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BackgroundFactors associated with outcome in dogs diagnosed with infective endocarditis (IE) are not well characterized.ObjectivesEvaluate outcome and prognostic factors in dogs with IE.AnimalsOne hundred and thirteen dogs with IE.MethodsMedical records for dogs that fulfilled the modified Duke criteria between 2005 and 2020 were retrospectively reviewed. Signalment, preexisting conditions, clinicopathologic findings, treatment regimen, and outcomes were recorded. Univariate logistic regression was performed to identify categorical factors associated with mortality, and then multivariate analysis was performed.ResultsDogs were categorized as survivors (n=47), non-survivors (n=57), or lost to follow-up (n=9). Survival to discharge and at 1month was documented in 79 (70%) of 113 and 56 (54%) of 104 dogs, respectively, with median survival time (MST) of 72 days. Risk factors associated with mortality included development of congestive heart failure (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.4-97.8), thromboembolic events (OR, 5.7; 95% CI, 2.3-14.4), and acute kidney injury (OR, 6.2; 95% CI, 2.0-18.8). Administration of antithrombotic medications was associated with survival (OR, 0.35; 95% CI, 0.13-0.97). Dogs that were not treated with antithrombotics had MST of 92 days, whereas dogs treated with antithrombotics did not reach MST during the study period. The heart valves involved and etiologic agent identified did not correlate with outcome.Conclusion and clinical importanceDogs with IE that had thromboembolic events, acute kidney injury, or congestive heart failure had higher risk of mortality. Administration of antithrombotics was associated with prolonged survival time.

BACKGROUND: There is evidence of unmet psychiatric needs in children under 6. These young children are dependent on their parents to identify their mental health needs. This study tested child and parent factors associations with Parent perception of mental health need in their young child. METHOD: Parents of 917 children (ages 2–6 years) completed a structured diagnostic interview about their child assessing depression, anxiety, ODD/CD, ADHD and impairment. Parents were surveyed about their own depression, anxiety and asked about their psychiatric impairment. Parents were also asked whether they perceived their child as having a mental health need. RESULTS: Only 38.8% of children who met criteria for a diagnosis were perceived by their parent as having a need, similar to previously studied rates in school-aged children. Perception of need was associated with higher levels of symptoms and impairment. Thresholds for at least half of parents perceiving their child as having a need were relatively high: 19 or more symptoms, or 4 or more impairments. There was also evidence of specificity: children with depressive disorders were more likely to be perceived as in need (OR: 6.53) compared with children with no disorder. In terms of parent factors, moderate-high parental depressive symptoms was associated with higher perception of child need when the child had a diagnosis than parents with no or mild depressive symptoms. CONCLUSIONS: Most preschool children that meet criteria for a psychiatric disorder are not perceived as needing help by their parents. Parent perception of need is dependent on both child and parent factors.

Radiographic assessment of heart size is important for clinical management of dogs with cardiovascular disease (CVDz). We sought to compare the ability of vertebral heart size (VHS), vertebral left atrial size (VLAS), and radiologists' assessment of left atrial size (RadLAE) to predict echocardiographic left atrial size (EchoLAE), an important marker of left heart disease severity. We also compared the ability of VHS and VLAS to predict echocardiographic criteria for ACVIM stage B2 (EchoB2) in dogs with myxomatous mitral valve disease (MMVD). This prospective observational study enrolled 183 dogs with known or suspected CVDz that had an echocardiographic examination and thoracic radiographs obtained within 24 h. Compared to increased VHS, VLAS 2.3 was a more accurate predictor of EchoLAE (P = .002). VLAS 2.3 and RadLAE (both P .0001) were independently associated with EchoLAE but VHS was not (P = .45). Optimal cutoffs for VLAS and VHS to predict EchoLAE were 2.3 vertebrae (sensitivity [Sn] = 90.3%, specificity [Sp] = 73.6%) and 11.1 vertebrae (Sn = 75.8%, Sp = 76.0%), respectively. Diagnostic accuracy of VLAS (AUC 0.84, 95% CI 0.73-0.92) and VHS (AUC 0.78, 95% CI 0.66-0.88) to predict EchoB2 in dogs with subclinical MMVD (n = 64) were not significantly different (P = .17). Results demonstrate that VLAS and RadLAE were superior indicators of EchoLAE compared to VHS in dogs with known or suspected CVDz. Both VLAS and VHS are useful predictors of EchoB2 in dogs with subclinical MMVD. When echocardiography is unavailable, VLAS represents a useful radiographic measurement to aid clinical management of dogs with known or suspected CVDz.

Background There is wide variability in radiographic grading systems in thoracolumbar spinous processes in horses. The aim of this study was to determine the agreement of grading different parameters, and combinations of those, in radiographs of the spinous processes of the equine thoracolumbar spine in the scope of a pre-purchase examination. We hypothesized that agreement is variable and interpretation of these radiographs is difficult. Methods Radiographs of the thoracolumbar spine of healthy horses (N = 100) were assessed by three observers. Spinous processes were separately graded for interspinous space width, modelling, radiopacities, radiolucencies and isolated opacities dorsally. Inter- and intra-observer agreement was assessed for individual and combinations of parameters. Results Agreement (inter- and intra-observer) was good for the following parameters: interspinous space width, isolated opacities dorsally, beak-shaped formations craniodorsally and modelling cranioventrally. The agreement increased slightly for a sum of specific parameters such as radiopacities, modelling, dorsal abnormalities and related abnormalities involving increased opacity, modelling and osseous cyst-like lesions. Agreement for the total radiographic abnormalities per back was moderate. Conclusions Grading of thoracolumbar radiographs in horses without back pain showed good inter- and intra-observer agreement for specific parameters and these should be used in future grading of spinous processes. Limitations should be considered in pre-purchase examinations.

Background Broadly applicable reference intervals (RIs) for measurements of left atrial (LA) and left ventricular (LV) size and function generated prospectively using statistically appropriate methods are limited. Objectives To generate body size-independent RIs for linear, area, and volume measurements of LA size and LV size and function. Animals Healthy adult dogs (n = 122) of variable size and somatotype. Methods Prospective study. All dogs underwent an echocardiogram performed by the same examiner. Effects of body weight, sex, age, and heart rate were evaluated by regression and correlation analyses. Scaling exponents and prediction intervals were generated for linear measurements using the allometric equation. After normalization to body weight, 95% RIs were determined using nonparametric methods with 2.5 and 97.5 percentiles serving as the lower and upper limits (each with 90% confidence intervals), respectively. Results Linear LA and LV measurements were strongly correlated (R2 ≥ 0.79) with body weight. Scaling exponents were close to the expected 1/3 (0.299-0.392). Prediction intervals for linear measurements of LV chamber size were considerably narrower than previously reported. Weak correlations (r = -0.42 to -0.50) among LV fractional shortening, fractional area change, and ejection fraction and body weight were identified. No other meaningful relationships were identified between the measurements and sex, age, and heart rate. Conclusions and clinical importance Body size-independent RIs for several linear, area, and volume measurements of LA and LV size and function were generated prospectively from a large and diverse reference population and are available for clinical use.

Coronary artery anomalies have been reported in Bulldogs and present an increased risk when performing balloon valvuloplasty. Identification of coronary anomalies has been reported using multidetector-row computed tomographic (MDCT) angiography with electrocardiographic gating. However, the utility of non-electrocardiographic-gated 16-row computed tomographic for MDCT for the identification of coronary artery anatomy or anomalies to the authors' knowledge has not been fully investigated. The purpose of this study was to evaluate the feasibility of non-electrocardiographic-gated computed tomographic (CT) angiography to identify coronary anomalies in Bulldogs with pulmonary valve stenosis. In this prospective, observational study, Bulldogs with echocardiographically diagnosed pulmonary valve stenosis, an echocardiographically derived transpulmonic pressure gradient >70 mm Hg, and a clinician recommendation for balloon valvuloplasty were included. Anesthetized dogs underwent a 16-row MDCT non-electrocardiographic-gated CT angiography. A board-certified veterinary radiologist and board-certified veterinary cardiologist reviewed the CT angiography studies and identified the coronary artery anatomy. When normal coronary artery anatomy was detected on CT angiography, a right ventricular outflow tract fluoroscopic angiogram was performed and evaluated during levophase to confirm normal coronary anatomy prior to balloon valvuloplasty. Dogs with coronary anomalies noted on CT angiography were recovered from anesthesia and balloon valvuloplasty was not performed. All dogs (10/10; 100%) had interpretable images from the non-electrocardiographic-gated CT angiography. Coronary anomalies were identified in six dogs based on non-electrocardiographic-gated CT angiography, five with type R2A anomaly and one had a single left coronary ostium. Four dogs had normal coronary anatomy based on non-electrocardiographic-gated CT angiography. Balloon valvuloplasty was performed without incident in these four dogs. We conclude that non-electrocardiographic-gated CT angiography represents a noninvasive method for diagnosing coronary anomalies in Bulldogs with pulmonary valve stenosis.

Author(s): Nishimura, Satoko; Visser, Lance C; Belanger, Catherine; Oldach, Maureen S; Gunther-Harrington, Catherine T; Stern, Joshua A | Abstract: BackgroundVelocity ratio, velocity time integral (VTI) ratio, and pulmonary valve area indexed to body surface area (iPVA) are methods of assessment of pulmonary valve stenosis (PS) severity that are less dependent on blood flow. Studies evaluating these methods are limited.ObjectivesTo determine the effects of butorphanol, atenolol, and balloon valvuloplasty (BV) on velocity ratio, VTI ratio, iPVA, mean PG, and max PG.AnimalsTwenty-seven dogs with PS (max PG g50 mm Hg).MethodsProspective study. All dogs underwent an echocardiogram at baseline, 5-minutes after administration of butorphanol (0.2-0.25 mg/kg IV), and 2-to-4 weeks after atenolol (1-1.5 mg/kg q12h). Twenty-one of these were evaluated 24-hours after BV.ResultsThere were no significant differences (P g .05) amongst any of the methods of assessment of PS severity after butorphanol. After atenolol, mean (SD) of mean (57.0 [21.0] mm Hg) and max PG (93.1 [33.8] mm Hg) were significantly decreased (P ≤ .047) compared with baseline (65.2 [26.2] mm Hg and 108 [44.4] mm Hg, respectively). After atenolol, there were no significant (P ≥ .12) differences in velocity ratio (0.29 [0.09]), VTI ratio (0.18 [0.05]), or iPVA (0.43 [0.16] cm2 /m2 ) compared with baseline (0.30 [0.09], 0.19 [0.09], 0.44 [0.17] cm2 /m2 , respectively).Conclusions and clinical importanceAtenolol might reduce mean and max PG but does not alter less flow-dependent methods of assessment of PS severity (velocity ratio, VTI ratio, and iPVA) in dogs with PS. Results support an integrative approach to assessment of PS severity that includes less flow-dependent methods, particularly in states of altered flow or right ventricular function.

Introduction: Fluoxetine is a selective serotonin reuptake inhibitor and long-lived open channel blocker of the acetylcholine receptor often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). Methods: We report a 42-year woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed prior to and 1 month after discontinuation of fluoxetine. Results: Two-Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. Conclusion: This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. This article is protected by copyright. All rights reserved.

Background Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin. Methods : Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan–Meier method and compared using log-rank and Cox regression analyses. Results From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P

SummaryReasons for performing study Intra-articular (IA) injection of corticosteroids with or without hyaluronate (HA) has been used for decades in equine practice for treatment of noninfectious synovitis and osteoarthritis. However, to date, no large-scale randomised equine field trials have been reported that address the supposed superior clinical efficacy of the combination of corticosteroid + HA compared with IA injection of corticosteroid alone. Objectives To compare the clinical efficacy of IA triamcinolone acetonide (TA, 12 mg) compared with IA TA (12 mg) + high molecular weight HA (20 mg) in horses with clinical joint disease. Study design Prospective, randomised, parallel, open label, multicentre clinical trial. Methods Eighty client-owned horses from 13 clinics were included. Lameness and effusion scores were assessed at baseline and 3 weeks after IA treatment. A standardised telephone questionnaire was completed between the owner and consulting veterinarian at 3 months. The primary outcome parameter was clinical success rate, defined as ≥2 grades lameness reduction (on a 0–5 scale) at 3 weeks. Chi-square statistics and binary logistic regression were used to analyse data on an intention-to-treat basis for the 3 week outcome. Results The success rate of IA TA 3 weeks after treatment was 87.8%, while that of TA+HA was 64.1% (P = 0.01). Age >13 years was associated with a reduced success rate for the combination treatment (P = 0.004) at 3 weeks. At 3 months, half the horses in each group had returned to their previous level of performance. Conclusions The combination of TA with HA was associated with a lower short-term clinical success rate and a similar medium-term outcome compared with IA TA, with only half of the horses performing at their previous level of exercise after 3 months regardless of treatment group allocation.

Objective To report signalment, history, indications, complications and outcome for 28 dogs and 5 cats in which 34 permanent epicardial pacing leads were surgically placed by transdiaphragmatic approach (32) or intercostal thoracotomy (2). Methods Medical records (2005–2010) were reviewed. Signalment, age, species, gender, clinical signs, presence of structural heart disease and/or congestive heart failure, ECG diagnosis, body weight ( 10 kg), and overall survival rate were recorded. Statistical correlations were made between these variables and major and minor complications rates. Results Except for body weight, no statistical differences were identified in prevalence of major (life threatening or requiring replacement of the pacemaker system) or minor (self-limiting) complications; dogs weighing >10 kg had significantly more major complications (P = .03). There was a trend (P = .051) for lower survival in animals that had major complications. Conclusions Larger dogs (>10 kg) may be predisposed to more major complications with epicardial pacemaker (EP) implantation. Major complication rate and survival time are similar to those reported for transvenous pacing and therefore implantation of EPs remains a suitable alternative.

Objective: To compare the concentration of a representative growth factor (transforming growth factor-beta [TGF-β]1) eluted from a platelet-rich fibrin matrix (PRFMatrix), a platelet-rich fibrin membrane (PRFMembrane), and a whole blood clot (BC) over time, and to compare the mitogenic effect of the eluents from each construct. Study Design: In vitro study. Sample Population: PRFMatrix, PRFMembrane, and BC (n=4/construct/time point). Methods: Each construct was placed in tissue culture wells containing media for 7 days. The media was collected and replenished on days 1, 3, 5, and 7 and the concentration of eluted TGF-β1 was measured by enzyme-linked immunosorbent assay. Canine tendon cells were subjected to additional aliquots of the conditioned media and the amount of cell proliferation compared. Results: The media from both PRFM (PRFMatrix and PRFMembrane) constructs contained significantly more (P≤.026) TGF-β1 at days 1 and 3 and produced a significant increase (P≤.044) in cell proliferation at all time points compared with the BC. The PRFMembrane media contained significantly more (P≤.05) TGF-β1 at days 1 and 3 and produced a significant increase (P≤.002) in cell proliferation at all time points compared with the PRFMatrix. Conclusions: Both PRFM constructs are comprised of a dense fibrin scaffold that contains increased concentrations of TGF-β1 and are capable of increasing tendon cell proliferation over time when compared with a BC. Clinical Relevance: The sustained increase in growth factor availability in PRFM constructs may be beneficial in the healing of biologically compromised tissues.

Background: The Social Communication Questionnaire (SCQ) is a screening instrument with established validity against the Autism Diagnostic Interview-Revised (ADI-R) in children aged 4 years and older. Indices of diagnostic accuracy have been shown to be strong in school-aged samples; however, relatively little is known about the performance of the SCQ in toddlers at risk of autism spectrum disorder (ASD). Methods: This study replicates and extends previous research by Corsello et al. (2007) in a comparatively large (N = 208), substantially younger (20–40 months) sample of children at high risk of ASD. The usefulness of the SCQ as a second-level screening instrument with different cut-off scores was evaluated in relation to IQ, age, and type of ASD diagnosis. The use of the SCQ as compared to the ADI-R was evaluated against clinical diagnosis, both alone and in combination with the ADOS. Results: The SCQ with different cut-offs consistently showed an unsatisfactory balance between sensitivity and specificity in screening for ASD in high-risk toddlers, with only a few exceptions for specific age, IQ, or diagnostic groups. Even though the SCQ and ADI-R were highly correlated, diagnostic agreement with the best evidence clinical diagnosis was poor for both measures. The ADOS used alone consistently had the highest predictive value. For autism versus not-autism, the combined SCQ and ADOS performed as well as the ADOS alone and notably better than the combination ADI-R and ADOS. Conclusions: The SCQ is likely to result in a number of false-positive findings, particularly in children with autism symptomatology, and the balance between sensitivity and specificity is poor. The ADOS should be considered the most valid and reliable diagnostic instrument in these very young at-risk children. Keywords: SCQ, ADI-R, ADOS, review, validity, toddlers, autism. Abbreviations: SCQ: Social Communication Questionnaire; ADI-R: Autism Diagnostic Interview-Revised; ADOS: Autism Diagnostic Observation Schedule; ASD: autism spectrum disorder.

BACKGROUND: The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity-modulated radiotherapy (IMRT) versus 3-dimensional conformal radiotherapy (3D CRT). METHODS: Fifty-seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n = 31), 5-fluorouracil (5-FU) (n = 25), or none (n = 1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups. RESULTS: The 2-year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P = .5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade ≥2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P = .02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P = .05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P = .17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P = .19). The median liver V30 was 16.1% and 28%, respectively (P < .001). CONCLUSIONS: Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function. Cancer 2010. © 2010 American Cancer Society.

Purpose To explore the value of diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) for the improved detection and quantification of cerebral tissue changes associated with ageing and white matter hyperintensities (WMH). Materials and Methods DWI (n = 340) and MTI (n = 177) were performed in nine centers of the multinational Leukoaraiosis And DISability (LADIS) study investigating the impact of WMH on 65- to 85-year-old individuals without prior disability. We assessed the apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT) and within WMH and related them to subjects' age and WHM severity according to the Fazekas score. Results ADC and MTR values showed a significant inter-site variation, which was stronger for the MTR. After z-transformation multiple regression analysis revealed WMH severity and age as significant predictors of global ADC and MTR changes. Only lesional ADC, but not MTR was related to WMH severity. Conclusion ADC and MTR are both sensitive for age and WMH related changes in NABT. The ADC is more sensitive for tissue changes within WMH and appears to be more robust for multicenter settings. J. Magn. Reson. Imaging 2009;29:268–274. © 2009 Wiley-Liss, Inc.

OBJECTIVES: To investigate, in a cohort of nondisabled elderly people, the association between urinary complaints and severity of age-related white matter changes (ARWMC). DESIGN: Cross-sectional data analysis from a longitudinal multinational study. SETTING: The Leukoaraiosis And DISability Study, assessing ARWMC as an independent predictor of the transition from functional autonomy to disability in elderly subjects. PARTICIPANTS: Six hundred thirty-nine subjects (288 men, 351 women, mean age 74.1±5.0) with magnetic resonance imaging (MRI)-detected ARWMC of different severity. MEASUREMENTS: ARWMC severity was graded on MRI as mild, moderate, and severe (Fazekas scale). MRI assessment also included ARWMC volumetric analysis and the count of infarcts. Urinary complaints (nocturia, urinary frequency, urgency, incontinence) were recorded based on subjects' answers to four questions. RESULTS: In comparing the three ARWMC severity groups, there was a significant difference only in prevalence of urgency, with 16% of subjects in the mild severity group, 17% in the moderate severity group, and 25% in the severe group (P=.03). Adjusting for age, sex, lacunar and nonlacunar infarcts, diabetes mellitus, and use of diuretics, severe ARWMC retained an independent effect in the association with urinary urgency (odds ratio=1.74, 95% confidence interval=1.04–2.90, severe vs mild group). Subjects with urinary urgency also had higher ARWMC volumes (25.2, vs 20.4 mm3 in those without urinary urgency; P

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age±standard deviation 74.1±5.0) with magnetic resonance imaging–detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P

Previous studies indicate that the low maximum rate of oxygen consumption (VO2max) of chronic heart failure (CHF) patients is not because of impaired pump function of the heart. We hypothesize that VO2 during maximum exercise is determined by the total oxidative capacity of skeletal muscle. VO2max of six controls and 14 CHF patients, New York Heart Association class I-III, was determined using an incremental bicycle ergometer test. Cryostat sections of a biopsy from the quadriceps femoris muscle were incubated for succinate dehydrogenase (SDH) using quantitative histochemistry. VO2max (range: 29 ml O2 kg muscle(-1) min(-1) in a class III patient to 118 ml O2 kg muscle(-1) min(-1) in a control subject) correlates with the mean SDH activity of skeletal muscle fibres (r=0.79 or r=0.81, including or excluding oxygen uptake at rest, respectively; P

BACKGROUND: During the baseline period of a clinical trial comparing different dosage schedules of inhaled steroids, asthmatic children (aged 6-10 years) were expected to meet the inclusion criterion of airways hyper-responsiveness (PD(20) methacholine < 80 micro g) after withdrawal of inhaled corticosteroids for 2-8 weeks. However, many children failed to do so. OBJECTIVE: It has been shown that young wheezing children may outgrow their symptoms. We investigated if differences between children with and without airways hyper-responsiveness after withdrawal of inhaled corticosteroids were compatible with differences between transient and persistent wheezers found in other studies. METHODS: Seventy-eight children entered the study, of which 41 developed airways hyper- responsiveness after withdrawal of inhaled corticosteroids, and 37 did not. These two groups of children were compared with respect to differences in demographic, clinical, and immunological features (IL-4, IL-5, IL-10, and IFN-gamma produced by Con A stimulated peripheral mononuclear cells (PBMCs) and serum IL-4, IL-5 and soluble intercellular adhesion molecule-1 (sICAM-1)). RESULTS: Hyper-responsive children had more atopic features (positive RAST, high IgE, eczema), lower levels of FEV1 and lower concentrations of sICAM-1 than non-hyper-responsive children. Apart from a borderline significantly higher IL-4 production in the hyper-responsive group, other immunologic parameters were comparable. Multivariate logistic regression analysis showed that high serum IgE, low FEV1, and low sICAM-1 levels were independently associated with the presence of airways hyper-responsiveness after stopping inhaled corticosteroids. Atopy was associated with higher concentrations of IL-4 in the hyper-responsive group. CONCLUSION: After withdrawal of inhaled corticosteroids many children previously diagnosed with asthma did not develop airways hyper-responsiveness. We conclude that hyper-responsive children share features with persistent wheezers as found in previous studies, whereas the non-hyper- responsive children may represent transient wheezers.

In patients with coronary artery disease (CAD), rate responsive pacing is considered to be contraindicated because an increase in heart rate may increase oxygen demand. Although previous studies have shown no subjective increase in ischemia during rate responsive pacing, data from objective assessment have not been documented. The goal of this study was to determine if there was an increase in ischemia on 201-Thallium ( 2 0 1 TI) exercise scintigraphy in this mode of pacing in patients with CAD and angina. Eighteen consecutive patients with chronic atrial fibrillation and symptomatic bradyarrhythmias with a pacemaker for more than 6 months participated in the study. In VVI and VVIR modes a symptom-limited exercise 2 0 1 TI scintigram was performed in a single blind randomized crossover fashion. Exercise duration, anginal attacks, use of nitroglycerine (NTG) tablets, blood pressure, and analysis of the scintigrams were assessed during each pacing mode. Fifteen men and three women were included (age 65.9 ′ 4.9 years, LVEF 0.44 ′ 0.07). Four were in Class III angina pectoris, and 14 in class II. The mean exercise duration increased 28% in the VVIR group without an increase in anginal attacks per week or the use of NTG tablets. On scintigrams, no differences were seen between the two groups. One patient was withdrawn from the study because of an increase in angina pectoris (AP) attacks during VVIR pacing. Rate responsive pacing is safe and effective in patients with CAD without an increase in subjective and objective signs of ischemia.

The interaction of 2-amino-3-benzoyl-thiophene derivative, PD81,723, as well as other G protein-coupled receptor (GPCR)-modulating agents such as suramin (SUR), N-ethylmaleimide (NEM), GTP, and NaCl with the rat adenosine A1 receptor was investigated using kinetic, saturation, as well as displacement experiments of various agonists, partial agonists or antagonists. PD81,723 enhanced agonist (CPA, R-PIA, NECA) binding ∼2-fold, while its effect on CPA binding was increased (4–11-fold) with other modulators present. In contrast, binding of antagonists (DPCPX, CPT, N-0840) was inhibited, while binding of partial agonists (8BCPA, MeSCPA) remained uninfluenced. The effect of PD81,723 is consistent with shifting A1 receptors to an “active” (R*) state with high affinity for agonists and low for antagonists. Further, all described allosteric modulators influenced both agonist and antagonist binding. The IC50 values observed for the agonist CPA, ranging from 4.7 nM in the presence of PD81,723 to a high value of 2.9 μM in the combined presence of NEM, NaCl, and GTP, represented a greater than 600-fold affinity shift. We suggest that the latter micromolar IC50 value may approximate CPA’s “true” affinity (KA) for the rat adenosine A1 receptor. Drug Dev. Res. 51:207–215, 2000. © 2001 Wiley-Liss, Inc.

The clinical value of magnetic resonance perfusion imaging (MRI) was investigated by quantitative comparison with 201thallium-single-photon emission computed tomography (201TI-SPECT) and quantitative coronary angiography (QCA). Short-axis imaging was performed during dipyridamole administration in 13 patients with single-vessel coronary artery disease. Using inner and outer contours, the myocardium was divided into 30 contiguous, radial regions. Defining a perfusion defect as a region with less than 90% of maximum 201TI intensity, nine patients had a matching perfusion defect, two had no defect on both 201TI-SPECT or MRI, and one had a defect on 201TI-SPECT but not on MRI. One patient had a defect on both modalities but with inaccurate localization. Three perfusion parameters were investigated: a) maximum contrast enhancement (MCE); b) slope of the signal intensity versus time curve; and c) inverse mean transit time (1/MTT). The sensitivity and specificity of MCE in the detection of perfusion abnormalities with TI-SPECT as the reference method were 71% and 71%, respectively (slope 77% and 61%, 1/MTT 44% and 70%). Furthermore, correlations were calculated per patient for the entire circumference of the short-axis myocardium. Median correlations were as follows: MCE 0.92, slope 0.91, and 1/MTT 0.40. Mismatches between 201TI defects and defects on MRI resulted in low mean correlations (MCE 0.45, slope 0.46, and 1/MTT 0.26). There was a trend between severity of perfusion defects on MRI (using MCE) and QCA stenosis area (r = −0.56, P = 0.06). Thus, MRI and 201TI-SPECT demonstrate fair agreement in the assessment of perfusion defects but show moderate correlation when the entire short-axis myocardium is correlated. J. Magn. Reson. Imaging 2000;11:607–615. © 2000 Wiley-Liss, Inc.

The feasibility and safety of transesophageal cardiac pacing during clinical MRI at 1.5 Tesla is considered. An MRI compatible pace catheter was developed. In vitro testing showed a normal performance of the pulse generator, image artifacts that extended less than 11 mm from the catheter, and a less than 5% increase in noise. Cardiac stimulation induced by MRI was not observed and, theoretically, is not expected. Potentially, tissue around the catheter tip may become heated. This heating (ΔT) was monitored. Eight dogs were exposed to MRI during pacing. For low RF radiation exposure, a time-averaged squared B1 field below 0.08 pT2 (SAR < 0.03 W/kg), ΔT was below 1°C. For high RF radiation exposure, but at normal RF radiation specific absorption rate (0.4 W/kg), ΔT was 5°C. Thus, transesophageal atrial pacing during MRI at low RF exposure seems to be possible to perform cardiac stress studies or to correct unstable heart rates.

Basket-shaped hosts were synthesized starting from the concave building block 4 To this end, oligo(oxyethylene) bridges, containing different aromatic rings, were attached to the 3,6- and 3′,6′-positions of the xylylene rings of 4. These bridges include 5,6-benzo-1,4,7,10-tetraoxadec-5-ene, 5,6,7-benzo-1,4,8,11-tetraoxaundeca-5,6-diene, 5,6-(2,3-naphtho)-1,4,7,10-tetraoxa-dec-5-ene, 8,9-benzo-1,4,7,10,13,16-hexaoxahexadec-8-ene and 8,9-(2,3-naph-tho)-1,4,7,10,13,16-hexaoxahexadec-8-ene chains. Alkali-metal ions and protonated aliphatic or aromatic diamines are bound in these baskets in a 1:1 host/guest ratio. For the metal ions, a clamshel-llike or a sandwich-like complex is proposed. Aliphatic diammonium guests are bound in such a way that the methylene chains are wedged in between the o-xylylene units of the host, as concluded from the upheld shifts observed in the 1H NMR spectra of the guest CH2 protons. Free energies of binding of the new hosts with nineteen guests were measured using the picrate extraction technique. The highest - ΔG° values were obtained for the complexes with the diammonium salts (- ΔG° values up to 13.4 kcal/mol).

Durch doppelte Alkeneliminierung entstehen aus den Molekulionen (El: 70 eV) von Dialkyldithiophosphinsauren R2P(S)SH (R: Et, nPr, nBu) Radikalkationen der Zusammensetzung [H3PS2]+. (m/z 98). Aus der Analyse des Stosaktivierungs(CA)-Massenspektrums und aus thermochemischen Daten ergibt sich, das [H3PS2]+. als ein Gemisch der Formen [HP(SH)2]+. und [HSPSH2]+. mit tri- bzw. dikoordiniertem Phosphor vorliegt. Eine Struktur mit tetrakoordiniertem Phosphor und P(S)-Gruppe, die einer ionisierten Dithiophosphinsaure H2P(S)SH entsprechen wurde, ist hingegen nicht zu beobachten. Mittels Neutralisations-Reionisations-Massenspektrometrie (NRMS) konnten neutrale Molekule „H3PS2” erzeugt werden, die sich als stabil in der verdunnten Gasphase erweisen und bevorzugt als HP(SH)2 vorliegen sollten. Die experimentellen Befunde stehen im Einklang mit den Ergebnissen semiempirischer MO-Rechnungen (MNDO). Gaseous “H3PS2” – Generation and Characterization Double alkene elimination from molecular ions (El: 70 eV) of dialkyldithiophosphinic acids R2P(S)SH (R: Et, nPr, nBu) leads to radical cations of composition [H3PS2]+. (m/z 98). By analysis of the collisional activation (CA) mass spectrum and using thermochemical data it was shown that [H3PS2]+. exists as a mixture of structures [HP(SH)2]+. and [HSPSH2]+. containing tri- or dicoordinated phosphorus, respectively. No structure corresponding to ionized dithiophosphinic acid H2P(S)SH was observed. Via neutralization reionization mass spectrometry (NRMS) neutral molecules „H3PS2” were obtained which proved to be stable in the dilute gas phase and most probably are of structure HP(SH)2. Experimental findings are in accordance with the results of semiempirical MO-calculations (MNDO).

The hosts (I) and (II) form 1:1 complexes with alkali-metal ions (clamshell or sandwich-like structure) or with protonated aliphatic or aromatic diamines (such as 1,7-diammoniumheptane or o-phenylenediammonium dipicrate).

A morphological and histological description of the reproductive system of O. polypunctata and O. nigropunctata is given and probable ancestral and derived features evaluated. As Oopelta possesses a composite male copulatory complex, the conditions that could lead to the evolution of such a complex were pointed out. These guidelines were used to establish some of the morphological differences that exist between the reproductive system of the Oopeltinae and that of the other subfamilies of the Arionidae. As a result of the differences encountered in the reproductive system, as well as the differences in the buccal retractor muscles, the central nervous system and the jaw, inter alia, and the “disjunct” distribution of the Oopeltinae, the inclusion of this subfamily in the Arionidae seems questionable. Due to lack of information a new sister group could not be pointed out.

The purpose of this paper is twofold: (1) to review the reproductive systems of the pulmonates in order to determine the inherent trends displayed by this system in these animals. The different elements composing this system, especially those of the pallial region, are homologised and the functional aspects (s. 1.) of the components described, including the origin and evolutionary development of the various prostatic elements of the pulmonates; and (2) to review ideas on and discuss the origin of the hermaphroditism of the pulmonate reproductive systems.

A comparison of the adult morphology, in conjunction with the ontogenetical development, of the terminal reproductive system elements of Pulmonata yield the following information. Basom-matophora and Systellommatophora are, in the retention of embryonic ditremy in adult conditions, completely neotenous (paedogenetic). In Basommatophora a ditrematic semi-diaulie to ditrematie diaulic lineage is apparent; a sequential monotrematie monaulie (Glacidorbidae) to simultaneous monotrematic monaulic (Siphonariidae) lineage, as a divergent condition, is proposed. The Systellommatophora, in view of similarities in proximal pallial duct development, are considered to be more closely related to Stylommatophora. Embryonic Stylommatophora recapitulate a ditrematic condition, but later ontogenetic stages, as well as adult morphology, indicate the establishment of a (primarily) semi-diaulic monotrematic system. The posterior ‘female’ position and anterior ‘male’ position of the genital orifice indicate an inherent divergent development in Stylommatophora. A series depicting possible trends in terminal duct development of Stylommatophora with anterior ‘male’ position gonopore is reconstructed from an analysis of the various (gross) features present. The genital systems with female properties resulting from apomixis take a terminal position in this series. Pulmonate. reproductive systems are regarded as having developed from intermediate stages in the life cycle of a sequential protandrous prosobranch ancestor.

A finite element analysis of a rotating ceramic gas turbine blade consisting of an airfoil and root is discussed. Three-dimensional results were obtained for the blade using both isotropic and orthotropic material properties. A two-dimensional study of the root considered the effects of friction, contact area, and root geometry.

Low-Molecular Phosphorus Sulfides in the Gas Phase Ionized low-molecular phosphorus sulfides, viz. PS+, PS, and P2S are generated by electron-impact (EI) fragmentation of P4S10. The results of collisional-activation (CA) mass spectra and semiempirical MO calculations suggest a linear structure for SPS+ (D∞;h) and a ring structure for P2S (D2h). As shown by neutralization-reionization mass spectrometry (NRMS) all the ions mentioned above can be reduced to the corresponding neutral molecules. Thus, low-coordinated phosphorus sulfides containing multiple-bond systems prove to be stable molecules in the dilute gas phase.

A finite element analysis of a rotating ceramic gas turbine blade consisting of an airfoil and root is discussed. Three-dimensional results were obtained for the blade using both isotropic and orthotropic material properties. A two-dimensional study of the root considered the effects of friction, contact area, and root geometry.