Mortality of women with ductal carcinoma in situ of the breast: a population-based study from the Girona province, Spain (1994-2013).

PURPOSE: We aim to comprehensively describe the incidence and mortality trends of ductal carcinoma in situ (DCIS) in the Girona province, Spain (1994-2013) and to estimate the all-cause mortality excess risk of diagnosed women. METHODS: Age-standardized rates of DCIS were estimated between 1994 and 2013. Standard mortality ratios (SMR) and absolute excess mortality were calculated overall and by tumor and patient characteristics. A sensitivity analysis was conducted excluding cases with a subsequent invasive breast cancer (sIBC). RESULTS: Of the 641 women included, 56 died (follow-up time: 8.4 person-years). Between 1994 and 2013, a significant increase in incidence and decrease in mortality was identified among women aged between 50 and 69 years old. Neoplasms and circulatory system disease were the most common causes of death. No excess risk of death was found overall, except for women aged < 50 years (SMR = 3.44, 95% CI 1.85; 6.40) and those with a sIBC (SMR = 2.51, 95% CI 1.26; 5.02), risk that lessened when cases with sIBC were excluded. Patients with sIBC also showed an excess risk (SMR = 2.29, 95% CI 1.03; 5.10). CONCLUSIONS: Among women aged 50-69 years old, incidence of DCIS has significantly increased yet mortality has decreased. Overall, the all-cause mortality risk of women diagnosed with DCIS remains similar to that of the general population except for women diagnosed before age 50 and those with sIBC, who showed a significant increased risk. Differential management of these patients should be considered.

Therapeutic potential of metabotropic glutamate receptor modulators.

Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is a major player in complex brain functions. Glutamatergic transmission is primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA and kainate receptors. However, glutamate exerts modulatory actions through a family of metabotropic G-protein-coupled glutamate receptors (mGluRs). Dysfunctions of glutamatergic neurotransmission have been implicated in the etiology of several diseases. Therefore, pharmacological modulation of ionotropic glutamate receptors has been widely investigated as a potential therapeutic strategy for the treatment of several disorders associated with glutamatergic dysfunction. However, blockade of ionotropic glutamate receptors might be accompanied by severe side effects due to their vital role in many important physiological functions. A different strategy aimed at pharmacologically interfering with mGluR function has recently gained interest. Many subtype selective agonists and antagonists have been identified and widely used in preclinical studies as an attempt to elucidate the role of specific mGluRs subtypes in glutamatergic transmission. These studies have allowed linkage between specific subtypes and various physiological functions and more importantly to pathological states. This article reviews the currently available knowledge regarding the therapeutic potential of targeting mGluRs in the treatment of several CNS disorders, including schizophrenia, addiction, major depressive disorder and anxiety, Fragile X Syndrome, Parkinson's disease, Alzheimer's disease and pain.

Presynaptic kainate receptors are localized close to release sites in rat hippocampal synapses.

The subsynaptic distribution of kainate receptors is still a matter of much debate given its importance to understand the way they influence neuronal communication. Here, we show that, in synapses of the rat hippocampus, presynaptic kainate receptors are localized within the presynaptic active zone close to neurotransmitter release sites. The activation of these receptors with low concentrations of agonists induces the release of [(3)H]glutamate in the absence of a depolarizing stimulus. Furthermore, this modulation of [(3)H]glutamate release by kainate is more efficient when compared with a KCl-evoked depolarization that causes a more than two-fold increase in the intra-terminal calcium concentration but no apparent release of [(3)H]glutamate, suggesting a direct receptor-mediated process. Using a selective synaptic fractionation technique that allows for a highly efficient separation of presynaptic, postsynaptic and non-synaptic proteins we confirmed that, presynaptically, kainate receptors are mainly localized within the active zone of hippocampal synapses where they are expected to be in a privileged position to modulate synaptic phenomena.

European health systems and cancer care.

INTRODUCTION: Data on the survival of all incident cases collected by population-based cancer registries make it possible to evaluate the overall performance of diagnostic and therapeutic actions on cancer in those populations. EUROCARE-3 is the third round of the EUROCARE project, the largest cancer registry population based collaborative study on survival in European cancer patients. The EUROCARE-3 study analysed the survival of cancer patients diagnosed from 1990 to 1994 and followed-up to 1999. Sixty-seven cancer registries of 22 European countries characterised by differing health systems participated in the study. This paper includes essays providing brief overviews of the state and evolution of the health systems of the considered countries and comments on the relation between cancer survival in Europe and some European macro-economic and health system indicators, in the 1990s. OVERVIEW OF THE EUROPEAN HEALTH SYSTEMS: The European health systems underwent a great deal of reorganisation in the last decade; a general tendency being to facilitate expanding involvement of the private sector in health care, a process which occurred mainly in the eastern countries (i.e. the Czech Republic, Estonia, Poland, Slovakia and Slovenia). In contrast, organisational changes in the northern European countries (i.e. Denmark, Iceland, Finland and Sweden) tended to confirm the established public sector systems. Other countries, including the UK and some southern European countries (i.e. England, Scotland, Wales, Malta and Italy) have reduced the public role while the systems remain basically public, at least at present. Our findings clearly suggest that cancer survival (all cancer combined) is related to macro-economic variables such as the gross domestic product (GDP), the total national (public and private) expenditure on health (TNEH) and the total public expenditure on health (TPEH). We found, however, that survival is related to wealth (GDP), but only up to a certain level, after which survival continues to be related to the level of health investment (both TNEH and TPEH). According to the Organisation for Economic Co-operation and Development (OECD), the TNEH increased during the 1990s in all EUROCARE-3 countries, while the ratio of TPEH to TNEH reduced in all countries except Portugal. CONCLUSIONS: Cancer survival depends on the widespread application of effective diagnosis and treatment modalities, but our enquiry suggests that the availability of these depends on macro-economic determinants, including health and public health investment. Analysis of the relationship between health system organisation and cancer outcome is complicated and requires more information than is at present available. To describe cancer and cancer management in Europe, the European Cancer Health Indicator Project (EUROCHIP) has proposed a list of indicators that have to be adopted to evaluate the effects on outcome of proposed health system modifications.

Cancer incidence and mortality in Portugal.

In this paper, we present estimates of national cancer incidence in Portugal in 1996-1998, predictions for the year 2000, and interpret the recent cancer mortality trends in light of observations from epidemiological research and risk factor patterns. In Portugal, national mortality data from vital statistics are available from 1960, while cancer registration has been mandatory since 1988, when three regional cancer registries covering the mainland of the Portuguese Republic were set up. Up until now, however, none of these registries has been able to produce data with an acceptable completeness of registration--hence this study. Mortality data from Portugal for 1996-1998 and incidence data for 1990-1995 from Vila Nova de Gaia (RVNG) (the most complete of the Portuguese cancer registries), 14 Italian registries and nine Spanish registries were assembled to produce the best possible estimates of numbers of incident cases for each age group and gender. A total of 19,880 new cancer cases are estimated to have been diagnosed among men in the year 2000, and nearly 17,000 new cancer cases in women. The most common cancer among Portuguese men in 2000 is cancer of the colorectum (3173 new cases), followed by cancers of the prostate (2973), lung (2611), stomach (2206) and urinary bladder (1360). In women, breast cancer is the most common cancer (4358) followed by cancers of the colorectum (2541), stomach (1494) and corpus uteri (1083). The overall age-standardised cancer mortality rate for men in Portugal increased steeply (1.4% annually) during the period 1988-1998, with prostate cancer (3.6% annually), colon and rectum (3.3%) and lung (2.4%) mostly contributing. Among women, the overall cancer mortality rate was stable (a non-significant decrease of approximately 0.2% per year). These remarkable results, particularly in males, demonstrate the need for a comprehensive national programme against cancer. Since the increasing epidemic of lung cancer (in men), as well as other tobacco-related cancers, is observed in Portugal, the important component of such a programme should be a nationwide tobacco control programme. Improving accessibility to highly effective diagnostic and treatment procedures for cancer in general and colorectal and prostatic cancers in particular should be a priority in the fight against cancer.

Unchanged survival of gastric cancer in the southeastern Netherlands since 1982: result of differential trends in incidence according to Laurén type and subsite.

Despite widespread use of endoscopy and improved surgical treatment, the prognosis for gastric cancer remains poor. Although the incidence has been declining for more than 2 decades, unfavourable changes in relative frequency of histological subtypes and subsites may have occurred. We therefore assessed the nature and impact of these changes in association with socio-economic status in a population-based study during the period 1983-1995. Furthermore, tumour characteristics were analysed as predictors of survival for 1,543 cases recorded in the Eindhoven Cancer Registry during the period 1983-1992. Overall 5-year relative survival remained at 22%, being 70%, 37% and 11% for stage I, II and III, respectively. The Laurén histological type and location were also found to have prognostic value. Tumours with the worst prognosis (diffuse type and located at the cardia) developed predominantly in younger patients and were increasing. Moreover, unlike for other tumours, high educational status was associated with unfavourable prognosis. Stage at diagnosis and survival have remained unchanged, despite likely improvements in early detection through better access to endoscopy and better supportive care after surgical treatment. The unfavourable, in part relative, changes in incidence are likely to be responsible for the lack of improvement of survival rates.

Acao do hidroxido de calcio como moluscicida. / Action of calcium hydroxide as molluscacides

Trata-se de uma experiencia realizada no foco de esquistossomose do municipio de Primavera, onde os criadouros de B. straminea e B. glabrata representam importante papel na cadeia de transmissao. Empregouse o hidroxido de calcio como moluscicida alternativo, obtendo-se execelentes resultados, sem danos significativos a flora e fauna aquaticas, como os que costumam ocorrer com os moluscicidas empregados nas grandes areas endemicas