Mucosal immunization of sheep with a Maedi-Visna virus (MVV) env DNA vaccine protects against early MVV productive infection

Gene gun mucosal DNA immunization of sheep with a plasmid expressing the env gene of Maedi-Visna virus (MVV) was used to examine the protection against MVV infection in sheep from a naturally infected flock. For immunization, sheep were primed with a pcDNA plasmid (pcDNA-env) encoding the Env glycoproteins of MVV and boosted with combined pcDNA-env and pCR3.1-IFN-gamma plasmid inoculations. The pcDNA plasmid used in the control group contained the lacZ coding sequences instead of the env gene. Within a month post-challenge, the viral load in the vaccinated group was lower (p < or = 0.05) and virus was only detected transiently compared with the control group. Furthermore, 2 months later, neutralizing antibodies (NtAb) were detected in all the control animals and none of the vaccinated animals (p < or = 0.01). These results demonstrated a significant early protective effect of this immunization strategy against MVV infection that restricts the virus replication following challenge in the absence of NtAb production. This vaccine protective effect against MVV infection disappeared after two years post-challenge, when active replication of MVV challenge strain was observed. Protection conferred by the vaccine could not be explained by OLA DRB1 allele or genotype differences. Most of the individuals were DRB1 heterozygous and none was totally resistant to infection.     

Adult health

The objective of this study is to analyse the social inequalities in health status, health related behaviours and mortality among the 25-64 years Spanish population. Data come from the 1997 Spanish National Health Survey, the 1999 Spanish National Survey on Working Conditions, the 2001 Yearbook of Labour and Social Affairs Statistics and the 1998 Mortality Statistics. Most health-related behaviours are more unfavourable for men (smoking, alcohol consumption and overweight) and for less privileged social classes. Among women, entrance into the labour market is associated with more unhealthy behaviours except for overweight. Low weight, however, is more frequent among employed females. Self-perceived health status is better among men, more privileged social class persons and among workers. Whereas classical physical job hazards and work injuries mostly affect men, the impact of psychosocial job hazards and of exposures derived from the domestic work is higher for women. As in other developed countries, the paradox exists that whereas women have a poorer self-perceived health status, mortality is higher among men. The male excess in mortality is related to health-related behaviours that to a great extent are determined by traditional values assigned to masculinity, with higher consumption of tobacco (lung cancer), alcohol (cirrhosis), drugs (HIV and AIDS) and risky behaviours related to injuries. Health policies should take into account social inequalities in health determined by gender, social class and employment status. For doing so, it is important to increase the development of research on social inequalities and of health information systems sensitive to social inequalities.     

Women, family demands and health: the importance of employment status and socio-economic position

Although it is generally assumed that women engaged in paid work have better health than full-time homemakers, little is known about the situation in Southern European countries like Spain or about differences in the impact of family demands by employment status or the potential interaction with educational level. The objectives of this study are to analyse whether inequalities in health exist among housewives and employed women, and to assess whether the relationship between family demands and health differs by employment status. Additionally, for both objectives we examine the potential different patterns by educational level. The data have been taken from the 1994 Catalonian Health Survey (Spain). The sample was drawn from all women aged 25-64 years who were employed or full-time homemakers and married or cohabiting. Four health indicators (self-perceived health status, limiting long-standing illness, chronic conditions and mental health) and two health related behaviours (hours of sleeping and leisure-time physical activity) were analysed. Family demands were measured through household size, living with children under 15 and living with elderly. Overall, female workers had a better health status than housewives, although this pattern was more consistent for women of low educational level. Conversely, the health related behaviours analysed were less favourable for workers, mainly for those of low educational level. Among workers of low educational level, family demands showed a negative effect in most health indicators and health related behaviours, but had little or no negative association at all in workers of high educational level or in full-time homemakers. Moreover, among women of low educational level, both workers and housewives, living with elderly had showed a negative association with poor health status and health related behaviours. These results emphasise the need of considering the interaction between family demands, employment status and educational level in analysing the impact of family demands on women's health as well as in designing family policies and programmes of women's health promotion.     

Supervivencia a largo plazo con quimioterapia a altas dosis de rescate en pacientes con cáncer de células germinales metastásico. Análisis de los patrones de recidiva

Objective

To evaluate survival and relapse patterns in 13 patients with recurrent, or refractory, germ-cell tumours treated with high-dose chemotherapy (HDC) and with peripheral blood stem-cell support.

Material and methods

All patients were treated in a single centre and received a median of 9 cycles (range 3–13) of cisplatinum-based chemotherapy (CT). The protocol consisted of: a) induction with ifosfamide-based CT (EPI: VP16 120 mg/m², ifosfamide 1.3 g/m², cisplatinum 25 mg/m²×4 days); b) mobilisation of PBSC with of either G-CSF (10 ug/kg/day) in 2 patients or EPI plus G-CSF, and c) HDC (carboplatin 350 mg/m², cyclophosphamide 1500 mg/m², VP16 400 mg/m²×3 days). G-CSF (5 μg/kg) was administered until haematopoietic graft. Median age=32 years (range 20–52); tumours=10/11 testicular (1 seminoma), 2 mediastinal. HDC was administered 21 months (range 6–66) post-diagnosis. Inclusion criteria: failure to achieve CR with conventional CT (n=5 patients), poor-prognosis mediastinal tumour (n=1), first recurrence after cisplatinum and ifosfamide-based CT (n=2) and second or third relapse (n=5). At the conclusion of HDC, 9/13 patients were in CR, 1 patient did not receive HDC because CNS progression but was included for survival analysis.

Results

Median times to graft were 9 and 13 days for leukocytes and platelets, respectively. Non-haematological toxicity was low and no therapy-related deaths occurred. Median disease free and overall survival were 19 and 30 months, respectively. Currently, 2 patients have not relapsed at 36 and 80 months. Previously-affected sites of disease were the unique sites of relapse in 5/11 (50%), concomitant distant relapse in 4/11 patients, CNS metastases in 1 patient. Rescue CT consisted of either oral VP16 or CBDCA/Taxol, which induced a new response in 6/10 patients.

Conclusions

HDC achieves 20% improved survival in patients refractory to conventional chemotherapy and non-resectable tumours. No benefit was observed in HDC treatment in patients having only partial response to conventional chemotherapy. Relapse following HDC occurred mainly at previously affected sites.     

Heparin and low molecular weight heparin decrease nitric oxide production by human polymorphonuclear cells.

BACKGROUND: Heparin and heparin derivatives with low anticoagulant activity exhibit a wide spectrum of biological functions affecting adhesion, activation and trafficking of leukocytes. METHODS: We investigated the in vitro effect of heparin and a low molecular weight heparin derivative (LMWH) on nitric oxide (NO) production by human polymorphonuclear leukocytes (PMN). RESULTS: N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated NO production was significantly decreased by heparin at doses of 0.5 and 5 micrograms/mL, while LMWH was only effective at doses of 50 and 200 micrograms/mL by means of a mechanism not related to NO synthase (NOS) activity. CONCLUSIONS: These results support the hypothesis that heparin and LMWH derivatives may offer therapeutic benefit for inflammatory diseases where NO plays a protagonic role.     

Mutación del gen BRAF V600E en el cáncer papilar de tiroides y su efecto en la terapia con yodo radiactivo (131I) posquirúrgica: ¿deberíamos modificar nuestra estrategia terapéutica?

Introduction

The BRAF V600E mutation in papillary thyroid cancer (PTC) has been associated with resistance to ¹³¹I. Our aim was to quantify the response to ¹³¹I after surgery in patients who had the mutation (BRAF+) and those who did not have the mutated gene (BRAF?).