Averting abnormal inheritance: potential of gene therapy and preimplantation diagnosis
KeywordsA, abnormal, Adult, ADULTS, AND, ANIMAL, animals, ARTICLE, BOTH, CARE, cell, CHILD, child health, CHILDREN, COMPLEX, COMPLEXES, Condition, DIAGNOSIS, DISEASE, Ethical, Fertilization in Vitro, FORM, GENE, Gene Therapy, Genetic, genetic diagnosis, Genetic Diseases, Inborn, genome, Genome Project, HEALTH, Human, HYBRIDIZATION, IM, immunology, INHERITANCE, IS, JOURNAL, LA, LONDON, METHODS, MOLECULAR, NEW, NEWBORN, OF, paediatric, PAPER, preimplantation, Preimplantation Diagnosis, Prenatal, PRENATAL DIAGNOSIS, PRENATAL-DIAGNOSIS, Reproductive Medicine, REVIEW, SAFETY, technique, techniques, THE, THERAPY, trends, UK, unit
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AbstractSerious inherited disease in children can be averted by preimplantation genetic diagnosis (PGD) and potentially by gene therapy in addition to prenatal diagnosis. PGD is now well established and provides a secure, if expensive and complex form of care. Gene therapy has been practised only in animals, although its success in alleviating various conditions in adults and newborns, together with the scientific drive of the genome project, make it a highly likely approach over coming years. Pros and cons of both approaches are contrasted and compared. Newer reproductive techniques such as somatic cell hybridization promise to add new dimensions to gene therapy, and could be combined with PGD. This paper discusses the finer details of these options, their safety and the ethical issues they have raised
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Differential diagnostic of the burnout syndromeKister, Christine; Huber, Beate; Korczak, Dieter (German Medical Science GMS Publishing House, 2010-01-01)Introduction: There is no consistent definition of burnout. It is neither a defined diagnosis in ICD-10 nor in DSM-IV. Yet it is diagnosed by office-based doctors and clinicians. Mainly due to reimbursement reasons, diagnoses like depression are used instead of burnout diagnoses. Therefore burnout has a very high individual, social and economic impact. Objectives: How is burnout diagnosed? Which criteria are relevant? How valid and reliable are the used tools? What kind of disorders in case of burnout are relevant for a differential diagnosis? What is the economic effect of a differential diagnosis for burnout? Are there any negative effects of persons with burnout on patients or clients? Can stigmatization of burnout-patients or -clients be observed? Methods: Based on a systematic literature research in 36 databases, studies in English or German language, published since 2004, concerning medical and differential diagnoses, economic impact and ethical aspects of burnout, are included and evaluated. Results: 852 studies are identified. After considering the inclusion and exclusion criteria and after reviewing the full texts, 25 medical and one ethical study are included. No economic study met the criteria.The key result of this report is that so far no standardized, general and international valid procedure exists to obtain a burnout diagnosis. At present, it is up to the physician’s discretion to diagnose burnout. The overall problem is to measure a phenomenon that is not exactly defined. The current available burnout measurements capture a three dimensional burnout construct. But the cutoff points do not conform to the standards of scientifically valid test construction. It is important to distinguish burnout from depression, alexithymia, feeling unwell and the concept of prolonged exhaustion. An intermittent relation of the constructs is possible. Furthermore, burnout goes along with various ailments like sleep disturbance. Through a derogation of work performance it can have also negative effects on significant others (for example patients). There is no evidence for stigmatization of persons with burnout. Discussion: The evidence of the majority of the studies is predominantly low. Most of the studies are descriptive and explorative. Self-assessment tools are mainly used, overall the Maslach Burnout Inventory (MBI). Objective data like medical parameters, health status, sick notes or judgements by third persons are extremely seldomly included in the studies. The sample construction is coincidental in the majority of cases, response rates are often low. Almost no longitudinal studies are available. There are insufficient results on the stability and the duration of related symptoms. The ambiguity of the burnout diagnosis is regularly neglected in the studies. Conclusions: The authors conclude, that (1) further research, particularly high-quality studies are needed, to broaden the understanding of the burnout syndrome. Equally (2) a definition of the burnout syndrome has to be found which goes beyond the published understanding of burnout and is based on common scientific consent. Furthermore, there is a need (3) for finding a standardized, international accepted and valid procedure for the differentiated diagnostics of burnout and for (4) developing a third party assessment tool for the diagnosis of burnout. Finally, (5) the economic effects and implication of burnout diagnostics on the economy, the health insurances and the patients have to be analysed.
Neurological aspects of hyperinsulinism-hyperammonaemia syndrome.Bahi-Buisson, Nadia; Roze, Emmanuel; Dionisi, Carlo; Escande, Fabienne; Valayannopoulos, Vassili; Feillet, François; Heinrichs, Claudine; Chadefaux-Vekemans, Bernadette; Dan, Bernard; de Lonlay, Pascale (2008-12)Hyperinsulinism-hyperammonaemia syndrome (HHS) is a rare cause of congenital hyperinsulinism, due to missense mutations in the GLUD1 gene, resulting in glutamate dehydrogenase (GDH) overactivity. The aim of this study was to document the spectrum of neurological disturbances associated with HHS and to identify possible phenotype-genotype correlations. We retrospectively analyzed the neurological outcomes of 22 consecutive patients (12 males, 10 females) aged from 18 months to 40 years and diagnosed with HHS. We analyzed demographic and clinical features and neuroradiological, biochemical, and genetic findings. Fourteen patients had childhood-onset epilepsy. Learning disability was found in 17 patients. Two patients had pyramidal involvement and one had generalized dystonia. Seizures were observed in 11 of 19 patients with documented GLUD1 mutations, and nine of these 11 patients had a mutation in the guanosine triphosphate (GTP) binding site. Our data demonstrate that neurological disorders in HHS are more frequent than previously thought and might suggest that mutations in the GTP binding site of GDH could be associated with more frequent epilepsy.
Complete callosal disconnection after closed head injury.Vuilleumier, P.; Assal, G. (1995-02)We report a patient with complete callosal disconnection syndrome after severe closed head injury. MRI showed a complete destruction of the corpus callosum throughout its length. Although traumatic callosal lesions are a frequent finding in autopsy studies, as well as in some recent MRI studies, clinical signs of callosal disconnection are rarely observed after head injuries and a complete disconnection syndrome has not been reported yet. This case study and the review of other reported cases suggest that posttraumatic callosal disconnection is probably often overlooked. Our patient had also a severe memory disorder that might be partly related to the bilateral involvement of the fornix, as this structure is closely adjacent to the posterior corpus callosum, and was also shown by MRI to be very probably damaged.