Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial.

RATIONALE: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. OBJECTIVES: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. METHODS: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. MEASUREMENTS AND MAIN RESULTS: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (ß-carotene, coenzyme Q10, γ-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P < 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. CONCLUSIONS: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

Effect of salt supplementation on the rate of inadequate sweat collection for infants less than 3 months of age referred for the sweat test.

BACKGROUND: Sweat testing in young infants (≤ 3 months) with a positive newborn screen for Cystic Fibrosis (CF) can yield higher rates of inadequate sweat collection. The role of salt supplements in improving sweat collection has not been studied before. METHODS: All young infants referred to our CF center for sweat testing were randomized to either receive salt supplements {1/8th teaspoon salt (750 mg)} mixed in formula feeds 1 day prior to sweat testing (study group) or no salt supplement (controls). RESULTS: Of the 151 young infants that underwent sweat testing over 18 months, 75 received salt supplements, while 76 did not. A total of 9 (11.8%) infants in the salt supplement group had inadequate sweat collection, as compared to 4 (5.2%) infants in the control group (p = 0.16, Fisher's Exact Test). CONCLUSIONS: Oral salt supplementation for young infants prior to sweat testing does not help to reduce the rates of inadequate sweat collection.

Improving screening for diabetes in cystic fibrosis.

PURPOSE: Annual screening for cystic fibrosis-related-diabetes (CFRD) using oral glucose tolerance test (OGTT) is recommended, but national testing rates are low. The purpose of this paper is to implement the quality improvement (QI) initiative to improve cystic fibrosis (CF) annual screening rates among patients at one CF center. DESIGN/METHODOLOGY/APPROACH: To improve screening for CFRD at the CF Center, the authors used the Dartmouth Microsystem Improvement Ramp method and formed a collaborative working group. A process map was created to outline the steps and a fishbone analysis was performed to identify barriers and to utilize resources for implementing new interventions. FINDINGS: Prior to these interventions, 21 percent of eligible patients had completed annual screening and after the intervention, it rose to 72 percent. The initial completion rate with the first prescription was only 50 percent, but it improved steadily to 54/75 (72 percent) in response to reminder letters sent six weeks after the initial script was given. PRACTICAL IMPLICATIONS: Close tracking and reminder letters can improve adherence with annual OGTT screening for CFRD among CF patients, with special emphasis on high-risk patients. ORIGINALITY/VALUE: There should be a special emphasis on screening for CFRD in high-risk CF patients (those with low BMI or higher age). This QI initiative brought about several operational changes in the annual OGTT screening process that have now become the standard operating procedure at the center.

Why does adenotonsillectomy not correct enuresis in all children with sleep disordered breathing?

PURPOSE: We analyzed the outcome of nocturnal enuresis after adenotonsillectomy in children with sleep disordered breathing. We also evaluated differences in demographic, clinical, laboratory and polysomnography parameters between responders and nonresponders after adenotonsillectomy. MATERIALS AND METHODS: We prospectively evaluated children 5 to 18 years old diagnosed with sleep disordered breathing (snoring or obstructive sleep apnea syndrome) on polysomnography and monosymptomatic primary nocturnal enuresis requiring adenotonsillectomy to release upper airway obstruction. Plasma antidiuretic hormone and brain natriuretic peptide were measured preoperatively and 1 month postoperatively. RESULTS: Sleep studies were done in 46 children and 32 also underwent blood testing preoperatively and postoperatively. Mean ± SD patient age was 8.79 ± 2.41 years and the mean number of wet nights weekly was 6.39 ± 1.26. Polysomnography revealed obstructive sleep apnea syndrome in 71.7% of patients and snoring in 28.3%. After adenotonsillectomy 43.5% of patients became dry. Preoperative polysomnography findings indicated that responders, who were dry, had significantly more arousals and obstructive apnea episodes but fewer awakenings than nonresponders, who were wet. Significant increases in plasma antidiuretic hormone and significant decreases in plasma brain natriuretic peptide were seen in all children with no difference between responders and nonresponders. No difference between the groups was noted in age, gender, race, body mass index, constipation, preoperative number of wet nights weekly or type of sleep disordered breathing. CONCLUSIONS: Nocturnal enuresis resolved after adenotonsillectomy in almost half of the children with sleep disordered breathing. Those who became dry had more frequent arousal episodes caused by apnea events than those who remained wet.

Sleep architecture parameters that predict postoperative resolution of nocturnal enuresis in children with obstructive sleep apnea.

OBJECTIVES: We performed a prospective cohort study in a pediatric tertiary care center to determine whether preoperative sleep architecture is associated with complete resolution of nocturnal enuresis (NE) after adenotonsillectomy. METHODS: Thirty-seven pediatric patients with primary NE who underwent adenotonsillectomy for obstructive sleep apnea (OSA) were evaluated. Preoperative polysomnograms, as well as preoperative and postoperative reports of NE, were recorded. We performed chi2 analysis, Fisher's exact test (for p values), and t-tests to evaluate the impact of multiple demographic characteristics on sleep architecture, comparing children with resolved NE to those with unresolved NE after adenotonsillectomy. RESULTS: The patients' mean age was 8.0 years (SD, 2.32 years). All children had presurgical primary NE. No age or gender differences were identified between children with resolved NE and those with unresolved NE. After surgery, more than half of the participants had resolution of NE. A higher percentage of boys had unresolved NE (chi2 = 3.63; p = 0.06). Improvement of NE was identified in children with a higher obstructive apnea-hypopnea index and more desaturation events. Eleven of the 12 children with prolonged stage 2 sleep reported resolution of NE (p = 0.001). Children with an obstructive apnea-hypopnea index of greater than 10 had a significantly greater rate of resolution of NE (p = 0.01). Logistic regression demonstrated that an elevated body mass index and the interaction of severe OSA and prolonged stage 2 sleep predicted resolution of NE. All 10 children with severe OSA and an abnormal total time spent in stage 2 sleep had resolution of NE. CONCLUSIONS: Adenotonsillectomy is a treatment option for children with OSA and NE. Postoperative resolution of NE was seen in 51.4% of patients who underwent adenotonsillectomy. The children with both severe OSA and prolonged stage 2 sleep were 3.4 times as likely to have postoperative resolution of NE. These results suggest that there are significant differences in preoperative sleep architecture between children whose NE resolves after adenotonsillectomy and those whose NE does not resolve.

Melatonin attenuates hypochlorous acid-mediated heme destruction, free iron release, and protein aggregation in hemoglobin.

In inflammatory diseases, where hypochlorous acid (HOCl) is elevated, iron homeostasis is disturbed, resulting in accumulation of free iron. Free iron is toxic by virtue of its ability to generate free radicals through the Fenton reaction. HOCl is generated by myeloperoxidase, (MPO) using chloride and hydrogen peroxide as substrates. Recent studies demonstrate that HOCl binds to the heme moiety of hemoglobin (Hb), which generates a transient ferric species whose formation and decay kinetics indicate it participates in protein aggregation, heme destruction, and free iron release. Here, we show that melatonin prevents HOCl-mediated Hb heme destruction and protein aggregation, using a combination of UV-vis spectrophotometry, ferrozine colorimetric assay, and in-gel heme staining. We also show that melatonin treatment prevents HOCl-mediated loss of red blood cell (RBC) viability, indicating biologic relevance of this finding. The mechanism by which melatonin prevents HOCl-mediated Hb heme destruction is by direct scavenging of HOCl and/or through the destabilization of the higher Hb oxidative states intermediates, ferryl porphyrin radical cation Hb-Fe(IV)=O(+π•) and Hb-Fe(IV)=O, which are formed through the reaction of HOCl with Hb. Our work establishes a direct mechanistic link between melatonin and its protective effect in chronic inflammatory diseases. Collectively, in addition to acting as an antioxidant and as a MPO inhibitor, melatonin can also exert its protective effect by inhibiting HOCl-mediated heme destruction of hemoproteins and subsequent free iron release.

Desensitization to inhaled aztreonam lysine in an allergic patient with cystic fibrosis using a novel approach.

OBJECTIVE: To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. CASE SUMMARY: A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. DISCUSSION: Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. CONCLUSIONS: Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to ensure that they can continue to receive these medications safely.

Willingness to Accept COVID-19 Vaccine and Associated Factors Among Adult Household Members in Dire Dawa City Administration, East Ethiopia.

Background: COVID-19 vaccine is a vital strategy to prevent and control this pandemic. This will depend principally on people's acceptance of COVID-19 vaccine. We aimed to determine the willingness to accept COVID vaccine among adult household members of Dire Dawa city administration. Methods: A community-based cross-sectional study was conducted among randomly selected 634 adult household members in the Dire Dawa city administration during January 16-31/2022. Data were collected using face-to-face interview. Extent of willingness was estimated using participants' self-report. Bivariate and multivariate logistic regression models were fitted, and statistical significance was set at p-value <0.05. Results: The estimated willingness to accept COVID-19 vaccine was 28.4% (95% CI 25.1, 31.5) in the study setting. The odds of willingness to accept COVID-19 vaccine was higher for household members living without at least one chronic disease (AOR 1.7, 95% CI 1.10, 2.70), who had good knowledge score (AOR 2.3, 95% CI 1.31, 2.18) and positive attitude score (AOR 5.5, 95% CI 2.1, 14.5) compared to their counterparts, respectively. The estimated willingness to accept COVID-19 vaccine among household members with good knowledge score was 47.4 (95% CI 42.1, 52.7) and 15.5 (95% CI 8.7, 22.2) among those with poor knowledge. Nearly, 90% of the study participants had limited knowledge about COVID 19 vaccine. Conclusion: The estimated willingness to accept COVID-19 vaccine in the study setting is very low and far from the set target to be reached by the end of 2022. Being free from chronic disease, and having good knowledge and positive attitude about COVID-19 vaccine were the main drivers for willingness. Public awareness directed to increase knowledge about COVID-19 vaccine and attitude change strategies should be scaled up to increase the COVID-19 vaccine uptake. Moreover, those individuals with chronic diseases need special attention.

Five cases of missed cystic fibrosis heterozygous mutations identified after a positive newborn screen on a sibling.

In Michigan (MI), NBS for CF was started in October 2007 using the IRT/DNA protocol. In 2016, a component of the Hologic molecular test kit used by the MI NBS lab was recalled (40 CF mutation 2nd tier test). This recall had a major impact on states using the Hologic test kits in their NBS programs. Michigan specimens were sent to another state's NBS Lab for 2nd tier testing using the Luminex 60 mutation test kit until the Luminex kit could be procured and validated in MI. In this report, we present five cases born during this time period. These cases were initially reported out as having normal NBS results for CF but had heterozygous F508 del (c.1521_1523delCTT) mutations later identified. Of the five cases, one was diagnosed with CF (Case1), one with CF related metabolic syndrome (CRMS), and the other three were carriers.

Drying temperature-dependent profile of bioactive compounds and prediction of antioxidant capacity of cashew apple pomace using coupled Gaussian Process Regression and Support Vector Regression (GPR-SVR) model.

Crude extracts from cashew apple pomace (CAP) dried at different temperatures were used in High-Pressure Liquid Chromatography to quantify total alkaloids content (TAC), total flavanoids content (TFC), total saponin content (TSC) and total phenolics content (TPC). Diphenyl-1-picrylhydrazyl (DPPH) was used to determine the antioxidant capacity (AOC) of CAP. Fourier-Transformed Infrared Spectroscopy-Attenuated Total Reflectance (FTIR-ATR) was used to identify the functional groups present in the pomace. TAC, TFC, TSC and TPC were used as inputs to model AOC using Gaussian Process Regression (GPR), and Support Vector Regression (SVR) and a coupled model was developed using the residuals of GPR and SVR. It was found that increasing drying temperature decreased TAC, TFC, TPC and AOC but TSC increased. Both GPR and SVR predicted AOC with high accuracy. Drying CAP at lower temperature preserved more bioactive compounds hence high AOC; FTIR-ATR showed that CAP has good hydration capacity and contains majorly inorganic phosphates, aliphatic hydrocarbons and primary alcohols. Model coupling enhanced AOC prediction.

Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung-function measures in urban family children.

PURPOSE: Understanding the interplay between genes and in-utero tobacco exposure in affecting child lung development is of great significance. In this study, we tested the hypothesis that tobacco-related lung-function reduction in children differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase Mu 1 (GSTM1). MATERIALS AND METHODS: Data were collected among 370 children (6-10 years old, 81.6% African-Americans) and their biological mothers visiting a large children's hospital. Study hypotheses were tested using multiple regression method. RESULTS: Among the study sample, 143 mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric measures (mean±SD) included were: forced vital capacity (FVC)=1635±431 mL, forced expiratory volume in the first 1s (FEV1)=1440 ±360 mL, percent FEV1/FVC ratio=89±12, and forced expiratory flow between the 25% and 75% of FVC (FEF25-75)=1745±603 mL. In addition to a tobacco effect on FVC (-131 mL, 95% CI: -245, -17) and FEV1/FVC ratio (42, 95% CI: 1, 83), regression analysis controlling for covariates indicated that for the subsample of children whose mothers were CYP1A1⁎2A homozygous, maternal daily smoking was associated with -734 mL (95% CI: -1206, -262) reductions in FEV1 and -825 mL (95% CI: -909, -795) reductions in FVC; reduced smoking was still associated with -590 mL (95% CI: -629, -551) reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with -176 mL (95% CI: -305, -47) reductions in FVC. DISCUSSION AND CONCLUSIONS: Maternal smoking during pregnancy was significantly associated with lung-function reduction in children, particularly for those whose mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion.

Allergic Broncho-Pulmonary Aspergillosis.

Allergic broncho-pulmonary aspergillosis (ABPA) is an immunologically mediated lung disease that usually occurs in people with a diagnosis of asthma or cystic fibrosis. It is a noninvasive lung disease caused by colonization of the airways with Aspergillus fumigatus. In people who are susceptible, Aspergillus leads to an exaggerated immune response and ultimately pulmonary inflammation and lung damage. Patients with ABPA typically present with poorly controlled asthma, recurrent pulmonary infiltrates, and bronchiectasis. Diagnosis of ABPA is established based on a combination of clinical manifestations as well as laboratory and radiological evaluations. Delay in diagnosis can result in airway destruction and pulmonary fibrosis, which may result in significant morbidity and mortality. This article discusses the clinical characteristics, diagnosis, and management of patients with ABPA. It aims to serve as a tool for pediatricians to aid in early recognition of this debilitating disease and consider referral, facilitating early diagnosis and treatment. [Pediatr Ann. 2021;50(5):e214-e221.].

Seroprevalence of SARS-CoV-2 antibody among individuals aged above 15 years and residing in congregate settings in Dire Dawa city administration, Ethiopia.

BACKGROUND: Determining the extent of seropositivity of SARS-CoV-2 antibody has the potential to guide prevention and control efforts. We aimed to determine the seroprevalence of SARS-CoV-2 antibody among individuals aged above15 years and residing in the congregate settings of Dire Dawa city administration, Ethiopia. METHOD: We analyzed COVID-19 seroprevalence data on 684 individuals from a community based cross-sectional survey conducted among individuals aged above 15 years and residing in congregate settings in Dire Dawa from June 15 to July 30, 2020. Data were collected using interview and blood sample collection. Participants were asked about demographic characteristics, COVID-19 symptoms, and their practice of preventive measures. Seroprevalence was determined using SARS-CoV-2 IgG test. Bivariate and multivariate multilevel mixed effects logistic regression model was fitted and statistical significance was set at p value < 0.05. RESULT: The estimated SARS-CoV-2 seroprevalence was 3.2% (95 % CI 2.0-4.8) in the study region with no differences by age and sex but considerable differences were observed by self-reported practice of COVID-19 preventive measures. The cluster effect is not significant (P = 0.396) which has suggested no evidence of heterogeneity in SARS-CoV-2 seroprevalence among the clusters. The odds of SARS-CoV-2 antibody seroprevalence were higher for individuals who were employed and work by moving from home to work area (AOR; 9.73 95% CI 2.51, 37.68), reported of not wearing facemasks when leaving home (AOR; 6.4 95% CI 2.30, 17.66) and did not practice physical distancing measures (AOR; 10 95% CI 3.01, 33.20) compared to their counterparts, respectively. Our estimated seroprevalence of SARS-CoV-2 among participants who reported not to have practiced social distancing measures was 12.8 (95% CI, 7.0, 19) and 1.5 (95% CI, 0.5, 2.5) among those who reported of practicing them. More than 80% of study participants reported of implementing infection prevention measures (face masks and physical distancing recommendations). CONCLUSION: The detected SARS-CoV-2 seroprevalence among the study participants was low at the time of the survey indicating higher proportion of population yet to be infected. COVID-19 preventive measures were associated with reduced seroprevalence and should be promoted to avoid transmission to the uninfected majority.

Ceftolozane/Tazobactam Treatment of Multidrug-resistant Pseudomonas aeruginosa Infections in Children.

The clinical use, safety and effectiveness of ceftolozane/tazobactam among 13 patients 3 months to 19 years of age infected with multidrug-resistant Pseudomonas aeruginosa are described. All but one patient achieved clinical cure after initial treatment. Adverse drug events attributed to treatment included transaminitis and neutropenia which occurred in 2 patients and resolved upon dose reduction.

Comorbid monosymptomatic nocturnal enuresis and snoring exhibit an additive effect on impairments in health-related quality of life.

INTRODUCTION/BACKGROUND: Health-related quality of life (HRQOL) is a relatively new concept in pediatrics, but it has shown to be extremely important in terms of clinical care, treatment planning, and compliance with medical and behavioral recommendations. Two groups of children who are at risk for impairments in HRQOL are those who have bed-wetting and those who snore or have sleep apnea. OBJECTIVE: The present study sought to determine whether the combination of monosymptomatic nocturnal enuresis (MNE) and sleep-disordered breathing (SDB) results in diminished HRQOL in a pediatric sample. STUDY DESIGN: A retrospective chart review was conducted in an outpatient pediatric urology clinic and in an outpatient pulmonology clinic. Parents of the patients completed the Pediatric Sleep Questionnaire (PSQ) to assess the presence of SDB and snoring, and HRQOL was assessed using the Obstructive Sleep Apnea Syndrome-18-item (OSAS-18) scale, both validated measures, as part of the child's clinical workup. RESULTS: One hundred fifty-two (85 males and 67 females ) patients were included and were categorized into any of the following four groups: (1) MNE only, (2) SDB only, (3) MNE + SDB, or (4) healthy control. Patients in the SDB-only group had significantly more severe SDB than those in the other groups. As such, severity of SDB was controlled for in analyses. Results revealed that the four groups significantly differed on all subscales of the OSAS-18, which are Sleep Disturbance, Physical Symptoms, Emotional Symptoms, Daytime Functioning, and Caregiver Concerns. Post hoc analyses revealed the MNE + SDB group had more impairments on each subscale. Analysis of the total impairments revealed that children with only one condition (MNE or SDB) reported similar levels of impairments in HRQOL and patients with MNE + SBD reported significantly higher levels of impairments, as it appears that these comorbid conditions have an additive effect on HRQOL. DISCUSSION: Children with comorbid MNE and SDB are at significantly higher risk for reporting impairments in their HRQOL than children who have only one of these conditions. While it is already known that children with MNE are at risk for emotional, behavioral, and social difficulties and children with SDB are at risk for neurobehavioral difficulties, it is possible that children with both conditions are at risk for a multitude of negative consequences. CONCLUSION: These data emphasize the importance of urologist screening for SDB and pulmonologist screening for MNE as part of their routine clinical practice.

Health Effects Reported by Adolescent Water Pipe and/or Cigarette Smokers Compared to Nonsmokers.

PURPOSE: The purpose of this study was to determine the prevalence of respiratory and/or physical fitness health problems in adolescent (ages 18-21) water pipe (WP) smokers (with or without cigarette smoking), cigarette-only smokers, and nonsmokers. METHODS: A comparative four-group study design was used to recruit a non-probability sample of 153 WP smokers only, 103 cigarette smokers only, and 102 cigarette+WP smokers along with 296 nonsmokers. Our hypothesis was that youth who smoked WPs and/or cigarettes would report more respiratory problems and/or poorer physical fitness than those who did not smoke. RESULTS: The results showed that coughs were significantly associated with smoking in all three of the smoking groups (p < .05). Cigarette-only smokers reported the most adverse outcomes with more wheezing, difficulty breathing, and less ability to exercise without shortness of breath. A dose-response analysis showed similar patterns of adverse health effects for both WP and cigarette smokers. The combined use of both products was not appreciably worse than smoking one product alone. This could be due to cigarette+WP smokers' reporting using less of the respective products when only one product was smoked. CONCLUSIONS: Even during the adolescent years, WP and/or cigarette smoking youth experienced reportable negative health effects.

Potential role of tryptophan and chloride in the inhibition of human myeloperoxidase.

Myeloperoxidase (MPO) binds H2O2 in the absence and presence of chloride (Cl-) and catalyzes the formation of potent oxidants through 1e(-) and 2e(-) oxidation pathways. These potent oxidants have been implicated in the pathogenesis of various diseases including atherosclerosis, asthma, arthritis, and cancer. Thus, inhibition of MPO and its by-products may have a wide application in biological systems. Using direct rapid kinetic measurements and H2O2-selective electrodes, we show that tryptophan (Trp), an essential amino acid, is linked kinetically to the inhibition of MPO catalysis under physiological conditions. Trp inactivated MPO in the absence and presence of plasma levels of Cl(-), to various degrees, through binding to MPO, forming the inactive complexes Trp-MPO and Trp-MPO-Cl, and accelerating formation of MPO Compound II, an inactive form of MPO. Inactivation of MPO was mirrored by the direct conversion of MPO-Fe(III) to MPO Compound II without any sign of Compound I accumulation. This behavior indicates that Trp binding modulates the formation of MPO intermediates and their decay rates. Importantly, Trp is a poor substrate for MPO Compound II and has no role in destabilizing complex formation. Thus, the overall MPO catalytic activity will be limited by: (1) the dissociation of Trp from Trp-MPO and Trp-MPO-Cl complexes, (2) the affinity of MPO Compound I toward Cl(-) versus Trp, and (3) the slow conversion of MPO Compound II to MPO-Fe(III). Importantly, Trp-dependent inhibition of MPO occurred at a wide range of concentrations that span various physiological and supplemental ranges.

Elevated serum tobramycin concentrations after treatment with tobramycin inhalation in a preterm infant.

High-dose inhaled tobramycin has been increasingly used for treatment and suppression of Pseudomonas aeruginosa pulmonary infections, especially in patients with cystic fibrosis. The advantage of inhalation over other routes of administration is minimal systemic absorption, which reduces the potential for adverse effects. However, cases of adults who had elevated serum concentrations and experienced systemic adverse effects due to excessive systemic absorption after inhaled tobramycin have been reported. We describe a prematurely born infant with numerous congenital and acquired disorders who required assisted mechanical ventilation and a 60-day stay in the neonatal intensive care unit (NICU). Tracheostomy and mechanical ventilatory support were required throughout the infant's hospital stay. The patient developed several pulmonary infections caused by various bacteria. He was treated with multiple antibiotics, including two different dose preparations of inhaled tobramycin 80 mg and 300 mg, administered through the tracheostomy and the ventilator. The infant was given a total of five preparations of tobramycin 80 mg/dose and three of 300 mg/dose, for a total cumulative dose of 1,300 mg over a 6-day period. His tobramycin concentrations increased, prompting discontinuation of the inhaled tobramycin. The infant died on day 60. To our knowledge, this is the first report of elevated tobramycin concentrations after inhalation in an infant. Although studies have found that tobramycin is safe and effective, certain patient populations are more at risk for toxicity. Tobramycin concentrations should be closely monitored in patients with significant underlying renal disorders, especially those in age-group extremes.

Home versus hospital intravenous antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis.

To compare the effectiveness of home versus hospital intravenous (IV) antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis (CF). A retrospective chart review was performed of 143 encounters for pulmonary exacerbations in 50 patients with CF. All encounters were categorized into two groups based on location of completion of antibiotic therapy: hospital group completed treatment in hospital (n = 64), home group completed treatment at home (n = 79). Percent change was calculated for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow rate between 25 percent and 75 percent of vital capacity (FEF(25-75%)), maximum forced expiratory flow (FEF(max)), oxygen saturation (O2 SAT), and weight. Means of percent change (PC) from the beginning to the end of IV antibiotic treatment in outcome variables were compared. Total duration of treatment was compared between the two groups. The two groups had no significant differences at baseline in all outcome variables. Treatment of exacerbations in both groups resulted in significant improvement of lung function, O2 SATS, and weight (P

Adenotonsillectomy improves quality of life in children with sleep-disordered breathing regardless of nocturnal enuresis outcome.

BACKGROUND: Nocturnal enuresis (NE) and sleep-disordered breathing (SDB) have both been associated with impaired health-related quality of life (HRQoL). The following were investigated: (1) whether tonsillectomy and/or adenoidectomy (T&A) significantly affect the HRQoL in children with NE and SDB, and 2) differences in HRQoL between children with NE persistence versus resolution post-T&A. METHODS: This was a prospective study comparing the HRQoL of children with SDB and NE (study group) pre- and 4 weeks post-T&A, and the HRQoL of children with SDB without NE (control group) (independent t-tests). HRQol was assessed using the Obstructive Sleep Apnea Quality of Life 18 questionnaire (OSAS-18), a validated measure containing five subscales that combine to create a total score. Individual items were scored on a Likert-type scale ranging from 1 (none of the time) to 7 (all of the time). Symptoms of SDB were evaluated using the validated Pediatric Sleep Questionnaire (PSQ). Mixed ANOVA was conducted to evaluate changes in the measures between the wet and dry children post-T&A. Pre- and post-T&A change scores were calculated for both the PSQ and the OSAS-18. RESULTS: There were 30 children in the study group (18 male, mean age 9.07 years, SD 2.19), and 30 age-matched controls (16 male). There were no statistically significant differences between the two groups in regards to OSAS-18 total, PSQ total, BMI, diagnosis of snoring or OSAS on sleep study, or race. Overall, OSAS-18 and PSQ scores significantly improved in all children post-surgery (p < 0.001; p < 0.001, respectively), with no significant differences between dry and wet children post-T&A. The correlation between the pre- and post-T&A change scores on the OSAS-18 and PSQ was significant (r(29) = 0.58, p = 0.001), suggesting that a reduction in SDB symptoms post T&A is related to improved HRQoL. CONCLUSIONS: T&A significantly improved HRQoL in all children with SDB and NE, regardless of NE outcomes. These findings support recommendations for T&A in children with SDB with or without NE.