A novel mutation in NCF1 in an adult CGD patient with a liver abscess as first presentation

Chronic granulomatous disease (CGD) is an immunodeficiency caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase complex and is usually diagnosed in early childhood. CGD patients suffer from severe, recurrent infections with bacteria, fungi and yeasts. We report a 25-year-old female with protracted fever because of a Staphylococcus aureus liver abscess, which did not resolve until breakthrough into the stomach. Despite her age, CGD was considered on diagnosis on the basis of the clinical symptoms. Analysis of the NADPH-oxidase activity confirmed CGD as the underlying condition. Western blotting revealed the absence of p47(phox) and subsequent sequencing of the p47(phox)-encoding gene, neutrophil cytosolic factor (NCF1), identified a deletion of 837C in the maternal NCF1 allele. The paternal allele contained a stopcodon because of a conversion between NCF1 and one of its Psi NCF1 pseudogenes. The patient had one novel mutation, c.837delC, and one conversion in NCF1, resulting in the complete absence of the p47(phox) component of the NADPH-oxidase complex. This p47(phox)-deficient CGD patient had the highest age at diagnosis reported thus far. Journal of Human Genetics (2009) 54, 313-316; doi:10.1038/jhg.2009.24; published online 27 March 200

Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature

To investigate the prevalence of subependymal giant cell ependymomas (SEGA) in patients with tuberous sclerosis complex (TSC). We performed a retrospective cross-sectional study in a cohort of 285 patients with known TSC. Institutional review board approval was obtained. We included all 214 TSC-patients who had received a contrast-enhanced computed tomography (CT) scan of the brain. The most recent scan was evaluated for SEGA and presence of hydrocephalus. Additionally, a literature search was performed, and pooled estimates of SEGA prevalence in TSC were calculated. We used descriptive statistics, two sample t-test, chi-squared-test, and meta-analysis as appropriate. Computed tomography showed radiological evidence of SEGA in 43 of the 214 TSC-patients (20%); 23 of 105 men (22%) and 20 of 109 women (18%; P = .52). Average maximum tumor size was 11.4 mm (range, 4-29 mm). Patients with SEGA (mean, 31 years; range, 16-58 years) were on average younger than patients without SEGA (mean, 37 years; range, 10-72 years; P = 0.007). No association between tumor size and patient age was detected. Nine patients had bilateral SEGA. Hydrocephalus was present in six of the 43 patients (14%). Meta-analysis of reported prevalence and our current study showed that studies using radiological evidence to diagnose SEGA gave a higher pooled estimate of the prevalence of SEGA in TSC (0.16; 95% CI: 0.12, 0.21) than studies using mainly histopathological evidence of SEGA (0.09; 95% CI: 0.07, 0.12). In our cohort, CT demonstrated evidence of SEGA in 20% of TSC-patients. Prevalence of SEGA in TSC is higher in studies using radiological evidence to diagnose SEGA than in studies using histopathological evidenc

Intention-based expressions in GASTINE

OBJECTIVES: 1) To evaluate the design of the framework for computerized intention-based clinical practice guidelines; 2) to implement runtime features such as plan recognition and backtracking. METHOD: To evaluate the design, we implemented the heart failure guideline into GASTINE, a tool for representing and executing intention-based clinical guidelines. RESULT: Description of the current implementation of intention-based expressions in GASTINE and analysis of some generic shortcomings. Explanation of how these shortcomings are addressed. Presentation of how plan recognition and backtracking work and how they improve the system. CONCLUSION: The improved guideline system is rather flexible, i.e., it allows deviations from the guideline as long as they are in the spirit of the guideline. The recognition of actions as intended by the users facilitates a flexible decision support system. The intentions are used to explain why certain actions were suggested. Therefore it is assumed that showing the intention behind suggested actions provides a better insight into why these actions are advise

Transfusion-transmitted infectious diseases

A spectrum of blood-borne infectious agents is transmitted through transfusion of infected blood donated by apparently healthy and asymptomatic blood donors. The diversity of infectious agents includes hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency viruses (HIV-1/2), human T-cell lymphotropic viruses (HTLV-I/II), Cytomegalovirus (CMV), Parvovirus B19, West Nile Virus (WNV), Dengue virus, trypanosomiasis, malaria, and variant CJD. Several strategies are implemented to reduce the risk of transmitting these infectious agents by donor exclusion for clinical history of risk factors, screening for the serological markers of infections, and nucleic acid testing (NAT) by viral gene amplification for direct and sensitive detection of the known infectious agents. Consequently, transfusions are safer now than ever before and we have learnt how to mitigate risks of emerging infectious diseases such as West Nile, Chikungunya, and Dengue viruse

Volumetric and functional recovery of the remnant liver after major liver resection with prior portal vein embolization : recovery after PVE and liver resection

INTRODUCTION: Portal vein embolization is an accepted method to increase the future remnant liver preoperatively. The aim of this study was to assess the effect of preoperative portal vein embolization on liver volume and function 3 months after major liver resection. MATERIALS AND METHODS: This is a retrospective case-control study. Data were collected of patients who underwent portal vein embolization prior to (extended) right hemihepatectomy and of control patients who underwent the same type of resection without prior portal vein embolization. Liver volumes were measured by computed tomography volumetry before portal vein embolization, before liver resection, and 3 months after liver resection. Liver function was assessed by hepatobiliary scintigraphy before and 3 months after liver resection. RESULTS: Ten patients were included in the embolization group and 13 in the control group. Groups were comparable for gender, age, and number of patients with a compromised liver. The mean future remnant liver volume was 33.0 +/- 8.0% prior to portal vein embolization in the embolization group and 45.6 +/- 9.1% in the control group (p 0.05). Remnant liver function increased up to 88.1 +/- 17.4% and 83.3 +/- 14% respectively of the original total liver function (p > 0.05). CONCLUSION: Preoperative portal vein embolization does not negatively influence postoperative liver regeneration assessed 3 months after major liver resectio

Markers of cerebral damage during delirium in elderly patients with hip fracture

ABSTRACT: BACKGROUND: S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized by temporal cognitive deficits and is an important risk factor for dementia. The aim of this study was to compare the level of S100B and NSE of patients before, during and after delirium with patients without delirium and investigate the possible associations with different subtypes of delirium. METHODS: The study population were patients aged 65 years or more acutely admitted after hip fracture. Delirium was diagnosed by the Confusion Assessment Method and the subtype by Delirium Symptom interview. In maximal four serum samples per patient S100B and NSE levels were determined by electrochemiluminescence immunoassay. RESULTS: Of 120 included patients with mean age 83.9 years, 62 experienced delirium. Delirious patients had more frequently pre-existing cognitive impairment (67% vs. 18%, p <0.001). Comparing the first samples during delirium to samples of non-delirious patients, a difference was observed in S100B (median 0.16 versus 0.10 ug/L, p= <0.001), but not in NSE (median 11.7 versus 11.7 ng/L, p=0.97). Delirious state (before, during, after) (p <0.001), day of blood withdrawal (p <0.001), pre- or postoperative status (p=0.001) and type of fracture (p=0.036) were all associated with S100B level. The highest S100B levels were found 'during' delirium. S100B levels 'before' and 'after' delirium were still higher than those from 'non-delirious' patients. No significant difference in S100B (p=0.43) or NSE levels (p=0.41) was seen between the hyperactive, hypoactive and mixed subtype of delirium. CONCLUSIONS: Delirium was associated with increased level of S100B which could indicate cerebral damage either due to delirium or leading to delirium. The possible association between higher levels of S100B during delirium and the higher risk of developing dementia after delirium is an interesting field for future research. More studies are needed to elucidate the role of S100B proteins in the pathophysiological pathway leading to delirium and to investigate its possibility as biomarker for deliriu

Sikkelcelziekte in de hielprikscreening. II

OBJECTIVE: Evaluation of the reporting of sickle cell trait during the first year (2007) in which sickle cell disease has been included in heel prick screening in the Netherlands. DESIGN: Descriptive. METHOD: Reporting of the number of children identified as having sickle cell trait and the number of subsequent referrals by general practitioners to 2 clinical genetics centres (CGC), at the Academic Medical Center in Amsterdam and the Erasmus MC in Rotterdam. RESULTS: In the first year sickle cell trait was found in 806 children. Only 20 couples were referred to the 2 CGCs, and these did not include any at-risk couples i.e. couples in which both partners have sickle cell trait. CONCLUSION: There is still a lack of clarity among primary care providers concerning the role of the general practitioner and of the midwife in the reportage procedure for sickle cell trai

Comparison of axial, coronal, and primary 3D review in MDCT colonography for the detection of small polyps: a phantom study

The purpose of this phantom study is to compare the influence of the reading technique (axial images alone in comparison to 3D endoluminal, coronal, and combined 2D/3D review methods) on the sensitivity and inter-reader variability with MDCT colonography for the detection of small colonic polyps. An anthropomorphic pig colon phantom with 75 randomly distributed simulated small polyps of 2-8mm size, was distended with air and scanned in a water phantom using multidetector-row CT with 4mm x 1mm collimation. Three radiologists rated the presence of polyps on a five-point scale. Performance with axial sections alone was compared to the performance with coronal sections, virtual endoscopy (VE), and a combined 2D/3D approach. We calculated sensitivities for polyp detection and used ROC analysis for data evaluation. There was no significant difference between the mean area under the curve (A(z)) for axial images and VE (A(z)=0.934 versus 0.932), whereas coronal images were significantly inferior (A(z)=0.876) to both. The combined 2D/3D approach yielded the best results, with an A(z) of 0.99. Differences in sensitivity between individual readers were significant in axial images (sensitivity, 75-93%, p=0.001) and coronal images (sensitivity, 69-80%, p=0.028), but became non-significant with VE (83-88%, p=0.144) and the combined 2D/3D approach (95-97%, p=0.288). Evaluation of axial sections alone leads to significant differences in detection rates between individual observers. A combined 2D/3D evaluation improves sensitivities for polyp detection and reduces inter-individual differences to an insignificant leve