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.

Common epitopes in Clq and collagen type II.

An epitope common for collagen type II and Clq was demonstrated by specific binding of a monoclonal anti-collagen type II antibody, MAb B1, to purified Clq. This was further substantiated by the affinity shown between F(ab')2 fragments of anti-Clq antibodies and rat chondrosarcoma collagen type II. The interaction between MAb B1 and Clq was demonstrated in hemolytic assays, in an enzyme-linked biotin-avidin assay and by the binding of Clq to MAb B1 immobilized on Sepharose 4B beads. MAb B1 recognized only purified Clq and not the macromolecular Cl complex, indicating that the epitope for MAb B1 was situated in the collagen-like region in Clq, where Clq and Cls are anchored. The binding of the purified collagen-like fragment of Clq to radiolabelled MAb B1 confirmed these findings. The affinity between MAb B1 and Clq was significantly increased if Clq was first reacted with heat aggregated IgG, indicating a demasking of the reactive epitope on binding to the aggregated IgG. The present findings raise the question of the pathogenetic significance of the presence of anti-collagen type II antibodies and free Clq, both of which are frequently seen in high amounts in rheumatoid arthritis.

Trimer and tetramer complexes containing C1 esterase inhibitor, C1r and C1s, in serum and synovial fluid of patients with rheumatic disease.

During activation, the first component of complement C1q (C1r-C1s)2 is dissociated in conjunction with the formation of complexes containing C1 esterase inhibitor (C1-INH). Trimer complexes, with zymogen C1s associated with a firm C1-INH-C1r complex (C1-INH-C1r-C1s) can be distinguished from tetramer complexes C1-INH-C1r-C1s-C1-INH) in which C1-INH is firmly bound to both proteases. In the present study a two-stage electroimmunoassay was developed for the specific measurement of C1-INH-C1r-C1s. In the first step, C1-INH and its complexes were immunoprecipitated with anti-C1-INH during electrophoresis in the presence of Ca2+. In the second step, C1s contained in C1-INH-C1r-C1s was dissociated in the presence of EDTA and was measured by immunoprecipitation with anti-C1s. C1-INH-C1r-C1s were consistently found in normal sera. Normal sera did not contain C1-INH-C1r-C1s-C1-INH as assessed with a previously described ELISA procedure. Sera and synovial fluids from two groups of patients with inflammatory arthritis were investigated. In rheumatoid arthritis patients (n = 15) C1-INH-C1r-C1s complexes were usually found at high concentration both in serum and synovial fluid. C1-INH-C1r-C1s-C1-INH complexes were also present with values that were higher in synovial fluid than in serum, in accord with previous findings of classical pathway activation in the inflamed joints of the patients. Patients with spondylarthritic syndromes (n = 7) had serum and synovial fluid C1-INH-C1r-C1s concentrations that were comparable to those of the rheumatoid arthritis patients. If at all present, C1-INH-C1r-C1s-C1-INH were detected in trace amounts. Thus, C1 activation in patients with spondylarthritic syndromes appeared to be efficiently controlled at the C1r level. Distinguishing between C1-INH-C1r-C1s and C1-INH-C1r-C1s-C1-INH may prove of value in further studies of the activation and control of C1 in disease.

C1 activation and dissociation in disease.

The composition of complexes containing C1 inactivator (C1 IA), C1r and C1s was investigated in normal serum after activation of C1 under various conditions. Analyses were performed with PAGE of eluates from Sepharose beads coated with F(ab')2 fragments of anti C1s followed by immunoblotting with anti C1 IA, anti C1s or anti C1r. Eluates obtained from serum treated with aggregated IgG (AGG) contained C1 IA in complex with C1r and C1s with both subcomponents in activated form. Eluates from serum incubated at 37 degrees C for 1, 2 or 3 days without activators showed C1 IA complexed with activated C1r and with C1s in proenzyme state associated to the complex. On analysis of serum, treated as mentioned above, by a variant of the electroimmunoassay using an intermediate gel containing anti-C1 IA and with anti-C1s in the anodal gel the two types of C1r--C1s--C1 IA complexes could be distinguished. Investigation of fresh sera and synovial fluids from patients with rheumatoid arthritis in this assay showed complexes containing C1 IA and C1r-C1s in activated form in the synovial fluids, while C1 IA-activated C1r-proenzyme C1s complexes were found in the corresponding sera.

Social analysis of collective health in Latin America.

During the last 15 years there has been an increasing interest in Latin America to study the collective health conditions as part of and determined by the social, economic and political processes. The present article analyzes the origins of this current of thought, known as Latin American social medicine, and its main theoretical and methodological approach. Since the two basic analytical concepts proposed by this current are 'social class' and 'work process', some examples of concrete studies that employ these are given to highlight the type of study designs used and the knowledge produced

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.

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.

Immune complexes and complement in serous and mucoid otitis media.

The occurrence and quantity of immune complexes in middle ear effusion (MEE) and serum, as well as serum levels of complement (C) factors were investigated in patients with chronic otitis media. Immune complexes were demonstrated in 85% of the serous MEE and in 28% of the sera. Depressed Clq values and presence of abnormal complexes, composed of subcomponents of the first C factor, indicated a disturbed function of the C system. Activation of C by the classical pathway was demonstrated in 23% of the patients. Decreased levels of properdin were also noted. The disorders within the C system tended to normalize as the otitis subsided.

Complement and C1q binding substances in otitis media.

Complement activation, as shown by increased amounts of complexes composed of C1r-C1s-C1 IA, and abnormal complexes of C1r-C1s were demonstrated in serum from patients with acute pneumococcal and chronic otitis media, serous or mucoid respectively. C1q binding substances were shown in middle ear effusions and in sera from patients with chronic serous otitis media. Presence of immune complexes and/or bacterial products capable of binding c1q results in formation of C1r-C1s-C1 IA complexes and may also cause the generation of C1r-C1s complexes. Such a dissociation of the C1 component will compromise the important opsonic function of the classical pathway.

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.

The role of union democracy in the struggle for workers' health in Mexico.

In this article, the author analyzes the struggle for workers' health in Mexico, emphasizing the importance of the general and specific political context. In an overview of the legislation on industrial health and safety, the state institutions involved in the issue, and the characteristics of union organization in Mexico, the author shows that the limited activities related to workers' health have more to do with the relative political weakness of the Mexican working class than with the formal structures of legislation, state institutions, and unions. The second part of the article deals with the four most important struggles for health and safety in Mexico during the last ten years, which show some similarities. These struggles are consistently linked to processes of union democratization and tend to decline when union democracy is lost. The strategies of the companies show a common pattern: removing health issues from collective bargaining and putting them in the hands of state institutions. When workers have opposed this solution, management has used selective repression to solve the conflict. The state institutions subordinate their position to the companies' by postponing action or by doing a technically poor job. Changing the existing situation involves the social legitimation of the workers' health issue, since this would have an impact on the political processes involved, i.e., corporate control over workers, authoritarian labor relations and professionalism, and resources of the state institutions.

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.

Work and health in Mexico.

It is suggested that the relationship between work and health and disease traditionally has been analyzed in a limited way in that work has been considered only as a situational factor which puts workers in contact with environmental risks. It is proposed that work is an essential category for the understanding of disease, if one tries to study disease not as an individual biological phenomenon but as a social (and biological) phenomenon that occurs to the collectivity. Furthermore, it is suggested that the relation between disease and work should be analyzed in terms of the elements of the work process, understood as a technical and social process, and the capacity of different social groups to realize their interests. Reviewing the general trends of development of the work process in Mexico, it is shown that a transformation in the causes of death among men of working age has occurred during the last 20 years and there has been an increase in the number and the rate of work accidents and occupational diseases, despite a significant under-registration factor. Finally, the labor legislation on health and safety is contrasted with its actual implementation. This problem is interpreted in the context of traditional Mexican trade unionism. It is shown that trade unions which have become democratic and have gained their independence have struggled more vigorously on occupational health and safety issues.

Mortality and working conditions in agriculture in underdeveloped countries.

The search for information and analysis of the mortality of agricultural workers in underdeveloped countries shows that there exists hardly any research on this subject. What little information that can be found is incomplete and scattered, making it difficult to gain systematic empirical knowledge of the problem. In addition, data are not collected for the purpose of explaining the patterns of mortality observed. It therefore seems necessary to generate a theoretical framework permitting the analysis of mortality among agricultural workers. This paper intends to point out the close relationship that exists between the mortality and the dynamic of the social and economic process of agriculture in the underdeveloped countries. By doing so, we hope to show that the problems of health, disease, and death of socially defined groups are not simply a matter of biology, but of the interrelation between biology and the historical process of which these groups are a part.

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.

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.

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.