Skin Prick Automated Test device offers more reliable allergy test results compared to a manual skin prick test.

BACKGROUND: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. OBJECTIVE: This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. METHODS: The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed. RESULTS: The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. CONCLUSION: SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

Aligning quality of life and guidelines for off-label psychotropic drugs in adults with intellectual disabilities and challenging behaviour.

Introduction: Adults with intellectual disabilities have an increased vulnerability to mental health problems and challenging behaviour. In addition to psychotherapeutic or psychoeducational methods, off-label pharmacotherapy, is a commonly used treatment modality. Objective: The aim of this study was to establish evidence-based guideline recommendations for the responsible prescription of off-label psychotropic drugs, in relation to Quality of Life (QoL). Method: A list of guidelines was selected, and principles were established based on international literature, guideline review and expert evaluation. The Delphi method was used to achieve consensus about guideline recommendations among a 58-member international multidisciplinary expert Delphi panel. Thirty-three statements were rated on a 5-point Likert-scale, ranging from totally disagree to totally agree, in consecutive Delphi rounds. When at least 70% of the participants agreed (score equal or higher than 4), a statement was accepted . Statements without a consensus were adjusted between consecutive Delphi rounds based on feedback from the Delphi panel. Results: Consensus was reached on 4 general:the importance of non-pharmaceutical treatments, comprehensive diagnostics and multidisciplinary treatment. Consensus was reached in 4 rounds on 29 statements. No consensus was reached on 4 statements concerning: freedom-restricting measures, the treatment plan, the evaluation of the treatment plan, and the informed consent. Conclusion: The study led to recommendations and principles for the responsible prescription - aligned with the QoL perspective - of off-label psychotropic drugs for adults with intellectual disabilities and challenging behaviour. Extensive discussion is needed regarding the issues on which there was no consensus to furthering the ongoing development of this guideline.

Comment on Neiser et al. Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA). Int. J. Mol. Sci. 2016, 17, 1185.

All IV iron complexes carry a risk of potentially fatal allergic type hypersensitivity reactions. The mechanism(s) behind these reactions is unknown but the limited data available suggests that classic IgE mediated allergy is exceedingly rare, if ever occurring. Iron-carbohydrate molecules are complex nano-particles and trying to reduce the risk of serious hypersensitivity to antibody binding of an artificial antibody seems meaningless. A recently published analysis of safety data from randomized clinical trials confirms the method reported by Neiser to be useless to predict reaction risk. In conclusion, the study by Neiser et al. is biased, contains no new information, and has no clinical relevance. We are concerned that the association of the authors with a commercial entity has caused a conflict of interest that biases not only the results, but the entire experimental setup against competitors. (Comment on Neiser et al. Int. J. Mol. Sci. 2016, 17, 1185, doi:10.3390/ijms17071185).

Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome.

Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non-synonymous variant in the LRP2 gene. Sanger sequencing confirmed the mutation and segregation in the family. No mutation was identified in COL9A1/2, COL11A1/2, or COL2A1 genes. The variant (c.11483A>G; p.Asp3828Gly) is predicted to be damaging and is conserved among vertebrate species. Mutations in LRP2 have been shown to cause the Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome, a syndrome associated with facial dysmorphism, ocular anomalies, sensorineural hearing loss, low molecular weight proteinuria, and diaphragmatic hernia and absent corpus callosum, although there is variability in the expression of some features. This family shows a milder phenotype with a predominant eye phenotype similar to the Stickler syndrome and only a few features of the DBS, including microglobulinuria. The presence of microglobulinuria was only detected after molecular results were known. In conclusion, with the identification of a new mutation in LRP2 associated with a predominant eye phenotype similar to the Stickler syndrome, we have broadened the phenotypic spectrum of LRP2 mutations.

Family quality of life in 25 Belgian families: quantitative and qualitative exploration of social and professional support domains.

BACKGROUND: This article reports on the results of a study conducted in Belgium on family quality of life situated within a larger project focusing on the development of support strategies for young and adolescent siblings of persons with intellectual disabilities. The objectives of this article are twofold: (1) to present the results of the measures contained in the nine domains of the Family Quality of Life Survey-2006 (FQOLS-2006) from the perspective of parents (quantitative analysis); and (2) to come to a more in-depth understanding of two important domains of the FQOLS-2006 by exploring and comparing the quantitative and qualitative data from open-ended interviews with parents. METHOD: The FQOLS-2006 was completed by the main caregivers of 25 families living in one typical Belgian province. Subsequently, semi-structured interviews with one or both parents were conducted within the same families. Content analysis was carried out on the transcribed interviews using the qualitative software package MaxQDA. RESULTS: A detailed analysis of the quantitative data together with data from the content analysis of the interviews revealed important issues with regard to two family quality of life domains, support from others and support from services. In general, parents were satisfied with the professional support they received, whereas they were more critical of support from others. CONCLUSIONS: The quantitative data from the FQOLS-2006 were supported and further explained by the qualitative data. These findings highlight the importance of adequate professional support, which is a flexible and capable answer to each family's individual needs. The authors warn of the dangers of 'handicapism' and plea for a family-centred support approach that takes the whole family into account. Finally, they indicate the benefits of increased practical-pedagogical support.

Evaluating the inter-respondent (consumer vs. staff) reliability and construct validity (SIS vs. Vineland) of the Supports Intensity Scale on a Dutch sample.

BACKGROUND: Despite various reliability studies on the Supports Intensity Scale (SIS), to date there has not been an evaluation of the reliability of client vs. staff judgments. Such determination is important, given the increasing consumer-driven approach to services. Additionally, there has not been an evaluation of the instrument's construct validity on a non-English speaking sample. This is important as the SIS is currently translated into 13 languages. METHOD: Data were collected in two different samples, using the Dutch translation of the SIS and the Vineland-Z. RESULTS: There was a significant correlation between ratings of staff and consumers on the SIS; however, the relationship between the mean scores of consumer and staff responses indicated significant differences in staff and consumer scores. All correlations between the Vineland-Z domains and the SIS subscales were significant and negative, ranging from -0.37 to -0.89. CONCLUSIONS: Analyses of the inter-respondent reliability suggest that one needs to consider the source of information regarding needed supports carefully. The significant negative correlations between SIS and Vineland-Z reflect that the SIS is measuring a different construct (needed support) than the Vineland-Z (adaptive behaviour). The results of the two studies provide additional support for the etic (universal) properties of the SIS, as both hypotheses were confirmed. In conclusion, SIS users are provided with a wealth of information that can be used for multiple purposes.

Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation.

AIM: To evaluate the implications of intravitreal bevacizumab on proangiogenic vascular endothelial growth factor (VEGF) with regard to the endogenous angiogenesis inhibitor endostatin in human choroidal neovascularisation (CNV) secondary to age-related macular degeneration. METHODS: Retrospective review of an interventional case series of 48 patients who underwent full macular translocation surgery with removal of CNV. Twenty-five patients were treated with intravitreal bevacizumab injection 1 to 154 days prior to surgery (bevacizumab CNV). Twenty-three CNV without any kind of previous treatment were used as controls (control CNV). CNV were stained for CD34, cytokeratin18, VEGF, endostatin and E-selectin. A "predominance score of VEGF over endostatin" (PS) was defined by the difference between VEGF and endostatin staining scores. RESULTS: Bevacizumab CNV revealed a weaker VEGF expression in endothelial cells (p = 0.0245) but significantly more intense endostatin in retina pigment epithelium (RPE) (p = 0.0001) and stroma (p<0.0001). Consequently, PS was significantly lower in RPE (p = 0.02), vessels (p = 0.03) and stroma (p = 0.0004) in bevacizumab CNV. The intensity of E-selectin expression in bevacizumab CNV was comparable with that in control CNV. CONCLUSIONS: A shift within the angiogenic balance in terms of decreased VEGF predominance over endostatin is detected in human CNV treated with bevacizumab.

S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes.

OBJECTIVE: The multifunctional Ca2+-binding protein S100A4 (also known as Mts1 and Fsp1) is involved in fibrosis and tissue remodeling in several diseases including cancer, kidney fibrosis, central nervous system injury, and pulmonary vascular disease. We previously reported that S100A4 mRNA expression was increased in hypertrophic rat hearts and that it has pro-cardiomyogenic effects in embryonic stem cell-derived embryoid bodies. We therefore hypothesized that S100A4 could play a supportive role in the injured heart. METHODS AND RESULTS: Here we verify by quantitative real-time PCR and immunoblotting that S100A4 mRNA and protein is upregulated in hypertrophic rat and human hearts and show by way of confocal microscopy that S100A4 protein, but not mRNA, appears in cardiac myocytes only in the border zone after an acute ischemic event in rat and human hearts. In normal rat and human hearts, S100A4 expression primarily colocalizes with markers of fibroblasts. In hypertrophy elicited by aortic banding/stenosis or myocardial infarction, this expression is increased. Moreover, invading macrophages and leucocytes stain strongly for S100A4, further increasing cardiac levels of S100A4 protein after injury. Promisingly, recombinant S100A4 protein elicited a robust hypertrophic response and increased the number of viable cells in cardiac myocyte cultures by inhibiting apoptosis. We also found that ERK1/2 activation was necessary for both the hypertrophy and survival effects of S100A4 in vitro. CONCLUSIONS: Along with proposed angiogenic and cell motility stimulating effects of S100A4, these findings suggest that S100A4 can act as a novel cardiac growth and survival factor and may have regenerative effects in injured myocardium.

Differential influence of different hepatitis viruses on quality of life in HIV positive patients.

UNLABELLED: HIV-infected individuals are frequently co-infected with different hepatitis viruses. HCV has been associated with impaired quality of life in non-HIV infected patients. Little is known concerning the quality of life in HIV-infected individuals in relation to the different viral co-infections. - PATIENTS AND METHODS: We investigated 250 patients who have answered HIV-SELT and EuroQoL (EQ-5D) questionnaires assessing quality of life. Data on HBsAg, anti-HBc, anti-HCV, and GBV-C-RNA were available for 191, 188, 189, 98 patients, respectively. HCV-RNA was tested in 33 of 35 anti-HCV positive patients. - RESULTS: There was no difference in quality of life in relation to active or past HBV-infection defined by HBsAg (n = 15) and anti-HBc in the absence of HBsAg (n = 84), respectively, for both overall HIV-SELT (p = 0.66, and p = 0.43, respectively) and visual EQ-5D (p = 0.93 and p = 0.64, respectively). However, anti-HCV positivity (n = 35) was associated with significantly impaired quality of life (HIV-SELT overall p<0.001). Importantly, no difference was found in relation to HCV-viraemia in anti-HCV positive patients (p = 0.77). In multivariate analysis anti-HCV positivity, employment status, HIV viral load and GBV-C were relevant to quality of life, with GBV-C being beneficial and HCV being negative. - CONCLUSIONS: While HBV seems to play no role concerning quality of live in HIV-infected patients, the flavi-viruses HCV and GBV-C display opposing influence on quality of life. As quality of life was similarly impaired in HCV-viraemic and HCV-non-viraemic anti-HCV positive patients but better in GBV-C viraemic patients, this should be taken into account in the indication case of planned interferon therapy.

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy.

Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system in regulation of natriuretic peptide and NPR gene expression. The ascending aorta was banded in 84 rats during Hypnorm/Dormicum-isoflurane anesthesia; after 4 wk the rats were randomized to treatment with losartan or placebo. The left ventricle of the heart was removed 1, 2, or 4 wk later. Aortic banding increased left ventricular expression of NPR-A and NPR-C mRNA by 110% (P < 0.001) and 520% (P < 0.01), respectively, after 8 wk; as expected, it also increased the expression of ANP and BNP mRNAs. Losartan induced a slight reduction of left ventricular weight but did not affect the expression of mRNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle.

Expression profiling reveals differences in metabolic gene expression between exercise-induced cardiac effects and maladaptive cardiac hypertrophy.

While cardiac hypertrophy elicited by pathological stimuli eventually leads to cardiac dysfunction, exercise-induced hypertrophy does not. This suggests that a beneficial hypertrophic phenotype exists. In search of an underlying molecular substrate we used microarray technology to identify cardiac gene expression in response to exercise. Rats exercised for seven weeks on a treadmill were characterized by invasive blood pressure measurements and echocardiography. RNA was isolated from the left ventricle and analysed on DNA microarrays containing 8740 genes. Selected genes were analysed by quantitative PCR. The exercise program resulted in cardiac hypertrophy without impaired cardiac function. Principal component analysis identified an exercise-induced change in gene expression that was distinct from the program observed in maladaptive hypertrophy. Statistical analysis identified 267 upregulated genes and 62 downregulated genes in response to exercise. Expression changes in genes encoding extracellular matrix proteins, cytoskeletal elements, signalling factors and ribosomal proteins mimicked changes previously described in maladaptive hypertrophy. Our most striking observation was that expression changes of genes involved in beta-oxidation of fatty acids and glucose metabolism differentiate adaptive from maladaptive hypertrophy. Direct comparison to maladaptive hypertrophy was enabled by quantitative PCR of key metabolic enzymes including uncoupling protein 2 (UCP2) and fatty acid translocase (CD36). DNA microarray analysis of gene expression changes in exercise-induced cardiac hypertrophy suggests that a set of genes involved in fatty acid and glucose metabolism could be fundamental to the beneficial phenotype of exercise-induced hypertrophy, as these changes are absent or reversed in maladaptive hypertrophy.

Validating the EQ-5D with time trade off for the German population.

The aim of this survey study was to derive the societal values of the general public for the EuroQol EQ-5D. Using the same protocol as previously used in the United Kingdom, we compared the German values with the British. In face-to-face interviews a sample of 339 individuals in northern Germany valued 15 different health states from a sample of 36 states. Values were derived using the York MVH protocol for time trade-off (TTO) and a visual analogue scale (VAS). Values for all 243 health states of the EQ-5D were estimated by a regression model. The VAS values revealed close a resemblance to the British VAS results. German TTO values were higher than the British. This was especially the case for the worse health states. The results suggest that the TTO values are more related to national variables than values derived by VAS. The use of the TTO values of this investigation makes it possible to anticipate these cultural differences in studies carried out in Germany.

Vitrectomy for epiretinal membranes: visual outcome and prognostic criteria.

The treatment of choice for epiretinal membranes (ERM) causing marked retinal distortion and substantial visual impairment remains vitreoretinal surgery. The purpose of this study was to evaluate the results of surgery performed in our department and to investigate the prognostic value of different factors such as preoperative best-corrected visual acuity (BCVA), pre-existing cystoid macular edema (CME), intra-operative peeling of the internal limiting membrane (ILM), age and duration of symptoms. Eighty-eight consecutive eyes of 88 patients were operated on for ERM from July 1998 to June 2000. Both idiopathic and secondary cases were included. In all cases the ERM was successfully removed from the fovea. Mean BCVA after surgery increased from Snellen 0.2 (hand motion (HM) - 0.6) to Snellen 0.5 (HM - 1.0) (p<0.0001). Our results confirm the efficacy of surgical removal of the ERM in improving the visual acuity. Although not statistically significant, mean postoperative BCVA was slightly better in the group without pre-existing CME (p>0.05) and in the group where peeling of the ILM was performed (p>0.05). The data suggest that early surgery is likely to decrease the risk of developing irreversible macular damage (p<0.05). Because accelerated nuclear sclerosis with visual impairment is a common phenomenon after vitrectomy, one might consider performing a phaco-emulsification at the same time, especially in the elderly.

Macular CMV retinitis: a case report.

PURPOSE: Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection associated with AIDS. It usually affects the peripheral retina, sparing the macula. We describe an atypical CMV retinitis exclusively confined to the macula. METHODS: A 43-year-old man with the diagnosis of AIDS developed a white retinal lesion confined to the macula of the right eye. Two weeks later, a more typical granular appearance was observed leading to presumption of CMV retinitis. RESULTS: The patient was treated with ganciclovir without success. With foscarnet, a good response was obtained, leading to total healing of the lesion. CONCLUSIONS: CMV retinitis has to be taken into consideration in all lesions confined to the macula in immunodepressed patients. An early diagnosis is crucial to avoid blindness.

Treatment costs and quality of life of patients with peripheral arterial occlusive disease--the German perspective.

BACKGROUND: To objectify the debate about the restricted resources of the health system, examinations about the treatment costs and quality of life implications of different illnesses are necessary. The aims of the examination were the quantification of costs that are caused by a patient with PAD per year and the determination of the quality of life. PATIENTS AND METHODS: 280 patients (mean 66.6 years) in Fontaine stages II to IV were included in the study to determine their treatment costs for the year 2001 retrospectively from patient records. Health-related quality of life was recorded through the standardized questionnaires PAVK-86, SF-36 and EQ-5D. RESULTS: A patient with PAD in stage Ila costs on average 1792.45 Euros, in stage IIb 2551.28 Euros, in stage III 4356.48 Euros and in stage IV 6225.89 Euros. The costs of the in-hospital treatment dominated the total result on average with 44.4% of the direct costs. Further cost factors were the drugs with 33.4%, the out-patient medical treatment with 9.9%, the expenditures for care with 6.7%, rehabilitation with 3.6% and adjuvants with a share of 1.9%. The indirect costs played a subordinate role with 9.67% of the total costs. The quality of life was clearly restricted in all stages of the PAD. The quality of life especially was strongly decreased from the Fontaine stage IIb on. The problems were mainly in the areas of the physicalfunctions and pain. CONCLUSION: The study showed that the treatment of patients with PAD is very cost-intensive and that patients have to suffer from a considerable loss of quality of life.

GB virus C infection and quality of life in HIV-positive patients.

It was recently shown that GBV-C infection is associated with prolonged survival of HIV-infected individuals. The GB virus C is the closest known relative of hepatitis C virus in man. The latter has been associated with significant impairment in quality of life, independent from the associated liver disease. We were thus interested in the impact of GB virus C infection on quality of life in HIV-infected individuals. We retrospectively analyzed a cohort of HIV-positive patients who previously answered the 'HIV-SELT' and the 'EQ-5D' questionnaires assessing quality of life and for whom data on GB virus C RNA status were available. In this study we identified no adverse effect of GB virus C on quality of life, but, in contrast, GB virus C viraemic patients showed better quality of life in all parameters for the scores in comparison to GB virus C-negative HIV-infected patients. HIV-positive patients with a GB virus C infection showed superior quality of life. These data further support the favourable course of HIV disease in GB virus C-positive patients.

Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy.

Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat.

Multiprotein bridging factor 1 cooperates with c-Jun and is necessary for cardiac hypertrophy in vitro.

Cardiac hypertrophy is induced by a number of stimuli and can lead to cardiomyopathy and heart failure. Cardiomyocyte hypertrophy is characterized by increased cell size and altered gene expression. By differential-display polymerase chain reaction and Western blotting we found that the transcriptional coactivator MBF1 was upregulated during hypertrophy in cardiomyocyte cultures. Furthermore, MBF1 protein level increased in two animal models of hypertrophy, angiotensin II treatment and aortic banding. MBF1 antisense oligodeoxynuclotides blocked phenylephrine-induced hypertrophy, suggesting MBF1 plays a key role in hypertrophic growth. In contrast, overexpression of MBF1 potentiated the hormone-induced response of the atrial natriuretic peptide promoter. MBF1 overexpressed by transient transfection cooperated with the transcription factor c-Jun in activation of transcription but not with GATA4. MBF1 and c-Jun induced the activity of a transiently transfected atrial natriuretic peptide promoter, whereas neither MBF1 nor c-Jun could induce the promoter alone. Moreover, MBF1 bound to c-Jun in vitro. These data suggest that MBF1 is a transcriptional coactivator of c-Jun regulating hypertrophic gene expression. Inhibitor studies suggested that MBF1 activates the atrial natriuretic peptide promoter independently of the calcineurin and CaMK signaling pathways. Our results indicate that MBF1 participates in hormone-induced cardiomyocyte hypertrophy and activates hypertrophic gene expression as a coactivator of c-Jun.