M.S. de Vries

Somatic hypotheses of war syndromes

Since the end of the American Civil War, unexplained symptoms in military personnel arising after a war or peace mission have frequently been described. The pattern of symptoms is highly similar for all of the various war syndromes although the conditions of each war or peace mission are widely different. Many somatic hypotheses have been formulated to explain these syndromes; a considerable proportion of them are already outdated. In the last few years much attention has been given to Gulf War Syndrome and to unexplained symptoms of military personnel who were sent to Cambodia, Rwanda, Burundi, Zaire, or the former Yugoslavia. In this review the symptoms of war syndromes will be considered in more detail and the suggested somatic explanations will be discussed. During the last decade the following somatic causes have been suggested as possible explanations for these symptoms: (persistent) infection, abnormal immune response, administration of multiple vaccinations within a short period of time, use of malaria chemoprophylaxis, neurological abnormalities, exposure to toxicological substances and environmental factors. The various investigations performed to study these hypotheses are discussed. The fact that bias regularly occurs in the course of these investigations is pointed out. For the future, a reliable investigation of a war syndrome should be a prospective multidisciplinary study and should distinguish between causative and sustaining factors.

The attack on the state: A comparison of arguments

Introduction In order to respond adequately to the challenges posed by globalization, it is necessary for national administrations to have a more specified insight into the consequences of globalization for the capacity of nation-states. Recently the sovereignty of the nation-state has been under attack from several sides, attacks sometimes erroneously summarized as globalization. Globalization has — according to many scholars — diminished the possibilities of nation-states to make public policies independently (Hirst and Thompson, 1996). It is claimed that globalization does not pose a threat so much to the external sovereignty of states, but rather to their internal sovereignty (Krasner, 1983; Reinicke, 1998). States exert external as well as internal sovereignty. The internal sovereignty of a state can be defined as the supremacy over all other authorities within its territory and over its population. Its external sovereignty refers not to supremacy but rather to its independence in relation to other nation-states. The internal sovereignty of states is said to be at stake, because what happens within their territory and among their population seems much less a consequence of the policies of the nationstates, but is rather becoming increasingly dependent upon international developments (Frieden and Rogowski, 1996). Four claims surface in the literature. First, globalization poses new problems, which states cannot handle on their own. International crime, international trade, foreign direct investments (FDI) and international finance are just some of the new policy areas in which the role of states is, at least, ambiguous. All types of firms have become much more mobile and now go to those places where they can profit most from the new developments. Nation-states adapt to these new circumstances to varying degrees and in different fashions. Some have adapted to the new situation to such an extent that the market ideology dominates their performance. They do everything to attract business and foreign investments. Others have tried to intensify their cooperation with other countries in order to standardize the boundary conditions within a

Dronabinol and chronic pain: importance of mechanistic considerations

Introduction: Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states. Areas covered: The pharmacokinetics, pharmacodynamics and mechanisms of action of products with a defined dronabinol content are summarized. Additionally, randomized clinical trials investigating the analgesic efficacy of pharmaceutical cannabis based products are reviewed for the treatment of chronic nonmalignant pain. Expert opinion: We suggest a mechanism-based approach beyond measurement of subjective pain relief to evaluate the therapeutic potential of dronabinol in chronic pain management. Development of objective mechanistic diagnostic biomarkers reflecting altered sensory and cognitive processing in the brain is essential to evaluate dronabinol induced analgesia, and to permit identification of responders and/or non-responders to dronabinol treatment.

Persistent symptoms in former UNTAC soldiers are not associated with shifted cytokine balance.

The pathogenesis of post‐combat syndromes, such as Gulf War syndrome, is poorly understood. Recently, it has been postulated that the symptoms of veterans with such syndromes are due to a disturbed cytokine balance shifted towards a T‐helper (Th) 2 profile. We investigated this hypothesis in 21 symptomatic former UNTAC soldiers and compared their results with those obtained in 21 healthy former UNTAC soldiers matched for age, sex and military force.

Natural course of symptoms in Cambodia veterans: a follow-up study

BACKGROUND Dutch (ex-)servicemen were deployed in the 1992-3-peace operation UNTAC in Cambodia. Since their return, they have voiced concerns about the health consequences of their service and they have reported symptoms such as fatigue and cognitive problems. The natural course of symptoms in Dutch Cambodia veterans was evaluated in a prospective study. METHODS At 18-months follow-up, a questionnaire was sent to 354 veterans who met a set case definition for symptoms in Cambodia veterans or who had sub-threshold scores. Initial measurement of fatigue severity, psychological well-being, depression, post-traumatic stress disorder, trait-anxiety, self-efficacy and causal attributions, was used to evaluate predictors for self-reported improvement and low levels of fatigue at follow-up. RESULTS At follow-up, 19% of the respondents reported complete recovery, 20% felt much better, 57% had the same complaints and 4% had become worse compared with their initial assessment. Self-reported improvement and less severe fatigue at follow-up were predicted by less severe fatigue at initial assessment and more perceived control over symptoms. CONCLUSIONS Self-reported improvement was reported in a considerable percentage of Cambodia veterans, whereas another substantial percentage of Cambodia veterans continued to suffer with severe levels of fatigue and related symptoms. Predictors of improvement in Cambodia veterans and patients with chronic fatigue syndrome show similarities and also seem to bear importance for Gulf War veterans.

Stability despite Reforms: Structural Asymmetries in Dutch Local Policy Networks

Abstract This article addresses the development of local policy networks in the Netherlands in the period 1996–2005. It is argued that there is a surprising stability in such networks seen from the perspective of local policymakers. Those working inside city hall as politicians and as members of the local administration remain the core members of the inner circle in policy networks, while societal groups remain outsiders and political party groups are absent from local policy networks. This conclusion is based on three identical standardised surveys among local politicians and top administrators at the local level, which were conducted in 1996, 2000 and 2005. This outcome is surprising, because it is contrary to the high expectations arising from numerous institutional reforms taking place in this period, aimed, among other things, at diminishing the gap between citizens and policymakers; the numerous experiments in co-production, public-private partnerships, and interactive policy processes; and the widespread documentation and dissemination of the outcomes of such experiments. Possible explanations for the results are that the experiments, however successful they might have been, never had a structural follow-up, and that the structural reforms, no matter what they accomplished otherwise, did not achieve their goal in enhancing interactive policymaking because they overlooked the fact that local policymakers see the local political system as a representative democracy and not as a direct or participatory one. On that basis it is to be expected that support for policies by policymakers is mainly sought among influential actors who are elected or appointed to develop policies and whose interests have to be taken into account. The public and societal groups do not satisfy that criterion. They can and do seek support from policymakers but the latter are hardly inclined to seek support from them.Abstract This article addresses the development of local policy networks in the Netherlands in the period 1996–2005. It is argued that there is a surprising stability in such networks seen from the perspective of local policymakers. Those working inside city hall as politicians and as members of the local administration remain the core members of the inner circle in policy networks, while societal groups remain outsiders and political party groups are absent from local policy networks. This conclusion is based on three identical standardised surveys among local politicians and top administrators at the local level, which were conducted in 1996, 2000 and 2005. This outcome is surprising, because it is contrary to the high expectations arising from numerous institutional reforms taking place in this period, aimed, among other things, at diminishing the gap between citizens and policymakers; the numerous experiments in co-production, public-private partnerships, and interactive policy processes; and the wide...

A mutation study of sperm head shape and motility in the mouse: lessons for the clinic

Mouse mutants that show effects on sperm head shape, the sperm tail (flagellum), and motility were analysed in a systematic way. This was achieved by grouping mutations in the following classes: manchette, acrosome, Sertoli cell contact, chromatin remodelling, and mutations involved in complex regulations such as protein (de)phosphorylation and RNA stability, and flagellum/motility mutations. For all mutant phenotypes, flagellum function (motility) was affected. Head shape, including the nucleus, was also affected in spermatozoa of most mouse models, though with considerable variation. For the mutants that were categorized in the flagellum/motility group, generally normal head shapes were found, even when the flagellum did not develop or only poorly so. Most mutants are sterile, an occasional one semi‐sterile. For completeness, the influence of the sex chromosomes on sperm phenotype is included. Functionally, the genes involved can be categorized as regulators of spermiogenesis. When extrapolating these data to human sperm samples, in vivo selection for motility would be the tool for weeding out the products of suboptimal spermiogenesis and epididymal sperm maturation. The striking dependency of motility on proper sperm head development is not easy to understand, but likely is of evolutionary benefit. Also, sperm competition after mating can never act against the long‐term multi‐generation interest of genetic integrity. Hence, it is plausible to suggest that short‐term haplophase fitness i.e., motility, is developmentally integrated with proper nucleus maturation, including genetic integrity to protect multi‐generation fitness. We hypothesize that, when the prime defect is in flagellum formation, apparently a feedback loop was not necessary as head morphogenesis in these mutants is mostly normal. Extrapolating to human‐assisted reproductive techniques practice, this analysis would supply the arguments for the development of tools to select for motility as a continuous (non‐discrete) parameter.

Trust and governance practices among local leaders

This article investigates patterns of generalized trust among local political and administrative leaders. It explains the differences therein and studies the impact of such trust on the inclination to involve people in policy-making processes. The research is based on a survey among approximately 16,000 local administrators and politicians in 665 communities in 18 countries. The findings are analyzed using a multi-level model. It is found that generalized trust among local policy-makers, as a form of low-level risk, can be explained by the judgment about past experiences with public participation, the judgment of the abilities of the constituency and the scope of problems in the community. Regarding the impact of trust on the propensity to involve people in the policy-making process, significant differences are found between old, new and newest democracies. In the old democracies there is hardly a relation between the tendency to seek the support of citizens on the one hand and generalized trust on the ot...This article investigates patterns of generalized trust among local political and administrative leaders. It explains the differences therein and studies the impact of such trust on the inclination to involve people in policy-making processes. The research is based on a survey among approximately 16,000 local administrators and politicians in 665 communities in 18 countries. The findings are analyzed using a multi-level model. It is found that generalized trust among local policy-makers, as a form of low-level risk, can be explained by the judgment about past experiences with public participation, the judgment of the abilities of the constituency and the scope of problems in the community. Regarding the impact of trust on the propensity to involve people in the policy-making process, significant differences are found between old, new and newest democracies. In the old democracies there is hardly a relation between the tendency to seek the support of citizens on the one hand and generalized trust on the other hand. The severity of social problems has in these countries a positive effect on involving citizens. In the new and especially the newest democracies, the relation between trust and support-seeking behavior is significantly stronger. When problems become less urgent in those countries and the local policy-maker does show generalized trust,(s)he is significantly more inclined than his/her colleagues to seek the support of the people. This implies that there might exist a paradox, namely that in order to enhance practices of good governance, claiming these are more effective, one already needs a society in which policy-making is relatively effective and that has adequate problem-solving capacity.

Cannabinoid Receptor Agonist Namisol Does Not Affect Cytokine Levels In Chronic Pancreatitis Patients

Cannabinoid Receptor Agonist Namisol Does Not Affect Cytokine Levels In Chronic Pancreatitis Patients

Cytological evaluation of spermatogenesis: a novel and simple diagnostic method to assess spermatogenesis in non-obstructive azoospermia using testicular sperm extraction specimens

Most of the non‐obstructive azoospermia (NOA)‐patients have only focal spermatogenesis which results in insufficient numbers of spermatozoa to reach the ejaculate. In ≈50% of these NOA‐patients testicular sperm extraction (TESE) is successful and intracytoplasmic sperm injection (ICSI) is pursued. We studied whether (i) spermatogenesis can be evaluated by defining the ratios between Sertoli cells, pachytene spermatocytes and spermatozoa in a testicular cell suspension, and (ii) these ratios are associated with the outcome of fertility treatment. A retrospective cohort study was conducted between June 2007 and August 2012. In this period, 441 consecutive ICSI‐TESE cycles were performed in 212 couples. For each TESE biopsy, the ratios between Sertoli cells, pachytene spermatocytes and spermatozoa were calculated. A control population of 32 vasectomized men was used to define cut‐off values for complete spermatogenesis. Based on the pachytene to sperm ratio (P/Sp) and number of spermatozoa per 100 Sertoli cells (#Sp/100SC) groups were defined as complete spermatogenesis, hypospermatogenesis and partial maturation arrest (MA). Validation of the cytological diagnoses was performed by comparing the results of cytology to the histological evaluation of spermatogenesis in 40 cases. In 92.5%, a perfect match was observed and in the three remaining cases cytology corresponded well with the results of TESE. Couples with complete spermatogenesis have a higher ongoing pregnancy rate after the first treatment cycle compared to couples with hypospermatogenesis (34 vs. 16%; p = 0.02) and partial MA (34 vs. 19%; p = 0.11). In conclusion, pachytene spermatocytes, spermatozoa and Sertoli cells can be easily identified and counted in a cell suspension and their ratios can be successfully used to diagnose the level of spermatogenic impairment. This pilot study indicates that once successful spermatozoa retrieval is achieved, treatment outcome declines when spermatogenesis is impaired in NOA. The predictive value of cytological evaluation of spermatogenesis has to be established in a future prospective trial.