Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer's disease.

The time course of formation of neurofibrillary tangles (NFT) and senile plaques (SP) in Alzheimer's disease (AD) brain is unknown. Above ground nuclear weapons testing in the late 1950s and early 1960s led to significantly increased levels of 14C in the atmosphere and carbon cycle. Because the amyloid beta peptide of SP and paired helical filaments of NFT, once formed, are relatively resistant to degradation, 14C levels observed in SP and NFT should reflect their year of formation. The purpose of this study was to develop a method to determine whether 14C levels could be used to define NFT and SP ages. Using accelerator mass spectrometry to measure bomb-pulse 14C levels, we determined the average age of formation of isolated SP and NFT fractions in bulk brain samples of 6 AD subjects. Although preliminary, the results demonstrate that it is possible to use bomb pulse 14C to determine the average year of formation of NFT and SP in the brain in AD. In addition, the data show that these structures, once formed, have a much slower carbon turnover rate than normal brain and are not in a formation/enzymatic degradation equilibrium.     

Development of brain stimulation reward in the medial prefrontal cortex: Facilitation by prior electrical stimulation of the sulcal prefrontal cortex

Electrical stimulation of the medial prefrontal cortex (MC) in rats delivered daily for seven days causes a marked improvement in the rate of acquisition of a self-stimulation response. In the present experiment, we looked at whether we could get the same facilitatory effect on self-stimulation of the MC by delivering pre-training stimulation to other points in the brain anatomically related to the MC. Electrical stimulation of the lateral hypothalamus was without effect. However, electrical stimulation of the sulcal prefrontal cortex (SC) either contralateral or ipsilateral to the MC electrode did facilitate acquisition of self-stimulation of the MC. Thus the SC and MC would appear to be part of the same substrate controlling the development of positive reinforcement in the MC.     

The use of detergents and immunoperoxidase reagents for the ultrastructural demonstration of internal immunoglobulin in lymph cells.

Lymph-borne immunoblasts were fixed in dilute glutaraldehyde and then treated with saponin. This treatment made most parts of the cells permeable to ferritin, so that anti-immunoglobulin (Ig) antibodies which had been conjugated to horse radish peroxidase (HRP) had no difficulty in gaining access to Ig which thus could be demonstrated at an ultrastructural level. Best results were obtained by fixing the cells in 0.1% glutaraldehyde for 7 min and then treating them with a 1% solution of saponin for 100 min at 55 degrees C before exposing them to the Ig-HRP conjugate. The method yielded reproducible results and although it causes a small amount of ultrastructural damage, it may be of value in detecting a variety of intracellular antigens.     

Amino acid uptake required for long-term memory formation

α-Amino-iso-butyrate (AIB) inhibits long-term, protein synthesis-dependent memory formation by reducing labelled leucine uptake in vivo without affecting leucine incorporation into protein. Unlike the antibiotic cycloheximide, AIB does not block long-term memory formation through inhibition of protein synthesis per se. The behavioural effect of AIB is restricted to times of administration between 5 min before and 5 min after learning a single trial passive avoidance task by day-old chickens. It is concluded that (1) AIB competes with normal amino acids for uptake into cells, and (2) the uptake of amino acids for protein synthesis specific to long-term memory formation takes place in the first few minutes following learning.     

Visual function and academic performance

Evaluation of 1,910 first-, second-, and third-grade students indicated that visual function and academic performance as measured by reading were not positively related. Visual function tests included visual acuity, muscle balance, preferred eye and hand, color vision, refraction, sensory and motor function, and a writing and drawing task. Academic tests included the Metropolitan Readiness Test, the Cognitive Abilities Test, the Iowa Test of Basic Skills, and the teacher's assessment of reading level. A simple test which can be completed during the office visit and interpreted by the ophthalmologist in the office included drawing, copying, and writing. A segment of this test, the "draw a bicycle test," can be used by an ophthalmologist to demonstrate the difference between vision and performance when examining a child up to third-grade level who is referred because of school failure.     

Safety of prolonged aortic clamping with blood cardioplegia. II. Glutamate enrichment in energy-depleted hearts

Cold blood cardioplegic techniques are limited in their ability to protect energy-depleted hearts during aortic clamping. This study extends our previous observations on the benefits of amino acid (L-glutamate) enrichment of blood cardioplegic solutions as well as the added metabolic benefits of normothermic induction of cardioplegic arrest to increase the rate of repair of energy-depleted hearts. The results demonstrate that L-glutamate enrichment of blood cardioplegic solutions significantly improves metabolic recovery (greater oxygen consumption, better anaerobic metabolism) and ventricular performance. Normothermic induction of glutamate-enriched cardioplegia allowed complete recovery of myocardial metabolism and function compared to cold blood cardioplegic technique and may be used as a form of "active resuscitation" of energy-depleted hearts.     

Resistant Starch Production and Glucose Release from Pre‐Prepared Chilled Food: The SPUD Project

With an increasing prevalence of diabetes worldwide, effective dietary strategies for blood glucose control are crucial. As carbohydrates make up approximately 50% of the diet, it is neither practical nor advisable to avoid them altogether. Most of the carbohydrate in the diet is derived from starch, found in potatoes, pasta, rice and bread. These foods are often processed in some way before consumption, yet little is known about the effects processing, such as chilling and reheating, has on the glycaemic response, particularly when the food is consumed in the context of a mixed meal. This article introduces the SPUD project, a BBSRC DRINC‐funded initiative. Taking the potato as the model carbohydrate, this project will investigate, via in vitro and in vivo studies, the effects of domestic food processing techniques on the glycaemic response. A final study, utilising intrinsically labelled potato and a dual stable isotope methodology, will model glucose flux data to determine the underlying mechanisms of action.     

Bioethics for clinicians: 23. Disclosure of medical error

ADVERSE EVENTS AND MEDICAL ERRORS ARE NOT UNCOMMON. In this article we review the literature on such events and discuss the ethical, legal and practical aspects of whether and how they should be disclosed to patients. Ethics, professional policy and the law, as well as the relevant empirical literature, suggest that timely and candid disclosure should be standard practice. Candour about error may lessen, rather than increase, the medicolegal liability of the health care professionals and may help to alleviate the patient's concerns. Guidelines for disclosure to patients, and their families if necessary, are proposed.