Homozygous deletion of RAG1, RAG2 and 5' region TRAF6 causes severe immune suppression and atypical osteopetrosis.

Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5' region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor-associated family member, plays an important role in T cell signaling and in RANKL-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported. The RAG proteins are essential for recombination of B and T cell receptors, and for the survival and differentiation of these cells. This is the first study to report a homozygous deletion of TRAF6 as a cause of human disease.

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs.

The IOP lowering effects of NCX 139, a new chemical entity comprising latanoprost amide and a NO-donating moiety, were compared to those of the respective des-nitro analog in in vitro assays and in rabbit and dog models of ocular hypertension. The NO donor, molsidomine as well as the prostamide bimatoprost (Lumigan(®)) and the prostaglandin agonist, latanoprost (Xalatan(®)) were also investigated for comparison. NCX 139 but not its des-nitro analog resulted in NO-mediated vascular relaxant effect in pre-contracted rabbit aortic rings (EC(50)=0.70±0.06 µM; E(max)=80.6±2.9%). Like bimatoprost (IC(50)=3.07±1.3 µM) or latanoprost (IC(50)=0.48±0.15 µM), NCX 139 displaced (3)H-PGF2α binding on recombinant human prostaglandin-F (FP) receptors with an estimated potency of 0.77±0.13 µM. In transient ocular hypertensive rabbits, bimatoprost and latanoprost were not effective while molsidomine elicited a dose-dependent reduction of IOP confirming the responsiveness of rabbits to NO but not to FP receptor agonists. NCX 139 tested at a therapeutically relevant dose, significantly lowered IOP while the des-nitro analog was not effective (0.03% NCX 139, Δ(max)=-12.8±2.0 mmHg). In glaucomatous dogs, 0.03% NCX 139 decreased IOP to a greater extent compared to an equimolar dose of the respective des-nitro derivative (Δ(max)=-4.6±1.0 and -2.7±1.3 mmHg, respectively for NCX 139 and its des-nitro analog). Albeit with low potency, NCX 139 also resulted effective in normotensive dogs while it did not reduce IOP in normotensive rabbits. NCX 139, a compound targeting two different and important mechanisms, is endowed with ocular hypotensive effects more evident in hypertensive conditions which may be of interest in the search of more effective treatments for hypertensive glaucoma.

Direct determination of [Formula: see text] for cylindrical ionization chambers in a 6 MV 0.35 T MR-linac.

To ensure accurate reference dosimetry with ionization chambers in magnetic resonance linear accelerators (MR-linacs), the influence of the magnetic field on the response of the ionization chambers must be considered. The most direct method considering the influence of magnetic fields in dosimetry is to apply an appropriate absorbed-dose-to-water primary standard. At PTB, a new water calorimeter has been designed which is capable to determine Dw,Q in an MR-linac. The new device allows the direct calibration of ionization chambers in terms of absorbed dose to water for MR-linac irradiation conditions. Hence, the correction factors [Formula: see text] can be determined which replace the current radiation-quality dependent correction factors [Formula: see text] for dosimetry in the presence of magnetic fields. In cooperation with Heidelberg University Hospital,[Formula: see text] factors were measured at the 6 MV 0.35 T Viewray MR-linac for different cylindrical ionization chambers with sensitive volumes ranging from 0.015 cm3 to 0.65 cm3. The chambers were placed both perpendicular and parallel in respect to the magnetic field. Standard uncertainties of about 0.5% were achieved.

MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade.

Signal transduction is controlled both by regulation of enzyme activation and by organization of enzymatic complexes with nonenzymatic adapters, scaffolds, and anchor proteins. The extracellular signal-regulated kinase (ERK) cascade is one of several evolutionarily conserved mitogen-activated protein (MAP) kinase cascades important in the regulation of growth, apoptosis, and differentiation. A two-hybrid screen was conducted to identify nonenzymatic components of this signaling cascade that might be important in regulating its activity. A protein called MP1 (MEK Partner 1) was identified that bound specifically to MEK1 and ERK1 and facilitated their activation. When overexpressed in cultured cells, MP1 enhanced activation of ERK1 and activation of a reporter driven by the transcription factor Elk-1. Expression of MP1 in cells increased binding of ERK1 to MEK1. MP1 apparently functions as an adapter to enhance the efficiency of the MAP kinase cascade.

Prostamides (prostaglandin-ethanolamides) and their pharmacology.

The prostamides are part of a large and continually expanding series of pharmacologically unique neutral lipids. They are COX-2 derived oxidation products of the endocannabinoid/endovanniloid anandamide. Prostamide pharmacology is unique and, as in the case of the endocannabinoids anandamide and 2-arachidonylglycerol, bears little resemblance to that of the corresponding free acids. By virtue of its close relationship to the anti-glaucoma drug bimatoprost, prostamide F(2alpha) has received the greatest research attention. Prostamide F(2alpha) and bimatoprost effects appear independent of prostanoid FP receptor activation, according to a litany of agonist studies. Studies involving freshly isolated and separate feline iridial smooth muscle cells revealed that bimatoprost and FP receptor agonists stimulated different cells, without exception. This suggests the existence of receptors that preferentially recognize prostamide F(2alpha). The recent discovery of prostamide antagonists has provided further support for prostamide receptors as discrete entities. The prototypical prostamide antagonists, AGN 204396 and 7, blocked the effects of prostamide F(2alpha) and bimatoprost but not those of PGF(2alpha) and FP receptor agonists in the feline iris. Second generation more potent prostamide antagonists, such as AGN 211334, should allow the role of prostamides in health and disease to be elucidated. From the therapeutics standpoint, the prostamide F(2alpha) analogue bimatoprost is the most efficacious ocular hypotensive agent currently available for the treatment of glaucoma.

Identification and pharmacological characterization of the prostaglandin FP receptor and FP receptor variant complexes.

BACKGROUND AND PURPOSE: A prostamide analogue, bimatoprost, has been shown to be effective in reducing intraocular pressure, but its precise mechanism of action remains unclear. Hence, to elucidate the molecular mechanisms of this effect of bimatoprost, we focused on pharmacologically characterizing prostaglandin FP receptor (FP) and FP receptor variant (altFP) complexes. EXPERIMENTAL APPROACH: FP receptor mRNA variants were identified by reverse transcription-polymerase chain reaction. The FP-altFP4 heterodimers were established in HEK293/EBNA cells co-expressing FP and altFP4 receptor variants. A fluorometric imaging plate reader was used to study Ca2+ mobilization. Upregulation of cysteine-rich angiogenic protein 61 (Cyr61) mRNA was measured by Northern blot analysis, and phosphorylation of myosin light chain (MLC) by western analysis. KEY RESULTS: Six splicing variants of FP receptor mRNA were identified in human ocular tissues. Immunoprecipitation confirmed that the FP receptor is dimerized with altFP4 receptors in HEK293/EBNA cells co-expressing FP and altFP4 receptors. In the studies of the kinetic profile for Ca2+ mobilization, prostaglandin F2alpha (PGF2alpha) elicited a rapid increase in intracellular Ca2+ followed by a steady state phase. In contrast, bimatoprost elicited an immediate increase in intracellular Ca2+ followed by a second phase. The prostamide antagonist, AGN211335, selectively and dose-dependently inhibited the bimatoprost-initiated second phase of Ca2+ mobilization, Cyr61 mRNA upregulation and MLC phosphorylation, but did not block the action of PGF2alpha. CONCLUSION AND IMPLICATIONS: Bimatoprost lacks effects on the FP receptor but may interact with the FP-altFP receptor heterodimer to induce alterations in second messenger signalling. Hence, FP-altFP complexes may represent the underlying basis of bimatoprost pharmacology.

Direct determination of k Q factors for cylindrical and plane-parallel ionization chambers in high-energy electron beams from 6 MeV to 20 MeV.

For the ionometric determination of the absorbed dose to water, D w, in high-energy electron beams from a clinical accelerator, beam quality dependent correction factors, k Q, are required. By using a water calorimeter, these factors can be determined experimentally and potentially with lower standard uncertainties than those of the calculated k Q factors, which are tabulated in various dosimetry protocols. However, one of the challenges of water calorimetry in electron beams is the small measurement depths in water, together with the steep dose gradients present especially at lower energies. In this investigation, water calorimetry was implemented in electron beams to determine k Q factors for different types of cylindrical and plane-parallel ionization chambers (NE2561, NE2571, FC65-G, TM34001) in 10 cm × 10 cm electron beams from 6 MeV to 20 MeV (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The measurements were carried out using the linear accelerator facility of the Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were achieved. For electron energies above 8 MeV, general agreement was found between the relative electron energy dependencies of the k Q factors measured and those derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as well as those from other experimental investigations. However, towards lower energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001 and the NE2571 chamber.

Determination of k Q factors for cylindrical and plane-parallel ionization chambers in a scanned carbon ion beam by means of cross calibration.

The accuracy in the dosimetry of therapeutically used carbon ion beams is predominantly affected by the large uncertainty of the so-called k Q factor of the ionization chamber used for the measurements. Due to a lack of experimental data, the k Q factor of ionization chambers in carbon ion beams is still derived by calculation, and, for instance, a standard uncertainty of about 3% is given for k Q factors tabulated in the TRS-398 dosimetric protocol. Recently, k Q factors for two Farmer-type ionization chambers have been determined experimentally in the entrance channel of 429 MeV/u carbon ions, achieving about a threefold reduction of the uncertainty. To further improve the data basis on experimental k Q factors with low uncertainties, k Q factors for the same irradiation condition have now been determined for eight different cylindrical ionization chambers (NE2571, FC65-P, FC23-C, CC25, CC13, TM30010, TM30011, TM30012) and three different plane-parallel ionization chambers (PPC-40, PPC-05, TM34001) by means of a cross-calibration procedure. Generally, standard measurement uncertainties of 1.1% could be achieved. Deviations of less than 1.2% were found between the experimental and the tabulated k Q values. Moreover, the consideration of the experimental values with their smaller uncertainties in updated versions of the dosimetric protocols might enable a substantial reduction of the uncertainties in the dosimetry of carbon ion beams.

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin-ethanolamides) in the feline iris.

BACKGROUND AND PURPOSE: The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. EXPERIMENTAL APPROACH: The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. KEY RESULTS: In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2alpha and the prostamide F2alpha analog bimatoprost but did not block the effects of PGF2alpha and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. CONCLUSIONS AND IMPLICATIONS: The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.

Direct determination of k Q for Farmer-type ionization chambers in a clinical scanned carbon ion beam using water calorimetry.

Until now, the dosimetry of carbon ions with ionization chambers has not reached the same level of accuracy as that of high-energy photons. This is mainly caused by the approximately threefold larger uncertainty of the k Q factor of ionization chambers, which, due to the lack of experimental data, is still derived by calculations. Measurements of absorbed dose to water, D w, by means of water calorimetry have now been performed in the entrance channel of a scanned 6 cm × 6 cm radiation field of 429 MeV/u carbon ions, allowing the direct calibration of ionization chambers and thus the experimental determination of k Q. Within this work, values for k Q have been determined for the Farmer-type ionization chambers FC65-G and TM30013. A detailed investigation of the radiation field enabled the accurate determination of correction factors needed for both calorimetric and ionometric measurements. Finally, a relative standard measurement uncertainty of 0.8% (k = 1) could be achieved for the experimental k Q values. For both chambers, the experimental k Q factors were found to be about 1% larger than those tabulated in the German DIN 6801-1 protocol, whereas compared to the theoretical values stated in the TRS-398 protocol, the experimental k Q value agrees within 0.4% for the TM30013 chamber but is about 1% lower in the case of the FC65-G chamber.

Deep hypothermia therapy attenuates LPS-induced microglia neuroinflammation via the STAT3 pathway.

Deep hypothermia therapy (HT) is a standard method for neuroprotection during complex pediatric cardiac surgery involving extracorporeal circulation and deep hypothermic cardiac arrest. The procedure, however, can provoke systemic inflammatory response syndrome (SIRS), one of the most severe side effects associated with pediatric cardiac surgery. To date, the cellular inflammatory mechanisms induced by deep HT remain to be elucidated. Therefore, we investigated the effects of deep HT (17°C) and rewarming on the inflammatory response in lipopolysaccharide (LPS) stimulated BV-2 murine microglia. Additionally, we also investigated the application of Stattic, a signal transducer and activator of transcription 3 (STAT3) activation inhibitor, as an alternative to physical cooling to attenuate the LPS-induced inflammatory response. Deep HT had no cytotoxic effect but attenuated microglia migration. IκBα degradation was delayed by deep HT resulting in the attenuation of pNF-κB p65 migration into the nucleus and significant decreases in pro-inflammatory IL-6, TNF-α, and MCP-1 expressions and secretions, as well as decreased anti-inflammatory IL-10 and SOCS3 expressions. Additionally, pStat3 was significantly down regulated under deep hypothermic conditions, also corresponding with the significant reduction in IL-6 and TNF-α expressions. Similar to the effects of HT, the application of Stattic under normothermic conditions resulted in significantly reduced IL-6 and TNF-α expressions. Moreover, attenuation of the inflammatory response resulted in decreased apoptosis in a direct co-culture of microglia and neurons. HT reduces the inflammatory response in LPS-stimulated BV-2 microglial cells, alluding to a possible mechanism of therapeutic hypothermia-induced neuroprotection. In the future, attenuating the phospho-STAT3 pathway may lead to the development of a neuroprotectant with greater clinical efficacy.

Comparison of leukotriene B4 and D4 effects on human eosinophil and neutrophil motility in vitro.

The motility of isolated normal human peripheral blood eosinophils and neutrophils in response to exogenous leukotrienes B4 and D4 was examined by means of a modified under-agarose technique and a novel quantitative sampling strategy. Leukotriene D4 was a potent chemoattractant for eosinophils, with a significant threshold chemotactic effect evident at 10(-10) M. The abolition of eosinophil chemotaxis by the potent and selective peptide-leukotriene-antagonist SK&F 104353 indicated the pharmacological specificity of the leukotriene D4-induced response. The chemokinetic response of eosinophils to leukotriene D4 generally did not differ significantly from spontaneous migratory activity of unstimulated cells. Leukotriene D4 did not, however, alter directed neutrophil motility until a very high concentration (10(-5) M) was achieved, although significant neutrophil chemokinesis relative to unstimulated movement was observed over the tested concentration range. Directional emigration of both eosinophils and neutrophils was induced by leukotriene B4 at concentrations as low as 10(-8) M. Analysis of leukocyte orientations provided evidence that chemokinetic responses were not being interpreted as indications of chemotactic behavior. These studies suggest that leukotriene D4 may behave as a potent and selective chemoattractant for human eosinophils at physiologically relevant concentrations.

Determination of leukotriene effects on human neutrophil chemotaxis in vitro by differential assessment of cell motility and polarity.

The effects of leukotriene (LT) B4 and D4 on the motility of human peripheral blood neutrophils were investigated employing a novel analytical method. Using the under-agarose technique, migration distance and vectorial orientation of neutrophils in response to selected LT concentrations were determined with the aid of digital image processing. Neutrophil polarization induced by a chemotactic gradient was very apparent even at fields taken adjacent to the cell seeding well where little directional cell motility had occurred. Thus, cell polarization appeared to be the earliest response to chemoattractive LTs. Cell motility occurred in a dose-dependent manner to LTB4 according to determination of the leading edge. LTD4 produced similar effects on neutrophil polarization and motility, but these occurred only at very high concentrations. These data support the view that vectorial orientation is a prerequisite for directional migration of cells and it is also feasible that these are separately regulated events. Furthermore, our studies confirm that LTB4 and, to a much lesser extent, LTD4 are chemotactic for human peripheral blood neutrophils.

Improved Image Quality in Head and Neck CT Using a 3D Iterative Approach to Reduce Metal Artifact.

BACKGROUND AND PURPOSE: Metal artifacts from dental fillings and other devices degrade image quality and may compromise the detection and evaluation of lesions in the oral cavity and oropharynx by CT. The aim of this study was to evaluate the effect of iterative metal artifact reduction on CT of the oral cavity and oropharynx. MATERIALS AND METHODS: Data from 50 consecutive patients with metal artifacts from dental hardware were reconstructed with standard filtered back-projection, linear interpolation metal artifact reduction (LIMAR), and iterative metal artifact reduction. The image quality of sections that contained metal was analyzed for the severity of artifacts and diagnostic value. RESULTS: A total of 455 sections (mean ± standard deviation, 9.1 ± 4.1 sections per patient) contained metal and were evaluated with each reconstruction method. Sections without metal were not affected by the algorithms and demonstrated image quality identical to each other. Of these sections, 38% were considered nondiagnostic with filtered back-projection, 31% with LIMAR, and only 7% with iterative metal artifact reduction. Thirty-three percent of the sections had poor image quality with filtered back-projection, 46% with LIMAR, and 10% with iterative metal artifact reduction. Thirteen percent of the sections with filtered back-projection, 17% with LIMAR, and 22% with iterative metal artifact reduction were of moderate image quality, 16% of the sections with filtered back-projection, 5% with LIMAR, and 30% with iterative metal artifact reduction were of good image quality, and 1% of the sections with LIMAR and 31% with iterative metal artifact reduction were of excellent image quality. CONCLUSIONS: Iterative metal artifact reduction yields the highest image quality in comparison with filtered back-projection and linear interpolation metal artifact reduction in patients with metal hardware in the head and neck area.

CT Metal Artifact Reduction in the Spine: Can an Iterative Reconstruction Technique Improve Visualization?

BACKGROUND AND PURPOSE: Metal-related artifacts from spine instrumentation can obscure relevant anatomy and pathology. We evaluated the ability of CT images reconstructed with and without iterative metal artifact reduction to visualize critical anatomic structures in postoperative spines and assessed the potential for implementation into clinical practice. MATERIALS AND METHODS: We archived CT projection data in patients with instrumented spinal fusion. CT images were reconstructed by using weighted filtered back-projection and iterative metal artifact reduction. Two neuroradiologists evaluated images in the region of spinal hardware and assigned a score for the visualization of critical anatomic structures by using soft-tissue and bone windows (critical structures totally obscured, n = 0; anatomic recognition with high diagnostic confidence, n = 5). Using bone windows, we measured the length of the most pronounced linear artifacts. For each patient, neuroradiologists made recommendations regarding the optimal use of iterative metal artifact reduction and its impact on diagnostic confidence. RESULTS: Sixty-eight patients met the inclusion criteria. Visualization of critical soft-tissue anatomic structures was significantly improved by using iterative metal artifact reduction compared with weighted filtered back-projection (median, 1 ± 1.5 versus 3 ± 1.3, P < .001), with improvement in the worst visualized anatomic structure in 88% (60/68) of patients. There was not significant improvement in visualization of critical osseous structures. Linear metal artifacts were reduced from 29 to 11 mm (P < .001). In 87% of patients, neuroradiologists recommended reconstructing iterative metal artifact reduction images instead of weighted filtered back-projection images, with definite improvement in diagnostic confidence in 32% (22/68). CONCLUSIONS: Iterative metal artifact reduction improves visualization of critical soft-tissue structures in patients with spinal hardware. Routine generation of these images in addition to routine weighted filtered back-projection is recommended.

Oxygen consumption in apneic premature infants after low-dose theophylline.

The effects of 2 mg/kg/day theophylline (serum concentrations, 2.9 to 4.7 micrograms/ml) on metabolic rate were observed in 11 premature infants with severe idiopathic apnea of prematurity. Oxygen consumption (VO2/kg) increased 25% from 6.5 +/- 0.4 (SEM) to 8.1 +/- 0.6 cc/min/kg after 24 to 48 hr of therapy. Respiratory quotient did not change. Apnea and bradycardia decreased from 8.6 +/- 1.4 to 1.6 +/- 0.5 episodes/hr and 4.4 +/- 1.1 to 1.2 +/- 0.4 episodes/hr, respectively. This dose of theophylline is effective in idiopathic apnea of prematurity and acts as a metabolic stimulant. In the premature infant, theophylline-induced increases in VO2 may be a result of changes in the sleep state.

Alterations in state in apneic pre-term infants receiving theophylline.

The present study is a report on 9 premature infants treated with aminophylline for relief of apnea. With serum theophylline levels of 2 to 10 microgram/ml, all infants experienced significant decrease of apneic episodes in association with increased wakefulness and increased amounts of active (REM) sleep. These effects may occur independently, but it is possible that the alteration of sleep states may be partially responsible for the decrease in apneic episodes in these infants.

Pharmacokinetics of betamethasone in twin and singleton pregnancy.

OBJECTIVE: The aims of the study were to compare the pharmacokinetics of betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy and to assess the adrenal suppression produced by betamethasone. STUDY DESIGN: We measured serial betamethasone and cortisol levels in 30 singleton and 21 twin pregnancies after the first dose of betamethasone and calculated the pharmacokinetic parameters for betamethasone including volume of distribution, half-life, and clearance. We also measured cord and maternal blood levels of betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies. RESULTS: The half-life of betamethasone in mothers with twin pregnancies was significantly shorter than that in mothers with singleton pregnancies (7.2 +/-2.4 versus 9.0 +/- 2.7 hours; P <.017). Clearance of betamethasone in the twin pregnancies appeared greater than in singleton pregnancies (8.4 +/- 6.4 versus 5.7+/- 3.1 L/h; P =.06) but did not reach statistical significance. Volume of distribution was similar in the two groups. Because the time between the last dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with a longer interval after treatment tended to have a higher cord-to-maternal betamethasone ratio than did mothers with a shorter interval in both twin and singleton pregnancies. This finding indicated delayed fetal clearance, but the correlation was weak (R (2) = 0.29 for twins and 0.08 for singletons). CONCLUSION: The shorter half-life of betamethasone in twin pregnancy than in singleton pregnancy may cause the level of betamethasone to be subtherapeutic for lung maturation in twin pregnancy.

Chronic pulmonary insufficiency of prematurity (CPIP).

This report describes a syndrome of delayed respiratory distress occurring in premature infants usually under 1,250 gm at birth. Unlike hyaline membrane disease, this syndrome occurs after four to seven days in a previously healthy infant; also unlike hyaline membrane disease, it persists for two to four weeks. Chronic pulmonary insufficiency of prematurity (CPIP) carries a 10% to 20% mortality rate. The infants are frequently apneic, require supplemental oxygen, but lack the radiologic findings of hyaline membrane disease or bronchopulmonary dysplasia. When compared with nondistressed infants of similar birthweight, infants with CPIP demonstrate slowly progressive atelectasis, hypoxemia, and hypercapnia. Recovery is usually complete by 60 days of age. The importance of CPIP is that an awareness of its existence can eliminate a false sense of security, often communicated to anxious parents, during the four-to-seven-day grace period before its appearance is clinically obvious. The physiologic similarities between CPIP and hyaline membrane disease suggest that lack of surfactant may play a role in the pathogenesis of CPIP.

Voiding after neonatal circumcision.

OBJECTIVE: To determine whether it is necessary to delay discharge of newly circumcised male neonates to observe voiding. SUBJECTS AND METHODS: A prospective study was conducted in 1992 and 1993 of 51 healthy male, newly circumcised neonates between 0 and 10 days of age. The neonates were observed for the time of first voiding after circumcision was performed. RESULTS: All neonates voided after circumcision at a mean age of 5.3 +/- 2.5 hours, and there were no complications noted in the study population. CONCLUSION: Healthy male infants who are circumcised without obvious complications can be expected to void, and it is unnecessary to delay hospital discharge to make this observation.