Biomedical subjects
Publications and source records attributed to C G Harper.
Pituitary glands, obtained at necropsy from a consecutive series of 100 patients who had died as a result of non-missile head injuries, were examined to define the incidence and pathogenesis of abnormality.
A recent necropsy study has shown that 80% of patients with the Wernicke-Korsakoff syndrome were not diagnosed as such during life. Review of the clinical signs of these cases revealed that only 16% had the classical clinical triad and 19% had no documented clinical signs. The incidence of clinical signs in this and other retrospective pathological studies is very different from that of prospective clinical studies. This discrepancy may relate to "missed" clinical signs but the magnitude of the difference suggests that at least some cases of the Wernicke-Korsakoff syndrome may be the end result of repeated subclinical episodes of vitamin B1 deficiency. In order to make the diagnosis, clinicians must maintain a high index of suspicion in the "at risk" group of patients, particularly alcoholics. Investigations of thiamine status may be helpful and if the diagnosis is suspected, parenteral thiamine should be given.
The clinical and pathological findings in nine cases of intramedullary spinal cord metastases are reported and are compared with those of previous studies. Intramedullary metastases are more common than is generally believed and the incidence is probably increasing with the more prolonged survival of cancer patients. A wide spectrum of symptoms and signs may be produced, frequently with attendant diagnostic difficulties. Most patients present with myelopathy as the first manifestation of cancer or of its recurrence. Symptoms may be present for several months, with few clinical signs, despite distortion and destruction of much of the spinal cord by tumour. The extent of metastatic disease remains limited in a significant proportion of patients. No neurological symptoms or signs differentiate intramedullary metastases clearly from the more common extradural deposits. However, the diagnosis should be considered when myelopathy evolves more slowly, where plain radiographic evidence of adjacent vertebral disease is absent, and particularly when myelography is normal. Early diagnosis and aggressive medical treatment may provide for a more favourable outcome.
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A quantitative neuropathological necropsy study of 22 control and 22 chronic alcoholic subjects showed a statistically significant loss of brain tissue in the chronic alcoholic group. The loss of tissue appeared to be from the white matter of the cerebral hemispheres rather than the cerebral cortex. This may reflect a primary alteration in the composition or structure of the white matter or it may be secondary to loss of nerve cells from the cortex with subsequent degeneration of the axons in the white matter. Further morphometric analyses including cortical neuronal counts will be necessary to clarify this issue.
Most seemingly well infants who die suddenly and unexpectedly have no adequate cause of death found on thorough postmortem examination. Respiratory and enteric viruses are often present, especially in the upper respiratory tract, but the infective process seems, of itself, insufficient to cause death. In the remainder of the cases, a variety of lesions will be discovered, including viral myocarditis, bronchiolitis, and sepsis. We report a case of sudden and unexpected death in a 5-week-old male infant due to acute anterior poliomyelitis. This case illustrates the importance of a thorough postmortem examination, including histologic studies of the brain stem and spinal cord in cases of sudden infant death syndrome.
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Clinical interest in spinal compression and resultant paraplegia due to metastases has mounted in recent years. This has stimulated attention to the neuropathology of the condition. Fourteen cases of spinal cord compression due to vertebral metastases are compared with over 100 traumatic cases. In the traumatic lesions there is central haemorrhagic necrosis leading to cavitation and gliosis with nerve root regeneration in the late stages. In the metastatic cases, lesions are often peripheral, pie-shaped and are related to vascular factors. The neuropathology of cord necrosis due to metastatic spinal disease is therefore different to trauma. These observations have clinical importance in planning treatment.
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An analysis of the brain weights of 168 alcoholics showed that the mean brain weight of male alcoholics was less (p less than 0.001) than that of a normal population. Two subgroups of alcoholics were identified. Firstly, those with nutritional brain damage (Wernicke's encephalopathy, caused by vitamin B1 deficiency) and, secondly, those with brains which appeared "normal" macroscopically and microscopically. Any change in the brain weights of this second group was unlikely to be caused by nutritional damage. Both groups had abnormally low brain weights which suggests that alcohol, the factor common to both groups, is more important than nutritional deficiencies in causing brain damage and a reduction in brain weight.
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In published studies we have shown that lectins and cholera toxin bind at 4 degrees C on surfaces in cultured neurons and neuroblastoma cells and, after incubations of labeled cells at 37 degrees C, undergo endocytosis (adsorptive endocytosis) into GERL (Golgi-endoplasmic reticulum-lysosome). In this study conjugates of wheat germ agglutinin (WGA) with horseradish peroxidase (HRP), or free HRP, were injected in rat submandibular glands or over superior cervical ganglia, and their uptake was examined by electron microscopic cytochemistry for HRP. Lysosomes and vesicles and cisternae of GERL were involved in the uptake of WGA-HRP injected into the submandibular gland or into the superior cerival ganglion; HRP, administered in a similar fashion, but in amounts 10-15-fold higher than WGA-HRP, underwent endocytosis into lysosomes. The present in vivo studies, as well as previous in vitro studies, indicate that neuronal GERL is part of the endocytic pathway of various ligands which bind on corresponding surface (plasma membrane) "receptors".
Wernicke's encephalopathy (WE) is thought to be largely confined to the alcoholic population. However, another "at risk" group of patients has been identified. Three patients maintained on prolonged intravenous feeding died suddenly and unexpectedly from acute WE. Six similar cases from the recent literature are reviewed. Six of these nine cases died as a result of this disease. Neuropathological examinations showed a prominent haemorrhagic component of the acute WE. Six patients did not exhibit any of the classical signs of WE.
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A preliminary observation from another laboratory recently suggested that a systemic microtubular defect may exist in Alzheimer disease. To investigate this hypothesis, we obtained skin biopsies from 4 patients with Alzheimer disease and 2 age-matched controls. Fibroblast cultures were established and the tubulin networks examined using immunoadsorbent purified antitubulin antibody and the indirect immunoperoxidase technique as well as electron microscopy. The cells were also examined after treatment with vinblastine and at senescence. The microtubular network appeared as delicate fibers radiating from the perinuclear region toward the cytoplasmic margins. No differences were recognized between the controls and the fibroblast cultures from patients with Alzheimer disease. Microtubules were not visualized following incubation with vinblastine, but positively staining intracytoplasmic paracrystalline inclusions were noted. No abnormalities of microtubules were recognized in the electron microscopic examinations. These findings suggest that the neurofibrillary neuronal degeneration of Alzheimer disease is not a manifestation of a systemic disorder of the microtubular network.