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Physician-assisted suicide in Germany is limited by criminal law and disapproved by professional authorities. A physician who is willing to help a demented patient in terminating his life has to be definitely sure that the disease does not interfere with the patient's capacity for decision-making. In cases of early dementia the reason why assisted suicide will usually be requested is not the actual suffering of the patient but his negative expectations for the future. As long as there are sufficient opportunities for palliative care, the progressive course of the dementia process does not imply a state of unbearable suffering which could justify an assisted suicide. Nevertheless there may be certain circumstances--as for instance the value that an individual attributes to his integrity or to the narrative unity of his life--which might possibly provide an ethical justification for the assistance in life termination. A physician who helps a demented person in performing a suicidal act does not necessarily oppose essential principles of medical ethics. Yet, especially with regard to possible societal consequences of physician-assisted suicide in dementia, the rejecting attitude of medical authorities against that activity must be considered as well founded and legitimate. Deviations from these general guidelines ought to be respected as long as they are limited to exceptional situations and correspond to a thorough consideration of a physician's professional duties. They should remain open to public control, but not be ultimately specified by unequivocal normative regulations.

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We demonstrate by neutron scattering that a localized superfluid component exists at high pressures within solid helium in aerogel. Its existence is deduced from the observation of two sharp phonon-roton spectra which are clearly distinguishable from modes in bulk superfluid helium. These roton excitations exhibit different roton gap parameters than the roton observed in the bulk fluid at freezing pressure. One of the roton modes disappears after annealing the samples. Comparison with theoretical calculations suggests that the model that reproduces the observed data best is that of superfluid double layers within the solid and at the helium-substrate interface.

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A short overview is given of the current debate on ethics and legal clarification of the range and binding force of so-called living wills demanding interruption of treatment in case of loss of autonomy due to persistent or progressive brain disease. Using the examples of dementia and persistent vegetative states - conditions with growing significance for psychiatrists - the binding force of living wills is examined for cases in which the irreversibility and extent of consciousness loss cannot be predicted with certainty. The range of living wills' authority appears also unclear. Legal proposals for limiting them to disease conditions near death are confronted by other proposals that reject such limitations. Added to this is the medical uncertainty of assessing the criterion nearness to death in irreversible and life-limiting diseases. The patient's right of self-determination, confirmed by high court decisions, to refuse in advance treatments that are life-prolonging but require consent is opposed to the medical obligation to save life and act in the patient's best interest. Moral dilemmas caused by this situation on the part of physicians, carepersons, and relatives or others, particularly authorized persons, should be solved by an exhaustive discussion with all persons who are involved in such decisions, and in a way that comes as near as possible to the patients living will.

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BACKGROUND: Leukotrienes are potent bronchoconstrictive and proinflammatory mediators in bronchial asthma. In a previous study on 16 subjects with bronchial asthma (two randomized groups) we showed that montelukast (10 mg daily) significantly suppressed allergen provocation with specific allergens (mites and pollen) (p = 0.0005). In a follow-up study we addressed the question as to when montelukast should be discontinued in order to avoid a relevant effect on inhalational bronchial allergen provocation. METHOD: At the end of the first study montelukast (10 mg daily) was given again to both groups (2 x 8 asthma patients) for 21 days. After a montelukast-free period of one and three days allergen provocation was repeated in the same manner and the results were compared with the historic baseline values without montelukast. RESULTS: The provocation dose for allergens was reduced by 39% after a montelukast-free period of one day and by 67% after three days. Only after three days was the difference significant (p = 0.017), at which time the control value was nearly reached again. CONCLUSION: We recommend that montelukast be discontinued at least three days prior to inhalational allergen provocation.

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Direct evidence of the nonuniformly canted state of the spin-flop phase induced by a magnetic field applied to Fe/Cr(100) superlattices is obtained by polarized neutron reflectometry. It is unambiguously demonstrated that the magnetization of the alternating Fe layers is twisted through the multilayer stack proving a stable noncollinear configuration. The maximal tilt at the end layers progressively reduces towards the center of the multilayer. The set of tilt angles is deduced from a model-free data evaluation employing the supermatrix routine. Spin-flip off-specular scattering is determined by the in-plane magnetization fluctuations and is fitted by a theoretical model of domains.

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BACKGROUND: Leukotrienes are potent bronchoconstrictive and proinflammatory mediators in bronchial asthma. A randomized, cross-over study on 16 subjects assigned to two groups investigated whether premedication with the leukotriene antagonist montelukast (10 mg daily for 21 days) has a relevant effect on inhalational bronchial allergen provocation. METHOD: Allergens were inhaled by atomizing commercial provocation solutions in dilutions of 1 : 1000, 1 : 100, 1 : 50, 1 : 10 and 1 : 5 with a nebulizer (Pari). The allergen dose was escalated every 20 minutes until the positive criteria (20 % fall in FEV1, doubling of oscillatory resistance) were met. The provocation tests were performed on days 1, 21 and 42 of the study. RESULTS: An allergen protective effect of variable magnitude (PD20 increased by a factor of 1.6 to 21) was observed in 12 of the 16 subjects following provocation with pollen and mite allergens. The mean for all 16 patients showed a highly significant increase (p = 0.0005) by a factor of 4.3. The extent of allergen protection cannot be predicted in individual cases and is independent of the chosen allergen and the PD20 without montelukast. However, a significant correlation (p = 0.0016) was found between unspecific bronchial hyperreactivity (histamine) and the PD20. The allergen protective effect of montelukast decreases with increasing unspecific hyperreactivity. CONCLUSION: We recommend that medication with montelukast be discontinued before allergen provocation because it cannot be predicted in individual cases whether and to what extent montelukast suppresses the immediate reaction following inhalational bronchial allergen provocation.

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The domain structure of an antiferromagnetic superlattice is studied. Synchrotron Mössbauer and polarized neutron reflectometric maps show micrometer-size primary domain formation as the external field decreases from saturation to remanence. A secondary domain state consisting mainly of at least 1 order of magnitude larger domains is created when a small field along the layer magnetizations induces a bulk-spin-flop transition. The domain-size distribution is reproducibly dependent on the magnetic prehistory. The condition for domain coarsening is shown to be the equilibrium of the external field energy with the anisotropy energy.

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Although pre-eclampsia (PE) is often associated with fetal hypoxia, hypertension and/or disturbed function of the fetal circulation, the effect of these altered hemodynamic parameters on the structure and composition of umbilical vessels has not been systematically investigated before. Therefore, this study focuses on PE-associated changes of the elastic fibre system in umbilical cord vessels investigated by light and electron microscopy, immunocytochemistry and biochemistry. In umbilical cord veins, no changes in thickness of the vessel wall or of any sublayer were observed. However, the internal elastic lamina of the veins was split in 80% of the PE-group in contrast to 20% in uncomplicated pregnancies. This effect was significant (alpha <0.01) from 36 weeks of gestation onwards. In umbilical cord arteries, the entire arterial vessel wall was found to be 15% thicker in PE than in uncomplicated pregnancies. The enlargement was caused by an increase of both the tunica intima and tunica media. The thickening of the tunica intima was attributed to a migration of smooth muscle cells towards the endothelium, accompanied by a splitting of the internal elastic lamina. Compared to uncomplicated pregnancies, smooth muscle cells of arteries and veins in PE showed a metabolic activation demonstrated by highly dilated endoplasmic reticulum. A semiquantitative score method as well as a quantitative dot blot assay indicated a PE-associated reduction of elastin expression in the arterial vessel walls. In summary, PE obviously induces a decrease of the elastin content accompanied by a thickening of the vessel wall in umbilical cord arteries. This remodeling of the elastic fibre system, together with an increased migration of smooth muscle cells, might represent part of the functional adaptation system of the umbilical cord arteries on the altered hemodynamic conditions in PE.

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The purpose of this study was to analyse the frequency of the different pathological perfusion patterns in SPECT in a clinical, unselected population of patients with Alzheimer's disease. In 91 patients and 16 control subjects regional cerebral blood flow (rCBF) was measured with Single Photon Emission Computed Tomography (SPECT) using 99mTc-hexa-methyl-propyleneamine oxime (HMPAO). 95% confidence intervals obtained from the perfusion values of the control subjects were used to define normal perfusion ranges. The frequency of perfusion deficits in the left frontal, temporal, parietal and occipital lobes were 62.2%, 60.4%. 70.3% and 23.1%, respectively. In the right hemisphere the corresponding values were 60.4%, 58.2%, 63.7% and 9.9%. With the exception of the occipital lobes these frequencies were not significantly different. The analysis of the perfusion pattern of each patient revealed 35 different combinations of lobes with perfusion deficits. The temporo-parietal perfusion deficits were not more frequent than the temporofrontal perfusion deficits. These results suggest that in the clinical routine a high variety of heterogeneous rCBF patterns have to be expected.

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The international discussion on physician-assisted dying as well as the recent development in North Australia and Oregon point to a growing tendency to favour assisted suicide as against killing on request--last not least for reasons of public acceptance. The decision of the Supreme Court of the Netherlands in a case of suicide assisted by a psychiatrist gives the opportunity to discuss the problem from the psychiatric point of view.

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The effect of the apolipoprotein E (apoE) genotype on the age at onset of Alzheimer's disease (AD) and the relative risk conferred by the apoE epsilon 4 allele were studied in 91 patients and 69 healthy age-matched controls. According to the age of presentation, which varied from 44 to 95 years, subjects were divided into four groups. The inheritance of at least one epsilon 4 allele was associated with a significant reduction of the age at onset by 7.7 years among patients who were 83 years or older when examined. A weaker inverse relationship between the epsilon 4 allele and the age at onset was also observed among patients who were aged 44-63 years at presentation. The effect of the epsilon 4 allele was minimal or absent in the two intermediate age categories. The relative risk of AD conferred by the inheritance of at least one epsilon 4 allele showed no consistent age-related pattern. The overall risk expressed as an odds ratio was 5.0 (95% CI 2.4-10.5). With respect to the limitations of the study, we tentatively conclude (1) that the effect of the apoE epsilon 4 allele on the age at onset is not restricted to AD patients of a particular age, in accordance with current hypotheses on the role of apoE gene products in the biology of AD; (2) that the relative risk of AD associated with the epsilon 4 allele is not significantly modulated by age. Although the apoE epsilon 4 allele is an important susceptibility factor for AD occurring in middle age as well as in later life, it is of limited value in routine clinical diagnosis and should not be used for predictive testing in asymptomatic individuals.

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The neuroleptic threshold theory raised the expectation that schizophrenic patients could be treated with an optimal, individual neuroleptic dosage, causing no side effects. Although most existing studies do not fulfill current methodological standards, a few methodologically convincing analyses confirm that good clinical results can be achieved with relatively low dosages (4 mg haloperidol equivalent per day). Thus, the neuroleptic threshold theory and methods related to it deserve further research.

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We investigated the willingness to participate in dementia research of relatives of demented (n = 52) and cognitively unimpaired elderly individuals (n = 42). This unrepresentative sample was given a questionnaire to determine the rate of approval with respect to two research examples, the first of which referred to a therapeutic study with potential individual benefits, the second to a diagnostic research project without such benefits. Independent of potential individual benefits, an overwhelming majority acknowledged the necessity for dementia research and consented to participate in the given research examples. The rate of approval was not related to the experiences of the interviewed persons in the care of relatives suffering from dementia.

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The apolipoprotein E genotype was determined in 50 patients with clinically diagnosed and prospectively confirmed Alzheimer's disease of mild to moderate severity and in 50 healthy age- and sex-matched controls. The frequency of the epsilon 4 allele was increased in the patients irrespective of the age at onset and of a possible familial transmission of the disease. It was associated with a relative risk of 2.97. In patients who experienced first symptoms after the age of 65 years there was an inverse correlation between the number of epsilon 4 alleles and age at onset. The results suggest that in the absence of amyloid precursor protein mutations and of a gene which has not yet been precisely localized on chromosome 14, apolipoprotein E is involved in the pathogenesis of Alzheimer's disease. It probably exerts its influence by an acceleration or retardation of amyloid formation and/or tau hyperphosphorylation.

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The practice to kill terminally ill patients on their own demand has resulted in the Netherlands in a decriminalisation of active euthanasia which thus has fundamentally changed the way to deal with dying patients. Sooner or later this development will extend to other European countries as well as to the USA. Involuntary euthanasia of severely handicapped newborn children or of demented persons is propagated by the practical ethics of P. Singer and other representatives of utilitarianistic philosophy. According to the standpoint of utilitarianism a human being should only have the right to live as long as he or she is a person, i. e. has rationality and self-consciousness. The next step toward the elimination of elderly people can easily be predicted. For economical reasons these persons may be withheld from life-saving medical treatment or may be supposed to commit suicide. A moral pressure is created to make a decision for suicide as soon as severe invalidity occurs. The consideration of such ideas shows that in today's debate on euthanasia the issue is no longer the right of a few severely and terminally ill human beings to their "own death". Instead, the right to live of a large group of handicapped and "socially useless" or "unproductive" persons is at stake. This is the danger of today's discussion of euthanasia.

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Harding et al. suggested at first that an increase of P2 latency in flash VEP without an increase of P2 latency in pattern reversal VEP may be a diagnostic marker of Alzheimer's disease. Up to now there is no convincing evidence for this hypothesis. The purpose of the present study was to examine this hypotheses in an extended group of patients with Alzheimer's disease (n = 36). In addition, a group of patients with Parkinson's disease (n = 8) without dementia syndrome and a group of healthy elderly controls (n = 46) was investigated in order to determine the sensitivity and specificity of these VEP parameters. The results confirmed significant group differences between patients with Alzheimer's disease and healthy controls concerning the increase of Flash P2 latency and unchanged latency of P2 in the pattern reversal VEP. No significant correlations were found between duration of illness and mental test scores. The group differences of P2 latency in the flash VEP for patients with Parkinson's disease and healthy controls were also significant. Therefore, the increase of flash P2 latency in VEP does not seem to be specific for Alzheimer's disease nor for dementia syndrome. The pathological mechanism causing the flash P2 latency increase in a remarkable number of neuropsychiatric patients should be elucidated in further experimental investigations.

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Some practical suggestions for the examination and treatment of patients with organic mental disorders are derived from the experience gathered in a special outpatient clinic. They refer to methods of obtaining necessary information, to the use of diagnostic criteria, and to the therapeutic possibilities in irreversible dementia.

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