Fatal brain damage after dental anaesthesia. Its nature, etiology, and prevention.
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Adult↗
Biomedical subjects
A A Miller
Publications and source records attributed to A A Miller.
Atypical teratomas of the pineal and hypothalamus.
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Adolescent↗
A cerebral neuroblastoma with unusual fibrous tissue reaction.
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Brain Neoplasms↗
Neural and visceral xanthomatosis in adults.
The clinical, pathological, and chemical findings in a fatal case of generalized Hand-Schüller-Christian disease in a man of 33 years are presented in case 1. The necropsy examination revealed granulomatous infiltration of the infra-orbital fat, the pituitary stalk, and the posterior lobe of the pituitary and also of the skull bones and the thyroid cartilage. The spinal dura mater contained multiple xanthomatous deposits which had produced degenerative changes in the cord substance by epidural compression. Interesting features were the tumour-like enlargement of the right heart, massive pancreatic and renal infiltration, also heavy constricting xanthomatous mantles which had produced compression of both kidneys and adrenal glands. Case 2 is an example of xanthomatous granuloma, confined to the lungs, in a man of 57 years, and not associated with diabetes insipidus. The histological appearances were those of long-standing chronic xanthoma with marked cystic changes in the lungs, dilated bronchioles, and thick-walled stenosed pulmonary arteries. The pathogenesis of Hand-Schüller-Christian disease is briefly discussed.
Adrenal Glands↗
Phase I and pharmacologic study of sequential topotecan, carboplatin, and etoposide.
Inhibition of topoisomerase I by topotecan results in a compensatory increase in topoisomerase II levels associated with increased in vitro sensitivity of tumors to etoposide. Maximum synergy has been observed for the sequence of topotecan followed by etoposide. This is the pharmacologic rationale for the sequence of topotecan 0.4 mg/m(2) per day for 7 days continuous i.v. infusion, carboplatin i.v. on day 8, and etoposide 50 mg per day p.o. days 9 through 20. The carboplatin dosage was escalated from an AUC of 4 to 5 to 6 (Calvert formula). Up to six treatment cycles were administered at 28-day intervals. Eligible patients had metastatic non-small cell lung cancer (NSCLC) or extensive disease small lung cell lung cancer (SCLC), no prior chemotherapy, performance status 0-2, and adequate organ function. Follow-up was twice weekly in the first cycle for CBC and for topotecan and etoposide concentrations. Follow-up, thereafter, was weekly. Tumor response was assessed after two and six cycles and then as clinically indicated. At carboplatin AUCs of 4 and 5, no NCI grade 4 toxicity was observed in cycle 1 in cohorts of three patients each. At the AUC of 5, two patients experienced dose-limiting events after cycle 3, one grade 4 neutropenia lasting >3 days (no fever) and one failure to recover an absolute neutrophil count >1500/microl by day 35. This was, therefore, deemed the maximal tolerable dose. Number of treatment cycles per patient ranged between 1 and 6, and three patients completed six cycles. All patients were male, age 47-71, with NSCLC in one and SCLC in six. The patient with NSCLC had progressive disease after one cycle. One complete and three partial responses were observed in five patients with SCLC. Mean steady-state plasma concentrations during topotecan infusion ranged from 0.73 to 1.69 ng/ml, and mean etoposide concentrations ranged from 60 to 230 ng/ml. This sequence of topotecan, carboplatin, and etoposide appeared tolerable and active. Neutropenia was the dose-limiting toxicity.
Aged↗
Acute effects of lamotrigine (BW430C) in persons with epilepsy.
Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photosensitivity after lamotrigine administration. Five subjects with frequent interictal spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half-life (t1/2) of lamotrigine in subjects taking sodium valproate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co-medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.
Adolescent↗
Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: I. Anticonvulsant profile in mice and rats.
Lamotrigine (LTG), 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, is a structurally novel anticonvulsant. The anticonvulsant profile of LTG following oral administration in two standard anticonvulsant tests, the maximal electroshock (MES) test in mice and rats and the pentylenetetrazol (PTZ) infusion test in mice, was studied in comparison with the known anticonvulsant drugs phenytoin (PHT), phenobarbitone, diazepam, carbamazepine (CBZ), sodium valproate, ethosuximide (ETH), and troxidone (TROX). ED50 values for the abolition of hindlimb extension (HLE) in the MES test and PTZ infusion tests and doses increasing the latency of PTZ-evoked clonus were determined. The duration of action of LTG was examined in rats and mice in the MES test by determining ED50 values for the abolition of HLE at various drug intervals to shock administration. In the MES test, LTG was well absorbed in both species, with peak activity at 1 h and persistence at this level of potency for at least 8 h. Of the drugs examined, LTG was ranked the most potent and persistent in both species. LTG also abolished PTZ-evoked HLE, while ETH and TROX were inactive. Clonus latency was not increased by LTG, PHT, or CBZ, but was significantly increased (p less than 0.05) by the remaining anticonvulsants. Thus, LTG resembled PHT and CBZ in its ability to block HLE but not to increase PTZ-induced clonus latency. Acute behavioural studies in mice and rats have suggested a wide separation between anticonvulsant doses and those producing behavioural impairment. These results suggest that LTG may be of value in the treatment of generalised tonic-clonic and partial seizures.
Animals↗
Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action.
Lamotrigine (LTG) [3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is a novel anticonvulsant chemically unrelated to current antiepileptic drugs and with a pharmacological profile similar to that of phenytoin. The effect of LTG has been compared with that of phenytoin, on the release of endogenous amino acids and radiolabelled acetylcholine evoked by veratrine or potassium, from slices of rat cerebral cortex in vitro. Both veratrine and potassium evoked a marked release of glutamate and gamma-aminobutyric acid (GABA), with a more moderate release of aspartate. LTG inhibited veratrine-evoked release of glutamate and aspartate, with ED50 values of 21 microM for both amino acids, but LTG was less potent in the inhibition of GABA release (ED50 = 44 microM). At concentrations up to 300 microM, LTG had no effect on potassium-evoked amino acid release or on spontaneous release. Also, LTG was some five times less potent in the inhibition of veratrine-evoked [3H]acetylcholine release (ED50 = 100 microM) than in glutamate or aspartate release. The total lack of effect of LTG on potassium-evoked release and the potent effect on veratrine-evoked release (at concentrations found in rat brain after anticonvulsant doses) strongly suggest that LTG acts at voltage-sensitive sodium channels to stabilise neuronal membranes and inhibit transmitter release, principally glutamate. The role of glutamate in the aetiology of epilepsy is discussed.
Acetylcholine↗
Effects of lamotrigine on electrically induced afterdischarge duration in anaesthetised rat, dog, and marmoset.
The effects of lamotrigine (LTG), a novel potent anticonvulsant, following intravenous (i.v.) bolus injection were studied on the durations of electrically induced afterdischarges of the EEG in halothane-anaesthetised dogs and marmosets, species used in toxicity studies. For comparison, the effect of LTG on hippocampal afterdischarge duration was also studied in halothane anaesthetised rats, a species in which the anticonvulsant action of LTG has been widely investigated. The known anticonvulsants phenytoin (PHT) and phenobarbital (PB) were included for comparison. LTG reduced afterdischarge duration in a dose-dependent manner in rat and dog; it was approximately twofold more potent than PHT in the dog and three- to fourfold more potent than PB in both dog and rat (LTG ED50 values = 4.5 and 11.7 mg.kg-1 i.v. in dogs and rats, respectively). PHT was ineffective in the rat at sublethal doses (less than 40 mg.kg-1 i.v.). In limited studies in marmosets, i.v. administration of both LTG and PHT (both 5-15 mg.kg-1) reduced or abolished afterdischarge. Thus, LTG was a potent anticonvulsant in rat, dog, and marmoset in afterdischarge models of partial (focal) seizures and may be of utility in the treatment of partial seizures in humans.
Anesthesia↗
[The characteristics of detecting the tick-borne encephalitis virus antigen in the ELISA and indirect hemagglutination reaction by means of scanning electron microscopy].
The surface of polystyrene plates was studied at different stages of the enzyme immunoassay (EIA) and the passive hemagglutination (PHA) test by the method of scanning electron microscopy in the detection of tick-borne encephalitis (TBE) virus antigen. The study revealed that in the process of EIA larger antigens were washed away from the plate surface. The objects detected on the polystyrene surface were identified as conglomerations of the virions of TBE virus, but whole virions were shown to play no decisive role in EIA. The conclusion was made that, due to some specific features of this method, EIA was more sensitive in reaction with small antigens (individual glycoproteids, their small complexes). And, respectively, the PHA test was more sensitive in reaction with large antigenic complexes (whole virions, their conglomerations, immune complexes).
Antigens, Viral↗
[Effects of combined influence of ionizing radiation and light on the retina].
The continuous irradiation of rats with a light (3500 1x) for 48 hours led to destruction of 7.5 +/- 0.43% of neurosensoric cells (the control value was 0.2 +/- (0.02%). Longer photodamage caused progressing decrease in a population of the cells, narrowing followed by disappearance of corresponding layers of retina by the 30th day of the experiment. Preliminary exposure to X-rays with a dose of 5 Gy modified light damages of retina. The combination of two factors caused death of more than 30% of neurosensoric cells and redused the number of rows of nucleis of the external nuclear layer twice for the first 48 hours of illumination. After a longer influence of light a preliminary ionizing irradiation increased the number of destructively changed neurosensoric cells, reaching minimun of 41.7% by 30th day of the experiment. At the same time after a long combined irradiation less changes in row number quantity, numerical density of nucleus of the external nuclear layer and a population of neurosesoric cells in general was observed than after only one light exposure. Changes of choriocapillaries (thrombosis, obliteration, narrowing of a gap) which were more expressed at a combination of factors, led to infringement of blood circulation and played the important role in mechanisms of retina degeneration. Radial glia and neurons of internal layers of retina showed relative resistance to the investigated influences.
Animals↗
[Morphofunctional state of the stomach in rats with hyposalivation].
Hypoptyalism and deficiency of physiologically active saliva substances induced by it cause some essential changes in the morphofunctional state of the stomach mucosa, ultrastructure of the gastrin-producing cells and gastrin quantity in blood that testifies to the disturbance of the neurohumoral stomach regulation.
Animals↗