Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature

BACKGROUND Cholesteryl ester storage disease(CESD)is a rare genetic disease.Its symptoms and severity are highly variable.CESD is a systemic disease that can lead to the accumulation of fat and inflammation in the liver,as well as gastrointestinal and cardiovascular disease.The majority of patients require liver transplantation due to decompensated cirrhosis.Enzyme replacement therapy has been approved based on a randomized trial.Our study aims to clinically and genetically evaluate two siblings with CESD who underwent liver transplantation,as well as their first-degree family members.CASE SUMMARY The siblings were compound heterozygous for the missense variant in LIPA exon 8,c.894G>A,(p.Gln298Gln)and a single base pair deletion,c.482del(p.Asn161Ilefs*19).Analyses of single nucleotide polymorphisms showed variants with an increased risk of fatty liver disease and fibrosis for both patients.Clinically,both patients show signs of recurrence of CESD in the liver after transplantation and additional gastrointestinal and cardiovascular signs of CESD.Three family members who were LIPA heterozygous had a lysosomal acid lipase activity below the reference value.One of these carriers,a seven-year-old boy,was found to have severe dyslipidemia and was subsequently treated with statins.CONCLUSION Our study underlines that CESD is a multi-organ disease,the progression of which may occur post-liver transplantation.Our findings underline the need for monitoring of complications and assessment of possible further treatment.     

How Do We Define Congenital Heart Defects for Scientific Studies?

Estimates of the prevalence of congenital heart defects (CHD) have been published over many years and from many regions. As they are based on different definitions of which cases to include in the CHD prevalence, published prevalence estimates vary substantially. With the increasing use of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population‐based data on CHD may be used: etiology, planning of treatment, or obtain information on outcome, including mortality. For etiology studies, it is important to include terminations of pregnancy as well as all births with CHD. For mortality studies in live births, inclusion of preterm born infants with PDA will increase overall mortality of CHD. The Danish Register of Congenital Heart Disease is based on hospital discharge diagnoses and diagnoses from outpatient visits. To increase the validity of these data, extensive data cleaning has been carried out based on record review and knowledge on the discharge coding practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD.     

Fourier analysis of video-keratographic data. A tool for separation of spherical, regular astigmatic and irregular astigmatic corneal power components

Topographic analysis of the cornea and computation of changes in corneal topography is difficult because of the lack of a standardized concept for analysing topographic information. We have used Fourier series harmonic analysis to decompose the often very complex information given in topographic images (TMS-1 video-keratograph). The polar data values arising from each mire were separated into spherical (average power), regular astigmatic (2′ harmonic) and non-regular astigmatic components. The non-regular astigmatic components were further divided into a decentration component (1′ harmonic) and a higher order irregular refractive component (root mean square (r.m.s.) of the residual between original data and the sum of spherical, 1′ and 2′ order components). Algorithms for utilizing the Fourier analysis technique on subjective refractive and on keratometric changes in regular astigmatism were also derived. Averages of the separate refractive components were calculated for groups of normal (right and left eye of 25 patients), keratoconic (13 eyes), and transplanted eyes (20 eyes), and average topographic maps were reconstructed and imaged. Changes in the separate topographic refractive components were compared with subjective refractive changes in eyes that had undergone combined myopic-astigmatic excimer laser ablation (8 eyes). Fourier series analysis was found superior to conventional keratometry in predicting spherical and regular astigmatic changes in subjective refraction. Fourier series analysis seems to be a powerful tool to decompose the information of complex topographic corneal images into rational optical components.     

Contextual effects in the occurrence of periodontal attachment loss and necrotizing gingival lesions among adolescents

The aim of this study was to assess and quantify the random effects resulting from clustering in the following individual-level periodontal outcomes: presence of clinical attachment loss of ≥ 1 mm (CAL1), presence of clinical attachment loss of ≥ 3 mm (CAL3), and presence of necrotizing ulcerative gingivitis (NUG); or in the following class-level periodontal outcomes: number of students with CAL1, number of students with CAL3, and number of students with NUG. Mixed-effects logistic regression analysis was used to model these outcomes among 9,162 adolescents in 310 classes in 98 schools spread over 20 communes in the Province of Santiago, Chile, who had been examined for clinical attachment level and NUG, and had completed questionnaires on oral health-related behaviors. The results of all six analyses demonstrated statistically significant random effects, which in all analyses were particularly related to the schools, whereas the class effects were smaller and the commune random effects were almost negligible. The random effects were quantified using the median odds ratio (MOR), and the class-level MOR ranged between 1.05 and 1.51, whereas the school-level MOR values ranged from 2.07 to 2.39. The results of the study demonstrate the potential of the application of multilevel modeling to periodontal epidemiologic data, over and beyond the conventional use of the technique to account for the intrinsic sites–teeth–subject hierarchy in periodontal data.     

Exploring the feasibility and possible efficacy of mass treatment and education of young females as schistosomiasis influences the HIV epidemic

Purpose  

Genital schistosomiasis may be a risk factor for HIV, but chronic lesions in adults may be refractory to standard treatment. We aimed to investigate young girls’ risk factors for gynaecological schistosomiasis, possible protective factors and possibilities for behavioural change and mass treatment in rural Tanzania.     

Quality of life for schizophrenic patients

Doctoral dissertation, Psychiatric Institute, Hillemod University of Copenhagen, Denmark. 2002.     

Subgingival bacterial clusters and serum antibody response as markers of extent and severity of periodontitis in adult Chinese

This study evaluated the associations between clinical, microbiological, and antibody activity manifestations of periodontitis in 123 adult rural Chinese subjects with no dental intervention. All participants were registered for full‐mouth clinical attachment level (CAL) and pocket probing depth (PD) measurements, and microbial samples were taken from four sites and analyzed for 18 different bacterial species using the ‘checkerboard’. Serum from each individual was analyzed to determine the antibody activity against the same 18 species. Exploratory factor analysis disclosed two microbial factors – Factor 1, consisting of seven species associated with periodontal health (‘early colonizers’); and Factor 2, consisting of eight species associated with periodontitis (‘putative periodontopathogens’) – which explained 87% of the variation among the microbial variables. Factor 2 was consistently associated with disease‐severity measures, whereas the ‘early colonizer’ factor was not. The antibody response showed weak or no correlations with bacterial load or with disease severity. We conclude that the bacteria investigated are resident in the subgingival plaque; that their load and proportions in the pocket may be ecologically driven; and that the antibody response is based on bacterial carrier state rather than on disease. The different antibody‐response pattern found between the individuals may suggest that each individual could be classified as a good or a weak immune responder.