Christian A. Gericke

Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography

We present a new approach for non-invasive localization of focal epileptogenic discharges in patients considered for surgical treatment. EEG-triggered functional MR imaging (fMRI) and 3D EEG source localization were combined to map the primary electrical source with high spatial resolution. The method is illustrated by the case of a patient with medically intractable frontal lobe epilepsy. EEG obtained in the MRI system allowed triggering of the fMRI acquisition by the patients habitual epileptogenic discharges. fMRI revealed multiple areas of signal enhancement. Three-dimensional EEG source localization identified the same active areas and provided evidence of onset in the left frontal lobe. Subsequent electrocorticography from subdural electrodes confirmed spike and seizure onset over this region. This approach, i.e. the combination of EEG-triggered fMRI and 3D EEG source analysis, represents a promising additional tool for presurgical epilepsy evaluation allowing precise non-invasive identification of the epileptic foci.

NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease

There is increasing evidence that in Alzheimers disease nerve growth factor (NGF)protein and NGF mRNA content in post‐mortem cortex is not decreased, but may evenbe elevated although the NGF‐sensitive cholinergic basal forebrain neurons are preferentiallyaffected. However, only little is known about the early pathophysiological events leading toAlzheimers disease. We therefore measured the post‐mortem NGF concentrations intemporal and frontal cortex of Alzheimers disease patients, non‐demented controls withoutAlzheimers disease‐related pathology, as well as non‐demented patients with βA4plaques who might be classified as preclinical cases. In the Alzheimers disease group we found upto 43% increase in NGF concentrations in the frontal and temporal cortex as compared to the twoother groups. In a subgroup analysis of the non‐demented patients with plaques, NGFconcentrations were lower in the frontal cortex when βA4 plaques were present (46% ofthe control temporal area) than in patients without evidence of frontal plaques (81% of the controltemporal area). This NGF decrease was paralleled to a similar decrease of cholineacetyltransferase activity, which is regulated by NGF in the cholinergic basal forebrain. Thesefindings support the hypothesis of lower cortical NGF content at the onset of plaque formationand of elevated NGF levels in the clinically manifest and neuropathologically advanced stage ofthe disease.

Intervention complexity: a conceptual framework to inform priority-setting in health

Health interventions vary substantially in the degree of effort required to implement them. To some extent this is apparent in their financial cost, but the nature and availability of non-financial resources is often of similar importance. In particular, human resource requirements are frequently a major constraint. We propose a conceptual framework for the analysis of interventions according to their degree of technical complexity; this complements the notion of institutional capacity in considering the feasibility of implementing an intervention. Interventions are categorized into four dimensions: characteristics of the basic intervention; characteristics of delivery; requirements on government capacity; and usage characteristics. The analysis of intervention complexity should lead to a better understanding of supply- and demand-side constraints to scaling up, indicate priorities for further research and development, and can point to potential areas for improvement of specific aspects of each intervention to close the gap between the complexity of an intervention and the capacity to implement it. The framework is illustrated using the examples of scaling up condom social marketing programmes, and the DOTS strategy for tuberculosis control in highly resource-constrained countries. The framework could be used as a tool for policy-makers, planners and programme managers when considering the expansion of existing projects or the introduction of new interventions. Intervention complexity thus complements the considerations of burden of disease, cost-effectiveness, affordability and political feasibility in health policy decision-making. Reducing the technical complexity of interventions will be crucial to meeting the health-related Millennium Development Goals.

Ethical issues in funding orphan drug research and development

This essay outlines the moral dilemma of funding orphan drug research and development. To date, ethical aspects of priority setting for research funding have not been an issue of discussion in the bioethics debate. Conflicting moral obligations of beneficence and distributive justice appear to demand very different levels of funding for orphan drug research. The two types of orphan disease, rare diseases and tropical diseases, however, present very different ethical challenges to questions about allocation of research funds. The dilemma is analysed considering utilitarian and rights based theories of justice and moral obligations of non-abandonment and a professional obligation to advance medical science. The limitations of standard economic evaluation tools and other priority setting tools used to inform health policy decision makers on research funding decisions are outlined.

Increase of hypoxic tolerance in rat hippocampal slices following 3-nitropropionic acid is not mediated by endogenous nerve growth factor

Chemical preconditioning with low dose inhibition of succinic dehydrogenase by 3-nitropropionic acid (3-np) increases tolerance against succeeding hypoxia. Supraphysiological doses of nerve growth factor (NGF) repeatedly were shown to protect against ischemic damage. We investigated whether increased tolerance against hypoxia results from increased or accelerated production of endogenous NGF. Average recovery of population spike amplitude after 15 min of hypoxia and 45 min of reoxygenation was 31 +/- 9% (mean +/- SE) in control hippocampal slices. After pretreatment with 3-np (single i.p. injection of 20 mg/kg body weight 1 h to 3 days prior to slice preparation), recovery exceeded 90% (P < 0.01). However, NGF content did not increase upon slice preparation, hypoxia in vitro, and pretreatment with 3-np in vivo 1 h to 1 day prior to slice preparation with and without additional hypoxia in vitro. We conclude that early-onset tolerance to hypoxia induced by 3-np treatment is not caused by induction of endogenous NGF production.

Drug prescription patterns in schizophrenia outpatients: analysis of data from a German health insurance fund.

INTRODUCTION The aim of this study was to investigate routine administrative data from a major German health insurance fund, Techniker Krankenkasse, which covers 5.4 million insured individuals. Using a retrospective cohort design, this study analysed data collected from patients with a hospital diagnosis of schizophrenia in 2003 (index hospitalisation) in order to evaluate prescription patterns of antipsychotic drugs. METHODS Patients with an ICD-10 diagnosis of schizophrenia, at least one year prior membership with the insurance fund and a follow-up period of one year were identified. Results were standardised by age and stratified by the severity of their illness, defined by the number of hospital bed days during the three years preceding the index hospitalisation. RESULTS A total of 3,121 patients with schizophrenia (male 56.4%, female 43.6%) received 56 692 single prescriptions of antipsychotics. Of these, 35.4% of the prescriptions were for typical and 64.6% for atypical antipsychotics; 55% were for high-potency, 45% for low-potency typical antipsychotics. The most frequently prescribed drugs were olanzapine (26.6%), clozapine (21.3%) and risperidone (19%). There were no relevant gender differences concerning prescription patterns. During a 12-month follow-up period after the first hospitalisation, 1 372 patients (43.9%) were treated exclusively with an atypical antipsychotic, another 499 patients (16%) had a combination of an atypical plus a low-potency typical antipsychotic. Thus, basal therapy with an atypical was observed in 59.9% of our study population. Only 327 patients (10.5%) were treated exclusively with a typical antipsychotic. A total of 645 patients (20.7%) were treated with a combination of atypical plus typical antipsychotic. Changes of medication within one substance group occurred more often with typical antipsychotics (50%) as compared to atypical antipsychotics (25%). DISCUSSION At 60%, the proportion of patients in this study treated with atypical antipsychotics was surprisingly high. Of significant interest is the frequent prescription of clozapine (14%). The results are discussed in comparison to comparable studies from other countries.

Chronic alcohol intoxication in rats leads to a strong but transient increase in NGF levels in distinct brain regions

Summary.Nerve growth factor (NGF), a member of the neurotrophin family, is an essential mediator of neuronal activity and synaptic plasticity of basal forebrain cholinergic neurons. In this study NGF-protein levels were determined in areas of the basal forebrain cholinergic system, its projection areas as well as the striatum and the cerebellum after long-term exposure (6 and 9 months) to ethanol and a phase of withdrawal in male Sprague-Dawley rats. 6-month alcohol treatment led to an increase of NGF to 650–850% of controls in the basal forebrain and the septum and to a 210–485% increase in the cholinergic projection areas (anterior cortex, hippocampus and olfactory bulb). After 9 months exposure to ethanol, a decrease of NGF by 16% in the frontal cortex was observed compared to controls. In the other brain regions no differences in NGF expression were detectable at this time-point. These results support the idea of an endogenous neuroprotective mechanism acting through a transient NGF induction followed by a decrease in NGF-levels during the course of further neuronal degeneration.

Effectiveness of interventions to promote healthy weight in general populations of children and adults: a meta-analysis

BACKGROUND Responding to the obesity epidemic requires robust evidence to help prioritize the allocation of scarce resources to preventive interventions. The aim of this study was to evaluate interventions that promote healthy weight [defined as reduction in body mass index (BMI) or percentage body fat] in general populations (unselected by weight) using a comprehensive meta-analysis. Interventions with both single and multiple components were considered. METHODS Studies were first identified through well-conducted systematic reviews complemented by a search for single studies in five large medical databases up to 6 November 2008. Sixty-eight controlled studies were included. For each intervention type and age group, all relevant studies were pooled in a random effects meta-analysis. RESULTS In children, the highest reductions in mean BMI were achieved through promoting reduced television viewing [-0.27 kg/m(2) (95% CI -0.4 to -0.13 kg/m(2))]. Programmes combining physical activity, specifically themed or general health education and nutrition achieved a lower reduction [-0.1 kg/m(2) (95% CI -0.17 to -0.04 kg/m(2))]. Other interventions had high heterogeneity or showed no statistically significant reduction in outcomes. In adults, single component interventions were found to reduce both outcome measures. Their mean percentage body fat was reduced through education by -1.22% (95% CI -1.92 to -0.52). CONCLUSION The evidence for the effectiveness of promoting healthy weight in general populations is limited, though multi-component interventions in schools and encouraging reduced childrens television viewing are promising strategies. Improving the reporting of outcomes is vital, as imputation of inadequately reported measures may have contributed to the observed heterogeneity. Longer follow-up is essential for understanding policy relevance.

Comprehensive postictal neuropsychology improves focus localization in epilepsy

In recent years, new techniques such as single photon emission computed tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI) have been used to improve the localization of epileptic foci during the noninvasive evaluation procedure for epilepsy surgery. Since ictal/or immediate postictal SPECT studies were shown to localize epileptic foci better than interictal SPECT, we addressed the question of whether immediate postictal neuropsychological examination would show the same effect. Neuropsychological examinations were carried out postictally and interictally using a broad range of tests. Postictal results were analyzed with regard to lateralizing and localizing information about the epileptogenic region. Seventeen patients suffering from temporal and extratemporal pharmacoresistant epilepsy were investigated postictally with a subset of tests used for the interictal neuropsychological examination. A significant improvement in focus localization was seen in comparison with interictal neuropsychology (p = 0.014). We conclude that neuropsychology can yield lateralizing and sometimes localizing information, even for extratemporal foci, if carried out during the postictal period and based on a global analysis of the clinical neuropsychological picture.

Emigration preferences and plans among medical students in Poland

BackgroundMigration and ethical recruitment of health care workers is receiving increased attention worldwide. Europe’s aging population is creating new opportunities for medical doctors for finding employment in other countries, particularly those of a better standard of living.MethodsWe conducted a survey among 1214 medical students in five out of eleven universities in Poland with medical schools in October 2008. A series of statistical tests was applied to analyse the characteristics of potential migrants. Projections were obtained using statistical analyses: descriptive, multifactorial logistic regression and other statistical methods .ResultsWe can forecast that 26–36% of Polish medical students will emigrate over the next few years; 62% of respondents estimated the likelihood of emigration at 50%. Students in their penultimate year of study declared a stronger desire to migrate than those in the final year. At the same time, many students were optimistic about career opportunities in Poland. Also noted among students were: the decline in interest in leaving among final year students, their moderate elaboration of departure plans, and their generally optimistic views about the opportunities for professional development in Poland.ConclusionsThe majority of Polish students see the emigration as a serious alternative to the continuation of their professional training. This trend can pose a serious threat to the Polish health care system, however the observed decline of the interest in leaving among final year students, the moderate involvement in concrete departure plans and the optimistic views about the opportunities for professional development in Poland suggest that the actual scale of brain drain of young Polish doctors due to emigration will be more limited than previously feared.