trisomy 21, trisomy 18, and trisomy 13. It is characteristic of all three genotypes that there are central anomalies, corresponding to the location of the notochord in normal corpora, and marked regional differences in metachromasia in the ground substance of the cartilage.
In earlier studies, a sella turcica bridge was stated to occur in 1.75 to 6 per cent of the population. The occurrence of a sella turcica bridge has not previously been studied in a group of patients with craniofacial deviations treated by surgery. Profile radiographs from 177 individuals who had undergone combined orthodontic and surgical treatment at the Copenhagen School of Dentistry were studied. A sella turcica bridge was registered in those subjects where the radiograph revealed a continuous band of bony tissue from the anterior cranial fossa to the posterior cranial fossa across the sella turcica. Two types of sella turcica bridge were identified. A sella turcica bridge occurred in 18.6 per cent of the subjects.
From early childhood, Turner syndrome patients have a flattened cranial base, maxillary retrognathism, and short hands. There are, however, no studies that show when these genotype-determined abnormalities occur prenatally. The purpose of the present study was to measure craniofacial profile and hand radiographs of second trimester foetuses with Turner syndrome and compare the results with similar measurements from normal foetuses. The subjects consisted of 12 Turner syndrome foetuses, gestational age (GA) varying between 15 and 24 weeks, and crown-rump length (CRL) between 108 and 220 mm. The mid-sagittal block of each cranium was analysed as part of the requested brain analysis (pituitary gland analysis). This block and the right hand from seven foetuses were radiographed, and the skeletal maturity of the cranial base complex, i.e. the cranial base and the maxilla, was evaluated from the profile radiographs. Shape and size measurements in the cranial base were performed, and compared with normal values according to cranial maturity and to CRL. The cranial base angle in Turner syndrome was greater and the maxillary prognathism was reduced compared with the normal group. The dimensions in the cranial complex and in the hand showed that the bone lengths and distances in relation to CRL were generally smaller compared with normal foetuses. This investigation showed that the abnormal shape of the cranial base complex and the short hands in Turner syndrome are present prenatally.
The purpose of the present study was to investigate persistent primary second molars in a group of young people in their late twenties with agenesis of one or two second premolars. In 1982-83 it was decided, in connection with the orthodontic evaluation of 25 patients, to allow 35 primary molars (one or two in each patient) to remain in situ. All patients had mixed dentitions and agenesis of one or two premolars. The primary teeth were generally in good condition, although root resorption and infra-occlusion (compensated by occlusal composite onlays) occurred. In 1997, 18 of the 25 patients with a total of 26 retained primary molars were reexamined, comprising a clinical examination for exfoliation, extraction, loosening, and ankylosis, and a radiographic examination for root resorption, tooth morphology (crown and root), and alveolar bone contour. The examination showed that the degree of root resorption was unaltered in 20 of the 26 primary molars. In the permanent dentitions, where these primary molars persisted, there were no morphological deviations. Three of the six remaining primary molars had been extracted and three showed extensive resorption. In three of the 26 primary molars the infra-occlusion had worsened. The present study shows that persistence of primary second molars in subjects with agenesis of one or two premolars, and normal morphology of the permanent dentition can be an acceptable, semi-permanent solution for the patient. Whether this could also be an acceptable long-term solution will be shown by follow-up studies.
The purpose of this study was to analyze the shape of the sella turcica in a group of patients with Down syndrome and compare the findings with those made earlier in human fetuses with Down syndrome. Profile radiographs from 78 patients (age 4 months to 50 3/12 years) were analyzed. A tracing was made of each sella turcica, and the shape was compared with that of a normal sella, including the normal growth pattern from childhood to adulthood. Sella turcica structure could be classified into three morphological types, defined as: type I, almost normal appearance; type II, deviations in the anterior wall; and type III, deviations in the floor of the sella turcica. Compared with previously registered prenatal structural deviations in the sella turcica, it can be concluded that the postnatal radiographic material reflects the prenatal findings, because type I, both prenatally and postnatally, is by far the most common, whereas the remaining types are uncommon, both prenatally and postnatally. The study confirms the relevance of prenatal investigations for postnatal diagnostics as previously documented in sella turcica analyses of prenatal and postnatal myelomeningocele cases.
In six fetuses with Meckel syndrome (gestational age 16-23 weeks, crown-rump length 130-170 mm) the skeleton was examined as part of the autopsy procedure using whole body radiography and special radiographic techniques. In the upper and lower limbs we found similar types of polydactyly. We noted four types, based on the number and morphology of metacarpals and metatarsals. In the individual fetus there was more often similarity in the pattern of malformation in the two hands or in the two feet than there was between the pattern of malformation seen in the hands and that seen in the feet. Only one foot was normal. Malformations of the cranial base (the basilar part of the occipital bone or the postsphenoid bone) occurred in five cases, and the vertebral bodies in the lumbar region of the spine were malformed (cleft) in three cases. It is proposed that a skeletal analysis be included in the future evaluation of phenotypes in Meckel syndrome.
Iniencephaly is a central nervous system malformation in which brain and spinal cord are not normally separated at the level of the foramen magnum. The occipital region is fastened to the back of the body at different levels. The purpose of this study of a 16-week human fetus with iniencephaly and holoprosencephaly was to examine the body axis for notochordal remnants in order to determine if an abnormality of dorsoventral axis signaling may be responsible for the development of the iniencephaly abnormality. This aspect of iniencephaly has not been described previously. Radiographic and histochemical investigations were performed. The fetus described here appeared to exhibit an abnormal notochordal course in the upper lumbar, thoracic, and cervical regions. This finding leads us to the hypothesis that iniencephaly might arise because of deviant gene expression in the embryonic period affecting the dorsoventral orientation of the body axis, anatomically indicated by the notochordal malpositions.
The purpose of the present study was to investigate the cranial base on profile radiographs of patients with cri-du-chat syndrome and to relate the findings to current knowledge of brain malformation in an attempt to localize the developmental field affected in cri-du-chat syndrome. The material of profile radiographs of 23 patients was collected in Denmark in the 1970s. Twenty-two patients had terminal deletions of chromosome 5 (5p13.3, 5p14.1, 5p14.2, and 5p14.3), and one patient had an interstitial deletion. The cranial base angle (n-s-ba) was in most cases reduced and in no cases increased compared to age-related standards for normal individuals. Malformations in the bony contours of the sella turcica and the clivus occurred in cri-du-chat patients with terminal deletions. This specific cranial base region develops around the notochord at the location from where the rhombencephalic-derived brainstem, pons, and cerebellum have developed dorsally, and from where the neurons to the larynx have migrated ventrally. As the cranial base, the cerebellum and the larynx are involved in cri-du-chat syndrome, and attention is drawn to a new developmental field which comprises the dorsum sellae, clivus, cerebellum, and larynx. This field seemingly originates from the same notochordal location. The study has demonstrated a cranial base malformation in cri-du-chat patients, which ought to be elucidated in future research and combined with neurological and chromosomal investigations.
The purpose of the present study was to describe the pituitary gland and axial skeleton, including the sella turcica, in human fetuses with spina bifida. Ten fetuses with gestational ages (GA) 15 1/2-28 weeks were investigated radiographically (Faxitron X-ray apparatus) and immunohistochemically. Four of the fetuses have been described previously. The study showed that nine fetuses had minor or no skeletal abnormalities in the vertebral bodies of the spine, and one fetus had severely malformed vertebral bodies. In all cases the sella turcica and the pituitary gland were malformed. Adenopituitary tissue was in all cases located in both the sella turcica and the pharyngeal submucosa. The most severe sella turcica/pituitary gland malformation was seen in the fetus with the malformed spine. The connection between the prenatally registered sella turcica/pituitary gland malformation and the endocrinological status of children with spina bifida should be emphasized in future studies.
The incidence of retention/impaction of the permanent lower second molar (M2inf) lies between 0.6/1000 and 3/1000. Therefore, the purpose of the present study was to investigate the craniofacial morphology, the frequency of dental anomalies and the inclination of the affected M2inf and the adjacent first molar in patients with arrested eruption of M2inf. The overall goal was to elucidate the aetiology of arrested tooth eruption and to present the characteristics of these patients in order to improve diagnosis and treatment planning. Radiographic material (profile radiographs and orthopantomograms) from 19 patients (nine females and 10 males; 13-19 years of age at the time of referral) were analysed. The ages of the patients when profile radiographs were taken for cephalometric analysis varied from 8 to 16 years. The study shows that this group of patients, compared with a reference group, had an increased sagittal jaw relationship (Class II). Specifically, the mandibular prognathism was less, the mandibular gonial angle smaller, the mandibular alveolar prognathism enlarged and the maxillary incisor inclination less than in the reference group. Furthermore, this group of patients had a more frequent occurrence of morphological tooth anomalies, such as root deflections, invaginations, and taurodontism. However, none of the patients with arrested eruption of M2inf had agenesis of the lower third molar. The study did not reveal an association between the degree of inclination of the M2inf and that of the first molar in the same region. The results of this investigation show that conditions such as the craniofacial morphology and deviations in the dentition are associated with arrested eruption of M2inf. Therefore, it is important to evaluate these conditions in future diagnosis and treatment planning of patients with arrested eruption of M2inf.
The sella turcica region, including the clivus and the pituitary gland, was studied histologically in five human fetuses with Meckel syndrome (MS). All cases had malformed sella turcica and malformed clivus with irregularly shaped notochordal remnants. We consider that these three characteristics are constant phenotypic traits in MS. The adenohypophysis was present in three cases. In one of these, ectopia of the gland occurred with adenopituitary tissue overlying the dorsum sella, and in another remnants were found in the pharyngeal submucosa. In two fetuses the neurohypophysis was not found. The findings in the region were compared to normal findings and to findings in trisomy 18, where cranial base structures radiographically appeared similar to those in MS. We conclude that in MS specific characteristics are found in the cranial base region and that radiographic analysis needs to be supplemented by histological analysis when studying this specific region.
The formation of the human alveolar process around the incisors and canines is a hitherto unreported aspect of fetal oral development. The question is how, where, and when the alveolar process is formed. The purpose of this study was to elucidate the questions where and when and hence to analyze the pattern of formation of the alveolar bone around developing human deciduous canine and incisor teeth. The study was conducted with material selected from a sample of 61 normal human fetuses, legally or spontaneously aborted. Fertilization ages ranged from 9 to 22 weeks, crown-rump Length from 25 to 205 mm, and foot length from 4 to 34 mm. From this material, 7 maxillae and 10 mandibles were selected for the study according to developmental stages of the canines and incisors and according to the orientation of the histological sections. The skeletal investigation consisted of macroscopic and microscopic analysis of the mandibles and maxillae. The investigations revealed the absence of bone between the central and lateral incisors in the mandibles and maxillae of fetuses below the ages of 21 and 22 weeks, respectively. In three specimens, alveolar bone between the central and lateral incisors was recorded (21, 21, and 22 weeks of fertilization). Absence of bone labial to the canine was recorded in all fetuses investigated. In all other regions, alveolar bone occurred as a regular finding. The present study has shown that alveolar bone formation is strictly coordinated with tooth formation. Alveolar bone occurs later in the area labial to the canine and in the region between the central and lateral incisors than it does in other areas associated with the incisor/canine regions. Knowledge of this pattern in the formation of the alveolar process seems to be of importance for a future elucidation of how the alveolar process is initially formed.
The purpose of the present investigation was to study the sella turcica/pituitary gland region in trisomy 21 fetuses and to relate the findings in the region to the ossification pattern in the axial skeleton formed by the cranial base and spine. Material from 22 human fetuses with trisomy 21, CRL 80 mm to CRL 190 mm, corresponding to gestational ages from 14 to 21 weeks, was examined and compared with material from gestation-matched normal controls. After radiography, tissue blocks from the cranial base, including the pituitary gland, were examined and compared with those of normal fetuses. Four different types of sella turcica/ pituitary gland morphology were observed. Thirteen fetuses (Type I) were morphologically normal. Minor abnormalities occurred in the sella turcica and pituitary gland (adenopituitary gland tissue pharyngeally) in six fetuses (Types II and III). There was agreement between the histologically recorded deviations in the sella turcica and the radiographic observations of the basisphenoid bone. In three cases (Type IV) out of 22, more pronounced structural abnormalities occurred in the sella turcica, and radiographically the basisphenoid bone appeared cleft. All sella turcica changes observed in trisomy 21 were situated anteriorly in the base of the sella. In all cases the basilar part of the occipital bone was normal. Minor changes in the sella turcica region were mainly accompanied by cervical vertebral abnormalities, while the most severe abnormalities occurred in association with malformations in the lumbar vertebrae. There was no association between sella turcica malformations and the absence or presence of the nasal bone.
STUDY DESIGN: Vertebral columns from 13 normal human fetuses (10-24 weeks of gestation) that had aborted spontaneously were investigated as part of the legal autopsy procedure. The investigation included spinal cord analysis. OBJECTIVES: To analyze the formation of the normal human vertebral corpora along the spine, including the early location and disappearance of the notochord. SUMMARY OF BACKGROUND DATA: Reference material on the development of the normal human vertebral corpora is needed for interpretation of published observations on prenatal malformations in the spine, which include observations of various types of malformation (anencephaly, spina bifida) and various genotypes (trisomy 18, 21 and 13, as well as triploidy). METHODS: The vertebral columns were studied by using radiography (Faxitron X-ray apparatus, Faxitron Model 43,855, Hewlett Packard) in lateral, frontal, and axial views and histology (decalcification, followed by toluidine blue and alcian blue staining) in and axial view. Immunohistochemical marking with Keratin Wide Spectrum also was done. RESULTS: Notochordal tissue (positive on marking with Keratin Wide Spectrum [DAKO, Denmark]) was located anterior to the cartilaginous body center in the youngest fetuses. The process of disintegration of the notochord and the morphology of the osseous vertebral corpora in the lumbosacral, thoracic, and cervical segments are described. Marked differences appeared in axial views, which were verified on horizontal histologic sections. Also, the increase in size was different in the different segments, being most pronounced in the thoracic and upper lumbar bodies. The lower thoracic bodies were the first to ossify. The morphologic changes observed by radiography were verified histologically. CONCLUSIONS: In this study, normal prenatal standards were established for the early development of the vertebral column. These standards can be used in the future--for evaluation of pathologic deviations in the human vertebral column in the second trimester.
The purpose of the present study was to evaluate hand size and maturity in fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length (CRL) 55-222 mm, foot length (FL) 8-42 mm, were included in the study. After whole-body radiography (Hewlett Packard Faxitron), special radiographs of the hand and foot were taken. Hand length was measured as the length of the third finger from the distal tip of the distal phalanx to the proximal tip of the metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL. The individual hand bones were evaluated with regard to time of appearance on radiographs, sequence in comparison with the normal sequence of appearance, and morphology. The hand length is normal during the first half of the fetal period, whereas the length of individual bones in the third finger is reduced. The normal sequence of ossification, with the middle phalanx of the fifth finger last to ossify, also occurred in Down syndrome; however, this bone appeared later in Down syndrome. In four of the fetuses it did not appear.