Search

Abstract Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory agents available for the treatment of asthma and represent the mainstay of therapy for most patients with the disease. Although these medications are considered safe at low-to-moderate doses, safety concerns with prolonged use of high ICS doses remain; among these concerns is the risk of adrenal suppression (AS). AS is a condition characterized by the inability to produce adequate amounts of the glucocorticoid, cortisol, which is critical during periods of physiological stress. It is a proven, yet under-recognized, complication of most forms of glucocorticoid therapy that can persist for up to 1 year after cessation of corticosteroid treatment. If left unnoticed, AS can lead to significant morbidity and even mortality. More than 60 recent cases of AS have been described in the literature and almost all cases have involved children being treated with ≥500 μg/day of fluticasone. The risk for AS can be minimized through increased awareness and early recognition of at-risk patients, regular patient follow-up to ensure that the lowest effective ICS doses are being utilized to control asthma symptoms, and by choosing an ICS medication with minimal adrenal effects. Screening for AS should be considered in any child with symptoms of AS, children using high ICS doses, or those with a history of prolonged oral corticosteroid use. Cases of AS should be managed in consultation with a pediatric endocrinologist whenever possible. In patients with proven AS, stress steroid dosing during times of illness or surgery is needed to simulate the protective endogenous elevations in cortisol levels that occur with physiological stress. This article provides an overview of current literature on AS as well as practical recommendations for the prevention, screening and management of this serious complication of ICS therapy.

Abstract Introduction Patients with severe idiopathic scoliosis are reported to have significant pulmonary complications, including recurrent chest infections, alveolar hypoventilation and respiratory failure. Case presentation We report a case of a 13-year-old boy with moderate-to-severe scoliosis resulting in torsion or twisting of the bronchus intermedius, which contributed to airflow obstruction defects, as revealed by both spirometry and bronchoscopy. Conclusion We recommend that inspection of the shape of the maximal expiratory flow-volume loop obtained from spirometry, as well as other parameters suggestive of obstructive lung disease, may be important in children with scoliosis. To the best of the authors' knowledge, this is the first report of a child in which pulmonary function testing and direct visualization via a flexible bronchoscope have been used to characterize intrathoracic large airway obstruction.

Abstract Background There is considerable evidence from the literature that children with chronic lung disease of infancy (CLD) have abnormal pulmonary function in childhood and this could have an impact on their life quality and overall health. There are similarities between CLD and asthma, and corticosteroids are the mainstay treatment for asthma. Many physicians use inhaled corticosteroids in children with CLD with no evidence. Therefore we wish to conduct a randomized double-blinded placebo controlled trial to test for the role of inhaled corticosteroids in children aged from3 to 9 years with a history of CLD. Our primary hypothesis will be that inhaled corticosteroids are beneficial in children with CLD. Methods Our primary hypothesis is that using inhaled steroids; Beclomethasone Dipropionate (QVAR) 100 mcg 2 puffs 2 times a day for 6 weeks will improve the respiratory system resistance and the quality of life in children with CLD. Discussion We propose that Beclomethasone Dipropionate (QVAR) will affect the pulmonary function after 6 weeks of treatment. In summary we think that our study will highlight knowledge on whether the use of inhaled steroids is clinically effective for CLD.

A letter to the editor is presented in response to the articles about psychiatric literature that were published in various journals on psychiatry.

Recent approval of transdermal flunixin meglumine (FM) (Banamine ® ) in cattle has opened the door for the drug's potential application in other species. Transdermal FM could provide a safe and effective form of pain relief in donkeys. In order to evaluate the pharmacokinetics and effects of FM on anti-inflammatory biomarkers in donkeys, a three-way crossover study design was employed. In total, 6 healthy donkeys were administered transdermal (TD) FM at a dosage of 3.3 mg/kg, and oral (PO) and intravenous (IV) doses of 1.1 mg/kg body weight. Blood samples were collected over 96 h to determine the concentration of flunixin, 5OH flunixin, and eicosanoids (TXB2 and PGF2 alpha) using LC-MS/MS. The results indicated that both flunixin and 5OH flunixin were detectable in blood samples collected during TD. The elimination of the drug was slower following the TD route compared to PO and IV. TD administration significantly decreased TXB2 levels in non-stimulated serum from 1 to 96 h post-administration, while IV and PO resulted in TXB2 reduction for 1 to 8 h. A significant reduction in PGF2 alpha was observed in PO and IV 1 h after administration, while TD resulted in a gradual decline from 4 to 72 h. The study concluded that the off-label use of transdermal FM at 3.3 mg/kg could be effective in controlling inflammation in donkeys.

Background: Corynebacterium pseudotuberculosis is classified into two biovars, nitrate-negative biovar Ovis which is the etiologic agent of caseous lymphadenitis in small ruminants and nitrate-positive biovar Equi, which causes abscesses and ulcerative lymphangitis in equines. The aim of this study was to develop a quadruplex PCR assay that would allow simultaneous detection and biovar-typing of C. pseudotuberculosis., Methods: In the present study, genomes of C. pseudotuberculosis strains were used to identify the genes involved in the nitrate reduction pathway to improve a species identification three-primer multiplex PCR assay. The nitrate reductase gene (narG) was included in the PCR assay along with the 16S, rpoB and pld genes to enhance the diagnosis of the multiplex PCR at biovar level., Results: A novel quadruplex PCR assay for C. pseudotuberculosis species and biovar identification was developed. The results of the quadruplex PCR of 348 strains, 346 previously well-characterized clinical isolates of C. pseudotuberculosis from different hosts (goats, sheep, horse, cattle, buffalo, llamas and humans), the vaccine strain 1002 and the type strain ATCC 19410 T , were compared to the results of nitrate reductase identification by biochemical test. The McNemar's Chi-squared test used to compare the two methods used for C. pseudotuberculosis biovar identification showed no significant difference (P = 0.75) [95% CI for odds ratio (0.16-6.14)] between the quadruplex PCR and the nitrate biochemical test. Concordant results were observed for 97.13% (338 / 348) of the tested strains and the kappa value was 0.94 [95% CI (0.90-0.98)]., Conclusions: The ability of the quadruplex assay to discriminate between C. pseudotuberculosis biovar Ovis and Equi strains enhances its usefulness in the clinical microbiology laboratory.

Background: Antibiotics are frequently used to treat wheezing children. Macrolides may be effective in treating bronchiolitis and asthma., Method: We completed a prospective, double-blinded, randomized placebo-control trial of azithromycin among pre-school children (12 to 60 months of age) presenting to the emergency department with wheeze. Patients were randomized to receive either five days of azithromycin or placebo. Primary outcome was time to resolution of respiratory symptoms after treatment initiation. Secondary outcomes included the number of days children used a Short-Acting Beta-Agonists during the 21 day follow-up and time to disease exacerbation during the following six months (unscheduled health care visit or treatment with an oral corticosteroid for acute respiratory symptoms)., Results: Of the 300 wheezing children recruited, 222 and 169 were analyzed for the primary and secondary outcomes, respectively. The treatment groups had similar demographics and clinical parameters at baseline. Median time to resolution of respiratory symptoms was four days for both treatment arms (interquartile range (IQR) 3,6; p = 0.28). Median number of days of Short-Acting Beta-Agonist use among those who received azithromycin was four and a half days (IQR 2, 7) and five days (IQR 2, 9; p = 0.22) among those who received placebo. Participants who received azithromycin had a 0.91 hazard ratio for time to six-month exacerbation compared to placebo (95% CI 0.61, 1.36, p = 0.65). A pre-determined subgroup analysis showed no differences in outcomes for children with their first or repeat episode of wheezing. There was no significant difference in the proportion of participants experiencing an adverse event., Conclusion: Azithromycin neither reduced duration of respiratory symptoms nor time to respiratory exacerbation in the following six months after treatment among wheezing preschool children presenting to an emergency department. There was no significant effect among children with either first-time or prior wheezing.

Corynebacterium pseudotuberculosis is the etiological agent of a caseous lymphadenitis disease. Herein, we present the first complete genome sequencing of C. pseudotuberculosis strain 226, isolated from an abscess of the sub-iliac lymph node of a goat from California (USA). The genome contains 2,138 coding sequences (CDSs), 12 rRNAs, 49 tRNAs, and 72 pseudogenes., (Copyright © 2016 Dias et al.)

Background: Newborns with Pierre Robin sequence (PRS) often experience chronic intermittent hypoxemia/hypoventilation associated with airway obstruction. The heterogeneity of the severity of upper airway obstruction makes management a challenge; the optimal intervention in individual cases is not clear., Objective: To investigate the prevalence of surgical/nonsurgical interventions for PRS at two children's hospitals. Patient characteristics and outcomes were examined., Methods: The present retrospective chart review identified 139 patients with PRS born between 2000 and 2010. Demographic information, mode of airway management, associated anomalies and syndromes, polysomnography results, length of intensive care unit and hospital stay, complications and deaths were extracted., Results: Interventions included prone positioning (alone [61%]), tongue-lip adhesion (45%), nasopharyngeal intubation (28%), continuous positive airway pressure (20%), tracheostomy (19%) and mandibular distraction osteogenesis (5%). Tracheostomies were more prevalent in syndromic patients (P=0.03). Patients who underwent tracheostomy had a lower birth weight (P=0.03) compared with newborns with other interventions. Patients who underwent surgical interventions had longer intensive care unit stays (P<0.001). No intervention was associated with a statistically significant likelihood of requiring a subsequent intervention. Thirty percent of patients underwent polysomnography, with a higher proportion of these using continuous positive airway pressure (n=15) (P<0.01)., Conclusions: In the present descriptive study, patients with syndromic PRS or low birth weight underwent early intervention, which included a tracheostomy. Objective measures of airway obstruction were underutilized. Decision making regarding evaluation and management of upper airway obstruction in this population remains clinician and resource dependent. Reporting data obtained from a large cohort of PRS patients is important to compare experiences and motivate future studies investigating this complex condition.

Background: Few studies report the minimum inhibitory concentrations for antimicrobials against equine Corynebacterium pseudotuberculosis isolates., Hypothesis/objectives: To evaluate trends in the in vitro activities of 20 antimicrobials against equine Corynebacterium pseudotuberculosis isolates from 1996 to 2012 and to determine if a relationship exists between the minimum inhibitory concentration (MIC) and location of the abscess., Animals: Corynebacterium pseudotuberculosis isolates from 196 horses with naturally occurring disease., Methods: Retrospective and cross-sectional design. Medical records were reviewed to obtain clinical and MIC data. Minimum inhibitory concentrations were determined by the microdilution technique. The MIC results over 3 periods were compared (1996-2001, 2002-2006, 2007-2012)., Results: The MIC90 values for clinically relevant antimicrobials were as follows: chloramphenicol ≤ 4 μg/mL, enrofloxacin ≤ 0.25 μg/mL, gentamicin ≤ 1 μg/mL, penicillin =0.25 μg/mL, rifampin ≤ 1 μg/mL, tetracycline ≤ 2 μg/mL, trimethoprim-sulfamethoxazole (TMS) ≤ 0.5 μg/mL, ceftiofur =2 μg/mL, and doxycycline ≤ 2 μg/mL. There were no significant changes in MIC results over the study period. There was no relationship between MIC patterns and abscess location., Conclusions and Clinical Importance: The MIC50 and MIC90 values of antimicrobials evaluated in this study for equine isolates of C. pseudotuberculosis did not vary over time. Abscess location was not associated with different MIC patterns in cultured isolates. Several commonly used antimicrobials are active in vitro against C. pseudotuberculosis in vitro., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.)

The bacterium Corynebacterium pseudotuberculosis is of major veterinary importance because it affects livestock, particularly sheep, goats, and horses, in several countries, including Australia, Brazil, the United States, and Canada, resulting in significant economic losses. In the present study, we describe the complete genome of the Corynebacterium pseudotuberculosis Cp316 strain, biovar equi, isolated from the abscess of a North American horse.

In this work we report the genome of Corynebacterium pseudotuberculosis strain 267, isolated from a llama. This pathogen is of great veterinary and economic importance, as it is the cause of caseous lymphadenitis in several livestock species around the world and causes significant losses due to the high cost of treatment.

This pilot study evaluated protection of an equine autogenous bacterin-toxoid vaccine against Corynebacterium pseudotuberculosis infection. Twenty-four BALB/c mice were inoculated with two doses of bacterin-toxoid vaccine or two injections of a placebo. Clinical, microbiologic, and pathologic outcomes were assessed after intradermal infection with one of two equine-origin C. pseudotuberculosis strains. Mice receiving bacterin-toxoid from fast-growing C. pseudotuberculosis showed significant protection from challenge infection, as evidenced by a higher survival rate, fewer gross and histopathologic lesions, and lower bacterial levels on culture. Successful protection via a vaccine against equine internal abscesses might provide supplementary management options against an important, potentially fatal disease.

We surveyed cognitively normal teens with and without chronic illness regarding the perceived physical and social impact of various chronic diseases including asthma. The overall physical impact of asthma was perceived equivalently to diabetes and arthritis, but less than epilepsy, Down's syndrome, leukemia, and human immunodeficiency virus infection. However, asthma was rated to more commonly cause physical disability (p < 0.001) and restrict activities (p < 0.0005). The social impact of asthma was perceived equivalently to diabetes, but more favorably than the other chronic diseases surveyed. Specifically, teens with asthma were perceived as having fewer behavior problems, being more honest, popular, and fun to be around, but less adept at sports. Only 6 of 149 (4%) teens surveyed expressed any degree of reluctance to befriend peers with asthma.

The authors describe a 10-year-old Caucasian boy who presented with abnormally low oxygen saturation values on pulse oximetry after a routine tonsillectomy. He was asymptomatic and there was no personal or family history of respiratory, cardiac, or hematologic disorders. Multiple initial investigations were completed without diagnostic yield. Eventually, hemoglobinopathy studies identified the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville. Hemoglobinopathies remain highly prevalent worldwide, with more than 65 low oxygen affinity hemoglobin variants identified to date. Early recognition of abnormal hemoglobin variants in asymptomatic patients may avoid extensive, unnecessary medical investigations.

Background: Although guidelines for the diagnosis and management of asthma have been published over the last 15 years, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian asthma consensus report, important new studies, particularly in children, have highlighted the need to incorporate this new information into asthma guidelines., Objectives: To review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the Canadian Asthma Consensus Report, 1999 and its 2001 update with a major focus on pediatric issues., Methods: Diagnosis of asthma in young children, prevention strategies, pharmacotherapy, inhalation devices, immunotherapy and asthma education were selected for review by small expert resource groups. In June 2003, the reviews were discussed at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published up to December 2004 were subsequently reviewed by the individual expert resource groups., Results: This report evaluates early life prevention strategies and focuses on treatment of asthma in children. Emphasis is placed on the importance of an early diagnosis and prevention therapy, the benefits of additional therapy and the essential role of asthma education., Conclusion: We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This guide for asthma management is based on the best available published data and the opinion of health care professionals including asthma experts and educators.

Background: There is considerable evidence from the literature that children with chronic lung disease of infancy (CLD) have abnormal pulmonary function in childhood and this could have an impact on their life quality and overall health. There are similarities between CLD and asthma, and corticosteroids are the mainstay treatment for asthma. Many physicians use inhaled corticosteroids in children with CLD with no evidence. Therefore we wish to conduct a randomized double-blinded placebo controlled trial to test for the role of inhaled corticosteroids in children aged from 3 to 9 years with a history of CLD. Our primary hypothesis will be that inhaled corticosteroids are beneficial in children with CLD., Methods: Our primary hypothesis is that using inhaled steroids; Beclomethasone Dipropionate (QVAR) 100 mcg 2 puffs 2 times a day for 6 weeks will improve the respiratory system resistance and the quality of life in children with CLD., Discussion: We propose that Beclomethasone Dipropionate (QVAR) will affect the pulmonary function after 6 weeks of treatment. In summary we think that our study will highlight knowledge on whether the use of inhaled steroids is clinically effective for CLD.

Unlabelled: In rat spinotrapezius muscle, chronic heart failure (CHF) speeds microvascular O2 pressure (pO2; index of O2 delivery-to-O2 uptake) dynamics across the rest-contractions transition [Cardiovasc. Res. 56 (2002) 479]. Due to the mosaic nature of this muscle, the effect of CHF on microvascular pO2 dynamics in different fiber types remains unclear., Objective: Based upon derangements of endothelial function and blood flow responses, we hypothesized that CHF would speed microvascular pO2 dynamics (reduced O2 delivery-to-O2 uptake ratio) in type I muscle (soleus, approximately 84% type I), but not in type II muscle (peroneal, approximately 86% type II [J. Appl. Physiol. 80 (1996) 261])., Methods: Using phosphorescence quenching, microvascular pO2 was measured at rest and across the rest-contractions transition (1 Hz) in soleus and peroneal of non-infarcted control (control; n=7), and Sprague-Dawley rats with moderate (moderate; elevated left ventricular end-diastolic pressure (LVEDP) 10 +/- 2 mm Hg; n=10) and severe (severe; LVEDP 28 +/- 4 mm Hg; n=5) CHF., Results: The microvascular pO2 mean response time (time delay+time constant) was progressively speeded with increasing severity of CHF in soleus (control, 38.7 +/- 2.0; moderate, 29.1 +/- 1.5; severe, 22.5 +/- 3.9 s; P< or =0.05), but not in peroneal (control=moderate=severe)., Conclusion: As type I fibers are recruited predominately for moderate intensity exercise, the more rapid lowering of soleus microvascular pO2 in CHF would reduce the blood-muscle O2 driving gradient, exacerbate phosphocreatine and glycogen breakdown, and provide a mechanism for slowed O2 uptake kinetics and premature fatigue in CHF.

Background: Because obesity promotes inflammation and imposes mechanical constraints to the airways, a high birth weight may be a risk factor for asthma in childhood. However, to our knowledge, few studies have examined this potential relationship., Objective: To determine the relationship between high birth weight and risk of emergency visits for asthma during childhood., Design: Population-based cohort study., Setting: Alberta, Canada., Participants: All neonates born at term (> or =37 weeks) between April 1, 1985, and March 31, 1988, in Alberta (N = 83,595). We divided the cohort into birth-weight categories: low (<2.5 kg), normal (2.5-4.5 kg), or high (>4.5 kg). The cohort was observed prospectively for 10 years.Main Outcome Measure Comparison of risk of emergency visits for asthma over 10 years across the birth-weight categories., Results: Neonates born with a high birth weight had a significantly increased risk of emergency visits for asthma during childhood compared with neonates born with a normal birth weight (relative risk [RR], 1.16; 95% confidence interval [CI], 1.04-1.29). The relationship between birth weight and emergency visits for asthma beyond a birth weight of 4.5 kg was linear, such that every increment of 0.10 kg in birth weight was associated with an additional 10% (95% CI, 2%-19%) increase in the risk of emergency visits for asthma. Other factors associated with an elevated risk for emergency asthma visits during childhood included male sex (RR, 1.26; 95% CI, 1.22-1.30), aboriginal status (RR, 1.20; 95% CI, 1.11-1.29), and low-income status (RR, 1.11; 95% CI, 1.06-1.16)., Conclusions: A high, but not low, birth weight is a risk factor for increased emergency visits during childhood. The risk increases linearly beyond a birth weight of 4.5 kg.

Objective: To compare effects of a commercially available omeprazole paste and a compounded omeprazole suspension on healing of gastric ulcers in Thoroughbred racehorses in active training., Design: Randomized controlled trial., Animals: 32 horses with gastric ulcers., Procedure: Horses were assigned to 2 groups on the basis of endoscopic gastric ulcer severity. Group-1 horses were treated with omeprazole suspension for 30 days and with omeprazole paste for an additional 30 days. Group-2 horses were treated with omeprazole paste for 30 days and omeprazole suspension for an additional 30 days. Serum omeprazole concentrations were measured in 4 additional healthy horses after administration of a single dose of each formulation. In all instances, omeprazole was administered at a dose of 4 mg/kg (1.8 mg/lb), p.o.., Results: Ulcer severity scores on day 0 were not significantly different between groups. On day 30, ulcer severity score was significantly decreased, compared with day-0 score, in group-2 but not in group-1 horses. On day 60, ulcer severity score was significantly decreased, compared with day-0 and day-30 scores, in group-1 horses. In group-2 horses, ulcer severity score on day 60 was significantly lower than the day-0 score but was not significantly different from the day-30 score. Maximum observed serum omeprazole concentration and area under the concentration-time curve were significantly higher after administration of the paste versus the suspension formulation., Conclusions and Clinical Relevance: Results suggest that although administration of the commercially available paste omeprazole formulation was effective in promoting healing of gastric ulcers in these horses, administration of the compounded omeprazole suspension was ineffective.

Background: Asthma is common and is often poorly controlled in adolescent subjects., Objective: To determine the impact of an age-specific asthma program on asthma control, particularly on exacerbations of asthma requiring emergency department treatment, and on the quality of life of adolescents with asthma., Methods: The present randomized, controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma. The interventional group attended an age-specific asthma program that included assessment, education and management by a team of asthma educators, respiratory therapists and respiratory physicians. In the control group, spirometry was performed, and the patients continued to receive usual care from their regular physicians. The outcomes were assessed by a questionnaire six months after entry into the study., Results: Ninety-three subjects entered the study and were randomly assigned to the intervention or control group. Of these, only 62 patients were available for review after six months. Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control, reflected primarily by a 73% reduction in the rate of emergency department attendance for asthma. Other indexes of disease control, including disease-specific quality of life, as assessed by questionnaires, were improved. There was, however, no discernible difference between the subjects in the two groups, with the exception of an improvement in favour of the intervention group in the symptom (actual difference 0.7, P=0.048) and emotional (actual difference 0.8, P=0.028) domains of the asthma quality of life questionnaire. The overall quality of life score favoured the intervention group by a clinically relevant difference of 0.6, but this difference did not reach statistical significance (P=0.06)., Conclusions: Although all subjects demonstrated a significant improvement in asthma control and quality of life, the improvement attributable to this intervention was limited to two domains in disease-specific quality of life.

The objective of the present document is to review the impact of new information on the recommendations made in the last (1999) Canadian Asthma Consensus Guidelines. It includes relevant published studies and observations or comments regarding what are considered to be the main issues in asthma management in children and adults in office, emergency department, hospital and clinical settings. Asthma is still insufficiently controlled in a large number of patients, and practice guidelines need to be integrated better with current care. This report re-emphasises the need for the following: objective measures of airflow obstruction to confirm the diagnosis of asthma suggested by the clinical evaluation; identification of contributing factors; and the establishment of a treatment plan to rapidly obtain and maintain optimal asthma control according to specific criteria. Recent publications support the essential role of asthma education and environmental control in asthma management. They further support the role of inhaled corticosteroids as the mainstay of anti-inflammatory therapy of asthma, and of both long acting beta2-agonists and leukotriene antagonists as effective means to improve asthma control when inhaled corticosteroids are insufficient. New developments, such as combination therapy, and recent major trials, such as the Children's Asthma Management Project (CAMP) study, are discussed.

Our objective was to determine if thiopurine methyltransferase (TPMT), the enzyme important in the metabolism of azathioprine in human beings, is detectable in red blood cell lysates (RBCL) of healthy dogs, cats, and horses. Values for TPMT activity were determined from blood collected from 20 healthy dogs, cats, and horses. The TPMT activity in each animal's RBCL was determined using a radioenzymatic end point involving TPMT-facilitated metabolism of 6-mercaptopurine to 6-methylmercaptopurine (6-MMP). One unit of TPMT activity represents the formation of 1 nmol of 6-MMP per milliliter of packed red blood cells per hour of incubation at 37 degrees C. TPMT activity in RBCL was detectable in all species, with mean RBC values +/- standard deviation of 17.9 +/- 3.79 U/mL in dogs; 2.76 +/- 0.70 U/mL in cats; and 2.185 +/- 0.36 U/mL in horses. Values for TPMT in the 3 species were significantly (P < .05) different from one another. TPMT values for dogs were significantly higher than the other species, and TPMT values for cats were significantly higher than those for horses. We conclude that RBCL TPMT values are measurable in dogs. cats, and horses and that dogs have higher values than cats or horses. These findings are consistent with the lower tolerance for azathioprine in cats as compared with dogs. It remains to be determined whether RBCL TPMT values in these species correlate with TPMT activity in the liver, where most of the metabolization of azathioprine is believed to occur.

Reductions in blood pressure that are associated with exercise training have been hypothesized to be the result of a sustained postexertional vascular alteration following single bouts of exercise. The purpose of this study was to determine whether a decrease in vascular sensitivity to vasoconstrictor agonists occurs after a single bout of exercise and whether this vascular alteration is sustained through various periods of exercise training. Vascular responses of abdominal aortic rings to norepinephrine (NE; 10(-9)-10(-4) M) were determined in vitro. Aortas were isolated from sedentary rats immediately after rats performed a single bout of treadmill exercise (30 m/min for 1 h); 24 h after the last exercise bout in rats exercised for 1 day; and 1, 2, 4, and 10 wk of training at 30 m/min, 60 min, 5 days/wk. Sensitivity to NE was only diminished after 10 wk of training. This diminished vascular sensitivity to NE was abolished with the removal of the endothelial cell layer. Furthermore, there were no reductions in developed tension or vascular sensitivity to the vasoconstrictor agonists KCl (10-100 mM), phenylephrine (10(-8)-10(-4) M), and arginine vasopressin (10(-9)-10(-5) M) in vessels either with or without the endothelial layer after a single bout of exercise. These data indicate that a single bout of exercise does not diminish aortic responsiveness to vasoconstrictor agonists and thus is not responsible for the diminished contractile responsiveness that occurs between 4 and 10 wk of moderate-intensity exercise training in rats. This vascular adaptation to exercise training appears to be mediated through an endothelium-dependent mechanism.

Infants are at increased risk of developing asthma after acute bronchiolitis. We assessed the hypothesis that cytokine production is related to the development of asthma after bronchiolitis. The smoking history and the presence of atopy or asthma in parents or siblings were recorded and blood mononuclear cell interferon (IFN)-gamma and interleukin (IL)-4 production in response to IL-2 were assessed in 32 infants hospitalized for bronchiolitis and in a subgroup (n = 19) in which pulmonary function tests were performed approximately 4.9 mo later. The presence of asthma was determined by the Delphi consensus method 2 yr after hospitalization. Infants were classified as follows: asthma absent (A, n = 14), possible (Po, n = 9), or probable (Pr, n = 9). Infants with possible and probable asthma had lower IFN-gamma production at the time of bronchiolitis and a trend to lower IFN-gamma production 4.9 mo later when compared with those who had no asthma. At the time of bronchiolitis, IFN-gamma production was: 123 +/- 31 versus 34 +/- 20 versus 21 +/- 14 pg/ml, A versus Po versus Pr (p = 0.02, ANOVA) and 4.9 mo after bronchiolitis, IFN-gamma production was: 147.3 +/- 45 versus 47.4 +/- 30 versus 22.3 +/- 32 pg/ml, No versus Po versus Pr (p = 0.08 ANOVA). IL-4 production did not differ between groups. Infants who went on to develop asthma had more parent smokers (21.4% versus 55. 6% versus 55.6%, A versus Po versus Pr, p < 0.04), lower VmaxFRC (122 +/- 18 versus 77 +/- 7 versus 67 +/- 8% predicted, A versus Po versus Pr, p < 0.02), lower PC40 histamine (6.4 +/- 3.3 versus 1.2 +/- 0.6 mg/ml, A versus Po+Pr, p < 0.03) but no increase in atopy or asthma in their family. Significant positive correlations were found between IFN-gamma production at the time of bronchiolitis and VmaxFRC (r = 0.606) or PC40 histamine (r = 0.648) 4.9 mo after bronchiolitis. Lower IFN-gamma production at the time of bronchiolitis is an indicator of lower pulmonary function and increased responsiveness to histamine 4.9 mo after bronchiolitis and is related to the development of asthma after bronchiolitis in infants.

Objective: To determine whether peritoneal fluid pH, glucose concentration, and lactate dehydrogenase activity can be used to differentiate horses with septic peritonitis from those with nonseptic peritonitis., Design: Prospective study., Animals: 46 horses, including 10 healthy horses, 15 horses with septic peritonitis, and 21 horses with nonseptic peritonitis., Procedure: Peritoneal fluid and blood samples were analyzed for pH, glucose concentration, and lactate dehydrogenase activity. Complete blood cell counts were performed, and peritoneal fluid samples were submitted for bacterial culture., Results: Horses with septic peritonitis had significantly lower peritoneal fluid pH and glucose concentrations than horses with nonseptic peritonitis and healthy horses. Compared with other tests, serum-to-peritoneal fluid glucose concentration differences > 50 mg/dl had the highest diagnostic use for detection of septic peritonitis. Peritoneal fluid pH < 7.3, glucose concentration < 30 mg/dl, and fibrinogen concentration > 200 mg/dl were also highly indicative of septic peritonitis., Clinical Implications: Peritoneal fluid pH and glucose concentration can be used to assist in the identification of horses with septic peritonitis. These measurements can provide an early indication of sepsis, especially if cytologic evaluation of peritoneal fluid is unavailable or results are equivocal and peritoneal fluid bacterial culture results are pending.

Because of reported efficacy of combining classes of antidepressants, 25 patients were treated with bupropion in combination with SRI's and venlafaxine. Fifteen patients inadequately responsive to monotherapy received combination treatment; ten patients without residual symptoms received adjunctive bupropion to treat SRI- or venlafaxine-induced side effects. Fourteen subjects (56%) responded, 11 (44%) did not. Twelve of 15 subjects receiving combination treatment to boost the effects of monotherapy responded, while only 2 of 10 subjects receiving combination treatment for side effects responded. Combination therapy was well tolerated even by geriatric and "medically frail" patients.

The purpose of this study was to evaluate the effects of probiotic administration on the prevalence of fecal shedding of Salmonella, the prevalence of postoperative diarrhea, the length of antimicrobial therapy, and the length of the hospitalization stay during the postoperative period in horses with colic. Two commercially available probiotics for horses were used in a double-blind prospective study of 200 horses undergoing surgery for colic. Probiotic or placebo was administered PO once a day for 7 days postoperatively, and fecal cultures for Salmonella were obtained daily for 10 days. After selection of 186 patients completing the treatment protocol, the results indicated that the commercial probiotic formulations had no effect on Salmonella shedding, prevalence of diarrhea, length of antimicrobial therapy, or length of hospitalization (P > .05). Twenty percent of the horses yielded 1 or more positive fecal cultures for Salmonella; of these horses, 74% were classified as asymptomatic shedders. Twenty-six percent of all horses had fluid diarrhea postoperatively, with only 12% of these horses having positive fecal cultures for Salmonella. The most common isolate was Salmonella krefeld (24 of 39 isolates). Among the different gastrointestinal disorders, horses with feed and sand impactions appeared to be more prone to shed Salmonella.

Objective: Evaluate histories, clinical signs, and laboratory data of 69 horses homozygous by DNA testing for hyperkalemic periodic paralysis (HPP)., Design: Cohort study., Sample Population: 69 of 189 horses testing homozygous for HPP between October 1992 and November 1994., Procedure: Questionnaires addressing signalment, training regimes, medical history, and current status of affected horses were sent to owners, trainers, or attending veterinarians. Data from completed questionnaires were tabulated and evaluated, using descriptive statistics., Results: Sixty-nine (37%) of 189 questionnaires were completed and returned. Clinical episodes of muscle weakness or paralysis varied in severity and frequency from mild muscle fasciculations to recumbency and death. Sixty-three of 68 HPP-affected horses were reported to have had stridor associated with exercise, excitement, stress, or episodes of muscle paralysis. Common endoscopic findings in affected horses included pharyngeal collapse, pharyngeal edema, laryngopalatal dislocation, and laryngeal paralysis. Twelve of 27 horses receiving acetazolamide had decreases in stridor while receiving medication., Clinical Implications: Most horses testing homozygous for HPP had clinical signs associated with pharyngeal and laryngeal dysfunction. Hyperkalemic periodic paralysis should be included on a differential list for horses examined for signs of laryngeal or pharyngeal dysfunction or stridor. Treatment with acetazolamide may help to control respiratory tract signs associated with this disease.

Objective: To describe clinical manifestations of Corynebacterium pseudotuberculosis infection in horses and to evaluate diagnostic methods for identification of this disease., Design: Retrospective case series., Animals: 538 horses with a diagnosis of C pseudotuberculosis infection., Results: Median age of horses with external abscesses was similar to that in horses with internal abscesses. Breed and sex did not appear to be associated with infection. Cases were detected during all 12 months; however, the disease was most common in the fall and early winter, with the highest incidence in September, October, and November in every year. Most horses (492/538, 91.4%) had a single episode of infection, without recurrence in subsequent years. Of 538 horses, 308 had pectoral abscesses, although infection was documented in many other anatomic locations. Forty-two horses had internal abscesses involving the abdomen or thoracic cavity. Corynebacterium pseudotuberculosis infection was readily identified by bacterial culture of aspirate samples from abscesses. The synergistic hemolysis inhibition test was useful for diagnosis of internal abscesses; however, it was unreliable for the diagnosis of external abscesses. Horses with external abscesses responded well to conventional treatment, in contrast to those with internal abscesses. The overall case fatality was low (3.9%), and was considerably lower for horses with external abscesses (0.8%) than for horses with internal abscesses (40.5%)., Clinical Implications: Serology (synergistic hemolysis inhibition titers > or = 512) is useful for diagnosis of internal abscesses, but not reliable for diagnosis in horses with external abscesses. Prognosis for horses with internal abscesses is considerably poorer than for those with external abscesses.

Concerns about the toxicities of psychomotor stimulants originate primarily from effects seen at high doses, when stimulants are abused. Low dose use in the apathetic medically ill patient has been generally associated with only minimal, short lived side effects, which are detailed herein. Confusion may be worsened in already delirious patients. Anxiety, psychosis, cardiovascular effects, insomnia, and tremor may occur but infrequently require discontinuation. Appetite is normally stimulated in the medically ill. In fact, stimulants are frequently utilized in the medically ill largely because of their minimal toxicity. The history of U.S. stimulant abuse in the twentieth century is briefly discussed. Abuse of prescribed stimulants appears to be infrequent. Over-zealous concern regarding abuse has previously led to unfortunate declines in appropriate utilization of stimulants, e.g., for attention deficit disorder. Guidelines for prescribing stimulants in light of abuse potential are included.

It is often suggested that polygenic or environmental factors are responsible for clinical variability between patients with identical mutations. However, most dominant diseases are caused by a change-of-function alteration in the mutant allele's protein product. All patients are heterozygous and presumably express both mutant and normal proteins from the corresponding genes. Thus, a possible molecular mechanism for clinical variability could be the difference in relative levels of mutant vs. normal mRNA in different patients with the same mutation. To investigate this hypothesis, it is necessary to have access to a series of tissue biopsies from many patients with the same mutation causing a clinically variable dominant disease. Human hyperkalemic periodic paralysis (HyperPP) has been shown to be a clinically variable disorder caused by change-of-function mutations of the skeletal muscle sodium channel protein. We recently identified a large (> 50,000) pedigree of affected Quarter Horses sharing the same causative amino acid alteration of the muscle sodium channel protein. The horses like humans show substantial clinical variability. In this report, we developed a fluorescent reverse transcription-polymerase chain reaction assay which quantifies the relative levels of normal and mutant mRNA expression of the horse adult skeletal muscle sodium channel gene in affected Quarter Horses. We found that asymptomatic horses showed more normal sodium channel mRNA, while moderately affected horses showed more mutant mRNA. The ratios of mutant/normal mRNA between these two groups are statistically different, suggesting that severity of HyperPP Quarter Horses may indeed be correlated to the ratio of mutant and normal sodium channel gene expression in skeletal muscle.

We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler, the Turbuhaler, or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age. The bronchodilator response did not differ between the two inhalational devices. The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used.

Pharyngeal flaps are often used to correct velopharyngeal insufficiency. They produce a permanent partial obstruction of the velopharyngeal space. Respiratory obstruction and obstructive sleep apnea have been reported following this surgery. We undertook a study to find out the incidence of sleep apnea associated with pharyngeal flap surgery. Forty-one children (aged 2 to 22 years) admitted for a pharyngeal flap underwent a polysomnographic recording prior to their surgery. One child with Steinert's disease showed some episodes of obstructive apnea, and the surgery was canceled. Forty children underwent pharyngeal flap surgery, and polysomnography with continuous arterial saturation was repeated following surgery. Postoperative polysomnograms were normal in 26 patients (65 percent) and abnormal in 14 patients (35 percent). Among the 14 abnormal patients, we found 6 with obstructive apneas, 6 with central apneas, and 2 with both central and obstructive apneas. Ten of the 14 abnormal patients were restudied in the following months. Eight children had normal recordings, while 2 had central apneas. The 4 patients who declined a follow-up recording had no clinical symptoms of respiratory difficulty when sleeping. Of the 2 children with abnormal recordings on long-term follow-up, 1 is asymptomatic, while the second has persistent snoring, nocturnal awakening, sweating, and daytime lethargy. A section of his flap has been recommended. Independent analysis of arterial oxygen saturation revealed that the percentage of time with a saturation of less than 90 percent identifies patients with clinically significant apneas. Our data show that significant sleep apneas following pharyngeal flaps may not be as frequent or permanent as previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study, one of the first of its kind, describes the characteristics of community living placements for insanity acquittees conditionally released following hospitalization, along with the "fit" between living placement and individual characteristics. Although the small number of insanity acquittees (n = 13) and community placements (n = 9) precluded meaningful statistical analyses of results, the study provides a model for studying the characteristics of placements as well as personal characteristics of acquittees, and the interaction between the two. It also suggests the possible importance of this interaction, operationalized as "fit" between characteristics and placement. Consistent with research findings for other criminal defendants and for nonforensic psychiatric patients released from hospitalization, a better fit between acquittee and community placement may be associated with increased likelihood of success on conditional release.

Salmonellosis is the most common infectious cause of diarrhea or colitis in horses. It can be associated with high fatality rates in patients with compromised host defenses. The increasing incidence of infection and antimicrobial resistance present a challenge for the practicing veterinarians. The epidemiology and pathogenesis of salmonellosis are reviewed. Diagnosis, treatment, and control of disease are discussed.

Ouabain, a cardiac glycoside, binds to the Na(+)-K(+)-adenosine triphosphatase (Na+ pump) and prevents active transport of Na+ and K+ across cell membranes. We used [3H]ouabain to quantify the number and affinity of Na+ pumps in skeletal muscle from Quarter Horses with the muscular disorder hyperkalemic periodic paralysis (HYPP). [3H]Ouabain-binding properties of gluteal muscle from clinically normal and affected horses were used to determine whether altered Na+ pump number or affinity could contribute to the pathologic features of muscle in affected horses. Foals and adult horses with HYPP were compared with age-matched clinically normal horses. The number of [3H]ouabain-binding sites in adult gluteal muscle was not different between the 2 types of horses (85.7 +/- 8.9 pmol of [3H]ouabain-binding sites/g [wet muscle weight] in horses with HYPP vs 100.2 +/- 8.8 pmol/g in clinically normal adult horses). Gluteal muscles in HYPP-affected and clinically normal foals also contained a similar number of [3H]ouabain-binding sites (222.3 +/- 21.0 pmol/g vs 225.3 +/- 24.2 pmol/g, respectively). The affinity of these binding sites for ouabain was not different, between adults or foals, in clinically normal or affected horses. Our results indicate that membrane events underlying the periodic episodes of paralysis in horses with HYPP are not attributable to quantitative changes in Na+ pump number or affinity. Our data cannot exclude the possibility that the specific activity of the Na+ pump is altered in muscle from HYPP-affected horses.

Four Quarter Horses (1 stallion, 3 mares) with hyperkalemic periodic paralysis were mated to unaffected horses to determine the genetic basis of the disease. The affected stallion was bred to 11 unaffected mares (4 Quarter Horses, 1 Arabian, 2 Standardbreds, and 4 Thoroughbreds). The 3 affected mares were bred to an unaffected Quarter Horse stallion. Of the 15 offspring obtained from these matings, 9 were affected with hyperkalemic periodic paralysis, and 6 were unaffected, consistent with an autosomal dominant mode of inheritance. Diagnosis was established by results of oral administration of potassium chloride and demonstration of characteristic clinical signs accompanied by hyperkalemia. Oral administration of potassium chloride resulted in marked increases in plasma potassium concentrations in affected and unaffected foals, although hyperkalemia was associated with clinical signs of hyperkalemic periodic paralysis in the affected foals. Evaluation of blood samples from affected and unaffected offspring revealed no linkage with erythrocyte and serum markers at 24 loci.

Five horses were admitted for treatment of smoke-inhalation injuries sustained in a barn fire. Three of the horses were mildly affected, with high respiratory rates (24 to 36 breaths/min) and normal to low arterial oxygen tensions (77.0 to 94.1 mm of Hg), and responded well to administration of diuretics, bronchodilators, corticosteroids, and antibiotics. The 2 remaining horses were severely affected. Both were in respiratory distress, with markedly low arterial oxygen tensions (50.4 and 57.1 mm of Hg) and cyanosis. These 2 horses required fluid resuscitation in addition to the treatments given to the less severely affected horses. Tracheostomy was performed to facilitate removal of large, obstructive, pseudomembranous tracheobronchial casts. Oxygen was administered by nasal or tracheal insufflation or by use of a high-frequency jet ventilator. The most severely affected horse developed hemorrhagic colitis and was euthanatized. The 4 surviving horses recovered in 2 to 5 months and resumed working without reduction in performance capability.

Packed cell volume, total plasma protein, serum sodium, potassium, and ionized Ca2+ concentrations, and blood pH were determined at the time of admission and following surgery in 147 horses with acute abdominal crisis. Horses were allotted to 3 categories on the basis of the surgical lesion: (1) nonstrangulating obstruction of the ascending or descending colon (category A, n = 76), (2) strangulating and nonstrangulating infarction of the cecum or ascending colon (category B, n = 37), and (3) strangulating and nonstrangulating infarction of the small intestine (category C, n = 25). Horses with low serum ionized Ca2+ concentration following surgery were given 23% calcium gluconate (100 to 300 ml) IV to effect, and ionized Ca2+ concentration was determined following treatment. The serum ionized Ca2+ concentrations of horses in categories A, B, and C before and after surgery were lower than our normal laboratory reference range. Prior to surgery, serum ionized Ca2+ concentration measured from horses in category B and C was lower than that in horses in category A. There was no difference in ionized Ca2+ concentration in serum samples obtained before surgery in horses from category B and C, and in serum samples obtained following surgery. There was a decrease in ionized Ca2+ concentration during surgery in horses in category A. There was no change between preoperative and postoperative ionized Ca2+ concentration in the samples obtained from horses in category B and C. After calcium gluconate administration, all horses with low serum ionized Ca2+ after surgery had concentrations within our normal range. Measurement of serum ionized Ca2+ in horses with an acute abdominal crisis is recommended.(ABSTRACT TRUNCATED AT 250 WORDS)