The management of high-grade soft tissue sarcoma of the extremities.
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Extremities↗
Biomedical subjects
A W Brown
Publications and source records attributed to A W Brown.
Insecticide resistance in mosquitoes: a pragmatic review.
Descriptions of the World Health Organization standard methods of assessing susceptibility or resistance in larval and in adult mosquitoes are presented, and the evaluation of their results are discussed. Other susceptibility test methods are also mentioned, including those based on esterase zymograms. Recent work on the biochemical mechanisms of resistance and cross-resistance are reviewed, along with possible countermeasures for the problem of mosquito resistance, now known in 113 species of culicines and anophelines.
Animals↗
The comparative toxicology of ethyl- and methylmercury.
Neurotoxicity and renotoxicity were compared in rats given by gastric gavage five daily doses of 8.0 mg Hg/kg methyl- or ethylmercuric chloride or 9.6 mg Hg/kg ethylmercuric chloride. Three or 10 days after the last treatment day rats treated with either 8.0 or 9.6 mg Hg/kg ethylmercury had higher total or organic mercury concentrations in blood and lower concentrations in kidneys and brain than methylmercury-treated rats. In each of these tissues the inorganic mercury concentration was higher after ethyl- than after methylmercury. Weight loss relative to the expected body weight and renal damage was higher in ethylmercury-treated rats than in rats given equimolar doses of methylmercury. These effects became more severe when the dose of ethylmercury was increased by 20%. Thus in renotoxicity the renal concentration of inorganic mercury seems to be more important than the concentration of organic or total mercury. In methylmercury-treated rats damage and inorganic mercury deposits were restricted to the P2 region of the proximal tubules, while in ethylmercury-treated rats the distribution of mercury and damage was more widespread. There was little difference in the neurotoxicities of methylmercury and ethylmercury when effects on the dorsal root ganglia or coordination disorders were compared. Based on both criteria, an equimolar dose of ethylmercury was less neurotoxic than methylmercury, but a 20% increase in the dose of ethylmercury was enough to raise the sum of coordination disorder scores slightly and ganglion damage significantly above those in methylmercury-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The neurotoxicity of trimethyltin chloride in hamsters, gerbils and marmosets.
Trimethyltin chloride (TMT) was given to Syrian hamsters, gerbils and marmosets, and the changes in the brain were studied 1 day to 7 weeks later by light and electron microscopy. Within the marmoset brain, TMT was found to be uniformly distributed, similar to that in the rat. In all three species, signs of poisoning included whole-body tremors and prostration, while death might occur in 3-4 days; in marmosets ataxia, agitation, aggression and occasional fits were also observed. Bilateral symmetrical neuronal necrosis and chromatolysis were seen in the majority, which involved the hippocampus, pyriform cortex, amygdaloid nucleus, neocortex, various brain stem nuclei and in marmosets the retina. The probably lethal dose of TMT in all three species is approximately 3 mg kg-1, while the LD50 for the rat is 12.6 mg kg-1. The lower figure is probably related to lack of binding to haemoglobin in contrast to the binding in the rat. TMT does not bind to human haemoglobin and thus the predicted lethal dose for humans may be about 3 mg kg-1 (15.1 mumol kg-1), while the dose required to produce neuronal damage could well be less.
Animals↗
The toxicity and neuropathology of 2,4,5-tribromoimidazole and its derivatives in rats.
2,4,5-tribromoimidazole and its 1-n-butylcarboxylate and 1-dimethylcarbamoyl derivatives, when administered to rats, induced poisoning typical of uncouplers of oxidative phosphorylation. At 48 h rats surviving a single toxic dose of 20-60 mg/kg developed permanent incoordination of the hindlimbs in the absence of brain oedema. Neuropathologic examination of brain and spinal cord from perfused fixed rats at 24 h revealed neuronal necrosis and chromatolysis in the vestibular nucleus, the outer parietal neocortex and red nucleus. Chromatolysis and necrosis in these areas had increased at 72-96 h and were also observed in the deeper layers of the neocortex, the medial entorhinal cortex, the reticular formation, the grey matter of the spinal cord extending into the ventral horns, the dorsal, and ventral cochlear nuclei and the deep cerebellar nuclei, in decreasing order of severity. Neuronal necrosis was accompanied by an increased glial response, including neuronophagia and at 16 days with astroglial hypertrophy and hyperplasia.
Administration, Oral↗
Vinblastine, bleomycin and cisplatin for recurrent or metastatic squamous cell carcinoma of the head and neck.
Forty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with vinblastine, bleomycin, and cisplatin. All patients had received prior surgery, radiation or chemotherapy and all had measurable disease. Forty-five percent of the patients responded with a median duration of response of eight months and median survival of nine months. Six patients (14%) were complete responders and had a median duration of response of 12 months and median survival of 24+ months. Thirteen patients (31%) were partial responders and had a median duration of response of seven months and survival of 13 months. Toxicity was mild with nausea and vomiting occurring in all patients after cisplatin. There were two cases of bleomycin-induced pulmonary fibrosis and two cases of mild renal insufficiency (creatinine clearance level, 45 cc/min). This regimen compares favorably with other published regimens for advanced head and neck cancer.
Bleomycin↗
The origin of lipid phagocytes in the central nervous system: I. The intrinsic microglia.
The potential for the transformation of the normal microglial cell to a lipid phagocyte was studied by light and electron microscopy in the brains of rodents and by light microscopy only in primates. All were subjected to some form of hypoxia-ischemia and the microglial response was examined in regions of selective neuronal destruction (SND) so that infarction was deliberately excluded. In vivo perfusion-fixation was employed in all animals and light microscopic examination was carried out on paraffin- and sometimes celloidin-embedded material. Semithin plastic sections from several regions of the rodent brains were used for light microscopy but ultrastructural studies were confined to the hippocampus. In all animals the microglia were activated and transformed into rod cells exhibiting phagocytic properties but only a minority gave rise to lipid phagocytes. Blood vessels were normal in all animals and no hematogenous elements were identifed in the the parenchyma. As neuronal ghosts could be identified for up to 3 weeks it was concluded that the capacity of the microglia for phagocytic activity was limited.
Animals↗
The origin of lipid phagocytes in the central nervous system: II. The adventitia of blood vessels.
The source of the lipid phagocytes that occupy a cerebral infarct has been determined by light and electron microscopy in the brains of rodents and by light microscopy only in the brains of primates. The infarcts (in neocortex, hippocampus, and thalamus) were the consequence of hypoxia-ischemia of various types. Hemorrhagic infarcts were excluded. After in vivo perfusion-fixation, paraffin- and celloidin-embedded material was used for light microscopy. Semithin plastic sections from the neocortex and thalamus were studied with the light microscope and ultrastructural studies were confined to the same regions. In all animals after about 2 days there was evidence of phagocytic activity in the fibroblasts in the adventitia of the remaining large vessels and also proliferation by mitotic division. At 5-7 days fibroblasts appeared to migrate from the vessels in a semifluid or fluid milieu and to give rise to typical phagocytes. These increased in size and number but signs of degeneration became apparent after 10 days and they had largely disappeared by 32 days. Smooth muscle cells and pericytes showed evidence of degeneration and phagocytic activity was never seen in the latter.
Animals↗
Brain damage due to trimethyltin compounds.
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Animals↗
Treatment experience with nonseminomatous testicular cancer in patients with stage II and stage III disease.
Thirty-eight patients with nonseminomatous testicular cancer were treated with cis-platinum, bleomycin, and vinblastine in combination without a prolonged maintenance phase. Twenty-Six patients with Stage III disease were treated. Seventy-six percent of those patients treated achieved complete remission. At a median survival time of 30 months, no patient who achieved a complete remission has relapsed. Twelve Stage II patients given adjuvant therapy remain free of disease at a median time of 23 months. Markedly elevated serum lactate dehydrogenase levels and massive disease were common findings in the patients who did not achieve complete remission. One drug death occurred secondary to sepsis. Symptoms of depression and anxiety were significant dose-limiting factors in this group of patients.
Adolescent↗
Remarks on the papers by C.-D. Agardh et al./H. Kalimo et al. "hypoglycemic brain injury, I, II".
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Animals↗
A microprocessor-based ultrasonic limb movement monitoring system.
A system has been devised, using a spark-gap ultrasonic transmitter and an array of four ultrasonic receivers, to monitor the unrestrained movement of a physically handicapped child's fingertip as he attempts to perform some specific task. A microprocessor is used to measure the time taken for a pulsed ultrasonic shock-wave to travel from the fingertip-mounted spark-transmitter to each of the four ultrasonic receivers, and hence compute the Cartesian co-ordinates of the transmitter. It is hoped that this equipment will enable the voluntary components in the poorly-controlled limb movements of some of the physically handicapped children to be isolated and used to control external equipment.
Child↗
Combination chemotherapy with vinblastine, bleomycin, and cis-diamminedichloroplatinum (II) in squamous cell carcinoma of the head and neck.
Forty-five patients with advanced squamous cell carcinoma of the head and neck, 23 of whom had received no prior therapy, were given the combination of vinblastine, 4 mg/m2 intravenously (IV) on Day 1; bleomycin, 15 mg/day intramuscularly on Days 1-7; and cis-diamminedichloroplatinum (II), 60 mg/m2 with mannitol diuresis on Day 8. The regimen was repeated at three-week intervals, for a maximum of three cycles. Among the 23 patients without prior surgery or radiation, there were 5 complete responses and 12 partial responses, a 74% response rate; whereas, among the 22 with prior therapy, there were 2 complete responses and 8 partial responses, a response rate of 45%. Nineteen of 23 previously untreated patients were subsequently given radiation, 1 had surgery, and 1 had surgery plus radiation. Twelve of these 19 patients are currently free of disease, with a median duration of ten months from initial response. Four of the 22 previously treated patients received radiation and 2, surgery; 4 of these 6 patients are without evidence of disease. Renal dysfunction with elevation of serum creatinine occurred in 5 patients, a leukocyte count of less than 3,000/mm3 in 3, a platelet count of less than 100,000/mm3 in 2, skin changes in 11, hearing loss in 1, and both peripheral neuropathy and pulmonary changes in 1 patient. This combination of agents has substantial activity in untreated patients and may be useful as initial therapy in advanced head and neck malignancies by diminishing the incidence of local recurrence and distant metastasis.
Adult↗
The pathogenesis of ischaemic neuronal damage along the cerebral arterial boundary zones in Papio anubis.
The pathogenesis of ischaemic neuronal damage along the arterial boundary zones of the forebrain was investigated in 20 lightly anaesthetized, spontaneously breathing baboons. A combination of bilateral common carotid artery occlusion and systemic hypoxia was used. An arterial PO2 of 21.2 +/- 2.5 mmHg was maintained for about 20 min. Additional occlusion of the left common carotid artery for 20 min had no effect on the EEG (except for one animal with a cerebrovascular anomaly). Only when occlusion of the right carotid artery was added did the EEG become almost or completely isoelectric after an interval ranging from 23 s to 44 min (sequential common carotid artery occlusion while breathing air did not affect the EEG). After a chosen period of electrical silence, hypoxia and carotid occlusion were terminated. Hypotension did not occur during carotid occlusion or the recovery period. Survival was deliberately limited to 46 h, during which neurological assessment was made and the EEG was recorded just before in vivo perfusion-fixation of the brain. Neurological deficits included asymmetrical quadriparesis and myoclonus epilepsy. The brains of 3 animals were normal and in the 15 with brain damage this was restricted in the cerebral cortex to the arterial boundary zones. In the presence of profound hypoxia the oligaemia due to bilateral carotid occlusion can reduce tissue oxygenation locally to a level critical for the production of ischaemic damage in the cortical boundary zones. Portions of the basal ganglia were also involved in 7. The quantified brain damage scores correlated with the EEG scored on a six-point scale during the perod of electrical silence and early recovery. Brain damage scores also correlated with the times for intracranial pressure to return to normal levels from the peaks recorded just after the end of arterial occlusion and hypoxia. As brain damage only occurred when the EEG during bilateral carotid occlusion and hypoxia was silent for at least 8 min, it was concluded that in a variety of clinical settings a simple EEG-based monitoring system would be optimal for the detection of an impending failure of cerebral oxygen supply.
Animals↗
Neuropathological changes caused by trialkyllead compounds in the rat.
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Animals↗
The use and abuse of Distalgesic.
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Acetaminophen↗
Selective chromatolysis of neurons in the gerbil brain: a possible consequence of "epileptic" activity produced by common carotid artery occlusion.
Unilateral (50 to 118 minutes) and bilateral (2 to 33 minutes) carotid artery occlusion in gerbils resulted in two distinct types of neuronal alteration: ischemic cell change (ICC) in selectively vulnerable brain regions, and selective chromatolysis (SC) confined to the deeper layers of the cortex, the Sommer sector of zone h-1, and the paramedian region (PM) of the hippocampus. In typical SC the nucleus was eccentric and the Nissl substance was lost in the central eosinophilic cytoplasm. In electron micrographs this area of cytoplasm showed disruption of smooth and rough endoplasmic reticulum with disaggregation of polyribosomes and accumulation of mitochrondria and various dense bodies. SC was identified at 2 to 3 hours and was still recognizable at five days. When bilateral carotid artery occlusion lasted 5 to 6 minutes, SC was seen in the hippocampal Sommer sector and cerebral cortex, while ICC was restricted to the endfolium (h3-5). Unlike ICC, the frequency of SC was not related to the duration of ischemia but probably to the epileptic seizures (overt and subclinical) initiated by ischemia in the gerbil. These changes must be considered when the gerbil is employed as a model of experimental stroke.
Animals↗
An audiovisual teaching model of the muscle spindle.
Students in biology and medicine often have difficulty in visualizing the structure, function and disease of complex integrated body systems. One example in neurophysiology is the muscle spindle and Golgi tendon organ. A model is described which demonstrates the properties of these two muscle receptors. The model combines mechanical elements, which can change their length to represent muscle contraction, with an electronic representation of the passage of action potentials along 'nerves', indicated by light-emitting diodes and loudspeakers. The model has been in use for some years as a supplement to conventional teaching methods. In a recent questionnaire about the model, a group of medical students responded favourably. We suggest that models such as this are valuable teaching aids.
Audiovisual Aids↗