A general approach to neuropathological problems.
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Autopsy↗
Biomedical subjects
R O Weller
Publications and source records attributed to R O Weller.
The fine anatomy of the human spinal meninges. A light and scanning electron microscopy study.
The fine anatomy of the human spinal meninges was examined in five postmortem spinal cords taken within 12 hours after death from patients aged 15 months to 46 years. Specimens of spinal cord were viewed in transverse section and from the dorsal and ventral aspects by scanning electron microscopy. Transverse sections of spinal cord and meninges were also examined by light microscopy. The arachnoid mater was seen to be closely applied to the inner aspect of the dura. An intermediate fenestrated leptomeningeal layer was observed attached to the inner aspect of the arachnoid mater and was reflected ventrally to form a series of dorsal septa. As it arborized laterally over the surface of the cord to surround nerves and blood vessels, the intermediate layer became highly fenestrated but remained distinct from the pia and arachnoid mater. The pia mater appeared to form a continuous layer which was reflected off the surface of the cord to coat blood vessels within the subarachnoid space in a manner similar to that described in the leptomeninges over the human cerebral cortex. Each dentate ligament consisted of a collagenous core which was continuous with the subpial connective tissue and was attached at intervals to the dura; pia-arachnoid cells coated the surface of the dentate ligaments. The present study suggests that the fine anatomy of the human spinal meninges differs significantly from that described in other mammals.
Adolescent↗
Antidesmosomal monoclonal antibody in the diagnosis of intracranial tumours.
Immunocytochemistry has been applied extensively to the diagnosis of intracranial tumours, but meningiomas still present a diagnostic problem. However, desmosomes have been shown by electron microscopy to be present in meningiomas, and this distinguishes them from gliomas. This paper describes a new monoclonal antibody, 11-5F, against desmosomal proteins 1 and 2 (desmoplakins) and assesses its usefulness in the diagnosis of meningiomas and other intracranial tumours. A total of 74 surgically removed intracranial tumours were examined by fluorescent antibody staining with 11-5F on frozen sections. In addition, a panel of antibodies against cytokeratin, vimentin, glial fibrillary acidic protein, and S100 protein was used. 11-5F stained 30/30 meningiomas and 14/14 metastatic carcinomas but 0/30 gliomas, thus distinguishing meningiomas and metastatic carcinomas from gliomas. The distinction between meningiomas and metastatic carcinomas on the basis of intermediate filaments staining was more difficult because neither the anticytokeratin nor the antivimentin antibody was specific for either tumour type. This study emphasizes the value of antidesmosomal antibodies as an important adjunct to the diagnosis of intracranial tumours.
Antibodies, Monoclonal↗
Prolonged expiratory apnoea (cyanotic 'breath-holding') in association with a medullary tumour.
From the age of four months to his sudden, unexpected death at 2 years 11 months, a child had severe cyanotic episodes attributed to cyanotic 'breath-holding' (prolonged expiratory apnoea). At postmortem he was found to have a previously undiagnosed gangliocytoma of the medulla, which had invaded the floor of the fourth ventricle and variably affected the 7th to 12th cranial-nerve nuclei.
Apnea↗
Insulinoma producing progressive neurological deterioration over 30 years.
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Adenoma, Islet Cell↗
Brain tumours in man.
Brain tumours occur at all ages but they differ in type depending upon the age of the patient. In adults, probably more than 50% of tumours in the brain are metastatic carcinomas or melanomas. The pathological classification of primary brain tumours depends largely upon the cell type involved. Recently, immunocytochemical identification of cell-specific proteins by the use of polyclonal or monoclonal antibodies has greatly enhanced the accuracy of cell identification within tumours. Primary brain tumours in children arise mainly in the brain stem and cerebellum and are astrocytomas, primitive neuroectodermal tumours (medulloblastomas) and ependymomas. Gliomas form the largest group of primary brain tumours in adults, with an annual incidence of 3.94/100,000 in Southern England. In young adults, well differentiated astrocytomas and oligodendrogliomas arise in the cerebral hemispheres. Poorly differentiated, malignant glial tumours include anaplastic astrocytomas and glioblastoma multiforme; these tumours are most common in older adults with a peak annual incidence of 7.3/100,000 in the sixth decade. The major complication of brain tumours is due to their mass effect from tumour growth and from peritumoral oedema. Surgical excision of gliomas is difficult and usually incomplete due to the infiltrative nature of the tumour. As yet these tumours respond poorly to irradiation and chemotherapy.
Adult↗
Mouse antisera specific for desmosomal adhesion molecules of suprabasal skin cells, meninges, and meningioma.
Mouse polyclonal antisera were raised to the Mr 130,000 and Mr 115,000 cell surface glycoproteins, desmocollins, of desmosomes from bovine nasal epithelium. Immunoblotting confirmed that the antisera were specific for the desmocollins. An immunofluorescence study showed that the antisera distinguished between the basal and suprabasal layers of bovine and human epidermis. The antibodies reacted with cultured keratinocytes only after calcium-induced stratification. In epidermis, therefore, there appears to be a difference between the desmocollins of basal and suprabasal cells that may be important in relation to epidermal differentiation. Previous work has shown that polyclonal antisera raised in other animals (guinea pigs and rabbits) against desmocollins, as well as against other desmosomal components, react with all desmosome-containing epithelia. In contrast, an immunofluorescence survey of bovine, rat, and human tissues showed that the present mouse antisera stained only suprabasal skin cells and the arachnoid layer of the meninges, demonstrating that these have common determinants that distinguished their desmocollins from those of all other tissues. The antibodies also stained 11 of 12 meningiomas and, therefore, may be useful as a marker not only for the diagnosis of these tumors but also for investigation of their histogenesis.
Animals↗
Anatomical relationships of the pia mater to cerebral blood vessels in man.
Using scanning and transmission electron microscopy and light microscopy, the authors studied the human pia mater and its relationship to the entry of blood vessels into the normal cerebral cortex. The purpose of this investigation was to examine the long-established concept that the subarachnoid space communicates directly with the perivascular spaces of the cerebral cortex. Brains obtained post mortem from subjects with recent subarachnoid hemorrhage (SAH) and purulent leptomeningitis were studied by light microscopy to determine the permeability of the pia mater to red blood cells and inflammatory cells. Scanning electron microscopy showed that the normal pia mater is a flat sheet of cells that is reflected from the surface of the brain to form the outer coating of the meningeal vessels in the subarachnoid space. Transmission electron microscopy confirmed that the cells of the pia mater are joined by junctional complexes and form a continuous sheet that separates the subarachnoid space on one side from the subpial and perivascular spaces on the other. Thus, neither the pia mater nor the subarachnoid space extends into the brain beside blood vessels as they enter the cerebral cortex. The perivascular spaces were, in fact, found to be confluent with the subpial space and not with the subarachnoid space. In cases of recent SAH, red blood cells did not enter the perivascular spaces from the subarachnoid space; neither did India ink injected post mortem into the subarachnoid space pass into the perivascular spaces. The results of these crude tracer studies suggest that the pia mater is an effective barrier to the passage of particulate matter. Histological examination of brains of patients who had died with purulent leptomeningitis showed that inflammatory cells were present in the cortical perivascular spaces and in the contiguous subpial spaces. The presence of a large number of inflammatory cells in the subarachnoid space suggests that inflammatory cells readily penetrate the pia mater that separates the perivascular spaces from the subarachnoid space. The permeability of the pia mater to small molecular weight substances is briefly discussed.
Adult↗
Creutzfeldt-Jakob disease after administration of human growth hormone.
A 2-year-old girl had a craniopharyngioma removed in 1964. She received human growth hormone (HGH) twice a week from July, 1972, until July, 1976. In March, 1984, a subacute dementing illness developed with neurological signs that included pronounced cerebellar ataxia. A clinical diagnosis of Creutzfeldt-Jakob disease (CJD) was made. The patient died in February, 1985. Necropsy revealed a spongiform encephalopathy compatible with the transmissible form of CJD. HGH administration may be implicated in the transmission of the disease in this case.
Child, Preschool↗
Calf muscle adaptation to peripheral vascular disease.
130 muscle biopsies were taken from the gastrocnemius of 82 patients with different degrees of peripheral vascular disease (PVD) and 19 normal controls for histochemical analysis, and 30 patients and 7 controls for biochemical analysis of "aerobic" and "anaerobic" enzymes. The results showed that the gastrocnemius of patients with PVD did not adapt by increasing its "aerobic" potential as previously suggested. Histochemical studies showed that the cross-sectional area of both Type 1 and Type 2 muscle fibres became smaller than those from age-matched controls in the presence of PVD, and in some cases biopsies from both legs confirmed that this trend was greater in those limbs with increasing evidence of PVD. There is also some evidence to suggest a decrease in absolute capillary numbers per muscle fibre. The biochemical assays confirmed decreased levels of aerobic enzymes with increasing evidence of PVD as judged by ankle systolic pressure, and those patients with intermittent claudication showed some evidence of increased anaerobic enzyme levels in comparison to both the normal controls and those with rest pain. Patients with PVD do not adapt to ischaemia/anoxia by increasing their aerobic capability, but show signs of muscle atrophy probably due to reduced mobility. Training regimes may benefit patients with intermittent claudication by reversing these changes.
Adaptation, Physiological↗
The use as a learning resource of the community in which the medical school is situated: the Medical School, Southampton.
Southampton University Medical School was established in 1971 and now takes 130 students each year for the 5-year course, and fifteen students for the premedical year. The school uses facilities within the whole Wessex region, population 2.5 million, for teaching. During the first year of the course, community-based learning is a feature of the 'Man, Medicine and Society' course and of Early Medical Contact (EMC). Each student has four half-day EMC visits to patients in their homes and these visits are followed by discussion with medical staff. Sociology, or the social context of health care, together with an epidemiology course are the main contacts with the community in the second year. In the third year, all students visit a general practice surgery for half a day per week for 40 weeks; this enables them to appreciate the natural history of common conditions in primary care and their management. There is also a course in occupational medicine in the third year. At the beginning of the fourth year, many students spend an elective in an underdeveloped country, but much of the year is concerned with a study in depth, in some cases involving the community. The fifth year of the course is a major clinical year, often spent in regional hospitals away from Southampton. Three weeks are spent in general practice somewhere in the Wessex region.
Community Medicine↗
The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations.
Arachnoid granulations and villi from 23 brains from subjects aged 9 to 84 years were examined post mortem by serial sections with the light microscope and as whole or fractured preparations in the scanning electron microscope. The object of the study was to investigate the pathways within the arachnoid granulations by which cerebrospinal fluid (CSF) drains from the subarachnoid space to the sinus endothelium. At the base of each granulation, a thin neck of arachnoid projects through an aperture in the dural lining of the sinus and expands to form a core of collagenous trabeculae and interwoven channels. An apical cap of arachnoid cells, about 150 microns thick, surmounts the collagenous core, and channels extend through the cap to reach subendothelial regions of the granulation. Channels within the granulation are lined by compacted collagen and may contain macrophages. Following recent subarachnoid hemorrhage, erythrocytes are found in the channels, suggesting that the channels are in continuity with the subarachnoid space and are CSF drainage pathways. The cap region of the granulation is only attached to the endothelium over an area 300 microns in diameter; the rest of the granulation core is separated from the endothelium by a subdural space and a fibrous dural cupola. Scanning electron microscopy reveals an intact endothelial surface to the granulations with small perforating venous channels present on the apex of some granulations. The differences between human arachnoid granulations and arachnoid villi in animals are discussed, together with preliminary observations regarding the transition of villi into granulations in man.
Adolescent↗
Malignant optic nerve gliomas in adults.
Two patients with malignant optic nerve gliomas are described. The clinical courses and radiographic appearances are discussed, with emphasis on the fact that this condition should be considered in the differential diagnosis of rapid visual failure. It can now be strongly suspected preoperatively on the basis of computed tomographic scan appearances.
Adult↗
Production of prostaglandins and thromboxane by isolated cells from intracranial tumours.
Tumour cell-rich platelet-free preparations were isolated from 21 fresh samples of human intracranial tumours using enzymic digestion, followed by discontinuous density gradient centrifugation on Percoll and (14 preparations) adherence on plastic. Of the disaggregated cells 79.8 to 97.7% (mean 86.2%) were tumour cells, and mean cell viability was 82.6%. All the tumours produced prostaglandin (PG), E2, F2 alpha, 6 oxo F1 alpha and Thromboxane B2 during 16 hours of incubation but the amount varied widely. Highest production of PGE2 and TXB2 per 10(5) cells was by the eight meningiomas in which the prostanoid profile closely resembled that of circulating monocytes.
6-Ketoprostaglandin F1 alpha↗
Biopsy and post-mortem findings in a patient receiving cerebellar stimulation for epilepsy.
Cerebellar stimulating equipment was implanted in a 24-year-old male with severe epilepsy. He received continuous alternating stimulation for at least two months, intermittent bilateral stimulation on demand for at least two months and numerous short bursts of stimulation during preliminary testing and calibration of the apparatus. The patient died during a prolonged grand mal seizure 16 months after implantation and this paper reports the findings at necropsy. A special study was made of the degree of tissue damage in the cerebellar hemispheres resulting from implantation of the electrodes and subsequent cerebellar stimulation. There was deep grooving of the upper aspect of the cerebellum under the electrodes but only a minor degree of neuronal loss and gliosis was observed in the underlying cortex. Purkinje cell populations in the cerebellum at necropsy were similar to those in a biopsy specimen taken 16 months previously during implantation. The electrodes were covered with a thick layer of fibrous tissue but they were not adherent to the cerebellar surface. Thus, the main significant findings in the present case were the very slight structural damage to the cerebellum in contact with the electrodes and the intense fibrosis around the electrodes themselves. These features are discussed in relation to the efficacy of long-term cerebellar stimulation.
Adult↗
Perinatal diagnosis of myotubular (centronuclear) myopathy: a case report.
This is a case report of a male infant who was hypotonic at birth, failed to maintain his respiratory effort, and despite ventilation died at 27 days of age. Infrequent fetal movements were noted and the possibility of a neuromuscular disorder was suggested antenatally. Electromyography in the neonatal period was indicative of a neurogenic disorder, but muscle biopsy at 16 days of age showed the characteristic histologic appearance of myotubular (centronuclear) myopathy. There was no family history of muscle disease, and the mother has subsequently given birth to a normal male child. The relationship of the present case to other reports of severe congenital myotubular myopathy is discussed.
Biopsy↗
Ultrastructural and capillary adaptation of gastrocnemius muscle to occlusive peripheral vascular disease.
The effect of chronic occlusive peripheral vascular disease (PVD) on the histochemistry and capillarity of the gastrocnemius muscle was studied in 129 biopsies taken from 93 subjects. Sixty-three patients underwent biopsy during surgical procedures, and data related to walking distance and ankle systolic pressure. Thirty biopsies taken from normal subjects post mortem served as a control group, and data were analyzed for fiber type distribution, fiber area, fiber type grouping, and fiber capillarity. Fiber type distribution did not alter significantly between the patients with PVD and the control group, but the mean fiber area of the type 1 fiber in male patients with intermittent claudication (IC) was reduced when compared to that in age-matched controls (4608 +/- 1181 mu 2, IC +/- 1 SD; 5795 +/- 1771 mu 2, controls +/- 1 SD) (P less than 0.05). When bilateral biopsies were taken from the gastrocnemii of patients with unilateral occlusions, the type 2 fibers in the diseased leg were significantly smaller than fibers of the control group (2821 +/- 953 mu 2, IC +/- 1 SD; 4318 +/- 1504 mu 2, controls +/- 1 SD) (P less than 0.02). Fiber type grouping, evidence of denervation and reinnervation of muscle, appeared to be more common in patients with more severe limb ischemia. Overall capillary numbers did not appear to alter with degree of ischemia, but fiber shrinkage appeared to compensate for any loss of capillaries in the more ischemic muscle. These data suggest that the limb of the untrained patient with IC does not adapt to ischemia by adjusting its exercise capacity but merely shows evidence of disuse. These adaptations suggest that there may be much to be gained by nonsurgical methods of treating IC.
Adaptation, Physiological↗
Cerebral ventriculitis in the hydrocephalic mouse: a histological and scanning electron microscope study.
Staphylococci are the commonest organisms found in infected cerebrospinal fluid shunts in hydrocephalic patients. In the present study, staphylococcus albus was injected (1200-500,000 organisms in 10 microliters saline) into the ventricles of the hydrocephalic mouse SUMS - hy - 3/+ (temporary strain name). The bacteria appeared to have little direct effect upon the ependymal cells lining the ventricles and were not found as free organisms in the subependymal tissue. Staphylococci were phagocytosed by polymorphonuclear leukocytes which entered the ventricle from the choroid plexus and through the ependyma from subependymal vessels. Macrophages on the lining of the hydrocephalic ventricles also played a significant role in the phagocytosis of bacteria in the early stages of infection.
Animals↗