Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Heavier-than-water silicone oil mixture as a long-term tamponade agent:A pilot study

Purpose: To evaluate the tamponade effect on the retina of a heavier-than-water silicone oil mixture and to compare it with the effect of silicone oil. Methods: Prospective, non-randomised, comparative pilot study. Phakic/pseudophakic patients with retinal detachment undergoing vitrectomy with Densiron 68 or silicone oil were recruited. The 'separation volume', defined as the relative volume of the space between intraocular tamponade agent and retina, was estimated using magnetic resonance imaging in both groups and compared. Results: Nine participants were included; 4 received silicone oil and 5 Densiron 68. The mean separation volume was statistically significantly larger in the silicone oil group (0.477 ± 0.419 cm ) than in the Densiron group (0.042 ± 0.013 cm ; p = 0.014). Conclusions: In this study Densiron achieved an excellent tamponade effect in the retina. © 2011 S. Karger AG, Basel.

The spark of life:The role of electric fields in regulating cell behaviour using the eye as a model system

Endogenous electric fields (EF) have long been known to influence cell behaviour during development, neural cell tropism, wound healing and cell behaviour generally. The effect is based on short circuiting of electrical potential differences across cell and tissue boundaries generated by ionic segregation. Recent in vitro and in vivo studies have shown that EF regulate not only cell movement but orientation of cells during mitosis, an effect which may underlie shaping of tissues and organs. The molecular basis of this effect is founded on receptor-mediated cell signalling events and alterations in cytoskeletal function as revealed in studies of gene deficient cells. Remarkably, not all cells respond directionally to EF in the same way and this has consequences, for instance, for lens development and vascular remodelling. The physical basis of EF effect may be related to changes induced in 'bound water' at the cell surface, whose organisation in association with trans-membrane proteins (e.g. receptors) is disrupted when EF are generated. Copyright © 2007 S. Karger AG.

Comparison of diagnostic ability between a fast strategy, tendency-oriented perimetry, and the standard bracketing strategy

Purpose: To compare the diagnostic abilities of the standard bracketing strategy (BR) and a fast strategy, the tendency-oriented perimetry (TOP). Methods: Seventy-seven controls and 91 eyes from patients with glaucoma were analyzed with the strategies TOP and BR. Sensitivity (Se), specificity (Sp), the area under the receiver operating characteristic (ROC) curve (AC) and the optimum cutoff value (CO) were calculated for the visual field indices mean defect (MD), the square root of the loss variance (sLV) and the number of pathological points (NPP). Results: In the glaucoma group, the mean MD value using TOP and BR was 7.5 and 8.3 dB, respectively. The mean sLV value using TOP and BR was 5.0 and 5.3 dB, respectively. Indices provided by TOP had higher ROC values than the ones provided by BR. Using TOP, the index with the best diagnostic ability was sLV (Sp = 94.8, Se = 90.1, AC = 0.966, CO = 2.5 dB), followed by NPP and MD. Using BR, the best results were obtained for MD (Sp = 92.2, Se = 81.3, AC = 0.900, CO = 2.5 dB) followed by sLV and NPP. Conclusions: A fast strategy, TOP, had superior diagnostic ability than the standard BR. Although TOP provided lower LV values than BR, the diagnostic ability of this index was higher than that of the conventional strategy. Copyright © 2005 S. Karger AG.

Reproducibility of optic disk topographic measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph

Objective: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. Methods: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. Results: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. Conclusion: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.

Treatment approaches for diabetes and dyslipidemia

Dyslipidemia is an important risk factor for cardiovascular complications in persons with diabetes. Low-density lipoprotein-cholesterol (LDL-C) is the 'cornerstone' for assessment of lipoprotein-associated risk. However, LDL-C levels do not reflect the classic 'diabetic dyslipidemia' of hypertriglyceridemia and low high-density lipoprotein-cholesterol (HDL-C). Measurements of plasma apolipoprotein B100 concentrations and non-HDL-C may improve the definition of dyslipidemia. Statins, nicotinic acid and fibrates have roles in treating dyslipidemia in diabetes. Residual risk (i.e. risk that persists after correction of 'conventional' plasma lipoprotein abnormalities) is a new concept in the role of dyslipidemia in the pathogenesis of diabetic vascular complications. For example, regardless of plasma levels, lipoprotein extravasation through a leaking retinal blood barrier and subsequent modification may be crucial in the development of diabetic retinopathy. The current approach to the management of dyslipidemia in diabetes is briefly summarized, followed by a discussion of new concepts of residual risk and emerging lipoprotein-related mechanisms for vascular disease in diabetes.

Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response

Multiple sclerosis is considered a disease of complex autoimmune etiology, yet there remains a lack of consensus as to specific immune effector mechanisms. Recent analyses of experimental autoimmune encephalomyelitis, the common mouse model of multiple sclerosis, have investigated the relative contribution of Th1 and Th17 CD4 T cell subsets to initial autoimmune central nervous system (CNS) damage. However, inherent in these studies are biases influenced by the adjuvant and toxin needed to break self-tolerance. We investigated spontaneous CNS disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. Analysis of naturally progressing disease shows that IFN?(+) cells dominate disease initiation with IL-17(+) cells apparent in affected tissue only once disease is established. Tregs accumulate in the CNS but are ultimately ineffective at halting disease progression. However, ablation of Tregs causes profound acceleration of disease, with uncontrolled infiltration of lymphocytes into the CNS. This synchronous, severe disease allows characterization of the responses that are deregulated in exacerbated disease: the correlation is with increased CNS CD4 and CD8 IFN? responses. Recovery of the ablated Treg population halts ongoing disease progression and Tregs extracted from the central nervous system at peak disease are functionally competent to regulate myelin specific T cell responses. Thus, in a clinically relevant mouse model of MS, initial disease is IFN? driven and the enhanced central nervous system responses unleashed through Treg ablation comprise IFN? cytokine production by CD4 and CD8 cells, but not IL-17 responses.

Management of Hyperphosphataemia in Chronic Kidney Disease:Summary of National Institute for Health and Clinical Excellence (NICE) Guideline

Bone disease and ectopic calcification are the two main consequences of hyperphosphataemia of chronic kidney disease (CKD). Observational studies have demonstrated that hyperphosphataemia in CKD is associated with increased mortality. Furthermore, the use of phosphate binders in dialysis patients is associated with significantly lower mortality. The UK Renal Registry data show significant underachievement of phosphate targets in dialysis patients. It is believed to be due to wide variation in how management interventions are used. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the management of hyperphosphataemia in CKD. This is based on the evidence currently available using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This review outlines the recommendations including research recommendations and discusses methodology, rationale and challenges faced in developing this guideline and the health economic model used to assess the cost-effectiveness of different phosphate binders. © 2013 S. Karger AG, Basel.

Induction of signalling in non-erythroid cells by pharmacological levels of erythropoietin

Erythropoiesis is maintained by the hormone erythropoietin (Epo) binding to its cognate receptor (EpoR) on erythroid progenitor cells. The Epo-EpoR interaction initiates a signal transduction process that regulates the survival, growth and differentiation of these cells. Originally perceived as highly lineage-restricted, Epo is now recognised to have pleiotropic effects extending beyond the maintenance of red cell mass. Functional interactions between Epo and EpoR have been demonstrated in numerous cells and tissues. EpoR expression on neoplastic cells leads to concern that recombinant human erythropoietin, used to treat anaemia in cancer patients, may augment tumour growth. Here we demonstrate that EPO, at pharmacological concentrations, can activate three major signalling cascades, viz. the Jak2/STAT5, Ras/ERK and PI3K/Akt pathways in non-small cell lung carcinoma (NSCLC) cell lines. EpoR synthesis is normally under the control of GATA-1, but NSCLC cells exhibit decreased GATA-1 levels compared to GATA-2, -3 and -6, suggesting that GATA-1 is not essential for EpoR production. The increased Epo-induced signalling was not associated with a growth advantage for the NSCLC cells.

Change of visual acuity recording methods in clinical studies across the years

Purpose: To report any differences in the visual acuity (VA) recording method used in peer-reviewed ophthalmology clinical studies over the past decade. Methods: We reviewed the method of assessing and reporting VA in 160 clinical studies from 2 UK and 2 US peer-reviewed journals, published in 1994 and 2004. Results: The method used to assess VA was specified in 62.5% of UK-published and 60% of US-published papers. In the results sections of the UK publications the VA measurements presented were Snellen acuity (n = 58), logMAR acuity (n = 20) and symbol acuity (n = 1). Similarly in the US publications the VA was recorded in the results section using Snellen acuity (n = 60) and logMAR acuity (n = 14). Overall 10% of the authors appeared to convert Snellen acuity measurements to logMAR format. Five studies (3%) chose to express Snellen-type acuities in decimal form, a method which can easily lead to confusion given the increased use of logMAR scoring systems. Conclusion: The authors recommend that to ensure comparable visual results between studies and different study populations it would be useful if clinical scientists worked to standardized VA testing protocols and reported results in a manner consistent with the way in which they are measured. Copyright © 2008 S. Karger AG.

A narrow-band ultraviolet B course improves vitamin D balance and alters cutaneous CYP27A1 and CYP27B1 mRNA expression levels in haemodialysis patients supplemented with oral vitamin D

Background: Chronic kidney disease (CKD) patients on dialysis are prone to vitamin D insufficiency despite oral vitamin D supplementation. Here, we studied whether narrow-band ultraviolet B (NB-UVB) exposures improve vitamin D balance.

Methods: 14 haemodialysis patients and 15 healthy subjects receiving oral cholecalciferol 20 µg daily got nine NB-UVB exposures on the entire body. Serum 25-hydroxyvitamin D (25(OH)D) was measured by radioimmunoassay. Cutaneous mRNA expression levels of CYP27A1 and CYP27B1, two enzymes required for hydroxylation of vitamin D into its active metabolite, were also measured.

Results: The baseline serum 25(OH)D concentration was 57.6 ± 18.2 nmol/l in the CKD patients and 74.3 ± 14.8 nmol/l in the healthy subjects. The NB-UVB course increased serum 25(OH)D by 14.0 nmol/l (95% CI 8.7-19.5) and 17.0 nmol/l (CI 13.7-20.2), respectively. At baseline the CKD patients showed significantly increased CYP27B1 levels compared to the healthy subjects.

Conclusions: A short NB-UVB course is an efficient way to improve vitamin D balance in CKD patients on dialysis who are receiving oral vitamin D supplementation. The increased cutaneous CYP27B1 levels in the CKD patients suggest that the loss of renal activity of this enzyme is at least partially compensated for by the skin.

Botulinum toxin A for the treatment of keloids

Keloids are the result of excessive scar tissue formation. Besides their poor aesthetic appearance, keloids can be associated with severe clinical symptoms such as pain, itching, and rigidity. Unfortunately, most therapeutic approaches remain clinically unsatisfactory. Recently, injections with botulinum toxin A (BTA) were proposed for the treatment of established keloids in a clinical trial. In this study, we aimed to verify the effects of intralesional BTA for the treatment of therapy-resistant keloids using objective measurements. In addition, the underlying molecular mechanisms were investigated using cultured keloid-derived fibroblasts.

Scientific standards for human intervention trials evaluating health benefits of foods, and their application to infants, children and adolescents

Associations between the consumption of particular foods and health outcomes may be indicated by observational studies. However, intervention trials that evaluate the health benefits of foods provide the strongest evidence to support dietary recommendations for health. Thus, it is important that these trials are carried out safely, and to high scientific standards. Accepted standards for the reporting of the health benefits of pharmaceutical and other medical interventions have been provided by the Consolidated Standards of Reporting Trials (CONSORT) statement. However, there are no generally accepted standards for trials to evaluate the health benefits of foods. Trials with foods differ from medical trials in issues related to safety, ethics, research governance and practical implementation. Furthermore, these important issues can deter the conduct of both medical and nutrition trials in infants, children and adolescents. This paper provides standards for the planning, design, conduct, statistical analysis and interpretation of human intervention trials to evaluate the health benefits of foods that are based on the CONSORT guidelines, and outlines the key issues that need to be addressed in trials in participants in the paediatric age range.