The dimensions of insight in people with dementia.

This study aims to characterize the factors determining the retention or loss of insight in dementia through: (i). a comparison of assessment procedures previously used to quantify loss of insight and (ii). a qualitative analysis of interviews with patients and carers. Semi-structured interviews were carried out with thirty-two people with dementia and their carers, which incorporated assessments via clinical interview, discrepancy ratings between patient and carer on an Activities of Daily Living scale, and prediction of performance on a memory task. The results of these were compared and supplemented with themes arising from qualitative analysis of the interviews. Significant differences were found between insight as measured by a prediction of performance paradigm and other methods of assessment. This may reflect a distinction between implicit and explicit knowledge. Analysis of interviews identified the following factors as contributing to people's awareness of their difficulties: (1). short-term frustration or distress; (2). continuous discontent; (3). lack of concern; (4). normalization of problems; (5). worry and anxiety; (6). defensiveness; (7). explicit denial; and (8). priority given to other problems. We conclude that insight in dementia is a complex, multi-dimensional, and value-laden concept. Emotional and behavioural aspects need to be considered as well as the cognitive, which is emphasized by traditional methods of assessment based on quantitative ratings. Implicit awareness may be accessible through subjects' predictions of performance on cognitive tasks and should be further investigated. An adequate account of insight in dementia should incorporate both objective and subjective measures in order to determine the interrelationships between organic changes, personality factors, and psychological mechanisms. A generally accepted, reliable protocol for the assessment of insight needs to be developed.

The small molecule FKBP ligand GPI 1046 induces partial striatal re-innervation after intranigral 6-hydroxydopamine lesion in rats.

Extensive unilateral striatal deafferentation was produced by intranigral 6-hydroxydopamine (6-OHDA) in rats. Beginning 60 days after 6-OHDA injection animals received a 14-day course of treatment with either the small molecule FKBP ligand GPI 1046 (10 mg/kg) or its vehicle alone. Striatal dopaminergic innervation density was determined from high power image analysis of striatal tyrosine hydroxylase (TH) immunohistochemistry. GPI 1046 treatment did not alter TH fiber density in the contralateral striatum but did produce significantly higher striatal TH fiber density in the ipsilateral caudate-putamen. This striatal re-innervation occurred in the absence of increased nigral sparing, and appears to reflect the GPI 1046 induced sprouting of residual TH+ fibers spared by the 6-OHDA lesion.

Lesions of the intermediate medial hyperstriatum ventrale impair sickness-conditioned learning in day-old chicks.

Lesion studies show that the intermediate medial hyperstriatum ventrale (IMHV), a forebrain visual association area in chicks, is involved in learning and memory for one-trial passive avoidance and imprinting. We examined the effects of IMHV lesions in a one-trial, nongustatory, sickness-conditioned learning task. This task is similar to passive avoidance and imprinting because all three tasks require the chick to remember visual cues in order to respond correctly. However, sickness-conditioned learning differs from imprinting and passive avoidance because it uses sickness as the aversive stimulus and there is a longer conditioned stimulus-unconditioned stimulus interval (30-min delay compared to seconds). Bilateral IMHV lesions given 24 h before training impaired the ability of the chicks to avoid a bead associated with sickness produced by lithium chloride injection, as did pretraining unilateral left or right IMHV lesions. Post-training IMHV lesions given 1 h after training did not impair avoidance of the test bead in the sickness-conditioned learning task. However, lesioned chicks showed generalized avoidance of all test beads. The pretraining lesion results are similar to those found in imprinting and passive avoidance learning; however, the effects of unilateral IMHV lesions differed. Post-training lesion effects are similar to those found in passive avoidance learning. We propose that both left and right IMHV are necessary for sickness-conditioned learning and that post-training IMHV lesions impair the ability of the chick to learn or remember the association between the color of the bead and the aversive consequences of LiCl injection.

The effect of tuberculosis and tuberculosis contact tracing on school function: an exploratory focus group study.

SETTING: Selected schools in East York, an ethnically diverse municipality of 110,000 people within Toronto. OBJECTIVE: To explore school staff's attitudes and beliefs about the nature of tuberculosis and its possible effect on the function and culture of schools. DESIGN: Four focus groups of 6-8 school staff, lasting from 1 to 1.5 hours, were held in the spring of 1997 at four different schools deemed to be at high risk for tuberculosis contact tracing. RESULTS: The study identified the following dominant themes: fear of tuberculosis and its impact on school, lack of knowledge and the need for education concerning tuberculosis, and issues in multiculturalism. CONCLUSION: Tuberculosis was perceived by staff of East York schools to be a source of fear. Lack of accurate and reliable information concerning tuberculosis contributes to this situation. Staff identified age-specific and culturally relevant, educational initiatives as means to reduce this fear.

A new look at an old task: advantages and uses of sickness-conditioned learning in day-old chicks.

In sickness-conditioned learning, animals become ill after sampling a new substance and develop an aversion that is expressed as avoidance of that substance in subsequent presentations. We examined the parameters of a one-trial, nongustatory, sickness-conditioned learning task in day-old chicks. Chicks pecked a bead and were made ill by i.p. injection of lithium chloride (LiCl). Both 0.5 and 1.0 M LiCl (0.1 ml) produced reliable avoidance at test. Chicks injected with LiCl between 15 and 45 min after training avoided the bead at test, whereas those injected within 5 or 10 min or more than 45 min after training did not. Avoidance was present until 24 h posttraining and absent after 48 h. Therefore, robust learning of the sickness-conditioned learning task occurs in one trial without the need for gustatory cues, and memory for the task lasts at least 24 h. Uses of this task to study memory formation in the day-old chick are discussed.

Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models.

Although immunosuppressant immunophilin ligands promote neurite outgrowth in vitro, their neurotrophic activities are clearly independent of their immunosuppressive activity. In the present report, a novel nonimmunosuppressive immunophilin ligand, GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate+ ++) is described. In vitro, GPI-1046 bound to FK506 binding protein-12 and elicited neurite outgrowth from sensory neuronal cultures with picomolar potency with maximal effects comparable to nerve growth factor. In vivo, GPI-1046 stimulated the regeneration of lesioned sciatic nerve axons and myelin levels. In the central nervous system, GPI-1046 promoted protection and/or sprouting of serotonin-containing nerve fibers in somatosensory cortex following parachloroamphetamine treatment. GPI-1046 also induced regenerative sprouting from spared nigrostriatal dopaminergic neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice or 6-hydroxydopamine (6-OHDA) toxicity in rats. The rotational abnormality in 6-OHDA treated rats was alleviated by GPI-1046. These neurotrophic actions in multiple models suggest therapeutic utility for GPI-1046 in neurodegenerative diseases.

The biochemistry of heat illness.

The two common forms of heat illness in the Services are heatstroke and heat exhaustion. Biochemical predisposing factors are considered for each. Susceptibility to malignant hyperthermia should be tested for in cases of heat stroke. The heterozygote status for cystic fibrosis should be established in cases of heat exhaustion.

The role of isotonic and hypertonic solutions in the resuscitation of shocked patients.

The role of intravenous salt solutions in resuscitation is reviewed historically. A brief account of the pathophysiology of shock is given. The particular use of hypertonic solutions in the resuscitation of severely shocked patients is reviewed and its mechanism of action discussed. It is considered that hypertonic solutions may find a role in any future major military conflict. Two hypertonic solutions that are suggested for consideration in this context are 12% sodium chloride (2 mmol/ml) and 8.4% sodium bicarbonate (1 mmol/ml).

The accuracy and standardization of TBG kits.

Three kits for measurement of serum thyroxine-binding globulin (TBG) were compared with a reference radioimmunoassay in forty-three normal euthyroid subjects. The Corning Immophase kit gave similar results to those with the reference method with satisfactory precision and accuracy. The Behringwerke AG RIA-gnost kit gave results with adequate but lower correlation with the reference method (r = 0.80) than that of the Corning kit trial (r = 0.92). The mean value was significantly greater than the reference method mean, indicating that the Behringwerke kit was inaccurately standardized. The CEA-Sorin TBG kit (Eurotope services) gave results with a poor correlation against the reference method (r = 0.59). The mean value was also significantly greater than the reference mean indicating that this kit is both inaccurately standardized and less precise than the other two. It is stressed that TBG-kits need to be periodically standardized against reference methods in the absence of properly validated primary standards in all batches.

A method for the preparation of human thyroxine-binding globulin; its importance in the establishment of an accurate and specific radioimmunoassay.

Pure thyroxine-binding globulin (TBG) is required in radioimmunoassay to prepare monospecific antisera, [125I]TBG and as primary standard. Homogeneous TBG was prepared by a three-stage affinity chromatography procedure; it could not be dissociated into subunits and its molecular weight by SDS polyacrylamide gel electrophoresis was 59 000. The amino acid composition was in agreement with two earlier reports. The secondary structure determined by circular dichroism in the far U.V. showed it to contain 24% each of alpha-helix and beta-pleated sheet. Serum TBG was determined by a 24-h radioimmunoassay using polyethyleneglycol to separate bound and free TBG. Serum TBG (mg/l, mean +/- S.D.) was: normal men 15.3 +/- 2.11 (n = 34), normal women 18.4 +/- 2.72 (n = 32) (P less than 0.005), in women on oral oestrogens 24.0 +/- 5.0 (n = 23), in normal pregnancy 38.6 +/- 3.0 (n =37), in cord blood 21.7 +/- 3.5 (n = 25) (P less than 0.001) and in euthyroid subjects aged over 60 years 17.8 +/- 4.5 (P n.s.). In women with thyroid disease TBG was reduced in hyperthyroidism: 15.5 +/- 2.5 (n = 28) and elevated in hypothyroidism: 21.0 +/- 4.0 (n = 25). Wider use in TBG-assay of non-denatured TBG of proven composition and structure should decrease the scatter in reference ranges and improve its value as a routine thyroid function test as both a primary measurement and as the T4 : TBG ratio.

Controlled trial of synthetic D-penicillamine and prednisone in maintenance therapy for active chronic hepatitis.

In view of promising, but uncontrolled, reports of the use of D-penicillamine in active chronic hepatitis, a randomised, prospective, controlled trial of this drug against prednisone was carried out. Of the 35 patients entered, 18 received D-penicillamine (increasing to 1-2 g daily) and 17 prednisone (15 mg daily). In all patients the disease had already been brought under biochemical control with corticosteroids. During the first year of the trial, the treatment of nine patients in the D-penicillamine group was discontinued (two because of lack of disease control and seven because of side-effects) compared with six patients in the prednisone group (four because of lack of disease control, one because of side-effects, and one because of the development of carcinomatosis. Detailed statistical analysis of the liver function tests in the patients remaining in the trial at the end of the year showed no significant differences. D-penicillamine is associated with a higher frequency of side-effects than is prednisone. However, in some patients it is as satisfactory as prednisone in keeping the disease under control.

Rapid radioimmunoassay of triiodothyronine on Sephadex G-25 by the Ames kit.

A rapid kit method for the determination of serum triiodothyronine levels is described. The method was satisfactory in cases of thyrotoxicosis, but its lower sensitivity in euthyroid patients gave higher levels (range 2.3-3.3 nM/liter) than normally found. The kit would be of value as a rapid method (little over 3 hr) to screen patients suspected of early or T3 thyrotoxicosis.

Evaluation of a kit (Thyrolute) for the combined determination of serum total thyroxine and sequential free thyroxine index using Sephadex G-25 and 125I-thyroxine.

A new kit (Thyrolute, Ames) for the combined determination of serum total thyroxine (T-4) and sequential free thyroxine index (F.T.I.) using Sephadex G-25 and 125-thyroxine was evaluated in 136 patients and normal subjects. The T-4 determination was virtually identical to that used in the Ames Tetralute kit and had a similar accuracy and precision. The sequential F.T.I. was compared with a two-stage F.T.I. The two F.T.I.s showed highly significant correlations in the various groups of patients except euthyroid women with raised thyroxine-binding globulin (TBG) (pregnant or oral contraceptive). The overlap found for the sequential F.T.I. between euthyroid, hypothyroid, and thyrotoxic patients was slightly inferior (9%) to that found with the two-stage F.T.I. (6%), but its diagnostic success rate was higher than that of the serum T-4 determination alone. Serial observations of serum T-4 and sequential F.T.I. were also made on eight patients receiving carbimazole-therapy for hyperthyroidism. The sequential F.T.I. showed complete parallelism with serum T-4 regardless of thyroid status, so that it was of no practical value in these patients. It was concluded that the sequential F.T.I kit would be of most value in the smaller hospital laboratory lacking facilities for the radioimmunoassay of thyroid hormones and thyroid stimulating hormone.