Dose response to postruminal urea in lactating dairy cattle.

Inclusion of urea in dairy cattle diets is often limited by negative effects of high levels of feed urea on dry matter intake (DMI) and efficiency of rumen N utilization. We hypothesized that supplying urea postruminally would mitigate these limitations and allow greater inclusion of urea in dairy cattle diets. Four rumen-fistulated Holstein-Friesian dairy cows (7 ± 2.1 lactations, 110 ± 30.8 d in milk; mean ± standard deviation) were randomly assigned to a 4 × 4 Latin square design to examine DMI, milk production and composition, digestibility, rumen fermentation, N balance, and plasma constituents in response to 4 levels of urea continuously infused into the abomasum (0, 163, 325, and 488 g/d). Urea doses were targeted to linearly increase the crude protein (CP) content of total DMI (diet plus infusion) by 0%, 2%, 4%, and 6% and equated to 0%, 0.7%, 1.4%, and 2.1% of expected DMI, respectively. Each 28-d infusion period consisted of a 7-d dose step-up period, 14 d of adaptation, and a 7-d measurement period. The diet was fed ad libitum as a total mixed ration [10.9% CP, 42.5% corn silage, 3.5% grass hay, 3.5% wheat straw, and 50.5% concentrate (dry matter basis)] and was formulated to meet 100%, 82%, and 53% of net energy, metabolizable protein, and rumen-degradable protein requirements, respectively. Linear, quadratic, and cubic effects of urea dose were assessed using polynomial regression assuming the fixed effect of treatment and random effects of period and cow. Dry matter intake and energy-corrected milk yield responded quadratically to urea dose, and milk urea content increased linearly with increasing urea dose. Apparent total-tract digestibility of CP increased linearly with increasing urea dose and ruminal NH3-N concentration responded quadratically to urea dose. Mean total VFA concentration was not affected by urea dose. The proportion of N intake excreted in feces decreased linearly and that excreted in urine increased linearly in response to increasing urea dose. The proportion of N intake excreted in milk increased linearly with increasing urea dose. Urinary urea excretion increased linearly with increasing urea dose. Microbial N flow responded cubically to urea dose, but the efficiency of microbial protein synthesis was not affected. Plasma urea concentration increased linearly with increasing urea dose. Regression analysis estimated that when supplemented on top of a low-CP diet, 179 g/d of postruminal urea would maximize DMI at 23.4 kg/d, corresponding to a dietary urea inclusion level of 0.8% of DMI, which is in line with the current recommendations for urea inclusion in dairy cattle diets. Overall, these results indicate that postruminal delivery of urea does not mitigate DMI depression as urea dose increases.

Review: Unlocking the limitations of urea supply in ruminant diets by considering the natural mechanism of endogenous urea secretion.

Ruminants have evolved with the capability to recycle endogenous urea to the gastrointestinal tract (GIT). Ruminal ammonia derived from urea recycling makes a net contribution to digestible N flow if it is used to synthesise microbial protein. The dynamics of urea recycling and its quantitative importance to the N economy of ruminants are affected by dietary and physiological factors. In general, the transfer of endogenous urea to the GIT is related positively to blood urea concentration and rumen-fermentable energy supply and negatively to ruminal ammonia concentration. After consumption of a meal rich in rumen-degradable N, ruminal ammonia concentrations peak and can exceed the rate of carbohydrate fermentation, resulting in inefficient ammonia capture by microbes. These periods are characterised by greater ruminal ammonia efflux and reduced urea influx. A low ruminal ammonia concentration over time can stimulate recycling of endogenous urea-N to the rumen and its capture into microbial protein and reduce N excretion. Shifting protein digestion to the postruminal GIT can reduce ruminal ammonia concentration and increase plasma urea concentration, conditions that should promote greater reliance on urea recycling to meet N requirements of the rumen. Their ability to use non-protein N, of dietary or endogenous origin, to synthesise metabolisable protein and subsequently meat and milk contributes positively to the human-edible protein efficiency of ruminants. Dietary urea is rapidly degraded to ammonia in the rumen, and high rates of ammonia absorption across the rumen wall when a urea-rich meal is consumed can lead to hypophagic and toxic effects associated with urea feeding. Non-protein N absorbed in the postruminal GIT can contribute substantially to net urea and ammonia uptake into the portal vein, which reflects the potential for targeted urea release in postruminal sections of the GIT. In this review, we suggest that the regulation of urea recycling to the rumen is a critical step towards improved efficiency of ruminal N utilisation. We describe an approach by which postruminal urea supplementation, as an alternative to its ruminal application, may allow a slow and steady return of N to the rumen, avoid peaks in ammonia concentration associated with feeding, confer a greater and more efficient microbial synthesis, and improve fibre digestion compared with conventional urea supplementation.

Muscle force and power in obese and overweight children.

The study investigated differences in skeletal muscle function between obese and non-obese children using a force platform. Forty obese children and adolescents (age range 8 to 18 years; 21 girls) and 40 age- and sex-matched controls performed two tests: (1) single two-legged jump, a countermovement jump for maximal height; (2) multiple one-legged hopping on the forefoot, a test of maximal force. In the single two-legged jump, obese subjects had higher absolute peak force (1.62 kN vs 1.09 kN) and peak power (2.46 kW vs 2.06 kW), but lower body weight-related peak force (2.10 vs 2.33) and lower peak power per body mass (30.9 W/kg vs 41.6 W/kg). Jump height (29.3 cm vs 37.5 cm) and maximal vertical velocity (1.92 ms(-1) vs 2.31 ms(-1)) were reduced in obese children. In multiple one-legged hopping, obese subjects had 72% and 84% higher absolute peak force on the left and right foot, respectively. However, forces relative to body weight were 24% and 23% lower in the obese group than in the control group. In conclusion, obese children and adolescents have increased muscle force and power. This partly compensates for the effect of high body weight on muscle performance.

Factor X deficiency and intracranial bleeding: who is at risk?

Very few mutations of the gene encoding for coagulation factor X (FX) have been found associated with intracranial haemorrhage (ICH) due to FX deficiency (FXD). No guidelines exist as to when prophylaxis in FXD should be started and how patients at risk for ICH can be identified. We report on a novel mutation causative for ICH in a family of Iranian origin and provide a summary of all published mutations in the FX gene related to ICH. The index patient is an infant with umbilical bleeding requiring blood transfusion in the postnatal period. The international normalized ratio (6.01) and activated partial thromboplastin time (117 s) were prolonged. Coagulation factor analysis was normal except for FX activity (<1%). At 4 months, the child suffered a spontaneous severe intracranial haemorrhage. The child was the product of a consanguineous union. Four of five available family members from three generations displayed minor bleeding symptoms and mildly reduced FX. Sequencing of FX gene demonstrated homozygosity for a novel duplication A (c.1402_1403dupA)* in exon 8 and heterozygosity in four family members. We compare this case to all 15 patients with FXD and ICH and their 11 known mutations described so far. This case illustrates a pattern of FXD (a male neonate with umbilical or gastrointestinal bleeding, very low FX:C (<1%) and an underlying homozygous genotype) who may be at high risk for ICH. In these cases, we recommend to start early prophylactic substitution of FX to prevent a possible life-threatening haemorrhage.

[Dimenhydrinate overdosage in a 3(1/2) year-old-girl with dilative cardiomyopathy]. / Dimenhydrinat-Intoxikation bei einem 3(1/2) Jahre alten Mädchen mit dilatativer Kardiomyopathie.

Dimenhydrinate overdosage in a 3(1/2) year-old-girl with dilative cardiomyopathy. Dimenhydrinate (Vomex(R)) is frequently used in the treatment of sickness and vomiting. The symptoms of overdosage present like an anticholinergic syndrome. We report on the clinical findings of an intoxication with dimenhydrinate in a 3(1/2) year-old-girl with functional dilative cardiomyopathy following a congenital left ventricular diverticle. Especially in small children, with the application of 40 mg suppositories once or twice per day the maximum dose of 3.75 mg/kgBW/d is achieved.

[Salmonella enteritidis infection presenting with septic shock, renal failure and cutaneous manifestations]. / Septischer Schock mit Niereninsuffizienz und Hautmanifestationen als Komplikation einer Salmonella-enteritidis-Infektion.

Infections by Salmonella enteritidis commonly present with diarrhoea, vomiting and fever and complications such as septicaemia, pleural effusion and acute renal failure are usually rare. There are only few reports of cutaneous manifestations and especially septic shock in patients with Salmonella enteritidis infection. We report on a previously healthy seven-year-old boy suffering from Salmonella enteritidis septicaemia presenting with septic shock, pleural effusion, renal failure and an unusual maculopapular skin eruption on both wrists and ankles. The boy had no underlying immunodeficiency.

Biglycan is required for adaptive remodeling after myocardial infarction.

BACKGROUND: After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI. METHODS AND RESULTS: Experimental MI was induced in wild-type (WT) and bgn(-/0) mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn(-/0) mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn(-/0) mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn(-/0) mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn(-/0) mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn(-/0), 111+/-4.2 microL versus WT, 96+/-4.4 microL; P<0.05) and LV end-diastolic pressure (bgn(-/0), 24+/-2.7 versus WT, 18+/-1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn(-/0), 12+/-2% versus WT, 21+/-4%; P<0.05) 21 days after MI. CONCLUSIONS: Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.

[A life-threatening cardiomyopathy following port-a-cath infection under immune tolerance therapy]. / Lebensbedrohliche Kardiomyopathie als Folge einer Portkatheterinfektion bei Immuntoleranztherapie.

The development of inhibitors in patients with severe haemophilia A is a serious complication requiring long term immune tolerance therapy (ITT). ITT frequently requires implantable central venous access, mostly port catheters. Their use may be complicated by thrombosis and infection. We report on an 18 year old patient with severe haemophilia A who had developed a high-titre factor VIII inhibitor in the age of five years. ITT required the implantation of a port system. The postoperative course was complicated by severe septicaemia with congestive cardiac failure. The port catheter was removed due to recurrent fever after 26 days. Our patient developed dilative cardiomyopathy. ITT had to be stopped and was replaced by on demand therapy with an activated prothrombin complex concentrate. Cardiomyopathy resulted in congestive heart failure, severe ventricular arrhythmias and the death of the young man. In patients with haemophilia, dilative cardiomyopathy and development of inhibitors the possibility of cardiac transplantation should be evaluated before increasing inhibitors and the development of pulmonary hypertension exclude this therapeutical option.

Modest phenotypic improvements in ASA-deficient mice with only one UDP-galactose:ceramide-galactosyltransferase gene.

BACKGROUND: Arylsulfatase A (ASA)-deficient mice are a model for the lysosomal storage disorder metachromatic leukodystrophy. This lipidosis is characterised by the lysosomal accumulation of the sphingolipid sulfatide. Storage of this lipid is associated with progressive demyelination. We have mated ASA-deficient mice with mice heterozygous for a non-functional allele of UDP-galactose:ceramide-galactosyltransferase (CGT). This deficiency is known to lead to a decreased synthesis of galactosylceramide and sulfatide, which should reduce sulfatide storage and improve pathology in ASA-deficient mice. RESULTS: ASA-/- CGT+/- mice, however, showed no detectable decrease in sulfatide storage. Neuronal degeneration of cells in the spiral ganglion of the inner ear, however, was decreased. Behavioural tests showed small but clear improvements of the phenotype in ASA-/- CGT+/- mice. CONCLUSION: Thus the reduction of galactosylceramide and sulfatide biosynthesis by genetic means overall causes modest improvements of pathology.

Exploring eye movement analysis as a measure of selective visual attention in brain injured individuals.

PRIMARY OBJECTIVE: To investigate the utility of using a new method of assessment for deficits in selective visual attention (SVA). METHODS AND PROCEDURES: An independent groups design compared six participants with brain injuries with six participants from a non-brain injured control group. The Sensomotoric Instruments Eye Movement system with remote eye-tracking device (eye camera) and two sets of eight stimuli were employed to determine if the camera would be a sensitive discriminator of SVA in these groups. MAIN OUTCOMES AND RESULTS: The attention profile displayed by the brain injured group showed that they were slower, made more errors, were less accurate and more indecisive than the control group. CONCLUSIONS: The utility of eye movement analysis as an assessment method was established, with implications for rehabilitation requiring further development.

Public attitudes towards survivors of brain injury.

PRIMARY OBJECTIVE: To explore the effects of religious identity, gender and socioeconomic status (SES) on public attitudes towards survivors of brain injury. RESEARCH DESIGN: An independent groups design was used to compare the attitudes of Northern Irish participants. METHODS AND PROCEDURES: The participants were asked to complete a modified form of the Community Attitudes to Mental Illness scale. The new questionnaire replaced the original scales' emphasis on mental illness with that of brain injury. Complete data was available for 179 participants for the religious identity and gender analysis and 124 for gender and SES. Analyses of variance were conducted on these variables. OUTCOMES AND RESULTS: Significant differences between male and female attitudes were found along with significant interactions between religious identity and gender and SES and gender. CONCLUSIONS: Religious, economic and gender-based divisions in society affect attitudes towards survivors of brain injury.

Recanalisation of bilateral superior vena cava after total cavopulmonary connection. Interventional occlusion with the Amplatzer VSD Occluder.

UNLABELLED: Formation of systemic to pulmonary venous or systemic venous left atrial collaterals frequently occurs in patients after Glenn or Fontan-type operations. Embolization with detachable metal coils is the therapy of choice for the closure of small vessels. These devices however are not appropriate for the occlusion of large collaterals, e. g. recanalized bilateral caval veins. We report two patients who presented late after Fontan-type operations with a gradual decrease in oxygen saturation due to recanalisation of bilateral caval veins. Interventional closure of these large veins was carried out successfully with the use of 8 mm Amplatzer muscular VSD Occluders, resulting in an increase of arterial oxygen saturations. CONCLUSION: The closure of recanalized bilateral superior caval veins after Fontan procedures is possible without technical problems by means of the Amplatzer muscular VSD Occluder. In order to avoid future formation of venous collaterals via the azygos or hemiazgos system, the occluder should be placed in the vena cava below the orifice of the azygos/ hemiazygos vein.

Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2.

INTRODUCTION: Clinical variability associated with the common 22q11.2 microdeletion is well known, and has led to a broad application of FISH diagnostics with probes for loci TUPLE1 or D22S75 (N25), although, rarely reported atypical deletions associated with the same phenotypic spectrum would not be discovered by these probes. As most types of 22q11.2 deletions occur between low copy repeats within the region (LCR22), we assumed that atypical deletions should be more common than has been reported. To address this question and the possibility of a deletion size related genotype-phenotype correlation, we systematically assessed the frequency of typical and atypical 22q11.2 deletions in a large cohort of patients. METHODS: We used a set of 10 fluorescent in situ hybridisation (FISH) DNA probes, capable of detecting all reported and hypothetical deletions between the LCR22, and analysed 350 patients. Deletion sizes in atypical deletions were established by use of further FISH probes. Frequency of certain atypical deletions was analysed in controls by FISH and quantitative PCR. RESULTS: Patients with conotruncal heart defects (ctCHD) and with typical VCFS phenotype showed the common 3 Mb or nested 1.5 Mb deletions (in 18.5% and 78.6%, respectively), but no atypical deletion, while 5% (3/63) of patients with a mildly suggestive, atypical phenotype showed atypical distal deletions, which were not detected in patients with mental retardation of unknown origin or in healthy controls. DISCUSSION: These statistically significant differences demonstrate that atypical distal 22q11.2 deletions are very uncommon in patients with ctCHDs, while atypical congenital heart defects and mild dysmorphism are recognisable feature of atypical distal deletions. Further phenotype-genotype analysis disclosed association of significant developmental delay with the distal part of the common deletion region, and choanal atresia and atypical CHDs with the adjacent distal deletion region.

[Cervical origin of the subclavian artery: echocardiographic diagnosis in patients with monosomy 22q11]. / Der zervikale Ursprung der Arteria subclavia: Echokardiographische Diagnose bei Patienten mit Monosomie 22q11.

OBJECTIVE: To assess the sensitivity and specificity of echocardiography in the detection of anomalies of the subclavian artery (cervical origin, aberrant origin from the descending aorta or isolation) in patients with monosomy 22q11. METHOD: From 1/1998 until 03/2002 we examined 57 patients with conotruncal cardiac malformations. 30 patients had pulmonary atresia and ventricular septal defect (53 %), 13 interrupted aortic arch (23 %), 9 tetralogy of Fallot (16 %) and 5 common truncus arteriosus (9 %). Echocardiographic examination included identification of the laterality of the aortic arch as well as examination of the origin of the brachiocephalic vessels. The results were compared with angiographic and intraoperative findings. Median age at echocardiographic investigation was 74 days (range 1 d - 33.4 yrs.). RESULTS: Laterality of the aortic arch was assessed correctly in all patients. 20/57 patients had a right-sided aortic arch (35 %). Echocardiography detected all anomalies of the subclavian artery (14/57 patients, 25 %, sensitivity 100 %) and excluded these anomalies correctly in 43 patients (specificity 100 %). Exact classification of the anomaly of the subclavian artery was possible in 6/6 patients with a cervical origin of the artery and in 7/8 patients with aberrant origin from the descending aorta. Monosomy 22q11 was diagnosed in 21 patients (37 %). CONCLUSION: Echocardiography achieves a high sensitivity in the detection of anomalies of the subclavian artery. The diagnosis of cervical origin of the artery, in particular, can be easily established. As this anomaly appears to be a specific marker for monosomy 22q11, echocardiography facilitates reliable identification of these patients in clinical practice.

Lysosomal sulfatide storage in the brain of arylsulfatase A-deficient mice: cellular alterations and topographic distribution.

Inherited deficiency for the lysosomal enzyme arylsulfatase A (ASA) leads to lysosomal storage of sulfatides and to dramatic demyelination in the CNS of humans (metachromatic leukodystrophy, MLD). As an animal model, ASA(-/-) mice have previously been generated by disruption of the ASA gene and are known to develop lysosomal sulfatide storage similar to that in human MLD, and, moreover, to become deaf because of degeneration of the primary neurons of the auditory pathway. The present study deals with the cellular and topographic distribution of sulfatide storage throughout the CNS of ASA(-/-) mice between a few days and 24 months of age. Sulfatide accumulation was detected on the ultrastructural level and by histochemical staining with alcian blue. Sulfatide storage was found in oligodendroglia and neurons in young mice, and in activated microglia (phagocytes) in adult mice. Neuronal sulfatide storage was most prominent in many nuclei of the medulla oblongata and pons, and in several nuclei of midbrain and forebrain. Sulfatide-storing phagocytes were most frequent in the white matter tracts of aged ASA(-/-) mice, whereas no widespread demyelination was obvious. Loss of neurons was found in two nuclei of the auditory pathway of aged ASA(-/-) mice (ventral cochlear nucleus and nucleus of trapezoid body). The distributional pattern of sulfatide storage throughout the CNS of ASA(-/-) mice largely corresponds to data reported for human MLD. An important difference, however, which remains unexplained at present, is the absence of obvious demyelination from the CNS of ASA(-/-) mice up to the age of 2 years.

[Echocardiographic diagnosis of the aorto-left ventricular tunnel]. / Echokardiographische Diagnose des aorto-linksventrikulären Tunnels.

AIM/METHOD: The aorto-left ventricular tunnel (ALVT) is a rare congenital cardiac malformation with clinical findings of severe aortic insufficiency. We report the echocardiographic differentiation of different anatomical variants of ALVT in two infants. RESULTS: Echocardiography in both patients demonstrated severe enlargement of the ascending aorta and the left ventricle. In the first patient the ALVT originated from the ascending aorta above the right coronary sinus and entered the left ventricle just below the aortic valve. In the second patient the ALVT originated above the left coronary sinus and took a lateral course to the left ventricle. Colour-Doppler-sonography in both patients confirmed a systolic-diastolic flow across the tunnel. Many patients have associated cardiac defects. Exact determination of the morphology of the aortic valve and coronary arteries is mandatory for surgical repair. Postoperative follow-up studies focus on the function of the aortic valve and the left ventricle. CONCLUSION: Differentiation of different anatomical variants of ALVT is possible trough echocardiography. Cardiac catheterization is required only in cases with inadequate information about coronary artery anatomy.

Intestinal perforations in a premature infant caused by Bacillus cereus.

Although Bacillus cereus is a ubiquitous bacterium, the incidence of neonatal infections is very low with only a few cases of B. cereus infections in neonates reported in the literature. We report the case of a premature infant with multiple intestinal perforations and an abdominal B. cereus infection. The initial course was characterized by severe cardiovascular shock, anemia, thrombocytopenia and disseminated intravascular coagulation, leading to periventricular leukomalacia, alopecia capitis and toxic epidermal necrolysis. The possible role of B. cereus-associated enterotoxins for the clinical manifestations are discussed. Our case confirms previous reports of severe clinical symptoms in B. cereus infection in premature neonates. We speculate that the systemic complications of B. cereus infection are at least partly related to the effect of B. cereus-associated enterotoxins.

Metachromatic leukodystrophy: consequences of sulphatide accumulation.

UNLABELLED: Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide). This membrane lipid can be found in various cell types, but in particularly high concentrations in the myelin of the nervous system. Patients suffer from progressive, finally lethal, demyelination due to accumulation of sulphatide. In the nervous system, lipid storage not only affects oligodendrocytes but also neurons and, in addition, leads to astrogliosis and activation of microglia. At the cellular level, lysosomal sulphatide storage also affects the lipid composition of myelin itself and has consequences for the amount and localization of particular myelin membrane-associated proteins. Here we review data, largely based on an arylsulphatase A knock-out mouse model of metachromatic leukodystrophy. CONCLUSION: The knock-out mouse model of metachromatic leukodystrophy has provided insights into the histopathological and cellular consequences of sulphatide storage.