Genetic Engineering and Medical Ethics

In the introduction I express the need of introducing the point of view of Ethics when we are dealing with problems of science, technology, and especially medicine. In the first part of my presentation I deal with the problem of the value of human life, coming to the conclusion that human life might not be completely absolute, but is extremely important and “ceteris paribus” should be respected, and the problem of when it starts. Some of the main arguments are discussed. In this connection the question of abortion is briefly discussed. In the second part I deal with some problems related to human reproduction. Most people will be willing to support programmes for treating individuals with genetic disease; but at the same time the dangers of increasing depersonalization of the reproductive process are pointed out. In the third part I take up the problem of In Vitro Fertilisation. IVF has certainly brought benefits to some couples suffering from infertility, but at the same time it has raised quite a few human and moral problems. Is it permissible to fertilise an egg with a donor sperm, replacing the embryo in the womb? What about fertilising a donor egg with the husband's sperm? Is it acceptable to store or freeze embryos for future use? Is it moral to implant such an embryo in a woman who has no genetic relationship with the embryo? Is it moral to use surrogate mothers? Is it moral for ‘spare’ embryos to be killed or used as tissue for research? At the end I stress the need of dialogue between life sciences and ethics.     

癫癎发作生物节律的研究进展

随着对癫癎研究的不断深入,癫癎发作的时相性越来越受到关注。癫癎发作存在生物节律,同一类型的癫癎在不同时间段、不同状态(睡眠/觉醒、昼夜更替)发作频率不同。癫癎生物节律的分子机制、内分泌机制相当复杂,目前存在多种假说。明确癫癎发作的生物节律,根据其发作节律予以预防及治疗,既可以有效控制癫癎发作,也可以减少药物不良反应。癫癎发作生物节律的研究将为癫癎治疗提供新的思路。     

Ethical dilemmas in neonatology: recommendations of the Ethics Working Group of the CESP (Confederation of European Specialists in Paediatrics)

Neonatal intensive care has greatly improved the survival chances of a very sick infant. At the same time, it has also given rise to serious ethical problems. In all circumstances, however, parents and paediatricians and other healthcare team workers should continuously evaluate together what is in the best interest of the infant and react accordingly. It is also clear that the principle “the best interests of the infant” can be interpreted in different ways; therefore no simple guideline is possible. Received: 13 November 2000 and in revised form: 4 January 2001 / Accepted: 7 January 2001     

The covariation of common psychosomatic symptoms among children from socio-economically differing residential areas. An epidemiological study

Psychosomatic symptoms among children are believed to be commonplace. In this investigation by questionnaire, 47% of 1333 schoolchildren reported one or several symptoms, such as recurrent abdominal pain, headache, chest pains, loss of appetite and disturbances in bowel function. Coexistence of such symptoms was considerable and if a child had one of these, the probability that it would have one or more other symptoms was significantly increased. This correlation may strengthen both the suspicion that these symptoms are often psychosomatic and the idea that they have common CNS origin. There were appreciable differences in the frequency of the symptoms, between children at the more socially stable schools and schools with social problems. In the latter, the frequencies of symptoms differed between Swedish and immigrant children, which was not the case in the more socially stable schools.     

Fifty years of paediatric ethics

In 1965, when the first issue of Journal of Paediatrics and Child Health appeared, medical ethics was just becoming established as a discipline. The sub‐speciality of paediatric ethics did not make an appearance until the late 1980s, with the first key texts appearing in the 1990s. Professional concern to practice ethically in paediatrics obviously goes much further back than that, even if not named as such. In clinical areas of paediatrics, the story of the last 50 years is essentially a story of progress – better understanding of disease, better diagnosis, more effective treatment, better outcomes. In paediatric ethics, the story of the last 50 years is a bit more complicated. In ethics, the idea of progress, rather than just change, is not so straightforward and is sometimes hotly contested. There has certainly been change, including some quite radical shifts in attitudes and practices, but on some issues, the ethical debate now looks remarkably similar to that of 40–50 years ago. This is the story of some things that have changed in paediatric ethics, some things that have stayed the same and the key ethical ideas lying beneath the surface.     

Gene-environment interaction in teacher-rated internalizing and externalizing problem behavior in 7- to 12-year-old twins

Background: Internalizing and externalizing problem behavior at school can have major consequences for a child and is predictive for disorders later in life. Teacher ratings are important to assess internalizing and externalizing problems at school. Genetic epidemiological studies on teacher‐rated problem behavior are relatively scarce and the reported heritability estimates differ widely. A unique feature of teacher ratings of twins is that some pairs are rated by different and others are rated by the same teacher. This offers the opportunity to assess gene–environment interaction. Methods: Teacher ratings of 3,502 7‐year‐old, 3,134 10‐year‐old and 2,193 12‐year‐old twin pairs were analyzed with structural equation modeling. About 60% of the twin pairs were rated by the same teacher. Twin correlations and the heritability of internalizing and externalizing behavior were estimated, separately for pairs rated by the same and different teachers. Socioeconomic status and externalizing behavior at age 3 were included as covariates. Results: Twin correlations and heritability estimates were higher when twin pairs were in the same class and rated by the same teacher than when pairs were rated by different teachers. These differences could not be explained by twin confusion or rater bias. When twins were rated by the same teacher, heritability estimates were about 70% for internalizing problems and around 80% in boys and 70% in girls for externalizing problems. When twins were rated by different teachers, heritability estimates for internalizing problems were around 30% and for externalizing problems around 50%. Conclusions: Exposure to different teachers during childhood may affect the heritability of internalizing and externalizing behavior at school. This finding points to gene–environment interaction and is important for the understanding of childhood problem behavior. In addition, it could imply an opportunity for interventions at school.     

Epilepsy-Induced Microarchitectural Changes in the Brain

Our understanding of the pathogenesis of the neuropathology of epilepsy has been challenged by a need to separate the “lesions” that cause epilepsy from the “lesions” that are produced by the epilepsy. Significant clinical, genetic, pathologic, and experimental studies of Ammon horn sclerosis (AHS) suggest that AHS is the result and cause of seizures. The data support the idea that seizures cause alterations in cell numbers, cell shape, and organization of neuronal circuitry, thus setting up an identifiable seizure-genic focus. As such, AHS represents a slowly progressive lesion and a search for the cause of the initiating seizure has led to the identification of ion channel mutations. In this report, the neuropathology of other conditions associated with intractable epilepsy is considered, suggesting that in them similar epilepsy-produced alterations in microarchitecture can be observed. The idea is important to define the optimum time for epilepsy surgery and the underlying etiology of these seizure-genic lesions.     

Has Medicaid promoted needless pediatric emergency department use?

The possibility that Medicaid has encouraged pediatric emergency department (ED) use was explored as part of a study of 8470 ED visits to a pediatric teaching hospital in the period from 1975 to 1976. The proportion of the population on Aid to Dependent Children (proportion on ADC) was taken as a reasonable proxy for prevalence of Medicaid coverage of children in an area. Visit subgroups were compared using mean proportions on ADC in the census tracts of origin to measure relative rates of ED use by poor children. If Medicaid has promoted use of the ED instead of other facilities, the data would be expected to indicate relatively heavy ED use by residents of tracts with a high prevalence of Medicaid: (1) during the week when other facilities are most available; and (2) for minor problems which do not result in admission. The data show no differences in the mean proportion on ADC in the census tracts of origin of ED visits on weekdays as compared to weekends or for visits which resulted in admission as compared with those which did not. The data challenge the idea that Medicaid has encouraged pediatric ED use.     

Do we need another NSAID instead of indomethacin for treatment of ductus arteriosus in preterm infants?

Up until now indomethacin is the most extensively evaluated non-steroidal anti-inflammatory drug (NSAID) in neonatal medicine. If used with due consideration to the physiologic role of prostaglandins, a 90 success rate can be reached and serious adverse drug effects prevented. Conclusion: The results reported by Bellander et al. support the idea that we do not need to study other substances of the same therapeutic class, with the same target--cyclooxygenase--in the prostaglandin cascade and with a similar pharmacological profile. Instead, indomethacin treatment regimes should be further improved with respect to their efficacy and safety.     

Research Review: Emanuel Miller Memorial Lecture 2012 – Neuroscientific studies of intervention for language impairment in children: interpretive and methodological problems

Background: Our ability to look at structure and function of a living brain has increased exponentially since the early 1970s. Many studies of developmental disorders now routinely include a brain imaging or electrophysiological component. Amid current enthusiasm for applications of neuroscience to educational interventions, we need to pause to consider what neuroimaging data can tell us. Images of brain activity are seductive, and have been used to give credibility to commercial interventions, yet we have only a limited idea of what the brain bases of language disorders are, let alone how to alter them. Scope and findings: A review of six studies of neuroimaging correlates of language intervention found recurring methodological problems: lack of an adequate control group, inadequate power, incomplete reporting of data, no correction for multiple comparisons, data dredging and failure to analyse treatment effects appropriately. In addition, there is a tendency to regard neuroimaging data as more meaningful than behavioural data, even though it is behaviour that interventions aim to alter. Conclusion: In our current state of knowledge, it would be better to spend research funds doing well‐designed trials of behavioural treatment to establish which methods are effective, rather than rushing headlong into functional imaging studies of unproven treatments.     

Nachsorge im Erwachsenenalter

Cancer and its treatment can lead to chronic or late occurring problems many years after therapy. The most important known late effects include second primary malignancies, caused by radiotherapy or alkylating agents, cardiomyopathy, endocrine late effects, and cardiovascular problems which are often exacerbated by obesity and subsequent metabolic syndrome. Knowledge about late effects in adulthood brings new problems, which can only be addressed in cooperation between pediatric oncologists and adult specialists in various disciplines. While scientifically gathered information is required to form a basis, we also need to develop new treatment models, which in principal have the same goals, but which are wholly location-specific. Ensuring that both patients and their treating physicians are well informed has been proven to form a strong basis for good treatment in adulthood.     

Angiography and digital subtraction angiography

In pediatrics angiography is a method that is used relatively rarely. During the last few years the introduction of nonionic contrast media has led to considerable progress in the field of conventional angiography since these contrast media are tolerated much better than the ionic ones. Also in the field of catheter techniques the introduction of new catheters has led to considerable progress. The new catheters are characterized by very thin walls and wide lumina which allow a high flow of contrast media. Their use in children has considerably reduced local complications at the puncture site. The introduction of digital subtraction techniques on the one hand made intravenous angiography in pediatric patients possible and on the other hand led to considerable reduction of contrast media as compared to conventional angiography. Motion artifacts, however, cause problems. In interventional radiology, as far as blood vessels are concerned, technical possibilities are the same for children as for adults. Dilatations of blood vessels are the main indications. For embolizations the indications are mainly tumor embolizations and bleeding embolizations.     

New perspectives on the treatment of growth hormone deficiency

In the last few years the therapeutic management of GHD children has been improved by the recent synthesis of GH by DNA recombinant technique (rGH). rGH made it possible to overcome the problems of availability and purity of extractive GH, obtaining the same results (in growth velocity) without any information as regards late side effects of such a treatment. GHRH therapy in GHD patients of hypothalamic origin is still on trial and a lot of aspects are to be pointed out (indications to treatment, schedule and route of administration, cost/benefit ration, side effects).     

Emotional and Behavioural Problems in Primary School Children from Nuclear and Extended Families in Korea

The changes occurring within Korean society provide an opportunity for studying the influence of family structure on children's emotional and behavioural problems. Children aged 7–13 years from two Korean cities were assessed for emotional and behavioural problems in school by their teachers, using the Children's Behaviour Questionnaire. In Study 1, 326 children from extended families were compared with demographically matched nuclear family children in the same school classes. In Study 2, a further sample of 204 extended family children was compared with pair-matched nuclear family children, in order to replicate the findings. Children from Study 1 were followed up 2.5 years later. Children from extended families had lower behaviour problems scores and the prevalence of serious problems was lower in extended family children. These differences were most marked in relation to externalising behaviour problems and were stable over the studies and time. Grandparents in extended families may increase children's resiliency by providing sources of attachment, affection, and knowledge, as well as having indirect effects through their support of parents. Consistent with recent ideas about the cognitive bases for behaviour problems, it may be that rules for behaviour derived from traditional cultural beliefs and values are internalised by children from extended families and generalise to prevent behaviour problems in school.     

Proximal humeral physeal widening: little leaguer's shoulder or a variation of normal development?

Little leaguer's shoulder is a syndrome involving the proximal humeral epiphyseal plate and has been reported in adolescent athletes between 13-16 years of age. We present an adolescent case with radiological findings of little leaguer's shoulder syndrome in a non-athletic patient. The patient had applied significant rotational stress to the proximal humeral physis as a result of overuse due to physiotherapy, but the left asymptomatic side appeared more affected radiologically, which led to the idea that this may be a physiological change that occurs in adolescents. We thus evaluated the anteroposterior radiography of 10 healthy male adolescents of the same age with no skeletal or muscular complaints. We demonstrated a minimal widening of the lateral part of the proximal humeral epiphysis in two of these 10 patients. We believe little leaguer's shoulder should also be considered in adolescents with proximal humeral pain and a history of overuse. A larger study must be conducted to investigate whether these finding may be a variation of physiological development.     

The siblings of childhood cancer patients need early support: a follow up study over the first year.

BACKGROUND AND METHODS: In a 1 year follow up study, we assessed the life situation of 33 siblings of childhood cancer patients and 357 healthy controls. The hypothesis was that siblings have more behavioural and health related problems just after the cancer diagnosis. Validated assessment methods were used. RESULTS: Siblings below school age tended to have conduct problems, psychosomatic problems, and a mixed group of other behavioural problems, when assessed 3 months after the cancer diagnosis. These symptoms became less evident during follow up. Among the school aged siblings, however, conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive symptoms, and other behavioural symptoms remained unchanged during follow up. In their self assessments, the school aged siblings showed both state and trait anxiety more often than controls at the first assessment, but later these symptoms settled to the same level as the controls. The overall Children's Depression Inventory (CDI) depression scores did not show differences between the study groups. CONCLUSIONS: The ratings of the parents were in keeping with the self assessment of the school aged siblings only in a few aspects; the emphasis of findings can be changed when proxies are used. The siblings have symptoms and adverse feelings which probably could be relieved by targeted, early information about the illness, and possibly by group discussions or activities, soon after the cancer diagnosis. In order to obtain necessary support for the siblings with educational problems, school personnel need to be informed about the sibling distress.     

Editorial: Factualities – establishing empirical truths in child psychology and psychiatry

Empirical science is a fact-finding enterprise. This raises the question when we know enough about a particular topic to draw firm conclusions and can stop searching for additional evidence in order to save efforts for issues that are less well-established. Clarity on when scientific evidence has passed the stage of to-be-tested hypotheses is important, and setting up criteria for such stopping rules is a necessary as well as thought-provoking challenge. Not only over-investigating phenomena is undesirable but the opposite, falsely assuming beliefs to be facts, as well. Two common reasons for such misperceptions are that negative news is more likely to spread around than positive news (negativity instinct), and that individuals tend to look at problems from always the same perspective (single-perspective instinct). Our field is not immune to those instincts: child psychologists and psychiatrists tend to focus on messages suggesting that the burden of children´s mental health problems calls for more intervention and research, rather than on reports that the majority of children are doing quite well. This focus on problems may obscure the reality that the vast majority of children and adolescents never experience severe mental health problems, despite the challenges of growing up in a complex world.     

Randomized clinical trials in perinatology in Latin America.

Latin America needs means to obtain accurate figures about its health conditions in order to apply its resources to priority areas. In addition, health actions must be carefully evaluated to assess their impact, operation and costs. The randomized clinical trial (RCT) is the only design able to show the effectiveness of interventions of moderate effect. Also, it gives appropriate information about the expected effect of the interventions and implies an expediate implementation of interventions in the same places where the project has been performed. In a review of RCTs performed in Latin America on perinatal medicine it can be concluded that some of the focus of research is irrelevant to the region and there is not an orientation towards the cooperative solution of predominant problems in the area. It is imperative for researchers, in Latin America to initiate joint activities in order to assess which are the research priorities of the area, to focus their research on these priorities and to join their efforts in collaborative studies.