Newborn screening for inborn errors of metabolism: a systematic review

OBJECTIVES. To establish a database of literature and other evidence on neonatal screening programmes and technologies for inborn errors of metabolism. To undertake a systematic review of the data as a basis for evaluation of newborn screening for inborn errors of metabolism. To prepare an objective summary of the evidence on the appropriateness and need for various existing and possible neonatal screening programmes for inborn errors of metabolism in relation to the natural history of these diseases. To identify gaps in existing knowledge and make recommendations for required primary research. To make recommendations for the future development and organisation of neonatal screening for inborn errors of metabolism in the UK. HOW THE RESEARCH WAS CONDUCTED. There were three parts to the research. A systematic review of the literature on inborn errors of metabolism, neonatal screening programmes, new technologies for screening and economic factors. Inclusion and exclusion criteria were applied, and a working database of relevant papers was established. All selected papers were read by two or three experts and were critically appraised using a standard format. Seven criteria for a screening programme, based on the principles formulated by Wilson and Jungner (WHO, 1968), were used to summarise the evidence. These were as follows. Clinically and biochemically well-defined disorder. Known incidence in populations relevant to the UK. Disorder associated with significant morbidity or mortality. Effective treatment available. Period before onset during which intervention improves outcome. Ethical, safe, simple and robust screening test. Cost-effectiveness of screening. A questionnaire which was sent to all newborn screening laboratories in the UK. Site visits to assess new methodologies for newborn screening. The classical definition of an inborn error of metabolism was used (i.e., a monogenic disease resulting in deficient activity in a single enzyme in a pathway of intermediary metabolism). RESEARCH FINDINGS. INBORN ERRORS OF METABOLISM. Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all the screening criteria and could be used as the 'gold standard' against which to review other disorders despite significant variation in methodologies, sample collection and timing of screening and inadequacies in the infrastructure for notification and continued care of identified patients. Of the many disorders of organic acid and fatty acid metabolism, a case can only be made for the introduction of newborn screening for glutaric aciduria type 1 (GA1; estimated incidence 1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD) deficiency (estimated incidence 1:8000-1:15,000). Therapeutic advances for GA1 offer prevention of neurological damage but further investigation is required into the costs and benefits of screening for this disorder. MCAD deficiency is simply and cheaply treatable, preventing possible early death and neurological handicap. Neonatal screening for these diseases is dependent upon the introduction of tandem mass spectrometry (tandem MS). This screening could however also simultaneously detect some other commonly-encountered disorders of organic acid metabolism with a collective incidence of 1:15,000.(ABSTRACT TRUNCATED)     

The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery

OBJECTIVE: Our goal was to evaluate the role of intraoperative cystoscopy during surgery for pelvic organ prolapse and urinary incontinence. STUDY DESIGN: Charts of 224 consecutive patients who had intraoperative cystoscopy performed after urogynecologic surgery were reviewed. RESULTS: Nine injuries occurred that were unsuspected before cystoscopy, for an incidence of 4%. Six ureteral ligations occurred, four after Burch cystourethropexy and two after vaginal culdoplasty. Intravesical sutures were noted after two Burch procedures, and another injury occurred with passage of fascia lata through the bladder during a pubovaginal sling procedure. Eight injuries were managed by removal and replacement of the suture or sling with only one requiring ureteroneocystotomy. When patients with injuries were compared with those without, there were no statistical differences in demographic or surgical parameters. CONCLUSIONS: The potential for damage to the lower urinary tract is significant with complex urogynecologic surgery. Because of the increased and delayed morbidity associated with unrecognized injury, intraoperative surveillance cystoscopy should be considered a part of all such procedures.     

Evaluating arrhythmias in ECG signals using wavelet transforms

Recent work has attempted to utilize wavelet techniques in the analysis of biomedical signals including ECGs. Here, the authors present an energy-based method of interrogating the ECG in VF using high-resolution, log-scale continuous wavelet plots. With this method, underlying structures within the VF waveform are made visible in the wavelet time-scale half space     

Distinctive messages in infant-directed lullabies and play songs.

Mothers were recorded singing a song of their choice in both a lullaby style and a play-song style to their 6-month-olds. Adult raters identified the play-song-style and lullaby-style versions with 100% accuracy. Play-song-style renditions were rated as being more brilliant, clipped, and rhythmic and as having more smiling and more prominent consonants. Lullaby-style renditions were characterized as being more airy, smooth, and soothing. Adults observed videotapes (without sound) of 6-month-olds listening to alternating lullaby-style and play-song-style trials and performed at above chance levels when determining which music the infants were hearing. Coding analyses revealed that infants focused their attention more toward themselves during lullaby-style trials and more toward the external world during play-song-style trials. These results suggest that singing may be used to regulate infants' states and to communicate emotional information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Studies of human diploid fibroblast growth. I. Responses of normal and hypopituitary cells to fibroblast growth factor, insulin, and serum

We have assayed the growth stimulating activity of bovine insulin, fibroblast growth factor (FGF), and fetal bovine serum (FBS) in diploid human fibroblasts from normal and idiopathic hypopituitary donors. All three factors stimulated DNA synthesis in cells arrested by serum starvation. FGF was active at concentrations as low as 5 ng/ml with maximum effect at 100 ng/ml. FGF stimualted DNA synthesis at lower concentrations than did insulin and also produced a greater maximum response. Only serum was capable of supporting cell division and growth, but FGF accellerated this growth rate when it was added to serum-containing medium. Hydrocortisone, actinomycin D, and cycloheximide inhibit FGF stimulation. There was no significant difference between fibroblasts from normal and hypopituitary donors.     

Effect of sleeve colour and background colour on change in colour assessments†

The two standard grey scales, ISO 105‐A02 and ISO 105‐A03, used for assessing change in colour and staining, respectively, are both typically provided mounted in black material and within a black sleeve. However, some grey scales are now provided mounted in grey material and within a grey sleeve. This paper reports psychophysical data and shows that the change in colour grades obtained from grey scales are not affected by the background colour of the viewing cabinet. A small, but statistically significant, effect is found for the colour of the sleeve with higher grades being found when using the black sleeve compared to when using the grey sleeve. However, when the samples being assessed are masked by a sleeve of the same colour as that used with the grey scale, an extensive field trial shows that the colour of the sleeve does not affect the change in colour grades obtained under commercial conditions.     

Energy and Force Analysis of Ti-6Al-4V Linear Friction Welds for Computational Modeling Input and Validation Data

The linear friction welding (LFW) process is finding increasing use as a manufacturing technology for the production of titanium alloy Ti-6Al-4V aerospace components. Computational models give an insight into the process, however, there is limited experimental data that can be used for either modeling inputs or validation. To address this problem, a design of experiments approach was used to investigate the influence of the LFW process inputs on various outputs for experimental Ti-6Al-4V welds. The finite element analysis software DEFORM was also used in conjunction with the experimental findings to investigate the heating of the workpieces. Key findings showed that the average interface force and coefficient of friction during each phase of the process were insensitive to the rubbing velocity; the coefficient of friction was not coulombic and varied between 0.3 and 1.3 depending on the process conditions; and the interface of the workpieces reached a temperature of approximately approximately 1273 K (1000 °C) at the end of phase 1. This work has enabled a greater insight into the underlying process physics and will aid future modeling investigations.     

In vitro bioactivity of titanium-doped bioglass

Previous studies have suggested that incorporating relatively small quantities of titanium dioxide into bioactive glasses may result in an increase in bioactivity and hydroxyapatite formation. The present work therefore investigated the in vitro bioactivity of a titanium doped bioglass and compared the results with 45S5 bioglass. Apatite formation was evaluated for bioglass and Ti-bioglass in the presence and absence of foetal calf serum. Scanning electron microscopy (SEM) images were used to evaluate the surface development and energy dispersive X-ray measurements provided information on the elemental ratios. X-ray diffraction spectra confirmed the presence of apatite formation. Cell viability was assessed for bone marrow stromal cells under direct and indirect contact conditions and cell adhesion was assessed using SEM.