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Biomedical subjects

M H Kaufman

Publications and source records attributed to M H Kaufman.

At least 19 recordsLinked to original sources

Howison, the Cramond Murderer, and last person to be hanged and dissected.

An articulated skeleton in Edinburgh University's Anatomy Museum of "Howison, The Cramond Murderer", shares a show-case with the articulated skeleton of "William Burke, The Murderer". While the murderous activities of William Burke are well known, because of his association and activities with William Hare, and because they sold the bodies of their victims to Dr Robert Knox, the anatomist, little these days is recalled of Howison. He was executed for the murder of a woman in Cramond in December 1831, and was hanged on 21st January 1832. The case is important because he was the last individual executed before the implementation of the Anatomy Act of 1832. Accordingly, under the conditions of the previous Act, of 1752, entitled "An Act for better preventing the horrid Crime of Murder", his body had to be handed across to the surgeons to be "dissected and anatomized", before it could be buried.

Anatomy↗

Excision of a remarkable tumour of the upper jaw in 1834 by Robert Liston.

A series of pre-operative casts of the head, one of plaster of Paris and the other of wax, have recently been discovered in the Department of Anatomy, Edinburgh, of a patient with an immense tumour of the left maxillary antrum which produced an enormous degree of facial distortion. These casts complement a series of engravings published in the contemporary literature. This lady's tumour was successfully excised by Robert Liston in 1834 in the Royal Infirmary of Edinburgh, only a month before he left Edinburgh for London. The tumour was believed to be benign, and was removed without the benefit of anaesthesia. The patient returned the following summer to have a gold palate fitted, and while her voice was initially indistinct, it subsequently recovered.

History, 19th Century↗

Studies of the mechanism of amniotic sac puncture-induced limb abnormalities in mice.

The principal advantage of chorionic villus sampling (cvs) over amniocentesis for the determination of the genetic constitution of the embryo is that it may be undertaken earlier in pregnancy. If carried out too early in pregnancy, it has the risk of inducing craniofacial and limb abnormalities, a condition termed the oromandibulofacial limb hypogenesis (OMFL) syndrome in genetically normal infants. It is believed that the defects observed have a vascular origin, possibly due to anoxia of tissues due to fetal blood loss or thrombus formation at the site of biopsy with distal embolization. We believe that this does not adequately explain the findings from the experimental animal literature involving amniotic sac puncture (ASP). Based on these experimental findings, we have hypothesised that (i) the defects observed following cvs may result from the consequences of oligohydramnios following the inadvertent puncturing of the amniotic sac during this procedure, and (ii) that cleft palate and the postural limb defects observed (e.g., clubfoot and clubhand) are secondary to embryonic/fetal compression. Our experimental studies shed new light on the mechanism of induction of the limb defects seen, but particularly syndactyly. Evidence of hypoperfusion of the peripheral part of the developing limb bud is observed, which interferes with apoptosis that occurs in the digital interzones, or induces an abnormal degree of cellular proliferation and/or tissue regeneration in these sites, possibly because of over-expression of critical genes involved in limb pattern specification. Cleft palate, tail abnormalities and abnormalities of sternal ossification are also observed in our model.

Amniocentesis↗

The Penman case: a re-evaluation.

One of the most remarkable operations carried out in the Royal Infirmary of Edinburgh during the early decades of the 19th century was the surgical excision of an enormous tumour, believed to be an osteosarcoma, of the lower jaw of Robert Penman, that produced severe disfigurement of his face. James Syme, then in his late twenties, was invited to see the patient by Professor Ballingall and Dr John Abercrombie and, in July 1828, he operated, without the benefit of an anaesthetic, to completely remove the tumour. The patient not only survived the operation, but also remained in excellent health for many years afterwards. He emigrated to the United States, but occasionally returned home to Scotland. In 1855, Lord Lister, who noted that his "deformity" had been wonderfully masked by a bushy beard, saw him. This case is re-evaluated in the light of information from the archives in the Royal College of Surgeons of Edinburgh and from the contemporary and more recent literature.

Face↗

Observations on some of the plates used to illustrate the Lymphatics section of Andrew Fyfe's Compendium of the Anatomy of the Human Body, Published in 1800.

An engraving displaying A General View of the Absorbent System was used as one of many plates illustrating the Lymphatics section of Andrew Fyfe's Compendium of the Anatomy of the Human Body published in 1800. It is a scaled-down version of a life-size engraving displayed in the museum of the Department of Anatomy at the University of Edinburgh, and is based on a cadaver specially dissected and injected with mercury in 1788 by Alexander Monro secundus, probably with the assistance of Fyfe, who was his 'dissector'. Only recently has the relationship between these two engravings been established, and the Figure Legend in Fyfe's Compendium now provides the missing key to the features illustrated in the life-size engraving. The source and very variable quality of some of Fyfe's other plates, both in the Lymphatics section and elsewhere in the book, are discussed.

Anatomy, Artistic↗

Surgical outcomes in pure frontal lobe epilepsy and foci that mimic them.

In this study we examined 37 subjects with a diagnosis of intractable frontal lobe epilepsy (FLE) based on non-invasive pre-surgical evaluation. Twenty-six underwent chronic intracranial ictal recordings (CIR) with video monitoring; 20 of these went on to surgical resection. Eleven underwent surgery without CIR. Retrospectively, we determined that 19 had pure FLE, 12 had frontal plus extrafrontal epileptogenic zones, and six others did not have FLE. We analysed the whole group and individual categories to evaluate the determinants of surgical outcome. Sixty percent of the pure frontal group is seizure free with all having > or = 75% reduction. The frontal-plus group had only 10% seizure free with 70% having > or = 75% reduction. Being in the pure frontal group was associated with better outcomes than the 'frontal-plus' group (P < 0.05; chi-square). Subjects with FSIQ > or = 85, focal pathologies and 18FDG-PET scans which were normal or had focal abnormalities (P < or = 0.05, all, chi-square) were more likely to have excellent outcomes. MRI abnormalities, surface EEG, and location and size of resection were not predictive of surgical outcomes. Rasmussen's encephalitis, incomplete surgical strategies and bilateral foci were apparent in those with poor outcomes, and surgical size predicted post-operative deficits (chi-square; P < 0.001). We conclude that careful, hypothesis-driven implants and operating procedures can result in good surgical outcomes for frontal lobe epilepsy subjects even when lesions are not apparent on routine neuroimaging.

Adolescent↗

An internet-accessible database of mouse developmental anatomy based on a systematic nomenclature.

This paper reports an internet-accessible database of mouse developmental anatomy (DMDA) that currently holds a hierarchy of the names and synonyms of the tissues in the first 22 Theiler stages of development (E1-E13.5), together with other appropriate information. The purposes of the database are to provide, first, a nomenclature for analyzing normal and mutant mouse anatomy, and second a language for inputting, storing and querying gene-expression and other spatially organized data. DMDA currently contains some 6900 named and staged tissues (e.g. 360 and 1161 tissues in Theiler stage (TS) 14 (E9) and TS22 (E13.5) embryos). DMDA will be extended to include further lineage and other data when it becomes available. The database can be interactively accessed over the internet using either a Java or a non-Java WWW browser at http://genex.hgu.mrc.ac.uk/.

Animals↗

Analysis of interdigital spaces during mouse limb development at intervals following amniotic sac puncture.

A spectrum of limb abnormalities ranging from adactyly, syndactyly, acrosyndactyly to nail hypoplasia was encountered in mouse embryos subjected to amniotic sac puncture at the corresponding gestational stage when human chorionic villus sampling (cvs) would normally be performed clinically. Previous skeletal studies revealed that, apart from the occasional incidence of fusion of 2 distal phalanges, syndactyly usually only affected the soft tissues within the interdigital spaces. A similar situation was also observed in cases of adactyly; while the skeletal elements of the digits were present, the soft tissues in the interdigital spaces failed to separate. A transient period of bradycardia is induced, possibly secondary to compression of the embryo by the extraembryonic membranes and uterine muscles following amniotic sac puncture. These factors, we believe, produce temporary hypoxia/ischaemia of the distal extremities, and may lead to the modification of the interdigital mesenchymal tissues within the autopods. In order to investigate the mechanism(s) underlying soft tissue syndactyly, limbs recovered at 0.5, 4, 8, 12, 24, or 36 h following amniotic sac puncture (ASP) were examined histologically. Vascular disruption in the form of localised areas of haemorrhage, vascular dilatation and congestion and the presence of fluid-filled cavities occurred in relation to the marginal vein and vascular plexus in the interdigital spaces. It is hypothesised that this interfered with the normal equilibrium of the preset programs of mitosis/cell death and apoptosis within the mesenchymal cells of the interdigital spaces. Apoptosis in these areas was inhibited in the majority of the experimental limbs analysed 4 h after ASP. Instead of undergoing necrosis/apoptosis, increased mitotic activity was usually observed from 8 h following ASP at the sites where apoptosis would normally be expected to be seen. The aberrant fate of the interdigital mesenchyme following ASP and the underlying mechanism(s) involved are discussed, as is the critical importance of an adequate vascular supply to the interdigital spaces during the morphogenesis of the autopod. We believe that this report contributes to understanding the mechanism(s) which lead to syndactyly following ASP, and the limb defects occasionally seen following cvs when this is undertaken during early gestation.

Animals↗

Computer-generated three-dimensional reconstructions of serially sectioned mouse embryos.

We have been involved with a group of computer scientists and anatomists in the development of computer-based methodologies that not only combine the advantages of scanning electron microscopy and conventional histology, but provide the additional dimension of tissue recognition. The latter is achieved by the appropriate labelling of tissues and structures by delineation or 'painting'. Individually segmented anatomically defined tissues can be highlighted in a particular colour and viewed either in isolation or in combination with other appropriately labelled tissues and organs. Tissues can be shown in any orientation either as a transparent overlay on computer-generated histological sections or as 3-D images without the histological background. An additional feature of the system is that computer graphics technology combined with 3-D glasses now also allows the viewer to see the object under analysis in stereo. This facility has been found to be particularly helpful in drawing attention to topological relationships that had not previously been readily noted. As the mouse is now the mammalian model of choice in many areas of developmental research, it is of critical importance that a basic level of skill is available in the research community in the interpretation of serially sectioned material, for example, for the rapidly expanding field in which gene expression studies play a significant role. It is equally important that there is an understanding of the dynamic changes that occur in relation to the differentiation of the various organ systems seen in these early stages of development. What we emphasise here is the additional information that it is possible to gain from the use of this tool which, in our view, could not readily have been gained from the analysis of scanning electron micrographs or by studying conventional serial histological sections of similar stages of mouse embryonic development. The methodology has been developed as part of a large project to prepare a database of mouse developmental anatomy covering all stages from fertilisation to birth in order to allow the accurate spatial mapping of gene expression and cell lineage data onto the digital Atlas of normal mouse development. In this paper we show how this digital anatomical Atlas also represents a valuable teaching aid and research tool in anatomy.

Anatomy, Cross-Sectional↗

Influence of anaesthetic agent on limb abnormalities observed following amniotic sac puncture.

In all of our previous studies into the effect of amniotic sac puncture (ASP) carried out on day 13 of pregnancy in mice, we have used intraperitoneal Avertin (tribromoethanol) as the general anaesthetic. In the present study, we used an inhalational anaesthetic (a mixture of halothane, oxygen and nitrous oxide in a ratio of 2:3:3). The principal difference between these two regimens is that even under optimal post-operative conditions when Avertin is used it can take between 45 and 90 min before complete recovery is achieved; when the inhalational anaesthetic is used, complete recovery is usually achieved within about 3-5 min. Because the experimental conditions were otherwise identical, this allowed the influence of the anaesthetic employed during ASP and the incidence of abnormalities induced on survival rate to day 19 of pregnancy to be studied. The survival rate was slightly higher when the inhalational anaesthetic was used, as was the incidence of limb abnormalities, although the overall incidence of gross abnormalities involving the palate, limbs and tail was not significantly different. The most marked difference, however, was in the incidence of syndactyly, which was significantly lower when the inhalational compared to the intraperitoneal anaesthetic was used: 26.6% v. 70.2% of the abnormal limbs analysed. A possible hypothesis is presented to explain this difference.

Amnion↗

Genetic background effects on dental and other craniofacial abnormalities in homozygous small eye (Pax6Sey/Pax6Sey) mice.

Small eye (Pax6Sey) is a semi-dominant mutation affecting development of the eyes, brain and nasal structures. The mutant phenotype arises from defects within the Pax6 gene and several mutant alleles have been identified. A previous study reported that Pax6Sey/Pax6Sey homozygotes, in a random-bred stock, had a median cartilaginous rod-like structure in the nasal region and 80% had supernumerary upper incisor teeth. In this study we show that supernumerary upper incisor teeth and a previously unreported nasal capsule-derived cartilaginous 'spur' occur in compound heterozygous Pax6Sey-Neu/Pax6Sey and homozygous Pax6Sey/Pax6Sey fetuses from several strains of mice. The frequencies of the abnormal phenotypes were not related to allele type but showed variable penetrance, which was dependent on genetic background. The median nasal cartilaginous rod-like structure was present in all homozygous small eye fetuses. The Pax6Sey/Pax6Sey homozygote may provide insight into the complex gene interactions involved in eye, nasal and craniofacial morphogenesis.

Animals↗

Transient bradycardia in a mouse model for the oromandibulofacial limb hypogenesis syndrome following chorionic villus sampling.

Amniotic sac puncture carried out on day 13 mouse embryos induces a high incidence of craniofacial and limb abnormalities that resemble the anomalies seen in the oromandibulofacial limb hypogenesis syndrome occasionally encountered following chorionic villus sampling carried out during early human pregnancy. It has been hypothesized that this syndrome probably has a vascular basis, possibly due to hypotension and hypoperfusion of tissues secondary to placental trauma, though no detailed aetiology has so far been described. We have determined embryonic heart rates in control embryos, in embryos at intervals following anaesthesia, and following amniotic sac puncture. An increased duration of bradycardia is seen following this procedure which is not observed in anaesthetic-only controls and in embryos in the contralateral (non-operated) uterine horns. We discuss why the incidence of oromandibulofacial limb hypogenesis syndrome is low following chorionic villus sampling, and propose a possible aetiology for the limb abnormalities seen in this condition.

Abnormalities, Multiple↗

Morphometric analysis of the postnatal mouse optic nerve following prenatal exposure to alcohol.

Pregnant female mice were divided on day 12 post coitum into a control and an experimental group. The experimental group was given a single intraperitoneal dose of 0.015 ml/g body weight of 25% solution of alcohol in distilled water while the control group was exposed to a similar weight related dose of normal saline. The optic nerves were isolated from the offspring of both control and experimental groups at wk 2, 3 and 5 (i.e. during the juvenile period of postnatal development) and analysed by light and electron microscopy. Although in both groups the optic nerve grew in size rapidly during the period studied, the rate of growth in the experimental groups lagged behind that of the controls. The difference was initially significant but tailed off, so that by wk 5 it was no longer significant. The time of initial onset and progression of myelinogenesis in the optic nerve of alcohol exposed mice also lagged behind that of controls. In both groups the size distribution of the myelinated nerve fibres in the optic nerve was unimodal with a positive skewing for all ages. The spectrum of size distribution of the nerve fibres was, however, broader in controls than in the corresponding experimental groups. With increasing age the proportion of small and medium size fibres was greater in the experimental group than in the controls, while for the large diameter fibres the reverse was observed. It is suggested that this study may shed light on the teratogenic effect of 'binge' drinking during pregnancy and that it is the critical period when exposure occurs that is more important than the duration of administration.

Animals↗

Analysis of fused maxillary incisor dentition in p53-deficient exencephalic mice.

Out of a total of 21 exencephalic p53-deficient embryonic and newborn mice, 6 (28.6%) possessed fused maxillary incisor teeth. On histological analysis of the 5 examples seen on day 19.5 of gestation and newborn mice, 3 varieties were observed: an example of 'simple' fusion, 3 examples of simple fusion each of which contained a 'dens in dente' ('tooth within a tooth'), and a single example in which the fused teeth were associated with a median supernumerary incisor tooth which, while deeply indenting the labial surface of the fused teeth, was in all locations a completely separate unit. 3-D reconstructions of the fused teeth demonstrated that they were all of the fusio subtotalis variety. No gross abnormalities were observed in the other dentition in these mice. It is noted that in mice fused maxillary incisor teeth are relatively commonly associated with both hypervitaminosis A-induced and trypan blue-induced exencephaly. It is believed that the presence of dens in dente within fused maxillary incisor teeth has only once been reported in mice, and the association between fused maxillary incisor teeth and a median supernumerary incisor tooth has not previously been reported in this species.

Animals↗

Myelinogenesis in the optic nerve of (C57BL x CBA) F1 hybrid mice: a morphometric analysis.

Myelinogenesis in the optic nerve of the mouse begins by the end of the first week of postnatal life and proceeds well into adulthood. The optic nerve from different postnatal age groups of (C57BL x CBA) F1 hybrid mice was analysed ultrastructurally and morphometrically. Features examined were the myelinated and unmyelinated nerve fibres, mean myelinated nerve fibre diameter, myelinated nerve fibre diameter spectrum, number of myelin sheath lamellae in relation to fibre diameter and age. Results obtained showed that the optic nerve of the mouse is populated entirely by unmyelinated nerve fibres at birth. Myelinogenesis begins at about the fifth postnatal day (pnd), with clearer evidence by the 6th pnd. It starts selectively with the largest fibres and then progresses to involve other fibres of decreasing diameter. After the onset, myelinogenesis progresses with increasing rapidity, becoming most intense from the second week up to the fifth week, so that by the end of the fifth week about 73% of fibres have become myelinated. From then onward, the process proceeds at a progressively diminishing rate until, by the 16th week, virtually all the remaining 27% fibres are myelinated. At onset, the myelin sheath is loosely wrapped around the axons, but with increasing age the myelin lamellae become more compact around the axons. The population of unmyelinated fibres continued to diminish so that at the completion of the process (16th week), they were only very rarely encountered. Myelinogenesis in the optic nerve of the mouse appears to follow a similar course to that seen in other central tracts having a similar fibre diameter spectrum.

Aging↗

Computer-aided 3-D reconstruction of serially sectioned mouse embryos: its use in integrating anatomical organization.

This paper reviews recent work on a project that uses a computer-aided approach for making 3-D reconstructions of serially sectioned mouse embryos (the digital mouse). The captured images are aligned using a warping program so that almost perfect alignment of adjacent sections is achieved with minimal deformation. The sections that are viewed on the computer screen are in fact computer-generated grey-level images with a resolution of about 10 microm. The reconstructed embryo may then be resectioned in any plane to simulate as near as possible an exact match on the computer screen to the viewer's own material. Individual anatomical domains may then be painted in different colors, and these domains may be selected by querying the textual database containing anatomical and other information. Further, it is now possible to generate 3-D images of individual anatomically-discrete components or related sets of components of a particular system in isolation from the rest of the embryo, or, if required, against a 'ghost-like' image of the intact embryo, or specific parts of an embryo. In the article, examples are given of the use of the system in interpreting the vascular, gut and paraxial mesoderm systems, while both the advantages and disadvantages of this approach are also discussed. The eventual aim will be to provide 3-D reconstructions of mouse embryos from fertilization up to 14 days postcoitum of development. When completed, this project will allow the accurate spatial mapping of gene-expression and cell lineage data onto the digital Atlas of normal mouse embryonic development.

Animals↗

The gunner with the silver mask: observations on the management of severe maxillo-facial lesions over the last 160 years.

We would like to present a case of severe maxillo-facial trauma occurring over 150 years ago. The case involves a French artillery gunner, Monsieur Alphonse Louis, who received shrapnel injuries from an exploding shell at the Siege of Antwerp in 1832. He sustained near fatal injuries. The fact that he survived is probably due to his rapid evacuation from the battle site, as the French did not like to leave their wounded lying in 'no man's land', prompt surgery and subsequent expert medical and nursing care. M. Louis' maxillo-facial injuries included loss of the entire mandible. As a consequence, the patient had a grotesque appearance and was unable to eat or talk properly. At this time the surgeons of the day had no specialist knowledge of how to reconstruct the lower jaw. Where specialist knowledge or facilities were absent, then as now, improvisation was called for. A silversmith was duly approached and asked to construct a mask to act as a replacement for the deficient lower face. We describe here what an excellent cosmetic and functional result the mask gave, and how it led to the patient being successfully rehabilitated. Almost a century later, during the First World War, pioneering work by Major Harold (later Sir Harold) Gillies and his colleagues led to the first attempts at anatomical mandibular reconstruction. His patients, like M. Louis, were soldiers injured in battle. We will describe his techniques and compare them with how this problem is approached in the modern era, although most reconstructive surgery to the maxillo-facial region these days follows the removal of comparably extensive areas of soft tissue and bone as a result of invasive tumour.

Europe↗