Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.     

Kinetics and viral protein specificity of the cytotoxic T lymphocyte response in healthy adults immunized with live attenuated varicella vaccine.

The cytotoxic T lymphocyte (CTL) response was evaluated in adults given live attenuated varicella vaccine, using target cells expressing varicella-zoster virus (VZV) immediate-early protein (IE62) or VZV glycoproteins gpI, gpIV, or gpV to determine viral protein specificity. The frequency of CTL that recognized IE62 was 1:171,000 +/- 46,000 SE in subjects tested 10 days to 8 weeks after the initial vaccine dose; the induction of CTL specific for gpI was equivalent. CTL recognition of VZV proteins was mediated by CD4+ or CD8+ cells. CTL recognition of IE62 and gpIV persisted in vaccinees (tested approximately 4 years later) and was comparable to that in the naturally immune. The mean frequency of CTL specific for gpV was lower (but not significantly) in vaccinees than in naturally immune subjects. Assay of responder cell frequencies showed persistence of equivalent numbers of T lymphocytes that recognized IE62 and gpI in vaccinees and naturally immune subjects. Immunization with this vaccine elicited memory T lymphocyte responses to VZV comparable to those induced by natural infection.     

Functional significance of prorenin internalization in the rat heart

Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2(d) renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.     

Inhibin bioactivity and pituitary cell mitogenic activity from cultured chicken ovarian granulosa and thecal/stromal cells

A sensitive bioassay for inhibin based on the suppression of FSH release from cultured sheep anterior pituitary cells was used to determine whether inhibin is present in the preovulatory follicle in the domestic hen. Granulosa and thecal/stromal layers were separated from the five largest (F1-F5) yellow yolky follicles in the ovary and incubated in culture medium for 18 h. Inhibin was found predominantly in the media in which granulosa layers had been incubated. There was a progressive increase in the amount of inhibin produced per mg granulosa layer protein during the 5-6 days before ovulation. The ovary was observed to contain a growth factor which stimulated the proliferation of ovine pituitary cells. Thecal/stromal layer-conditioned medium (ThCM) but not granulosa layer-conditioned medium had a dose- and time-dependent mitogenic effect on cultured sheep pituitary cells. The maximal mitogenic effect achieved for ThCM was four to fivefold greater than control media and was significantly higher than the maximal mitogenic effects of epidermal growth factor (250 ng/ml; 1.5 x control) and transforming growth factor-beta (500 ng/ml; 1.2 x control). It is concluded that inhibin is produced by the granulosa layers in the large yellow yolky preovulatory ovarian follicles of the domestic hen. The thecal/stromal layers in these follicles produce a potent mitogenic factor, not produced by the granulosa layers, which stimulates the division of ovine anterior pituitary cells in vitro.     

Nerve growth factor enhances [3H]nicotine binding to a nicotinic cholinergic receptor on PC 12 cells.

Although nicotinic cholinergic agonists have functional effects on PC 12 cells, radioligand-binding sites have not been detected. We, therefore, studied PC 12 cells incubated in the presence of nerve growth factor (NGF) and determined that specific [3H]nicotine-binding sites were induced approximately 2.5-fold in the presence of NGF (50 or 100 ng/ml). Specific binding was maximal between the first (100 ng/ml NGF) and seventh (50 ng/ml NGF) days of treatment and was stable for 2 weeks with addition of NGF every 3 days. Using intact cells, average association and dissociation rates for [3H]nicotine were 0.00021 min-1 nM-1 (n = 2) and 0.048 min-1 (n = 2), respectively, at 4 C, yielding an average apparent Kd of 229 nM. At 22 C, stable equilibrium was not attained during association studies. A similar Kd value for broken cell preparations was obtained by kinetic analysis (i.e. an average association rate of 0.00042 min-1 nM-1 and dissociation rate of 0.087 min-1), yielding an average Kd value of 207 nM (n = 2) at 4 C. By saturation binding analysis of intact cells, an average Kd of 292 nM (n = 2) and a binding capacity (Bmax) of 15,118 molecules/cell were obtained. [3H]Nicotine binding was inhibited on an equimolar basis by L-(-)nicotine and N-methylcarbamylcholine. D-(+) Nicotine was 7-fold less potent, whereas alpha-bungarotoxin, mecamylamine, and atropine showed no significant inhibition. [3H]Nicotine binding was also inhibited quantitatively by mono-specific polyclonal antibodies raised against the predicted alpha 3-subunit sequence (amino acids 130-139) of the rat neuronal nicotinic cholinergic receptor. This study represents the first biochemical characterization of NGF-stimulated nicotine-binding sites on PC 12 cells and confirms previous evidence of the presence of functional nicotinic cholinergic receptors on these cells.     

Key High‐efficiency Practices of Emergency Department Providers: A Mixed‐methods Study

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed‐methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety‐nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000‐ to 55,000‐visit) community EDs during two 4‐hour periods and recorded in minute‐by‐minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, “inefficiency practices,” demonstrated significant negative correlations: non–work‐related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.