Arginine appearance and nitric oxide synthesis in critically ill infants can be increased with a protein-energy-enriched enteral formula.

BACKGROUND: Arginine is considered an essential amino acid during critical illness in children, and supplementation of arginine has been proposed to improve arginine availability to facilitate nitric oxide (NO) synthesis. Protein-energy-enriched enteral formulas (PE-formulas) can improve nutrient intake and promote anabolism in critically ill infants. However, the effect of increased protein and energy intake on arginine metabolism is not known. OBJECTIVE: We investigated the effect of a PE-formula compared with that of a standard infant formula (S-formula) on arginine kinetics in critically ill infants. DESIGN: A 2-h stable-isotope tracer protocol was conducted in 2 groups of critically ill infants with respiratory failure because of viral bronchiolitis, who received either a PE-formula (n = 8) or S-formula (n = 10) in a randomized, blinded, controlled setting. Data were reported as means ± SDs. RESULTS: The intake of a PE-formula in critically ill infants (aged 0.23 ± 0.14 y) resulted in an increased arginine appearance (PE-formula: 248 ± 114 µmol · kg(-1) · h(-1); S-formula: 130 ± 53 µmol · kg(-1) · h(-1); P = 0.012) and NO synthesis (PE-formula: 1.92 ± 0.99 µmol · kg(-1) · h(-1); S-formula: 0.84 ± 0.36 µmol · kg(-1) · h(-1); P = 0.003), whereas citrulline production and plasma arginine concentrations were unaffected. CONCLUSION: In critically ill infants with respiratory failure because of viral bronchiolitis, the intake of a PE-formula increases arginine availability by increasing arginine appearance, which leads to increased NO synthesis, independent of plasma arginine concentrations. This trial was registered at www.trialregister.nl as NTR515.

Urgent-SQ implant in treatment of overactive bladder syndrome: 9-year follow-up study.

AIMS: Electrical stimulation of the posterior tibial nerve (PTN) is an established therapy for the treatment of refractory overactive bladder syndrome (OAB). The Urgent-SQ™ is an implant that is surgically placed near the PTN and activated by an external pulse generator, allowing for "on demand" PTN stimulation, without the need for needle insertion. The current study presents results of a 9-year, open-label, follow-up of eight patients to address the long term safety and efficacy of the implant. METHODS: In 2003, eight patients with refractory OAB received a Urgent-SQ™ implant and were systematically followed up for 1 year. After that, the follow up continued as open-label study. The seven patients who still had the implant were contacted after 9 years and evaluated with an interview, physical exam, ankle X-ray, voiding diaries, and completed questionnaires about adverse events, performance, efficacy, safety, and quality of life (validated iQoL). RESULTS: Six of the seven patients still had sensory and loco-motor responses on stimulation at 9-year follow-up. Three of four patients who had a successful treatment response at 1 year, still use the device. The fourth patient restarted therapy. The implants are intact with no migration and/or displacement. All patients reported easy handling of the Urgent-SQ™. One patient reported sporadic spontaneous sensory responses. One patient reported occasional localized ankle discomfort. CONCLUSIONS: After 9 years of clinical experience, we demonstrated that implant driven PTNS with the Urgent-SQ™ is a safe therapy for OAB. The implant has a long lifespan and is well tolerated by patients.

Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double-blind randomised controlled trial.

OBJECTIVE: The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPE(Phe)). DESIGN: This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1 ± 0.3 g protein/kg/24 h, 119 ± 25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7 ± 0.2 g protein/kg/24 h, 84 ± 15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants <6 months). A combined intravenous-enteral phenylalanine stable isotope protocol was used on day 5 after admission to determine whole body protein metabolism and SPE(Phe). RESULTS: Protein balance was significantly higher with PE-formula than with S-formula (PE-formula: 0.73 ± 0.5 vs S-formula: 0.02 ± 0.6 g/kg/24 h) resulting from significantly increased protein synthesis (PE-formula: 9.6 ± 4.4, S-formula: 5.2 ± 2.3 g/kg/24 h), despite significantly increased protein breakdown (PE-formula: 8.9 ± 4.3, S-formula: 5.2 ± 2.6 g/kg/24 h). SPE(Phe) was not statistically different between the two groups (PE-formula: 39.8 ± 18.3%, S-formula: 52.4 ± 13.6%). CONCLUSIONS: Increasing protein and energy intakes promotes protein anabolism in critically ill infants in the first days after admission. Since this is an important target of nutritional support, increased protein and energy intakes should be preferred above standard intakes in these infants. Dutch Trial Register number: NTR 515.

Critically ill infants benefit from early administration of protein and energy-enriched formula: a randomized controlled trial.

BACKGROUND & AIMS: Nutritional support improves outcome in critically ill infants but is impeded by fluid restriction, gastric intolerance and feeding interruptions. Protein and energy-enriched infant formulas may help to achieve nutritional targets earlier during admission and promote anabolism. METHODS: Randomized controlled design. Infants with respiratory failure due to RSV-bronchiolitis received a protein and energy-enriched formula (PE-formula, n=8) or a standard formula (S-formula, n=10) during 5 days after admission. PRIMARY OUTCOME: nutrient delivery, energy and nitrogen balance and plasma amino acid concentrations. Secondary outcome: tolerance and safety. RESULTS: Nutrient intakes were higher in PE fed infants and met population reference intake (PRI) on day 3-5 whilst in S-fed infants PRI was met on day 5 only. Cumulative nitrogen balance (cNB) and energy balance (cEB) were higher in PE-infants compared to S-infants (cNB: 866+/-113 vs. 296+/-71 mg/kg; cEB: 151+/-31 and 26+/-17 kcal/kg, both P<0.01). Essential amino acid levels were higher in PE-infants but within reference limits whereas below these limits in S-infants. Both formulas were well tolerated. CONCLUSIONS: Early administration of a protein and energy-enriched formula in critically ill infants is well tolerated, promotes a more adequate nutrient intake and improves energy and nitrogen balance without adverse effects.

Induction or suppression of a B cell-specific response to self antigen in vivo is dependent upon dendritic cell activation via the TNF-alpha receptor at the time of antigen uptake.

In this study we show that the retinal autoantigen, S-antigen, contains a functional TNF-alpha homologous domain which stimulates maturation and differentiation of cultured dendritic cells (DC) or tissue DC via the p55 TNF-alpha receptor. Tissue DC became more dendritiform in shape, and migrated into culture supernatant. S-antigen also stimulated accumulation of cell surface MHC class II antigen with a corresponding loss of acidic intracellular vesicles, and induced IL-1beta and IL-12 mRNA expression in cultured bone marrow-derived DC. In addition, cultured splenic DC primed immune responses to S-antigen in vivo in the absence of other, exogenous cytokine sources. DC pulsed with either retinal S-antigen or another retinal autoantigen, interphotoreceptor retinoid binding protein (IRBP), were able to stimulate naive T cell proliferation in vitro, but only S-antigen-pulsed DC were able to induce an immune response in vivo and initiate antibody class switching. In contrast, IRBP-pulsed DC had no detectable in vivo priming effect and IgG antibody levels remained suppressed even after immunization with IRBP in complete Freund's adjuvant. These results indicate that DC from the same precursor population can either induce or suppress a B cell-specific response to self antigen in vivo, the outcome being dependent upon DC activation at the time of antigen uptake and presentation.

Antegrade colonic enemas.

Thirteen children aged 6-14 (mean 8) years in whom an antegrade colonic enema procedure was performed were reviewed retrospectively. All presented with refractory constipation or faecal soiling over a 3-year period. Nine of the children had previously undergone pull-through procedures for Hirschsprung's disease or high anorectal malformations. Two were suffering from spina bifida and two from idiopathic functional constipation. The operation was performed through a right iliac fossa incision. A catheterizable conduit was created. The appendix was brought out to the wound edge and made continent by intussuscepting the appendix base into the caecum. When the appendix was absent or unusable, a caecal tube was formed. Five patients suffered minor morbidity, six required a further operative procedure and two eventually required a sigmoid colostomy. However, the eventual outcome of a continent stoma was attained in 11 of the 13 children, all of whom would have been considered for sigmoid colostomy before introduction of the antegrade colonic enema procedure.

Topographical and topological organization of the thalamocortical projection to the striate and prestriate cortex in the marmoset (Callithrix jacchus).

In eleven hemispheres of nine marmoset monkeys (Callithrix jacchus), we have investigated the thalamo-cortical organization of the projections from the pulvinar to the striate and prestriate cortex. In each experiment, single or multiple injections of various retrograde fluorescent tracers were injected into adjacent regions or areas. In two experiments, horseradish peroxidase (HRP) was injected into the lateral geniculate nucleus (LGN) and the lateral pulvinar, respectively. The results show that the thalamo-cortical projection from LGN to striate cortex and from pulvinar to the prestriate cortex are similarly organized, but the geniculo-striate projection is more precise than the pulvinar-prestriate projection. The pulvinar-prestriate projection is topographically organized and preserves topological neighbourhood relations. Projection zones to the various visual areas are concentrically wrapped around each other. The projection zone to area 18 constitutes a central core region. It begins ventro-laterally in PuL where the pulvinar is in contact with the LGN. This contact zone we called the hilus region of the pulvinar. The area 18-projection zone stretches as a central cone into the posterior pulvinar through PuL and into PuM. It is surrounded by the projection zone to the posterior belt of area 19 and this in turn is surrounded by the projection zone to the anterior belt of area 19. The projection zones to area 19 are then surrounded medially and dorsally by zones projection to the temporal and parietal association cortex, respectively. The projection zone to area MT is located medio-ventrally in the posterior pulvinar (PuIP and surrounding nuclei) and coincides with a densely myelinated region. Area 17 also receives input from the pulvinar but probably predominantly in the region of the central visual field. The pulvinar zone projecting to area 17 is located ventrolaterally from the central core region projecting to area 18 and is contiguous laterally with the LGN. If the positions of the vertical and the horizontal meridian in the pulvinar correspond to those in the respective cortical projection zones, a second order visual field representation such as found in area 18, with the horizontal meridian split at an eccentricity of about 7-10 degrees, can also be recognized in the pulvinar.

Effect of dexamethasone on experimental brain edema in cats.

The authors studied the effects of dexamethasone, 0.3 mg/kg/hr administered intravenously beginning 1 hour before injury, in adult cats with brain edema secondary to cold-induced cortical lesions. Edema was quantitatively measured in cortex, gyral white matter, and central (deep) white matter at 3, 24, 48, and 72 hours, with and without dexamethasone, by determining specific gravity (density) of samples in a continuous gradient column. Cold-induced lesions resulted in edema, which was greatest in the white matter of the injured hemisphere but also present in the contralateral hemisphere. Except for a slight but significant increase in density (decreased edema) of cortex at 24 hours, dexamethasone therapy resulted in no reduction of cold-induced edema, and in some cases increased the edema.