Measurement of ductions and fields of binocular single vision (BSV): orthoptic practice in the UK and Ireland.

To evaluate the current clinical practice of quantifying ductions and fields of BSV in the UK and Ireland using an online questionnaire. An anonymous online questionnaire with twenty-one questions was distributed in February 2019 via the British and Irish Orthoptic Society (BIOS) members' newsletter. Objectives were to investigate: methods used, frequency of assessment, limiting factors and opinions of importance. Informed consent was gained to include the responses in the study. The data was analyzed using descriptive statistics and Wilcoxon Signed Ranks Testing. The questionnaire was completed by 105 orthoptists. The methods reported to quantify ductions and fields of BSV respectively were: Goldmann (33% and 34%), Aimark (22 and 23%), Lister (7%), Octopus (5 and 4%), Thomson ocular motility analyzer (2 and 3%), Binocular vision analyzer (2%) and no method reported (30% and 32%). The frequency of measuring ductions and fields of BSV per week (median 1-2) was significantly less than the number of patients seen with limited ocular motility per week (median 6-9). The main reasons for never or rarely measuring ductions or fields of BSV were not enough time, no method available and only on selected patients. Respondents indicated that they would measure ductions and fields of BSV more frequently if a quicker portable method was available (median 3-5 times per week). Most agreed that measurements of ductions and fields of BSV are important (89 and 95% respectively). There is no standardized method of quantitively measuring ductions or fields of BSV, with almost a third of respondents not measuring either. Although most orthoptists agreed these measurements are important, they are infrequently performed. The main factors limiting these assessments are insufficient time and lack of a testing method. If a faster portable device was available, orthoptists would measure ductions and fields of BSV more frequently.

Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry.

BACKGROUND: Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. METHODS: Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. RESULTS: In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. CONCLUSION: Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.

Inter-examiner variability and agreement of the alternate prism cover test (APCT) measurements of strabismus performed by 4 examiners.

PURPOSE: To investigate the inter-examiner variability and agreement of the alternate prism cover test (APCT) measurements of strabismus at near and distance fixation performed by 4 examiners. METHODS: Forty-one participants (median age 12 years, range 3-74) with horizontal strabismus completed APCT measurements at near (1/3 m) and distance (5 m) fixation. Each participant was assessed by 4 masked experienced orthoptists on the same visit. Bland-Altman plots and inter-examiner variability (1.96xSD of the difference) were used to determine a clinical value suggestive of real change. RESULTS: The inter-examiner variability was ±10 prism diopters (PD) at near and ±9 PD at distance fixation. The mean difference between measurements per examiner pair for near fixation ranged between -3 and 1.5 PD, with inter-examiner variability ranging between ±6.9 and ±12.5 PD, and mean difference for distance fixation between -0.8 and 1.6 PD, with inter-examiner variability ranging between ±7.5 and ±11.7 PD. Larger variability was found between some examiner pairs than others. Magnitude of the deviation, test distance, and age had no significant influence on the variation in APCT measurement. CONCLUSION: A variation in APCT measurement between 4 examiners of less than 10 PD for both near and distance fixation is likely to be due to inter-examiner variability. Changes of 10 PD or more are suggestive of a real change and may be employed as a management threshold.

New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients.

CMV infections are common after SOT. v-GCV is increasingly used in children. The aim of this study was to evaluate presently used dosing algorithms. Data from 104 pediatric SOT recipients (kidney, liver, and heart) aged 0.3-16.9 yr and receiving v-GCV once a day were used for model development and validation with the Pmetrics package for R. Monte Carlo simulations were performed to compare the probability of a GCV AUC 40-60 mg*h/L with the different algorithms across a range of ages, weights, and GFRs. GCV pharmacokinetics was well described by the non-parametric model. Clearance was dependent on GFR and Cockcroft-Gault estimates improved the model fit over Schwartz. Simulations showed that our new algorithm, where v-GCV dose is: Weight [kg]*(0.07*GFR [mL/min]+k), where k = 5 for GFR ≤ 30 mL/min, k = 10 for GFR > 30 mL/min and weight > 30 kg and k = 15 for GFR > 30 mL/min and weight ≤ 30 kg, outperformed the other algorithms. Thirty-three percent of all patients achieve an exposure above and 21% within the therapeutic window. We propose a simple algorithm for initial v-GCV dosing that standardizes plasma drug exposure better than current algorithms. Subsequent TDM is strongly suggested to achieve individual drug levels within the therapeutic window.

The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans.

Intense exercise decreases the cerebral metabolic ratio of O(2) to carbohydrates (glucose + (1/2) lactate) and the cerebral lactate uptake depends on its arterial concentration, but whether these variables are influenced by O(2) availability is not known. In six males, maximal ergometer rowing increased the arterial lactate to 21.4 +/- 0.8 mm (mean +/- s.e.m.) and arterial-jugular venous (a-v) difference from -0.03 +/- 0.01 mm at rest to 2.52 +/- 0.03 mm (P < 0.05). Arterial glucose was raised to 8.5 +/- 0.5 mm and its a-v difference increased from 1.03 +/- 0.01 to 1.86 +/- 0.02 mm (P < 0.05) in the immediate recovery. During exercise, the cerebral metabolic ratio decreased from 5.67 +/- 0.52 at rest to 1.70 +/- 0.23 (P < 0.05) and remained low in the early recovery. Arterial haemoglobin O(2) saturation was 92.5 +/- 0.2% during exercise with room air, and it reached 87.6 +/- 1.0% and 98.9 +/- 0.2% during exercise with an inspired O(2) fraction of 0.17 and 0.30, respectively. Whilst the increase in a-v lactate difference was attenuated by manipulation of cerebral O(2) availability, the cerebral metabolic ratio was not affected significantly. During maximal rowing, the cerebral metabolic ratio reaches the lowest value with no effect by a moderate change in the arterial O(2) content. These findings suggest that intense whole body exercise is associated with marked imbalance in the cerebral metabolic substrate preferences independent of oxygen availability.

Motor and sensory characteristics of infantile nystagmus.

BACKGROUND/AIMS: Past studies have explored some of the associations between particular motor and sensory characteristics and specific categories of non-neurological infantile nystagmus. The purpose of this case study is to extend this body of work significantly by describing the trends and associations found in a database of 224 subjects who have undergone extensive clinical and psychophysical evaluations. METHODS: The records of 224 subjects with infantile nystagmus were examined, where 62% were idiopaths, 28% albinos, and 10% exhibited ocular anomalies. Recorded variables included age, mode of inheritance, birth history, nystagmus presentation, direction of the nystagmus, waveform types, spatial and temporal null zones, head postures and nodding, convergence, foveation, ocular alignment, refractive error, visual acuity, stereoacuity, and oscillopsia. RESULTS: The age distribution of the 224 patients was between 1 month and 71 years, with the mean age and mode being 23 (SD 16) years and 16-20 years respectively. By far the most common pattern of inheritance was found to be autosomal dominant (n = 40), with the nystagmus being observed by the age of 6 months in 87% of the sample (n = 128). 139 (62%) of the 224 subjects were classified as idiopaths, 63 (28%) as albinos, and 22 (10%) exhibited ocular anomalies. Conjugate uniplanar horizontal oscillations were found in 174 (77.7%) of the sample. 32 (14.3%) had a torsional component to their nystagmus. 182 (81.2%) were classed as congenital nystagmus (CN), 32 (14.3%) as manifest latent nystagmus (MLN), and 10 (4.5%) as a CN/MLN hybrid. Neither CN nor MLN waveforms were related to any of the three subject groups (idiopaths, albinos, and ocular anomalies) MLN was found in idiopaths and albinos, but most frequently in the ocular anomaly group. The most common oscillation was a horizontal jerk with extended foveation (n = 49; 27%). The amplitudes and frequencies of the nystagmus ranged between 0.3-15.7 degrees and 0.5-8 Hz, respectively. Periodic alternating nystagmus is commonly found in albinos. Albino subjects did not show a statistically significantly higher nystagmus intensity when compared with the idiopaths (p>0.01). 105 of 143 subjects (73%) had spatial nulls within plus or minus 10 degrees of the primary position although 98 subjects (69%) employed a compensatory head posture. Subjects with spatial null zones at or beyond plus or minus 20 degrees always adopted constant head postures. Head nodding was found in 38 subjects (27% of the sample). Horizontal tropias were very common (133 out of 213; 62.4%) and all but one of the 32 subjects with MLN exhibited a squint. Adult visual acuity is strongly related to the duration and accuracy of the foveation period. Visual acuity and stereoacuity were significantly better (p<0.01) in the idiopaths compared to the albino and ocular anomaly groups. 66 subjects out of a sample of 168 (39%) indicated that they had experienced oscillopsia at some time. CONCLUSIONS: There are strong ocular motor and sensory patterns and associations that can help define an infantile nystagmus. These include the nystagmus being bilateral, conjugate, horizontal uniplanar, and having an accelerating slow phase (that is, CN). Decelerating slow phases (that is, MLN) are frequently associated with strabismus and early form deprivation. Waveform shape (CN or MLN) is not pathognomonic of any of the three subject groups (idiopaths, albinos, or ocular anomalies). There is no one single stand alone ocular motor characteristic that can differentiate a benign form of infantile nystagmus (CN, MLN) from a neurological one. Rather, the clinician must consider a host of clinical features.

Neisseria meningitidis lipopolysaccharides in human pathology.

Neisseria meningitidis causes meningitis, fulminant septicemia or mild meningococcemia attacking mainly children and young adults. Lipopolysaccharides (LPS) consist of a symmetrical hexa-acyl lipid A and a short oligosaccharide chain and are classified in 11 immunotypes. Lipid A is the primary toxic component of N. meningitidis. LPS levels in plasma and cerebrospinal fluid as determined by Limulus amebocyte lysate (LAL) assay are quantitatively closely associated with inflammatory mediators, clinical symptoms, and outcome. Patients with persistent septic shock, multiple organ failure, and severe coagulopathy reveal extraordinarily high levels of LPS in plasma. The cytokine production is compartmentalized to either the circulation or to the subarachnoid space. Mortality related to shock increases from 0% to > 80% with a 10-fold increase of plasma LPS from 10 to 100 endotoxin units/ml. Hemorrhagic skin lesions and thrombosis are caused by up-regulation of tissue factor which induces coagulation, and by inhibition of fibrinolysis by plasminogen activator inhibitor 1 (PAI-1). Effective antibiotic treatment results in a rapid decline of plasma LPS (half-life 1-3 h) and cytokines, and reduced generation of thrombin, and PAI-1. Early antibiotic treatment is mandatory. Three intervention trials to block lipid A have not significantly reduced the mortality of meningococcal septicemia.

[Pyelonephritis in children--a retrospective study]. / Pyelonefritt hos barn--en retrospektiv undersøkelse.

BACKGROUND: Urinary tract infection (UTI) is a common bacterial infection in childhood, sometimes associated with urological malformations and, in a few cases, causing permanent renal damage. MATERIAL AND METHODS: A retrospective study was performed of children with UTI first time admitted to Ullevål Hospital during the period 1988-97. All medical records with diagnoses related to the urinary tract were investigated. Criteria for inclusion were bacteriuria and temperature > or = 38.5 degrees C in children over one year of age, and bacteriuria below one year of age. RESULTS: Age, sex, symptoms, urine sampling method, medical treatment and radiological investigations were evaluated. 180 children were included, (38% boys, 62% girls), 87% of the boys were referred during this first year of life. Fever as sole symptom was found in one of six. Urinary tract related symptoms were rare. Urine sampling was performed by suprapubic aspiration in only 7%, and was not specified in half of the samples. Imaging evaluation was performed in almost all children. More than half of the evaluated children had one or more abnormalities, vesicoureteric reflux being the most frequent. INTERPRETATION: In our material we find a high frequency of urological malformations. Better routines for urine sampling and evaluation of long term complications are suggested.

Fulminant meningococcal septicemia: dissociation between plasma thrombopoietin levels and platelet counts.

Thrombopoietin (TPO), interleukin (IL)-6, and platelets were measured serially in 9 patients with fulminant meningococcal septicemia and consumption coagulopathy. The results were compared with those of patients with meningococcal meningitis and mild meningococcemia (n=10) and with those of healthy control subjects (n=19). TPO levels in control subjects were below the detection limit (<63 pg/mL). In patients with fulminant meningococcal septicemia, the median TPO level on admission was 193 pg/mL (range, 133-401 pg/mL), and the level peaked within 3-7 days (median, 488 pg/mL; range, 239-1334 pg/mL). Platelet counts remained low, despite the elevated TPO levels. In patients with meningitis or meningococcemia, the median TPO level on admission was 112 pg/mL (range, <63-695 pg/mL), and the TPO level was not detectable within 48 h. Platelet counts for these patients remained within normal limits. Maximum IL-6 levels in patients with septicemia were observed on admission (median, 5317 pg/mL; range, 188-651,000 pg/mL) and increased earlier than TPO levels. In patients with fulminant septicemia, TPO level increases significantly whereas the level of circulating platelets does not.

Cellular activating properties and morphology of membrane-bound and purified meningococcal lipopolysaccharide.

Neisseria meningitidis, the cause of epidemic meningitis and acute lethal sepsis, synthesizes surplus lipopolysaccharides (LPSs) during growth, which are released as outer membrane vesicles (OMV) or "blebs". Meningococcal disease severity is related to plasma LPS levels. We have compared the biological activities of native outer membrane vesicles (nOMV) to those of purified Nm-LPS (Nm-LPS) and LPS-depleted OMV (dOMV) prepared from N. meningitidis. The LPS content of nOMV was determined spectrophotometrically by quantifying KDO and by silver-stained SDS-PAGE gels. The morphology of the preparations was studied by transmission electron microscopy. The Limulus amoebocyte lysate (LAL) assay was used to quantify LPS in the plasma solutions. The preparations were diluted in endotoxin-free heparin plasma to equal amounts of LPS (w/w) in the range 50-5000 pg/ml. The biological reactivity was tested by: (i) a monocyte target-assay (monocyte purity > or =96%); and (ii) a whole blood model, measuring the secretion of TNF-alpha and IL-6 induction of procoagulant activity in monocytes (PCA). In both models, nOMV induced dose-dependent cell responses (TNF-alpha, IL-6, PCA) similar to purified Nm-LPS, whereas dOMV induced minimal responses. However, LAL activity was significantly higher for nOMV than for purified Nm-LPS and dOMV. The cellular responses of purified Nm-LPS and nOMV were reduced (>95%) by a specific anti-CD14-antibody.

MR urography: the future gold standard in paediatric urogenital imaging?

BACKGROUND: Examination of the paediatric urogenital tract is traditionally performed using methods that utilise ionising radiation, such as intravenous urography (IVU), computerised tomography (CT), voiding cystourethrography (VCU), and scintigraphy, in addition to ultrasound (US). OBJECTIVE: To determine the potential and effectiveness of MR urography (MRU) in infants and children. Materials and methods. 44 MRU examinations were prospectively performed in 39 patients (21 infants, mean age 3.5 months, and 18 children, mean age 6 years 2 months) with known or suspected pathology of the urinary tract. Non-enhanced, fast spin-echo sequences (TSE) were performed in all patients. In 70 % of the patients a contrast-enhanced, fast gradient-echo sequence (TFE) was included. The dynamic sequence was prolonged and supplemented with furosemide provocation in some patients with suspected urinary-tract obstruction. RESULTS: Nine percent of examinations were non-diagnostic or interrupted due to movement. MRU contributed additional information in 66 %. Nine patients with suspected urinary-tract obstruction were examined with both contrast-enhanced MRU and scintigraphy. Three MRU examinations were less informative and one equal to scintigraphy when obstruction was the diagnosis. When using a technique with a prolonged dynamic sequence, including frusemide provocation, four MRU examinations were equal and one was superior to scintigraphy. CONCLUSIONS: MRU has the potential to replace traditional diagnostic methods which use ionising radiation in paediatric patients. Further studies are needed before definite conclusions can be drawn.

A report of the 1995 and 1996 Paternity Testing Workshops of the English Speaking Working Group of the International Society for Forensic Haemogenetics.

We report the results of the 1995 and 1996 Paternity Testing Workshops of the English Speaking Working Group of the International Society for Forensic Haemogenetics. In 1995, 18 laboratories participated and in 1996, 21 laboratories participated. Each year, blood samples from three persons (child, mother and alleged father) were sent to participating laboratories which performed paternity testing according to their usual protocols. The results and answers to questionnaires concerning methods were compiled and are presented in this report. From the questionnaires, a general tendency to a more frequent use of polymerase chain reaction (PCR) based methods was seen. In 1996, 62% of the laboratories used PCR based methods. Ten per cent of the laboratories used only PCR based methods. The remaining 90% of the laboratories performed restriction fragment length polymorphism (RFLP) investigations of variable numbers of tandem repeat (VNTR) loci with single locus probes (SLPs) either alone or in combination with PCR based typing, multi locus probing, classical systems (ABO etc.), or serological HLA typing. In 1996, typing with classical systems was used in 29% of the laboratories. The majority of the laboratories performed RFLP typing of VNTR loci using very similar methods. The results and the inter-laboratory variations of the measured lengths of the DNA-fragments of the VNTR regions D2S44, D7S21, D7S22, and D12S11 of the trios were analysed. The overall coefficient of variation was 2.15% in 1995 and 1.43% in 1996. During the period 1991-1996, the inter-laboratory variation has decreased, most probably due to the fact that the methods have now been optimised and the majority of the participating laboratories have adopted the standardised method for RFLP typing with SLPs which was agreed upon for investigations in crime cases by the European DNA Profiling Group. In 1996, eight laboratories reported the results of PCR based typing of the short tandem repeat (STR) locus HumTH01, six laboratories reported results of HumVWA31A typing, and five laboratories reported the results of typing of the STR locus HumF13A1 and the VNTR locus D1S80. The results were concordant although the nomenclature was slightly inconsistent concerning the classification of an irregular repeat of the HumTH01 system.

[Light sedation in children. Midazole as nasal drops is a good alternative]. / Lett sedasjon av barn. Midazolam som nesedråper er et aktuelt alternativ.

Many of the procedures carried out on paediatric patients are both painful and frightening to the child. To increase the child's comfort and to promote good working conditions, it may be necessary and advisable to sedate the child. In this study, 125 children (63 boys and 62 girls) were sedated with midazolam. For most children (n = 110) the medication was administered as nose drops. The reasons for sedation were echocardiography (n = 51), venous or lumbar punction (n = 53) and computer tomography scan (n = 21). The overall success rate was 78%. Minor complications were registered in four children. Two children vomited and one child developed a facial rash. One child had prolonged sedation, but this did not affect its respiration. We conclude that midazolam given as nose drops is a safe and convenient way of sedating paediatric patients.

Pretreatment of wheat straw using combined wet oxidation and alkaline hydrolysis resulting in convertible cellulose and hemicellulose.

The wet oxidation process of wheat straw has been studied as a pretreatment method to attain our main goal: To break down cellulose to glucose enzymatic, and secondly, to dissolve hemicellulose (e.g., for fermentation) without producing microbial inhibitors. Wet oxidation combined with base addition readily oxidizes lignin from wheat straw facilitating the polysaccharides for enzymatic hydrolysis. By using a specially constructed autoclave system, the wet oxidation process was optimized with respect to both reaction time and temperature. The best conditions (20 g/L straw, 170 degrees C, 5 to 10 min) gave about 85% w/w yield of converting cellulose to glucose. The process water, containing dissolved hemicellulose and carboxylic acids, has proven to be a direct nutrient source for the fungus Aspergillus niger producing exo-beta-xylosidase. Furfural and hydroxymethyl-furfural, known inhibitors of microbial growth when other pretreatment systems have been applied, were not observed following the wet oxidation treatment.

On the stabilization of niobium(V) solutions by zirconium(IV) and hafnium(IV).

Niobium cannot be separated from zirconium or hafnium when these elements occur together in solution with common anions such as chloride and sulphate. This is ascribed to the co-polymerization of niobium(V) and the hydrolysed ionic species of zirconium(IV) and hafnium(IV) to form colloidal particles. In hydrochloric acid the particles are positively charged, whereas in sulphate solution the Zr-and Hf-sulphate complexes confer a negative charge. The two cases are considered separately.

Assessing exposure to solvent vapour during the application of paints, etc.--model calculations versus common sense.

Simple formulae expressing average and maximum concentrations of solvent vapour in indoor air during the application of paints, glues, and the like, have been derived using a six parameter mathematical exposure model MEM 1. The model is valid for solvents that evaporate from the liquid without fractionation and at a constant rate. Some features of the relation between exposure level and system parameters were found to be considerably more tricky than expected.