Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA).

BACKGROUND: The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter >4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. PATIENTS AND METHODS: From 2007 to 2010, 897 patients were included in a prospective, population-based, risk-adapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (n = 469) or surveillance (n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. RESULTS: At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, P = 0.011] and tumor diameter >4 cm (HR 2.7, P < 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin <7 × AUC compared with that in patients receiving ≥7 × AUC. CONCLUSION: Stromal invasion in the rete testis and tumor diameter >4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.

One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group.

BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. PATIENTS AND METHODS: In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. CONCLUSIONS: The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.

The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia.

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL.

Health reform in Mexico: the promotion of inequality.

The Mexican health reform can be understood only in the context of neoliberal structural adjustment, and it reveals some of the basic characteristics of similar reforms in the Latin American region. The strategy to transform the predominantly public health care system into a market-driven system has been a complex process with a hidden agenda to avoid political resistance. The compulsory social security system is the key sector in opening health care to private insurance companies, health maintenance organizations, and hospital enterprises mainly from abroad. Despite the government's commitment to universal coverage, equity, efficiency, and quality, the empirical data analyzed in this article do not confirm compliance with these objectives. Although an alternative health policy that gradually grants the constitutional right to health would be feasible, the new democratically elected government will continue the previous regressive health reform.

Risk indicator of dust exposure and health effects in cement plant workers.

A frequent practical problem of research in developing countries is the lack of reliable records on occupational hazards. To improve this situation, this article suggests and evaluates a two-phase method for estimating particle exposure. The first phase uses the focal group, or homogeneous group, technique to reconstruct the production process and estimate the level of dust exposure. The second phase applies the technique of individual history of exposure to hazards at work, an index that accumulates current and previous exposure. This method was introduced in a Portland cement plant to assess the dust-exposure levels of workers and to evaluate its usefulness in the association between estimated exposure levels and the frequency of health effects--particularly respiratory effects--that occurred as a result of such exposures. The results obtained from the analysis of the production process and of the exposure levels determined by the cement workers showed that it is possible to reconstruct the history of exposure to cement dust during each worker's occupational history. The results also showed that estimated exposure is related to respiratory damage; higher exposure resulted in more serious diseases. This supports the usefulness of the suggested methodology.

The Mexican Social Security counterreform: pensions for profit.

The social security counterreform, initiated in 1997, forms part of the neoliberal reorganization of Mexican society. The reform implies a profound change in the guiding principles of social security, as the public model based on integrality, solidarity, and redistribution is replaced by a model based on private administration of funds and services, individualization of entitlement, and reduction of rights. Its economic purpose is to move social services and benefits into the direct sphere of private capital accumulation. Although these changes will involve the whole social security system--old-age and disability pensions, health care, child care, and workers' compensation--they are most immediately evident in the pension scheme. The pay-as-you-go scheme is being replaced by privately managed individual retirement accounts which especially favor the big financial groups. These groups are gaining control over huge amounts of capital, are authorized to charge a high commission, and run no financial risks. The privatization of the system requires decisive state intervention with a legal change and a sizable state subsidy (1 to 1.5 percent of GNP) over five decades. The supposed positive impact on economic growth and employment is uncertain. A review of the new law and of the estimates of future annuities reveals shrinking pension coverage and inadequate incomes from pensions.

Market commodities and poor relief: the world bank proposal for health.

Investing in Health is the World Bank's blueprint for a new health policy within the context of structural adjustment. While this document includes a broad range of arguments, its implicit premises are neoliberal as can be deduced from its "agenda for action." Health is defined as a private responsibility and health care as a private good. This leads to a health policy based on two complementary principles: the reduction of state intervention and public responsibility, and the promotion of diversity and competition (i.e., privatization). Thus, public institutions should provide only a limited number of public goods and narrowly defined, cost-efficient forms of relief for the poor. All other health-related activities are considered private duties, to be resolved by the market, NGOs, or families. The World Bank policy provides a pragmatic contribution to efforts to achieve fiscal balance. However, it also pushes to recommodify health care and to turn health into a terrain for capital accumulation through the selective privatization of health-related financial and "discretionary" services. The proposal implies large-scale experimentation and dismantling of public institutions which are the only alternative now accessible to the majority. It rejects health as a human need and a social right, and violates basic values by claiming that life and death decisions can be justly made by the market or through a cost-effectiveness formula.

Do poverty programs alleviate poverty? The case of the Mexican National Solidarity Program.

In recent years, compensatory poverty programs have been adopted in several countries in response to the social and political effects of structural adjustment programs implemented by most Latin American and African countries. The authors analyze the Mexican National Solidarity Program "Pronasol," often cited as an exemplary social compensation program, by inquiring into its impact on poverty. The authors first investigate the relationship between structural adjustment and the process of impoverishment, in order to establish the dynamics and magnitude of poverty in Mexico. They find that the structural adjustment program has considerably increased poverty, mainly through a sustained wage decrease and job losses. The authors next discuss whether Pronasol complies with the requisites of a program that warrants a social minimum for the poor, and whether the resource allocation complies with objective criteria of the sociogeographic distribution of poverty. The data suggest that Pronasol cannot be considered to guarantee a social minimum for the poor, given the magnitude of poverty, the scarce resources allocated, the orientation of the subprograms, and the regional distribution of funds. Nor does it qualify as a social compensation program of any importance. Finally, an alternative interpretation of Pronasol is offered in the field of legitimation and political control.

C1 subcomponent complexes: basic and clinical aspects.

C1 subcomponents form a variety of complexes that can be detected in normal and pathological sera. Since aberrations of C1 subcomponents in disease could reflect in vivo interactions with influence on complement function, studies of C1 subcomponent complexes might provide insight into pathogenetic mechanisms. C1 inhibitor (C1Inh)-dependent dissociation of the C1q(C1r-C1s)2 complex gives rise to C1Inh-C1r-C1s or C1Inh-C1r-C1s-C1Inh complexes. Increased concentrations of C1Inh-C1r-C1s probably signify prevention of C1 activation, while C1Inh-C1r-C1s-C1Inh appears to be a clinically useful marker of efficient classical pathway activation. "Free" C1q as found in some pathological sera, and in joint fluids of patients with rheumatoid arthritis could be a result of C1Inh-dependent dissociation of C1q(C1r-C1s)2. The presence in serum of zymogen (C1r-C1s)2 is an expected finding in various conditions with low C1q concentrations without evidence of C1 activation. It is not excluded that circulating (C1r-C1s)2 might sometimes be acquired due to factors capable of interacting with the collagenous part of the C1q molecule.

Western blot analysis of human IgG reactive with the collagenous portion of C1q: evidence of distinct binding specificities.

An enzyme-linked immunosorbent assay (ELISA) with purified collagenous C1q fragments in the solid phase was used for detection of C1q-specific immunoglobulins in the sera of twelve patients with systemic lupus erythematosus (SLE) or the SLE-like disease hypocomplementemic urticarial vasculitis syndrome (HUVS). By clinical criteria, four patients had SLE, and three HUVS. Five patients had overlap syndromes. All patients demonstrated high concentrations of C1q-specific IgG and markedly low concentrations of circulating C1q. Detection of C1q-specific IgG in SLE sera was facilitated by employment of saturating concentrations of collagenous C1q fragments in the solid-phase ELISA. When added to SLE serum, immune complex-fixed C1q inhibited binding of IgG to the C1q fragments, whereas addition of C1q alone had limited inhibitory effects. Under similar conditions, using approximately equimolar amounts of C1q relative to solid-phase C1q fragments, no ELISA inhibition was obtained after addition of C1q or immune complex-fixed C1q to a HUVS serum. Even in large excess, purified C1q did not inhibit binding of HUVS-IgG to solid-phase C1q fragments. Thus, possible interactions between HUVS-IgG and native Clq are probably of low affinity. By Western blot analysis, IgG reactive with the B and C chains of C1q was found in the eight patients with evidence of HUVS, five of whom also showed IgG binding to C'-C' and A'-B' dimers of collagenous C1q fragments. Sera from SLE patients were negative by Western blot analysis. It seems likely that C1q-specific IgG in SLE primarily recognizes assembled C1q molecules or collagenous C1q fragments expressing conformational epitopes of bound C1q. Interestingly, patients with evidence of HUVS fairly consistently had zymogen (C1r-C1s)2 complexes in their serum, while patients with SLE showed high concentrations of complexes containing Cl inhibitor, C1r and C1s. Different binding specificities of C1q-reactive IgG could be of importance with regard to pathogenetic mechanisms in SLE and HUVS. There was no correlation between findings of C1q-specific IgG and a variety of autoantibodies associated with SLE and SLE-like disease.

Participatory research on workers' health.

The concern for workers' health has increased in Latin America during the last decade both on the part of research institutions and trade unions. A special emphasis has been given to active participation of workers not just in the transformation of working conditions to improve health but also in generation of knowledge. This paper presents an action oriented participatory research methodology based on a collective questionnaire that permits the recollection of data on characteristics of the labour process, risks and health damage. A comparison between the information on risks, health damage and the relationship risks-damage obtained with this methodology and those of an individual questionnaire applied at the same steel factory shows that the results produced are very similar. In view of these findings it is concluded that the participatory methodology has some important advantages over traditional methodologies since it provides qualitative information on the labour process, a precise picture of the main risks and how they are produced and semi-quantitative data on health damage, and at the same time, generates a process of consciousness and organization among workers that enables them to promote health oriented action.

The Free Trade Agreement and the Mexican health sector.

This article presents a discussion of the probable implications for the Mexican health sector of the Free Trade Agreement (FTA) between the United States, Canada, and Mexico. The authors argue that the FTA should be seen as part of neoliberal policies adopted by the Mexican government in 1983 that are based on large-scale privatization and deregulation of labor relations. In this general context the health sector, which traditionally has been dominated by public institutions, is undergoing a deep restructuring. The main trends are the decapitalization of the public sector and a selective process of privatization that tends to constitute the private health sector in a field of capital accumulation. The FTA is likely to force a change in Mexican health legislation, which includes health services in the public social security system and recognizes the right to health, and to accelerate selective privatization. The U.S. insurance industry and hospital corporations are interested in promoting these changes in order to gain access to the Mexican market, estimated at 20 to 25 million persons. This would lead to further deterioration of the public institutions, increasing inequalities in health and strengthening the private sector. The historical trend toward the integration of a National Health Service in Mexico would be interrupted in favor of formation of a dual private-public system.

C1 subcomponent complexes and C2 cleavage in active systemic lupus erythematosus.

We studied the activation and C1 inactivator-dependent dissociation of the first component of complement, the C1q(C1r-C1s)2 complex, in relation to recruitment of the classical activation pathway in the circulation of 24 patients with systemic lupus erythematosus (SLE). The patients were divided into three groups on a clinical basis, and were investigated during flares of disease activity. Group I had mild symptoms, group II major extrarenal manifestations, and group III manifest renal disease. High serum concentrations of trimer complexes containing C1 inactivator, activated C1r and zymogen C1s(C1 IA-C1r-C1s) were found in the majority of the patients. Some patients with high C1 IA-C1r-C1s concentrations showed no evidence of classical pathway activation, indicating that C1 activation was controlled by the action of C1 IA at the C1r level. By contrast, formation in serum of tetramer complexes in which C1 IA was firmly bound to both C1r and C1s (C1 IA-C1r-C1s-C1 IA) was associated with C2 and C3 cleavage in EDTA plasma, and with manifest hypocomplementemia. Low C1 IA-C1r-C1s-C1 IA values were observed in conjunction with substantial C2 cleavage in a few patients. Thus, C1 IA-C1r-C1s-C1 IA may not always be a sensitive indicator of classical pathway activation. Efficient recruitment of the classical pathway was related to disease severity, with some overlap between the clinical groups. In conclusion, C1 dissociation with formation of C1 IA-containing complexes was consistently found in patients with active SLE. The results suggested that C1 IA-dependent control of C1 activation was of biological significance in the disease.

Crisis, neoliberal health policy, and political processes in Mexico.

The Mexican case represents an orthodox neoliberal health policy in the context of the structural adjustment adopted by the Mexican government in 1983. The social costs of this strategy are very high, including an increase in unemployment, wage depression, regressive redistribution of wealth, and profound changes in social policies. These transformations are reflected in the health sector, where the four main axes of neoliberal policy--expenditure restrictions, targeting, decentralization, and privatization--have been implemented. This represents a change in social policy from a model based on citizens' social rights and the state's obligation to guarantee them, to a model characterized by selective public charity. This strategy has been imposed on society as a result of the Mexican corporative political regime based on a state party system. Since 1985, however, there has been a growing process of independent organization of civil society. This led in the presidential elections of 1988 to the defeat of the candidate of the governing party by the candidate of a popular-democratic opposition front. Although the government party imposed its candidate through electoral fraud, social mobilization against neoliberal policies continues in the midst of an important political crisis that can only be resolved by profound democratization of Mexican society.