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BACKGROUND: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, genetically heterogeneous, autosomal recessive disorder. Patients suffer from recurrent infections caused by reduced levels or absence of serum immunoglobulins. Genetically, 4 subtypes of ICF syndrome have been identified to date: ICF1 (DNMT3B mutations), ICF2 (ZBTB24 mutations), ICF3 (CDCA7 mutations), and ICF4 (HELLS mutations). AIM: To study the mutation spectrum in ICF syndrome. MATERIALS AND METHODS: Genetic studies were performed in peripheral blood lymphocyte DNA from suspected ICF patients and family members. RESULTS: We describe 7 ICF1 patients and 6 novel missense mutations in DNMT3B, affecting highly conserved residues in the catalytic domain. We also describe 5 new ICF2 patients, one of them carrying a homozygous deletion of the complete ZBTB24 locus. In a meta-analysis of all published ICF cases, we observed a gender bias in ICF2 with 79% male patients. DISCUSSION: The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24. The observed gender bias seems to be restricted to ICF2 as it is not observed in the ICF1 cohort. CONCLUSION: Our study expands the mutation spectrum in ICF syndrome and supports that DNMT3B and ZBTB24 are the most common disease genes.

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Telomere length can be considered as a biological marker for cell proliferation and aging. Obesity is associated with adipocyte hypertrophy and proliferation as well as with shorter telomeres in adipose tissue. As adipose tissue is a mixture of different cell types and the cellular composition of adipose tissue changes with obesity, it is unclear what determines telomere length of whole adipose tissue. We aimed to investigate telomere length in whole adipose tissue and isolated adipocytes in relation to adiposity, adipocyte hypertrophy and adipose tissue inflammation and fibrosis. Telomere length was measured by real-time PCR in visceral adipose tissue, and isolated adipocytes of 21 obese women with a waist ranging from 110 to 147 cm and age from 31 to 61 years. Telomere length in adipocytes was shorter than in whole adipose tissue. Telomere length of adipocytes but not whole adipose tissue correlated negatively with waist and adipocyte size, which was still significant after correction for age. Telomere length of whole adipose tissue associated negatively with fibrosis as determined by collagen content. Thus, in extremely obese individuals, adipocyte telomere length is a marker of adiposity, whereas whole adipose tissue telomere length reflects the extent of fibrosis and may indicate adipose tissue dysfunction.

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The aim of this study was to evaluate the use of Healthcare Failure Mode and Effect Analysis (HFMEA) in Dutch health care by means of user feedback. Thirteen HFMEA analyses of various health care processes were successfully concluded and on average took 69 person-hours (excluding reporting). These results show that HFMEA can successfully be applied in Dutch health care. However, the user feedback also uncovered several perceived drawbacks, such as the fact that HFMEA is very time-consuming and that, particularly, the risk assessment part of HFMEA is difficult to carry out. Moreover, a lack of guidance with regard to the identification of failure mode causes and effective actions might influence the quality of the outcomes of an HFMEA analysis. Several suggestions are put forward to improve the perceived utility and acceptance of HFMEA. Nevertheless, future research is necessary to evaluate the actual effects of these recommendations. Error modelling and risk analysis, and their contribution to explaining human performance in socio-technical systems, traditionally belong to the field of ergonomics. The user feedback on HFMEA and the suggestions that are put forward may also be useful for (H)FMEA and hazard analysis and critical control point applications in sectors other than health care.

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OBJECTIVE: To evaluate the anti-HCV (hepatitic C virus) reactivity for the development of an individual donor counseling strategy which would prevent unnecessary donor deferment without compromising the safety of blood products. DESIGN: All donors, who were repeatedly reactive in the Ortho HCV ELISA as well as the Abbott HCV EIA screening tests were selected for follow-up testing. At follow-up three screening tests (Ortho, Abbott, and UBI HCV EIA) and two confirmation tests (Riba 4 and PCR HCV RNA) were performed. During the counseling interview risk factors and medical history were recorded. SETTING: Blood bank Zuid-Limburg, Maastricht, the Netherlands; estimated donor population 17,500. PARTICIPANTS: A total of 54 donors could be completely evaluated. RESULTS: The participants could be divided into five different categories, requiring specific donor information and different blood bank policies. The donors in categories 1 and 2 (n = 11) had false-positive reactions and were kept active. Category 3 and 4 donors (n = 28) showed indeterminate results and were permanently or temporarily excluded. Finally, in category 5 donors (n = 15) a HCV infection could be diagnosed on the basis of either Riba-positive or PCR-positive results. CONCLUSIONS: An anti-HCV screening policy should include a careful evaluation and confirmation of antibody reactivity. A strategy is suggested which allows an individual donor counseling, prevents unnecessary donor deferment, and avoids unnecessary fear of seropositivity.

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Classification of subjects with a partial D antigen is traditionally performed with immune anti-D sera. The development of monoclonal antibodies enables a fine analysis to be made of the specificity of the epitopes that are present or missing in these cases. A systematic search in a Caucasian donor population of 17,500 revealed 8 unrelated male individuals (frequency 0.05%) with a red cell phenotype characteristic of partial D category VI, but without anti-D in their serum. The relation to the 'classic' partial D category VI was investigated and is discussed, as is the observed serological heterogeneity of the partial D category VI group. Clinical consequences for the prevention of immunization of these subjects are mentioned.

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In 1987 the definition of an Rh-negative donor in the Netherlands was changed from C-, E- as well as Du-negative to D-negative only. The use of 2 different strong anti-D sera without an antiglobulin phase (Du test) was considered sufficient to reveal the clinically important D antigen. In applying this policy, we identified 32 donors in 13,500 consecutive blood donations whose indirect antiglobulin test (IAT) (Du)-positive red cells gave negative reactions with at least 2 out of 11 anti-D sera and whose cells might therefore be typed as Rh(-D-)-negative in routine investigations. IgG anti-D used by a one-stage bromelain technique and anti-D with modified IgG appeared to be relatively insensitive in detecting Du in this study. Polyclonal anti-D in an enhancement medium and monoclonal anti-D scored better, although differences exist between the products of various manufacturers. It is suggested that if IAT (Du) testing is omitted, only anti-D sera with a high index of detectability of cells expressing weak D antigens should be accepted.

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An automated flow-injection system with a computer-controlled sample changer, injection device and digital photometer is described, for use with an Apple II. The software is understandable, flexible and easily adaptable to different computers provided with the programming language FORTH.

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An automated flow-injection system is described, with a computer-controlled sample changer, injection device and photometer. The modular software package is understandable, flexible and easily adaptable to different computers.