Impact of sleep opportunity on asthma outcomes in adolescents.

RATIONALE: Insufficient sleep is associated with a number of negative health outcomes; as most adolescents obtain <7 h of sleep per night, it is important to understand how sleep impacts asthma among adolescents. OBJECTIVES: To examine the impact of sleep opportunity on asthma in adolescents. METHODS: In this study, 54 adolescents with asthma (12-17 years, 69% female, 65% Caucasian) participated in a randomized, cross-over sleep manipulation trial, including a sleep stabilization week, five nights of a "Short" sleep opportunity (time in bed: 6.5 h/night), and five nights of a "Long" sleep opportunity (time in bed: 9.5 h/night). Wake times were consistent across all three study weeks. Primary outcomes were lung function (daily peak expiratory flow rate, weekly spirometry) and functional asthma outcomes (daily asthma symptoms, Asthma Control Questionnaire, PROMIS Asthma Impact Scale). Markers of inflammation were also explored. MEASUREMENTS AND MAIN RESULTS: Compared to the Long sleep week, during the Short sleep week, morning FEV1 was lower (p = 0.006), while asthma symptoms and albuterol use was higher (p < 0.05), and asthma showed a trend towards greater negative impact on daily life (p = 0.07). No differences were found for weekly measures of lung function or inflammation. CONCLUSIONS: An insufficient sleep opportunity negatively impacts objective and subjective daily symptoms of asthma in adolescents, as well as health related quality of life. As most adolescents are significantly sleep deprived, it is important to target sleep health in the treatment of asthma.

Retrospective evaluation of the efficacy of isolating bacteria from synovial fluid in dogs with suspected septic arthritis.

OBJECTIVE: To evaluate the efficacy of synovial fluid culture in obtaining the causative organism from dogs with suspected septic arthritis. METHODS: In this retrospective evaluation, synovial fluid cytology and microbiology submissions from dogs with suspected septic arthritis from March 2007 to August 2011 were reviewed. Synovial fluid cytology consistent with joint sepsis was identified. Cultures of synovial fluid from dogs with clinical histories and abnormalities consistent with septic arthritis were used to evaluate the efficacy of bacterial isolation. RESULTS: In total, 36 dogs met the inclusion criteria. Initial aerobic cultures of joint fluid yielded bacterial growth in 44% of these dogs. All anaerobic cultures were negative. In 19% of the dogs with positive cultures, antibiotics had been administered prior to arthrocentesis compared with 10% of dogs with negative cultures. There was no association between culture efficacy and the administration of antimicrobial treatment prior to synovial fluid culture or recent surgery involving the affected joint (P=0.637 and P=0.106, respectively). CONCLUSION: Culture of synovial fluid from dogs with suspected septic arthritis has a low yield, necessitating a more effective means of identifying bacteria from suspected septic joints in dogs.

Chronic nicotine effects on left ventricular function in healthy middle-aged people: an echocardiographic study.

AIMS: Cigarettes and Swedish snuff influence the cardiovascular system in many ways. Cigarette and snuff usage have been linked with an acute impairment in several diastolic cardiac parameters during intake. The aim of this study is to investigate whether long-term usage of Swedish snuff or cigarettes also causes a more permanent impairment of systolic and/or diastolic cardiac parameters in the left ventricle in otherwise healthy middle-aged snuffers and smokers. METHODS AND RESULTS: Eighty-seven age-matched volunteers were included and examined with echocardiography. The volunteers were divided into three subgroups; one group with non-tobacco users, one group with long-term smokers and finally one group with long-term snuffers. The smokers and snuffers were instructed not to use these products for at least 5 h before the examination. The systolic and diastolic cardiac parameters were collected at one time. Most of the systolic parameters measured were unaltered between the tobacco subgroups and non-tobacco users, and therefore, no alteration of significance was found in systolic parameters. Also, almost all of the diastolic parameters measured were not significantly impaired in the tobacco subgroups compared with non-tobacco users. However, the deceleration time (DT) was slightly prolonged (P<0·05) and thus statistically significant in the tobacco subgroups. This finding is somewhat difficult to interpret but may be seen as random. CONCLUSIONS: This study reveals that most systolic- and diastolic cardiac parameters are not chronically significantly altered in middle-aged long-term tobacco users compared with age-matched non-tobacco users.

Adherence in single-parent households in a long-term asthma clinical trial.

Adherence of participants in a long-term clinical trial is necessary to assure validity of findings. This article examines adherence differences between single-parent and two-parent families in the Childhood Asthma Management Program (CAMP). Adherence was defined as the percentage of completed daily diary cards and scheduled study visits during the course of the trial. Logistic regression and ordinal logistic regression analyses were used. Children from single-parent families had a lower percentage of completed diary cards (72% vs. 84%) than two-parent families. Single-parent families were also more likely to reschedule visits (62% vs. 45%) and miss more clinic visits (23% vs. 17%) than two-parent families. Suggestions are given for study coordinators to assist participants in completing a long-term clinical trial. Many suggestions may be adapted for nurses in inpatient or outpatient settings for assisting parents of patients with chronic diseases.

Acute effects on the ventricular function in Swedish snuffers: an echocardiographic study.

AIMS: Cigarettes and Swedish snuff contain nicotine, which influence the cardiovascular system. Cigarette smoke has been shown to give an acute impairment in diastolic heart parameters. The systolic and diastolic heart function in snuff users is not thoroughly enough investigated. The aim of this study was to investigate if Swedish snuff will give an acute decrease in systolic and diastolic heart parameters in the left and right ventricles in healthy Swedish snuffers. METHODS AND RESULTS: Thirty healthy volunteers were examined with echocardiography. The study involved recordings from four different times: before snuff intake, 5 and 30 min after intake and finally 30 min after snuff withdrawal. The systolic and diastolic heart parameters were collected with conventional echocardiographic methods. In addition, the heart frequency and blood pressure response were measured. The pulse and blood pressure response were significantly altered (P < 0.01) during the test. Left ventricular ejection fraction and the amplitudes of mitral and tricuspid annulus motion did not alter significantly. The main finding in the study was the significant decrease (P < 0.05) in several diastolic heart parameters for both the left and right ventricles. CONCLUSIONS: This study shows that snuff intake causes a significant decrease in E/A ratio and a delay in ventricular relaxation and therefore a decrease in diastolic heart function in the left and right ventricles. The mechanism behind these alterations is probably very complex, but a combination of nicotine effects and loading conditions is probably the main factor.

Safety and application of induced sputum analysis in childhood asthma.

BACKGROUND: The value of sputum induction in pediatric asthma lies in its potential to directly and noninvasively assess airway inflammation in children, because bronchoscopy and biopsy carry some risk. The Childhood Asthma Management Program (CAMP) study was designed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers. OBJECTIVE: At the Denver CAMP site, we sought to evaluate the safety of sputum induction, to determine differences in airway inflammation between treatment groups by using induced sputum analysis, and to examine correlations between other biomarkers and sputum eosinophils. METHODS: Sputum induction was performed, and exhaled nitric oxide, circulating eosinophil counts, and serum eosinophil cationic protein were obtained at treatment discontinuation and after washout. Spirometry and a methacholine challenge were also performed according to the CAMP protocol. RESULTS: Ninety of 117 children provided an adequate sputum sample for analysis. In 9 subjects (3 nedocromil and 6 placebo), sputum induction resulted in bronchospasm. These subjects had greater disease severity, as measured by a lower median prebronchodilator FEV 1 percentage predicted (85.0% vs 96.0%; P =.024) and FEV 1 /FVC ratio (70.0% vs 79.0%; P =.0008); greater bronchodilator reversibility (16.5% vs 6.8%; P =.004); higher serum IgE (1390.0 vs 495.0 ng/mL; P =.017) and circulating eosinophil count (757.0 vs 282.0/mm 3; P =.04); greater use of prednisone (1.9 vs 0.9 courses per 100 person-years; P =.05); and greater supplemental inhaled steroid doses (85.3 vs 0 mg; P =.016). At treatment discontinuation, budesonide-treated patients had a lower median (1st, 3rd quartile) sputum percentage eosinophil (SPEos) (0.2% [0%, 1.2%] vs 0.8% [0.2%, 4.6%]; P =.03) compared with those treated with placebo; no significant difference was noted between nedocromil- and placebo-treated patients. Higher SPEos at the time of treatment discontinuation was associated with asthma worsening that required rescue prednisone (n = 23) during the washout period compared with patients who remained stable (3.6% [0.4%, 6.4%] vs 0.6% [0.2%, 3.2%] SPEos; P =.023). Finally, greater SPEos was associated with atopy, higher bronchodilator reversibility, lower FEV 1 /FVC ratio, higher exhaled nitric oxide levels, circulating eosinophils, sputum and serum eosinophil cationic protein, more prednisone courses during the treatment period, and greater asthma severity. CONCLUSIONS: Sputum induction is a relatively noninvasive and safe procedure that can provide information on eosinophilic inflammation and treatment response and is also associated with several measures of asthma control. However, this procedure still remains a research tool in asthma because of its requirements for technical expertise.

Minimizing attrition in a long-term clinical trial of pediatric asthma.

BACKGROUND: Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials, high dropout rates have threatened the success of numerous studies. OBJECTIVE: To evaluate the disease, demographic, and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials. METHODS: Predictors of attrition were examined within the Childhood Asthma Management Program (CAMP), a large, multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years. RESULTS: Eighty-two percent of patients attended all study visits. The tendency to miss visits was increased among older children with milder asthma, lower intellectual and social competence, and more symptoms of behavioral problems and emotional distress. Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts; these patients at baseline had milder asthma; lower cognitive, academic, and social competence skills; and more family conflict and distress than found among participants who remained in the study. The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support. CONCLUSIONS: The 4% dropout rate in CAMP was lower than reported in any previous long-term asthma trial. The findings of milder disease, decreased psychological resources, and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial.

Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma.

OBJECTIVE: Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed. STUDY DESIGN: FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout. RESULTS: Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly. CONCLUSIONS: Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.

Serum ascorbic acid concentrations in previously unsupplemented greyhounds after administration of a single dose of ascorbic acid intravenously or per os.

Plasma vitamin C concentrations (mean + SD) were measured after a large (1 g) dose of vitamin C was administered orally or intravenously to each of four trained greyhounds in a randomized cross-over design. Concentrations increased (p<0.05) for 2 h but returned to baseline by 6 h after supplementation. Peak concentrations were greater (p<0.01) after intravenous than oral administration (6.1+/-1.2 vs. 0.54+/-0.23 mg/dl). This suggests that vitamin C must be administered many times daily to maintain plasma concentrations above normal.

Effect of alpha-tocopheryl acetate supplementation on vitamin E concentrations in Greyhounds before and after a race.

OBJECTIVES: To determine effect of alpha-tocopherol supplementation on serum vitamin E concentrations in Greyhounds before and after a race. ANIMALS: 8 adult racing Greyhounds. PROCEDURE: Dogs were given 2 capsules of alpha-tocopheryl acetate (total, 680 units [0.5 g]) with food that contained < or = 15 mg of vitamin E/kg each morning for 7 days. Dogs were exercised in a 30 X 30-m grass paddock for 15 minutes twice a day and raced for 500 m twice a week. Blood samples were collected before and 5 minutes after a race, before supplementation was begun, and after 7 days of supplementation. Blood and diet samples were analyzed for tocopherols and alpha-tocopheryl acetate. RESULTS: Before supplementation, serum alpha-tocopherol concentration after racing (mean +/- SD, 6.7 +/- 2.4 mg/L ) was significantly lower than before racing (12.2 +/- 3.1 mg/L). After supplementation, alpha-tocopherol concentrations were significantly higher overall, although values obtained before (26.6 +/- 5.2 mg/L) and after (29.8 +/- 3.6 mg/L) racing were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: Supplementation with alpha-tocopheryl acetate increased serum alpha-tocopherol concentrations and eliminated the decrease in alpha-tocopherol concentration that was detected after a race, which may decrease oxidation during exercise and improve performance or recovery.

Effect of increased dietary protein and decreased dietary carbohydrate on performance and body composition in racing Greyhounds.

OBJECTIVE: To determine effects of increased dietary protein and decreased dietary carbohydrate on hematologic variables, body composition, and racing performance in Greyhounds. ANIMALS: 8 adult Greyhounds. PROCEDURE: Dogs were fed a high-protein (HP; 37% metabolizable-energy [ME] protein, 33% ME fat, 30% ME carbohydrate) or moderate-protein (MP; 24% ME protein, 33% ME fat, 43% ME carbohydrate) extruded diet for 11 weeks. Dogs subsequently were fed the other diet for 11 weeks (crossover design). Dogs raced a distance of 500 m twice weekly. Rectal temperature, hematologic variables before and after racing, plasma volume, total body water, body weight, average weekly food intake, and race times were measured at the end of each diet period. RESULTS: When dogs were fed the MP diet, compared with the HP diet, values (mean +/- SD) differed significantly for race time (32.43 +/- 0.48 vs 32.61 +/- 0.50 seconds), body weight (32.8 +/- 2.5 vs 32.2 +/- 2.9 kg), Hct before (56 +/- 4 vs 54 +/- 6%) and after (67 +/- 3 vs 64 +/- 8%) racing, and glucose (131 +/- 16 vs 151 +/- 27 mg/dl) and triglyceride (128 +/- 17 vs 104 +/- 28 mg/dl) concentrations after racing. CONCLUSIONS AND CLINICAL RELEVANCE: Greyhounds were 0.18 seconds slower (equivalent to 0.08 m/s or 2.6 m) over a distance of 500 m when fed a diet with increased protein and decreased carbohydrate. Improved performance attributed to feeding meat to racing Greyhounds apparently is not attributable to increased dietary protein and decreased dietary carbohydrate.

Effects of racing and training on serum thyroid hormone concentrations in racing Greyhounds.

OBJECTIVES: To determine the effects of racing and training on serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations in Greyhounds. ANIMALS: 9 adult racing Greyhounds. PROCEDURE: Serum thyroid hormone concentrations were measured before and 5 minutes after a race in dogs trained to race 500 m twice weekly for 6 months. Resting concentrations were measured again when these dogs had been neutered and had not raced for 3 months. Postrace concentrations were adjusted relative to albumin concentration to allow for effects of hemoconcentration. Thyroid hormone concentrations were then compared with those of clinically normal dogs of non-Greyhound breeds. RESULTS: When adjusted for hemoconcentration, total T4 concentrations increased significantly after racing and TSH concentrations decreased; however, there was no evidence of a change in free T4 or total or free T3 concentrations. Resting total T4 concentrations increased significantly when dogs had been neutered and were not in training. There was no evidence that training and neutering affected resting TSH, total or free T3, or free T4 concentrations. Resting concentrations of T3, TSH, and autoantibodies against T4, T3, and thyroglobulin were similar to those found in other breeds; however, resting free and total T4 concentrations were lower than those found in other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Except for total T4, thyroid hormone concentrations in Greyhounds are affected little by sprint racing and training. Greyhounds with low resting total and free T4 concentrations may not be hypothyroid.

Maintenance energy requirements and the effect of diet on performance of racing Greyhounds.

OBJECTIVES: To determine maintenance energy requirements and effect of diet on performance of racing Greyhounds. ANIMALS: 7 adult racing Greyhounds. PROCEDURE: Dogs were fed a higher fat and protein (HFP) or a lower fat and protein (LFP) diet for 8 weeks in a crossover design. Dogs were exercised for 15 minutes twice daily in a paddock and raced 500 m twice weekly. Blood gas, hematologic, and serum biochemical analyses were performed before and after racing, and race times were compared at the end of each diet period. RESULTS: Mean race time was significantly shorter (32.81+/-0.65 seconds vs. 33.05+/-0.71 seconds), and mean racing speed over 500 m was significantly faster (15.25+/-0.30 vs. 15.13+/-0.30 m x s(-1)) when dogs were fed the HFP diet than when they were fed the LFP diet. Diet had little or no effect on results of blood gas, hematologic, and serum biochemical analyses, except that Hct was 4% greater before and after racing when the HFP diet was fed than when the LFP diet was fed. Mean SD metabolizable energy intake from weeks 1 through 16 was 155+/-9 kcal x kg(-0.75) x d(-1). CONCLUSIONS AND CLINICAL RELEVANCE: Racing Greyhounds ran faster when fed a diet containing higher fat and protein and lower carbohydrate contents. Their maintenance metabolizable energy requirement was slightly higher than that of moderately active dogs.

Effect of acute induced metabolic alkalosis on the acid/base responses to sprint exercise of six racing greyhounds.

To investigate the effect of acute induced metabolic alkalosis on the haematological, biochemical and metabolic responses to sprint exercise, six greyhound dogs with previously placed carotid arterial catheters were raced four times over a distance of 400 metres. Each dog was raced twice after receiving oral sodium bicarbonate solution (NaHCO3) (400 mg kg-1) or lactated Ringer's solution (LRS). Before, and for intervals of up to one hour after, the exercise arterial blood samples were collected for the measurement of blood gases, packed cell volume, total protein, serum biochemistry and plasma lactate. The time to complete the 400 metre sprint ranged from 32.7 seconds to 36.9 seconds. There was no significant difference in racing times between the dogs treated with NaHCO3 and LRS, and there was no significant difference between the plasma lactate measurements after the treatments with NaHCO3 or LRS. Serum chloride concentrations were significantly lower after NaHCO3 than after LRS, and there was a trend towards a lower serum potassium concentration after NaHCO3 treatment. Plasma lactate concentrations showed a similar increase and time course of disappearance after both LRS and NaHCO3 treatments. There were significant changes in all the parameters measured after the exercise, but there were large variations between individual dogs and between races when the dogs were receiving the same treatment.

Optimization of a pellicular biocatalyst for penicillin G production by Penicillium chrysogenum.

A previously developed immobilization technique involving latex coatings on solid particulate supports was investigated further for penicillin G production by Penicillium chrysogenum. Several modifications were found to decrease the germination lag time, including a higher spore concentration, a thinner latex layer, an increased latex porosity, and a decreased drying time. This approach enabled the development of immobilized mycelial pellets within 2-3 days from the onset of biocatalyst preparation and incubation.A continuous immobilized-cell airlift bioreactor produced penicillin G in a series of runs in which the production phase lasted up to 30 days. The productivity of this system was 3-6 times greater than the productivity of the corresponding free-cell shake flask fermentation.

Effect of phorbol esters on the susceptibility of a glioma cell line to lymphokine-activated killer cell activity.

The mechanisms by which lymphokine-activated killer (LAK) cells exert their cytotoxic effects are not well understood. This study demonstrates that phorbol ester pretreatment of a LAK cell-sensitive glioma cell line (SNB-19) induced a significant decrease in the susceptibility of cells to LAK cell-mediated lysis. This effect was produced by low concentrations of the tumor-promoting phorbol ester, phorbol-12,13-myristate acetate (PMA), and was reversible. Protein kinase C (PKC) inhibitors failed to block this phenomenon. No apparent alteration in the ability of LAK cells to bind to their targets was observed. Thus, PMA may have exerted its effects by a mechanism that does not require PKC, or these glioma cells may possess an isozyme of PKC which is insensitive to the inhibitors used in these studies.

In vitro mechanism of inhibition of bacterial cell growth by allicin.

Diallyl thiosulfinate (allicin) is the agent found in garlic which is responsible for the antibacterial and antifungal activity of extracts of this plant. The effect of bacteriostatic concentrations of allicin (0.2 to 0.5 mM) on the growth of Salmonella typhimurium revealed a pattern of inhibition characterized by: (i) a lag of approximately 15 min between addition of allicin and onset of inhibition, (ii) a transitory inhibition phase whose duration was proportional to allicin concentration and inversely proportional to culture density, (iii) a resumed growth phase which showed a lower rate of growth than in uninhibited controls, and (iv) an entry into stationary phase at a lower culture density. Whereas DNA and protein syntheses showed a delayed and partial inhibition by allicin, inhibition of RNA synthesis was immediate and total, suggesting that this is the primary target of allicin action.

Capillary viscometer for use with crosslinking polymer melts.

A capillary viscometer is described which adapts a conventional capillary rheometer for use with crosslinking polymers. Illustrative data obtained with the viscometer using diallyl phthalate resin are included.