Working memory after traumatic brain injury in children

To investigate the effects of traumatic brain injury on working memory in children, we administered semantic (letter identity) and phonological (letter rhyme) N-back tasks to children who were on average 5 years post-mild (n = 54) or -severe (n = 26) traumatic brain injury and 44 typically developing children who were comparable in age. The correct detection of targets and false alarms were measured for each task. Memory load (which varied from 0 to 3 letters back) and age significantly affected the detection of targets and false alarms in both tasks. The severity of traumatic brain injury affected the correct detection of letters on the identity task and false alarms on the rhyme task. Traumatic brain injury severity also interacted with memory load in its effect on false alarms on the rhyme task. Traumatic brain injury results in impaired working memory and diminished inhibition in children. The N-back working memory task is feasible for administration to brain-injured children and potentially could be useful for studying brain activation associated with working memory and effects of drug therapy in this group of patients.     

Beta-endorphin cells in the arcuate nucleus: projections to the supraoptic nucleus and changes in expression during pregnancy and parturition

Supraoptic nucleus oxytocin neurone activity and secretion are inhibited in late pregnancy and parturition by endogenous opioids. Here, we investigated alterations in the projections and gene expression of beta-endorphin/pro-opiomelanocortin neurones in the arcuate nucleus in the pregnant rat. All regions of the arcuate nucleus were found to contain cells immunoreactive for beta-endorphin fluorescent microbeads retrogradely transported from the supraoptic nucleus, and double-labelled neurones (beta-endorphin plus microbeads), showing that beta-endorphin neurones throughout the arcuate nucleus project to the supraoptic nucleus. There was an increase in the number of beta-endorphin-immunoreactive cells in the arcuate nucleus and an increase in the density of beta-endorphin fibres within the supraoptic nucleus and peri-supraoptic region in late pregnancy and parturition, suggesting enhanced expression of beta-endorphin and increased beta-endorphin innervation of the supraoptic nucleus. Pro-opiomelanocortin mRNA expression in the arcuate nucleus increased in late compared to early pregnancy: the number of positive neurones significantly increased in the caudal region. Fos expression (an indicator of neuronal activation) in the arcuate nucleus was colocalized in beta-endorphin neurones in both proestrus and parturient rats, but the number of positive cells did not increase during parturition, suggesting lack of activation of beta-endorphin neurones at birth. Thus, beta-endorphin cells in the arcuate nucleus project to the supraoptic nucleus and increased innervation during pregnancy may explain the enhanced endogenous opioid inhibition of oxytocin neurones.     

Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001

The authors present estimates of the economic costs to agriculture and industries affected by tourism of the outbreak of foot and mouth disease (FMD) in the United Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to about Pound Sterling3.1 billion. The majority of the costs to agriculture have been met by the Government through compensation for slaughter and disposal as well as clean-up costs. Nonetheless, agricultural producers will have suffered losses, estimated at Pound Sterling355 million, which represents about 20% of the estimated total income from farming in 2001. Based on data from surveys of tourism, businesses directly affected by tourist expenditure are estimated to have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2 billion) as a result of reduced numbers of people visiting the countryside. The industries which supply agriculture, the food industries and tourist-related businesses will also have suffered losses. However, the overall costs to the UK economy are substantially less than the sum of these components, as much of the expenditure by tourists was not lost, but merely displaced to other sectors of the economy. Overall, the net effect of FMD is estimated to have reduced the gross domestic product in the UK by less than 0.2% in 2001.     

Shared care in gastroenterology: GPs' views of open access to out-patient follow-up for patients with inflammatory bowel disease

OBJECTIVE: The aim of this study was to ascertain GPs' views about open access to out-patient follow-up for patients with inflammatory bowel disease (IBD). METHODS: Semi-structured interviews and a postal survey were carried out in general practices in West Glamorgan UK, each with at least one IBD patient taking part in a randomized trial of open access versus routine follow-up, which has been reported elsewhere. A total of 112 GPs from 53 general practices who referred the 180 study patients to specialist gastroenterological care in Neath or Swansea were included in the study. Main outcome measures were GPs' experience of the trial; preferences between methods of out-patient follow-up; and their views about enhancing open access follow-up. RESULTS: Sixty-nine GPs from 40 practices took part in the practice-specific data collection and 91 returned 156 patient-specific questionnaires. They expressed a strong preference for open access follow-up, for both specific patients (108/156 patients) and IBD patients in general (47/69 GPs). Preference for extending open access follow-up to other chronic conditions was not so strong (21/69 GPs). A substantial number of GPs considered their experience of the trial limited (30/69), and few GPs were aware of the shared care guideline distributed before the trial started (8/69). Few GPs encountered any problems in the management of the study patients (9/69) and <50% of the GPs used a Cumulative Encounter Form (29/69) developed for the study. Most GPs were supportive of giving patients written guidelines (56/69) and establishing a gastroenterological (GI) nurse practitioner (45/69). CONCLUSIONS: Open access follow-up of patients with IBD is supported by GPs. The approach would probably be improved by the distribution of written information to patients, the establishment of a GI nurse practitioner and an integrated approach between the nurse, hospital specialist, GP and patient.     

Transcription-targeted gene therapy for androgen-independent prostate cancer

The Escherichia coli enzyme (purine nucleoside phosphorylase, PNP) gene is delivered directly into PC3 tumors by one injection of replication-deficient human type-5 adenovirus (Ad5). Expressed PNP converts the systemically administered prodrug, 6MPDR, to a toxic purine, 6MP, causing cell death. We sought to increase the specificity of recombinant Ad vectors by controlling PNP expression with the promoter region from the androgen-dependent, prostate-specific rat probasin (Pb) gene. To increase its activity, the promoter was combined with the SV40 enhancer (SVPb). Cell lines were transfected with plasmids containing both a reporter gene, under SVPb control, and a reference gene cassette to allow normalization of expression levels. Plasmids expressed approximately 20-fold more reporter in prostate cancer than in other cells, but surprisingly, the SVPb element was both androgen-independent and retained substantial prostate specificity. Killing by Ad5-SVPb-PNP vector of cell lines cultured with 6MPDR for 6 days was 5- to 10-fold greater in prostate cancer than in liver or lung cells. In vivo, a single intratumoral injection of Ad5-SVPb-PNP (4 x 10(8) pfu), followed by 6MPDR administration twice daily for 6 days, significantly suppressed the growth of human prostate tumors in nude mice and increased their survival compared to control animals. Thus, the androgen-independent, prostate-targeting Ad5 vector reduces human prostate cancer growth significantly in vitro and in vivo. This first example of an androgen-independent vector points the way toward treatment of emerging androgen-independent prostate cancer in conjunction with hormone ablation therapy at a time when the tumor burden is low.     

Multiple myeloma associated with lactic acidosis

Type B lactic acidosis is rare among patients with malignant diseases. To date only one case report has documented lactic acidosis occurring in a patient with multiple myeloma (MM). Our patient, a 55-year-old black man, was diagnosed with stage IIIA immunoglobulin G-kappa (IgG-kappa) MM in September 1995. He was found to have severe lactic acidosis at the time of second relapse. During the terminal phase of his disease, he required multiple hospitalizations for management of lactic acidosis and other complications of his MM. No other cause of his elevated lactate levels was identified. Although type B lactic acidosis may more commonly occur in patients with leukemia or lymphoma, it may rarely present in patients with rapidly progressive and refractory MM.