Long-term results of Armstrong beveled grommet tympanostomy tubes in children

OBJECTIVE: Many different tympanostomy tubes have been developed with different sizes, shapes, compositions, and coatings. Despite the frequency of ventilation tube placement, very few large studies have examined the outcomes of patients receiving this procedure. An ideal tube would be easy to insert and would extrude at a predictable interval without complications. This study was performed to assess outcome measures and complication rates of the Armstrong beveled grommet tube. DESIGN: A retrospective case series of patients who had Armstrong beveled grommet tympanostomy tubes placed over a 3 year period by two Children's Hospital of Wisconsin pediatric Otolaryngology staff. MAIN OUTCOME MEASURES: Patient age, diagnosis, operative findings, and time to tube extrusion were reviewed. Otorrhea, perforation, and cholesteatoma rates were also assessed. RESULTS: Five hundred seven consecutive patients who had Armstrong tubes placed were reviewed. One thousand ninety-six Armstrong tubes were placed in these patients. Follow-up to extrusion rates were available for 756 tubes. The mean patient age at tube placement was 33.3 months, and the median age was 23 months. Mean and median times to extrusion were 16.5 and 15.5 months. One hundred sixty episodes of otorrhea were noted in 148 patients. Four patients had histories of cholesteatoma, none of which developed in conjunction with Armstrong tubes. Ten (1.32%) perforations that have not resolved over time were noted after Armstrong tube placement. CONCLUSIONS: Armstrong beveled grommet tympanostomy tubes have complication rates comparable with those reported for Armstrong or other short-acting tubes in smaller series.     

Differential modulation of beta2 and beta4 subunits of human neuronal nicotinic acetylcholine receptors by acidification

We have shown previously that acidification increases the affinity of agonists to rat alpha3beta4 nicotinic acetylcholine receptors (nAChR) and accelerates both the activation and decay kinetics of agonist-induced currents recorded from human embryonic kidney 293 cells stably expressing the receptor (Abdrakhmanova et al., 2002b). Here, we report on experiments examining the effect of rapid acidification on four different subtypes (alpha3beta4alpha5, alpha4beta2, alpha3beta2, and alpha3beta2alpha5) of human neuronal nAChRs stably expressed in tsA201 cells using a piezoelectric device for rapid (<5 ms) solution application. Application of ACh, at its EC(50) concentration for each nAChR subtype, at pH values 7.4 and 6.0, showed that acidification, similarly to that reported for rat alpha3beta4 acetylcholine receptors (AChRs), increased the amplitude and accelerated the activation and decay kinetics of the currents in human alpha3beta4alpha5 AChRs by increasing their affinity to the agonist. In sharp contrast, acidification reduced the amplitude but accelerated the decay kinetics of the current in all human beta2-containing nAChR subtypes (alpha3beta2, alpha3alpha5beta2, alpha4beta2) examined in this study. Brief application of ACh at saturating concentration (1 mM) on alpha3beta4alpha5 AChRs induced a "rebound current" upon rapid washout of the agonist at pH 7.4, but no "rebound current" was observed in alpha3beta2 AChRs. Surprisingly, acidification, pH 6.0, applied only during the agonist pulse also accelerated the decay kinetics of the "rebound current". Our data provide evidence for the specificity of proton-induced modulation of neuronal nAChRs based on their beta subunit composition. Furthermore, in alpha3beta4alpha5 AChR, we find that protonation effects may persist, after washout of acidic solutions, consistent with proton-induced conformational changes of the receptor.     

Analogs of alpha-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors

Neuronal nicotinic acetylcholine receptors (nAChRs) both mediate direct cholinergic synaptic transmission and modulate synaptic transmission by other neurotransmitters. Novel ligands are needed as probes to discriminate among structurally related nAChR subtypes. Alpha-conotoxin MII, a selective ligand that discriminates among a variety of nAChR subtypes, fails to discriminate well between some subtypes containing the closely related alpha3 and alpha6 subunits. Structure-function analysis of alpha-conotoxin MII was performed in an attempt to generate analogs with preference for alpha6-containing [alpha6(*) (asterisks indicate the possible presence of additional subunits)] nAChRs. Alanine substitution resulted in several analogs with decreased activity at alpha3(*) versus alpha6(*) nAChRs heterologously expressed in Xenopus laevis oocytes. From the initial analogs, a series of mutations with two alanine substitutions was synthesized. Substitution at His9 and Leu15 (MII[H9A;L15A]) resulted in a 29-fold lower IC(50) at alpha6beta4 versus alpha3beta4 nAChRs. The peptide had a 590-fold lower IC(50) for alpha6/alpha3beta2 versus alpha3beta2 and a 2020-fold lower IC(50) for alpha6/alpha3beta2beta3 versus alpha3beta2 nAChRs. MII[H9A;L15A] had little or no activity at alpha2beta2, alpha2beta4, alpha3beta4, alpha4beta2, alpha4beta4, and alpha7 nAChRs. Functional block by MII[H9A;L15A] of rat alpha6/alpha3beta2beta3 nAChRs (IC(50) = 2.4 nM) correlated well with the inhibition constant of MII[H9A;L15A] for [(125)I]alpha-conotoxin MII binding to putative alpha6beta2(*) nAChRs in mouse brain homogenates (K(i) = 3.3 nM). Thus, structure-function analysis of alpha-conotoxin MII enabled the creation of novel selective antagonists for discriminating among nAChRs containing alpha3 and alpha6 subunits.     

Is the BPD epidemic diminishing?

In a previous study of very low birth weight neonates, < or = 1500 g, admitted to the Vanderbilt University Neonatal Intensive Care Unit (NICU) from 1976-1990, improvements in survival were accompanied by a corresponding increase in the incidence of bronchopulmonary dysplasia (BPD). Since then, certain neonatal and perinatal interventions have been introduced and may influence neonatal outcomes. In this study, we have continued the analysis of the incidence of 3 outcomes: 1) Neonatal death (NEOD), 2) BPD, and 3) NEOD or BPD (NEOD/BPD) for an additional 7 years, 1991-1997. A retrospective study was performed of 3,837 patients with birth weight < or = 1500 g and admitted to the Vanderbilt NICU within 24 hours of birth from 1976 through 1997. The outcomes NEOD, BPD, or NEOD/BPD were modeled by using multiple logistic regression with the following risk factors included as covariates: birth weight, gestational age, Apgar scores at 1 and 5 minutes, gender, race, birth location, diagnosis of hyaline membrane disease, maternal age, maternal diabetes, delivery method, multiple births, duration of ruptured membranes, and biologically relevant interactions among these covariates. To assess time trends in the risk factors and outcomes, patients were divided into time periods (1 = 1976-80, 2 = 1981-85, 3 = 1986-90, 4 = 1991-95, and 5 = 1996-97). For each outcome, only covariates or interactions among covariates found to be significant were retained in the final model. Adjusted odds ratios and 95% confidence intervals were calculated to measure the risk associated with a given time period in comparison to the preceding period. There was a progressive decline in NEOD across all time periods. The previously described increase in BPD from period 1 through period 3 is followed by a decrease in periods 4 and 5. The risk of NEOD/BPD remained fairly constant from period 1 to period 3, but then showed a significant decrease over the two most recent periods. Prior to 1991, the cost of improved survival among very low birth weight infants in this large NICU was an increased incidence of BPD. Since 1991, the risk of BPD has been decreasing even though survival continues to improve. If these findings are also representative of other NICUs, they signify an important reduction in the impact of BPD as one of the costly sequelae of prematurity.     

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

The proximate determinants of the decline to below-replacement fertility in Addis Ababa,Ethiopia

Between 1990 and 2000, the total fertility rate (TFR) in Ethiopia declined moderately from 6.4 to 5.9 children per woman of reproductive age. During the same period, the TFR in the capital city of Addis Ababa declined from 3.1 to 1.9 children per woman. Even more striking than the magnitude of this decline is that it occurred in the absence of a strong and effective national family planning program. In this study, the components of this fertility decline are identified using the Bongaarts framework of the proximate determinants of fertility. The results of a decomposition analysis indicate that a decrease in the age-specific proportions of women who are married, followed by an increase in contraceptive use are the most important mechanisms by which fertility has declined in Addis Ababa. Poor employment prospects and relatively high housing costs are likely factors that encourage couples to delay marriage and reduce marital fertility.     

In vitro inhibition of adrenal catecholamine secretion by steroidal metabolites of ginseng saponins

We reported previously that the protopanaxatriol saponins in Panax ginseng greatly reduce the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh). However, protopanaxadiol saponins showed only slight inhibitory effects. Recent studies have demonstrated that oligosaccharides connected to the hydroxyl groups of the aglycone in ginseng saponins (ginsenosides) are in turn hydrolyzed in the digestive tract and absorbed into the circulation following oral administration of ginseng. Therefore, the present study was performed to investigate the effects of the major ginsenoside metabolites (M1, M2, M3, M4, M5, M11, and M12) on catecholamine secretion. All of these metabolites were shown to be potent inhibitors of ACh-evoked secretion, and M4 was the most effective. M4 blocked not only the ACh-induced Na(+) influx into the chromaffin cells but also the ACh-induced inward current into Xenopus oocytes expressing human alpha 3 beta 4 neuronal nicotinic ACh receptors. M4 reduced the secretion induced by high K(+), an activator of voltage-sensitive Ca(2+) channels, to a much lesser extent than that evoked by ACh. M1, M2, M3, M5, and M12 are protopanaxadiol saponin-derived metabolites. Therefore, these results imply that the protopanaxadiol saponins are prodrugs, and they show more potent inhibitory activity following metabolism in the digestive tract. The results further suggest that the metabolites act on nicotinic ACh receptors, blocking Na(+) influx through the receptors, and consequently reduce the catecholamine secretion from bovine adrenal chromaffin cells. The inhibitory effect of ginsenoside metabolites is probably one of the mechanisms of action responsible for the pharmacological effects of ginseng.