Forecasting the prognosis of a patient with a tumour.
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Astrocytoma↗
Biomedical subjects
R O Weller
Publications and source records attributed to R O Weller.
Pathways of fluid drainage from the brain--morphological aspects and immunological significance in rat and man.
There is firm physiological evidence for the lymphatic drainage of interstitial fluid and cerebrospinal fluid from the brains of rats, rabbits and cats. The object of this review, is to describe firstly the morphological aspects of lymphatic drainage pathways from the rat brain and secondly, to explore through scanning and transmission electron microscope techniques, the possibility of similar lymphatic drainage pathways in man. Interstitial and oedema fluid spreads diffusely through the white matter in the rat and appears to drain into the ventricular cerebrospinal fluid. In grey matter, however, tracers pass along perivascular spaces to the surface of the brain and into the cerebrospinal fluid. Paravascular compartments in the subarachnoid space follow the course of major arterial branches to the circle of Willis and thence along the ethmoidal arteries to the cribriform plate of the ethmoid bone. Particulate tracers, such as Indian ink, enter channels in the arachnoid beneath the olfactory bulbs and connect directly with nasal lymphatics through channels which pass through holes in the cribriform plate. Proteins and other solutes may also drain along other cranial nerves. Thus, there is a bulk flow pathway for interstitial and cerebrospinal fluid from the rat brain into cervical lymphatics. In man, it is probable that diffuse interstitial drainage of fluid from the white matter occurs in a similar way to that in the rat. Furthermore, the anatomical pathways exist by which bulk drainage of fluid could occur along perivascular spaces from the grey matter into perivascular spaces of the leptomeningeal arteries and thence into the cerebrospinal fluid (CSF).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A further British case of growth hormone induced Creutzfeldt-Jakob disease.
Transmission of Creutzfeldt-Jakob disease (CJD) from cadaveric growth hormone injections had previously been reported in 7 cases, including one from Britain. As a result, the treatment was abandoned in 1985 and superceded by safer recombinant DNA growth hormone injections. Recent reports now record the number of cases worldwide as 23, but with the incubation period being measured in years, new cases of CJD can still present. We give a detailed report of one of the recent cluster of British cases and aim to highlight the problem to clinicians who may encounter further patients with cadaveric growth hormone induced CJD.
Adult↗
Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity.
Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis--motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles ('skeins') of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intraneuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.
Adult↗
Spindle-cell glioblastoma or gliosarcoma?
'Gliosarcomas' have long been considered to be mixed gliomas and sarcomas. The present study failed to define criteria which clearly delineate 'gliosarcomas' from glioblastoma multiforme and suggests that 'gliosarcomas' should be considered as spindle cell glioblastomas. A total of six cases originally diagnosed as 'gliosarcomas' were compared with four cases of glioblastoma multiforme. No clinical or prognostic features were defined which would clearly separate 'gliosarcomas' from glioblastoma multiforme. Macroscopically, biopsies from 'gliosarcomas' ranged from firm, apparently well-circumscribed tumours to poorly circumscribed lesions with a soft consistency resembling glioblastoma multiforme. Histology revealed a continuous spectrum in which 'gliosarcomas' with large reticulin-rich areas of spindle cells merged with typical glioblastomas containing only small islands of spindle cells and reticulin staining. Immunocytochemistry for glial fibrillary acidic protein (GFAP); S100 protein and alpha-smooth muscle actin (ASMA) showed that the majority of cells in reticulin-poor areas of 'gliosarcoma' and glioblastomas expressed S100 protein and GFAP; many expressed ASMA and some expressed both GFAP and ASMA. Spindle cells in reticulin-rich areas of 'gliosarcomas' and glioblastomas most frequently expressed ASMA but many cells also expressed S100 protein and GFAP; some cells expressed both GFAP and ASMA. The results of this study and a review of the literature suggests that there is a clinical, radiological and pathological continuum with glioblastoma and 'gliosarcoma' at different ends of the spectrum. It is suggested, therefore, that most, if not all, 'gliosarcomas' be redesignated as spindle cell glioblastomas and not be considered as a mixture of glioma and sarcoma.
Actins↗
Barrier functions of the leptomeninges: a study of normal meninges and meningiomas in tissue culture.
The anatomical arrangement of the pia mater suggests that it may act as a regulatory interface between cerebrospinal fluid and the surface of the brain and between arterioles within the brain and the surrounding neural tissue. However, the functional aspects of such a barrier are difficult to evaluate in vivo. In the present study, the enzymic content and endocytotic capacities of normal leptomeningeal cells in situ and meningioma cells in confluent tissue culture are examined in relation to barrier functions of meningeal cells. Growth of cells in culture was obtained from human fetal and newborn rat leptomeninges and from 9/13 meningiomas. But, in only two meningiomas were the cultured cells characterized as meningeal in origin by using the strict criteria of desmosomes identified by immunocytochemistry or by electron microscopy. These two tumours had high (8-8.7%) Ki-67 labelling indices. Glutamine synthetase activity is present in normal meninges and in meningioma cells in culture; this enzyme together with catechol-O-methyltransferase could play a role in limiting the diffusion of neurotransmitters into brain tissue. A steady rate of endocytosis of carbon particles and fluorescent latex beads, 0.2-1 microns in diameter, was observed in cultured meningioma cells. Such endocytosis was inhibited by cytochalasin B indicating the active participation of intracellular microfilaments. Similar endocytosis has been observed in normal leptomeninges in vivo. The results of this study suggest that meningioma cells in culture reflect the barrier functions of the pia mater and may be used as a model to further investigate the functions of the pia mater.
Animals↗
Complete infarction of the eye complicating a choroidal malignant melanoma.
Infarction of malignant melanoma of the choroid has been previously reported, but infarction of the whole eye in association with infarction of melanoma is a rare event that has not been previously described. We present such a case and discuss the possible pathogenesis.
Aged↗
Unusual sciatica: traumatic rupture of the ligamentum flavum.
We describe a case of acute traumatic rupture of the ligamentum flavum. A condition occurring where there had been histological evidence of previous ligamentous damage. The symptoms were extreme and the surgical treatment highly effective.
Humans↗
The structure of the lamina cribrosa of the human eye: an immunocytochemical and electron microscopical study.
The structure of the lamina cribrosa was studied by histological and immunocytochemical techniques and by scanning and transmission electron microscopy in four eyes removed surgically and in 21 normal eyes obtained from an eye bank. Dissection of the eyes emphasised the relatively fragile links between lamina and sclera. Reticulin staining of the fibrous trabeculae in the posterior (scleral) part of the lamina revealed a structure composed of interweaving skeins of collagen fibres frequently arranged tangentially around the canals, 40-220 microns in diameter, through which optic nerve axons pass. Immunocytochemistry for glial fibrillary acidic protein demonstrated the intimate web that astrocyte processes form around axons within the canals of the lamina and the close association of astrocyte processes and fibrous trabeculae in the posterior part of the lamina. Scanning electron microscopy clearly demonstrated anatomical relationships of the lamina cribrosa and the wide variation in the size of the canals in the lamina. Transmission electron microscopy confirmed the close association of astrocyte processes with axons demonstrated in the immunocytochemical preparations. The results of this study emphasise the complex relationships between astrocytic, neural and fibrous elements in the lamina cribrosa and how more information is required regarding the mechanical and metabolic properties of the astrocyte web and the fibrous trabeculae before the role of the lamina cribrosa in the pathogenesis of nerve damage in glaucoma can be fully assessed.
Adolescent↗
Protein gene product (PGP) 9.5 as a reliable marker in primitive neuroectodermal tumours--an immunohistochemical study of 21 childhood cases.
A number of antibodies to neural proteins have been used to demonstrate neuronal differentiation in primitive neuroectodermal tumours. One of them is protein gene product (PGP) 9.5, a neuronal protein isolated from brain, whose function is unknown at present. We have studied differentiation in 21 cases of primitive neuroectodermal tumours of the CNS in children. Immunocytochemical staining was performed for such neuronal markers as: PGP 9.5, neuron specific enolase and synaptophysin, a glycosylated protein associated with synaptic vesicles. Positive staining for PGP 9.5 was present in 16 cases (strong staining in 12), for neuron-specific enolase in 16 cases (strong staining in 10) and for synaptophysin in 10 cases (strong staining in six). Both PGP 9.5 and synaptophysin showed a clear staining pattern with less non-specific background than with neuron-specific enolase. Our findings demonstrate the value of using more than one antibody marker in assessing neuronal differentiation in tumours. The high incidence of positive staining with antibody to PGP 9.5 suggests that this is an essential marker in the panel of antibodies used for the identification of primitive neuroectodermal tumours.
Adolescent↗
Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study.
Although astrocytomas, anaplastic astrocytomas and glioblastoma multiforme differ in their clinical courses, histological distinction between these three tumours and between astrocytomas and anaplastic astrocytomas in particular may be unclear on histology alone especially in small biopsies. In the present study, a more objective way of distinguishing between the three types of tumour is sought. Frozen sections from 26 astrocytomas, 26 anaplastic astrocytomas and 38 glioblastomas were stained by an indirect immunoperoxidase technique using the monoclonal antibody Ki-67 which binds to nuclear proteins in the G1, S, G2 and M phases of the cell cycle. The Ki-67 staining was assessed quantitatively through direct observation of the stained sections by the use of a drawing tube attached to a microscope. A minimum of 1000 cells was counted in each case and labelled cells were expressed as a percentage of the total number of cells. These results, when correlated in each case with the histology of the tumour in paraffin sections, showed Ki-67 labelling indices ranging from 0 to 1.9% (mean 0.5% SD +/- 0.54) in astrocytomas, 0.6 to 10.9% (mean 4.1% SD +/- 2.8) in anaplastic astrocytomas and 0.9 to 16.2% (mean 6.4% SD +/- 3.34) in glioblastoma multiforme. The differences in the three types of tumour were statistically significant. The results suggest that Ki-67 staining is a useful addition to the panel of techniques for distinguishing between astrocytomas, anaplastic astrocytomas and glioblastoma multiforme.
Antibodies, Monoclonal↗
Role of the basement membrane in the regeneration of skeletal muscle.
In many experimental models of skeletal muscle damage and in human muscle disease, empty basement membrane tubes remain following the destruction of muscle fibres. In the present study we test the hypothesis that the empty basement membrane tubes play an essential role in the orientation of regenerating muscle fibres. Two groups of 15 Wistar rats were used. In one group, aqueous barium chloride (BaCl2) solution was injected into the right quadriceps muscle; in the other group, freshly prepared 2% trypsin solution was similarly injected. The different stages of muscle cell necrosis and regeneration were observed by histology, by immunofluorescence using an anti-basement membrane antibody, and by transmission (TEM) and scanning electron microscopy (SEM) in animals killed 1-77 days following injection. Although there was muscle fibre necrosis at sites of BaCl2 injection, empty basement membrane tubes were well preserved. Myoblasts grew along the empty basement membrane tubes and by 77 days, the regenerated muscle fibres at the site of the injection were well oriented. Trypsin not only destroyed muscle fibres but also destroyed the basement membrane tubes; in the early stages of regeneration the myoblasts were disorientated but by 77 days, regeneration was comparable to that seen in the barium chloride injected muscle. The results of this study suggest that preservation of empty basement membrane tubes is not essential for the orientation of regenerating myoblasts in skeletal muscle.
Animals↗
Stiffman syndrome: a rare paraneoplastic disorder?
An unusual case of the stiffman syndrome, associated with an oat cell carcinoma of the bronchus, is reported. Pathological examination showed that it was due to an encephalomyelitis similar to that seen in paraneoplastic disorders. This suggests that atypical cases of the stiffman syndrome may occasionally be paraneoplastic.
Aged↗
Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum.
Biopsies of histologically normal adult human cerebral cortex, underlying white matter and overlying leptomeninges were taken from frontal and temporal lobectomy specimens excised during the removal of cerebral tumours. Multiple blocks from 6 patients (aged 18-53 years) were examined by light and transmission electron microscopy. A thin sheath of pia mater cells was found to surround completely arterioles and arteries in the brain, in the subpial space and in the subarachnoid space. Pia mater cells, forming the perivascular sheath, were identified by the presence of desmosomes or small nexus junctions and by continuity with the pia mater itself. The presence of the pial sheath suggests that the perivascular spaces around intracerebral arteries are in direct continuity with the perivascular spaces around subarachnoid arteries. No similar pial sheath was observed around intracerebral or subpial venules. The role of the periarterial spaces, enclosed by the pial sheath, is discussed in relation to the results of physiological experiments suggesting drainage of interstitial fluid from brain tissue into the perivascular pathways along major cerebral arteries in the subarachnoid space. As arterioles in the brain become smaller and lose their smooth muscle coats, the pial sheath becomes incomplete. The anatomical relationships between the pia mater and blood vessels in the human cerebrum is summarised diagrammatically, and a possible role for pial cells as an enzymic barrier protecting the brain from exogenous catecholamines is discussed.
Adolescent↗
Iatrogenic transmission of Creutzfeldt-Jakob disease.
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Animals↗
Normal pressure hydrocephalus and cerebrovascular disease: findings of postmortem.
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Aged↗
A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus.
The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn. Numerous somatostatin-immunoreactive cell bodies were also present. In the ventral horn, immunoreactive fibres were less abundant. Most motoneurones were closely apposed by fibres immunoreactive for enkephalin, neurokinin, somatostatin and thyrotrophin-releasing hormone (TRH). A subpopulation of motoneurones, most notable in lumbar segments, displayed CGRP immunoreactivity. In common with autonomic nuclei, Onuf's nucleus, which is thought to innervate perineal striated muscle and external urethral and anal sphincters, was densely innervated with CPON-, enkephalin-, and in particular somatostatin-immunoreactive fibres, thus suggesting Onuf's nucleus may have an autonomic component. In the diseased cords, there was a reduction in the area of the ventral horn and numbers of motoneurones as revealed by conventional histological staining and immunostaining of neurofilament triplet proteins. No changes in the distribution of peptides was noted in the dorsal horn or autonomic nuclei. By contrast, in the ventral horn, neurokinin-, enkephalin-, somatostatin- and TRH-immunoreactive fibres, which are normally found associated with motoneurones, were absent. Therefore, not only are motoneurones lost in MND, but also the fibres which innervate them. CGRP-immunoreactive motoneurones were not observed, a finding consistent with the proposed role of this peptide as a muscle-trophic factor. In contrast to the large motoneurone groups in the ventral horn, the neuronal integrity of Onuf's nucleus and the peptides associated with it were spared. These data further imply that Onuf's nucleus is not a typical motor nucleus and it is not purely somatic. The coincident loss of peptide immunoreactivity and motoneurones from the large motor nuclei and sparing of Onuf's nucleus and its peptide-containing constituents in the diseased state suggests that peptides contribute to maintenance of neural integrity.
Adolescent↗
Loss of evoked potentials during spinal surgery due to spinal cord hemorrhage.
The cortical somatosensory evoked potential (SEP) disappeared during corrective spinal surgery in a patient with muscular dystrophy. The patient died 18 hours after surgery. Autopsy revealed an intramedullary hemorrhage 4 mm in diameter in the posterior horn of the cervical spinal cord. Microscopically, hypoxic neurons were seen adjacent to the hemorrhagic area, implying that the lesion was at least 6 hours old. The hemorrhage corresponded to the loss of SEPs and confirms that spinal cord monitoring can detect such lesions.
Adolescent↗