Aspects of the history of osteogenesis imperfecta (Vrolik's syndrome).

Osteogenesis imperfecta (OI) or Vrolik's syndrome is a heterogeneous group of inherited conditions arising from a variety of biochemical and morphological collagen defects. It was Willem Vrolik, Professor of Anatomy, Pathological Anatomy and Zoology at the Athenaeum Illustre (University of Amsterdam), who described in his Handbook of Pathological Anatomy (1842-1844) and Tabulae ad illustrandam embryogenesin hominis et mammalium, naturalem tam abnormem (1844-1849) a newborn infant with numerous fractures and hydrocephalus. In the Tabulae, having both Latin and Dutch texts, in the Latin text Vrolik used in the heading of Plate 91 the term Osteogenesis imperfecta (in Dutch: gebrekkige beenwording). Vrolik also mentioned that the infant lived three days and that both the parents were suffering from lues universalis at the time of birth. On our reexamination, the whole skeleton appeared poorly mineralised. The fairly large skull exhibited a broad and high forehead, large fontanels, frontal and temporal bossing, shallow orbits, and a protruding occiput. The calvaria consisted of many Wormian bones. The tubular bones, although of normal length and only slightly curved, were very thin, as were the ribs. All the skeletal structures showed one or more fractures and many fractures showed callus formation. In 1998 we re-diagnosed the condition of the specimen as osteogenesis imperfecta type II. Willem Vrolik was one of the first to realize that many skeletal dysplasias were not the result of a postnatal acquired disease, such as "rickets" or "osteomalacia" as many of his contemporaries believed. He thought that it might be due to insufficient intrinsic "generative energy." He substantiated this by stating that in this specimen a primary impairment of ossification is present and not a secondary degeneration. The descriptions given by Willem Vrolik in some of the specimens generated the term Osteogenesis imperfecta and the eponym Vrolik's syndrome for this genetic disorder characterized by increased fragility.

Processed porcine collagen tubulization versus conventional suturing in peripheral nerve reconstruction: an experimental study in rabbits.

In peripheral nerve reconstruction, various procedures are used. One of the procedures that received the most interest in the past decade is the tubulization technique for small nerve gaps. A disadvantage in the use of non-biodegradable tubes is that the material often has to be removed owing to its mechanical properties. Some investigators, in exploring the use of collagen tubes, being a natural biodegradable material, found either allogenicity or xenogenicity and immune responses that may inhibit nerve regeneration. Processed porcine collagen (PPC) is a new inert and biodegradable material that has a favorable effect on wound healing, as demonstrated by experiments on other tissues. The aim of our study was to compare the healing of nerve sutures with PPC tubes with conventional end-to-end sutures. In our experiments, we reconstructed the saphenous nerves of 27 rabbits. In series 1 (n = 12) and 2 (n = 12), PPC tubes were slid over an end-to-end nerve suture without or with a 10-mm nerve gap, respectively. In series 3 (n = 12), conventional suturing was performed in the collateral saphenous nerves of the animals of series 1. Epineurial suturing was performed. Three other non-operated saphenous nerves served as controls. The healing was studied after 3, 6, and 12 months in sections stained by monoclonal antibodies and by conventional histologic staining. Morphometric analysis of the regenerating axons was done by using confocal scanning laser microscopy (CLSM). Data analysis was carried out using a software program especially developed for this purpose. All results were evaluated statistically. Our results showed that during the healing period in the distal nerve stump, the number of axons of the PPC procedure with a 10-mm gap was significantly higher than that in the procedure without a gap. At 12 months, the mean number of axons of all procedures was significantly lower than in the non-operated nerve, and the mean axon diameter in all distal stumps did not differ significantly from that of the non-operated nerve. In the distal nerve stump, the ratio of total axon area to total fascicle area in the PPC procedure with a gap was significantly higher than that in the conventional suturing procedure. After 12 months, there was no significant difference between the percentages of axon outgrowth of the PPC procedure without a gap, the conventional suturing procedure, and the non-operated nerve (100%). The percentage of axon outgrowth in PPC with a gap was significantly higher than in the other procedures.

Silicone rubber tubulization in peripheral sensory nerve reconstruction: an experimental study in rabbits.

Silicone rubber (polydimethyl siloxane) tubes are used clinically in peripheral nerve reconstruction. A disadvantage of this procedure is that the material often has to be removed owing to its mechanical properties. The aim of our study was to investigate the healing of reconstructed sensory nerves tubulized by silicone rubber in an animal model. In our experiments, we reconstructed the saphenous nerves in 27 rabbits. In series 1 (n = 12), silicone rubber tubes were slid over a nerve suture without a gap. In series 2 (n = 12), silicone rubber tubes were slid over a 10-mm nerve gap. In series 3 (n = 12), conventional suturing was performed in the collateral saphenous nerves of the animals of the series 1. Epineurial suturing was performed. Three other collateral nonoperated saphenous nerves served as controls. The healing was studied after 3, 6, and 12 months. Morphometric analysis of the regenerating axons was performed by using our new method for quantification of nerve fibers in cross sections stained by immunohistochemistry and using confocal laser scanning microscopy. Data analysis was carried out using a software program especially developed for this purpose. Our results showed in the silicone procedures that at 12 months significantly fewer axons per fascicle area were present compared with conventional suturing. However, mean axon diameters in the distal nerve stump of the silicone procedures did not differ significantly compared with the conventional suturing procedure. The ratio of total axon area to total fascicle area in the distal nerve stumps of the silicone procedure without gap was significantly smaller compared with the conventionally sutured nerve. The percentage outgrowing axons from the proximal nerve stump into the distal one in the silicone rubber procedure without gap was 57%. This was significantly higher than in the silicone rubber procedure with 10-mm gap (48%). However, in conventional suturing, the percentage of outgrowing axons (99%) was significantly higher than in both tubulization procedures. It appeared that tubulization by silicone rubber of sutured nerves without gap did not enhance axon regeneration. Conventional suturing gave significantly better results. If a gap was present, the use of a silicone rubber tube was preferable to non-suturing.

Method for morphometric analysis of axons in experimental peripheral nerve reconstruction.

A new method for morphometric analysis of axons in experimental peripheral nerve reconstruction is presented. Twelve adult female rabbits were used. In nine animals the saphenous nerve was transected and stitched epineurially. Three animals functioned as control. After 3, 6, and 12 months, the nerves were harvested, fixed in Kryofix and embedded in Histowax. Transverse sections of 6 microm were cut, immunohistochemically stained for NF 90, and counterstained by Sirius Red. Quantification of nerve fibers in cross sections was performed by using a confocal laser scanning microscope (CLSM), and the images were stored digitally. Data analyzing was performed by the Optimas program (5.2). Calculations were done with Microsoft Excel. The total number of axons, the mean axon diameter and the percentage axon area/fascicle area were evaluated statistically. This method for morphologic analysis provides automatically complete registration of axons and so different methods of experimental nerve reconstruction can be compared in a fast and reliable way.

The painted Amsterdam anatomy lessons: anatomy performances in dissecting rooms?

The Anatomy Lesson of Dr. Nicolaes Tulp, painted by Rembrandt in 1632, has recently been fully restored. From 02-10-98 to 10-01-99 this painting and some other Amsterdam painted anatomy lessons were exhibited in the Mauritshuis in The Hague, with the title "Rembrandt under the scalpel". The unique Tulp painting is one of those portraits painted in the tradition of the famous group portraits which flourished in 17th-century Holland, a predominantly urban, middle-class society where the main patrons of the arts were the leading citizens of the various towns. Moreover, it is a portrait in the tradition of the anatomy lessons especially painted for the Guild of Surgeons for their Guild Room. Nine such lessons have been painted for the guild and are still to be found in Dutch museums (Mauritshuis and Amsterdam Historical Museum). The anatomy lesson of Prof. Andreas Bonn, dated 1792, as well as some group portraits of the leading persons of the guild also play an important role in the Amsterdam group portraits. In 1925 the Amsterdam anatomist Louis Bolk commissioned Martin Monnickendam to paint another anatomy lesson. The restoration of the painting of Dr. Tulp has provided new information concerning the original composition of Rembrandt and the later additions. However, from an anatomical point of view, it is doubtful whether the Amsterdam anatomy lessons depict a real contemporary anatomical demonstration. They provide, together with archival sources, reliable information about the praelectores anatomiae and the leading persons of the guild, but fail to give much information about the dissecting room, the anatomy theatre or the procedure. The anatomical demonstration procedures of the guild are discussed in relation to the painted anatomy lessons.

A 100-year-old anatomical specimen presenting with boomerang-like skeletal dysplasia: diagnostic strategies and outcome.

The Museum Vrolik collection of human anatomy comprises 360 recently redescribed specimens with congenital anomalies. The specimen described here dated from 1881 and presented with a general embryonic appearance, disproportionate short stature, brachycephaly, widened cranial sutures, hypertelorism, microphthalmia, bilateral cleft lip and palate, micrognathia, short and curved limbs, polysyndactyly, and abnormal female genitalia. Conventional radiography was hampered by decalcification of the skeleton, due to acidification of the preservation fluid. The use of additional imaging techniques, i.e., mammography, computerized tomography with three-dimensional reconstruction, and magnetic resonance imaging eventually led us to conclude that the condition of our specimen was similar to Piepkorn type skeletal dysplasia, boomerang dysplasia, and a condition described by Carpenter and Hunter [1982: J Med Genet 19:311-315], though none of these diagnoses seemed fully applicable.

Digital data and the 19th century teratology collection.

The golden age of descriptive teratology (congenital anomalies) was between 1750 and 1850. During that period, the study of human congenital malformations, especially those dramatic examples designated as 'monsters', attracted special attention. One of the finest collections in this field was Museum Vrolikianum, the collection of father and son, Gerardus (1775-1859) and Willem Vrolik (1801-1863). Willem, a specialist in teratology, described many of these specimens in his Handbook of Pathological Anatomy (1844) and his teratology atlas Tabulae ad illustrandam embryogenesin hominis et mammaliam tam naturalem quam abnormem (1849). This collection is still an integral part of the Museum Vrolik in the Academic Medical Center in Amsterdam. From 1991 to 1994, the collection of congenital anomalies was re-catalogued and re-described according to contemporary syndromological views. We diagnosed rare syndromes with multiple congenital anomalies, rare skeletal dysplasias, closure defects of the neural tube and conjoined and acardiac twins. We came to the conclusion that some anomalies of the conditions diagnosed have been reported only a few times. Certain cases demonstrate relationships between different malformations, and provide critical 'missing links' in the teratological series. For the diagnosis of the clinical syndromes in some of the specimens magnetic resonance imaging (MRI), computed tomography (CT), spiral CT and radiographical techniques were of crucial importance and are discussed in this paper.

[Cynocephali and Blemmyae. Congenital anomalies and medieval exotic races]. / Cynocephali en Blemmyae. Aangeboren afwijkingen en middeleeuwse wonderbaarlijke rassen.

In the mediaeval Dutch manuscript Der naturen bloeme ('On the flowers of nature') by Jacob van Maerlant (circa 1230-circa 1296), an encyclopaedia of descriptions of people, animals, plants and minerals dating from about 1270, many illustrations refer to the text. An intriguing part of the book is called 'Vreemde volkeren' ('Exotic people'). In another manuscript of Van Maerlant, Dit is die istory van Troyen ('The history of Troyes') in the chapter 'De wonderen van het Verre Oosten' ('The miracles of the Far East') the exotic people are also described. These exotic people have many features similar to congenital malformations. 'Hippopodes' are probably based on the lobster claw syndrome, 'Cynocephali' on anencephaly, 'Arimaspi' on cyclopia, 'Blemmyae' on acardiacus, the double-faced on diprosopus, 'Sciopods' on polydactyly and 'Antipodes' on the sirenomelia sequence.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. IV: closure defects of the neural tube.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than 5,000 specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies, comprising 360 specimens, was recatalogued and redescribed according to contemporary morphogenetic opinions. The original descriptions, as far as preserved, were compared with the clinical and additional findings. Based on the classification by closure site, proposed by Van Allen et al. [1993], the following closure defects of the neural tube were diagnosed in 107 specimens: craniorachischisis, holoacranium with partial rachischisis, faciocranioschisis, holoacranium, meroacranium, occipital cranioschisis, frontal encephalocele, parietal encephalocele, occipital encephalocele, occipital encephalocele with rachischisis, occipito-cervical encephalocele, thoracolumbar spina bifida, lumbosacral spina bifida, occult sacral dysraphism, and sacrococcygeal dysgenesis. Furthermore, we diagnosed three conditions that did not appear in the aforementioned classification; we named these conditions craniorachischisis totalis, occipital craniorachischisis, and thoracolumbosacral spina bifida. The results of our study are in line with the assumption that particularly occipito-cervical neural tube defects are associated with concomitant anomalies and are more common in females. The results support the idea of multisite closure of the human neural tube.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. III: primary field defects, sequences, and other complex anomalies.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the Academic Medical Center, University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than 5,000 specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies, comprising 360 specimens, was recatalogued and redescribed according to contemporary morphogenetic views. The original descriptions, if preserved, were compared with the clinical, radiographical, and magnetic resonance imaging findings. In 120 specimens the following midline anomalies, primary field defects, and sequences were diagnosed: holoprosencephaly sequence; aprosencephaly/atelencephaly; cleft lip; Pierre Robin sequence; omphalocele; diaphragmatic hernia; ectopic heart; bladder exstrophy; cloacal exstrophy; caudal dysgenesis; prune belly sequence; sirenomelia; fetal akinesia sequence; and disruption sequences. Polytopic field defects and associations were diagnosed in 25 specimens. We discuss the opinions of Gerardus and Willem Vrolik, who tried to find reasonable explanations for the dysmorphogenetic entities they investigated, rather than accepting the traditional superstitions.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. V: conjoined and acardiac twins.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the Academic Medical Center, University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than 5,000 specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies, comprising 360 specimens, was recatalogued and redescribed according to contemporary perspectives. The original descriptions, as far as preserved, were compared with the clinical, radiographic, and magnetic resonance imaging findings. We diagnosed 30 symmetrical conjoined twins (CTs), 11 parasitic CTs, and 16 acardiac twins. Within the group of symmetrical CTs, the following concomitant external anomalies were found in 15 specimens: neural tube defects, holoprosencephaly, cleft lip/palate, umbilical hernia, omphalocele, cloacal exstrophy, peromelia, polydactyly, and facial abnormalities suggestive of a chromosomal abnormality. We discuss the results in the light of historical and contemporary explanations regarding conjoined twinning, including the opinions of Gerardus and Willem Vrolik and of Louis Bolk, one of their successors.

Historical aspects of the study of malformations in The Netherlands.

The collection of malformed ("teratological") specimens of man and other mammals of Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), dating from the beginning of the 19th century, continues to function as a central part of the Department of Anatomy and Embryology in the Academic Medical Center at the University of Amsterdam. Recently, many specimens in the collection were reexamined, using radiographic, CT scan, and MRI methods. In order to provide background information concerning Dutch teratological research and anatomical cabinets, some aspects of the history of Dutch morphology during the 17th-19th centuries are briefly described in this paper. Special attention is paid to the scientific work and cabinet of Frederik Ruijsch (1638-1731), who sold this cabinet to Czar Peter the Great; Bernard Siegfried Albinus (1697-1770); Wouter van Doeveren (1733-1783), Andreas Bonn (1738-1818), and Sebald Justinus Brugmans (1763-1819), who sold or donated parts of their collections of malformed specimens to Leiden University; Petrus Camper (1722-1789) and Jan Bleuland (1756-1838), whose collections are still in the Department of Anatomy at Groningen University and the Departments of Anatomy and Pathology of Utrecht University; and Gerard and Willem Vrolik.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. I: Syndromes with multiple congenital anomalies.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than 5,000 thousand specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies was recatalogued and redescribed according to contempory syndromological views. The original descriptions, as far as preserved, were compared with the clinical and radiographical findings. In 13 specimens the following multiple congenital anomalies (MCA) syndromes were diagnosed: acrofacial dysostosis, Apert syndrome, Brachmann-De Lange syndrome, ichthyosis congenita gravis, Jarcho-Levin syndrome, Meckel syndrome, oro-facio-digital syndrome type IV, Roberts syndrome, Smith-Lemli-Opitz syndrome, Treacher Collins syndrome, and trisomy 13. It appeared that the founders of the museum studied and described several of these syndromes many years before they became established as such. In some specimens a reliable diagnosis is still pending. The use of additional diagnostical techniques, such as MRI, CT scanning, and fluorescence in situ hybridization, in these specimens is currently being investigated.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. II: Skeletal dysplasias.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than five thousand specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies was recatalogued and redescribed according to contempory syndromological views. The original descriptions, as far as preserved, were compared with the clinical and radiographical findings. In 18 specimens the following skeletal dysplasias were diagnosed: achondrogenesis, achondroplasia, Blomstrand chondrodysplasia, Majewski syndrome, osteodysplastic primordial dwarfism, osteogenesis imperfecta type I, osteogenesis imperfecta type II, and thanatophoric dysplasia with and without cloverleaf skull. Radiography did not yield a diagnosis in 4 specimens. The use of additional diagnostical techniques, such as MRI and CT scanning and fluorescence in situ hybridization in these specimens, is currently being investigated.

[Veterinary double-monsters historically viewed]. / Als twee animalcula in het ovum komen. Veterinaire dubbelmonstra in historisch perspectief.

A large number of duplication monstrosities have been observed in cattle, sheep, pigs, horses, goats, cats and dogs, ever since the publication of the famous woodcut of a swine double monster by J. S. Brant in Basel in 1496, better known as the "wunderbare Sau von Landser im Elsass". Albrecht Dürer also made a woodcut of this double monster in front of the village Landser in 1496. A picture of a deer double monster was published in 1603 by Heinrich Ulrich in Germany. In the monograph De monstrorum causis, natura et differentiis ..., published by the Italian Fortunius Licetus in 1616 pictures of double monsters being half man half dog are found. These fantasy figures have been popular for a long time and were supposed to be really in existence. Apart from these fantasy figures many pictures are known from real veterinary double monsters. U. Aldrovandus described in 1642 in his Monstrorum historia, besides many fantasy figures, also real human and veterinary double monsters and he gave also good pictures of them. In the 19th century examples of veterinary duplication monstrosities were published by I. Geoffroy Saint-Hilaire (1832-37), E. F. Gurlt (1832), W. Vrolik (1840) and C. Taruffi (1881); they proposed also concepts concerning the etiology. In the second volume of his famous handbook of teratology (1907), E. Schwalbe described many veterinary double monsters and discussed the theories of the genesis of congenital malformations. Various theories concerning the genesis of double monsters have been given since Aristotle (384-322 B.C.). ...

A retrograde double fluorescent tracing study of the levator palpebrae superioris muscle in the cynomolgus monkey.

In the cynomolgus monkey, motoneurons innervating the levator palpebrae superioris muscle form a nucleus within the oculomotor nuclei called the central caudal nucleus. After double fluorescent neuronal retrograde tracing experiments, using fast blue and diamidino yellow as tracers in the levator palpebrae superior muscles, labelled motoneurons (30%) were found in an unpaired central caudal nucleus. Approximately 2% of the labelled motoneurons were double-labelled. The labelled and double-labelled neurons were distributed randomly over the central caudal nucleus, lateralization of populations of levator motoneurons within this nucleus was not observed. The afferent innervation of the levator palpebrae superioris muscle was restricted to the ophthalmic branch area of the gasserian ganglion. Primary afferent labelled neurons were absent from the mesencephalic nucleus of the fifth nerve. Surprisingly, fast blue was also found in the ophthalmic branch area of the contralateral ganglion of Gasser, while diamidino yellow was present only ipsilaterally. About 1% of the afferent labelled neurons were double-labelled. The results reveal that in the cynomolgus monkey the central caudal nucleus is not only topographically but also functionally one nucleus. Afferent innervation of the levator palpebrae superioris muscle is probably bilaterally organized.

Smith-Lemli-Opitz syndrome diagnosed in a 130-year-old anatomical specimen.

The Museum Vrolik collection of human anatomy comprises 360 recently re-described specimens with congenital anomalies. The external findings in one of these specimens, originally described by Willem Vrolik (1801-1863) 130 years ago, were suggestive of Smith-Lemli-Opitz (SLO) syndrome. Cholesterol synthesis was analyzed in skin biopsies, obtained from the suspected SLO specimen and a control specimen. The cholesterol levels in the SLO specimen and in the control specimen were in the proportion of 1 to 45. This confirms the diagnosis in this specimen which, to our knowledge, represents the oldest known case of SLO syndrome.

Innervation of the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey: a retrograde fluorescent tracing study.

Retrograde fluorescent transport of Fast Blue (FB) and Diamidino Yellow (DY) was used to study the localisation of neurons that innervate the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey. Labelled cell bodies of sensory neurons including a few double labelled cell bodies were found in the ophthalmic part of the ipsilateral trigeminal ganglion. Labelled cell bodies of the sympathetic neurons including a few double labelled cell bodies were located in the middle and cranial part of the ipsilateral superior cervical ganglion, with a few in the contralateral ganglion. Labelled cell bodies of the parasympathetic neurons were all found in the ipsilateral pterygopalatine ganglion and randomly distributed. Neurons were disposed in the opthalmic part of the trigeminal and superior cervical ganglia, whereas parasympathetic neurons were distributed randomly. Cells of the nodose, ciliary, geniculate, otic and first 3 spinal ganglia were unlabelled. Tracing FB and DY from the palpebral conjunctiva and superior tarsal muscle respectively, revealed double labelled neurons in the trigeminal and superior cervical ganglia, probably indicating the presence of collaterals of axons serving both the palpebral conjunctiva and the superior tarsal muscle.

Innervation of the lacrimal gland in the cynomolgous monkey: a retrograde tracing study.

Retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was used to study the localisation of neurons that innervate the lacrimal gland of the cynomolgous monkey. WGA-HRP-labelled neurons were localised in the ipsilateral trigeminal, superior cervical and ciliary ganglia and in the ipsilateral and contralateral pterygopalatine ganglia. In the trigeminal ganglion WGA-HRP-labelled somata were found in the ophthalmic part (18%) and the maxillary part (5%). Identification of labelled neurons in the ciliary and pterygopalatine ganglia indicates a dual parasympathetic innvervation of the lacrimal gland. There is no known pathway to account for the contralateral location or pterygopalatine neurons. These novel findings are incorporated in a concept of a neural control mechanism for the lacrimal gland.