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PubMed2000

Leg development in flies versus grasshoppers: differences in dpp expression do not lead to differences in the expression of downstream components of the leg patterning pathway.

All insect legs are structurally similar, characterized by five primary segments. However, this final form is achieved in different ways. Primitively, the legs developed as direct outgrowths of the body wall, a condition retained in most insect species. In some groups, including the lineage containing the genus Drosophila, legs develop indirectly from imaginal discs. Our understanding of the molecular mechanisms regulating leg development is based largely on analysis of this derived mode of leg development in the species D. melanogaster. The current model for Drosophila leg development is divided into two phases, embryonic allocation and imaginal disc patterning, which are distinguished by interactions among the genes wingless (wg), decapentaplegic (dpp) and distalless (dll). In the allocation phase, dll is activated by wg but repressed by dpp. During imaginal disc patterning, dpp and wg cooperatively activate dll and also indirectly inhibit the nuclear localization of Extradenticle (Exd), which divide the leg into distal and proximal domains. In the grasshopper Schistocerca americana, the early expression pattern of dpp differs radically from the Drosophila pattern, suggesting that the genetic interactions that allocate the leg differ between the two species. Despite early differences in dpp expression, wg, Dll and Exd are expressed in similar patterns throughout the development of grasshopper and fly legs, suggesting that some aspects of proximodistal (P/D) patterning are evolutionarily conserved. We also detect differences in later dpp expression, which suggests that dpp likely plays a role in limb segmentation in Schistocerca, but not in Drosophila. The divergence in dpp expression is surprising given that all other comparative data on gene expression during insect leg development indicate that the molecular pathways regulating this process are conserved. However, it is consistent with the early divergence in developmental mode between fly and grasshopper limbs.

Animals↗
PubMedDate not supplied

Meeting the challenge of funding and allocating resources to mental health across Europe: developing the Mental Health Economics European Network.

AIMS: There is growing demand for economic analysis to support strategic decision-making for mental health but the availability of economic evidence, in particular on system performance remains limited. The Mental Health Economics European Network (MHEEN) was set up in 2002 with the broad objective of developing a base for mental health economics information and subsequent work in 17 countries. METHODS: Data on financing, expenditure and costs, provision of services, workforce, employment and capacity for economic evaluation were collected through bespoke questionnaires developed iteratively by the Network. This was augmented by a literature review and analysis of international databases. RESULTS: Findings on financing alone suggest that in many European countries mental health appears to be neglected while mechanisms for resource allocation are rarely linked to objective measure of population mental health needs. Numerous economic barriers and potential solutions were identified. Economic incentives may be one way of promoting change, although there is no 'one size fits all solution. CONCLUSIONS: There are significant benefits and synergies to be gained from the continuing development of networks such as MHEEN. In particular the analysis can be used to inform developments in Central and Eastern Europe. For instance there is much that can be learnt on both how the balance of care between institutional and non-institutional care has changed and on the role played by economic incentives in ensuring that resources were used to develop alternative community-based systems.

Capital Financing↗
PubMed1982

Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. II. Results of long-term therapy. Veterans Administration Cooperative Study Group on Antihypertensive Agents.

As described in the preceding communication, either propranolol hydrochloride or hydrochlorothiazide were randomly allocated in a double-blind manner to 683 patients with initial diastolic BP in the range of 95 to 114 mm Hg. Of this number, 394 entered the long-term treatment phase. During the subsequent 12 months of long-term treatment, hydrochlorothiazide was more effective than propranolol in controlling BP (mean reductions, -17.5/-13.1 mm Hg with hydrochlorothiazide compared with -8.3/-11.3 with propranolol. After treatment with hydrochlorothiazide, a greater percentage of patients achieved the goal diastolic BP of less than 90 mm Hg (65.5% compared with 52.8% taking propranolol). Also during treatment, fewer patients receiving hydrochlorothiazide required termination as compared with those receiving propranolol; comparative dosage requirements were lower; additional titration during long-term treatment was required less often, and BP remained lower after withdrawal of the active drugs. However, biochemical abnormalities were greater with hydrochlorothiazide. Although not statistically significant, the antihypertensive effects of hydrochlorothiazide were greater in blacks than in whites. Whites, on the other hand, had a greater response to propranolol than blacks, although it was still less than the response of the whites to hydrochlorothiazide.

Adult↗
PubMedDate not supplied

Aminoglutethimide in advanced breast cancer: prospective, randomized comparison of two dose levels. Italian Cooperative Group.

In a multicenter randomized clinical trial 106 post-menopausal patients with progressive metastatic breast cancer were allocated to receive 500 mg or 1000 mg Aminoglutethimide (AG) per os daily. Cortisone Acetate (CA) replacement dose was 37.5 mg/day orally in both groups. In 91 fully evaluable patients, no statistically significant difference was observed between the two therapeutic regimens, neither in terms of overall response (28 vs 35%) and by site responses, nor in terms of median time to progression (10.5 vs 14.5 months) and median overall survival (20 vs. 22 months). The tolerability was satisfactory in both regimens. Although no statistically significant differences occurred, in the low dose regimen we observed fewer patients with side-effects (25% vs 6%) and induced grade 3 side-effects (4% vs 9%). Our results confirm that AG daily doses of 500 and 1000 mg associated with corticosteroids have a comparable effect. Because of its slight but clinically noticeable better tolerability, the lower dose is the preferable regimen in the treatment of advanced breast cancer.

Administration, Oral↗
PubMed1992

A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens.

A new, highly purified inactivated tick-borne encephalitis (TBE) vaccine (FSME-Vaccine Behring, BI 71.061) was recently registered in Germany. A multinational phase II study was performed in seven centres located in areas endemic for TBE. A total of 379 healthy adults were randomly allocated into three dosage groups (1.0, 1.5 and 2.0 micrograms antigen per dose, respectively) and into two immunization schedules [vaccination with one dose of 0.5 ml intramuscularly on days 0, 7 and 21 (abbreviated schedule), or on days 0, 28 and 300 (conventional schedule)]. Antibody response to vaccination was assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test (HIT) and neutralization test (NT). Seroconversion rates in the different groups 28 days after one single dose were 75.3-83.5% in ELISA, 35.8-50.6% in HIT, and 100% in NT. All vaccinees showed seroconversion in all tests on day 42 in the conventional schedule and on day 35 in the abbreviated schedule, with the exception of one subject, who remained seronegative in HIT only. Geometric mean titres (GMT) of about 3000 in ELISA were achieved by two vaccinations in the conventional schedule and showed a booster increase to 5500-8000 GMT after revaccination on day 300. Overall frequency of adverse events (related and unrelated) was 37% (conventional schedule) and 46% (abbreviated schedule) after the first, 9% and 21% after the second, and 5% and 15% after the third vaccination, respectively. Generally, side effects were mild and transient, including mainly headache, fever, malaise and local irritation. Serious, vaccine-related side effects did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles.

In adult animals, peptide hormones, including oxytocin and arginine vasopressin, have been implicated in both parental behavior and the modulation of anxiety. The purpose of this study was to examine the consequences of developmental manipulations of oxytocin for the later expression of alloparental behavior as well as behavioral responses to a novel environment, the elevated plus maze (EPM). Prairie voles (Microtus ochrogaster), a cooperatively breeding species, were selected for this study. On neonatal Day 1, pups received an ip injection of oxytocin or oxytocin antagonist, or were controls, receiving either saline or handling only. At 21 and approximately 60 days of age, each animal was tested for parental care toward novel stimulus pups. At approximately 67 days, an EPM test was administered. Control females at 60 days of age were more likely to attack pups and spent less time in the open arm of the EPM, both of which might reflect higher levels of anxiety in females than males. In males, neonatal treatment with oxytocin antagonist was associated with reductions in parental care, especially during the initial exposure to pups on Day 21. Female behavior was not significantly changed as a function of neonatal treatments. Findings to date implicate vasopressin in the behavioral changes in males, that in later life followed a single exposure to an oxytocin antagonist, and suggest caution in the clinical use of agents such as Atosiban, which may have the potential to influence infant development.

Animals↗
PubMed2006

Health Impact Assessment: how the Canton of Ticino makes health a common issue.

HIA is based on the theory of health determinants, which recognizes that well-being is determined by a wide range of economic, social and environmental factors, by heredity and medical intervention. The intended HIA procedure represents a new approach to the evaluation of all cantonal policies in order to assess their potential health impacts and to improve the quality of governmental decisions, through recommendations to enhance predicted positive health impacts and minimize negative ones.

Environment↗