Bone characteristics, pre-caecal phytate degradation, mineral digestibility and tissue expression were marginally affected by zinc level and source in phytase-supplemented diets in 21-day-old broiler chickens.

1. This study determined the effect of dietary Zn concentration and source in phytase-supplemented diets on bone mineralisation, gastrointestinal phytate breakdown, mRNA-level gene expression (in jejunum, liver and Pectoralis major muscle) and growth performance in broiler chickens.2. Male Cobb 500 broilers were housed in floor pens (d 0-d 21) to test seven treatments with six replicate pens (12 birds per pen). Diets were arranged in a 2 × 3 + 1-factorial arrangement. The experimental factors were Zn source (Zn-oxide (ZnO) or Zn-glycinate (ZnGly) and Zn supplementation level (10, 30 or 50 mg/kg of diet). A maize-soybean meal-based diet without supplementation and formulated to contain 28 mg Zn/kg (analysed to be 35 mg Zn/kg), served as a control.3. Zinc source and level did not influence (p > 0.05) bone ash concentration and quantity or mineral concentrations in bone ash. Tibia thickness was greater in the treatment ZnO10 than in the treatments ZnO30 and ZnGly50 (Zn level × Zn source: p = 0.036), but width and breaking strength were not affected.4. Pre-caecal P digestibility and concentrations of phytate breakdown products in the ileum, except for InsP5, were not affected by Zn source or level. Only the expression of EIF4EBP1 (eukaryotic translation initiation factor 4E-binding protein 1) and FBXO32 (F-box only protein 32) in Pectoralis major muscle was affected by source, where expression was increased in ZnO compared to ZnGly diets (p < 0.05).5. In conclusion, Zn level and source did not affect gastrointestinal phytate degradation and bone mineralisation in phytase-supplemented diets. The intrinsic Zn concentration appeared to be sufficient for maximum bone Zn deposition under the conditions of the present study but requires validation in longer-term trials.

Assessment of two diet types in reduced-crude protein diets with or without phytase supplementation - implications on key phenotypic responses in 21-day-old broiler chickens.

1. Two concurrent experiments were conducted to investigate the effect of using the crude protein (CP) value of supplemental amino acids (AA) in formulating reduced-crude protein (RCP) diets. The RCP diets formulated without accounting for CP values of supplemental AA (RCPN) or otherwise (RCPY) or a positive control (PC) diet were fed without (Experiment 1) or with (Experiment 2) phytase.2. Each experiment utilised 105 male broiler chicks. Birds were provided a common starter diet from d 0-7. On d 21, ileal digesta were collected from the distal half of the ileum. For mRNA expression analysis, tissues were collected from the mid-jejunum and the liver. Excreta grab samples were collected for analysis for N content.3. In Experiment 1, there was a stepwise decrease (p < 0.01) in weight gain and excreta N for birds receiving PC, RCPN and RCPY diets. The coefficients of ileal digestibility of His, Leu, Phe and Trp were greater (p < 0.05) in birds that received RCPY rather than the PC diets. The relative mRNA expression of CAT1 was greater (p < 0.05) for birds that received the PC diet.4. In Experiment 2, growth performance and excreta N were not different between the PC and RCPN diets, but weight gain, feed intake and excreta N were greater (p < 0.01) in birds receiving PC or RCPN diets. The coefficients of digestibility were greater (p < 0.01) in RCP than PC diets for Lys, Thr, Cys, Gly and Ser. The mRNA expression for S6kinase and PRKAß2 was greater (p < 0.05) for birds fed RCPN compared to PC.5. In conclusion, accounting for the N content of supplemental AA during feed formulation for RCP diets will influence the effect of CP reduction on growth performance and ileal amino acid digestibility.

Expanding CEP290 mutational spectrum in ciliopathies.

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.

Epileptic phenotypes, electroclinical features and clinical characteristics in 17 children with anti-NMDAR encephalitis.

BACKGROUND: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis is a rare disorder characterized by seizures, neuropsychiatric symptoms, dyskinesia and autonomic instability. OBJECTIVE: Aim of the present study was to evaluate the seizure phenotypes and electroencephalogram (EEG) features in children with anti-NMDAR encephalitis. METHODS: Seizure types, electroclinical features and clinical characteristics of 17 children with anti-NMDAR encephalitis were analysed in a retrospective case series from nine centres in Europe. RESULTS: Nearly half (8/17) of the children presented with psychiatric symptoms, whereas in 4/17 patients seizures were the first symptom and in 5/17 both symptoms occurred at the same time. During the following course seizures were reported in 16/17 children. The first EEG detected generalized slowing in 11/17 patients, focal slowing in 3/17 and normal background activity in only 3/17 children. The extreme delta brush (EDB) pattern was detected in 9/17 (53%) patients. CONCLUSION: In addition to psychiatric symptoms, children with anti-NMDAR encephalitis often show generalized slowing in EEG with or without seizures at initial presentation. EDB is present in half of all children and is potentially a helpful tool for early detection of this immune-mediated disease.

Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.

OBJECTIVE: Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. METHOD: Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. RESULTS: The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. SIGNIFICANCE: Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation.

Acetazolamide treatment for infantile central sleep apnea.

Central sleep apnea is a common respiratory pattern in healthy neonates. Nevertheless, frequent central sleep apnea associated with drops in oxygen saturation may contribute to infantile morbidity. Recently, low-dose acetazolamide was shown to reduce symptomatic central sleep apnea in adults. We treated 12 infants, median conceptional age 42 weeks (range, 40-44 weeks), with central sleep apnea. In all cases, the central apnea index was >40/h total sleeping time (apnea > or = 3 sec). The cumulative duration of drops in oxygen saturation below 90% was more than 3 min/h total sleeping time. All individuals received acetazolamide 7 mg/kg/day (orally, divided in three doses) for 11 weeks. Polysomnography was begun 10 hours before the first dose and continued for 10 hours after the third dose. Polysomnography was repeated after 6 weeks of treatment and 1 week after acetazolamide therapy was discontinued. Comparison of the respiratory patterns before and after treatment (10-hour recording after the third dose) showed a decrease in the median central apnea index from 74/h (range, 42-152/h) to 13/h (range, 6-49/h). The median of the cumulative duration of drops in oxygen saturation below 90% decreased from 3.6 min/h (range, 3.1-9.2 min/h) to 0.07 min/h (range, 0-0.5 min/h). Basal oxygen saturation increased from 95 (92-97%) to 98% (96-99%). This improvement was maintained in the final polysomnography (12 weeks after therapy was begun and 1 week after completion of the 11-week course). No adverse effects were noted. We conclude that low-dose acetazolamide treatment may be useful for the treatment of central infantile sleep apnea associated with hypoxemia.

Educating nurses in blood pressure measurement and hypertension control.

Today, self-measurement of blood pressure is seen as the optimal goal in improving the compliance of the hypertensive patient, but it can only be reached by using well trained medical staff. In this, the role of nurses is particularly vital. We administered a questionnaire to 77 nurses and 146 doctors to determine their levels of knowledge concerning blood pressure measurement techniques and pitfalls, and definition of hypertension. The general knowledge of both groups was insufficient. Whereas doctors showed greater medical knowledge, nurses were better at the techniques. Both were equally deficient in defining hypertension. We therefore set up a short course (3h) in blood pressure measurement to evaluate knowledge and provide further training. The course consisted of a pretest, a short training programme and a post-training test. Post-training test results showed an average improvement in defining hypertension from 5% to 85%. We conclude that short-term training courses in blood pressure measurement are needed for nurses and doctors, particularly young doctors. We also need more coverage in the medical press to stimulate interest in this vital topic.

Group exercise improves patient compliance in mild to moderate hypertension.

One of the major problems of both pharmacological and non-pharmacological treatment is compliance of the patient. We attempted to reduce compliance problems by using group exercise in hypertensive patients. A group of 29 hypertensive patients (aged 54 +/- 10 years) met weekly for nearly 2 years. Each session (90-120 min) comprised four parts: endurance training, gymnastics and relaxation, education and a discussion of related problems such as nutrition and lifestyle. There was a significant decrease in systolic (9%) and diastolic (6%) blood pressures at rest and during exercise (systolic 12%), and an increased maximal work load (18%). In addition, drug treatment was substantially reduced (reduced in 56% of patients abandoned in 10% of patients). Cholesterol levels were reduced by 18%, although, during a 6-10 day nutritional report, fat made up 40% of the total calorific intake, indicating the need for individualized dietary advice. The major goal was to improve compliance and increase non-pharmacological treatment, exercise being a minor consideration which may have relevance for the treatment of hypertension.

Quantitative score for the evaluation of kinematic recordings in neuropediatric diagnostics. Detection of complex patterns in spontaneous limb movements.

OBJECTIVE: Evaluation of spontaneous infant movements is an important tool for the detection of neurological impairments. One important aspect of this evaluation is the observation of movements which exhibit certain complex properties. This article presents a method to automatically extract segments which contain such complex patterns in order to quantitatively assess them. METHODS: Expert knowledge is represented in a principal component model which captures the term complexity as the multivariate interactions in the kinematic chains of the upper and the lower limb. A complexity score is introduced which is used to quantify the similarity of new movements to this model. It was applied to the recordings of 53 infants which were diagnosed by physicians as normal or pathologic. RESULTS: Time segments marked as complex (from five infants) by physicians could be detected with a mean accuracy of 0.77 by the automated approach. The median of the best complexity scores of the pathologic group (n = 21) is significantly lower (p = 0.001) than the median of the normal group (n = 27). CONCLUSION: Using the complexity score we were able to quantify movement complexity in regard of the understanding of physicians. This could be useful for clinical applications.

Parent based language intervention for 2-year-old children with specific expressive language delay: a randomised controlled trial.

OBJECTIVE: The aim of this randomised controlled trial was to evaluate the effectiveness of a short, highly structured parent based language intervention group programme for 2-year-old children with specific expressive language delay (SELD, without deficits in receptive language). METHODS: 61 children with SELD (mean age 24.7 months, SD 0.9) were selected between October 2003 and February 2006 during routine developmental check-ups in general paediatric practices, using a German parent-report screening questionnaire (adapted from the MacArthur Communicative Development Inventories). Standardised instruments were used to assess the language and non-verbal cognitive abilities of these children and of 36 other children with normal language development (reference group; mean age 24.6 months, SD 0.8). 58 children with SELD were sequentially randomly assigned to an intervention group (n = 29) or a 12-month waiting group (n = 29). In the intervention group, mothers participated in the 3-month Heidelberg Parent-based Language Intervention (HPLI). All children were reassessed 6 and 12 months after pretest. Assessors were blind to allocation and previous results. RESULTS: 47 children were included in the analysis. At the age of 3 years, 75% of the children in the intervention group showed normal expressive language abilities in contrast to 44% in the waiting group. Only 8% of the children in the intervention group versus 26% in the waiting group met the criteria for specific language impairment (t score < or =35). CONCLUSIONS: By applying the short, highly structured HPLI in children with SELD, the rate of treatment for language impairment at the age of 3 years can be significantly reduced.

[Color Doppler echocardiography in the diagnosis of aortic dissection and aortic wall abscesses]. / Farb-Doppler-Echokardiographie bei der Diagnostik von Aortendissektionen und Aortenwandabszessen.

In eleven patients with aortic dissection or perforated endocarditic aortic wall abscess cavity, the diagnostic usefulness of Color Doppler Echocardiography (CDE) for the identification of true and false lumen as well as the perforation jet was assessed by comparison with the findings of angiography, digital subtraction angiography, computed tomography and surgery. The information gained in addition to that of these procedures, as well as to that of the four conventional echocardiographic techniques was evaluated. Six patients had aortic dissections of DeBakey type I or III; in all of them the diagnosis had been established with conventional ultrasonic techniques. Similarly, in all patients with aortic dissection of DeBakey type I, a clear differentiation between true and false lumen in the aortic root and ascending aorta could already be made by grey-scaled echocardiography. In these patients, however, CDE made the additional demonstration of the perforation jet into the false lumen possible. In those three patients with aortic dissection of DeBakey type III as well as in the abdominal aortic region of DeBakey type I, color Doppler echocardiography was the only method to define true and false lumen and to clearly localize the perforation sites. Two further patients were found to have a small, local dissection, which could only be assumed by conventional echocardiography; the color Doppler M-mode image led to a clear diagnosis. In three patients an endocarditic abscess cavity of the aortic wall could be detected by conventional echocardiography. Two-dimensional color Doppler echocardiography additionally enabled us to visualize the presence and the course of perforation flows. In two patients color-coded Doppler echocardiography made it possible to detect perforations in regions which could not be localized either with conventional echocardiographic techniques or the above-mentioned control procedures.

Simultaneous stimulation of growth hormone, adrenocorticotropin and cortisol with L-dopa/L-carbidopa and propranolol in children of short stature.

In 59 otherwise healthy children of short stature, the simultaneous response of growth hormone, cortisol and plasma adrenocorticotropin (ACTH) to L-dopa/L-carbidopa and propranolol at 45 and 90 min after administration were investigated. A growth hormone response of 10 microg/l or higher was considered positive. The definition of a positive cortisol response included either a hormone increase of at least 193 nmol/l or a peak hormone level of at least 497 nmol/l. The ACTH increase had to be fourfold above 11 pmol/l to be considered positive. In the 59 investigated children, the median basal growth hormone levels increased from 1.35 microg/l to 18.05 microg/l and 10.15 microg/l at 45 and 90 min after stimulation (p < 0.05). The median cortisol levels rose from 242 nmol/l to 439 nmol/l and 612 pmol/l, and the corresponding median ACTH levels from 2.94 pmol/l to 9.63 pmol/l and 11.13 pmol/l at 45 and 90 min after stimulation. Significant positive hormone response rates were 88.1% for growth hormone, 88.1% for cortisol and 69% for ACTH. These results could be attributed to the enhanced stimulating effect of the additional administration of L-carbidopa and propranolol. We conclude that the administration of L-dopa/L-carbidopa and propranolol is useful for the simultaneous evaluation of growth hormone, cortisol and ACTH secretion in children of short stature.

[Optimal long-term control of arterial hypertension. Experiences with ambulatory, sports-oriented groups of patients with hypertension]. / Optimierte Langzeitkontrolle der arteriellen Hypertonie. Erfahrungen mit ambulanten, sportorientierten Hochdruckgruppen.

Out-patient groups of hypertensives were organized in an effort to improve long-term treatment results with greater attention to general measures and to increase compliance. Under supervision of a doctor and a physiotherapist 45 patients (aged 54 +/- 10 years) with mild or moderately severe hypertension were enrolled in a sports training programme after thorough examination. At the same time they were given advice and instructions on self-measurement of blood pressure, diet, medication, general life style and relaxation techniques. In the first 20 patients (observation period of more than one year) a significant reduction in both resting (systolic of -9%) and exercise (systolic of -12%) blood pressures was noted. At the same time exercise tolerance was raised (+18%), while body-weight and total cholesterol concentrations were lowered. It was possible to reduce drug dosage in seven patients, in three more it was discontinued. Left-ventricular wall thickness fell slightly but not significantly. There were no complications. It is concluded that group therapy with sport as a vehicle and advice on general life style are satisfactory means for controlling hypertension and achieve better compliance.

Hemofiltration and plasmapheresis in premature infants and newborns.

Extracorporal detoxication methods in newborns are most unavailable, contraindicated because of technical problems. Herein are reported the experiences with a blood pump unit that was miniaturized for hemodialysis, hemofiltration, and plasmapheresis in newborns. In three premature infants with acute renal failure of different etiology (two newborns with severe Rh-erythroblastosis, 1 premature infant with hypoproteinemia) 13 single-needle hemofiltrations and 6 single-needle plasmaphereses were performed with double head pump, special tube systems, and small modules. The age of the patients ranged from 1 to 14 days, body weight was between 800 and 2,800 g. Four umbilical veins and two femoral veins were used as vascular access. The ultrafiltration rate during the treatment averaged 0.3 ml/min in single-needle hemofiltration and the plasma filtrate flow rate 1.3 ml/min in single-needle plasmapheresis. All treatments were well tolerated. Four patients died due to complications unrelated to the treatment, two patients recovered. These preliminary results show that both hemofiltration and plasmapheresis may be carried out without major problems in premature infants and newborns.

Prenatal diagnosis of bilateral proximal femoral hypoplasia.

Proximal femoral focal deficiency is a rare skeletal disorder, with an estimated incidence of 0.11 to 0.2/10,000 births. The bilateral form is uncommon, occurring in 10 to 15% of cases. We report a case of bilateral proximal femoral focal deficiency diagnosed by ultrasound at 30 weeks' gestation. Differential diagnosis, prognosis and management are discussed.