Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Iberian Cured-Ham Consumption Improves Endothelial Function in Healthy Subjects.

OBJECTIVES: Previous studies have shown that dietary components such as oleic acid or polyphenols exert beneficial effects on endothelium. We aimed to assess the impact of regular consumption of Iberian cured-ham (ICH) on endothelial function. DESIGN: An open-label, randomized controlled parallel study. SETTING: Volunteers recruited through advertisements at a hospital in Madrid, Spain. PARTICIPANTS: 102 Caucasian adults (76.8% females) aged 25-55 years, and free from cardiometabolic disease. INTERVENTION: Participants were randomized to an ICH-enriched ad libitum diet or an ad libitum diet without ICH for 6 weeks. Subjects in ICH group were randomly provided with either acorn- or mixed-fed ICH, and followed up for an additional 6-week period under their usual diet. MEASUREMENTS: Clinical parameters, biomarkers of endothelial function and oxidative stress, microvascular vasodilatory response to hyperemia and arterial stiffness were measured before and after the intervention. RESULTS: After 6 weeks, a larger decrease in PAI-1 was observed in subjects consuming ICH compared to the Control group (-6.2±17.7 vs. 0.3±1.4 ng/ml; p=0.020). Similarly, microvascular vasodilatory response to hyperemia showed a significant increase (112.4±391.7 vs. -56.0±327.9%; p=0.007). However, neither oxidative stress, hemodynamic nor clinical parameters differed significantly over the study. Additionally, after stopping ICH consumption, improvements in PAI-1 remained for 6 additional weeks with respect to baseline (p=0.006). CONCLUSION: The present study demonstrates, for the first time, that regular consumption of ICH improves endothelial function in healthy adults. Strategies aimed to preserve or improve the endothelial function may have implications in vascular aging beyond the prevention of the atherothrombotic disease.

Use of polymethylmethacrylate to treat pigmented villonodular synovitis in the posterior compartment of the knee.

Pigmented villonodular synovitis (PVNS) is a benign process that mainly affects the knee joint. There are two types of PVNS, a localised and a diffuse form. Although adjuvant therapies are possible, the treatment consists of arthroscopic or open synovectomy of the affected area. The most common complication is local recurrence. We report the case of a patient with PVNS and osteolysis of the femoral condyle, treated with anterior arthroscopic synovectomy and posterior approach for the treatment of the femoral condyle erosion. The bone erosion was treated with polymethylmethacrylate (PMMA) cement. There are no publications indexed in our knowledge that explain the treatment of PVNS associated with bone erosion by PMMA. Nine years after the procedure, the patient is leading a fully active life with no evidence of active disease.

Peritraumatic dissociation, acute stress, and early posttraumatic stress disorder in victims of general crime.

OBJECTIVE: To compare the relation between peritraumatic dissociation and acute stress and the early development of posttraumatic stress disorder (PTSD) in victims of general crime. METHOD: A total of 48 subjects were assessed within 24 hours of the trauma, using the Peritraumatic Dissociative Experiences Questionnaire Self-Report Version (PDEQ-SRV). They were followed longitudinally to assess acute stress (2 weeks after the assault,) using the Standford Acute Stress Reaction Questionnaire (SASRQ), and posttraumatic stress (at 5 weeks), using the Clinician-Administered PTSD Scale (CAPS) and the Impact of Event Scale (IES). RESULTS: Among PTSD subjects mean PDEQ scores were significantly higher (mean 3, SD 0.9) than in those without PTSD (mean 2.3, SD 0.7) (t = 2.78, df 46, P = 0.007). Among PTSD subjects, mean SASRQ scores were significantly higher (mean 97.9, SD 29.2) than in those without PTSD (mean 54.8, SD 28.2) (t = 4.9, df 46, P = 0.00007). CONCLUSIONS: High levels of peritraumatic dissociation and acute stress following violent assault are risk factors for early PTSD. Identifying acute reexperiencing can help the clinician identify subjects at highest risk.

Automated sample preparation and gas chromatographic-mass spectrometric analysis of urinary androgenic anabolic steroids.

This paper presents an automated method for extracting anabolic agents from urine samples for their GC-MS analysis by selected-ion monitoring. The sample preparation was carried out in a Hewlett-Packard 7686 SPE PrepStation system. Each 0.6-ml aliquot was hydrolyzed, extracted, dried and trimethylsilyl (TMS) derivatized in a 2-ml vial without any hands-on labor. When sample preparation was finished 2 microl of the extract was injected into the gas chromatograph by split (1:10) mode. Due to the small amount of free space in the 2-ml vials for handling the sample, parameters like time of hydrolysis, type of shaking, number of extractions and some TMS derivatization parameters had to be adjusted to achieve the best recovery for all of the compounds in the screening. Manual and automated sample preparation schemes were compared in terms of linearity, precision, accuracy, limit of detection and recovery data. When large concentrations were analyzed using the automated method no carry-over effect was observed.

[Victims of general crimes. Prospective and longitudinal assessment of psychological injuries]. / Victimes d'agression physique: évaluation prospective et longitudinale des blessures psychologiques.

OBJECTIVE: The aim of this study was to assess the relations between acute psychological injury, particularly peritraumatic dissociation, and early development of posttraumatic stress disorder in victims of violence. METHODS: Thirty-five subjects were prospectively assessed in an emergency department, within 24 hours of the trauma, for acute dissociative experiences with the Peritraumatic Dissociative Experiences Questionnaire (PDEQ). All of them were followed longitudinally to assess post traumatic stress disorder (PTSD) 5 weeks after with the Clinician-administered PTSD scale (CAPS) and the Impact of event scale (IES). RESULTS: Of the 35 victims 10 (28%) were diagnosed with a posttraumatic stress disorder at 5 weeks. Among PTSD subjects mean PDEQ scores were significantly higher (3+/-1.1) than in those without PTSD (2.3+/-0.7) (t=2.24, df=33, p=0.029). The PTSD subjects reported more "out of body experience" (p=0.015) and more "sense of body distorsion" (p=0.03) than non PTSD subjects. CONCLUSION: High levels of peritraumatic dissociation following violent assault are risk factors for early posttraumatic stress disorder. Psychological assessment of acute traumatic dissociative experiences must be included in emergency departments.

Comparison of various reversed-phase columns for the simultaneous determination of ephedrines in urine by high-performance liquid chromatography.

Different reversed-phase columns for basic analytes were compared for the simultaneous determination of ephedrines in urine, such as LiChrospher 60 RP-Select B, LiChrospher 100 RP18, Hypersil BDS-C18, Inertsil ODS-2, Spherisorb ODS-B and Symmetry Shield RP8. Symmetry Shield was the only column which did not require the use of high concentrations of buffer and triethylamine. With this column, a good separation of the six ephedrines and the internal standard was achieved using 50 mM phosphate buffer-25 mM triethylamine as a mobile phase. Linearity, precision and accuracy were satisfactory for the levels usually found in urine. Due to these all parameters the developed analytical method was found to be suitable for the application in the doping field.

Use of ion trap gas chromatography-tandem mass spectrometry for detection and confirmation of anabolic substances at trace levels in doping analysis.

A procedure for detecting and confirming 23 anabolic substances and/or metabolites has been developed using a GC-MS-MS ion trap system in full-scan mode. The process used to select the precursor ion, and the optimization of the system parameters used to obtain the daughter ion spectra, are explained. Urine samples were prepared using solid-phase extraction and enzymatic hydrolysis, and after TMS derivatives had been formed, they were injected into the mass spectrometer. This method permits confirmation of the presence of anabolic substances at low ng ml(-1) levels without the need of further purification procedures on the samples. This procedure has been used on more than 2000 urine samples collected from sporting competitions and has made it possible to confirm more than 45 true positive cases which could not have been confirmed using routine GC-MS methods.

Automated analysis of drugs in urine.

A totally automated procedure has been developed for the preparation and analysis of 34 basic and neutral drugs in urine samples using an integrated HP 7686 PrepStation-HP 6890 gas chromatographic system. The automated preparation of the sample consisted of a liquid-liquid extraction of 250 microliters urine at alkaline pH with 100 microliters of methyl tert.-butyl ether. After phase separation the organic solvent was automatically placed in the injector of the gas chromatograph and analysed. High recoveries of extraction were obtained. The limits of detection of most of the drugs were less than 0.5 microgram/ml. The method, which allows the preparation and analysis of the samples to be completely synchronised, showed good accuracy and precision.

Determination of epitestosterone and testosterone in urine by high-performance liquid chromatography.

This paper describes an alternative HPLC method for the determination of testosterone and epitestosterone, which is simple, rapid, selective, sensitive and reproducible. Samples were prepared using a previous enzymatic hydrolysis with liquid-liquid extraction. The determination was carried out on a Hypersil BDS-C18 reversed-phase column with gradient elution and UV absorbance detection (240 nm). The limits of quantification (signal-to-noise ratio = 6) were 20 ng/ml for testosterone and 30 ng/ml for epitestosterone.

Comparison of derivatization procedures for the determination of diuretics in urine by gas chromatography-mass spectrometry.

Three different GC-MS screening procedures, which use different ways of derivatization (methylation), are compared. In the first one, derivatization with iodomethane in acetone and a previous solid-liquid extraction is used; the second one is based on an extractive alkylation method using iodomethane in toluene (liquid-liquid extraction); and the last one is flash methylation by pyrolysis of tetraalkylammonium salts in the injector of the gas chromatograph using trimethylanilinium as the derivatization agent. The speed of the extraction, reproducibility and accuracy have been compared for 20 diuretics including the ones most often used in sports, such as bumetanide, ethacrynic acid, acetazolamide, dichlorphenamide, furosemide, hydroflumethiazide, hydrochlorothiazide and chlorthalidone; they have also been applied to the two uricosuric agents probenecid and benzbromarone.

Determination of ephedrines in urine by high-performance liquid chromatography.

An improved high-performance liquid chromatographic method with ultraviolet detection for the simultaneous determination of norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine and ethylephedrine in urine is described. The six substances were separated on a reversed-phase column with phosphate buffer-triethylamine (pH 5.5) as the mobile phase. The linearity and reproducibility were satisfactory for the levels usually found in urine (1-30 micrograms/ml).