Background Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. MethodsIn this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.
THE abundance of the fat-soluble vitamins A and D in the liver of the cod has led many investigators to examine the food supplies of the cod for the source of these vitamins. In the case of vitamin A these researches have been successful. Drummond and Zilva [1922] searching for the ultimate source of vitamin A in nature found that the marine diatom, Nitzschia closterium, was capable of synthesising a fat-soluble growth factor. Jameson et al. [1922] also demonstrated that N. closterium could synthesise this factor under controlled conditions in the laboratory, but Leigh-Clare [1927], while confirming the synthesis of vitamin A by this organism, was unable to prove the presence of vitamin D in' such cultures. Thus while the diatom might be the ultimate source of vitamin A in the food of the cod, it was extremely improbable that it could be the source ofAs the cod is a deep-water fish, it is unlikely that any synthesis of vitamin D in the cod itself can take place by the action of ultraviolet irradiation, since such irradiation has been shown to be reduced to 1 % of its sub-surface value at a depth of 1 1-2*2 m. and to 0-001 % at 2-9-5-5 m. [Atkins and Poole, 1933].Bills [1927] has suggested that the cod might be able to synthesise vitamin D in its liver by some process as yet undetermined, since no rich source of the vitamin has been found in its food, but Hess et al. [1932] were unable to show any increase of vitamin D in the livers of fish which had received ergosterol intramuscularly or by mouth. Drummond and Hilditch [1930], in examining the relative vitamin values of cod-liver oils from various sources, also investigated the food supplies of the fishing grounds and reported that there was no significant content of vitamin D in the zooplankton (copepods, etc.) and only very little in the small fish on which the cod was known to feed. In the same year and later, Drummond and Gunther [1930; 1934] tested extracts of zoo-and phyto-plankton, prepared as described by Collin et al. [1934] and showed that vitamin D was probably absent from the phytoplankton but present in the zooplankton extract, to the extent of less than 100 "Coward" (International) units per ml. (equivalence of extract in terms of original matter not stated), by giving small doses to rats in curative tests. They suggested that the zooplankton might derive the vitamin D from irradiation while in surface waters, rather than from ingestion of phytoplankton. Belloc et al. [1930] tested the antirachitic potency of the sterols of plankton. They found that the sterols obtained by the saponification of the oils extracted from copepods were antirachitically active without previous irradiation, but that the sterols from ctenophores required to be treated with ultraviolet light before they had any activity. The crystalline sterol from copepods was active in doses of 0-01 mg., but no figures are given by means of which this potency can be correlated with the amount of original material from which the sterol was derived.
Histochemical methods offer the advantage, in the study of vitamin deficiency states, that a considerable amount of information can be obtained from each animal. The amount of tissue required for the demonstration of any one enzyme is small; thus the number of enzymes that can be examined is virtually unlimited.In this study a comparison was made of enzyme activities in tissues of normal and vitamin D-deficient rats. The tissues, other than bone, where lack of vitamin D is considered to have an effect, are those associated with calcium and phosphorus absorption and excretion and those associated with the control of calcium and phosphorus metabolism. The intestine and its associated glands, and the kidney and the parathyroid gland have therefore been selected for investigation. EXPERIMENTAL AnimalsThe rats were of the Lister Institute black and white stock maintained at Queen Elizabeth College. They were weaned at 23 days and taken for experiment at 28-30 days at weights ranging from 57 to 80 g. The histological procedure required pairs of animals for comparison, and limitation of time permitted only two or four animals to be dealt with in a week. Pairs of male rats were therefore taken for experiment at intervals, caged separately and fed on Steenbock's rachitogenic diet 2965 (Steenbock & Black, 1925) with or without a dose of vitamin D. Vitamin D was given as a solution of Adexolin (a concentrate of vitamins A and D ; Glaxo Research Ltd) in arachis oil in a single weekly dose of 10 i.u. vitamin D. The animals without vitamin D received arachis oil to compensate for any effect of the inclusion of the small amount of oil in the diet. The diet was offered as a dry powder and was made once or twice weekly. It consisted of freshly ground whole yellow maize complete with the germ 76%, wheat gluten 20%, calcium carbonate 3 yo, and sodium chloride I %, with a Ca:P ratio of 4:'.At the beginning of the experiment 'line tests' (Bills, Honeywell, Wirick & Nussmeier, 1931) were made on the right radius and ulna of every rat on the day it was killed. The left radius and ulna were put into the deep freeze and examined all at the same time at the end of the experiment. The femur, tibia and fibula from all rats were kept in the deep freeze until the end of the experiment so that all bone ash determinations could be done at the same time. Bone ash was measured by the method of 10-2
IT has already been recorded that the fresh egg-white of the hen's egg contains vitamin B2 unaccompanied by the antineuritic vitamin B1 [Chick and Roscoe, 1929, 1]. In this property egg-white stands alone amongst the foodstuffs hitherto examined, for in all others in which vitamin B2 has been found, vitamin B has also been present, although the relative amounts of the two have shown a wide variation [Aykroyd and Roscoe, 1929;Roscoe, 1930].This unusual property makes egg-white a valuable material for use in the investigation of the various members of the B group of vitamins. It has, therefore, seemed worth while to publish a short account of the evidence upon which the above statement is based.Vitamin B1 deficiency of egg-white. If young rats immediately after weaning receive an artificial diet deprived of vitamin B1, but otherwise complete and containing egg-white as source of protein and of vitamin B2 [see Chick and Copping, 1930, 3, p. 1765, Diet II], growth takes place for 2-3 weeks, after which appetite fails and a decline in weight sets in. If this is not checked death will often follow and will be preceded by the paralysis characteristic of vitamin B1 deficiency, which is promptly cured if vitamin B1 is given. If, at the point where weight has become stationary or has begun to decline, vitamin B1 is given as a daily dose of some foodstuff containing it, or as Peters's antineuritic concentrate, growth is immediately restored and the gain in weight will be in relation to the amount of vitamin B1 administered. These facts have been applied in a method for estimation of vitamin B1 in foodstuffs [Chick and Roscoe, 1929, 1].Vitamin B2 content of egg-white. The content of vitamin B2 can be estimated by measuring the minimal daily dose required to restore growth which has ceased in young rats after short periods, 1-2 weeks, on a synthetic diet containing vitamin B1 and lacking only vitamin B2 [Chick and Roscoe, 1928]. It has been found that a daily dose of 2-5-5-0 g. of fresh, cooked, egg-white (dry weight 0-3-0-6 g.) or of an
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