Biomedical subjects
Publications and source records attributed to D G Thomas.
Results of 280 radiofrequency lesions on 229 patients with trigeminal neuralgia are presented with three months to eight years (average 3.8 years) follow up. The patients were aged from 18-91 years. There was a high overall success rate of 94%. The complication rate has been low, with sensory paraesthesiae the commonest (15%) and cranial nerve palsies very rare (2.4%) compared to other reported series.
Rainbow trout were exposed to defined levels of cadmium in their aquarium water for differing periods at a variety of near-lethal concentrations that ensured the survival of the majority of the fish. The gills, liver and kidney together accounted for 99% of the accumulated load of body cadmium in the fish under these conditions. Although the proportion of total cadmium present in the liver remained relatively constant throughout, the distribution of the remainder between gill and kidney altered with the time of exposure. The cadmium in all three organs was bound by two low molecular weight proteins distinct in character from metallothionein. The isoforms of metallothionein were also present but were found to bind only zinc and copper. By contrast, when trout were injected with cadmium intraperitoneally, most of the metal accumulated in the liver where it was sequestered by the two isoforms of metallothionein. Pre-exposure of the trout to either a low concentration of cadmium (for several months) or to an elevated concentration of zinc (for 5 days) allowed the animals to survive a subsequent exposure to a high, otherwise lethal concentration of cadmium. The proteins responsible for sequestration of the two metals were identified, but two different mechanisms seemed to be involved in the protection of the animals. The significance of these observations in terms of the induction of proteins and the prevention of the toxic effects of cadmium is considered.
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The concentration of soluble glial fibrillary acidic (GFA) protein and the specific activity of glutamine synthetase (GS) were estimated in 11 central nervous system (CNS) regions of the 90-day-old rat. Marked differences were observed in the regional distribution of these astrocyte marker proteins. The striatum and spinal cord contained the lowest concentration (per g wet weight) of GFA protein and GS activity, respectively, while the olfactory bulbs had the highest level of both astrocytic proteins. Differences between the lowest and the highest values were 3-fold for GS and 4-fold for GFA protein. More significant was the marked variation in the ratio of GS to GFA protein in different CNS regions; the highest and lowest values were in the striatum and the spinal cord respectively, and the difference between the highest and the lowest value was about 5-fold. The spinal cord contained low GS and high GFA protein; on the other hand, the colliculi had high GS and relatively low GFA protein. Immunochemical detection of GS and GFA proteins in whole homogenates of different regions showed that the variation of the specific activities of GS and the concentration of soluble GFA protein were due to the differences in their absolute protein concentrations. In different regions of the brain the activity of GS was significantly correlated with that of glutamate decarboxylase, but not with that of choline acetyltransferase. These observations provide further evidence for differing biochemical properties of astrocytes from various CNS regions and for the involvement of GS in processes associated with amino acid neurotransmission.
Concentrations of seven neuropeptides have been determined in 69 human neurological tumours. The majority of tumours were intrinsic to the central nervous system, being astrocytomas. In general, within the the better differentiated tumours (Grade I/II astrocytomas) higher concentrations of five neuropeptides (neuropeptide Y, somatostatin, substance P, vasoactive intestinal peptide and cholecystokinin) were measured in comparison to the poorly differentiated tumours. Of the metastatic tumours, five were derived from oat cell carcinoma of the bronchus. Very high concentrations of bombesin were identified in these metastases.
Three cell lines (VMDk), derived from a spontaneous murine astrocytoma, which exhibit both morphological and antigenic characteristics of astrocytes in vitro (Pilkington et al. 1983), have been injected intracerebrally and subcutaneously into syngeneic mice at a range of concentrations in order to assess the number of cells required to produce the highest yield of tumours with the shortest possible latent period. Light- and electron-microscopical studies of the tumours confirmed their glial nature, however immunocytochemical staining for the astrocyte-specific markers glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) and for vimentin suggest that the tumours are composed mainly of poorly-differentiated neoplastic glial cells. Although the best-differentiated of the three cell lines failed to produce tumours, an invasive transplantable astrocytoma model has, nevertheless, been characterised fully and can now be used to study the effects of various therapeutic regimens.
Rainbow trout were exposed to either cadmium (9 micrograms/l) or zinc (100 micrograms/l) in their aquarium water. They were then transferred to water containing concentrations of cadmium (54 micrograms/l) that would have otherwise proved fatal to the majority of the fish without the pretreatment. Most of the fish survived under both sets of conditions. However, two different mechanisms seem to be involved in the protection of the animals against the toxic manifestations of cadmium. In both cases, more than 99% of the total body load of cadmium was found in the liver, kidney and gills of the animals. Analysis of the metal-binding proteins in these organs was carried out. In the fish exposed to the two concentrations of cadmium, the toxic metal was found only in association with two low mol. wt specific binding proteins despite the presence of zinc- (and copper)-containing isometallothioneins in all three organs. On the other hand, cadmium was distributed between these binding-proteins and metallothioneins in the liver, kidney and gill of the trout pretreated with zinc before their exposure to cadmium.
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One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.
Cerebrospinal fluid (CSF) myelin basic protein (MBP) was measured blind by double antibody competitive inhibition radioimmunoassay (RIA) in 20 children who had seizures and 17 children with hydrocephalus. MBP values correlated with clinical outcome and mean maximum intracranial pressure (ICP) in the hydrocephalic group, and with type of convulsion in the epileptic group. A value of 20ng/ml or more was regarded as significantly raised. A significant rise in MBP levels could be demonstrated in those with ICP alone and in patients with additional problems, whose levels tended to be even higher. Hydrocephalic children with normal ICP and children with seizures had similar normal MBP levels, and in the latter group clinical outcome was not related to MBP levels. For individual patients CSF MBP is of little value as a prognostic indicator, or as a method of quantifying cerebral damage.
Using positron emission tomography, regional cerebral blood flow and oxygen utilisation were measured in the contralateral cortex of 14 patients with a variety of intracranial tumours. A comparison was made with cortical values derived from 14 normal controls. Compared with normal subjects, patients with brain tumours had a significant reduction in oxygen utilisation and blood flow in their contralateral cortex. Decompression resulting from craniotomy and biopsy, led to a partial reversal of this cerebral hypofunction.
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The blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume were measured in brain tumours and the surrounding cerebral tissues. A total of 21 patients were studied. These included 10 primary tumours, eight secondary and three with unknown histology. Measurements were performed using the oxygen-15 steady state inhalation technique and positron emission tomography. Within the tumours no relation between blood flow, oxygen utilisation and blood volume was found. In all tumours oxygen supply was in excess of the oxygen demand of the tissues as reflected in oxygen extraction ratios that were lower than those of normal brain tissue. No indication of local ischaemia in peritumour oedema was found.
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Twenty-four patients with relapsed primary intracranial tumors were treated with high-dose etoposide (600-1000 mg/m2). All patients had received previous radiotherapy and 15 had had previous chemotherapy. The treatment was well-tolerated, with little toxicity. Only one patient showed a partial response, which was maintained for 78 weeks. Four patients had stable disease, for a median of 15 weeks. Etoposide failed to show useful activity in relapsed brain tumors.
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A sensitive radioimmunoassay that can detect brain damage in cases of head injury and stroke was applied to blood samples from 13 patients before and after they received multiple treatments with electroconvulsive therapy for psychiatric disorder. None of the patients showed a significant increase in serum myelin basic protein immunoreactivity. As increased serum myelin basic protein immunoreactivity may reflect myelin damage it is apparent that in these patients electroconvulsive therapy did not cause measureable breakdown of myelin.