Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios

OBJECTIVE: We determined whether inhaled nitric oxide (NO) could improve systemic oxygenation in human neonates with hypoplastic lungs. METHODS: A multicenter nonrandomized investigation was performed to study the efficacy of short-term NO inhalation. Inhaled NO was administered at 80 ppm to nine neonates without evidence of structural cardiac disease by echocardiography. Lung hypoplasia was due to congenital diaphragmatic hernia (CDH) in eight patients and to oligohydramnios in one patient. A total of 15 trials of NO inhalation were performed in these nine patients. Eight trials in seven patients were performed before extracorporeal membrane oxygenation ((ECMO); one patient had two trials) and seven trials were performed in five patients after decannulation from ECMO (two patients had two trials each). RESULTS: NO inhalation before ECMO did not change postductal PaO2 (42 +/- 3 mmHg vs 42 +/- 4 mmHg), oxygen saturation (SpO2; 89% vs 88%) or oxygenation index (31 +/- 4 cm H2O/torr vs 31 +/- 4 cm H2O/torr) for the group. All patients required ECMO support, which lasted from 5 to 17 days (mean 9). After decannulation from ECMO, NO inhalation increased postductal PaO2 from a median of 56 mm Hg (range 41 to 94) to a median of 113 mm Hg (range 77 to 326), P < .05. It decreased the oxygenation index from a median of 23 cm H2O/torr (range 11 to 7) to a median of 11 cm H2O/torr (range 4 to 21), P < .05. It increased SpO2 from 91% to 96% (P < .05) and pH from 7.48 +/- .03 to 7.50 +/- .03. CONCLUSION: In our patients with hypoplastic lungs, inhaled NO was effective only after ECMO. This could be due to maturational changes such as activating the endogenous surfactant system. Inhaled NO may be effective in neonates with hypoplastic lungs who have recurrent episodes of pulmonary hypertension after ECMO, even if they were previously unresponsive.     

Repeated doses of combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine

The combination of lysine acetylsalicylate and metoclopramide is effective in the treatment of migraine attacks. It was unknown whether repeated doses could improve efficacy. The aim of this open trial was to evaluate the effects of a second, and eventually a third dose of lysine acetylsalicylate and metoclopramide when a first dose of the treatment was ineffective. Patients were asked to take a second dose 2 hours after a first dose when they thought that the first dose was ineffective. They were allowed to take a third dose or their rescue medication 2 hours after the second dose when they judged that the treatment remained ineffective. Two hundred ninety-two patients were included in the study; 262 of the 292 patients treated 517 attacks. Headache relief (reduction in headache severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks after a third dose. Complete headache relief without recurrence and without use of a rescue medication was reported in 37% of the total attacks. The patients judged their treatment as good or excellent in 78% of attacks treated with one dose, in 41% of those treated with two doses, and in 19% of those treated with three doses. Tolerance, as judged by the patients, was considered good in 92% of treated attacks. Minor side effects occurred in 6% of attacks after a first dose, in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in 2% after unspecified delay, and in 14% overall. In conclusion, the efficacy of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks can be improved by repeated doses. It is well tolerated.     

Identification of a motif associated with the lactogenic actions of human growth hormone

Human growth hormone (hGH) stimulates somatogenic and lactogenic actions through the GH and prolactin (PRL) receptors, respectively. In contrast, non-primate GHs stimulate only somatotropic action. Phe44, of the human GH sequence is present in all hormones stimulating lactogenic action and absent in all hormones stimulating only somatotropic action. We speculate that the presence of Phe44 is a feature necessary for specifying lactogenic activity. In this report, the role of Phe44 was investigated by its deletion or substitution with alanine or leucine. Deletion of Phe44 or substitution with leucine did not significantly change the structure of hGH as determined by circular dichroism, absorbance, and fluorescence spectroscopies. In contrast, substitution of alanine perturbed the structure. Deletion of Phe44 reduced binding affinity for the lactogenic receptor, resulting in a reduced activation. Substitution with either alanine or leucine partially restored lactogenic receptor binding affinity, which correlated with the hormones' activity in the Nb2 rat lymphoma cells. All the recombinant hGHs had similar somatotropic activities in FDC-P1 cells transfected with the hGH receptor. These data indicate that the hydrophobic side chain of Phe44 is required for lactogenic receptor binding and activation but is unnecessary for somatotropic action.     

The Alkali-Silica Reaction in a Monolithic Opal

The alkali–silica reaction in opal was studied in the SEM with backscattered electrons, combined with quantitative image analysis, and also in an electron microprobe. A system of cracks was observed in the bands of gel in the opal, ahead of narrow fingers of gel into the unreacted opal and running across the aggregate–cement paste interface into the cement paste. There appeared to be good adhesion of the cement paste to the opal at the interface. Chemical analysis of the gel indicated the presence of calcium-rich gel with various compositions (CaO:SiO₂= 0.5–1.0) in the opal. There was considerable variation in the concentrations of K₂O and Na₂O in the gel. The analyses of the gel fell into three distinct composition ranges, with distinct boundaries between gels of different composition. Close to the interface there was depletion of calcium in the cement paste inner product.     

The distally based forearm island flap in hand reconstruction

The distally based forearm island flap is vascularized by the perforators of the distal radial artery. The skin flap is along the axis of the radial artery, and the pivot point of its subcutaneous pedicle is about 2 to 4 cm above the radial styloid process. We have treated 12 patients with 12 flaps for soft-tissue defects of the hand. Of these recipient sites, seven were in dorsal hands, two were in thumbs, two were in forearms, and one was in the palmar area. The donor-tissue variants included eight skin flaps, two adipofascial flaps, and two sensate flaps. The sizes of the flaps ranged from 6 x 4 cm to 14 x 6 cm. The donor site wound could be closed primarily in five patients. Two sensate flaps, innervated by the lateral antebrachial cutaneous nerve, could provide sensation for thumb reconstruction. The advantage of this flap is its constant and reliable blood supply without sacrifice of the main radial artery. The elevation of the flap is simple and rapid. There is the potential that this flap can be used as an innervated flap, and there is no need of microsurgical technique.     

Diisopropyl fluorophosphate inhibits receptor-activated Ca2+ influx in isolated rat hepatocytes

The influence of diisopropyl fluorophosphate (DFP) on receptor-activated increases in cytosolic free Ca2+ concentration ([Ca2+]i) in isolated rat hepatocytes was monitored by measuring phosphorylase a activity and the fluorescence ratio of the Ca2+ sensitive dye Indo-1. Pretreatment (2 min) of hepatocytes with DFP (1 mM) inhibited maximal increases in phosphorylase a activity stimulated by phenylephrine (1 microM), angiotensin II (5 nM), or vasopressin (10 nM) by 36, 35, and 17%, respectively, when the cells were incubated in Ca2+ (1 mM)-containing medium. In contrast, agonist-stimulated increases in phosphorylase a activity were similar in control and DFP-pretreated cells when cells were incubated in medium containing very low (10 nM) Ca2+. Addition of Ca2+ (1 mM) to hepatocytes maintained in the low Ca2+ buffer and exposed to agonists rapidly increased phosphorylase a activity in control cells; however, increases in DFP-pretreated cells were markedly attenuated. Changes in [Ca2+]i similar to those noted with phosphorylase a were observed using Indo-1. Addition of calcium ionophore A23187 to control or DFP-pretreated hepatocytes increased phosphorylase a activity to a similar extent in control and DFP-pretreated cells, demonstrating that DFP pretreatment did not alter the ability of the enzyme to respond to elevation in [Ca2+]i. Collectively, these data indicate that DFP pretreatment of hepatocytes irreversibly inhibits one or more components of the Ca2+ influx pathway.     

NGF-response of EGF-dependent progenitor cells obtained from human sympathetic ganglia

Signalling molecules are thought to play a significant role in determining the fate of neural crest progenitor cells. The human sympathetic chain was identified at 6.5, 7.5, 8.2, 10.2 and 11.4 postconception (PC) weeks demonstrating low affinity nerve growth factor (NGF) receptors, and was processed for tissue culture. In the presence of epidermal growth factor (EGF), floating spheres of proliferating progenitor cells were developed in vitro. In the absence of EGF progenitor cells differentiated into tyrosine hydroxylase (TH)-immunoreactive neuronal and TH-negative flat cells. NGF treatment significantly increased neurite outgrowth and survival of TH-immunoreactive cells. The multipotent cells we isolated differ from previously reported sympathoadrenal progenitors in that they give rise to TH immunoreactive neurones precociously sensitive to NGF.