Learned suppression of stereotypy in amphetamine-treated rats: implications for understanding tolerance to amphetamine 'anorexia'

The purpose of this study was to determine whether amphetamine-treated rats can learn to suppress stereotyped movements in order to feed. Rats implanted with cannulae were reinforced with intraoral infusions of milk for holding their heads stationary within a narrow area of space defined by intersecting photobeams. Four of six rats given chronic injections of amphetamine (2mg/kg) learned the response. The amount of milk ingested as a result of the infusions increased over trials at a rate that was comparable to that of rats given milk in bottles. Despite the development of such 'tolerance', analysis of the temporal distribution of photobeam interruptions revealed residual effects of the drug. Specifically, amphetamine-treated rats had longer latencies to initiate infusions and displayed a more fragmented pattern of responding than did saline controls. These results demonstrate that rats can learn to inhibit amphetamine-induced sterotypy and support the view that tolerance to amphetamine 'anorexia' involves learning to suppress stereotyped movements that interfere with feeding. Parallels to the suppression of involuntary movements in humans are noted.     

Advance directives: the experience of health care professionals across the continuum of care.

This study explored the perceptions of health care providers across the continuum of care as to how effective advance directive arrangements were in assuring compliance with the patients' wishes, as well as their overall satisfaction levels with the process. The health care providers who responded to the survey indicated high levels of overall satisfaction with advance directives, despite low patient completion rates and, most significantly, low confidence levels that surrogate decision making accurately reflected the patient's wishes. A secondary analysis compared the perceptions of health care providers with consumers' reasons for failing to complete advance directives. The need for further education was perceived as a primary need by the health care professionals but not by the consumers. Recommendations for policy initiatives and further research are then presented.     

Cost effectiveness of danaparoid compared with enoxaparin as deep vein thrombosis prophylaxis after hip replacement surgery

Guidelines for prophylaxis of deep vein thrombosis (DVT) after hip replacement surgery suggest the use of twice-daily low-molecular-weight heparin as one treatment option. Danaparoid, a low-molecular-weight heparinoid, and once-daily enoxaparin are recently released dosage forms that have been evaluated as pharmacoprophylaxis for DVT after hip replacement surgery. Incremental cost-effectiveness ratio calculations using published efficacy and safety data suggest that enoxaparin (40 mg) daily is the more cost effective of these two agents as routine prophylaxis after hip replacement surgery.     

Spike voltage topography identifies two types of frontotemporal epileptic foci

We characterized voltage topography of frontotemporal EEG spikes in 24 patients with complex partial seizures and identified two distinct patterns. "Type 1" spikes possessed a "dipolar" field with a negative region over the inferolateral temporal scalp and a positive region over the contralateral, centroparietal scalp. "Type 2" spikes showed only a broad, frontotemporal negative field. One or the other spike type predominated in all but two patients. Correlations with clinical data and intracranial EEG suggest that type 2 spikes arise from temporal or frontal neocortex, while type 1 spikes involve mesial temporal structures as well as lateral cortex.     

Interference between gait and cognitive tasks in a rehabilitating neurological population

OBJECTIVES: To quantify the extent of interference between gait and cognitive tasks after brain injury; to investigate whether such interference is common to various cognitive tasks, or confined to specific cognitive modules; to investigate whether such interference declines during recovery from brain injury. METHOD: Fifty participants were recruited from a neurological rehabilitation unit (33 people, 75% of sample); the stroke rehabilitation ward of an acute hospital (11 people, 20%); and a young disabled unit (six people, 5%). Measures of stride duration were taken in single task conditions, and in conjunction with each of four cognitive tasks. Outcome measures were dual task decrements in gait and in cognitive task performance. RESULTS: Overall, a 7% decrement in stride duration was recorded under dual task conditions compared with single task, with stride duration being significantly longer during simultaneous performance of each cognitive task. There was a 4% decrement on average in cognitive task performance under dual task conditions, with significant decrements being recorded for word generation while walking and paired associate monitoring while walking. A significant correlation (r=0.45) was found between dual task decrements and scores on a standard measure of disability-the Barthel activities of daily living scale-but the correlation with 10 m walking time was not significant (r=0.18). CONCLUSION: Interference between cognitive tasks and motor control activities such as gait is a problem in neurological rehabilitation settings. Interference between cognition and locomotor tasks may be important in assessing neurological patients' ability to function independently, and in designing therapies for both cognitive and motor rehabilitation.     

Phase II study of theophylline in chronic lymphocytic leukemia: a study of the Eastern Cooperative Oncology Group (E4998).

The Eastern Cooperative Oncology Group (ECOG) performed a phase 2 study in B-cell chronic lymphocytic leukemia (CLL) of oral theophylline, a methylxanthine that inhibits cyclic nucleotide phosphodiesterases, thereby inducing the intracellular accumulation of cyclic adenosine monophosphate (cAMP). In 25 patients with Rai stages 0-I, theophylline, 200 mg given orally every 12 h was well tolerated. There was one complete response after 22.5 months of treatment, which continues at 27+ months, and 18 other patients had stable disease. In vitro exposure of patients' lymphocytes to aminophylline (75-250 microg/ml), the soluble form of theophylline, resulted in dose- and time-dependent induction of apoptosis in 9/20 patients studied. Apoptosis was documented flow-cytometrically by monitoring the expression of bcl-2 and bax, forward light scatter, fluorescence intensity of binding of CD45 antibody, and the binding of annexin. Patients whose leukemic lymphocytes were susceptible to apoptosis induction by aminophylline in vitro experienced a significantly longer progression-free survival than patients whose cells were resistant to the drug in culture (P=0.025). This suggests that in a CLL population treated with theophylline, induction of an apoptotic response to the drug in vitro is prognostic for absence of clinical progression.     

Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway.

INTRODUCTION: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce risk of colorectal cancer. Although inhibition of cyclooxygenase (COX)-2 is generally thought to be the relevant mechanism, aspirin-like drugs apparently are involved in other pathways and mechanisms. We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer. METHODS: Genetic polymorphisms of five genes identified as being involved in an insulin-related pathway were genotyped using data collected in a case-control study of 1346 incident colon cancer cases and 1544 population-based controls and 952 incident rectal cancer cases and 1205 controls. Genotypes assessed were the 3' untranslated region poly(A) and the intron 8 BsmI polymorphisms of the VDR gene, a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the Gly972Arg polymorphism of the IRS1 gene, and the Gly1057Asp polymorphism of the IRS2 gene. RESULTS: Use of aspirin and NSAIDs was associated with a decreased risk of colorectal cancer, with slightly greater protection from NSAIDs than aspirin for rectal cancer. We observed a significant interaction between IRS1 genotype and aspirin/NSAIDs use and risk of colorectal cancer. Relative to the GR/RR IRS1 genotype, a protective effect from the GG IRS1 genotype was seen in those who did not use NSAIDs; use of NSAIDs was protective for all genotypes. These associations were especially strong for those diagnosed prior to age 65 (P interaction = 0.0006). We also observed a significant interaction between aspirin/NSAIDs use and the VDR gene. Having the SS or BB VDR genotypes reduced risk of colorectal cancer among non-aspirin/NSAID users; however, aspirin/NSAIDs reduced risk for all VDR genotypes. CONCLUSIONS: These data support the protective effect of aspirin and NSAIDs on colorectal cancer risk. In addition, the observed interactions for aspirin/NSAIDs and IRS1 and VDR genotypes suggest that mechanisms other than COX-2 inhibition may be contributing to the protective effect of aspirin and NSAIDs on colorectal cancer risk.     

Urinary antimony in infancy

OBJECTIVE: To determine whether antimony may be detected in the urine during infancy and early childhood and its association with passive exposure to tobacco smoke, as assessed by urinary cotinine. DESIGN: Analysis of spare aliquots of urine collected from infants participating in studies of respiratory function and passive smoking. Urinary antimony was assayed using inductively coupled plasma mass spectroscopy in 201 urine specimens collected at different ages throughout the first two years of life from 122 term and 26 preterm infants. Urinary cotinine was measured using gas liquid chromatography. MAIN OUTCOME MEASURE: Urinary antimony concentrations. RESULTS: Absolute antimony concentrations varied widely between infants, being below the laboratory detection limit of 0.02 microgram/l in 7% of samples, below 0.5 microgram/l in 90.5%, and above the reference value of 1 microgram/l reported for non-occupationally exposed UK populations in 4%. Creatinine standardised antimony values were unrelated to postnatal age or urinary cotinine concentrations and were highest in urine collected from preterm infants within 24 hours of birth (geometric mean (95% confidence interval): 2.3 ng/mg (1.5 to 3.4)). CONCLUSIONS: Although antimony is present at very low concentrations in urine during infancy and early childhood, the relevance to health is uncertain. The higher levels found in preterm infants may reflect prematurity or fetal assimilation of antimony. Tobacco is unlikely to be an important source of environmental exposure to antimony during infancy and early childhood.