Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany

The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000–1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000–1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. Conclusion: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.Abbreviations ESPED Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) - MCADD medium-chain acyl-CoA dehydrogenase deficiency - MS-MS tandem mass spectrometry - mtFATOD mitochondrial fatty acid transport and oxidation disorders - NBS newborn screening - OA organic acidurias     

Familiality of symptom dimensions in depression

BACKGROUND: Depression is a clinically heterogeneous disorder thought to result from multiple genes interacting with environmental and developmental components. A dimensional rather than a categorical approach to depressive phenotype definition may be more useful for identification of susceptibility genes. OBJECTIVES: To perform an exploratory factor analysis on a range of depressive and anxiety symptoms in a large, well-defined sample of depressed siblings, as well as a confirmatory factor analysis in a separate large group of unrelated depressed subjects, and to analyze correlations of identified symptom dimensions between depressed siblings. DESIGN: Subjects (N = 1034), including 475 sibling pairs, with a history of at least 2 depressive episodes were recruited from the Depression Network Study, a large-scale multicenter collection of families affected by recurrent unipolar depression. Subjects were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to the DSM-IV and the International Classification of Diseases, 10th Revision, using a computerized scoring program (CATEGO5). Factor analysis was carried out on 26 depression symptom items, including 4 anxiety screening items. Confirmatory factor analysis was performed on an independent sample of 485 depressed individuals. RESULTS: Four interpretable factors were identified: (1) mood symptoms and psychomotor retardation; (2) anxiety; (3) psychomotor agitation, guilt, and suicidality; and (4) appetite gain and hypersomnia. For each symptom group, a quantitative scale was constructed, and correlations between siblings were calculated. There was a moderate degree of sibling homotypia for some depressive symptoms, and factors 1, 2, and 3 showed significant positive familial correlation (0.145 [P =.001], 0.335 [P<.001], and 0.362 [P<.001], respectively). CONCLUSIONS: This is the first study of large, well-defined samples of depressed subjects in whom symptom dimensions have been derived and then confirmed using independent material. The significant correlations between siblings for 3 of the dimensions suggest substantial familial, perhaps genetic, etiologies.     

Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts

Deoxyguanosine kinase is a constitutively expressed, mitochondrial enzyme of the deoxyribonucleoside salvage pathway. Deficiency of deoxyguanosine kinase causes early-onset, hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome. To clarify the molecular mechanism of the disease, a skin fibroblast culture was studied from a patient carrying a homozygous nonsense mutation in the gene for deoxyguanosine kinase. In situ examination of DNA synthesis demonstrated that, although mtDNA synthesis is cell cycle independent in control fibroblasts, mtDNA synthesis occurs mainly during the S-phase in deoxyguanosine kinase-deficient cells. Consistent with this observation, it was found that the mtDNA content of exponentially growing, deoxyguanosine kinase-deficient cells is only mildly affected. When cycling is inhibited by serum-deprivation and cells are in a resting state, however, the mtDNA content drops considerably in deoxyguanosine kinase-deficient cells, yet remains stable in control fibroblasts. The decline in mtDNA content in resting, deoxyguanosine kinase-deficient cells can be prevented by dGMP and dAMP supplementation, providing conclusive evidence that substrate limitation triggers mtDNA depletion in deoxyguanosine kinase-deficient cells.     

Laparoscopic ileocecal resection for bowel endometriosis

Background  

Ileocecal endometriosis is a very rare entity, and its diagnosis is usually made during surgery for other endometriosis sites or, rarely, because of direct complications of ileal involvement. This study was designed to analyze perioperative and long-term outcomes after bowel resection for ileocecal endometriosis.     

Identifying the barriers to conducting outcomes research in integrative health care clinic settings - a qualitative study

Background  

Integrative health care (IHC) is an interdisciplinary blending of conventional medicine and complementary and alternative medicine (CAM) with the purpose of enhancing patients' health. In 2006, we designed a study to assess outcomes that are relevant to people using such care. However, we faced major challenges in conducting this study and hypothesized that this might be due to the lack of a research climate in these clinics. To investigate these challenges, we initiated a further study in 2008, to explore the reasons why IHC clinics are not conducting outcomes research and to identify strategies for conducting successful in-house outcomes research programs. The results of the latter study are reported here.     

Standardized care plans in Swedish health care: their quality and the extent to which they are used

Objectives:  To investigate the quality of standardized care plans and the extent to which they are used within Swedish in-hospital somatic care. Further, to examine the quality of the knowledge summaries on which existing standardized care plans were supposed to be based.
Design:  Submitted documents were reviewed with study-specific protocols.
Setting:  A national survey, based on a structured selection of Swedish hospitals.
Participants:  A total of 25 Swedish hospitals participated, and were asked to submit all documents in use that were labelled standardized care plan.
Results:  Only 4% (34 out of 782) of the reviewed documents fulfilled the criteria for being a standardized care plan. None of the 34 knowledge summaries (an accompanying document with a compilation of scientific facts and reliable experience) was evidence-based.
Conclusions:  There is a lack of knowledge regarding what a standardized care plan is, and how such a document should emanate from evidence-based knowledge. Our results raise the question of how recent developments in research are used to create standardized care plans for the best possible care. In the process of developing standardized care plans it is important to acknowledge that staff who develop these plans need scientific training and experience. Standardized care plans are in the early stages of development, and at this stage it seems appropriate to initiate a discussion regarding possible cooperation at national level when developing standardized care plans for certain large groups of patients suffering from specific diseases, or undergoing the same treatment.     

Support in nursing--an evolutionary concept analysis

BACKGROUND: This research into the concept of support was undertaken because of the recurrent use of the concept in nursing research and especially because of the vital importance of support to family carers of older persons. AIM: To inductively develop a definition of support, specifically in the context of family care of frail aged persons. METHOD: The study followed the evolutionary method of concept analysis. The study was based on data from scientific publications, encyclopaedias and dictionaries. In order to secure a representative sample, highly systematic means of sampling were used. RESULTS: Working with the data underpinning this study, it was possible to put forward a definition of support for family carers who care for a frail aged person at home. The two major dimensions, as described under attributes, were merged into the following definition: "Support entails the provision of general tangibles such as information, education, economic aid, goods and external services. They are prerequisites for facilitating the family carers' competence or capacity in care. Moreover it entails necessary qualities such as individualization, adaptability, lastingness, room for verbalizing emotions as well as an idea of reciprocal symmetrical exchange between involved parties.     

The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance

We show that the mouse macrophage-restricted F4/80 protein is not required for the development and distribution of tissue macrophages but is involved in the generation of antigen-specific efferent regulatory T (T reg) cells that suppress antigen-specific immunity. In the in vivo anterior chamber (a.c.)-associated immune deviation (ACAID) model of peripheral tolerance, a.c. inoculation of antigen into F4/80(-/-) mice was unable to induce efferent T reg cells and suppress delayed-type hypersensitivity (DTH) responses. Moreover, the use of anti-F4/80 mAb and F4/80(-/-) APCs in an in vitro ACAID model showed that all APC cells in the culture must be able to express F4/80 protein if efferent T reg cells were to be generated. In a low-dose oral tolerance model, WT but not F4/80(-/-) mice generated an efferent CD8(+) T reg cell population that suppressed an antigen-specific DTH response. Peripheral tolerance was restored in F4/80(-/-) mice by adoptive transfer of F4/80(+) APCs in both peripheral tolerance models, indicating a central role for the F4/80 molecule in the generation of efferent CD8(+) T reg cells.     

Health risks and occupational exposure to volatile anaesthetics--a review with a systematic approach

Aims and objectives. To provide practicing nurse anaesthetists with evidence based knowledge as to whether they are at risk handling volatile anaesthetics by answering the question: What are the health risks threatening health care personnel occupationally exposed to volatile anaesthetics? Background. The interpretations of results from specific scientific studies vary and preliminary research results indicate that occupational exposure to volatile anaesthetics affects the health of operating room personnel. Design. Review of scientific literature with a systematic approach. Method. The review included a systematic search in three major databases, a screening process of abstracts/articles followed by a quality assessment of the included studies. The screening process and the quality assessment were done independently by the six reviewers and followed specific protocols. Results. A systematic search of The Cochrane Library, MedLine and CINAHL resulted in a screening of 413 abstracts of which 31 articles were assessed for quality, all done independently by the reviewers. Finally, the reviewers agreed upon how to interpret the results of the assessed articles. Conclusions. The 31 articles assessed covered areas such as genotoxic effects, neurobehavioural effects, immunology, and general health effects. In the scientific literature reviewed there is no evidence of occupational exposure to volatile anaesthetics either being associated with health risks or being harmless. Studies indicating a potential health risk are all investigating circumstances ignorant of modern environmental regulations and/or with no scavenging equipment. Relevance to clinical practice. Although no answer has been given, this review illuminates the methodological difficulties encountered in designing studies. The result of this review further stresses the need for scientific knowledge in this area and enhances the extensive use of scavenging equipment.